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  • 1. Andersson, Ola
    et al.
    Lindquist, Barbro
    Lindgren, Magnus
    Stjernqvist, Karin
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hellstrom-Westas, Lena
    Effect of Delayed Cord Clamping on Neurodevelopment at 4 Years of Age: A Randomized Clinical Trial2015In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 169, no 7, p. 631-638Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayuci umbilical cord clamping (CC) prevents iron deficiency at 4 to 6 months of age, but long-term effects after 12 months of age have not been reported. OBJECTIVE To investigate the effects of delayed CC compared with early CC on neurodevelopment at 4 years of age. DESIGN, SETTING, AND PARTICIPANTS Follow-up of a randomized clinical trial conducted from April 16, 2008, through May 21, 2010, at a Swedish county hospital. Children who were included in the original study (n = 382) as full-term infants born after a low-risk pregnancy were invited to return for follow-up at 4 years of age. Wechsler Preschool and Primary Scale of Intelligence (WPPSI-111) and Movement Assessment Battery for Children (Movement ABC) scores (collected between April 18, 2012, and July 5, 2013) were assessed by a blinded psychologist. Between April 11, 2012, and August 13, 2013, parents recorded their child's development using the Ages and Stages Questionnaire, Third Edition (ASQ) and behavior using the Strengths and Difficulties Questionnaire. All data were analyzed by intention to treat. INTERVENTIONS Randomization to delayed CC (>= 180 seconds after delivery) or early CC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was full-scale IQ as assessed by the were development as assessed by the scales from the WPPSI-III and Movement ABC, development as recorded using the ASQ, and behavior using the Strengths and Difficulties Questionnaire. RESULTS We assessed 263 children (68.8%). No differences were found in WPPSI-III scores between groups. Delayed CC improved the adjusted mean differences (AMDs) in the ASQ personal-social (AMD, 2.8; 95% Cl, 0.8-4.7) and fine-motor (AMD, 2.1; 95% Cl, 0.2-4.0) domains and the Strengths and Difficulties Questionnaire prosocial subscale (AMD, 0.5; 95% Cl, >0.0-0.9). Fewer children in the delayed-CC group had results below the cutoff in the ASQ fine-motor domain (11.0% vs 3.7%; P =.02) and the Movement ABC bicycle-trail task (12.9% vs 3.8%; P =.02). Boys who received delayed CC had significantly higher AMDs in the WPPSI-III processing-speed quotient (AMD, 4.2; 95% Cl, 0.8-7.6; P =.02), Movement ABC bicycle-trail task (AMD, 0.8; 95% Cl, 0.1-1.5; P =.03), and fine-motor (AMD, 4.7; 95% Cl, 1.0-8.4; P =.01) and personal-social (AMD, 4.9; 95% Cl, 1.6-8.3; P =.004) domains of the ASQ. CONCLUSIONS AND RELEVANCE Delayed CC compared with early CC improved scores in the fine-motor at 4 years of age, especially in boys, indicating that optimizing the time to CC may affect neurodevelopment in a low-risk population of children born in a high-income country.

  • 2. Bolk, Jenny
    et al.
    Farooqi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hafstrom, Maria
    Aden, Ulrika
    Serenius, F.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Developmental Coordination Disorder and Its Association With Developmental Comorbidities at 6.5 Years in Apparently Healthy Children Born Extremely Preterm2018In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 172, no 8, p. 765-774Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE There are concerns that apparently healthy extremely preterm children face a risk of developing motor impairments, such as developmental coordination disorder. OBJECTIVE To evaluate the prevalence of developmental coordination disorder and associated comorbidities in a national cohort of apparently healthy children born at 22 to 26 gestational weeks, compared alongside term-born peers. DESIGN, SETTING, AND PARTICIPANTS This prospective, population-based cohort study included all children who were consecutively born at 22 to 26 gestational weeks in Sweden from April 1, 2004, through March 31, 2007. At 6.5 years, 441 preterm children were evaluated alongside 371 controls. A total of 275 preterm children (62.4%) and 359 term-born children (96.8%) did not have neurodevelopmental disabilities. Motor assessments were completed for 229 of 275 preterm children (83.3%) and 344 of 359 (95.8%) term-born children, who composed the final study sample. MAIN OUTCOMES AND MEASURES Developmental coordination disorder was defined as a score of the fifth percentile or lower on the Movement Assessment Battery for Children-Second Edition scale, using control group scores. Assessment tools included the Wechsler Intelligence Scale for Children-Fourth Edition, the Brown Attention-Deficit Disorder Scales, the Five to Fifteen questionnaire, and the Strengths and Difficulties questionnaire. RESULTS Of the 229 extremely preterm children and 344 term-born controls who underwent motor assessments, 115 (50.2%) and 194 (56.4%) were boys, respectively. Developmental coordination disorder was present in 85 of 229 (37.1%) preterm children and in 19 of 344 controls (5.5%) (adjusted odds ratio [OR], 7.92; 99% CI, 3.69-17.20). When preterm children with developmental coordination disorder were compared with term-born peers, the risk was increased for total behavioral problems, internalizing, externalizing, attentional problems, hyperactivity, perceptual problems, executive dysfunction, and poor social skills, with adjusted ORs varying from 2.66 (99% CI, 1.09-6.48) for time concepts to 9.06 (99% CI, 3.60-22.8) for attentional problems (all P < .01). When preterm children with and without developmental coordination disorder were compared, preterm children with developmental coordination disorder had more behavioral problems; the adjusted OR for total behavioral problems was 2.71 (99% CI, 1.15-6.37); for externalizing problems, 2.80 (99% CI, 1.10-7.12); for inattention, 3.38 (99% CI, 1.39-8.18); and for combined attention/hyperactivity problems, 3.68 (99% CI, 1.47-9.16) (all P < .01). Parents underestimated the children's motor problems and only a few of the children had received psychological care or physiotherapy. CONCLUSIONS AND RELEVANCE Children who were born extremely preterm faced a high risk for developmental coordination disorder with associated comorbidities. Our findings support the importance of a structured follow-up of motor function, behavior, and cognition. 

