Looking at trends in the years following guidelines change, there was a steady increase in the proportion of vaginal deliveries, and very few vaginal deliveries occurred among women with detectable VL (Fig. 3). However, CS was the mode of delivery in 104 of 188 (55.3%) of women with fully suppressed VL at delivery (Fig. 2). In 37 of104 women, there was a contraindication for vaginal delivery (8 previous CS, 27 < 37 weeks, 1 multiple pregnancy, 1 zidovudine monotherapy). The reason for CS was documented in 63 of the remaining 67 patients with undetectable VL. In 35% of cases (22/63), these women could have had a vaginal delivery, as for 19 cases, the reason given for CS was maternal HIV infection, and in 3 cases, it was ROM.
Median gestational age at delivery was 38 weeks (IQR: 37–39 weeks); 20.7% deliveries were premature (Table 1), with 1.0% (n = 29) of all deliveries being extremely premature (<28 weeks), 2.5% (n = 74) severely premature (28–31 weeks), and 3.0% (n = 88) moderately premature (32–33 weeks). Late preterm deliveries (34–36 weeks) accounted for 14.2% of all deliveries overall (Table 1), with a significant decrease after the introduction of the new guidelines from 16.0% (377/2354) to 7.0% (42/599) (χ2 = 6.26, P < 0.001). Of the late preterm deliveries (n = 419), 55.7% (n = 209) of those taking place before the guidelines were performed as elective CS versus 28.6% (n = 12) afterward. Median birth weight was 2.9 kg (IQR: 2.5–3.2 kg). Overall, the HIV mother to child transmission rate was 1.6% (36/2329; 95% CI: 1.1 to 2.1), with a rate of 1.7% (34/1991; 95% CI: 1.2 to 2.4) before and 0.6% (2/338; 95% CI: 0.07 to 2.1) after guidelines.
Our findings quantify the impact of a policy change for mode of delivery options among HIV-positive pregnant women in the largest European cohort across Europe described to date. As expected, we observed an increasing proportion of women with undetectable VL at delivery (63% to 78%) and increasing rates of vaginal deliveries from 17% before to 52% after the updated guidelines. Of note, rates of vaginal deliveries were increasing before the updated guidelines were published indicating that formulation of new guidelines was driven by clinical practice.
In the context of the new guidelines and in the absence of an obstetric indication for elective CS, decisions about mode of delivery largely depend on maternal VL. We found that 14% of the women receiving ART did not achieve an undetectable VL (>400 copies/mL) at the time of delivery, and overall, 7% women did not receive any antenatal ART. There is a substantial proportion of women with ongoing viral replication at delivery, which is supported by comparable findings of a Brazilian cohort with 43%,17 a U.S. cohort with 32%,18 and a Canadian cohort with 16%19 of women with a detectable HIV VL at delivery. Comparisons between studies are complicated by variable definitions of undetectable VL according to different assays used. We found an association between having a detectable VL at delivery and late HIV diagnosis, younger maternal age, and history of injecting drug use. In the American study, younger age and illicit drug use and lower CD4 cell count at start of therapy were significantly associated with having a detectable HIV VL at the time of giving birth, whereas as in our study, the type of ART used was not significant.18 The association with younger age may be explained by worse adherence to ART in younger age groups. In an Italian study, the probability of having a detectable VL (19%) at delivery was associated with lower CD4 cell count at enrollment and treatment modification during pregnancy (adjusted odds ratio: 1.66, 95% CI: 1.07 to 2.57, P = 0.024).20 In contrast, a former report of the ECS showed 27% of women with a detectable VL at delivery with shorter time to achieving an undetectable VL, associated with African origin and baseline VL but not with baseline CD4 cell counts.21 However, in this analysis, white women were more likely to have a detectable VL; this may reflect residual confounding, as our analysis did not include baseline VL or adherence.
