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Proton MR spectroscopy for the evaluation of brain injury in asphyxiated, term neonates.

BACKGROUND AND PURPOSE: Neurologic and developmental outcomes of asphyxiated, term neonates are difficult to predict applying clinical or laboratory criteria. In this study, we investigated the association of MR spectroscopy (MRS) results with neurodevelopmental status at age 12 months. METHOD: Thirty-one term neonates, who were enrolled in a prospective study of the utility of MR imaging for the determination of neurologic and developmental status, underwent single-voxel proton MRS of the basal nuclei and intervascular boundary zones. Ratios of lactate, choline, creatine, and N-acetylaspartate (NAA) peaks were calculated and tested for association with neuromotor scores and Mental Development Index of the Bayley Scores of Infant Development obtained at age 12 months. RESULTS: Elevated lactate and diminished NAA were the most common findings in infants with neurologic and developmental abnormalities at age 12 months. Although many ratios had statistically significant associations with outcome (P<.05), the highest significance was obtained with lactate/choline ratios in the basal nuclei. A false-positive finding was seen in a patient who was born after a 36-week gestation period (high lactate/choline but normal neurodevelopmental status at 12 months) and in three patients with apparent watershed injury (high watershed lactate/choline but normal neurodevelopmental status at 12 months). A false-negative MRS finding (normal lactate/choline but abnormal outcome) was seen in a patient who had an apparent prenatal injury. CONCLUSION: Proton MRS appears to be a useful tool for assessing brain injury in neonates who have suffered hypoxia or ischemia. Correlation with gestational age and imaging findings are essential for proper interpretation of the spectra. Patients with apparent watershed injuries may have normal neurodevelopmental status at age 12 months.

Aspartic Acid↗

Measurement of antibody against contemporary virus lineages of human respiratory syncytial virus sub-group A in infants and their mothers.

BACKGROUND: Human respiratory syncytial virus (hRSV) infects the majority of infants in their first year of life. Maternal antibodies offer some protection although a small proportion of infected infants develop bronchiolitis and require admission to hospital. A number of lineages of the virus co-circulate in the population and the prevalent virus lineage changes from epidemic to epidemic. The effect of antigenic variation between virus lineages upon the protection offered by maternal antibodies has not been assessed. OBJECTIVES: To explore the possibility that infants may develop bronchiolitis because of a virus lineage-specific deficiency in their maternal antibodies. STUDY DESIGN: Virus isolates from infants admitted to hospital in Newcastle upon Tyne with hRSV infection during two consecutive winter epidemics were classified into lineages by genotypic analysis. Antibodies to the surface glycoproteins of contemporary sub-group A lineages and to the A2 virus strain were assayed in the acute sera of infected infants, in a group of uninfected infants and in the mothers of both groups. RESULTS: Four lineages of sub-group A hRSV were found circulating during the study period. Antibody titres measured against all virus lineages in the acute serum of infants with hRSV bronchiolitis were similar. In the uninfected infants and in the mothers of both infected and uninfected groups antibody titres to all four contemporary virus lineages were also similar. However, in these groups antibodies to the A2 virus strain were four-fold lower than those to contemporary isolates. CONCLUSIONS: Infants admitted to hospital with hRSV bronchiolitis exhibited no apparent selective deficiency in maternal antibodies to the viral glycoproteins of the infecting virus strain or lineage.

Antibodies, Viral↗

Infants of postpartum depressed mothers: temperament and cognitive status.

This study examined the association of postpartum depression with specific infant characteristics. Twenty-five diagnosed depressed and 25 nondepressed mothers and their 2-month-old infants participated in the study. The mothers completed measures of infant temperament and difficulty associated with infant care, and the infants were assessed using the Bayley Scales of Infant Development. Group comparisons indicated that, compared with the infants of the nondepressed mothers, the infants of the depressed women were less competent cognitively and expressed more negative emotions during the testing. The depressed mothers perceived their infants as more difficult to care for and more bothersome than did the nondepressed mothers, but did not attribute these difficulties to the temperament of their infants. These findings suggest that postpartum depression is associated with an identifiable pattern of infant behavior that may exacerbate depressed women's mood.

Adult↗

Correlations between antepartum maternal metabolism and intelligence of offspring.

