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Amar S, Badeghiesh A, Baghlaf H, Dahan MH. Gout in pregnancy: Obstetric and neonatal outcomes. Int J Gynaecol Obstet 2025; 169:349-355. [PMID: 39560012 PMCID: PMC11911954 DOI: 10.1002/ijgo.16025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 10/25/2024] [Accepted: 10/29/2024] [Indexed: 11/20/2024]
Abstract
OBJECTIVE The pregnancy, delivery, and neonatal outcomes of pregnancies complicated by gout have yet to be evaluated in a population-based study. We sought to evaluate the obstetric and neonatal outcomes in pregnant patients with gout using a national population database. METHODS This is a retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS). All women who delivered or had a maternal death in the USA (2004-2014) were included in the study. Pregnancy, delivery, and neonatal outcomes were compared between women with an ICD-9 diagnosis of gout to those without. RESULTS Overall, 9 096 788 women met the inclusion criteria. Of these, 168 women (1.8/100000) had gout. Patients with gout, compared to those without, were more likely to be older and obese and to have chronic hypertension, pregestational diabetes mellitus, and thyroid disease. Pregnant women with gout were more likely to develop gestational diabetes mellitus (aOR 1.78 [95% CI 1.17-2.72], P = 0.008), to require operative vaginal delivery (aOR 3.26 [95% CI 2.03-5.22], P = 0.0001), and to experience venous thromboembolism (aOR 8.47 [95% CI 2.06-34.82], P = 0.003) compared to pregnant patients without gout. Patients with gout were more likely to deliver a neonate with congenital anomalies compared to those without gout (aOR 3.38 [95% CI 1.24-9.20], P = 0.02). CONCLUSION Gout in pregnancy, or pregnancies complicated by a history of gout, are associated with increased risk of gestational diabetes mellitus, pulmonary embolism, and neonatal anomalies.
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Affiliation(s)
- Sam Amar
- Faculty of Medicine and Health SciencesMcGill UniversityMontrealQuebecCanada
| | - Ahmad Badeghiesh
- Department of Obstetrics and GynecologyKing Abdulaziz UniversityRabighSaudi Arabia
| | - Haitham Baghlaf
- Department of Obstetrics and GynecologyUniversity of TabukTabukSaudi Arabia
| | - Michael H. Dahan
- Department of Obstetrics and GynecologyMcGill UniversityMontrealQuebecCanada
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Xia L, Fan L, Huang J, Zhao Y, Tian L, Chen H, Cai L, Wu Q, Xia L. Effect of serum uric acid level on reproductive outcome in women without polycystic ovary syndrome undergoing in vitro fertilization. Reprod Biol Endocrinol 2024; 22:149. [PMID: 39574097 PMCID: PMC11580555 DOI: 10.1186/s12958-024-01313-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 11/03/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Prior research showed that elevated serum uric acid (SUA) levels in women with polycystic ovary syndrome (PCOS) before in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) treatment can lead to a lower rate of live birth and an increased risk for low birthweight. Nonetheless, it is not known whether elevated SUA results in similar reproductive outcome in women without PCOS. This study aimed to exploring the relationship between pre-pregnancy SUA levels and reproductive outcomes in non-PCOS women undergoing IVF/ICSI treatment. METHODS This single-center, retrospective study included 13,325 women without PCOS undergoing their first IVF/ICSI fresh embryo transfer cycles from January 2014 to December 2022 at a university-affiliated reproductive medicine center in China. The trends for pregnancy, obstetric and perinatal outcomes across quartiles of SUA levels were assessed. A logistic regression analysis was applied to control for baseline and cycle characteristics. Generalized addition model was used to draw spline smoothing plot. RESULTS There was no significant decreasing or increasing trend in the clinical pregnancy rate and live birth rate with the increase in quartiles of SUA levels. For Obstetric and perinatal outcomes following a single live birth, the percentage of hypertensive disorders in pregnancy (1.6-4.1%, Ptrend<0.001), gestational diabetes mellitus (5.9-13.9%, Ptrend<0.001), premature rupture of membranes (0.6-1.5%, Ptrend=0.016), preterm birth (6.3-9.2%, Ptrend=0.009), macrosomia (2.3-5.5%, Ptrend<0.001), large for gestational age (10.8-14.9%, Ptrend=0.002) all increased significantly from the lowest quartile to the highest. Logistic regression results showed that compared with those in quartile 1, the risk of maternal and infant complications mentioned above was still significantly higher in quartile 4 after adjusting for reproductive related factors. When further confounding factors were added, including body mass index (BMI), blood pressure, fasting blood glucose, and blood lipids related indicators, only gestational diabetes mellitus and macrosomia showed a significant increase. CONCLUSION In women without PCOS, SUA levels before IVF/ICSI treatment do not affect the probabilities of clinical pregnancy and live birth. An elevated SUA level is associated with an increased risk for hypertensive disorders in pregnancy, gestational diabetes mellitus, premature rupture of membranes, preterm birth, macrosomia, and large for gestational age. For gestational diabetes mellitus and macrosomia, the association is independent of BMI, blood pressure, blood glucose, and blood lipid.
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Affiliation(s)
- Leizhen Xia
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China
- Jiangxi Key Laboratory of Reproductive Health, Nanchang, China
| | - Lu Fan
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China
| | - Jialyu Huang
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China
- Jiangxi Key Laboratory of Reproductive Health, Nanchang, China
| | - Yan Zhao
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China
| | - Lifeng Tian
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China
| | - Houyang Chen
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China
- Jiangxi Key Laboratory of Reproductive Health, Nanchang, China
| | - Li Cai
- Department of Child Health, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China
| | - Qiongfang Wu
- Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital Affiliated to Nanchang Medical College, Nanchang, China.
| | - Leixiang Xia
- Department of Acupuncture, the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
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Chen S, Shi W, Ran F, Liu C, Luo H, Wu L, Wu Y, Zhang T, Yang Z. The activation of cGAS-STING pathway causes abnormal uterine receptivity in aged mice. Aging Cell 2024; 23:e14303. [PMID: 39113346 PMCID: PMC11561655 DOI: 10.1111/acel.14303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 07/11/2024] [Accepted: 07/24/2024] [Indexed: 11/15/2024] Open
Abstract
Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.
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Affiliation(s)
- Si‐Ting Chen
- Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of EducationGuizhou UniversityGuiyangChina
- College of Animal ScienceGuizhou UniversityGuiyangChina
- College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouChina
| | - Wen‐Wen Shi
- College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouChina
| | - Feng Ran
- Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of EducationGuizhou UniversityGuiyangChina
- College of Animal ScienceGuizhou UniversityGuiyangChina
| | - Cheng‐Kan Liu
- College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouChina
| | - Hui‐Na Luo
- College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouChina
| | - Li‐Juan Wu
- Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of EducationGuizhou UniversityGuiyangChina
- College of Animal ScienceGuizhou UniversityGuiyangChina
| | - Ying Wu
- College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouChina
| | - Tong‐Tong Zhang
- College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouChina
| | - Zeng‐Ming Yang
- Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of EducationGuizhou UniversityGuiyangChina
- College of Animal ScienceGuizhou UniversityGuiyangChina
- College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouChina
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Duo Y, Song S, Zhang Y, Qiao X, Xu J, Zhang J, Peng Z, Chen Y, Nie X, Sun Q, Yang X, Wang A, Sun W, Fu Y, Dong Y, Lu Z, Yuan T, Zhao W. Relationship between serum uric acid in early pregnancy and gestational diabetes mellitus: a prospective cohort study. Endocrine 2024; 83:636-647. [PMID: 37782356 DOI: 10.1007/s12020-023-03544-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 09/18/2023] [Indexed: 10/03/2023]
Abstract
PURPOSE The association between serum uric acid (UA) and gestational diabetes mellitus (GDM) was still unclear. Serum UA levels in pregnancy differed from that in non-pregnancy. This study aimed to investigate the changes of serum UA in early pregnancy, and to explore the association of serum UA with the risk of GDM. METHODS A prospective double-center study including 873 singleton pregnant women was conducted in Beijing, China since 2019 (clinical trial number: NCT03246295). Seventy-eight healthy non-pregnant women were selected to compare the changes of biomarkers in pregnancy. Spearman correlation and logistic regression analysis were performed to measure the relationship between serum UA in early pregnancy and GDM. RESULTS The incidence of GDM in our cohort was 20.27%(177/873). Compared with non-pregnant women, serum UA and creatinine decreased significantly during early pregnancy. Serum UA concentration in early pregnancy was significantly higher in GDM women than that in normal glucose tolerance (NGT) women [217.0(192.9, 272.0) μmol/l vs. 201.9(176.0, 232.0) μmol/l, p < 0.001]. After adjusted for confounding factors, elevated serum UA remained as an independent risk factor for GDM. The risk of GDM increased when serum UA was above 240 μmol/l (adjusted OR 1.964, 95% CI 1.296-2.977, p < 0.001), and stronger relationships between serum UA and GDM were observed in pregnant women aged over 35 years old and preBMI ≥ 24 kg/m2. CONCLUSION The normal range of serum UA and creatinine in pregnant women were lower than those in non-pregnant women. It is essential to monitor serum UA concentrations since early pregnancy to alert and prevent GDM, especially in older and heavier pregnant women. CLINICAL TRIAL NUMBER NCT03246295.
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Affiliation(s)
- Yanbei Duo
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China
| | - Shuoning Song
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China
| | - Yuemei Zhang
- Department of Obstetrics, Haidian District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Xiaolin Qiao
- Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Jiyu Xu
- Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People's Republic of China
| | - Jing Zhang
- Department of Laboratory, Haidian District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Zhenyao Peng
- Department of Dean's Office, Haidian District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Yan Chen
- Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Xiaorui Nie
- Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Qiujin Sun
- Department of Clinical Laboratory, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Xianchun Yang
- Department of Clinical Laboratory, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People's Republic of China
| | - Ailing Wang
- National Center for Women and Children's Health, China CDC, Beijing, People's Republic of China
| | - Wei Sun
- Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People's Republic of China
| | - Yong Fu
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China
| | - Yingyue Dong
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China
| | - Zechun Lu
- National Center for Women and Children's Health, China CDC, Beijing, People's Republic of China
| | - Tao Yuan
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.
| | - Weigang Zhao
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.
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Yan N, Song J, Jie H, Lee P, Liu S, Yuan Y. Serum uric acid did not affect embryonic and pregnancy outcomes in women without PCOS during IVF procedures. Front Endocrinol (Lausanne) 2024; 15:1310122. [PMID: 38444583 PMCID: PMC10912854 DOI: 10.3389/fendo.2024.1310122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 01/30/2024] [Indexed: 03/07/2024] Open
Abstract
Objectives Serum uric acid (UA) levels are associated with many systemic diseases. A previous study confirmed the association between high serum uric acid levels and poor prognosis of in vitro fertilization (IVF) treatment in polycystic ovary syndrome (PCOS) patients. This study aimed to explore the correlation between serum uric acid levels and reproductive outcomes in patients without PCOS. Methods A retrospective study that included 1057 patients who underwent pre-implantation genetic testing for monogenic disorders (PGT-M) treatment from January 2013 to December 2020 was conducted. The study population was further divided into 3 groups according to serum UA levels: the ≤250 μmol/L group, the 251-360 μmol/L group, and the >360 μmol/L group. The controlled ovarian hyperstimulation (COH) treatment outcomes, embryonic treatment outcomes and pregnancy outcomes of the first frozen embryo transfer (FET) cycle were compared among groups. Multivariable linear regression and binary regression were applied to detect the association between IVF outcomes and serum uric acid levels. Results The number of retrieved oocytes, fertilization rate, viable embryo rate, blastocyst formation rate and euploid rate were not associated with serum uric acid levels. The mature oocyte rate was negatively correlated with serum uric acid levels. The pregnancy outcomes of the first FET cycle were also not associated with serum uric acid levels. After adjustment for BMI, the perinatal outcomes were not associated with serum uric acid levels. Conclusion IVF treatment outcomes were not associated with serum uric acid levels in patients without PCOS.
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Affiliation(s)
- Niwei Yan
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
- Department of Surgery, Li Ka-shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Junli Song
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Huiying Jie
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Pingyin Lee
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Simin Liu
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
| | - Yuan Yuan
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, China
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Tan J, Fei H, Chen L, Zhu X. The association of hyperuricemia and maternal and fetal outcomes among pregnant women: a meta-analysis. J Matern Fetal Neonatal Med 2023; 36:2212830. [PMID: 37193631 DOI: 10.1080/14767058.2023.2212830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/18/2023] [Accepted: 05/04/2023] [Indexed: 05/18/2023]
Abstract
OBJECTIVE This meta-analysis aimed to investigate the relationship between hyperuricemia and maternal and neonatal complications in pregnant women. METHODS We searched PubMed, Embase, Web of Science, and the Cochrane Library from the databases' inception to August 12, 2022. We included studies that reported results on the association between hyperuricemia and maternal and fetal outcomes among pregnant women. Using the random-effects model, the pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated for each outcome analysis. RESULTS A total of 7 studies, including 8104 participants, were included. The pooled OR for pregnancy-induced hypertension (PIH) was 2.61 [0.26, 26.56] (z = 0.81, p = .4165; I2 = 96.3%). The pooled OR for preterm birth was 2.52 [1.92, 3.30] (z = 6.64, p < .0001; I2 = 0%). The pooled OR for low birth weight (LBW) was 3.44 [2.52, 4.70] (z = 7.77, p < .0001; I2 = 0%). The pooled OR for small gestational age (SGA) was 1.81 [0.60, 5.46] (z = 1.06, p = .2912; I2 = 88.6%). CONCLUSION Results of this meta-analysis indicate a positive relationship between hyperuricemia and PIH, preterm birth, LBW, and SGA in pregnant women.
