Preterm Labor and Birth

In general, a normal human pregnancy lasts about 40 weeks, or just more than 9 months, from the start of the last menstrual period to childbirth. Labor that begins before 37 weeks is called preterm labor (or premature labor). A birth that occurs before 37 weeks is considered a preterm birth.

Preterm birth is the most common cause of infant death and is the leading cause of long-term disability related to the nervous system in children.

The NICHD is working both on its own and in collaboration with other agencies and organizations to learn more about the causes of preterm labor and birth, improve ways to predict which women are at risk for preterm delivery, and identify prevention methods to reduce the number of infants born early.

The NICHD also is studying ways to improve care for infants born too early in order to reduce death and disability associated with preterm birth.

Common Names

  • Early labor
  • Premature labor
  • Premature delivery
  • Premature birth
  • Preemie (for infant born preterm)

Medical or Scientific Name

  • Preterm labor
  • Preterm birth
  • Preterm infant
  • Late-preterm birth

Preterm Labor and Birth: Condition Information

What is preterm labor and birth?

In general, a normal human pregnancy is about 40 weeks long (9.2 months). Health care providers now define “full-term” birth as birth that occurs between 39 weeks and 40 weeks and 6 days of pregnancy.1 Infants born during this time are considered full-term infants.

Infants born in the 37th and 38th weeks of pregnancy—previously called term but now referred to as “early term”—face more health risks than do those born at 39 or 40 weeks.2

Deliveries before 37 weeks of pregnancy are considered “preterm” or premature:

  • Labor that begins before 37 weeks of pregnancy is preterm or premature labor.
  • A birth that occurs before 37 weeks of pregnancy is a preterm or premature birth.
  • An infant born before 37 weeks in the womb is a preterm or premature infant. (These infants are commonly called “preemies” as a reference to being born prematurely.)

“Late preterm” refers to 34 weeks through 36 weeks of pregnancy. Infants born during this time are considered late-preterm infants, but they face many of the same health challenges as preterm infants. More than 70% of preterm infants are born during the late-preterm time frame.3

Preterm birth is the most common cause of infant death and is the leading cause of long-term disability in children.4 Many organs, including the brain, lungs, and liver, are still developing in the final weeks of pregnancy. The earlier the delivery, the higher the risk of serious disability or death.

Infants born prematurely are at risk for cerebral palsy (a group of nervous system disorders that affect control of movement and posture and limit activity), developmental delays, and vision and hearing problems.

Late-preterm infants typically have better health outcomes than those born earlier, but they are still three times more likely to die in the first year of life than are full-term infants.3 Preterm births can also take a heavy emotional and economic toll on families.5

Citations

  1. American College of Obstetricians and Gynecologists. (2013). Definition of term pregnancy. Committee Opinion No. 579. Obstetrics and Gynecology, 122, 1139–1140.
  2. Spong, C. Y. (2013). Defining “term” pregnancy: recommendations from the Defining “Term” Pregnancy Workgroup. Journal of the American Medical Association, 309, 2445–2446.
  3. March of Dimes. (2011). Prematurity research. Retrieved September 17, 2013, from http://www.marchofdimes.com/research/prematurity-research.aspx External Web Site Policy
  4. Centers for Disease Control and Prevention. (n.d.). Preterm birth. Retrieved September 17, 2013, from http://www.cdc.gov/reproductivehealth/maternalinfanthealth/PretermBirth.htm
  5. March of Dimes. (2012). The March of Dimes Foundation Data Book for Policy Makers: Maternal, Infant, and Child Health in the United States 2012. Retrieved March 5, 2014, from http://www.marchofdimes.com/materials/Databookforpolicymakers.pdf (PDF – 10.1 MB) External Web Site Policy

What are the symptoms of preterm labor?

Preterm labor is any labor that occurs from 20 weeks through 36 weeks of pregnancy. Here are the symptoms1:

  • Contractions (tightening of stomach muscles, or birth pains) every 10 minutes or more often
  • Change in vaginal discharge (leaking fluid or bleeding from the vagina)
  • Feeling of pressure in the pelvis (hip) area
  • Low, dull backache
  • Cramps that feel like menstrual cramps
  • Abdominal cramps with or without diarrhea

It is normal for pregnant women to have some uterine contractions throughout the day. It is not normal to have frequent uterine contractions, such as six or more in one hour. Frequent uterine contractions, or tightenings, may cause the cervix to begin to open.

If a woman thinks that she might be having preterm labor, she should call her doctor or go to the hospital to be evaluated.

