Effects of HIV infection on maternal and neonatal health in southern Mozambique: A prospective cohort study after a decade of antiretroviral drugs roll out

Raquel González, María Rupérez, Esperança Sevene, Anifa Vala, Sónia Maculuve, Helder Bulo, Arsénio Nhacolo, Alfredo Mayor, John J Aponte, Eusébio Macete, Clara Menendez, Raquel González, María Rupérez, Esperança Sevene, Anifa Vala, Sónia Maculuve, Helder Bulo, Arsénio Nhacolo, Alfredo Mayor, John J Aponte, Eusébio Macete, Clara Menendez

Abstract

Introduction: The HIV epidemic is concentrated in sub-Saharan Africa. However, limited information exists on its impact on women and infant's health since the introduction of antiretroviral drugs in this region, where health resources are often scarce.

Methods: The effect of HIV infection on maternal health, birth outcomes and infant health was analysed in two contemporary cohorts of HIV-uninfected and HIV-infected pregnant women from southern Mozambique. Pregnant women attending the first antenatal care visit were followed until one month after delivery. Antiretroviral therapy was administered based on CD4+T cell count and clinical stage. Maternal and neonatal morbidity and mortality, as well as pregnancy outcomes were assessed by mother's HIV status.

Results: A total of 1183 HIV-uninfected and 561 HIV-infected pregnant women were enrolled. HIV-infected women were more likely to have anaemia both at the first antenatal care visit and at delivery than HIV-uninfected women (71.5% versus 54.8% and 49.4% versus 40.6%, respectively, p<0.001). Incidence of hospital admissions during pregnancy was increased among HIV-infected women (RR, 2.04, [95%CI, 1.45; 2.86]; p<0.001). At delivery, 21% of HIV-infected women reported being on antiretroviral therapy, and 70% having received antiretroviral drugs for prevention of mother to child transmission of HIV. The risk of stillbirths was doubled in HIV-infected women (RR, 2.16 [95%CI 1.17; 3.96], p = 0.013). Foetal anaemia was also increased among infants born to HIV-infected women (10.6% versus 7.3%, p = 0.022). No differences were found in mean birth weight, malaria, prematurity and maternal and neonatal deaths between groups.

Conclusions: HIV infection continues to be associated with significant maternal morbidity and poor neonatal health outcomes. Efforts should urgently be made to identify the barriers that impede improvements on the devastating effects of HIV in African women and their infants.

Trial registration: ClinicalTrials.gov NCT 00811421.

Trial registration: ClinicalTrials.gov NCT00811421.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Study flow.
Fig 1. Study flow.

