Unintended pregnancies are a major public health concern, with global estimates suggesting that 44% of pregnancies were unintended in 2010–2014 . In low-income and middle-income country (LMIC) settings, unintended pregnancies are similarly prevalent: population-level surveys have reported that 65% of pregnancies during 2012 in South Africa  and 46% during 2001–2013 in Uganda were unplanned ; 69% of women in Swaziland have reported that their most recent pregnancy was unintended . Outside the context of HIV, there are data to suggest that unintended pregnancy may be associated with a range of maternal health concerns  such as depression [6–9] or risk behaviours such as delayed initiation of antenatal care [5,10,11].
Despite the frequency of unintended pregnancy there have been few considerations of long-term effects among women living with HIV. In South Africa, fewer than 30% of pregnant women living with HIV report that their pregnancy was planned [12,13], and experiencing an unintended pregnancy after being diagnosed HIV positive is common in the United States [14,15]. An unintended pregnancy may further heighten the psychosocial and economic vulnerabilities of pregnant women living with HIV [16,17], and case–control studies have suggested that unintended pregnancies may be associated with mother-to-child HIV transmission [18,19]. However, there are few data on the long-term effects on maternal and child outcomes.
In particular there has been no consideration of the long-term impact of an unintended pregnancy on maternal HIV treatment outcomes, including adherence to antiretroviral therapy (ART). The WHO's policy of universal use of lifelong ART in all pregnant and breastfeeding women (Option B+)  has contributed to major increases in ART uptake but adherence to ART remains a major concern, particularly during the postpartum period [21–23]. Existing understandings of the drivers of suboptimal adherence in women living with HIV remain limited, including the potential role of unintended pregnancy. We have previously shown that unintended pregnancy is associated with elevated viral load at entry into antenatal care among women already on ART . Here, we explored factors associated with the intendedness of the pregnancy among women who initiated ART during pregnancy; and examined the association between unintended pregnancy and elevated viral load through 36–60 months postpartum.
We recruited consecutive pregnant women living with HIV from a public sector antenatal clinic in Gugulethu, Cape Town, for the Maternal and Child Health (MCH)-ART study (ClinicalTrials.gov NCT01933477). The design and primary results of the study have been previously described [25,26]. In this setting, women receive integrated prevention of mother-to-child transmission services and antenatal care within the broader maternal and child healthcare platform during pregnancy. Women who were eligible to initiate ART were followed through delivery. Women who then opted to breastfeed were randomized immediately postpartum to different models for delivering HIV care and were followed at repeated study measurement visits up to 18 months postpartum. Women were randomized to either the local standard of care (referral out of the maternal and child health clinic to general adult ART services at their first postpartum visit), or to the MCH-ART intervention of integrated concurrent and colocated maternal ART and paediatric care in the maternal and child health clinic through the end of breastfeeding. The trial found that there were significant improvements in the combined endpoint of viral suppression and retention in HIV care through 12 months postpartum among women randomized to the intervention arm; retention in the MCH-ART trial did not differ across allocation . We later extended follow-up to include one additional study visit between 36 and 60 months postpartum.
The secondary analysis includes all women who initiated ART during pregnancy and were followed as part of the randomized trial. ART eligibility was determined based on local guidelines: eligibility was based on CD4+ cell count or clinical disease staging until June 2013, after which all pregnant women were ART-eligible under Option B+ guidelines. All women provided written informed consent prior to enrolment, and the study was approved by the University of Cape Town's Faculty of Health Sciences Human Research Ethics Committee and by Columbia University Medical Center's Institutional Review Board.
Enrolment into the study coincided with women's entry into antenatal care. Women attended a maximum of two additional antenatal and one early postpartum study visit. Further study visits were then completed at 6 weeks and at 3, 6, 9, 12, 18 and 36–60 months postpartum, for a maximum of seven postpartum study visits. All study visits were completed separately from any routine HIV or antenatal/postpartum care.
