Neurodevelopmental Outcome Of Infants Research Articles

Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program

Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program

Clinical trials with thyroid hormone supplementation in preterm infants with transient hypothyroidism

The morbidity of transient hypothyroxinemia of prematurity （THOP） was high. There is controversial about thyroid hormone supplementation in THOP. Clinical studies suggest that thyroid hormone supplementation can reduce the incidence of patent ductus arteriosus,but no effect on the mortality and the incidence of respiratory disease. Thyroid hormone supplementation can improve the neurodevelopmental outcomes in infants with gestational age less than 28 weeks with THOP, but no effect on infants with gestational age more than 28 weeks. Future research should focus on the normal range of thyroid hormone according to gestational age in preterm infarlts, and randomized clinical trial well- designed stratified according to gestational age to study the long-term neurodevelopmental outcome of thyroid hormone replacement therapy in infants with THOP . Key words: Preterm; Transient hypothyroxinemia of prenmturity

1035 The Role of Hyperglycemia on Neurodevelopmental Outcome in Infants Operated for Congenital Heart Disease with Open-Heart Surgery

Background: It is unclear whether hyperglycemia after infant cardiac surgery adversely affects neurodevelopmental outcome.Methods: Secondary analysis of a prospective cohort study on neurodevelopmental outcome after infant cardiac surgery. Exclusion criteria were: older than one year of age at first surgery, genetic disorders or dysmorphic syndromes and birth weight < 2000 grams and postoperative death. Of 368 children, 172 met inclusion criteria. Ten children did not yet return for the one year follow up examination and two were lost to follow-up. Follow-up examination at four years was available for 56 children, the remaining children were too young. Postoperative highest and lowest glucose levels within 24 hours after bypass surgery were prospectively collected. Neurodevelopmental outcome at one year of age was assessed with the Bayley Scales of Infant Development II (Mental Developmental Index-MDI, Psychomotor Developmental Index-PDI) in 160 children and at four years with the WPPSI.Results: Mean age at surgery was 2.9 months (0.1-10.7 months). Mean highest postoperative glucose values were 12.76 (SD 4.9), mean lowest were 6.82 (SD 1.9). Glucose values normalized in all children within 48 hours, seven children (4%) received insulin infusions. Postoperative highest and lowest glucose levels were not associated with neurodevelopmental outcome at one year or at four years, whereas more abnormal preoperative neurological findings were associated with poorer one-year outcome (MDI p< 0.001, PDI=0.03).Conclusion: In our population glucose values normalized within 48 hours and had no adverse effect on neurodevelopmental outcome.

Early Neurodevelopmental Outcomes of Infants with Congenital Heart Disease

Early Neurodevelopmental Outcomes of Infants with Congenital Heart Disease

Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program

Purpose The purpose of the study was to evaluate the neurodevelopmental outcome in infants with congenital diaphragmatic hernia (CDH). Methods Between June 2004 and September 2007, 41 CDH survivors were prospectively enrolled in an interdisciplinary follow-up program. Neurodevelopmental status was evaluated using the Bayley Scales of Infant Development II (prior 2006, n = 9), the Bayley Scales of Infant Development III (after 2006, n = 27), or the Wechsler Preschool and Primary Scale of Intelligence III (children older than 4 years, n = 5). Scores were grouped as average, mildly delayed, and severely delayed by standard deviation intervals (115-85, 71-84, <70), and mixed if average and mildly delayed in either cognitive or language. Results Median age at last assessment was 24 months (range, 6-62). Average, mixed, mildly delayed, and severely delayed scores for neurocognitive and language skills were found in 49%, 19%, 17%, and 15%, respectively. Psychomotor scores were normal, mildly delayed, and severely delayed in 46%, 23%, and 31%, respectively. Autism was present in 7%. Abnormal muscle tonicity was found in 51% (49% hypotonic, 2% hypertonic). Multivariate risk factors for borderline or delayed neurodevelopmental, neurocognitive, and/or psychomotor outcome were intrathoracic liver position ( P = .02), presence of a right-sided CDH ( P = .02), extracorporeal membrane oxygenation need ( P < .001), Gore-Tex patch repair ( P = .02), O 2 requirement at 30 days of life ( P < .01), and hypotonicity ( P < .01). Conclusions The prospective evaluation in an interdisciplinary follow-up program uncovered striking morbidities in neurodevelopmental status in approximately half of the CDH infants. The most common neurologic sequelae are neuromuscular hypotonicity and psychomotor dysfunction. Patient-specific factors are important determinants of adverse neurologic outcome.