Citations

  1. March of Dimes. (2008, 2010). Preterm labor. Retrieved April 18, 2012, from http://www.marchofdimes.com/pregnancy/preterm_indepth.html External Web Site Policy

What causes preterm labor and birth?

The causes of preterm labor and premature birth are numerous, complex, and only partly understood. Medical, psychosocial, and biological factors may all play a role in preterm labor and birth.

There are three main situations in which preterm labor and premature birth may occur:

  • Spontaneous preterm labor and birth. This term refers to unintentional, unplanned delivery before the 37th week of pregnancy. This type of preterm birth can result from a number of causes, such as infection or inflammation, although the cause of spontaneous preterm labor and delivery is usually not known. A history of delivering preterm is one of the strongest predictors for subsequent preterm births.1
  • Medically indicated preterm birth. If a serious medical condition—such as preeclampsia—exists, the health care provider might recommend a preterm delivery. In these cases, health care providers often take steps to keep the baby in the womb as long as possible to allow for additional growth and development, while also monitoring the mother and fetus for health issues. Providers also use additional interventions, such as steroids, to help improve outcomes for the baby.
  • Non-medically indicated (elective) preterm delivery. Some late-preterm births result from inducing labor or having a cesarean delivery even though there is not a medical reason to do so, even though this practice is not recommended. Research indicates that even babies born at 37 or 38 weeks of pregnancy are at higher risk for poor health outcomes than are babies born at 39 weeks of pregnancy or later. Therefore, unless there are medical problems, health care providers should wait until at least 39 weeks of pregnancy to induce labor or perform a cesarean delivery to prevent possible health problems.2

    The National Child and Maternal Health Education Program, led by the NICHD in collaboration with 33 other agencies, organizations, and groups focused on maternal and child health, offers videos and other information about why it’s best to wait until at least 39 weeks of pregnancy to deliver unless there is a medical reason. Learn more about the “Is It Worth It?” initiative.

Citations

  1. Ekwo, E. E., Gosselink, C. A., & Moawad, A. (1992). Unfavorable outcome in penultimate pregnancy and premature rupture of membranes in successive pregnancy. Obstetrics and Gynecology, 80, 166–172.
  2. American Congress of Obstetricians and Gynecologists. (2013). Committee Opinion: Non-Medically Indicated Early Term Deliveries. Retrieved September 11, 2013, from https://www.ncbi.nlm.nih.gov/pubmed/23635710 External Web Site Policy

What are the risk factors for preterm labor and birth?

There are several risk factors for preterm labor and premature birth, including ones that researchers have not yet identified. Some of these risk factors are "modifiable," meaning they can be changed to help reduce the risk. Other factors cannot be changed.

Health care providers consider the following factors to put women at high risk for preterm labor or birth:

  • Women who have delivered preterm before, or who have experienced preterm labor before, are considered to be at high risk for preterm labor and birth.1
  • Being pregnant with twins, triplets, or more (called "multiple gestations") or the use of assisted reproductive technology is associated with a higher risk of preterm labor and birth. One study showed that more than 50% of twin births occurred preterm, compared with only 10% of births of single infants.2
  • Women with certain abnormalities of the reproductive organs are at greater risk for preterm labor and birth than are women who do not have these abnormalities. For instance, women who have a short cervix (the lower part of the uterus) or whose cervix shortens in the second trimester (fourth through sixth months) of pregnancy instead of the third trimester are at high risk for preterm delivery.

Certain medical conditions, including some that occur only during pregnancy, also place a woman at higher risk for preterm labor and delivery. Some of these conditions include3:

  • Urinary tract infections
  • Sexually transmitted infections
  • Certain vaginal infections, such as bacterial vaginosis and trichomoniasis
  • High blood pressure
  • Bleeding from the vagina
  • Certain developmental abnormalities in the fetus
  • Pregnancy resulting from in vitro fertilization
  • Being underweight or obese before pregnancy
  • Short time period between pregnancies (less than 6 months between a birth and the beginning of the next pregnancy)
  • Placenta previa, a condition in which the placenta grows in the lowest part of the uterus and covers all or part of the opening to the cervix
  • Being at risk for rupture of the uterus (when the wall of the uterus rips open). Rupture of the uterus is more likely if you have had a prior cesarean delivery or have had a uterine fibroid removed.
  • Diabetes (high blood sugar) and gestational diabetes (which occurs only during pregnancy)
  • Blood clotting problems

Other factors that may increase risk for preterm labor and premature birth include:

