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To compare the long-term respiratory morbidity of offspring born by cesarean delivery for breech presentation with that of those delivered vaginally.A population-based cohort analysis including all singleton breech deliveries between the years 1991 and 2014, comparing long-term respiratory morbidity of offspring born in breech presentation, according to mode of delivery. Offspring with congenital malformations, perinatal deaths, and instrumental deliveries were excluded. Respiratory morbidity included hospitalizations (up to age 18 years), as recorded in hospital records. A Kaplan-Meier survival curve compared cumulative respiratory morbidity. A Weibull parametric survival model controlled for confounders and repeat deliveries.A total of 7337 breech deliveries were included; 6376 (86.9%) cesarean deliveries and 961 (13.1%) vaginal breech deliveries. The Kaplan-Meier survival curve demonstrated higher cumulative incidence of respiratory morbidity in the cesarean delivery group compared with vaginal delivery (log rank test P = 0.006). Using a Weibull parametric survival model to control for confounders, cesarean delivery was found to be an independent risk factor for long-term respiratory morbidity of the offspring (adjusted hazard ratio 1.87, 95% confidence interval 1.32-2.65, P 0.001).Cesarean versus vaginal delivery for breech presentation is an independent risk factor for long-term pediatric respiratory morbidity of the offspring.

BACKGROUND AND GOALS While evidence suggests short-term benefits in neonatal morbidity and mortality from cesarean delivery of the fetus in breech presentation, the long-term implications for the offspring are less clear. To assess the implications of the mode of delivery on offspring's health, we have evaluated the long-term gastrointestinal (GI) morbidity of offspring with a breech presentation delivered in either way. MATERIALS AND METHODS A population-based retrospective cohort study including singleton deliveries in breech presentation occurring between 1991 and 2014 at a tertiary referral hospital. Incidence of hospitalizations of the offspring up to the age of 18 years involving GI morbidity was compared between those delivered via cesarean section or vaginally. A Kaplan-Meier survival curve compared cumulative GI morbidity. A Weibull parametric survival model controlled for confounders while accounting for repeated occurrence of mothers and dependence among siblings. RESULTS Overall, 86.9% (n=6376) of the 7337 fetuses in breech presentation, were delivered abdominally. Hospitalizations involving GI morbidity were higher in offspring delivered by cesarean section, specifically due to inflammatory bowel disease (IBD). Kaplan-Meier survival curve revealed the higher cumulative incidence of total GI morbidity and IBD specifically in the cesarean delivery group (P

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus. This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns. Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables. Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns. This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.

Background Previous findings concerning the risk for preeclampsia following exposure to particulate matter are inconclusive. Methods We used data from all singleton pregnancies of women insured by the “Clalit health services” (CHS) maintenance organization in southern Israel that resulted in delivery or perinatal mortality at Soroka Medical Center (SMC). Daily PM2.5 concentrations were estimated by a hybrid satellite-based model at one-squared kilometer spatial resolution. We used Cox proportional hazard models coupled with distributed lag models to examine the association between the mean exposure to PM2.5 in every gestational week and the diagnosis of preeclampsia, adjusting for maternal age, parity, year of birth, season of birth and socio-economic status. Hazard Ratios (HR) and 95% Confidence Intervals (CI) were calculated for individual gestational weeks and for cumulative exposure until the 25th gestational week. Results A total of 133,197 pregnancies ended at SMC during the study period, of which 68,126 (51.1%) were Jewish and 65,071 (48.9%) were Bedouin. For pregnancies of Jewish women, exposure to PM2.5 from the 7th until the 14st gestational week was significantly associated with preeclampsia (maximal HR = 1.06; 95%CI: 1.01 – 1.11 during the 10th gestational week per 10 μg/m3 increase in PM2.5). Cumulative exposure to PM2.5 during the first 25th gestational weeks was also significantly associated with preeclampsia (HR = 2.08; 95%CI: 1.10 – 3.94 per 10 μg/m3 increase in PM2.5). We observed no association for pregnancies of Bedouin women. Conclusions Exposure to PM2.5 between the 7th and the 14st gestational weeks was associated with preeclampsia among Jewish women but not among Bedouin women.

Objective This study was aimed to assess the association between ovarian hyperstimulation syndrome (OHSS) and pregnancy complications among women who conceived following fertility treatment. Study Design A retrospective population-based cohort study, including all singleton deliveries of patients conceived following ovulation induction (OI) or in vitro fertilization (IVF) between 1988 and 2016, was conducted. All births occurred in a single tertiary medical center. A comparison was performed between deliveries of women who had experienced OHSS at early gestation and subsequently had a pregnancy and women without OHSS. Women lacking prenatal care, multiple gestations, and stillbirths were excluded from the analyses. A multivariable logistic regression model was used to control for confounders. Results During the study period, 351,373 deliveries met the inclusion criteria, of which 6,748 were deliveries of infants who were conceived by either IVF or OI. Of this study population, 105 cases (1.6%) composed the exposed group, that is, women who had experienced OHSS with a subsequent live birth. In the multivariate analyses, after controlling for confounders, OHSS was not found as an independent risk factor for preeclampsia, gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), preterm delivery (both Conclusion In our population, OHSS was not found as a risk factor for adverse pregnancy and perinatal outcome. In IVF patients, OHSS is a risk factor for preterm delivery before 34 weeks of gestation. Key Points

