Israel Medical Association Journal

Background: A substantial number of premature deliveries occur in hospitals lacking neonatal intensive care facilities. We previously demonstrated a comparable outcome of very low birth weight infants delivered in a level II nursery to that of inborn infants delivered in our tertiary care center, but a similar comparison of extremely low birth weight infants has not been done.

Objectives: To compare the neonatal outcome (mortality, severe intraventricular hemorrhage/periventricular leukomalacia, bronchopulmonary dysplasia and intact survival) of inborn and outborn ELBW[1] infants, accounting for sociodemographic, obstetric and perinatal variables.

Methods: We compared 97 ELBW infants (birth weight ≤ 1000 g.) delivered between the years 2000 and 2004 in a hospital providing neonatal intensive care to 53 ELBW babies delivered in a referring hospital. A univariate model was first applied to examine the associations of the individual independent variables with the outcome variable, followed by a logistic stepwise regression analysis for each of the outcome variables. The odds ratios for each predictor were reported as well as their P values and 95% confidence intervals.

Results: In the stepwise logistic regression analysis, accounting for a possible confounding effect of the independent variables, ‘hospital of birth’ remained a statistically significant predictor in the final step only for mortality, with odds ratio (inborns relative to outborns) of 3.32 (95%CI[2] 1.19–9.28, P = 0.022). No statistically significant associations with the other outcome variables were found (severe IVH[3]/PVL[4] odds ratio = 1.99, 95%CI = 0.77–5.14, P = 0.155; BPD[5] odds ratio = 0.60, 95%CI = 0.19–1.91, P = 0.384; intact survival OR[6] = 0.56, 95%CI = 0.23–1.35, P = 0.195).

Background: Many centers in Israel still use pre-1970 reference data for neonatal weight, length and head circumference. A recently published population-based reference overestimated the weight of premature infants.

Objective: To develop a national reference for birth weight, birth length, and head circumference by gestational age for singleton infants in Israel.

Methods: Data were collected on all singleton live births documented in the neonatal registry of Rabin Medical Center from 1991 to 2005 (n=82,066). Gestational age estimation was based on the last menstrual period until 1977 and early fetal ultrasound thereafter. Neonates with an implausible birth weight for gestational age (identified by the rule of median ± 5 standard deviations or expert clinical opinion) were excluded. Reference tables for fetal growth by gestational age were created for males and females separately.

Results: The growth references developed differed markedly from the Usher curves currently used in our department. Compared to the recently published population-based birth weight reference, our data were free of the problem of differential misclassification of birth weight for gestational age for the premature infants and very similar for the other gestational age groups. This finding reinforced the validity of our measurements of birth weight, as well as of birth length and head circumference.

Conclusions: Use of our new (birth length and head circumference) and improved (birth weight) gender-specific hospital-based reference for fetal growth may help to define normal and abnormal growth in the neonatal population of Israel and thereby improve neonatal care and public health comparisons.
 

Background: Babies born with extreme prematurity and low birth weight (< 1000 g) present a unique treatment challenge. In addition to the complexity of achieving survival, they may require surgical interventions for abdominal emergencies. Usually, these infants are transferred to a referral center for surgery treatment. Since 2000 our approach is bedside abdominal surgery at the referring center.

Objectives: To evaluate whether the approach of bedside abdominal surgery at the referring center is safe and perhaps even beneficial for the baby.

Methods: We retrospectively reviewed our data since 2000 and included only babies weighing < 1000 g who were ventilated, suffered from hemodynamic instability and underwent surgery for perforated bowel at the referring neonatal unit. Results were analyzed according to survival from the acute event (> 1 week), survival from the abdominal disease (> 30 days) and survival to discharge.

Results: Twelve babies met the inclusion criteria. Median weight at operation was 850 g (range 620–1000 g) and median age at birth was 25 weeks (range 23–27). Eleven infants survived the acute event (91.7%), 9 survived more than 30 days (81.8%), and 5 survived to discharge.

Conclusions: Our results show that bedside laparotomy at the referring hospital is safe and feasible. A larger randomized study is indicated to prove the validity of this approach.

Background: A paradoxical secular trend of an increase in preterm births and a decrease in low birth weights has been reported in many developed countries over the last 25 years.

