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Khalilipalandi S, Lemieux A, Lauzon-Schnittka J, Perreault L, Dubois M, Tousignant A, Watelle L, Pratte G, Dallaire F. Systematic Review and Meta-analysis of Prenatal Risk Factors for Congenital Heart Disease: Part 1, Maternal Chronic Diseases and Parental Exposures. Can J Cardiol 2024; 40:2476-2495. [PMID: 38996968 DOI: 10.1016/j.cjca.2024.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 06/14/2024] [Accepted: 07/05/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND There is considerable heterogeneity in studies on prenatal risk factors for congenital heart diseases (CHDs). We performed a meta-analysis of all nongenetic factors of CHDs. This report presents results of factors related to maternal chronic diseases and parental exposures. METHODS A systematic search encompassing concepts of CHD and risk factors was used, using the following inclusion criteria: (1) original peer-reviewed articles, (2) quantifying the effects of risk factors for CHDs, (3) between 1989 and 2022. Pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated using a random-effect model. RESULTS Inclusion criteria were met for 170 studies. There was an association between being overweight or obese and CHDs (OR, 1.26; 95% CI, 1.15-1.37), with a dose-effect relationship. Pregestational diabetes (PGDM) was associated with CHDs (OR, 3.51; 95% CI, 2.86-4.3), without difference between type 1 and type 2 PGDM. The effect size of gestational diabetes was less than that of PGDM (OR, 1.38; 95% CI, 1.18-1.61). There was an association between CHDs and pre-eclampsia (OR, 2.01; 95% CI, 1.32-3.05), paternal smoking (OR, 1.32; 95% CI, 1.03-1.70), and alcohol use (OR, 1.50; 95% CI, 1.08-2.08). A smaller association was found with maternal smoking and advanced maternal age. CONCLUSIONS There exists robust evidence for increased risk of CHD in the presence of obesity, maternal diabetes, maternal smoking, and increased maternal age. The effect sizes were relatively modest, except for PGDM. The robustness of the evidence decreased when CHDs were divided into subgroups or when the analyses were restricted to severe CHDs.
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Affiliation(s)
- Sara Khalilipalandi
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Alyssia Lemieux
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Jonathan Lauzon-Schnittka
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Laurence Perreault
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Mélodie Dubois
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Angélique Tousignant
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Laurence Watelle
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Gabriel Pratte
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada
| | - Frédéric Dallaire
- Faculty of Medicine and Health Sciences, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebéc, Canada.
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Kawai S, Pak K, Iwamoto S, Kawakami C, Inuzuka R, Maeda J, Furutani Y, Kamisago M, Takatsuki S, Uyeda T, Yamagishi H, Ito S, Kobayashi T. Association Between Maternal Factors in Early Pregnancy and Congenital Heart Defects in Offspring: The Japan Environment and Children's Study. J Am Heart Assoc 2023; 12:e029268. [PMID: 37642029 PMCID: PMC10547327 DOI: 10.1161/jaha.122.029268] [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: 01/21/2023] [Accepted: 08/01/2023] [Indexed: 08/31/2023]
Abstract
Background Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large-scale birth cohorts. Methods and Results We evaluated a data set of the Japan Environmental and Children's Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30-14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51-15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74-8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14-2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03-1.17]) were associated with CHD in offspring. Conclusions Using a Japanese large-scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.