BACKGROUND: It is not clear to what extent maternal metabolism during pregnancy affects the cognitive and behavioral function of the offspring by altering brain development in utero. To investigate this question, we correlated measures of metabolism in pregnant diabetic and nondiabetic women with the intellectual development of their offspring. METHODS: The study included 223 pregnant women and their singleton offspring: 89 women had diabetes before pregnancy (pregestational diabetes mellitus), 99 had the onset of diabetes during pregnancy (gestational diabetes mellitus), and 35 had normal carbohydrate metabolism during their pregnancy. We correlated measures of maternal glucose and lipid metabolism (fasting plasma glucose levels, hemoglobin A1c levels, episodes of hypoglycemia, episodes of acetonuria, and plasma beta-hydroxybutyrate and free fatty acid levels) with two measures of intellectual development in the offspring--the mental development index of the Bayley Scales of Infant Development, given at the age of two years, and the Stanford--Binet Intelligence Scale, given at the ages of three, four, and five years and expressed as an average of the three scores. RESULTS: After correction for socioeconomic status, race or ethnic origin, and patient group, the children's mental-development-index scores at the age of two years correlated inversely with the mothers' third-trimester plasma beta-hydroxybutyrate levels (r = -0.21, P less than 0.01); the average Stanford-Binet scores correlated inversely with third-trimester plasma beta-hydroxybutyrate (r = -0.20, P less than 0.02) and free fatty acid (r = -0.27, P less than 0.002) levels. No other correlations were significant. Including various perinatal events (e.g., prematurity and acidemia) in the analyses did not alter the results. CONCLUSIONS: Maternal diabetes during pregnancy may affect behavioral and intellectual development in the offspring. The associations between gestational ketonemia in the mother and a lower IQ in the child warrant continued efforts to avoid ketoacidosis and accelerated starvation in all pregnant women.

3-Hydroxybutyric Acid↗

Mental development and learning disorders in children with single suture craniosynostosis.

OBJECTIVE: This study examined the global intellectual development and presence/absence of learning disorders in children with nonsyndromic metopic, sagittal, and unilateral coronal synostosis who had early surgery (under 1 year of age), late surgery (over 1 year of age), or no surgery to correct the synostosis across three time periods. DESIGN: The design was longitudinal. Children were assessed at initial team evaluation, 1 year after surgery or initial evaluation if surgery was not performed, and annually thereafter. PARTICIPANTS: Participants included 84 consecutively evaluated patients. Seventy-two children were evaluated at Time 1 (T1), 8 months; 57 at Time 2 (T2), 21 months; and 39 at Time 3 (T3), 50 months. Data on learning disorders or mental retardation were available on 34 children who were school age. MAIN OUTCOME MEASURES: The Mental Development Index from the Bayley Scales of Infant Development was the main outcome measure for T1 and T2. The General Cognitive Index from the McCarthy Scales of Children's Abilities was the main outcome measure for T3. Learning disorders were determined from school and clinical records. RESULTS: Repeated measures analyses of variance found no statistical differences in the development of children based on diagnosis or surgical status across time. Base rate of mental retardation at T1 was consistent with normative data; however, the incidence of retardation was two to three times the expected rate at T2 and T3. Learning disorders were present in 47% of school-age children who were not retarded. Chi-square analysis showed no significant differences between rates of retardation or learning disorders based on surgical status. CONCLUSIONS: Most children with nonsyndromic craniosynostosis obtain developmental quotients within the normal range in infancy. Rates of retardation may increase relative to normative expectations as children mature. A high rate of learning disorders was identified. Results are preliminary due to sample size.

Age Factors↗

Assessing the early characteristics of autistic disorder using video analysis.

The behaviours of infants were observed using home videos, in an attempt to identify social difficulties characteristic of infants with autistic disorder. Three groups of infants were analysed: 15 infants who had later been diagnosed with autism, 15 infants who had a developmental or language delay, and 15 typically developing infants. Social behaviours were coded using both quantitative and qualitative measures. The principal discriminating items between the groups were found to be 'peer interest', 'gaze aversion', 'anticipatory postures', and 'proto-declarative showing'. The results suggest that these children later diagnosed with autism are clinically distinct from their peers before the age of two years, and that there are clearly observable behaviours which are important predictors of autistic disorder in pre-verbal children.

Autistic Disorder↗

Antidiuretic hormone excess in infant botulism.

Two infants developed evidence of antidiuretic hormone excess as a complication of infant botulism. Neither child received mechanical ventilatory support before the development of hyponatremia, serum hyposmolality, and urinary hyperosmolality. Both infants responded to fluid-intake restriction. The appearance of hyponatremia in an infant with botulism should suggest antidiuretic hormone excess. The recognition of this entity will lead to its appropriate management with fluid-intake restriction.