  • Ethnicity. Preterm labor and birth occur more often among certain racial and ethnic groups. For example, infants of African American mothers are more likely to be born preterm than infants of white mothers. American Indian/Alaska Native mothers are also more likely to give birth preterm than are white mothers.4
  • Age of the mother.
    • Women younger than age 18 are more likely to have a preterm delivery.
    • Women older than age 35 are also at risk of having preterm infants because they are more likely to have other conditions (such as high blood pressure and diabetes) that can cause complications requiring preterm delivery.4
  • Certain lifestyle and environmental factors, including:3
  • Late or no health care during pregnancy
  • Smoking
  • Drinking alcohol
  • Using illegal drugs
  • Domestic violence, including physical, sexual, or emotional abuse
  • Lack of social support
  • Stress
  • Long working hours with long periods of standing
  • Exposure to certain environmental pollutants

Citations

  1. Ekwo, E. E., Gosselink, C. A., & Moawad, A. (1992). Unfavorable outcome in penultimate pregnancy and premature rupture of membranes in successive pregnancy. Obstetrics and Gynecology, 80, 166–172.
  2. The American College of Obstetricians and Gynecologists. (2015). Multiple Pregnancy. Retrieved May 16, 2018, from https://www.acog.org/Patients/FAQs/Multiple-Pregnancy#most External Web Site Policy
  3. March of Dimes. (2008, 2010). Preterm labor and birth: A serious pregnancy complication. Retrieved April 23, 2012, from http://www.marchofdimes.com/pregnancy/preterm_indepth.html External Web Site Policy
  4. Centers for Disease Control and Prevention. (2018). Births: Final Data for 2016. Retrieved May 16, 2018, from https://www.cdc.gov/nchs/data/nvsr/nvsr67/nvsr67_01.pdf

Is it possible to predict which women are more likely to have preterm labor and birth?

Currently, there is no definitive way to predict preterm labor or premature birth. Many research studies are focusing on this important issue. By identifying which women are at increased risk, health care providers may be able to provide early interventions, treatments, and close monitoring of these pregnancies to prevent preterm delivery or to improve health outcomes.

However, in some situations, health care providers know that a preterm delivery is very likely. Some of these situations are described below.

Shortened Cervix

As a preparation for birth, the cervix (the lower part of the uterus) naturally shortens late in pregnancy. However, in some women, the cervix shortens prematurely, around the fourth or fifth month of pregnancy, increasing the risk for preterm delivery.

In some cases, a health care provider may recommend measuring a pregnant woman’s cervical length, especially if she previously had preterm labor or a preterm birth. Ultrasound scans may be used to measure cervical length and identify women with a shortened cervix.1

"Incompetent" Cervix

The cervix normally remains closed during pregnancy. In some cases, the cervix starts to open early, before a fetus is ready to be born. Health care providers may refer to a cervix that begins to open as an "incompetent" cervix. The process of cervical opening is painless and unnoticeable, without labor contractions or cramping.2

To try to prevent preterm birth, a doctor may place a stitch around the cervix to keep it closed. This procedure is called cervical cerclage (pronounced sair-KLAZH). NICHD-supported research has found that, in women with a prior preterm birth who have a short cervix, cerclage may improve the likelihood of a full-term delivery.4

Citations

  1. Society for Maternal-Fetal Medicine Publications Committee, with the assistance of Vincenzo Berghella, M.D. (2012). SMFM Clinical Guideline: Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. American Journal of Obstetrics and Gynecology, 206, 376–386.
  2. Drakeley, A. J., Roberts, D., & Alfirevic, Z. (2003; published online 2010). Cervical stitch (cerclage) for preventing pregnancy loss in women. Cochrane Database of Systematic Reviews, 1. Retrieved May 4, 2012, from, http://summaries.cochrane.org/CD003253/cervical-stitch-cerclage-for-preventing-pregnancy-loss-in-women External Web Site Policy
  3. Denney, J. M., Culhane, J. F., & Goldenberg, R. L. (2008, November 5). Prevention of preterm birth. Women's Health, 4, 625–638. Retrieved April 17, 2012, from http://www.medscape.com/viewarticle/582761_10 External Web Site Policy
  4. Owen, J., Hankins, G., Iams, J. D., Berghella, V., Sheffield, J. S., Perez-Delboy, A., et al. (2009, October). Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. American Journal of Obstetrics and Gynecology, 201(4), 375.e1–375.e8.

How do health care providers diagnose preterm labor?

If a woman is concerned that she could be showing signs of preterm labor, she should call her health care provider or go to the hospital to be evaluated. In particular, a woman should call if she has more than six contractions in an hour or if fluid or blood is leaking from the vagina.

Physical Exam

If a woman is experiencing signs of labor, the health care provider may perform a pelvic exam to see if:

  • The membranes have ruptured
  • The cervix is beginning to get thinner (efface)
  • The cervix is beginning to open (dilate)

Any of these situations could mean the woman is in preterm labor.
Providers may also do an ultrasound exam and use a monitor to electronically record contractions and the fetal heart rate.

