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Baines KJ, West RC. Sex differences in innate and adaptive immunity impact fetal, placental, and maternal health†. Biol Reprod 2023; 109:256-270. [PMID: 37418168 DOI: 10.1093/biolre/ioad072] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/08/2023] Open
Abstract
The differences between males and females begin shortly after birth, continue throughout prenatal development, and eventually extend into childhood and adult life. Male embryos and fetuses prioritize proliferation and growth, often at the expense of the fetoplacental energy reserves. This singular focus on growth over adaptability leaves male fetuses and neonates vulnerable to adverse outcomes during pregnancy and birth and can have lasting impacts throughout life. Beyond this prioritization of growth, male placentas and fetuses also respond to infection and inflammation differently than female counterparts. Pregnancies carrying female fetuses have a more regulatory immune response, whereas pregnancies carrying male fetuses have a stronger inflammatory response. These differences can be seen as early as the innate immune response with differences in cytokine and chemokine signaling. The sexual dimorphism in immunity then continues into the adaptive immune response with differences in T-cell biology and antibody production and transfer. As it appears that these sex-specific differences are amplified in pathologic pregnancies, it stands to reason that differences in the placental, fetal, and maternal immune responses in pregnancy contribute to increased male perinatal morbidity and mortality. In this review, we will describe the genetic and hormonal contributions to the sexual dimorphism of fetal and placental immunity. We will also discuss current research efforts to describe the sex-specific differences of the maternal-fetal interface and how it impacts fetal and maternal health.
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Affiliation(s)
- Kelly J Baines
- Anatomy, Physiology, Pharmacology Department, Auburn University, Auburn, AL 36849, USA
| | - Rachel C West
- Anatomy, Physiology, Pharmacology Department, Auburn University, Auburn, AL 36849, USA
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Grunnet LG, Bygbjerg IC, Mutabingwa TK, Lajeunesse-Trempe F, Nielsen J, Schmiegelow C, Vaag AA, Ramaiya K, Christensen DL. Influence of placental and peripheral malaria exposure in fetal life on cardiometabolic traits in adult offspring. BMJ Open Diabetes Res Care 2022; 10:e002639. [PMID: 35379692 PMCID: PMC8981354 DOI: 10.1136/bmjdrc-2021-002639] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 03/13/2022] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Fetal malaria exposure may lead to intrauterine growth restriction and increase the risk of developing diabetes and cardiovascular diseases in adulthood. We investigated the extent to which fetal peripheral and placental malaria exposure impacts insulin sensitivity and secretion, body composition and cardiometabolic health 20 years after in utero malaria exposure. RESEARCH DESIGN AND METHODS We traced 101 men and women in Muheza district, Tanga region whose mothers participated in a malaria chemosuppression during a pregnancy study in 1989-1992. All potential participants were screened for malaria, hepatitis B and HIV to ascertain study eligibility. Seventy-six individuals (44 men, 32 women) were included in this cohort study. The participants underwent a thorough clinical examination including anthropometric measurements, ultrasound scanning for abdominal fat distribution, blood pressure, 75 g oral glucose tolerance test, an intravenous glucose tolerance test followed by a hyperinsulinemic euglycemic clamp and a submaximal exercise test. RESULTS Offspring exposed to placental malaria during pregnancy had significantly higher 30-minute plasma post-glucose load levels, but no significant difference in peripheral insulin resistance, insulin secretion or other cardiometabolic traits compared with non-exposed individuals. CONCLUSIONS Using the state-of-the-art euglycemic clamp technique, we were unable to prove our a priori primary hypothesis of peripheral insulin resistance in young adult offspring of pregnancies affected by malaria. However, the subtle elevations of plasma glucose might represent an early risk marker for later development of type 2 diabetes if combined with aging and a more obesogenic living environment.
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Affiliation(s)
- Louise G Grunnet
- Clinical Prevention Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Ib C Bygbjerg
- Global Health Section, University of Copenhagen, Copenhagen, Denmark
- Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Theonest K Mutabingwa
- Faculty of Medicine, Hubert Kairuki Memorial University, Dar es Salaam, United Republic of Tanzania
| | | | - Jannie Nielsen
- Global Health Section, University of Copenhagen, Copenhagen, Denmark
- Hubert Department of Gobal Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Christentze Schmiegelow
- Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
| | - Allan A Vaag
- Clinical Prevention Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Kaushik Ramaiya
- Shree Hindu Mandal Hospital, Dar es Salaam, United Republic of Tanzania
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Bar J, Weiner E, Levy M, Gilboa Y. The thrifty phenotype hypothesis: The association between ultrasound and Doppler studies in fetal growth restriction and the development of adult disease. Am J Obstet Gynecol MFM 2021; 3:100473. [PMID: 34481995 DOI: 10.1016/j.ajogmf.2021.100473] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 08/19/2021] [Accepted: 08/19/2021] [Indexed: 12/13/2022]
Abstract
Barker pioneered the idea that the epidemic of coronary heart disease in Western countries in the 20th century, which paradoxically coincided with improved standards of living and nutrition, has its origin in fetal life. Indeed, there is substantial evidence associating low birthweight because of fetal growth restriction with an increased risk of vascular disease in later adult life. These conclusions led to the second part of the Barker hypothesis, the thrifty phenotype, in which adaptation to undernutrition in fetal life leads to permanent metabolic and endocrine changes. Such changes are beneficial if the undernutrition persists after birth but may predispose the individual to obesity and impaired glucose tolerance if conditions improve. The hypothesis assumes that a poor nutrient supply during a critical period of in utero life may "program" a permanent structural or functional change in the fetus, thereby altering the distribution of cell types, gene expression, or both. The fetus, in response to placental undernutrition and to maintain sufficient vascular supply to the brain, decreases resistance to blood flow in the middle cerebral artery. Simultaneously, because of the limited blood supply to the fetus, the arterial redistribution process is accompanied by increased resistance to flow to other fetal vital organs, such as the heart, kidneys, liver, and pancreas. It may explain why individuals exposed to ischemic changes in utero develop dyslipidemia, lower nephron number, and impaired glucose tolerance, all factors contributing to metabolic syndrome later in life. Nevertheless, support for the hypotheses comes mainly from studies in rodents and retrospective epidemiologic studies. This review focused on ultrasound and Doppler studies of human fetal growth restriction in several fetal organs: the placenta, fetal circulation, brain, heart, kidneys, adrenal glands, liver, and pancreas. Support for the hypothesis was provided by animal studies involving conditions that create fetuses with growth restriction with effects on various fetal organs and by human studies that correlate impaired fetal circulation with the in utero development and function of fetal organs.
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Affiliation(s)
- Jacob Bar
- Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa)
| | - Eran Weiner
- Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa).
| | - Michal Levy
- Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy)
| | - Yinon Gilboa
- Ultrasound Unit, Helen Schneider Comprehensive Women's Health Center, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel (Dr. Gilboa); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa)
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Longo M, Alrais M, Tamayo EH, Ferrari F, Facchinetti F, Refuerzo JS, Blackwell SC, Sibai BM. Vascular and metabolic profiles in offspring born to pregnant mice with metabolic syndrome treated with inositols. Am J Obstet Gynecol 2019; 220:279.e1-279.e9. [PMID: 30521799 DOI: 10.1016/j.ajog.2018.11.1101] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 11/11/2018] [Accepted: 11/24/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOS+/-) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype. OBJECTIVE Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS. MATERIALS AND METHODS Heterozygous eNOS+/- mice fed an HFD manifest a MS phenotype. Female eNOS+/- mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOS+/- offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9-10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed. RESULTS The GTT showed lower glucose levels in both eNOS+/-INOs (P = .03) and WT-INOs (P = .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOS+/- offspring compared to WT (169 ± 7 vs 142 ± 9 mm Hg, respectively, P = .04) and INOs treatment decreased SBP in WT-INOs (110 ± 10 mm Hg, P = .01) but not in eNOS+/-INOs offspring. Maximal (%Max) contractile response to PE was higher in eNOS+/- offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOS+/-, 123 ± 7 vs eNOS+/-INOs, 82 ± 11 mm Hg, P = .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 ± 4 vs WT-INOs, 75 ± 7). The L-NAME response was decreased in eNOS+/-INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOS+/- and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P = .01 and P = .03, respectively). No differences were seen in response to SNP. CONCLUSION Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOS+/- and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOS+/- offspring and exhibit an improved response to INOs treatment. Our findings suggest that the benefits of INOs treatment are more pronounced in offspring exposed to environmental factors in utero, and less likely in those due to genetic factors.
