Asthma and lower airway disease
Prenatal determinants of neonatal lung function in high-risk newborns

https://doi.org/10.1016/j.jaci.2008.11.036Get rights and content

Background

Neonatal lung function is suspected to be associated with wheezy disorders, but little is known about risk factors for the early lung function.

Objectives

To study prenatal determinants of neonatal lung function.

Methods

This is a clinical, prospective birth cohort study of 411 newborns, the Copenhagen Prospective Study on Asthma in Childhood, in a single-center research clinic dedicated solely to this longitudinal birth cohort study. Lung function was determined at 1 month of age by infant spirometry (the raised volume rapid thoraco-abdominal compression technique) and bronchial responsiveness to methacholine by transcutaneous oxygen measurements.

Risk factor analyses included anthropometrics; demographics; socioeconomic factors; parental atopic history; previous deliveries; exposures during the third trimester to the mother's smoking, alcohol, and medicines; third trimester pregnancy complications including mother's asthma status; and mode of delivery.

Results

Lung function was determined in 404 neonates, age 6 weeks. Neonates with body mass index in the upper quartile had 14% lower baseline forced expiratory volume at 0.5 second, and neonates of mothers smoking during the third trimester had 7% lower baseline forced expiratory volume at 0.5 second. Sex or parental atopic disease did not affect the neonatal lung function and bronchial responsiveness. Maternal intake of paracetamol during the third trimester was associated with doubling of the bronchial responsiveness in the neonates, but the statistical significance may have been driven by outliers. Bronchial responsiveness exhibited a parabola development with tripling of bronchial responsiveness reaching the nadir at 3 months of age, but this needs replication in a study with repetitive measurements within individuals.

Conclusion

High body mass index in newborns and mothers smoking is associated with reduced neonatal lung function. This suggests that the association between body proportion and wheezing disorders may be a result of shared genes or prenatal nutrition.

Section snippets

Study design

The study was conducted in accordance with the guiding principles of the Declaration of Helsinki and approved by the Ethics Committee for Copenhagen (KF 01-289/96) and the Danish Data Protection Agency (2008-41-1754). Before enrollment, informed consent was obtained from both parents. Data validity and quality control procedures followed “Good Clinical Practice” guidelines. History was recorded online during visits to the COPSAC clinical research unit. Objective assessments were double-checked

Results

Lung function was analyzed in 404 of 411 infants. The median age was 6 weeks at the time of testing. Mean birth length was 52.3 cm and birth weight 3.52 kg. BMI at birth for girls was 12.84 ± 1.25 and for boys was 12.77 ± 1.37. The covariants analyzed together with univariate analyses of their estimated effect on the baseline FEV0.5 and PD15(PTcO2) are presented in Table E1.

Summary of principal findings

Baseline FEV0.5 was 14% lower in neonates with BMI in the upper quartile and 7% lower in neonates whose mothers reported smoking during pregnancy.

Maternal intake of paracetamol during the third trimester was associated with increased bronchial responsiveness (PD15[PtcO2] reduced) in the neonates, but the statistical significance may have been driven by outliers, as suggested from the lack of significance in the robustness test, taking such outliers into account.

Bronchial responsiveness

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    The Copenhagen Prospective Studies on Asthma in Childhood are supported by private and public research funds. Grants above 100.000 Euro were donated by the Lundbeck Foundation, the Pharmacy Foundation of 1991, the Augustinus Foundation, the Danish Medical Research Council, and the Danish Pediatric Asthma Center.

    Disclosure of potential conflict of interest: H. Bisgaard has been a consultant to, has been a paid lecturer for, and holds sponsored grants from Aerocrine, AstraZeneca, Altana, GlaxoSmithKline, Merck, MedImmune, NeoLab, and Pfizer. His employer, the Danish Pediatric Asthma Center, has received unrestricted institutional grants from Aerocrine, AstraZeneca, GlaxoSmithKline, Merck, and MedImmune and has provided legal consultation for NeoLab. The rest of the authors have declared that they have no conflict of interest.

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