Previous findings concerning the risk for preeclampsia following exposure to particulate matter are inconclusive.We used data from all singleton pregnancies of women insured by the "Clalit health services" (CHS) maintenance organization in southern Israel that resulted in delivery or perinatal mortality at Soroka Medical Center (SMC). Daily PMA total of 133,197 pregnancies ended at SMC during the study period, of which 68,126 (51.1%) were Jewish and 65,071 (48.9%) were Bedouin. For pregnancies of Jewish women, exposure to PMExposure to PM

Adverse drug reactions (ADRs) are associated with morbidity and mortality worldwide. Although national systems for reporting ADRs exist there is a low reporting rate. The aim of the current study was to evaluate an intervention plan for improving ADRs reporting among medical professionals (physicians and nurses). A multicentre intervention study was conducted, in which one medical centre was randomly assigned to the intervention group and two medical centres to the control group. The study consisted of 3 phases: baseline data collection, intervention and follow-up of the reporting rate. The questionnaire that was filled in at base line and at the end of study, contained questions about personal/professional demographic variables, and statements regarding knowledge of and behaviour toward ADRs reporting. The intervention program consisted of posters, lectures, distant electronic learning and reminders. An increase in the number of ADRs reports was noted in the intervention group (74 times higher than in the control group) during the intervention period, which was gradually decreased with as the study progressed (adjusted O.R = 74.1, 95% CI = 21.11-260.1, p

Enoxaparin is widely used during pregnancy as pregnancy is a hypercoagulable state; however, its fetal safety has scarcely been investigated. Our study aimed to examine fetal safety following enoxaparin exposure during pregnancy. 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. 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). 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.

Objective To evaluate whether exposure to clomiphene citrate (CC) for ovulation induction is associated with major malformations overall or with specific fetal anomalies. Design We conducted a population-based retrospective cohort study. Exposure was defined as CC dispension from 2 months before conception through the first month of pregnancy. Settings Four databases were combined: medication, birth, hospitalization, and terminations of pregnancy. Population The study included all women in southern Israel who gave birth or underwent termination of pregnancy at Soroka Medical Center, from 1998 to 2009. Methods The rates of major malformations overall and six different subcategories of anomalies were evaluated. The crude odds ratio (OR) was calculated with a 95% confidence interval (95% CI). Subsequently the adjusted odds ratio (aOR) was calculated using multiple logistic regression models controlling for maternal age, pre-pregnancy diabetes, parity, ethnicity, the calendar year in which the birth/termination of pregnancy took place, smoking, and the use of gonadotropins and progesterone. Main outcome measures Major malformations overall and specific fetal malformations by organ systems. Results Of 114 961 pregnant women, 1872 were exposed to CC. No association was detected between exposure to CC and rates of major malformations overall (aOR 1.08, 95% CI 0.88-1.32) or rates of subcategories of malformations. Exposure was not associated with anencephaly (aOR 2.27, 95% CI 0.44-11.71) or oesophageal atresia (aOR 3.681, 95% CI, 0.65-20.76). Conclusions In this large population-based retrospective cohort study, exposure to CC was not associated with an increased risk of either rates of major malformations overall or rates of specific malformations. Tweetable abstract An observational study: no increased risk for fetal malformations following exposure to clomiphene citrate.

PURPOSE Adverse drug reactions (ADRs) are a growing important public health problem; however, underreporting of ADRs is very common. The aim of the current study was to explore the effect of an intervention program on the knowledge and attitudes among physicians and nurses regarding ADRs reporting. METHODS A multicentre study consisted of three phases: filling out a questionnaire; an intervention program; filling out the same questionnaire again. The intervention program consisted of posters, lectures, and distant electronic learning. The questionnaire contained questions about personal/professional demographic variables, and statements regarding knowledge and attitudes regarding ADR reporting. RESULTS The data revealed that the intervention program significantly elevated the "Objective knowledge" (P

IntroductionOpioids constitute a cornerstone of pain relief treatment. However, opioid safety during pregnancy has not been well established. Recent studies reported an association between in utero opioid exposure and spina bifida.MethodsIn order to further evaluate the association of opioids exposure during pregnancy with adverse pregnancy outcomes, we conducted a large historical cohort by linking four databases: medications dispensations, births, pregnancy terminations for medical reasons and infant hospitalizations during the years of 1999-2009. Confounders that were controlled for included maternal age, ethnicity, maternal diabetes, smoking status, parity, obesity, year and folic acid intake. A secondary analysis for total major malformations and for spina bifida was performed using propensity score matching for first trimester exposure.ResultsOf the 101,586 women included in the study, 3003 were dispensed opioids during the first trimester. Intrauterine exposure to opioids was not associated with overall major malformations (adjusted odds ratio (aOR) 0.97, 95% CI 0.83-1.13), cardiovascular malformations (aOR = 0.89, 95% CI 0.70-1.13) other malformations by systems or spina bifida in particular. However, the risk for spina bifida among newborns and abortuses who were exposed to codeine was four times higher than that of the unexposed (aOR = 4.42, 95% CI 1.60-12.23). This association remained significant in a secondary analysis using propensity score matching. Third trimester exposure to opioids was not associated with low birth weight (aOR = 1.08, 95% CI 0.77-1.52), perinatal death (aOR = 1.38, 95% CI 0.64-2.99) and other adverse pregnancy outcomes.ConclusionsThese findings suggest that opioids exposure (as a homogenous group) is not a significant risk factor for overall major malformations. Exposure to codeine during the first trimester was found to be associated with increased risk of spina bifida. However, this finding was based on a small number of cases and need to be verified in future work.