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Kidneys in 5-year-old preterm-born children: a longitudinal cohort monitoring of renal function. Pediatr Res 2017; 82:979-985. [PMID: 28665930 DOI: 10.1038/pr.2017.148] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 05/28/2017] [Indexed: 11/09/2022]
Abstract
BackgroundBeing aware of the impact of low birth weight on late-onset hypertension, our aim was to describe systolic blood pressure (sBP) and renal function in 3-5-year-old preterm-born children and to determine which perinatal factors or childhood factors were associated with an altered renal function at 5 years in these children.MethodsThis was a prospective longitudinal cohort study of children born at 27-31 weeks of gestation and included at birth and examined at 3, 4, and 5 years of age. The primary outcome was renal function at 5 years: BP, estimated glomerular filtration rate, and albuminuria.ResultsOne hundred and sixty five children were examined, of whom 93 (56.4%) were male. Gestational age was 29.2±1.4 weeks and birth weight was 1,217±331 g. Overall, 25% children had sBP ≥90th percentile at age 3 and 4 years and 11% at 5 years. In multivariate analysis, sBP ≥90th percentile at 5 years was associated with the use of antenatal steroids (OR=0.19(0.05;0.65)). There was a significant association between protein intake on day 28 and sBP at 5 years (β=2.1±1.0, P=0.03). Glomerular filtration rate at 5 years was significantly decreased in case of hyaline membrane disease or necrotizing enterocolitis. High urine albumin was not predictable from one year to another.ConclusionIn preterm-born children, sBP was often high and neonatal protein intake was associated with increased blood pressure during childhood.
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Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe? BIOMED RESEARCH INTERNATIONAL 2017; 2017:1438038. [PMID: 28828381 PMCID: PMC5554551 DOI: 10.1155/2017/1438038] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 05/22/2017] [Accepted: 06/11/2017] [Indexed: 12/19/2022]
Abstract
In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen) recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment.
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Olgun G, John E. Hypertension in the Pediatric Intensive Care Unit. J Pediatr Intensive Care 2016; 5:50-58. [PMID: 31110885 PMCID: PMC6512408 DOI: 10.1055/s-0035-1564796] [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: 10/15/2014] [Accepted: 11/01/2014] [Indexed: 10/22/2022] Open
Abstract
Hypertension in the pediatric intensive care unit (PICU) is common and it contributes to the overall morbidity and mortality. Patients may present with hypertensive emergencies or hypertension can manifest itself later in PICU course. Although hypertension can be seen in most patients during hospitalization, patients with some specific diseases and conditions are more prone to hypertension. Hypertension should be recognized promptly and treated accordingly. Different pathophysiologic mechanisms can be responsible for the hypertension and management differs based on the underlying etiology. Any patient with a hypertensive emergency must be admitted to PICU, and treatment and diagnostic workup should be initiated immediately.
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Affiliation(s)
- Gokhan Olgun
- Department of Pediatric Critical Care Medicine, University of Chicago, Chicago, Illinois, United States
| | - Eunice John
- Department of Pediatric Nephrology, University of Illinois at Chicago, Illinois, United States
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Perrone S, Santacroce A, Picardi A, Buonocore G. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases. World J Clin Pediatr 2016; 5:172-181. [PMID: 27170927 PMCID: PMC4857230 DOI: 10.5409/wjcp.v5.i2.172] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Revised: 10/30/2015] [Accepted: 02/16/2016] [Indexed: 02/06/2023] Open
Abstract
Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.
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Placental weight and foetal growth rate as predictors of ischaemic heart disease in a Swedish cohort. J Dev Orig Health Dis 2015; 5:164-70. [PMID: 24901654 DOI: 10.1017/s2040174414000142] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Studies on placental size and cardiovascular disease have shown inconsistent results. We followed 10,503 men and women born in Uppsala, Sweden, 1915-1929 from 1964 to 2008 to assess whether birth characteristics, including placental weight and placenta/birth weight ratio, were predictive of future ischaemic heart disease (IHD). Adjustments were made for birth cohort, age, sex, mother's parity, birth weight, gestational age and social class at birth. Placental weight and birth weight were negatively associated with IHD. The effect of placental weight on IHD was stronger in individuals from medium social class at birth and in those with low education. Men and women from non-manual social class at birth had the lowest risk for IHD as adults. We conclude that low foetal growth rate rather than placental weight was more predictive of IHD in the Swedish cohort. However, the strong effect of social class at birth on risk for IHD did not appear to be mediated by foetal growth rate.
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Zohdi V, Lim K, Pearson JT, Black MJ. Developmental programming of cardiovascular disease following intrauterine growth restriction: findings utilising a rat model of maternal protein restriction. Nutrients 2014; 7:119-52. [PMID: 25551250 PMCID: PMC4303830 DOI: 10.3390/nu7010119] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 12/08/2014] [Indexed: 12/11/2022] Open
Abstract
Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of "programming". The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype.
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Affiliation(s)
- Vladislava Zohdi
- Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC 3800, Australia.
| | - Kyungjoon Lim
- Neuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, P.O. Box 6492 St Kilda Rd Central, Melbourne 8008, Australia.
| | - James T Pearson
- Department of Physiology, Monash University, Melbourne, VIC 3800, Australia.
| | - M Jane Black
- Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC 3800, Australia.
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Moreira NF, Muraro AP, Brito FDSB, Gonçalves-Silva RMV, Sichieri R, Ferreira MG. [Obesity: main risk factor for systemic arterial hypertension in Brazilian adolescents from a cohort study]. ACTA ACUST UNITED AC 2014; 57:520-6. [PMID: 24232816 DOI: 10.1590/s0004-27302013000700004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Accepted: 03/11/2013] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To identify the prevalence and factors associated with hypertension in adolescents. SUBJECTS AND METHODS Cross-sectional study of 1,716 adolescents of a cohort study, aged from 10 to 16 years old sociodemographic, economic, and lifestyle characteristics were obtained from an interview, and birth weight from hospital records. Hypertension was defined as systolic or diastolic blood pressure above the 95th percentile according to the classification recommended by the Second Task Force High Blood Pressure in Children and Adolescents. Nutritional status was diagnosed by body mass index (BMI), according to the z score from curves published by the World Health Organization. Waist circumference was measured at the natural waist. The association between hypertension and the explanatory variables was measured using logistic regression. RESULTS The adolescents interviewed represent 71.4% of the baseline, and 50.7% of them were males. The prevalence of hypertension was 11.7%. In the multivariate analysis, after adjustment for age sex and skin color, hypertension was associated with obesity [OR = 2.27, (95%) CI = 1.64 to 3.14] but not associated with waist circumference after adjusting for BMI. Early life factors were not associated with hypertension in adolescence. CONCLUSION The results show an association between obesity and hypertension among adolescents.
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Wolfenstetter A, Simonetti GD, Pöschl J, Schaefer F, Wühl E. Altered cardiovascular rhythmicity in children born small for gestational age. Hypertension 2012; 60:865-70. [PMID: 22733461 DOI: 10.1161/hypertensionaha.112.196949] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Low birth weight is frequently associated with a disproportionately high incidence of cardiovascular disease, diabetes mellitus, and kidney disease in adulthood. Epidemiological studies have identified an inverse association between low birth weight or being small for gestational age and hypertension in adulthood. We hypothesized that children born with low birth weight might have altered circadian and ultradian cardiovascular rhythmicity independent of the prevailing blood pressure level. Twenty-four-hour ambulatory blood pressure and heart rate rhythmicity was prospectively evaluated by Fourier analysis in a cohort of healthy children born with low birth weight and compared with normative pediatric data. Seventy-five children born small for gestational age (mean age, 8.1±2.2 years) and 139 controls matched for age and sex were investigated. In addition to increased 24-hour, daytime, and especially nighttime blood pressure levels (P<0.05), children born small for gestational age exhibited blunted circadian (24-hour) and ultradian (12-, 8-, and 6-hour) blood pressure rhythmicity (P<0.05). In a multivariate analysis including children born with low birth weight and controls, being born with low birth weight independently influenced ultradian blood pressure rhythmicity, whereas in a multivariate analysis including children born with low birth weight only, circadian and ultradian rhythms were independently influenced by catch-up growth, gestational age, and blood pressure level. This study demonstrates blunted circadian and ultradian cardiovascular rhythmicity in prepubertal children born small for gestational age, independent from the presence of arterial hypertension. Circadian and ultradian rhythms may be sensitive indicators for detecting subtle early abnormalities of cardiovascular regulation.
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Affiliation(s)
- Ann Wolfenstetter
- Center for Pediatric and Adolescent Medicine, Division of Pediatric Nephrology, University of Heidelberg, Heidelberg, Germany
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Huang RC, Mori TA, Burrows S, Le Ha C, Oddy WH, Herbison C, Hands BH, Beilin LJ. Sex dimorphism in the relation between early adiposity and cardiometabolic risk in adolescents. J Clin Endocrinol Metab 2012; 97:E1014-22. [PMID: 22442267 DOI: 10.1210/jc.2011-3007] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
Abstract
CONTEXT Birth weight and childhood adiposity are associated with subsequent cardiovascular risk. OBJECTIVE We investigated the associations between metabolic clusters in young adults with body fat distribution from early childhood, focusing on sex differences. DESIGN, SETTING, AND PATIENTS A total of 1053 17 yr olds from an Australian birth cohort had measures of anthropometry, blood pressure, and fasting insulin, glucose, and lipids. MAIN OUTCOME MEASURES Two-step cluster analysis identified 17 yr olds at high metabolic risk. The two risk groups were compared by sex with regard to birth weight and serial anthropometry, including skinfold thickness from nine time-points. RESULTS The "high-risk" metabolic cluster at age 17 yr included 16% of males and 19% of females. Compared to the "low-risk" group, the high-risk cluster participants had greater waist circumference, triglycerides, insulin, and systolic blood pressure and lower high-density lipoprotein-cholesterol (all P <0.0001). There was a significant birth weight by sex interaction upon the metabolic cluster outcome (P = 0.011). Compared to their low-risk counterparts, females in the high-risk cluster at 17 yr were heavier from birth (odds ratio, 1.8; 95% confidence interval, 1.0, 3.2) (P = 0.034), with consistently higher body mass index and skinfold thickness thereafter. In contrast, there was no statistical difference in birth weight between high- and low-risk males (odds ratio, 0.62; 95% confidence interval, 0.38, 1.02). CONCLUSIONS These data show sexual dimorphism in effects of early life body mass index and fat distribution upon cardiometabolic risk factors. Females in a contemporary population are particularly prone to increased risk when born heavier. This has implications for targeted prevention of obesity and metabolic diseases with increasing maternal obesity and gestational diabetes.