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Affiliation(s)
- Jie Tan
- Department of Nutrition, Hangzhou Women's Hospital, Hangzhou, China
| | - Huali Fei
- Department of Reproduction and Family Planning, Hangzhou Women's Hospital, Hangzhou, China
| | - Lumeng Chen
- Department of Outpatient, Hangzhou Women's Hospital, Hangzhou, China
| | - Xuhong Zhu
- Department of Ministry of Women's health, Hangzhou Women's Hospital, Hangzhou, China
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Varghese B, Jala A, Meka S, Adla D, Jangili S, Talukdar RK, Mutheneni SR, Borkar RM, Adela R. Integrated metabolomics and machine learning approach to predict hypertensive disorders of pregnancy. Am J Obstet Gynecol MFM 2023; 5:100829. [PMID: 36464239 DOI: 10.1016/j.ajogmf.2022.100829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 11/28/2022] [Indexed: 12/05/2022]
Abstract
BACKGROUND Hypertensive disorders of pregnancy account for 3% to 10% of maternal-fetal morbidity and mortality worldwide. This condition has been considered one of the leading causes of maternal deaths in developing countries, such as India. OBJECTIVE This study aimed to discover hypertensive disorders of pregnancy-specific candidate urine metabolites as markers for hypertensive disorders of pregnancy by applying integrated metabolomics and machine learning approaches. STUDY DESIGN The targeted urinary metabolomics study was conducted in 70 healthy pregnant controls and 133 pregnant patients having hypertension as cases. Hypertensive disorders of pregnancy-specific metabolites for disease prediction were further extracted using univariate and multivariate statistical analyses. For machine learning analysis, 80% of the data were used for training (79 for hypertensive disorders of pregnancy and 42 for healthy pregnancy) and validation (27 for hypertensive disorders of pregnancy and 14 for healthy pregnancy), and 20% of the data were used for test sets (27 for hypertensive disorders of pregnancy and 14 for healthy pregnancy). RESULTS The statistical analysis using an unpaired t test revealed 44 differential metabolites. Pathway analysis showed mainly that purine and thiamine metabolism were altered in the group with hypertensive disorders of pregnancy compared with the healthy pregnancy group. The area under the receiver operating characteristic curves of the 5 most predominant metabolites were 0.98 (adenosine), 0.92 (adenosine monophosphate), 0.89 (deoxyadenosine), 0.81 (thiamine), and 0.81 (thiamine monophosphate). The best prediction accuracies were obtained using 2 machine learning models (95% for the gradient boost model and 98% for the decision tree) among the 5 used models. The machine learning models showed higher predictive performance for 3 metabolites (ie, thiamine monophosphate, adenosine monophosphate, and thiamine) among 5 metabolites. The combined accuracies of adenosine from all models were 98.6 in the training set and 95.6 in the test set. Moreover, the predictive performance of adenosine was higher than other metabolites. The relative feature importance of adenosine was also observed in the decision tree and the gradient boost model. CONCLUSION Among other metabolites, adenosine and thiamine metabolites were found to differentiate participants with hypertensive disorders of pregnancy from participants with healthy pregnancies; hence, these metabolites can serve as a promising noninvasive marker for the detection of hypertensive disorders of pregnancy.
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Affiliation(s)
- Bincy Varghese
- Departments of Pharmacy Practice (Mses Varghese and Meka and Dr Adela) and Pharmaceutical Analysis (Ms Jala and Dr Borkar)
| | - Aishwarya Jala
- National Institute of Pharmaceutical Education and Research, Guwahati, India
| | - Soumya Meka
- Departments of Pharmacy Practice (Mses Varghese and Meka and Dr Adela) and Pharmaceutical Analysis (Ms Jala and Dr Borkar)
| | - Deepthi Adla
- Bioinformatics Group, Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India (Mses Adla and Jangili and Dr Mutheneni)
| | - Shraddha Jangili
- Bioinformatics Group, Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India (Mses Adla and Jangili and Dr Mutheneni)
| | - R K Talukdar
- Department of Obstetrics and Gynecology, Gauhati Medical College, Guwahati, India (Dr Talukdar)
| | - Srinivasa Rao Mutheneni
- Bioinformatics Group, Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India (Mses Adla and Jangili and Dr Mutheneni)
| | - Roshan M Borkar
- National Institute of Pharmaceutical Education and Research, Guwahati, India
| | - Ramu Adela
- Departments of Pharmacy Practice (Mses Varghese and Meka and Dr Adela) and Pharmaceutical Analysis (Ms Jala and Dr Borkar).
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Suliman NA, Awadalla KE, Bakheit KH, Mohamed AO. Cancer antigen 125 and C-reactive protein inflammatory mediators and uric acid in association with preeclampsia in North Kordofan State, Western Sudan. PLoS One 2023; 18:e0280256. [PMID: 36689404 PMCID: PMC9870111 DOI: 10.1371/journal.pone.0280256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 12/07/2022] [Indexed: 01/24/2023] Open
Abstract
Pathophysiology of pre-eclampsia depends on a defective trophoblastic invasion of uteroplacental blood vessels that leads to placental ischemia and induction of an inflammatory process within the placenta. This process may trigger the expression of Cancer antigen 125 (CA 125), C-reactive protein (CRP) and uric acid (UA). This research aimed to evaluate the association of serum CA 125, CRP and uric acid with Preeclampsia. The study recruited 200 singleton Sudanese pregnant women, who were divided into three groups: controls (n = 100), mild preeclampsia (n = 46) and severe preeclampsia (n = 54). The study subjects were matched for maternal age, gestational age and body mass index. Blood samples were taken for measurement of the different variables using immune- assay and enzymatic automated chemical analysis. The levels of CA 125 in mild and severe preeclampsia were (21.94±0.749 IU/ml) and (40.78±1.336 IU/ml) respectively, which was significantly different (P<0.001) from the control mean (16.48±0.584 IU/ml). There was also a significant difference between the mean levels of CRP in mild and severe preeclampsia (15.17±0.788 mg/L), (31.50±1.709 mg/L) compared with controls (4.79±0.178 mg/L), (P<0.01). There was also a significant difference in the mean levels of UA in mild and severe cases (6.44±0.293 and7.37±0.272) in comparison with the controls (4.00±0.061); (P<0.001). There were significant differences between severe and mild groups (P<0.05). Cancer antigen 125, CRP and UA levels correlated positively with mean arterial blood pressure (MAP) where (r >0.7; P < 0.001). ROC curve validates the utility of these biomarkers for monitoring preeclampsia (AUC >0.8; P < 0.001). In conclusion CA 125, CRP and UA were significantly higher in preeclampsia compared with the controls. The rise of the analytes was directly associated with the severity of the disease.
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Affiliation(s)
| | - Khidir Elamin Awadalla
- Department of Obstetrics & Gynecology, Faculty of Medicine, University of Kordofan, Elobaied, Sudan
| | - Khalid Hussein Bakheit
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
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Hyperuricemia during Pregnancy Leads to a Preeclampsia-Like Phenotype in Mice. Cells 2022; 11:cells11223703. [PMID: 36429132 PMCID: PMC9688737 DOI: 10.3390/cells11223703] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 11/09/2022] [Accepted: 11/11/2022] [Indexed: 11/23/2022] Open
Abstract
Hyperuricemia is a common feature in pregnancies compromised by pre-eclampsia, a pregnancy disease characterized by hypertension and proteinuria. The role of uric acid in the pathogenesis of pre-eclampsia remains largely unclear. The aim of this study was to investigate the effect of elevated uric acid serum levels during pregnancy on maternal blood pressure and neonatal outcome using two different murine knockout models. Non-pregnant liver-specific GLUT9 knockout (LG9KO) mice showed elevated uric acid serum concentrations but no hypertensive blood pressure levels. During pregnancy, however, blood pressure levels of these animals increased in the second and third trimester, and circadian blood pressure dipping was severely altered when compared to non-pregnant LG9KO mice. The impact of hyperuricemia on fetal development was investigated using a systemic GLUT9 knockout (G9KO) mouse model. Fetal hyperuricemia caused distinctive renal tissue injuries and, subsequently an impaired neonatal growth pattern. These findings provide strong evidence that hyperuricemia plays a major role in the pathogenesis of hypertensive pregnancy disorders such as pre-eclampsia. These novel insights may enable the development of preventive and therapeutic strategies for hyperuricemia-related diseases.
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Tesfa E, Munshea A, Nibret E, Mekonnen D, Sinishaw MA, Gizaw ST. Maternal serum uric acid, creatinine and blood urea levels in the prediction of pre-eclampsia among pregnant women attending ANC and delivery services at Bahir Dar city public hospitals, northwest Ethiopia: A case-control study. Heliyon 2022; 8:e11098. [PMID: 36303922 PMCID: PMC9593197 DOI: 10.1016/j.heliyon.2022.e11098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 09/05/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022] Open
Abstract
Background Pre-eclampsia (PE) is a metabolic disorder that adversely affects the lives of mother and their infants. Even though, several studies have been conducted on PE, no effective diagnostic and therapeutic agents were developed so far. Hence, this study was designed to evaluate serum uric acid, blood urea and creatinine levels in the prediction of PE. Methods A hospital-based case-control study was conducted among pregnant women. A simple random sampling technique was applied to select study participants. The socio-demographic and clinical data were collected using an interview-administered questionnaire. Serum samples were used to determine the maternal uric acid, urea and creatinine levels via an automated chemistry analyzer. Independent sample t-test, Pearson correlation test and receiver operating characteristic (ROC) curve analysis were performed to check the association and diagnostic accuracy of variables to PE. Results The mean ages (in years) of the case and control groups were 27.98 ± 5.64 and 27.33 ± 4.45, respectively. The mean serum uric acid and blood urea levels were significantly higher in pre-eclamptic women than in normotensive pregnant women (6.27 ± 0.20 vs 4.43 ± 0.15, and 8.50 ± 3.99 vs 5.67 ± 2.19), respectively but the serum creatinine level is non-significantly increased in cases as compared to controls (0.70 ± 0.05 vs 0.50 ± 0.01). The areas under the ROC curve of serum uric acid, creatinine and blood urea levels were 0.785, 0.735 and 0.764 (sensitivity: 69%, 60.7%, 67.9%; specificity: 73.8%, 75%, 71.4%) with the cutoff points of ≥5.25 mg/dL, ≥0.565 mg/dL and ≥6.5 mg/dL, respectively. Conclusion In this study, we observed a significantly higher concentration of serum uric acid and blood urea values in pre-eclampsia as compared with normotensive pregnant women. Therefore, this suggested that serum uric acid; blood urea and creatinine values can be associated with PE. Moreover, serum uric acid, blood urea and creatinine levels could be carefully utilized as a diagnostic marker for PE, but their inclusion in routine diagnostic test to PE requires large-scale multi-center prospective studies that corroborate our findings.
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Affiliation(s)
- Endalamaw Tesfa
- Department of Medical Biochemistry, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia,Health Biotechnology Division, Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia,Corresponding author.;
| | - Abaineh Munshea
- Health Biotechnology Division, Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia,Department of Biology, College of Science, Bahir Dar University, Bahir Dar, Ethiopia
| | - Endalkachew Nibret
- Health Biotechnology Division, Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia,Department of Biology, College of Science, Bahir Dar University, Bahir Dar, Ethiopia
| | - Daniel Mekonnen
- Health Biotechnology Division, Institute of Biotechnology, Bahir Dar University, Bahir Dar, Ethiopia,Department of Medical Laboratory Science, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Mulusew Alemneh Sinishaw
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Solomon Tebeje Gizaw
- Department of Medical Biochemistry, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia
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11
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Wu DY, Feng L, Hao XY, Huang SB, Wu ZF, Ma S, Yin YL, Tan CQ. Effects of dietary supplementation of gestating sows with adenosine 5 '-monophosphate or adenosine on placental angiogenesis and vitality of their offspring. J Anim Sci 2022; 100:6628671. [PMID: 35781577 DOI: 10.1093/jas/skac237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 07/01/2022] [Indexed: 11/12/2022] Open
Abstract
Our previous study found that dietary nucleotide supplementation, including adenosine 5 '-monophosphate (AMP), could increase AMP content in sow milk and promote piglet growth, but its effects on placental efficiency and piglet vitality remains unknown. This experiment aimed to investigate the effects of dietary AMP or its metabolite adenosine (ADO) supplementation on sow reproductive performance and placental angiogenesis. A total of 135 sows with a similar farrowing time were blocked by backfat and body weight (BW) at day 65 of gestation, and assigned to 1 of 3 dietary treatment groups (n = 45 per treatment): basal diet, basal diet supplemented with 0.1% AMP, or 0.1% ADO, respectively. Placental analysis and the characteristics of sows and piglets unveiled that compared with control (CON) group, AMP or ADO supplementation could improve sow placental efficiency (P<0.05) and newborn piglet vitality (P<0.05), increase piglet birth weight (P<0.05), and reduce stillbirth rate (P<0.05). More importantly, AMP or ADO supplementation could increase the contents of AMP, ADO, and their metabolites in placentae (P<0.05). Meanwhile, AMP or ADO supplementation could also increase placental vascular density (P<0.05) and the expression of vascular endothelial growth factor A (P<0.05), as well as promote the migration and tube formation of porcine iliac artery endothelial cells (P<0.05). Overall, maternal dietary AMP or ADO supplementation could increase their contents in the placenta, thereby improving placental angiogenesis and neonatal piglet vitality.
