Longitudinal developmental trajectories of weight-standardized lung function in preterm (28-36 + 6 weeks) vs. term...

To compare weight-normalized tidal lung function trajectories from corrected 40 weeks to 6 months postmenstrual age (PMA) between preterm infants (28-36 + 6 weeks gestation, including 23 infants born <32 weeks) and term infants (≥37 weeks); identify independent perinatal-neonatal risk factors disrupting early pulmonary maturation; and validate the predictive value of term-equivalent lung indices for composite respiratory morbidity in Chinese preterm infants.

This single-center prospective cohort enrolled 111 infants (75 preterm, 36 term) from 2020 to 2024. Standardized tidal spirometry was conducted at corrected 40 weeks, 3 and 6 months PMA following ATS/ERS guidelines; weight-normalized tidal volume (VT/kg) was designated as the primary endpoint to eliminate confounding derived from somatic growth differences. Linear mixed models (LMM) with random infant intercepts were used to model longitudinal pulmonary developmental changes. Multivariate linear and logistic regression analyses were fully adjusted for gestational age, birth weight, bronchopulmonary dysplasia (BPD), total ventilation duration, antenatal glucocorticoid exposure and small-for-gestational age (SGA) status. Sample size calculation confirmed ≥33 participants per group was required to detect a 0.7 mL/kg intergroup VT/kg difference with 80% power; both cohorts exceeded this threshold.

A total of 19/111 infants (17.1%) developed composite respiratory morbidity (physician-diagnosed pneumonia combined with recurrent wheezing ≥2 episodes) by 6 corrected months, with a significantly higher burden among preterm infants (16/75, 21.3%) relative to term infants (3/36, 8.3%, P = 0.049). At corrected 40 weeks PMA, preterm infants displayed impaired expiratory function (lower TPEF/TE, TEF50) and elevated resting respiratory rate (RR, all P < 0.05), while intergroup disparities in raw tidal volume disappeared entirely after weight normalization. Preterm infants exhibited partial compensatory lung catch-up growth: moderate and late preterm infants (32-36 + 6 weeks) achieved lung function comparable to term infants by 6 months PMA, whereas infants born <32 weeks maintained persistent deficits in VT/kg and TEF50 (P < 0.05). Fully adjusted regression identified advanced maternal age, neonatal positive-pressure resuscitation and low 5-min Apgar score as independent factors hindering early lung maturation. Gestational diabetes mellitus showed no independent correlation with VT/kg after weight normalization; its crude positive association with raw tidal volume was fully explained by fetal macrosomia. Higher VT/kg (OR = 0.74, 95%CI 0.55-0.95, P = 0.030), TEF75 (OR = 0.93, 95%CI 0.85-0.99, P = 0.048) and TEF50 (OR = 0.89, 95%CI 0.78-0.98, P = 0.030) at corrected 40 weeks independently reduced the odds of subsequent composite respiratory morbidity.

Birth before 32 weeks gestation leads to sustained weight-standardized pulmonary dysfunction at 6 corrected months despite partial compensatory lung development. Multiple modifiable antenatal and neonatal exposures regulate infant pulmonary maturation. Weight-standardized tidal indices measured at term-equivalent age serve as practical screening biomarkers for respiratory risk stratification among preterm infants, supporting standardized routine pulmonary monitoring in neonatal clinical practice.