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Affiliation(s)
- Rae-Chi Huang
- The University of Western of Australia, Royal Perth Hospital Unit, Perth, Western Australia 6840, Australia.
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Vieux R, Hascoët JM, Franck P, Guillemin F. Increased albuminuria in 4-year-old preterm-born children with normal height. J Pediatr 2012; 160:923-8.e1. [PMID: 22261507 DOI: 10.1016/j.jpeds.2011.12.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2011] [Revised: 11/22/2011] [Accepted: 12/06/2011] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To determine risk factors for high blood pressure (BP), increased markers of glomerulosclerosis, and tubular dysfunction in 4-year-old preterm-born children. STUDY DESIGN The study group was a longitudinal cohort of 119 children with BP, albuminuria, and β2 microglobulin measurements obtained during the neonatal period and at age 4 years. RESULTS Systolic BP was >95(th) percentile in 15 (12.6%) of the children at age 4 years and lower in those born small for gestational age compared with those born appropriate for gestational age. Preterm-born 4-year-olds with height <-1 SD had lower systolic and diastolic BP, and 14.4% of the 4-year-olds had albuminuria. Albuminuria was less prevalent in the 4-year-olds with height <-1 SD than in those with height ≥-1 SD (6.8% vs 19.3%; P=.04). Mean albuminuria level was 1.0±0.7 mg/mmol in 4-year-olds with height <-1 SD and 1.4±1.3 mg/mmol in those with height ≥-1 SD. In multivariate analysis, albuminuria level was increased by 0.4±0.2 mg/mmol in preterm-born children with normal height at age 4, and by 0.5±0.2 mg/mmol in females, after adjustment for gestational age, sex, neonatal morbidity, and intrauterine growth restriction. These results were unchanged after adjustment for body mass index. CONCLUSION Normal height at age 4 years may be associated with an increased risk for glomerulosclerosis in preterm-born children.
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Differences in association between birth parameters and blood pressure in children from preschool to high school. J Hum Hypertens 2012; 27:79-84. [PMID: 22534831 DOI: 10.1038/jhh.2012.16] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
We aimed to investigate the association between birth parameters with blood pressure (BP) among preschool- and school-aged children. Two separate childhood datasets were used: (1) 1295 children aged 3-6 years were examined during 2007-2009; and (2) 1741 and 2353 children aged 6 and 12 years, respectively, were examined during 2004-2006. Birth parameter data were obtained from parental records. BP was measured using standard protocols. Among 6-year-old children, each 1 kg decrease in birth weight was associated with a 1.33- and 1.20-mm Hg higher systolic and diastolic BP, respectively, after multivariable adjustment. In 6-year-old children, a decrease of 1 week in gestational age was independently associated with a 0.33- and 0.37-mm Hg higher systolic and diastolic BP, respectively. Six-year-old children in the low birth weight category (≤ 2499 g) versus those in the normal/high birth weight category (≥ 2500 g) had significantly higher systolic BP (P<0.0001). Girls in the low birth weight category versus those in the normal/high weight category had higher systolic BP (P=0.02). Significant associations were not observed among preschool-aged children and preadolescents. Birth weight and gestational age were strongly associated with BP among 6-year-old children, particularly girls, but not among preschoolers or preadolescents.
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16
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Zhang A, Hu H, Sánchez BN, Ettinger AS, Park SK, Cantonwine D, Schnaas L, Wright RO, Lamadrid-Figueroa H, Tellez-Rojo MM. Association between prenatal lead exposure and blood pressure in children. ENVIRONMENTAL HEALTH PERSPECTIVES 2012; 120:445-50. [PMID: 21947582 PMCID: PMC3295346 DOI: 10.1289/ehp.1103736] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Accepted: 09/21/2011] [Indexed: 05/20/2023]
Abstract
BACKGROUND Lead exposure in adults is associated with hypertension. Altered prenatal nutrition is associated with subsequent risks of adult hypertension, but little is known about whether prenatal exposure to toxicants, such as lead, may also confer such risks. OBJECTIVES We investigated the relationship of prenatal lead exposure and blood pressure (BP) in 7- to 15-year-old boys and girls. METHODS We evaluated 457 mother-child pairs, originally recruited for an environmental birth cohort study between 1994 and 2003 in Mexico City, at a follow-up visit in 2008-2010. Prenatal lead exposure was assessed by measurement of maternal tibia and patella lead using in vivo K-shell X-ray fluorescence and cord blood lead using atomic absorption spectrometry. BP was measured by mercury sphygmomanometer with appropriate-size cuffs. RESULTS Adjusting for relevant covariates, maternal tibia lead was significantly associated with increases in systolic BP (SBP) and diastolic BP (DBP) in girls but not in boys (p-interaction with sex = 0.025 and 0.007 for SBP and DBP, respectively). Among girls, an interquartile range increase in tibia lead (13 μg/g) was associated with 2.11-mmHg [95% confidence interval (CI): 0.69, 3.52] and 1.60-mmHg (95% CI: 0.28, 2.91) increases in SBP and DBP, respectively. Neither patella nor cord lead was associated with child BP. CONCLUSIONS Maternal tibia lead, which reflects cumulative environmental lead exposure and a source of exposure to the fetus, is a predisposing factor to higher BP in girls but not boys. Sex-specific adaptive responses to lead toxicity during early-life development may explain these differences.
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Affiliation(s)
- Aimin Zhang
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109-2029, USA.
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Christensen K, Wienke A, Skytthe A, Holm NV, Vaupel JW, Yashin AI. Cardiovascular Mortality in Twins and the Fetal Origins Hypothesis. ACTA ACUST UNITED AC 2012. [DOI: 10.1375/twin.4.5.344] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AbstractThe intrauterine growth patterns for twins are characterized by normal development during the first two trimesters and reduced growth during the third trimester. According to the fetal origins hypothesis this growth pattern is associated with risk factors for cardiovascular morbidity and mortality. We studied cause-specific mortality of 19,986 Danish twin individuals from the birth cohorts 1870–1930 followed from 1952 through 1993. Despite the large sample size and follow-up period we were not able to detect any difference between twins and the general population with regard to all-cause mortality or cardiovascular mortality. Hence, the intrauterine growth retardation experienced by twins does not result in any “fetal programming” of cardiovascular diseases. There is still an important role for twins (and other sibs) to play in the testing of the fetal origins hypothesis, namely in studies of intra-pair differences, which can assess the role of genetic confounding in the association between fetal growth and later health outcome.
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Nowson CA, MacInnis RJ, Hopper JL, Alexander JL, Paton LM, Margerison C, Wark JD. Association of Birth Weight and Current Body Size to Blood Pressure in Female Twins. ACTA ACUST UNITED AC 2012. [DOI: 10.1375/twin.4.5.378] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AbstractIt has been proposed that low birth weight is associated with high levels of blood pressure in later life. The aim of this study was to assess the relationship of blood pressure to birth weight and current body size during growth and adulthood. A total of 711 female multiple births, with one group of 244 in their growth phase mean age 12.0 (2.3)(SD) years and the other of 467 adults (mean age 35.2 (12.6) years), had height, weight and both systolic (SBP) and diastolic (DBP) blood pressures measured, and self-reported their birth weight. Regression analyses were performed to assess the cross-sectional and within-pair associations of blood pressure to birth weight, with and without adjustments for current body size. Within-pair analysis was based on 296 twin pairs. Cross-sectionally, a reduction in birth weight of 1 kg was associated with 2 to 3 mm Hg higher age-adjusted SBP, which was of marginal significance and explained about 2% of the population variance. Adjustment for body mass index did not significantly change this association. Within-pair analyses found no association between birth weight and SBP or DBP, even after adjusting for current body size. After age, current body size was the strongest predictor of systolic BP. The weak association of blood pressure to birth weight cross-sectionally is of interest, but any within-pair effect of birth weight on blood pressure must be minimal compared with the effect of current body size.
