Pregnancy rate and birth outcomes among women receiving antiretroviral therapy in Burkina Faso: a retrospective cohort study

Pregnancy rate and birth outcomes among women receiving antiretroviral therapy in Burkina Faso: a retrospective cohort study

Armel Poda^1,2,&, Arsène Hema¹, Aina Konaté¹, Firmin Kaboré¹, Jacques Zoungrana¹, Euloges Kamboulé¹, Ibrahim Soré¹, Guillaume Bado¹, Abdoul-Salam Ouédraogo^2,3, Macaire Ouédraogo^2,4, Nicolas Meda^5,6, Adrien Bruno Sawadogo^1,5

¹Hôpital de Jour, Service des Maladies Infectieuses, CHU Souro Sanou, Bobo Dioulasso, Burkina Faso, ²Institut Supérieur des Sciences de la Santé (INSSA), Université Polytechnique de Bobo Dioulasso (UPB), Bobo Dioulasso, Burkina Faso, ³Service de Bactériologie Virologie, CHU Souro Sanou, Bobo Dioulasso, Burkina Faso, ⁴Service de Médecine Interne, CHU Souro Sanou, Bobo Dioulasso, Burkina Faso, ⁵Unité de Formation et de Recherche en Sciences de la Santé, Université de Ouagadougou, Ouagadougou, Burkina Faso, ⁶Centre Muraz, Bobo Dioulasso, Burkina Faso

^&Corresponding author
Armel Poda, Hôpital de Jour, Service des Maladies Infectieuses, CHU Souro Sanou, Bobo Dioulasso, Burkina Faso

Introduction    

Sub-Saharan Africa is the most HIV affected area, with women as the most vulnerable population. Indeed, 58% of people living with HIV/AIDS (PLWHA) in Sub-Saharan Africa was women of childbearing age [1]. Improving life expectancy and quality for PLWHA on antiretroviral therapy (ART) increases their desire for bearing children [2-7] even though HIV infection is associated with a 25 to 40% decrease in fertility among women of childbearing age [8-10]. Pregnancy is not likely to influence the progression of the infection [11]. Additionally, as long as the mother is in good health, HIV does not impact the course of the pregnancy [12]. The risks of complications are higher for the mother and her fetus when mother develops an HIV-related opportunistic disease and when the CD4 cells count is below 200/µl [13]. Miscarriages, abortions, ectopic pregnancies and stillborns delivery seem to be as recurrent among HIV positive women (some of whom were under ART) as among non infected women [8, 14-16]. According to the UNAIDS Report on Global AIDS Epidemic, 60% of HIV-infected people in Burkina Faso are women of childbearing age [17]. Besides, the desire for bearing children is quite high among women in general in Burkina Faso including HIV infected women [18]. However, there are little data on the frequency of pregnancies among HIV-infected women under antiretroviral treatment. We therefore deemed it necessary to study the incidence and outcome of pregnancies in Bobo-Dioulasso Day Hospital cohort. Knowing the status of women under ART who get pregnant will help provide appropriate care to countries with limited resources.

Methods     

Framework and period of the study : the study was conducted from January 1st, 2005 to June 30, 2011 at the Souro Sanou Teaching Hospital, Bobo-Dioulasso, a public referral hospital in Burkina Faso offering outpatient care services to people living with HIV [19].

Type of study : this is a retrospective cohort study.

Targeted population: patients targeted in the study include non pregnant women of childbearing age (18- 49 years) under antiretroviral treatment between January 2005 and December 2010. They were followed up until June 30, 2011 (reference date).

Data collection: data for the follow up of people living with HIV were collected at Bobo-Dioulasso day hospital using the ESOPE software that was regularly filled in by doctors during medical visits. The socio-demographic, biological and therapeutic data of the study were taken from ESOPE database. For the diagnosis of pregnancies, immunologic tests (BBtestR) were conducted at the beginning of the antiretroviral treatment and at the occurrence of amenorrhea during the follow up. Positive pregnancy tests were confirmed by pelvic scan. Pregnancy development and outcome-related data were collected from patients' antenatal care records. Childbirth was defined by the expulsion of a fetus after 22 weeks of amenorrhea. Before this term, it is an abortion. Childbirth is said premature if it occurs before 37 weeks of gestation, to term if it occurs between the 38th and the 42nd week.

