Subclinical thyroid dysfunction in pregnant women, particularly increased free thyroxine level, is inversely associated with fetal growth indicators, including birth weight, study data show.
“Thyroid hormones play a crucial, physiological role in early placental development as well as intrauterine growth and fetal tissue accretion and differentiation,” Lauren E. Johns, PhD, MPH, of the department of environmental health sciences at the University of Michigan School of Public Health in Ann Arbor, and colleagues wrote. “Overt thyroid dysfunction in pregnancy (hyper- and hypothyroidism) has been consistently linked to abnormal fetal growth and development, including low birth weight, preterm birth, decreased head circumference and neurodevelopmental delays. Investigations of the effects of milder forms of thyroid dysfunction on fetal growth are less conclusive.”
Johns and colleagues analyzed data from 439 pregnant women without diagnosed thyroid disease who were participating in a nested, case-control study of preterm birth, drawn from the LIFECODES cohort based in Boston (56% white; 116 women with preterm births; 323 women with full-term births). Women were recruited during their first trimester between 2006 and 2008 and were followed until delivery at Brigham and Women’s Hospital. Researchers assessed ultrasound measurements completed during at least one of four follow-up visits and thyroid hormone measurements, including free T4, total T4, total triiodothyronine and thyroid-stimulating hormone. To combine and compare fetal growth measurements across different time points, researchers standardized raw ultrasound measurements, estimated fetal weight and birth weight using z scores based on gestational, age-specific means measured in the larger population. Researchers used linear regression models, stratified by study visit, to analyze the relationship between continuous thyroid hormone concentrations measured at each study visit and birth weight z scores.
Within the cohort, the weighted median gestation age at delivery was 38.9 weeks; mean birth weight was 3,345 g. Weighted median concentrations of the four thyroid hormone parameters in the overall cohort were 1.26 IU/mL for TSH, 1.08 ng/dL for free T4, 10.2 g/dL for T4 and 1.56 ng/mL for T3.
Researchers observed inverse associations between free T4 and birth weight, with the greatest association at visit one, in which a 10% increase in free T4 was associated with a 0.02 z score decrease in birth weight (beta = –0.41 for natural log-transformed free T4; 95% CI, –0.64 to –0.18). This translates to approximately 8.5 g based on birth weight standard deviation at 40 weeks estimated for the reference population, according to researchers. Associations between total T4 and birth weight z score were weaker; however, researchers observed an association between the parameters at visit three (beta = –0.08; 95% CI, –0.13 to –0.02). Total T3 was positively associated with birth weight z scores.
Free T4 was also inversely associated with repeated measurements of estimated fetal weight, head circumference and abdominal circumference. Birth weight did not statistically significantly differ between women with subclinical hypothyroidism (n = 10) and those without (n = 426). Researchers observed no associations between TSH and fetal growth markers and no interactions with fetal sex, although they noted that finding may be due to sample size limitations.
“Future animal and human health studies are needed to elucidate the biological mechanisms underlying the relationship between free T4 and fetal growth in generally euthyroid pregnancies,” the researchers wrote. – by Regina Schaffer
Disclosures: Abbott Diagnostics provided initial funding for the recruitment of the birth cohort. The authors report no relevant financial disclosures.