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.

Additional Value of 3-Month Cranial Magnetic Resonance Imaging in Infants with Neonatal Encephalopathy following Perinatal Asphyxia.

OBJECTIVE: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia. METHODS: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy. RESULTS: Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59. CONCLUSIONS: In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI.

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.

Clinical Practice Guidelines on the Treatment of Patients with Cleft Lip, Alveolus, and Palate: An Executive Summary.

Significant treatment variation exists in the Netherlands between teams treating patients with cleft lip, alveolus, and/or palate, resulting in a confusing and undesirable situation for patients, parents, and practitioners. Therefore, to optimize cleft care, clinical practice guidelines (CPGs) were developed. The aim of this report is to describe CPG development, share the main recommendations, and indicate knowledge gaps regarding cleft care. Together with patients and parents, a multidisciplinary working group of representatives from all relevant disciplines assisted by two experienced epidemiologists identified the topics to be addressed in the CPGs. Searching the Medline, Embase, and Cochrane Library databases identified 5157 articles, 60 of which remained after applying inclusion and exclusion criteria. We rated the quality of the evidence from moderate to very low. The working group formulated 71 recommendations regarding genetic testing, feeding, lip and palate closure, hearing, hypernasality, bone grafting, orthodontics, psychosocial guidance, dentistry, osteotomy versus distraction, and rhinoplasty. The final CPGs were obtained after review by all stakeholders and allow cleft teams to base their treatment on current knowledge. With high-quality evidence lacking, the need for additional high-quality studies has become apparent.

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.

Quality of Life and Patient Satisfaction in Adults Treated for a Cleft Lip and Palate: A Qualitative Analysis.

OBJECTIVE: Long-term outcomes of patients born with a cleft lip and palate (CLP) are scarcely investigated. Yet, this patient group is of particular interest, as they can provide a valuable retrospective view upon their treatment experiences and psychological adjustment. Qualitative accounts may be especially useful in understanding the patient journey. DESIGN: The present study set out to evaluate quality of life and satisfaction with treatment in adult patients previously treated for CLP at the Wilhelmina Children's Hospital. Semistructured interviews were performed. PATIENTS: A total of 22 patients aged 17 to 35 years (mean: 25 years) were interviewed about their experiences of growing up with CLP and of the treatment they received. Interviews were audio-recorded and factors thought to influence psychological adjustment were identified. RESULTS: Four main themes were identified: background factors, support systems, treatment factors, and coping/internal factors. Each theme was described with illustrative quotes. CONCLUSION: This study underlines that psychological adjustment can fluctuate over time and greatly differs between individuals, even during adulthood. Psychological support should therefore be available beyond the finalization of the treatment course. Furthermore, the majority of participants stated they had wanted more psychological support as a child to facilitate resilience and to help them cope with challenges.

Parental Attitude Toward the Prenatal Diagnosis of Oral Cleft: A Prospective Cohort Study.

OBJECTIVES: The prenatal diagnosis of oral clefts (OCs) by ultrasound can pose an ethical dilemma. The purpose of this study was to obtain insight into the psychosocial and moral considerations of prospective parents concerning OCs, the burden of OCs and parents' attitude toward possible termination of pregnancy (TOP) in order to improve counseling in the future. DESIGN: Between August 2011 and August 2014, a prospective cohort questionnaire study was administered. SETTING: Prenatal care clinic of the Wilhelmina's Children hospital, a Tertiary Care Centre. PARTICIPANTS: Parents expecting a child with an OC. MAIN OUTCOME MEASURES: Expectation of OCs in general and attitudes toward the impact and expected burden of the OC of their child. Furthermore, parents were asked if they had considered TOP. RESULTS: Most of the parents described an OC as a cosmetic disability (50.6%) or as "just a little different" (29.4%). These parents expected that the OC would not affect their own happiness and have only minor influence on the happiness of their future child. Health professionals had a considerable influence on parental opinion. A minority (6.4%, 5/85) of the respondents considered TOP, and none of the responders chose to terminate the pregnancy. CONCLUSIONS: This study suggests that future parents have very few negative perceptions of OC after prenatal counseling. Caregivers should be aware that their counseling is important for decision-making of parents.

Professional opinion on oral cleft during pregnancy: a comparison between Israel and The Netherlands.

