Less postnatal steroids, more bronchopulmonary dysplasia: a population-based study in very low birthweight infants.

OBJECTIVE: To study the association between reduced use of postnatal steroids for bronchopulmonary dysplasia (BPD) in very low birthweight (VLBW) infants and oxygen (O(2))-dependency at 28 days of age and at 36 weeks postmenstrual age. DESIGN: Large national database study. SETTING: The Israel National VLBW Neonatal Database. PATIENTS: The sample included infants born between 1997 and 2004, of gestational age 24-32 weeks, who required mechanical ventilation or O(2) therapy. Four time periods were compared: 1997-8 (era 1, peak use), 1999-2000 (era 2, intermediate), 2001-2 (era 3, expected reduction) and 2003-4 (era 4, lowest). The outcome variable "oxygen dependency" was based on clinical criteria. Multivariate regression models were used to account for confounding variables. RESULTS: Steroid use fell significantly from 23.5% in 1997-8 to 11% in 2003-4 (p<0.005). After adjustment for relevant confounding variables, the odds ratio for O(2) therapy at 28 days in era 4 versus era 1 was 1.75, 95% confidence interval (CI) 1.47 to 2.09 and 1.41, 95% CI 1.15 to 1.73 at 36 weeks postmenstrual age. The mean duration of O(2) therapy increased from 25.3 days (95% CI 23.3 to 26.3) in era 1, to 28.0 days (95% CI 26.6 to 29.4) in era 4. Survival increased from 78.5% in era 1 to 81.6% in era 4 (p<0.005). CONCLUSIONS: The use of steroids has fallen considerably since the awareness of the adverse effects of this treatment. This change has been temporally associated with increased O(2) dependency at 28 days of age and at 36 weeks postmenstrual age. The prolongation of O(2) therapy was modest in degree.

Bronchopulmonary dysplasia in very low birth weight infants is associated with prolonged hospital stay.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with prolonged hospital length of stay (LOS) and delayed discharge home. OBJECTIVES: To evaluate the association between BPD and LOS and to assess the contribution of concomitant major morbidities on LOS among infants with BPD. STUDY DESIGN: A population-based observational study of very low birth weight (VLBW) infants born from 1995 through 2003. Multivariate analyses, adjusted for perinatal variables, assessed the association between BPD and concomitant morbidities on LOS. RESULTS: Of 10 134 survivors, 1926 (19.0%) had BPD. The adjusted LOS for infants with and without BPD was 84.1 days (95% CI, 82.8, 85.6) and 58.1 days (95% CI, 57.2, 59.0), respectively. Addition of a single concomitant morbidity increased mean LOS by 4 to 13 days. CONCLUSIONS: BPD is a major cause of increased length of hospitalization among VLBW infants. Preventive or therapeutic modalities are required to reduce the significant burden of this condition.

Effect of birth order on neonatal morbidity and mortality among very low birthweight twins: a population based study.

OBJECTIVE: To study the effect of birth order on the risk for respiratory distress syndrome (RDS), chronic lung disease (CLD), adverse neurological findings, and death in very low birthweight (VLBW; < 1500 g) twins. METHODS: A population based study of VLBW infants from the Israel National VLBW Infant Database. The sample included all complete sets of VLBW twin pairs admitted to all 28 neonatal intensive care units between 1995 and 1999. Outcome variables were compared by birth order and stratified by mode of delivery and gestational age, using General Estimating Equation models, with results expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Second twins were at increased risk for RDS (OR 1.51, 95% CI 1.29 to 1.76), CLD (OR 1.36, 95% CI 1.11 to 1.66), and death (OR 1.24, 95% CI 1.02 to 1.51) but not for adverse neurological findings (OR 1.20, 95% CI 0.91 to 1.60). Mode of delivery did not significantly influence outcome. The odds ratio for RDS in the second twin was inversely related to gestational age, and the increased risk for RDS and CLD was found in both vaginal and caesarean deliveries. CONCLUSIONS: VLBW second twins are at increased risk for acute and chronic lung disease and neonatal mortality, irrespective of mode of delivery.