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Affiliation(s)
- D Y Wu
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - L Feng
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - X Y Hao
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - S B Huang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - Z F Wu
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - S Ma
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - Y L Yin
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China.,National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China
| | - C Q Tan
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China
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12
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Zhang Y, Chen Y, Dai B, Bai M, Lu S, Lin N, Zhou H, Jiang H. Bilirubin Reduces the Uptake of Estrogen Precursors and the Followed Synthesis of Estradiol in Human Placental Syncytiotrophoblasts via Inhibition and Downregulation of Organic Anion Transporter 4. Drug Metab Dispos 2022; 50:341-350. [PMID: 35074787 DOI: 10.1124/dmd.121.000685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/10/2022] [Indexed: 02/13/2025] Open
Abstract
Estrogen biosynthesis in human placental trophoblasts requires the human organic anion transporter 4 (hOAT4)-mediated uptake of fetal derived precursors such as dehydroepiandrosterone-3-sulfate (DHEAS) and 16α-hydroxy-DHEA-S (16α-OH-DHEAS). Scant information is available concerning the contribution of fetal metabolites on the impact of placental estrogen precursor transport and the followed estrogen synthesis. This study substantiated the roles of bilirubin as well as bile acids (taurochenodeoxycholic acid, taurocholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid) on the inhibition of hOAT4-mediated uptake of probe substrate 6-carboxylfluorescein and DHEAS in stably transfected hOAT4-Chinese hamster ovary cells, with the IC50 of 1.53 and 0.98 μM on 6-carboxylfluorescein and DHEAS, respectively, for bilirubin, and 90.2, 129, 16.4, and 12.3 μM on 6-CF for taurochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, and chenodeoxycholic acid. Bilirubin (2.5-10 μM) concentration-dependently inhibited the accumulation of estradiol precursor DHEAS in human choriocarcinoma JEG-3 cells (reduced by 60% at 10 μM) and primary human trophoblast cells (reduced by 80% at 10 μM). Further study confirmed that bilirubin (0.625-2.5 μM) concentration-dependently reduced the synthesis and secretion of estradiol in primary human trophoblast cells, among which 2.5 μM of bilirubin reduced the synthesis of estradiol by 30% and secretion by 35%. In addition, immunostaining and Western blot results revealed a distinct downregulation of hOAT4 protein expression in primary human trophoblast cells pretreated with 2.5 μM of bilirubin. In conclusion, this study demonstrated that bilirubin reduced the uptake of estrogen precursors and the followed synthesis of estradiol in human placenta via inhibition and downregulation of organic anion transporter 4. SIGNIFICANCE STATEMENT: Fetal metabolites, especially bilirubin, were first identified with significant inhibitory effects on the hOAT4-mediated uptake of estrogen precursor DHEAS in hOAT4-CHO, JEG-3 and PHTCs. Bilirubin concentration-dependently suppressed the estradiol synthesis and secretion in PHTCs treated with DHEAS, which was synchronized with the decline of hOAT4 protein expression. Additionally, those identified bile acids exhibited a weaker inhibitory effect on the secretion of estradiol.
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Affiliation(s)
- Yingqiong Zhang
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
| | - Yujia Chen
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
| | - Binxin Dai
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
| | - Mengru Bai
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
| | - Shuanghui Lu
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
| | - Nengming Lin
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
| | - Hui Zhou
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
| | - Huidi Jiang
- Institute of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences (Y.Z., Y.C., B.D., S.L., H.Z., H.J.) and Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, China (Y.Z., M.B., N.L.)
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Glucose Transporter 9 (GLUT9) Plays an Important Role in the Placental Uric Acid Transport System. Cells 2022; 11:cells11040633. [PMID: 35203284 PMCID: PMC8870656 DOI: 10.3390/cells11040633] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Revised: 01/30/2022] [Accepted: 02/08/2022] [Indexed: 01/09/2023] Open
Abstract
Background: Hyperuricemia is a common laboratory finding in pregnant women compromised by preeclampsia. A growing body of evidence suggests that uric acid is involved in the pathogenesis of preeclampsia. Glucose transporter 9 (GLUT9) is a high-capacity uric acid transporter. The aim of this study was to investigate the placental uric acid transport system, and to identify the (sub-) cellular localization of GLUT9. Methods: Specific antibodies against GLUT9a and GLUT9b isoforms were raised, and human villous (placental) tissue was immunohistochemically stained. A systemic GLUT9 knockout (G9KO) mouse model was used to assess the placental uric acid transport capacity by measurements of uric acid serum levels in the fetal and maternal circulation. Results: GLUT9a and GLUT9b co-localized with the villous (apical) membrane, but not with the basal membrane, of the syncytiotrophoblast. Fetal and maternal uric acid serum levels were closely correlated. G9KO fetuses showed substantially higher uric acid serum concentrations than their mothers. Conclusions: These findings demonstrate that the placenta efficiently maintains uric acid homeostasis, and that GLUT9 plays a key role in the placental uric acid transport system, at least in this murine model. Further studies investigating the role of the placental uric acid transport system in preeclampsia are eagerly needed.
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14
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Riis JL, Cook SH, Letourneau N, Campbell T, Granger DA, Giesbrecht GF. Characterizing and Evaluating Diurnal Salivary Uric Acid Across Pregnancy Among Healthy Women. Front Endocrinol (Lausanne) 2022; 13:813564. [PMID: 35370953 PMCID: PMC8971544 DOI: 10.3389/fendo.2022.813564] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 02/14/2022] [Indexed: 11/26/2022] Open
Abstract
Uric acid levels during pregnancy have been examined as a potential indicator of risk for gestational diabetes mellites, hypertension, and related adverse birth outcomes. However, evidence supporting the utility of serum uric acid levels in predicting poor maternal and fetal health has been mixed. The lack of consistent findings may be due to limitations inherent in serum-based biomeasure evaluations, such as minimal repeated assessments and variability in the timing of these assessments. To address these gaps, we examined repeated measurements of diurnal salivary uric acid (sUA) levels in a sample of 44 healthy women across early-mid and late pregnancy. We assessed potential covariates and confounds of sUA levels and diurnal trajectories, as well as associations between maternal weight gain and blood pressure during pregnancy and sUA concentrations. Using multilevel linear models, we found sUA increased across pregnancy and displayed a robust diurnal pattern with the highest concentrations at waking, a steep decline in the early morning, and decreasing levels across the day. Maternal pre-pregnancy BMI, age, prior-night sleep duration, and fetal sex were associated with sUA levels and/or diurnal slopes. Maternal blood pressure and gestational weight gain also showed significant associations with sUA levels across pregnancy. Our results expand upon those found with serum UA measurements. Further, they demonstrate the feasibility of using at-home, minimally-invasive saliva sampling procedures to track UA levels across pregnancy with potential applications for the long-term monitoring of maternal cardiometabolic risk.
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Affiliation(s)
- Jenna L. Riis
- Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, Irvine, CA, United States
- Department of Psychological Science, School of Social Ecology, University of California, Irvine, Irvine, CA, United States
- *Correspondence: Jenna L. Riis,
| | - Stephanie H. Cook
- Social and Behavioral Sciences, School of Global Public Health, New York University, New York, NY, United States
- Biostatistics, School of Global Public Health, New York University, New York, NY, United States
| | - Nicole Letourneau
- Alberta Children’s Hospital Research Institute, Calgary, AB, Canada
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Faculty of Nursing, University of Calgary, Calgary, AB, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada
- Department of Psychiatry, University of Calgary, Calgary, AB, Canada
| | - Tavis Campbell
- Department of Psychology, University of Calgary, Calgary, AB, Canada
| | - Douglas A. Granger
- Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, Irvine, CA, United States
- Department of Psychological Science, School of Social Ecology, University of California, Irvine, Irvine, CA, United States
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Gerald F. Giesbrecht
- Alberta Children’s Hospital Research Institute, Calgary, AB, Canada
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Faculty of Nursing, University of Calgary, Calgary, AB, Canada
- Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada
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15
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Singh SK, Singh R, Singh SK, Iquebal MA, Jaiswal S, Singh A. Prevalence of Hyperuricemia and the Relationship Between Serum Uric Acid and Hypertension in New Onset Diabetic Patients: A Cross-Sectional Indian Study. Diabetes Metab Syndr Obes 2022; 15:1809-1817. [PMID: 35726334 PMCID: PMC9206514 DOI: 10.2147/dmso.s363311] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/17/2022] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE Prevalence of hyperuricemia (HU) is increasing and it is associated with hypertension, metabolic syndrome, diabetes mellitus (DM), obesity, chronic kidney disease, gout and cardiovascular disease. Elevated level of serum uric acid (SUA) has been shown to be associated with hypertension and diabetes in many countries but there is lack of evidence from India. The aim of this study is to know the prevalence of HU and to know the relationship between SUA and hypertension in newly onset DM. METHODS This is a cross-sectional study from a tertiary center. A total of 305 (males: 212; females: 93) newly diagnosed diabetic patients were enrolled. All patients were categorized as normotensive (<140/90) and hypertensive (≥140/90) based on ADA criteria. Based on SUA level participants were grouped into 3 tertile (T1: <4.52; T2: 4.52-5.64; T3: >5.64 mg/dl). RESULTS The mean age, systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the patients were 46.76 ±0.61 years, 130.6±1.06 mmHg and 84.11±0.63 mmHg, respectively. The mean level of SUA was 5.14±0.073 mg/dl and level was significantly higher in males compared with females (P <0.000). Overall prevalence of HU and hypertension was 12.13% and 44.59%, respectively. There was an increase in the prevalence of hypertension across the SUA tertile. SBP and DBP significantly increased across the SUA tertile (P <0.014 and <0.001, respectively). A multiple logistic regression analysis revealed that SUA tertile was independently associated with presence of hypertension (P <0.01). CONCLUSION This first report on the population of the eastern part of India indicates a significant positive relationship between SUA and hypertension among the newly onset Indian diabetic patients. Therefore, routine measurement of SUA is recommended in newly onset hypertensive diabetic patients to prevent HU and its related complications.
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Affiliation(s)
- Shailendra Kumar Singh
- Department of Endocrine, Endocrine Clinic, Varanasi, Uttar Pradesh, India
- Visiting Endocrinologist, Opal Hospital, Varanasi, Uttar Pradesh, India
- Correspondence: Shailendra Kumar Singh, Email
| | - Rina Singh
- Department of Endocrine, Endocrine Clinic, Varanasi, Uttar Pradesh, India
| | | | - Mir Asif Iquebal
- Center for Agricultural Bioinformatics, ICAR-IASRI, New Delhi, India
| | - Sarika Jaiswal
- Center for Agricultural Bioinformatics, ICAR-IASRI, New Delhi, India
| | - Archana Singh
- Department of Extension and Communication Management & Home Science, Acharya Narendra Deva University of Agriculture and Technology, Ayodhya, Uttar Pradesh, India
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16
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Sakr HI, Khowailed AA, Al-Fakharany RS, Abdel-Fattah DS, Taha AA. Serum Uric Acid Level as a Predictive Biomarker of Gestational Hypertension Severity; A Prospective Observational Case-Control Study. Rev Recent Clin Trials 2021; 15:227-239. [PMID: 32646363 DOI: 10.2174/1574887115666200709142119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 06/08/2020] [Accepted: 06/19/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pre-eclampsia poses a significant potential risk of hypertensive disorders during pregnancy, a leading cause of maternal deaths. Hyperuricemia is associated with adverse effects on endothelial function, normal cellular metabolism, and platelet aggregation and adhesion. This study was designed to compare serum urate levels in normotensive pregnant women to those with pregnancy-induced hypertension, and to evaluate its value as a potential predictive marker of hypertension severity during pregnancy. METHODS A prospective, observational, case-control study conducted on 100 pregnant women in their third trimester. Pregnant women were classified into two groups (n=50) according to arterial blood pressure measurements: group I had normal blood pressure, and group II had a blood pressure of ≥ 140/90, which was further subdivided according to hypertension severity into IIa (pregnancy- induced hypertension, IIb (mild pre-eclampsia), and IIc (severe pre-eclampsia). Blood samples were obtained on admission. Serum urate, high sensitive C-reactive protein, and interleukin-1β levels, and lipid profile were compared among the groups. RESULTS A significant increase in the mean values of serum urate, C-reactive protein, and interleukin- 1β levels was detected in gestational hypertensives. In addition, there was a positive correlation between serum urate levels and C-reactive protein and interleukin-1β, as well as between serum urate levels and hypertension severity. CONCLUSION Hyperuricemia and increased C-reactive protein and interleukin-1β serum levels correlate with the severity of pregnancy-induced hypertension, and these biomarkers may play a role in the pathogenesis of pre-eclampsia. Serum urate measurement is sensitive, reliable markers that correlate well with the severity of hypertension in pregnant females with pre-eclampsia.
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Affiliation(s)
- Hader I Sakr
- Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Akef A Khowailed
- Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Reham S Al-Fakharany
- Department of Medical Physiology, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt
| | - Dina S Abdel-Fattah
- Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed A Taha
- Department of Obstetrics and Gynecology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
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17
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Zhu YY, Wu Y, Chen ST, Kang JW, Pan JM, Liu XZ, Li SY, Yan GJ, Liu AX, Huang QT, Yang ZM, Su RW. In situ Synthesized Monosodium Urate Crystal Enhances Endometrium Decidualization via Sterile Inflammation During Pregnancy. Front Cell Dev Biol 2021; 9:702590. [PMID: 34434930 PMCID: PMC8380953 DOI: 10.3389/fcell.2021.702590] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 07/14/2021] [Indexed: 11/13/2022] Open
Abstract
High level of uric acid (UA) is the major origin of gout, and is highly associated with various pregnant complications, such as preeclampsia and gestational diabetes. However, UA’s level and role in the very early stage of pregnancy has not been uncovered. This study aims to investigate the relevance of serum UA and decidualization, an essential process for the establishment and maintenance of pregnancy in women and mice during the early stage of pregnancy. In this study, we first proved that expression level of UA synthase xanthine dehydrogenase (XDH) is highly increased along with decidualization of endometrial stromal cells in both in vitro and in vivo models. Furthermore, serum and endometrial levels of UA are higher in mice with decidualized uterin horn and in vitro decidualized stromal cells. The existence of monosodium urate (MSU) crystal was also confirmed by immunostaining. Next, the roles of MSU on decidualization were explored by both in vitro and in vivo models. Our data shows MSU crystal but not UA enhances the decidualization response of endometrial stromal cells, via the upregulation of inflammatory genes such Ptgs2 and Il11. inhibiting of Cox-2 activity abolishes MSU crystal induced higher expression of decidualization marker Prl8a2. At last, in women, we observed enriched expression of XDH in decidua compare to non-decidualized endometrium, the serum level of UA is significantly increased in women in very early stage of pregnancy, and drop down after elective abortion. In summary, we observed an increased serum UA level in the early stage of women’s pregnancy, and proved that the increased level of UA results from the expressed XDH in decidualizing endometrium of both human and mouse, leading to the formation of MSU crystal. MSU crystal can enhance the decidualization response via inflammatory pathways. Our study has uncovered the association between UA, MSU, and decidualization during the early stage of pregnancy.
