Deficits in the processing of local and global motion in very low birthweight children.

This study evaluated the impact of premature birth on the development of local and global motion processing in a group of very low birthweight (<1500 g), 5- to 8-year-old children. Sensitivity to first- and second-order local motion stimuli and coherence thresholds for global motion in random dot kinematograms were measured. Relative to full-term controls, premature children showed deficits on all three aspects of motion processing. These problems could not be accounted for by stereo deficits, amblyopia, or attentional problems. A history of mild retinopathy of prematurity and/or intraventricular hemorrhage increased risk, but deficits were observed in some children with no apparent ocular or cerebral pathology. It is important to note that, despite the observed group differences, individual profiles of performance did vary; the results suggest that these three forms of motion processing may involve separate neural mechanisms. These findings serve to increase our understanding of the organization and functional development of motion-processing subsystems in humans, and of the impact of prematurity and associated complications on visual development.

Liver development in a rat model of fetal alcohol syndrome.

The inhibitory effects of alcohol on hepatic growth in adults raises the possibility that the liver may be involved in fetal alcohol syndrome (FAS) in infants. To test this hypothesis, pregnant Sprague-Dawley rats were fed liquid diets containing either ethanol as 36% of the total calories, or were allowed ad libitum feeding of a control liquid diet (controls) throughout pregnancy. Other dams were exposed to the ethanol diet only during the first or last half of pregnancy. Pups delivered of dams exposed to the various diets (N = 40-45/group) were killed at 1, 3, 7, and 14 days of age. In addition to brain weights, crown-rump lengths, and facial features, the following parameters of liver development were documented; liver weight, liver/body weight ratio, liver histology, hepatic ornithine decarboxylase activity (ODC), hepatic protein content, and rate of hepatic DNA synthesis (as determined by [3H]thymidine incorporation). The results revealed that pups exposed to ethanol throughout pregnancy but not ad libitum control diet pups had brain weights, crown-rump lengths, and facial features in keeping with FAS. With respect to liver development, the livers in FAS pups were consistently smaller than in the control group. However, total body weights were decreased to a greater extent, such that when corrected for body weights, the smaller livers in FAS pups only became significant on day 14 of life. Liver histology was similar in the two groups with no signs of active inflammation or fibrosis. Hepatic ODC activity was also similar, indicating no impairment in polyamine synthesis. Hepatic DNA synthesis rates were decreased in FAS pups at all time intervals. Pups delivered of dams exposed to ethanol during either the first or last half of pregnancy had results comparable to those of controls. To identify the mechanism(s) responsible for these findings, a second series of experiments was performed wherein the hepatic expression of the following factors associated with liver development were documented by northern-blot analyses; growth hormone receptor (GHr), insulin-like growth factor-I (IGF-I) and -II (IGF-II) and IGF binding proteins (IGFBPs) 1, 2, 3, and 4 mRNA on gestational days 16 and 20 and postpartum days 1 and 7. In this series, a third group of pups derived from dams in whom caloric consumption was matched to that of the ethanol-fed dams (isocaloric controls) were also studied. The results revealed no consistent differences in GHr, IGF, or IGFBP mRNA expression in the three groups. In conclusion, liver development and hepatic DNA synthesis were significantly impaired in this animal model of FAS. That impairment, however, was not associated with decreases in either polyamine synthesis or disturbances in the hepatic component of the GH/IGF/IGFBP axis.

Alveolar capillary dysplasia. Report of a case of prolonged life without extracorporeal membrane oxygenation (ECMO) and review of the literature.

