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PubMed2005

Folate status of mothers during pregnancy and mental and psychomotor development of their children at five years of age.

OBJECTIVE: There are limited data relating folate nutritional status of mothers during pregnancy to mental and psychomotor development of their offspring. Using an existing data set from a study on the effect of prenatal zinc supplementation on child neurodevelopment, we evaluated the association between folate nutritional status of mothers during pregnancy and neurodevelopment of their children. METHODS: Maternal blood folate and total homocysteine (tHcy) concentrations were measured at 19, 26, and 37 weeks of gestation. At a mean of 5.3 years of age, 355 black children with low-socioeconomic background were given 6 tests: Differential Ability Scales, Visual and Auditory Sequential Memory, Knox Cube Test, Gross Motor Scale, and Grooved Pegboard. The scores of the tests between the 2 groups of mothers with poor versus adequate folate nutritional status classified by blood folate or tHcy concentrations were compared. RESULTS: There were no differences in the test scores of neurodevelopment between the 2 groups. CONCLUSION: Folate nutritional status of mothers in the later half of pregnancy assessed by plasma and erythrocyte folate and plasma tHcy concentrations had no impact on neurodevelopment of their children at age 5. It is unknown whether our findings in a low-socioeconomic population can be readily extrapolated to other populations.

Adult↗

PubMed1998

Neurodevelopmental anomalies in children with neuroblastoma.

BACKGROUND: Case reports have associated neuroblastoma, a cancer derived from the embryonal neural crest, with aganglionosis coli and neurofibromatosis type I. The aim of the current study was to test the hypothesis that neuroblastoma is part of a global defect in neurodevelopment. METHODS: Neuropathologic findings from autopsies of children who died of neuroblastoma during the period 1980-1995 at the Children's Hospital of Pittsburgh were reviewed for macroscopic and microscopic abnormalities. As controls, autopsies of children who had died of other primary extracranial cancers over the same time period also were studied. Medical records of neuroblastoma patients for whom autopsies were available were reviewed for clinical evidence of preexisting nonmalignant neurologic disease. RESULTS: Of 145 children diagnosed with neuroblastoma, 49 had died, and autopsies not restricting examination of the brain had been performed on 13. Macroscopic anatomic abnormalities (a small cerebellum and the absence of the corpus callosum) were noted in one patient who was known to have been mentally retarded without having a defined syndrome. Microscopic abnormalities of cytoarchitecture were noted in that patient as well as 3 of the 12 other patients (focal cortical dysplasia [fcd], n = 3; leptomeningeal heterotopia, n = 1; abortive sulcation or flattened gyri, n = 2). None of 3 patients with only microscopic abnormalities had clinical evidence of problems with neurodevelopment. Of the 26 children with nonneuroblastoma cancers for whom complete autopsies were available, 1 infant had major macroscopic structural abnormalities of the brain. None of these patients had microscopic abnormalities (P < 0.01). CONCLUSIONS: Children with neuroblastoma have an increased incidence of abnormalities of brain cytoarchitecture, particularly fcd. These abnormalities are generally asymptomatic and are diagnosed by histologic examination. Such abnormalities cannot be attributed to chemotherapy and are not observed in other children with non-central nervous system tumors. These findings are consistent with the concept that neuroblastoma may occur in the setting of a more global defect in neurodevelopment. A blinded review of larger numbers of cases will be needed to verify these data.

Adolescent↗

PubMed2000

Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage.

BACKGROUND: Preterm infants are at risk of periventricular haemorrhage. This can damage the brain and lead to neurodevelopmental abnormalities, including cerebral palsy. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the brain. OBJECTIVES: The objective of this review was to assess the benefits and harms of giving phenobarbital to women at risk of imminent very preterm birth with the primary aim of preventing periventricular haemorrhage in the infant. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies. Date of last search: December 1998. SELECTION CRITERIA: Randomised trials with reported data which compare outcomes, such as neonatal mortality, neonatal neurological and other morbidity, longterm neurodevelopment and maternal morbidity, following prenatal exposure to phenobarbital, with outcomes in controls with or without placebo. DATA COLLECTION AND ANALYSIS: Assessments of trial eligibility, quality and data extractions were done by the two authors independently. Eligible trials were included in the initial analysis and prespecified sensitivity analyses done to evaluate the effect of trial quality. MAIN RESULTS: Over 1600 women were entered into the eight trials included. Analyses showed a significant reduction in the rates of all grades of periventricular haemorrhage (PVH) (relative risk 0.75, 95% confidence interval 0.65 to 0.88) and severe grades PVH (3 and 4) (relative risk 0.49, 95% confidence interval 0.32 to 0.74) in infants whose mothers had been given prenatal phenobarbital. These results were influenced by the earlier trials which were of poorer quality and contributed excessive weight in the analysis due to their higher rates of severe PVH. Over time, and with improved trial quality, these beneficial effects disappeared. No difference was found in the incidence of neurodevelopmental abnormalities at paediatric follow-up assessed between 18-36 months of age. Maternal sedation was more likely in women receiving phenobarbital. REVIEWER'S CONCLUSIONS: Phenobarbital administration to women prior to preterm birth cannot be recommended for routine clinical practice. Any future trials should examine the effects of phenobarbital prior to preterm birth at gestational ages with a high risk of PVH, stratify for gestational age and ensure minimal exclusions after randomisation. Neurodevelopmental status at follow-up should be measured as the most important outcome.