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Affiliation(s)
- Shun Kawai
- Department of PediatricsYokohama City UniversityYokohamaJapan
| | - Kyongsun Pak
- Biostatistics Unit, Department of Data ScienceNational Center for Child Health and DevelopmentTokyoJapan
| | - Shintaro Iwamoto
- Biostatistics Unit, Department of Data ScienceNational Center for Child Health and DevelopmentTokyoJapan
| | | | - Ryo Inuzuka
- Department of PediatricsThe University of Tokyo HospitalTokyoJapan
| | - Jun Maeda
- Department of CardiologyTokyo Metropolitan Children’s Medical CenterTokyoJapan
| | - Yoshiyuki Furutani
- Department of Pediatric Cardiology and Adult Congenital CardiologyTokyo Women’s Medical UniversityTokyoJapan
| | - Mitsuhiro Kamisago
- Department of PediatricsNippon Medical School Tama Nagayama HospitalTokyoJapan
| | | | - Tomomi Uyeda
- Department of Pediatric CardiologySakakibara Heart InstituteTokyoJapan
| | | | - Shuichi Ito
- Department of PediatricsYokohama City UniversityYokohamaJapan
| | - Tohru Kobayashi
- Department of Data ScienceNational Center for Child Health and DevelopmentTokyoJapan
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Dyląg KA, Anunziata F, Bandoli G, Chambers C. Birth Defects Associated with Prenatal Alcohol Exposure-A Review. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10050811. [PMID: 37238358 DOI: 10.3390/children10050811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/20/2023] [Accepted: 04/25/2023] [Indexed: 05/28/2023]
Abstract
Since the recognition of fetal alcohol syndrome, alcohol has been accepted as a human teratogen. However, little is known about the relation between prenatal alcohol exposure and the spectrum of associated major birth defects. The objective of this review was to summarize data on the association of major congenital abnormalities and prenatal alcohol exposure. We included all major birth defects according to ICD-10 classification. We found that the strongest evidence to date lies in the research examining herniation (gastroschisis and omphalocele), oral clefts (cleft lip with or without palate and cleft palate) and cardiac defects. There is less consistent evidence supporting the association between prenatal alcohol exposure and anomalies of gastrointestinal system, diaphragmatic hernia, genitourinary system and neural tube defects. We found no material support for PAE and choanal atresia, biliary atresia or clubfoot.
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Affiliation(s)
- Katarzyna Anna Dyląg
- Department of Pathophysiology, Jagiellonian University Medical College, Czysta 18, 31-121 Krakow, Poland
- St. Louis Children Hospital, ul. Strzelecka 2, 31-503 Krakow, Poland
| | - Florencia Anunziata
- Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, MC0828, La Jolla, CA 92093-0412, USA
| | - Gretchen Bandoli
- Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, MC0828, La Jolla, CA 92093-0412, USA
| | - Christina Chambers
- Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, MC0828, La Jolla, CA 92093-0412, USA
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Wu L, Li N, Liu Y. Association Between Maternal Factors and Risk of Congenital Heart Disease in Offspring: A Systematic Review and Meta-Analysis. Matern Child Health J 2023; 27:29-48. [PMID: 36344649 PMCID: PMC9867685 DOI: 10.1007/s10995-022-03538-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/09/2022] [Indexed: 11/09/2022]
Abstract
INTRODUCTION This study aimed to summarize the evidence describing the relationship between maternal factors during gestation and risk of congenital heart disease (CHD) in offspring. METHODS PubMed, EMBASE, and the Cochrane Library were searched for potentially relevant reports from inception to May 2021. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated by the random-effects model were used to evaluate the association between maternal factors and CHD risk. RESULTS There was a significant association between CHD risk and obesity in pregnancy (OR 1.29, 95% CI 1.22-1.37; P < 0.001), smoking in pregnancy (OR 1.16, 95% CI 1.07-1.25; P < 0.001), maternal diabetes (OR 2.65, 95% CI 2.20-3.19; P < 0.001), and exposure of pregnant women to organic solvents (OR 1.82, 95% CI 1.23-2.70; P = 0.003). No correlations were revealed between CHD susceptibility and advanced maternal age (OR 1.04, 95% CI 0.96-1.12; P = 0.328), underweight (OR 1.02, 95% CI 0.96-1.08; P = 0.519), alcohol intake in pregnancy (OR 1.08, 95% CI 0.95-1.22; P = 0.251), coffee intake (OR 1.18, 95% CI 0.97-1.44; P = 0.105), and exposure to irradiation (OR 1.80, 95% CI 0.85-3.80; P = 0.125). DISCUSSION Maternal factors including maternal obesity, smoking in pregnancy, maternal diabetes and exposure to organic solvents might predispose the offspring to CHD risk.