References

    1. UNAIDS. HIV/AIDS Fact Sheet 2015. UNAIDS; 2015;Available at: [accessed May 2016].
    1. Zaba B, Calvert C, Marston M, Isingo R, Nakiyingi-Miiro J, Lutalo T, et al. Effect of HIV infection on pregnancy-related mortality in sub-Saharan Africa: secondary analyses of pooled community-based data from the network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA). Lancet. 2013;381(9879):1763–71. Epub 2013/05/21. PubMed Central PMCID: PMCPMC4325135. doi:
    1. UNAIDS. AIDS by the numbers UNAIDS; 2013;JC2571/1/E.
    1. Boyer S, Koulla-Shiro S, Abe C, Spire B, Moatti JP. Implementing operational research to scale-up access to antiretroviral therapy for HIV infection: lessons learned from the Cameroonian experience. Curr Opin HIV AIDS. 2011;6(4):239–44. Epub 2011/05/04. doi:
    1. Wedi CO, Kirtley S, Hopewell S, Corrigan R, Kennedy SH, Hemelaar J. Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis. The lancet HIV. 2016;3(1):e33–48. Epub 2016/01/15. doi:
    1. WHO. Born to soon: the global action report on preterm birth [Internet]. 2012;Available at: [accessed March 2017].
    1. Lee AC, Katz J, Blencowe H, Cousens S, Kozuki N, Vogel JP, et al. National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010. The Lancet Global health. 2013;1(1):e26–36. Epub 2014/08/12. PubMed Central PMCID: PMCPMC4221634. doi:
    1. Lopez M, Palacio M, Gonce A, Hernandez S, Barranco FJ, Garcia L, et al. Risk of intrauterine growth restriction among HIV-infected pregnant women: a cohort study. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2015;34(2):223–30. Epub 2014/08/12.
    1. Braddick MR, Kreiss JK, Embree JB, Datta P, Ndinya-Achola JO, Pamba H, et al. Impact of maternal HIV infection on obstetrical and early neonatal outcome. AIDS (London, England). 1990;4(10):1001–5. Epub 1990/10/01.
    1. Temmerman M, Plummer FA, Mirza NB, Ndinya-Achola JO, Wamola IA, Nagelkerke N, et al. Infection with HIV as a risk factor for adverse obstetrical outcome. AIDS. 1990;4(11):1087–93. Epub 1990/11/01.
    1. Rollins NC, Coovadia HM, Bland RM, Coutsoudis A, Bennish ML, Patel D, et al. Pregnancy outcomes in HIV-infected and uninfected women in rural and urban South Africa. J Acquir Immune Defic Syndr. 2007;44(3):321–8. Epub 2007/01/02. doi:
    1. Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet. 2004;364(9441):1236–43. Epub 2004/10/07. doi:
    1. Naniche D, Bardaji A, Lahuerta M, Berenguera A, Mandomando I, Sanz S, et al. Impact of maternal human immunodeficiency virus infection on birth outcomes and infant survival in rural Mozambique. Am J Trop Med Hyg. 2009;80(5):870–6.
    1. Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, Scott N, et al. Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants? Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2005;41(11):1654–61. Epub 2005/11/04. PubMed Central PMCID: PMCPMC1351118.
    1. Brocklehurst P, French R. The association between maternal HIV infection and perinatal outcome: a systematic review of the literature and meta-analysis. Br J Obstet Gynaecol. 1998;105(8):836–48. Epub 1998/09/24.
    1. Uneke CJ, Ogbonna A. Malaria and HIV co-infection in pregnancy in sub-Saharan Africa: impact of treatment using antimalarial and antiretroviral agents. Trans R Soc Trop Med Hyg. 2009;103(8):761–7. doi:
    1. UNAIDS. Mozambique HIV and AIDS estimates (2015) 2015;Available at [accessed January 2017].
    1. Instituto-Nacional-de-Saúde., Instituto-Nacional-de-Estatística., ICF-Macro. Inquérito Nacional de Prevalência, Riscos Comportamentais e Informaçao sobre o HIV e SIDA em Moçambique 2009. Calverton, Maryland, EUA:INS,INE e ICF Macro; 2010.
    1. Gonzalez R, Munguambe K, Aponte J, Bavo C, Nhalungo D, Macete E, et al. High HIV prevalence in a southern semi-rural area of Mozambique: a community-based survey. HIV Med. 2012;13(10):581–8. Epub 2012/04/17. doi:
    1. Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, et al. Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg. 2005;73(1):191–8.
    1. WHO. Consolidated Guidelines on The Use of Antiretroviral Drugs for Treating And Preventing HIV infection. WHO; 2013;Available at: [accessed May 2016].
    1. Hog E. HIV scale-up in Mozambique: exceptionalism, normalisation and global health. Global public health. 2014;9(1–2):210–23. Epub 2014/02/07. PubMed Central PMCID: PMCPMC4066904. doi:
    1. Sacoor C, Nhacolo A, Nhalungo D, Aponte JJ, Bassat Q, Augusto O, et al. Profile: Manhica Health Research Centre (Manhica HDSS). International journal of epidemiology. 2013;42(5):1309–18. Epub 2013/10/26. doi:
    1. WHO. Interim WHO Clinical Staging of HIV/AIDS and HIV/AIDS Case definitions for surveillance. WHO African Region; 2005;Available at [accessed February 2015].
    1. Gonzalez R, Desai M, Macete E, Ouma P, Kakolwa MA, Abdulla S, et al. Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial. PLoS Med. 2014;11(9):e1001735 Epub 2014/09/24. doi:
    1. Gonzalez R, Mombo-Ngoma G, Ouedraogo S, Kakolwa MA, Abdulla S, Accrombessi M, et al. Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial. PLoS Med. 2014;11(9):e1001733 Epub 2014/09/24. doi:
    1. Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, et al. Comparison of methods for the rapid laboratory assessment of children with malaria. Am J Trop Med Hyg. 2001;65(5):599–602. Epub 2001/11/22.
    1. Swysen C, Vekemans J, Bruls M, Oyakhirome S, Drakeley C, Kremsner P, et al. Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine. Malaria journal. 2011;10:223 Epub 2011/08/06. PubMed Central PMCID: PMCPMC3220650. doi:
    1. Alonso PL, Smith T, Schellenberg JR, Masanja H, Mwankusye S, Urassa H, et al. Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet. 1994;344(8931):1175–81. Epub 1994/10/29.
    1. Ordi J, Ismail MR, Ventura PJ, Kahigwa E, Hirt R, Cardesa A, et al. Massive chronic intervillositis of the placenta associated with malaria infection. Am J Surg Pathol. 1998;22(8):1006–11. Epub 1998/08/26.
    1. Rogerson SJ, Mkundika P, Kanjala MK. Diagnosis of Plasmodium falciparum malaria at delivery: comparison of blood film preparation methods and of blood films with histology. J Clin Microbiol. 2003;41(4):1370–4. Epub 2003/04/19. PubMed Central PMCID: PMCPMC153918. doi:
    1. Menendez C, Romagosa C, Ismail MR, Carrilho C, Saute F, Osman N, et al. An autopsy study of maternal mortality in Mozambique: the contribution of infectious diseases. PLoS Med. 2008;5(2):e44 doi:
    1. Tobin J. Estimation of relationships for limited dependent variables. Econometrica. 1958;26:24–36.
    1. Wooldridge JM. Introductory Econometrics: A Modern Approach. 5th ed. Mason, OH (USA): South-Western Cengage Learning; 2013.
    1. WHO. WHO child growth standards and the identification of severe acute malnutrition in infants and children WHO; [Internet]. 2009 March 2016:[Available at [accessed March 2017] p.].
    1. Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159(7):702–6. Epub 2004/03/23.
    1. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC pediatrics. 2013;13:59 Epub 2013/04/23. PubMed Central PMCID: PMCPMC3637477. doi:
    1. Antelman G, Msamanga GI, Spiegelman D, Urassa EJ, Narh R, Hunter DJ, et al. Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania. J Nutr. 2000;130(8):1950–7. Epub 2000/08/05.
    1. Belperio PS, Rhew DC. Prevalence and outcomes of anemia in individuals with human immunodeficiency virus: a systematic review of the literature. The American journal of medicine. 2004;116 Suppl 7A:27S–43S. Epub 2004/03/31.
    1. Dairo MD, Lawoyin TO, Onadeko MO, Asekun-Olarinmoye EO, Adeniji AO. HIV as an additional risk factors for anaemia in pregnancy: evidence from primary care level in Ibadan, Southwestern Nigeria. African journal of medicine and medical sciences. 2005;34(3):275–9. Epub 2006/06/06.
    1. Ramon R, Sawadogo D, Koko FS, Noba V, Likikouet R, Gourvellec G, et al. Haematological characteristics and HIV status of pregnant women in Abidjan, Cote d'Ivoire, 1995–96. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1999;93(4):419–22. Epub 2000/02/16.
    1. Meda N, Dao B, Ouangre A. HIV, maternal anemia and perinatal intervention using zidovudine. DITRAME Study Group (ANRS 049 Clinical Trial). International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 1998;61(1):65–6. Epub 1998/06/11.
    1. McDermott JM, Slutsker L, Steketee RW, Wirima JJ, Breman JG, Heymann DL. Prospective assessment of mortality among a cohort of pregnant women in rural Malawi. Am J Trop Med Hyg. 1996;55(1 Suppl):66–70. Epub 1996/01/01.
    1. Nandlal V, Moodley D, Grobler A, Bagratee J, Maharaj NR, Richardson P. Anaemia in pregnancy is associated with advanced HIV disease. PLoS One. 2014;9(9):e106103 Epub 2014/09/16. PubMed Central PMCID: PMCPMC4164466. doi:
    1. WHO. Global nutrition targets 2025: anaemia policy brief World Health Organization; 2014;Available at: [accessed May 2016]((WHO/NMH/NHD/14.4)):Geneva.
    1. De Sa SA, Willner E, Duraes Pereira TA, De Souza VR, Teles Boaventura G, Blondet de Azeredo V. Anemia in pregnancy: impact on weight and in the development of anemia in newborn. Nutricion hospitalaria. 2015;32(n05):2071–9. Epub 2015/11/08.