Effect of ethnicity on mortality of very low birthweight infants in Israel.

BACKGROUND: Multiple demographic, genetic, and environmental factors differ between Muslim and Jewish infants in Israel. OBJECTIVE: To evaluate whether, after adjustment for perinatal factors associated with mortality, excess mortality occurs in very low birthweight (VLBW) Muslim compared with Jewish infants. DESIGN: The Israel National VLBW infant database includes data on 99% of all VLBW births in Israel. The study population comprised 5015 Jewish and 1549 Muslim VLBW infants of more than 23 weeks gestation, born between 1995 and 1999. The Mantel-Haenszel test was used for stratified analysis and logistic regression analysis to assess the effect of ethnic origin on mortality. RESULTS: The death rate was significantly higher among Muslim infants (22.7% v 17.2%; crude odds ratio 1.42; 95% confidence interval 1.24 to 1.63). Excess mortality in Muslims occurred mainly in the 32-33 week (8.0% v 2.8%) and >33 week (14.7% v 4.7%) gestational age groups, and in birthweight groups of 1000-1249 g (17.6% v 9.3%) and 1250-1500 g (9.1% v 3.6%). In VLBW infants without congenital malformations, there was a significantly higher risk of mortality among Muslim infants (odds ratio 1.28; 95% confidence interval 1.04 to 1.57) compared with Jewish infants, after adjustment for gestational age, birth weight, small for gestational age, prenatal care, prenatal steroid treatment, plurality, mode of delivery, and Apgar score. CONCLUSIONS: Excess mortality was present among Muslim VLBW infants without congenital malformations. Perinatal factors associated with increased risk of mortality were more prevalent in the Muslim VLBW population. The pattern of disparities suggests inadequate access to, or utilisation of, effective perinatal technology in the Muslim population in Israel.

Excess risk of mortality in very low birthweight triplets: a national, population based study.

BACKGROUND: Neonatal morbidity and mortality differ between singletons, twins, and triplets. OBJECTIVE: To evaluate whether plurality is associated with excess risk of neonatal morbidity and poor outcome (death, chronic lung disease, or adverse neurological findings) in very low birthweight (VLBW) infants from a national, population based cohort. METHODS: The Israel national VLBW infant database has prospectively collected extensive perinatal and neonatal data on all liveborn VLBW infants since 1995. The study sample (n = 5594) consisted of all singletons (n = 3717) and all complete sets of twins (n = 1394) and triplets (n = 483) born during 1995-1999. To account for differences in case-mix, both univariate and multivariate comparisons that included confounding variables such as antenatal steroid treatment and mode of delivery were performed for each of the outcome variables. RESULTS: There was a small inverse correlation between gestational age (GA) and birth weight (BW) and the number of fetuses (singletons: GA 28.9 (2.6) weeks, BW 1096 (269) g; twins: GA 28.4 (2.3) weeks, BW 1062 (271) g; triplets: GA 28.5 (2.4) weeks, BW 1049 (259) g). Triplets were significantly more likely to have been conceived following fertility treatments, to have received antenatal steroids, and to be delivered by caesarean section. Respiratory distress syndrome was significantly more common in twins and triplets in spite of the increased exposure to antenatal steroids. Multivariate logistic regression analysis using all significant perinatal covariates showed that triplets were at increased risk of death (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.13 to 2.11), but not of adverse neurological outcome (OR 1.29, 95% CI 0.91 to 1.85) or chronic lung disease (OR 0.69, 95% CI 0.46 to 1.02). CONCLUSION: Despite considerable differences in the incidence of confounding variables between the groups, VLBW triplets are at increased risk of death compared with twins and singletons. In addition, VLBW twins and triplets more often have respiratory distress syndrome but not chronic lung disease or adverse neurological findings.

Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants.

AIM: To examine the relation between grade III-IV periventricular/intraventricular haemorrhage (PVH/IVH) and antenatal exposure to tocolytic treatment in very low birthweight (VLBW) premature infants. STUDY DESIGN: The study population consisted of 2794 infants from the Israel National VLBW Infant Database, of gestational age 24-32 weeks, who had a cranial ultrasound examination during the first 28 days of life. Infants of mothers with pregnancy induced hypertension or those exposed to more than one tocolytic drug were excluded. Of the 2794 infants, 2013 (72%) had not been exposed to tocolysis and 781 (28%) had been exposed to a single tocolytic agent. To evaluate the effect of tocolysis and confounding variables on grade III-IV PVH/IVH, the chi(2) test, univariate analysis, and a logistic regression model were used. RESULTS: Of the 781 infants (28%) exposed to tocolysis, 341 (12.2%) were exposed to magnesium sulphate, 263 (9.4%) to ritodrine, and 177 (6.3%) to indomethacin. The overall incidence of grade III-IV PVH/IVH was 13.4%. In the multivariate logistic regression analysis, the following factors were related significantly and independently to grade III-IV PVH/IVH: no prenatal steroid treatment, low gestational age, one minute Apgar score 0-3, respiratory distress syndrome, patent ductus arteriosus, mechanical ventilation, and pneumothorax. Infants exposed to ritodrine tocolysis (but not to the other tocolytic drugs) were at significantly lower risk of grade III-IV PVH/IVH after adjustment for other variables (odds ratio = 0.3; 95% confidence interval 0.2 to 0.6). CONCLUSION: This study suggests that antenatal exposure of VLBW infants to ritodrine tocolysis, in contrast with tocolysis induced by magnesium sulphate or indomethacin, was associated with a lower incidence of grade III-IV PVH/IVH.

Fetal hemoglobin-expressing nucleated red blood cell frequencies in pregnancies with intrauterine growth restriction.

The objective of this study was to examine whether there is a difference in the frequency of fetal erythroblasts in maternal blood in pregnancies with intrauterine growth restriction (IUGR) as compared with normal pregnancies. Nucleated red blood cells (NRBC) were isolated from nine pregnant women with ultrasonically diagnosed IUGR (estimated fetal weight less than the 10th percentile for gestational age) and 11 women with appropriately grown fetuses. The frequency of fetal hemoglobin-expressing NRBC (FHE-NRBC) in maternal blood was evaluated by triple density centrifugation and anti-CD71+ magnetic cell sorting, followed by indirect immunocytochemistry for the detection of gamma-chain fetal hemoglobin. The number of FHE-NRBC in 10 ml maternal blood in the IUGR group was higher than in the control group (454.5 vs 56.7, p<0.05). This difference was even more pronounced when FHE-NRBC frequency was calculated relative to the total CD71+ population of cells. There were 118.9 FHE-NRBC per 10(5) CD71+ cells in IUGR pregnancies as compared with 11.5 cells in the control group (p<0.01). There was no difference in the total mean number of CD71+ mononuclear cells between the two groups. The observed increase in the frequency of fetal cells in the maternal circulation found in IUGR pregnancies may be a result of an increase in total NRBC in the fetal circulation or rather of abnormalities in placental structure. This phenomenon may assist in identifying pregnancies at risk for this complication early in the course of the pregnancy, even before actual growth restriction presents itself ultrasonically.

The value of the occipitomental (Waters') view in diagnosis of sinusitis: a comparative study with computed tomography.

