Neurodevelopmental outcomes following two different treatment approaches (early ligation and selective ligation) for patent ductus arteriosus.

OBJECTIVE: To examine whether a change in the approach to managing persistent patent ductus arteriosus (PDA) from early ligation to selective ligation is associated with an increased risk of abnormal neurodevelopmental outcomes. STUDY DESIGN: In 2005, we changed our PDA treatment protocol for infants born at ≤27 6/7 weeks' gestation from an early ligation approach, with prompt PDA ligation if the ductus failed to close after indomethacin therapy (period 1: January 1999 to December 2004), to a selective ligation approach, with PDA ligation performed only if specific criteria were met (period 2: January 2005 to May 2009). All infants in both periods received prophylactic indomethacin. Multivariate analysis was used to compare the odds of a composite abnormal neurodevelopmental outcome (Bayley Mental Developmental Index or Cognitive Score <70, cerebral palsy, blindness, and/or deafness) associated with each treatment approach at age 18-36 months (n = 224). RESULTS: During period 1, 23% of the infants in follow-up failed indomethacin treatment, and all underwent surgical ligation. During period 2, 30% of infants failed indomethacin, and 66% underwent ligation after meeting prespecified criteria. Infants treated with the selective ligation strategy demonstrated fewer abnormal outcomes than those treated with the early ligation approach (OR, 0.07; P = .046). Infants who underwent ligation before 10 days of age had an increased incidence of abnormal neurodevelopmental outcome. The significant difference in outcomes between the 2 PDA treatment strategies could be accounted for in part by the earlier age of ligation during period 1. CONCLUSION: A selective ligation approach for PDAs that fail to close with indomethacin therapy is not associated with worse neurodevelopmental outcomes at age 18-36 months.

Cerebellar hemorrhage on magnetic resonance imaging in preterm newborns associated with abnormal neurologic outcome.

OBJECTIVE: To investigate the relationship between cerebellar hemorrhage in preterm infants seen on magnetic resonance imaging (MRI), but not on ultrasonography, and neurodevelopmental outcome. STUDY DESIGN: Images from a cohort study of MRI in preterm newborns were reviewed for cerebellar hemorrhage. The children were assessed at a mean age of 4.8 years with neurologic examination and developmental testing using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. RESULTS: Cerebellar hemorrhage was detected on both ultrasonography and MRI in 3 of the 131 preterm newborns evaluated, whereas smaller hemorrhages were seen only on MRI in 10 newborns (total incidence, 10%). Adjusting for gestational age at birth, intraventricular hemorrhage, and white matter injury, cerebellar hemorrhage detectable solely by MRI was associated with a 5-fold increased odds of abnormal neurologic examination compared with newborns without cerebellar hemorrhage (outcome data in 74%). No association with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition score was found. CONCLUSIONS: Cerebellar hemorrhage is not uncommon in preterm newborns. Although associated with neurologic abnormalities, hemorrhage seen only on MRI is associated with much more optimistic outcomes than that visible on ultrasonography.

Patent ductus arteriosus and its treatment as risk factors for neonatal and neurodevelopmental morbidity.

OBJECTIVES: The purpose of this work was to determine whether the reported association between neonatal morbidities and a patent ductus arteriosus is because of the left-to-right patent ductus arteriosus shunt itself, the therapies used to treat it, or the immaturity of the infants who are likely to develop a patent ductus arteriosus. METHODS: A total of 446 infants (<28 weeks' gestation) were treated with the same patent ductus arteriosus care-oriented protocol, and logistic regression analysis was used to examine the effects of several patent ductus arteriosus-related variables (presence of a symptomatic patent ductus arteriosus, the number of indomethacin doses used, the ductus response to indomethacin, and the use of surgical ligation) on the incidence of retinopathy of prematurity, necrotizing enterocolitis, chronic lung disease, death, and neurodevelopmental impairment. RESULTS: Most of the predictive effects that the presence of a patent ductus arteriosus and its treatment had on neonatal morbidity could be accounted for by the infants' immature gestation. Use of surgical ligation, however, was significantly associated with the development of chronic lung disease and was independent of immature gestation, other patent ductus arteriosus-related variables, or other perinatal and neonatal risk factors known to be associated with chronic lung disease. CONCLUSIONS: These findings add to the growing uncertainty about the benefits and risks of surgical ligation during the neonatal period.

