Use of antenatal corticosteroids and tocolytic drugs in preterm births in 29 countries: an analysis of the WHO Multicountry Survey on Maternal and Newborn Health

Summary

Background

Despite the global burden of morbidity and mortality associated with preterm birth, little evidence is available for use of antenatal corticosteroids and tocolytic drugs in preterm births in low-income and middle-income countries. We analysed data from the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS) to assess coverage for these interventions in preterm deliveries.

Methods

WHOMCS is a facility-based, cross-sectional survey database of birth outcomes in 359 facilities in 29 countries, with data collected prospectively from May 1, 2010, to Dec 31, 2011. For this analysis, we included deliveries after 22 weeks' gestation and we excluded births that occurred outside a facility or quicker than 3 h after arrival. We calculated use of antenatal corticosteroids in women who gave birth between 26 and 34 weeks' gestation, when antenatal corticosteroids are known to be most beneficial. We also calculated use in women at 22–25 weeks' and 34–36 weeks' gestation. We assessed tocolytic drug use, with and without antenatal corticosteroids, in spontaneous, uncomplicated preterm deliveries at 26–34 weeks' gestation.

Findings

Of 303 842 recorded deliveries after 22 weeks' gestation, 17 705 (6%) were preterm. 3900 (52%) of 7547 women who gave birth at 26–34 weeks' gestation, 94 (19%) of 497 women who gave birth at 22–25 weeks' gestation, and 2276 (24%) of 9661 women who gave birth at 35–36 weeks' gestation received antenatal corticosteroids. Rates of antenatal corticosteroid use varied between countries (median 54%, range 16–91%; IQR 30–68%). Of 4677 women who were potentially eligible for tocolysis drugs, 1276 (27%) were treated with bed rest or hydration and 2248 (48%) received no treatment. β-agonists alone (n=346, 7%) were the most frequently used tocolytic drug. Only 848 (18%) of potentially eligible women received both a tocolytic drug and antenatal corticosteroids.

Interpretation

Use of interventions was generally poor, despite evidence for their benefit for newborn babies. A substantial proportion of antenatal corticosteroid use occurred at gestational ages at which benefit is controversial, and use of less effective or potentially harmful tocolytic drugs was common. Implementation research and contextualised health policies are needed to improve drug availability and increase compliance with best obstetric practice.

Funding

UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.

Introduction

More than 15 million infants are born preterm every year and preterm birth is the largest cause of death among newborn babies (age up to 28 days) and the second largest cause of death in children younger than 5 years.¹ More than 60% of preterm deliveries occur in Africa and Asia. The deleterious effects of preterm delivery on newborn babies can be mitigated through appropriate use of proven interventions such as antenatal corticosteroids for fetal lung maturation (along with other benefits)² and tocolytic drugs to delay delivery and potentiate the effects of antenatal corticosteroids or allow transfer to a higher-level facility before delivery.³

Injections of corticosteroids before delivery to induce fetal lung maturation and thereby prevent newborn morbidity and mortality has been comprehensively studied for nearly four decades.⁴ The most recent Cochrane review (2006) for use of antenatal corticosteroids in women with preterm delivery included 21 randomised controlled trials of 3885 women and 4269 babies.² Investigators concluded that antenatal corticosteroid use was associated with an overall 31% reduction in neonatal deaths, and significant reductions in risks of respiratory distress syndrome (34%), cerebroventricular haemorrhage (46%), necrotising enterocolitis (54%), need for respiratory support or intensive-care admission (20%), and systemic infections in the first 48 h of life (44%). Antenatal corticosteroids were effective when given from 26 weeks' to 34 weeks' plus 6 days gestation (even if given less than 24 h before delivery) and did not increase risk of maternal death, chorioamnionitis, or puerperal sepsis. A meta-analysis of the four randomised controlled trials for antenatal corticosteroids for preterm births in middle-income countries suggested that the reduction in mortality might be greater in these countries than in high-income countries.⁵ Benefit of antenatal corticosteroids outside this gestational age range is controversial; however, observational evidence suggests effectiveness when given between 22 weeks' and 26 weeks' gestation,⁶ and investigators of one trial reported that antenatal betamethasone given to women pregnant with term infants reduced neonatal respiratory distress and admission to neonatal special-care units in newborn babies born by elective caesarean section.⁷ Despite the global burden of newborn morbidity and mortality related to preterm births, uptake of antenatal corticosteroids worldwide has been poor—the Bellagio Child Survival Study group⁸ estimated antenatal corticosteroid coverage in 2000 to be just 5% for the 42 countries that had 90% of the world's under-5 deaths. Recent data for worldwide use of antenatal corticosteroids are not available.

Spontaneous preterm labour causes 40–45% of preterm births.⁹ Tocolytic drugs (such as β-agonists, calcium-channel blockers, and oxytocin antagonists) can be used as temporising measures to inhibit labour progression for up to 7 days.10, 11, 12 Use of tocolytic drugs alone has not been shown to reduce perinatal mortality (although trials have been underpowered for this outcome).³ However, use of the drugs to delay delivery is recommended to permit transfer to a higher-level facility and to potentiate the effects of corticosteroids (and hence should be used in conjunction with antenatal corticosteroids).11, 12 We did not find any published reports on patterns of tocolytic drug use in preterm labour in low-income and middle-income countries, despite its importance in the management of preterm birth.

We did an analysis of the WHO Multicountry Survey of Maternal and Newborn Health (WHOMCS) dataset for more than 314 000 facility-based deliveries in 29 countries. We aimed to describe patterns of use of antenatal corticosteroids in preterm deliveries and assess the use of tocolytic drugs in spontaneous preterm deliveries.