Neurodevelopmental outcome in very-low-birth-weight infants with or without periventricular haemorrhage and/or leucomalacia

The aim of the study was to verify the predictive value of ultrasound performed in the neonatal period for short-term neurodevelopmental prognosis in 122 preterm very-low-birth-weight infants followed-up at 36 months. Neuromotor development was favourable in 53 (87%) subjects with normal ultrasound findings and in 21 (81%) subjects presenting uncomplicated haemorrhage. However, sensory and/or cognitive sequelae developed in 13% and 19% of the two groups, respectively. Outcome was unfavourable in 14 (50%) of 28 patients with ultrasound findings of complicated cerebral haemorrhages and in 5 (71%) of those (7) with ultrasound findings of parenchymal lesions without haemorrhage. Neonatal ultrasound examination seems to be fundamental in predicting neuromotor, but not cognitive, outcome in very-low-birth-weight infants.     

Neurodevelopmental outcome after COX inhibitor treatment for patent ductus arteriosus

Aim

To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA).

Methods

We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen.

Results

Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2 wks d) in early (median CRIB 6 and 5, respiratory distress > 2° in 36 and 34 infants) and late morbidities (intraventricular hemorrhage > 2° in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0 wks d) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24 months corrected age.

Conclusion

Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.     

Neurodevelopmental outcome of very low birth weight babies admitted to a Malaysian nursery

OBJECTIVE: To examine the prevalence and pattern of neurodevelopmental handicap at 2 years of age in very low birth weight infants (VLBW) admitted in 1993 to a level 3 Malaysian nursery. METHODS: All VLBW babies born in the hospital or referred for neonatal care during 1993 were enrolled prospectively in the study. At 2 years of age development was assessed using the Griffiths mental scales. Neurological, hearing and visual assessments were graded into five groups according to functional handicap. Control infants were randomly selected during attendance at a primary health care clinic. RESULTS: One hundred and fifty VLBW infants were admitted and 82 (54.6%) survived to 2 years, of whom 77 (93.9%) were assessed. The mean General Quotient (GQ) on the Griffiths Scales was 94 (15.7) for the study group and 104 (8.3) for the 60 controls. For GQ, 21 (27.3%) of the study population were 1 or more SD below the mean (18 between 1 and 2 SD and 3 > 2 SD) compared with 1 (1.6%) of the controls who was 1-2 SD below the mean. Visual impairment occurred in 2 study infants and none of the controls. There was no hearing impairment in either group. Cerebral palsy occurred in 3 (1 mild and 2 moderate-severe) of the study group and none of the controls. Functionally 18 (23.3%) of the study group had mild handicap, 1 (1.3%) moderate, 2 (2.5%) severe, 2 (2.5%) multiply severe and 54 (70.2%) were normal. CONCLUSION: Although survival was low, overall rates of functional handicap were similar to those reported in developed countries but the proportion with moderate or severe handicap was low.     

Neurodevelopmental and audiological outcome of healthy term newborns with moderately severe non‐haemolytic hyperbilirubinemia

Objective: Our objective was to examine the outcome of term infants who developed moderate non‐haemolytic jaundice as information regarding the neurodevelopmental outcome of term infants with moderately severe non‐haemolytic hyperbilirubinemia remains controversial. Study design: Thirty‐nine term infants rehospitalised with non‐haemolytic hyperbilirubinemia (serum bilirubin levels: 20–30 mg/dL) during the first 2 weeks of life (study group), were assessed and compared to 36 children born at term who did not develop neonatal jaundice (control group). Assessment consisted of the Bailey 2 test, speech evaluation, behavioural hearing test and a neurological examination. Results: The subjects were assessed at a mean age of 3 years. There was no difference between the groups with regard to background data, except for the mean gestational age (38 + 1.3 weeks (study group) vs. 39.5 + 1.4 weeks (control group), P= 0.01). There were no significant differences between the groups in outcome parameters initially, and after correcting for possible confounding factors. None of the children in either of the groups had a neurosensory hearing deficit or any significant neurological deficiency. There was no correlation of outcome parameters with the admission serum Bilirubin levels or with the duration of hyperbilirubinemia. Conclusion: No untoward outcome was found in term healthy infants with moderately severe non‐haemolytic hyperbilirubinemia. Moreover, we did not find a correlation of outcome with serum bilirubin levels or with the duration of the hyperbilirubinemia in the study group.     

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.     