In a French cohort, the elective CS rate in HIV-positive women decreased between 1997 and 2004 from 56% to 41% and in a national study in the United Kingdom and Ireland, the elective CS rate declined from 66% in 1999 to 50% in 2006. The likelihood of having an elective CS varies according to the geographic location, as does the background rate of elective CS in the population.22 However, the rates of emergency CS are stable in the French cohort at 29%,5 whereas in the United Kingdom and Ireland and in this cohort, the rate of emergency CS marginally increased from 17% in 1999% to 23% in 2006 and from 17.2% to 20.8%, respectively. Indeed, we had expected higher rates of emergency CS associated with the new guidelines, given that more pregnancies not delivered by elective CS were potentially at risk of non–HIV-related obstetric complications, but this was not confirmed by our data.
Of concern, in this cohort, despite viral suppression, the rates of vaginal deliveries were lower than expected. Nearly half of women with an undetectable VL after the change of guidelines had a CS and 35% of these were performed because of maternal HIV or ROM. This might be attributable to the fact that implementation of a vaginal delivery policy was difficult after the era of recommended elective CS. In addition, the theoretical risk of HIV transmission associated with obstetrical interventions such as fetal pH measurement, episiotomy, instrumental deliveries,23,24 and with duration of ruptured membranes,25 described in the era before ART was broadly available, may have favored the CS choice. Maternal request is another important factor influencing mode of delivery decisions. The CS rate based on mother’s demand can be quite substantial and varies between countries.22,26 Our results suggest that the policy for vaginal delivery among women with undetectable or very low VL is only slowly becoming established within practice over time.
Two smaller European studies have shown that only 57% and 65%, respectively, of HIV-positive women with undetectable VL at delivery and planned vaginal delivery were ultimately able to deliver this way.26,27 In a Canadian cohort, reasons for the high elective CS rate were multiparity, maternal request, and origin from resource-poor countries with different approaches for prevention of MTCT.19 Livingston et al28 found the following reasons for elective CS in women who could have had a vaginal delivery based on their suppressed VL: fear of HIV transmission in 39.3%, history of previous CS in 29.8%, request of mother in 5.8%, and hypertension and preeclampsia in 4.6%. For emergency CS in women with fully suppressed viral replication, the same study found a nonreassuring fetal heart rate to be the most common reason (21.8%).28 Azria et al29 reported that CS for failure to progress in labor was performed in HIV-positive women an average of 1 hour earlier compared with uninfected controls, indicating that maternal HIV infection even with suppressed VL influenced the mode of delivery. All these studies highlight the issue that mode of delivery continues to be influenced to some extent by HIV status irrespective of viral suppression.
The preterm delivery rate in our study was high at around 20%. The former recommendations were to perform elective CS before ROM or onset of labor to prevent increased MTCT risk. This might have had an impact on the decision to perform CS in the late preterm period, for example 36 weeks. It is noteworthy that neonates at 36 weeks remain at higher risk of morbidity compared with those born at 37–40 weeks of gestation regarding respiratory distress, jaundice, and hypoglycaemia.11,30 A positive finding of this study confirmed a significant reduction of elective CS in the late preterm period after the new guidelines. We anticipate this trend to continue over time. Furthermore, our results indicate the need to consider how a reduction of the CS rates in women with undetectable VL in the future could be achieved.
This analysis represents the first study describing rates of mode of delivery in HIV-positive women across Europe taking into account varying national MTCT policies and health care structures. We are aware that our findings are limited by the observational nature of our data, the missing information about planned mode of delivery, and differences between countries in decision-making processes. Lack of detailed and/or comprehensive data on drug adherence on baseline VL and missing information on exact duration of ART precluded use of these variables in our analyses. Our dataset does not include information of all Western European countries (eg, no French data), as not all countries participate in the ECS.
Rates of vaginal delivery in HIV-positive pregnant women are increasing in Europe for women with suppressed VL. Despite this, there is evidence of missed opportunities for viral suppression and for having a vaginal delivery in women with suppressed HIV VL. Barriers to HIV testing before or during early pregnancy and to commencing an effective ART sufficiently early in pregnancy need to be addressed. Furthermore, future research is needed to address how to promote earlier engagement in care among HIV-positive pregnant women, and retention in HIV care postnatally, to achieve viral suppression and the opportunity for vaginal delivery for HIV positive pregnant women in both their index and subsequent pregnancies.