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Affiliation(s)
- Yu-Yuan Zhu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Yao Wu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Si-Ting Chen
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Jin-Wen Kang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Ji-Min Pan
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Xiao-Zheng Liu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Shu-Yun Li
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Gui-Jun Yan
- Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Ai-Xia Liu
- Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qi-Tao Huang
- Division of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Division of Obstetrics, Foshan Maternal and Child Health Care Hospital, Southern Medical University, Foshan, China
| | - Zeng-Ming Yang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Ren-Wei Su
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
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18
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Association between Serum Uric Acid Levels and Perinatal Outcome in Women with Preeclampsia. Obstet Gynecol Int 2021; 2021:6611828. [PMID: 33953752 PMCID: PMC8064794 DOI: 10.1155/2021/6611828] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 03/02/2021] [Accepted: 04/07/2021] [Indexed: 11/21/2022] Open
Abstract
Objectives To compare serum uric acid levels with disease severity and perinatal outcome among preeclamptic and normal pregnant women. Materials and Methods This was a case-control study carried out in Federal Medical Centre, Umuahia, Nigeria. Consenting pregnant women were consecutively recruited into two groups comprising pregnant women diagnosed with preeclampsia and normotensive nonproteinuric pregnant women. Exclusion criteria included pregnant women who were current smokers, took alcohol, and diagnosed with multiple gestation, diabetes mellitus, or renal failure. Associations between categorical variables such as preeclampsia severity and perinatal outcomes were done using logistic regression while means of continuous variables such as serum uric acid were compared using Student's t-test. Data were presented using odds ratios (ORs) with 95% confidence intervals (95% CI) and a statistical significance level set at P value ˂ 0.05. Data analysis was done using Statistical Package for Social Sciences version 22. Results One hundred and two participants were finally analysed. Fifty-one participants were recruited in each arm. Women with preeclampsia had significantly high serum uric acid level versus controls (6.08 ± 0.49 mg/dL vs. 5.20 ± 0.19; P < 0.001). Women with elevated serum uric acid levels (˃6 mg/dL) were found to be 4 times more likely to have severe preeclampsia (P=0.022, OR = 4.00, 95% CI = 1.225–13.056), 66 times more likely to have APGAR score ˂7 in the first minute (P < 0.001, OR = 66.00, 95% CI = 6.991–623.128), and 3 times more likely to have lower birth weight (P=0.038, OR = 3.400, 95% CI = 1.073–10.775) than those with normal serum uric acid levels. Conclusions The mean serum uric acid level in a preeclamptic is higher than that of normal pregnant control, and higher levels are associated with severity of the disease and significantly associated with poorer perinatal outcome.
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Olaniyi KS, Sabinari IW, Olatunji LA. Oral L-glutamine rescues fructose-induced poor fetal outcome by preventing placental triglyceride and uric acid accumulation in Wistar rats. Heliyon 2020; 6:e05863. [PMID: 33426346 PMCID: PMC7777114 DOI: 10.1016/j.heliyon.2020.e05863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 11/08/2020] [Accepted: 12/23/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Metabolic adaptation of pregnant mothers is crucial for placental development and fetal growth/survival. However, evidence exists that indiscriminate consumption of fructose-enriched drink (FED) during pregnancy disrupts maternal-fetal metabolic tolerance with attendant adverse fetal outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic disorders. Nevertheless, the effects of GLN on FED-induced poor fetal outcome, and in particular the impacts on placental uric acid/lipid accumulation are unknown. The present study was conducted to test the hypothesis that oral GLN improves fetal outcome by attenuating placental lipid accumulation and uric acid synthesis in pregnant rats exposed to FED. MATERIALS AND METHODS Pregnant Wistar rats (160-180 g) were randomly allotted to control, GLN, FED and FED + GLN groups (6 rats/group). The groups received vehicle by oral gavage, glutamine (1 g/kg) by oral gavage, fructose (10%; w/v) and fructose + glutamine, respectively, through gestation. RESULTS Data showed that FED during pregnancy caused placental inefficiency, reduced fetal growth, and caused insulin resistance with correspondent increase in fasting blood glucose and plasma insulin. FED also resulted in an increased placental triglyceride, total cholesterol and de novo uric acid synthesis by activating adenosine deaminase and xanthine oxidase activities. Moreover, FED during pregnancy led to increased lipid peroxidation, lactate production with correspondent decreased adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense. These alterations were abrogated by GLN supplementation. CONCLUSION These findings implicate that high FED intake during pregnancy causes poor fetal outcome via defective placental uric acid/triglyceride-dependent mechanism. The findings also suggest that oral GLN improves fetal outcome by ameliorating placental defects through suppression of uric acid/triglyceride accumulation.
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Affiliation(s)
- Kehinde Samuel Olaniyi
- HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria
- Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
| | - Isaiah Woru Sabinari
- HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria
| | - Lawrence Aderemi Olatunji
- HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, Nigeria
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20
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Pecoraro V, Trenti T. Predictive value of serum uric acid levels for adverse maternal and perinatal outcomes in pregnant women with high blood pressure. A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2020; 252:447-454. [PMID: 32736271 DOI: 10.1016/j.ejogrb.2020.07.042] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/18/2020] [Accepted: 07/21/2020] [Indexed: 02/01/2023]
Abstract
OBJECTIVE High serum uric acid seems to be associated with pre-eclampsia. The expected utility of uric acid is related to the probability of occurrence of maternal and neonatal complications. We evaluated the accuracy of uric acid in predicting adverse maternal and perinatal outcomes in pregnant women with high blood pressure. METHODS We performed an electronic search for studies evaluating the accuracy of high serum uric acid levels in pregnant women with high blood pressure. The assessment of risk of bias was performed using the QUIPS tool. For each included study, we collected data about study characteristics and diagnostic test accuracy to construct 2 × 2 tables. Pooled sensitivity (Se), specificity (Sp) and diagnostic odds ratio (DOR) were estimated using a bivariate model. Grading the quality of the evidence was assessed using the GRADE approach. RESULTS Twenty-one studies, testing more than 6,000 women, met the inclusion criteria. The majority of studies were at low risk of bias. Ten studies evaluated the role of serum uric acid to predict pre-eclampsia, the pooled Se was 0.74 (95%CI 0.71-0.77), Sp was 0.66 (95%CI 0.63-0.68), and DOR was 9.67 (95%CI 4.57-20.47). The overall quality of evidence was evaluated as low. The GRADE rating was downgraduate for risk of bias and inconsistency. CONCLUSIONS No robust evidence currently exists to suggest that uric acid measurement is useful in predicting maternal and perinatal adverse outcomes.
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Affiliation(s)
- Valentina Pecoraro
- Department of Laboratory Medicine, OCSAE, Azienda USL of Modena, Via Pietro Giardini 1355, 41126, Modena, Italy.
| | - Tommaso Trenti
- Department of Laboratory Medicine, OCSAE, Azienda USL of Modena, Via Pietro Giardini 1355, 41126, Modena, Italy.
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21
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Brien ME, Boufaied I, Bernard N, Forest JC, Giguere Y, Girard S. Specific inflammatory profile in each pregnancy complication: A comparative study. Am J Reprod Immunol 2020; 84:e13316. [PMID: 32761668 DOI: 10.1111/aji.13316] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/20/2020] [Accepted: 07/29/2020] [Indexed: 01/01/2023] Open
Abstract
PROBLEM Pre-eclampsia (PE), preterm birth (PTB) and intra-uterine growth restriction (IUGR) affect 5%-12% of pregnancies. They have been associated with placental inflammation, although the detection of inflammatory mediators in the maternal circulation is still controversial. Our goal was to determine the inflammatory changes occurring in the second part of pregnancy to identify profiles distinguishing pathological pregnancies from each other. METHOD OF STUDY We performed a nested case-control study of 200 women randomly selected from a cohort recruited at the CHU de Quebec-Universite Laval, Quebec, Canada. Women with uncomplicated term pregnancy (CTRL); PE (severe or not); PTB or IUGR (N = 50/each) were included. Plasma samples, obtained from the late second trimester and at delivery, were analysed for over 30 selected mediators (including cytokines/alarmins), by multiplex, ELISA or specific assays. Demographic and obstetrical information were obtained for classification. RESULTS In CTRL, we observed significant differences between 2nd trimester and delivery, with increased levels of inflammatory mediators (ex. MCP-1, IL-6), supporting an inflammatory profile towards term. Increased levels of IL-6, CXCL10 and CRP were observed in PE as compared to CTRL. In PTB, we observed increased CXCL9 in 2nd trimester and decreased progesterone at delivery. In IUGR, increased HMGB1 and IL-1α were observed only in the 2nd trimester. CONCLUSIONS Our work showed significant inflammatory changes in uncomplicated pregnancies towards delivery, supporting that normal delivery is pro-inflammatory, although not to the same extent as in pathological pregnancies. Inflammatory profiles are specific to each pregnancy complication which may help to understand the contribution of inflammation to the clinical presentation of these conditions.
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Affiliation(s)
- Marie-Eve Brien
- Ste-Justine Hospital Research Center, Montreal, QC, Canada.,Department of Obstetrics and Gynecology, Université de Montreal, Montreal, QC, Canada.,Department of Microbiology, Infectiology and Immunology, Université de Montreal, Montreal, QC, Canada
| | - Ines Boufaied
- Ste-Justine Hospital Research Center, Montreal, QC, Canada
| | - Nathalie Bernard
- Centre de Recherche du CHU de Quebec-Université Laval, Quebec City, QC, Canada
| | - Jean-Claude Forest
- Centre de Recherche du CHU de Quebec-Université Laval, Quebec City, QC, Canada.,Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Quebec City, QC, Canada
| | - Yves Giguere
- Centre de Recherche du CHU de Quebec-Université Laval, Quebec City, QC, Canada.,Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Quebec City, QC, Canada
| | - Sylvie Girard
- Ste-Justine Hospital Research Center, Montreal, QC, Canada.,Department of Obstetrics and Gynecology, Université de Montreal, Montreal, QC, Canada.,Department of Microbiology, Infectiology and Immunology, Université de Montreal, Montreal, QC, Canada
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Liu D, Li C, Huang P, Fu J, Dong X, Tang Y, Li X, Chen Q. Serum levels of uric acid may have a potential role in the management of immediate delivery or prolongation of pregnancy in severe preeclampsia. Hypertens Pregnancy 2020; 39:260-266. [PMID: 32345065 DOI: 10.1080/10641955.2020.1761377] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
OBJECTIVE To investigate the biomarker(s) that could affect the decision for immediate or delayed delivery in severe preeclampsia. METHODS Data on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine, blood urea nitrogen (BUN), uric acid (UA) and platelet counts from 134 cases were collected and analysed. RESULTS Higher UA levels were seen in case with immediate delivery. Higher stillbirth was seen in cases with delayed delivery. CONCLUSION UA levels could be a potential management biomarker for immediate or delayed delivery in severe preeclampsia. However, the higher risk of stillbirth must be considered in delayed delivery.
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Affiliation(s)
- Dan Liu
- Department of Obstetrics & Gynaecology, First Affiliated Hospital of Xi'an Jiaotong University China , Xi'an, China
| | - Chunfang Li
- Department of Obstetrics & Gynaecology, First Affiliated Hospital of Xi'an Jiaotong University China , Xi'an, China
| | - Pu Huang
- Department of Obstetrics & Gynaecology, First Affiliated Hospital of Xi'an Jiaotong University China , Xi'an, China
| | - Jing Fu
- Department of Obstetrics & Gynaecology, First Affiliated Hospital of Xi'an Jiaotong University China , Xi'an, China
| | - Xin Dong
- Department of Obstetrics & Gynaecology, First Affiliated Hospital of Xi'an Jiaotong University China , Xi'an, China
| | - Yunhui Tang
- The Hospital of Obstetrics & Gynaecology, Fudan University China , Shanghai, China
| | - Xuelan Li
- Department of Obstetrics & Gynaecology, First Affiliated Hospital of Xi'an Jiaotong University China , Xi'an, China
| | - Qi Chen
- The Hospital of Obstetrics & Gynaecology, Fudan University China , Shanghai, China.,Department of Obstetrics & Gynaecology, The University of Auckland , Auckland, New Zealand
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Ababio GK, Adu-Bonsaffoh K, Abindau E, Narh G, Tetteh D, Botchway F, Morvey D, Neequaye J, Quaye IK. Effects of factor v Leiden polymorphism on the pathogenesis and outcomes of preeclampsia. BMC MEDICAL GENETICS 2019; 20:189. [PMID: 31775662 PMCID: PMC6882245 DOI: 10.1186/s12881-019-0924-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 11/12/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Factor V Leiden polymorphism is a well-recognized genetic factor in the etiology of preeclampsia. Considering that Ghana is recording high incidence of preeclampsia, we examined if factor V Leiden is a contributory factor to its development and pregnancy outcomes. METHODS STROBE consensus checklist was adopted to recruit eighty-one (81) consenting subjects after ethical clearance. Subjects were followed up till delivery to obtain outcomes of PE. Routine blood chemistry and proteinuria were done on all samples. Factor V Leiden was characterized by polymerase chain reaction and restriction fragment length polymorphism (RFLP). The data was captured as protected health information (PHI) and analyzed with SPSS version 22. RESULTS Overall allelic frequencies found in FVL exon 10 were 0.67 and 0.33 for G and A alleles respectively. The FVL mutation was more in PE and hypertensive patients. Increased white blood cells, increased uric acid and a three - fold increment of AST / ALT ratio was observed in PE cases when stratified by FVL exons (exon 8 and 10). Significant differences were also observed between FVL and age, systolic blood pressure (SBP), diastolic blood pressure (DBP), liver enzymes, white blood cells (wbc), hemoglobin levels. CONCLUSION FVL mutation allele frequency was 0.33, a first report. The mutation was associated with increased uric acid, liver enzymes and blood cell indices suggestive of acute inflammation.