Central Nervous System Agents↗

PubMed2004

Width of the fetal lateral ventricular atrium between 10 and 12 mm: a simple variation of the norm?

OBJECTIVES: The prognosis of borderline forms of anomalies that can be detected by ultrasound is one of the most challenging issues in prenatal diagnosis. The aim of this study was to determine the prognosis for fetuses presenting with isolated mild ventriculomegaly (MVM). METHODS: Fetuses in which the width of the lateral ventricular atria was 10-12 mm and which had no other detectable chromosomal or morphological anomalies were followed by monthly ultrasound examinations until delivery. For the cases identified up to December 1997, postnatal information was gathered retrospectively through interviews. Children born from January 1998 onwards were included in a protocol involving planned neuropsychiatric visits at 12 and 18 months of age in which the Griffith scale was used to assess neurodevelopment. RESULTS: Between September 1992 and January 2001, 60 fetuses with isolated MVM were identified. Ventricular dilatation diminished in 18 cases (and became normal in nine of these) and stabilized in 42 cases. Information was obtained on 38 children born up to December 1997 and their neurodevelopment was found to be completely normal. The 22 children born from January 1998 onwards showed normal development at 12 and 18 months of age. CONCLUSIONS: When MVM is observed on prenatal ultrasound examination it can be very difficult to offer parents appropriate counseling. It is important to exclude aneuploidy or morphological abnormalities but even then there will be anxieties about long-term neurological outcome. Our data, which show normal neurodevelopment between 18 months and 10 years after birth in cases of MVM (10-12 mm), should provide a basis for reassuring counseling.

Adult↗

PubMed2006

Neurosteroids in child and adolescent psychopathology.

Neurosteroids play a significant role in neurodevelopment and are involved in a wide variety of psychopathological processes. There is accumulating evidence on their role in adult psychopathology, including Alzheimer disease, schizophrenia, mood disorder, anxiety disorders and post-traumatic stress disorder. Little is known, however, about the possible role of neurosteroids in child and adolescent psychopathology although there is increasing evidence for their critical role from the early stages of brain development until adolescence. In this review we focus on the involvement of neurosteroids in neurodevelopment and mental disorders in children and adolescents. Adequate physiological levels protect the developing neural system from insult and contribute to the regulation of brain organization and function. Neurosteroids may be involved in the pathophysiology and pharmacotherapy of a variety of disorders in children and adolescents, including schizophrenia, depression, eating disorders, aggressive behavior and attention deficit. The complex interaction between neurosteroids, neurodevelopment, life-events, genetics and mental disorders in children and adolescents merits further investigation.

Adolescent↗

PubMed1998

Brain torque and sex differences in schizophrenia.

The opposing asymmetry of the frontoparietal brain regions has been referred to as 'torque' and may be used as an index of speed of neurodevelopment. It has been recently suggested that torque is minimized in male schizophrenia, reflecting anomalous neurodevelopment. This study examined volumetric and linear torque in a group of 20 schizophrenia patients and 20 healthy individuals; all were right-handed and under the age of 46 years. None of the main or interaction effects on torque were statistically significant, although the sex difference in torque among schizophrenia patients (male larger than female) was more than seven times that in healthy subjects. Torque was significantly associated with years of education and age of illness onset (schizophrenia). These findings support the hypothesis that slowed neurodevelopment may be associated with male schizophrenia and may contribute to earlier age of onset and fewer years of education.

Adult↗

PubMed2002

[Early cerebral MRI in preterm infants: correlations with EEG and outcome].