Study measures based on self-report were administered in isiXhosa, the predominant local language, by trained study interviewers. Measures were translated from English into isiXhosa and were back-translated using standard procedures to ensure accuracy . A composite poverty score was calculated based on employment, housing type and access to household resources . At all study visits, women underwent phlebotomy for batched HIV viral load testing (Abbott RealTime HIV-1) conducted by the South African National Health Laboratory Services (NHLS). Infants underwent phlebotomy for HIV PCR testing at the 12 month study visit, conducted by the NHLS using the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 assay (Roche Diagnostics, Florham Park, New Jersey, USA).
The intendedness of the current pregnancy was assessed at enrolment, coinciding with entry into antenatal care, using the 6-item London Measure of Unplanned Pregnancy (LMUP) tool . Each item was scored 0, 1 or 2, and all items were summed to create a score between 0 and 12, with higher scores indicating higher levels of intendedness; total scores were then categorized into unplanned (a score of 0–3), ambivalent (4–9) or planned pregnancy (10–12) . The performance of the LMUP has been evaluated in both high-income and LMIC settings . We have previously shown that the LMUP is a valid and reliable tool (Cronbach's alpha, 0.84) in pregnant women living with and without HIV in South Africa .
The Edinburgh Postnatal Depression Scale (EPDS)  was administered at participants’ second antenatal study visit and at 6 weeks and 12, 18 and 36–60 months postpartum. A score of 13 or more was used to indicate elevated depressive symptoms . The Alcohol Use Disorders Identification Test (AUDIT)  was administered at participants’ second antenatal study visit to assess alcohol use in the year prior to pregnancy recognition, and at 6, 12 and 36–60 months postpartum to assess postpartum alcohol use. In analysis, the AUDIT-Consumption scoring system was used, in which a score of 3 or more on the first three items of the tool was used to indicate risky alcohol use [33,34]. The WHO Violence Against Women tool was used to assess intimate partner violence . Violence in the year prior to pregnancy recognition was assessed at participants’ second antenatal study visit, and postpartum violence was assessed at 12 and 36–60 months postpartum. In analysis, we categorized women as reporting any versus no violence.
Data were analysed using Stata 14 (StataCorp Inc, College Station, Texas, USA). We used mixed effects models to examine the impact of the intendedness of the pregnancy on elevated viral load of 50 or more copies/ml during the postpartum period. Throughout, we compared women reporting each of ambivalence or an unplanned pregnancy, respectively, to those reporting a planned pregnancy; and also examined the effect of increasing intendedness of the pregnancy using continuous LMUP scores. We conducted sensitivity analyses using viral load of 1000 or more copies/ml and restricted to women who were virally suppressed less than 50 copies/ml at delivery. We explored the impact of missing data by assuming that women who did not attend a study visit had suppressed and then elevated viral load at that visit.
Given the potential for confounding of the putative association between the intendedness of the pregnancy and elevated viral load we present results from unadjusted models and then: (A) adjusting for demographic and clinical characteristics only; (B) additionally adjusting for psychosocial factors measured at participants’ second antenatal study visit; and (C) additionally adjusting for postpartum psychosocial factors. To account for differences in viral suppression at 12 months postpartum observed in the primary trial analysis, all adjusted models were adjusted for women's allocation in the MCH-ART trial. For postpartum psychosocial factors, we categorized women as scoring above the threshold value at any study visit at which these were assessed versus scoring below threshold at all visits. Possible modifiers of the association between the intendedness of the pregnancy and postpartum viral load were examined in stratified analyses. Using standard formulae and assuming that unplanned pregnancy is an independent cause of elevated viral load for these purposes, we calculated the population attributable fraction for the proportion of elevated viral load that may be due to unplanned pregnancy. Finally, we used product-limit methods and the log-rank test to compare vertical transmission across LMUP categories.