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19
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20
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Christensen DL, Kapur A, Bygbjerg IC. Physiological adaption to maternal malaria and other adverse exposure: Low birth weight, functional capacity, and possible metabolic disease in adult life. Int J Gynaecol Obstet 2011; 115 Suppl 1:S16-9. [DOI: 10.1016/s0020-7292(11)60006-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Abstract
OBJECTIVES The long-term consequences of extreme prematurity are becoming increasingly important, given recent improvements in neonatal intensive care. The aim of the current study was to examine the cardiovascular consequences of extreme prematurity in 11-year-olds born at or before 25 completed weeks of gestation. METHODS Age and sex-matched classmates were recruited as controls. Information concerning perinatal and maternal history was collected, and current anthropometric characteristics were measured in 219 children born extremely preterm and 153 classmates. A subset of the extremely preterm children (n = 68) and classmates (n = 90) then underwent detailed haemodynamic investigations, including measurement of supine blood pressure (BP), aortic pulse wave velocity (aPWV, a measure of aortic stiffness) and augmentation index (AIx, a measure of arterial pressure wave reflections). RESULTS Seated brachial systolic and diastolic BP were not different between extremely preterm children and classmates (P = 0.3 for both), although there was a small, significant elevation in supine mean and diastolic BP in the extremely preterm children (P < 0.05 for both). Arterial pressure wave reflections were significantly elevated in the extremely preterm children (P < 0.001) and this persisted after adjusting for confounding variables. However, aortic stiffness was not different between the groups (P = 0.1). CONCLUSIONS These data suggest that extreme prematurity is associated with altered arterial haemodynamics in children, not evident from the examination of brachial BP alone. Moreover, the smaller, preresistance and resistance vessels rather than large elastic arteries appear to be most affected. Children born extremely preterm may be at increased future cardiovascular risk.
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22
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Winder NR, Krishnaveni GV, Hill JC, Karat CLS, Fall CHD, Veena SR, Barker DJP. Placental programming of blood pressure in Indian children. Acta Paediatr 2011; 100:653-60. [PMID: 21166711 PMCID: PMC3107945 DOI: 10.1111/j.1651-2227.2010.02102.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Aim To determine whether the size and shape of the placental surface predict blood pressure in childhood. Methods We studied blood pressure in 471 nine-year-old Indian children whose placental length, breadth and weight were measured in a prospective birth cohort study. Results In the daughters of short mothers (<median height), systolic blood pressure (SBP) rose as placental breadth increased (β = 0.69 mmHg/cm, p = 0.05) and as the ratio of placental surface area to birthweight increased (p = 0.0003). In the daughters of tall mothers, SBP rose as the difference between placental length and breadth increased (β = 1.40 mmHg/cm, p = 0.007), that is as the surface became more oval. Among boys, associations with placental size were only statistically significant after adjusting for current BMI and height. After adjustment, SBP rose as placental breadth, area and weight decreased (for breadth β = −0.68 mmHg/cm, p < 0.05 for all three measurements). Conclusions The size and shape of the placental surface predict childhood blood pressure. Blood pressure may be programmed by variation in the normal processes of placentation: these include implantation, expansion of the chorionic surface in mid-gestation and compensatory expansion of the chorionic surface in late gestation.
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Affiliation(s)
- Nicola R Winder
- MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, UK.
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23
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Barker DJP, Thornburg KL, Osmond C, Kajantie E, Eriksson JG. The surface area of the placenta and hypertension in the offspring in later life. THE INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY 2010; 54:525-30. [PMID: 19876839 DOI: 10.1387/ijdb.082760db] [Citation(s) in RCA: 139] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Hypertension is more common among people who had low birthweight. Birthweight depends on the mothers body size and on the growth of the placenta. We studied a group of 2003 subjects, of whom 644 were being treated for hypertension. They were born during 1934-44 in a hospital that kept detailed records of maternal and placental size. Hypertension was associated with reduced placental weight and surface area. These associations were strongest in the offspring of mothers with below average height or low socioeconomic status. In people whose mothers had below average height (160 cm) the prevalence of hypertension fell from 38% if the placental area was 200 cm(2) or less to 21% if the area was more than 320 cm(2) (p=0.0007). In the offspring of tall, middle class mothers, who were likely to have been the best nourished, hypertension was predicted by large placental weight in relation to birthweight. The odds ratio rose from 1.0 if the ratio of placental weight to birthweight was 0.17 or less to 1.9 (95% confidence interval 0.8 to 5.0) if the ratio was more than 0.21 (p for trend =0.03). We conclude that the effects of placental area on hypertension depend on the mothers nutritional state. Poor maternal nutrition may compound the adverse effects of small placental size. In better-nourished mothers the placental surface may expand to compensate for fetal undernutrition. Growth along the minor axis of the surface may be more nutritionally sensitive than growth along the major axis.
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Affiliation(s)
- David J P Barker
- MRC Epidemiology Resource Centre (University of Southampton), Southampton General Hospital, Southampton, UK.
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24
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Ojeda NB, Grigore D, Alexander BT. Role of fetal programming in the development of hypertension. Future Cardiol 2009; 4:163-74. [PMID: 19672482 DOI: 10.2217/14796678.4.2.163] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Epidemiological studies have suggested that size at birth contributes to increased cardiovascular disease (CVD) risk in later life. Findings from experimental studies are providing insight into the mechanisms linking impaired fetal growth and the increased risk of CVD and hypertension in adulthood. This article summarizes potential mechanisms involved in the fetal programming of hypertension and CVD, including alterations in the organs and regulatory systems critical to long-term control of sodium and volume homeostasis.
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Affiliation(s)
- Norma B Ojeda
- University of Mississippi Medical Center, Department of Physiology & Biophysics, The Center for Excellence in Cardiovascular-Renal Research, 2500 North State Street, Jackson, MS 39216-4505, USA.
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25
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Misra DP, Salafia CM, Miller RK, Charles AK. Non-linear and gender-specific relationships among placental growth measures and the fetoplacental weight ratio. Placenta 2009; 30:1052-7. [PMID: 19875166 DOI: 10.1016/j.placenta.2009.09.008] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2009] [Revised: 08/17/2009] [Accepted: 09/21/2009] [Indexed: 11/26/2022]
Abstract
GOALS Fetal growth depends on placental growth; the fetoplacental weight ratio (FPR) is a common proxy for the balance between fetal and placental growth. Male and female infants are known to have differing vulnerabilities in fetal life, during parturition and in infancy. We hypothesized that these differences may be paralleled by differences in how birth weight (BW) and the fetoplacental weight ratio (FPR) are affected by changes in placental proportions. MATERIALS AND METHODS Placental proportion measures (disk shape, larger and smaller chorionic diameters, chorionic plate area calculated as the area of an ellipse with the 2 given diameters, disk thickness, cord eccentricity and cord length) were available for 24,601 participants in the Collaborative Perinatal Project delivered between >34 and <43 completed weeks. The variables were standardized and entered into multiple automated regression splines (MARS 2.0, Salford Systems, Vista CA) to identify nonlinearities in the relationships of placental growth measures to BW and FPR with results compared for male and female infants. RESULTS Changes in chorionic plate growth in female compared to male infants resulted in a greater change in BW and FPR. The positive effects of umbilical cord length on BW reversed at the mean umbilical cord length in females and at +0.08 SD in male infants. CONCLUSIONS Female infants' BW and FPR are each more responsive to changes in placental chorionic plate growth dimensions than males; this may account for greater female resilience (and greater male vulnerability) to gestational stressors. The effect of umbilical cord length on FPR may be due to longer cords carrying greater fetal vascular resistance. Again male fetuses show a higher "threshold" to the negative effects of longer cords on FPR.
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Affiliation(s)
- D P Misra
- Division of Epidemiology and Biostatistics, Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Room 203, Detroit, MI 48201, USA.
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26
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Beardsall K, Ong KK, Murphy N, Ahmed ML, Zhao JH, Peeters MW, Dunger DB. Heritability of childhood weight gain from birth and risk markers for adult metabolic disease in prepubertal twins. J Clin Endocrinol Metab 2009; 94:3708-13. [PMID: 19723754 DOI: 10.1210/jc.2009-0757] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
OBJECTIVE Associations between size at birth, postnatal weight gain, and potential risk for adult disease have been variably explained by in utero exposures or genetic risk that could affect both outcomes. We utilized a twin model to explore these hypotheses. METHODS One hundred pairs of healthy twins aged 8.9 yr (range, 7.2-10.9 yr) had fasting blood samples collected, blood pressure (BP) measured, and anthropometry assessed. All measurements were converted to sd scores (SDS) to adjust for age and sex. RESULTS Mean birth weights in both monozygotic and dizygotic twins were -0.90 SDS lower than the UK reference. In postnatal life, 58% of monozygotic twins and 59% of dizygotic twins showed rapid weight gain (a change of more than +0.67 in weight SDS) from birth. Postnatal weight gain was positively associated with sum of skinfolds (r = 0.51; P < 0.0005), fasting insulin levels (r = 0.35; P < 0.0005), systolic BP (r = 0.30; P < 0.0005), and diastolic BP (r = 0.15; P < 0.05) at follow-up. Heritability estimates (additive genetic components) were calculated using variance components models for: birth weight, 44%; postnatal weight gain, 80%; childhood height, 89%; body mass index, 72%; sum of skinfolds, 89%; waist circumference, 74%; fasting insulin, 65%; systolic BP, 33%; and diastolic BP, 29%. CONCLUSIONS Postnatal weight gain from birth, rather than birth weight, was associated with childhood risk markers for adult metabolic disease. Childhood weight gain was highly heritable, and genetic factors associated with postnatal weight gain are likely to also contribute to risks for adult disease.