Fetal Fibronectin (fFN) Test

This test is used to detect whether the protein fetal fibronectin (pronounced fy-broh-NEK-tun) is being produced. fFN is like a biological “glue” between the uterine lining and the membrane that surrounds the fetus.1

Normally fFN is detectable in the pregnant woman's secretions from the vagina and cervix early in the pregnancy (up to 22 weeks, or about 5 months) and again toward the end of the pregnancy (1 to 3 weeks before labor begins). It is usually not present between 24 and 34 weeks of pregnancy (5½ to 8½ months). If fFN is detected during this time, it may be a sign that the woman may be at risk of preterm labor and birth.

In most cases, the fFN test is performed on women who are showing signs of preterm labor. Testing for fFN can help predict which pregnant women showing signs of preterm labor will have a preterm delivery.2 It is typically used for its negative predictive value, meaning that if it is negative, it is unlikely that a woman will deliver within the next 7 days.

Citations

  1. Berghella, V., Hayes, E., Visintine, J., & Baxter, J. K. (2008, October 8). Fetal fibronectin testing for reducing the risk of preterm birth. Cochrane Database of Systematic Reviews, (4), CD006843. Retrieved April 18, 2012, from http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006843.pub2/abstract External Web Site Policy
  2. Goldenberg, R., Mercer, B., Meis, P., Copper, R., Das, A., McNellis, D., & the NICHD Maternal Fetal Medicine Units Network. (1996). The Preterm Prediction Study: Fetal fibronectin testing and spontaneous preterm birth. Obstetrics and Gynecology, 87, 643–648.

What treatments are used to prevent preterm labor and birth?

Currently, treatment options for preventing preterm labor or birth are somewhat limited, in part because the cause of preterm labor or birth is often unknown. But there are a few options, described below.

Hormone treatment. The only preventive drug therapy is progesterone (pronounced proh-JES-tuh-rohn), a hormone produced by the body during pregnancy, which is given to women at risk of preterm birth, such as those with a prior preterm birth. The NICHD’s Maternal-Fetal Medicine Units Network found that progesterone given to women at risk of preterm birth due to a prior preterm birth reduces chances of a subsequent preterm birth by one-third. This preventive therapy is given beginning at 16 weeks of gestation and continues to 37 weeks of gestation.1,2 The treatment works among all ethnic groups and can improve outcomes for infants.

Cerclage. A surgical procedure called cervical cerclage (pronounced sair-KLAZH) is sometimes used to try to prevent early labor in women who have an incompetent (weak) cervix and have experienced early pregnancy loss accompanied by a painless opening (dilation) of the cervix (the bottom part of the uterus). In the cerclage procedure, a doctor stitches the cervix closed. The stitch is then removed closer to the woman's due date.

Bed rest. Contrary to expectations, confining the mother to bed rest does not help to prevent preterm birth. In fact, bed rest can make preterm birth even more likely among some women.3,4

Women should discuss all of their treatment options—including the risks and benefits—with their health care providers. If possible, these discussions should occur during regular prenatal care  visits, before there is any urgency, to allow for a complete discussion of all the issues.

Citations

  1. Meis, P. J., Klebanoff, M., Thom, E., Dombrowski, M. P., Sibai, B., Moawad, A. H., et al. (2003). Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. New England Journal of Medicine, 348, 2379–2385.
  2. American Congress of Obstetricians and Gynecologists, District II. (2009). Preventing preterm birth: The role of 17α hydroxyprogesterone caproate. Retrieved September 18, 2013, from https://www.acog.org/~/media/Announcements/20111013MakenaLtr.pdf (PDF – 1.84 MB) External Web Site Policy
  3. Neergard, Lauran. (May 14, 2013). Bed rest during pregnancy could worsen risk for premature birth, study shows. Associated Press. Retrieved October 24, 2013, from http://www.foxnews.com/health/2013/05/14/bed-rest-during-pregnancy-may-not-prevent-premature-births-could-worsen-risk.html External Web Site Policy
  4. Grobman, W. A., Gilbert, S. A., Iams, J. D., Spong, C. Y., Saade, G., Mercer, B. M. (2013). Activity restriction among women with a short cervix. Obstetrics and Gynecology, 121(6), 1181–1186.

«How is it diagnosed?         What treatments can reduce the chances of preterm labor and birth?»

What treatments can reduce the chances of preterm labor & birth?