A series of selenium-bridged and tellurium-bridged heteromerous bistricyclic aromatic enes (BAEs) 15–25 with six-member and seven-member central rings have been synthesized by Barton–Kellogg olefination, twofold extrusion coupling method between tricyclic aromatic thiones and tricyclic aromatic diazo derivatives. The crystal structures of thioxanthenylidene-anthracenone (15), selenoxanthenylidene-anthracenone (20), and telluroxanthenylidene-anthracenone (21) were determined. The ordered crystal structure of 21 showed a very high degree of folding of the telluroxanthenylidene moiety (58.5°) and very short intramolecular Te···C9′ contact distance, indicating >20 % penetration which may reflect secondary nonbonding interactions and lack of aromatic telluroxanthenylium-anthracenolate contribution. The BAEs were subjected to a 1H-, 13C-, 77Se-, and 125Te-NMR spectroscopic study. The 1H-NMR spectra indicated anti-folded conformations in solution. The measured pronounced downfield 77Se- and 125Te-NMR shifts in 20 and 21, relative to the corresponding spectra of homomerous BAEs diselenoxanthylene (7) and ditelluroxanthylene (8), may be due to the proximity of the Se and Te bridges to the carbons of the central enes in the anti-folded conformations. This deshielding effect was larger in 21 than in 20, δ(125Te)/δ(77Se) = 1.53, a ratio higher than in any other member of the series.

BACKGROUND The high frequency of readmissions in patients with COPD remains a significant problem. The impact of a pulmonologist follow-up visit during the month after discharge from hospital because of COPD exacerbation on reducing readmissions was examined. A profile of patients who did not attend the follow-up visits was built. METHODS Our population-based retrospective cohort study analyzed the data of all patients with COPD who were treated at a lung institute in an Israeli hospital and were hospitalized between January 1, 2004, and December 31, 2010. Multivariate logistic regression was used to characterize the patient who did not attend the follow-up visit and to examine the effect of lack of visit on rehospitalization within 90 days of discharge. Cox proportional hazards analysis was used to model the effect of lacking visit on additional hospitalization or death during the study period. RESULTS Of the 195 patients enrolled in the study, 44.1% had follow-up visits with pulmonologists within 30 days of discharge. Not attending the follow-up visit was associated with distant residence, a higher number of hospitalizations in the previous year, a lack of a recommendation in the discharge letter for a follow-up visit, and a lower frequency of follow-up visits with pulmonologists in the previous year. Moreover, not attending the follow-up visit was associated with a significant increased risk of rehospitalization within 90 days of discharge (OR, 2.91;95% CI, 1.06-8.01). CONCLUSIONS Early follow-up visits with pulmonologists seem to reduce the exacerbationrelated rehospitalization rates of patients with COPD. We recommend that patients have early postdischarge follow-up visits with pulmonologists.

Aim The aim of the study was to characterize the extent of indication bias resulting from the excessive use of NSAIDs on the days preceding a spontaneous abortion to relieve pain. Methods We used data from a retrospective cohort study assessing the risk for spontaneous abortions following exposure to NSAIDs. Three definitions of exposure for cases of spontaneous abortions were compared, from the first day of pregnancy until the day of spontaneous abortion and until 3 and 2 days before a spontaneous abortion. Statistical analysis was performed using multivariate time programmed Cox regression. Results A sharp increase was observed in the dispensation of indomethacin, diclofenac and naproxen, and a milder increase was found in the use of ibuprofen during the week before a spontaneous abortion. Non- selective COX inhibitors in general and specifically diclofenac and indomethacin were found to be associated with spontaneous abortions when the exposure period was defined until the day of spontaneous abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR 1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect disappears by excluding exposures occurring on the day before the spontaneous abortion for non-selective COX inhibitors and on the last week before the spontaneous abortion for indomethacin. In general, decreasing HRs were found with the exclusion of exposures occurring on the days immediately before the spontaneous abortion. Conclusions The increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage could bias studies assessing the association between exposure to NSAIDs and spontaneous abortions.