The authors thank the women who participated in this research.
The European Collaborative Study Group (Western Europe) consists of the following members: Dr C. Thorne, H. Bailey; Dr C. Giaquinto, Dr O. Rampon, Dr A. Mazza, and Professor A. De Rossi; Professor I. Grosch Wörner; Dr J. Mok; Dr Ma I. de José, Dra B. Larrú Martínez, Dr J. Ma Peña, Dr J. Gonzalez Garcia, Dr J.R. Arribas Lopez, and Dr M.C. Garcia Rodriguez; Professor F. Asensi-Botet, Dr M.C. Otero, Dr D. Pérez-Tamarit; Dr H.J. Scherpbier, M. Kreyenbroek, Dr M.H. Godfried, Dr F.J.B. Nellen, and Dr K. Boer; Dr L. Navér, Dr A.B. Bohlin, Dr S. Lindgren, Dr A. Kaldma, and Dr E. Belfrage; Professor J. Levy, Dr P. Barlow, Dr Y. Manigart, Dr M. Hainaut, and Dr T. Goetghebuer; Professor B. Brichard, J. De Camps, N. Thiry, G. Deboone, H. Waterloos; Professor C. Viscoli; Professor A. De Maria; Professor G. Bentivoglio, Dr S. Ferrero, Dr C. Gotta; Professor A. Mûr, Dr A. Payà, Dr M.A. López-Vilchez, Dr R. Carreras; Dr N.H. Valerius, Dr V. Rosenfeldt; Dr O. Coll, Dr A. Suy, Dr J.M. Perez; Dr C. Fortuny, Dr J. Boguña; Dr V. Savasi, Dr S. Fiore, Dr M. Crivelli; Dr A. Viganò, Dr V. Giacomet, Dr C. Cerini, Dr C. Raimondi, and Professor G. Zuccotti; Dr S. Alberico, Dr G. Maso, Dr M. Tropea, Dr V. Barresi. Dr G.P. Taylor, Dr E.G.H. Lyall; Ms Z. Penn; Drssa W. Buffolano, Dr R. Tiseo, Professor P. Martinelli, Drssa M. Sansone, Dr G. Maruotti, Dr A. Agangi; Dr C. Tibaldi, Dr S. Marini, Dr G. Masuelli, Professor C. Benedetto; Dr T. Niemieç, Professor M. Marczynska, Dr S. Dobosz, Dr J. Popielska, Dr A. Oldakowska. The members of the Swiss HIV Cohort Study and the Swiss Mother and Child HIV Study are V. Aubert, J. Barth, M. Battegay, E. Bernasconi, J. Böni, P. Brazzola, H.C. Bucher, C. Burton-Jeangros, A. Calmy, M. Cavassini, J.J. Cheseaux, G. Drack, A. Duppenthaler, M. Egger, L. Elzi, J. Fehr, J. Fellay, K. Francini, H. Furrer, C.A. Fux, M. Gorgievski, C. Grawe, H. Günthard (President of the SHCS), D. Haerry (deputy of “Positive Council”), B. Hasse, H.H. Hirsch, I. Hösli, C. Kahlert, L. Kaiser, O. Keiser, T. Klimkait, H. Kovari, B. Ledergerber, G. Martinetti, B. Martinez de Tejada, K. Metzner, N. Müller, D. Nadal, G. Pantaleo, Ch. Polli, K. Posfay-Barbe, A. Rauch, S. Regenass, M. Rickenbach, C. Rudin (Chairman of the Mother & Child Substudy), P. Schmid, K. Scheibner, D. Schultze, F. Schöni-Affolter, J. Schüpbach, R. Speck, P. Taffé, P. Tarr, A. Telenti, A. Trkola, P. Vernazza, R. Weber, C.A. Wyler, and S. Yerly.
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Keywords:© 2013 by Lippincott Williams & Wilkins
HIV; pregnancy; mode of delivery; Europe