If a pregnant woman is showing signs of preterm labor, her doctor will often try treatments to stop labor and prolong the pregnancy until the fetus is more fully developed. Treatments include therapies to try to stop labor (tocolytics) and medications administered before birth to improve outcomes for the infant if born preterm (antenatal steroids to improve the respiratory outcomes and neuroprotective medications such as magnesium sulfate).

Medications to Delay Labor

Drugs called tocolytics (pronounced toh-coh-LIT-iks) can be given to many women with symptoms of preterm labor. These drugs can slow or stop contractions of the uterus and may prevent labor for 2 to 7 days. One common treatment for delaying labor is magnesium sulfate (pronounced mag-NEEZ-ee-um SUL-fate), given to the pregnant woman intravenously through a needle inserted in an arm vein.

Medications to Speed Development of the Fetus

Tocolytics may provide the extra time for treatment with corticosteroids (pronounced kohr-tuh-koh-STER-oids) to speed up development of the fetus's lungs and some other organs or for the pregnant woman to get to a hospital that offers specialized care for preterm infants. Corticosteroids can be particularly effective if the pregnancy is between 24 and 34 weeks (between 5½ and 7¾ months) and the woman's health care provider suspects that the birth may occur within the next week.1 Intravenously delivered magnesium sulfate may also reduce the risk of cerebral palsy if the child is born early.2

Citations

  1. American Congress of Obstetricians and Gynecologists. (2011). Early preterm birth FAQ. Retrieved April 23, 2012, from http://www.acog.org/~/media/For Patients/faq173.pdf?dmc=1&ts=20120323T1605318647 External Web Site Policy (PDF - 282 KB)
  2. Rouse, D. J., Hirtz, D. G., Thom, E., Varner, M. W., Spong, C. Y., Mercer, B. M., et al. (2008). A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. New England Journal of Medicine, 359, 895–905.

What methods do not work to prevent preterm labor?

Researchers have found that some methods for trying to stop preterm labor are not as effective as once thought. These include:

  • Home uterine monitors1
  • Routine screening of all asymptomatic women for bacterial vaginosis (Trichomonas vaginalis) infection.2 Routine screening and treatment with antibiotics did not reduce preterm birth; in fact, the latter increased the risk of preterm birth.2

Citations

  1. Iams, J. D., Newman, R. B., Thom, E. A., Goldenberg, R. L., Mueller-Heubach, E., Moawad, A., et al. (2002). Frequency of uterine contractions and the risk of spontaneous preterm delivery. New England Journal of Medicine, 346, 250–255.
  2. Carey, J. C., Klebanoff, M. A., Hauth, J. C., Hillier, S. L., Thom, E. A., Ernest, J. M., et al. (2000). Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis.New England Journal of Medicine, 342, 534–540.

Preterm Labor and Birth: NICHD Research Goals

Preterm birth, defined as the birth of a fetus before 37 weeks of gestation, is a major public health priority for the United States and an important research focus for the NICHD. Preterm infants are at high risk for a variety of disorders, including cerebral palsy, intellectual and developmental disabilities, and vision impairment. These infants are also at high risk for long-term health issues, including cardiovascular disease (heart attack, stroke, and high blood pressure) and diabetes.

The NICHD supports and conducts a large portfolio of research on preterm labor and birth. Among its comprehensive goals are the following:

  • Preventing preterm labor and delaying birth until 39 weeks of gestation. Because women who have one preterm birth are considered to be at high risk for another preterm birth, investigators have focused much of their attention on trying to prevent preterm birth among these high-risk women. Current research efforts also are directed toward the significant problem of preterm labor and birth among women who have not given birth before (referred to as being "nulliparous").
  • Understanding and preventing non-medically indicated preterm deliveries. The NICHD is working with professional organizations to educate health care providers and the public about the significant risks to infants born even a few weeks early.
  • Addressing health disparities in preterm birth. Race/ethnicity is an independent risk factor for preterm labor and birth. NICHD research is improving our understanding of health disparities and how they influence risk of preterm birth.
  • Studying risk factors for preterm labor. NICHD-supported researchers are elucidating the effect of various risk factors—biological, environmental, genetic, and maternal.
  • Improving outcomes for preterm infants. Infants born too early are at heightened risk for short- and long-term consequences. NICHD researchers are testing the safety and efficacy of interventions to see which ones work—and which ones don't.

Preterm Labor and Birth: Research Activities and Scientific Advances

Preterm labor and birth is the most common cause of infant death and is the leading cause of long-term neurological disability in the United States. The NICHD conducts and supports research on preterm labor and birth, seeking ways to reduce the incidence, prevent adverse effects, and improve outcomes for mothers and infants.