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Affiliation(s)
- G. K. Ababio
- Department of Medical Biochemistry, University of Ghana School of Medicine and Dentistry, P. O. Box 4236, Accra, Ghana
| | - K. Adu-Bonsaffoh
- Department of Obstetrics and Gynecology, University of Ghana School of Medicine and Dentistry, Accra, Ghana
| | - E. Abindau
- Department of Physiology, University of Ghana School of Medicine and Dentistry, Accra, Ghana
| | - G. Narh
- Department of Biochemistry, University of Ghana, Accra, Ghana
| | - D. Tetteh
- National Diabetic Research Lab, Korle-Bu Teaching Hospital, Accra, Ghana
| | - F. Botchway
- Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana
| | - D. Morvey
- Clinical Documentation Improvement Specialist, Southern California Hospital, Culver City, CA 90232 USA
| | - J. Neequaye
- Biochemistry, Kwame Nkrumah University of Science And Technology, Kumasi, Ghana
| | - I. K. Quaye
- Department of Applied Health Sciences, Regent University of Science and Technology, Accra, Ghana
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Barneo-Caragol C, Martínez-Morillo E, Rodríguez-González S, Lequerica-Fernández P, Vega-Naredo I, Álvarez FV. Increased serum strontium levels and altered oxidative stress status in early-onset preeclampsia. Free Radic Biol Med 2019; 138:1-9. [PMID: 31055131 DOI: 10.1016/j.freeradbiomed.2019.05.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 04/29/2019] [Accepted: 05/01/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Correctly distinguishing preeclampsia (PE), gestational hypertension (GH), and intrauterine growth retardation (IUGR) is a challenge for clinicians due to existing similarities. In our previous study, we showed that serum strontium (Sr) levels were elevated in preeclamptic women compared to healthy and GH pregnant women at the end of pregnancy. The main aim of this study was to evaluate Sr and oxidative stress in PE at the time of symptoms onset and before and compare it with IUGR/GH. METHODS Samples collected at symptoms onset included 77 preeclamptic women and 72 women diagnosed with IUGR/GH divided into two groups according to the gestational extraction week (<34 and ≥ 34). Fifteen patients were also serialized until delivery. Samples collected before symptoms onset included 140 women who developed early-onset PE (E-PE, n = 9), late-onset PE (L-PE, n = 13), IUGR (n = 9), GH (n = 32) and no pathologies (n = 77). Strontium, placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), uric acid (UA), creatinine, lipid peroxidation, and total antioxidant activity (TAA) were measured. RESULTS Mean Sr, sFlt-1/PIGF ratio, UA, and lipid peroxidation/TAA ratio levels were significantly higher (p = 0.002, <0.0001, <0.0001 and = 0.03, respectively) and estimated glomerular filtration rate (eGFR) and TAA significantly lower (p = 0.0008 and < 0.0001, respectively) in E-PE vs other pathologies when gestational extraction week was <34. There was a significant correlation between Sr and eGFR (r = 0.43, p = 0.02), sFlt-1/PIGF ratio (r = 0.56, p = 0.002), TAA and gestational week of sampling (r = -0.45, p = 0.02) and UA (r = -0.82, p < 0.0001) in the E-PE serial samples. No differences were found in Sr levels before symptoms onset. CONCLUSION Serum Sr concentration and oxidative status are increased in E-PE when compared to other pathologies at the time of symptoms onset. More studies are needed to elucidate the causes of Sr levels elevation and its role in the pathophysiology of PE.
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Affiliation(s)
- Clara Barneo-Caragol
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, S/n, 33011, Oviedo, Asturias, Spain.
| | - Eduardo Martínez-Morillo
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, S/n, 33011, Oviedo, Asturias, Spain.
| | - Susana Rodríguez-González
- Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, Av. Julián Clavería, S/n, 33006, Oviedo, Asturias, Spain.
| | - Paloma Lequerica-Fernández
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, S/n, 33011, Oviedo, Asturias, Spain.
| | - Ignacio Vega-Naredo
- Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, Av. Julián Clavería, S/n, 33006, Oviedo, Asturias, Spain.
| | - Francisco V Álvarez
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, S/n, 33011, Oviedo, Asturias, Spain; Department of Biochemistry and Molecular Biology, University of Oviedo, C/ Fernando Bongera S/n, 33006, Oviedo, Asturias, Spain.
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Hou H, Geng M, Zhang R, Liu W, Wang J, Li J, Lin Y, Liu S, Wang Z, Guo H, Guan H, Tan P. Value of ABCG2 Q141K and Q126X genotyping in predicting risk of preeclampsia in Chinese Han women population. Pregnancy Hypertens 2019; 17:197-202. [PMID: 31487640 DOI: 10.1016/j.preghy.2019.06.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 06/06/2019] [Accepted: 06/25/2019] [Indexed: 11/30/2022]
Abstract
Hyperuricemia (HUA) in women with preeclampsia (PE) not only indicates a reminder of severity but also contributes directly to the pathogenesis of PE. ATP-binding cassette subfamily G member 2 (ABCG2) has a very strong effect on the serum urate concentrations. Our aim was to investigate the association between polymorphisms of ABCG2 with PE in Chinese Han female population. A cohort of 793 preeclamptic women (466 PE with HUA and 327 PE without HUA) and 744 normal pregnant women recruited in this study were genotyped for genetic distribution of Q141K (rs2231142) and Q126X (72552713) in ABCG2 by the TaqMan allelic discrimination real-time PCR. There was no statistically significant difference of genotypic and allelic frequencies between PE and the normal pregnant women in Q141K (Χ2 = 1.11, P = 0.58 by genotype; Χ2 = 0.32, P = 0.57 by allele) and Q126X (P = 0.33 by genotype; P = 0.33 by allele), and no significant difference was found in the genetic distribution of Q141K and Q126X between PE with HUA, PE without HUA and controls. Additionally, this study observed no significant difference in genotypic and allelic distribution between early/late-onset PE with/without HUA or mild/severe PE with/without HUA and control subgroups. Based on our findings, the ABCG2 Q141K and Q126X polymorphisms may not be associated with PE in Chinese Han women.
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Affiliation(s)
- Huabin Hou
- Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China; Clinical Hematology, Department of Medical College, Qingdao University, Qingdao, Shandong 266071, China
| | - Meiyun Geng
- Health Education Department, Qingdao Center For Disease Control And Prevention, China
| | - Ru Zhang
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China; Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Wenmiao Liu
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China; Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Jingli Wang
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China; Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Jing Li
- Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Yan Lin
- Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Shiguo Liu
- Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China; Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Zhongjun Wang
- Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Hui Guo
- Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Hongzai Guan
- Clinical Hematology, Department of Medical College, Qingdao University, Qingdao, Shandong 266071, China.
| | - Ping Tan
- Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
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Abstract
Preeclampsia is a multisystem disorder associated with pregnancy and is a common cause of perinatal morbidity. The aim of this study was to determine whether elevated serum uric acid levels, alone or in combination with other laboratory factors could predict preeclampsia in women with adverse perinatal outcomes.We conducted a prospective observational study of women who were admitted to Soonchunhyang University Cheonan Hospital from January 2016 to December 2016. Demographic, clinical and laboratory data were collected for each pregnancy at the time of delivery. Women were grouped according to status (preeclampsia or normotensive), and a logistic regression analysis was used to determine the relationship between serum uric acid levels and adverse outcomes.The mean age of the study participants was 31.3 ± 5.0 years. In patients with preeclampsia, serum uric acid level was associated with the severity of preeclampsia, including blood pressure (R = 0.321, P = .014), serum creatinine levels (R = 0.505, P < .001), and proteinuria (P = .014), as well as adverse fetal outcomes, including preterm labor (P = .027) and low birth weight delivery (P = .001). The optimal maternal serum uric acid threshold that predicted low birth weight at delivery was 6.35 mg/dL (sensitivity, 0.58; specificity, 0.95). The multivariable logistic regression model that was used to predict low birth weight at delivery displayed an area under the receiver-operating characteristic curve of 0.902 (95% confidence interval, 0.817-0.986).In women with preeclampsia, maternal serum uric acid level is an important parameter for predicting low birth weight. Additionally, the combination of uric acid, hemoglobin, and bilirubin levels appear to be optimal for predicting low birth weight in women with preeclampsia.
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Affiliation(s)
- Aelie Ryu
- Department of Obstetrics and Gynecology
| | - Nam Jun Cho
- Department of Nephrology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | | | - Eun Young Lee
- Department of Nephrology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
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Liu L, Yu C, Yang F, Yuan Z, Wang Q, Liu S, Zuo C, Guan Q. Maternal hyperuricemia superimposed on maternal hypertension aggravates the risk of small-for-gestational-age fetus. Life Sci 2019; 228:215-220. [PMID: 31002916 DOI: 10.1016/j.lfs.2019.04.033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 04/14/2019] [Accepted: 04/15/2019] [Indexed: 10/27/2022]
Abstract
AIMS Small-for-gestational-age (SGA) fetus is an important public health issue because of its high mortality and long-term effects on health. Maternal hyperuricemia is associated with diverse adverse pregnant outcomes and neonatal disturbance. We aimed to evaluate whether maternal hyper-uric acid (HUA) is associated with the risk of SGA fetus and to explore whether it can modify the association between maternal hyper-blood pressure (HBP) and SGA fetus. MATERIALS AND METHODS We performed a population-based cross-section retrospective study, a total of 6715 pregnant females were recruited. Multiple logistic regression analysis was performed to identify risk factors significantly correlated with SGA fetus, and then studied the effect of maternal HUA on the association between maternal HBP and SGA fetus. KEY FINDINGS We collected 537 SGA fetuses among 6715 pregnant females. Maternal HUA was an independent risk factor for SGA delivery (odds ratio (OR), 2.737; 95% confidence interval (CI), 2.110-3.551). A dose-response association between maternal uric acid and SGA delivery was found among normotensive and hypertensive group. Compared with those whose uric acid was lower than 270 μmo/L with normal-blood pressure (NBP), the risk for SGA delivery in those whose uric acid was higher than 370 μmo/L with stage 2 or 3 hypertension increased 12.695-fold. SIGNIFICANCE Our results suggest that maternal HUA could increase the risk of neonatal SGA, and maternal HUA could be superimposed upon pre-existing maternal HBP and increase the risk for SGA fetus.
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Affiliation(s)
- Luna Liu
- Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong 250021, China
| | - Chunxiao Yu
- Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong 250021, China; Department of Biological Sciences, The University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX 75080, USA
| | - Feifei Yang
- Department of Pediatrics, TengZhou Central People's Hospital, Tengzhou, Shandong 277500, China
| | - Zhongshang Yuan
- Department of Biostatistics, School of Public Health, Shandong University, China
| | - Qian Wang
- Department of Ultrasound, Shandong Provincial Hospital affiliated to Shandong University, China
| | - Shuang Liu
- Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong 250021, China
| | - Changting Zuo
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital affiliated to Shandong University, China.
| | - Qingbo Guan
- Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong 250021, China.
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Žák P, Souček M. Correlation of tumor necrosis factor alpha, interleukin 6 and interleukin 10 with blood pressure, risk of preeclampsia and low birth weight in gestational diabetes. Physiol Res 2019; 68:395-408. [PMID: 30904009 DOI: 10.33549/physiolres.934002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Several pathophysiological mechanisms have been proposed in the development of pregnancy complications, including endothelial dysfunction, an inflammatory pathway and oxidative stress. The aim of the present study was to evaluate the correlation between proinflammatory cytokines TNF-alpha, IL-6 and dual cytokine IL-10 in the mother's peripheral blood and systolic blood pressure, risk of preeclampsia and low birth weight in gestational diabetes (GDM). We observed 40 women with GDM divided into a gestational hypertension group (n=20) and comparison group (n=20) with normal blood pressure. We found a significant positive correlation between TNF-alpha; IL-6; IL-10 levels and systolic blood pressure (SBP) in the second trimester (p<0.001; p<0.001; p<0.001); the third trimester (p<0.001; p<0.001; p<0.05). We also proved correlations for diastolic blood pressure (DBP) during the second; third trimester (p<0.001; p<0.001; p<0.001); (p<0.001; p<0.001; p<0.0015). We demonstrated a statistically significant positive association between high TNF-alpha group and preeclampsia risk in the third trimester (p=0.04). We also determined the negative correlation in the second trimester between birth weight and TNF-alpha; IL-6, IL-10 levels (p<0.05; p<0.001; p<0.001). To conclude, our data highlight the importance of cytokines TNF-alpha, IL-6 and IL-10 in blood pressure regulation. In addition, high levels of TNF-alpha have been associated with increased risk of preeclampsia. We found a significant negative correlation between levels of TNF-alpha, IL-6, IL-10 and birth weight.