The long-term neurodevelopmental outcome for very low birthweight (VLBW) infants with 'dystonic' signs at 4 months of age

Abstract  As very low birthweight (VLBW) infants are at a high risk of developmental handicap, it is important to establish predictors of long-term adverse outcome at an early age so that early intervention can be instituted. Longitudinal neurodevelopmental assessments were performed in 107 VLBW infants at 1,4, 8 and 12 months corrected age. Eighteen were diagnosed as 'dystonic' at 4 months of age.
This study compared the outcomes at 4 and 6 years for 15 of the 18 dystonic with 75 of the 89 non-dystonic VLBW infants, respectively. At 9 years of age, nine dystonic and 54 non-dystonic infants were assessed on the Rutter Behaviour Questionnaire. Dystonic children had a lower mean General Cognitive Index (GCI; P= 0.001) and a higher incidence of disability as measured by the Burns Neuro-Sensori-Motor Developmental Assessment Scale (P = 0.0005) and Kitchen disability grading (P = 0.001). Even if the minor neurological aberrations of the premature dystonia syndrome in VLBW infants abate by one year of life, these infants still constitute a high-risk group for subsequent neurodevelopmental disability and therefore require close observation and probably early intervention.     

Neurodevelopmental outcome in congenital diaphragmatic hernia: Evaluation,predictors and outcome

To review the reported neurodevelopmental outcome of congenital diaphragmatic hernia (CDH) survivors, identify important predictors of developmental disabilities, and describe the pathophysiological mechanisms contributing to adverse outcome. A Medline search was performed for English-language articles cross-referencing CDH with pertinent search terms. Retrospective, prospective, and longitudinal follow-up studies were examined. The reference lists of identified articles were also searched. Neurodevelopmental dysfunction has been recognized as one of most common and potentially most disabling outcome of CDH. Intelligence appears to be in the low normal to mildly delayed range. Neuromotor dysfunction is common during early childhood. Behavioral problems, hearing impairment, and quality of life related issues are frequently encountered in older children and adolescence. Disease severity correlates with the degree of neurological dysfunction. Neurodevelopmental follow-up in CDH children should become standard of care to identify those who would benefit from early intervention services and improve neurological outcomes.     

Neurodevelopmental outcome in high-risk patients after renal transplantation in early childhood

Patient and graft survival rates of pediatric renal transplant recipients are currently excellent, but there are few reports regarding the long-term neurodevelopmental outcome after renal transplantation (Tx) in early childhood. Children with renal failure from infancy would be expected to have a less favorable developmental prognosis. We report the neurodevelopmental outcome in 33 school-age children transplanted between 1987 and 1995 when < 5 yr of age. We prospectively performed a neurological examination, magnetic resonance imaging (MRI) of the brain, electroencephalograms (EEGs), audiometry, and neuropsychological tests (NEPSY), and measured cognitive performance (WISC-R); we related these results to school performance and to retrospective risk factors prior to Tx. Twenty-six (79%) children attended normal school and 76% had normal motor performance. Six of the seven children attending a special school had brain infarcts on MRI. The EEG was abnormal in 11 (35%), and five (15%) received anti-convulsive treatment after Tx. Sensorineural hearing loss was documented in six patients. The mean intelligence quotient (IQ) was 87, and 6-24% showed impairment in neuropsychological tests. The children attending a special school had been more premature, but had not had a greater number of pre- or neonatal complications. They had experienced a greater number of hypertensive crises (p = 0.002) and seizures (p = 0.03), mainly during dialysis, but the number of septic infections and the mean serum aluminum levels were not significantly greater than in the children with normal school performance. In these previously lethal diseases, the overall neurodevelopmental outcome is reassuring. However, it is of crucial importance to further minimize the risk factors prior to Tx.     

Behavioural outcome of school-age children after prenatal exposure to coumarins

In utero exposure to coumarin derivatives may affect the development of the central nervous system of the child, irrespective of the period of exposure in pregnancy. Little is known about effects on development in the long term. The aim of the present study was to determine whether prenatal exposure to coumarins affects behavioural outcome in children at school age. Behavioural outcome was assessed in a cohort of 305 exposed children, aged 7-15 years. Findings were compared with those in a cohort of 263 non-exposed controls, matched for sex, age, and demographic region. Behaviour was rated by parents and teachers using standardized questionnaires: the Groningen Behaviour Checklist Family situation (GBF) and the Groningen Behaviour Checklist School situation (GBS), respectively. The findings of the GBF were supported by the results of the GBS, filled in by teachers who were blind for the exposure status of the child. In comparison to the non-exposed children, the coumarin-exposed children scored lower on the cluster 'positive task orientation' (GBF P<0.05, GBS P<0.01), they scored higher on 'emotional instability' (GBF P<0.001, GBS P<0.05), and they had more problems on the social clusters (P<0.01). Based on the results of both questionnaires, we conclude that behavioural development may be negatively influenced in school-age children after in utero exposure to coumarins, leading to less favourable task-oriented and social-emotional behaviour. However, the frequency of clinically relevant 'problem behaviour' (GBF) was not increased in relation to coumarin exposure, the odds ratio was 1.2 (CI(95) 0.7-1.8).     

