Maternal thyroid hormones during pregnancy, childhood adiposity and cardiovascular risk factors: the Generation R Study

Godoy, Guilherme A. F.; Korevaar, Tim I M; Peeters, Robin P.; Hofman, Albert; Rijke, Yolanda B. de; Bongers-Schokking, Jacoba J.; Tiemeier, Henning; Jaddoe, Vincent W. V.; Gaillard, Romy

doi:10.1111/cen.12399

Cited by 36 publications

(23 citation statements)

References 34 publications

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“…Only one study has previously investigated the association between maternal thyroid dysfunction and offspring cardiometabolic risk factors (26). In this study, no association was found with either subclinical or overt maternal thyroid disease.…”

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confidence: 57%

Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age

et al. 2016

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Background: Experimental evidence exists indicating that maternal thyroid hormones during pregnancy may affect the metabolic set point and cardio-vascular function in the offspring. The objective of this study was to investigate the association between maternal thyroid function in week 30 of gestation and offspring adiposity and blood pressure at 20 y. Methods: The study was based on the follow up of a Danish birth cohort from 1988 to 1989 (n = 965). A blood sample was drawn from the pregnant women in week 30 of gestation (N = 877). In 2008-2009, the offspring were followed up with selfreported anthropometrics (N = 645) and a clinically measured blood pressure (N = 425). Multiple linear regressions were used to estimate the association between maternal thyroid function and offspring BMI, waist circumference, and blood pressure. results: Offspring of subclinical hypothyroid women had higher systolic blood pressure (adjusted difference = 3.6, 95% confidence interval: 0.2, 7.0 mmHg) and a tendency toward higher diastolic blood pressure (adjusted difference = 2.3, 95% confidence interval: −0.2, 4.9 mmHg) compared to offspring of euthyroid women. No association was found with offspring BMI and waist circumference. conclusion: Maternal thyroid function during third trimester of pregnancy may affect long-term blood pressure in the offspring. t hyroid disease is a relatively common disorder in women of reproductive age (1-3) and overt as well as subclinical disease has been shown to be associated with increased risk of adverse pregnancy outcomes such as miscarriage, preterm birth, small for gestational age, and stillbirth (1,(4)(5)(6)(7)(8)(9)(10)(11).The development of many diseases takes years and factors affecting disease risk may operate throughout life. Hence, the programming theory proposes that an unsuitable environment at sensitive periods of development might result in long-term changes in the structure and function of the organism and thereby increase the risk of developing diseases later in life (12).The fetal thyroid gland is not capable of producing hormones during the first half of pregnancy, making the fetus entirely dependent on maternal supply. Thyroid hormones are important for proper regulation of fetal brain development (13,14) and overt maternal hypothyroidism during pregnancy has been found to be associated with impaired neurological development in the offspring, (11,15,16) whereas the association with subclinical hypothyroidism is less clear (17)(18)(19)(20).Generally, little is known about the possible long-term consequences in offspring exposed to maternal thyroid disease during fetal life. However, recent evidence points toward a programming effect on neurodevelopmental disorders such as seizure disorders, autism, and attention deficit hyperactivity disorder (ADHD) (21-23). Also, experimental studies in mice have shown that thyroid hormones may be important for the development of specific hypothalamic centres governing cardio-vascular function (24), indicating that maternal thyroid function dur...

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confidence: 57%

Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age

et al. 2016

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“…Recent studies in experimental animals (30) and in humans (31,32,33) have considered thyroid hormone abnormalities as the exposure and cardiovascular function as the outcome. A study in rats (30) suggested that maternal thyroid hormone levels are important in the development of hypothalamic neurons regulating cardiovascular functions.…”

Section: Hypothesis Of Fetal Programing By Maternal Thyroid Dysfunctionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

Andersen¹,

Carlé²,

Karmisholt³

et al. 2017

European Journal of Endocrinology

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Fetal programming is a long-standing, but still evolving, concept that links exposures during pregnancy to the later development of disease in the offspring. A fetal programming effect has been considered within different endocrine axes and in relation to different maternal endocrine diseases. In this critical review, we describe and discuss the hypothesis of fetal programming by maternal thyroid dysfunction in the context of fetal brain development and neurodevelopmental disorders in the offspring. Thyroid hormones are important regulators of early brain development, and evidence from experimental and observational human studies have demonstrated structural and functional abnormalities in the brain caused by the lack or excess of thyroid hormone during fetal brain development. The hypothesis that such abnormalities introduced during early fetal brain development increase susceptibility for the later onset of neurodevelopmental disorders in the offspring is biologically plausible. However, epidemiological studies on the association between maternal thyroid dysfunction and long-term child outcomes are observational in design, and are challenged by important methodological aspects.

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“…However, how alterations in maternal and foetal TH levels may affect child development is an important area of study. Data from the Generation R study reveal that maternal thyroid levels during pregnancy may influence childhood adiposity and potentially cardiovascular development . Lower maternal TSH levels and higher maternal fT4 levels were associated with lower childhood BMI.…”

Section: Introductionmentioning

confidence: 99%

Increasing maternal obesity is associated with alterations in both maternal and neonatal thyroid hormone levels

Kahr

Antony

DelBeccaro

et al. 2015

Clinical Endocrinology

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Objective Obesity is associated with alterations in thyroid hormone (TH) levels in obese, pregnant individuals. The maintenance of TH levels throughout gestation is important for proper fetal development. The aim of this study was to measure levels of fT3, fT4 and TSH in maternal and matched cord blood serum from normal weight, overweight and obese gravidae to determine alterations in maternal and neonatal TH levels by virtue of maternal obesity. Design, Setting, Subjects, Outcome Measures ELISA was utilized to measure fT3, fT4 and TSH levels from banked, matched maternal and neonatal (cord blood) serum (N=205 matched pairs). Data was stratified according to pre-pregnancy or first trimester BMI. Results Both maternal and neonatal fT3 levels consistently increased with increasing maternal obesity, and maternal and neonatal fT3 were significantly correlated (r =0.422, p<0.001). Maternal and neonatal fT3 were also significantly associated with birthweight (β=0.155, p=0.027 and β=0.171, p=0.018 respectively). Both the maternal and neonatal fT3 to fT4 ratio significantly increased with increasing maternal obesity. We further found that excess gestational weight gain was associated with a decrease in maternal fT4 compared with gravidae who had insufficient gestational weight gain (0.86±0.17 vs. 0.95±0.22, p<0.01). Conclusion Maternal obesity is not only associated with maternal alterations in TH, but with accompanying neonatal changes. Because both maternal obesity and alterations in TH levels are associated with childhood obesity, based on these findings and our prior analyses in a non-human primate model we propose that changes in fT3 levels in the offspring of obese mothers may be a potential molecular mediator of fetal overgrowth and childhood obesity.

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Maternal thyroid hormones during pregnancy, childhood adiposity and cardiovascular risk factors: the Generation R Study

Cited by 36 publications

References 34 publications

Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age

Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

Increasing maternal obesity is associated with alterations in both maternal and neonatal thyroid hormone levels

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