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Affiliation(s)
- P Žák
- Second Department of Internal Medicine, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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Increased proteinuria and uric acid levels are associated with eclamptic crisis. Pregnancy Hypertens 2019; 15:93-97. [DOI: 10.1016/j.preghy.2018.12.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 11/18/2018] [Accepted: 12/10/2018] [Indexed: 12/22/2022]
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Harville EW, Catov J, Lewis CE, Bibbins-Domingo K, Gunderson EP. Pre-pregnancy kidney function and subsequent adverse pregnancy outcomes. Pregnancy Hypertens 2019; 15:195-200. [PMID: 30825922 PMCID: PMC6484837 DOI: 10.1016/j.preghy.2019.01.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 01/09/2019] [Accepted: 01/28/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Renal insufficiency is associated with pregnancy complications including fetal growth restriction, preterm birth (PTB), and pre-eclampsia. OBJECTIVE To determine the effect of preconception kidney function within the normal range on pregnancy outcome. METHOD 1043 (50% black, 50% white) women who participated in the CARDIA study who had kidney function and biochemical analyses measured before at least one pregnancy delivered during the 20 years post-baseline period were included in analysis. Kidney function estimated as glomerular filtration rate (eGFR) via modified CKD-EPI equations, serum creatinine, and urinary albumin/creatinine ratio were evaluated as predictors of infant birthweight, gestational age, birthweight-for-gestational-age, and hypertensive disorders of pregnancy via self-report, using multiple regression with adjustment for confounders (age, race, smoking, BMI, center, parity, systolic blood pressure at baseline). Serum uric acid was also examined at both baseline and year 10. RESULTS Unadjusted pre-pregnancy eGFR (baseline) was associated with lower average birthweight-for-gestational-age, but this disappeared after adjustment for confounders. A decline in GFR from baseline to year 10 was associated with lower birthweight (adjusted estimate -195 g, p = 0.03 overall), especially among whites. After adjustment for confounders, no association was found with gestational age or hypertensive disorders. CONCLUSIONS No strong evidence for an association between preconception kidney function in the normal range and birthweight or gestational age was found. Possible racial differences in these relationships warrant further examination.
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Affiliation(s)
- Emily W Harville
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States.
| | - Janet Catov
- University of Pittsburgh, Departments of OB/GYN and Epidemiology, Pittsburgh, PA, United States.
| | - C Elizabeth Lewis
- Department of Epidemiology, School of Public Health University of Alabama at Birmingham, Birmingham, AL, United States.
| | - Kirsten Bibbins-Domingo
- Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA, United States.
| | - Erica P Gunderson
- Cardiovascular and Metabolism Section, Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States.
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31
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Oladosu-olayiwola O, Olawumi H, Babatunde A, Ijaiya M, Durotoye I, Biliaminu S, Ibraheem R. Fibrinolytic proteins of normal pregnancy and pre-eclamptic patients in North West Nigeria. Afr Health Sci 2018; 18:576-583. [PMID: 30602990 PMCID: PMC6307030 DOI: 10.4314/ahs.v18i3.15] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The hypercoagulability of pregnancy is exaggerated in pre-eclamptic state because of endothelial activation with resultant production of some endothelial derived proteins that are said to be inhibitors of fibrinolysis. This study compares these proteins like tPA, PAI-1 and D-dimers in normal pregnant women and the pre-eclamptic women. METHODOLOGY This was a comparative cross-sectional study. Eighty-five pre-eclamptic women were recruited as subjects and eighty five age, trimester and parity matched normotensive pregnant women as controls. Levels of PT, aPTT, tPA, PAI-1, D-dimer protein were determined in blood samples of subjects and controls. Urinalysis was performed with dipstick method on their urine samples. Data generated was analysed using the IBM®SPSS 20.0 (2011) soft ware packages and the level of significance was a p-value <0.05. RESULTS The mean age of the respondents was 29.9±5.2 years. The median(25th-75th percentile) values of D-dimer, tPA, and PAI-1 of subjects were 730 (305.000-1560.000ng/ml), 0.11 (0.065-0,300ng/ml) and 3.65 (2.970-4,400ng/ml) respectively which were significantly higher than the corresponding values in the controls of 520 (24.000-1030.000ng/ml), 0.05 (0.040-0.090ng/ml and 2.650 (2.125-3.400ng/ml) respectively, p<0.05 each. CONCLUSION The abnormal levels of PAI-1, D-dimer and tPA imply that they contribute to the exaggerated hypercoagulabilty state in pre-eclampsia thus, measuring their levels can help in the management of the condition.
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Affiliation(s)
| | | | | | - Munirdeen Ijaiya
- University of Ilorin / University of Ilorin teaching hospital., Obstetrics & Gynaecology
| | | | - Sikiru Biliaminu
- University of Ilorin Teaching Hospital, Chemical Pathology and Immunology
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Biochemical Assessment of Renal and Liver Function among Preeclamptics in Lagos Metropolis. Int J Reprod Med 2018; 2018:1594182. [PMID: 30155474 PMCID: PMC6091329 DOI: 10.1155/2018/1594182] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 06/11/2018] [Accepted: 06/14/2018] [Indexed: 11/17/2022] Open
Abstract
Objectives Preeclampsia is a pregnancy specific syndrome. Studies have shown that preeclampsia has multiorgan dysfunction effects. This study evaluated biomarkers of renal and liver function among preeclamptic Nigerian women. Study Design This was a cross-sectional study conducted among 49 preeclamptic women and 50 normotensive healthy pregnant women. Method The baseline data comprising age, gestational age, and blood pressure were obtained. Venous blood and spot urine samples were collected from each participant. Plasma obtained from blood samples taken into lithium heparinized vacutainer bottles was assayed for electrolytes, urea, creatinine, total protein, albumin, and uric acid, while sera samples from blood samples taken into serum separation tube- (SST-) gel vacutainer were assayed for aspartate transaminase and alanine transaminase using ion selective electrode technique and Cobas autoanalyzer. Spot urine samples were assayed for protein and creatinine using Pyrogallol's reagent and Jaffe's methods, respectively. Microalbuminuria (protein/creatinine ratio) was generated from spot urine protein and creatinine data. Result The plasma sodium, total protein, and albumin in preeclamptic group were significantly decreased (p<0.05) when compared with control. There was statistically significant increase (p<0.05) in microalbuminuria, plasma potassium, urea, creatinine, uric acid levels, serum AST, and ALT activities in preeclamptic group. A positive association (p<0.05) between alanine aminotransferase and biomarkers of renal function was observed. Conclusion Preeclampsia has deleterious effects on renal and liver function as shown by alteration of these parameters.
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Marrs CC, Rahman M, Dixon L, Olson G. The association of hyperuricemia and immediate postpartum hypertension in women without a diagnosis of chronic hypertension. Hypertens Pregnancy 2018; 37:126-130. [PMID: 30014728 DOI: 10.1080/10641955.2018.1493494] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Our objective was to determine if elevated uric acid (UA) is associated with postpartum hypertension (PP HTN) in women without chronic hypertension. This is a secondary analysis of a randomized trial. We compared those with elevated UA to those with normal UA. Logistic regression was conducted to determine the association of elevated UA with PP HTN. Five hundred and fifty-six women met criteria. An UA level ≥ 5.2 mg/dL was associated with immediate PP HTN (adjusted odds ratio 2.44, 95% CI 1.63-3.64). The association was stronger among overweight and obese women. We conclude that hyperuricemia is associated with PP HTN, especially among obese women.
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Affiliation(s)
- Caroline C Marrs
- a Division of Maternal Fetal Medicine , The University of Texas Medical Branch , Galveston , TX , USA
| | - Mahbubur Rahman
- a Division of Maternal Fetal Medicine , The University of Texas Medical Branch , Galveston , TX , USA
| | - Luke Dixon
- a Division of Maternal Fetal Medicine , The University of Texas Medical Branch , Galveston , TX , USA
| | - Gayle Olson
- a Division of Maternal Fetal Medicine , The University of Texas Medical Branch , Galveston , TX , USA
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Khaliq OP, Konoshita T, Moodley J, Naicker T. The Role of Uric Acid in Preeclampsia: Is Uric Acid a Causative Factor or a Sign of Preeclampsia? Curr Hypertens Rep 2018; 20:80. [PMID: 29992361 DOI: 10.1007/s11906-018-0878-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE OF REVIEW Because of the significant discrepancies on this topic, this review will focus on the role of uric acid in PE, uric acid as a predictor of preeclampsia and fetal growth retardation. We considered eligible review and original articles relevant to the research question. RECENT FINDINGS Hypertensive disorders of pregnancy such as preeclampsia (PE) are a major cause of both maternal and fetal morbidity and mortality worldwide. Uric acid has been reported as a key factor contributing to the pathogenesis of PE. Some studies have indicated that serum uric acid levels increase with the severity of PE, while several studies have shown contradictory results. Some studies suggested high uric acid levels lead to PE, while others state that PE causes an increase in uric acid levels. Despite the strong association of uric acid in the pathogenesis of preeclampsia, current data is still contradictory hence genetic and high-end laboratory investigations may clarify this enigma.
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Affiliation(s)
- Olive P Khaliq
- Optics and Imaging Centre, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
| | - Tadashi Konoshita
- Third Department of Internal Medicine, University of Fukui Faculty of Medicine Sciences, Fukui, Japan
| | - Jagidesa Moodley
- Department of Obstetrics and Gynaecology and Women's Health and HIV Research Group, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
| | - Thajasvarie Naicker
- Optics and Imaging Centre, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
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Singh U, Solanki V, Mehrotra S, Sharma R. An Evaluation of Applicability of Salivary Uric Acid Measurement in Preeclampsia and Normal Pregnancy and Its Correlation with Serum Uric Acid. J Obstet Gynaecol India 2018; 69:62-68. [PMID: 30814812 DOI: 10.1007/s13224-018-1124-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 04/21/2018] [Indexed: 12/22/2022] Open
Abstract
Purpose Hypertensive disorders complicate 5-10% of all pregnancies and contribute greatly to maternal morbidity and mortality. There are various biomarkers for detection of preeclampsia. Several studies have reported that positive correlation exists between serum uric acid (UA) levels and adverse maternal and fetal outcome. Significant advances have been made toward validation of salivary biomarkers. We conducted this study to determine levels of salivary UA and its correlation with serum UA normal pregnancy and preeclampsia. Methods Present cross-sectional study was conducted in tertiary care teaching hospital in North India. One hundred and fifty participants were divided into control group (50 healthy non-pregnant females), study group I (50 normotensive pregnant females), study group II (50 pregnant females with preeclampsia), and both salivary and serum UA was estimated at the same time. Results Saliva UA of study group II (4.86 ± 2.37 mg/dl) was significantly higher (p < 0.001) than that of control group (2.09 ± 1.33 mg/dl) and study group I (3.32 ± 1.77 mg/dl). Serum UA of study group II (6.63 + 2.78 mg/dl) was significantly higher (p < 0.001) than that of control group (2.94 + 1.94 mg/dl) and also study group I (5.18 + 2.31 mg/dl) (p = 0.0006). Conclusion UA is present in the saliva of women with preeclampsia and has linear correlation with serum UA. Therefore, salivary UA can be used in place of invasive serum UA to monitor women with preeclampsia. Saliva collection is easy, noninvasive and cost-effective. Salivary UA testing may be useful for monitoring preeclampsia at home-based and hospital setting.
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Affiliation(s)
- Urmila Singh
- Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh India
| | - Vandana Solanki
- Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh India
| | - Seema Mehrotra
- Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh India
| | - Ruchita Sharma
- Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh India
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Barneo-Caragol C, Martínez-Morillo E, Rodríguez-González S, Lequerica-Fernández P, Vega-Naredo I, Álvarez Menéndez FV. Strontium and its role in preeclampsia. J Trace Elem Med Biol 2018; 47:37-44. [PMID: 29544806 DOI: 10.1016/j.jtemb.2018.01.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Revised: 01/08/2018] [Accepted: 01/12/2018] [Indexed: 01/15/2023]
Abstract
BACKGROUND Preeclampsia (PE) is considered a specific vascular disease in which endothelial dysfunction may be the crucial factor of its pathogenesis. It has been suggested that strontium (Sr) may play a role in the pathophysiology of PE. Our group established in a previous study the serum levels of Sr in healthy pregnancies, and the main aim of the present study was to evaluate Sr concentrations and oxidative status in preeclamptic women. METHODS The study population included women with early-onset PE (E-PE, n = 39), late-onset PE (L-PE, n = 67) and serial samples from a subset of preeclamptic women (PE-ss, n = 20). The control group included women with gestational hypertension (GH, n = 56) and healthy pregnancies (samples collected in the 1st (n = 50), 2nd (n = 51) and 3rd trimesters (n = 53)). Strontium, calcium (Ca), uric acid (UA), placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), lipid peroxidation and total antioxidant activity (TAA) were measured in these samples. RESULTS Mean Sr levels were significantly higher in PE than in control groups (p ≤ 0.0001). Calcium values were found to be significantly lower in E-PE compared to control groups (p = 0.03). Higher levels of NT-proBNP were found in PE vs. control groups (p < 0.001). sFlt-1/PlGF ratio was higher in E-PE compared to L-PE and GH (p < 0.001). Uric acid levels in PE were significantly higher than in control groups (p < 0.0001). There was a strong positive correlation between UA and Sr in the E-PE serial samples (r = 0.80, p < 0.0001). Lipid peroxidation and lipid peroxidation/TAA ratios were found to be higher in PE, with lower values of TAA. CONCLUSION The higher levels of Sr and the alterations of redox status found in preeclamptic women, along with the strong correlation between UA and Sr suggest that this element may be involved in the pathogenesis of PE.
