Mortality and major morbidities in very preterm infants born from assisted conception or naturally conceived: results of the area-based ACTION study

Background: The use of assisted conception (AC) has been associated with higher risk of adverse perinatal outcome. Few data are available on the outcome of AC-neonates when pregnancy ends before 32 weeks of gestational age. The aim of this study was to compare the short-term outcome of AC-and naturally conceived preterm infants <32 weeks gestation. Methods: The area-based cohort study ACTION collected data on births 22-31 weeks gestation occurred in 2003-05 in 6 Italian regions. Infants born to 2529 mothers with known mode of conception were studied. The main outcomes were hospital mortality and survival free from major morbidities (IVH grade 3-4, cPVL, ROP stage >= 3, BPD), and were assessed separately for single and multiple infants. Other outcomes were also investigated. Multivariable logistic analyses were used to adjust for maternal and infants' characteristics. To account for the correlation of observations within intensive care units, robust variance and standard error estimates of regression parameters were computed. Results: AC was used in 6.4% of mothers. Infants were 2934; 314 (10.7%) were born after AC. Multiples were 86.0% among AC and 21.7% among non-AC babies. In multivariable analysis no statistically significant difference in hospital mortality and survival without major morbidities was found between AC and non-AC infants. The risk of BPD was lower in AC than in non-AC multiples (aOR 0.41, CI 0.20-0.87), and this finding did not change after controlling for mechanical ventilation (aOR 0.42, CI 0.20-0.85) or presence of a patent ductus arteriosus (aOR 0.39, CI 0.18-0.84). Conclusion: When the analysis is restricted to very preterm infants and stratified by multiplicity, no significant associations between AC and increased risk of short-term mortality and survival without major morbidities emerge. This result is consistent with previous studies, and may confirm the hypothesis that the adverse effects of AC are mediated by preterm birth. However, larger appropriately powered studies are needed before definitely excluding the possibility of adverse events linked to AC in infants born before 32 weeks gestation.