They used the collected data to also study another important public health problem: inappropriate use of oxytocics before childbirth. While oxytocin to prevent postpartum bleeding is life-saving, its’ use before birth without adequate monitoring may actually harm babies.

Two sides to a story

For a variety of reasons, including initiating labour, increasing the speed of labour, and for stopping bleeding following delivery, women may be given drugs that contract the uterus, such as oxytocin. Such drugs are also called oxytocics or uterotonics. When such drugs are given to women before birth, they may reduce the blood flow to the placenta, and therefore its supply of oxygen to the foetus. This may increase the risk of stillbirth, birth asphyxia, and neonatal encephalopathy. It is important, therefore, that antenatal oxytocin, if indicated, be administered in compliance with approved guidelines using an intravenous drip together with close monitoring of the foetal heart rate and uterine contractions. It should only be administered in facilities where emergency obstetric care, including caesarean section, is available, so that a woman receiving oxytocin can be immediately taken for surgery if foetal distress appears.

Unfortunately, in many developing countries today, including India, there is widespread use of oxytocics before delivery even in settings where intravenous drip, foetal and maternal monitoring, and emergency obstetric care is not available.

There have been few studies to properly evaluate the risks involved in this use of oxytocics.  To address this knowledge gap, an international research team, led by Drs. Sanjana Brahmawar Mohan, Halvor Sommerfelt and Nita Bhandari, undertook a population-based case-control study using data from a large randomized trial evaluating IMNCI in Haryana, India. This research aimed to estimate whether and to what extent antenatal administration of uterotonics increased the risk of babies’ dying during childbirth and on the day of birth.

Quantifying danger potential

Verbal autopsy is a method used to understand the cause of and circumstances around death. It is used for maternal and child deaths in developing countries, where appropriate death certificates, hospital records or documented detailed information around death, are often not available.  When the researchers reviewed the verbal autopsies of stillbirth and neonatal death in the IMNCI trial, they observed that more than half of the women, including those who delivered at home, seemed to have received injections of uterotonic drugs to initiate or augment labour. The drug oxytocin is the most commonly used uterotonic in India. To assess whether such injections increased the risk of death around birth, the researchers undertook a case–control analysis to estimate the extent to which antenatal uterotonic administration was associated with stillbirth or day-1 death.

Their findings showed that administration of uterotonics was reported in 62% of home deliveries, and 81% of the deliveries in health facilities, findings consistent with those in other community- and hospital-based studies in other Asian countries. Their large sample size (over 2000 cases and over 500 controls) enabled them to separately estimate the strength of such an association for babies born at home, in private, and in government facilities. They were also able to measure the association between such administration and the risk of death during childbirth and death on day 1, day 2, or day 3, and from day 4 to 7.

Sobering findings

The analyses showed that the administration of an injectable uterotonic during labour occurred during 74% of early (stillbirths or day-1 deaths) and 62% of late neonatal deaths (day 8-28 of life). Use of uterotonics increased the risk of dying in the womb after the onset of labour, or soon after birth, by 70%. This translates to a population attributable risk of 31%. This is a staggering and disturbing finding, especially as this procedure was intended to be in the mother and child’s best interests, and instead it seems to contribute substantially to stillbirths and day-1 deaths.

If the findings apply to the rest of India, this means that should oxytocics be used as directed by current Indian and international guidelines, it would be possible to save at least 130,000 Indian babies from dying every year. Although derived from a sub-group analysis, which carries some uncertainty, it is noteworthy that women who received oxytocics in government birth facilities did not experience an increased risk of baby death.

The researchers hold that a treatment that should be used to stop life-threatening post-partum bleeding, should be used with great caution before the baby is born.

 

When its use is deemed necessary, appropriate clinical evaluation needs to be undertaken to ascertain indications for its use and this should only take place when the emergency back-up options as outlined in the current Indian and international guidelines are in place.  

 

They hope that their work will encourage other studies in this area and reinforce evidence-based policy decisions regarding the use of these drugs.

Paper: 

Antenatal Uterotonics as a Risk Factor for Intrapartum Stillbirth and First-day Death in Haryana, India: A Nested Case-control Study (external link)

by: Sanjana Brahmawar Mohan (India), Halvor Sommerfelt (Norway), J. Frederik Frøen (Norway), Sunita Taneja (India), Tivendra Kumar (India), Kiran Bhatia (India), Lize van der Merwe (Norway), Rajiv Bahl (WHO), Jose C. Martines (Norway), Sarmila Mazumder (India), Nita Bhandari (India)

Video presentation of paper. (external link)

 

Facts:

  • The day of birth carries the greatest lifetime risk of death.
  • Half of the annual global 2.6 million stillbirths are reported to be during childbirth (intrapartum).
  • One third of the almost 2.5 million babies who die annually in the first month after birth (neonatal death), die during the first 24 hours (day-1).
  • Over 95% of all stillbirths and neonatal deaths occur in low- and middle-income countries.
  • A substantial proportion of neonatal deaths are associated with asphyxiating complications of the birth process. Birth asphyxia is the cause of about one fourth of neonatal deaths globally, also in India.

 

Study Results:

  • the use of antenatal oxytocics was associated with a substantially increased risk of intrapartum stillbirth and day-1 death.
  • antenatal administration of oxytocics more strongly predicted early death among boys than among girls. This is of interest because it is known that boys are more likely to die from asphyxia than are girls
  • Women giving birth for the first time (nulliparous women), who are given oxytocics, had an even higher risk of having their baby die than women who have previously given birth (multiparous women). This is interesting because nulliparous women are known to be more prone to experience obstructed labour and babies who die from asphyxia.
  • When the researchers in a mediation analysis adjusted for asphyxia among the live-born babies, the association between oxytocin injections and day-1 death evaporated, indicating that such injections indeed caused asphyxia which could kill the babies.