Longitudinal phenotyping of maternal antenatal depression in obese pregnant women supports multiple-hit hypothesis for fetal brain development, a secondary analysis of the UPBEAT study

Background Maternal antenatal depression is associated with offspring psychological disorders, but obesity is also widely implicated in maternal depression and neurodevelopment. In pregnant women with obesity we explored interrelationships between antenatal depressive symptom trajectories and multiple exposures implicated in fetal neurodevelopment which could explain these associations, as a prelude to exploring associations with infant mental health. Methods The UK Pregnancies Better Eating and Activity Trial (UPBEAT) recruited multi-ethnic pregnant women with obesity (BMI >= 30kg/m2) between March 2009 and June 2014 from 8 UK sites and 1369 were included to model longitudinal antenatal depressive symptoms from Edinburgh Postnatal Depression Scale (EPDS) scores using Latent Class Growth Analysis. Classes were compared on maternal baseline demography, biomarkers of metabolism, inflammation and placental function, infection, diet and by pregnancy and birth outcomes. Odds ratios, mean differences and 95% Confidence Intervals were calculated using robust auxiliary modelling techniques. Findings The chosen model produced four classes: Not Depressed (n=575 [42%], reference ), Mild (n=523 [37.5%]), Moderate (n=219 [16%]) and Severe (n=62 [4.5%]) symptom trajectories. Socio-economic deprivation and ethnic diversity were greater in Severe and Moderate classes. Dietary glycaemic load and saturated fat intake were higher in Severe and Moderate classes (at 17 and 27 weeks). Higher Interleukin-6, glycoprotein acetyls (17 weeks), glucose (34 weeks) and lower placental growth factor (PlGF, 17 and 27 weeks) was found in the Severe class. PlGF was lower in the Moderate class (27 weeks). Infection was least likely in the Not Depressed class across gestation. Risks of preterm birth were associated with Severe depressive symptoms (aOR 3.05[1.11 to 8.36]). Interpretation Comprehensive phenotyping exposes important fetal exposures implicated in adverse neurodevelopment, differing by depression class. This study expands substantially on causal models of suboptimal fetal neurodevelopment and offers potential new targets for intervention in obese pregnant women.Copyright (c) 2022 The Authors. Published by Elsevier Ltd.

Automated summary

This study examines the interrelationships between antenatal depressive symptom trajectories and fetal neurodevelopment in pregnant women with obesity. It identifies different fetal exposures associated with different depression classes and highlights the association between severe depressive symptoms and the risk of preterm birth.