Data analysis: the data collected were analyzed using STATA version 12. A description of the socio-demographic, biological and clinical characteristics of the survey population was made. Common statistics including the median and inter quartile range (IQR) and percentages (%) were used to describe the survey population. The exact Fischer test was used to compare proportions, while Student t test served to compare continuous variables. The pregnancy incidence was estimated from the number of pregnancies based on the sum of observation periods for each patient. Only the first pregnancies under ART were considered in calculating the incidence. The pregnancy occurrence risk according to the ART time was estimated using the Kaplan Meier method. The outcome of pregnancies was described. The fertility rate in terms of number of live births for 1,000 women was estimated in the survey population. The annual age-standardized rates (indirect standardization) were calculated using the baseline population from the 2010 demographic and health survey (DHS) in Burkina Faso [10]. The agreed significance threshold was 5% for all analyses.

Ethical considerations: this observational study was conducted as part of the routine care services and therefore presented no risk to patients. For confidentiality purposes, the data collected were made anonymous.

Results     

Socio-demographic characteristics of the survey population : on December 31st, 2010 a total number of 2,717 patients including 74.0% women were under antiretroviral treatment. Between January 2005 and December 2010, a total of 1,763 women of childbearing age under ART were included in the cohort survey. They were aged between 18 and 48 years with a median age of 35 years (IQR: 30-40). Almost half of the patients (49.0%) were aged between 30 and 39. Table 1 summarizes the socio-demographic characteristics of the patients. They were mainly uneducated (42.5%; n=749), unemployed (75.7%; n=1334), almost 44.6% (n=787) living as a couple. The average number of children per woman was 2 (IQR: 2-3) with 0 and 9 children as the extremes. More than half of the women (52%; n=919) had at least two children.

Biological and therapeutic characteristics : HIV-1 infection and combined HIV-1+2 infection respectively represented 94.2% and 4.0% of cases. At the beginning of the antiretroviral combined therapy, the median of CD4 cell count was 126 c/µl (IQR: 70-213 cells/µl); with extremes (1- 412 cells/µl); more than two-thirds (70.7%; n=1,246) of patients had less than 200 CD4 cells count. The combination of two nucleoside reverse transcriptase inhibitors (NRTI) plus one non-nucleoside inhibitor of reverse transcriptase (NNRTI) was prescribed as first line therapy in 85.7% of cases and 2 NRTI+1 PI (protease inhibitor) in 14.2% of cases. Nevirapine was the most commonly prescribed (54.1%) medication. Out of the 1,763 women of childbearing age, 558 (31.6%) were under ART which includes Efavirenz. The average duration of the follow up period was 29 months (IQR: 13-48 months) with extremes (1 - 74 months).

Incidence of pregnancies in the cohort : throughout the study, 222 pregnancies were observed among 1,763 women, with a follow-up of 4,639 women-years, corresponding to an incidence density of 5 pregnancies for 100 women-years (IC 95%: 4, 2-5, 5). The median time between the beginning of the ART and the occurrence of the pregnancy was 19 months (IQR: 9-36 months). The incidence of the pregnancy increased with the length of the exposure to the treatment; it was respectively 1.4%, 4.2% and 9.1% women-years at 6, 12 and 24 months of treatment. Among the 558 patients under Efavirenz, 46 (8.2%) became pregnant. Only 18 had their treatment changed due to the pregnancy. Efavirenz was replaced by Nevirapine or Lopinavir boosted with Ritonavir.

Outcome of pregnancies: no information on the outcome 8 out of 222 pregnancies (3.6%) was recorded. The outcome of 214 pregnancies was registered and resulted in 9 cases of abortion (4.0%); with a median gestational age of 12 weeks of amenorrhea (IQR, 8-13); 205 pregnancies (92.4%) resulted in childbirths including 15 premature childbirths. Natural delivery represent 90.2%, (185/205) compared to 9.8% (20/205) caesarean sections. The frequency of live births and stillborns was respectively 94.0% (193/205) and 6.0% (12/205). Babies' median weight was 2,800g (IQR: 2,550g; 3,100g); 30 babies (representing 14.6% of live births) were born with less than the median weight (below 2,500g).

