Maternal pre-pregnancy body mass index is associated with newborn offspring hypothalamic mean diffusivity: a prospective dual-cohort study.

BACKGROUND: An extensive body of animal literature supports the premise that maternal obesity during pregnancy can alter the development of the fetal hypothalamus (HTH, a critical regulator of energy balance) with implications for offspring obesity risk (i.e., long-term energy imbalance). Yet, the relationship in humans between maternal overweight/obesity during pregnancy and fetal hypothalamic development remains largely unknown. Here, using an international (Finland and California, USA) multi-site diffusion tensor imaging (DTI) dataset, we test the hypothesis that maternal pre-pregnancy BMI is associated with newborn offspring HTH mean diffusivity (HTH MD, a replicable neural correlate of BMI in adults). METHODS: HTH MD was independently quantified in two separate BMI-matched cohorts (up to class II obesity; BMIRange = 17-35) using a high-resolution atlas-based definition of HTH. A total of n = 231 mother-child dyads were available for this analysis (nSite,1 = 152, age at MRI = 26.7 ± 8.1 days, gestational age at birth = 39.9 ± 1.2 weeks, nM/F = 82/70, BMI = 24.2 ± 3.8; nSite,2 = 79, age at MRI = 25.6 ± 12.5 days, gestational age at birth = 39.3 ± 1.5 weeks, nM/F = 45/34, BMI = 25.1 ± 4.0). The association between maternal pre-pregnancy BMI and newborn offspring HTH MD was examined separately in each cohort using linear regression adjusting for gestational age at birth, postnatal age at scan, sex, whole white matter mean diffusivity, and DTI quality control criteria. In post hoc analyses, additional potentially confounding factors including socioeconomic status, ethnicity, and obstetric risk were adjusted where appropriate. RESULTS: The distribution of maternal pre-pregnancy BMI was comparable across sites but differed by ethnicity and socioeconomic status. A positive linear association between maternal pre-pregnancy BMI and newborn offspring HTH MD was observed at both sites ([Formula: see text]Site,1 = 0.17, pSite,1 = 0.01; [Formula: see text]Site,2 = 0.22, pSite,2 = 0.03) and remained significant after adjusting for cohort-relevant covariates. CONCLUSIONS: These findings translate the preclinically established association between maternal obesity during pregnancy and offspring hypothalamic microstructure to the human context. In addition to further replication/generalization, future efforts to identify biological mediators of the association between maternal obesity and fetal HTH development are warranted to develop targeted strategies for the primary prevention of childhood obesity.

Auditory Mismatch Responses to Emotional Stimuli in 3-Year-Olds in Relation to Prenatal Maternal Depression Symptoms.

Maternal depression symptoms are common in pregnant women and can have negative effects on offspring's emotional development. This study investigated the association between prenatal maternal depression symptoms (assessed with the Edinburgh Postnatal Depression Scale at 24 weeks of gestation) and auditory perception of emotional stimuli in 3-year-olds (n = 58) from the FinnBrain Birth Cohort Study. Using electroencephalography (EEG), we examined mismatch responses for happy, sad, and angry sounds presented among neutral stimuli. A positive association between maternal depression symptoms and the emotional mismatch responses in an early time window (80-120 ms) was found, indicating that brain responses of children of mothers with depressive symptoms were weaker to happy sounds, though the results did not survive Bonferroni correction. There were no clear associations in the sad and angry emotional categories. Our results tentatively support that the 3-year-old children of mothers with depression symptoms may be less sensitive to automatically detect happy sounds compared to children whose mothers do not display symptoms of depression.

Newborn white matter microstructure moderates the association between maternal postpartum depressive symptoms and infant negative reactivity.

Maternal postpartum depression is a prominent risk factor for aberrant child socioemotional development, but there is little understanding about the neural phenotypes that underlie infant sensitivity to maternal depression. We examined whether newborn white matter fractional anisotropy (FA), a measure of white matter maturity, moderates the association between maternal postpartum depressive symptoms and infant negative reactivity at 6 months. Participants were 80 mother-infant dyads participating in a prospective population-based cohort, and included families whose newborns underwent a magnetic resonance/diffusion tensor imaging scan at 2-5 weeks of age and whose mothers reported their own depressive symptoms at 3 and 6 months postpartum and infant negative emotional reactivity at 6 months. The whole-brain FA moderated the association between maternal depressive symptoms and mother-reported infant negative reactivity at 6 months after adjusting for the covariates. Maternal depressive symptoms were positively related to infant negative reactivity among infants with high or average FA in the whole brain and in corpus callosum and cingulum, but not among those with low FA. The link between maternal depressive symptoms and infant negative reactivity was moderated by newborn FA. The variation in white matter microstructure might play a role in child susceptibility to parental distress.

Maternal sleep quality during pregnancy is associated with neonatal auditory ERPs.

Poor maternal sleep quality during pregnancy may act as a prenatal stress factor for the fetus and associate with neonate neurocognition, for example via fetal programming. The impacts of worsened maternal sleep on neonatal development and, more specifically on neonatal auditory brain responses, have not been studied. A total of 155 mother-neonate dyads drawn from the FinnBrain Birth Cohort Study participated in our study including maternal self-report questionnaires on sleep at gestational week 24 and an event-related potential (ERP) measurement among 1-2-day-old neonates. For sleep quality assessment, the Basic Nordic Sleep Questionnaire (BNSQ) was used and calculated scores for (1) insomnia, (2) subjective sleep loss and (3) sleepiness were formed and applied in the analyses. In the auditory ERP protocol, three emotionally uttered pseudo words (in happy, angry and sad valence) were presented among neutrally uttered pseudo words. To study the relations between prenatal maternal sleep quality and auditory emotion-related ERP responses, mixed-effects regression models were computed for early (100-200 ms) and late (300-500 ms) ERP response time-windows. All of the selected BNSQ scores were associated with neonatal ERP responses for happy and angry emotion stimuli (sleep loss and sleepiness in the early, and insomnia, sleep loss and sleepiness in the late time-window). For sad stimuli, only maternal sleep loss predicted the neonatal ERP response in the late time-window, likely because the overall ERP was weakest in the sad condition. We conclude that maternal sleep quality during pregnancy is associated with changes in neonatal auditory ERP responses.