Two-thirds of perinatal deaths are antepartum stillbirths, and two-thirds of these are referred to as “unexplained” because no apparent direct cause is identified. It has long been recognized that women who have had an unexplained stillbirth in one pregnancy are at increased risk of preeclampsia, preterm birth, or intrauterine growth restriction (IUGR) in the next pregnancy, most likely because all these outcomes are associated with placental dysfunction. The authors hypothesized that the reverse is also true, that women with a history of preeclampsia, preterm birth, or intrauterine growth restriction are at increased risk of having an unexplained stillbirth in subsequent pregnancies. This theory was tested by analyzing 133,163 second pregnancies in the Scottish Morbidity Record 2. The study population included all second births in Scotland in the years 1992–2001 to mothers whose first infant was live-born. Deaths taking place before the onset of labor were considered to be stillbirths.
Of 357 antepartum stillbirths not due to a fetal abnormality or rhesus isoimmunization, the cause of death was known in 105 (29.4%) and unexplained in 252 (70.6%). Women whose second pregnancy ended in antepartum stillbirth were more likely to have previously delivered a small-for-gestational-age (SGA) or preterm infant, had preeclampsia, or required a cesarean delivery in their first pregnancy. The risk of explained stillbirth in the second pregnancy was increased 6-fold in women with a previous preterm delivery, 3-fold in those who had delivered a SGA infant, and 3-fold in those who had preeclampsia.
When stillbirths were categorized by their respective causes, previous preeclampsia carried an 11-fold risk of stillbirth due to recurrent preeclampsia and a 6-fold risk of stillbirth due to maternal disease. Previous preterm birth was associated with a 16-fold increased risk of stillbirth due to maternal disease, a 6-fold increased risk of subsequent stillbirth due to preeclampsia, and a 4-fold increased risk of stillbirth due to hemorrhage. A previous SGA infant was associated with a 6-fold increased risk of stillbirth due to preeclampsia and a 4-fold increased risk due to hemorrhage.
When unexplained stillbirths were examined, preterm birth, delivery of a SGA infant, and preeclampsia in the first pregnancy were each associated with a 2-fold increased risk of stillbirth, and a history of both preeclampsia and delivery of a SGA infant increased the risk of unexplained stillbirth 5-fold. A past diagnosis of preeclampsia was not associated with a later risk of unexplained stillbirth if the infant was appropriate for gestational age. The hazard ratio for unexplained stillbirth associated with previous cesarean delivery in the years 1999–2001 was 2.27 (95% confidence interval, 1.38–3.73).
Women who have previously experienced placental dysfunction-related complications in a live birth are more likely than others to have an unexplained stillbirth in their next pregnancy. This association is especially strong for women who have a past history of preeclampsia and who also delivered a SGA infant. The placental dysfunction underlying these combined events may be the same or similar to the defect that predisposes to stillbirth.
Department of Obstetrics and Gynaecology, Cambridge University, The Rosie Hospital, Cambridge, United Kingdom; Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom; Department of Public Health, Greater Glasgow National Health Service Board, Glasgow, United Kingdom; and Information and Statistics Division, Common Services Agency, Edinburgh, United Kingdom
Am J Epidemiol 2007;165:194–202