AIM: Sinus X-rays are still frequently used in the evaluation of paranasal sinusitis. Many radiology departments nowadays provide the referring doctors with a single Waters' projection. Our purpose was to evaluate the diagnostic accuracy of a single Waters' view vs high resolution computed tomography (CT) in the diagnosis of paranasal sinusitis. SUBJECTS AND METHODS: A total of 134 patients with suspected paranasal sinusitis underwent a Waters' view X-ray and high resolution CT on the same day. The radiographs were evaluated independently by nine experienced radiologists, who observed each sinus separately. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each sinus and for each observer, using the CT findings as a 'gold standard'. RESULTS: The weighted mean sensitivity for diagnosis of any abnormality in the maxillary sinus was 67.7%, specificity 87.6%, accuracy 78.6%, positive predictive value 82.5% and negative predictive value 76.9%. For this sinus the variation between observers was small, however, the sensitivity for diagnosis of any disease in the frontal and ethmoid sinuses varied widely between observers (range 1.9-54.0% and 0-58.9%, respectively). The sensitivity for the sphenoid sinus was very low (range 0-3.8%), even in radiographs which seemed to demonstrate it well. CONCLUSION: The Waters' view has its limits in the diagnosis of sinusitis of the maxillary sinuses and its contribution for diagnosing lesions in the remaining sinuses is very poor. Whenever access to CT is available, a low dose high-resolution CT study of the paranasal sinuses is highly recommended.Konen, E. (2000). Clinical Radiology55, 856-860.

Postpartum depression in an Israeli cohort: demographic, psychosocial and medical risk factors.

Demographic, psychosocial and medical risk factors for postpartum depression (PPD) were studied prospectively in a community cohort of 288 Israeli women. An Edinburgh Postnatal Depression Scale score of > or = 10 at 6 weeks postpartum was the criterion for PPD. Psychosocial risk factors were found to be the most potent. Lack of social support, marital disharmony, depressive symptoms during pregnancy, history of emotional problems and prolonged infant health problems were most predictive of PPD. The major role of psychosocial factors in PPD was similar to that found in other countries. The results were somewhat different for new Russian immigrants. These findings indicate that early identification of women at risk for PPD is feasible, and that consideration should be taken of subgroups that may be at heightened risk, or for whom risk factors play different roles.

Body mass index in 17-year-old Israeli males of different ethnic backgrounds; national or ethnic-specific references?

OBJECTIVE: To evaluate whether a single national reference is appropriate for assessing prevalence of overweight in heterogeneous populations, or whether ethnic-specific references are needed. DESIGN: A population-based study of Israeli Jewish males who underwent routine physical and clinical examinations prior to army recruitment served as the basis for the development of two types of references for body mass index (BMI): a national reference (NR) and an ethnic-specific reference (ER). SUBJECTS: Consecutive cohorts of all 17-y-old Jewish male recruits (n=109, 570). MEASUREMENTS: Weight, height and blood pressure values were obtained. BMI was calculated, and the 85th percentile of BMI was used as a cut-off point for overweight, using both types of references. Prevalence of hypertension among recruits was used as a biomarker to support the reliability of the ER when discrepancy in classification between the two references was found. RESULTS: As compared to the NR, three ethnic groups had a BMI distribution shifted to the left (light sub-population) and five were shifted to the right (heavy sub-population). In the light sub-population, 7% of the inductees who were classified as having normal weight by the NR were considered overweight by the ER and had a hypertension rate similar to that of those defined as overweight by both references (3.1 per 1000). In the heavy sub-population the 4% of subjects who were overweight by NR and normal by ER had hypertension rates similar to those defined as normal weight by both references (2.7/1000), and significantly lower than that of those classified as overweight by both references (10.8/1000). CONCLUSION: In heterogeneous populations, ethnic references should be used to evaluate prevalence of overweight, rather than one national reference. International Journal of Obesity (2000)24, 88-92

The effect of oophorectomy and estrogen replacement therapy on Doppler derived parameters of aortic flow.