Botulism↗

Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new insight into the development of ROP.

Cryosurgery↗

[Developmental changes in the Collis horizontal reaction analyzed using a three-dimensional video motion analysis system. II. Examination of upper-limb movement during the Collis horizontal reaction].

At four months old, infants of 72% challenged with the Collis horizontal reaction touch the floor with the back of their free hand. As the infants grow older, the ratio of infants that open their free hand and perform a support reaction increases from 0% to 100%. At nine months old, all infants perform this support reaction with their free hand palm-side down. To assess infant development more accurately, we used a three-dimensional video motion analysis system to evaluate upper limb movement in 38 infants (total 151 times) from 4-9 months old during the second and third phases determined by the Collis horizontal reaction. By analyzing the constituent components of upper limb movement during the Collis horizontal reaction, we assessed the usefulness of the reactions as an objective tool to measure developmental changes in infants. During the analysis, we thought to assess the speed of the upper limb reaction was respect to pronating the forearm, supporting the body with the palm down, and location of their free hand. The analysis shows that if development progresses normally and infants pronate the forearm to support the body with the palm down, the central value at which their free hand is located moves to a point under the shoulder. The results suggest that in infants four to nine months old, the Collis horizontal reaction is an excellent method to assess not only the present physical development level, but also future physical development attainment by only evaluating developmental changes of upper limb movement only.

Child Development↗

Surgery is safe in very low birthweight infants with necrotizing enterocolitis.

The aim of this study was to determine how the operative event itself affects very low birthweight (VLBW) infants (< 1500 g) with necrotizing enterocolitis (NEC) undergoing surgery, and to try to identify preventable factors leading to perioperative morbidity and mortality. Eighty-five VLBW infants developed NEC during a 6-year period; 34 of those required emergent celiotomies. Data were collected retrospectively from hospital charts available on 33 infants. Birthweight ranged from 566 g to 1415 g (mean +/- SD: 961+/-262 g) and gestational age from 24 to 34 wk (28+/-3.2 wk). Thirty infants had been fed premature formula (first feed at 5+/-3.6 d) prior to the onset of symptoms and three had not been fed at all. Age at NEC symptoms was 19+/-15 d. Infants < 1000 g developed NEC much longer after the first feed compared to infants > 1000 g (p < 0.002; t-test). In 42% of the children, intraoperative blood pressure fell at least 20% from the preoperative value. Body temperature dropped from a preoperative 36.5+/-0.340 degrees C to 35.5+/-1.20 degrees C (p < 0.005), although in all children two or more heating devices were employed in the operating room. All infants survived the procedure. Six infants with pannecrosis died within 72 h of the operative event. In an appropriate setting, operative intervention under general anesthesia is well tolerated by VLBW infants with NEC. Since hypothermia was a major problem, the authors have modified their approach and now no longer transport these infants to the operating room. Instead, these infants are operated upon in the neonatal intensive care unit, directly on an infant radiant warmer system.

Digestive System Surgical Procedures↗

Salmonella meningitis and its complications in infants.

OBJECTIVE: To review the presenting features, complications and outcome of infants with Salmonella meningitis. METHODOLOGY: Retrospective review of all cultures of cerebrospinal fluid positive for bacteria in children below 12 years of age, processed at the Department of Medical Microbiology, University of Malaya Medical Centre, Kuala Lumpur from 1973 to 1997. Records of all cases positive for Salmonella species were retrieved and studied. RESULTS: Thirteen infants aged 3 days to 9 months with Salmonella meningitis were included. The median age of onset of symptoms was 4 months. The clinical and laboratory features were similar to other causes of bacterial meningitis. Salmonella enteritidis was the commonest serotype isolated. Nine infants developed fits, six of which were difficult to control. Other complications noted were hydrocephalus (five), subdural effusions (four), empyema (three), ventriculitis (two), intracranial haemorrhage and cerebral abscess (one each). The use of ampicillin and/or chloramphenicol and inadequate duration of therapy resulted in recrudescence or relapse in five infants. The overall mortality was 18%. The presence of empyema, intracerebral abscess, ventriculitis, hydrocephalus, and intracranial haemorrhage were associated with adverse neurodevelopmental sequelae or death. More than half of those who survived had normal long-term outcome. CONCLUSION: Infants who developed neurological complications as a result of Salmonella meningitis had significant mortality and adverse long-term neurodevelopment outcome.

