Mortality and Health Outcomes of HIV-Exposed and Unexposed Children in a PMTCT Cohort in Malawi

Abstract

BackgroundMortality and morbidity among HIV-exposed children are thought to be high in Malawi. We sought to determine mortality and health outcomes of HIV-exposed and unexposed infants within a PMTCT program.MethodData were collected as part of a retrospective cohort study in Zomba District, Malawi. HIV-infected mothers were identified via antenatal, delivery and postpartum records with a delivery date 18–20 months prior; the next registered HIV-uninfected mother was identified as a control. By interview and health record review, data on socio-demographic characteristics, service uptake, and health outcomes were collected. HIV-testing was offered to all exposed children.Results173 HIV-infected and 214 uninfected mothers were included. 4 stillbirths (1.0%) occurred; among the 383 livebirths, 41 (10.7%) children died by 20 months (32 (18.7%) HIV-exposed and 9 unexposed children (4.3%; p<0.0001)). Risk factors for child death included: HIV-exposure [adjOR2.9(95%CI 1.1–7.2)], low birthweight [adjOR2.5(1.0–6.3)], previous child death (adjOR25.1(6.5–97.5)] and maternal death [adjOR5.3(11.4–20.5)]. At 20 months, HIV-infected children had significantly poorer health outcomes than HIV-unexposed children and HIV-exposed but uninfected children (HIV-EU), including: hospital admissions, delayed development, undernutrition and restrictions in function (Lansky scale); no significant differences were seen between HIV-EU and HIV-unexposed children. Overall, no difference was seen at 20 months among HIV-infected, HIV-EU and HIV-unexposed groups in Z-scores (%<−2.0) for weight, height and BMI. Risk factors for poor functional health status at 20 months included: HIV-infection [adjOR8.9(2.4–32.6)], maternal illness [adjOR2.8(1.5–5.0)] and low birthweight [adjOR2.0(1.0–4.1)].ConclusionChild mortality remains high within this context and could be reduced through more effective PMTCT including prioritizing the treatment of maternal HIV infection to address the effect of maternal health and survival on infant health and survival. HIV-infected children demonstrated developmental delays, functional health and nutritional deficits that underscore the need for increased uptake of early infant diagnosis and institution of ART for all infected infants.

Maternal HIV infection is an important health determinant in non-HIV-infected infants

“…The risk of all-cause hospital admissions in the first 18 months of life was significantly higher in HEU children compared with HIV-unexposed children, which is consistent with the findings of previous studies conducted in the context of available antiretrovirals for PMTCT [7,9,32]. Diarrhea (loose or watery stools more than three times in 1 day according to ICD-10 coding system) was more frequent among HEU compared with HIV-unexposed children.…”

“…Direct or indirect HIV exposure in utero, intra partum or during breastfeeding may confer risks even in the absence of infection. Several studies have described increased mortality and enhanced risk of poor health and growth outcomes in HEU compared with HIV-unexposed children [4][5][6][7][8][9][10][11]. However, the nature of the vulnerability of the HEU children is not entirely clear.…”

Maternal Highly Active Antiretroviral Therapy and Child HIV-Free Survival in Malawi, 2004–2009

“…Assessment of the impact of maternal HAART on infant outcomes should thus consider the HIV-free survival endpoint. Furthermore, several reports indicate that HIV-exposed but uninfected children experience adverse outcomes at higher rates than HIV-unexposed children and that low maternal CD4 cell count during pregnancy is associated with higher mortality in HIV-exposed, uninfected children (13-16). …”

The aetiology of diarrhoea, pneumonia and respiratory colonization of HIV-exposed infants randomized to breast- or formula-feeding

“…[1][2][3] Mortality in HIV-infected and HIV-exposed but uninfected (HEU) infants is primarily caused by respiratory and diarrhoeal diseases. [4][5][6][7][8][9] However, the specific pathogens causing these infections are largely unknown because of barriers to diagnostic testing in resource-limited settings.…”