Hypoglycemia in Infants with Hypoxic-Ischemic Encephalopathy Is Associated with Additional Brain Injury and Worse Neurodevelopmental Outcome.

OBJECTIVE: To determine the incidence of hypoglycemia among infants with hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia, and to assess whether infants with hypoglycemia had more brain injury on magnetic resonance imaging (MRI) or differences in neurodevelopmental outcome. STUDY DESIGN: Single-center, retrospective cohort study including infants cooled for HIE. Hypoglycemia (blood glucose <36.0 mg/dL <2 hours and <46.8 mg/dL ≥2 hours after birth) was analyzed in the period before brain MRI. Brain injury was graded using a validated score. Motor and neurocognitive outcomes were assessed at 2 years for all survivors, and 5.5 years for a subset who had reached this age. RESULTS: Of 223 infants analyzed, 79 (35.4%) had hypoglycemia. MRI was performed in 187 infants. Infants with hypoglycemia (n = 65) had higher brain injury scores (P = .018). After adjustment for HIE severity, hypoglycemia remained associated with higher injury scores (3.6 points higher; 95% CI, 0.8-6.4). Hyperglycemia did not affect MRI scores. In survivors at 2 years (n = 154) and 5.5 years (n = 102), a univariable analysis showed lower 2-year motor scores and lower motor and cognitive scores at preschool age in infants with hypoglycemia. After adjustment for HIE severity, infants with hypoglycemia had 9 points lower IQs (P = .023) and higher odds of adverse outcomes at preschool age (3.6; 95% CI, 1.4-9.0). CONCLUSIONS: More than one-third of infants cooled for HIE had hypoglycemia. These infants had a higher degree of brain injury on MRI and lower cognitive function at preschool age. Strategies to avoid hypoglycemia should be optimized in this setting.

Perioperative neonatal brain injury is associated with worse school-age neurodevelopment in children with critical congenital heart disease.

AIM: To assess the impact of perioperative neonatal brain injury and brain volumes on neurodevelopment throughout school-age children with critical congenital heart disease (CHD). METHOD: Thirty-four survivors of neonatal cardiac surgery (seven females, 27 males) were included. Neonatal preoperative and postoperative cerebral magnetic resonance imaging was performed and neurodevelopment was assessed at 24 months (SD 0.7, n=32, using Bayley Score of Infant and Toddler Development, Child Behavior Checklist) and 6 years (mean age 5y 11mo; SD 0.3, n=30, using Movement Assessment Battery for Children, Wechsler Preschool and Primary Scale of Intelligence, Child Behavior Checklist, Teacher Report Form). Brain injury, brain volumes, and cortical measures were related to outcome with adjustment for maternal educational level. RESULTS: Two-year cognitive score and 6-year Full-scale IQ were poorer in children with neonatal white matter injury (n=21, all p<0.05), with higher teacher-reported attention problems (p=0.03). Five of six children with involvement of the posterior limb of the internal capsule showed motor problems (p=0.03). Children with a below-average Fulll-scale IQ (<85, n=9) showed smaller volumes of basal ganglia thalami (-8%, p=0.03) and brain stem (-7%, p=0.03). INTERPRETATION: Our findings provide evidence of unfavourable outcome in school-age children with critical CHD who acquire perioperative neonatal brain injury. WHAT THIS PAPER ADDS: This paper extends knowledge about neonatal brain injury and long-term outcome in congenital heart disease. Children with white matter injury show lower IQ and more attention problems at school age. Injury of the posterior limb of the internal capsule increases the risk of motor problems. This study provides evidence for worse outcomes in neonates acquiring brain injury around cardiac surgery.

Role of patent ductus arteriosus in preterms in long-term outcome.

OBJECTIVE: This study aimed to determine long-term neurodevelopmental outcome and cerebral oxygenation in extremely preterm infants, comparing those with a hemodynamic significant patent ductus arteriosus (hsPDA) to those without. STUDY DESIGN: We included infants born before 28 weeks of gestation from 2008 to 2010 with routine echocardiography. Prior to echocardiography, regional cerebral oxygen saturation was measured. At 5 years of age, we evaluated neurodevelopmental outcomes using the Movement Assessment Battery for Children 2nd Dutch edition for motor skills and the Wechsler Preschool and Primary Scale of Intelligence 3rd Dutch edition for cognition. RESULTS: A total of 66 infants (gestational age 26.6 ± 0.9 weeks, birth weight 912 ± 176 g) were included, 34 infants with a hsPDA (including treatment). The group infants with hsPDA showed lower pre-closure cerebral saturation levels (58.2 % ±7.8 % versus 62.8 % ±7.0 %; p = 0.01). At 5 years, impaired motor outcome occurred more often in infants with hsPDA (17 (53 %) vs. 7 (23 %); p = 0.01). In multivariate analysis existence of hsPDA remained unfavourably related to the motor subdomain "aiming and catching". There were no potential effects of hsPDA on cognitive performance at 5 years of age. CONCLUSION: Treatment-receiving infants with hsPDA appear to exhibit motor deficits, specifically in "aiming and catching", by the age 5. Persistent ductal patency could be a contributing factor.