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Affiliation(s)
- Clara Barneo-Caragol
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, s/n, 33011, Oviedo, Asturias, Spain.
| | - Eduardo Martínez-Morillo
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, s/n, 33011, Oviedo, Asturias, Spain.
| | - Susana Rodríguez-González
- Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, Av. Julián Clavería, s/n, 33006, Oviedo, Asturias, Spain.
| | - Paloma Lequerica-Fernández
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, s/n, 33011, Oviedo, Asturias, Spain.
| | - Ignacio Vega-Naredo
- Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, Av. Julián Clavería, s/n, 33006, Oviedo, Asturias, Spain.
| | - Francisco V Álvarez Menéndez
- Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Av. de Roma, s/n, 33011, Oviedo, Asturias, Spain; Department of Biochemistry and Molecular Biology, University of Oviedo, C/ Fernando Bongera s/n, 33006, Oviedo, Asturias, Spain.
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Stødle GS, Silva GB, Tangerås LH, Gierman LM, Nervik I, Dahlberg UE, Sun C, Aune MH, Thomsen LCV, Bjørge L, Iversen AC. Placental inflammation in pre-eclampsia by Nod-like receptor protein (NLRP)3 inflammasome activation in trophoblasts. Clin Exp Immunol 2018; 193:84-94. [PMID: 29683202 DOI: 10.1111/cei.13130] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/18/2018] [Accepted: 03/19/2018] [Indexed: 12/28/2022] Open
Abstract
Pre-eclampsia is associated with increased levels of cholesterol and uric acid and an inflamed placenta expressing danger-sensing pattern recognition receptors (PRRs). Crystalline cholesterol and uric acid activate the PRR Nod-like receptor protein (NLRP)3 inflammasome to release interleukin (IL)-1β and result in vigorous inflammation. We aimed to characterize crystal-induced NLRP3 activation in placental inflammation and examine its role in pre-eclampsia. We confirmed that serum total cholesterol and uric acid were elevated in pre-eclamptic compared to healthy pregnancies and correlated positively to high sensitivity C-reactive protein (hsCRP) and the pre-eclampsia marker soluble fms-like tyrosine kinase-1 (sFlt-1). The NLRP3 inflammasome pathway components (NLRP3, caspase-1, IL-1β) and priming factors [complement component 5a (C5a) and terminal complement complex (TCC)] were co-expressed by the syncytiotrophoblast layer which covers the placental surface and interacts with maternal blood. The expression of IL-1β and TCC was increased significantly and C5a-positive regions in the syncytiotrophoblast layer appeared more frequent in pre-eclamptic compared to normal pregnancies. In-vitro activation of placental explants and trophoblasts confirmed NLRP3 inflammasome pathway functionality by complement-primed crystal-induced release of IL-1β. This study confirms crystal-induced NLRP3 inflammasome activation located at the syncytiotrophoblast layer as a mechanism of placental inflammation and suggests contribution of enhanced NLRP3 activation to the harmful placental inflammation in pre-eclampsia.
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Affiliation(s)
- G S Stødle
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Gynecology and Obstetrics, St Olav's Hospital, Trondheim, Norway
| | - G B Silva
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Gynecology and Obstetrics, St Olav's Hospital, Trondheim, Norway
| | - L H Tangerås
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Gynecology and Obstetrics, St Olav's Hospital, Trondheim, Norway
| | - L M Gierman
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - I Nervik
- Cellular and Molecular Imaging Core Facility (CMIC), Faculty of Medicine and Health Science, NTNU, Trondheim, Norway
| | - U E Dahlberg
- Department of Gynecology and Obstetrics, St Olav's Hospital, Trondheim, Norway
| | - C Sun
- Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
| | - M H Aune
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - L C V Thomsen
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.,Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
| | - L Bjørge
- Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
| | - A-C Iversen
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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Asgharnia M, Mirblouk F, Kazemi S, Pourmarzi D, Mahdipour Keivani M, Dalil Heirati SF. Maternal serum uric acid level and maternal and neonatal complications in preeclamptic women: A cross-sectional study. Int J Reprod Biomed 2017. [DOI: 10.29252/ijrm.15.9.583] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
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Brien ME, Duval C, Palacios J, Boufaied I, Hudon-Thibeault AA, Nadeau-Vallée M, Vaillancourt C, Sibley CP, Abrahams VM, Jones RL, Girard S. Uric Acid Crystals Induce Placental Inflammation and Alter Trophoblast Function via an IL-1-Dependent Pathway: Implications for Fetal Growth Restriction. THE JOURNAL OF IMMUNOLOGY 2016; 198:443-451. [PMID: 27903743 DOI: 10.4049/jimmunol.1601179] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 10/24/2016] [Indexed: 12/21/2022]
Abstract
Excessive placental inflammation is associated with several pathological conditions, including stillbirth and fetal growth restriction. Although infection is a known cause of inflammation, a significant proportion of pregnancies have evidence of inflammation without any detectable infection. Inflammation can also be triggered by endogenous mediators, called damage associated molecular patterns or alarmins. One of these damage-associated molecular patterns, uric acid, is increased in the maternal circulation in pathological pregnancies and is a known agonist of the Nlrp3 inflammasome and inducer of inflammation. However, its effects within the placenta and on pregnancy outcomes remain largely unknown. We found that uric acid (monosodium urate [MSU]) crystals induce a proinflammatory profile in isolated human term cytotrophoblast cells, with a predominant secretion of IL-1β and IL-6, a result confirmed in human term placental explants. The proinflammatory effects of MSU crystals were shown to be IL-1-dependent using a caspase-1 inhibitor (inhibits IL-1 maturation) and IL-1Ra (inhibits IL-1 signaling). The proinflammatory effect of MSU crystals was accompanied by trophoblast apoptosis and decreased syncytialization. Correspondingly, administration of MSU crystals to rats during late gestation induced placental inflammation and was associated with fetal growth restriction. These results make a strong case for an active proinflammatory role of MSU crystals at the maternal-fetal interface in pathological pregnancies, and highlight a key mediating role of IL-1. Furthermore, our study describes a novel in vivo animal model of noninfectious inflammation during pregnancy, which is triggered by MSU crystals and leads to reduced fetal growth.
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Affiliation(s)
- Marie-Eve Brien
- Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Microbiology, Virology and Immunology, University of Montreal, Montreal, Quebec H3T 1C5, Canada
| | - Cyntia Duval
- Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec H3T 1C5, Canada
| | - Julia Palacios
- Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec H3T 1C5, Canada
| | - Ines Boufaied
- Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec H3T 1C5, Canada
| | | | - Mathieu Nadeau-Vallée
- Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Pharmacology, University de Montreal, Montreal H3T 1C5, Canada
| | - Cathy Vaillancourt
- Institut de la Recherche Scientifique, Centre Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada
| | - Colin P Sibley
- Maternal and Fetal Health Research Centre, University of Manchester, Manchester, M13 9WL, United Kingdom.,St. Mary's Hospital, Central Manchester University Hospital National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom; and
| | - Vikki M Abrahams
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, CT 06510
| | - Rebecca L Jones
- Maternal and Fetal Health Research Centre, University of Manchester, Manchester, M13 9WL, United Kingdom.,St. Mary's Hospital, Central Manchester University Hospital National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, United Kingdom; and
| | - Sylvie Girard
- Ste-Justine Hospital Research Centre, Feto-Maternal and Neonatal Pathologies Research Axis, University of Montreal, Montreal, Quebec H3T 1C5, Canada; .,Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Microbiology, Virology and Immunology, University of Montreal, Montreal, Quebec H3T 1C5, Canada.,Department of Pharmacology, University de Montreal, Montreal H3T 1C5, Canada
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Nadeau-Vallée M, Obari D, Palacios J, Brien MÈ, Duval C, Chemtob S, Girard S. Sterile inflammation and pregnancy complications: a review. Reproduction 2016; 152:R277-R292. [PMID: 27679863 DOI: 10.1530/rep-16-0453] [Citation(s) in RCA: 194] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 09/27/2016] [Indexed: 02/06/2023]
Abstract
Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.
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Affiliation(s)
- Mathieu Nadeau-Vallée
- Departments of PediatricsOphthalmology and Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.,Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada
| | - Dima Obari
- Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada
| | - Julia Palacios
- Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada
| | - Marie-Ève Brien
- Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada.,Department of MicrobiologyVirology and Immunology, Université de Montréal, Montreal, Quebec, Canada
| | - Cyntia Duval
- Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada
| | - Sylvain Chemtob
- Departments of PediatricsOphthalmology and Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada .,Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada
| | - Sylvie Girard
- Department of PharmacologyUniversité de Montréal, Montreal, Quebec, Canada .,Department of Obstetrics & GynecologyCHU Sainte-Justine Research Center, Montreal, Quebec, Canada.,Department of MicrobiologyVirology and Immunology, Université de Montréal, Montreal, Quebec, Canada
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41
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Nair A, Savitha C. Estimation of Serum Uric Acid as an Indicator of Severity of Preeclampsia and Perinatal Outcome. J Obstet Gynaecol India 2016; 67:109-118. [PMID: 28405118 DOI: 10.1007/s13224-016-0933-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 08/12/2016] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Uric acid is a marker of oxidative stress tissue injury and renal dysfunction, hence a correlation hypothesized. OBJECTIVES (1) To evaluate severity of preeclampsia with raised serum uric acid. (2) To evaluate perinatal outcome in preeclampsia with raised serum uric ccid. MATERIALS AND METHODS 50 pregnant women with severe preeclampsia and 50 normotensive women were included in the study and maternal serum uric acid was estimated in both the groups. RESULTS In the study group comprising of 50 cases of preeclampsia, there is a positive correlation (r = 0.695 & +0.359) between the variables in study group, and as the SBP or DBP increases, the MSUA concentration also increases. In control group, there is a negative correlation (r = -0.083 & -0.095). Perinatal complication was more in study group, 54 % were preterm compared to 4 % in control group also as MSUA value increased average gestational age decreased. Mean birth weight in study group was 1.8 kg study group of which 13 (26 %) babies were VLBW, 28 (56 %) were LBW, and 9 (18 %) babies had normal birth weight, in control group mean birth weight was 2.99 kg. There were 6 cases of ELBW babies in study group which were included in VLBW group for statistical calculation. The difference was found to be statistically significant (p < 0.05). In the study group, the MSUA concentration is found higher in LBW and VLBW babies compared to normal birth weight babies. CONCLUSION There is a positive correlation between SUA & severity of preeclampsia, and a significant adverse fetal outcome is observed with raised MSUA in preeclamptic patients.
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Affiliation(s)
- Aparna Nair
- Department of Obstetrics & Gynecology, Vydehi Institute of Medical Sciences & Research Institute, Whitefield, Bangalore, Karnataka 560048 India
| | - C Savitha
- Department of Obstetrics & Gynecology, Bangalore Medical College & Research Institute, K.R.Fort road, Bangalore, India
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Wang IK, Chen JH, Muo CH, Chou CY, Liu YL, Lin SY, Liang CC, Yen TH, Sung FC. Subsequent risk of gout for women with hypertensive disorders in pregnancy: a retrospective cohort study. J Hypertens 2016; 34:914-919. [PMID: 26886561 DOI: 10.1097/hjh.0000000000000888] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The association between the risk of subsequent gout and hypertensive disorders in pregnancy (HDP), including gestational hypertension and preeclampsia has not been well investigated. We investigated the risk of gout in later life for women with a history of HDP. METHODS We identified 1133 newly diagnosed HDP women aged 14-40 years from Taiwan insurance claims data from the period of 2000-2010. From the same database, 9064 women without HDP were randomly selected as the control cohort, with frequency matched by age and diagnosis year. Those with a baseline history of hypertension or gout were excluded from this study. All study participants were followed until the development of gout, withdrawal from the insurance program, or the end of 2011. Cox proportional hazards regression was used to assess the risk for gout in the HDP cohort compared with the controls. RESULTS The incidence of gout was 2.83 folds higher in the HDP cohort than in the control cohort (2.66 vs. 0.94 per 1000 person-years) with an adjusted hazard ratio of 2.34 (95% confidence interval = 1.36-4.02) and 1.84 (95% confidence interval = 1.03-3.32) after controlling for comorbidities prior to and after pregnancy, respectively. In addition, the risk for gout increased as the severity of HDP increased. CONCLUSION Women with HDP are at higher risk of developing gout in their later life. Close surveillance for hyperuricemia and lifestyle intervention should be considered for these high risk women. Further prospective study is needed for investigating the relationship between HDP and subsequent gout.
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Affiliation(s)
- I-Kuan Wang
- aGraduate Institute of Clinical Medical Science bDepartment of Internal Medicine, College of Medicine cDivision of Nephrology dDivision of Rheumatology eManagement Office for Health Data, China Medical University Hospital, Taichung, Taiwan fDivision of Nephrology, Chang Gung Memorial Hospital, Taipei gChang Gung University College of Medicine, Taoyuan hDepartment of Health Services Administration, China Medical University, Taichung, Taiwan
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Kell DB, Kenny LC. A Dormant Microbial Component in the Development of Preeclampsia. Front Med (Lausanne) 2016; 3:60. [PMID: 27965958 PMCID: PMC5126693 DOI: 10.3389/fmed.2016.00060] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Accepted: 11/04/2016] [Indexed: 12/12/2022] Open
Abstract
Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of "preeclampsia" that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.