Abcès cérébraux multiples à Enterobacter cloacae chez un prématuré. Intérêt de la ciprofloxacine

A neonatal infection with Enterobacter cloacae was diagnosed at day 21 in a premature infant. Five cerebral abscesses were discovered 6 days while a treatment with cefotaxim and amikacin was administered. We switched for axepim during 4 weeks and ciprofloxacin until complete regression of cerebral abscesses. At 13 months of age, the infant neurodevelopmental outcome was normal. Ciprofloxacin indications and tolerance during neonatal period are discussed.

Echocardiography predicts closure of patent ductus arteriosus in response to ibuprofen in infants less than 28 week gestational age

Background Patent ductus arteriosus (PDA) is a frequent problem in preterm infants, and its incidence is inversely correlated with gestational age. The efficacy of medical treatment decreases with decreasing gestational age (GA), and failure rates as well as ductus ligation rates of 40% have been reported in < 28 week GA newborns. The aim of this study was to determine whether echocardiographic parameters can predict response to ibuprofen treatment of PDA. Study design In a longitudinal study, 29 infants born < 28 week GA were screened for a significant PDA (left atrial to aortic root ratio > 1.4, anterior cerebral artery resistance index > 0.8, and oxygen requirement > 35%) at 24–72 h of life and, if a PDA was found, treated with 10–5–5 mg/kg ibuprofen intravenously every 24 h. Ductal parameters were monitored by serial echocardiography. Infant neurodevelopmental outcomes were assessed at 24 month corrected age. Results All 15 infants with significant PDA responded to the ibuprofen loading dose indicated by reduced PDA diameters or increased PDA maximum flow velocities (PDA V max), and 7 patients showed an ongoing response resulting in a closed PDA after the 1st cycle (47%). Of the 8 non-responders, 7 received a 2nd cycle with 2 further responders (29%). All non-responders to the 2nd course had a PDA V max ≤ 180 cm/s and increasing ductal diameters after the 3rd ibuprofen dose of the 1st course. Conclusion Maximum flow velocity and diameter of the PDA at the end of the 1st cycle discriminate between responders and non-responders to further ibuprofen treatment.

Neurodevelopmental Outcome of Premature Infants After Exposure to Antenatal Indomethacin

Objective This study was undertaken to evaluate the effect of antenatal indomethacin exposure on neurodevelopmental outcomes of premature infants. Study Design A retrospective cohort study was performed to compare neurodevelopmental outcomes between premature infants exposed to antenatal indomethacin and infants unexposed to antenatal indomethacin. Inclusion criteria included all 23-29 weeks' gestational age infants delivered between January 1998 and December 2002 who had neurodevelopmental evaluation performed at 16-24 months corrected age. Outborn infants and those with major congenital malformations or chromosomal problems were excluded. Continuous and categorical variables were analyzed by using t test and χ 2 test, respectively. Results A total of 255, 23-29 weeks' gestational age infants were delivered between January 1998 and December 2002. Of the 87 infants who met inclusion criteria, 29 infants were exposed to antenatal indomethacin (mean dose 267 mg and median duration 3 days) and 58 infants were unexposed to antenatal indomethacin. There were no significant differences between the 2 groups in clinical characteristics, except for gestational age, mode of delivery, and antenatal steroid exposure. There was no significant difference in major neurosensory abnormality (cerebral palsy and/or deafness and/or blindness); however, the proportion of infants with subnormal Bayley-Mental Developmental Index (70 or less) and neurodevelopmental impairment (neurosensory abnormality and/or Mental Developmental Index 70 or less) was significantly less in the group exposed to antenatal indomethacin compared with unexposed group. When controlled for confounders including antenatal steroids, antenatal indomethacin was not associated with Mental Developmental Index 70 or less (odds ratio 0.44, 95% confidence interval 0.12-1.5) and neurodevelopmental impairment (odds ratio 0.4, 95% confidence interval 0.13-1.2) by using logistic regression. Subgroup analysis of 12 infants exposed to antenatal indomethacin within 48 hours of birth was not associated with neurodevelopmental impairment (odds ratio 0.2, 95% confidence interval 0.03-1.02) compared with unexposed group. Conclusion Antenatal indomethacin is not associated with abnormal neurodevelopmental outcome in infants 29 or less weeks' gestational age.

