Prenatal Exposure to Acid Suppressor Medications and Development of Ductus Arteriosus in Term Newborns.

OBJECTIVE: The ductus arteriosus normally closes after birth. Histamine 2 receptor antagonist (H2RA) has been associated with patent ductus arteriosus (PDA). We aimed to study the characteristics of term infants with PDA and their possible association with prenatal exposure to antacids-proton pump inhibitors (PPIs) and H2RA. STUDY DESIGN: This was a population-based matched case-control study of mothers registered at "Clalit" Health Maintenance Organization (HMO) and their infants born at "Soroka" University Medical Center (SUMC) between 2001 and 2018. Cases are defined as term infants born with PDA diagnosed by echocardiography and registered in the postdelivery discharge form. Each case was matched with four term newborns without PDA diagnosis. Exposure window was defined by the timing of first purchase of H2RA or PPI during pregnancy and based on information from a computerized medication database (Clalit HMO, SUMC). RESULTS: PDA was diagnosed in 1,884 term infants (4.9%). Characteristics included a significantly higher percentage of lack of prenatal care, cesarean section, in vitro fertilization, polyhydramnios, oligohydramnios, Apgar 1 minute <5, and prenatal exposure to H2RA (odds ratio [OR] 4.18) and PPIs (OR 3.50; all p < 0.001). PDA association with exposure window was similar in each trimester (1.5-2%) for both H2RA and PPI. CONCLUSION: PDA incidence in term infants in our population was greater than previously reported. PPI and H2RA are both antiacids with different mechanisms of action. The similar OR for exposure to one as well as the other, and the lack of influence of the initial exposure period, are compatible with bias. KEY POINTS: · Term newborns with PDA have different characteristics than newborns without PDA.. · Prenatal exposure to PPIs or H2RA is associated with greater risk of PDA in term newborns.. · The possible effect mechanism of PPIs on the ductus is unclear and understudied..

Prenatal Exposure to Antibiotics and Development of Epilepsy in Children.

We aimed to confirm or reject previous reports on the association of prenatal antibiotic exposure and development of epilepsy in offspring by accounting for known and unidentified confounding factors. In a retrospective cohort investigation, we enrolled children aged 3-18 years born between 1998 and 2012 at a single regional hospital and their mothers. A computerized medication database was linked with hospital records. The exposed group included children whose mothers purchased 1 or more antibiotic medications for use during pregnancy. Epilepsy was defined by epilepsy diagnosis and/or by chronic dispensing of antiepileptic drugs. We analyzed maternal exposure to antibiotics 2 years after delivery (but not during pregnancy and/or the 2 years following delivery) as part of the specificity analysis. We enrolled 88 899 children and their 74 416 mothers. The group exposed prenatally to antibiotics comprised 36 622 children (41.2%). Of them, 326 (0.9%) developed epilepsy compared with 370 of 52 277 (0.7%) in the unexposed group (relative risk [RR], 1.24; 95% confidence interval [CI], 1.07-1.44: P = .004). Exposure during the first, second, and third trimesters was characterized by incidence of epilepsy in 0.8% (P = .943), 0.9% (P = .266), and 0.9% (P = .073) of children, respectively, compared with the unexposed group, with an RR of 1.01 (95%CI, 0.83-1.23), 1.12 (95%CI, 0.92-1.36), and 1.19 (95%CI, 0.98-1.45), respectively. Similarly, prenatal exposure by antibiotic class was associated with epilepsy. Nevertheless, the specificity analysis strongly suggested the possibility of confounding by indication. Our findings indicated that pregnant women should receive the indicated antibiotic treatment with no fear of the development of epilepsy in their children.

The Fetal Safety of Enoxaparin Use During Pregnancy: A Population-Based Retrospective Cohort Study.