OBJECTIVES: The immediate consequences of surgical castration and estrogen replacement therapy (ERT) on left ventricular systolic performance as assessed by Doppler-derived parameters of aortic flow were examined. METHODS: A follow up study comprising two groups: eight premenopausal women who underwent hysterectomy and bilateral oophorectomy and started ERT 1 week after surgery - the study group, and a control group consisted of eight premenopausal women who did not start ERT following hysterectomy. Doppler echocardiography was performed before surgery, 1 week and 1 month post surgery. RESULTS: In both groups significant increase in heart rate was observed after 1 week, remaining high after 1 month in the control group only. The early post-operative period in all women was characterized by an increase in aortic flow velocity, but was statistically significant in the study group only. After initiation of ERT a significant decrease in peak flow velocity (PFV) and mean acceleration (MA) was recorded. CONCLUSIONS: Changes in estradiol level may be associated with alterations in left ventricular function. The initial and acute effect of estrogen on the heart muscle after surgical castration is towards a decrease in Doppler-derived parameters of aortic flow. Whether these effects represent a depression of left ventricular function, or alternatively, reflect peripheral vasculature reactivity, requires further evaluation.

Decreased density of epidermal dendritic cells in melanocytic naevi: the possible role of in vivo sun exposure.

Melanocytic naevi are benign skin tumours that originate in the epidermis. The pathogenesis of naevi and cutaneous malignant melanoma has been linked to sun exposure. This study evaluates alterations in the density of immunologically active epidermal dendritic cells (EDCs) in naevi in response to sun exposure. Immunohistologically stained sections of 266 naevi from patients from Israel (n=135) and Germany (n=131) were evaluated. The proportion of naevi with decreased density of HLA-DR+ (dDR+) and CD1a+ (dCD1a+) EDCs was analysed according to country, last exposure to sunlight, anatomical location and histological subtype. The risk of dDR+ was found to be linked to residence in Israel compared with Germany (odds ratio [OR] = 4.2; 95% confidence interval [CI] = 2.0-8.9), suggesting a latitude-dependent effect. Naevi removed in summer had a higher risk of dCD1a+ (OR = 4.7; 95% CI = 2.3-9.8) compared with those removed in winter. The most conspicuous dDR+ among the German cases, and dCD1a+ among the Israelis, occurred in naevi located on commonly exposed skin. The similar densities of EDCs in the lesional and perilesional skin of the majority of the naevi indicates that the underlying naevus cells have no effect on EDC density. It is not unlikely that an altered immune response due to dDR+ and dCD1a+ in sun-exposed skin in the vicinity of naevi contributes to the subsequent melanoma risk in highly susceptible individuals.

Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies.

Activity levels of total and placental alkaline phosphatase (AP) were determined in maternal serum and neutrophils of normal and Down syndrome pregnancies. The placental iso-enzyme (PAP) was identified by its relative stability to urea and heat. Significant increase in the activity of all iso-enzymes across gestational stages was observed in maternal sera of 28 normal pregnancies. However, in the neutrophil extracts of the same blood samples no differences were detected between trimesters. Another set of experiments was aimed at finding diagnostic differences of PAP activity in maternal neutrophils of normal and trisomy 21 affected pregnancies. No differences of heat stable AP activity were found in maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea resistant AP proportions were also similar when measured after 40 minutes of exposure (13 samples in each group). However, a marginally significant increase was observed in the mean value of the Down syndrome affected samples, after 60 minutes of urea treatment. In view of the above results we conclude that neutrophil AP activity is not as yet a useful marker for the screening of trisomy 21 fetuses.

Cognitive status at admission: does it affect the rehabilitation outcome of elderly patients with hip fracture?