Association between iron status and neurodevelopmental outcomes among VLBW infants

Objective: Our purpose was to evaluate iron status and neurodevelopmental outcomes in infants with and without extrauterine growth restriction (EUGR). Methods: This observational study evaluated 38 medically stable premature infants, with birth weights below 1500 g. Iron status was determined by measuring venous levels of Hb, Fe, and serum ferritin. The infants were divided into EUGR and non-EUGR groups. At a corrected age of 18 months, neurodevelopmental outcomes were checked using the Bayley scales, and body weight, body length, and head circumference were measured. Results: Hb levels at corrected ages of 1 and 3 months and iron at a corrected age of 1 and 9 months were significantly lower in the EUGR group compared with those of the non-EUGR group. There was no significant difference in the MDI score between the groups, but the PDI score at a corrected age of 18 months was significantly lower in the EUGR group. We found a positive correlation between the serum level of Fe at 1 month of age and PDI score at 18 months of age. Head circumference at a corrected age of 18 months did not differ between two groups, although body weight and length were lower in the EUGR group. Conclusions: Developmental outcome in preterm infants at a corrected age of 18 months may be influenced by nutritional factors, including iron status, during their early life.

Prospective, interdisciplinary follow-up of children with prenatally diagnosed giant omphalocele: short-term neurodevelopmental outcome

Purpose The objective of this study is to determine the short-term neurodevelopmental outcome in infants with giant omphalocele (GO). Materials and Methods Between January 2002 and December 2007, 31 consecutive infants with GO received prenatal and postnatal care at our institution. Overall survival was 81% (25/31). Twenty (80%) of the survivors were enrolled in a prospective interdisciplinary follow-up program. Fifteen were at least 6 months of age and received detailed neurodevelopmental evaluation using the Bayley Scales of Infant Development II (BSID-II [before 2006, n = 3]) or BSID-III (after 2006, n = 12). Scores were grouped as average, mildly delayed, and severely delayed by SD intervals (115-85, 71-84, <70). Scores were considered mixed if cognitive or language skills were in different ranges. Results Median age at evaluation was 12 months (range, 6-26 months). Average, mildly delayed, and severely delayed scores for cognitive and language skills were found in 6 (40%), 2 (13%), and 6 (40%), respectively. One child had mixed scores (severely delayed for cognitive and mildly delayed for language skills). Motor scores were normal, mildly delayed, and severely delayed in 6 (40%), 2 (13%), and 7 (47%), respectively. The neuromuscular examination was abnormal in 8 patients (62%). Five (33%) scored within the average range, whereas 6 (40%) demonstrated severe delays for cognitive, language, and motor outcome. Of the 6 children with severe delays, 2 (13% of total) have autism, 4 required tracheostomy, and 1 was diagnosed with Williams syndrome. Conclusions The presence of GO is associated with deficits in developmental achievements in most of the affected infants ranging from mild to profound delays. These findings underscore the importance of early and standardized neurodevelopmental evaluation throughout childhood for all survivors with GO. Larger studies are warranted for risk factor stratification.