Institute Activities and Advances

The NICHD supports a broad range of research on understanding the causes of preterm birth and reducing its incidence. Areas of research related to preterm birth include the following:

Underlying Mechanisms

Past NICHD research has identified various causes of spontaneous preterm birth, including intrauterine inflammation or infection (PMID: 18240548, PMID: 22752762), uterine or vaginal bleeding (PMID: 21142755, PMID: 21890016), excessive uterine stretch (PMID: 19834610, PMID: 22811574), maternal or fetal stress (PMID: 21958433, PMID: 23447915, PMID: 21890014, PMID: 20195952), and premature rupture of fetal membranes (PMID: 10992202). Much of this research was supported through the Pregnancy and Perinatology Branch (PPB) in the Division of Extramural Research (DER).

PPB-supported researchers recently announced findings from their research on the association of bacteria and the risk of preterm birth. Infections in the mother's genital tract are thought to be a major cause of preterm birth, accounting for approximately 25% to 40% of all preterm births. Many different types of infections, caused by different combinations of micro-organisms, are apparently related to an increased risk of preterm birth. For example, a common infection called bacterial vaginosis (BV) has been associated with a sharp rise in the risk of preterm birth. However, scientists have found that although infections cause the risk of preterm birth to rise, treating an infection does not necessarily cause the risk to fall. To help understand why, researchers conducted a study to assess the relationship between preterm birth and selected vaginal bacteria.

Scientists collected vaginal fluid at 17 to 22 weeks' gestation from about 500 pregnant women who had previously had a preterm birth (and thus were at risk for another early delivery). The researchers found that several types of bacteria—mycoplasma, mobiluncus, and atopobium—were correlated with increased risk of preterm birth. However, the extent of the increased risk was sometimes different for women of different racial and ethnic groups. For example, the presence of mobiluncus bacteria is usually considered to indicate BV. Mobiluncus was associated with a nearly two-fold increase in the risk of preterm birth for Hispanic women, but there was no association between mobiluncus and preterm birth in the other racial and ethnic groups. By contrast, another organism also associated with BV appeared to decrease, rather than increase, the risk of preterm birth for all racial/ethnic groups. These findings help scientists understand why treating BV may not always reduce risk of preterm birth.  The results suggest that focusing on specific bacterial types, rather than the infections that may result, could help scientists develop new ways to prevent preterm deliveries. (PMID: 24096128)

Researchers in the Program in Perinatal Research and Obstetrics (PPRO), within the Division of Intramural Research (DIR), have proposed that allogeneic "rejection" of the fetus may be responsible for several obstetrical syndromes, including spontaneous preterm labor and delivery. (The mammalian fetus is a semi-allograft, as 50% of its genome is of paternal origin.) Program investigators have demonstrated that women with a type of inflammation of the fetal membranes known as chronic chorioamnionitis have circulating anti-fetal antibodies that cross the placenta and induce fetal inflammation and spontaneous preterm birth (PMID: 22092404). Future studies will focus on identifying biomarkers for this mechanism of disease.

Predicting Preterm Birth

Past and current NICHD research also aims to more accurately predict which women will experience preterm labor or who will deliver preterm. Reliable methods of prediction enable health care providers to provide interventions and treatments to prevent preterm delivery.

A recent study conducted by the PPRO evaluated the effectiveness of transabdominal sonography versus the gold standard of transvaginal ultrasound to determine cervical length in pregnant women. In the study, the transabdominal ultrasound screening correctly identified only 43% of women with a short cervix. Based on the results, the researchers recommend continuing use of the transvaginal ultrasound. (PMID: 22273078)

The Population Dynamics Branch, within the DER, supports research helping to identify the factors that do and do not contribute to the likelihood a woman will deliver preterm. Researchers analyzed data on birth outcomes in a large cohort of women who had been evaluated or treated for infertility, comparing the data with outcomes of infertile women who were able to achieve pregnancy without treatment and with fertile women. The researchers analyzed outcomes in women with singleton pregnancies in women who had not previously given birth.

The analysis showed that infertility treatment did not elevate the risk of preterm birth, although it did seem to increase the risk of low weight of an infant at birth. The researchers also found that women who were giving birth to their first child were at elevated risk of preterm birth, regardless of which group they were in. (PMID: 22633266)

Researchers in the Maternal-Fetal Medicine Units (MFMU) Network, which is funded by the PPB, analyzed the blood serum of women at the sixth and seventh weeks of their pregnancies, searching for possible protein abnormalities that could warn of early, spontaneous labor. They identified three peptides (short sections of proteins) that were present in significantly lower concentrations in the serum of women who later delivered prematurely.

