Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus.

Despite publication of guidelines for the prevention and management of hyperbilirubinemia in term and late-preterm newborn infants, kernicterus, although rare, continues to occur. Guidelines written for use in one country may not always be universally appropriate. Bearing this in mind, a committee appointed by the Israel Neonatal Society has formulated a set of guidelines, based on those of the American Academy of Pediatrics (2004), but adapted to the realities of the Israeli scene. The guidelines include methods of surveillance of jaundice, prediction of jaundice, assessment of risk factors, discharge planning and post-discharge follow-up, in addition to therapeutic guidelines including indications for phototherapy, exchange transfusion and the use of intravenous immune globulin. Availability of these guidelines to the international community may offer direction to physicians of other countries who may be setting up guidelines for use in their own communities.

Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis.

OBJECTIVES: To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit. STUDY DESIGN: Full-term infants <72 h of age, who had risk factors and/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h post sepsis evaluation. Thirty matched infants served as a control group for comparing SAA concentrations. RESULTS: Of 104 infants eligible for entry to the study, 23 had sepsis and 81 had not sepsis. The SAA levels of the septic group were significantly higher than those of the nonseptic group at 0, 24 and 48 h (P<0.01 for all time points). In comparison with C-reactive protein (CRP), SAA levels rose earlier and in a sharper manner, had higher levels and returned faster to normal values in infants with early onset sepsis. At 0 h post-sepsis evaluation, serum SAA had an overall better diagnostic accuracy for predicting early onset sepsis than CRP (sensitivity (96 vs 30%), specificity (95 vs 98%), positive predictive value (85 vs 78%), negative predictive value (99 vs 83%), positive likelihood ratio (19 vs 12), and negative likelihood ratio (0.05 vs 0.71). CONCLUSIONS: SSA is advocated as an inflammatory marker of neonatal early-onset sepsis.

Delivery room resuscitation and adverse outcomes among very low birth weight preterm infants.

OBJECTIVE: To evaluate risk factors and impact of delivery room cardiopulmonary resuscitation (DR-CPR) on very low birth weight (VLBW) preterm infants. STUDY DESIGN: A national, population-based, observational study evaluating risk factors and short-term neonatal outcomes associated with DR-CPR among VLBW, extremely preterm infants (EPIs, 24 to 27 weeks' gestation) and very preterm infants (VPI, 28 to 31 weeks' gestation) born in 1995 to 2010. RESULTS: Among 17 564 VLBW infants, 636 (3.6%) required DR-CPR. In the group of 6478 EPI, 412 (6.4%) received DR-CPR compared with 224 of 11 086 infants (2.0%) in the VPI group. EPI who underwent DR-CPR had higher odds ratios (ORs (95% confidence interval)) for mortality compared to EPI not requiring DR-CPR (OR 3.32 (2.58, 4.29)), grades 3 to 4 intraventricular hemorrhage (IVH) (OR 1.59 (1.20, 2.10)) and periventricular leukomalacia (OR 1.81 (1.17, 2.82)). DR-CPR among VPI was associated with higher ORs for mortality (OR 4.99 (3.59, 6.94)), early sepsis (OR 2.07 (1.05, 4.09)), grades 3 to 4 IVH (OR 3.74 (2.55, 5.50)) and grades 3 to 4 retinopathy of prematurity (ROP) (OR 2.53 (1.18, 5.41)) compared to VPI not requiring DR-CPR. Only 11% of infants in the EPI DR-CPR group had favorable outcomes compared with 44% in the VPI DR-CPR group. Significantly higher ORs for mortality, IVH and ROP were found in the VPI compared to the EPI group. CONCLUSION: Preterm VLBW infants requiring DR-CPR were at increased risk of adverse outcomes compared to those not requiring CPR. This effect was more pronounced in the VPI group.

Localized cerebral infarction in the premature infant: an ultrasound diagnosis correlated with computed tomography and magnetic resonance imaging.

Findings on cranial ultrasonography strongly suggested the diagnosis of a localized infarct in four premature infants. CT was performed to differentiate between hemorrhagic and nonhemorrhagic lesions, and magnetic resonance imaging was used to obtain information about the late effect of the lesions. The clinical findings, imaging findings, and later outcome in these premature infants were compared with the existing knowledge of this type of lesion in the full-term infant. A localized infarct appears to carry a good prognosis in the premature infant and should be differentiated from other types of lesions, such as periventricular leukomalacia or parenchymal hemorrhage, which are more common in the premature infant and carry a worse prognosis.

Predictive value of early continuous electroencephalogram monitoring in ventilated preterm infants with intraventricular hemorrhage.