Fertility rate of HIV infected patients : Table 2 provides details of the age-standardized fertility rate and standardized incidence ratios. The standardized crude fertility rate in our cohort was 45 live births for 1,000 women-years. The fertility rate has changed in all age groups of PLWHA compared to the baseline, except for the 15 to 19 years old group. The standardized incidence ratios (SIR) are low and the overall decrease in fertility was 66.0% compared to the entire population. According to the age groups, this decrease in fertility varies from 15.0% to 70.0%.

Discussion     

This retrospective study has some limitations. Despite it is condemned by the law in Burkina Faso, pregnancy termination is still performed. Therefore, we cannot assert that all cases of pregnancy have been registered. However, this innovative study made it possible to assess the frequency of pregnancies among patients on ART in Burkina Faso. The incidence of pregnancy was 5 for 100 women-years. However, this number is below most of rates found in African studies [8,9,20-23] with a frequency ranging from 7.9 to 24.6 for 100 women-years. The incidence of pregnancy could vary from one study to another depending on how patients are selected and on the pregnancy diagnosis criteria as well. The relative high number of our patients (median age 35) and the low proportion of people living as husband and wife (44.6%) could account for the low frequency of pregnancies in our study. Performing systematic and regular pregnancy tests would help determine the number of pregnancies ending up into miscarriage. The proportion of abortion was 4.0% (n=9) in our study. It is lower compared to that reported by Homsy et al. [24] in Uganda and Bussman et al. [8] in Botswana, respectively with 58.6% and 42.3%. High abortion prevalence in the two later surveys was due to the high number of induced abortion. The information collected as part of our study does not enable us to differentiate spontaneous abortion (miscarriages) from induced abortions. In our survey, live births represent 94.0%. A total of 12 stillborns were recorded, representing 6.0% of pregnancies. Our results are close to those found by Ekouevi et al. [25] in Côte d'Ivoire and Liu et al [26] in South Africa and Zambia. The median weight of babies born from mothers under ART was 2,800g, whereas the lower weight was 14.6% for live babies. The finding of our investigations is close to those made by researchers from sub-Saharan Africa [8, 25-27]. Some of them related low weight at birth to mothers undergoing an antiretroviral treatment [28]. However, the findings of studies conducted on this issue remain quite controversial. This study shows a 15 to 70% decrease in fertility rates among HIV infected women compared to the overall population, except for the age group of 15 to 19. This corroborates the findings from existing literature papers [10,29]. Poor information provided to patients in relation with the impact of antiretroviral treatment on reduction of mother-to-child transmission and high frequency of non severe amenorrhea during the infection could account for the decrease in fertility among those women. Low fertility can also be explained by the increased use of condoms by HIV infected women fearing to pass on the infection [30]. PLWHA care services should provide them reproductive health care in order to help those women exercise their sexual and reproductive rights in the best and safe conditions both for the couple and the baby to be born [31,32].

Conclusion     

This study highlights a low pregnancy incidence among women under art compared to the population in general. Women who became pregnant while on ART treatment delivered live babies in most cases. The care package for HIV infected women of childbearing age should include reproductive services. Women willing to give birth must be supported through counseling and with health care to ensure better conditions for the couple and the fetus. The follow up of such pregnancies should involve specialists of infection, obstetricians, and pediatricians collaborating for more favorable outcome.

Competing interests     

The authors have no competing interests to declare.

Authors’ contributions     

Arsène Héma, Armel Poda contributed to conception and design; Armel Poda, Arsène Héma and Nicolas Meda contributed to analysis and interpretation of data; All of authors contributed to data collection and involved in drafting this manuscript. Armel Poda, Arsène Héma and Nicolas Meda revised this article critically for important intellectual content. All authors contributed to the interpretation of data, and reviewed and approved the final manuscript.

Acknowledgments     

The authors thank all patients of the Day Care Unit of Bobo Dioulasso, the male nurses, and all non-medical staff of our department.