OBJECTIVE: The aim of this study was to assess the opinion of obstetric care providers who perform prenatal ultrasounds to screen for anomalies and who advise women about their options, including termination of pregnancy, when an oral cleft is detected. We compared providers' opinions about pregnancy termination for isolated oral cleft in The Netherlands, where the number of terminations is low, and in Israel, where the number is high. METHODS: Online questionnaires were used. The questions assessed the providers' views regarding the estimated burden of treatment, the functioning ability, and the level of happiness of children with an oral cleft and their parents. Additionally, we assessed providers' opinions on pregnancy termination for isolated oral cleft. RESULTS: In The Netherlands, more professionals considered oral cleft a disability (rate differences 17.8%, 95% confidence interval: 0.5-33.1%) than in Israel. In the Netherlands, 10.6% of respondents (compared with 11.1% in Israel) thought that an isolated cleft was a reason for terminations of pregnancy (TOP) (rate differences 0.6%, 95% confidence interval: -12% to 10.9%). CONCLUSIONS: Prenatal care providers in The Netherlands and Israel do not differ in their opinions about the severity of oral cleft and the acceptability of TOP for an isolated oral cleft. This study shows that prenatal care providers' attitudes do therefore not explain the dramatic difference between these countries in the number of TOP for isolated oral cleft.

Behavioral phenotype in children with 22q11DS: agreement between parents and teachers.

Patients with the 22q11-deletion syndrome (22q11DS) are at an increased risk of developing schizophrenia. Besides the effects of genetic variation, environmental factors could also be important in modifying the risk of schizophrenia in 22q11DS patients. In particular, previous studies have shown the importance of stress as a precipitating factor of psychosis. An incongruence between the perceived and actual severity of behavioral and cognitive domains could lead caregivers, and even the children themselves, to make demands that are insufficiently adapted to the child's abilities, causing stress and anxiety. Here, we investigate whether such diagnostic discrepancies are indeed present by comparing parent and teacher reports on behavioral concerns in children with 22q11DS. Behavioral questionnaires (CBCL and TRF) were prepared for both parents and teachers of 146 children with 22q11DS. We found that in line with previous reports, internalizing behavior was more frequently reported than externalizing behavior. While the behavioral profiles reported by parents and teachers were remarkably similar, the teachers' ratings were significantly lower (Total problem score p = .002). Age and IQ were not significantly associated with the severity of reported concerns. Our results indicate that indeed a disparity often exists between parents' and teachers' perceptions of the severity of a child's behavioral deficits. This may result in (substantially) different demands and expectations being placed on the child from the two fronts. We speculate that the stress resulting from this lack of cohesion between parents and teachers could precipitate, at least in some 22q11DS children, the emergence of psychosis.

Cognitive and behavioral trajectories in 22q11DS from childhood into adolescence: a prospective 6-year follow-up study.

Patients with 22q11DS are at risk of behavioral problems and cognitive impairment. Recent studies suggest a possible intellectual decline in 22q11DS children. To date it is unknown if cognitive development is related to the behavioral problems in 22q11DS. We studied 53 children with 22q11DS who underwent cognitive and behavioral assessments at 9.5 years (T1) and 15.3 years (T2). In about one third, IQ data obtained at 7.5 years (T0) were also available. Results showed that internalizing behaviors intensified while externalizing behaviors decreased. Simultaneously, in about a third a significant decline in IQ was found, which, surprisingly, was unrelated to the behavioral changes. It can be concluded that children with 22q11DS follow a unique developmental trajectory. Cognitive deterioration is severe in some but does not appear to predict behavioral problems in early adolescence.

An investigation of the relationship between associated congenital malformations and the mental and psychomotor development of children with clefts.

OBJECTIVE: This research studied the relationship between associated congenital malformations and the mental and psychomotor development of children with clefts. DESIGN: The study was cross-sectional. SETTING: The study was conducted in a university hospital for children. PARTICIPANTS: The sample consisted of 148 children with cleft lip, cleft palate, or both. MAIN OUTCOME MEASURES: The children were assessed by a clinical geneticist at the age of 18 months. The children's level of development was determined by means of the Dutch version of the Bayley Scales of Infant Development. RESULTS: One-third of the total sample had associated malformations. Children with an isolated cleft lip showed the least. Children with an isolated cleft palate showed the highest percentage of minor malformations that are minor yet possibly worrisome. The total group achieved a mean developmental index (DI) on the mental scale of 98.9 with SD of 20.9. The motor scale showed a mean DI of 104.9 and SD of 24.7. Analysis of variance (ANOVA) showed that on the mental scale, the three main effects (diagnosis, evaluation, and sex) were significant at the 5% level. On the motor scale, only the main effect "evaluation" was significant. CONCLUSIONS: This study demonstrated that children with associated congenital malformations might be disadvantaged with respect to their development. These malformations occurred most frequently with the cleft lip and palate and cleft palate only subgroups. More research, especially concerning the cleft palate only subgroup is needed because they are most at risk.