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Affiliation(s)
- Kathryn Beardsall
- Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Box 116, Cambridge CB2 0QQ, United Kingdom
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27
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Birth Weight and Optic Nerve Head Parameters. Ophthalmology 2009; 116:1112-8. [PMID: 19395087 DOI: 10.1016/j.ophtha.2008.12.061] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2008] [Revised: 12/06/2008] [Accepted: 12/22/2008] [Indexed: 11/22/2022] Open
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Coall DA, Charles AK, Salafia CM. Gross placental structure in a low-risk population of singleton, term, first-born infants. Pediatr Dev Pathol 2009; 12:200-10. [PMID: 19007303 DOI: 10.2350/08-02-0413.1] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2008] [Accepted: 10/19/2008] [Indexed: 11/20/2022]
Abstract
Suboptimal fetal growth has been associated with an increased risk of adult disease, which may be exacerbated by an increased placental weight-to-fetal weight ratio. Placental weight is a summary measure of placental growth and development throughout pregnancy. However, measures of placental structure, including the chorionic disk surface area and thickness and eccentricity of the umbilical cord insertion, have been shown to account for additional variance in birth weight beyond that explained by placental weight. Little is known of the variability of these placental parameters in low-risk populations; their association with maternal, pregnancy, and neonatal characteristics; and the agreement between manual and digital measures. This study used manual and digital image analysis techniques to examine gross placental anatomy in 513 low-risk, singleton, term, first-born infants. Parametric methods compared groups and examined relationships among variables. Maternal birth weight, prepregnancy weight, and body mass index were associated with increased placental and birth weight (all P < 0.005), but only maternal birth weight was associated with increased placental surface area (P < 0.0005) and thickness (P = 0.005). Smoking during pregnancy reduced birth weight and increased the eccentricity of umbilical cord insertion (P = 0.012 and 0.034, respectively). The variability in these placental parameters was consistently lower than that reported in the literature, and correlations between digital and manual measurements were reasonable (r = .87-.71). Detailed analyses of gross placental structure can provide biologically relevant information regarding placental growth and development and, potentially, their consequences.
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Affiliation(s)
- David A Coall
- Center for Cognitive and Decision Sciences, Institute of Psychology, University of Basel, Missionsstrasse 64a, 4055 Basel, Switzerland.
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29
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Gardner DSL, Hosking J, Metcalf BS, Jeffery AN, Voss LD, Wilkin TJ. Contribution of early weight gain to childhood overweight and metabolic health: a longitudinal study (EarlyBird 36). Pediatrics 2009; 123:e67-73. [PMID: 19117849 DOI: 10.1542/peds.2008-1292] [Citation(s) in RCA: 166] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Early weight gain (0-5 years) is thought to be an important contributor to childhood obesity and consequently metabolic risk. There is a scarcity of longitudinal studies in contemporary children reporting the impact of early weight gain on metabolic health. OBJECTIVE We aimed to assess the impact of early weight gain on metabolic health at 9 years of age. METHOD Two hundred thirty-three children (134 boys, 99 girls) with a gestational age of >37 weeks were assessed at birth, 5 years of age, and 9 years of age. Measures included weight SD scores at each time point and excess weight gained (Delta weight SD score) between them. The outcome measure included composite metabolic score (sum of internally derived z scores of insulin resistance, mean blood pressure, triglyceride level, and total cholesterol/high-density lipoprotein cholesterol ratio). RESULTS Weight SD score increased by 0.29 SD score in girls and 0.26 SD score in boys from 0 to 5 years of age and by 0.03 SD score in girls and 0.11 SD score in boys from 5 to 9 years of age. Weight SD score correlated poorly to moderately before 5 years of age but strongly after 5 years of age. Birth weight SD score predicted (girls/boys) 2.4%/0% of the variability in composite metabolic score at 9 years of age. Adding Delta weight SD score (0-5 years old) contributed (girls/boys) 11.2%/7.0% to the score, and adding Delta weight SD score (5-9 years old) additionally contributed (girls/boys) 26.4%/16.5%. Importantly, once weight SD score at 9 years of age was known, predictive strength was changed little by adding Delta weight SD score. CONCLUSIONS Most excess weight before puberty is gained before 5 years of age. Weight at 5 years of age bears little relation to birth weight but closely predicts weight at 9 years of age. Single measures of current weight are predictive of metabolic health, whereas weight gain within a specific period adds little. A single measure of weight at 5 years of age provides a pointer to future health for the individual. If metabolic status at 9 years of age means future risk, diabetes/cardiovascular prevention strategies might better focus on preschool-aged children, because the die seems to be largely cast by 5 years of age, and a healthy weight early in childhood may be maintained at least into puberty.
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Affiliation(s)
- Daphne S L Gardner
- Department of Endocrinology and Metabolism, Peninsula College of Medicine and Dentistry, Plymouth Campus, Plymouth, UK
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30
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Grigore D, Ojeda NB, Alexander BT. Sex differences in the fetal programming of hypertension. ACTA ACUST UNITED AC 2008; 5 Suppl A:S121-32. [PMID: 18395678 DOI: 10.1016/j.genm.2008.03.012] [Citation(s) in RCA: 159] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2007] [Indexed: 01/21/2023]
Abstract
BACKGROUND Numerous clinical and experimental studies support the hypothesis that the intrauterine environment is an important determinant of cardiovascular disease and hypertension. OBJECTIVE This review examined the mechanisms linking an adverse fetal environment and increased risk for chronic disease in adulthood with an emphasis on gender differences and the role of sex hormones in mediating sexual dimorphism in response to a suboptimal fetal environment. METHODS This review focuses on current findings from the PubMed database regarding animal models of fetal programming of hypertension, sex differences in phenotypic outcomes, and potential mechanisms in offspring of mothers exposed to an adverse insult during gestation. For the years 1988 to 2007, the database was searched using the following terms: fetal programming, intrauterine growth restriction, low birth weight, sex differences, estradiol, testosterone, high blood pressure, and hypertension. RESULTS The mechanisms involved in the fetal programming of adult disease are multifactorial and include alterations in the regulatory systems affecting the long-tterm control of arterial pressure. Sex differences have been observed in animal models of fetal programming, and recent studies suggest that sex hormones may modulate activity of regulatory systems, leading to a lower incidence of hypertension and vascular dysfunction in females compared with males. CONCLUSIONS Animal models of fetal programming provide critical support for the inverse relationship between birth weight and blood pressure. Experimental models demonstrate that sex differences are observed in the pathophysiologic response to an adverse fetal environment. A role for sex hormone involvement is strongly suggested,with modulation of the renin-angiotensin system as a possible mechanism.
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Affiliation(s)
- Daniela Grigore
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA
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31
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Simonetti GD, Raio L, Surbek D, Nelle M, Frey FJ, Mohaupt MG. Salt sensitivity of children with low birth weight. Hypertension 2008; 52:625-30. [PMID: 18695145 DOI: 10.1161/hypertensionaha.108.114983] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.
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Affiliation(s)
- Giacomo D Simonetti
- Department of Nephrology, Inselspital, Bern University Hospital, University of Bern, Berne, Switzerland
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32
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Mitchell P, Liew G, Rochtchina E, Wang JJ, Robaei D, Cheung N, Wong TY. Evidence of Arteriolar Narrowing in Low-Birth-Weight Children. Circulation 2008; 118:518-24. [DOI: 10.1161/circulationaha.107.747329] [Citation(s) in RCA: 100] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background—
Cardiovascular disease may have its origins in utero, but the influence of in utero growth on microvascular structure in children is unknown. We hypothesized that poor in utero growth is associated with narrower arteriolar caliber, which may help explain the established association of low birth weight with hypertension and cardiovascular disease in adulthood.
Methods and Results—
We examined the relation of birth weight and other markers of in utero growth to microvascular caliber in the retina in a population-based study of 1369 6-year-old children in Sydney, Australia (Sydney Childhood Eye Study). Birth weight, birth length, and head circumference were obtained from parental records. Retinal arteriolar and venular calibers were measured from digitized retinal photographs by a validated computer-assisted method. Lower birth weight, shorter birth length, and smaller head circumference were associated with narrower retinal arteriolar caliber. Each kilogram decrease in birth weight was associated with a 2.3-μm (95% CI 0.6 to 3.9,
P
=0.01) narrower retinal arteriolar caliber after controlling for age, gender, ethnicity, height, body mass index, axial length, mean arterial blood pressure, and prematurity. Similar associations were observed between shorter birth length and smaller head circumference with narrower retinal arteriolar caliber.
Conclusions—
Children who had lower birth weight, shorter birth length, and smaller head circumference had narrower retinal arteriolar calibers. These data support the concept that poor in utero growth may have an adverse influence on microvascular structure.