Clinical course of asymmetric motor performance and deformational plagiocephaly in very preterm infants.

OBJECTIVES: To describe the clinical courses of positional preference and deformational plagiocephaly up to 6 months corrected age (CA) in infants born at gestational age <30 weeks or birth weight <1000 g, and to explore predictive factors for the persistence of these phenomena. STUDY DESIGN: A total of 120 infants were examined 3 times each. The presence of deformational plagiocephaly and a score of 0-6 on an asymmetry performance scale served as outcome measures at 6 months CA. Predictive factors were determined using regression analysis. RESULTS: The prevalence of a positional preference of the head was 65.8% (79 of 120) at term-equivalent age (TEA) and 36.7% (44 of 120) at 3 months CA and that of deformational plagiocephaly was 30% (36 of 120) at TEA and 50% (60 of 120) at 3 months CA. At 6 months CA, 15.8% of the infants (19 of 120) scored ≥ 2 of a possible 6 on the asymmetry performance scale and 23.3% (28 of 120) had deformational plagiocephaly. Sleeping in the supine position was predictive of an asymmetric motor performance at 6 months CA. Chronic lung disease and/or slow gross motor maturation at 3 months CA predicted the persistence of deformational plagiocephaly. CONCLUSION: Infants born very preterm may develop deformational plagiocephaly. A positional preference of the head at TEA seems to be a normal aspect of these infants' motor repertoire, with limited ability to predict persistence of an asymmetric motor performance. The decreased prevalence of deformational plagiocephaly between 3 and 6 months CA indicates an optimistic course. Infants with a history of chronic lung disease and/or slow gross motor maturation merit timely intervention.

Active head lifting from supine in early infancy: an indicator for non-optimal cognitive outcome in late infancy.

AIM: To explore whether active head lifting from supine (AHLS) in early infancy is associated with cognitive outcome in the second year of life. METHOD: The presence of AHLS was always recorded in the notes of infants admitted to our tertiary neonatal intensive care unit. Random sampling was used to pair infants with AHLS with two comparison infants without AHLS whose sex, gestational age, birth year (1993-2009), time of assessment, and developmental test (Griffiths Mental Development Scales, Mental Scale of the Bayley Scales of Infant Development-II, or cognitive subtest of the Bayley Scales of Infant and Toddler Development-III) were comparable. Brain injury identified from neonatal cranial ultrasound scans was classified as no - mild or moderate - severe. Z-scores of cognitive test outcomes were calculated for multivariable analysis. RESULTS: Eighty-seven preterm (34 males, 53 females) and 40 term (17 males, 23 females) infants with AHLS were identified. AHLS was documented at a mean (corrected) age of 7.0 (SD 1.7) and 8.1 (SD 2.2) months respectively. The cognitive assessments were performed at a mean corrected age of 15.7 (SD 1.7) and 23.9 (SD 1.6) months in preterm infants, and 19.1 (SD 2.3) months in term infants. The mean cognitive outcome of preterm and term infants with AHLS was lower than that of infants without AHLS (p=0.002 and p=0.004 respectively). This remained after excluding infants with cerebral palsy with matching comparison infants (p=0.001 in preterm and p=0.001 in term infants). The mean difference was highest (1.35SD) between term male infants and comparison infants (p=0.001). INTERPRETATION: AHLS is associated with a less favourable cognitive outcome in the second year of life in preterm as well as in term-born infants than in comparison infants.

Decreasing incidence and severity of cerebral palsy in prematurely born children.

OBJECTIVE: To examine incidence and severity of cerebral palsy (CP), and associated factors among preterm survivors (gestational age <34 weeks), admitted to a neonatal intensive care unit from 1990-2005. STUDY DESIGN: Eighteen antenatal, perinatal and postnatal factors were analyzed. The cohort was divided in four birth periods: 1990-1993 (n=661), 1994-1997 (n=726), 1998-2001 (n=723), and 2002-2005 (n=850). The Gross Motor Function Classification System was used as primary outcome measure (mean age: 32.9 ± 5.3 months). Logistic regression analyses were used. RESULTS: CP incidence decreased from 6.5% in period I, to 2.6%, 2.9% and 2.2% (P<.001) in period II-IV, respectively. Simultaneously, cystic periventricular leukomalacia (c-PVL) decreased from 3.3% in period I to 1.3% in period IV (P=.004). Within the total cohort (n=3287), c-PVL grade III decreased from 2.3% in period I to 0.2% in period IV (P=.003). The number of children with Gross Motor Function Classification System levels III-V decreased from period I to IV (P=.035). Independent risk factors for CP were c-PVL and severe intraventricular hemorrhage, whereas antenatal antibiotics, presence of an arterial line, Caesarean section, and gestational age were independent protective factors. CONCLUSION: CP incidence and severity decreased from 1990-1993 onward, which could be attributed to a reduction of 93% in severe c-PVL.