Growth and neurodevelopmental outcome in extremely-low-birth-weight infants after laparotomy

Twenty-one extremely-low-birth-weight (ELBW) and premature infants (<29 weeks' gestation and/or <1,000 g) underwent emergency laparotomy for acute intra-abdominal pathology (necrotising enterocolitis [NEC] 16, other bowel pathology 5) during the 4-year period from 1990 to 1993; 11 died. The neurodevelopmental outcome of the 10 survivors was assessed and compared with 20 living, otherwise normal controls matched for gestational age, birth weight, and year of birth to asses the effect of the abdominal event on quality of survival. Those who survived after laparotomy had a worse neurodevelopmental outcome than controls (P < 0.05). During this period, we also compared 24 infants in the ELBW category who developed NEC but did not require a laparotomy with the 16 ELBW infants with NEC who required a laparotomy. Those who required a laparotomy had worse disease and had significantly worse neurodevelopmental outcomes (P < 0.01). ELBW and premature infants who have acute intra-abdominal pathology requiring a laparotomy are thus at increased risk of neurodevelopmental problems and poor growth. Close long-term follow-up is important, and the families of such infants should be made aware before surgery of the increased risk the abdominal event has on their babies' developmental outcome if they survive. Accepted 18 November 1999     

Poor repertoire General Movements predict some aspects of development outcome at 2 years in very preterm infants

Background

Observation of the quality of endogenously generated “General Movements” has been proved to be a reliable and sensitive tool in the assessment of fragile neonates. The absence of fidgety movements at 2–4 months post-term is highly predictive of Cerebral Palsy. On the contrary, the presence of a poor repertoire pattern during the writhing period is not reliable in predicting motor or neurobehavioral disorders at any stage of development.

Aim

To examine if the presence of a PR pattern at 1 month post-term was associated with lower neurodevelopmental quotients at 2 years.

Study design

General Movements evaluation at 1 and 3 months and the Griffiths Scales of Mental Development at 2 years were administered to a sample of very preterm infants. Infants were divided into two groups: poor repertoire pattern group and normal pattern group. Student's t Test and Chi squared test and ANOVA were used to compare neonatal variables and results between the two groups.

Subjects

79 very preterm infants (birthweight ≤ 1500 g or gestational age ≤ 32 weeks), born January 2003 to December 2006 who had a follow-up at 2 years.

Outcome measure

Griffiths developmental quotient at 2 years.

Results

The Poor Repertoire group had lower Gestational Age, lower Birth Weight, lower Apgar scores at birth and lower Developmental Quotient at 2 years. Eye and Hand Coordination (subscale D) was the domain mostly responsible for such a difference. Quality of fidgety movements (normal or abnormal fidgety) at 3 months did not show any correlation with outcome measures at 2 years.

Conclusion

The presence of a PR pattern at 1 month post-term seems to predict lower neurodevelopmental scores at 2 years especially in the domain of eye and hand coordination. Longer follow-up is necessary in order to ascertain if such difference will continue to persist at older ages.     

Neurodevelopmental outcomes of very low birth weight and extremely low birth weight infants at 18 months of corrected age associated with prenatal risk factors

Background

Very premature infants occasionally have neurodevelopmental disabilities. However, there have been quite limited data on prenatal risk factors associated with their neurodevelopmental outcomes.

Aim

To clarify the relationship between prenatal risk factors and neurodevelopmental outcomes of very premature infants.

Study design

The study design is a retrospective review.

Subjects

One hundred seventy Japanese women with a singleton pregnancy and their infants whose birth weight being less than 1500 g were included. We classified those infants into 118 appropriate for gestational age (AGA) and 52 small for gestational age (SGA) infants.

Outcome measures

Infants' neurodevelopmental outcomes at 18 months of corrected age were evaluated by the Kyoto Scale of Psychological Development 2001 (KSPD). We analyzed and compared the infants' outcomes and prenatal risk factors between two groups.

Results

Mortality and rate of infants unevaluable by KSPD because of severe impairment were not significantly different between those groups. However, the developmental quotient score of the cognitive-adaptive area in SGA infants born between 25 and 31 weeks of gestation was significantly lower than that in AGA infants randomly selected as gestation-matched controls. More advanced gestational age and heavier birth weight protected against adverse neurodevelopmental outcomes in both groups. Moreover, male infants were related to the excess risk of adverse neurodevelopmental outcomes in the SGA group.

Conclusion

In view of the neurodevelopment of the infants, it seems that the most efficient obstetric strategy for improving prognosis of premature infants should be targeted to prolong the pregnancy period as long as the reassuring fetal status and maternal stable health condition are being confirmed.     

