Studies identify causes, risk factors for stillbirth

December 13, 2011

CHICAGO - Common causes for stillbirth include obstetric complications and placental abnormalities, while factors that could be known at the start of pregnancy, such as previous stillbirth or pregnancy loss, were associated with an increased risk for stillbirth, although these and other factors accounted for only a small proportion of the overall risk, according to two studies in the December 14 issue of JAMA.

"Stillbirth, defined as fetal death at 20 weeks' gestation or later, is one of the most common adverse pregnancy outcomes in the United States and affects approximately 1 in 160 pregnancies. These approximately 26,000 stillbirths per year are equivalent to the number of infant deaths. The stillbirth rate in the United States is higher than that of many other developed countries," according to background information in the first article. "Since 2003 the stillbirth rate in the United States has remained stagnant at 6.2 stillbirths per 1,000 births, 59 percent higher than the Healthy People 2010 target goal of 4.1 fetal deaths per 1,000 births."

Robert M. Silver, M.D., of the University of Utah School of Medicine, Salt Lake City, and colleagues with the Stillbirth Collaborative Research Network Writing Group, conducted a study to determine the causes of stillbirth in a racially and geographically diverse population in the United States. The study was conducted from March 2006 to September 2008 with surveillance for all stillbirths at 20 weeks or later in 59 tertiary care and community hospitals in 5 areas defined by state and county boundaries to ensure access to at least 90 percent of all deliveries. Standardized evaluations were performed at delivery.

Of 663 women with stillbirth enrolled, 500 women consented to complete postmortem examinations of 512 neonates. A probable cause of death was found in 312 of the stillbirths (60.9 percent) and a possible or probable cause in 390 cases (76.2 percent). There was more than 1 probable or possible cause of death in 161 stillbirths (31.4 percent). The researchers found that obstetric complications were the most common category for cause of death (150 cases [29.3 percent]); placental abnormalities were indicated in 121 cases (23.6 percent). "Other causes included fetal genetic/structural abnormalities in 70 cases (13.7 percent), infection in 66 (12.9 percent), umbilical cord abnormalities in 53 (10.4 percent), hypertensive disorders in 47 (9.2 percent), and maternal medical complications in 40 (7.8 percent)," the authors write.

The researchers also found that non-Hispanic black women experienced a higher proportion of stillbirths associated with obstetric complications compared with non-Hispanic white women and Hispanic women combined (43.5 percent [50] vs. 23.7 percent [85]); and infections (25.2 percent [29] vs. 7.8 percent [28]). Cord abnormalities were associated with a higher proportion of stillbirths in non-Hispanic white and Hispanic women compared with non-Hispanic black and other women.

The authors note that the sources most likely to provide positive information regarding cause of death were placental histology, perinatal postmortem examination, and karyotype (an evaluation of the chromosomes).

"The U.S. stillbirth rate has remained unacceptably high, affecting 1 in 160 pregnancies each year. Reduction in the stillbirth rate will require thorough investigation into the cause of death. After a systematic and thorough evaluation, a cause of death was determined in the majority of cases of stillbirth in our study. Therefore, postmortem examination, placental histology, and karyotype are strongly recommended as part of the diagnostic evaluation. In addition, the development of interventions to prevent stillbirth should consider the observed differential distribution of causes of death as gestational age advances, as well as variation by race/ethnicity," the researchers conclude.

(JAMA. 2011;306[22]:2459-2468. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Various Risk Factors Known At Time of Pregnancy May Help Gauge Risk of Stillbirth

In another study in the December 14 JAMA, George R. Saade, M.D., of the University of Texas Medical Branch at Galveston, and colleagues with the Stillbirth Collaborative Research Network Writing Group, examined the relation between stillbirths and risk factors that could be ascertained at the start of pregnancy, particularly the contribution of these factors to the racial disparities that exist with stillbirths.

"Many of the factors associated with stillbirth need to be addressed early in pregnancy. Although other factors may be important later in pregnancy, clinicians providing obstetrical care frequently spend relatively more time at the initial visits counseling patients regarding their risk of adverse pregnancy outcomes," the authors write.

The multisite population-based case-control study was conducted between March 2006 and September 2008 at 59 U.S. tertiary care and community hospitals, with access to at least 90 percent of deliveries within 5 areas defined by state and county lines. The study enrolled residents with deliveries of 1 or more stillborn fetuses and a representative sample of deliveries of only live-born infants, which was supplemented by oversampling of women delivering at less than 32 weeks' gestation and those of African descent delivering at 32 weeks' gestation or greater. The analysis included 614 case and 1,816 control deliveries.