  • 3. Persson, Martina
    et al.
    Shah, Prakesh S.
    Rusconi, Franca
    Reichman, Brian
    Modi, Neena
    Kusuda, Satoshi
    Lehtonen, Liisa
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Yang, Junmin
    Isayama, Tetsuya
    Beltempo, Marc
    Lee, Shoo
    Norman, Mikael
    Association of Maternal Diabetes With Neonatal Outcomes of Very Preterm and Very Low-Birth-Weight Infants: an International Cohort Study2018In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 172, no 9, p. 867-875Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Diabetes in pregnancy is associated with a 2-times to 3-times higher rate of very preterm birth than in women without diabetes. Very preterm infants are at high risk of death and severe morbidity. The association of maternal diabetes with these risks is unclear.

    OBJECTIVE: To determine the associations between maternal diabetes and in-hospital mortality, as well as neonatal morbidity in very preterm infants with a birth weight of less than 1500 g.

    DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at 7 national networks in high-income countries that are part of the International Neonatal Network for Evaluating Outcomes in Neonates and used prospectively collected data on 76 360 very preterm, singleton infants without malformations born between January 1, 2007, and December 31, 2015, at 24 to 31 weeks' gestation with birth weights of less than 1500 g, 3280 (4.3%) of whom were born to diabetic mothers. EXPOSURES Any type of diabetes during pregnancy.

    MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality. The secondary outcomes were severe neonatal morbidities, including intraventricular hemorrhages of grade 3 to 4, cystic periventricular leukomalacia, retinopathy of prematurity needing treatment and bronchopulmonary dysplasia, and other morbidities, including respiratory distress, treated patent ductus arteriosus, and necrotizing enterocolitis. Odds ratios (ORs) with 95% confidence intervals were estimated, adjusted for potential confounders, and stratified by gestational age (GA), sex, and network.

    RESULTS: The mean (SD) birth weight of offspring born to mothers with diabetes was significantly higher at 1081 (262) g than in offspring born to mothers without diabetes (mean [SD] birth weight, 1027 [270] g). Of 76 360 infants, 25 962 (34%) and 33 598 (44%) were born before 28 weeks of gestation to mothers with and without diabetes, respectively. Mothers with diabetes were older and had more hypertensive disorders, antenatal steroid treatments, and deliveries by cesarean delivery than mothers without diabetes. Infants of mothers with diabetes were born at a later GA than infants of mothers without diabetes. In-hospital mortality (6.6% vs 8.3%) and the composite of mortality and severe morbidity (31.6% vs 40.6%) were lower in infants of mothers with diabetes. However, in adjusted analyses, no significant differences in in-hospital mortality (adjusted OR, 1.16 (95% CI, 0.97-1.39) or the composite of mortality and severe morbidity (adjusted OR, 0.99 (95% CI, 0.88-1.10) were observed. With few exceptions, outcomes of infants born to mothers with and without diabetes were similar regardless of infant sex, GA, or country of birth.

    CONCLUSIONS AND RELEVANCE: In high-resource settings, maternal diabetes is not associated with an increased risk of in-hospital mortality or severe morbidity in very preterm infants with a birth weight of fewer than 1500 g.

  • 4.
    Serenius, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Section for Pediatrics, Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Ewald, Uwe
    Farooqi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fellman, Vineta
    Hafstrom, Maria
    Hellgren, Kerstin
    Marsal, Karel
    Ohlin, Andreas
    Olhager, Elisabeth
    Stjernqvist, Karin
    Stromberg, Bo
    Aden, Ulrika
    Kallen, Karin
    Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden2016In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 170, no 10, p. 954-963Article in journal (Refereed)
    Abstract [en]

    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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