INTRODUCTION: Enoxaparin is widely used during pregnancy as pregnancy is a hypercoagulable state; however, its fetal safety has scarcely been investigated. OBJECTIVE: Our study aimed to examine fetal safety following enoxaparin exposure during pregnancy. METHODS: A population-based, retrospective cohort study was performed by linking computerized databases, including the drug dispensing registries of Clalit Health Services in Israel and maternal and infant hospital records, between 1998 and 2009. Multivariate logistic regression models were used to examine associations between first- and third-trimester exposure to enoxaparin, major malformations, and other adverse birth outcomes, adjusted for confounders. RESULTS: From a total of 109,473 singleton pregnancies, 418 and 572 were exposed to enoxaparin during the first and third trimesters, respectively. Exposure to enoxaparin during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations [adjusted odds ratio (aOR) 1.1, 95% confidence interval (CI) 0.8-1.6], while exposure during the third trimester was not associated with an increased risk of low birth weight (aOR 1.1, 95% CI 0.8-1.4), low Apgar score (aOR 0.9, 95% CI 0.4-1.8), or risk of perinatal mortality (aOR 0.6, 95% CI 0.1-2.9). CONCLUSION: Exposure to enoxaparin during pregnancy was not associated with an increased risk of major malformations in general or according to organ systems. Nonetheless, risk for specific malformations cannot be ruled out.

Prenatal exposure to H2 blockers and to proton pump inhibitors and asthma development in offspring.

Fetal exposure to H2 blockers (H2 Bs) or proton pump inhibitors (PPIs) has been reported to be associated with asthma in children. We evaluated the risk of asthma in offspring following prenatal H2 Bs. We enrolled 91 428 children and their mothers who resided in southern Israel during 1998-2011. The computerized medications database was linked with records from the district hospital. Of the eligible children, 11 227 developed asthma, and overall 5.5% had been exposed to H2 Bs or PPIs prenatally. The risk of developing asthma was slightly higher in the group exposed to H2 Bs or PPIs (RR, 1.09; P = .023). At greater risk were children whose mothers purchased these medications more than 3 times (RR, 1.22; P = .038) or exposed to >20 defined daily doses or prenatally exposed to lansoprazole. The statistical association was significant and depended on magnitude of exposure and specific medication, but the absolute risk was low. The association between maternal consumption of H2 Bs or PPIs and asthma and childhood remained statistically significant 2 years after delivery, raising the possibility of confounding by the indication phenomenon. In view of the findings, a causal relationship could not be ascertained, and an unidentified etiological factor could be operative.

Non-anthropogenic dust exposure and asthma medication purchase in children.

Air pollution has been shown to increase frequency of asthma attacks, as usually measured by hospitalisation rates. We hypothesise that purchase of asthma reliever medications will reflect a broader association between the environmental exposure and asthma exacerbations. In a time series analysis, we estimated the association of dust storms with mild asthma manifestations, as indicated by medication purchases, during 2005-2011. We compared our results with the estimation of the association of dust storms with hospitalisations due to asthma and asthma-like symptoms. We detected 289 dust storms characterised by high levels of particulate matter <10 µm in diameter. We identified 42,920 children with asthma, wheezing or asthma-like symptoms, of whom 2418 were hospitalised. We observed a higher risk of asthma medication purchase on the day of a mild dust storm (relative risk 1.05, 95% CI 1.00-1.10). The next peak in drug purchases was 3 days later and was more pronounced among Bedouin-Arab children. Stratified analyses showed higher risks for hospitalisation among Bedouin-Arab children; especially among children living in temporary houses (relative risk 1.33, 95% CI 1.04-1.71). We observed an increased risk of asthma medication purchase associated with mild dust storms. The risk observed for hospitalisation was more pronounced among the rural Bedouin-Arab population.

Fetal safety of macrolides.

Macrolide antibiotics are largely used in pregnancy for different bacterial infections. Their fetal safety has been studied by several groups, yielding opposing results. In particular, there have been studies claiming an association between macrolides and cardiovascular malformations. Exposure in early infancy has been associated with pyloric stenosis and intussusception. This has led to an avoidance in prescribing macrolides to pregnant women in several Scandinavian countries. The Objectives of the present study was to investigate the fetal safety of this class of drug by linking a large administrative database of drug dispensing and pregnancy outcome in Southern Israel. A computerized database of medications dispensed from 1999 to 2009 to all women registered in the Clalit health maintenance organization in southern Israel was linked with two computerized databases containing maternal and infant hospitalization records. Also, medical pregnancy termination data were analyzed. The following confounders were controlled for: maternal age, ethnicity, maternal pregestational diabetes, parity, and the year the mother gave birth or went through medical pregnancy termination. First- and third-trimester exposures to macrolide antibiotics as a group and to individual drugs were analyzed. During the study period there were 105,492 pregnancies among Clalit women that met the inclusion criteria. Of these, 104,380 ended in live births or dead fetuses and 1,112 in abortion due to medical reasons. In the first trimester of pregnancy, 1,033 women were exposed to macrolides. There was no association between macrolides and either major malformations [odds ratio (OR), 1.08; 95% confidence interval (CI), 0.84 to 1.38)] or specific malformations, after accounting for maternal age, parity, ethnicity, prepregnancy diabetes, and year of exposure. During the third trimester of pregnancy, 959 women were exposed to macrolides. There was no association between such exposure and perinatal mortality, low birth weight, low Apgar score, or preterm delivery. Similarly, no associations were demonstrated with pyloric stenosis or intussusception. Use of macrolides in the first trimester of pregnancy is not associated with an increased risk of major malformations. Exposure in the third trimester is not likely to increase neonatal risks for pyloric stenosis or intussusception in a clinically meaningful manner.

Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes.

OBJECTIVE: Despite high rates of hypertension in pregnancy, the effects of hypertension have not been separated appropriately from the effects of the medications that are used. We evaluated the safety of exposure to antihypertensive medications during pregnancy, while accounting for disease effects. STUDY DESIGN: A population-based retrospective cohort study was performed that compared all pregnancies of women with hypertension who were either exposed or unexposed to antihypertensive medications. A computerized database of the medications that were dispensed to pregnant women from 1998-2008 was linked with computerized databases that contained maternal and infant hospitalization records from the district hospital during the same period. RESULTS: During the study period, 100,029 deliveries occurred; of those, 1964 pregnant women experienced chronic hypertension, and 620 neonates (0.6%) were exposed to at least 1 antihypertensive medication (methyldopa or atenolol) during pregnancy. A higher rate of intrauterine growth restriction (7.2% vs 2.1%, respectively; adjusted odds ratio [OR], 4.37; 95% confidence interval [CI], 3.00-6.36; P < .001), small for gestational age (3% vs 1.7%, respectively; adjusted OR, 2.23; 95% CI, 1.27-3.92; P = .005), and preterm deliveries (<37 weeks, 22.9% vs 8.0%, respectively; adjusted OR, 3.69; 95% CI, 2.90-4.69; P < .001) were noted among the pregnancies of women who were exposed to antihypertensive medications during the third trimester. Importantly, a similar association was detected when we compared women with chronic hypertension who were not treated during pregnancy (n = 1074) to women who had no chronic hypertension and who were unexposed to antihypertensive medications (n = 97,820). CONCLUSION: Chronic hypertension with or without treatment during pregnancy is an independent and significant risk factor for adverse perinatal outcomes such as intrauterine growth restriction, small for gestational age, and preterm delivery.

Major malformations following exposure to nonsteroidal antiinflammatory drugs during the first trimester of pregnancy.

OBJECTIVE: Nonsteroidal antiinflammatory drugs (NSAID) are among the most common medicines used by pregnant women. Published data are controversial regarding fetal safety following intrauterine exposure to NSAID. We investigated exposure to NSAID in the first trimester in a large cohort of infants and fetuses. METHODS: A computerized database of medications dispensed from 1998 to 2009 to all women registered in the "Clalit" health maintenance organization in Southern Israel was linked with 2 computerized databases containing maternal and infant hospitalization records. Pregnancy terminations for medical reasons were analyzed. The following confounders were controlled for: parity, maternal age, ethnicity, maternal pregestational diabetes, maternal inflammatory disease, and year of birth or pregnancy termination. First trimester exposure to nonselective cyclooxygenase (COX) inhibitors and to selective COX-2 inhibitors as groups and to individual drugs was analyzed. RESULTS: There were 110,783 pregnancies during the study period: 109,544 singleton births and 1239 pregnancy terminations for medical reasons. In total, 5267 mothers were exposed to NSAID during the first trimester of pregnancy: 5153 to nonselective COX inhibitors and 114 to COX-2 selective inhibitors. Exposure to NSAID in the first trimester, as groups (nonselective COX and selective COX-2 inhibitors) and as individual drugs, was not associated with an increased risk of major congenital malformations in general (adjusted OR 1.07, 95% CI 0.96-1.21 for nonselective; and adjusted OR 1.40, 95% CI 0.70-2.78, for selective COX-2 inhibitors), although an increased risk for musculoskeletal malformations was found following exposure to COX-2 selective inhibitors (adjusted OR 3.39, 95% CI 1.37-8.34). CONCLUSION: Intrauterine exposure to NSAID was not associated with increased risk for major congenital malformations. Further studies are needed to assess the risk for malformations after exposure to COX-2 selective inhibitors.