Tables     

Table 1: women characteristics by age at the beginning of ART in Bobo Dioulasso Day Care Unit, Souro Sanou Teaching Hospital, Burkina Faso, 2005-2011

Table 2: number of newborns, incidence ratio and age-standardized fertility rate of women on ART at the Bobo-Dioulasso Day Care Unit, Souro Sanou Teaching Hospital, Burkina Faso, 2005-2011

References     

1. UNAIDS. UNAIDS Report on the Global AIDS Epidemic. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS (UNAIDS); 2012. Google Scholar


2. Tubiana R, Le Chenadec J, Rouzioux C, Mandelbrot L, Hamrene K, Dollfus C, et al. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load <500 copies/ml at delivery: a case-control study nested in the French perinatal cohort (EPF-ANRS CO1). Clin Infect Dis. 2010;50(4):585-596. PubMed | Google Scholar


3. Kouanda S, Tougri H, Cisse M, Simpore J, Pietra V, Doulougou B, et al. Impact of maternal HAART on the prevention of mother-to-child transmission of HIV: results of an 18-month follow-up study in Ouagadougou, Burkina Faso. AIDS Care. 2010;22(7):843-850. PubMed | Google Scholar


4. Mmbaga EJ, Leyna GH, Ezekiel MJ et al. Fertility desire and intention of people living with HIV/AIDS in Tanzania: a call for restructuring care and treatment services. BMC Public Health. 2013; 86(13):1-8. PubMed | Google Scholar


5. Badell ML, Lathrop E, Haddad LB et al. Reproductive healthcare needs and desires in a cohort of HIV-positive women. Infect Dis Obstet Gynecol. 2012;2012:1-6. PubMed | Google Scholar


6. Mmeje O, Cohen CR, Cohan D. Evaluating safer conception options for HIV serodiscordant couples (HIV-infected female/HIV-uninfected male): a closer look at vaginal insemination. Infect Dis Obstet Gynecol. 2012;2012:1-7. PubMed | Google Scholar


7. Demissie DB, Tebeje B, Tesfaye T. Fertility desire and associated factors among people living with HIV attending antiretroviral therapy clinic in Ethiopia. BMC Pregnancy Childbirth. 2014; 382(14):1-10. PubMed | Google Scholar


8. Bussmann H, Wester CW, Wester CN, Lekoko B, Okezie O, Thomas AM, et al. Pregnancy rates and birth outcomes among women on efavirenz-containing highly active antiretroviral therapy in Botswana. J Acquir Immune Defic Syndr. 2007;45(3):269-273. PubMed | Google Scholar


9. Myer L, Carter RJ, Katyal M, Toro P, El-Sadr WM, Abrams EJ. Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in Sub-Saharan Africa: a cohort study. PLoS Med. 2010;7(2):e1000229. PubMed | Google Scholar


10. Zaba B, Gregson S. Measuring the impact of HIV on fertility in Africa. AIDS. 1998;12( Suppl 1):S41-50. PubMed | Google Scholar


11. Calvert C, Ronsmans C. Pregnancy and HIV disease progression: a systematic review and meta-analysis. Trop Med Int Health. 2015;20(2):122-145. PubMed | Google Scholar


12. Tai JH, Udoji MA, Barkanic G, Byrne DW, Rebeiro PF, Byram BR et al. Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy. J Infect Dis. 2007;196(7):1044-1052. PubMed | Google Scholar


13. El Beitune P, Duarte G, Quintana SM, Figueiró-Filho EA. HIV-1: maternal prognosis. Rev Hosp Clin Fac Med Sao Paulo. 2004 ;59(1):25-31. PubMed | Google Scholar


14. Massad LS, Springer G, Jacobson L, Watts H, Anastos K, Korn A et al. Pregnancy rates and predictors of conception, miscarriage and abortion in US women with HIV. AIDS. 2004;18(2):281-286. PubMed | Google Scholar


15. Wilcox AJ, Weinberg CR, O'Connor JF et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319(4):189-194. PubMed | Google Scholar


16. Kolte L, Gaardbo JC, Karlsson I et al. Dysregulation of CD4+CD25 +CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women. Blood. 2011;117(6):1861-1868. PubMed | Google Scholar


