Impact of mode of conception on neonatal and neurodevelopmental outcomes in preterm infants.

STUDY QUESTION: Is assisted conception associated with neonatal morbidity and mortality and with neurodevelopmental impairment at 2 years of corrected age in preterm infants born before 34 weeks of gestational age? SUMMARY ANSWER: Assisted conception is not associated with an increase in neonatal morbidity and mortality and is even significantly associated with a better 2-year neurodevelopmental outcome in preterm infants. WHAT IS KNOWN ALREADY: Assisted conception appears to increase the rate of preterm births, though few studies have analysed outcomes for these preterm infants. STUDY DESIGN, SIZE, DURATION: This prospective observational study included 703 preterm infants born between January 2009 and December 2013 and 573 of them were assessed at 2 years of corrected age. PARTICIPANTS/MATERIALS, SETTING, METHODS: All infants born alive between 24+0 and 33+6 weeks of gestational age and hospitalised at the Angers University Hospital were eligible as long as the mode of conception was known for neonatal outcome assessment. They were enroled in the Loire Infant Follow-up Team (LIFT) prospective longitudinal cohort and included for neurodevelopmental outcome assessment. Neonatal morbidity and mortality were evaluated during hospitalisation based on a composite score including death, intraventricular haemorrhage Grade ≥3, periventricular leukomalacia, treated patent ductus arteriosus and bronchopulmonary dysplasia at 36 weeks of gestational age. The neurodevelopmental outcome at 2 years of corrected age was determined by a physical examination, a neuropsychological test and a parental questionnaire. In order to ensure comparability, infants were matched 1:1 according to maternal age, twin status and propensity score,calculated from variables usually associated (positively or negatively) with assisted conception, including gestational age, z-score of birth weight, antenatal corticosteroids and magnesium sulphate treatments, gender, parity, maternal body mass index, tobacco consumption, outborn delivery (i.e. not at a tertiary-care medical centre) and maternal socio-economic status. MAIN RESULTS AND THE ROLE OF CHANCE: There were 703 preterm infants included in the analysis of neonatal morbidity and mortality, including 137 born after assisted conception. After matching, 184 preterm infants were included for neonatal morbidity and mortality analysis. There was no significant association between assisted conception and neonatal morbidity and mortality (aOR 0.67, 95% CI [0.25, 1.77], P = 0.422). 573 infants were assessed at 2 years, including 121 born after assisted conception. After matching, 154 preterm infants were included for neurodevelopmental outcome analysis. Assisted conception was significantly associated with a reduction in the probability of non-optimal neurological development at 2 years (aOR 0.26, 95% CI [0.09, 0.80], P = 0.019). LIMITATION, REASONS FOR CAUTION: Further studies remain necessary to fully confirm these results. This was a monocentric study and 14% of enroled infants were lost to follow up at 2 years of corrected age. WIDER IMPLICATIONS OF THE FINDINGS: These findings are relevant for providing appropriate information to parents considering assisted conception, and more importantly for those with a preterm infant following a pregnancy achieved by assisted conception. STUDY FUNDING/COMPETING INTEREST(S): The authors report external funding and no conflicts of interest for this work. TRIAL REGISTRATION NUMBER: N/A.

Neonatal and neurodevelopmental outcomes in preterm infants according to maternal body mass index: A prospective cohort study.

OBJECTIVE: Maternal obesity is associated with an increase in maternal, foetal and neonatal morbidity and mortality. The aim of our study was to evaluate the relationships between maternal pre-pregnancy body mass index and (1) neonatal outcome in preterm infants, and (2) neurodevelopmental outcome at 2 years of corrected age. METHOD: We conducted a single-centre cohort study. Infants born between 24+0 and 33+6 weeks of gestation between January 2009 and December 2013, hospitalised in the neonatal intensive care unit of Angers University Hospital, and with available data regarding maternal pre-pregnancy body mass index were eligible. Three groups were defined according to maternal body mass index: normal (n = 418), overweight (n = 136) and obese (n = 89). The primary outcome was neurodevelopment at 2 years of corrected age. Children with a non-optimal neuromotor and/or psychomotor assessment and/or a sensory disability were regarded as having a "non-optimal neurodevelopmental outcome". Neuromotor function was regarded as non-optimal when cerebral palsy was present or when the clinical examination revealed neurological signs of abnormal muscular tone. Psychomotor assessment was regarded as non-optimal if the revised Brunet-Lézine test was < 85 or when the overall score in the parental Ages and Stages Questionnaire (ASQ) was < 185. Finally, sensory disabilities such as blindness and children who required a hearing aid were taken into account. The secondary outcome was the composite criteria of neonatal complications. Multivariable analysis included the following variables: mother's age, gestational age, smoking during pregnancy, magnesium sulphate and steroid treatment during pregnancy, twin status, gender, socioeconomic status and social security benefits for those with low incomes. RESULTS: The study population was composed of 643 preterm infants. Among them, 520 were assessed at 2 years. There was no difference in the proportion of infants with non-optimal neurodevelopmental outcomes between the three groups (16.6% for obese, 13.5% for overweight, 16.9% for normal body mass index mothers; p = 0.73). According to multivariable analysis, being born from an overweight or obese mother was not associated with an increased risk of non-optimal neuro-development at 2 years (adjusted OR = 0.84 [0.40-1.76] for obese, adjusted OR = 0.83 [0.43-1.59] for overweight mothers). There was no difference in the proportion of preterm infants with a non-optimal composite criterion of neonatal complications between the three groups. In the multivariable analysis, being born from an overweight or obese mother was not associated with an increased risk of non-optimal neonatal outcomes (adjusted OR = 0.95 [0.49-1.83] for obese, adjusted OR = 1.18 [0.69-2.01] for overweight mothers). CONCLUSION: In this large prospective cohort of preterm infants born before 34 weeks of gestation, we found no relationship between maternal body mass index and neurodevelopmental outcomes at 2 years of corrected age and no relationship between maternal body mass index and neonatal outcomes. Other prematurity-related factors may be more relevant for neurodevelopmental outcome than the mother's pre-pregnancy BMI.