Early Pubertal Maturation and Risk of Childhood Asthma: A Mendelian Randomization and Longitudinal Study

To explore the correlation, if any, between precocious puberty on the incidence of asthma and any combined effect of early puberty and being overweight.

The data were obtained using the Taiwan Children Health Study of children 11–17 years old (2991 children).

Parents, or patients themselves if they were 17 years old, completed a questionnaire to classify the child’s asthma. Staging of puberty was performed in 112 patients; 12-year-old children were assessed using a questionnaire and definitions were derived using the Tanner composite stage (TDCS). If a child met a certain pubertal stage earlier than the median age for that developmental stage, they were classified as having early pubertal maturation. To calculate the incidence of asthma, children with history of asthma prior to the age of 12 were excluded. Children were classified as overweight if their calculated BMI was ≥ 85th percentile. Using findings from a prior meta-analysis of genome wide association studies, 6 single nucleotide polymorphisms (SNPs) associated with early pubertal maturation were used for Mendelian randomization (MR) analysis. Longitudinal follow up survey was conducted at 17 years of age to assess for new onset asthma and the temporal relation to onset of puberty.

When evaluating both genders together, early pubertal maturation was associated with increased risk of asthma history, current wheeze, and active asthma. A statistically significant increased risk of active asthma in male adolescents was seen in those with early pubertal maturation (OR=1.38, 95% CI: 1.01–1.90). Furthermore, there was a statistically significant increased risk of new-onset physician diagnosed asthma (HR 1.57, 95% CI: 1.08–2.28) and incident current wheeze in the past 12 months (HR 2.15, 95% CI: 1.21–3.84) in children with early pubertal maturation. There was an increased risk of incident current wheeze in male adolescents with early puberty (HR 2.63, 95% CI: 1.27–5.34) and incident risk physician-diagnosed asthma in female adolescents with early puberty (HR 2.05, 95% CI: 1.10–3.82). Children who were defined as overweight and having early pubertal maturation had a statistically significant increased risk of physician-diagnosed asthma (OR 1.08, 95% CI: 1.04–1.11) and current wheeze (OR 1.04, 95% CI: 1.02–1.07).

There is a synergistic effect of early puberty and obesity on the development of asthma in both genders.

This study concluded that early pubertal maturation increases risk of asthma in male and female children with weight playing a synergistic role. This study highlights 3 commonly encountered conditions in the general pediatric practice: asthma, overweightness or obesity, and precocious puberty. Clinicians should consider screening for each condition when one of these is present.