NIH Study Reveals Factors that Influence Premature Infant Survival, Disability

Based on observations of more than 4,000 infants, researchers in an NIH newborn research network have identified several factors that influence an extremely low birth weight infant’s chances for survival and disability. The findings offer new information to physicians and families considering the most appropriate treatment options for this category of infants.

Every day, physicians and new parents must struggle with the type of care to provide to extremely low birth weight infants, the smallest, most frail category of preterm infants. These infants are born in the 22nd through the 25th week of pregnancy—far earlier than the 40 weeks of a full term pregnancy. Many die soon after birth, despite the best attempts to save them, including the most sophisticated newborn intensive care available. Some survive and reach adulthood, relatively unaffected. The rest will experience some degree of life long disability, ranging from minor hearing loss to blindness, to cerebral palsy, to profound intellectual disability.

The study authors referred to the issue of providing intensive care for extremely low birth weight infants. For example, physicians and family members may be reluctant to expose an infant to painful life support procedures if the infant is unlikely to survive. In such cases, they may opt for “comfort care,” which provides for an infant’s basic needs, but foregoes painful medical procedures. In deciding the kind of care to provide, specialists at intensive care facilities traditionally have relied heavily on an infant’s gestational age—the week of pregnancy a premature infant is born. Gestational age is known to play a large role in the infant’s survival. For this reason, in many facilities, intensive care is likely to be routinely given to infants born in the 25th week of pregnancy, whereas infants born in the 22nd week may be more likely to receive comfort care.

The study authors noted, however, that it is often difficult to assess gestational age. Moreover, an estimate that is inaccurate by only a week could result in an infant receiving care that was not appropriate for his or her individual case. To identify other factors that influenced survival and disability risk, the study authors observed more than 4,000 extremely low birth weight infants in their network.

The researchers published their findings in the April 17 New England Journal of Medicine. In addition to gestational age, factors influencing survival and risk of disability consisted of: whether the baby is male or female (sex); birthweight; whether the baby was a single baby, or one of two or more infants born; and whether the baby’s mother was given medication during pregnancy to prompt the development of the baby’s lungs. Known as antenatal steroids, these drugs are typically given to women in premature labor, or who are at known risk for giving birth prematurely.

Physicians and parents may access an online tool that generates statistics, based on the factors the researchers listed in their article, at By specifying the baby’s sex, weight, and information related to each of the variables listed above, physicians and family members can generate composite statistics on infant outcomes, based on the experiences of extremely low birthweight infants in the NICHD Neonatal Research Network study. The Web tool is not a substitute for a physician’s careful assessment, but physicians and families may find the statistics it generates useful when considering the most appropriate care to provide an infant.

“Every individual is different, and no single tool can precisely predict a given baby’s chances of survival or disability,” said Duane Alexander, M.D., director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH Institute that supports the Neonatal Research Network. “However, the researchers’ findings, and the tool they developed, provide important information that physicians and family members can consult to help them make the most informed treatment decisions possible.”

Additional funding for the study was provided by NIH’s National Center for Research Resources.

The researchers were led by Jon E. Tyson, M.D., of the University of Texas Medical School at Houston. Other authors of the study were Nehal A. Parikh, D.O., and Charles Green, Ph.D., also of the University of Texas Medical School at Houston; John Langer, M.S., of the Research Triangle Institute,Research Triangle Park, NC, and Rosemary Higgins, M.D., the program scientist for the NICHD Neonatal Research Network.

The study involved only infants born at level III neonatal intensive care facilities. For this reason, the study findings may not apply to infants born at level I and level II facilities.

Level III facilities are the most advanced of neonatal care facilities. They offer the highly specialized medical care that extremely low birth weight infants need to survive. Most extremely low birth weight infants are born in level III facilities, as it is routine practice to rush women likely to give birth prematurely to level III facilities. However, in some cases, a woman may give birth before she can be brought to a level III facility. These infants are typically cared for at level I and II facilities until they are stable enough to transport to a level III facility.

To conduct their analysis, researchers in the NICHD Neonatal Research Network observed 4,446 infants born at 22-25 weeks’ gestational age at hospitals around the United States, explained the NICHD co-author of the study, Rosemary Higgins, M.D. Dr. Higgins said that extremely low birthweight infants (those weighing less than 1,000 grams, or 2.2 pounds) make up about 1 percent of babies born in the United States each year, or roughly 40,000 babies a year.

Using standardized measures of mental development, vision, and hearing, the researchers assessed the health status of surviving infants when the infants were from 18 to 22 months corrected age—the age they would have been, had they been born full term. Dr. Higgins said that 49 percent of the infants in the study had died, 21 percent lived and did not have a disability, while the remainder experienced some degree of disability.

After conducting mathematical analyses of all the infants’ cases, the researchers determined that infants were more likely to survive—and more likely to survive without disability—if they were of older gestational age, their mothers had been given corticosteroids, if they were female, were single born rather than part of a multiple birth, and been of a higher birthweight.

“Many neonatal intensive care units base treatment decisions mainly on gestational age,” said Dr. Higgins. “We found that it’s much more accurate if the assessment is based on the combination of 5 factors, rather than just on gestational age.”

Dr. Higgins added that it is often difficult to accurately estimate gestational age, and a preterm infant may be as much as a week or two younger, or older, than believed.

She noted that the researchers found that race appeared to play no role in subsequent survival or chances of disability.

She stressed that the study data could not be used to predict with certainty the outcome of individual cases.

“A lot of medicine is a judgment call,” Dr. Higgins said. “We provided our data in the hope that it would be helpful for making the best judgments for a particular situation.”

A video interview with Dr. Higgins in which she provides additional information about the study and the online tool is available at


The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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