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Affiliation(s)
- Lina Wu
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Na Li
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yong Liu
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
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Nie Z, Qu Y, Han F, Bell EM, Zhuang J, Chen J, François M, Lipton E, Matale R, Cui W, Liang Q, Lu X, Huang H, Lv J, Ou Y, Mai J, Wu Y, Gao X, Huang Y, Lin S, Liu X. Evaluation of interactive effects between paternal alcohol consumption and paternal socioeconomic status and environmental exposures on congenital heart defects. Birth Defects Res 2020; 112:1273-1286. [PMID: 32696579 DOI: 10.1002/bdr2.1759] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 06/16/2020] [Accepted: 06/17/2020] [Indexed: 01/13/2023]
Abstract
BACKGROUND While the maternal risk factors on congenital heart defects (CHDs) have often been assessed, paternal contribution to CHDs, especially the joint effects of paternal risk factors on CHDs remain unknown. This study examined the major impacts of paternal alcohol consumption and its interaction (on multiplicative and additive scales) with paternal socioeconomic status (SES) and environmental exposures on CHDs in China. METHODS A population-based case-control study involving 4,726 singleton CHDs cases and 4,726 controls (without any malformation and matched on hospital, gender, and gestational age) was conducted in Guangdong, China, 2004-2014. Information on parental demographics, behavioral patterns, disease/medication, and environmental exposures (3 months before pregnancy) was collected through face-to-face interviews. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) while controlling for all parental factors. RESULTS Paternal alcohol consumption was associated with an increased OR of CHDs (adjusted OR = 2.87, 95% CI: 2.25-3.65). Additionally, paternal smoking, industry occupation, organic solvent contact, virus infection and antibiotic use, living in rural areas, low household income, and migrant status were significantly associated with CHDs (ORs ranged: 1.42-4.44). Significant additive or multiplicative interactions were observed between paternal alcohol consumption and paternal smoking, industrial occupation, and low income on any CHDs (interaction contrast ratio [ICR] = 4.72, 95% CI: 0.96-8.47] and septal defects (ICRs ranged from 2.04 to 2.79, p < .05). CONCLUSIONS Paternal alcohol consumption and multiple paternal factors were significantly associated with CHDs in China. Paternal smoking and low SES factors modified paternal alcohol consumption-CHDs relationships. Further studies are needed to confirm these findings.
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Affiliation(s)
- Zhiqiang Nie
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Yanji Qu
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Fengzhen Han
- Department of Obstetrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Erin M Bell
- Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, New York, USA.,Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Albany, New York, USA
| | - Jian Zhuang
- Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Jimei Chen
- Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Melissa François
- Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, New York, USA.,Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Albany, New York, USA
| | - Emily Lipton
- Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, New York, USA.,Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Albany, New York, USA
| | - Rosemary Matale
- Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, New York, USA.,Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Albany, New York, USA
| | - Weilun Cui
- Department of Neonatology, Panyu General Hospital, Guangzhou, Guangdong, China
| | - Qianhong Liang
- Department of Echocardiography, Panyu Maternal and Child Care Service Centre, Guangzhou, Guangdong, China
| | - Xiangzhang Lu
- Department of Echocardiography, Huadu Maternal and Child Care Service Centre, Guangzhou, Guangdong, China
| | - Huiwen Huang
- Department of Neonatology, Zhuhai Maternal and Child Care Service Center, Zhuhai, Guangdong, China
| | - Junfeng Lv
- Department of Neonatology, Boai Hospital of Zhongshan, Zhongshan, Guangdong, China
| | - Yanqiu Ou
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Jinzhuang Mai
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Yong Wu
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Xiangmin Gao
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Yating Huang
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Shao Lin
- Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, New York, USA.,Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Albany, New York, USA
| | - Xiaoqing Liu
- Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
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Chen Z, Li S, Guo L, Peng X, Liu Y. Prenatal alcohol exposure induced congenital heart diseases: From bench to bedside. Birth Defects Res 2020; 113:521-534. [PMID: 32578335 DOI: 10.1002/bdr2.1743] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 05/22/2020] [Accepted: 05/23/2020] [Indexed: 12/27/2022]
Abstract
Alcohol consumption is increasing worldwide. Many child-bearing-aged women consume alcohol during pregnancy, intentionally or unintentionally, thereby increasing the potential risk for severe congenital diseases. Congenital heart disease (CHD) is the most common birth defect worldwide and can result from both hereditary and acquired factors. Prenatal alcohol exposure (PAE) is considered a key factor that leads to teratogenesis in CHD and its specific phenotypes, especially defects of the cardiac septa, cardiac valves, cardiac canals, and great arteries, adjacent to the chambers, both in animal experiments and clinical retrospective studies. The mechanisms underlying CHD and its phenotypes caused by PAE are associated with changes in retinoic acid biosynthesis and its signaling pathway, apoptosis and defective function of cardiac neural crest cells, disturbance of the Wntβ-catenin signaling pathway, suppression of bone morphogenetic protein (BMP) signaling, and other epigenetic mechanisms. Drug supplements and early diagnosis can help prevent PAE from inducing CHDs.
