ESPE Abstracts

Context: Pregnancy and parturition involve a complex interplay between maternal health and that of her offspring. Graves’ disease and its management have been associated with adverse pregnancy, labor and delivery, as well as neonatal outcomes. Adaptation of the hypothalamic-pituitary-thyroid axis can be reflected by measuring thyroid function levels in newborn screening (NBS).

Objective: To investigate the characteristics of the mother-infant dyad of term infants born to mothers with Graves’ disease.

Methods: The Israeli National NBS Program thyroid dataset was linked with the electronic medical records to generate a unified database of mothers and their term infants born between 2011 and 2021 at Lis Maternity and Women's Hospital, Tel-Aviv Sourasky Medical Center. The MDClone big data platform was utilized to extract maternal, pregnancy, disease course, labor and delivery, and neonatal characteristics from the medical records of mother-infant dyads. Dyads with maternal Graves’ disease were compared to those of the general population.

Results: Out of 103,899 mother-infant dyads, 292 (0.3%) mothers had gestational Graves’ disease. A forward multivariate linear regression demonstrated that Graves’ disease (history and active) did not significantly affect NBS total thyroxine (TT4) levels (P=0.252). A subgroup analysis of infants born to mothers with active gestational Graves’ disease exhibited higher NBS TT4 levels compared to the general population (P<0.001). Mothers with Graves’ disease had higher rates of assisted reproductive technology utilization (12.7% vs 9.0%, P=0.012; OR 1.46 [95%CI 1.03–2.07], P=0.031), gestational hypertension (3.9% vs 1.1%, P<0.001; OR 3.53 [95%CI 1.92-6.47], P<0.001) and proteinuria (2.5% vs 0.9%, P<0.001; OR 3.03 [95%CI 1.43-6.45], P=0.004). They had higher rates of cesarean sections (26.4% vs 19.7%, P=0.029; OR 1.46 [95%CI 1.13-1.90], P=0.004), prelabor rupture of membranes (15.4% vs 4.1%, P<0.001; OR 4.3 [95%CI 3.13-5.91], P<0.001), and placental abnormalities (5.1% vs 2.0%, P<0.001; OR 2.64 [95%CI 1.57-4.44], P<0.001). Their infants had lower adjusted birthweight z-scores (-0.18±0.94 vs -0.03±0.90, P=0.007) and were more likely to be small for gestational age (12.0% vs 8.1%, P=0.005; OR 1.54 [95%CI 1.08-2.19], P=0.018). No differences in the infants’ hospitalization venue or length of stay were observed.

Conclusion: Our findings demonstrate that neonatal thyroid function levels were affected by maternal Graves’ disease only when the disease was active. Moreover, gestational Graves' disease was associated with an increased risk of adverse outcomes for the mother-infant dyad. Further research is needed to elucidate the role of neonatal thyroid secretion in modulating infants’ metabolic outcomes.