We describe an unusual infant with the diagnosis of alveolar capillary dysplasia who had a relatively prolonged life without extracorporeal membrane oxygenation (ECMO). We have used this case as a springboard for a thorough review of the literature. This was a full-term female infant who presented with a picture of persistent pulmonary hypertension of the newborn. She was treated as such, with various ventilatory modes, alkalinizing agents, surfactant therapy, tolazoline, prostacyclin and nitric oxide. Because of the prolonged clinical course the possibility of alveolar capillary dysplasia was raised. The parents refused ECMO. Despite all efforts she progressively deteriorated and died at 22 days of age. Macro- and microscopic examination of the lung at autopsy were diagnostic of alveolar capillary dysplasia. A detailed review of 39 cases published in the literature with comments regarding incidence, etiology, pathophysiology, clinical picture, diagnosis and treatment is presented.

Hepatic carnitine palmitoyltransferase I deficiency presenting as maternal illness in pregnancy.

The spectrum of clinical presentation of fatty acid oxidation defects (FAOD) continues to expand. One FAOD, L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been associated with liver disease in pregnancies involving a heterozygous mother carrying an affected fetus. Hepatic carnitine palmitoyltransferase (CPT I) deficiency typically presents as a Reyelike syndrome in children between 8 and 18 mo. of age. We have investigated a family in which the mother developed liver disease consistent with acute fatty liver of pregnancy (AFLP) and hyperemesis gravidarum in her two successive pregnancies. Neither child nor their mother was found to carry the common LCHAD G1528C mutation. Both children were subsequently shown to have absent activity of CPT I. This is the first report of CPT I deficiency presenting as maternal illness in pregnancy.

Treatment of children with autism: a randomized controlled trial to evaluate a caregiver-based intervention program in community day-care centers.

This study reports on the results of a randomized controlled trial that evaluated a caregiver-based intervention program for children with autism in community day-care centers. Thirty-five preschool children with a DSM III-R diagnosis of autism or pervasive developmental disorder were randomized to an experimental or control group. Children in the experimental group were enrolled in day care and their parents and child care workers received a 12-week intervention consisting of lectures and on-site consultations to day-care centers. In addition, supportive work was undertaken with families. Control subjects received day care alone. In the experimental group, there were greater gains in language abilities, significant increases in caregivers' knowledge about autism, greater perception of control on the part of mothers, and greater parent satisfaction. We conclude that this research design demonstrated that the intervention was significantly superior to day care alone.

Fetal assessment based on fetal biophysical profile scoring. VIII. The incidence of cerebral palsy in tested and untested perinates.

OBJECTIVE: The intent of this comparative clinical study was fourfold: (1) to determine the incidence of cerebral palsy in a large obstetric population, (2) to compare the incidence of cerebral palsy in patients at high risk referred for and managed according to the fetal biophysical profile score result with the incidence among unreferred and untested patients, (3) to determine the relationship, if any, between the last fetal biophysical profile score and the incidence of cerebral palsy, and (4) to categorize cases of cerebral palsy according to the clinical parameters and the probable time and nature of the damaging insult. STUDY DESIGN: In this retrospective 5-year comparative study (1987 to 1991) the incidence of cerebral palsy was determined by analysis of International Classification of Diseases, Ninth Revision, -coded related medical services. The clinical records were then sought and reviewed in index cases and obstetric, neonatal, and postnatal clinical data were abstracted. Cross-correlation with partial registries was done to confirm completeness of capture of index cases. The population of referred high-risk patients who received serial fetal biophysical profile scoring and were managed according to test results was determined by review of a prospective computer-stored database and by review of patient log books. The population of untested patients was calculated as the residual of total cases minus tested cases. The rate of cerebral palsy for all patients and for the tested and untested population was calculated and compared. The tested and untested perinates were compared for birth age, weight, and assigned timing or etiology of cerebral palsy. In the tested population the distribution of test results by last recorded biophysical profile score was determined and the relationship between the last test result and cerebral palsy and predictive accuracy parameters of the fetal biophysical profile score were calculated. RESULTS: The incidence of cerebral palsy among the 84,947 live births was 3.68 per 1000 live births (313 cases). The rate of cerebral palsy in the 26,290 referred high-risk tested patients was 1.33 per 1000 (35 cases) compared with a rate of 4.74 per 1000 live births in the 58,657 untested mixed low-risk/high-risk patients (278 cases). These differences were highly significant. A significant declining trend in the annual incidence of cerebral palsy was observed in the total population and the untested population, whereas the rate in the tested population remained relatively constant over the 5-year study interval. The differences in the cerebral palsy rate between the tested and untested population were not related to differences in gestational age, birth weight, or assigned timing or etiology category. In the tested population the relationship between the incidence of cerebral palsy and the last test fetal biophysical profile score was inverse, exponential, and highly significant. CONCLUSIONS: Antepartum assessment by fetal biophysical profile scoring is associated with a significant reduction in the incidence of cerebral palsy compared with untested patients. The relationship between the last test score and the incidence of cerebral palsy is inverse and exponential, suggesting that antenatal asphyxia is an important and potentially avoidable cause of cerebral palsy.

