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Premature Newborn

By Robert L. Stavis, PhD, MD, Clinical Director, Neonatal ICUs;Associate Professor, Department of Pediatrics, Main Line Health, Bryn Mawr, PA; Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children;Thomas Jefferson University Hospital

A premature newborn is a baby delivered before 37 weeks. Depending on when they are born, premature newborns have underdeveloped organs, which may not be ready to function outside of the uterus.

  • A previous premature birth, multiple births, poor nutrition during pregnancy, late prenatal care, infections, assisted reproductive techniques (such as in vitro fertilization), and high blood pressure can increase the risk of a premature birth.

  • Because many organs are underdeveloped, premature newborns may have difficulty breathing and feeding and are prone to bleeding in the brain, infections, and other problems.

  • The earliest and smallest premature newborns are at far greater risk of having problems, including developmental problems.

  • Although some premature newborns grow up with permanent problems, the majority of survivors are normal.

  • Early prenatal care may decrease the risk of a premature birth.

  • Premature birth can sometimes be delayed for a brief period by giving the mother drugs to slow or stop contractions.

  • When an infant is expected to be delivered significantly early, doctors can give the mother injections of a corticosteroid to speed the development of the fetus’s lungs and help prevent bleeding in the brain (intraventricular hemorrhage).

Gestational age refers to how far along the pregnancy is. The gestational age is the number of weeks that have passed since the first day of the mother's last menstrual period. This time frame is often adjusted according to other information doctors receive, including the results of early ultrasound scans, which give additional information regarding the gestational age. The baby is estimated to be due (the due date) at 40 weeks of gestation.

Newborns are classified by gestational age as

  • Premature: Delivered before 34 weeks of gestation.

  • Late preterm: Delivered at 34 to before 37 weeks of gestation.

  • Full term: Delivered at 37 to before 41 weeks of gestation.

  • Late term: Delivered at 41 to before 42 weeks of gestation.

  • Postmature: Delivered at 42 weeks or more of gestation.

About 1 of every 10 infants born in the United States is born before full term. The more prematurely newborns are born, the more they are prone to serious and even life-threatening complications.

Extreme prematurity is the single most common cause of death in newborns. Also, newborns born very prematurely are at increased risk of long-term problems, especially delayed development, cerebral palsy, and learning disorders. Nonetheless, most infants who are born prematurely grow up with no long-term difficulties.

Causes

The causes of premature birth are frequently unknown. However, there are many known risk factors for premature birth. Adolescents and older women, women of lower socioeconomic status, women who have less formal education, and unwed mothers are at increased risk of premature birth.

Risk factors from a previous pregnancy:

Risk factors before or during pregnancy:

However, most women who deliver a premature newborn have no known risk factors.

Early prenatal care may decrease the risk of premature birth.

Symptoms

Premature newborns usually weigh less than 5½ pounds (2.5 kilograms), and some weigh as little as 1 pound (½ kilogram). Symptoms often depend on immaturity of various organs.

Extremely premature newborns tend to require a longer stay in the neonatal intensive care unit (NICU) in the hospital until their organs can function well on their own. Late preterm newborns, on the other hand, may have only a few organ systems, if any, that need time to mature. Late preterm newborns may stay in the hospital until they can regulate their body temperature and the level of sugar (glucose) in their blood, eat well, and gain weight.

The immune system in any premature newborn is also underdeveloped, and therefore premature newborns are prone to infections.

Complications

Most complications of prematurity are caused by underdeveloped and immature organs and organ systems. The risk of complications increases with the degree of prematurity. Risk of complications also depends in part on the presence of certain causes of prematurity, such as infection, diabetes, high blood pressure, or preeclampsia.

Underdeveloped brain

Several problems arise when an infant is born before the brain is fully developed. These problems include

  • Inconsistent breathing: The part of the brain that controls regular breathing may be so immature that premature newborns breathe inconsistently, with short pauses in breathing or periods during which breathing stops completely for 20 seconds or longer (apnea of prematurity).

  • Difficulty coordinating feeding and breathing: The parts of the brain that control reflexes involving the mouth and throat are immature, so premature newborns may not be able to suck and swallow normally, resulting in difficulty coordinating feeding with breathing.

  • Bleeding (hemorrhage) in the brain: Newborns born very prematurely are at increased risk of bleeding in the brain.