AIM OF THE STUDY: Assess the potential benefits of performing an early cerebral MRI to evaluate the gravity of cerebral lesions among premature neonates at risk of neurologic sequels and establish correlations between EEG findings, abnormal neuroimaging findings and neurodevelopment. METHODS: A MRI was performed in 34 premature newborn babies with abnormal neurological clinical signs, and/or with two abnormal EEG and/or with two abnormal cerebral ultrasound scans. The mean age and the adjusted age of our population were 5 weeks (range 1-11 weeks) and 35 weeks of adjusted age (range 29-40 weeks) respectively. The neuroimaging findings were correlated to the results of three EEGs (recorded before 15 days old, between 15 days and one month old, and after the first month of life) and to neurodevelopment. RESULTS: Two statically significant correlations were found between: 1) the severity of brain injuries observed in MRI and the results of the latest EEG (sensitivity 100%, specificity 60%), 2) the severity of brain injuries observed in MRI and abnormal neurodevelopment (sensitivity 75%, specificity 80%). There was no correlation between the abnormal development and the results of EEG recordings. CONCLUSION: Early cerebral MRI is justified in a selected premature population. It is useful for the diagnosis, the evaluation of the severity of brain injury and for the management of these children. The correlation with EEGs traces allows the detection of the majority of prematures babies that will develop sequels.

Brain Diseases↗

PubMed2006

Health before and after adoption from Eastern Europe.

DESIGN: A population-based study of pre-adoption, arrival and post-adoption health. AIM: To report prenatal and postnatal background factors, morbidity, growth and development in adoptees from Eastern Europe. SUBJECTS AND METHODS: All 99 children born in Eastern Europe between 1990 and 1995 and adopted to western Sweden during 1993-1997 were invited to participate in the study. Altogether, 76 (77%) participated. Medical records from the birth countries, from the examination at arrival and from medical reports made during a mean post-adoption period of 5 years were evaluated. RESULTS: Low birth weight (< or = 2500 g) occurred in 48%. Congenital malformations were found in 22%. The biological mothers of 33% of the children had been considered alcoholics, and 16% of the children's mothers had been diagnosed with a psychiatric disability. A high incidence of infectious diseases, neurodevelopment disorders and growth retardation had been noted during the pre-adoption period. Upon arrival in Sweden 75% were diagnosed with a medical condition, most often an infection. After a 5-year post-adoption period, small head circumference was associated with alcohol exposure during pregnancy and 46% had at least one neurodevelopment or behavioural disorder. CONCLUSION: Adverse prenatal and perinatal factors, congenital malformations and post-adoption neurodevelopment disorders were common. Adoptees and adopters have complex needs for health support and information.

Adoption↗

PubMedDate not supplied

Effects of maternal prenatal stress on infant outcomes: a synthesis of the literature.

There is growing evidence that maternal prenatal stress may be hazardous to infant health. Changes in maternal hormonal and immune function as a result of stress may adversely affect the immune function and neurodevelopment of the fetus. Prenatal stress in the mother may produce lasting effects on the (1) infant's health status, (2) development and function of the infant's immune system, and (3) neurocognitive development of the infant. This article provides a synthesis of current human and animal literature on the effects of maternal prenatal stress on the developing fetus and the infant, with the resulting model evolving out of the framework of psychoneuroimmunology. The intent of the authors is an integrative review. The authors examined the following research question: What effect does maternal prenatal stress have on infants' immune development and neurodevelopment? All relevant studies were reviewed with no exclusion criteria. Major databases (CINAHL, MEDLINE, PsychINFO) were searched using a combination of the following key words: prenatal stress, cytokines, thymus, and infant neurodevelopment.

Animals↗

PubMed2006

Usefulness of an early neurofunctional assessment in predicting neurodevelopmental outcome in very low birthweight infants.

OBJECTIVE: To evaluate whether early neurofunctional assessment may be useful in predicting neurodevelopmental outcome in children of very low birth weight (VLBW). DESIGN: Observational longitudinal study. SETTINGS: Northern Italy. PATIENTS: A total of 250 VLBW children (129 boys, 121 girls) born consecutively 1996-1999. MAIN OUTCOME MEASURES: Neurodevelopment at 36 months of chronological age, classified in accordance with the classification of Tardieu and the International classification of functioning. RESULTS: Of the infants exhibiting normal neurodevelopment (n = 183) or major dysfunction (n = 17) at 3 months of corrected age, 72% and 94% respectively did not change their score during the study. Minor dysfunctions at 3 months of corrected age were transient in 17 (34%) children. After adjustment for neonatal variables, neurodevelopment at 3 months of corrected age remained predictive of dysfunction at 36 months (odds ratio = 4.33, 95% confidence interval 2.05 to 9.12). If the results for the normal and minor dysfunction groups were pooled, the predictive qualities of the 3 month neurofunctional assessment were: sensitivity 0.5, specificity 0.99, positive predictive value 0.94, negative predictive value 0.93. CONCLUSION: Early neurofunctional evaluation may be useful in predicting later neurodevelopmental outcome in VLBW children.