Persistent neonatal hypoglycemia: Diagnosis and management.

Maintenance of plasma glucose depends on a normal endocrine system, functional enzyme levels for glycogenolysis, gluconeogenesis and other processes, and there must be an adequate supply of endogenous fat, glycogen and substrates of gluconeogenesis. Neonatal hypoglycemia should be defined as serum glucose less than 2.2 mmol/L in the first 72 h of life and less than 2.5 mmol/L thereafter. The purpose of this paper is to review the more uncommon causes of hypoglycemia in the full term, apparently healthy neonate. Most of these conditions are inborn errors of metabolism. A protocol for investigation of these conditions and some of the more common diseases, such as hyperinsulinism, is provided, with a rationale explaining why these tests may be helpful.

Fetal assessment based on the fetal biophysical profile score: relationship of last BPS result to subsequent cerebral palsy.

OBJECTIVE: The prime intent of this study was to determine the relationship if any between the last fetal biophysical profile score and the risk of cerebral palsy at age 3 years. The secondary objective was to examine the clinical characteristics of infants with cerebral palsy whose obstetric management included serial fetal biophysical profile scores. STUDY DESIGN: The incidence of a high risk pregnant population whose antenatal assessment was by serial fetal biophysical profile scoring was determined by cross-referencing two discrete data bases. The completeness and reliability of the data bases was confirmed by secondary audit. Obstetrical, neonatal and post-natal clinical records of index cases of cerebral palsy were subsequently reviewed, categorized and analyzed. RESULTS: Fetal biophysical profile scores (BPS) were recorded in 22,336 high risk pregnancies: 27 patients delivered an infant subsequently identified as having cerebral palsy (rate 1.21 per 1000). The relationship between last BPS result and cerebral palsy was inverse, exponential and highly significant (R2 = 0.987; p < 0.001). Affected infants with a last abnormal BPS result were significantly more likely to exhibit fetal distress (88.8%), acidosis (77.7%), and have neonatal seizures (88.8%). Antenatal asphyxia was the apparent cause of cerebral damage in 29.6% of cases. CONCLUSION: The last fetal biophysical profile score is a predictor of the risk of cerebral palsy.

Use of tolazoline to counteract vasospasm in peripheral arterial catheters in neonates.

Arterial access for blood sampling and continuous blood pressure monitoring is the cornerstone of modern neonatal intensive care. Although umbilical arterial catheters have traditionally been utilized for arterial access, they are associated with potentially devastating complications. Consequently, there has been an increase in the use of peripheral arterial catheters. Unfortunately, these catheters have a limited useful lifespan secondary to vasospasm, intimal damage and/or thrombus formation. In this report, we describe the use of tolazoline (0.02 to 0.2 mg/kg/h) to counteract local arterial vasospasm in five critically ill neonates, where arterial access was vital for care but difficult to maintain.

Neonatal withdrawal from maternal volatile substance abuse.