Intendedness of the pregnancy
A total of 471 women who had initiated ART during pregnancy and opted to breastfeed were followed postpartum. Seven women had not completed the LMUP and were excluded from analysis; a further five women attended no follow-up visits and were excluded. The remaining 459 women were enrolled while pregnant between March 2013 and April 2014. Approximately two thirds of women reported that they were not using contraception during the month prior to the pregnancy; had not discussed getting pregnant with their partner; and did not want a baby or intend to get pregnant (Table 1). However, 49% of women who reported not wanting a baby and not intending to get pregnant, respectively, reported that the timing of the pregnancy was okay, although not quite right. Using the LMUP tool, 20, 20 and 60% of women reported that their current pregnancy was intended, ambivalent and unplanned, respectively.
Demographic, clinical and psychosocial characteristics
Overall the median age was 27.9 years, and women had entered antenatal care at a median gestation of 21 weeks (Table 2). Women reported low levels of educational attainment and employment; 83% reported one or more previous pregnancies; and 58% were diagnosed HIV-positive during their current pregnancy. Psychosocial risk factors were commonly reported; 61% had disclosed their HIV status to their male partner by delivery; and 75% were virally suppressed less than 50 copies/ml at delivery. Women reporting lower levels of intendedness related to their current pregnancy were significantly less likely to be married and/or cohabiting; had entered antenatal care at a later gestation with consequent ART initiation at a later gestation; and were somewhat less likely to have viral load less than 50 copies/ml at delivery. In addition, women reporting lower levels of intendedness were more likely to report risky alcohol use prior to pregnancy and during the postpartum period and were less likely to disclose to their male partner by delivery. No differences in intendedness of the pregnancy were observed by age; timing of HIV diagnosis (before versus during the pregnancy); or allocation in the MCH-ART trial.
Impact of the intendedness of the pregnancy on postpartum viral load
Women were followed for a median of 42.6 months postpartum, contributing a total of 2535 viral load measures (median per woman: 6; interquartile range: 5–7). The proportion of women with viral load of 50 or more copies/ml increased from 16% at 6 weeks postpartum to 43% by 36–60 months postpartum. Overall, 56% of women had viral load of 50 or more copies/ml at one or more postpartum study visit. At most visits, a dose–response association was observed: elevated viral load was more common among women who had reported ambivalence compared with a planned pregnancy, with the prevalence of elevated viral load even higher among those who had reported that their pregnancy was unplanned (Fig. 1). Viral load of 50 or more copies/ml at one or more postpartum study visit was observed among 60% of women who reported that their pregnancy was unplanned, 62% of women who reported ambivalence and 41% of women who reported that their pregnancy was planned.
In unadjusted analyses, lower levels of intendedness were associated with elevated viral load at postpartum study visits: compared with women who had reported a planned pregnancy, those who had reported an unintended pregnancy had almost three times the odds [odds ratio (OR): 2.87; 95% confidence interval (CI): 1.46–5.64] of elevated viral load across study visits, with a trend towards a higher odds among those reporting ambivalence (OR: 2.19; 95% CI: 0.97–4.92; Table 3). Elevated viral load was also more common among women who were younger; were neither married nor cohabiting; had entered antenatal care at a later gestation and with higher viral load; and reported risky preconception alcohol use or intimate partner violence. In addition, the odds of elevated viral load increased with increasing duration on ART, and elevated viral load was more common among women reporting risky alcohol use or intimate partner violence during the postpartum period.
The effect of the intendedness of the pregnancy on elevated viral load persisted after adjustment for demographic and clinical characteristics (adjusted model A); additional adjustment for preconception and antenatal psychosocial factors (B); and after additional adjustment for postpartum psychosocial factors (C), although the associations did not reach statistical significance in all instances. Results were similar when elevated viral load was defined as 1000 or more copies/ml and when models were restricted to women who were virally suppressed less than 50 copies/ml at delivery (data not shown) but were slightly attenuated when assuming that missing viral load measures were suppressed or elevated (Supplemental Table 1, http://links.lww.com/QAD/B429).