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Affiliation(s)
- Paul Mitchell
- From the Centre for Vision Research (P.M., G.L., E.R., J.J.W., D.R.), Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Australia; Centre for Eye Research Australia (J.J.W., N.C., T.Y.W.), University of Melbourne, Melbourne, Australia; and Singapore Eye Research Institute (T.Y.W.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Gerald Liew
- From the Centre for Vision Research (P.M., G.L., E.R., J.J.W., D.R.), Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Australia; Centre for Eye Research Australia (J.J.W., N.C., T.Y.W.), University of Melbourne, Melbourne, Australia; and Singapore Eye Research Institute (T.Y.W.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Elena Rochtchina
- From the Centre for Vision Research (P.M., G.L., E.R., J.J.W., D.R.), Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Australia; Centre for Eye Research Australia (J.J.W., N.C., T.Y.W.), University of Melbourne, Melbourne, Australia; and Singapore Eye Research Institute (T.Y.W.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Jin Wang
- From the Centre for Vision Research (P.M., G.L., E.R., J.J.W., D.R.), Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Australia; Centre for Eye Research Australia (J.J.W., N.C., T.Y.W.), University of Melbourne, Melbourne, Australia; and Singapore Eye Research Institute (T.Y.W.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Dana Robaei
- From the Centre for Vision Research (P.M., G.L., E.R., J.J.W., D.R.), Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Australia; Centre for Eye Research Australia (J.J.W., N.C., T.Y.W.), University of Melbourne, Melbourne, Australia; and Singapore Eye Research Institute (T.Y.W.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ning Cheung
- From the Centre for Vision Research (P.M., G.L., E.R., J.J.W., D.R.), Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Australia; Centre for Eye Research Australia (J.J.W., N.C., T.Y.W.), University of Melbourne, Melbourne, Australia; and Singapore Eye Research Institute (T.Y.W.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Tien Y. Wong
- From the Centre for Vision Research (P.M., G.L., E.R., J.J.W., D.R.), Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Australia; Centre for Eye Research Australia (J.J.W., N.C., T.Y.W.), University of Melbourne, Melbourne, Australia; and Singapore Eye Research Institute (T.Y.W.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Abstract
OBJECTIVES To examine anthropometric measures and birthweight as predictors of blood pressure (BP) in a cohort of children. DESIGN Cross-sectional and longitudinal study comprising baseline anthropometric and BP measurements conducted in 1994 (n=1230), with follow-up in 1997 (n=628). SETTING Seventy-five inner-Sydney primary schools. PARTICIPANTS School children aged 8-9 years at baseline and 11-12 years at follow-up. MAIN OUTCOME MEASURES Systolic and diastolic BP (SBP and DBP). STUDY FACTORS Current weight, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHR), weight gain since birth and birth weight. Potential confounders: age, sex and socioeconomic status (on the basis of the area of residence). RESULTS Current weight was significantly associated with both SBP and DBP in boys and girls at baseline and follow-up. BMI and WC were similar predictors of SBP and DBP in each survey, but longitudinal BMI change has a stronger association with SBP (r=0.43, P<0.001) and DBP (r=0.26, P<0.001) than changes in WC (r=0.18, P<0.001 for SBP and r=0.16, P<0.001 for DBP) and WHR in boys with the similar results for girls. The unadjusted associations between SBP and DBP and birthweight were nonsignificant. After adjustments for age, height and socioeconomic status, however, the association becomes negative and significant in boys (beta=-1.47, P=0.04 for SBP and beta=-1.33, P=0.03 for DBP). CONCLUSION Longitudinal change in BMI is a better predictor of BP than change in WC or the WHR, although cross-sectional measurements of BMI and WC are very similar predictors of BP. In preventing subsequent adverse effects on BP, attending to body weight during childhood is important.
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Abstract
We previously reported that in 2003 people from the Helsinki birth cohort whose blood pressures were measured, 2 different paths of growth preceded the development of hypertension. People already diagnosed with hypertension were small at birth but of average body size at age 11 years. People newly diagnosed with hypertension grew slowly in utero and through childhood. We have now examined how the mother’s body size, placental size, and living conditions after birth, 3 influences that affect growth, affect hypertension. Diagnosed hypertension was associated with low placental weight and poor living conditions after birth. The odds ratios were 1.6 (95% CI, 1.1 to 2.3) in people with placental weights <550 g, compared with those with weights >750 g, and 2.2 (95% CI, 1.5 to 3.3) in people whose fathers were laborers compared with those in upper middle-class families. Newly diagnosed hypertension was associated with a small anteroposterior diameter of the mother’s bony pelvis, a known consequence of rickets or lesser degrees of malnutrition in infancy. The odds ratio was 2.2 (95% CI, 1.4 to 3.5) in people whose mothers’ pelvic external conjugate diameters were <18 cm when compared with people whose mothers’ diameters were ≥19 cm. We conclude that one path of growth that leads to hypertension is initiated by fetal undernutrition, which may make a baby vulnerable to postnatal stress, whereas the other originates in a functional incapacity in the mother’s metabolism, possibly protein metabolism, which she acquired through undernutrition during her infancy.
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Affiliation(s)
- David J P Barker
- Heart Research Center, Oregon Health and Science University, Portland, USA.
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35
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Li L, Law C, Power C. Body mass index throughout the life-course and blood pressure in mid-adult life: a birth cohort study. J Hypertens 2007; 25:1215-23. [PMID: 17563534 DOI: 10.1097/hjh.0b013e3280f3c01a] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The contribution of body mass index (BMI) at different life stages to adult blood pressure (BP) is not well known. We investigated whether changes in BMI across childhood and adulthood, and birthweight, influence BP in mid-adulthood. METHODS AND RESULTS In 9297 participants in the 1958 British birth cohort, we analysed BMI measures at several ages (7, 11, 16, 33 and 45 years) and BP at 45 years. Positive BMI/BP associations strengthened with age; at 45 years a standard deviation (SD) increase in concurrent BMI was associated with an increase in systolic blood pressure (SBP) of 3.9 mmHg [95% confidence interval (CI) 3.6-4.2] and an elevated risk of hypertension (odds ratio 1.68; 95% CI 1.60-1.76). The effect of concurrent BMI on BP strengthened with decreasing childhood BMI; among the thinnest 10% at 11 years, SBP increased by 5.5 mmHg per SD increase in concurrent BMI; among the heaviest 10% the increase was 3.3 mmHg. Excessive BMI gain, especially recently, was associated with raised BP; allowing for BMI at 33 years, a SD increase in BMI between 33 and 45 years was associated with an SBP increase of 4.1 mmHg (95% CI 3.6-4.6). Birthweight was inversely associated with BP; SBP reduced by 1.3 mmHg (95% CI 0.9-1.7) per SD increase in birthweight, independently of BMI. CONCLUSION High BMI and excessive BMI gain at any life stage, particularly recently, is associated with increased adult BP. Relatively thin children were vulnerable to BMI gain and increased BP in adulthood. Elevated BP associated with low birthweight was not caused by 'catch-up' growth.
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Affiliation(s)
- Leah Li
- Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, UK.
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36
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Hemachandra AH, Klebanoff MA, Duggan AK, Hardy JB, Furth SL. The association between intrauterine growth restriction in the full-term infant and high blood pressure at age 7 years: results from the Collaborative Perinatal Project. Int J Epidemiol 2006; 35:871-7. [PMID: 16766538 DOI: 10.1093/ije/dyl080] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVE To use neonatal and placental anthropometry as proxy measures of intrauterine growth restriction (IUGR) and to relate these to blood pressure later in childhood. STUDY DESIGN A post hoc analysis of full-term white and black children from the Collaborative Perinatal Project, followed from birth until age 7 years (n = 29,710). Blood pressure above the 90th percentile by gender and race was considered high blood pressure. Anthropometric measures at birth included birth weight, ponderal index (PI, birth weight/birth length(3)), head to chest circumference (HCC) ratio, and placental ratio percentage (PRP, placental weight(*)100/birth weight). RESULTS Among anthropometric measures, PI, HCC, and birth weight were not associated with high systolic blood pressure at age 7 years, but PRP was. In multiple logistic regression, high systolic blood pressure and widened pulse pressure were both predicted by increased PRP [odds ratio (OR) 1.03 and 1.04, P < 0.001] but not by birth weight, when adjusted for gender, race, and maternal education. High diastolic blood pressure was weakly predicted by birth weight (OR 1.10, P = 0.05) but not by PRP. CONCLUSIONS PRP is associated with an increased risk for high systolic blood pressure and pulse pressure later in childhood, whereas birth weight, PI, and HCC are not. The proportion of placental weight to birth weight is a useful marker of IUGR for studying the developmental origins of adult disease hypothesis.
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Affiliation(s)
- Anusha H Hemachandra
- Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Lewis RM, Poore KR, Godfrey KM. The role of the placenta in the developmental origins of health and disease—Implications for practice. ACTA ACUST UNITED AC 2006. [DOI: 10.1016/j.rigapp.2005.12.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Tu YK, Gilthorpe MS, Ellison GTH. What is the effect of adjusting for more than one measure of current body size on the relation between birthweight and blood pressure? J Hum Hypertens 2006; 20:646-57. [PMID: 16691183 DOI: 10.1038/sj.jhh.1002044] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The statistical validity of the negative associations observed between birthweight and disease in later life has recently been questioned, because these associations might be due, in part, to inappropriate adjustment for current body size, creating a statistical artefact known as the 'reversal paradox'. The aim of this study was to explore the effect of adjusting for more than one measure of current body size on the association between birthweight and disease in later life using simulations and meta-analyses of empirical studies. The simulations examined the relation between birthweight and adult systolic blood pressure before and after adjusting for one, two or three measures of current body size by including current weight and subsequently adding body mass index and height in successive analytical models. Meta-analyses were then performed to compare the effect sizes observed among empirical studies reporting associations between birthweight and blood pressure before and after adjusting for one or two measures of current body size. The meta-analyses confirmed the results of the simulations - both showed that associations between birthweight and blood pressure tend to become increasingly negative following adjustment for current body size, and that this effect is enhanced after adjusting for additional measures of current body size.