Quality-of-care indicators for the neurodevelopmental follow-up of very low birth weight children: results of an expert panel process.

OBJECTIVE: To develop a set of quality indicators for the neurodevelopmental follow-up care of very low birth weight (VLBW; <1500 g) children. METHODS: We reviewed the scientific literature on predictors of neurodevelopmental outcomes for VLBW children and the clinical practice guidelines relevant to their care after hospital discharge. An expert panel with members nominated by the American Academy of Pediatrics, the National Institute of Child Health and Human Development, the Vermont Oxford Network, and the California Children's Service was convened. We used a modified Delphi method to evaluate and select the quality-of-care indicators. RESULTS: The panel recommended a total of 70 indicators in 5 postdischarge follow-up areas: general care; physical health; vision, hearing, speech, and language; developmental and behavioral assessment; and psychosocial issues. Of these, 58 (83%) indicators were in preventive care, 5 (7%) were in acute care, and 7 (10%) were in chronic care. CONCLUSION: The quality indicators cover follow-up care for VLBW infants with various medical conditions. Given the elevated rates of long-term neurodevelopmental disabilities and the potential impact of poor health care, this new set of indicators provides an opportunity to assess and monitor the quality of follow-up care with the ultimate aim of improving the quality of care for this high-risk population.

Effect of less frequent bathing on premature infant skin.

OBJECTIVE: To evaluate the effect of less frequent bathing on skin flora of premature infants. DESIGN: Randomized clinical trial comparing the impact of every other day bathing to every 4th day bathing on skin flora type and colony count. SETTING: University of California, San Francisco, Medical Center Level IV neonatal intensive-care unit. PARTICIPANTS: Fifty-three premature infants less than 37 weeks gestational age, 14 days or older, and receiving a bath. INTERVENTION: Premature infants were randomized to either every other day bathing (control group, n = 28) or every 4th day bathing (intervention group, n = 25). MAIN OUTCOME MEASURE: Skin flora type and colony count obtained weekly. RESULTS: Repeated-measures ANOVA was used to test the main effect of group, time, and Group x Time interaction. These factors were not statistically significant; group F(1,21) = 1.842, p = .189; time F(3,63) = 1.359, p = .263; Group x Time interaction F(3,63) = 0.753, p = .525. None of the infants developed an infection as a result of participating in the study protocol. CONCLUSION: Every 4th day bathing of premature infants appears to be safe.

Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome.

OBJECTIVE: To determine the neurodevelopmental outcome of prematurely born newborns with magnetic resonance imaging (MRI) abnormalities. STUDY DESIGN: A total of 89 prematurely born newborns (median age 28 weeks postgestation) were studied with MRI when stable for transport to MRI (median age, 32 weeks postgestation); 50 newborns were studied again near term age (median age, 37 weeks). Neurodevelopmental outcome was determined at 18 months adjusted age (median) using the Mental Development Index (Bayley Scales Infant Development II) and a standardized neurologic exam. RESULTS: Of 86 neonatal survivors, outcome was normal in 51 (59%), borderline in 22 (26%), and abnormal in 13 (15%). Moderate/severe MRI abnormalities were common on the first (37%) and second (32%) scans. Abnormal outcome was associated with increasing severity of white matter injury, ventriculomegaly, and intraventricular hemorrhage on MRI, as well as moderate/severe abnormalities on the first (relative risk [RR] = 5.6; P = .002) and second MRI studies (RR = 5.3; P = .03). Neuromotor abnormalities on neurologic examination near term age (RR = 6.5; P = .04) and postnatal infection (RR = 4.0; P = .01) also increased the risk for abnormal neurodevelopmental outcome. CONCLUSIONS: In premature newborns, brain abnormalities are common on MRI early in life and are associated with adverse neurodevelopmental outcome.

