Assessing the Independent and Joint Effects of Unmedicated Prenatal Depressive Symptoms and Alcohol Consumption in Pregnancy and Infant Neurodevelopmental Outcomes

Abstract

Background Prenatal alcohol exposure (PAE) is an established risk factor for neurodevelopmental deficits in the offspring. Prenatal depression has been associated with neurodevelopmental deficits in the offspring, although investigations into un-medicated prenatal depression have been inconsistent. We hypothesized that un-medicated prenatal depressive symptoms would independently and jointly with PAE predict neurodevelopmental outcomes in infant offspring. Methods We studied 344 participants from a randomized clinical trial of multivitamin supplements in pregnant women in Ukraine. Women were recruited based upon peri-conceptional alcohol use and followed up to 12 months postpartum. Prenatal depressive symptoms were assessed at approximately 32 weeks of gestation using the Beck Depression Scale. Neurodevelopment was assessed with the Bayley Scales for Infant Development II Mental Development Index (MDI) and Psychomotor Development Index (PDI) at 6 and 12 months postpartum. Generalized linear regression models were constructed to assess the independent and joint effects of prenatal depressive symptoms and PAE in models adjusted for sociodemographic and pregnancy characteristics. Results PAE was independently associated with deficits in neurodevelopmental outcomes at 6 and 12 months, however, level of prenatal depressive symptoms was not. We found marginal evidence of synergism of depressive symptoms and PAE, with larger deficits in those with both exposures observed for the PDI-6 months (p=0.05) and MDI-12 months (p=0.09). Additionally, there was a suggestion of sexual dimorphism; females had stronger deficits from joint exposures than males (depressive symptom (MDI-6 months) female: −8.28, 95% CI −13.06, −3.49; male: 0.68, 95% CI −4.58, 5.94; p for interaction 0.04). While not statistically significant for the MDI or PDI at 12 months, the trend persisted. Conclusion Infants exposed to PAE and prenatal depression may be at an increased risk of neurodevelopmental deficits. Healthcare providers should be aware of this possible synergism in their efforts to mitigate the neurodevelopmental effects of these co-occurring exposures.

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

“…In the group of infants with prenatal alcohol exposure, there was a significant interaction of maternal prenatal depressive symptoms and child sex in predicting motor development. Among alcohol-exposed girls, but not boys, maternal prenatal depressive symptoms were positively associated with 6-month motor deficits [41•]. Finally, in a prospective birth cohort study ( N  = 288), there was no evidence of sex-dependent associations between maternal psychopathology symptoms and child motor skills at age 4 [27].…”

“…Bandoli et al also reported a sex interaction ( N  = 344): Prenatal depression, in conjunction with prenatal alcohol exposure, was associated with developmental deficits in 6-month-old girls, but not boys [41•]. In contrast, several studies provided no evidence of sex-dependent effects of PNMS on child cognitive development.…”

Forty Years of Assessing Neurodevelopmental and Behavioral Effects of Prenatal Alcohol Exposure in Infants: What Have We Learned?

“…BSID Mental/Cognitive scale findings related to PAE in the large cohort studies reviewed here were mixed. Notably, PAE was associated with poorer BSID Mental/Cognitive scores in the Detroit ( r = −0.22 at 13 months, p < 0.05 for a 1‐sided test [Kaplan‐Estrin et al., ]), Ottawa ( r = −0.19 at 13 months, p < 0.05 [Gusella and Fried, ]), and Ukraine ( β = −2.91 at 6 months, β = −2.67 at 12 months, p 's < 0.05 [Bandoli et al., ]) cohorts. No significant differences on the BSID Mental/Cognitive scores in relation to PAE were found in the Australia ( β = 3.06, 95% confidence interval (CI): −1.19 to 7.30 at 24 months [Halliday et al., ]), New Mexico (mean cognitive scores in the moderate/mild PAE group: 102.4 ± 7.5 vs. No PAE: 101.3 ± 9.3 at 6 months, p > 0.05 [Bakhireva et al., ]), and Scotland (PAE 50 to 99 g AA/wk: β = 1.57; PAE ≥ 100 g AA/wk: β = −2.00; all analyses at 18 months, p 's > 0.05 [Forrest et al., ]) cohorts.…”

“…Some comment on the quality of included studies and interpretation of findings is needed. Studies in which infant NDB effects were found in association with periconceptional alcohol use but not gestational alcohol use (Bandoli et al., ) might represent possible underreporting of alcohol use during pregnancy. However, it may also be related to the assessment of gestational drinking later in pregnancy when many women have substantially reduced or stopped alcohol use, while the periconceptional period might be indicative of alcohol use in early pregnancy.…”

Molecular-Cellular Targets of the Pathogenetic Action of Ethanol in the Human Brain in Ontogenesis and the Possibility of Targeted Therapy Aimed at Correcting the Effect of Pathogenic Factors

“…Prenatal alcohol exposure at moderate and higher levels increases the odds of child behavior problems with the dose, pattern and timing of exposure affecting the type of behavior problems expressed [1,2]. Disruption in the neural activation of the prefrontal cortex (PFC) and neurobehavioral disorders were detected in children with severe prenatal exposure to alcohol (PAE) [3][4][5][6]. The developing brain is extremely sensitive to the effects of ethanol [6,7].…”