Underdeveloped digestive tract and liver

An underdeveloped digestive tract and liver can cause several problems, including the following:

  • Frequent episodes of spitting-up: Initially, premature newborns may have difficulty with feedings. Not only do they have immature sucking and swallowing reflexes, but their small stomach empties slowly, which can lead to frequent episodes of spitting up (reflux).

  • Frequent episodes of not tolerating feedings: The intestines of premature newborns move very slowly, and premature newborns frequently have difficulty passing stools. Because of the slow movement of the intestinal tract, premature infants do not easily digest the breast milk or formula they are given.

  • Intestinal damage: Very premature newborns may develop a serious condition in which part of the intestine becomes severely damaged and may cause infection (called necrotizing enterocolitis).

  • Hyperbilirubinemia: Premature newborns are prone to developing hyperbilirubinemia. In hyperbilirubinemia, the newborn's liver is slow in clearing bilirubin (the yellow bile pigment that results from the normal breakdown of red blood cells) from the blood. Thus, the yellow pigment accumulates, giving the skin and the whites of the eyes a yellow color (jaundice). Premature newborns tend to become jaundiced in the first few days after birth. Usually, jaundice is mild and resolves as newborns take in larger amounts during feedings and have more frequent bowel movements (bilirubin is removed in the stool, giving it its bright yellow color at first). Rarely, very high levels of bilirubin accumulate and put newborns at risk of developing kernicterus. (Kernicterus is a form of brain damage caused by deposits of bilirubin in the brain.)

Underdeveloped immune system

Infants born very prematurely have low levels of antibodies, which are proteins in the blood that help protect against infection. Antibodies from the mother cross the placenta late in the pregnancy and help protect the newborn from infection at birth. Premature newborns have fewer of their mother's protective antibodies and therefore are at higher risk of developing infections, especially infection in the blood (sepsis in the newborn) or tissues around the brain (meningitis). The use of invasive devices for treatment, such as catheters in blood vessels and breathing (endotracheal) tubes, further increases the risk of developing serious bacterial infections.

Underdeveloped kidneys

Before delivery, waste products produced in the fetus are removed by the placenta and then excreted by the mother’s kidneys. After delivery, the newborn’s kidneys must take over these functions. Kidney function is diminished in very premature newborns but improves as the kidneys mature. Newborns with underdeveloped kidneys may have difficulty regulating the amount of salt and other electrolytes as well as water in the body. Kidney problems may lead to growth failure and a buildup of acid in the blood (called metabolic acidosis).

Underdeveloped lungs

The lungs of premature newborns may not have had enough time to fully develop before birth. The tiny air sacs called alveoli that absorb oxygen from the air and remove carbon dioxide from the blood are not formed until about the beginning of the last third of pregnancy (3rd trimester). In addition to this structural development, the tissues of the lungs must make a fatty material called surfactant. Surfactant coats the inside of the air sacs and allows them to remain open throughout the breathing cycle, making it easy to breathe. Without surfactant, the air sacs tend to collapse at the end of each breath, making breathing very difficult. Usually, the lungs do not make surfactant until about 32 weeks of pregnancy, and production is typically not adequate until about 34 to 36 weeks.

These factors mean that babies born early are at risk of breathing problems, including respiratory distress syndrome (RDS). Newborns with breathing problems may need help with breathing with a ventilator (a machine that helps air get in and out of the lungs). The more premature the newborn, the less surfactant is available, and the greater the likelihood that respiratory distress syndrome will develop.

There is no treatment to make the lung structure mature more rapidly, but with adequate nutrition, the lungs continue to mature over time.

There are two approaches to increase the amount of surfactant and reduce the likelihood and severity of respiratory distress:

  • Before birth: Corticosteroid drugs such as betamethasone increase surfactant production in the fetus and are given to the mother by injection when a premature delivery is anticipated, typically 24 to 48 hours before delivery.

  • After birth: Doctors may give surfactant directly into the newborn's windpipe (trachea).

Bronchopulmonary dysplasia (BPD) is a chronic lung disorder that can occur in premature newborns, particularly the least mature infants. Most infants who have BPD have had respiratory distress syndrome and needed treatment with a ventilator. In BPD, the lungs develop scar tissue and the infant needs continued help with breathing, sometimes with a ventilator. In most cases, the infant very slowly recovers from the disease.