Anti-Bacterial Agents↗

Clinical course and outcome of fetuses with isolated cystic nuchal lesions and normal karyotypes detected in the first trimester.

OBJECTIVE: We assessed newborn outcome and infant development in cases of first-trimester fetal cystic nuchal lesion and normal karyotype. STUDY DESIGN: Information regarding newborn outcomes and infant growth and development was prospectively obtained from 32 consecutive pregnancies characterized by fetal cystic nuchal lesions detected in the first trimester (< or = 13.9 weeks' gestation) and normal karyotypes. RESULTS: Cystic nuchal lesions spontaneously resolved by the twentieth gestational week in 31 cases; all 31 infants had normal results at newborn examination and demonstrated normal growth and development at 12 months of age. Resolution did not occur in one case; prominent hygromas were repaired at birth with normal growth and development through 2 1/2 years of age. CONCLUSIONS: In most affected fetuses with normal karyotypes, spontaneous resolution will occur with favorable newborn and infant outcomes. However, patients should be counseled that resolution may not occur or that nonchromosome abnormalities may result in a less favorable outcome.

Chromosomes↗

Epidemiology of necrotizing enterocolitis: a case control study.

All neonates with necrotizing enterocoltis cared for at Grady Memorial Hospital from July, 1977, through February, 1979, were compared with controls matched for birth weight and time of admission to the nursery, to examine risk factors which have been implicated in the etiology of the disease. Data on maternal history, birth history, and hospital course were uniformly collected and contrasted for 35 cases and 98 controls. Low birth weight was associated with an increased incidence of NEC and an increased case fatality rate. All babies 36 weeks or more at birth were diagnosed by seven days. More immature infants developed the disease later in their hospital course. In addition, preterm babies who developed NEC after 2 weeks of age appear to be smaller and sicker. Factors previously thought to predispose an infant to the development of the disease, such as prolonged rupture of membranes, infectious complications of pregnancy, low Apgar scores, patent ductus arteriosus, and use of umbilical catheters, were found with equal frequency in cases and controls and may simply represent the descriptive characteristics of a population of sick premature infants. Feeding history and antibiotic use were examined in depth and were not correlated with the development of NEC.

Anti-Bacterial Agents↗

Neurodevelopmental outcome of 'at risk' nursery graduates.

A cohort study at a tertiary care neonatal service was undertaken to determine the neurodevelopmental outcome of neonates who required intensive care. One hundred and nineteen nursery graduates were enrolled for follow up if they fulfilled any of the following risk factors: birth weight less than 1500 g, Apgar score less than 4 at 5 minutes, seizure(s), and required assisted ventilation for more than 24 hours. They were subjected to periodic clinical evaluation and administered the Bayley Scales of Infant Development in early childhood. Of the total infants enrolled, 101 completed the required follow up. They included 55 infants with birth weight < 1500 g, 45 with low Apgar scores, 12 with seizure(s) and 28 who received assisted ventilation. An overwhelming majority of subjects (85%) had normal neurodevelopmental outcome. The adverse outcome in the remaining 15 included mental retardation in all, subnormal motor development in 14, microcephaly in 1, hearing loss in 2 and visual impairment in 4. Among the neonatal risk factors, seizures, sepsis and hypoxic ischemic encephalopathy had a significant association with adverse outcome. Despite serious neonatal morbidity, the early neurodevelopmental outcome of nursery graduates was reasonably good. The association of neonatal sepsis with neurodevelopmental sequelae merits a prospective evaluation.

Brain Damage, Chronic↗

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.

Brain↗

The relationship between generalized joint hypermobility and motor development.

PURPOSE: The aim of this study was to investigate the relationship between the presence and localization of joint hypermobility and delay in motor development. METHODS: A retrospective chart review was performed. All children younger than 2.5 years of age and between four and 12 years of age with generalized joint hypermobility were included. Generalized joint hypermobility was assessed using the criteria of Bulbena. In children between one and 2.5 years of age, motor development was measured using the Bayley Scales of Infant Development. In children four to 12 years of age, the Movement Assessment Battery for Children was used. RESULTS: Data from 72 children were available for analysis. In nine of 16 children younger than 2.5 years of age, a delay in motor development was found without a significant association between the delay in motor development (yes/no) and the Bulbena score (odds ratio: 0.4; 95% confidence interval: 0.07-2.1). In children between four and 12 years of age, a severe delay in motor development was present in 14 of 56 children (25%), while 12 of 56 children (21%) were at risk and 30 of 56 (54%) were age appropriate. No significant association between delay in motor development and the Bulbena score was found (odds ratio: 1.3; 95% confidence interval: 0.8-2.1). The age of independent walking was not significantly associated with the number of hypermobile joints (Bulbena score) (linear regression coefficient: 0.3; 95% confidence interval: -1.5 - 2.1). CONCLUSIONS: Although severe delays in motor development may be observed in approximately one third of children with generalized joint hypermobility, there is no association between the amount of generalized joint hypermobility and delay in motor development.