Bias toward the null hypothesis in pregnancy drug studies that do not include data on medical terminations of pregnancy: the folic acid antagonists.

Most studies on safety/risk of drugs in pregnancy consider the proportion of births (but not pregnancy terminations) affected by the drug from all exposed infants. Lack of data on pregnancy terminations could bias results. A computerized database for medications dispensed to pregnant women in southern Israel was linked with records from the district hospital; 84 823 deliveries and 998 medical pregnancy terminations took place; 571 of the women were exposed to folic acid antagonists in the first trimester. When only births were examined, there was no association between folic acid antagonists and fetal malformations. When data on pregnancy terminations were examined and births and pregnancy terminations were combined, there was a significant risk (neural tube defects: odds ratio 18.83, 95% confidence interval 9.24-38.37; cardiovascular defects: odds ratio 3.86, 95% confidence interval 1.67-8.88; and neural tube defects: odds ratio 6.30, 95% confidence interval 3.34-9.15; cardiovascular defects: odds ratio 1.76, 95% confidence interval 1.05-2.92, respectively). Inclusion of only birth data in observational studies of drugs in pregnancy constitutes a source of bias toward the null hypothesis.

Kidney function and retinol status in type 2 diabetes mellitus patients.

Kidneys play an important role in retinol turnover. We postulated that retinol homeostasis is disturbed in diabetic nephropathy. The aim of this research was to study the effect of kidney impairment on urinary excretion and on serum concentrations of retinol in type 2 diabetes mellitus patients. For this purpose, 41 type 2 diabetes patients and 9 sex -and age-matched healthy subjects were enrolled. Serum and urinary retinol and retinol-binding protein (RBP) were assessed by high-pressure liquid chromatography and enzyme-linked immunosorbent assay, respectively. The study showed that 17 out of 41 diabetic patients (41.5%) and none of the controls excreted retinol in urine (P < 0.02). Retinol excretion in the urine in these patients was 1.5-fold more prevalent than hypercreatininemia. Urinary retinol significantly correlated with clinically diagnosed nephropathy (P = 0.02). All but one of the patients with hypercreatininemia excreted retinol in the urine. Serum retinol and RBP in patients with hypercreatininemia were higher than in controls (P < 0.002). Values of urinary retinol, unlike urinary RBP, albumin and total protein, did not overlap between patients and controls. Our results indicate that (i) urinary retinol is a specific sign of tubular damage in type 2 diabetic patients and (ii) urinary retinol enables a more clear-cut identification of proximal tubule dysfunction in type 2 diabetes patients than urinary RBP or albumin.

Teratogenic determinants of first-trimester exposure to antiepileptic medications.

OBJECTIVE: To investigate the potential impact of exposure to anti epileptic medications during the first-trimester of pregnancy on major malformations. STUDY DESIGN: A retrospective cohort study comparing all pregnancies of women with and without exposure to antiepileptic medications during pregnancy was performed. A computerized database of medications dispensed from 1998 to 2008 to all women registered in the "Clalit" health maintenance organization, was linked with computerized and non computerized databases containing maternal and infant hospitalization records from the district hospital. Exposed women were further analyzed by mono and poly- antiepileptic therapy during pregnancy. Stratified analyses, using multiple logistic regression models were performed to control for confounders. RESULTS: During the study period 99,724 deliveries and 1012 pregnancy terminations occurred; of those, 421 (0.42%) were exposed to one or more antiepileptic medications during the first trimester. A higher rate of major congenital malformations was detected among women who were exposed, as compared to those unexposed to antiepileptic medications during the first-trimester (10.0% vs. 7.0%; P=0.02). The association remained significant after adjusting for maternal age, ethnicity, smoking, diabetes and parity (adjusted OR= 1.50; 95% CI 1.06-2.12; p=0.02). Specifically, the risk was significant for antiepileptic anti folate drugs (n=210; adjusted OR= 1.95; 95% CI 1.25-3.03; P=0.003). Poly-antiepileptic therapy was significantly associated with major congenital malformations (26.5% vs. 5.7%, P<0.001). Using a multiple logistic regression model, controlling for ethnicity, diabetes, smoking, maternal age and parity, poly-antiepileptic therapy was an independent risk factor for major congenital malformations (adjusted OR= 7.98; 95% CI 3.4-18.7; P<0.001), while mono-therapy lost its independent association with major congenital malformations (adjusted OR= 1.23; 95% CI 0.8-1.8; P=0.28). CONCLUSION: First-trimester exposure to antiepileptic medications is an independent risk factor for major congenital malformations. The risk is significantly higher for anti folate antiepileptic drugs and for poly-antiepileptic therapy.

