Birth is dangerous, especially for infants born too small or too soon. Although much is known about the mortality risk for such infants in high-income countries, little is known about the risk in poorer countries. In The Lancet, Joanne Katz and colleagues begin to fill in the gap on just how dangerous it is to be born too small or too soon in a low-income or middle-income country.1 The investigators analysed more than 2 million birth outcomes from resource-poor countries in Asia, Africa, and Latin America and calculated the regional risk of neonatal and post-neonatal mortality associated with being born preterm, small-for-gestational age (SGA), or both.

Using data from 20 cohorts in 13 countries, Katz and colleagues show that being born SGA increased the risk of neonatal mortality by two to five times across the three regions, but being born preterm (<37 completed weeks of gestation) raised the risk by six to 26 times. When children were born both SGA and preterm, neonatal mortality was ten to 39 times higher than in otherwise normal neonates. These findings provide the first solid estimates of the excess risk of dying for infants in these categories of births for countries where 135 million babies are born every year.

Katz and colleagues’ findings advance our knowledge by going beyond the use of low birthweight (<2500 g) as a means of identifying infants in danger. The low birthweight category includes both premature and growth-restricted infants. It excludes newborn babies heavier than 2500 g who might also be premature or have restricted growth and therefore still have an increased risk of dying. As a result of these findings, the sources of neonatal mortality are now better known in the regions studied and appropriate interventions to prevent early deaths can be developed.

Katz and colleagues are also the first to document the high proportion of Asian and African newborn babies (21% and 16%, respectively) who are SGA (defined as the lowest tenth percentile of the growth reference) but neither preterm nor low birthweight. In view of the surprisingly high proportion of such infants, it is disappointing that the authors did not provide the associated mortality risk. Term-SGA infants had about three times higher risk of death (across all regions) during the early and late neonatal as well as the postneonatal periods, but these included a high proportion of low-birthweight (LBW) infants. The investigators state that the large group of infants who are SGA but not preterm or LBW have a higher mortality risk than term, appropriate weight-for-gestational-age infants, but we are left to wonder: how much higher?

The high prevalence of term SGA births and their excess risk of death throughout infancy suggest that there is more to know about these babies than just their weight-for-gestational age. They could also be shorter, as documented in Guatemala,2where linear growth failure was detectable as early as 15 weeks of gestation, and infants tend to be born “short and round”.3 Infants of HIV-infected mothers on antiretroviral therapy in Haiti and Zambia were also born small, largely because of shortness at birth rather than thinness.4, 5 There has been much discussion about the causes and consequences of proportional (ie, short and round) versus disproportional (long and thin) phenotypes of SGA babies, with some evidence that thin SGA babies are at higher risk of adverse outcomes.6, 7 Elucidation of the differences in mortality risk among types of SGA infants will require datasets that include infant length at birth, but such data are rare.

Katz and colleagues’ findings present important methodological challenges. The investigators included cohorts on the basis of completeness and quality of their data. Nonetheless, in six of the cohorts, they imputed some birthweights because some data were missing or measured too late. Some of the variability in birthweight might have resulted from the 72 h observation window used (during which breastfed neonates can lose up to 10% of their weight8). Unfortunately, the preferred reference dataset for calculating birthweight-for-gestational age (the Alexander reference9) provides data at only the tenth percentile, so the authors used a different reference dataset to identify infants below the third percentile.10 Both references are from large US populations, with data obtained in 1972—76 and 1991, respectively. The appropriateness of these reference populations, especially for the cohorts from South Asia, is unknown and might be among the factors that account for the high proportions of SGA births seen. Again, not knowing the excess mortality associated with the SGA babies who were term and not LBW, we wonder whether the use of the tenth percentile of the Alexander reference put too many babies in this risk category.

The analysis presented by Katz and colleagues is a substantial contribution, and points the way to further advances. Most of the cohort studies included were not representative of the country where they were done, and the studies included in a given region were also not representative of that region—eg, the vast majority of data from Latin America was from Chile. More representative data are surely needed. Also, many low-income or middle-income countries are in eastern Europe and central Asia, regions not represented in these analyses. The scarcity of data from these regions, however, is because of a dearth of global resources and attention rather than a product of poor study design. We hope that this important study can serve as a catalyst for the development of stronger datasets that require fewer assumptions and include additional essential information, including length at birth.

Source: Lancet