Abstract

Preterm birth is the leading cause of neonatal and child mortality worldwide. Globally, 1.4 million pregnant women are estimated to be living with HIV/AIDS, the majority of whom live in sub-Saharan Africa. Maternal HIV infection and antiretroviral treatment (ART) have been associated with increased rates of preterm birth, but the underlying mechanisms remain unknown. Acute HIV infection is associated with a rapid depletion of all three subsets of innate lymphoid cells (ILCs), ILC1s, ILC2s and ILC3s, which is not reversed by ART. ILCs have been found at the maternal–fetal interface and we therefore investigated the potential association between maternal HIV infection, peripheral ILC frequencies and preterm birth. In our study of pregnant South African women with accurately dated pregnancies, we show that maternal HIV infection is associated with reduced levels of all three ILC subsets. Preterm birth was also associated with lower levels of all three ILC subsets in early pregnancy. ILC frequencies were lowest in HIV positive women who experienced preterm birth. Moreover, ILC levels were reduced in pregnancies resulting in spontaneous onset of preterm labour and in extreme preterm birth (< 28 weeks gestation). Our findings suggest that reduced ILC frequencies may be a link between maternal HIV infection and preterm birth. In addition, ILC frequencies in early pregnancy may serve as predictive biomarkers for women who are at risk of delivering preterm.

Highlights

  • Preterm birth is the leading cause of neonatal and child mortality worldwide

  • In line with previous reports in non-pregnant ­individuals[16,21,23,24], we demonstrate that the frequencies of ILC1, ILC2 and ILC3 cells are reduced in pregnant HIV+ women compared to HIV− women

  • HIV+ women were older than HIV− women, there is no significant association between maternal age and innate lymphoid cells (ILCs) frequencies in our data set

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Summary

Introduction

Preterm birth is the leading cause of neonatal and child mortality worldwide. Globally, 1.4 million pregnant women are estimated to be living with HIV/AIDS, the majority of whom live in sub-Saharan Africa. In our study of pregnant South African women with accurately dated pregnancies, we show that maternal HIV infection is associated with reduced levels of all three ILC subsets. Preterm birth (PTB) is the leading cause of neonatal and child mortality, accounting for approximately 18% of deaths in ­20161 In those infants who survive, PTB is associated with an increased risk of short- and longterm ­morbidities[2]. ILCs are enriched in tissues, at mucosal surfaces e.g. of the intestines, lungs, uterus and skin but are found in lower frequencies in the peripheral b­ lood[17] Their location at barrier surfaces aids their role as early responders during an immune response, they are involved in a number of ­immunopathologies[19]

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