Nutritional Intake, White Matter Integrity, and Neurodevelopment in Extremely Preterm Born Infants.

BACKGROUND: Determining optimal nutritional regimens in extremely preterm infants remains challenging. This study aimed to evaluate the effect of a new nutritional regimen and individual macronutrient intake on white matter integrity and neurodevelopmental outcome. METHODS: Two retrospective cohorts of extremely preterm infants (gestational age < 28 weeks) were included. Cohort B (n = 79) received a new nutritional regimen, with more rapidly increased, higher protein intake compared to cohort A (n = 99). Individual protein, lipid, and caloric intakes were calculated for the first 28 postnatal days. Diffusion tensor imaging was performed at term-equivalent age, and cognitive and motor development were evaluated at 2 years corrected age (CA) (Bayley-III-NL) and 5.9 years chronological age (WPPSI-III-NL, MABC-2-NL). RESULTS: Compared to cohort A, infants in cohort B had significantly higher protein intake (3.4 g/kg/day vs. 2.7 g/kg/day) and higher fractional anisotropy (FA) in several white matter tracts but lower motor scores at 2 years CA (mean (SD) 103 (12) vs. 109 (12)). Higher protein intake was associated with higher FA and lower motor scores at 2 years CA (B = -6.7, p = 0.001). However, motor scores at 2 years CA were still within the normal range and differences were not sustained at 5.9 years. There were no significant associations with lipid or caloric intake. CONCLUSION: In extremely preterm born infants, postnatal protein intake seems important for white matter development but does not necessarily improve long-term cognitive and motor development.

Prediction of gross motor development and independent walking in infants born very preterm using the Test of Infant Motor Performance and the Alberta Infant Motor Scale.

BACKGROUND: One objective of a neonatal follow-up program is to examine and predict gross motor outcome of infants born preterm. AIMS: To assess the concurrent validity of the Test of Infant Motor Performance (TIMP) and the Alberta Infant Motor Scale (AIMS), the ability to predict gross motor outcome around 15 months corrected age (CA), and to explore factors associated with the age of independent walking. METHODS: 95 infants, born at a gestational age <30 weeks, were assessed around 3, 6 and 15 months CA. At 3 months CA, correlations of raw-scores, Z-scores, and diagnostic agreement between TIMP and AIMS were determined. AIMS-score at 15 months CA and parental-reported walking age were outcome measures for regression analyses. RESULTS: The correlation between TIMP and AIMS raw-scores was 0.82, and between Z-scores 0.71. A cut-off Z-score of -1.0 on the TIMP had 92% diagnostic agreement (κ = 0.67) with an AIMS-score < P10. Neither TIMP- nor AIMS-scores at 3 months CA were associated with the gross motor outcome at 15 months CA. The AIMS-scores at 6 months CA predicted the AIMS-scores at 15 months CA with an explained variance of 19%. Median walking age was 15.7 months CA, with which only the hazard ratio of the AIMS at 6 months CA and ethnicity were significantly associated. CONCLUSIONS: Prediction of gross motor development at 15 months CA and independent walking was not possible prior to 6 months CA using the AIMS, with restricted predictive value. Cultural and infant factors seem to influence the onset of independent walking.

Prevalence and predictors of idiopathic asymmetry in infants born preterm.

BACKGROUND: An idiopathic asymmetry in posture of the head is recognized as a risk factor to develop a deformational plagiocephaly (DP). In our neonatal follow-up clinic, an IA is often observed in infants born preterm at term-equivalent age (TEA). AIMS: To explore (1) the prevalence of an idiopathic asymmetry in 192 infants (gestational age ≤32.0 weeks) at TEA and 6 months corrected age (CA), (2) whether demographical, perinatal, and medical factors were predictors of the asymmetry, and (3) differences in motor maturation between infants with and without asymmetry. METHODS: In a retrospective study, frequencies of idiopathic asymmetry and DP, putative predictors, and Alberta Infant Motor Scale scores at 6 months CA were abstracted and analyzed with Chi(2), Mann-Whitney, logistic regression and T-test. RESULTS: The prevalence rate of a positional preference of the head at TEA was 44.8% (n=86), 10.4% (20/192) had a DP at TEA and 13% (25/192) at 6 months CA. Positional preference, multiple birth and male gender predicted the presence of DP (p<.05, odds ratio 3.0, 3.2, and 3.1 respectively). Gross motor maturity at 6 months CA was less developed in infants with a positional preference at TEA compared to preterm norms (p=0.01). CONCLUSIONS: The high prevalence of a positional preference in infants born preterm at term equivalent age requires extra alertness to prevent the development of a deformational plagiocephaly, especially in boys and twins. Although, considering the lower prevalence of plagiocephaly at 6 months CA, therapists should be aware of over treating these infants.