Determinants of body weight gain and association with neurodevelopmental outcome in infants operated for congenital heart disease☆

The aim of this prospective study was to examine the determinants of growth failure and the association with neurodevelopmental outcome in infants undergoing open-heart surgery. In 107 infants undergoing open-heart surgery for congenital heart disease (CHD), we evaluated weight at birth, at surgery, and at one year of age (expressed as z-scores). Neurodevelopmental status was assessed before surgery and at one year of age. Median age at surgery was 3.9 months (range: 0.1-10.2). Mean [+/-standard deviation (S.D.)] weight z-score at birth was -0.27 (+/-1.45), before surgery -1.34 (+/-1.45) (P<0.001 vs. birth weight), and at one year -0.86 (+/-1.35), (P<0.001 vs. weight at surgery). Poor preoperative weight (<10th percentile) was associated with genetic disorders [odds ratio (OR) 5.9, P<0.001], preoperative neurological abnormalities (OR 3.41, P<0.05), and older age at surgery (OR 1.01, P<0.05). Weight <10th percentile at one year was associated with the same factors as poor preoperative weight, however, also with risk adjustment for congenital heart surgery-1 (RACHS) score >3 (OR 3.22, P<0.05). Neurodevelopmental outcome at one year was not determined by growth failure. In conclusion, impaired body weight gain before surgery is followed by a catch-up growth after surgery. However, there is no relationship to neurodevelopmental outcome. Genetic comorbidity is the most significant factor for poor weight gain.

Neurodevelopmental Outcomes in Infants after Surgery for Congenital Heart Disease: A Comparison of Single-Ventricle vs. Two-Ventricle Physiology

The neurodevelopmental outcome of children with repaired congenital heart defect has risen in importance with improved survival. This study compares neurodevelopmental outcomes of children who had CHD with single ventricle physiology with those who had CHD with two-ventricle physiology. Participants included 112 infants discharged from the NICU between February 1999 to August 2006. The 12 infants who had a known genetic defect were excluded. Of the 100 infants 26 had single ventricle physiology and 74 had CHD with two-ventricle physiology. The children were seen in a follow-up clinic and growth parameters and standardized instruments were used to evaluate development. The referral rate to early intervention services was also compared. The number of functional ventricles did not significantly differentiate growth parameters at 6-8 months of age. Early cognitive outcomes were relatively unimpaired in both the groups (single ventricle vs. two ventricle physiology). Early motor outcomes were worse in (p < 0.05) CHD with single ventricle physiology. The rate of referral for early intervention services was high in both groups compared to the average rate of referral in the state, but there was not a significant difference between the CHD groups. Significant differences noted on motor outcomes at the 6-8 month visit were no longer apparent in later visits. Referral to early intervention services is high in both the groups. These findings are important to those caring for infants with CHD because many of these patients may need referral for early intervention.

Maternal anxiety is related to infant neurological condition, paternal anxiety is not

Background Parental anxiety and stress may have consequences for infant neurological development. Aims To study relationships between parental anxiety or well-being and infant neurological development approximately one year after birth. Study design Longitudinal study of a birth cohort of infants born to subfertile couples. Subjects: 206 parent–child dyads. Outcome measures Infant neurology was assessed with the Touwen Infant Neurological Examination (TINE) at 10 months and a developmental questionnaire at 12 months. Parental measures included trait anxiety measured by the State-Trait Anxiety Inventory (STAI) and well-being measured by the General Health Questionnaire (GHQ). Results Maternal trait anxiety was associated with a less optimal neurological condition ( r s = − 0.19, p < 0.01) of the infant. This association persisted after adjusting for confounders and results were confirmed by the outcome of the developmental questionnaire. Paternal trait anxiety and parental well-being were not related to the infant's neurodevelopmental outcome. Conclusions Infants of mothers with high trait anxiety have an increased vulnerability to develop a non-optimal nervous system. The association may be mediated in part by early programming of monoaminergic systems. Future research should include an exploration of specific windows of vulnerability to maternal anxiety.

Partial exchange transfusion to prevent neurodevelopmental disability in infants with polycythemia

Hyperviscosity of blood results in increased resistance to blood flow and decreased oxygen delivery. In the neonate, hyperviscosity can cause abnormalities of central nervous system function, hypoglycemia, decreased renal function, cardiorespiratory distress, and coagulation disorders. Hyperviscosity has been reported to be associated with long-term motor and cognitive neurodevelopmental disorders. Blood viscosity exponentially increases when an infant has polycythemia (hematocrit >/= 65%). Partial exchange transfusion (PET) is traditionally used as the method to lower the hematocrit and treat hyperviscosity. To evaluate the effect of PET on mortality and neurodevelopmental outcome in infants with neonatal polycythemia. Electronic databases searched included: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (1966 to October 2009), EMBASE (1980 to October 2009) and CINAHL (1982 to October 2009). Randomized controlled clinical trials or quasi-randomized trials comparing partial exchange transfusion to control (non-treatment) in infants with neonatal polycythemia Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. One study (Kumar 2004) reported no demonstrable effect on the risk of neonatal mortality (RR 5.23, 95% CI 0.66, 41.26).Four studies reported on neurodevelopmental assessment at 18 months or older. The completeness of follow-up differed widely between the studies. Overall, no difference was seen in developmental delay when all trials are analysed based on available cases (typical RR 1.45, 95% CI 0.83 to 2.54) and when only the randomized controlled trials are analysed (typical RR 1.35, 95% CI 0.68 to 2.69). A best case/worst case analysis of developmental delay is consistent with large benefit or harm from PET.Two studies reported on necrotizing enterocolitis (Van der Elst 1980; Black 1985). An increase in the risk of NEC was noted in infants receiving PET (typical RR 11.18, 95% CI 1.49, 83.64; typical RD 0.14, 95% CI 0.05, 0.22). No differences in short-term complications including hypoglycemia (two studies) and thrombocytopenia (one study) were noted. There are no proven clinically significant short or long-term benefits of PET in polycythemic newborn infants who are clinically well or who have minor symptoms related to hyperviscosity. PET may lead to an increase in the risk of NEC. The data regarding developmental follow-up is extremely imprecise due to the large number of surviving infants who were not assessed and, therefore, the true risks and benefits of PET are unclear.

Neurodevelopmental Outcome in Infants Undergoing Early Surgery for Congenital Heart Disease

Neurodevelopmental Outcome in Infants Undergoing Early Surgery for Congenital Heart Disease

Neurodevelopmental Outcome of Infants With Unilateral or Bilateral Periventricular Hemorrhagic Infarction

Periventricular hemorrhagic infarction (PVHI) is a major contributing factor to poor neurodevelopmental outcomes in preterm infants. We hypothesized that surviving infants with unilateral PVHI would have more favorable outcomes than those with bilateral PVHI. This was a multicenter, retrospective study of infants who were admitted to 3 NICUs in North Carolina from 1998 to 2004. The clinical course and late neuroimaging studies and neurodevelopmental outcomes of 69 infants who weighed <1500 g and had confirmed PVHI on early cranial ultrasonography were reviewed. A predictive model for Bayley Scales of Infant Development, Second Edition, Mental Developmental Index (MDI) <70 was constructed by using radiologic and clinical variables. Infants with unilateral PVHI had higher median MDI (82 vs 49) and Psychomotor Developmental Index (53 vs 49) than infants with bilateral PVHI. Infants with unilateral PVHI were less likely to have severe cerebral palsy (adjusted odds ratio: 0.15 [95% confidence interval (CI): 0.05-0.45]) than infants with bilateral PVHI. Infants who had unilateral PVHI and developed periventricular leukomalacia and retinopathy of prematurity that required surgery had an increased probability of having MDI <70 compared with those without these complications (probability of MDI <70: 89% [95% CI: 0.64-1.00] vs 11% [95% CI: 0.01-0.28]). Infants with unilateral PVHI had better motor and cognitive outcomes than infants with bilateral PVHI. By combining laterality of PVHI, periventricular leukomalacia, and retinopathy of prematurity it is possible to estimate the probability of having an MDI <70, which will assist clinicians when counseling families.

