Mortality risk among preterm babies: immaturity versus underlying pathology

Abstract

Background: Deaths among preterm births are presumably due to both immaturity and the conditions that cause preterm birth. Their relative contributions are unknown.

Methods: Using US birth certificates (1995-2002), we estimated what portion of preterm neonatal mortality may be attributable to immaturity alone. Twins have elevated mortality, yet they usually have lower mortality than singletons at most preterm weeks. Twinning itself is a cause of early birth. Thus, at any given preterm week, singletons are more likely than twins to have pathologic causes of preterm delivery. If any such cause is associated with a mortality risk higher than that conferred by twinning, it is possible for singletons to have higher mortality than twins at some preterm weeks. Thus, mortality of twins at those weeks comes closer to describing the risk due to immaturity itself. To exclude high-risk babies, we focused on singletons and twins least likely to have suffered fetal growth disruptions (ie, those with "optimal" birth weight). At each gestational week from 24 to 36, we identified (for twins and singletons separately) the 500-gram weight category with the lowest neonatal mortality, and selected the lower of the 2 mortality rates.

Results: Using the above as our best estimates of mortality due to immaturity alone, we calculated that about half the mortality of singleton preterm babies was due to the pathologies that cause early delivery.

Conclusions: Factors that cause preterm birth apparently contribute a large proportion of preterm mortality. If so, the prevention of preterm mortality requires more than the postponement of delivery.

Figure 1

Gestational-age-specific neonatal mortality rates (per 1,000 births) in singletons, twins, and triplets. Gestational age is a mixture of last menstrual period (LMP) and clinical estimates. Data from National Center for Health Statistics, US Live Births, 1995–2002.

Figure 2

Graphic representation of the interrelation of twinning, mortality, and gestational age at birth, in the presence of a third factor, U, which decreases gestational age at birth and increases mortality. In this situation, gestational age is a collider, and the estimated effect of twinning on mortality will be altered when stratifying by gestational age, as such stratification creates a spurious relation between U and twinning.

Figure 3

Steps to define the study population. GA: gestational age

Figure 4

Weight-specific neonatal mortality of A. singletons and B. twins at gestational weeks 24 to 36. Data from National Center for Health Statistics, US Live Births, 1995–2002. Each point represents a 500-g category. Mid-point in the interval is marked.

Figure 5

A. Gestational-age-specific neonatal mortality for singletons and twins at the optimal birth weight and B. synthetic set of rates representing the lowest mortality at each week between singletons and twins. The mortality for all singletons is reported for comparison purposes. Data from National Center for Health Statistics, US Live Births, 1995–2002.