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Affiliation(s)
- Y-K Tu
- Biostatistics Unit, Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, UK.
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39
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Franco MCP, Christofalo DMJ, Sawaya AL, Ajzen SA, Sesso R. Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels. Hypertension 2006; 48:45-50. [PMID: 16682609 DOI: 10.1161/01.hyp.0000223446.49596.3a] [Citation(s) in RCA: 115] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Low birth weight has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and high levels of serum uric acid are associated with hypertension. In this study, we have determined whether uric acid is related to blood pressure and vascular function in children with low birth weight. We evaluated vascular function using high-resolution ultrasound, blood pressure, and uric acid levels in 78 children (35 girls, 43 boys, aged 8 to 13 years). Increasing levels of uric acid and systolic blood pressure were observed in children with low birth weight. Birth weight was inversely associated with both systolic blood pressure and uric acid; on the other hand, uric acid levels were directly correlated with systolic blood pressure in children of the entire cohort. Low birth weight was associated with reduced flow-mediated dilation (r=0.427, P<0.001). Because the children with low birth weight had elevated uric acid as well as higher systolic blood pressure levels, we evaluated the correlation between these variables. In the low birth weight group, multiple regression analysis revealed that uric acid (beta=-2.886; SE=1.393; P=0.040) had a graded inverse relationship with flow-mediated dilation, which was not affected in a model adjusting for race and gender. We conclude that children with a history of low birth weight show impaired endothelial function and increased blood pressure and uric acid levels. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.
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Affiliation(s)
- Maria C P Franco
- Division of NephrologyFederal University of São Paulo, São Paulo, Brazil.
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40
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Kim CS, Park JS, Park J, Nam JS, Kang ES, Ahn CW, Cha BS, Lim SK, Kim KR, Lee HC, Huh KB, Kim DJ. The relation between birth weight and insulin resistance in Korean adolescents. Yonsei Med J 2006; 47:85-92. [PMID: 16502489 PMCID: PMC2687585 DOI: 10.3349/ymj.2006.47.1.85] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-beta, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-beta were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight.
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Affiliation(s)
- Chul-Sik Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jong-Suk Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jina Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ji-Sun Nam
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Eun-Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Chul-Woo Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Bong-Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung-Kil Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung-Rae Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun-Chul Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kap-Bum Huh
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Dae-Jung Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea
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Kim CS, Park JS, Park J, Nam JS, Kang ES, Ahn CW, Cha BS, Lim SK, Kim KR, Lee HC, Huh KB, Kim DJ. Does birthweight predict adolescent adiponectin levels? Clin Endocrinol (Oxf) 2006; 64:162-8. [PMID: 16430715 DOI: 10.1111/j.1365-2265.2006.02443.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Low birthweight is associated with insulin resistance later in life, and adiponectin is known to play an important role in insulin resistance. We have investigated whether birthweight has a relationship with adiponectin levels in adolescence. PATIENTS An at-home questionnaire survey was completed by 660 middle-school students (aged 12-15 years) in Seoul, Korea, and 152 participants were selected randomly based on their birthweight. MEASUREMENTS Subjects were separated into three groups according to birthweight. We recorded the birthweight and measured anthropometric factors including blood pressure, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta), and adiponectin levels of the subjects. These parameters were compared among the groups. The relationship between birthweight and physiological characteristics in adolescence was examined. RESULTS Systolic blood pressure, lipid profiles and fasting plasma glucose were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide and HOMA-IR were higher in the low birthweight tertile. After adjustment for confounding factors, birthweight was inversely related to diastolic blood pressure, insulin, C-peptide and HOMA-IR. Adiponectin level had a significant relationship with current body mass index (BMI) (r=-0.291; P< 0.001) but not with birthweight (r = 0.117; P = 0.166). CONCLUSIONSP: Although birthweight is closely related to insulin resistance during adolescence, adiponectin levels during adolescence had no significant relationship with birthweight. This result implies that low birthweight may not permanently affect adiponectin levels, but current body size is more closely associated with a decreased adiponectin level. However, the limited importance of birthweight as a determining factor on the adiponectin level later in life needs to be further evaluated.
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Affiliation(s)
- Chul Sik Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Abstract
Hypertension (HTN) and chronic kidney disease are highly prevalent diseases that tend to occur more frequently among disadvantaged populations, in whom prenatal care also tends to be poor. More and more evidence is emerging highlighting the important role of fetal programming in the development of adult disease, suggesting a possible common pathophysiologic denominator in the development of these disorders. Epidemiologic evidence accumulated over the past 2 decades has demonstrated an association between low birth weight and subsequent adult HTN, diabetes, and cardiovascular disease. More recently, a similar association has been found with chronic kidney disease. Animal studies and indirect evidence from human studies support the hypothesis that low birth weight, as a marker of adverse intrauterine circumstances, is associated with a congenital deficit in nephron number. The precise mechanism of the reduction in nephron number has not been established, but several hypotheses have been put forward, including changes in DNA methylation, increased apoptosis in the developing kidney, alterations in renal renin-angiotensin system activity, and increased fetal glucocorticoid exposure. A reduction in nephron number is associated with compensatory glomerular hypertrophy and an increased susceptibility to renal disease progression. HTN in low birth weight individuals also appears to be mediated in part through a reduction in nephron number. Increased awareness of the implications of low birth weight and inadequate prenatal care should lead to public health policies that may have long-term benefits in curbing the epidemics of HTN, diabetes, and kidney disease in generations to come.
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Affiliation(s)
- Kambiz Zandi-Nejad
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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Abstract
More and more evidence is emerging that highlights the far-reaching consequences of prenatal (intrauterine) programming on organ function and adult disease. In humans, low birth weight (LBW) occurs more frequently in disadvantaged communities among whom there is often a disproportionately high incidence of adult cardiovascular disease, hypertension, diabetes mellitus, and kidney disease. Indeed, many epidemiologic studies have found an inverse association between LBW and higher blood pressures in infancy and childhood, and overt hypertension in adulthood. Multiple animal models have demonstrated the association of LBW with later hypertension, mediated, at least in part, by an associated congenital nephron deficit. Although no direct correlation has been shown between nephron number and birth weight in humans with hypertension, nephron numbers were found to be lower in adults with essential hypertension, and glomeruli tend to be larger in humans of lower birth weight. An increase in glomerular size is consistent with hyperfiltration necessitated by a reduction in total filtration surface area, which suggests a congenital nephron deficit. Hyperfiltration manifests clinically as microalbuminuria and accelerated loss of renal function, the prevalence of which are higher among adults who had been of LBW. A kidney with a reduced nephron number has less renal reserve to adapt to dietary excesses or to compensate for renal injury, as is highlighted in the setting of renal transplantation, where smaller kidney to recipient body-weight ratios are associated with poorer outcomes, independent of immunologic factors. Both hypertension and diabetes are leading causes of end-stage renal disease worldwide, and their incidences are increasing, especially in underdeveloped communities. Perinatal programming of these 2 diseases, as well as of nephron number, may therefore have a synergistic impact on the development of hypertension and kidney disease in later life. Existing evidence suggests that birth weight should be used as a surrogate marker for future risk of adult disease. Although the ideal solution to minimize morbidity would be to eradicate LBW, until this panacea is realized, it is imperative to raise awareness of its prognostic implications and to focus special attention toward early modification of risk factors for cardiovascular and renal disease in individuals of LBW.
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Affiliation(s)
- Valerie A Luyckx
- Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
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Abstract
Our objective was to compare the blood pressure of 20-y-old very low birth weight (VLBW; <1.5 kg) individuals with that of normal birth weight (NBW) control individuals. The population included 195 VLBW (92 female and 103 male) and 208 NBW (107 female and 101 male) individuals who were born between 1977 and 1979. Independent effects of birth weight status (VLBW versus NBW) and within the VLBW cohort of intrauterine growth (birth weight z score) were examined via multiple regression analyses. VLBW individuals had a higher mean systolic blood pressure (SBP) than NBW control individuals (114 +/- 11 versus 112 +/- 13 mm Hg). SBP for VLBW female infants was 110 +/- 9 versus NBW 107 +/- 12 and for VLBW male individuals was 118 +/- 11 versus NBW 117 +/- 11 mm Hg. After adjustment for gender, race, and maternal education, the difference in SBP between VLBW and NBW individuals was 1.9 mm Hg but was 3.5 mm after also adjustment for later size (20-y weight and height z scores), which reflects catch-up growth. For female individuals, the difference in SBP between VLBW and NBW individuals was significant both unadjusted and adjusted for later size, whereas for male individuals, the difference was significant only after adjustment for later size. Intrauterine growth did not have a significant effect on SBP within the VLBW group, even after adjustment for later size. VLBW individuals, specifically female individuals, have a higher SBP than NBW control individuals. This is not explained by intrauterine growth failure.
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Affiliation(s)
- Maureen Hack
- Rainbow Babies and Childrens Hospital, Cleveland, OH 44106, USA.
