One size may not fit all when it comes to growth references for preterm infants

Growth monitoring is a fundamental part of preventive child health care in developed countries. It aims to diagnose childhood growth disorders at an early stage, which can prevent additional morbidity and potential permanent health deficits or loss in adult height. Postnatal growth is associated with later health outcomes in preterm infants. There is consistent evidence linking poor postnatal growth in preterm infants with adverse neurocognitive outcomes and a lower level of evidence that states that rapid postnatal growth may lead to adverse metabolic outcomes and later cardiovascular risks after 2 years of age (1). The most important tools in growth monitoring are upto-date growth references for length and height, weight and head circumference, which define normative values for age-specific and sex-specific growth. Numerous published growth references are available. For example, the authors of a systematic review on references for neonatal size found more than 100 publications describing neonatal anthropometric charts on variable populations and statistical methodology (2). Similar heterogeneity can be demonstrated in the existing growth references after the neonatal period. The growth reference that is chosen for clinical use is important, as shown by the Neubauer et al. (3) paper in this issue. Neubauer et al. (3) evaluated the postnatal growth of 551 very preterm Austrian infants by using four different growth references intended for international use to convert their length, weight and head circumference measurements at birth, discharge and at the corrected ages of three, 12 and 24 months, into standard deviation Z-scores. The results of the study were confusing and depending on the reference that they used, the interpretation of the postnatal growth of preterm infants seemed completely different. The most striking example was the proportion of preterm infants with microcephaly, defined as a head circumference of more than of more than two standard deviations below the mean. This varied from 2.7% to around 25% at the corrected age of 24 months, depending on the reference used. Less striking but still statistically and clinically significantly different interpretations of postnatal weight and length growth were also shown. Today, the most important question in the field of childhood growth monitoring, which was also raised by the observations in the Neubauer et al. cohort of Austrian preterm infants, is whether growth references should be the same for children all over the world, or adapted to the population. In 2006, the World Health Organization (WHO) published multiethnic growth charts for children under the age of five that comprised growth data on around 7000 children from six different countries: the United States, Norway, Oman, Brazil, India and Ghana (4). The rationale for the construction of the multiethnic WHO standards stemmed from the hypothesis that growth patterns are similar in children from diverse ethnic backgrounds when their physiological needs are met and their environment supports healthy development. Multiethnic foetal and birth size references from the Intergrowth 21st Project were published in 2014 (5), based on same methodology and conceptual approach as the generation of the WHO charts. All these international standards were generated using up-to-date statistical methodology. However, criticism of these basic conceptual ideas that similar growth occurs in foetuses and infants and children in ideal living conditions has been raised. Human growth is strongly genetically determined, resulting in significant variations in adult heights, body compositions or height circumferences among populations, with heritability estimates of around 80% in height. Therefore, childhood growth patterns among populations, which were assumed to show a level of uniformity by the WHO growth charts and Intergrowth 21st Project, may not be based on nutritional, environmental and psychosocial factors as strongly as assumed. A study on foetal growth references in four racial and ethnic groups living in optimal conditions in the USA demonstrated significant variability between the ethnic groups, which supported the strong role of genetic regulation of growth in utero (6). Clinical studies have also raised concerns about the performance of international WHO growth references in assessing children’s height. Measurements for children growing at the outer percentiles with potential morbidity may be flawed if we use WHO standards. In studies from Norway, Belgium and Finland, the proportions of the healthy children outside the 2 SDs of the WHO standards were not as expected (7,8). Thus, the concept of similar heights, weights or head circumferences