Maternal psychosocial risk factors and lower respiratory tract infection (LRTI) during infancy in a South African birth cohort

Objective To investigate the association between maternal antenatal and/or postnatal psychosocial risk factors (including depression, psychological distress, alcohol abuse and intimate partner violence (IPV) and infant lower respiratory tract infection (LRTI) in a low- and middleincome- country (LMIC). Study design Pregnant women (n = 1137) enrolled in a South African birth cohort study, the Drakenstein Child Health Study (DCHS) were longitudinally assessed for psychosocial risk factors including depression, psychological distress, alcohol abuse and/or intimate partner violence (IPV). Infants were followed from birth until one year of age for the development of LRTI by active surveillance. Two outcomes were evaluated: any LRTI, and severe and/or hospitalised LRTI. Logistic regression was used to identify associations between individual maternal psychosocial risk factors and LRTI outcomes. Analyses stratified by age were also performed to determine which age groups related to infant LRTI were linked with maternal psychosocial risk factors. Results There were 606 LRTI episodes in 369 infants in the first year (crude incidence rate = 0.53 episodes per person-year, 95%CI: 0.50; 0.56); 31% (n = 186) of episodes were severe or hospitalised events. Maternal psychosocial risk factors were associated with LRTI and severe LRTI, particularly postnatal and long-term maternal psychological distress, antenatal maternal alcohol consumption, and postnatal maternal IPV. Age stratified analyses found that antenatal maternal alcohol consumption was associated with early infant LRTI, while antenatal maternal depression was linked with infant severe LRTI between 3 and 6 months of age, and postnatal maternal IPV was associated with early LRTI and severe forms of LRTI. Conclusion The associations between maternal psychosocial risk factors and infant LRTI highlight the potential value of screening for maternal psychosocial risk factors in clinical settings and developing targeted interventions. Such interventions may not only improve maternal wellbeing, but also help reduce the burden of infant LRTI in LMIC settings. Women in the 2nd trimester of pregnancy were enrolled between March 2012 and March 2015 in the Drakenstein Child Health Study (DCHS), a South African birth cohort study investigating the early life determinants of child health. Mothers were then followed through childbirth and mother-child dyads continue to be followed. For this study, the follow up period was censored at one year of age. The study was located in a peri-urban area in, South Africa, in a low socioeconomic population in which more than 90% of the population access public healthcare services [3, 24]. Enrolment occurred at two antenatal clinics (Mbekweni, serving predominately a population of black African ancestry, or TC Newman, serving a mixed-ancestry population). Consenting pregnant women 18 years or older, and who intended to remain in the area for at least 1 year were enrolled [3, 26]. Infants attended study visits at 6, 10, 14 weeks, 6, 9, 12 months, and were actively followed and investigated for any LRTI episode during the first year. In addition, a follow up visit 48 hours and 4–6 weeks after the LRTI episode was conducted. For the purpose of this study, a cut-off date for each participant was considered and any LRTI episode that happened prior to this date was included. The cut-off date was either the date of early termination, the date of the 12-month scheduled visit, or the expected date of the 12-month visit if this visit was missed but the child was still active in the study. Two binary LRTI outcomes were considered in this study; any LRTI episode and severe or hospitalised LRTI, as a measure of severity, in the first year of life. These outcomes were collected through active surveillance of LRTI episodes diagnosed by trained study staff (nurses) and assessed in real time [3, 27]. LRTI was defined according to World Health Organization (WHO) criteria, which included a cough or difficulty breathing with age-appropriate tachypnoea or lower chest wall indrawing [27, 28]. Study nurses were trained in respiratory examination of children with frequent re-training [27]. Severe LRTI, defined by WHO criteria, included any general danger sign in children older than 2 months or age specific tachypnea, lower chest indrawing or general danger sign in infants less than 2 months [27, 28]. Children were hospitalised or discharged based on a treating clinician’s recommendation. Maternal psychosocial risk factor data were collected at a scheduled antenatal visit during the third trimester (between 28–32 weeks of gestation) and postnatal visits at 10 weeks, 6 months and 12 months postpartum. Several validated questionnaires, that were administered in the preferred language (English, Afrikaans or isiXhosa) of the participant, were used to measure psychosocial risk factors as has been described [24]: The Edinburgh Postnatal Depression Scale (EPDS), was used to measure maternal depression [29]. The EPDS measure asked 10 questions related to how the women felt in the previous 7 days from the time of the visit. Each of 10 questions were scored 0–3 and summed [24]. A cut-off value of 13 was used to separate the participants into above- or below-threshold for depression [29, 30]. The presence of maternal psychological distress in the past month from the time of the visit was assessed with the validated Self-Reporting Questionnaire 20-item (SRQ20) [31, 32]. Each item had a binary scoring option (0–1), and a total score was generated [24]. A cut-off value of 8 dichotomised participants into an above- or below-threshold for psychological distress [24, 33, 34]. The Intimate Partner Violence (IPV) Questionnaire was used to assess maternal physical, emotional and sexual violence exposure. The questionnaire was adapted from previous studies and measures both lifetime IPV exposure as well as recent (past 12 months) IPV exposure [35, 36]. Exposure to emotional, physical and sexual abuse were considered individually. Participants were categorised as having experienced no IPV (either emotional, physical or sexual) if all responses for that exposure were “never”; an isolated incident of IPV if one response for that exposure happened “once”; a low frequency of exposure if the response was “once” to more than one item for a particular exposure; a mid-frequency if the participant responded “a few times” to at least one item, but did not respond “many times” to any item for a particular exposure; and a high frequency if there were any responses of “many times” for a particular exposure [24]. These were further categorised into above and below threshold; where