Discussion
Our analyses leveraged longitudinal data to examine associations between maternal psychological functioning and respiratory outcomes in childhood. Our findings suggest that exposure to postpartum and recurrent maternal depression are associated with higher risk of wheeze and asthma in childhood. The observed associations remained significant after adjustment for a number of important potential confounders and covariates. We also found that child sex modified the association between maternal depression and respiratory outcomes; the association between postpartum and recurrent depression and higher risk of current wheeze was stronger in females when compared to males.
Prospective birth cohorts examining maternal depression at different time points in relation to wheeze and asthma development in childhood have produced mixed results5, 9, 12. A Canadian population based birth cohort study found that continued exposure to maternal anxiety or depression from birth into early childhood was associated with a twofold increase in the risk of asthma at age 7 years5. This is fairly consistent with the results our study although we observed an association earlier at 48 months (4 years of age)5. Also in line with our results, Ramratnam et al. assessed the associations between maternal stress and depression during pregnancy and early life, and recurrent wheezing utilizing the Urban Environment and Childhood Asthma (URECA) birth cohort12 and found an association between cumulative maternal depression in the first 3 years of life and recurrent wheezing12. However, we did not find any associations between prenatal depression and any of our outcomes like previous studies have reported9, 11. Differences in our findings may be attributable to our classification of depression (e.g., limited only to the prenatal period), the prevalence of our outcome and sample size.
The assessment of maternal mental health in the first postnatal year signifies an important critical window as the biological systems of children are rapidly maturing within the first two years of life, and may be compromised by exposure to more severe and enduring maternal mental health problems beyond the first postnatal year25. A potential mechanism for the observed relationships between postpartum and recurrent maternal depression and respiratory outcomes in our study may be through dysfunction of the hypothalamic pituitary adrenal (HPA) axis. McLearn et al reported that depressed women had reduced odds of playing or talking with their infants 4, 26 and animal studies have reported that decreased maternal attention enhanced hypothalamic-pituitary-adrenal (HPA) axis stress response in their offspring4, 27, 28. These interactions could be associated with symptoms of distress and raised cortisol levels in infants4, 29 and recurrent infections and asthma in preschool children4, 30. Additionally, previous studies have reported that maternal postnatal depression and anxiety strongly correlate with infant cortisol levels31, 32. HPA dysregulation and the production of proinflammatory cytokines could increase children’s susceptibility and sensitivity to persistent maternal distress and other co-occurring sources of chronic stress throughout the early childhood period32, 33. As a result, this could manifest as high allostatic load or a blunted cortisol response, increasing children’s vulnerability for the development of asthma5, 34, 35.
There is also growing evidence that the effects of maternal mental health on children’s health outcomes may differ by sex. Previous studies have shown that the prenatal environment seems to impact males more than females whereas, females may be more susceptible to the postnatal environment. Lee et al. examined the associations between pre- and/ or postnatal stress and children’s asthma, along with their effect modification by sex in a prospective cohort study utilizing the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project10. Increased maternal stress during the postnatal period was more strongly associated with higher odds of asthma in females10, which is in line with our study findings. Previous studies have also shown that females may be more adaptive in utero, though at a cost of adverse health effects later in life10, 36. As a result, the usual increase in stress reactivity in females exposed to in utero stress could explain their greater vulnerability to stress- induced health effects after birth10, 36. Alton et al concluded that wheeze at 3 years of age was nearly 5 times more likely in girls of mothers who experienced postpartum depression, which is fairly similar to the results seen in this paper4.
Utilizing the PROGRESS cohort in Mexico City is an important contribution to this growing body of work as the prevalence of postnatal and recurrent depression varies widely across cultures and geographic regions10. This study has several strengths, which include a prospective study design, large urban population and sample size of participants, and validated methods for measuring maternal depression and childhood respiratory health outcomes. Additionally, we had the ability to adjust for important environmental factors, including prenatal and early life exposure to PM2.5.
Our study also had some limitations. Asthma and wheeze outcomes are based on caregiver report which might be subject to recall bias. However, given the logistical and technical complexity of objectively recording asthma and wheeze in children, caregiver-reported wheeze and asthma is commonly utilized in moderate- to larger-sized population level studies. The ISAAC survey has been validated internationally and in Spanish-Speaking populations37. Future work should examine more objective respiratory outcomes, such as lung function as these children continue to be followed. As with any observational study, we cannot rule out residual confounding due to unmeasured factors that may influence depression and wheezing/asthma in childhood. PROGRESS is composed of urban, low-income families and our results may translate to other populations who face similar rates of depression. Research into the respiratory childhood health risks of maternal depression may be particularly clinically relevant in countries with high maternal depression such as the United States where 1/8 women experience symptoms of postpartum depression23.