Chatzi, Lida

Abstract Context Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. Objective (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. Methods (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. Results (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody–positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from –10.8% to –21.8% for TSH and –1.2% to –13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. Conclusion We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

SummaryBackgroundVitamin D may modulate adipogenesis. However, limited studies have investigated the effect of maternal vitamin D during pregnancy on offspring adiposity or cardiometabolic parameters with inconclusive results.ObjectivesThe objective of this study is to examine the association of maternal 25(OH)‐vitamin D [25(OH)D] status with offspring obesity and cardiometabolic characteristics in 532 mother–child pairs from the prospective pregnancy cohort Rhea in Crete, Greece.MethodsMaternal 25(OH)D concentrations were measured at the first prenatal visit (mean: 14 weeks, SD: 4). Child outcomes included body mass index standard deviation score, waist circumference, skin‐fold thickness, blood pressure and serum lipids at ages 4 and 6 years. Body fat percentage was also measured at 6 years. Body mass index growth trajectories from birth to 6 years were estimated by mixed effects models with fractional polynomials of age. Adjusted associations were obtained via multivariable linear regression analyses.ResultsAbout two‐thirds of participating mothers had 25(OH)D concentrations <50 nmol L−1. Offspring of women in the low 25(OH)D tertile (<37.7 nmol L−1) had higher body mass index standard deviation score (β 0.20, 95% CI: 0.03, 0.37), and waist circumference (β 0.87 95% CI: 0.12, 1.63) at preschool age, compared with the offspring of women with higher 25(OH)D measurements (≥37.7 nmol L−1), on covariate‐adjusted analyses. The observed relationships persisted at age 6 years. We found no association between maternal 25(OH)D concentrations and offspring blood pressure or serum lipids at both time points.ConclusionsExposure to very low 25(OH)D concentrations in utero may increase childhood adiposity indices. Given that vitamin D is a modifiable risk factor, our findings may have important public health implications.