AIM: To determine whether neonates born to mothers who are volatile substance abusers are at risk for an abstinence syndrome. METHODS: A consecutive sample of infants born to volatile substance abusing mothers was studied over four years, in a university affiliated medical centre with a variable mix of primary, secondary, and tertiary care patients. Infants were clinically scored with the Finnegan Neonatal Abstinence Scoring System. Those who fulfilled a priori scoring criteria were treated with phenobarbital and scoring was continued. RESULTS: There were 48 babies of whom 32 fulfilled the criteria for pharmacotherapy. All eight babies with the characteristic odour, and 15 of the 21 born to mothers with that odour, fulfilled these criteria. The typical symptoms were excessive and high pitched cry, sleeplessness, hyperactive Moro reflex, tremor, hypotonia, and poor feeding. Mean age of onset of treatment was 27.1 hours and mean duration was 5.8 days. Treatment was judged effective in 17 of 27, while benefit was borderline in three and absent in seven. CONCLUSIONS: It is suggested that there is an identifiable neonatal volatile substance abuse abstinence syndrome. The characteristic chemical odour in the neonate or mother is a marker for its occurrence, and phenobarbital treatment seems to be effective. The Finnegan Scoring System seems to be useful for grading its severity.

Subarachnoid fluid collections: a cause of macrocrania in preterm infants.

We report the outcome of 12 very low birth weight infants with macrocrania caused by subarachnoid fluid collections. By the age of 15 to 18 months, head growth had stabilized along a curve above and parallel to the 95th percentile. No infant required neurosurgical intervention, nor was cerebral palsy or mental retardation diagnosed in any of the infants.

Neurodevelopmental outcome of infants exposed to indomethacin antenatally.

The use of indomethacin as a tocolytic agent has been limited because of potential fetal and neonatal complications. We investigated the neonatal and neurodevelopmental outcome of preterm infants exposed antenatally to this drug. The records of 779 women admitted in premature labor during a five year period were reviewed. Nineteen women who received indomethacin (initial dose of 50-100 mg followed by 50-100 mg/day) and their 25 infants were identified. Delivery was delayed for a week or longer in 86.6% of the mothers. There were two deaths: a stillborn with multiple congenital anomalies and a neonate with congenital listeriosis. Seven infants were born at term without complications. Fifteen infants born prematurely were compared to 15 control infants not exposed to indomethacin antenatally. There were no statistically significant differences between the two groups in the prevalence or severity of thrombocytopenia, hyperbilirubinemia, intraventricular hemorrhages, patent ductus arteriosus, persistent pulmonary hypertension, bronchopulmonary dysplasia, and necrotizing enterocolitis. Mean BUN, creatine, and urine output for the first three days of life were similar in the two groups. No differences were found at the 6-12 month neurodevelopment assessment. We found no neonatal complications attributable to the antenatal use of indomethacin.

One-year follow-up of 89 infants with birth weights of 500 to 749 grams and respiratory distress syndrome randomized to two rescue doses of synthetic surfactant or air placebo. Canadian Exosurf Neonatal Study Group. Canadian Exosurf Neonatal Follow-Up Group.

Double-blind neurodevelopmental and physical evaluations were conducted at 1-year adjusted age in 89 infants with birth weights of 500 to 749 gm who had respiratory distress syndrome in the neonatal period and were randomized to receive two rescue doses of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co., Research Triangle Park, N.C.) or air placebo. The trial used a common protocol and was conducted at 13 hospitals; patients were entered in the trial between February 1988 and September 1990. Ninety-five percent of surviving infants were assessed. Growth and development in the two groups were equivalent. Mean Bayley Scales of Infant Development scores were comparable (mental development index, 79 +/- 22 vs 87 +/- 20; psychomotor development index, 73 +/- 18 vs 81 +/- 19 for air placebo and synthetic surfactant, respectively). The incidence of severe retinopathy of prematurity was significantly decreased in the surfactant group compared with the air placebo group (15% vs 34%; relative risk 0.428; 95% confidence interval 0.2 to 0.9). Overall, administration of surfactant appeared to increase the probability of a favorable outcome. Confirmation of the trends observed in this study would provide a strong rationale for the rescue use of synthetic surfactant in extremely low birth weight infants with respiratory distress syndrome even if overall mortality is not reduced.