Objective Because of an increased resistance of urinary pathogens to penicillin derivatives, nitrofurantoin is commonly used as an alternative in treating urinary tract infection because a wide range of both Gram negative and positive organisms are sensitive to it. The safety of the fetus after exposure to nitrofurantoin remains controversial. Methods We conducted a systematic review and meta-analysis to evaluate the fetal safety of nitrofurantoin. We searched Medline, EMBASE, references from published reports, and meeting abstracts for relevant studies. Articles were included in the review if they were human studies, reported pregnancy outcomes, reported the use of nitrofurantoin in the first trimester of pregnancy, and included a comparator group of unexposed pregnancies. The primary outcome was the rate of major malformations; secondary outcomes were rates of craniosynostosis, cleft lip or palate defects, cardiovascular defects, and hypoplastic left heart syndrome. Results Eight studies reporting on 91 115 exposed cases and 1 578 745 unexposed controls were included in the primary meta-analysis examining the risk of major malformation. Five cohort studies reported on 9275 exposed and 1 491 933 unexposed infants, resulting in an overall RR of 1.01 (95% CI 0.81 to 1.26); however, three case–control studies with a total of 39 268 cases of major malformations and 129 394 controls gave an overall OR of 1.22 (95% CI 1.02 to 1.45). No increased risk for cardiovascular malformations, oral cleft, or craniosynostosis was identified. For assessing risk of hypoplastic left heart syndrome, only three articles were eligible; these demonstrated an OR of 3.07 (95% CI 1.59 to 5.93). Conclusion While no association was found between fetal exposure to nitrofurantoin and major malformation in cohort studies, there was a slight but significant teratogenic risk in case–control studies, which are more sensitive to adverse effects.

IntroductionPolybrominated Diphenyl Ethers (PBDEs) are non-biodegradable flame retardants, accumulated in biological systems and acting as endocrine disruptors. Breast feeding is a major route of exposure in infancy. Taken together with the critical development of this age and the potential adverse effects of PBDEs, it is important to monitor these contaminants in breastmilk.ObjectiveTo evaluate the exposure of infants to PBDEsMethods343 families were recruited during 2013–2016 in Assaf Harofeh and Ichilov to create the AHI-EHF cohort. Maternal blood and urine, cord blood, breast milk and meconium were collected. Participants filled out questionnaires about socio-demographic status, medical history, exposures and life habits. Colostrum samples were collected from women at the maternity department. PBDEs in colostrum and Infant formulas levels were analyzed using GC-MSResults and discussionOut of 183 serum samples, only 11(6%) detectable levels of PBDEs. PBDEs were found in all colostrum samples. The average concentration of total PBDEs in breastmilk was 714ng/L. PBDEs levels were also measured in three infant formulas. Unlike breastmilk, infant formulas had of only 3 congeners and levels were relatively low. The average concentration of total PBDEs in infant formulas was 153ng/L. PBDEs, were found to be negatively correlated to anno-penile index (API) which serve as a marker for endocrine disruption.ConclusionsPBDEs levels in breast milk are higher than levels in some European countries, but lower than in North America. PBDEs might have negative influence on AGD in boys. Maternal exposure to PBDEs and the significance of it should be further investigated.Disclosure(s)Nothing to disclose

To investigate pregnancy outcome in patient who conceived by assisted reproductive techniques.A retrospective population-based study was conducted, comparing obstetrical complications and neonatal outcomes of singleton pregnancies conceived by in vitro fertilization (IVF; n = 1296) and ovulation induction (n = 1988) as compared to singleton pregnancies conceived spontaneously (n = 172 288). Multivariable models were constructed to control for confounders.A significant linear association (using the chi-square test for trends) was documented among the three groups in adverse outcomes such as gestational diabetes mellitus (17.3% in the IVF, 14.2% in the ovulation induction, 6.6% in the comparison group, p 0.001), severe preeclampsia (2.7% in the IVF, 1.8% in the ovulation induction, 1.1% in the comparison group, p 0.001) and perinatal mortality (3.3% in the IVF, 2.1% in the ovulation induction, 1.3% in the comparison group, p 0.001). In vitro fertilization and ovulation induction treatments were found to be independent risk factors for gestational diabetes mellitus, using two different multiple logistic regression models controlling for confounders such as maternal age (adjusted OR = 1.77, 95% CI:1.52-2.07, p 0.001 and adjusted OR = 1.93, 95% CI:1.69-2.21, p 0.001; respectively).Pregnancies conceiving following assisted reproductive techniques are at an increased risk for adverse obstetrics outcomes. The risk is higher for pregnancies following IVF compared with these conceived following ovulation induction.

Antibacterial drugs are among the most common medications used by pregnant women. While medical literature generally defines nitrofurantoin as an antibiotic that is safe for use during the first trimester of pregnancy, new concerns about a possible association between congenital malformations following exposure to nitrofurantoin during the first trimester of pregnancy have recently surfaced. To address these concerns, we conducted a large population-based retrospective cohort study to assess this possible association (including cases of medical terminations of pregnancy or stillbirth) and congenital malformations. A computerized database for medications dispensed to pregnant women in southern Israel was linked with records from the district hospital. Associations between exposure to nitrofurantoin during the first trimester and major malformations were assessed. Our research included a total of 105,492 pregnancies, 1,112 of which involved pregnancy terminations for medical reasons. A total of 1,329 infants and abortuses had been exposed to nitrofurantoin during the first trimester of pregnancy. Exposure to nitrofurantoin was not associated with increased risk of major malformations in general (adjusted OR = 0.85, 95% CI 0.67-1.08) or with specific malformations. First trimester exposure to nitrofurantoin was not associated with increased risk for total major congenital malformations or with specific malformations.

