NICHD Stillbirth Research Information

NICHD’s research goals related to stillbirth include:

• Understanding the causes of stillbirths
• Detailing the demographic and population factors related to stillbirth
• Improving prediction of stillbirth risk
• Improving stillbirth post-mortem examination and reporting
• Outlining evidence-based measures to prevent or reduce stillbirth
• Linking in utero developmental phenotypes to gene expression, epigenetic changes, maternal physiology, and environmental exposures
• Improving our understanding of the morphology, function, genetics, and metabolism of the placenta and uterine blood flow
• Improving methods for antenatal diagnosis of placental disease or fetal health conditions that increase risk of stillbirth

Through its intramural and extramural organizational units, NICHD conducts and supports a broad range of research projects on stillbirth. Short descriptions of this research are included below.

• Institute Activities and Advances
• Other Activities and Advances

Institute Activities and Advances

A large portion of the Institute’s support for research on stillbirth is provided through the extramural Pregnancy and Perinatology Branch (PPB), whose interests encompass all research that seeks to improve health outcomes associated with pregnancy, birth, and early infancy. PPB supported the Stillbirth Collaborative Research Network (SCRN), which was founded to examine the etiology and epidemiology of stillbirth.

The Network has made some important findings, including the following:

• An SCRN study compared the use of illicit drugs and cigarettes in U.S. pregnancies with and without stillbirth. They found that a pregnant mother’s use of cigarettes, marijuana, or other illicit drugs and her exposure to secondhand smoke were linked to an increased risk of stillbirth. (PMID: 24463671)
• SCRN researchers compared microarray analysis to the standard karyotyping for examining stillborn fetuses’ genetic material and found that microarrays may help detect abnormalities in 40% more cases than the traditional method. (PMID: 23215556)
• One Network study of women giving birth in 59 hospitals around the country found that about one-half of stillbirths were caused by pregnancy complications and conditions affecting the placenta, although most were not linked to any known risk factors the women had at the beginnings of their pregnancies. (PMID: 22166606)
• Another SCRN study found that stressful events in the mother’s life 1 year prior to delivery seemed to increase risk of stillbirth. (PMID: 23531847)

Outside of the SCRN, other recent PPB-supported grants have studied new methods and biomarkers for predicting stillbirth and other adverse outcomes to the fetus. Additional areas of recent support include the risks of smoking, maternal infections, and overweight/obesity during pregnancy as well as the benefits of interventions for these risks. One Branch-supported investigator recently developed an experimental vaccine that significantly reduces stillbirths among rodents that were born to mothers infected with cytomegalovirus (CMV). If pregnant women become infected with the virus, it can result in stillbirth or other negative consequences in the fetus, and currently no preventive measures are available. (PMID: 17299708)

NICHD also supports the Global Network for Women’s and Children’s Health Research, which tests cost-effective interventions to improve maternal and infant health outcomes, including stillbirth, in resource-poor settings. Recently, a Global Network training program for health care workers in six resource-poor countries resulted in a sharp drop in the rate of stillbirths among mothers attended by workers who had been trained through the program, from 23 stillbirths per 1,000 deliveries to fewer than 16 stillbirths per 1,000 deliveries. This was most likely due to a drop in deaths among newborns who would not have taken a breath on their own without resuscitation from the trained attendants, the researchers concluded. (PMID: 20164485)

This training program has now grown into the Helping Babies Breathe initiative, a newborn-care education project active in more than 30 low-income countries around the world. NICHD is one of several international partners leading this initiative, which shows health care providers resuscitation techniques and other basics of newborn care for the first minute of life. The goal of Helping Babies Breathe is to have at least one person with newborn resuscitation skills attending the birth of every baby in the world. Learn more about NICHD’s role in the Helping Babies Breathe initiative.

The Division of Population Health Research (DiPHR) also conducts research on factors affecting risk for stillbirth, primarily through these three studies:

• Longitudinal Investigation of Fertility and the Environment (LIFE) Study
  The LIFE Study is designed to examine the relationship between ubiquitous environmental chemicals, lifestyle, and human fecundity and fertility, including stillbirth and other pregnancy outcomes.
• Effects of Aspirin in Gestation and Reproduction (EAGeR) Study
  This multisite, randomized placebo-controlled clinical trial is designed to evaluate the effect of daily low-dose aspirin on live-birth rates. Stillbirth is one of the outcomes it is evaluating.
• Consortium on Safe Labor
  This observational study of more than 200,000 deliveries aimed to explore contemporary labor progression and the use of cesarean section. Although stillbirth was not a primary focus of the study, the researchers have collected and published data on risk factors for stillbirth.

In addition to the efforts of PPB and DiPHR, other NICHD organizational units support or conduct research with relevance to stillbirth. For example:

• The Fertility and Infertility Branch (FIB), as part of its portfolio on the mechanisms of fertility and treatments for infertility, supports research on the very early processes in embryonic development that result in aneuploidy, which can cause stillbirth.
• The Maternal and Pediatric Infectious Disease Branch (MPIDB) focuses on HIV and other infectious diseases (including CMV) in pregnant women and children. The MPIDB supports research on the effects of antiretroviral drugs during pregnancy on pregnancy outcomes such as stillbirth.

Other Activities and Advances

• The Stillbirth Collaborative Research Network (SCRN), supported by the PPB, was established in 2003 to understand the causes of stillbirth, improve stillbirth reporting, and develop preventive interventions for the condition. In addition, the SCRN is leading to the standardization of reporting procedures and post-mortem examination protocols, which allow more accurate data on the topic.
• The Prenatal Alcohol and SIDS and Stillbirth (PASS) Network, supported by the PPB and two other NIH Institutes, conducts community-linked studies to investigate the role of prenatal alcohol exposure in the risk for SIDS and adverse pregnancy outcomes, such as stillbirth and fetal alcohol spectrum disorders, and how they may be interrelated.
• The Global Network for Women and Children’s Health Research, a partnership between NICHD, the Bill and Melinda Gates Foundation, and other organizations, is committed to improving maternal and infant health outcomes and building health research capacity in resource-poor settings by testing cost-effective, sustainable interventions for adverse maternal and child health outcomes such as stillbirth.
• The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), supported by the PPB, aims to study the underlying causes of adverse pregnancy outcomes (preterm birth, preeclampsia, fetal growth abnormalities, and stillbirth) among a cohort of 10,000 women in their first pregnancy. This prospective observational study is expected to lead to a better understanding of how genetics, biomarkers, environmental exposures, and psychosocial factors interact to result in these adverse outcomes. The recruitment and ascertainment of outcomes of the final cohort was completed in September 2014. A substudy of nuMoM2b—co-funded by the National Heart, Lung, and Blood Institute—is studying the effect of sleep disordered breathing during pregnancy and various sleep parameters, including sleep position, on these adverse pregnancy outcomes.
• The Maternal-Fetal Medicine Units (MFMU) Network, supported by the PPB, is conducting a trial of women who are diagnosed with primary cytomegalovirus (CMV) infection early in pregnancy. Primary CMV infection is associated with stillbirth, placental damage, and poor fetal growth. This trial is studying whether treatment with hyperimmune CMV globulin versus placebo decreases CMV infection and consequences in the offspring.