Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies.

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance.

Anxiety and depressive symptoms in pregnancy predict low birth weight differentially in male and female infants-findings from an urban pregnancy cohort in India.

PURPOSE: This study examined the contributions of antenatal anxiety, depression, and partner violence to low birth weight (LBW) in infants and to sex-specific birth weight outcomes among mothers from a cohort in urban India. METHODS: Data from 700 mothers from the PRAMMS cohort (Prospective Assessment of Maternal Mental Health Study) were used. Pregnant women were assessed in each trimester-T1, T2 and T3, for symptoms of anxiety, and depression as well as partner violence. Multivariate analyses were performed for the whole sample and then for male and female infants separately. The final multivariable logistic regression models were each built using a backward selection procedure and controlling for confounders. To accommodate longitudinally measured data, change in scores (T2-T1 and T3-T2) of anxiety and depression were included in the model. RESULTS: Of the 583 women with a singleton live birth, birth weight was available for 514 infants  and LBW was recorded in 80 infants (15.6%). Of these, 23 infants were preterm. Overall, higher T1 Depression scores (OR: 1.11; 95% CI 1.040, 1.187) and an increase in both Depression scores (OR: 1.12; 95% CI 1.047, 1.195) from T1 to T2 and Anxiety scores (OR: 1.32; 95% CI 1.079, 1.603) between T2 and T3 were predictors of LBW. Female infants had a higher chance of LBW with increase in maternal anxiety between T1-T2 (OR: 1.69; 95% CI 1.053, 2.708) and T2-T3 (OR: 1.49; 95% CI 1.058, 2.086); partner violence during pregnancy just failed to reach conventional statistical significance (OR: 2.48; 95% CI 0.810, 7.581) in girls. Male infants had a higher chance of LBW with higher baseline depression scores at T1 (OR: 1.23; 95% CI 1.042, 1.452) and an increase in depression scores (OR: 1.25; 95% CI 1.060, 1.472) from T1 to T2. CONCLUSION: Increasing prenatal anxiety and depressive symptoms in different trimesters of pregnancy were associated with LBW with sex-specific patterns of association in this sample from a Low and Middle Income Country.

Lifetime traumatic experiences and postpartum depressive symptoms in a cohort of women in South India.

Studies in western cultures have proposed mechanisms by which adverse childhood experiences can affect mental health, including mediating variables such as social support and resilience. However, research replicating these findings in perinatal populations are sparse in Asia. This study assessed the association between lifetime trauma and postpartum depressive symptoms. Additionally, the study examined the mediating role that resilience and social support can play in this association. This study was conducted on 458 women participating in the PRAMMS cohort in urban Bangalore. Information on lifetime trauma was collected through a culturally appropriate trauma interview and postpartum depressive symptoms (8 weeks) were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Resilience was assessed using the Connor-Davidson Resilience Scale-10 and social support was assessed through the Zimet's Multidimensional Scale of Perceived Social Support. A linear model was used to measure the association between lifetime trauma and postpartum depression and mediation analysis was used to assess the role of resilience and social support in the primary association. All analyses were conducted using SPSS. In this cohort, 254 women reported at least one trauma and 204 reported no trauma. A higher number of lifetime traumatic events was associated with higher EPDS scores (ß = 0.487, 95%CI: 0.267-0.707). Social support was found to have a negative association between the predictor and the outcome; however, resilience was not a statistically significant mediator. Lifetime trauma was associated with postpartum depressive symptoms in our study and social support negatively mediated the association between lifetime trauma and postpartum depressive symptoms.

Suicidality in early pregnancy among antepartum mothers in urban India.

This study assessed the prevalence and predictors of suicidality among 462 pregnant women in South India. Women in early pregnancy (<20 weeks) attending an urban public hospital antenatal center were assessed for suicidality using a modified version of the Suicide Behaviors Questionnaire-Revised (SBQR) and a single-item (item 10) from the Edinburgh Postnatal Depression Scale (EPDS). Severity of depressive symptoms, family violence, and perceived social support were also measured. The prevalence of suicidality in pregnancy was 7.6 % (35/462). Eleven women (2.4 %) reported having had suicidal plans, and 8 (1.7 %) had made a suicidal attempt during the current pregnancy. Younger age, belonging to a middle socioeconomic status, poor perceived support, domestic violence, depressive symptoms, and having a past history of suicidality predicted suicidal ideation during the current pregnancy. Multivariate analysis revealed depression severity and a life time history of suicidal ideation as being the strongest predictors. The findings underscore the need for assessment of psychiatric and psychosocial factors that confer risk among women in this vulnerable period. The results of the study however may be specific to low-income urban women from this geographical location limiting the external validity of our findings.