NICHD Pregnancy Loss (Before 20 Weeks) Research Information

NICHD conducts and sponsors research on pregnancy and its many outcomes, including pregnancy loss before 20 weeks of gestation. Through this work, the Institute aims to improve the health of mothers and their fetuses by understanding conditions and situations that lead to poor outcomes, including pregnancy loss. The Institute also supports professional training and funding opportunities that enable research on pregnancy loss to continue into the future.

NICHD conducts and supports research on pregnancy outcomes, including pregnancy loss, and ways to treat or prevent poor pregnancy outcomes.

This type of research can be done in multiple ways. Some Institute research is aimed at understanding the normal progress of a healthy pregnancy and factors that contribute to it, including prenatal care, maternal characteristics, and health history. Other work strives to understand pregnancy-related disorders and their contributions to risk for poor outcomes.

NICHD also studies specific outcomes, such as pregnancy loss, to understand causes and risk factors and identify treatments and possible methods of prevention.

NICHD supports and conducts a variety of research on pregnancy loss before 20 weeks of gestation through several organizational units.

Institute Activities and Advances

Pregnancy loss before 20 weeks gestation falls into the research portfolios of several NICHD components, including:

  • The Pregnancy and Perinatology Branch (PPB) supports research related to pregnancy loss, including studying pregnancy complications, placental problems, and the impact of lifestyle influences, such as prenatal alcohol exposure, on pregnancy loss.
  • The Fertility and Infertility (FI) Branch focuses on expanding knowledge of the factors contributing to pregnancy loss and on methods of detecting pregnancy problems early, particularly as they relate to infertility issues or fertility treatments.
  • The Division of Population Health Research studies factors that influence human reproduction and development across the lifespan, including environmental factors, to increase our understanding of pregnancy loss.

Institute research focuses not only on the basic mechanisms of pregnancy loss before 20 weeks of gestation but also on the conditions that increase the likelihood of its occurrence and the best treatment options. NICHD also studies stillbirth, defined as pregnancy loss after 20 weeks of gestation, including its causes, its mechanisms, risk factors for the condition, and treatments; this information is provided elsewhere on this website.

Although some causes for or factors contributing to pregnancy loss before 20 weeks of gestation, such as chromosomal abnormalities and uterine or cervical abnormalities, are known, many causes and factors remain unknown. Some of the Institute's activities related to understanding pregnancy loss include the following:

  • Institute research on morning sickness and miscarriage has discovered that women who experience nausea and vomiting during pregnancy have a lower risk of miscarriage. In the study, women kept diaries detailing their symptoms of nausea or vomiting throughout their pregnancies. More than half experienced nausea, and more than a quarter experienced nausea with vomiting. Compared with women who did not have these symptoms, women with morning sickness were 50% to 75% less likely to have a miscarriage.1
  • Institute research on preeclampsia and eclampsia has increased our understanding of the role of the angiotensin pathway and angiogenesis in the etiology of these conditions. Furthermore, the focus on the major angiotensin receptor, AT1R, and angiogenesis-related signaling molecules, such as placental growth factor and soluble fms-like tyrosine kinase 1 (sFlt1), has revealed novel opportunities for therapeutic interventions that could prevent a loss later in pregnancy (i.e., stillbirth).2,3,4
  • Other Institute research focuses on understanding conditions and factors affecting the endometrium, which can lead to implantation failures and recurrent pregnancy loss.5
  • Maternal health issues, such as infection, nutrition, and high blood glucose, can affect pregnancy outcomes and thus are areas of active Institute research. Ongoing research includes:
    • Research aimed at understanding how the innate immune system's response to infection changes the placental environment and fetal development. Some current work examines the expression and regulation of a group of innate immune receptors, called Toll-like receptors (TLRs), which may play a role in infection-associated pregnancy complications through regulation of infection-induced inflammatory responses at the maternal-fetal interface.6
    • Research oriented to identify new therapeutic opportunities. For example, through the Effects of Aspirin in Gestation and Reproduction (EAGeR) Study, scientists have found that daily low-dose aspirin (LDA) may help certain women at risk for miscarriage to carry a pregnancy to term.7 Current work suggests that LDA may positively affect several aspects of reproduction, including conception, implantation, and placental insufficiency. Further EAGeR research will analyze the effects of LDA in combination with folic acid treatment on the incidence of live births compared with the effects of folic acid alone.8
    • Research focused on understanding the relationship between poorly controlled diabetes and pregnancy loss. One NICHD-funded study on transient fluctuations in glucose concentration found that an acute increase in extra embryonic fluid glucose concentration is unlikely to cause spontaneous pregnancy loss.9
    • Research on the relationship between Zika virus and miscarriage. Institute researchers have developed mouse models and primate models that can be used to study how Zika causes problems during pregnancy, including miscarriage. These mouse models can also be used to test new vaccines and other therapies.10 NICHD is also leading a study of pregnant women in areas where Zika is spreading to document the relationship between when the virus is contracted and pregnancy outcomes, including miscarriage and stillbirth.11
  • NICHD's Longitudinal Investigation of Fertility and the Environment (LIFE) Study examines the relationship among environmental chemicals, lifestyle, and human fertility. NICHD also has supported research on Weight Management for Improved Pregnancy Outcomes, aiming to evaluate the efficacy and feasibility of minimizing weight gain during pregnancy in obese women in an effort to reduce the risk and serious consequences of pregnancy-related disorders.
  • Recent NICHD research also found that exposure to air pollution in early pregnancy is linked to pregnancy loss.

