Association of Umbilical Cord Blood Serotonin Levels with Neurodevelopmental Outcomes

Abstract

Introduction: Serotonin (5-hydroxytryptamine [5-HT]) plays an important role in early development, and fetal 5-HT has been reported to arise from placental and maternal sources. Previous human studies have established an association between maternal 5-HT levels and neurodevelopmental outcomes in populations with autism. In this study, we analyze umbilical cord blood and placental 5-HT levels at birth to further investigate the relationship of gestational 5-HT levels with birth outcomes and offspring cognitive development.

Methods: Participants were enrolled in the Safe Passage Study conducted by the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network. Infant cord blood and placental samples were collected postdelivery, and 5-HT levels were measured using high-performance liquid chromatography-fluorometric analysis. The Mullen Scales of Early Learning (MSEL) assessed child development at 12 months. Associations between 5-HT levels and birth outcomes or developmental outcomes were assessed using linear regression models.

Results: No significant association was found between cord blood (n = 418) and placental (n = 89) 5-HT levels. Preterm birth was associated with lower cord blood 5-HT levels, and increasing gestational age among full-term infants was associated with higher cord blood 5-HT levels. Cord blood 5-HT was significantly associated with the Mullen Scales of Early Learning Composite Score, and follow-up analyses revealed a significant association between cord blood 5-HT and fine motor skills. No association was found between placental 5-HT and the Mullen composite score.

Conclusion: To our knowledge, this study is the first to evaluate the relationship between placental 5-HT levels and cord blood 5-HT levels at birth. The lack of association suggests that cord blood 5-HT levels are likely to be a better index of fetal 5-HT exposure. Associations between cord blood 5-HT and child cognitive development are consistent with previous studies showing an association between maternal 5-HT levels and neurodevelopmental trajectories. Further research is needed to better characterize these relationships and to elucidate the distinct contributions of maternal, placental, and fetal 5-HT sources across developmental time points.

Keywords: Cord blood; Mullen; Neurodevelopmental outcomes; Placenta; Serotonin.