Antenatal Uterotonics as a Risk Factor for Intrapartum Stillbirth and First-day Death in Haryana, India

Abstract

Background: Use of uterotonics like oxytocin to induce or augment labor has been shown to reduce placental perfusion and oxygen supply to the fetus, and studies indicate that it may increase the risk of stillbirth and neonatal asphyxia. Antenatal use of uterotonics, even without the required fetal monitoring and prompt access to cesarean section, is widespread, yet no study has adequately estimated the risk of intrapartum stillbirth and early neonatal deaths ascribed to such use. We conducted a case–control study to estimate this risk. Methods: We conducted a population-based case–control study nested in a cluster-randomized trial. From 2008 to 2010, we followed pregnant women in rural Haryana, India, monthly until delivery. We visited all live-born infants on day 29 to ascertain whether they were alive. We conducted verbal autopsies for stillbirths and neonatal deaths. Cases (n = 2,076) were the intrapartum stillbirths and day-1 deaths (early deaths), and controls (n = 532) were live-born babies who died between day 8 and 28 (late deaths). Results: Antenatal administration of uterotonics preceded 74% of early and 62% of late deaths, translating to an adjusted odds ratio (95% confidence interval [CI]) for early deaths of 1.7 (95% CI = 1.4, 2.1), and a population attributable risk of 31% (95% CI = 22%, 38%). Conclusions: Antenatal administration of uterotonics was associated with a substantially increased risk of intrapartum stillbirth and day-1 death. See video abstract: http://links.lww.com/EDE/B707.

Perinatal Asphyxia and Its Associated Factors among Live Births in the Public Health Facilities of Bahir Dar City, Northwest Ethiopia, 2021

“…For those mothers who gave birth by the administration of uterotonic drug, their newborns were 2.8 times more likely to be asphyxiated. This finding was agreed with studies done in India and Bangladesh [ 23 , 32 , 48 ]. This might be because uterotonics can cause hyperstimulation (tachysystole) and decrease blood flow to the fetus through the placenta [ 47 ].…”

Labor augmentation with oxytocin in low- and lower-middle-income countries: a systematic review and meta-analysis

“… 21 Studies from India, Côte d'Ivoire, and Nepal reported intramuscular oxytocin injections during labor. 24 , 31 , 35 , 37 , 38 , 39 No studies reported on titration practices and maximum doses of oxytocin.…”

“…To assess risks of oxytocin for labor augmentation, 4 cohort 20 , 21 , 22 , 23 and 7 case–control studies were identified in Tanzania, Nepal, Benin, Democratic Republic of the Congo, Senegal, Papua New Guinea, Uganda, Nigeria, and Ethiopia ( Table ). 24 , 25 , 26 , 27 , 28 , 29 , 30 The studies had varying quality (Supplementary table 3); all but 2 studies 20 , 22 used nonvalidated records 21 , 23 , 25 , 26 , 27 , 28 , 29 , 30 or verbal autopsies 24 to assess oxytocin exposure; 4 studies assessed used clinical observations to assess outcomes, 22 , 25 , 26 , 28 whereas the remaining studies used nonvalidated records. All studies had high risk of confounding because they did not adequately adjust for labor duration.…”

“…Finally, 6 studies did not adjust for any confounders. 20 , 23 , 27 , 28 , 29 , 30 Results of the meta-analysis unanimously suggest that oxytocin used for labor augmentation may be associated with adverse perinatal outcomes ( Figure 4 ), including: stillbirth and day-1 neonatal mortality (RR, 1.45; 95% CI, 1.02–2.06; N=84,077; 6 studies) 21 , 22 , 23 , 24 , 27 , 30 ; low Apgar score (RR, 1.54; 95% CI, 1.21–1.96; N=80,157; 4 studies) 21 , 23 , 28 , 29 ; NE (RR, 2.90; 95% CI, 1.87–4.49; N=1383; 2 studies) 25 , 26 ; and neonatal resuscitation (RR, 2.69; 95% CI, 1.87–3.88; N=86,750; 3 studies). 20 , 21 , 22 No studies assessed association with cesarean birth rate, labor duration, or uterine rupture.…”

“…A recent study in India, furthermore, supports a causal link between oxytocin augmentation and adverse effects given that the association between oxytocin augmentation and day-1 neonatal mortality seemed to be mediated entirely by birth asphyxia. 24 The association was strongest for stillbirths, waned during the first 24 hours, and was negligible in the subsequent 6 days of life. 24 Yet, a few inconsistent results related to stillbirths require further discussion.…”