low to high frequency was considered above threshold and no exposure or an isolated incident was considered to be below threshold. A participant was determined to be above threshold for “recent” IPV exposure if the participant was above threshold for any of the three IPV sub-types in the past 12 months. In addition, alcohol consumption during and post pregnancy were measured by the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) [37], which considers exposure of alcohol, smoking, and substance abuse in the previous 3 months from the time of the study visit. The scoring of ASSIST has been previously described [24, 37]. For this study, item responses related to frequency and timing of alcohol consumption were used to dichotomise into daily/weekly alcohol use vs no use. Since there were 3 postnatal time points considered in this study, each of these were considered in independent regression models for maternal depression, psychological distress, and alcohol use. The 12-month visit was used to investigate postnatal IPV exposure, as the measure enquired about physical, emotional and sexual abuse by a partner in the previous 12 months. This was done to avoid any overlap between the antenatal and postnatal periods. Clinical and socio-demographic risk factors were longitudinally measured including child feeding practices; HIV exposure; maternal smoking and environmental tobacco smoke (ETS) exposure, assessed by self-report and urine cotinine results (from the mother collected antenatally and at birth; infant results were collected within the first year of life). Continuous cotinine values were categorised into three levels: a score less than or equal to 10 ng/mL was consider not exposed, a score greater than 10 ng/mL and less than 500 ng/mL was considered to have passive smoke exposure, and a result greater than 500 ng/mL, was recorded as active smoking [38]. Indoor air pollution (IAP) related to the child’s home environment, was measured at an antenatal (within 4 weeks of enrolment) and postnatal (between 4 and 6 months postpartum) home visit [38]. The only pollutant considered was particulate matter (PM10), as this pollutant was previously found to be associated with LRTI in the DCHS [38]. The South African National Ambient Air Quality Standards [39] were used to define expected exposure levels for each pollutant based on an averaging period of 1 year for each measure: PM10 = 40 μg/m3 [38, 39]. Birth characteristics were collected, including gestational age and birth weight, measured by study staff as previously described [40]. Birth weight/height standardised z-scores were calculated using the updated Fenton new born growth charts, which account for prematurity [41]. In addition, socio-economic status (SES) at baseline was collected, based on a composite validated score comprising four socio-economic variables: level of maternal education, employment status, household income, and asset ownership [42]. Standardised scores were divided into quartiles, which are labelled ‘low’, ‘low-moderate’, ‘high-moderate’, and ‘high’ groups [42]. The infant’s vaccination schedule was also recorded longitudinally, at scheduled visits. The DCHS was approved by the Faculty of Health Sciences, Human Research Ethics Committee (HREC), University of Cape Town (401/2009) and by the Western Cape Provincial Health Research committee [3]. Mothers provided written informed consent at enrolment and annually thereafter. Analyses were conducted with STATA version 14.0 (College Station, Texas, USA). Descriptive data were presented as medians, interquartile range (IQR) and frequencies (proportions), as appropriate. Mann-Whitney rank sum and Kruskal-Wallis tests were used to test for associations between categorical and continuous variables, as all continuous variables were non-Gaussian. Pearson Chi-square test or Fisher Exact tests were used to determine if significant associations existed between categorical variables. Multiple logistic regression was used to model the association of maternal antenatal, postnatal, and long-term psychosocial risk factors with any LRTI and any severe/hospitalised LRTI episode in the first year of life adjusting for critical clinical and sociodemographic covariates. Directed acyclic graphs (DAGs) were used to identify the minimum set of confounding variables, which included sex, recruitment site, SES, maternal education achievement and HIV exposure (see Figs ​Figs11 and ​and2).2). Two sets of multiple regression models were run for each of the maternal psychosocial risk factors: the first set included the minimum set of confounder variables identified by the DAGs, and the second set included the confounding variables as well as additional variables (including mediators) based on prior literature: smoke exposure (maternal & infant urine cotinine results), indoor air pollution (assessed by PM10), weight for age z-score at birth, duration of exclusive breastfeeding and season of birth. [2, 23]. Season of birth was included to adjust for seasonality, as winter and autumn months are more commonly linked with LRTI episodes [27]. Each maternal psychosocial risk factor was considered in an individual model. In addition, antenatal and postnatal psychosocial risk factors were considered separately to estimate the association each of these exposures had on LRTI outcomes at different time points. The association of long-term psychosocial risk factor exposure on LRTI outcomes was also analysed; long-term exposure for each individual maternal psychosocial risk factor was defined as being above threshold for that psychosocial risk factor at two or more of the four time points considered in this analysis. Since LRTI episodes are more common in earlier months of age, stratified analyses by age were also constructed [43]. Four time points were considered: 0- 3months, 3–6 months, 6–9 months and 9–12 months of age. Stratifying by age presented an opportunity to consider temporality, particularly with postnatal psychosocial risk factors, as episodes after the exposure could be analysed. This analysis also provided an opportunity to determine if the exposure took place after the outcome (reverse causation). The stratified models adjusted for sex, recruitment site, HIV exposure, maternal education achievement, SES quartile, maternal urine cotinine (smoke exposure), PM10 exposure, weight for age z-score at birth, duration of breastfeeding, season of birth and LRTI in previous age period. Diagnostic checks were performed for all the multiple logistic regression models. These included checks for specification error, Hosmer and Lemeshow’s goodness of fit test, and checks for multicollinearity using the variance inflation factor (VIF). Influential observations were also considered using Pearson residuals, deviance residuals and leverage.