Dora A. Stinson

Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy An Updated Systematic Review and Meta-analysis

OBJECTIVE To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy(HIE). DATA SOURCES Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and previous reviews. STUDY SELECTION Randomized controlled trials that compared therapeutic hypothermia to normothermia for newborns with HIE. INTERVENTION Therapeutic hypothermia. MAIN OUTCOME MEASURES Death or major neurodevelopmental disability at 18 months. RESULTS Seven trials including 1214 newborns were identified. Therapeutic hypothermia resulted in a reduction in the risk of death or major neurodevelopmental disability(risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and increase in the rate of survival with normal neurological function (1.63; 1.36-1.95) at age 18 months. Hypothermia reduced the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate HIE (RR, 0.67; 95% CI, 0.56-0.81) and in newborns with severe HIE (0.83; 0.74-0.92). Both total body cooling and selective head cooling resulted in reduction in the risk of death or major neurodevelopmental disability(RR, 0.75; 95% CI, 0.66-0.85 and 0.77; 0.65-0.93,respectively). CONCLUSION Hypothermia improves survival and neurodevelopment in newborns with moderate to severe HIE.Total body cooling and selective head cooling are effective methods in treating newborns with HIE. Clinicians should consider offering therapeutic hypothermia as part of routine clinical care to these newborns.

Increasing Prevalence of Cerebral Palsy Among Very Preterm Infants: A Population-Based Study

OBJECTIVES. It is unclear whether declines in neonatal and infant mortality have led to changes in the occurrence of cerebral palsy. We conducted a study to examine and investigate recent temporal changes in the prevalence of cerebral palsy in a population-based cohort of very preterm infants who were 24 to 30 weeks of gestational age. METHODS. A population-based cohort of very preterm infants who were born between January 1, 1993, and December 31, 2002, was evaluated by the Perinatal Follow-up Program of Nova Scotia. Follow-up extended to age 2 years to ascertain the presence or absence of cerebral palsy and for overall survival. Infant survival and cerebral palsy rates were compared by year and also in two 5-year periods, 1993–1997 and 1998–2002. Logistic regression analyses were used to identify factors that potentially were responsible for temporal changes in cerebral palsy rates. RESULTS. A total of 672 liveborn very preterm infants were born to mothers who resided in Nova Scotia between 1993 and 2002. Infant mortality among very preterm infants decreased from 256 per 1000 live births in 1993 to 114 per 1000 live births in 2002, whereas the cerebral palsy rates increased from 44.4 per 1000 live births in 1993 to 100.0 per 1000 live births in 2002. Low gestational age, postnatal dexamethasone use, patent ductus arteriosus, severe hyaline membrane disease, resuscitation in the delivery room, and intraventricular hemorrhage were associated with higher rates of cerebral palsy, whereas antenatal corticosteroid use was associated with a lower rate. CONCLUSION. Cerebral palsy has increased substantially among very preterm infants in association with and possibly as a consequence of large declines in infant mortality.

Unconjugated Estrogens in the Perinatal Period

Extract: High levels of unconjugated estrone ((E1) 3-hydroxyestra-1,3,5(10)-triene-17-one) and estradiol ((E2) estra-1,3,5(10)-triene-3,17β-diol) were found at term in maternal venous, umbilical vein, and umbilical artery plasma. For estrone the respective values in nanograms per milliliter ±SD were 12.8 ± 5.9, 25.1 ± 6.5, and 13.2 ± 7.7. For estradiol the respective values were 17.3 ± 9.2, 8.1 ± 4.0, and 5.1 ± 3.2. For estrone, levels for umbilical vein were higher than those in the paired maternal and umbilical artery; estradiol was higher in maternal vein than in the paired umbilical vessels. Absence of the fetal adrenals was associated with low levels of estrone and estradiol for maternal and umbilical vessels, whereas, in anencephaly, only the maternal levels were markedly diminished. An initially rapid, and then a slower decline in both estrogens was found in normal infants during the first 72 hr of life.Speculation: Despite extensive metabolism of unconjugated estrogen by the fetus, umbilical arterial levels of estrone and estradiol are high. Nevertheless, the neonate shows scant clinical evidence of those high levels. This could be due to incomplete development of estrogen receptors in target tissues, plasma protein binding of estrogen, competition between the biologically most potent estrogen estradiol and the less potent estrone and estriol ((E3) estra-1,3,5(10)-triene-3,16α;,17β-triol), or other factors.