Underdeveloped eyes

The retina is the light-sensitive tissue at the back of the eye. The retina is nourished by blood vessels on its surface. The blood vessels grow from the center of the retina to the edges during the course of the pregnancy and do not finish growing until near term. In premature infants, particularly the least mature infants, the blood vessels may stop growing and/or grow abnormally. The abnormal vessels can bleed or cause scar tissue that can pull on the retina. This disorder is called retinopathy of prematurity. In the most severe cases, the retina detaches from the back of the eye and causes blindness. Premature babies, particularly those born before 31 weeks of gestational age, typically have periodic eye examinations so doctors can look for abnormal development of the blood vessels. If there is a high risk of retinal detachment, doctors may use laser treatments or give a drug called bevacizumab.

Premature newborns are also at increased risk of developing other eye problems, such as nearsightedness (myopia), misalignment of the eyes (strabismus), or both.

Difficulty regulating blood sugar levels

Because premature newborns have difficulty feeding and maintaining normal blood sugar (glucose) levels, they are often treated with glucose solutions given by vein (intravenously) or given small, frequent feedings. Without regular feedings, premature newborns may develop low blood glucose levels (hypoglycemia). Most newborns with hypoglycemia do not develop symptoms. Other newborns become listless with poor muscle tone, feed poorly, or become jittery. Rarely, seizures develop.

Premature newborns are also prone to developing high blood sugar levels (hyperglycemia) if they have an infection or bleeding in the brain or receive too much glucose intravenously. However, hyperglycemia rarely causes symptoms and can be controlled by limiting the amount of glucose given to the newborn or by using insulin for a short period of time.

Heart problems

A common issue among less mature infants is a patent ductus arteriosus (PDA). The ductus arteriosus is a blood vessel in the fetus that connects the two large arteries leaving the heart, the pulmonary artery and the aorta (see Normal Fetal Circulation). In a full-term infant, the muscle wall of the ductus arteriosis closes the blood vessel in the first few hours or days of life. In premature infants, however, the blood vessel may stay open, resulting in excessive blood flow through the lungs and requiring more work from the heart. In most premature infants, the PDA eventually closes on its own, but drugs are sometimes given to help the PDA close more quickly. In some cases, a surgical procedure to close the PDA is done.

Difficulty regulating body temperature

Because premature newborns have a large skin surface area relative to their weight compared to full-term newborns, they tend to lose heat rapidly and have difficulty maintaining normal body temperature, especially if they are in a cool room, there is a draft, or they are near a window when it is cold outside. If the baby is not kept warm, the body temperature falls (called hypothermia). Newborns who have hypothermia gain weight poorly and may have a number of other complications. To prevent hypothermia, premature babies are kept warm in an incubator or with an overhead radiant warmer (see Neonatal intensive care units (NICUs)).

Diagnosis

  • Appearance of the newborn

  • Gestational age

Doctors usually know whether a baby is born prematurely based on the newborn's calculated gestational age and physical features observed after birth. They examine the newborn and do any needed blood, laboratory, hearing, eye, and imaging tests as part of the routine newborn evaluation and screening. These screenings may need to be repeated frequently as the newborn grows and before discharge from the hospital.

Prognosis

Over recent decades, the survival and overall outcome of premature newborns has improved dramatically, but problems such as delayed development, cerebral palsy, vision and hearing impairments, attention-deficit/hyperactivity disorder (ADHD), and learning disorders are still more common among premature infants than full-term infants. The most important factors in determining outcome are

  • Birth weight

  • Degree of prematurity

  • Whether the mother was given corticosteroids for 24 to 48 hours before a premature delivery

  • Complications that arise after birth

The sex of the baby (girls have a better prognosis than boys who have the same degree of prematurity) also affects the likelihood of a good outcome.

Survival itself is rare if infants are born at less than 23 weeks gestation. Infants born at 23 to 24 weeks may survive, but few have normal neurologic function. Most infants born after 27 weeks gestation survive with normal neurologic function.

Because of the potential for a poor outcome, experts in newborns (neonatologists) vary in how aggressively they recommend treating infants born in the range of 22 to 25 weeks gestation. For such children, parents should discuss prognosis and options with the neonatologist, ideally before delivery if there is sufficient time for such a discussion.