Aging↗

PubMed2026

Paediatric outcomes after maternal nipocalimab for haemolytic disease of the fetus and newborn: an open-label, single-arm study.

OBJECTIVES: To describe haemolytic disease outcomes, growth, neurodevelopment and health-related quality of life (HRQoL) through 24 months of life in infants exposed to nipocalimab in pregnancies at high risk of early-onset severe haemolytic disease of the fetus and newborn (EOS-HDFN). DESIGN: A multicentre, open-label, single-arm trial. SETTING: Centres with expertise in HDFN management. PATIENTS: Pregnant individuals with previous EOS-HDFN and maternal anti-D titres ≥32 or anti-K titres ≥4. INTERVENTIONS: Weekly nipocalimab (30 and/or 45 mg/kg) from 14 to 35 gestational weeks. MAIN OUTCOME MEASURES: Infants' cord-blood alloantibody titres at birth, HDFN management, growth through 6 months, neurodevelopment (caregiver-reported Ages and Stages Questionnaire, third edition (ASQ-3)) and HRQoL assessments through 24 months of life. RESULTS: Of 13 pregnancies, 12 resulted in live births; one fetal loss occurred due to intrauterine transfusion (IUT) complications. A single simple transfusion was administered in one of seven infants delivered after a maternal nipocalimab course without IUTs, where cord blood alloantibody titres were <8. Multiple transfusions (one to seven simple transfusions/infant; one exchange transfusion) were administered to five infants delivered after early nipocalimab discontinuation and IUTs, with cord-blood alloantibody titres ranging from 512 to 32 768. No unusual growth patterns were observed through 6 months. No neurodevelopmental delays were identified through 24 months of life, with mean ASQ-3 domain scores within normal ranges. HRQoL outcomes were positive across physical, emotional, social and cognitive functioning. CONCLUSIONS: Maternal nipocalimab in pregnancies at high risk of EOS-HDFN may reduce adverse neonatal outcomes correlating with low cord-blood alloantibody titres, without affecting growth through 6 months, neurodevelopment or HRQoL through 24 months of life. TRIAL REGISTRATION NUMBER: NCT03842189.

Child Health↗

PubMed2004

Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat.

Until recently, the synthetic glucocorticoid dexamethasone was commonly used to lessen the morbidity of chronic lung disease in premature infants. This practice diminished as dexamethasone use was linked to an increased incidence of cerebral palsy and short-term neurodevelopmental delay. Of more concern is the fact that we know little regarding dexamethasone effects on long-term neurodevelopment. To study the effects of neonatal dexamethasone exposure on long-term neurodevelopment, we have developed a rat model where newborn pups are exposed to tapering doses of dexamethasone at time points corresponding to the neurodevelopmental age when human infants are traditionally exposed to this drug in the neonatal intensive care unit. Using a within-litter design, pups were assigned to one of three groups on postnatal day 2 (P2): handled controls, saline-injected controls, and animals receiving intramuscular dexamethasone between P3 and P6. Somatic growth was decreased in dexamethasone-treated animals. Dexamethasone-treated animals demonstrated slight delays in indexes of neurodevelopment and physical maturation at P7 and P14, but not P20. In adolescence (P45), there was no difference between groups in an open field test. However, as adult dexamethasone-treated animals were less active in the open field and spent more time in closed arms of the elevated plus maze. The serum corticosterone response to crowding stress in dexamethasone-treated animals was no different from controls, but they demonstrate a delay in return of corticosterone levels to baseline. These differences in behavior and hormonal stress responsiveness suggest that neonatal dexamethasone exposure may permanently alter function of the neuroendocrine stress axis.

Adrenocorticotropic Hormone↗

PubMed2003

Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability.

OBJECTIVE: Epidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and young adulthood. The authors describe basic and clinical data supporting adolescent neurodevelopment as a biologically critical period of greater vulnerability for experimentation with substances and acquisition of substance use disorders. METHOD: The authors reviewed recent literature regarding neurocircuitry underlying motivation, impulsivity, and addiction, with a focus on studies investigating adolescent neurodevelopment. RESULTS: Adolescent neurodevelopment occurs in brain regions associated with motivation, impulsivity, and addiction. Adolescent impulsivity and/or novelty seeking as a transitional trait behavior can be explained in part by maturational changes in frontal cortical and subcortical monoaminergic systems. These developmental processes may advantageously promote learning drives for adaptation to adult roles but may also confer greater vulnerability to the addictive actions of drugs. CONCLUSIONS: An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood.