BeMORE: a novel method for detection of adverse fetal effects induced by drugs.

We describe a unique new collaboration which allows linkage of administrative databases in Southern Israel, and hence ascertain risk/safety of prescription drugs in pregnancy. The advantages of this system include availability of rigorous data confounders, solid data on maternal conditions for which the drug is given, ability to capture all cases of elective abortions and not just live births, and ability to construct drug doses.

Prenatal exposure to mycophenolate mofetil: an updated estimate.

Mycophenolate mofetil (MMF) has become a major therapeutic option in the management of patients undergoing transplantation, as well as in the treatment of autoimmune conditions. Case reports have suggested that MMF use during pregnancy is associated with a specific pattern of congenital malformations. Because many pregnancies are unplanned, it is imperative to assess the teratogenic risk of MMF. Using the Organization of Teratology Information Specialists network, we prospectively identified and followed pregnant women exposed to MMF during pregnancy to update this teratogenic potential. Ten cases were identified and all received the drug during embryogenesis at the recommended doses (500 to 1500 mg daily). There were four miscarriages and one elective abortion due to fear of teratogenesis. None of the five live births had malformations. It is possible that, similar to other human teratogens discovered first by case reports, the absolute risk from MMF may be smaller than originally calculated based on case reports. Because the major malformations phenotypic of MMF may be visualized in utero (e.g., microtia, cleft palate, congenital diaphragmatic hernia, and cardiac malformation), diagnostic imaging should be performed.

The safety of H(2)-blockers use during pregnancy.

Little data exist on the safety of H(2)-blockers during pregnancy. A computerized database of medications dispensed from 1998 to 2007 to all women registered in the "Clalit" health maintenance organization, in the Southern District of Israel, was linked with computerized databases containing maternal and infant hospitalization records from the district hospital. The following confounders were controlled for: parity, maternal age, ethnic group, maternal diabetes, smoking, and peripartum fever. Also, therapeutic pregnancy termination data were analyzed. A total of 117 960 infants were born during the study period, 84 823 of them (72%) to women registered at Clalit; 1148 of the latter were exposed to H(2)-blockers during the first trimester of pregnancy. Exposure to H(2)-blockers was not associated with an increased risk for congenital malformations (adjusted odds ratio [OR] = 1.03, 95% confidence interval [CI]: 0.80-1.32); also, no such association was found when therapeutic pregnancy terminations were included in the analysis (adjusted OR = 1.17, 95% CI: 0.93-1.46). Exposure to H(2)-blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores.

Beta lactam allergy in children from two ethnically different populations.

BACKGROUND: The effects of ethnicity on beta lactam allergy have not been reported. The Negev Desert in Southern Israel is inhabited by two ethnically distinct populations: Jews and Bedouin Muslims. Approximately 60% of the pediatric population of the area is Jewish. Whereas most Jews live in Westernized urban centers, Bedouins are in the process of transition from semi-nomadic conditions to a sedentary lifestyle and the majority of them now live in towns and villages. We sought to determine the rate and characteristics of physician-reported beta lactam allergy in Jewish and Bedouin children. METHODS: The medical records of all children registered in five primary community clinics were reviewed and screened for allergy to beta lactam antibiotics. RESULTS: A total of 26,655 medical records were reviewed: of 11,069 Jewish children and 15,586 Bedouin children. Beta lactam allergy was registered in 344 records (1.3%), and was more frequent in Jewish (n= 226, 2.1%) than in Bedouin children (n= 118, 0.8%, P < 0.0001). Beta lactam allergy was more common in boys in both populations (P < 0.01). The clinical features of the reaction that led to the diagnosis of beta lactam allergy were not significantly different between the two ethnic populations, although the specific antibiotics prescribed and the diagnoses for which they were prescribed were different in the two ethnic populations. CONCLUSIONS: We concluded in this study that pediatric beta lactam allergy was registered more frequently in Jewish than in Bedouin children, and in boys more than in girls.