Effect of high-dose vitamin D supplementation on radiographically detectable bone disease of very low birth weight infants

To test the hypothesis that high-dose vitamin D2 supplementation would result in a lower incidence of radiographically detectable bone disease, we randomly assigned 40 very low birth weight infants to a control group who received vitamin D2 in a dosage of 400 IU/day and 41 to an experimental group who received a dosage of 2000 IU/day. After 6 weeks, radiographs from all infants were scored blindly for degree of radiographic bone disease, and serum osteocalcin and 25-hydroxyvitamin D levels were measured. Mean vitamin D intake was 360 +/- 141 (SD) IU/day in the control group and 2170 +/- 144 (SD) IU/day in the experimental group. Median 6-week serum 25-hydroxyvitamin D levels were 24 ng/ml (range 3 to 60 ng/ml) in the control group and 68 ng/ml (range 9 to 150 ng/ml) in the experimental group (p less than 0.001). Overall, 20% of the infants had evidence of moderate radiographic bone disease and only 2% were severely affected. The radiographic bone score (median = 2.5) and serum osteocalcin concentration (mean = 21.7 +/- 8.7 ng/ml) in the control subjects did not differ significantly from those in the experimental group (median bone score = 2.0; mean osteocalcin level = 24.1 +/- 7.9 ng/ml). Although there may be a subset of very low birth weight infants who would benefit from high doses of vitamin D, we conclude that no generalized clinical improvement can be attributed to this regimen alone.

Benign Unexplained Respiratory Distress of the Newborn Infant

The role of pulmonary edema in the pathogenesis of benign respiratory distress, and its relation to hyaline membrane disease.

Successful outcome in pregnancy with arterial tortuosity syndrome.

BACKGROUND: Arterial tortuosity syndrome is a rare, autosomal recessive, severe, connective tissue disorder caused by a mutation in the SLC2A10 gene. We describe the pregnancy and delivery with this high-risk connective tissue disorder involving generalized abnormalities of the vasculature. CASE: A woman with an undefined connective tissue disorder was referred for tertiary prenatal care. Diagnostic imaging demonstrated multiple pulmonary artery aneurysms and arterial tortuosity, consistent with a clinical diagnosis of arterial tortuosity syndrome. With a team considering all potential complications, a delivery plan was undertaken involving cesarean delivery and intensive perioperative and postpartum monitoring. The outcome was optimal for mother and neonate. Concurrent molecular testing demonstrated homozygosity for the SLC2A10 gene. CONCLUSION: Optimal maternal, fetal and neonatal outcomes were obtained with comprehensive multidisciplinary care and close maternal and fetal surveillance.

The 2-year Outcomes of VLBW Infants from a Regional Perinatal Follow-up Program: A Comparison of the 1984-88 and 1989-93 Cohorts. 1236

The 2-year Outcomes of VLBW Infants from a Regional Perinatal Follow-up Program: A Comparison of the 1984-88 and 1989-93 Cohorts. 1236

A COMPARISON OF ALVEOLAR METABOLISM BETWEEN NATURAL AND SYNTHETIC SURFACTANTS IN PRETERM RABBITS. † 1924

A COMPARISON OF ALVEOLAR METABOLISM BETWEEN NATURAL AND SYNTHETIC SURFACTANTS IN PRETERM RABBITS. † 1924

1553 EARLY IHDOMETHACIN (IND) DOES NOT PREVENT BRONCHOPULMONARY DYSPLASIA (BPD) IN A RANDOMIZED CLINICAL TRIAL

Thirty infants < 1500 g at birth on IPPB or CPAP by 12 hours were entered in a randomized double blind controlled trial to test the efficacy of IND in preventing BPD. 15 treated infants received IND at 12, 24 and 36 hours of age while 15 control infants received normal saline at these times. The groups were similar for birth weight, gestational age and sex.Although there was a 65% probability of detecting a 50% reduction in BPD, there was in fact no difference in the incidence of BPD between the two groups. The incidence of IRDS and IVH was similar in the two groups. There was a tendency towards reduced incidence of symptomatic PDA (SPDA) in the IND group but it did not reach significance. There were no cases of NEC in either group and the incidence of pneumothorax and RLF was similar. Length of stay, length of ventilator support and length of oxygen therapy did not differ between the two groups.IND may reduce the incidence of SPDA. However, when given within 12 hr of birth, IND does not reduce the incidence or severity of BPD, or the need for ventilation or oxygen.

PROLONGED RESPONSE TO NATURAL VS SYNTHETIC SURFACTANT IN PRETERM RABBITS: EFFECTS ON LUNG WATER CLEARANCE. 2049

To compare the effects of two natural surfactant preparations [term fetal rabbit surfactant (FRS) and adult rabbit surfactant (ARS)] and two commercially available preparations [apoprotein-based Survanta® (S) and totally synthetic Exosurf® (E)] on lung water clearance in preterm rabbits following prolonged ventilation (3 hr), pups were delivered at 27 days gestation, treated with one of the surfactant preparations (FRS, ARS: 1250μg phospholipid per pup; S,E: according to manufacturers directions), ventilated with 100% oxygen for 180 min, sacrificed and their extravascular lung water (EVLW) (ml H2O per g dry lung) determined. EVLW content was also determined on pups which did not survive the 180 min ventilation period. Untreated, ventilated pups served as controls.