Background Acute kidney injury (AKI) is a devastating postoperative complication. Intraoperative urine output is assumed to reflect patient's intravascular volume and kidney function. We thus evaluated the incidence of postoperative AKI and its association with intraoperative urine output and the volume of fluid administered. Methods A retrospective study on 153 consecutive patients admitted to Tel Aviv Medical Center for pancreatic surgery. Results The incidence of AKI in patients undergoing pancreatic surgery was 9.8%. Oliguria was not a predictor of AKI. There was no association between the amount of fluids administered and AKI. Pulmonary disease is an independent predictor of AKI. AKI is an independent predictor of mortality. Conclusions AKI is common in patients undergoing pancreas surgeries and is associated with high mortality. Neither urine output, nor the volume of fluids administered correlate with postoperative AKI. Low diuresis is therefore not a sole marker for fluid administration. Short summary for table of contents Acute kidney injury is common in patients undergoing pancreas surgeries and is associated with high mortality. Neither urine output, nor the volume of fluids administered correlate with postoperative AKI.

The purpose of the present study was to examine obstetric outcome of patients following conization and specifically the risk for preterm delivery (PTD).A population-based study was performed comparing pregnancies in women following conization with those who had not undergone the procedure. Stratified analysis, using a multiple logistic regression model was performed to control for confounders.Out of 104,670 deliveries, 53 women (0.05%) had undergone conization. Most conizations were performed using loop electrosurgical excision procedure (LEEP). Using multivariable analysis, the following conditions were significantly associated with conization: advanced maternal age, PTD before the 34th week, low birth weight, and cervical incompetence with cerclage. Higher rates of perinatal mortality were noted in pregnancies of women with conization, but after controlling for PTD, the association lost its significance. The risk of PTD34 weeks was significantly higher than the comparison group (OR 7.73 95% CI 3.77-15.85, p0.001). This association remained significant after controlling for confounders, such as cervical incompetence, smoking, maternal age, birth order and year of delivery (OR 2.8 95% CI 1.3-6.1, p = 0.008). When comparing pregnancy outcomes of women with and without cerclage due to cervical incompetence, no significant differences were documented.A clear association exists between conization and PTD before the 34th week. This association persists after controlling for variables considered to coexist with PTD. Careful surveillance is required in pregnancies of women following conization for early detection of preterm contractions and PTD.

To investigate time trends and risk factors for peripartum cesarean hysterectomy.A population-based study comparing all deliveries that were complicated with peripartum hysterectomy to deliveries without this complication was conducted. Deliveries occurred during the years 1988-2007 at a tertiary medical center. A multiple logistic regression model was constructed to find independent risk factors associated with peripartum hysterectomy.Emergency peripartum cesarean hysterectomy complicated 0.06% (n=125) of all deliveries in the study period (n=211,815). The incidence of peripartum hysterectomy increased over time (1988-1994, 0.04%; 1995-2000, 0.05%; 2001-2007, 0.095%). Independent risk factors for emergency peripartum hysterectomy from a backward, stepwise, multivariable logistic regression model were: uterine rupture (OR=487; 95% CI 257.8-919.8, p0.001), placenta previa (OR=66.4; 95% CI 39.8-111, p0.001), postpartum hemorrhage (PPH) (OR=40.8; 95% CI 22.4-74.6, p0.001), cervical tears (OR=22.3; 95% CI 10.4-48.1, p0.001), second trimester bleeding (OR=6; 95% CI 1.8-20, p=0.003), previous cesarean delivery (OR=5.4; 95% CI 3.5-8.4, p0.001), placenta accreta (OR=4.7; 95% CI 1.9-11.7, p=0.001), and grand multiparity (above five deliveries, OR=4.1; 95% CI 2.5-6.6, p0.001). Newborns of these women had lower Apgar scores (7) at 1 and 5 min (32.7% vs.4.4%; p0.001, and 10.5% vs. 0.6%; p0.001, respectively), and higher rates of perinatal mortality (18.4% vs. 1.4%; p0.001) as compared to the comparison group.Significant risk factors for peripartum hysterectomy are uterine rupture, placenta previa, PPH, cervical tears, previous cesarean delivery, placenta accreta, and grand multiparity. Since the incidence rates are increasing over time, careful surveillance is warranted. Cesarean deliveries in patients with placenta previa-accreta, specifically those performed in women with a previous cesarean delivery, should involve specially trained obstetricians, following informed consent regarding the possibility of peripartum hysterectomy.

