The New York Times published a report this week, based on a New England Journal of Medicine (NEJM) article, that claimed “a small number” of extremely premature babies could survive outside the womb at 22 weeks, “earlier…than doctors once thought possible.” The study, the Times said, raised “questions about how aggressively [the infants] should be treated and pos[es] implications for the debate about abortion.”
I want to make a strong argument that this overstates the data and we are nowhere near such a debate.
For a newborn to survive at birth, the lungs must have the capacity to “breathe” and deliver oxygen to the body. There is abundant evidence that developing lungs are capable of doing so at approximately 24 weeks of gestation (although there is inherent variability in development even at 24 weeks). This is the basis for the statement in the same New York Times report yesterday “that most medical experts regard 24 weeks as the lower limit of viability.”
An accurate estimation of the fetus’s age becomes a critical first step in the discussion of what constitutes the lower limit of viability. As acknowledged by the authors in the New England Journal of Medicine (NEJM) article, “except for conception via in vitro fertilization, all obstetrics estimates have a margin of error of at least 5 days with a potentially greater error in the extremely preterm fetus.”
In an important series of articles on this subject, published by the same Neonatal Network Group over the years, a major limitation has been the unavailability of data on how doctors estimate the age of a fetus. It becomes even more complicated as this group has identified other factors that may influence outcome, including a one-week advantage of the female over the male sex (i.e. a 23-week female fetus has the same risk as a 24-week male fetus), the presence or absence of multiple fetuses, whether the fetus has impaired growth, and the administration of antenatal glucocorticosteroids. If these latter, known commonly as steroids or antenatal steroids, are given every 24 hours, for 48 hours prior to delivery, it improves lung function at birth.
In our institution, the average length of stay for a surviving infant born at 24 weeks estimated gestational age is approximately 120 days. If you lower that estimate to 23 weeks and 5 days, the average length of stay increases to approximately 160 days. A one or two day difference in estimating gestational age may have serious implications, as it relates to survival chances as well as long-term complications for the baby. Thus accurate estimation of gestational age, as mentioned previously, is critical.
During a prolonged hospitalization, these infants are at high risk for developing medical and/or or surgical conditions including brain bleeds, recurrent infections, serious damage to the eyes, perforation or infection in the intestines, as well as being subjected to multiple medical interventions to keep them alive. For the infants who do survive, they often need multiple hospital revisits. All extremely premature infants will require early intervention, to help with their universal weakness and many other sensory problems. These interventions are essential to the recovery process.
How should one interpret the findings in the NEJM report? Importantly, when one evaluates evidence, it needs to be done in a systematic, unbiased and unemotional manner. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) is a systematic and explicit approach to making judgments about quality of evidence and strength of recommendations, and has been adopted by many organizations such as the World Health Organization, as the framework for developing evidence-based recommendations.
Evidence is classified as high, moderate, low and very low quality, and there are many factors that go into determining the quality of a study with study design of paramount important. Randomized studies start off as high quality and maybe downgraded if there are any methodological issues. An observational study starts off as low quality, and if there are additional methodological issues such as bias they are downgraded as very low quality.
Despite the meticulous attention to the presentation of the available and informative data, it is important to recognize that the NEJM study was an observational study, subjected to tremendous bias, particularly as it relates to the issue of when to intervene or to offer comfort care. If the study is randomized and the decision to intervene is random, then bias is taken out. Nobody is prepared to such as a study—for obvious reasons. But a very low-quality study cannot serve as the basis for sweeping change to medical practice.
At our institution, we regard 24 weeks as the lower limit of viability and will invariably intervene in such cases after discussions with the parents. If the fetus is at 23 weeks, we regard this as a gray zone, and will talk to the family and explain to them that for us the outcome is unknown. Any younger than that, we do not recommend any intervention. Our approach is one of pragmatism and constant reevaluation, with parental involvement an integral part of this process.
Jeffrey Perlman is a Professor of Pediatrics at Weill Cornell Medical College.