Adaptation, Psychological↗

PubMed2004

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

Adult↗

PubMed2006

Effects of prenatal exposure to polychlorinated biphenyls and dioxins on mental and motor development in Japanese children at 6 months of age.

Several studies have shown that prenatal and/or postnatal background-level exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs) and dioxins, induces adverse effects on the neurodevelopment of children. However, other studies have not detected any harmful influences on neurodevelopment. Furthermore, except in western countries, no developmental tests have been carried out in relation to detailed assessment of exposure to PCBs and dioxins. In this study (the Hokkaido Study on Environment and Children's Health), the effect of prenatal exposure to background levels of PCBs and dioxins on infant neurodevelopment in Japan/Sapporo was elucidated. The associations between the total or individual isomer level of PCBs and dioxins in 134 Japanese pregnant women's peripheral blood and the mental or motor development of their 6-month-old infants were evaluated using the second edition of the Bayley Scales of Infant Development. The mean level of total toxicity equivalency quantity (TEQ) was 18.8 (4.0-51.2) pg/g lipid in blood of 134 mothers. After adjustment for potential confounding variables, the total TEQ value was shown not to be significantly associated with mental developmental index (MDI) or psychomotor developmental index (PDI). However, the levels of one polychlorinated dibenzo-p-dioxin (PCDD) isomer, total PCDDs, and total PCDDs/polychlorinated dibenzofurans (PCDFs) were significantly negatively associated with MDI, and the levels of two PCDD isomers and three PCDF isomers were significantly negatively associated with the PDI. In conclusion, the background-level exposure of several isomers of dioxins during the prenatal period probably affects the motor development of 6-month-old infants more than it does their mental development.

Dioxins↗

PubMed2006

Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development.

BACKGROUND: The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure. OBJECTIVE: We studied prenatal lead exposure's impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels. METHODS: We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose. RESULTS: Maternal lead levels were moderately high with a first-trimester blood lead mean (+/- SD) value of 7.1 +/- 5.1 microg/dL and 14% of values >or=10 microg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores. CONCLUSIONS: Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.

Adolescent↗

PubMedDate not supplied

An evidence-based guideline for introducing oral feeding to healthy preterm infants.

The ability of a preterm infant to make the transition from gavage to oral nipple feeding depends on the infant's neurodevelopment in relation to behavioral organization, to a rhythmic suck-swallow-breathe pattern, and to cardiorespiratory regulation. Research-based knowledge about infant neurodevelopment in these three areas has led to the creation of a semidemand feeding method to aid in this transition. The method combines the use of nonnutritive sucking to promote awake behavior for feeding, use of behavioral assessment to identify readiness for feeding, and systematic observation of and response to infant behavior cues to regulate frequency, length, and volume of oral feedings. Semidemand feeding may be individualized for healthy preterm infants. This article discusses both the relevant knowledge about neurodevelopment and the semidemand feeding method itself.

Bottle Feeding↗

PubMed1997

Approaches to the definition of neonatal hypoglycemia.

There is no current agreement on the definition of neonatal hypoglycemia. Three different bases for the definition are presented, with a review of evidence of relevant to each approach. (1) Not commonly encountered; requires evidence of normal distribution of blood glucose concentrations. (2) Increased risk of adverse sequelae; requires evidence of short-term and long-term sequelae of different blood glucose concentrations. (3) Benefits of intervention outweigh risks; requires evidence from randomized trials of intervention. The usual distribution of neonatal blood glucose concentrations varies with birthweight, postnatal age, nutritional intake and other factors. Clinical signs occur in some but not all babies with low blood glucose concentrations, but such signs lack specificity. Abnormality in sensory evoked potentials is associated with variations in blood glucose concentrations; these changes suggest that values less than 2.6 mmol/L have acute effects in areas of the brain with high glucose demand. Among low birthweight babies, case series suggest a high risk of impairment (50%) following symptomatic hypoglycemia, and controlled studies generally confirm an association between very low neonatal blood glucose concentrations and adverse neurodevelopment. However, these studies do not establish a level of blood glucose concentration or duration of hypoglycemia that is critical. There are no reports of randomized trials that have assessed the effect on neurodevelopment of alternative policies of glucose provision in the neonatal period. There is a need for a randomized controlled trial to assess reliably the short- and long-term clinical effects of alternative policies of the clinical management of blood glucose concentration in babies at high risk both of low neonatal blood glucose concentrations and adverse neurodevelopment.

Central Nervous System↗