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Affiliation(s)
- Zhiyan Chen
- Department of Basic Medical Sciences, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan, China.,Department of Research, Zigong First People's Hospital, Zigong, Sichuan, China
| | - Sheng Li
- Department of Basic Medical Sciences, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan, China.,Department of Research, Zigong First People's Hospital, Zigong, Sichuan, China
| | - Linghong Guo
- Department of Pharmacology, West China School of Basic Sciences & Forensic Medicine; Animal Research Institute, Sichuan University, Chengdu, Sichuan, China
| | - Xu Peng
- Department of Pharmacology, West China School of Basic Sciences & Forensic Medicine; Animal Research Institute, Sichuan University, Chengdu, Sichuan, China
| | - Yin Liu
- Department of Basic Medical Sciences, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan, China.,Department of Research, Zigong First People's Hospital, Zigong, Sichuan, China.,Department of Pharmacology, West China School of Basic Sciences & Forensic Medicine; Animal Research Institute, Sichuan University, Chengdu, Sichuan, China.,Department of Anesthesiology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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Zhang S, Wang L, Yang T, Chen L, Zhao L, Wang T, Chen L, Ye Z, Zheng Z, Qin J. Parental alcohol consumption and the risk of congenital heart diseases in offspring: An updated systematic review and meta-analysis. Eur J Prev Cardiol 2019; 27:410-421. [PMID: 31578093 DOI: 10.1177/2047487319874530] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The aim of this study was to provide updated evidence to assess the association between parental alcohol consumption and the risk of total congenital heart diseases (CHDs) and specific CHD phenotypes in offspring, and explore the possible dose-response pattern. METHODS PubMed, Embase and Chinese databases were searched with an end-date parameter of July 24, 2019 to identify studies meeting pre-stated inclusion criteria. A random-effects model was used to calculate the overall combined risk estimates. A meta-analysis of the dose-response relationship was performed. Subgroup analysis, sensitivity analysis, and Galbraith plot were conducted to explore potential heterogeneity moderators. RESULTS A total of 55 studies involving 41,747 CHD cases and 297,587 controls were identified. Overall, both maternal (odds ratio (OR) = 1.16; 95% confidence interval (CI): 1.05-1.27) and paternal (OR = 1.44; 95% CI: 1.19-1.74) alcohol exposures were significantly associated with risk of total CHDs in offspring. Additionally, a nonlinear dose-response relationship between parental alcohol exposure and risk of total CHDs was observed. With an increase in parental alcohol consumption, the risk of total CHDs in offspring also gradually increases. For specific CHD phenotypes, a statistically significant association was found between maternal alcohol consumption and risk of tetralogy of fallot (OR = 1.20; 95% CI: 1.08-1.33). Relevant heterogeneity moderators have been identified by subgroup analysis, and sensitivity analysis yielded consistent results. CONCLUSIONS Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, our review indicates that parental alcohol exposures are significantly associated with the risk of CHDs in offspring, which highlights the necessity of improving health awareness to prevent alcohol exposure during preconception and conception periods.