Other Activities and Advances

To achieve its goals related to pregnancy loss research, NICHD supports and participates in a variety of other activities, including NIH-wide efforts. Some of these are listed below.

  • The FI Branch–supported Reproductive Medicine Network (RMN) carries out large, multicenter clinical trials of diagnostic and therapeutic interventions for reproductive diseases and disorders, such as PCOS, and observational trials of pregnancy outcomes after treatment for infertility.
  • The National Centers for Translational Research in Reproduction and Infertility (NCTRI) (formerly the Specialized Cooperative Centers Program in Reproduction and Infertility Research [SCCPIR]), also supported by the FI Branch, promotes training and career development for research scientists in the areas of reproduction and infertility.
  • The Human Placenta Project aims to improve understanding of the placenta by developing new ways to study it during pregnancy. Such research could help to identify placental problems before they occur and provide avenues for treatments that may reduce pregnancy loss.
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Citations

  1. NICHD. (2016). NIH study links morning sickness to lower risk of pregnancy loss. Retrieved July 25, 2017, from https://www.nichd.nih.gov/news/releases/Pages/92616_nauseapregnancy.aspx
  2. Xia, Y., & Kellems, R. E. (2011). Receptor-activating autoantibodies and disease: Preeclampsia and beyond. Expert Review of Clinical Immunology, 7(5), 659–674. PMID 21895478
  3. Perni, U., Sison, C., Sharma, V., Helseth, G., Hawfield, A., Suthanthiran, M., et al. (2012). Angiogenic factors in superimposed preeclampsia: A longitudinal study of women with chronic hypertension during pregnancy. Hypertension, 59(3), 740–746. PMID 22311907
  4. Rajakumar, A., Cerdeira, A. S., Rana, S., Zsengeller, Z., Edmunds, L., Jeyabalan, A., et al. (2012). Transcriptionally active syncytial aggregates in the maternal circulation may contribute to circulating soluble fms-like tyrosine kinase 1 in preeclampsia. Hypertension, 59(2), 256–264. PMID 22215706
  5. NICHD. (2011, February 18). Research identifies protein essential for embryo implantation. Retrieved March 8, 2017, from http://www.nichd.nih.gov/news/releases/pages/021811-progesterone-and-Hand2.aspx
  6. Rose, J. A., Rabenold, J. J., Parast, M. M., Milstone, D. S., Abrahams, V. M., & Riley, J. K. (2011). Peptidoglycan induces necrosis and regulates cytokine production in murine trophoblast stem cells. American Journal of Reproductive Immunology, 66(3), 209–222. PMID 21385270
  7. Sjaarda, L. A., Radin, R. G., Silver, R. M., Mitchell, E., Mumford, S. L., Wilcox, B., et al. (2017). Preconception low-dose aspirin restores diminished pregnancy and live birth rates in women with low-grade inflammation: A secondary analysis of a randomized trial. Journal of Clinical Endocrinology and Metabolism, 102(5), 1495–1504. Retrieved July 25, 2017, from https://academic.oup.com/jcem/article/2967890/Preconception-low-dose-aspirin-restores-diminished 
  8. NICHD. (2008, July 25). Effects of Aspirin in Gestation and Reproduction (EAGeR) Study. Retrieved March 8, 2017, from http://www.nichd.nih.gov/about/org/despr/eb/research/Pages/effects-aspirin.aspx
  9. Santolaya-Forgas, J., Mittal, P., De Leon-Luis, J., Than, N. G., Hong, J. S., Wolf, R., & Wildman, D. (2012). A prospective and controlled in vivo study to determine if acute episodes of high glucose concentrations in the extra-embryonic celomic cavity could be related to spontaneous abortion. Journal of Maternal-Fetal & Neonatal Medicine, 25(10), 1848–1851. Retrieved July 25, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/22372954
  10. Miner, J. J., Cao, B., Govero, J., Smith, A. M., Fernandez, E., Cabrera, O. H., et al. (2016). Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell, 165(5), 1081–1091. Retrieved July 25, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874881/
  11. Spong, C. Y. (2016). Understanding Zika virus pathogenesis: An interview with Catherine Spong. BMC Medicine, 14, 84. Retrieved July 25, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895956/
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