One-year outcome in 232 premature infants with birth weights of 750 to 1249 grams and respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air placebo. Canadian Exosurf Neonatal Study Group.

A randomized, double-blind, placebo-controlled trial was performed in 13 hospitals in Canada to assess whether two rescue doses of a synthetic surfactant (Exosurf Neonatal) would reduce mortality and morbidity rates in neonates with respiratory distress syndrome who weighed from 750 to 1249 gm. As part of the original trial design, double-blind follow-up evaluations were performed at 1-year adjusted age. A total of 118 patients who received air placebo and 114 patients who received synthetic surfactant were evaluated at 1 year. Growth and development in the two groups were equivalent. Scores on the Bayley Scales of Infant Development were within the normal range for both groups (mental development index, 90 +/- 22 vs 92 +/- 22; psychomotor development index, 81 +/- 19 vs 87 +/- 22 for the air placebo and synthetic surfactant groups, respectively). However, in both groups the proportion of infants with any impairment (air placebo group, 43 of 118 (36%); synthetic surfactant group, 41 of 114 (36%) and severe impairment (air placebo group, 29 of 118 (25%); synthetic surfactant group, 21 of 114 (18%)) was substantial. We conclude that two rescue doses of synthetic surfactant in infants with RDS who weighed 750 to 1249 gm had no detrimental effect on developmental outcome or late morbidity. No long-term benefits to 12-months corrected age were observed with the use of surfactant in this weight class. Larger studies or meta-analyses of existing trials will be required to determine if there are any late outcome advantages associated with rescue use of synthetic surfactant in infants weighing 700 to 1249 gm.

The impact of very low-birth-weight infants on the family is long lasting. A matched control study.

OBJECTIVE: To test the hypothesis that parental stress associated with long-term morbidity of very low-birth-weight infants (VLBWIs) is long lasting. DESIGN: Matched case-control study. SETTING: High-risk newborn follow-up program, Winnipeg, Manitoba. PARTICIPANTS: Parents of 96 Manitoban VLBWIs born from July 1986 through June 1990, compared with parents of full-term controls matched for age, sex, race, domicile, singleton or multiple pregnancy, and birth order. MAIN OUTCOME MEASURES: Mailed questionnaire, including Stein's Impact on Family Scale, positive impact of parenthood, and attitudes toward treating VLBWIs. RESULTS: Families were demographically similar. The parents of VLBWIs had higher scores for financial burden, familial/social impact, personal strain, and mastery (P < .0001). The parents of VLBWIs experienced more impact when children had a functional handicap or low adaptive developmental quotient. Scores were highest when the adaptive developmental quotient was 70 to 85. High scores were associated with low family income and less parental education. Impact did not change over time. Only half of the parents in each group felt that "doctors should try to save every baby." The parents of VLBWIs felt more strongly that cost should never enter into the decision to treat a tiny baby (P < .005). The families of VLBWIs expressed a stronger desire for more children (P < .01), but control families were more likely to have given birth again (46.3% vs 28.2%). CONCLUSIONS: The birth and upbringing of a VLBWI is associated with more long-term stress, even for well-educated nuclear families whose health care is financed by government. Caregivers need increased awareness of the needs of these families so that their medical and social needs are met effectively. Support services should be targeted toward low income, poorly educated parents whose children have functional handicaps.

Public awareness of the risks of drinking alcohol during pregnancy: the effects of a television campaign. Child Health Committee, Manitoba Medical Association.