17. UNAIDS. UNAIDS Report on the Global AIDS Epidemic. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS (UNAIDS); 2014. Google Scholar


18. Enquête Démographique et de Santé (EDS-IV) et à Indicateurs Multiples (MICS) EDSBF-MICS IV 2010. Available from:http: //www.measuredhs.com/pubs /pdf/PR9/PR9.pdf. Google Scholar


19. Fontaine C, Hema A, Kamboule E, Guiard-Schmid J-B, Lescure F-X, Slama L et al. Bobo Dioulasso Teaching Hospital day-care hospital: a reference structure for the management of HIV infected patients in Burkina Faso. Med Mal Infect. 2010;40(7):393-397. PubMed | Google Scholar


20. Makumbi FE, Nakigozi G, Reynolds SJ, Ndyanabo A, Lutalo T, Serwada D et al. Associations between HIV Antiretroviral Therapy and the Prevalence and Incidence of Pregnancy in Rakai, Uganda. AIDS Res Treat. 2011; 2011:1-10. PubMed | Google Scholar


21. Westreich D, Maskew M, Rubel D et al. Incidence of pregnancy after initiation of antiretroviral therapy in South Africa: a retrospective clinical cohort analysis. Infect Dis Obstet Gynecol. 2012; 2012:1-7. PubMed | Google Scholar


22. Schwartz SR, Rees H, Mehta S, Venter WD, Taha TE, Black V. High incidence of unplanned pregnancy after antiretroviral therapy initiation: findings from a prospective cohort study in South Africa. PLoS One. 2012;7(4):e36039. PubMed | Google Scholar


23. Kabami J, Turyakira E, Biraro S, Bajunirwe F. Increasing incidence of pregnancy among women receiving HIV care and treatment at a large urban facility in western Uganda. Reprod Health. 2014; 81(11):1-11. PubMed | Google Scholar


24. Homsy J, Bunnell R, Moore D, King R, Malamba S, Nakityo R et al. Reproductive intentions and outcomes among women on antiretroviral therapy in rural Uganda: a prospective cohort study. PLoS ONE. 2009;4(1):e4149. PubMed | Google Scholar


25. Ekouevi DK, Coffie PA, Ouattara E, Moh R, Amani-Bosse C, Messou E et al. Pregnancy outcomes in women exposed to efavirenz and nevirapine: an appraisal of the IeDEA West Africa and ANRS Databases, Abidjan, Côte d'Ivoire. J Acquir Immune Defic Syndr. 2011; 56(2):183-187. PubMed | Google Scholar


26. Liu KC, Farahani M, Mashamba T, Mawela M, Joseph J, Van Schaik N, Honey E, Gill M, Jassat W, Stringer EM, Chintu N, Marlink RG. Pregnancy outcomes and birth defects from an antiretroviral drug safety study of women in South Africa and Zambia. AIDS. 2014; 28(15):2259-2268. PubMed | Google Scholar


27. Van der Merwe K, Hoffman R, Black V, Chersich M, Coovadia A, Rees H. Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study. J Int AIDS Soc. 2011; 42(14):1-11. PubMed | Google Scholar


28. Coovadia H. Current issues in prevention of mother-to-child transmission of HIV-1. Curr Opin HIV AIDS. 2009; 4(4):319-324. PubMed | Google Scholar


29. Lewis JJC, Ronsmans C, Ezeh A, Gregson S. The population impact of HIV on fertility in sub-Saharan Africa. AIDS. 2004; 18 Suppl 2:S35-43. PubMed | Google Scholar


30. Kaida A, Laher F, Strathdee SA, Janssen PA, Money D, Hogg RS, et al. Childbearing intentions of HIV-positive women of reproductive age in Soweto, South Africa: the influence of expanding access to HAART in an HIV hyperendemic setting. Am J Public Health. 2011; 101(2):350-358. PubMed | Google Scholar


31. UNAIDS. Countdown to Zero. Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive. Geneva: UNAIDS; 2011. Google Scholar


32. Baumgartner JN, Green M, Weaver MA et al. Integrating family planning services into HIV care and treatment clinics in Tanzania: evaluation of a facilitated referral model. Health Policy Plan. 2014;29(5):570-579. PubMed | Google Scholar