Steroids Boost Survival, Reduce Brain Injury for Infants Born at 23 Weeks

Prenatal steroids—given to pregnant women at risk for giving birth prematurely—appear to improve survival and limit brain injury among infants born as early as the 23rd week of pregnancy, according to a study by a National Institutes of Health research network.

Current guidelines recommend giving prenatal steroids to women at risk of delivering between the 24th and 34th weeks of pregnancy. 

“These findings provide strong evidence that prenatal steroids can benefit infants born as early as the 23rd week of pregnancy,” said study author Rosemary D. Higgins, M.D., of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). 

The study was conducted by researchers participating in the NICHD Neonatal Research Network and led by Waldemar A. Carlo, director of the Division of Neonatology at the University of Alabama at Birmingham. The findings appear in the Dec. 7 Journal of the American Medical Association.

When given to pregnant woman at risk for preterm delivery, steroid hormones help the fetus’s lungs to mature. For infants born preterm, increased lung development improves the chances for survival and may decrease the risk of brain injury.

Infants born in the 22nd through the 25th week of pregnancy—far earlier than the 40 weeks of a full term pregnancy—are the smallest, most frail category of newborns. 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 lifelong disability, including minor hearing loss, cerebral palsy, and intellectual disability.

Before the present study, little information was available to guide practitioners in the use of prenatal steroids for infants born before the 24th week. For this reason, the decision to prescribe steroids for pregnant women at risk of delivering before the 24th week varies from physician to physician.

To conduct the study, the researchers analyzed medical records from network hospitals for 10,541infants born preterm from 1993 to 2009. The researchers also performed neurological examinations on the 4,924 surviving infants who were born between 1993 and 2008. The examinations were conducted 18-22 months after the infants’ original due dates. All of the infants were born in the 22nd through the 25th weeks of pregnancy.

The researchers found that there were 33 percent fewer deaths among infants born to mothers who received prenatal steroids, compared with those whose mothers did not. In addition to lower death rates, the researchers found that among infants who survived, rates of blindness, hearing impairment, cerebral palsy or severe delays in motor and cognitive development were more than 20 percent lower in cases in which mothers had received antenatal steroids, compared with cases in which they did not.

The researchers also compared infant outcomes separately for each gestational week. For each age group, the researchers calculated a single combined outcome measure: the proportion of infants who died before 18-22 months with the proportion of surviving infants who experienced a neurological impairment. The researchers found that for each age group, the likelihood of this combined outcome—death or neurological impairment— was smaller for infants whose mothers received steroids than those whose mothers did not:

• For those born at 25 weeks, 53 percent for the steroid group, compared with 68 percent in the untreated group
• For those born at 24 weeks, 68 percent in the steroid group, compared with 80 percent in the untreated group
• For those born at 23 weeks, 83 percent in the steroid group, versus 90 percent in the untreated group

For infants born at 22 weeks, this combined outcome measure did not differ significantly (90 percent for the steroid group compared with 93 percent for the untreated group). However, a smaller proportion of infants in the steroid group who were born at 22 weeks experienced another combined outcome, death or necrotizing enterocolitis, than did those in the untreated group: 73.5 percent versus 84.5 percent. Necrotizing enterocolitis is a serious infection that can occur in the intestines of preterm infants. 

The study compared infants receiving prenatal steroid treatment (cases) to those who had not (controls). Although such case-control studies often provide useful information, researchers typically do not consider them to be as informative as controlled clinical studies, in which study participants are assigned either to receive a new treatment or, instead, to forego the new treatment.

“We knew that many physicians were exercising their medical judgment to prescribe the treatment in cases not covered by the guidelines,” Dr. Higgins said. “So our strategy was to assess the outcomes of patients who had already been treated.”

A limitation of case-control studies is that researchers may not be able to account for all the factors that influenced the study results.  It’s possible, Dr. Higgins said, that some factor the researchers were not aware of could have influenced physicians’ decisions to prescribe the steroids.   For example, a physician might be less inclined to prescribe steroids in cases in which the fetus had a serious birth defect or other condition.

The study authors noted that a controlled study would have provided more definitive results, but would have been very difficult to undertake.  First, Dr. Higgins explained, enrolling a large enough number of patients to provide statistically meaningful results would take a long time.  Moreover, many physicians and expectant mothers might not want to participate. Knowing that prenatal steroids were beneficial for older preterm infants, they might be reluctant to decline what could be a potentially life-saving therapy.

The authors added that a major strength of their study is that it included more infants than did any prior study of prenatal steroids in this class of preterm infants. Moreover, benefits of the treatment were seen in all categories of infants in the study.

“Among infants born at 23-25 weeks gestation, use of antenatal corticosteroids compared to non-use was associated with a lower rate of death or neurodevelopmental impairment at 18-22 months,” they wrote.

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About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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 http://www.nichd.nih.gov/.

About the National Institutes of Health (NIH)

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. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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