Objective: To determine if this trend is true for Israeli neonates, and to add new information on secular trends in crown-heel length and head circumference.

Methods: A hospital-based historic cohort design was used. Anthropometric data for 32,062 infants born at Rabin Medical Center in 1986–1987, 1994–1996, and 2003–2004 were collected from the hospital’s computerized registry and compared over time for absolute values and proportional trends.

Results: For the whole sample (gestational age 24–44 weeks) there was a significant increase in mean birth weight (by 41 g), crown-heel length (by 1.3 cm), and head circumference (by 0.1 cm) from 1986 to 2004 (P < 0.001). A similar trend was found on separate analysis of the post-term babies. Term infants showed an increase in mean length and head circumference (P < 0.001), but not weight, and moderately preterm infants (33–36 weeks) showed an increase in mean weight (81 g, P < 0.001) and mean length (1.0 cm, P < 0.001), but not head circumference. The proportion of post-term (42–44 weeks), preterm (24–36 weeks), very preterm (29–32 weeks), extremely preterm (24–28 weeks), low birth weight (< 2500 g) and very low birth weight (< 1500 g) infants decreased steadily and significantly over time (P < 0.002).

Conclusions: Babies born in our facility, term and preterm, are getting bigger and taller. This increase is apparently associated with a drop (not a rise) in the proportion of preterm infants. These results might reflect improvements in antenatal care and maternal determinants.
 

Background: The management of aspirin therapy before an invasive procedure poses a frequent clinical dilemma due to uncertainty regarding b[AS1] leeding versus thromboembolic risks associated with continuation or withdrawal of the drug. There is no evidence-based data to refer to.

Objectives: To assess the opinions of internal medicine physicians regarding aspirin therapy prior to an invasive procedure.

Methods: A questionnaire presenting nine hypothetical cases with different combinations of bleeding and thromboembolic risk was given to physicians in an Internal Medicine Division during a personal interview. For each case the participants had to choose between withdrawal of aspirin prior to an invasive procedure, continuation of aspirin, or substitution of low molecular weight heparin for aspirin. Results: Sixty-one physicians participated in the survey. For a patient with low thromboembolic risk, 77% (95% confidence interval 65.3–86.3%), 95% (87.2–98.7%) and 97% (89.6–99.5%) of physicians elected to discontinue aspirin prior to a low, intermediate or high bleeding risk procedure, respectively. For intermediate risk patients, 23% (95% CI[1] 13.7–34.7%), 59% (46.4–70.8%) and 74% (61.7–83.6%) would discontinue aspirin prior to a low, intermediate or high risk procedure, and 5% (95% CI 1.3–12.8%), 23% (13.7–34.7%) and 18% (9.9–29.2%) would substitute LMWH[2] for aspirin. For a patient with high thromboembolic risk, 1.6% (95% CI 0.08–7.8%), 11.5% (5.2–21.4%) and 18% (9.9–29.2%) recommended discontinuing aspirin prior to a low, intermediate or high risk procedure, respectively. In these situations, 18% (95% CI 9.9–29.2%), 53% (40.0–64.7%) and 57% (44.8–69.3%), respectively, would substitute LMWH for aspirin.

Conclusions: The results of the current investigation may help practicing physicians to decide whether to discontinue aspirin therapy prior to invasive procedures. The possible use of LMWH to replace aspirin as suggested here should be further evaluated in a controlled clinical study.

 

Background: Necrotizing enterocolitis is a common progressive gastrointestinal disease affecting more than 5% of very low birth weight infants and associated with a high mortality rate.

Objectives: To determine whether excessive weight gain in preterm infants is an early sign of NEC[1].

Methods: Seventeen preterm infants with perforated NEC were identified and matched with 17 control subjects for birth weight and gestational age. The postnatal age (days) at diagnosis of NEC was identified, and weight changes as well as clinical and laboratory data were recorded and compared for 7 days prior through 7 days post-diagnosis.

Results: A significant difference in weight gain was noticed between D-1 and D 0. The NEC and control groups gained 5.1% and 1.2%, respectively (P = 0.002). None of the sick infants lost weight on days -1 to D 0.

Conclusions: Excessive weight gain was observed in premature infants who subsequently developed NEC. Daily evaluation of weight changes should be considered part of a strategy for early identification of infants at risk for developing NEC. Future studies are needed to confirm this finding in a prospective manner and to investigate its pathogenesis.