Child↗

Sequential acquisition of toilet-training skills: a descriptive study of gender and age differences in normal children.

OBJECTIVE: To compare the ages, by gender, at which normally developing children acquire individual toilet-training skills and to describe the typical sequence by which children achieve complete toileting success. METHODS: A longitudinal survey was conducted of a cohort of children who were 15 to 42 months of age and attending 4 pediatric practices in the Milwaukee area (2 inner city and 2 suburban) from 1995 through 1997. Parents completed background surveys, and each child's development was assessed using the Bayley Scales of Infant Development II. Each week for 12 to 16 months, parents completed a training status survey (TSS). The TSS, designed for this project, included information on daily toilet-training status (eg, number of urine successes on a 5-point scale) and 28 weekly toilet-training behaviors rated on a 5-point Likert scale from 1 (never) to 5 (always). Children were considered to have acquired a particular skill when they received a rating of 4 or 5 on the TSS scale. The median age and interquartile range for children for each toilet-training skill are reported for girls and boys separately using survival curve analysis. Ages at which each gender achieved these skills are compared using a log-rank test. RESULTS: The study included 126 girls and 141 boys; 88% were white. Parents submitted a total of 10 741 weekly surveys (range: 1--73; median: 49 per child). Girls demonstrated toilet-training skills at earlier ages than boys. The median ages for "staying dry during the day" were 32.5 months (95% confidence interval: 30.9--33.7) and 35.0 months (95% confidence interval: 33.3--36.7) for girls and boys, respectively. The median ages for readiness skills for girls and boys, respectively, were as follows: "showing an interest in using the potty," 24 and 26 months; "staying dry for 2 hours," 26 and 29 months; "indicating a need to go to the bathroom," 26 and 29 months. There was a marked concordance in the sequences in which girls and boys achieve individual skills. In addition, the interquartile ranges of the toileting skills varied from 6.9 to 11.4 months in girls and from 7.5 to 14.6 months in boys. CONCLUSIONS: In this study population, girls achieve nearly all toilet-training skills earlier than boys, including successful completion. Most children do not master the readiness skills until after the second birthday. The range of normalcy for the attainment of individual skills may vary by as much as a year.

Age Factors↗

Outcome of very low birth weight infants at 12 to 18 months of age in Soweto, South Africa.

OBJECTIVE: To describe the long-term outcome of very low birth weight infants growing up in poor socioeconomic conditions in Soweto, South Africa. METHODS: A stratified sample of infants weighing < 1500 g surviving to hospital discharge was enrolled. Group 1 consisted of 49 infants 1000 to 1499 g who required mechanical ventilation; group 2 consisted of 39 infants 1000 to 1499 g who did not require mechanical ventilation; and group 3 consisted of 25 infants < 1000 g (such infants are not routinely ventilated). Growth and neurological status were recorded at follow-up visits at 3, 6, and 12 months' corrected age and the infants were evaluated further using the Bayley scales of infant development between 12 and 18 months. RESULTS: Fifteen infants died during the period between hospital discharge and 1 year corrected age, and 12 others were lost to follow-up. Although some catch-up growth was noted in the early months, all group means for weight and length were below the 25th percentile at 1 year. Cerebral palsy was diagnosed in nine infants (8 from group 1). Periventricular leukomalacia and/or porencephaly was diagnosed in eight of the nine infants during their initial hospital stay and was also the strongest negative predictor of the Bayley scores. Higher maternal education and better intrauterine growth were associated with higher Bayley scores. CONCLUSIONS: Mortality after hospital discharge in this study cohort was extremely high. However, despite marked differences in socioeconomic conditions and tertiary care facilities, the handicap rates were comparable with recent studies from developed countries, and some of the predictors of handicap, eg, periventricular leukomalacia and porencephaly, were also similar.

Cerebral Palsy↗