Specifically, two-thirds of the women with lower peptide concentrations were unable to carry their pregnancies to term. The researchers also found that concentrations of the peptides fell even lower as the women neared delivery. Early identification of pregnant patients who are more likely to experience preterm birth could help clinicians to take preventive measures. (PMID: 21074133)
Other work includes:

  • Identifying the timing of cerclage to prolong pregnancy and improve infant survival rates
  • Distinguishing women having true preterm labor from those having false labor
  • Refining resuscitation methods for preterm infants to minimize lung injury

Preventing Preterm Birth

Women with a prior preterm birth are at increased risk for subsequent preterm birth. Some NICHD-supported research has focused on the use of progesterone agents to help prevent recurrent preterm births in this population.

An MFMU Network study that began in 2003 set out to determine whether injections of a synthetic type of progesterone called 17-alpha-hydroxyprogesterone caproate (17P) could reduce the number of preterm births among women who had already had one preterm birth. The results were remarkable: for women carrying one baby and with a history of preterm delivery, injections of 17P reduced preterm birth by one-third. Additionally, infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen. (PMID: 12802023)

On February 3, 2011, the U.S. Food and Drug Administration (FDA) approved the use of 17P to reduce the risk of preterm birth in women with a history of at least one prior spontaneous preterm delivery. This is the first time that the FDA has approved a medication for the prevention of preterm birth and the first approval of a drug specifically for use in pregnancy in nearly 15 years. (PMID: 22102929)

A follow-up study, also conducted through the MFMU Network, tested the effectiveness of 17P for first-time mothers with a short cervix. The study found that it did not reduce the risk for preterm birth before 37 weeks of gestation. (PMID: 23010094) The MFMU investigators also learned that 17P did not reduce the rate of preterm births among women carrying twins or triplets. (PMID: 17671253)

Another study by MFMU collaborators demonstrated that the common recommendations to prevent preterm delivery—activity restriction and bed rest—did not reduce the rate of preterm birth among asymptomatic, nulliparous women with a short cervix. (PMID: 23812450) The researchers found that women who were at risk for preterm birth and who restricted their activity were actually more likely to deliver early than those who did not.

Recently, the PPRO concluded a clinical trial that screened 30,000 women for short cervical length, a primary risk factor for premature delivery. Women who were found to have a shortened cervix were given either vaginal progesterone or a placebo. The progesterone reduced the rate of preterm birth at less than 28 weeks gestation by 50%. Learn more about this study in the 2012 Annual Report of the Division of Intramural Research.

Caring for Preterm Infants

Getting adequate nutrition, preventing infection, and improving lung function are significant issues for preterm infants, particularly those born at very low birth weight (VLBW).

Researchers funded by the NICHD's Obstetric and Pediatric Pharmacology and Therapeutics Branch (OPPTB) recently investigated the variable effect of medication to ease infants' breathing. Pregnant women who are in danger of giving birth too early are often treated with medications that help the baby's lungs mature faster. These medications can reduce the newborn's risk of a dangerous breathing difficulty called respiratory distress syndrome (RDS). However, the medicines seem to help babies of certain races and ethnicities more than others, even when other factors, like birth weight, are taken into account. The researchers suspected that this difference may be caused by genetics. They analyzed DNA samples and medical records from 117 mother-infant pairs in which the mother was treated with a specific anti-inflammatory medication before giving birth prematurely. In about half of the cases, the infants developed RDS. The scientists found that several specific variants in genes involved in the breakdown of the medication were also associated with the preterm newborns' risk of RDS. Some of the risk variants were in the mother, and others were in the fetus, meaning that the ways both the mother and the placenta break down the drug can affect how much of the drug reaches the developing fetus. The researchers are using this information to design a larger, more powerful study that will let them control for other factors that might be influencing the results and get a more accurate picture of the effects of these gene variants on infant health. This work could lead to the development of more personalized treatments. (PMID: 22445700)

Researchers in the Neonatal Research Network (NRN), funded by the PPB, recently reported that VLBW infants infected with methicillin-susceptible Staphylococcus aureus (MSSA) have similar morbidity and mortality rates as VLBW infants infected with methicillin-resistant S. aureus (MRSA). These study findings suggest that clinicians may consider applying prevention and treatment approaches for MRSA to MSSA among VLBW infants to improve their chances for survival and reduce complications. The findings are important for informing clinical practice because there is a general perception that MRSA leads to more complications than MSSA. (PMID: 22412036)

The NRN also completed a study showing that corticosteroids could be effective for improving infant survival and limiting brain injury when given to the mother as early as the 23rd week of pregnancy, although current recommendations suggest they not be prescribed until the 24th week. A MFMU trial showed that repeated courses of corticosteroids in pregnant women do not differ from a single course in their effects on child outcomes at 2 to 3 years of age. (PMID: 17881751)

A recent follow-up study on the benefits of higher oxygen levels for preterm infants found that the toddlers given the therapy as infants continued to thrive. Read more about the study.

