Michael Davidovitch1,2, Jacob Kuint3,4, Liat Lerner-Geva4,5, Inna Zaslavsky-Paltiel5, Ran Shmuel Rotem3,6, Gabriel Chodick3,4, Varda Shalev3,4, Brian Reichman4,5. 1. Child Development, Medical Division, Maccabi Healthcare Services, Tel Aviv, Israel. davidom@netvision.net.il. 2. Maccabitech, Maccabi Healthcare Services, Tel Aviv, Israel. davidom@netvision.net.il. 3. Maccabitech, Maccabi Healthcare Services, Tel Aviv, Israel. 4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Women and Children's Health Research Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel. 6. Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND: This study evaluates the association between major neonatal morbidities and autism spectrum disorder (ASD) in children and adolescents born of very low birth weight (VLBW). METHODS: Historical cohort study using the Israel national VLBW infant database linked with the Maccabi Healthcare Services (MHS) medical records. The study cohort comprised 4963 VLBW subjects born from 1999 to 2012, >1 year of age. Multivariable logistic regression analyses were used to assess factors associated with ASD. RESULTS: The diagnosis of ASD was confirmed in 113 children (2.3%). Infants with major neonatal morbidities had higher rates of ASD; however, in the multivariable analyses these were not significantly associated with ASD: severe intraventricular hemorrhage (OR 1.21 [95% CI 0.60-2.45]), post-hemorrhagic hydrocephalus (OR 1.77 [0.73-4.29]), periventricular leukomalacia (OR 1.02 [0.42-2.51]), severe retinopathy of prematurity (OR 1.91 [0.995-3.67]), and bronchopulmonary dysplasia (OR 1.44 [0.84-2.45]). Postnatal steroid therapy when included separately was associated with an OR of 1.97 [1.18-3.29] for ASD. This association remained significant when postnatal steroid therapy was included with each of the neonatal morbidities (ORs ranging from 1.91 to 2.11). CONCLUSIONS: This study suggests a significant association between postnatal steroid therapy and ASD in VLBW infants. This possible association should be considered in future studies evaluating potential risk factors for ASD in preterm infants.
BACKGROUND: This study evaluates the association between major neonatal morbidities and autism spectrum disorder (ASD) in children and adolescents born of very low birth weight (VLBW). METHODS: Historical cohort study using the Israel national VLBW infant database linked with the Maccabi Healthcare Services (MHS) medical records. The study cohort comprised 4963 VLBW subjects born from 1999 to 2012, >1 year of age. Multivariable logistic regression analyses were used to assess factors associated with ASD. RESULTS: The diagnosis of ASD was confirmed in 113 children (2.3%). Infants with major neonatal morbidities had higher rates of ASD; however, in the multivariable analyses these were not significantly associated with ASD: severe intraventricular hemorrhage (OR 1.21 [95% CI 0.60-2.45]), post-hemorrhagic hydrocephalus (OR 1.77 [0.73-4.29]), periventricular leukomalacia (OR 1.02 [0.42-2.51]), severe retinopathy of prematurity (OR 1.91 [0.995-3.67]), and bronchopulmonary dysplasia (OR 1.44 [0.84-2.45]). Postnatal steroid therapy when included separately was associated with an OR of 1.97 [1.18-3.29] for ASD. This association remained significant when postnatal steroid therapy was included with each of the neonatal morbidities (ORs ranging from 1.91 to 2.11). CONCLUSIONS: This study suggests a significant association between postnatal steroid therapy and ASD in VLBW infants. This possible association should be considered in future studies evaluating potential risk factors for ASD in preterm infants.
Authors: Nelly Padilla; Eva Eklöf; Gustaf E Mårtensson; Sven Bölte; Hugo Lagercrantz; Ulrika Ådén Journal: Cereb Cortex Date: 2017-02-01 Impact factor: 5.357