Institute Activities and Advances
Research related to pregnancy is supported through several NICHD organizational units, including (but not limited to) the Pregnancy and Perinatology Branch (PPB), which seeks to improve the health of mothers and children through basic science and clinical research on maternal health, pregnancy, and fetal well-being; and the Fertility and Infertility (FI) Branch, which focuses on expanding the NICHD's knowledge of the molecular and cellular processes that underlie the success or failure of human reproduction; and the Division of Epidemiology, Statistics, and Prevention Research (DESPR).
Institute research focuses not only on the basic mechanisms of pregnancy loss, but also on the conditions that increase the likelihood of its occurrence. Some of these activities are described below.
Although some causes for miscarriage are known, such as preeclampsia/eclampsia and high blood pressure, polycystic ovary syndrome (PCOS), and uterine or cervical abnormalities, many causes of this type of pregnancy loss remain unknown. Some of the Institute’s activities related to understanding miscarriage include (but are not limited to) the following.
- 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 pregnancy loss.1,2,3
- Other Institute research focuses on understanding endometriosis and other conditions and factors affecting the endometrium, which can lead to implantation failures and recurrent pregnancy loss.
- 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.5
- Research oriented to identify new therapeutic opportunities. For example, through the Effects of Aspirin in Gestation and Reproduction (EAGeR) Study, scientists are examining the therapeutic value of low-dose aspirin (LDA) in prenatal care. 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.6
- 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 abortion.7
- The NICHD's Longitudinal Investigation of Fertility and the Environment (LIFE) Study examines the relationship among environmental chemicals, lifestyle, and human fertility. The NICHD also has supported research on Weight Management Programs during Pregnancy 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.
- The NICHD also promotes research aimed at understanding basic cellular and molecular mechanisms. For example, studies by the Unit on Reproductive and Regenerative Medicine examine the role of endometrial stem cells in gynecologic problems, such as scarring of the uterine cavity, endometriosis, and recurrent pregnancy loss. Other NIH research aimed at understanding the mechanisms for endometrial cell survival has focused on differences in protein expression between uterine endometriosis cells and normal cells to reveal altered growth signatures. Additional NIH work studying gap junction communication between uterine stromal cells examines intercellular communication and its role in uterine neovascularization during implantation.12
Within the Stillbirth Collaborative Research Network (SCRN), a network funded through the NICHD's PPB, studies focus on the causes of intrauterine fetal death, including placental abnormalities, fetal/genetic/structural abnormalities, infection, hypertension, and other maternal medical conditions, fetal stress hormones, and unexplained fetal death.8,10,11 Additional SCRN work centers on identifying and understanding additional stillbirth risk factors. Although to prospectively identify woman who are at risk of stillbirth is difficult, previous work has shown that past pregnancy history is a significant risk factor for stillbirth.9
Other Activities and Advances
To achieve its goals related to pregnancy loss research, the NICHD supports and participates in a variety of other activities, including NIH-wide efforts. Some of these are listed below.
- 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 [top]
- 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 [top]
- 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 [top]
- National Institute of Child Health and Human Development. NIH News. (2011, February 18). Research identifies protein essential for embryo implantation. Retrieved June 2, 2012, from http://www.nichd.nih.gov/news/releases/pages/021811-progesterone-and-Hand2.aspx [top]
- 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 [top]
- National Institute of Child Health and Human Development. (2008, July 25). The effects of aspirin in Gestation and Reproduction (EAGeR) Study. Retrieved June 2, 2012, from http://www.nichd.nih.gov/about/org/despr/eb/research/Pages/effects-aspirin.aspx [top]
- Santolaya-Forgas, J., Mittal, P., De Leon-Luis, J., Than, N. G., Hong, J. S., Wolf, R., et al. (2012, February 28). A prospective and controlled in vivo study to determine if acute episodes of high glucose concentrations within the gestational sac compartment could be related to spontaneous abortion [Epub ahead of print]. Journal of Maternal-Fetal Neonatal Medicine. PMID 22372954 [top]
- Stillbirth Collaborative Research Network Writing Group. (2011). Causes of death among stillbirths. Journal of the American Medical Association, 306(22), 2459-2468. PMID 22166605 [top]
- Stillborn Collaborative Research Network Writing Group. (2011). Association between stillbirth and risk factors known at pregnancy confirmation. Journal of the American Medical Association, 306(22), 2469-2479. PMID 22166606 [top]
- Sarr, D., Smith, G. M., Poovassery, J. S., Nagy, T., & Moore, J. M. (2012). Plasmodium chabaudi AS induces pregnancy loss in association with systemic pro-inflammatory immune responses in A/J and C57BL/6 mice. Parasite Immunology, 34(4), 224-235. PMID 22251385Wood, C. E. (2011). Fetal hypothalamus-pituitary-adrenal responses to estradiol sulfate. Endocrinology, 152(12), 4966-4973. PMID 21952234 [top]
- Espinoza, J., Chaiworapongsa, T., Romero, R., Kim, Y. M., Kim, G. J., Nien, J. K., et al. (2007). Unexplained fetal death: Another anti-angiogenic state. Journal of Maternal-Fetal Neonatal Medicine, 20(7), 495-507. PMID 1767462 [top]
- Laws, M. J., Taylor, R. N., Sidell, N., DeMayo, F. J., Lydon, J. P., Gutstein, D. E., et al. (2008). Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival. Development, 135(15), 2659-2668. PMID 18599509 [top]
- Erez, O., Hoppensteadt, D., Romero, R., Espinoza, J., Goncalves, L., Nien, J. K., et al. (2007). Preeclampsia is associated with low concentrations of protein Z. Journal of Maternal-Fetal Neonatal Medicine, 20(9), 661-667. PMID 17701666 [top]