The contribution of early continuous four-channel EEG monitoring to the evaluation of intraventricular hemorrhage in acutely ill preterm infants mechanically ventilated for acute respiratory distress was assessed in a prospective study of 54 infants of less than 34 weeks' gestation. Early abnormal EEG results correlated significantly with later outcome. They often preceded ultrasound evidence of hemorrhage and provided prognostically significant functional correlation with the grade of hemorrhage. Continuous EEG monitoring allows collection of significant data with minimal interference and could contribute to clinical management of high-risk preterm infants.

Flip-flop of doxorubicin across erythrocyte and lipid membranes.

Doxorubicin, an anticancer drug, is extruded from multidrug resistant (MDR) cells and from the brain by P-glycoprotein located in the plasma membrane and the blood-brain barrier, respectively. MDR-type drugs are hydrophobic and, as such, enter cells by diffusion through the membrane without the requirement for a specific transporter. The apparent contradiction between the presumably free influx of MDR-type drugs into MDR cells and the efficient removal of the drugs by P-glycoprotein, an enzyme with a limited ATPase activity, prompted us to examine the mechanism of passive transport within the membrane. The kinetics of doxorubicin transport demonstrated the presence of two similar sized drug pools located in the two leaflets of the membrane. The transbilayer movement of doxorubicin occurred by a flip-flop mechanism of the drug between the two membrane leaflets. At 37 degrees, the flip-flop exhibited a half-life of 0.7 min, in both erythrocyte membranes and cholesterol-containing lipid membranes. The flip-flop was inhibited by cholesterol and accelerated by high temperatures and the fluidizer benzyl alcohol. The rate of doxorubicin flux across membranes is determined by both the massive binding to the membranes and the slow flip-flop across the membrane. The long residence-time of the drug in the inner leaflet of the plasma membrane allows P-glycoprotein a better opportunity to remove it from the cell.

Krabbe disease: increased incidence in a highly inbred community.

Krabbe disease (globoid cell leukodystrophy) was found with very high incidence (6/1,000 live births) in a large Druze kindred in Israel. The clinical data on 12 of the affected children demonstrated clinical variability even though these children are homozygous for the same mutation by descent from a common ancestor.

Dichloroacetate treatment for severe refractory metabolic acidosis during neonatal sepsis.

We describe a preterm neonate with documented group B Streptococcus sepsis and associated metabolic acidosis whose lactic acidemia was refractory to conventional sodium bicarbonate therapy but responded well to dichloroacetate treatment.

Prenatal diagnosis of Krabbe disease using a fluorescent derivative of galactosylceramide.

A fluorescent substrate 12-(N-methyl-N(7-nitro-2-oxa-1,3-diazol-4-yl) aminododecanoyl sphingosyl beta-D-galactoside ('NBD galactocerebroside') was synthesized and used for the detection of galactocerebrosidase activity. The enzyme determinations using this substrate were found to be extremely sensitive yielding unambiguous results. This substrate was used for the prenatal diagnosis of a fetus affected with Krabbe disease; the diagnosis was later confirmed in the aborted fetus.

Birth weight and physical ability in 5- to 8-yr-old healthy children born prematurely.

Recent advances in perinatal care have resulted in increased survival rates of extremely small and immature newborns. This has resulted in some neurodevelopmental impairment. The purpose of this study was to quantitatively evaluate and compare neuromuscular performance in children born prematurely at various levels of subnormal birth weight (BW). Subjects were 5- to 8-yr-old children born prematurely at different levels of subnormal BW (535-1760 g, N = 22, PM), and age-matched controls born at full term (> 2500 g, N = 15, CON). None of the subjects had any clinically defined neuromuscular disabilities. Body mass (BM) of PM was lower than that of CON (18.3 +/- 2.7 vs 21.7 +/- 3.8 kg) with no difference in height or sum of 4 skinfolds. Peak mechanical power output determined with a 15-s modified Wingate Anaerobic Test and corrected for BM was lower (P = 0.07) in PM than in CON (5.11 +/- 1.07 vs 5.94 +/- 1.00 W.kg-1). This was especially noticeable in children born at extremely low BW (ELBW, < 1000 g, 4.49 +/- 1.04 W.kg-1, P < 0.01). Peak power, determined in a force-plate vertical jump, corrected for BM was lower in PM vs CON (25.5 +/- 5.4 vs 30.8 +/- 5.2 W.kg-1, respectively P = 0.01), especially in the ELBW group (20.0 +/- 5.5 W.kg-1). Similarly, the elapsed time between peak velocity and actual jump take-off was longer in PM than in CON (41.2 +/- 9.4 vs 35.8 +/- 5.8 ms, respectively, P = 0.04). No differences were observed in peak force. The results suggest that performance deficiencies of prematurely-born children may be a result of inferior inter-muscular coordination. The precise neuromotor factors responsible for this should be identified by future research.

