Mortality Risk and Associated Factors in HIV-exposed, Uninfected Children

Overview

Journal Trop Med Int Health

Specialties Public Health
Tropical Medicine

Date 2016 Apr 20

PMID 27091659

Citations 25

Authors

Shino Arikawa

Nigel Rollins

Marie-Louise Newell

Renaud Becquet

Affiliations

Soon will be listed here.

Abstract

Objective: With increasing maternal antiretroviral treatment (ART), the number of children newly infected with HIV has declined. However, the possible increased mortality in the large number of HIV-exposed, uninfected (HEU) children may be of concern. We quantified mortality risks among HEU children and reviewed associated factors.

Methods: Systematic search of electronic databases (PubMed, Scopus). We included all studies reporting mortality of HEU children to age 60 months and associated factors. Relative risk of mortality between HEU and HIV-unexposed, uninfected (HUU) children was extracted where relevant. Inverse variance methods were used to adjust for study size. Random-effects models were fitted to obtain pooled estimates.

Results: A total of 14 studies were included in the meta-analysis and 13 in the review of associated factors. The pooled cumulative mortality in HEU children was 5.5% (95% CI: 4.0-7.2; I(2) = 94%) at 12 months (11 studies) and 11.0% (95% CI: 7.6-15.0; I(2) = 93%) at 24 months (four studies). The pooled risk ratios for the mortality in HEU children compared to HUU children in the same setting were 1.9 (95% CI: 0.9-3.8; I(2) = 93%) at 12 months (four studies) and 2.4 (95% CI: 1.1-5.1; I(2) = 93%) at 24 months (three studies).

Conclusion: Compared to HUU children, mortality risk in HEU children was about double at both age points, although the association was not statistically significant at 12 months. Interpretation of the pooled estimates is confounded by considerable heterogeneity between studies. Further research is needed to characterise the impact of maternal death and breastfeeding on the survival of HEU infants in the context of maternal ART, where current evidence is limited.

Citing Articles

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References

Shapiro R, Lockman S, Kim S, Smeaton L, Rahkola J, Thior I . Infant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and HIV-uninfected women in Botswana. J Infect Dis. 2007; 196(4):562-9. DOI: 10.1086/519847. View

Jones C, Naidoo S, De Beer C, Esser M, Kampmann B, Hesseling A . Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. JAMA. 2011; 305(6):576-84. DOI: 10.1001/jama.2011.100. View

Chopra M, Doherty T, Goga A, Jackson D, Persson L . Survival of infants in the context of prevention of mother to child HIV transmission in South Africa. Acta Paediatr. 2010; 99(5):694-698. DOI: 10.1111/j.1651-2227.2009.01675.x. View

Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, Scott N . Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants?. Clin Infect Dis. 2005; 41(11):1654-61. PMC: 1351118. DOI: 10.1086/498029. View

Chilongozi D, Wang L, Brown L, Taha T, Valentine M, Emel L . Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania. Pediatr Infect Dis J. 2008; 27(9):808-14. PMC: 2739309. DOI: 10.1097/INF.0b013e31817109a4. View

Guyatt G, Oxman A, Montori V, Vist G, Kunz R, Brozek J . GRADE guidelines: 5. Rating the quality of evidence--publication bias. J Clin Epidemiol. 2011; 64(12):1277-82. DOI: 10.1016/j.jclinepi.2011.01.011. View

Becquet R, Bequet L, Ekouevi D, Viho I, Sakarovitch C, Fassinou P . Two-year morbidity-mortality and alternatives to prolonged breast-feeding among children born to HIV-infected mothers in Côte d'Ivoire. PLoS Med. 2007; 4(1):e17. PMC: 1769413. DOI: 10.1371/journal.pmed.0040017. View

Singh H, Gupte N, Kinikar A, Bharadwaj R, Sastry J, Suryavanshi N . High rates of all-cause and gastroenteritis-related hospitalization morbidity and mortality among HIV-exposed Indian infants. BMC Infect Dis. 2011; 11:193. PMC: 3161884. DOI: 10.1186/1471-2334-11-193. View

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

10.

Kuhn L, Sinkala M, Semrau K, Kankasa C, Kasonde P, Mwiya M . Elevations in mortality associated with weaning persist into the second year of life among uninfected children born to HIV-infected mothers. Clin Infect Dis. 2010; 50(3):437-44. PMC: 2805776. DOI: 10.1086/649886. View

11.

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

12.

Cournil A, De Vincenzi I, Gaillard P, Cames C, Fao P, Luchters S . Relationship between mortality and feeding modality among children born to HIV-infected mothers in a research setting: the Kesho Bora study. AIDS. 2012; 27(10):1621-30. DOI: 10.1097/QAD.0b013e32835d5226. View

13.

Rollins N, Ndirangu J, Bland R, Coutsoudis A, Coovadia H, Newell M . Exclusive breastfeeding, diarrhoeal morbidity and all-cause mortality in infants of HIV-infected and HIV uninfected mothers: an intervention cohort study in KwaZulu Natal, South Africa. PLoS One. 2013; 8(12):e81307. PMC: 3846835. DOI: 10.1371/journal.pone.0081307. View

14.

Bork K, Cournil A, Read J, Newell M, Cames C, Meda N . Morbidity in relation to feeding mode in African HIV-exposed, uninfected infants during the first 6 mo of life: the Kesho Bora study. Am J Clin Nutr. 2014; 100(6):1559-68. PMC: 4232020. DOI: 10.3945/ajcn.113.082149. View

15.

Kafulafula G, Hoover D, Taha T, Thigpen M, Li Q, Fowler M . Frequency of gastroenteritis and gastroenteritis-associated mortality with early weaning in HIV-1-uninfected children born to HIV-infected women in Malawi. J Acquir Immune Defic Syndr. 2009; 53(1):6-13. DOI: 10.1097/QAI.0b013e3181bd5a47. View

16.

Munyagwa M, Baisley K, Levin J, Brian M, Grosskurth H, Maher D . Mortality of HIV-infected and uninfected children in a longitudinal cohort in rural south-west Uganda during 8 years of follow-up. Trop Med Int Health. 2012; 17(7):836-43. DOI: 10.1111/j.1365-3156.2012.03000.x. View

17.

Marinda E, Humphrey J, Iliff P, Mutasa K, Nathoo K, Piwoz E . Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr Infect Dis J. 2007; 26(6):519-26. DOI: 10.1097/01.inf.0000264527.69954.4c. View

18.

Mofenson L . Editorial commentary: New challenges in the elimination of pediatric HIV infection: the expanding population of HIV-exposed but uninfected children. Clin Infect Dis. 2015; 60(9):1357-60. DOI: 10.1093/cid/civ064. View

19.

Chatterjee A, Bosch R, Hunter D, Fataki M, Msamanga G, Fawzi W . Maternal disease stage and child undernutrition in relation to mortality among children born to HIV-infected women in Tanzania. J Acquir Immune Defic Syndr. 2007; 46(5):599-606. DOI: 10.1097/QAI.0b013e31815a5703. View

20.

Marquez C, Okiring J, Chamie G, Ruel T, Achan J, Kakuru A . Increased morbidity in early childhood among HIV-exposed uninfected children in Uganda is associated with breastfeeding duration. J Trop Pediatr. 2014; 60(6):434-41. PMC: 4303769. DOI: 10.1093/tropej/fmu045. View