Optimizing Neurodevelopmental Outcomes in Infants and Children Following Prenatal SSRI Exposure

Optimizing Neurodevelopmental Outcomes in Infants and Children Following Prenatal SSRI Exposure

Clinical Neonatal Seizures are Independently Associated with Outcome in Infants at Risk for Hypoxic-Ischemic Brain Injury

To examine whether neonatal seizures are associated with neurodevelopmental outcomes in infants with hypoxia-ischemia independent of the presence and severity of brain injury seen on magnetic resonance imaging (MRI). We used multivariate regression to examine the independent effect of clinical neonatal seizures and their treatment on neurodevelopment in 77 term newborns at risk for hypoxic-ischemic brain injury. Clinical seizures were recorded prospectively, and high-resolution newborn MRI measured the severity of brain injury. The outcome measure was the Full-Scale Intelligence Quotient (FSIQ) of the Wechsler Preschool and Primary Scale of Intelligence-Revised and neuromotor score at age 4 years. After controlling for severity of injury on MRI, the children with neonatal seizures had worse motor and cognitive outcomes compared with those without seizures. The magnitude of effect varied with seizure severity; children with severe seizures had a lower FSIQ than those with mild/moderate seizures (P < .0001). Clinical neonatal seizures in the setting of birth asphyxia are associated with worse neurodevelopmental outcome, independent of the severity of hypoxic-ischemic brain injury. Randomized controlled trials are needed to determine whether differences in seizure treatment can improve outcome.

Pitfalls, Problems, and Progress in Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia is a chronic lung disease associated with premature birth and characterized by early lung injury. In this review we discuss some pitfalls, problems, and progress in this condition over the last decade, focusing mainly on the last 5 years, limited to studies in human neonates. Changes in the definition, pathogenesis, genetic susceptibility, and recent biomarkers associated with bronchopulmonary dysplasia will be discussed. Progress in current management strategies, along with novel approaches/therapies, will be critically appraised. Finally, recent data on long-term pulmonary and neurodevelopmental outcomes of infants with bronchopulmonary dysplasia will be summarized.

Posthemorrhagic Hydrocephalus in Newborns: Clinical Characteristics and Role of Ventriculoperitoneal Shunts

The incidence of neonatal intraventricular hemorrhage (IVH) does not decrease even after using a surfactant and advanced intensive care. Posthemorrhagic hydrocephalus (PHH) is major complication after IVH. The roles of the ventricuLoperitoneal (VP) shunt and the prognostic factors of neurodevelopmental outcomes in infants with PHH remain controversial. We compared the neurodevelopmental outcomes in newborns with and without VP shunts to delineate the clinical characteristics of patients with PHH and to determine the useful prognostic factors of short-term outcomes and neurodevelopmental results at a corrected age of more than 1 year old. We retrospectively reviewed the records of 83 cases of neonatal IVH, grades 2-4. Thirty (36%) of the cases were complicated with PHH. We classified survivors into four groups by outcome-normal, mildly abnormal, moderately abnormal, and severely abnormal-to compare prognoses. Among the 30 PHH cases, 10 patients died during their first admission (early deaths), and four died after their first discharge (late deaths). We found no statistically significant differences in gestational age, birth weight, gender, the maximum number of red blood cells in cerebral ventricular fluid, the lowest glucose levels, or total protein. Patients with grade 3 IVH were more likely to have shunts than were patients with grade 2 IVH. Patients with shunts had more late deaths and fewer normal neurodevelopmental outcomes than those without shunts. Patients who were shunt-dependent had worse neurodevelopmental outcomes and greater mortality than those without shunts. The results appeared to depend on how far the hydrocephalus had progressed and on the degree of IVH, but the necessity of VP shunts requires reevaluation before they are implanted.