Natural History of Cow's Milk Protein Allergy in Preterm Infants: Insights from a Retrospective Cohort Study.

Introduction: Cow's milk protein allergy (CMPA) affects approximately 2-3% of healthy children. The natural history of CMPA is poorly described in preterm infants. The aim of the study was to determine disease characteristics and long-term natural history of CMPA in preterm infants.

Methods: This was a retrospective cohort study of Clalit Health Services (CHS) members (the largest of 4 integrated health care organizations in Israel). The medical records of children, who developed, as preterm infants, symptoms suggestive for CMPA during their hospitalization at the neonatal intensive care unit between June 2009 and June 2020 and subsequently were attending primary care clinics of the CHS in Northeastern Israel, were retrospectively reviewed for clinical manifestation and laboratory variables at disease onset and during follow-up.

Results: Among 141 preterm infants (mean gestational age 31 weeks, median follow-up 3.4 years), CMPA persistence was 16% at 1 year, 1.8% at 3 years, and 1.5% at 6 years. Atopic conditions developed at 39%, with asthma being most frequent (31%). Cesarean delivery was associated with higher risk of subsequent atopic disease (HR 1.22, p = 0.009).

Conclusions: CMPA in preterm infants is often resolved by 1 year. Accurate diagnosis and earlier reintroduction of cow milk protein may improve outcomes and reduce unnecessary interventions.