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Affiliation(s)
- Senmao Zhang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Lesan Wang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Tubao Yang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Lizhang Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Lijuan Zhao
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Tingting Wang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Letao Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Ziwei Ye
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Zan Zheng
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Jiabi Qin
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
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8
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Kesmodel US. Risks and guidelines for the consumption of alcohol during pregnancy. World J Obstet Gynecol 2016; 5:162-174. [DOI: 10.5317/wjog.v5.i2.162] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 11/13/2015] [Accepted: 01/22/2016] [Indexed: 02/05/2023] Open
Abstract
Daily average intake of alcohol during pregnancy has consistently been associated with short term adverse outcomes such as miscarriage, preterm birth and intrauterine growth restriction, a large variety of malformations, as well as long term adverse outcomes such as foetal alcohol syndrome, mental retardation and general impairment of cognitive functions including intelligence, attention, learning abilities as well as social and behavioural functions. Weekly average consumption and alcohol binge drinking (usually defined as ≥ 5 drinks on a single occasion) independently of high daily average intake has not been consistently associated with short and long term adverse outcomes. Health authorities in most countries recommend that pregnant women completely abstain from alcohol. Even so, many health professionals including doctors, midwives and nurses do not provide information to pregnant women in accordance with the official recommendations, although a large proportion of women of child bearing age and pregnant women drink alcohol, especially before recognition of pregnancy. The discrepancy between guidelines and the information practice of health personnel is likely to continue to exist because guidelines of abstinence are not clearly evidence-based and not in line with current focus on autonomy and informed choice for patients, and because guidelines do not consider the everyday clinical communication situation.
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9
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Wen Z, Yu D, Zhang W, Fan C, Hu L, Feng Y, Yang L, Wu Z, Chen R, Yin KJ, Mo X. Association between alcohol consumption during pregnancy and risks of congenital heart defects in offspring: meta-analysis of epidemiological observational studies. Ital J Pediatr 2016; 42:12. [PMID: 26843087 PMCID: PMC4739085 DOI: 10.1186/s13052-016-0222-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Accepted: 01/27/2016] [Indexed: 01/19/2023] Open
Abstract
Background To explore the association between maternal alcohol consumption and/or binge drinking and congenital heart defects (CHDs), we conducted a meta-analysis for more sufficient evidence on this issue. Methods We searched Medline, EMBASE, and the Cochrane Library from their inceptions to December 2014 for case-control and cohort studies that assessed the association between maternal alcohol consumption and CHD risk. Study-specific relative risk estimates were calculated using random-effect or fixed-effect models. Results A total of 19 case-control studies and 4 cohort studies were included in the meta-analysis. We observed a null association between maternal alcohol consumption during pregnancy and the risk of CHDs. Even in the analysis of different trimesters of pregnancy, we found little association between the two. Conclusions This meta-analysis suggests that maternal alcohol consumption is modestly not associated with the risk of CHDs. However, further investigation is needed to confirm this conclusion.
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Affiliation(s)
- Zhongyuan Wen
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Di Yu
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Weiyan Zhang
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Changfeng Fan
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Liang Hu
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Yu Feng
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Lei Yang
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Zeyu Wu
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Runsen Chen
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
| | - Ke-Jie Yin
- Department of Neurology, Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, MO, 63110, USA.