NRN collaborators conducted a trial of whole-body hypothermia for treating neonatal hypoxic-ischemic encephalopathy (HIE). They found that the treatment was safe and effective and reduced the risk of death and disability among infants with moderate or severe encephalopathy. (PMID: 18829776).

Necrotizing enterocolitis (NEC) is the most common, serious gastrointestinal disease affecting newborn infants. It is most commonly seen in infants born preterm. Recent NRN studies included an observational trial of NEC that found survival was only 51% after hospital discharge in infants who had surgery for NEC or intestinal perforation. Follow-up at 18 months found continued poor outcomes. Children who underwent laparotomy, which involves making a large incision in the abdomen and removing dead tissue, were less likely to have neurodevelopmental impairment than were those who underwent intestinal drain placement, also called primary peritoneal drainage. The latter technique involves a small incision and the insertion of a 4-inch soft drain tube. A randomized trial comparing drain versus laparotomy is under way.

Late-preterm infants (born between 34 and 36 weeks of gestation) are more likely to suffer respiratory complications than infants born at term. Previous research by the NRN showed that a single course of antenatal corticosteroids improved lung function in very premature infants, but this therapy has not been evaluated in those born during the late preterm period. The NRN is currently evaluating whether treatment with antenatal steroids in the late-preterm period will improve infant outcomes. A previous NRN study previously found that weekly steroid treatments were harmful.

In addition, the PPB supported a study on the long-term effects of pain and stress in preterm infants. Researchers measured the level of cortisol in children who were born preterm and full-term and found that the children born preterm had higher levels of cortisol and were most likely to show symptoms of anxiety and depression in their daily lives. (PMID: 21298633)

Findings from the NICHD-supported MFMU also show that treating women at risk of preterm delivery with magnesium sulfate can reduce the risk of cerebral palsy in the infants born to these women. (PMID: 18753646) A third of all cases of cerebral palsy are associated with preterm birth. Read the ACOG Committee Opinion External Web Site Policy on the use of magnesium sulfate before anticipated early preterm birth for neuroprotection of the infant.

Other Activities and Advances

To achieve its goals for research on preterm labor and birth, the NICHD supports a variety of other activities. Some of these activities are managed through the components listed above; others are part of NIH-wide or collaborative efforts in which the NICHD participates. A number of examples are listed below.

  • Two research networks—the Neonatal Research Network and Maternal-Fetal Medicine Units Network—are funded through the Institute's PPB and conduct well-designed clinical trials in large enough populations to have adequate statistical power to answer many research questions.
  • The NICHD's Obstetric-Fetal Pharmacology Research Unit Network provides the infrastructure needed to test therapeutic drugs during pregnancy.
  • The National Child and Maternal Health Education Program Initiative to Reduce Elective Deliveries Before 39 Weeks of Pregnancy provides information to patients and health care providers about the additional risks to mother and child that accompany early delivery.
  • Conferences related to preterm birth and preterm infants are a continuing part of the NICHD research agenda. These include the Surgeon General's Conference on the Prevention of Preterm Birth, the Timing of Indicated Late-Preterm and Early Term Birth Workshop, and the Neonatal Encephalopathy and Hypoxic Ischemic Encephalopathy: Advancing the Science and Improving Outcomes meeting.
  • The NICHD NRN Extremely Preterm Birth Data Outcome Tool is intended to inform health care providers and families about possible infant outcomes. The tool is based on standardized assessment data collected through the Neonatal Research Network.
  • Through the Neonatal Research Network, the Generic Database of Moderate Preterm Infants aims to establish a registry of moderate preterm infants, born alive at 29 to 33 weeks gestational age. The registry collects baseline data on both mothers and infants, the therapies used, and outcomes of the infants. The information collected is not specific to a disease or treatment (i.e., it is "generic"). Data are analyzed to find associations and trends between baseline information, treatments, and infant outcome, and to develop future trials.
  • The NICHD-funded Genomic and Proteomic Network for Preterm Birth Research is a research network that aims to accelerate the pace of preterm birth research by focusing on global genomic and molecular research strategies and to rapidly disseminate the data to the scientific community for secondary analyses. The network's projects consist of three collaborative core components: the clinical core, comprising three clinical sites; the analytical core; and the data management, statistics, and informatics core.
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