OBJECTIVE: To evaluate the impact of a television public awareness campaign on knowledge of the dangers of drinking alcohol during pregnancy. DESIGN: A survey with five questions on alcohol and pregnancy and five health questions unrelated to alcohol was administered before and after the campaign. PARTICIPANTS: Three thousand women aged 15-45 years. INTERVENTION: A 30-second announcement with a message on alcohol and pregnancy was broadcast over ten weeks by five television stations in Manitoba. RESULTS: More respondents after the campaign thought that alcohol consumption in pregnancy would put the baby at risk, and attributed this information to "television". There were no differences in the responses to the five health questions unrelated to alcohol. CONCLUSIONS: An increase in awareness of the risks of drinking alcohol during pregnancy was observed after a mass media campaign.

Intravenous pentazocine and methylphenidate abuse during pregnancy. Maternal lifestyle and infant outcome.

OBJECTIVE: To report the effects of intravenous abuse of pentazocine hydrochloride and methylphenidate hydrochloride during pregnancy. DESIGN: Retrospective chart review. PATIENTS: All pregnant women and their offspring, whose hospital records indicated prenatal abuse of pentazocine and methylphenidate during the 2-year study period. RESULTS: The median for maternal age was 22 years and the median number of prenatal visits was two. Twenty mothers had sexually transmitted diseases, 27 abused alcohol, 10 abused other drugs, and all smoked cigarettes. Eight infants were premature, and 12 were growth retarded. Four infants had congenital anomalies: fetal alcohol syndrome (two [twins]), structural heart defect (one), and polydactyly (one). Eleven infants were treated for neonatal abstinence syndrome. Seventeen infants had normal developmental quotients, and four had low-normal developmental quotients. CONCLUSIONS: Intrauterine exposure to pentazocine and methylphenidate appears to be associated with prematurity, growth retardation, and signs of neonatal withdrawal, but not with any particular teratogenic anomaly or severe developmental delay.

Earlier discharge with community-based intervention for low birth weight infants: a randomized trial.

BACKGROUND: Prolonged hospitalization of low birth weight infants increases the risk of medical and psychosocial complications. The feasibility of earlier discharge with community-based follow-up of infants of < or = 2000 g birth weight, without the use of home apnea monitors, was investigated. METHODS: One hundred infants of < or = 2000 g birth weight were randomized to either an intervention or control group. Intervention infants were discharged when readiness criteria were met. Based on assessed need, intervention group families received public health nursing and homemaker services for up to 8 weeks. Control infants were discharged to their homes at the discretion of the attending physician. All infants were assessed blindly at age 1 year with the Bayley and Home Observation for Measurement of the Environment (HOME) scales. RESULTS: There were no group differences in baseline infants' characteristics or in neonatal complications. Infants in the intervention group were discharged from the hospital at an earlier postconceptional age (mean +/- SD 36.6 +/- 1.5 weeks vs 37.3 +/- 1.6 weeks; P < .04). Median length of hospital stay (23 days vs 31.5 days) and mean weight at the time of discharge (2200 +/- 288 g vs 2275 +/- 301 g) were lower, but not significantly, for infants in the intervention group. A secondary analysis by birth weight strata (< or = 1500 g and 1501 through 2000 g) revealed that the most significant reductions in hospital stay and weight at discharge were realized in infants of 1501 through 2000 g birth weight. The persistence of apneic episodes and need for electronic monitoring prevented earlier discharge of infants of < or = 1500 g birth weight. Postdischarge services to the intervention group included 185 public health nurse home visits (3.8 +/- 0.91), 410 phone contacts (8.4 +/- 5), and 2298 homemaker hours (46 +/- 78) of service. At 1 year, there were no deaths and no group differences in rehospitalization rates, use of ambulatory services, or Bayley scores. Intervention families had significantly higher 1-year HOME scores. Minimum cost of hospital care was $873 per day, while the total cost of community-based services averaged $626 per infant. CONCLUSIONS: A significant reduction in average length of hospital stay was achieved for infants of 1501 through 2000 g birth weight. Earlier discharge of infants weighing < or = 1500 g at birth was hampered by persistent apneic episodes and feeding difficulties. A community-based program designed to provide individualized support and education for families of low birth weight infants was cost-effective and had a positive influence on the home environment.