Born too small or too soon
Authors: Michael S Kramer
Journal: The Lancet Global Health (2013)

In The Lancet Global Health, Anne Lee and colleagues from the Child Health Epidemiology Reference Group (CHERG)1Lee AC Katz J Blencowe H et al.for the CHERG SGA-Preterm Birth Working GroupNational and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010.Lancet Glob Health. 2013; 1: e26-e36Summary Full Text Full Text PDF PubMed Scopus (510) Google Scholar make an important contribution to our understanding of the global burden of intrauterine growth restriction. What is new in this work is the evidence that the majority of growth-restricted neonates (assessed with the proxy of small-for-gestational-age birth) weigh 2500 g or more at birth, even in low-income and middle-income countries. In high-income countries, most preterm infants—particularly those born at 34–36 completed weeks of gestation—also weigh at least 2500 g. Lee and colleagues show that nearly half of preterm infants from countries of low and middle income also are born above this birthweight threshold. Thus, globally, the traditional maternal and child health indicator of low birthweight (defined as <2500 g) fails to identify most newborn babies who are born either too small or too soon. This fact alone undermines Lee and colleagues' claim that "low birthweight is an important population indicator for tracking neonatal health". Not only does the definition of low birthweight exclude most preterm and small-for-gestational-age neonates, it also conflates two problems. First, difficulties arise when distinguishing countries and regions where most low-birthweight infants are born small for gestational age (eg, south Asia) from those where most such babies are preterm (eg, sub-Saharan Africa). Second, understanding temporal trends within countries or regions is tricky. In Canada, for example, rates of low birthweight fell steadily during the 1980s and 1990s, hiding opposite trends in small-for-gestational-age births (decline) and preterm births (rise).2Health CanadaCanadian Perinatal Surveillance SystemCanadian perinatal health report.http://publications.gc.ca/collections/Collection/H49-142-2000E.pdfDate: 2000Google Scholar For this reason, Canada and some other high-income countries no longer include low birthweight as a perinatal health surveillance indicator. Of course, in settings in which either a large proportion of pregnant women do not have access to antenatal care or many births occur in the home, valid estimates for gestational age might be more difficult to obtain than birthweight. In those settings, low birthweight might indicate the need for extra clinical surveillance and intervention in the postnatal period. If the 2500 g cutoff for low birthweight is arbitrary, what about the cutoffs used by Lee and colleagues to define preterm birth (<37 completed weeks of gestation) and small for gestational age (<10th centile birthweight for gestational age)? These cutoffs are the conventional accepted ones recommended by WHO yet they are no less arbitrary than that for low birthweight. Study findings show that infants born at 37–38 completed weeks of gestation, compared with those born at 39–41 weeks, are at increased risk of neonatal mortality and morbidity3Zhang X Kramer MS Variations in mortality and morbidity by gestational age among infants born at term.J Pediatr. 2009; 154: 358-362Summary Full Text Full Text PDF PubMed Scopus (129) Google Scholar and later neurocognitive difficulties.4Noble KG Fifer WP Rauh VA Nomura Y Andrews HF Academic achievement varies with gestational age among children born at term.Pediatrics. 2012; 130: e257-e264Crossref PubMed Scopus (114) Google Scholar The same is true for fetal growth. In fact, the optimum birthweight for gestational age, at least from the viewpoint of minimising risk of neonatal death, is not the 10th or even the 50th centile but is close to the 90th centile, the conventional cutoff for defining large-for-gestational-age births.5Graafmans WC Richardus JH Borsboom GJJM et al.Birth weight and perinatal mortality: a comparison of "optimal" birth weight in seven western European countries.Epidemiology. 2002; 13: 569-574Crossref PubMed Scopus (57) Google Scholar, 6Joseph KS Fahey TJ Platt RW et al.An outcome-based approach for the creation of fetal growth standards: do singletons and twins need separate standards?.Am J Epidemiol. 2009; 169: 616-624Crossref PubMed Scopus (57) Google Scholar Why has evolution selected for birthweights that are so far below the weight that minimises the risk for the newborn baby? Probably because of competition from the mother. Without the option of caesarean or forceps delivery, a large fetus was a major risk to the mother's own survival and, thus, her ability to have other babies. When considering birthweight-for-gestational-age as an indicator of newborn health, perhaps we should seek a more functionally defined cutoff—eg, based on the relative risk of neonatal death or serious morbidity.6Joseph KS Fahey TJ Platt RW et al.An outcome-based approach for the creation of fetal growth standards: do singletons and twins need separate standards?.Am J Epidemiol. 2009; 169: 616-624Crossref PubMed Scopus (57) Google Scholar The conventional cutoff for small for gestational age is based on birthweight, which is suitable for infants born at term but is far less appropriate for those born preterm. Preterm birth is itself pathological, and ultrasound-based estimates of fetal weight show that infants born preterm are much smaller than their peers who remain in utero at the same gestational age.7Hutcheon JA Platt RW The missing data problem in birth weight percentiles and thresholds for "small-for-gestational-age".Am J Epidemiol. 2008; 167: 786-792Crossref PubMed Scopus (85) Google Scholar Thus, at preterm gestational ages, the poorly sensitive cutoff of lower than the 10th centile for birthweight will be even less sensitive for identification of suboptimum fetal growth when it is based on the distribution of birthweights, rather than estimated fetal weights. The ongoing Intergrowth study will provide improved ultrasound-based estimates for identification of growth-restricted preterm newborn babies. What is the public health use of any indicator of gestational age or fetal growth? Although findings of randomised trials of balanced energy–protein and micronutrient supplementation show some effects of reducing preterm birth8Hofmeyr GJ Lawrie TA Atallah AN Duley L Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.Cochrane Database Syst Rev. 2010; 8 (CD001059)PubMed Google Scholar and small-for-gestational-age births,9Kramer MS Effects of energy and protein intakes on pregnancy outcome: an overview of the research evidence from controlled clinical trials.Am J Clin Nutr. 1993; 58: 627-635PubMed Scopus (93) Google Scholar, 10Haider BA Bhutta ZA Multiple-micronutrient supplementation for women during pregnancy.Cochrane Database Syst Rev. 2012; 11 (CD004905)PubMed Google Scholar most countries (including those of high, middle, and low income) have seen important reductions in infant mortality despite rises in preterm birth (mostly attributable to increases in obstetric intervention) and only modest reductions in small-for-gestational-age birth. Most recent progress in reducing infant mortality has been achieved by lowering mortality across the entire range of gestational ages and birthweights, including that of term infants of normal birthweight, not by preventing preterm or small-for-gestational-age birth.11Kramer MS Barros FC Demissie K Liu S Kiely J Joseph KS Does reducing infant mortality depend on preventing low birthweight? An analysis of temporal trends in the Americas.Pediatr Perinat Epidemiol. 2005; 19: 445-451Crossref PubMed Scopus (37) Google Scholar, 12Gonzalez R Merialdi M Lincetto O et al.Reduction in neonatal mortality in Chile between 1990 and 2000.Pediatrics. 2006; 117: e949-e954Crossref PubMed Scopus (58) Google Scholar In other words, a focus on reducing infant mortality and severe morbidity is likely to pay higher dividends for public health than are attempts to prevent preterm or small-for-gestational-age birth. I declare that I have no conflicts of interest. National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. Full-Text PDF Open Access