Extra-uterine growth in preterm: an independent factor for neurological outcome.

Introduction: Extrauterine growth restriction(EUGR) is a common complication in preterm. Literature reports that EUGR is a risk factor for cerebral palsy and worse long-term neurological outcome. We report our experience of EUGR and neurological outcome in a large population of very low birth weight (VLBW) preterms without major lesions at MRI. Methods: we selected all VLBW patients born between 2012 and 2018 who perform an MRI study at term age. We exclude all patients with congenital malformations or major brain lesions (patients with low-grade IVH, punctate lesions, and micro-cerebellar hemorrhage were included). Neurological outcomes were evaluated with Griffiths II scale (GMDS II) at 2 and 3 years of age. Perinatal and neonatal risk factors such as gestational age (GA), born weight, Apgar, sepsis, NEC, bronchopulmonary dysplasia, and surgery were collected. Weight growth was evaluated at term age, 6 months, and 12 months of correct age. EUGR was defined as “cross-sectional” if the weight z-score was < 1,282 (<10° percentile) at TEA, 6 months, and 12 months; “longitudinal” EUGR was defined if the z-score decreased by 1-point SDS from birth to TEA and from TEA to 6 months .Multivariate analysis was done. Results: Of 498 VLBWs, 210 were excluded for severe brain lesions, congenital malformation, or incomplete data. Statistical analysis was performed in 288 patients (mean GA 28,9 + 2,1 weeks). “Cross-sectional” EUGR was found in 50% at term age, 46.2% at 6 months, 48,3% at 12 months while “longitudinal” EUGR was found in 43,8% at TEA and 16% at 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for global developmental quotient (DQ) at 2y of age (OR 0.74;CI 95% 0.59-0.93; p=0,01). In particular, “cross-sectional” EUGR at 6 months had a higher risk for worse locomotor (OR 1.96; CI 95% 1.10-3.47; p=0,02), language (OR 1,87; CI 95% 1,05-3,29 p=0,02) and adaptive behavior DQ (OR 1,94; CI 95% 1.12-3.37; p=0,02) at 2 years GMDS, and for worse language DQ (OR 1.63; 0.99-2.69 p 0,05) at 3 years of age. Furthermore, "longitudinal" EUGR from TEA to 6 months had a higher risk for worse performance DQ (OR 2,10;CI 95% 1,03-4,30; p=0,04) at 2 years and practical reasoning DQ (OR 2,07; CI 95% 1,02-4,17; p=0,04) at 3 years. NEC (OR 2,55; CI 95% 1.11-5.86; p= 0.03) and male sex (OR 1.94; CI 95% 1.16 - 3.24; p= 0,01) seems to be the major risk factors for lower global DQ at 3 years of age. Conclusion: EUGR has a high incidence in the preterm population. Both “cross-sectional” and “longitudinal” EUGR at 6 months of age seems to be an independent risk factor for worse GMDS in many areas. These results draw attention to nutrition after discharge and complementary feeding that can affect neurological outcome in preterm infants.