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

Abstract

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...

Maternal thyroid hormone is required for parvalbumin neurone development in the anterior hypothalamic area

“…Because these neurones control cardiovascular functions, and can cause hypertension if not developed properly, our data reveal an important neuroanatomical target of maternal hypothyroxinemia and provide further mechanistic evidence for the link between maternal TH concentrations during pregnancy and offspring blood pressure. Given that this correlation is also observed in humans, the present study has potentially great clinical relevance for the ongoing controversial discussions concerning the treatment of thyroid disorders during pregnancy.…”

“…This suggests that the development of the central control of cardiovascular functions might also be dependent on maternal TH in humans, although there are certain species specific differences between thalamic neuronal migration mechanisms . Indeed, a recent observation on a Danish cohort revealed that children from subclinical hypothyroid women display a higher systolic blood pressure at the age of 20 years compared to the control group . Most remarkably, hypertension was also found in children from subclinically hyperthyroid mothers, which indicates that the dual role of TH during neuronal development might also exists in humans.…”

Antenatal/early postnatal hypothyroidism increases the contribution of Rho-kinase to contractile responses of mesenteric and skeletal muscle arteries in adult rats

“…5 Recently it was shown that subclinical hypothyroidism during pregnancy is associated with higher blood pressure in adult offspring. 6 Similar observation was made in an animal study of maternal hypothyroidism. 7 On the other hand, high blood pressure does not always develop in adult progeny of hypothyroid rats.…”

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

“…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.…”

“…A study in rats (30) suggested that maternal thyroid hormone levels are important in the development of hypothalamic neurons regulating cardiovascular functions. Studies in humans have shown that maternal hypothyroidism may be associated with congenital heart defects in the offspring (32), and that maternal thyroid function in pregnancy may program offspring blood pressure at the age of 20 (33). Still, another study found no association with offspring blood pressure at the age of 6 years (31).…”