Background Spontaneous abortions are the most common complication of pregnancy. Clotrimazole and miconazole are widely used vaginal-antimycotic agents used for the treatment of vulvovaginal candidiasis. A previous study has suggested an increased risk of miscarriage associated with these azoles, which may lead health professionals to refrain from their use even if clinically indicated. Objective The aim of the current study was to assess the risk for spontaneous abortions following first trimester exposure to vaginal antimycotics. Study Design A historical cohort study was conducted including all clinically apparent pregnancies that began from January 2003 through December 2009 and admitted for birth or spontaneous abortion at Soroka Medical Center, Clalit Health Services, Beer-Sheva, Israel. A computerized database of medication dispensation was linked with 2 computerized databases containing information on births and spontaneous abortions. Time-varying Cox regression models were constructed adjusting for mother’s age, diabetes mellitus, hypothyroidism, obesity, hypercoagulable or inflammatory conditions, recurrent miscarriages, intrauterine contraceptive device, ethnicity, tobacco use, and the year of admission. Results A total of 65,457 pregnancies were included in the study: 58,949 (90.1%) ended with birth and 6508 (9.9%) with a spontaneous abortion. Overall, 3246 (5%) pregnancies were exposed to vaginal antimycotic medications until the 20th gestational week: 2712 (4.2%) were exposed to clotrimazole and 633 (1%) to miconazole. Exposure to vaginal antimycotics was not associated with spontaneous abortions as a group (crude hazard ratio, 1.11; 95% confidence interval, 0.96–1.29; adjusted hazard ratio, 1.11; 95% confidence interval, 0.96–1.29) and specifically for clotrimazole (adjusted hazard ratio, 1.05; 95% confidence interval, 0.89–1.25) and miconazole (adjusted hazard ratio, 1.34; 95% confidence interval, 0.99–1.80). Furthermore, no association was found between categories of dosage of vaginal antimycotics and spontaneous abortions. Conclusion Exposure to vaginal antimycotics was not associated with spontaneous abortions.

To investigate whether symphysiolysis during pregnancy is a risk factor for cesarean delivery (CD).A retrospective population-based study comparing all singleton pregnancies of women with and without symphysiolysis was conducted. Deliveries occurred between the years 2000 and 2007. Multiple logistic regression models were used to control for confounders.Out of 80,898 patients, 0.2% (n = 154) were diagnosed with symphysiolysis during pregnancy. Patients with symphysiolysis were significantly older as compared to the comparison group. These patients had higher rates of mild pre-eclampsia, gestational diabetes mellitus (GDM) and labor induction as compared to patients without symphysiolysis. Higher rates of CD were noted in pregnancies complicated by symphysiolysis [22.1% vs. 15.9%; Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.02-2.2; P = 0.036]. Using multiple logistic regression model, with symphysiolysis as the outcome variable, controlling for labor induction, mild pre-eclampsia and GDM, symphysiolysis was noted as an independent risk factor for CD (weighted OR = 1.7, 95% CI 1.1-2.5; P = 0.009). Perinatal outcomes such as low Apgar scores (7) at 1 and 5 min and perinatal mortality were comparable between the groups.Symphysiolysis is an independent risk factor for CD.

To investigate pregnancy and labour outcomes in grand and great grand multiparous women.A retrospective population-based study was conducted between the years 1988 and 2007. Parturients were classified into three groups: multiparous; 2-5 deliveries, grand multiparous; 6-9 deliveries, and great grand multiparous; 10+ deliveries. Stratified analyses included multiple logistic regression models.A significant linear association was found between parity and adverse maternal and perinatal outcomes such as malpresentation, labour dystocia, caesarean delivery, postpartum haemorrhage, maternal anaemia (HB10), congenital malformations and perinatal mortality. Using multivariable logistic regression models, grand multiparity was found an independent risk factor for labour dystocia, first stage (OR=1.5, P0.001), and perinatal mortality (OR=2.0, P0.001). Great grand multiparity was found an independent risk factor for labour dystocia, first stage (OR=2.6, P0.001), labour dystocia, second stage (OR=2.1, P0.001), and perinatal mortality (OR=2.5, P0.001).Women with high birth order are at increased risk for adverse obstetric outcomes. The risk is higher for great grand multiparous women compared to grand multiparous women. Grand and great grand multiparity are independent risk factors for labour dystocia and perinatal mortality.

The present study was aimed to investigate perinatal outcome of elderly nulliparous patients. A retrospective study was performed comparing pregnancy outcomes of nulliparous patients at three age groups: less than 35 years (reference group), 35–40 years, and above 40 years. The linear-by-linear association test was used to examine linear association between advanced maternal age and adverse pregnancy outcomes. A multiple logistic regression model was used to control for confounders. Out of 45,033 nulliparous women with singleton gestations, 1,036 were of women over the age of 35, and 188 over 40. A significant linear association was documented between advanced maternal age and adverse outcomes, such as intra uterine growth restriction, low birth weight, congenital malformations, and perinatal mortality. Using a multiple logistic regression model, controlling for gestational age, IUGR and malformations, advanced maternal age was not found to be an independent risk factor for perinatal mortality (adjusted odds ratio = 1.04, 95% confidence interval 0.7–1.4). A significant linear association exists between advanced maternal age and adverse maternal and perinatal outcomes. Nevertheless, in our population, advanced maternal age is not an independent risk factor for perinatal mortality.