OBJECTIVES: To determine the effect of cognitive status at admission on functional gain during rehabilitation of elderly hip-fractured patients. DESIGN: Cohort study. SETTING: A hospital geriatric rehabilitation department. PATIENTS: Two hundred twenty-four elderly patients admitted consecutively for rehabilitation after surgery for hip fracture. MEASUREMENTS: Cognitive status was assessed by the Mini-Mental State Examination and the cognitive subscale of the Functional Independence Measure (cognFIM); functional status was assessed by the motor subscale of FIM; absolute functional gain was determined by the motor FIM gain (deltamotFIM); and relative functional gain (based on the potential for improvement) by the Montebello rehabilitation factor score (MRFS). RESULTS: A significant increase in FIM scores (19.7) occurred during rehabilitation, mainly due to motor functioning (19.1). When the relative functional gain (as measured by both motor MRFS efficacy [r = .591] and efficiency [r = .376] was compared with the absolute gain (as measured by deltamotFIM [r = .304]), a stronger association between cognFIM and the relative measures was found. In addition, motor FIM efficacy and efficiency were significantly lower in the cognitively impaired patients (p<.01). A better rehabilitation outcome was seen in patients with higher admission cognitive status, adjusting for the effects of age, sex, length of stay, and type of fracture (odds ratio = 2.2, 95% confidence interval 1.5-3.7). CONCLUSIONS: Impaired cognitive status at admission lowered the rehabilitation outcome of elderly hip fracture patients. Cognitive impairment was strongly and directly associated with functional gain in these patients. Absolute motor gain appeared to be independent of cognitive status, whereas the relative motor gain depended on it. These findings support the implementation of comprehensive rehabilitation for selected cognitively impaired elderly hip fracture patients.

Prospective study of postpartum depression in an Israeli cohort: prevalence, incidence and demographic risk factors.

This study aimed to assess the prevalence and incidence of postpartum depression (PPD) and to identify risk factors in a community cohort of Israeli-born, as well as new and veteran immigrant women. A random sample of 288 registrants at a community clinic was assessed for depressive symptoms at 26 weeks' pregnancy using the Beck Depression Inventory (BDI) and at 6 weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Information regarding risk factors was gathered through interviews and medical record abstracting. The prevalence of PPD was 22.6%. Two-thirds of the women had scored 'depressed' during pregnancy, and one-third (6.9%) were new incident cases. Immigrant status was the only significant demographic predictor of PPD identified by either univariate or multivariate analysis, with Russian new immigrants having over twice the risk for PPD as Israeli-born subjects. The rate of PPD in this Israeli cohort was comparable to that found in other countries. The finding that immigrant status was the most potent demographic predictor may support the role of stressful life events in the etiology of PPD. The use of the EPDS for PPD screening was found acceptable and feasible in the primary health setting.

Increased risk of salivary gland tumors after low-dose irradiation.

OBJECTIVE: To assess the risk of neoplastic development among persons exposed to scalp irradiation. STUDY DESIGN: Historical cohort study initially; prospective follow-up subsequently. METHOD: Two control groups--population and siblings--matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. RESULTS: A 4.5-fold incidence of cancer (P < .01) and a 2.6-fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. CONCLUSIONS: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.

Methodology of a two-step quantified nutritional questionnaire and its effect on results.

The effects of methodology on the results of epidemiologic studies that involve collection of nutritional data, especially those involving long-term-onset illnesses such as cancer, have not yet been carefully evaluated. We present methodological features of a quantitative dietary history and physical activity questionnaire and discuss their contribution to the final results. The results of our analysis are as follows: 1) Forty-seven percent of the population consumed > 100 food items yearly. 2) The mean number of calories contributed by items eaten less than once a week exceeded 200 kcal/day in 50% of interviewees. 3) Seventy-six percent of the patients had undergone dietary changes during the course of adult life. Of the 379 individuals who reported no changes when asked general questions, 61.8% reported changes when asked specifically about each food item in the questionnaire. 4) Physical activity was significantly correlated with mean daily energy intake (r = 0.208, p < 0.001). We conclude that certain methodological features of questionnaires, such as extensive listing of food items, precise documentation of food quantity, inquiries about former eating habits, and inclusion of questions about physical activity, increase accuracy in evaluations of dietary habits. Our analysis provides practical information for future planning of nutritional questionnaires.