Survival of severe congenital diaphragmatic hernia has morbid consequences.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes. METHODS: At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression. RESULTS: Infants with TO were significantly more premature at birth (control vs TO, 37.4 +/- 1.0 vs 31.1 +/- 1.7 weeks; P < .01). Growth failure ( z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0). CONCLUSIONS: In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.

Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia.

OBJECTIVES: To determine if the incidence of sonographically detected cystic periventricular leukomalacia (PVL) and periventricular hemorrhagic infarction (PVHI) have changed over the past decade and to determine if a decline in cystic PVL was associated with a change in neurodevelopmental outcome. STUDY DESIGN: Premature newborn infants admitted to our intensive care nursery from 1992 to 2002 were identified in a comprehensive nursery database. Premature newborn infants had routine neurosonography by means of a standardized protocol. Infants weighing < or =1500 g at birth surviving to nursery discharge were enrolled in a nursery follow-up clinic. RESULTS: Adjusting for gestational age, there was a significant decrease in cystic PVL from 1992 to 2002 (P=.003) without a concurrent decrease in PVHI (P=0.5). Cystic PVL and PVHI accounted for only 9 of the 28 cases of cerebral palsy and 12 of 90 cases of abnormal Developmental Scores in infants weighing <1500 g at birth. The decline in cystic PVL was not associated with improved developmental outcome from 1992 to 2002. CONCLUSIONS: The incidence of cystic PVL declined significantly from 1992 to 2002 at our center. Cystic PVL was detected by ultrasound in a minority of infants with abnormal neurodevelopmental outcome, indicating that other forms of cerebral injury account for the majority of abnormal neurodevelopmental outcomes in premature newborn infants.

Neurodevelopmental outcome of infants supported with extracorporeal membrane oxygenation after cardiac surgery.

OBJECTIVES: To evaluate the long-term neurodevelopmental outcome of infants who underwent cardiac surgery and required extracorporeal membrane oxygenation (ECMO) support, and to examine variables that predict death or disability in these patients. METHODS: We studied all infants who had congenital heart disease and were supported postoperatively with ECMO from 1990 to 2001 at our institution (n = 53). Medical records were reviewed retrospectively to obtain clinical variables. Neurologic and age-appropriate developmental examinations occurred at ages 1, 1.5, 2.5, and 4.5 years. Median age at follow-up was 55 months (9-101). Cognitive outcome was defined as suspect when scores were between 1 and 2 SD below the mean for age and abnormal when scores were >2 SD below mean for age. Neuromotor outcome was defined as suspect when the patient manifested clumsiness, tremor, or mild tone and reflex changes without functional limitations, and abnormal when there were functional limitations. RESULTS: In-hospital survival was 17 (32%) of 53. Of survivors, 14 (88%) of 16 are living and 1 patient was lost to follow-up. Of the 53 patients, 7 survived completely intact (13%). Seven (50%) of 14 patients had a normal cognitive outcome, 3 (21%) had a suspect cognitive outcome, and 4 (29%) were abnormal. Ten (72%) of 14 patients had a normal neuromotor outcome, 1 (7%) patient had a suspect neuromotor outcome, and 3 (21%) were abnormal. No survivor with an aortic cross-clamp time >40 minutes had a normal cognitive outcome. Nonsurvivors were more likely than survivors to have had cardiac arrest as an indication for ECMO (31% vs 6%), to have had a longer aortic cross-clamp time (mean 73 minutes vs 32 minutes), and to have required continuous arteriovenous hemofiltration (78% vs 35%). The age and weight at cannulation, gender, cardiac diagnosis, interval from surgery to ECMO, cardiopulmonary bypass time, diagnosis of sepsis or mediastinitis, and duration of ECMO were not significantly associated with survival. CONCLUSIONS: Although mortality was 68% in infants who had congenital heart disease and were treated with ECMO postoperatively, of those who survive to hospital discharge, 75% have a normal neuromotor outcome and 50% have a normal cognitive outcome. These high rates of mortality and disability suggest that increased attention be paid to neuroprotection in these complex disorders.