We scrutinized the role of apoptosis of the Hodgkin-Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) and critically reviewed its features in the light of conflicting evidence. In this study, we found that tumor cells in this neoplasm showed inhibition of apoptosis in 55% of the 217 cHL cases only. It is also suggested that the two factors considered responsible for apoptosis inhibition in HRS cells, nuclear factor-kappaB and the latent membrane protein-1 of the Epstein-Barr virus, do not correlate with apoptosis inhibition, in contrast with the findings in the consensual pathogenetic scheme. The most significant association of HRS cell apoptosis was with p53, the negative expression of which related with a high apoptotic index (p = 0.001). These findings support our contention that the role of apoptosis in the HRS cells of Hodgkin lymphoma has not been completely elucidated and is at variance with that in the consensus.

To test the association between familial history of diabetes mellitus and birth-weight as well as mode of delivery stratified for the presence of the disease.A population-based study, comparing birth outcome of patients with and without familial history of diabetes mellitus was conducted. Patients lacking prenatal care were excluded from the analysis. Multiple logistic regression models were used to control for confounders. The Mantel-Haenszel procedure was used to obtain the weighted odds ratios while controlling for the presence of diabetes mellitus (either gestational or pre-gestational).Out of 181,479 deliveries, 7.6% (n = 13,813) were in patients with familial history of diabetes mellitus. These patients had higher rates of diabetes mellitus (either gestational or pre-gestational) as compared with patients without familial history of diabetes mellitus (13.7% vs. 6.3%, OR = 2.3; 95% CI 2.2-2.5, p0.001). Patients with familial history of diabetes mellitus had higher rates of macrosomia (birth-weight4 kg; 5.7% vs. 4.6%, p0.001). Also, a 1.3-fold increase in the risk for cesarean delivery (CD) was found in patients with familial history of diabetes mellitus as compared with the comparison group (17.1% vs. 13.8%, p0.001). Using two different multiple logistic regression models, one with CD and the second with macrosomia as the outcome variable, the association between familial history of diabetes mellitus and these complications remained significant (OR = 1.2; 95% CI 1.1-1.2; p0.001 and OR = 1.2; 95% CI 1.03-1.2; p = 0.005, respectively). The two models controlled for important confounders such as diabetes mellitus and the year of delivery, in order to control for ascertainment bias.Family history of diabetes mellitus has a significant, independent association with the risk for macrosomia and CD during pregnancy, regardless the presence of the disease.

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 present study was aimed to compare term versus preterm placental pathologies associated with fetal growth restriction (FGR).A retrospective cohort study was performed, including all singleton deliveries of FGR with placental pathology examination. Comparison of placental findings was performed between neonates who were born at term versus preterm. Preterm was defined as37 completed weeks of gestation, and34 weeks gestation in another analysis. When one or more of the following pathology was found in microscopic examination of the placental tissue, the term uteroplacental insufficiency was defined: placental infarct, fibrosis of chorionic villi, thickening of blood vessels and poor vascularity of the chorionic villi.Macroscopic placental findings were available for 1,104 singleton FGR neonates; of these, 395 placentas had microscopic examinations. A significant greater proportion of preterm FGR cases had pathology findings associated with uteroplacental insufficiency as compared to term FGR (29.4 vs. 36.7%; OR = 1.4 95%, CI = 1.05-1.9; P = 0.019). The same pattern was seen while comparing placentas of FGR neonates who were born before and after 34 weeks (32.4 vs. 39.4%; OR = 1.4, 95% CI 1.02-1.8; P = 0.028). Syncytial knots were significantly more common in placentas from neonates who were delivered before 34 weeks of pregnancy (15.2 vs. 6.3%; OR = 2.6, 95% CI 1.3-5.6; P = 0.005). This trend was not statistically significant while comparing FGR before and after 37 weeks gestation (10.9 vs. 4.6%; OR = 2.4, 95% CI 0.99-7.7; P = 0.052). Meconial impregnation was more common among term versus preterm FGR neonates37 weeks (22.4% vs. 7.2% OR = 3.7, 95% CI 2.3-5.9; P 0.001), as well as among neonates who were born before and after 34 weeks of gestation (14.5 vs. 5.9%; OR = 0.4, 95% CI 0.2-0.6; P 0.001).Placentas of preterm FGR neonates (either37 weeks or34 weeks gestation) reveal numerous pathologies reflecting uteroplacental insufficiency and abnormal blood supply. The presence of increased syncytial knots in preterm FGR neonates is probably due to exposure to hypoxia and reactive oxygen agents.

