ANNOUNCEMENT: Research to identify families with repeated premature births. Families with more than one member being born at least one month early are likely to provide an important resource for identifying genes that increase the risk of preterm birth. If you belong to this category of families, you may be able to help scientists in their search for causes of prematurity. The March of Dimes, through its Prematurity Research Initiative, has supported research to reveal genes that increase prematurity in these families to help develop new treatments and preventive measures. If you would like to help with this effort, please go to the Web site of the FETAL Study at Washington University in St. Louis. You participation can make a difference!


What is preterm birth?
Most pregnancies last around 40 weeks. Babies born between 37 and 42 completed weeks of pregnancy are called full term. Babies born before 37 completed weeks of pregnancy are called premature. About 12.5 percent of babies (more than half a million a year) in the United States are born prematurely (1). For reasons that doctors don't fully understand, the rate of premature birth has increased by more than 30 percent since 1981 (1).

Premature birth is a serious health problem. Premature babies are at increased risk for newborn health complications, as well as lasting disabilities, such as mental retardation, cerebral palsy, lung and gastrointestinal problems, vision and hearing loss, and even death. Many premature babies require care in a neonatal intensive care unit (NICU), which has specialized medical staff and equipment that can deal with the multiple problems faced by premature infants.

Most premature babies (71.2 percent) are born between 34 and 36 weeks of gestation (1). These are called late preterm births. Almost 13 percent of premature babies are born between 32 and 33 weeks of gestation, about 10 percent between 28 and 31 weeks, and about 6 percent at less than 28 weeks of gestation (1).

All premature babies are at risk for health problems, but those born before about 32 weeks of gestation face the highest risk. These babies usually are very small, and their organs are less developed than those of babies born later. Fortunately, advances in obstetrics and neonatology (the branch of pediatrics that deals with newborns) have improved the chances of survival for even these smallest babies.

Not only are premature babies often small and sick, but also they may look and behave very differently than full-term babies. For example, their skin may be thin and wrinkled, and their heads may look too large for their bodies. But these babies look the way they should at their stage of development. They will begin to appear and act more like full-term babies as they continue to develop and grow. Throughout their first year of life, these babies should be evaluated according to their adjusted age (which takes the extent of their prematurity into account).

What causes preterm birth?
About 25 percent of preterm births result from early induction of labor or cesarean delivery due to pregnancy complications or health problems in the mother or the fetus (2). In most of these cases, early delivery is probably the safest approach for mother and baby.

Most preterm births are a result of spontaneous preterm labor, either by itself or following spontaneous premature rupture of the membranes (PROM), when the sac inside the uterus that holds the baby breaks too soon. The causes of preterm labor and PROM are not fully understood. The latest research suggests that many cases are triggered by the body's natural response to certain infections, including infections involving the amniotic fluid and fetal membranes. However, in about 40 percent of all cases of preterm birth, the doctor cannot determine why a woman delivered preterm.

Which women are at increased risk for preterm delivery?
Any woman can deliver prematurely, but some women are at greater risk than others. Researchers have identified some risk factors, but doctors still can't predict which women will deliver prematurely.

Three groups of women are at greatest risk for preterm delivery:

• Women who have had a previous preterm birth
• Women who are pregnant with twins, triplets or more
• Women with certain uterine or cervical abnormalities

Certain lifestyle factors may put a woman at greater risk for preterm labor. These include:

• Late or no prenatal care
• Smoking
• Drinking alcohol
• Using illegal drugs
• Exposure to the medication DES
• Domestic violence (including physical, sexual or emotional abuse)
• Lack of social support
• Extremely high levels of stress
• Long working hours with long periods of standing

Certain medical conditions during pregnancy also may increase the likelihood that a woman will have preterm labor. These include:

• Infections (including urinary tract, vaginal, sexually transmitted and, possibly, other infections)

• High blood pressure

• Diabetes

• Clotting disorders (thrombophilia)

• Being underweight before pregnancy

• Obesity

• Short time period between pregnancies (less than 6 to 9 months between birth and the beginning of the next pregnancy)

• Being pregnant with a single fetus after in vitro fertilization

• Certain birth defects in the baby

• Bleeding from the vagina

Even if a woman has one or more of these risk factors, it does not mean that she will have preterm labor. However, every woman should learn the signs and symptoms of preterm labor and what to do if she has any of them.

