Untreated maternal HIV infection and poor perinatal outcomes

Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis.

Wedi CO, Kirtley S, Hopewell S, Corrigan R, Kennedy SH, Hemelaar J. Lancet HIV. 2016 Jan;3(1):e33-48. doi: 10.1016/S2352-3018(15)00207-6. Epub 2015 Nov 27.

Background: The HIV pandemic affects 36.9 million people worldwide, of whom 1.5 million are pregnant women. 91% of HIV-positive pregnant women reside in sub-Saharan Africa, a region that also has very poor perinatal outcomes. We aimed to establish whether untreated maternal HIV infection is associated with specific perinatal outcomes.

Methods: We did a systematic review and meta-analysis of the scientific literature by searching PubMed, CINAHL (Ebscohost), Global Health (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials and four clinical trial databases (WHO International Clinical Trials Registry Platform, the Pan African Clinical Trials Registry, the ClinicalTrials.gov database, and the ISRCTN Registry) for studies published from Jan 1, 1980, to Dec 7, 2014. Two authors independently reviewed the studies retrieved by the scientific literature search, identified relevant studies, and extracted the data. We investigated the associations between maternal HIV infection in women naive to antiretroviral therapy and 11 perinatal outcomes: preterm birth, very preterm birth, low birthweight, very low birthweight, term low birthweight, preterm low birthweight, small for gestational age, very small for gestational age, miscarriage, stillbirth, and neonatal death. We included prospective and retrospective cohort studies and case-control studies reporting perinatal outcomes in HIV-positive women naive to antiretroviral therapy and HIV-negative controls. We used a random-effects model for the meta-analyses of specific perinatal outcomes. We did subgroup and sensitivity analyses and assessed the effect of adjustment for confounders. This systematic review and meta-analysis is registered with PROSPERO, number CRD42013005638.

Findings: Of 60 750 studies identified, we obtained data from 35 studies (20 prospective cohort studies, 12 retrospective cohort studies, and three case-control studies) including 53 623 women. Our meta-analyses of prospective cohort studies show that maternal HIV infection is associated with an increased risk of preterm birth (relative risk 1.50, 95% CI 1.24-1.82), low birthweight (1.62, 1.41-1.86), small for gestational age (1.31, 1.14-1.51), and stillbirth (1.67, 1.05-2.66). Retrospective cohort studies also suggest an increased risk of term low birthweight (2.62, 1.15-5.93) and preterm low birthweight (3.25, 2.12-4.99). The strongest and most consistent evidence for these associations is identified in sub-Saharan Africa. No association was identified between maternal HIV infection and very preterm birth, very small for gestational age, very low birthweight, miscarriage, or neonatal death, although few data were available for these outcomes. Correction for confounders did not affect the significance of these findings.

Interpretation: Maternal HIV infection in women who have not received antiretroviral therapy is associated with preterm birth, low birthweight, small for gestational age, and stillbirth, especially in sub-Saharan Africa. Research is needed to assess how antiretroviral therapy regimens affect these perinatal outcomes.

Abstract access  [1]

Editor’s notes:  Maternal HIV infection is associated with maternal morbidity and mortality and risk of mother-to-child transmission of HIV. Whether maternal HIV infection affects perinatal outcomes, which are major contributors to poor health worldwide, is less well understood. This systematic review and meta-analysis of retrospective and prospective cohort studies and case-control studies demonstrates that untreated maternal HIV infection is associated with increased risk of pre-term birth, low birthweight, small for gestational age and stillbirth. The risk of adverse perinatal outcomes appeared to increase with more advanced HIV disease, although only three of the 35 studies reported perinatal outcomes according to HIV disease stage. These findings persisted even after controlling for potential confounding factors and irrespective of the method used for determining gestational age. None of the studies used a first trimester ultrasound scan, the gold standard for determining gestational age. The association of perinatal outcomes with the infant’s HIV status was not investigated. The strongest evidence for these associations was found in sub-Saharan Africa, where the majority of the studies were conducted.

These findings suggest that HIV is an important contributor to the global burden of perinatal and child morbidity and mortality particularly in countries with the highest burden of maternal HIV infection.     Sub-Saharan Africa has the highest rates of stillbirths and neonatal deaths and is also the region where more than 90% of the world’s pregnant women living with HIV reside.

This study has important implications. Firstly, the coverage of antiretroviral therapy (ART) among pregnant women worldwide still remains suboptimal (estimated to be 68% in 2013), exposing women living with untreated HIV to an increased risk of adverse perinatal outcomes. The biological mechanisms underlying adverse perinatal outcomes in the context of HIV infection are not understood. ART in pregnancy may also adversely affect perinatal outcomes, and there is a pressing need to investigate this as ART is rapidly scaled up.     

Africa [5], Europe [6], Northern America [7]
Côte d'Ivoire [8], Haiti [9], India [10], Italy [11], Kenya [12], Malawi [13], Mozambique [14], Nigeria [15], Republic of the Congo [16], Rwanda [17], South Africa [18], Thailand [19], Uganda [20], United Kingdom [21], United Republic of Tanzania [22], United States of America [23], Zimbabwe [24]
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