The researchers found that after analyses, a number of maternal factors were independently associated with stillbirth: non-Hispanic black race/ethnicity; diabetes; age 40 years or older; AB blood type; history of drug use with addiction; history of cigarette smoking during the 3 months prior to pregnancy; being overweight or obese; and not living with a partner.

Several reproductive history factors were strongly associated with stillbirth, including previous stillbirth and nulliparity (a woman who has never borne a child) with and without a history of prior spontaneous losses at less than 20 weeks' gestation and plural (multiple, i.e., twins) birth in the current pregnancy.

The authors note that overall, pregnancy factors known at the start of pregnancy accounted for little of the stillbirth risk. Apart from occurrence of previous stillbirth or pregnancy loss, the other risk factors have limited predictive value, they write.

"Further research is needed to identify pregnancies at highest risk overall and for specific causes. Although some of the risk factors may not be modifiable (e.g., race/ethnicity), knowledge of interactions between these factors and other modifiable ones may be useful. In addition, association studies aid in the identification of areas of investigation and preventive approaches. For example, non-Hispanic black women have a more than 2-fold increase in risk of stillbirth. However, the disparity in risk largely occurs at less than 24 weeks' gestation. Therefore, focusing on the pathophysiology of early preterm birth may reduce racial disparity in stillbirth," the researchers conclude.

(JAMA. 2011;306[22]:2469-2479. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Stillbirth and Lessons for Pregnancy Care

Jay D. Iams, M.D., and Courtney D. Lynch, Ph.D., M.P.H., of The Ohio State University Medical Center, Columbus, comment on the findings of these studies in an accompanying editorial.

"The Stillbirth Collaborative Research Network (SCRN) reports add to the increasing realization that the current obstetrical taxonomy [classifications] is an obstacle to improving pregnancy outcomes. Optimal investigation of the origins, treatment, and prevention of stillbirth and preterm birth will require data collected on deliveries before and after 20 weeks, regardless of whether the fetus is alive or not at the time of presentation for care."

"As the SCRN work highlights, pregnancies involving fetal death near the limit of viability, including those before 20 weeks, share important commonalities with pregnancies resulting in early preterm birth. As such, the reports from the SCRN will not only further the understanding of stillbirth but should also encourage the need to reframe thinking about how to address the problem of spontaneous preterm birth and the associated racial/ethnic disparities."

(JAMA. 2011;306[22]:2506-2507. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
To contact Robert M. Silver, M.D., call Phil Sahm at 801-581-2517 or email To contact George R. Saade, M.D., call Kristen Hensley at 409-772-8772 or email To contact editorial co-author Jay D. Iams, M.D., call Marti Leitch at 614-293-3737 or email

The JAMA Network Journals

Related Preterm Birth Articles from Brightsurf:

Researchers develop app to determine risk of preterm birth
An improved mobile phone app will help identify women who need special treatments at the right time and reduce emotional and financial burden on families and the NHS.

Point-of-care diagnostic for detecting preterm birth on horizon
A new study provides a first step toward the development of an inexpensive point-of-care diagnostic test to assess the presence of known risk factors for preterm birth in resource-poor areas.

WVU biostatistician studies link between microbiome and preterm birth
Pregnant African American women are more likely than white women to give birth prematurely, but they're underrepresented in studies of preterm birth rates.

3D-printed device detects biomarkers of preterm birth
Preterm birth (PTB) -- defined as birth before the 37th week of gestation -- is the leading complication of pregnancy.

Association of quitting smoking during pregnancy, risk of preterm birth
This study of more than 25 million pregnant women reports on rates of smoking cessation at the start of and during pregnancy and also examines the association of quitting cigarette smoking and the risk of preterm birth.

Blood test developed to predict spontaneous preterm birth
Results from a multicenter study show that five circulating microparticle proteins found in first-trimester blood samples may provide important clues about risk of spontaneous preterm birth.

Scientists gain new insight on triggers for preterm birth
A group of scientists led by Ramkumar Menon at The University of Texas Medical Branch at Galveston have gained new insight on a poorly-understood key player in the timing of labor and delivery.

Medically assisted reproduction does not raise risk of preterm birth and low birth weight
Study shows that couples can decide about using medically assisted reproduction free from concerns about increasing the health risks to their baby.

Risk of preterm birth reliably predicted by new test
Scientists at UC San Francisco have developed a test to predict a woman's risk of preterm birth when she is between 15 and 20 weeks pregnant, which may enable doctors to treat them early and thereby prevent severe complications later in the pregnancy.

Preterm birth leaves its mark in the functional networks of the brain
Researchers at the University of Helsinki and the Helsinki University Hospital, Finland, have proven that premature birth has a significant and, at the same time, a very selective effect on the functional networks of a child's brain.

Read More: Preterm Birth News and Preterm Birth Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to