What medical complications are common in premature babies?
There are a number of complications that are more likely in premature than full-term babies. Late preterm babies generally have few or mild problems. Babies born before about 32 to 34 weeks gestation may have a number of complications, ranging from mild to severe.

• Respiratory distress syndrome (RDS). About 23,000 babies a year (most of whom were born before the 34th week of pregnancy) suffer from this breathing problem (3). Babies with RDS lack a protein called surfactant that keeps small air sacs in the lungs from collapsing. Treatment with surfactant helps affected babies breathe more easily. Since treatment with surfactant was introduced in 1990, deaths from RDS have been reduced by about half (4).
  
  A doctor may suspect a baby has RDS if she is struggling to breathe. A lung X-ray and blood tests often confirm the diagnosis. Along with surfactant treatment, babies with RDS may need additional oxygen and mechanical breathing assistance to keep their lungs expanded. They may receive a treatment called continuous positive airway pressure (CPAP), which delivers pressurized air to the baby's lungs. The air may be delivered through small tubes in the baby's nose, or through a tube that has been inserted into his windpipe. CPAP helps a baby breathe, but it does not breathe for him. The sickest babies may temporarily need the help of a respirator to breathe for them while their lungs mature.  
• Apnea. Premature babies sometimes stop breathing for 20 seconds or more. This interruption in breathing is called apnea, and it may be accompanied by a slow heart rate. Premature babies are constantly monitored for apnea. If the baby stops breathing, a nurse will stimulate the baby to start breathing by patting him or touching the soles of his feet.
• Intraventricular hemorrhage (IVH). Bleeding in the brain occurs in some premature babies, with those born before about 32 weeks of pregnancy at highest risk. The bleeds usually occur in the first three days of life and generally are diagnosed with an ultrasound examination. Most brain bleeds are mild and resolve themselves with no or few lasting problems. More severe bleeds can cause the fluid-filled structures (ventricles) in the brain to expand rapidly, causing pressure on the brain that can lead to brain damage (such as cerebral palsy and learning and behavioral problems). In such cases, surgeons may insert a tube into the brain to drain the fluid and reduce the risk of brain damage. In milder cases, drugs sometimes can reduce fluid buildup. IVH also is associated with a risk for developing cerebral palsy.
• Patent ductus arteriosis (PDA). PDA is a heart problem that is common in premature babies. Before birth, a large artery called the ductus arteriosus lets the blood bypass the lungs because the fetus gets its oxygen through the placenta. The ductus normally closes soon after birth so that blood can travel to the lungs and pick up oxygen. When the ductus does not close properly, it can lead to heart failure. PDA can be diagnosed with a specialized form of ultrasound (echocardiography) or other imaging tests. Babies with PDA are treated with a drug that helps close the ductus, although surgery may be necessary if the drug does not work.
• Necrotizing enterocolitis (NEC). Some premature babies develop this potentially dangerous intestinal problem (usually two to three weeks after birth). It can lead to feeding difficulties, abdominal swelling and other complications. NEC can be diagnosed with imaging tests, such as X-rays, and blood tests. Affected babies are treated with antibiotics and fed intravenously (through a vein) while the bowel heals. In some cases, surgery is necessary to remove damaged sections of the intestine.
• Retinopathy of prematurity (ROP). ROP is an abnormal growth of blood vessels in the eye that can lead to vision loss. It occurs mainly in babies born before 32 weeks of pregnancy. ROP is diagnosed during an examination by an ophthalmologist (eye doctor). Most cases are mild and heal themselves with little or no vision loss. In more severe cases, the ophthalmologist may treat the abnormal vessels with a laser or with cryotherapy (freezing) to protect the retina and preserve vision.   
• Jaundice. Premature babies are more likely than full-term babies to develop jaundice because their livers are too immature to remove a waste product called bilirubin from the blood. In addition, premature infants may be more sensitive to the ill effects of excess bilirubin. Babies with jaundice have a yellowish color to their skin and eyes. Jaundice often is mild and usually is not harmful; however, if the bilirubin level gets too high, it can cause brain damage. This generally can be prevented because blood tests show when bilirubin levels are too high, so the baby can be treated with special lights (phototherapy) that help the body eliminate bilirubin. Occasionally, a baby may need a blood transfusion.
• Anemia. Premature infants often are anemic, which means they do not have enough red blood cells. Normally, the baby stores iron during the later months of pregnancy and uses it late in pregnancy and after birth to make red blood cells. Infants born too soon may not have had enough time to store iron. Babies with anemia tend to develop feeding problems and grow more slowly; anemia also can worsen any heart or breathing problems. Anemic infants may be treated with dietary iron supplements, drugs that increase red blood cell production or, in severe cases, blood transfusion.
• Chronic lung disease (also called bronchopulmonary dysplasia or BPD). Chronic lung disease most commonly affects premature infants who require ongoing treatment with supplemental oxygen. The risk of BPD is increased in babies who still need oxygen when they reach 36 weeks after conception (weeks of pregnancy plus weeks after birth adding up to 36 or more weeks). These babies develop fluid in the lungs, scarring and lung damage, which can be seen on an X-ray. Affected babies are treated with medications that make breathing easier and are slowly weaned from the ventilator. Their lungs usually improve over the first two years of life. However, many children develop chronic lung disease resembling asthma.   
• Infections. Premature babies have immature immune systems that are inefficient at fighting off bacteria, viruses and other organisms that can cause infection. Serious infections that are commonly seen in premature babies include pneumonia (lung infection), sepsis (blood infection) and meningitis (infection of the membranes surrounding the brain and spinal cord). Babies can contract these infections at birth from their mother, or they may become infected after birth. Infections are treated with antibiotics or antiviral drugs.