    1. Laar AK, Grant FE, Addo Y, Soyiri I, Nkansah B, Abugri J, et al. Predictors of fetal anemia and cord blood malaria parasitemia among newborns of HIV-positive mothers. BMC research notes. 2013;6:350 Epub 2013/09/07. PubMed Central PMCID: PMCPMC3844504. doi:
    1. Ahmed M, Abdullatif M. Fetomaternal transfusion as a cause of severe fetal anemia causing early neonatal death: a case report. Oman medical journal. 2011;26(6):444–6. Epub 2012/01/19. PubMed Central PMCID: PMCPMC3251192. doi:
    1. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutrition reviews. 2006;64(5 Pt 2):S34–43; discussion S72-91. Epub 2006/06/15. PubMed Central PMCID: PMCPMC1540447.
    1. Langston C, Lewis DE, Hammill HA, Popek EJ, Kozinetz CA, Kline MW, et al. Excess intrauterine fetal demise associated with maternal human immunodeficiency virus infection. The Journal of infectious diseases. 1995;172(6):1451–60. Epub 1995/12/01.
    1. WHO. HIV in Pregnancy: a review. WHO UNAIDS; 1998;Available at: [accessed March 2015].
    1. Moraleda C, de Deus N, Serna-Bolea C, Renom M, Quinto L, Macete E, et al. Impact of HIV Exposure on Health Outcomes in HIV-Negative Infants Born to HIV-Positive Mothers in Sub-Saharan Africa. J Acquir Immune Defic Syndr. 2014;65(2):182–9. Epub 2014/01/21. doi:
    1. Menendez C, Ordi J, Ismail MR, Ventura PJ, Aponte JJ, Kahigwa E, et al. The impact of placental malaria on gestational age and birth weight. J Infect Dis. 2000;181(5):1740–5. Epub 2000/05/24. doi:
    1. Siza JE. Risk factors associated with low birth weight of neonates among pregnant women attending a referral hospital in northern Tanzania. Tanzania journal of health research. 2008;10(1):1–8. Epub 2008/08/07.
    1. Valero De Bernabe J, Soriano T, Albaladejo R, Juarranz M, Calle ME, Martinez D, et al. Risk factors for low birth weight: a review. European journal of obstetrics, gynecology, and reproductive biology. 2004;116(1):3–15. Epub 2004/08/06. doi:
    1. Sappenfield E, Jamieson DJ, Kourtis AP. Pregnancy and susceptibility to infectious diseases. Infectious diseases in obstetrics and gynecology. 2013;2013:752852 PubMed Central PMCID: PMC3723080. doi:
    1. Ladner J, Leroy V, Simonon A, Karita E, Bogaerts J, De Clercq A, et al. HIV infection, malaria, and pregnancy: a prospective cohort study in Kigali, Rwanda. Am J Trop Med Hyg. 2002;66(1):56–60.
    1. Steketee RW, Wirima JJ, Bloland PB, Chilima B, Mermin JH, Chitsulo L, et al. Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1. Am J Trop Med Hyg. 1996;55(1 Suppl):42–9.
    1. van Eijk AM, Ayisi JG, ter Kuile FO, Misore AO, Otieno JA, Rosen DH, et al. HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya. AIDS. 2003;17(4):595–603. Epub 2003/02/25. doi:
    1. Menendez C, Bardaji A, Sigauque B, Romagosa C, Sanz S, Serra-Casas E, et al. A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic. PLoS One. 2008;3(4):e1934 doi:
    1. Ticconi C, Mapfumo M, Dorrucci M, Naha N, Tarira E, Pietropolli A, et al. Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe. Journal of acquired immune deficiency syndromes (1999). 2003;34(3):289–94. Epub 2003/11/06.
    1. Brahmbhatt H, Sullivan D, Kigozi G, Askin F, Wabwire-Mangenm F, Serwadda D, et al. Association of HIV and malaria with mother-to-child transmission, birth outcomes, and child mortality. J Acquir Immune Defic Syndr. 2008;47(4):472–6. doi:
    1. Kendall T, Danel I, Cooper D, Dilmitis S, Kaida A, Kourtis AP, et al. Eliminating preventable HIV-related maternal mortality in sub-Saharan Africa: what do we need to know? J Acquir Immune Defic Syndr. 2014;67 Suppl 4:S250–8. Epub 2014/12/02. PubMed Central PMCID: PMCPMC4251907.
    1. Myer L. Maternal deaths and HIV treatment in sub-Saharan Africa. Lancet. 2013;381(9879):1699–700. Epub 2013/05/21. doi:
    1. Naniche D, Lahuerta M, Bardaji A, Sigauque B, Romagosa C, Berenguera A, et al. Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria. HIV Med. 2008;9(9):757–64. doi:
    1. WHO. Consolidated guidelines on the Use of Antiretroviral Drugs for treating and Preventing HIV infection. Recommendations for a public health approach. WHO; 2013;ISBN 978 92 4 150572 7.
    1. Namusoke F, Ntale M, Wahlgren M, Kironde F, Mirembe F. Validity of self-reported use of sulphadoxine-pyrimethamine intermittent presumptive treatment during pregnancy (IPTp): a cross-sectional study. Malar J. 2012;11:310 Epub 2012/09/07. PubMed Central PMCID: PMCPMC3457910. doi:
    1. WHO. Guideline on When to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV. WHO; 2015;Available at [accessed October 2015].

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel