Major Neurodevelopmental Disability Research Articles

Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age

The purpose of this study was to determine the association between in utero exposure to acute inflammation and long-term major neurodevelopmental disability at age 6 years among children born prior to 32 weeks' gestation. This was a follow-up investigation of a cohort of maternal-infant dyads delivered between 23 and < 32 weeks' gestation. Surviving infants (and their mothers or caregivers) underwent a battery of psychological and neurodevelopmental tests between 5 and 8 years of age. Pregnancy and neonatal data were analyzed among children with versus those without major neurodevelopmental disability (including IQ < 70 [n = 41], cerebral palsy [CP, n = 11], and a composite major disability [n = 52]). A total of 261 (70%) of the 375 maternal-infant dyads with surviving children were successfully recruited and evaluated at 6.8 +/- 0.7 years. Mean delivery gestational age (GA) and birthweight were 28.8 +/- 2.2 weeks and 1163 +/- 382 g, respectively. Neither surrogate indicators for nor direct markers of in utero exposure to acute inflammation were significantly associated with severe adverse outcomes. Delivery GA was significantly associated with outcome. Logistic regression indicated that each increasing gestational week was associated with a significantly decreased risk of an IQ < 70 (OR 0.75, 95% CI 0.6-0.9). An average 1.9 point increase in IQ at 6 years of age was observed per gestational week gained (23 to 32 weeks). Periventricular leukomalacia was associated with a 9.6 point mean deficit in IQ. The perceptive vocabulary scores (IQ proxy) of primary caregivers were significantly lower among children with an IQ < 70 vs > or = 70 (87.5 +/- 11.5 vs 92.1 +/- 11.2, P = .016). Among children born between 23 and 32 weeks' gestation, neonatal complications, GA at delivery, and caregiver IQ, but not in utero exposure to acute inflammation, were associated with increased risk of severe adverse neurodevelopmental outcomes at age 6 years.

608: Apgar scores in very preterm births and risk of long-term severe neurodevelopmental disability

NEURODEVELOPMENTAL DISABILITY TAMULA PATTERSON, ALAN TITA, FRED BIASINI, SUZANNE CLIVER, ROBERT GOLDENBERG, WILLIAM ANDREWS, University of Alabama at Birmingham, Obstetrics and Gynecology, Birmingham, Alabama, University of Alabama at Birmingham, Psychology, Birmingham, Alabama, Drexel University College of Medicine, Obstetrics & Gynecology, Philadelphia, Pennsylvania OBJECTIVE: To assess the relationship between Apgar scores and long-term major neurodevelopmental disability at age 6 years among very preterm births (VPTB) 32 weeks. STUDY DESIGN: Secondary analysis of a follow-up study of long-term outcome in survivors among 375 consecutive births between 23 and 32 weeks was conducted at our institution. Surviving infants (and their mothers or caregivers) underwent a battery of psychological and neurodevelopmental tests. Risk of major neurodevelopmental disability (including IQ 70, cerebral palsy, and a composite major disability) were compared by low ( 6) vs. normal (7-10) Apgar score at 1 and 5 minutes. RESULTS: A total of 261 (70%) of 375 surviving infants were successfully recruited and evaluated at a mean of 6.8 0.7 years. The mean delivery gestational age and birthweight were 28.8 2.2 weeks and 1163 382 grams, respectively. Univariate analysis suggested an association between low Apgar scores and severe long-term neurodevelopmental disability at 1, but not at 5 minutes (Table). However, after adjusting for differences in gestational age, there was no association between Apgar scores and long-term outcome. CONCLUSION: Apparent associations between a one minute Apgar score of 6 and long-term adverse neurodevelopmental outcomes (including low IQ and cerebral palsy) are actually due to confounding by gestational age.

Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight ≤1250 g?

To compare the long-term growth and neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birthweight (BW) < or = 1250 g) with necrotising enterocolitis (NEC) with BW-matched controls. This is a case control study performed at a regional tertiary care neonatal intensive care unit. Infants with stage II or III NEC admitted to a regional tertiary care neonatal unit between 1995 and 2000 were identified. Each infant with NEC was matched by BW (+/-100 g) to next two infants admitted in the unit without NEC. Growth and neurodevelopmental outcomes at 36 months are compared. In total, 51 infants with NEC and 102 controls met study eligibility criteria and 146/153 (94.3%) were prospectively followed for 36 months. Infants with NEC had more culture-proven sepsis (35.3% vs. 10.8%, P < 0.001); patent ductus arteriosus requiring therapy (64.7% vs. 45%, P = 0.02), chronic lung disease (60.7% vs. 45%, P = 0.04) and longer hospital stay (84 days vs. 71 days, P < 0.0001). There were no significant differences in growth outcomes between the two groups at 36 months. Overall 24% of infants with NEC had one major neurodevelopmental disability compared with 10% among control infants. Infants who developed NEC had significantly higher cognitive delay (i.e. cognitive index <70) and visual impairment. A logistic regression model identified NEC as a predictor of cognitive delay. Preterm infants who develop NEC are at a significantly higher risk for developing neurodevelopmental disability. We recommend close neurodevelopmental follow up for all < or =1250 g infants who develop stage II or III NEC.

181 Cooling for Newborns with Hypoxic Ischaemic Encephalopathy

Background: Experimental studies suggest that hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae. Aims: To determine whether therapeutic hypothermia in encephalopathic asphyxiated newborn infants reduces mortality and neurodevelopmental disability, without clinically important side effects. Methods: Randomised controlled trials (RCTs) evaluating therapeutic hypothermia in newborns with hypoxic ischaemic encephalopathy (HIE) were identified using the standard search strategy of the Neonatal Review Group of the Cochrane Library. The primary outcome was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling. Three reviewers independently selected, assessed the quality of and extracted data. Meta-analyses were performed using relative risk and risk difference for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals. Results: Four RCTs were included in this review, comprising 349 term infants with HIE. Two studies (Gunn 1998, Gluckman 2005) achieved excellent follow-up rates at 18 months of age; one (Eicher 2005) had incomplete follow-up at 12 months (81.5%) and one (Shankaran 2002) has not reported long-term outcomes. The pooled analysis of the 2 higher quality studies showed no significant effect of therapeutic hypothermia on the combined outcome of death or major neurodevelopmental disability in survivors followed (RR 0.89 [95% CI 0.69, 1.05]). Inclusion of the poorer quality study (Eicher 2005) resulted in a significant reduction in death or major disability in infants allocated to therapeutic hypothermia (RR 0.80 [95% CI 0.66, 0.96]). No adverse effects of hypothermia on short term outcomes were detected. Conclusions: Four RCTs showed no evidence of harm from therapeutic hypothermia. Evidence of efficacy remains inconclusive. Therapeutic hypothermia for infants with HIE should continue to be evaluated in well designed RCTs. This abstract is a preliminary version of the update to be included in the Cochrane Library Issue 4 2005.

Cooling for newborns with hypoxic ischaemic encephalopathy.

Newborn animal and human pilot studies suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae, without adverse effects. To determine whether therapeutic hypothermia in encephalopathic asphyxiated newborn infants reduces mortality and long-term neurodevelopmental disability, without clinically important side effects. The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library (Issue 2, 2003) was used. Randomised controlled trials evaluating therapeutic hypothermia in term newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue Issue 2, 2003), MEDLINE (1966 to July 2003), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching. Randomised controlled trials comparing the use of therapeutic hypothermia with normothermia in encephalopathic newborn infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies were included. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Three reviewers independently selected, assessed the quality of and extracted data from the included studies. Authors were contacted for further information. Meta-analyses were performed using relative risk and risk difference for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals. Two randomised controlled trials were included in this review, comprising 50 term infants with moderate/ severe encephalopathy and evidence of intrapartum asphyxia. There was no significant effect of therapeutic hypothermia on the combined outcome of death or major neurodevelopmental disability in survivors followed. No adverse effects of hypothermia on short term medical outcomes or on some 'early' indicators of neurodevelopmental outcome were detected. Although two small randomised controlled trials demonstrated neither evidence of benefit or harm, current evidence is inadequate to assess either safety or efficacy of therapeutic hypothermia in newborn infants with hypoxic ischaemic encephalopathy. Therapeutic hypothermia for encephalopathic asphyxiated newborn infants should be further evaluated in well designed randomised controlled trials.

The outcome of extreme prematurity

Significant advances in perinatology and neonatology in the last decade have resulted in increased survival of extremely premature infants. Survival rates for infants born in tertiary perinatal and neonatal care centers in the United States in the 1990s increase with each week of gestational age from 22 through 26 weeks. Reported survival rates at 22 weeks range from 0% to 21% in the few reporting studies. Reported survival rates at 23 and 24 weeks range from 5% to 46% and from 40% to 59%, respectively. These may not be the maximum survival rates possible because at these gestational ages information is either insufficient to determine that obstetric and neonatal intensive care strategies to maximize neonatal survival were used or it is specified that such strategies were not used. Reported survival rates at 25 and 26 weeks range from 60% to 82% and from from 75% to 93%, respectively. The literature regarding the prevalence of major neurodevelopmental disabilities among extremely premature survivors in the last 25 years is heteogeneous, and the reported prevalances of major disability vary much more than do survival rates. However, the majority of extremely premature infants who survive will be free of major disability. Overall, approximately one fifth to one quarter of survivors have at least one major disability-impaired mental development, cerebral palsy, blindness, or deafness. Impaired mental development is the most prevalent disability (17%-21% [95% CI] of survivors affected), followed by cerebral palsy (12%-15% of survivors affected). Blindness and deafness are less common (5% to 8% and 3% to 5% of survivors affected, respectively). Approximately one half of disabled survivors have more than one major disability. Based on studies of infants less than 750 to 1,000 grams birth weight, it can be anticipated that approximately another half of all extremely premature survivors will have one or more subtle neurodevelopmental disabilities in the school and teenage years. There is little evidence to suggest that long-term neurodevelopmental outcome has changed from the late 1970s to the early 1990s or with increasing survival. Survival of individual extremely premature infants cannot be accurately predicted in the immediate perinatal period. Major disability cannot be accurately predicted for individual survivors during the course in the newborn intensive care unit.

Treatment decisions for the extremely premature infant

Treatment decisions for the extremely premature infant

Growth of adolescents who were born at extremely low birth weight without major disability

To compare growth between adolescents who were born at extremely low birth weight (ELBW, </=1000 g) and adolescents who were born at normal birth weight (NBW, >/=2500 g). Cross-sectional design. Fifty-three ELBW and 53 NBW adolescents without a major neurodevelopmental disability were matched by sex, race, age, and socioeconomic status. Anthropometrics (z scores), bone age, body composition (Lunar DPX-L densitometry), and sexual maturity were assessed. ELBW adolescents were classified as being born small for gestational age (SGA) or not (NSGA). Subjects were 58.5% female, 43.4% black, and 56.6% white. The mean birth weight for ELBW subjects was 849 g and 3355 g for NBW subjects. The mean age was 14.85 years. On average, ELBW adolescents were 4.8 cm shorter and 9.1 kg lighter than NBW adolescents. ELBW adolescents had lower mean z scores for height (P <.0001), weight (P <.0001), and head circumference (P <.0001) than NBW adolescents. ELBW/SGA subjects had lower mean z scores for height (P <.0001) and weight (P =.001) than NBW subjects. Head circumference z scores were lower for the ELBW/SGA group than the ELBW/NSGA group or the NBW group (P =. 003). Sexual maturity and relative body composition were similar between groups. Bone age, measured in SD units, was more advanced in the ELBW group (0.86 vs. 0.42, P =.039). ELBW adolescents who survive without a major neurodevelopmental disability attain lower growth measurements compared with NBW adolescents but have similar sexual maturation and relative body composition.

Disabilities among preemies

[unknown] Kilbride HW, Daily DK. Journal of Perinatology. 1998;18(2):102-6. [unknown] Lorenz JM, et al. Archives of Pediatrics & Adolescent Medicine. 1998;152:425-35. Although more extremely premature neonates are surviving, the prevalence of major neurodevelopmental disabilities has not changed over time, according to two studies. In the first study, researchers compared 405 infants weighing 450 grams to 800 grams (about 1 pound to 1 pound, 12 ounces) born between 1983 and 1989 at two Kansas City, Mo., hospitals. When the children were 5 years old, the authors assessed their cognitive, psychomotor and language performance and evaluated them for cerebral palsy (CP) and visual and hearing impairments. Forty-seven percent of infants born between 1983 and 1985 with a gestational age ≥24 weeks survived compared to 60 percent born in the 1986 to 1989 time period. There was no change in the percentage of infants suffering long-term disabilities. In the second study, researchers used Medline to analyze 42 studies from 1970 to 1997 on mortality and disability in infants born at or before 26 weeks9 gestation (extremely immature) or with a birth weight of 800 grams or less (extremely small).

A quantitative review of mortality and developmental disability in extremely premature newborns.

To summarize the literature on mortality rates and prevalences of major neurodevelopmental disabilities and to examine trends of these outcomes over time in extremely premature neonates. MEDLINE was used to search the English literature for studies published since 1970 reporting on both mortality and disability in infants born at or before 26 weeks' gestation (extremely immature [EI] cohort), with a birth weight of 800 g or less (extremely small [ES] cohort), or subgroups of these. Studies were included in the analysis if all of the following were reported: mortality; direct examination of 75% or more of the survivors; and the proportion of patients with at least 1 of the following disabilities: cerebral palsy, mental retardation, blindness, and deafness. Studies reporting cohorts included as a subset of cohorts in another study were excluded. Forty-two studies providing mortality and disability data for 20 cohorts of 4116 EI infants and 38 cohorts of 4345 ES infants born after 1972 met the inclusion criteria. Data were abstracted from all studies that met these criteria by two of us (J.M.L. and D.E.W.), independently; the data were then cross-checked to ensure accuracy. Survival averaged 41% for EI infants and 30% for ES infants, and it increased significantly with time. In contrast to mortality, the prevalences of major neurodevelopmental disabilities among survivors have not changed over time. The most common major disability was mental retardation, found in 14% of EI and ES survivors. Cerebral palsy was found in 12% of EI survivors and 8% of ES survivors, blindness was found in 8% of EI and ES survivors, and deafness was found in 3% of EI and ES survivors. Overall, 22% of EI survivors and 24% of ES survivors were classified as having at least 1 major disability. Each 100 EI or ES livebirths yielded 7 children with major disabilities; this prevalence was correlated with survival across cohorts. The prevalence of disabilities had not changed among EI or ES survivors with increasing survival. However, increasing survival of these infants has resulted in a steadily increasing prevalence of children with disabilities.

A biochemical study on mothers of children with congenital neurodevelopmental abnormalities

A biochemical study has been undertaken on the mothers of children with a major neurodevelopmental disability, without known etiology (study group), and an appropriate control group. Two hundred seventy-four mothers were studied, 137 in each group. Social and environmental details were recorded in earch of the two major groups. Biochemical studies included the assay of plasma and urinary amino acids and appropriate screening tests for carbohydrate and organic acid abnormalities. To introduce an element of standardization and also to enhance the opportunities for identifying possible biochemical heterozygote states, a 50-g protein mean was given to all subjects approximately three-quarters of an hour before blood and urine samples were taken. Difference of means tests on 22 amino acids revealed 9 significant t values at the 0.05 level and all means were significantly lower in the study groups. Because of the differences noted a discriminant analysis was carried out which demonstrated an extremely high proportion of correctly classified subjects (98%) when biochemical parameters were used to attempt to classify subjects into the study or control group.