Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children

Abstract

Background: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results.

Objectives: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years).

Methods: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes.

Results: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27).

Conclusion: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Keywords: Gestational age; asthma; children; cohort studies; epidemiology; infant growth; low birth weight; wheezing.

Fig E1

Fig E2

Fig 1

Associations of gestational age at birth, birth weight, and infant weight gain with preschool wheezing and school-age asthma. Values are ORs (95% CIs) from multilevel models for the associations of gestational age at birth (A and B), gestational age–adjusted birth weight (C and D), and gestational age–and birth weight–adjusted infant weight gain (E and F) with asthma outcomes. Models are adjusted for confounders (see the Methods section). Reference groups are represented by open circles.

Fig 2

Combined associations of gestational age at birth, birth weight, and infant weight gain with preschool wheezing and school-age asthma. Values are ORs (95% CIs) from multilevel models for the associations of gestational age at birth and birth weight SDSs (A and B), gestational age at birth and infant weight gain (C and D), and birth weight SDSs and infant weight gain (E and F) with asthma outcomes. Models are adjusted for confounders (see the Methods section). Reference groups are represented by a white bar. P values for gestational age*SD birth weight interactions are as follows: wheezing, .97; asthma, .04. P values for gestational age*weight gain interaction are as follows: wheezing, .05; asthma, .23. P values for birth weight SDS*weight gain interactions are as follows: wheezing, .15; asthma, .57. *P < .05, **P < .01, and ***P < .001.

Fig 3

Meta-analysis for associations of preterm birth and low birth weight with preschool wheezing and school-age asthma. A, Preterm birth and preschool wheezing. B, Preterm birth and school-age asthma. C, Low birth weight and preschool wheezing. D, Low birth weight and school-age asthma. Values from random-effects models reflect ORs (95% CIs) of preschool wheezing and school-age asthma in preterm children (<37 weeks) compared with those in children born at term (≥37 weeks) adjusted for birth weight (A and B) and of preschool wheezing and school-age asthma in low-birth-weight children (<2500 g) compared with children born with a normal birth weight (≥2500 g) adjusted for gestational age at birth (C and D). Arrows represent 95% CIs that exceed the outer limits (0.1-10). Models are adjusted for confounders (see the Methods section).

Fig 3

Meta-analysis for associations of preterm birth and low birth weight with preschool wheezing and school-age asthma. A, Preterm birth and preschool wheezing. B, Preterm birth and school-age asthma. C, Low birth weight and preschool wheezing. D, Low birth weight and school-age asthma. Values from random-effects models reflect ORs (95% CIs) of preschool wheezing and school-age asthma in preterm children (<37 weeks) compared with those in children born at term (≥37 weeks) adjusted for birth weight (A and B) and of preschool wheezing and school-age asthma in low-birth-weight children (<2500 g) compared with children born with a normal birth weight (≥2500 g) adjusted for gestational age at birth (C and D). Arrows represent 95% CIs that exceed the outer limits (0.1-10). Models are adjusted for confounders (see the Methods section).