Early erythrocyte heterogeneity in very preterm infants conceived by in vitro fertilization: a multicenter study

Abstract Background To evaluate the association between in vitro fertilization (IVF) conception and early hematological indices reflecting erythrocyte heterogeneity and platelet characteristics in preterm infants, and to explore their relationship with morbidities. Methods This multicenter retrospective cohort study included preterm infants (< 34 weeks’ gestation, ≤ 2000 g). Red cell distribution width (RDW), mean platelet volume (MPV), platelet distribution width, RDW-to-platelet ratio, and platelet count obtained on admission were compared between IVF- and non-IVF-conceived infants. Multivariable linear regression analyses adjusted for gestational age, maternal preeclampsia, and plurality were used to identify independent associations with hematological indices. Multivariable logistic regression analysis assessed determinants of severe composite morbidity (Bronchopulmonary dysplasia, intraventricular hemorrhage grade III-IV, necrotizing enterocolitis stage ≥ 2, treatment-requiring retinopathy of prematurity). Results Among 453 infants, 17.7% were conceived by IVF. IVF-conceived infants had lower MPV and higher RDW in univariable analyses, while other platelet-related indices did not differ. After adjustment for gestational age, preeclampsia, and plurality, IVF conception remained independently associated with higher RDW (B = 0.95, 95% CI 0.36–1.54; p = 0.002). Retinopathy of prematurity and treatment-requirement were more frequent among IVF infants in unadjusted analyses, whereas severe composite morbidity was less frequent. In multivariable logistic regression, gestational age and prolonged rupture of membranes were the main determinants of morbidity; while RDW was not. Conclusions IVF conception is independently associated with higher early RDW values in preterm infants, indicating increased erythrocyte size heterogeneity at birth. Platelet-related indices were not independently associated with mode of conception. RDW was not associated with neonatal morbidity suggesting that this hematologic difference reflects variation in early neonatal hematologic characteristics rather than a predictor of adverse outcomes.