Prevention

Regular prenatal care, combined with identification and treatment of any risk factors or complications of pregnancy, and stopping smoking may be the best approach to reducing the risk of prematurity. However, many of the conditions that increase the risk of prematurity cannot be avoided. In all cases, women who think they may be in premature labor or have had rupture of the membranes should contact their obstetrician immediately to arrange for appropriate evaluation and treatment.

Assisted reproductive techniques often result in multi-fetal pregnancies (twins, triplets, and more). Because multi-fetal pregnancies have a significantly increased risk of premature delivery, parents should discuss with their doctor the possible poor outcomes and their likelihood.

Treatment

  • Treatment of complications

Treatment of prematurity involves managing the complications resulting from underdeveloped organs. All specific disorders are treated as needed. For instance, premature newborns may be given treatments that help with breathing problems (such as mechanical ventilation for lung disease and surfactant treatment), antibiotics for infections, blood transfusions for anemia, and laser surgery for eye disease or they may need special imaging studies like echocardiography for heart problems.

Parents are encouraged to visit and interact with their newborn as much as possible. Skin-to-skin contact (also called kangaroo care—see Neonatal intensive care units (NICUs)) between the newborn and the mother or father is beneficial to the newborn.

Parents should remove fluffy materials including blankets, quilts, pillows, and stuffed toys from the infant's crib at home because these items may increase the risk of sudden infant death syndrome (SIDS). Infants at home should be placed on their back and not their stomach to sleep because sleeping on the stomach also increases the risk of SIDS.

Very premature newborns

Very premature newborns may need to be hospitalized in a neonatal intensive care unit for days, weeks, or months. They may require a breathing tube and a machine that helps air get in and out of the lungs (ventilator) until their lungs are able to breathe air.

They receive nutrition into their veins until they can tolerate feedings into their stomach through a feeding tube and eventually feedings by mouth. The mother’s breast milk is the best food for premature infants. Use of breast milk decreases the risk of developing an intestinal problem called necrotizing enterocolitis and infections. Because breast milk is low in some nutrients like calcium, it may need to be mixed with a fortifying solution for newborns who have a very low birth weight. Infant formulas made specifically for premature infants that are high in calories also can be used when necessary.

Very premature newborns may require a drug that prompts them to breathe, such as caffeine, until the part of the brain that controls regular breathing has matured.

To keep warm, these newborns need to be kept in an incubator until they are able to maintain a normal body temperature.

Extremely premature newborns

Extremely premature newborns require all the same care as very premature newborns. Like very premature newborns, these newborns cannot be released from the hospital until they are able to breathe on their own, take oral feedings, maintain a normal body temperature, and gain weight.

Discharge from the hospital

Premature infants typically remain hospitalized until their medical problems are under satisfactory control and they are

  • Taking an adequate amount of milk without special assistance

  • Gaining weight steadily

  • Able to maintain a normal body temperature in a crib

Most premature infants are ready to go home when they are at 35 to 37 weeks gestational age and weigh 4 to 5 pounds (2 to 2.5 kilograms). However, there is wide variation. The length of time the infant stays in the hospital does not affect the long-term prognosis.

Because premature newborns are at risk of stopping breathing (apnea), and having low levels of oxygen in the blood and a slow heart rate while in a car seat, many hospitals in the United States do a car seat challenge test before premature babies are discharged. The test is done to determine whether babies are stable in the semi-reclined position of a car seat. This test is usually done using the car seat provided by the parents. The car seat challenge test is not highly accurate and is not used by doctors in some other countries. Premature babies, including those who pass the test, should be observed by a non-driving adult during all car seat travel until the babies have reached the due date and have remained consistently able to tolerate being in the car seat. Because the baby's color should be observed, travel should be limited to daylight hours. Long trips should be broken up into 45- to 60-minute segments so that the baby can be taken out of the car seat and repositioned.

Surveys show that most car seats are not installed optimally, so a check of the car seat by a certified car seat inspector is recommended. Inspection sites can be found here. Some hospitals offer an inspection service, but casual advice provided by an uncertified hospital staff member should not be considered equivalent to inspection by a certified car seat expert.

The American Academy of Pediatrics recommends that car seats be used only for vehicular transportation and not as an infant seat or bed at home. Many doctors also recommend not to put premature infants in swings or bouncy seats for the first few months at home.

After discharge, premature infants are carefully monitored for developmental problems and receive physical, occupational, and speech and language therapy as needed.

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