What is the outlook for babies born at less than 28 weeks?
Less than 1 percent of babies in this country are born this early, but these babies have the most complications (1). Most of these babies are born at extremely low birthweight (less than 2 pounds, 3 ounces). Almost all require treatment with oxygen, surfactant and mechanical assistance to help them breathe. These babies are too immature to suck, swallow and breathe at the same time, so they must be fed through a vein (intravenously) until they develop these skills. They often cannot yet cry (or you cannot hear them due to the tube in their throat) and they sleep most of the day. These tiny babies have little muscle tone, and most move very little.

Babies born at this time look very different than full-term babies. Their skin is wrinkled and reddish-purple in color and is so thin that you can see the blood vessels underneath. Their face and body are covered in soft hair called lanugo. Because these babies have not had time to put on fat, they appear very thin. Most likely, their eyes are closed and they have no eyelashes.

These babies are at high risk for one or more of the complications discussed above. However, most babies born after about 26 weeks gestation do survive to one year (about 80 percent at 26 weeks and about 90 percent at 27 weeks), although they may face an extended stay in the NICU (5). Unfortunately, about 25 percent of these very premature babies develop serious lasting disabilities, and up to half may have milder problems, such as learning and behavioral problems (5).

What about babies born at 28 to 31 weeks gestation?
These babies look quite similar to babies born earlier, although they are larger (usually between 2 and 4 pounds) and even more likely to survive (about 90 to 95 percent) (5). Most require treatment with oxygen, surfactant and mechanical assistance to help them breathe. Some of these babies can be fed breast milk or formula through a tube placed through their nose or mouth into the stomach, although others will need to be fed intravenously. 

Some of these babies can cry. They can move more, although their movements may be jerky. A baby born at this time can grasp your finger. These babies can open their eyes, and they begin to stay awake and alert for short periods.

Babies born at 28 to 31 weeks are at risk for the complications discussed above; however, when complications occur, they may not be as severe as in babies born earlier. Babies born with very low birthweight (less than 3 pounds, 4 ounces) remain at risk for serious disabilities.   

What about babies born at 32 to 33 weeks gestation?
About 95 percent of babies born at this time survive (5). Most weigh between 3 and 5 pounds and appear thinner than full-term babies. Some can breathe on their own, and many just need supplemental oxygen to help them breathe. Some can be breast- or bottle-fed, but those who have breathing difficulties will probably need tube-feeding. Babies born at this time are less likely than babies born earlier to develop serious disabilities resulting from premature birth, though they remain at increased risk for learning and behavioral problems. 

Are babies born at 34 to 36 weeks gestation at risk for medical problems?
Late preterm infants are usually healthier than babies born earlier, and they are almost as likely as full-term babies to survive. Late preterm babies often weigh between 4 1/2 and 6 pounds, and they may still appear thinner than full-term babies. These babies remain at higher risk than full-term babies for newborn health problems, including breathing and feeding problems, difficulties regulating body temperature, and jaundice (6). These problems are usually mild, and most babies make a quick recovery. Most of these babies can be breast- or bottle-fed, although some (especially those with mild breathing problems) may need tube-feeding for a brief time. It is estimated that at 35 weeks gestation, the weight of the brain is only around 60 percent that of term infants (6). Late preterm babies are unlikely to develop serious disabilities resulting from premature birth, but they may be at increased risk for subtle learning and behavioral problems (6).