Exposure to folic acid antagonists during the first trimester of pregnancy and the risk of major malformations.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Previous studies have suggested a tendency of antifolate drugs to be associated with higher rates of neural tube defects. WHAT THIS STUDY ADDS: * This study makes use of the data on abortuses, which is missed in many other studies. In this case, the abortion data were critical. * The study documents that clinicians should avoid, as much as possible, the use of folic acid antagonists during the first trimester of pregnancy, when embryogenesis takes place. AIM: To investigate the safety of folic acid antagonists during the first trimester of pregnancy in a large cohort. METHODS: Computerized databases for medications dispensed from 1998 to 2007 to women registered in 'Clalit' HMO, Israel southern district, was linked with maternal and infant hospitalization records, and to therapeutics abortions data. The risk for adverse pregnancy outcomes of folic acid antagonists exposure was assessed by adjusting for known confounders. RESULTS: Eighty-four thousand, eight hundred and twenty-three infants were born and 998 therapeutic abortions took place; 571 fetuses and infants were exposed to one or more folic acid antagonists in the first trimester of pregnancy. Exposure was associated with an overall increased risk of congenital malformations [odds ratio (OR) 2.43, 95% confidence interval (CI) 1.92, 3.08], due mainly to increased risk for neural tube (adjusted OR 6.5, 95% CI 4.34, 9.15) and cardiovascular defects (OR 1.76, CI 1.05, 2.95). CONCLUSION: First-trimester exposure to folic acid antagonists is associated with increased risk of congenital malformations.

The safety of metoclopramide use in the first trimester of pregnancy.

BACKGROUND: In various countries, metoclopramide is the antiemetic drug of choice in pregnant women, but insufficient information exists regarding its safety in pregnancy. METHODS: We investigated the safety of metoclopramide use during the first trimester of pregnancy by linking a computerized database of medications dispensed between January 1, 1998, and March 31, 2007, to all women registered in the Clalit Health Services, southern district of Israel, with computerized databases containing maternal and infant hospital records from the district hospital during the same period. We assessed associations between the use of metoclopramide in pregnancy and adverse outcomes for the fetus, adjusting for parity, maternal age, ethnic group, presence or absence of maternal diabetes, smoking status, and presence or absence of peripartum fever. RESULTS: There were 113,612 singleton births during the study period. A total of 81,703 of the infants (71.9%) were born to women registered in Clalit Health Services; 3458 of them (4.2%) were exposed to metoclopramide during the first trimester of pregnancy. Exposure to metoclopramide, as compared with no exposure to the drug, was not associated with significantly increased risks of major congenital malformations (5.3% and 4.9%, respectively; odds ratio, 1.04; 95% confidence interval [CI], 0.89 to 1.21), low birth weight (8.5% and 8.3%; odds ratio, 1.01; 95% CI, 0.89 to 1.14), preterm delivery (6.3% and 5.9%; odds ratio, 1.15; 95% CI, 0.99 to 1.34), or perinatal death (1.5% and 2.2%; odds ratio, 0.87; 95% CI, 0.55 to 1.38). The results were materially unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis. CONCLUSIONS: In this large cohort of infants, exposure to metoclopramide in the first trimester was not associated with significantly increased risks of any of several adverse outcomes. These findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy.

Unrealistic concerns about fever in children: the influence of cultural-ethnic and sociodemographic factors.

BACKGROUND: Parental fear and misconceptions about fever are widespread in western society. Ethnicity and sociodemographic factors have been suggested as contributing factors. OBJECTIVES: To test the hypothesis that undue parental concern about fever is less in traditional than in western cultural-ethnic groups. METHODS: Bedouin (traditional society) and Jewish (western society) parents of children aged 0-5 years with fever were interviewed in a pediatric emergency unit. Interviews were conducted in the parents' most fluent language (Arabic or Hebrew). A quantitative variable (a 9 item "fever phobia" scale) was constructed. RESULTS: The parents of 101 Jewish and 100 Bedouin children were interviewed. More Bedouin parents were unemployed, had less formal education and had more and younger children than the Jewish parents. Parents in both groups expressed erroneous beliefs and practices about fever; quantitative but not qualitative differences in fever phobia variables were documented. Compared with their Jewish counterparts, more Bedouin parents believed that fever may cause brain damage and death, administered antipyretic medications for temperature < or = 38 degrees C and at excessive doses, and consulted a physician within 24 hours even when the child had no signs of illness other than fever (all Pvalues <0.001). The mean fever phobia score was higher in the Bedouin than in the Jewish group (P< 0.001). By multivariate analysis, only the cultural-ethnic origin correlated with fever phobia. CONCLUSIONS: A higher degree of fever phobia was found among parents belonging to the traditional Bedouin group as compared to western society parents.

