In developing countries, stillbirths occur at a rate of about 13 per 1,000 births and early infant deaths at a rate of nine per 1,000 live births—even when women receive antenatal care and deliver in hospitals prepared to handle obstetrical and newborn complications.¹ According to a multinational study among women giving birth for the first time, the leading causes of fetal and early infant deaths combined are spontaneous preterm delivery (accounting for 29% of the deaths) and hypertensive disorders (accounting for 26%). Prematurity is responsible for fully 61% of early infant deaths and is the leading cause of death even in pregnancies near term.

Study data came from a randomized trial of calcium supplementation to prevent pre-eclampsia, conducted among women who were at elevated risk because they had a low calcium intake and had not previously given birth. Pregnant women visiting general antenatal clinics in six countries—Argentina, Egypt, India, Peru, South Africa and Vietnam—during 2001–2003 were eligible if they had a pregnancy of less than 20 weeks' gestation, had never given birth and did not have hypertension or a history of the condition. Participating women took calcium or a placebo daily until delivery and were examined monthly at the clinics, which were located in hospitals that had neonatal intensive care units or could refer women to such hospitals. The rates of stillbirth (fetal deaths among all births) and early neonatal death (newborn deaths during the first seven days of life among all live births) were determined for pregnancies of at least 28 weeks' gestation. A single cause of each fetal or newborn death was determined from data-collection forms and hospital records.

Analyses were based on 7,993 pregnancies among 8,325 women; the women were nearly equally divided between the calcium and placebo groups. About 1% of the pregnancies were multiple pregnancies.

Overall, 100 pregnancies ended in death of the fetus, corresponding to a rate of about 13 stillbirths per 1,000 births. An additional 71 pregnancies ended in death of the newborn within seven days, corresponding to a rate of nine early neonatal deaths per 1,000 live births. Fully 63% of the pregnancies with an outcome of stillbirth or early neonatal death ended before term; of these pregnancies, four-fifths ended by spontaneous preterm delivery, while one-fifth ended by preterm delivery induced because of medical complications.

As pregnancy advanced, the rates of stillbirth and early neonatal death decreased. Each outcome occurred at a rate of about 400 per 1,000 births at 28 weeks of gestation, but fell sharply to a rate of roughly 20 per 1,000 births at 40 weeks of gestation. In contrast, the risks of these outcomes, as determined by Kaplan-Meier analyses, declined initially but rose later in pregnancy, peaking at 39 weeks of gestation. At that gestational age, the risk of stillbirth was about 350 per 100,000 undelivered fetuses and the risk of early neonatal death was about 400 per 100,000 live births.

On the basis of an obstetric classification system, the leading cause of stillbirths and early neonatal deaths combined was spontaneous preterm labor (labor starting before 37 weeks of gestation), which was the cause in 29% of pregnancies with these outcomes, followed by hypertensive disorders, the cause in 26%. Less common causes were fetal abnormalities (13%), intrapartum-related causes (9%) and unexplained intrauterine fetal death (8%), among others. Compared with women in the placebo group, women in the calcium group had a significantly lower risk of their pregnancy ending in stillbirth or early neonatal death because of hypertensive disorders.

On the basis of an international disease classification system, 61% of the early neonatal deaths were due to prematurity, 23% to asphyxia and birth trauma, 13% to congenital anomalies, 1% to infection and the rest to unknown causes. When these deaths were stratified by the gestational age of the infant at delivery, prematurity was the most common cause of death among infants born before 37 weeks of gestational age; thereafter, asphyxia was the most common cause. The pattern was similar in the calcium group and in the placebo group individually.

An important finding of the study, the researchers point out, was that even though the women and infants received care in secondary and tertiary hospitals, the observed rates of perinatal death still exceed those in developed countries. Another important finding, with implications for the future, was the pattern of causes of deaths; specifically, they assert, the study's results suggest that as obstetric and newborn care becomes more accessible in developing countries, preterm delivery and hypertensive disorders may increase in relative importance as causes of fetal and newborn death, while intrapartum complications may decrease in relative importance. They therefore advocate research into the causes of preterm delivery and hypertensive disorders, with the aim of translating the findings into life-saving interventions. "Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries," they conclude.—S. London

REFERENCE

1. Ngoc NTN et al., Causes of stillbirths and early neonatal deaths: data from 7993 pregnancies in six developing countries, Bulletin of the World Health Organization, 2006, 84(9):699–705.