How can a woman reduce her risk for preterm delivery?
A woman may be able to reduce her risk for preterm delivery by visiting her health care provider before pregnancy and, once pregnant, seeking early and regular prenatal care. A preconception visit is especially crucial for women with chronic disorders, such as diabetes and high blood pressure, which sometimes can contribute to preterm birth. When a woman receives adequate preconception and prenatal care, problems often can be identified early and treated, helping to reduce the risk for preterm birth.

Studies suggest that consuming the recommended amount of folic acid throughout pregnancy may reduce the risk for preterm birth (7). A woman should avoid alcohol, smoking and illicit drugs beginning before pregnancy and throughout pregnancy. She should try to reach a healthy weight before pregnancy because women who are overweight or underweight are at increased risk for premature delivery. She also should gain the recommended amount of weight during pregnancy. Recommended weight gain during pregnancy is generally 25 to 35 pounds for women who begin pregnancy at a normal weight and less for women who start out overweight or obese (8).

One new treatment may help prevent a subsequent preterm delivery in women who have already had a premature baby. This treatment is currently recommended only for women with a previous spontaneous (not induced) preterm birth who are currently pregnant with one fetus. Studies show that treatment with the hormone progesterone (called 17P) reduces the risk for preterm delivery by about one-third in these women (9). Progesterone is given as weekly injections beginning at 16 to 20 weeks of pregnancy. 

Can medical problems in premature newborns be prevented?
When a doctor suspects that a woman may deliver preterm, he may suggest treatment with corticosteroid drugs. Corticosteroids speed maturation of fetal lungs and significantly reduce the risk of RDS, IVH, NEC, infection and infant death (10). The doctor will give the pregnant woman two or more shots containing these drugs. Treatment is most effective when administered at least 24 hours before delivery. The doctor also may suggest treatment with medications (called tocolytics) that may postpone labor (often for only a couple of days). Even this short delay can give the doctor time to treat the pregnant woman with corticosteroids and arrange for delivery in a hospital with a NICU that can give appropriate care to a premature infant, which could make a lifesaving difference for the baby.

Is the March of Dimes supporting research into the causes of preterm birth?
The March of Dimes supports many grants aimed at improving understanding of the causes of preterm labor, with the goal of learning how to prevent it. For example, Prematurity Research Initiative grantees are studying the roles of genes, uterine muscle activity, cervical ripening and surfactant production in triggering preterm labor. Others are looking at how infections may contribute to preterm labor. Grantees also are seeking to improve treatment for premature babies, including those with RDS and NEC.

The March of Dimes Campaign to Reduce Preterm Birth
To learn more, visit the campaign Web site.

If your family has a premature baby in a neonatal intensive care unit, read our information for NICU families.

References

1. Martin, J.A., et al. Births: Final Data for 2004. National Vital Statistics Reports, volume 55, number 1, September 29, 2006.
2. Iams, J.D. The Epidemiology of Preterm Birth. Clinics in Perinatology, volume 30, 2003, pages 651-654.
3. Martin, J.A., et al. Births: Final Data for 2003. National Vital Statistics Reports, volume 54, number 2, September 8, 2005.
4. Analysis by March of Dimes Perinatal Center.
5. American College of Obstetricians and Gynecologists. Perinatal Care at the Threshold of Viability. ACOG Practice Bulletin, number 38, September 2002.
6. Ragu, T.N.K., et al. Optimizing Care and Outcome for Late-Preterm (Near-Term) Infants: A Summary of the Workshop Sponsored by the National Institute of Child Health and Human Development. Pediatrics, volume 118, number 3, September 2006, pages 1207-1214.
7. Siega-Riz, A.M., et al. Second Trimester Folate Status and Preterm Birth. American Journal of Obstetrics and Gynecology, volume 191, number 6, December 2004, pages 1851-1857.
8. American College of Obstetricians and Gynecologists (ACOG). Obesity in Pregnancy. ACOG Committee Opinion, number 315, September 2005.
9. Meis, P.J., et al. Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate. New England Journal of Medicine, 2003, volume 348, pages 2379-2385.
10. Dalziel, S. Antenatal Corticosteroids for Accelerating Fetal Lung Maturation for Women at Risk of Preterm Birth. Cochrane Database System Review, July 19, 2006, 3: CD004454.

February 2007