| | - Xuming Mo
- Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
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Zhu Y, Romitti PA, Caspers Conway KM, Shen DH, Sun L, Browne ML, Botto LD, Lin AE, Druschel CM. Maternal periconceptional alcohol consumption and congenital heart defects. ACTA ACUST UNITED AC 2015; 103:617-29. [PMID: 26118863 DOI: 10.1002/bdra.23352] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Revised: 12/04/2014] [Accepted: 12/08/2014] [Indexed: 01/14/2023]
Abstract
BACKGROUND Congenital heart defects (CHDs) are the leading cause of infant death from birth defects. Animal studies suggest in utero alcohol exposure is a teratogen for cardiogenesis; however, results from epidemiologic studies are mixed. METHODS Data from the National Birth Defects Prevention Study were used to estimate associations between CHDs and case (n = 7076) and control (n = 7972) mother reports of periconceptional (1 month before pregnancy through the first trimester) alcohol consumption with expected delivery dates during 1997 to 2007. CHDs were examined by category (conotruncal, septal, left ventricular outflow tract obstruction, and right ventricular outflow tract obstruction, heterotaxy with CHD) and subtype (e.g., tetralogy of Fallot [TOF]). Alcohol measures examined were any consumption, maximum average drinks per month, binge drinking, and alcohol type. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression analysis. RESULTS Increased risks, albeit marginally statistically significant, were observed for TOF and each maternal alcohol measure examined and for right ventricular outflow tract obstruction and heterotaxy with CHD and consumption of distilled spirits. Significantly reduced risks were observed for several CHD categories (septal defects, left ventricular outflow tract obstruction, and right ventricular outflow tract obstruction) and some corresponding subtypes with different alcohol measures. Significant risks were not observed for the other CHDs examined. CONCLUSION Analysis of this large, well-defined study sample did not show statistically significant increased risks between measures of maternal alcohol consumption and most CHDs examined. These findings may reflect, in part, limitations with retrospective exposure assessment or unmeasured confounders. Additional studies with continued improvement in measurement of alcohol consumption are recommended.
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Affiliation(s)
- Yong Zhu
- Department of Epidemiology, The University of Iowa, Iowa City, Iowa
| | - Paul A Romitti
- Department of Epidemiology, The University of Iowa, Iowa City, Iowa
| | | | - Dereck H Shen
- Department of Epidemiology, The University of Iowa, Iowa City, Iowa
| | - Lixian Sun
- Department of Epidemiology, The University of Iowa, Iowa City, Iowa
| | - Marilyn L Browne
- New York State Department of Health, Albany, New York.,School of Public Health, University at Albany, Rensselaer, New York
| | - Lorenzo D Botto
- Department of Pediatrics, University of Utah, Salt Lake City, Utah
| | - Angela E Lin
- Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts
| | - Charlotte M Druschel
- New York State Department of Health, Albany, New York.,School of Public Health, University at Albany, Rensselaer, New York
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11
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Yang J, Qiu H, Qu P, Zhang R, Zeng L, Yan H. Prenatal Alcohol Exposure and Congenital Heart Defects: A Meta-Analysis. PLoS One 2015; 10:e0130681. [PMID: 26110619 PMCID: PMC4482023 DOI: 10.1371/journal.pone.0130681] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 05/02/2015] [Indexed: 11/18/2022] Open
Abstract
Background There are still inconsistent conclusions about the association of prenatal alcohol drinking with congenital heart defects (CHDs). We conducted this meta-analysis to investigate the association between prenatal alcohol exposure and the risk of overall CHDs and the CHDs subtypes. Methods Case-control and cohort studies published before March 2015 were searched through PubMed and Embase. Two authors independently extracted data and scored the study quality according to the Newcastle-0ttawa Scale. The pooled ORs and 95%CI were estimated using the random-effects model and heterogeneity was assessed by the Q test and I2 statistic. Results A total of 20 studies were finally included. The results provided no evidence of the association between prenatal alcohol exposure and the risk of overall CHDs (OR = 1.06, 95%CI = 0.93–1.22), ventricular septal defects (VSDs) (OR = 1.04, 95%CI = 0.86–1.25), or atrial septal defects (ASDs) (OR = 1.40, 95%CI = 0.88–2.23). However, prenatal alcohol drinking was marginally significantly associated with conotruncal defects (CTDs) (OR = 1.24, 95%CI = 0.97–1.59) and statistically significantly associated with d-Transposition of the Great Arteries (dTGA) (OR = 1.64, 95%CI = 1.17–2.30). Moreover, both prenatal heavy drinking and binge drinking have a strong association with overall CHDs (heavy drinking: OR = 3.76, 95%CI = 1.00–14.10; binge drinking: OR = 2.49, 95%CI = 1.04–5.97), and prenatal moderate drinking has a modest association with CTDs (OR = 1.35, 95%CI = 1.05–1.75) and dTGA (OR = 1.86, 95%CI = 1.09–3.20). Conclusions In conclusion, the results suggested that prenatal alcohol exposure was not associated with overall CHDs or some subtypes, whereas marginally significant association was found for CTDs and statistically significant association was found for dTGA. Further prospective studies with large population and better designs are needed to explore the association of prenatal alcohol exposure with CHDs including the subtypes in specific groups.