Hypoparathyroidism, retardation, and dysmorphism syndrome: impaired early growth and increased susceptibility to severe infections due to hyposplenism and impaired polymorphonuclear cell functions.

Hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome is the first reported disease caused by a defect in the tubulin folding and assembly pathway. We aimed to summarize our experience with a cohort of patients with HRD, analyze their growth, and evaluate patients' polymorphonuclear cell (PMN) functions. The records of 22 HRD patients in a single medical center were reviewed. Growth during infancy and early childhood were analyzed by the Infancy-Childhood-Puberty (ICP) growth model. PMN functions were compared with healthy controls. Twelve patients died and many hospitalizations due to infections and convulsions were recorded. Growth measurements, expressed as weight and height SD scores in boys at a mean age of 4 y were -13.1+/-3.8 and -8.7+/-1 and -16.6+/-4.4 and -9.5+/-2.4, respectively, in girls at a mean age of 6.4 y. Chemotactic migration, random migration, and phagocytosis of PMN from HRD patients were significantly lower than that of PMN from healthy controls. No significant differences were found in superoxide production of PMN from patients compared with controls. Functional hyposplenism has been demonstrated in most of the studied patients. The defect in the tubulin folding and assembly pathway, previously described in HRD, has grave consequences on growth and PMN functions.

Determinants of antipyretic misuse in children up to 5 years of age: a cross-sectional study.

BACKGROUND: Fever in children is a common and usually benign symptom. It is known that antipyretic treatment is ineffective in the prevention of simple febrile seizures. Caregivers' administration of antipyretic medications to children has been reported, but data concerning the formulations used, actual doses administered, and effects of ethnicity and socioeconomic status on administration practices are incomplete. OBJECTIVE: The aim of this study was to identify the factors affecting antipyretic administration (higher-than-recommended doses in particular) by caregivers to their febrile children in 2 differing cultural-ethnic backgrounds. METHODS: This cross-sectional survey study, conducted from January to March 2002, was part of a larger, ongoing survey study of the differences in care givers' knowledge, beliefs, and attitudes concerning children's fever in the 2 major cultural-ethnic groups in the Negev District in Israel: Jews and Bedouin Moslems. It was conducted at the Pediatric Emergency Department (PED), Soroka Medical Center, Beer-Sheva, Israel. A structured questionnaire was administered to Jewish and Bedouin Moslem parents or usual caregivers of young (age, 0-60 months) children attending the PED due to fever. Each child's weight was obtained from the PED medical record. After completion of the interview, the reported antipyretic dose per kilogram of body weight was calculated. Less-than-recommended dose was defined as <9 mg/kg for acetaminophen and <4.5 mg/kg for ibuprofen. Higher-than-recommended dose was defined as >16.5 mg/kg for acetaminophen and >11 mg/kg for ibuprofen. RESULTS: The caregivers of a total of 201 children (mean [SD] age, 20 [17] months; mean [SD] weight, 10.4 [4.0] kg) were included in the study. The study included 101 Jewish and 100 Bedouin Moslem caregivers. The proportion of people surveyed who were parents was 98%; grandmothers, 2%. Differences existed between the 2 cultural-ethnic groups in the source of knowledge regarding antipyretic use in children (a significantly larger proportion of Jewish caregivers received their knowledge concerning antipyretic use from package inserts compared with Bedouin caregivers [25.7% vs 6.0%; P < 0.001], and a significantly lower proportion of Jewish caregivers used "other" sources [15.8% vs 39.0%; P < 0.001]). Most (65.2%) caregivers indicated that they administered antipyretics for no or minimal elevations in body temperature (<-38 degrees C); 52.7% administered individual acetaminophen doses within 10% of the recommended dose, 34.8 % administered a higher-than-recommended dose, and 21.4% repeated the dose at intervals of