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Affiliation(s)
- Douglas B. Kell
- School of Chemistry, The University of Manchester, Manchester, UK
- The Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK
- Centre for Synthetic Biology of Fine and Speciality Chemicals, The University of Manchester, Manchester, UK
- *Correspondence: Douglas B. Kell,
| | - Louise C. Kenny
- The Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland
- Department of Obstetrics and Gynecology, University College Cork, Cork, Ireland
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Inoue M, Tsuchihashi T, Hasuo Y, Ogawa M, Tominaga M, Arakawa K, Oishi E, Sakata S, Ohtsubo T, Matsumura K, Kitazono T. Salt Intake, Home Blood Pressure, and Perinatal Outcome in Pregnant Women. Circ J 2016; 80:2165-72. [DOI: 10.1253/circj.cj-16-0405] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Minako Inoue
- Clinical Research Institute, National Hospital Organization Kyushu Medical Center
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University
| | - Takuya Tsuchihashi
- Clinical Research Institute, National Hospital Organization Kyushu Medical Center
- Steel Memorial Yawata Hospital
| | - Yasuyuki Hasuo
- Division of Obstetrics and Gynecology, National Hospital Organization Kyushu Medical Center
| | - Masanobu Ogawa
- Division of Obstetrics and Gynecology, National Hospital Organization Kyushu Medical Center
| | - Mitsuhiro Tominaga
- Division of Hypertension, National Hospital Organization Kyushu Medical Center
| | - Kimika Arakawa
- Division of Clinical Laboratory, National Hospital Organization Kyushu Medical Center
| | - Emi Oishi
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University
| | - Satoko Sakata
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University
| | - Toshio Ohtsubo
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University
| | - Kiyoshi Matsumura
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University
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An analysis of the differences between early and late preeclampsia with severe hypertension. Pregnancy Hypertens 2015; 6:47-52. [PMID: 26955772 DOI: 10.1016/j.preghy.2015.12.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 11/27/2015] [Accepted: 12/14/2015] [Indexed: 01/15/2023]
Abstract
Preeclampsia is clinically divided into early onset and late onset preeclampsia based on the gestational age at delivery. Although the diagnostic criteria are the same in each subgroup of preeclampsia, it has been suggested that the maternal and perinatal mortalities of early onset and late onset preeclampsia are different. However, studies that compare clinical parameters or laboratory biomarkers between early onset and late onset preeclampsia are limited. Data on 177 women with early or late preeclampsia with severe hypertension were collected from a University Teaching Hospital from January 2010 to January 2011 and analysed. Data included all the clinical parameters and laboratory biomarkers of liver and renal function. 63 women and 114 women were diagnosed with early and late preeclampsia with severe hypertension, respectively. There was no difference in the maternal age and the incidence of clinical symptoms including edema, vision disturbance, severe headache and stillbirth between two groups. There was a decrease in alkaline phosphatase levels in early preeclampsia with severe hypertension but other markers of liver function were not altered. However, renal function including blood urea nitrogen, creatinine and uric acid were significantly higher in early preeclampsia with severe hypertension. Umbilical artery systolic velocity/diastolic velocity ratio was significantly higher in early preeclampsia with severe hypertension. Our data demonstrates that the laboratory biomarkers of renal function differ between early and late preeclampsia with severe hypertension. The severity of renal dysfunction correlated with the time of delivery in preeclampsia with severe hypertension.
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Maternal serum uric acid concentration is associated with the expression of tumour necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia. J Hum Hypertens 2015; 30:456-62. [PMID: 26511169 DOI: 10.1038/jhh.2015.110] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Revised: 08/31/2015] [Accepted: 09/17/2015] [Indexed: 11/08/2022]
Abstract
We aimed to investigate whether there is a correlation between elevated serum uric acid (SUA) concentration and endothelial inflammatory response in women with preeclampsia (PE). On the basis of clinical and laboratory findings, patients were assigned to three groups: normal blood pressure (Control (Con)), gestational hypertension (GH) and PE (n=50 in each group). SUA concentration was measured by spectrophotometry, and serum tumour necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were measured by enzyme-linked immunosorbent assay. Western blotting and immunohistochemical staining were also used to detect the changes in TNF-α and ICAM-1 expression in subcutaneous fat tissue. PE patients showed significantly higher systolic and diastolic blood pressures compared with Con and GH pregnant women (P=0.02 and P=0.02, respectively). The changes of body mass index (ΔBMI) before and after pregnancy and 24-h urine protein were significantly different among the three groups (P<0.001). Maternal SUA, TNF-α and soluble ICAM-1 (sICAM-1) levels were significantly increased in the patients with PE (P<0.05) compared with the other two groups. Scatterplot analysis revealed that elevated SUA concentration positively correlated with TNF-α and sICAM-1 in pregnant women. Moreover, vessels in subcutaneous fat tissues of preeclamptic patients showed intense TNF-α and ICAM-1 staining compared with Con and GH patients. The results support that, to a certain extent, elevated SUA concentration is significantly associated with inflammation of maternal systemic vasculature as indicated by increased TNF-α and ICAM-1 expression in women with PE.
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47
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Weissgerber TL, Milic NM, Turner ST, Asad RA, Mosley TH, Kardia SLR, Hanis CL, Garovic VD. Uric Acid: A Missing Link Between Hypertensive Pregnancy Disorders and Future Cardiovascular Disease? Mayo Clin Proc 2015; 90:1207-16. [PMID: 26260220 PMCID: PMC4567408 DOI: 10.1016/j.mayocp.2015.05.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Revised: 05/07/2015] [Accepted: 05/22/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To determine whether women who had a hypertensive pregnancy disorder (HPD) have elevated uric acid concentrations decades after pregnancy as compared with women who had normotensive pregnancies. PATIENTS AND METHODS The Genetic Epidemiology Network of Arteriopathy study measured uric acid concentrations in Hispanic (30%), non-Hispanic white (28%), and non-Hispanic black (42%) women (mean age, 60 ± 10 years). This cross-sectional study was conducted between July 1, 2000, and December 31, 2004. Hispanic participants were recruited from families with high rates of diabetes, whereas non-Hispanic participants were recruited from families with high rates of hypertension. This analysis compared uric acid concentrations in women with a history of normotensive (n = 1846) or hypertensive (n = 408) pregnancies by logistic regression. RESULTS Women who had an HPD had higher uric acid concentrations (median, 5.7 mg/dL vs 5.3 mg/dL; P < .001) and were more likely to have uric acid concentrations above 5.5 mg/dL (54.4% vs 42.4%; P = .001) than were women who had normotensive pregnancies. These differences persisted after adjusting for traditional cardiovascular risk factors, comorbidities, and other factors that affect uric acid concentrations. A family-based subgroup analysis comparing uric acid concentrations in women who had an HPD (n = 308) and their parous sisters who had normotensive pregnancies (n = 250) gave similar results (median uric acid concentrations, 5.7 mg/dL vs 5.2 mg/dL, P = 0.02; proportion of women with uric acid concentrations > 5.5 mg/dL, 54.0% vs 40.3%, P < .001). CONCLUSION Decades after pregnancy, women who had an HPD have higher uric acid concentrations. This effect does not appear to be explained by a familial predisposition to elevated uric acid concentrations.
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Affiliation(s)
| | - Natasa M Milic
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Medical Faculty, Department of Biostatistics, University of Belgrade, Belgrade, Serbia
| | - Stephen T Turner
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
| | - Reem A Asad
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Al Adan Hospital, Ministry of Health, Kuwait
| | | | | | - Craig L Hanis
- Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston
| | - Vesna D Garovic
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
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Madero M, Rodríguez Castellanos FE, Jalal D, Villalobos-Martín M, Salazar J, Vazquez-Rangel A, Johnson RJ, Sanchez-Lozada LG. A pilot study on the impact of a low fructose diet and allopurinol on clinic blood pressure among overweight and prehypertensive subjects: a randomized placebo controlled trial. ACTA ACUST UNITED AC 2015; 9:837-44. [PMID: 26329473 DOI: 10.1016/j.jash.2015.07.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 07/17/2015] [Accepted: 07/20/2015] [Indexed: 02/07/2023]
Abstract
Fructose and sodium intake have been associated with hypertension and metabolic syndrome. Although various mechanisms are involved, fructose causes hypertension partly through rising intracellular and serum uric acid. To date, there are no studies in adults that have evaluated the impact of low fructose diets and allopurinol on prehypertensive and overweight subjects. The objective of this study was to compare the effect of low fructose diet and allopurinol or placebo on blood pressure (BP) and metabolic syndrome components The study was a controlled clinical trial and consisted of two phases; in the first phase of intervention (4 weeks), patients were randomized to either low fructose diet (34 patients) or control diet (38 patients). In the second phase of intervention (weeks 4-8), the same groups continued with the same diet prescriptions but were further randomized to receive placebo or allopurinol (300 mg/d). Clinic and 24-hour ambulatory BP, anthropometric measures, and laboratory data were determined at baseline, weeks 4 and 8. Seventy-two patients were included in the trial. At the end of the dietary phase, both diet groups significantly reduced their BP, but there were no between-group differences. Compared to placebo, at the end of follow-up, subjects in the allopurinol group had a lower clinic systolic blood pressure and this was significant within- and between-group comparisons. The percentage of dippers was higher in the allopurinol group, and weight was reduced significantly despite the absence of caloric restriction Allopurinol was associated with a significant reduction in clinic BP, an increase in the percentage of dippers, and significant weight loss. Larger studies with longer follow-up are needed to confirm our findings.
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Affiliation(s)
- Magdalena Madero
- Division of Nephrology and Renal Pathophysiology, National Heart Institute of Mexico, Mexico City, Mexico.
| | | | - Diana Jalal
- Division of Nephrology, University of Colorado, Denver, Colorado, USA
| | - Maria Villalobos-Martín
- Division of Nephrology and Renal Pathophysiology, National Heart Institute of Mexico, Mexico City, Mexico
| | - Jonathan Salazar
- Division of Nephrology and Renal Pathophysiology, National Heart Institute of Mexico, Mexico City, Mexico
| | - Armando Vazquez-Rangel
- Division of Nephrology and Renal Pathophysiology, National Heart Institute of Mexico, Mexico City, Mexico
| | - Richard J Johnson
- Division of Nephrology, University of Colorado, Denver, Colorado, USA
| | - L Gabriela Sanchez-Lozada
- Division of Nephrology and Renal Pathophysiology, National Heart Institute of Mexico, Mexico City, Mexico
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49
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Serum uric acid may not be involved in the development of preeclampsia. J Hum Hypertens 2015; 30:136-40. [PMID: 25994995 DOI: 10.1038/jhh.2015.47] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 03/18/2015] [Accepted: 04/09/2015] [Indexed: 01/16/2023]
Abstract
Higher serum levels of uric acid are associated with preeclampsia and may signal an early change in preeclampsia. However there is less evidence suggesting there is a meaningful association between uric acid and the development of preeclampsia. A total of 877 women with preeclampsia at presentation and 580 normotensive pregnancies were retrospectively recruited from January 2009 to May 2014. In addition, 5556 pregnant women were also prospectively recruited from September 2012 to December 2013. Retrospective serum levels of uric acid were obtained from women with preeclampsia at the time of presentation (n=877), and serum levels of uric acid in the first, second and third trimester were prospectively collected in women who later developed preeclampsia (n=78), as well as those who did not (n=5478). The serum levels of uric acid were significantly increased in women with preeclampsia at presentation from retrospective samples and this increase correlated with the time of onset and the severity of preeclampsia. However, in prospective samples, serum levels of uric acid were not increased in the first and second trimesters in women who later developed preeclampsia compared with those who did not. The serum level of uric acid in the first and second trimesters in women who developed preeclampsia was not different. Our results demonstrate that the serum levels of uric acid were only increased after the presentation of clinical symptoms of preeclampsia. Therefore, it is likely that uric acid is not involved in the development of preeclampsia and cannot be an early prediction biomarker of this disease.
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Nasri K, Razavi M, Rezvanfar MR, Mashhadi E, Chehrei A, Mohammadbeigi A. Mid-gestational serum uric acid concentration effect on neonate birth weight and insulin resistance in pregnant women. Int J Crit Illn Inj Sci 2015; 5:17-20. [PMID: 25810959 PMCID: PMC4366822 DOI: 10.4103/2229-5151.152309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Objective To investigate the relationship between mid-gestational serum uric acid and birth weight in diabetic pregnant women with or without insulin resistance. Methods: In a prospective cohort study, fasting uric acid, blood glucose, and serum insulin were measured in 247 pregnant women between 20-22 weeks of gestational period. Insulin resistance was estimated using the homeostasis model assessment-insulin resistance (HOMA-IR). Stratification analysis and independent t-test was used to assess the association between uric acid and birth weights regarding to insulin resistance. Results: The means of the mid-gestational serum uric acid concentrations were not significantly different in women with and without insulin resistance. But stratification analysis showed that there was a significant difference between uric acid concentration and macrosomic birth in diabetic women without insulin resistance. Conclusions: Higher mid – gestation serum uric acid concentration, even if it does not exceed the normal range, is accompanied by lower birth weight only in non-insulin resistance women. Insulin resistance could have a negative confounding effect on hyperuriemia and birth weight.
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Affiliation(s)
- Khadijeh Nasri
- Department of Obstetrics and Gynecology, Arak University of Medical Sciences, Arak, Iran
| | - Maryamsadat Razavi
- Department of Obstetrics and Gynecology, Arak University of Medical Sciences, Arak, Iran
| | | | - Esmat Mashhadi
- Department of Obstetrics and Gynecology, Arak University of Medical Sciences, Arak, Iran
| | - Ali Chehrei
- Thyroid Research Center, Arak University of Medical Sciences, Arak, Iran
| | - Abolfazl Mohammadbeigi
- Department of Epidemiology and Biostatistics, Health Policy and Promotion Research Center, Qom University of Medical Sciences, Qom, Iran
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