Neurodevelopmental Outcome Of Infants Research Articles

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.

Neurodevelopmental outcome of infants with meconium aspiration syndrome: report of a study and literature review

There is a paucity of information on long-term outcome of infants who have suffered from meconium aspiration syndrome (MAS) in the neonatal period. We analyzed long-term developmental outcome data of 35 infants who were admitted to the neonatal intensive care unit (NICU) at the University of Illinois Hospital at Chicago (UICMC) with a diagnosis of MAS, and we reviewed the literature pertinent to the subject. The objective of the study was to assess the neurodevelopment status of MAS infants and compare the possible effects of different variables that are known to affect the later developmental outcome. The variables included mode of delivery, APGAR score, cord pH, mode of treatment, and neurological findings during the course of NICU. The infants were enrolled in the developmental follow-up program (DFUP) after discharge from the nursery for assessment of long-term developmental status and neurodevelopmental outcome. In order to assess the impact of the treatment on long-term outcome and compare our findings with previously published reports, we also reviewed the previously published literature on neurodevelopment outcome of infants treated for MAS (with different modalities) during the last three decades. Total of 35 infants with a diagnosis of MAS admitted to the NICU at UICMC were followed in the DFUP clinic for 3 years during January 1999 to September 2001. The medical records of these infants were reviewed for the mode of delivery, APGAR score, birth weight (BW), gestational age, mode of treatment during the neonatal period, and neurodevelopment status. 19/35 (54%) infants were delivered vaginally, 16/35 (46%) by cesarean section (C-section). All were treated in the delivery room using the standard resuscitation protocol. Following initial resuscitation, all except three required intubation and ventilation for varying duration. One infant required inhaled nitric oxide therapy, and two required extracorporeal membrane oxygenation treatment. Subsequent to discharge, the infants were evaluated in the clinic at 2 months of age, and then every 4 months up to 3 years. The developmental assessment of mental development index (MDI), psychomotor development index (PDI), and behavior rating scale (BRS) were obtained using the Bayley II infant motor scale, and neurodevelopment evaluation was performed using the Amiel-Tison technique. Speech evaluation was performed in infants >18 months using the Rossetti Infant-Toddler language scale. Infants were considered normal when MDI and PDI scores were >85 to 110; mildly delayed when scores were >70 to 84; and severely delayed if the scores were <69. In addition, neurological evaluation also confirmed the disability. The report is based on the final analysis of 29 infants. Data of six infants were not included in the final analysis because of incomplete information. The mean BW of the infants was 3269+/-671 g; mean gestational age was 39.5+/-3.1 weeks. The median APGAR score at 1' was 4, and at 5' was 6. Out of 29, 11 (38%) infants were normal. Out of 29, 2 infants (7%) had cerebral palsy (CP) and 4 (14%) had severe delay at 12 months of age. Out of 29, 2 who were neurologically disabled had PDI <69. Out of 29, 12 (41%) had mild delay in speech. No statistical difference in neurodevelopment was found in infants born vaginally or by C-section. Our findings show poor outcome (CP and global delay) in 21% of infants who suffered MAS, even though the majority of the infants (26/29) responded to conventional ventilator support alone. No difference was found in the outcome of infants between NSVD vs C-section delivery. These findings suggest that infants with the diagnosis of MAS manifest later neurodevelopmental delays, even if they respond well to conventional treatment. This abstract was presented at the Society for Pediatric Research Annual Meeting, 2000.

Serial brain MRI and ultrasound findings: Relation to gestational age, bilirubin level, neonatal neurologic status and neurodevelopmental outcome in infants at risk of kernicterus

Aims To describe cranial ultrasound (cUS) and magnetic resonance imaging (MRI) findings in neonates at risk of kernicterus, in relation to gestational age (GA), total serum bilirubin (TSB), age at imaging and neurodevelopmental outcome. Patients and methods Neonates with peak TSB > 400 μmol/L and/or signs of bilirubin encephalopathy. Review of neonatal data, cUS, preterm, term and later MRI scans and neurodevelopmental outcome. Results 11 infants were studied, two < 31, four 34–36 and five 37–40 weeks GA. TSB levels: 235–583 μmol/L (preterms); 423–720 μmol/L (terms). Neonatal neurological examination was abnormal in 8/10. cUS showed increased basal ganglia (BG) in 4/9 infants and white matter (WM) echogenicity, lenticulostriate vasculopathy (LSV) and caudothalamic hyperechogencity/cysts (GLCs) in 5/9 infants. MRI showed abnormal signal intensity (SI) in the globus pallidum (GP) in 1/2 preterm, 8/9 term and 9/11 later scans. Abnormal WM SI occurred in 2 preterm, 7 term and 10/11 later scans. Seven infants developed athetoid/dystonic cerebral palsy (CP) and 6 hearing loss (HL). Adverse outcome was associated with abnormal BG on cUS (3/4 CP, 4/4 HL), with high SI in GP (7/9 CP, 6/9 HL) on late T2-weighted MRI (all GA) and on T1/T2-weighted term MRI, mainly in term-born infants. WM abnormalities, GLCs and LSV did not correlate with outcome. Conclusions Severe CP occurred with relatively low TSB levels in preterms but only at high levels in full-terms; HL was difficult to predict. Early scans did not reliably predict motor deficits whilst all children with CP had abnormal central grey matter on later scans. Abnormal WM was seen early suggesting primary involvement rather than change secondary to grey matter damage. Why characteristic central grey matter MRI features of kernicterus are not seen early remains unexplained.

Upper limb movements and outcome in intrauterine-growth-retarded infants at 2 years

This study aims to examine the usefulness of spontaneous upper limb movements (ULM) as an early marker for predicting neurodevelopmental outcome in infants with intrauterine-growth retardation (IUGR). The assessment of general movements (GMs) during the first 20 weeks is an accepted method for early detection of brain dysfunction. During this period, spontaneous upper limb movements were examined in 32 infants with IUGR and 32 appropriate-for-gestational-age-matched controls. ULM (arms, forearms and hands) were scored as optimal or suboptimal by sequential videotape recordings in the writhing (term-2 weeks: score 0–5); early fidgety (9–11 weeks: score 0–6); and late fidgety (14–16 weeks: score 0–6) periods, and correlated with neurodevelopmental score at 2 years of age. The mean ULM score was lower in the IUGR infants than the controls ( p < 0.05) and in the IUGR group was lower in the infants with abnormal outcome ( p < 0.05). Significant correlations were found between ULM and 2-year neurodevelopmental scores in the IUGR group. The ULM during late-fidgety period was most predictive for 2-year neurodevelopmental score. No difference was found in the mean ULM score between the pre-term and term IUGR infants. We conclude that ULM score can serve as an early predictor for neurodevelopmental outcome at 2 years of age in infants with IUGR.

Neurodevelopmental outcome of premature infants after exposure to antenatal indomethacin

This study was undertaken to evaluate the effect of antenatal indomethacin exposure on neurodevelopmental outcomes of premature infants. 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 chi(2) test, respectively. 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. Antenatal indomethacin is not associated with abnormal neurodevelopmental outcome in infants 29 or less weeks' gestational age.

Long-chain ??-3 fatty acid supply in pregnancy and lactation

Long-chain omega-3 fatty acids are essential for the developing fetus. Docosahexaenoic acid, the most important omega-3 fatty acid, is an important component of neural and retinal membranes, and rapidly accumulates in the brain during gestation and the postnatal period. Positive associations have been shown between maternal intake of fish, seafood and omega-3 fatty acids during pregnancy and/or lactation and visual and cognitive development. The review focuses on new findings by both observational and interventional studies on the influence of omega-3 fatty acids during pregnancy or lactation on gestation length and birth weight, preterm delivery, preeclampsia, maternal depression and infant visual function and neural development. Omega-3 fatty acids have been associated with reduced risk of cardiovascular and other diseases. Observational and interventional studies indicate a significant association with prolonging gestation and reducing the risk of preterm delivery both in low-risk and in high-risk pregnancies. Further benefits have been suggested for intrauterine growth restriction, preeclampsia and postpartum depression, but the evidence is inconclusive. Higher maternal docosahexaenoic acid intake both in pregnancy and lactation is associated with positive infant neurodevelopmental outcomes. Women of reproductive age should achieve an average dietary docosahexaenoic acid intake of at least 200 mg/day.

Neurodevelopmental outcome of infants with apnea of infancy.

The neurodevelopmental outcome of premature infants with persistent apnea of prematurity (AOP) is reported. Sixty premature infants (birthweight [BW], 1469 +/- 533 gm; gestational age [GA , 31 +/- 3 weeks) with AOP were compared to 47 control infants (BW, 1586 +/- 581 gm; GA, 31 +/- 3 weeks) matched for gestational age and degree of neonatal illness. The infants were enrolled in a multidisciplinary follow-up program, and outcome data between 12 and 24 months are reported. Assessments included the Bayley Scores of Infant Development, neurologic examinations, speech and hearing examinations. There were no significant differences in the cognitive outcome between the premature infants with AOP and the premature control group. In 50 of 60 infants the Bayley Mental Developmental Index was in the normal range (112 +/- 18) as was 39 of 47 of the control group (112 +/- 13). Delays in motor development were seen in both premature groups, although a greater percentage of premature infants with persistent apnea had mild motor delays than did control infants. There was a comparable incidence of cerebral palsy (8% vs 11%), speech delays (20% vs 23%), retinopathy (8% vs 13%), and esotropia (7% vs 4%) between the infants with AOP and the premature control infants. The presence of persistent neonatal apnea without additional adverse perinatal events did not appear to be associated with a higher incidence of significant developmental problems.

Relationship Between White Matter Apparent Diffusion Coefficients in Preterm Infants at Term-Equivalent Age and Developmental Outcome at 2 Years

The aim of this study was to develop a simple reproducible method for the measurement of apparent diffusion coefficient values in the white matter of preterm infants using diffusion-weighted imaging to test the hypothesis that elevated mean apparent diffusion coefficient values are associated with lower developmental quotient scores at 2 years' corrected age. We obtained diffusion-weighted imaging in 38 preterm infants at term-equivalent age who had no evidence of overt cerebral pathology on conventional MRI. Mean apparent diffusion coefficient values at the level of the centrum semiovale were determined. The children were assessed using a standardized neurologic examination, and the Griffiths Mental Development Scales were administered to obtain a developmental quotient at 2 years' corrected age. The relationship between mean apparent diffusion coefficient values and developmental quotient was examined. Clinical data relating to postnatal sepsis, antenatal steroid exposure, supplemental oxygen, gender, patent ductus arteriosus, and inotrope requirement were collected, and the mean apparent diffusion coefficient values for each group were compared. The mean (+/-SD) apparent diffusion coefficient value in the white matter was 1.385 +/- 0.07 x 10(-3) mm2/second, and the mean developmental quotient was 108.9 +/- 11.5. None of the children had a significant neurologic problem. There was a significant negative correlation between mean apparent diffusion coefficient and developmental quotient. These findings suggest that higher white matter apparent diffusion coefficient values at term-equivalent age in preterm infants without overt lesions are associated with poorer developmental performance in later childhood. Consequently, apparent diffusion coefficient values at term may be of prognostic value for neurodevelopmental outcome in infants who are born preterm and who have no other imaging indicators of abnormality.

Prenatal Low Levels Mercury Exposure on Infant Development: A Prospective Study in Zhoushan Islands, China

ISEE-505 Objective: To explore the relationship between prenatal mercury exposure and infant neurodevelopmental outcomes in Zhoushan cohort. Material and Methods: Four hundred eight mother-infant pairs were enrolled in the cohort of Zhoushan Islands. Prenatal mercury exposure was determined by measuring cord blood mercury (CBHg, range 1.34–18.34 μg/L). On the basis of their CBHg, children were divided into 2 groups: 80 in low mercury group (LG, CBHgP80, 8.09 μg/L). Children were followed up at 3 (n = 149) and 12 (n = 123) months of age with evaluated BSID, hair mercury, and questionnaire. The association between CBHg and neurodevelopmental outcomes at 3 and 12 months of age was examined by multiple regression analysis with adjustment for confounding variables. Results: The average hair mercury levels were 1058.71 ± 69.58 (LG), 1903.06 ± 139.37 μg/kg (HG) of 3-month-infant and 906.05 ± 110.26 (LG), 1512.41 ± 93.85 μg/kg (HG) of 12-month-infant. The hair mercury of 12-month were lower than that of 3-month significantly in both group. MDI of 3-month-infant were 109.01 ± 4.16 of LG, 108.32 ± 4.23 of HG, PDI were 99.91 ± 3.28 of LG, and 98.71 ± 5.21 of HG. MDI of 12-month-infant were 110.60 ± 4.29 of LG, 109.56 ± 4.29 of HG; PDI were 104.06 ± 3.75, and 101.70 ± 3.59 of HG. There were no significant differences of MDI and PDI between the 2 groups in both ages. At 3 months, high risk factors for MDI were hair mercury of 3 months and head circumference; and those for PDI were hair mercury of 3 months and gender. At 12 months, the high risk factors for MDI scores were hemoglobin of 3 months, age when children stood up and those for PDI were age when children stood up, average times of fish dinners of mother and hemoglobin of 12 months. Conclusions: The hair mercury level was significantly related with CBHg. The mercury exposure level of 12-month-infant was lower than that of 3-month-infant. Prenatal low level mercury exposure of Zhoushan cohort had no significantly impacts on infants' development.

Should cranial MRI screening of preterm infants become routine?

Recent data show that MRI at term-equivalent age can predict neurodevelopmental outcomes in infants born far before term. So should cranial MRI screening replace cranial ultrasound in preterm babies? The authors of this Viewpoint weigh up the options.

Adverse neurodevelopmental outcome of infants exposed to opiate in-utero

In-utero drug exposure is associated with increased risks of perinatal morbidity and mortality, however longer term neurodevelopmental outcome of survivors is poorly described. Aims: The aims of this paper are: (1) to review the published literature which examines neurodevelopmental outcome in infants with Neonatal Abstinence Syndrome (NAS) and (2) to report developmental follow-up data from a case-control study of babies exposed to opiate in-utero. Methods: This study was conducted at Royal Prince Alfred Hospital in Sydney, NSW, through the multidisciplinary NAS service. Literature was reviewed after searching MEDLINE for relevant studies. Our own case-control study was conducted to examine neurodevelopmental outcome. A number of standardized neuropsychological tools were employed to assess these infants. Results: Results from previously published studies on outcome of infants with NAS were not reassuring as to reported ‘normal development’. In our own case-control study, opiate-exposed infants were significantly more likely to have neurodevelopmental impairment compared to healthy control infants, when assessed at 18 months and 3 years of age. Conclusions: Infants exposed to opiates in-utero are at increased risk of neurodevelopmental problems throughout early childhood.

Five-Year Neurodevelopmental Outcome of Neonatal Dehydration

To determine the long-term outcome of neonatal dehydration. We identified 182 newborns who were rehospitalized with dehydration (weight loss > or =12% of birth weight and/or serum sodium > or =150 mEq/L) and 419 randomly selected controls from a cohort of 106,627 term and near-term infants with birth weight > or =2000 g born between 1995 and 1998 in northern California Kaiser Permanente hospitals. Outcomes data were obtained from electronic records, interviews, questionnaire responses, and neurodevelopmental evaluations performed in a masked fashion. Follow-up data to age at least 2 years were available for 173 of 182 children with a history of dehydration (95%) and 372 of 419 controls (89%) and included formal evaluation at a mean age (+/-standard deviation) of 5.1 +/- 0.12 years for 106 children (58%) and 168 children (40%), respectively. None of the cases developed shock, gangrene, or respiratory failure. Neither crude nor adjusted scores on cognitive tests differed significantly between groups. There was no significant difference between groups in the proportion of children with abnormal neurologic examinations or neurologic diagnoses. Frequencies of parental concerns and reported behavior problems also were not significantly different in the 2 groups. Neonatal dehydration in this managed care setting was not associated with adverse neurodevelopmental outcomes in infants born at or near term.

Single Versus Repeat Courses of Antenatal Steroids to Improve Neonatal Outcomes: Risks and Benefits

Recent additions to the literature provide evidence supporting the use of repeat courses of antenatal steroids. Both human and animal studies offer evidence that repeat courses of corticosteroids improve neonatal pulmonary outcomes, especially for the infants delivered at earlier gestational ages. Although there is also evidence to suggest altered neuronal maturation and intrauterine growth restriction in animals treated with repeat steroids, randomized controlled studies in humans have shown that birth weight reduction was only seen in those infants treated with 4 or more courses of corticosteroids. In addition, the reduction in neonatal birth weight and head circumference seen after multiple courses of antenatal corticosteroids normalizes by the time of hospital discharge. Studies are ongoing to investigate the 24-month post delivery physical and neurodevelopmental outcomes in infants exposed to repeat courses of antenatal corticosteroids. Although there is evidence demonstrating the safety of a single repeat, or 'rescue', dose of antenatal corticosteroids, this must be tempered against the adverse effects seen after multiple courses of weekly repeat steroids. Randomized controlled trials are needed to determine the optimal number of courses of antenatal steroids to reduce the frequency of neonatal respiratory distress syndrome (RDS) without adversely affecting other neonatal outcomes.

Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants

Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxinaemia) and abnormal neurodevelopmental outcome. Thyroid hormone replacement might prevent this. To determine whether prophylactic thyroid hormones given to preterm infants without congenital hypothyroidism result in clinically important changes in neonatal and long term outcomes. The standard search strategy of the Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), EMBASE, PREMEDLINE, and searches of abstracts of conference proceedings, citations of published articles and expert informants. All trials using random or quasi-random patient allocation in which prophylactic thyroid hormone treatment was compared to control in premature infants. Assessment of trial quality, data extraction and synthesis of data, using relative risk (RR) and weighted mean difference (WMD), were performed using standard methods of the Cochrane Collaboration and its Neonatal Review Group. Four studies enrolling 318 infants were included. All studies enrolled preterm infants on the basis of gestational age criteria. All studies commenced treatment in the first 48 hours, but used different regimens, dose and durations of treatment. All four studies used thyroxine (T4). Valerio 2004 incorporated one arm with an early short course of T3, then T4 for 6 weeks. Only two studies with neurodevelopmental follow-up were of good methodology (van Wassenaer 1997; Vanhole 1997). All studies were small with the largest (van Wassenaer 1997) enrolling 200 infants.No significant difference was found in neonatal morbidity, mortality or neurodevelopmental outcome in infants who received thyroid hormones compared to control. van Wassenaer 1997 reported no significant difference in abnormal mental development at 6, 12, 24 months (RR 0.67, 95% CI 0.28, 1.56) or five years (RR 0.66, 95% CI 0.22, 1.99) or cerebral palsy assessed at five years (RR 0.72, 95% CI 0.28, 1.84). Meta-analysis of two studies (van Wassenaer 1997, Vanhole 1997) found no significant difference in the Bayley MDI (WMD -1.14, 95% CI -5.46, 3.19) and PDI (WMD 0.22, 95% CI -4.80, 5.24) at 7 - 12 months. van Wassenaer 1997 reported no significant difference in the Bayley MDI (MD -3.50, 95% CI -11.21, 4.21) and PDI (MD 3.10, 95% CI -3.31, 9.51) at 24 months, IQ scores at 5 years (MD -2.10, 95% CI -7.91, 3.71) and children in special schooling at 10 years (RR 0.88, 95% CI 0.43, 1.83). Meta-analysis of all four trials found no significant difference in mortality to discharge (typical RR 0.76, 95% CI 0.46 to 1.24). van Wassenaer 1997 reported no significant difference in death or cerebral palsy at five years (RR 0.70, 95% CI 0.43 to 1.14). No significant differences were reported for neonatal morbidities, including the need for mechanical ventilation, duration of mechanical ventilation, air leak, CLD in survivors at 28 days or 36 weeks, intraventricular haemorrhage, severe intraventricular haemorrhage, periventricular leucomalacia, patent ductus arteriosus, sepsis, necrotising enterocolitis or retinopathy of prematurity. This review does not support the use of prophylactic thyroid hormones in preterm infants to reduce neonatal mortality, neonatal morbidity or improve neurodevelopmental outcomes. An adequately powered clinical trial of thyroid hormone supplementation with the goal of preventing the postnatal nadir of thyroid hormone levels seen in very preterm infants is required.

Maternal Leukocytosis After Preterm Premature Rupture of Membranes and Infant Neurodevelopmental Outcome: A Prospective,Population-Based Study (Décrire L’ouverture des Membranes Inopinée le Nouveau-né et l’Organisation des Soins [DOMINOS] Study)

ObjectiveTo evaluate the relationship between maternal leukocytosis in women admitted after preterm premature rupture of the membranes (PPROM) and the neurodevelopmental outcomes of their infants at two years of age. MethodsA prospective cohort study of women with PPROM occurring between 24 weeks and 33 weeks and 6 days of gestation was conducted in a region of France over two years. The primary outcome was a composite of neurodevelopmental variables, including motor impairment (an inability to stand without support, walk, run, or climb or descend stairs alone), auditory impairment, visual impairment, or the presence of monoplegia, diplegia, or hemiplegia at two years of age. Multiple logistic regression analysis was used to adjust for confounding factors. ResultsOf 394 cases, 6/64 neonates (9.4%) born to mothers with leukocytosis were no longer alive at the two-year follow-up, compared with 14/330 (4.2%) born to mothers with no leukocytosis (P = 0.09). At two years of age, 28 (56%), 22 (52%), 34 (49%), and 52 infants (37%) showed at least one of the primary outcome features for PPROM occurring at 24–27, 28–29, 30–31, and 32–33 weeks’ gestation, respectively. In univariate analysis, PPROM at less than 30 weeks, leukocytosis, and cerclage were associated with a higher rate of the primary outcome. In logistic regression analysis, only leukocytosis remained significant (odds ratio [OR] 2.92; 95% confidence intervals [CI] 1.33–6.39, P = 0.02). Fewer infants whose mothers had a leukocyte count (WBC) ≤15 000/mm3 at the time of PPROM showed a feature of the primary outcome at two years of age than infants whose mothers had a higher WBC (P < 0.01). ConclusionMaternal leukocytosis at admission is associated with higher adverse infant neurodevelopmental outcomes at two years of age. Guidelines for the management of women with PPROM who do not begin to labour should include consideration of the degree of leukocytosis.

Early Assessment of Visual Information Processing and Neurological Outcome in Preterm Infants

Psychological tests based on visual information processing have shown to be promising in predicting neurodevelopmental outcome in infants at risk. In the present study we prospectively investigated the early development in a group of 20 high-risk preterm infants by means of i) the Fagan Test of Infant Intelligence at 7, 9, and 12 months postterm and ii) a detailed battery for the early assessment of visual functions at 6 and 10 months postterm. The results were then correlated to the Griffiths development scales at two years. At around 7 months no correlation was found in our infants between the Fagan test and neurodevelopmental outcome, possibly as a consequence of the influence of abnormal oculomotor behaviour. At around 9 months most of the visual abnormalities were no more present and the Fagan test was significantly correlated with the outcome. At 12 months postterm a decline of the predictive value of the FTII was observed. In conclusion, nine months postterm age appears to be the best age for the early assessment of neurodevelopmental outcome in high-risk preterm infants, as the maturation of the attentional and visual systems allows a more reliable evaluation.

Outcomes among newborns with total serum Bilirubin levels of 25 mg per deciliter or more

. Newman, T.B., Liljestrand, P., Jeremy, R.J., Ferriero, D.M., Wu, Y.W., Hudes, E.S., Escobar, G.J. , ( 2006 ) , 354 , 1889 – 1900 . Background The neurodevelopmental risks associated with high total serum bilirubin levels in newborns are not well defined.Methods We identified 140 infants with neonatal total serum bilirubin levels of at least 25 mg per deciliter (428 µmol per litre) and 419 randomly selected controls from a cohort of 106 627 term and near‐term infants born from 1995 to 1998 in Kaiser Permanente hospitals in northern California. Data on outcomes were obtained from electronic records, interviews, responses to questionnaires and neurodevelopmental evaluations that had been performed in a blinded fashion.Results Peak bilirubin levels were between 25 and 29.9 mg per deciliter (511 µmol per litre) in 130 of the newborns with hyperbilirubinemia and 30 mg per deciliter (513 µmol per litre) or more in 10 newborns; treatment involved phototherapy in 136 cases and exchange transfusion in five. Follow‐up data to the age of at least 2 years were available for 132 of 140 children with a history of hyperbilirubinemia (94%) and 372 of 419 controls (89%) and included formal evaluation at a mean (±SD) age of 5.1 ± 0.12 years for 82 children (59%) and 168 children (40%) respectively. There were no cases of kernicterus. Neither crude nor adjusted scores on cognitive tests differed significantly between the two groups; on most tests, 95% confidence intervals excluded a 3‐point (0.2 SD) decrease in adjusted scores in the hyperbilirubinemia group. There was no significant difference between groups in the proportion of children with abnormal neurologic findings on physical examination or with documented diagnoses of neurologic abnormalities. Fourteen of the children with hyperbilirubinemia (17%) had ‘questionable’ or abnormal findings on neurologic examination, as compared with 48 controls (29%; P = 0.05; adjusted odds ratio, 0.47; 95% confidence interval, 0.23–0.98; P = 0.04). The frequencies of parental concern and reported behavioural problems also were not significantly different between the two groups. Within the hyperbilirubinemia group, those with positive direct antiglobulin tests had lower scores on cognitive testing but not more neurologic or behavioural problems.Conclusions When treated with phototherapy or exchange transfusion, total serum bilirubin levels in the range included in this study were not associated with adverse neurodevelopmental outcomes in infants born at or near term.

Metabolic Alterations and Neurodevelopmental Outcome of Infants with Transposition of the Great Arteries

Abnormal neurodevelopment has been reported for infants who were born with transposition of the great arteries (TGA) and underwent arterial switch operation (ASO). This study evaluates the cerebral metabolism of TGA infants at birth and before ASO and neurodevelopment 1 year after ASO. Proton magnetic resonance spectroscopy (1H-MRS) was performed on 16 full-term TGA brains before ASO within 3-6 days after birth. The brain metabolite ratios of [NAA/Cr], [Cho/Cr], and [mI/Cr] evaluated measured. Ten infants were evaluated at 1 year using the Bayley Scales of Infants Development II (BSED II). Cerebral metabolism of infants with TGA was altered in parietal white matter (PWM) and occipital gray matter (OGM) at birth before ASO. One year after ASO, [Cho/Cr] in PWM remained altered, but all metabolic ratios in OGM were normal. The results of BSID II at 1 year showed delayed mental and psychomotor development. This delayed neurodevelopmental outcome may reflect consequences of the altered cerebral metabolism in PWM measured by 1H-MRS. It is speculated that the abnormal hemodynamics due to TGA in utero may be responsible for the impaired cerebral metabolism and the subsequent neurodevelopmental deficit.

Neurodevelopmental Implications of Congenital Heart Disease

After completing this article, readers should be able to: 1. Describe the causes of central nervous system injury for infants who have congenital heart disease. 2. List genetic causes of congenital heart disease associated with developmental delay. 3. Identify potential intraoperative mechanisms for neurologic injury for infants who have congenital heart disease. 4. Identify risk factors for adverse neurodevelopmental outcomes for infants who have congenital heart disease. 5. Describe which long-term developmental deficits are common among children who have congenital heart disease. Among the more than 40,000 infants born with congenital heart disease (CHD) annually in the United States, one third require surgery during the first year after birth. (1) As advances in prenatal diagnosis, perioperative management, and surgical techniques have contributed to reduce rates of mortality, attention has shifted toward the neurodevelopmental morbidity among the growing cohort of survivors. Supportive surgical techniques, including cardiopulmonary bypass and deep hypothermic cardiac arrest (DHCA), have been a focus of outcome investigation, but mounting evidence suggests that multiple risk factors contribute significantly toward neurodevelopmental impairment. Long-term deficits in domains of cognition, attention, and neuromotor functioning among patients likely reflect the cumulative impact of features present before, during, and after surgical intervention. ### Genetic Implications Genetic abnormalities and syndromes are present in many infants who have CHD and may be associated with neurodevelopmental delay (Table 1). Trisomy 21 affects 1 in 660 newborns; 40% of affected infants have CHD. Neurodevelopmental deficits, including hypotonia and mental retardation, are common among all patients who have trisomy 21. (5)(6) Among infants who have conotruncal defects, 18% have been found to have a microdeletion on chromosome 22. (17) Evaluation of children who have the 22q11 deletion, present in most infants who have velocardiofacial and DiGeorge syndromes, has revealed a unique profile of cognitive deficits. Impairments in visuospatial memory, attention, and language are common, and …

Neurodevelopmental outcome of infants with birth asphyxia treated with magnesium sulfate

A neuroprotective effect of MgSO(4) has been shown in some animal models of perinatal hypoxic-ischemic brain damage. The aim of the present paper was to determine whether postnatal MgSO(4) infusion (250 mg/kg per day i.v. for 3 days, in combination with dopamine) is safe in infants with severe birth asphyxia, and also observe effects on neurodevelopmental outcome at 18 months. Inclusion criteria were clinical history consistent with perinatal asphyxia; gestational age at least 37 weeks; 5 min Apgar score < or =6; failure to initiate spontaneous respiration within 10 min after birth; and symptoms of encephalopathy. On each day MgSO(4) was infused over 1 h in combination with dopamine (5 microg/kg per min). Changes in vital signs, clinical course of encephalopathy, laboratory variables, and adverse events were monitored. Infants were followed for 18 months. Thirty infants were studied. Mean birthweight was 2878 g; mean gestational age, 39.6 weeks, and median 5 min Apgar score, 3. All required endotracheal intubation for resuscitation. Median age at MgSO(4) initiation was 5 h. All infants had moderate or severe hypoxic-ischemic encephalopathy. Mean serum Mg(2+) concentration remained at least 1.3 mmol/L. MgSO(4) caused no change in physiological variables including mean arterial pressure. Two infants died as neonates, while six of 28 survivors had severe neurodevelopmental disability at 18 months; the remaining 22 had no neurodevelopmental disability. Postnatal infusion of MgSO(4) with dopamine caused no change in physiological variables. Deaths and severe sequelae were less frequent than in reported cases with the same grade of hypoxic-ischemic encephalopathy severity, and this treatment may improve neurodevelopmental outcome in infants with severe birth asphyxia.