Results were consistent when examining the effect of continuous LMUP scores: increasing intendedness of the pregnancy was strongly associated with a reduced odds of elevated viral load in unadjusted models, with associations only slightly attenuated in adjusted models (Supplemental Table 2, http://links.lww.com/QAD/B429). In a graphical portrayal of LMUP scores and the predicted probability of experiencing elevated viral load at each score (Fig. 2), the magnitude of these results is clearly seen. First, the distribution of LMUP scores is bimodal, but the majority of women fall within the range of an unplanned pregnancy. Second, the highest probability of elevated viral load falls in the large group of women who reported that their pregnancy was unintended, and the probability decreases in a dose–response relationship as the intendedness of the pregnancy increases.
Impact of the intendedness of the pregnancy across subgroups
The association between continuous LMUP scores and elevated viral load of 50 or more copies/ml was examined across subgroups (Supplemental Fig. 1, http://links.lww.com/QAD/B429). Overall, increasing intendedness of the pregnancy reduced the relative odds of elevated viral load in most subgroups explored. However, this effect appeared to be stronger among women who had completed less than secondary education and who reported more disadvantage. In addition, the effect was stronger among women who were married and/or cohabiting and who reported no previous pregnancies. Although HIV-status disclosure to a male partner was not associated with elevated viral load in the total sample (Table 3), the effect of the intendedness of the pregnancy on elevated viral load appeared to be stronger among women who had disclosed to their male partner by delivery.
The role of HIV-status disclosure to a male partner was further explored in stratified analyses (Supplemental Table 2, http://links.lww.com/QAD/B429). Among women who had not disclosed to their male partner by delivery, the intendedness of the pregnancy was not associated with elevated viral load in either unadjusted or adjusted models. Among women who had disclosed by delivery, increasing intendedness of the pregnancy was strongly associated with a reduced odds of elevated viral load (OR: 0.85; 95% CI: 0.77, 0.94); this effect persisted after adjustment for demographic and clinical factors but was slightly attenuated after additional adjustment for antenatal and postpartum psychosocial factors.
Impact of the intendedness of the pregnancy on vertical transmission
A total of 466 infants were born to the 459 women included in analysis, with five infants testing HIV-positive in the first 12 months postpartum. The rate of transmission at 12 months postpartum was 1.2% overall, with no difference across LMUP categories (P = 0.999).
The analysis presents novel data suggesting that unplanned pregnancy may be a common and persistent risk factor for poor ART outcomes among women initiating ART during pregnancy. We observed a dose–response association between lower levels of pregnancy intendedness and elevated viral load, with elevated viral load most common among women who had reported an unplanned pregnancy. This association persisted up to 36–60 months postpartum and was observed independent of demographic, clinical and psychosocial factors. To our knowledge, these data are the first to demonstrate a long-term effect of the intendedness of a pregnancy on viral load and, given the high frequency of unintended pregnancy in women living with HIV in many LMIC settings, make an important new contribution to our understanding of the drivers of suboptimal adherence during the postpartum period.
Unintended pregnancies have been previously linked to other adverse health behaviours including delays in seeking antenatal care [5,11,36–38], substance use during pregnancy [36,37] and lower levels of breastfeeding . Further, the psychosocial consequences may be profound: an unintended pregnancy can cause severe disruption to preexisting life plans  and may lead to common mental disorders such as depression [5,7,36,38], as well as relationship dissolution or intimate partner violence [5,36]. Our finding that unintended pregnancy affects maternal ART outcomes extends these findings to the biomedical outcomes of HIV treatment viral suppression. Preventing unintended pregnancies is a central aspect of the approach to reduce vertical HIV transmission ; further, our data suggest that an unintended pregnancy may compromise the benefits of ART for maternal health in the long term.