Neurologic outcome after fetal inflammatory response syndrome: Trimester-specific considerations

Clinical signs and neuroimaging patterns associated with the fetal inflammatory response syndrome (FIRS) worsen or mimic the clinical repertoire after intrapartum hypoxic-ischemic encephalopathy (HIE) during labor and/or parturition. Diagnostic considerations expressed as neonatal encephalopathy (NE) must consider chronic as well as acute factors associated with FIRS. Trimester-specific factors adversely alter the interactions of the maternal/placental/fetal (MPF) triad and influence the postnatal phenotype of FIRS. Anticipatory guidance for families by clinicians caring for survivors with FIRS, as well as researchers, must consider acute and chronic effects that influence neurologic outcome. Novel neurotherapeutic interventions must include prenatal preventive as well as peripartum/postnatal rescue and repair strategies to effectively reduce the presence and severity of sequelae from FIRS.     

Infantile hypertrophic pyloric stenosis after prenatal exposure to thalidomide

In a retrospective study of 832 cases of thalidomide embryopathy (ThE) between October 1, 1959 and July 31, 1962, a highly significant accumulation of cases with infantile hypertrophic pyloric stenosis (IHPS) was registrated. Clinical course, X-ray and surgical findings and the sex ratio (male preponderance) were identical to IHPS occurring spontaneously. In the order of frequency of defects in ThE, IHPS is on position 11; among inner organ abnormalities, IHPS is on position 3 after heart and kidney defects. Thus, IHPS is the predominant gastrointestinal abnormality in ThE. For the first time, a substance (thalidomide) could be identified which obviously is able to influence manifestation of IHPS. There is a remarkable coincidence of IHPS and malformations such as hiatus hernia and tracheo-oesophageal fistula with or without oesophagus atresia. From the male preponderance, which is also observed in the ThE type of IHPS, it is concluded that thalidomide is not a primary cause in this process, but that disease manifestation is decisively influenced by thalidomide on the base of a genetic or familiar predisposition. Cause and development of IHPS are multifactorial; the mode of inheritance is polygenic. Probably, other substances may replace thalidomide.Abbreviations ThE thalidomide embryopathy - IHPS infantile hypertrophic stenosis     

Development after prenatal exposure to cocaine, heroin and methadone

In Amsterdam a longitudinal, prospective and multidisciplinary study on the development of infants of drug-dependent mothers (IDDM) was started in 1983: 35 IDDM and 35 reference infants were originally enrolled. The drug-dependent women had used combinations of methadone, heroin, cocaine and other drugs during pregnancy. Of the IDDM, 80% had to be treated pharmaceutically for neonatal abstinence symptoms (NAS). Physical, neurological, cognitive and the socio–emotional development of the children were studied regularly from birth until 5.5 years of age. Differences between the reference group and the IDDM were found most clearly in cognitive development. The IDDM also had more behavioural problems at some of the ages studied. No group differences were seen in motor development. So far the results of the study show that IDDM and their caregivers need extra support in order to improve early communication and the children's cognitive development.     

Associations between term birth dimensions and prenatal exposure to essential and trans fatty acids

Background

Certain essential long-chain polyunsaturated fatty acids (LCPUFAs) are considered important for fetal growth and brain development, whereas industrial trans fatty acids (mainly 18:1trans) have been associated with negative effects. The aim of this study was to investigate associations between term birth dimensions and prenatal exposure to some of these fatty acids, reflected by neonatal fatty acid concentrations at birth.

Methods

Data of up to 700 infant-mother pairs from the Maastricht Essential Fatty Acid Birth Cohort were used for the present study. Unadjusted and multivariable-adjusted linear regression analyses were performed to investigate associations between birth weight, birth length or head circumference and relative concentrations of docosahexaenoic acid (DHA), arachidonic acid (AA), dihomo-γ-linolenic acid (DGLA) and trans-octadecenoic acids (18:1t) measured in phospholipids of the walls of umbilical arteries and veins, and in umbilical cord plasma and erythrocytes.

Results

After optimal adjustment, a significant negative association was observed between birth weight and umbilical plasma DHA concentrations. Negative associations were also found for AA concentrations measured in umbilical plasma and in arterial and venous vessel walls. Birth length was negatively related to arterial vessel wall AA concentrations only. A significant negative association was observed for the relationship between 18:1t in cord erythrocytes and birth weight. For DGLA no significant associations were observed.

Conclusions

Results seem to preclude a role of DHA and AA as growth factors per se. Their negative relationships with birth dimensions may result from a limited maternal-fetal LCPUFA transfer capacity. Potential effects of 18:1t and DGLA on birth dimensions are probably small or non-existing.