Objectives: To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very low birth weight infants, accounting for sociodemographic, obstetric and perinatal variables, with reference to earlier published data.

Methods: We compared 129 premature infants with birth weights of 750–1250 g delivered between 1996 and 2000 in a hospital providing neonatal intensive care to 99 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistical significant association with the outcome variables and dissimilar distribution in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression.

Results: Accounting for the covariates, the odds ratios (outborns relative to inborns) were 0.31 (95% confidence interval = 0.11–0.86, P = 0.03) for mortality, 1.37 (95%CI[1] = 0.64–2.96, P = 0.42) for severe intraventricular hemorrhage, and 0.86 (95%CI = 0.38–1.97, P = 0.78) for bronchopulmonary dysplasia. The odds ratio for survival without severe intraventricular hemorrhage was 1.10 (95%CI = 0.55–2.20, P = 0.78). Comparing the current results with earlier (1990–94) published data from the same institution showed that mortality decreased in both the outborn and inborn infants (OR[2] = 0.23, 95%CI = 0.09–0.58, P = 0.002 and 0.46; 95%CI = 0.20–1.04, P = 0.06, respectively), but no significant change in the incidence of severe intraventricular hemorrhage or brochopulmonary dysplasia was observed. Increased survival was observed also in these infants receiving surfactant, more so among the outborn. The latter finding could be attributed to the early, pre-transport surfactant administration, implemented only during the current study.

Conclusions: Our data suggest that very low birth weight outborn infants may share an outcome comparable with that of inborn babies, if adequate perinatal care including surfactant administration is provided prior to transportation to a tertiary center.

Objective: To establish population-based standards of birth weight of singletons in Israel.

Methods: Data on birth weight and gestational age were obtained from the registries of the Israel Ministry of Health and Ministry of the Interior. During the 8 year study period there were 1,074,122 infants delivered in Israel; 787,710 (73%) were included in this analysis.

Results: In this study we provide data of birth weight by gestational age of live infants born in Israel between 1993 and 2001. Ranges of birth weight by gestational age are also depicted for singleton and multiple pregnancies. Fetuses in multiple pregnancies grow in a similar manner to singletons until 30 weeks of gestation, after which their growth slows down.

Conclusions: Use of these data as a standard for “intrauterine” growth better represents the Israeli neonatal population than the American standards. In addition, curves of multiple pregnancies are significantly different from those of singleton pregnancies and might be more appropriate in these pregnancies.

Background: Venous thromboembolic diseases are treated initially with low molecular weight heparin followed by oral coumarins.

Objectives: To investigate an orally available direct thrombin inhibitor for the acute treatment of venous thromboembolism as well as for prophylaxis of recurrent events.

Methods: The direct thrombin inhibitor ximelagatran was compared with subcutaneous LMW[1] heparins followed by oral warfarin in a double-blind randomized prospective multicenter trial in patients with acute VTE[2]. A pharmacokinetic study was performed in the VTE patients. For assessing the prevention of recurrent VTE, double-blind prospective randomized studies were conducted as follows: a) ximelagatran compared to warfarin for 6 months, and b) prolonged anticoagulation of ximelagatran vs. placebo for 18 months after termination of 6 months coumarin therapy.

Results: Two dose-finding studies and the pharmacokinetic analysis of ximelagatran in acute VTE were completed. About 2,500 patients were randomized to investigate 2 x 36 mg ximelagatran versus 2 x 1 mg/kg body weight enoxaparin followed by warfarin. The study hypothesized that the efficacy was equal in both treatment regimens for recurrent VTE documented by objective methods. The second study, with 1,234 patients, aimed to demonstrate a reduced incidence of recurrent thromboembolic events documented by objective methods after 18 months of treatment with 2 x 24 mg ximelagatran daily compared to placebo.

Conclusion: These large-scale clinical trials will soon yield the results of the comparison between oral ximelagatran and subcutaneous LMW heparin for treatment of acute VTE, and of warfarin for prophylaxis of recurrent events for 6 months and for a prolonged prophylaxis for another 18 months.

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[1] LMW = low molecular weight

[2] VTE = venous thromboembolism