Although the impact of pregnancy intention persisted despite adjustment for multiple other risk factors, direct causality is difficult to determine . Unintended pregnancies occur in complex social contexts and relationships , including being more common among unmarried women , and may heighten existing vulnerabilities [16,17]. It is likely that an unintended pregnancy is one of several risk factors that contribute to women's vulnerability, rather than a standalone factor that independently predicts elevated viral load. Indeed, both the intendedness of a pregnancy and subsequent health outcomes may be determined by the same underlying factors . In this study, several factors were associated with both lower levels of pregnancy intendedness and elevated viral load: each was more common among women who were neither married nor cohabiting; had entered antenatal care at a later gestation; and who reported risky alcohol use. Here we posit that an unintended pregnancy heightens women's vulnerability as part of a constellation of risk factors. In addition, we posit that unintended pregnancy may be a marker of some degree of ambivalence both towards pregnancy and towards one's own health, with these ambivalences reflected in women's adherence to ART. Additional sociobehavioural research is needed to explore these possibilities and the mechanisms of these novel findings.
If unplanned pregnancy can be viewed as an independent cause of elevated viral load for the purpose of considering population-level impacts, then it is possible to calculate a population attributable fraction for the proportion of elevated viral load in the cohort that may be due to unplanned pregnancy. Using standard formulae, we estimate that approximately 16% of elevated viral load may be associated with unplanned pregnancy in this population, compared with either ambivalence or a planned pregnancy; if we include ambivalence to pregnancy in the calculations this estimate increases to 28%. Given that unintended pregnancies are preventable (e.g. through effective contraception), an alternate way to conceptualize this is to consider the possibility that only women with planned pregnancies entered the cohort. In this case, we estimate that 64 and 85% of all episodes of elevated viral load would be prevented by the prevention of unplanned, or unplanned and ambivalent, pregnancies, respectively. Regardless of the formula used, these estimates speak to the population-level implications of the associations observed here.
A strength of this study is the inclusion of longitudinal data with long-term follow-up and the use of a robust biological endpoint. However, our results must be interpreted in light of several limitations. Unintended pregnancy is a complex construct to measure [37,38] but the LMUP has been validated widely, including in this population , and is robust enough to be recommended as an outcome measure for preconception care . We assessed the intendedness of the pregnancy at entry into antenatal care, but the desirability of the pregnancy may change during the course of pregnancy . Indeed, we did not assess how quickly women adapted in psychosocial terms to the pregnancy but note that 49% of women who reported not wanting a baby and not intending to get pregnant, respectively, reported that the timing of the pregnancy was okay. Preconception measurement of pregnancy intentions would be ideal but is challenging. As these data arise from a periurban setting in South Africa in the context of a research study, our findings should be generalized to other settings with caution, but we note that high levels of both unplanned pregnancy and elevated viral load have been observed in many high-burden settings [3,4,21–23]. Finally, this research focussed on women initiating ART in pregnancy, and the question of how unplanned pregnancy effects outcomes among women who initiated ART before conception needs further investigation.
Despite these limitations, these results clearly warrant further attention. Given the high levels of unintended pregnancy and elevated postpartum viral load observed here and in other settings, we argue that unintended pregnancy needs to be escalated as a global public health concern for maternal and child health in the context of HIV. Moreover, these data shed light on a unique factor in this patient population that may shape adherence behaviours and suggest that postpartum women who report antenatally that they did not intend their pregnancy may require specific attention from counselling and support interventions. Further, we argue that pregnancy planning needs to be incorporated into routine care for all women living with HIV: preventing unintended pregnancies may reduce the prevalence of elevated viral load in this population and maximize maternal health.
The authors would like to thank the women who participated in this study, as well as the study staff for their support of this research. This research was supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the National Institute of Child Health and Human Development (NICHD), grant numbers 1R01HD074558 and 1R01HD080465. Additional funding comes from the Elizabeth Glaser Pediatric AIDS Foundation. K.B. is supported by the South African Medical Research Council under the National Health Scholars Programme. K.B. conducted the analysis, led data interpretation and drafted the article. T.K.P. and A.Z. directed data collection and assisted with data interpretation. E.J.A. and L.M. conceptualized the study, were responsible for funding, implementation and overall leadership, and assisted with data interpretation. All authors read and approved the final article.
Conflicts of interest
There are no conflicts of interest.
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