Head growth and neurodevelopmental outcome in neonates with intracranial haemorrhage and leukomalacia.

Head growth was correlated with outcome in 12 infants with major intracranial haemorrhages and in 9 with extensive cystic leukomalacia. Decreasing head growth was associated with a poor neurodevelopmental outcome whereas a normally growing head did not necessarily correlate with a normal outcome.

Ultrasound evolution and later outcome of infants with periventricular densities.

The evolution of ultrasound findings in 59 infants with transient periventricular densities is described and the neurodevelopmental outcome of 53 of these infants was compared with 92 of 107 infants with normal ultrasound scans, born during the same 24-month period. Four of the 53 infants with transient periventricular densities developed spastic diplegia and 24 developed transient dystonia, whereas only 8 of the 92 children with normal ultrasound scans demonstrated this finding (P less than 0.001). Persistence of the densities for more than 10 days and the presence of densities in the trigone were especially related with subsequent problems. Postmortem findings in two infants and MRI studies in six infants also suggested that transient periventricular densities represent the milder end of the spectrum of periventricular leukomalacia.

Evolution of periventricular leukomalacia during the neonatal period and infancy: correlation of imaging and postmortem findings.

Eighteen of 68 infants born over a 4-year period who had cranial ultrasound studies and later came to necropsy were found to have periventricular leukomalacia (PVL). Thirteen were diagnosed in life and there was one false positive diagnosis giving an accuracy of 91%, sensitivity of 72% and specificity of 98%. In 11 infants with sequential studies, who died at ages from 43 h to 3 years, the ultrasound findings were correlated with those at postmortem to establish the natural history of the condition. In infants who died within 7 days following the onset of the ultrasound changes, postmortem revealed early PVL without cysts: there were small haemorrhages into the affected areas in three of the four cases. In the five infants who died between 10 days and 9 weeks, cystic lesions were identified in life and at postmortem, but in two long-term survivors cysts resolved on ultrasound at 3-4 months of age. Correlation of ultrasound with postmortem findings demonstrated that, although the ultrasound lesions resolve, glial scarring and impaired myelination can still be demonstrated on careful pathological examination.

A holistic transition programme for persons with learning disabilities in Israel.

This paper describes a two year holistic transition programme for persons with a learning disability in Israel and a follow-up of the first cohort of trainees. The programme which was initiated by the National Insurance Institution and 'Nitzan' a parent voluntary organization was developed to provide these persons with the vocational, personal and social skills required for successful independent living and vocational adjustment. The training was carried out in a residential setting and included vocational training, activities of daily living, educational activities and personal adjustment counselling. The results indicated that two years after completing the programme the trainees were generally meeting the expectations of the goals of the project.

Iron supplementation for preterm infants receiving restrictive red blood cell transfusions: reassessment of practice safety.

OBJECTIVE: To reassess iron supplementation practice safety in very low birth weight (VLBW) preterm infants receiving restrictive red blood cell transfusions during initial hospitalization. STUDY DESIGN: Iron status, including hemoglobin (Hb), serum iron, ferritin, and soluble transferrin receptor (sTfR) levels and reticulocyte count of transfused (n=236) and non-transfused (n=166) preterm infants at ≤24 h and 2, 4 and 8 weeks were recorded. As per protocol, a restrictive blood transfusion policy and supplementation of 5 mg kg(-1) per day of iron polymaltose complex from 4 weeks and 25 mg(-1) per day of vitamin E from 2 weeks were imposed for all infants. Normative reference cord-blood ferritin value of preterm infants was used for comparison. Vitamin E levels and incidence of morbidities associated with prematurity were recorded. RESULT: At ≤24 h, the characteristics and iron status of both groups were similar. At 2, 4 and 8 weeks, the transfused group had significantly higher Hb, iron and ferritin levels; sTfR levels were lower at 4 and 8 weeks (all indices, P<0.05). At 8 weeks, the median ferritin levels of our transfused group were lower than that of normative reference cord-blood value (115 (50th percentile) vs 79 (43 to 107) µg l(-1), respectively). Vitamin E levels and the incidence of morbidities associated with prematurity of the transfused and non-transfused groups were not different (both indices, P>0.18). CONCLUSION: Adding iron supplementation to preterm infants receiving restrictive blood transfusions has shown to be a judicious and safe practice in terms of iron status for VLBW preterm infants.