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45
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Hardy R, Sovio U, King VJ, Skidmore PML, Helmsdal G, Olsen SF, Emmett PM, Wadsworth MEJ, Järvelin MR. Birthweight and blood pressure in five European birth cohort studies: an investigation of confounding factors. Eur J Public Health 2005; 16:21-30. [PMID: 16141297 DOI: 10.1093/eurpub/cki171] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND It has been suggested that the association between birthweight and blood pressure has been overstated as a result of publication bias and, within studies, a lack of adjustment for potentially important maternal and socioeconomic confounding factors and 'overadjustment' for current body size. This study investigates the impact of potential confounding variables on the birthweight-blood pressure association in birth cohort studies from different time periods and geographical locations in Europe. METHODS Data from five European birth cohort studies (from Finland, the UK, and the Faroe Islands) taking part in the European Birth-Lifecourse-Studies (EURO-BLCS) project were analysed. Birthweight was measured at birth in all cohorts and confounding variable information was collected prospectively at subsequent follow-ups in all cohorts. Regression models were used to assess the unadjusted association between birthweight and blood pressure and then to assess the impact of potential maternal and socioeconomic confounding variables and adjustment for later body size. Analyses were carried out in the same way across all five cohorts. RESULTS Birthweight was consistently negatively associated with systolic blood pressure (SBP) across all cohorts. Gestational age and possibly maternal pre-pregnancy weight, but not socioeconomic status, may be important confounding factors of the relationship between birthweight and SBP. The size of the birthweight-SBP association in adulthood may be larger than in childhood before adjustment for current body size, although a cohort effect cannot be ruled out. CONCLUSION This study highlights the value of future cross-cohort comparisons in the investigation of the foetal origins of adult disease.
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Affiliation(s)
- Rebecca Hardy
- Medical Research Council National Survey of Health and Development, Department of Epidemiology and Public Health, Royal Free and University College Medical School, London, UK.
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Tamim H, Beydoun H, Itani M, Khogali M, Chokr I, Yunis KA. Predicting neonatal outcomes: birthweight, body mass index or ponderal index? J Perinat Med 2005; 32:509-13. [PMID: 15576272 DOI: 10.1515/jpm.2004.120] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AIMS To compare birthweight (BW), body mass index (BMI) and ponderal index (PI) as predictors of selected short-term (ST) outcomes, namely Neonatal Intensive Care Unit (NICU) admission and prolonged hospitalization (PH), among newborn (NB) infants. METHODS Data was collected prospectively on 9,226 infants born during one year at nine tertiary care hospitals in Greater Beirut, Lebanon. The predictive abilities of BW, BMI and PI were compared using the area under the receiver operator characteristic (ROC) curves and sensitivity analysis was performed at the optimal cut-off points for the best anthropometric measurement. RESULTS The area under the ROC curve suggested superior discriminative power for BW as compared to BMI or PI, as a predictor of NICU admission (ROC area = 0.73) and PH (ROC area = 0.74). The optimal BW cut-off point was 2750 g (sensitivity: 0.49; specificity: 0.89) and 2950 g (sensitivity: 0.62; specificity: 0.78) for NICU admission and PH, respectively. CONCLUSION In our population of NB infants, BW--a crude measure of fetal growth--is a better predictor than either BMI--a measure of adiposity in adults and children--or PI--a measure of thinness at birth--for selected ST outcomes in NB infants.
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Affiliation(s)
- Hala Tamim
- Department of Epidemiology and Biostatistics, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
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47
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Ashdown-Lambert JR. A review of low birth weight: predictors, precursors and morbidity outcomes. ACTA ACUST UNITED AC 2005; 125:76-83. [PMID: 15819182 DOI: 10.1177/146642400512500211] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
This paper reviews the global evidence concerning infant low birth weight (LBW) (2.500kg and below) in relation to suggested causative factors, such as undernutrition, stress, smoking, drug abuse and deprived living environments. In addition, health promotion strategies in place to reduce LBW incidence in both developed and underdeveloped countries are reviewed. The paper also focuses on the high incidence of LBW in the UK in comparison to other European and developed countries. Predictors of LBW are then considered comparing findings of a study conducted in the UK with findings in underdeveloped countries. In addition, LBW risk is discussed in the context of vulnerability factors, such as teen pregnancy, child abuse and domestic violence. In conclusion, the author argues for a health promotion policy in the UK to reduce incidence of LBW in areas of deprivation and suggests that the improvement of maternal health is key in improving the health of today's infants and children who will one day become the adults of tomorrow.
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Abstract
The fetal programming theory that birth weight contributes to blood pressure or body size in later life is examined in this study. A prospective longitudinal study was conducted on subjects who were examined as newborns and prospectively interviewed and re-examined at 11 to 14 years old. Low birth weight (<2500 g) was present in 36% of the sample. The adolescent examination included measurements of blood pressure (BP), both auscultation and oscillometric methods; anthropometrics (height, weight, and body mass index [BMI]); health status; and health behaviors. Data were analyzed on 250 subjects. Correlation coefficients of birth weight with all BP measures were nonsignificant, except for the last auscultated diastolic BP (
r
=0.19,
P
<0.01), which had a positive relationship. The simple correlation coefficients of birth weight with adolescent body size were significant and positive for weight and BMI. After multiple linear regression analyses with adjustments for age, Tanner stage, and gestational age, there was no significant effect of birth weight on adolescent weight or BMI. No significant correlations were detected for ponderal index at birth with adolescent measures. This study, which includes a substantial portion of low-birth-weight cases (36%), indicates that birth weight does not correlate negatively with later BP. These results do not support the low-birth-weight theory and indicate that childhood factors that are more proximal have a greater effect on adolescent BP than intrauterine factors.
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Affiliation(s)
- Bonita Falkner
- Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
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49
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Martin RM, McCarthy A, Smith GD, Davies DP, Ben-Shlomo Y. Infant nutrition and blood pressure in early adulthood: the Barry Caerphilly Growth study. Am J Clin Nutr 2003; 77:1489-97. [PMID: 12791629 DOI: 10.1093/ajcn/77.6.1489] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Evidence suggests that environmental factors acting early in life may affect blood pressure in adulthood. OBJECTIVE The objective was to test the hypothesis that dried formula milk (derived from cow milk) intake in infancy is positively associated with blood pressure in early adulthood. DESIGN We conducted a long-term follow-up (1997-1999) of the Barry Caerphilly Growth study cohort (1972-1974) into which mothers and their offspring had originally been randomly assigned to receive a milk supplement or usual care. Participants were the offspring, who were aged 23-27 y at follow-up. The main outcome measures were systolic and diastolic blood pressure. RESULTS The social and demographic characteristics of the subjects who were (n = 679) and were not (n = 272) followed up were similar. For each increase in quartile of dried milk consumption (in oz) at 3 mo of age, there was a 1.28-mm Hg (95% CI: 0.46, 2.10 mm Hg) increase in systolic and a 0.63-mm Hg (95% CI: 0.04, 1.22 mm Hg) increase in diastolic blood pressure after adjustment for sex, intervention group, birth weight z scores, social class in childhood, age at follow-up, alcohol consumption, and pack-years of smoking. These coefficients were attenuated when adult body mass index and height were included in the models, but the association of dried milk consumption at 3 mo of age with systolic pressure remained significant (1.07 mm Hg; 95% CI: 0.27, 1.87 mm Hg). CONCLUSIONS Our findings are consistent with the hypothesis that high blood pressure in later life is influenced by early postnatal nutrition. Thus, interventions to optimize infant nutrition may have important long-term health benefits.
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Affiliation(s)
- Richard M Martin
- Department of Social Medicine, University of Bristol, United Kingdom.
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50
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Owen CG, Whincup PH, Odoki K, Gilg JA, Cook DG. Birth weight and blood cholesterol level: a study in adolescents and systematic review. Pediatrics 2003; 111:1081-9. [PMID: 12728092 DOI: 10.1542/peds.111.5.1081] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE To examine the relationship between birth weight and blood total cholesterol (TC) and to compare its strength with that of the relationship between current body mass index and TC. METHODS 1). Cross-sectional study of adolescents, with retrospective ascertainment of birth weight from birth records or parental recall; 2). systematic review of studies examining the relations between birth weight and cholesterol at all ages. PARTICIPANTS 1). 1532 individuals (92% white, 55% male) in 10 British towns; 2). 28 studies with 32 observations showing the change in TC per 1 kg increase in birth weight-6 in infancy, 14 in adolescents, 12 in adults. RESULTS In the cross-sectional study, there was a weak inverse relation between birth weight and TC level (-.061 mmol/L fall in TC per kg increase in birth weight, 95% confidence interval -.131 to.008 mmol/L per kg) which was little affected by adjustment for current body size. The difference in TC corresponding to an interquartile range increase in birth weight (-.03 mmol/L) was approximately a quarter of that for an equivalent increase in body mass index (.11 mmol/L). In the systematic review, an inverse association between birth weight and TC of a similar size to that in the cross-sectional study was observed (-.048 mmol/L per kg, 95% confidence interval -.078 to -.018 mmol/L per kg) similar in strength at all ages. CONCLUSION The relation of fetal nutrition to TC appears to be weak and is probably of limited public health importance when compared with the effects of childhood obesity.
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Affiliation(s)
- Christopher G Owen
- Department of Public Health Sciences, St George's Hospital Medical School, London, United Kingdom.
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