Objective To investigate pregnancy outcome for patients with treated hyperthyroidism. Methods A population-based study was performed comparing all singleton pregnancies of women with and women without hyperthyroidism at the Soroka University Medical Center, Be'er-Sheva, Israel, between January 1988 and January 2007. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders. Results During the study period, there were 185 636 singleton deliveries in the medical center. Of these, 189 (0.1%) were from women with hyperthyroidism. Using multivariate analysis with backward elimination, the following risk factors were significantly associated with hyperthyroidism: placental abruption; cesarean delivery; and advanced maternal age. No significant differences regarding perinatal outcome were noted between the groups. Women with hyperthyroidism had significantly higher rates of cesarean delivery than did women without hyperthyroidism (20.1% vs 13.1%; P Conclusions Treated hyperthyroidism was not associated with adverse perinatal outcome. However, hyperthyroidism was found to be an independent risk factor for cesarean delivery.

We sought to identify whether schizophrenia during pregnancy is associated with adverse perinatal outcomes. A population-based study comparing women with and without schizophrenia and schizoaffective disorders was performed. Stratified analysis using multiple logistic regression models was performed to control for confounders. During the study period, there were 186,554 deliveries, of which 97 occurred in patients with schizophrenia and schizoaffective disorders. The schizophrenic patients were significantly older (mean age 30.6 versus 28.6, P = 0.001), with higher prevalence of diabetes mellitus as compared with the comparison group (13.4% versus 6.7%, P = 0.009). The need for induction and augmentation of delivery, congenital malformations, and low birth weight (

The naphthalogous mono-bridged tetraarylethylenes 9,9′-di-(1-naphthylmethylene)-9H-fluorene (5) and 9,9′-di-(1-naphthylmethylene)-9H-xanthene (6), analogs of bifluorenylidene (1) and bixanthenylidene (2), have been synthesized and their molecular and crystal structures have been determined. Ene 5 has been prepared by two alternative synthetic routes. The molecular structures of 5 and 6 show that each of these enes has very small twist around the central double bond, but the two naphthalene rings in both 5 and 6 are highly twisted. According to the NMR study, 5 and 6 in solution adopt conformations which are similar to those found by X-ray crystal structure analysis. The notable upfield shifts of H1 and H8 (6.11 and 6.83 ppm, respectively) and H2 and H7 (6.70 and 6.44 ppm, respectively) in 5 and 6 are due to the shielding caused by the nearly orthogonally twisted naphthalene rings. The B3LYP/6-31G(d) calculations of 5, 6, and their 2-naphthyl and phenyl analogs have been performed. In the 1-naphthyl series, the more efficient conjugation between the naphthyl substituents and the central C=C and the overcrowding due to the peri-hydrogen atoms lead to higher twists of the naphthyl groups and to lower twists of the central C=C. In the 2-naphthyl series, the opposite effects are noted.

Objective To examine pregnancy outcomes associated with diet-controlled gestational diabetes mellitus (GDM A1). Methods A retrospective cohort study compared pregnancy characteristics of women with and without GDM A1 at a center where GDM A1 patients are routinely induced at 40 weeks. Results Higher rates of complications such as shoulder dystocia, congenital malformation, and macrosomia were observed in GDM A1 patients. A lower incidence of perinatal mortality was present in GDM A1 women compared with women without GDM A1. This association lost its significance when controlled for maternal age, ethnicity, induction, cesarean delivery, and birth weight in a multivariate model. Although the stillbirth rate before 40 weeks of gestation was identical among all participants, after 40 weeks it was significantly higher in women without GDM A1. Conclusion Induction of women with GDM A1 at 40 weeks may play a role in lowering perinatal mortality to below that of the general population.

The present study was aimed to test the association between asymptomatic bacteriuria during pregnancy, among patients in whom antibiotic treatment was recommended, and perinatal outcome. Our study was also designed to characterize common bacteria and risk factors associated with asymptomatic bacteriuria during pregnancy.A retrospective population-based study comparing all singleton pregnancies of women with and asymptomatic bacteriuria was conducted. Patients with urinary tract infection were excluded from the analysis. Multiple logistic regression model was used to control for confounders.Out of 199,093 deliveries, 2.5% (n = 4890) were in patients with asymptomatic bacteriuria. E. coli was the most common pathogen associated with asymptomatic bacteriuria, representing 78.6% of the cultures with specified growth. Patients with asymptomatic bacteriuria were more likely to deliver preterm (PTD, 13.3%vs. 7.6%, odd ratio (OR) = 1.9, 95% confidence interval CI 1.7-2.0; P0.001) and deliver low birth-weight neonates (2500 g, 13.3%vs. 7.9%, OR = 1.8; 95% CI 1.6-2.0; P0.001). Asymptomatic bacteriuria was independently associated with PTD (adjusted OR = 1.6; 95% CI 1.5-1.7; P0.001), fertility treatments, hypertensive disorders, recurrent abortions, diabetes mellitus, intrauterine growth restriction, polyhydramnion and oligohydramnion, premature rupture of membranes and labour induction, in a multivariable analysis with backwards elimination. Perinatal mortality rates (1.5%vs. 1.4%; P = 0.707) as well as low 5 min Apgar scores (0.8%vs. 0.6%; P = 0.065) were comparable between the groups.Asymptomatic bacteriuria is an independent risk factor for preterm delivery.