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Original Investigation |

Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden ONLINE FIRST

Fredrik Serenius, MD, PhD1,2; Uwe Ewald, MD, PhD1; Aijaz Farooqi, MD, PhD2; Vineta Fellman, MD, PhD3; Maria Hafström, MD, PhD4,5,6; Kerstin Hellgren, MD, PhD7; Karel Maršál, MD, PhD8; Andreas Ohlin, MD, PhD9; Elisabeth Olhager, MD, PhD10; Karin Stjernqvist, PhD11; Bo Strömberg, MD, PhD1; Ulrika Ådén, MD, PhD12; Karin Källén, PhD13 ; for the Extremely Preterm Infants in Sweden Study Group
[+] Author Affiliations
1Section for Pediatrics, Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
2Department of Pediatrics, Institute of Clinical Sciences, Umeå University, Umeå, Sweden
3Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden
4Department of Pediatrics, Institute of Clinical Sciences, The Queen Silvia Children’s Hospital, University of Gothenburg, Göteborg, Sweden
5Department of Paediatrics, St Olavs Hospital Trondheim, Trondheim, Norway
6Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology Trondheim, Trondheim, Norway
7Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
8Department of Obstetrics and Gynecology, Clinical Sciences Lund, Lund University, Lund, Sweden
9Department of Pediatrics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
10Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
11Department of Psychology, Lund University, Lund, Sweden
12Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
13Centre of Reproductive Epidemiology, Lund University, Lund, Sweden
JAMA Pediatr. Published online August 01, 2016. doi:10.1001/jamapediatrics.2016.1210
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Importance  Active perinatal care increases the rate of survival of extremely preterm infants, but there are concerns that improved survival might increase the rate of disabled survivors.

Objective  To determine the neurodevelopmental outcomes of a national cohort of children 6.5 years of age who had been born extremely preterm (<27 weeks’ gestational age) in Sweden.

Design, Setting, and Participants  Population-based prospective cohort study of consecutively born extremely preterm infants. All of these infants were born in Sweden during the period from April 1, 2004, to March 31, 2007. Of 707 live-born extremely preterm infants, 486 (68.7%) survived to 6.5 years of age. These children were assessed and compared with matched controls who had been born at term. Comparison estimates were adjusted for demographic differences. Assessments ended in February 2014, and analysis started thereafter.

Main Outcomes and Measures  Cognitive ability was measured with the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV), and the mean (SD) scores of the children who had been born extremely preterm were compared with those of the controls. Clinical examinations and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments, and cognition for the children who were not assessed with the WISC-IV.

Results  Of 486 eligible infants who were born extremely preterm, 441 (90.7%) were assessed at 6.5 years of age (59 by medical record review only) alongside 371 controls. The adjusted mean (SD) full-scale WISC-IV score was 14.2 (95% CI, 12.1-16.3) points lower for children who had been born extremely preterm than for controls. Cognitive disability was moderate for 18.8% of extremely preterm children and 2.2% of controls (P < .001), and it was severe for 11.1% of extremely preterm children and 0.3% of controls (P < .001). Cerebral palsy was observed in 9.5% of extremely preterm children and 0.0% of controls (P < .001), blindness was observed in 2.0% of extremely preterm children and 0.0% of controls (P < .001), and hearing impairment was observed in 2.1% of extremely preterm children and 0.5% of controls (P = .07). Overall, 36.1% (95% CI, 31.7%-40.6%) of extremely preterm children had no disability, 30.4% (95% CI 26.3%-34.8%) had mild disability, 20.2% (95% CI, 16.6%-24.2%) had moderate disability, and 13.4% (95% CI, 10.5%-16.9%) had severe disability. For extremely preterm children, moderate or severe overall disability decreased with gestational age at birth (adjusted odds ratio per week, 0.65 [95% CI, 0.54-0.79]; P < .001) and increased from 26.6% to 33.5% (P = .01) for children assessed both at 2.5 and 6.5 years.

Conclusions and Relevance  Of the 441 extremely preterm infants who had received active perinatal care, 293 (66.4%) had no or mild disability at 6.5 years; of the 371 controls, 11 (3.0%) had moderate or severe disability. Disability rates at 6.5 years increased relative to the rates at 2.5 years. Results are relevant for health care professionals and planners, and for clinicians counseling families facing extremely preterm births.

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