Neonatal factors predicting childhood height in preterm infants: Evidence for a persisting effect of early metabolic bone disease?

Objectives: Preterm infants are known to remain small during childhood. We previously found that evidence of neonatal metabolic bone disease was associated with reduced length at 18 months. We aimed to further investigate factors predicting childhood height and to test the hypothesis that evidence of early metabolic bone disease is associated with reduced later height. Study design: A cohort of preterm infants was measured prospectively at 18 months (n = 765), 7.5 to 8 years (n = 772), and 9 to 12 years of age (n = 503). Results: Preterm infants remained short for their age and sex at all follow-ups. Later height was most strongly predicted by parental height and, at 9 to 12 years, by pubertal status. Neonatal factors associated with later height were birth weight SD score, maternal hypertension/toxemia, and a high peak plasma alkaline phosphatase during the neonatal period. After adjustment for these factors plus interim heights, height at 9 to 12 years was greatest in those who were tallest at 7.5 to 8 years, those who had shown the greatest increase in height percentile between 18 months and 7.5 to 8 years and, as expected, those who were pubertal, whereas children with a peak neonatal plasma alkaline phosphatase >1200 IU were significantly shorter. Conclusions: Childhood height in preterm infants is strongly influenced by genetic factors. However, biochemical evidence of metabolic bone disease during the neonatal period may have a long-term stunting effect persisting up to 12 years later, providing support for current practices that aim to prevent this condition.