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Affiliation(s)
- Jiaomei Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China
| | - Huizhen Qiu
- Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China
| | - Pengfei Qu
- Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China
| | - Ruo Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China
| | - Lingxia Zeng
- Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China
| | - Hong Yan
- Department of Epidemiology and Health Statistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China
- Nutrition and Food Safety Engineering Research Center of Shaanxi Province, Xi’an, Shaanxi, People’s Republic of China
- * E-mail:
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12
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Sun J, Chen X, Chen H, Ma Z, Zhou J. Maternal Alcohol Consumption before and during Pregnancy and the Risks of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis. CONGENIT HEART DIS 2015; 10:E216-24. [PMID: 26032942 DOI: 10.1111/chd.12271] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/17/2015] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Epidemiologic studies have reported conflicting results regarding maternal alcohol consumption before and during pregnancy, and the risk of congenital heart defects (CHDs). However, a systematic review and meta-analysis of the association between maternal alcohol consumption and CHDs in offspring has not been conducted. DESIGN We searched MEDLINE and EMBASE for articles catalogued between their inception and February 16, 2015; we identified relevant published studies that assessed the association between maternal alcohol consumption and CHD risk. Two authors independently assessed the eligibility of the retrieved articles and extracted data from them. Study-specific relative risk estimates were pooled by random-effects or fixed-effects models. RESULTS From the 1527 references, a total of 19 case-control studies and four cohort studies were enrolled in this meta-analysis. The summary of 23 studies related to CHDs indicated an overall pooled relative risk of 1.13 (95% confidence interval: 0.96, 1.29) among mothers drinking before or during pregnancy. Statistically significant heterogeneity was detected (Q = 196.61, P < .001, I(2) = 88.8%) with no publication bias (Egger's test: P = .157). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among studies. CONCLUSION In summary, this meta-analysis provided no positive association between maternal alcohol consumption and risk of CHDs.
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Affiliation(s)
- Jian Sun
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Anesthesiology, Huai'an Maternal and Child Health Hospital, Huai'an, Jiangsu, China
| | - Xiaoling Chen
- Department of Nephrology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
| | - Huajun Chen
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Zhengliang Ma
- Department of Anesthesiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jianwei Zhou
- School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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13
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Feng Y, Yu D, Yang L, Da M, Wang Z, Lin Y, Ni B, Wang S, Mo X. Maternal lifestyle factors in pregnancy and congenital heart defects in offspring: review of the current evidence. Ital J Pediatr 2014; 40:85. [PMID: 25385357 PMCID: PMC4243331 DOI: 10.1186/s13052-014-0085-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2014] [Accepted: 10/17/2014] [Indexed: 02/01/2023] Open
Abstract
The prognosis of children with congenital heart defects(CHDs) continues to improve with advancing surgical techniques; however, lack of information about modifiable risk factors for malformations in cardiovascular development impeded the prevention of CHDs. We investigated an association between maternal lifestyle factors and the risk of CHDs, because epidemiological studies have reported conflicting results regarding maternal lifestyle factors and the risk of CHDs recently. A review published on 2007 provided a summary of maternal exposures associated with an increased risk of CHDs. As part of noninherited risk factors, we conducted a brief overview of studies on the evidence linking common maternal lifestyle factors, specifically smoking, alcohol, illicit drugs, caffeine, body mass index and psychological factors to the development of CHDs in offspring. Women who smoke and have an excessive body mass index(BMI) during pregnancy are suspected to be associated with CHDs in offspring. Our findings could cause public health policy makers to pay more attention to women at risk and could be used in the development of population-based prevention strategies to reduce the incidence and burden of CHDs. However, more prospective studies are needed to investigate the association between maternal lifestyle factors and CHDs.
