Fetal Death Risk Climbs With First Signs of Preeclampsia

Laurie Barclay, MD

February 06, 2015

Pregnancies diagnosed with preeclampsia in the preterm period have a very high relative risk for fetal death, according to findings of a population-based cohort study published online February 4 and in the March issue of Obstetrics & Gynecology.

"Although the pathologic origins of preeclampsia likely occur during placentation, the clinical signs and symptoms typically do not emerge until after 20 weeks of gestation," write Quaker E. Harmon, MD, PhD, from the Epidemiology Branch and Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, and colleagues. "The most relevant estimate of fetal risk in the presence of preterm preeclampsia would be one that considers the timing of preeclampsia diagnosis — a diagnosis that often occurs well before the time of delivery.

"[O]ur analysis documents the fetal risk that accompanies preeclampsia in early pregnancy," the authors write. "Although this risk to the fetus is generally recognized, the extent of risk is far higher than previously estimated."

The authors estimated gestational age-specific risks for fetal death in pregnancies complicated by preeclampsia but without preexisting chronic hypertension among all 554,333 singleton births recorded in the Norwegian Medical Birth Registry from 1999 to 2008.

The investigators also studied medical records in a subset of preeclamptic pregnancies enrolled in the Norwegian Mother and Child Cohort Study (n = 3037). Using a life table approach, they calculated the risk for fetal death per 1000 fetuses exposed to preeclampsia.

Among all pregnancies in the birth registry, 21,020 (3.8%) had preeclampsia. Risk for stillbirth was 45% higher among pregnancies with preeclampsia (3.6 per 1000 overall vs 5.2 per 1000 among pregnancies with preeclampsia; relative risk, 1.45; 95% confidence interval [CI], 1.20 - 1.76).

Among women with preeclampsia in early pregnancy, relative risk for stillbirth was even higher. Stillbirths at 26 weeks of gestation occurred in 11.6 of 1000 pregnancies with preeclampsia but in only 0.1 stillbirths per 1000 pregnancies without preeclampsia (relative risk, 86; 95% CI, 46 - 142).

With increasing gestational age, risk for fetal death with preeclampsia fell. However, risk for fetal death at 34 weeks of gestation was still increased more than sevenfold compared with pregnancies without preeclampsia.

The authors note several possible limitations, including incomplete capture or false-positive diagnoses of preeclampsia by the Medical Birth Registry of Norway, relatively few stillbirths, and lack of data on obesity and other maternal factors that might confound analyses of preeclampsia and stillbirth. In addition, the birth registry lacks dates of preeclampsia diagnosis and specific features of severe disease at the time of diagnosis.

The Norwegian Ministry of Health and the Ministry of Education and Research, National Institutes of Health, National Institute of Environmental Health Sciences, National Institute of Neurological Disorders and Stroke, and the Norwegian Research Council supported the Norwegian Mother and Child Cohort Study. The National Institute of Child Health and Human Development funded the validation of preeclampsia diagnoses. The authors have disclosed no relevant financial relationships.

Obstet Gynecol. 2015;125:628-635. Abstract

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