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Affiliation(s)
- Yu Feng
- Department of Cardiothoracic Surgery, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Di Yu
- Department of Cardiothoracic Surgery, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Lei Yang
- Department of Cardiothoracic Surgery, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Min Da
- Department of Cardiothoracic Surgery, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Zhiqi Wang
- Department of Cardiothoracic Surgery, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Yuan Lin
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Bixian Ni
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Song Wang
- Department of Cardiothoracic Surgery, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
| | - Xuming Mo
- Department of Cardiothoracic Surgery, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
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14
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Sarmah S, Marrs JA. Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: prevention with folic acid. Dev Dyn 2013; 242:1184-201. [PMID: 23832875 DOI: 10.1002/dvdy.24015] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Revised: 06/13/2013] [Accepted: 07/01/2013] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbs multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis, and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenetic events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects.
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Affiliation(s)
- Swapnalee Sarmah
- Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana
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15
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Larsen PS, Kamper-Jørgensen M, Adamson A, Barros H, Bonde JP, Brescianini S, Brophy S, Casas M, Charles MA, Devereux G, Eggesbø M, Fantini MP, Frey U, Gehring U, Grazuleviciene R, Henriksen TB, Hertz-Picciotto I, Heude B, Hryhorczuk DO, Inskip H, Jaddoe VWV, Lawlor DA, Ludvigsson J, Kelleher C, Kiess W, Koletzko B, Kuehni CE, Kull I, Kyhl HB, Magnus P, Momas I, Murray D, Pekkanen J, Polanska K, Porta D, Poulsen G, Richiardi L, Roeleveld N, Skovgaard AM, Sram RJ, Strandberg-Larsen K, Thijs C, Van Eijsden M, Wright J, Vrijheid M, Andersen AMN. Pregnancy and birth cohort resources in europe: a large opportunity for aetiological child health research. Paediatr Perinat Epidemiol 2013; 27:393-414. [PMID: 23772942 DOI: 10.1111/ppe.12060] [Citation(s) in RCA: 214] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.
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Affiliation(s)
- Pernille Stemann Larsen
- Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen.
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16
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Conover EA, Jones KL. Safety concerns regarding binge drinking in pregnancy: a review. ACTA ACUST UNITED AC 2012; 94:570-5. [PMID: 22706886 DOI: 10.1002/bdra.23034] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 04/17/2012] [Accepted: 04/24/2012] [Indexed: 01/18/2023]
Abstract
BACKGROUND There is ongoing debate about the risks to the fetus associated with maternal binge drinking. This makes it difficult to counsel patients about the potential risks associated with their use of alcohol during pregnancy. METHODS This article reviews the literature on animal and human studies regarding binge drinking (four to five drinks at one time in humans, or the equivalent in laboratory animals). RESULTS Animal studies provide evidence that high doses of alcohol over a short period of time can be more damaging than lower doses over a long period of time. Human data are more inconsistent, especially in terms of the association with malformations. Although neurobehavioral effects are the most commonly reported adverse outcome, some studies do not find such an association. Conclusions are confounded by the design of many studies, which fail to document pattern and total amount of alcohol consumption at one time. In addition, it has been suggested there is a bias against the null effect in publications. CONCLUSION Although the evidence in humans is not conclusive, the incidence of binge exposures in pregnancy is high, and it appears prudent to counsel patients to avoid this exposure whenever possible. Women inadvertently exposed to a single binge episode of alcohol early in the first trimester before pregnancy recognition can be reassured that the risks for adverse effects in their baby are likely low if they are able to discontinue use for the duration of the pregnancy. Unfortunately, there may be some residual fetal risk.
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Affiliation(s)
- Elizabeth Ann Conover
- Division of Clinical Genetics, Munroe Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA.
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The problem of confounding in studies of the effect of maternal drug use on pregnancy outcome. Obstet Gynecol Int 2011; 2012:148616. [PMID: 22190949 PMCID: PMC3236404 DOI: 10.1155/2012/148616] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Accepted: 08/29/2011] [Indexed: 11/17/2022] Open
Abstract
In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes.
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