Twins vs singletons-Long-term health outcomes.

INTRODUCTION: Multiple gestations are a risk factor for most pregnancy complications. The current study aimed to study whether offspring born after twin pregnancies are at increased risk for long-term health complications. MATERIAL AND METHODS: A retrospective cohort study was conducted in a large medical center, including all offspring born between the years 1991-2021, which were followed-up until 18 years of age. Hospital-based diagnoses of the offspring were categorized into main groups of morbidities: cardiac, respiratory, infectious, neurological, malignancy, and metabolic. Incidence of hospitalization with diagnoses from each main group was compared between twins and singletons, as well as time to first hospitalization. Cox proportional hazard models were used to study the association between twins vs singletons and hospitalizations by grouped morbidities, while adjusting for maternal age, ethnicity and gender, besides maternal recurrence in the cohort. RESULTS: A total of 369 478 offspring were included in the analysis; of these 11 986 (3.2%) were twins and 357 492 (96.8%) were singletons. Twins were more likely to be delivered preterm (odds ratio = 17.65, 95% CI: 16.74-18.60), by cesarean delivery and following infertility treatments. Incidence of hospitalizations with all morbidity groups was slightly, some significantly, higher among twins, including cardiac: 1.9% vs 1.5%, respiratory; 8.4% vs 7.1%, neurological: 7.7% vs 7.4%, infectious: 26.0% vs 24.1%, and malignancies: 0.7% vs 0.4%. The risk remained higher in the multivariable analyses (adjusted hazard ratios ranging between 1.09-1.75). When stratifying by gestational age at delivery, the risk for most morbidities was lower among twins vs singletons born in similar gestational ages. CONCLUSIONS: Twins as compared to singletons are at increased risk for most morbidities due to their risk of being born earlier.

Early childhood allergy linked with development of attention deficit hyperactivity disorder and autism spectrum disorder.

BACKGROUND: Previous studies reported controversial results regarding the association between allergic disorders and attention deficit hyperactivity disorder (ADHD)/autism spectrum disorder (ASD). The aim of this article was to investigate whether allergic disorders are associated with ADHD/ASD in a large cohort of pediatric patients. METHODS: A retrospective study using the pediatric (0-18 year) database (ICD-9-CM codes) of Clalit Health Services during the years (2000-2018). Diagnosis of all disorders was made by specialist physicians. RESULTS: A total of 117 022 consecutive non-selective allergic children diagnosed with one or more allergic disorder (asthma, rhinitis, conjunctivitis, skin, food, or drug allergy) and 116 968 non-allergic children were enrolled to our study. The mean follow-up period was 11 ± 6 years. The presence of allergic disorders in early childhood (mean age of allergic diagnosis 4.5 ± 4.3 years) in boys as well as in girls significantly increased the risk to develop ADHD (O.R 2.45, CI 2.39-2.51; p < .0001), ASD (O.R 1.17, CI 1.08-1.27; p < .0001), or both ADHD + ASD (O.R 1.5, CI 1.35-1.79; p < .0001). Children with more than one allergic comorbidity revealed a much higher risk. In a multivariable analysis (adjusted for age at study entry, number of yearly visits, and gender), the risk of allergic children to develop ADHD and ADHD + ASD, but not ASD alone, remained significantly higher. CONCLUSION: Allergic disorder in early childhood significantly increased the risk to develop ADHD, and to a less extend ASD, in later life.

Normal labor curve in twin gestation.

BACKGROUND: Failure to progress is one of the leading indications for cesarean delivery in trials of labor in twin gestations. However, assessment of labor progression in twin labors is managed according to singleton labor curves. OBJECTIVE: This study aimed to establish a partogram for twin deliveries that reflects normal and abnormal labor progression and customized labor curves for different subgroups of twin labors. STUDY DESIGN: This was a multicenter, retrospective cohort analysis of twin deliveries that were recorded in 3 tertiary medical centers between 2003 and 2017. Eligible parturients were those with twin gestations at ≥34 weeks' gestation with cephalic presentation of the presenting twin and ≥2 cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, major fetal anomalies, and fetal demise. The study group comprised twin gestations, whereas singleton gestations comprised the control group. Statistical analysis was performed using Python 3.7.3 and SPSS, version 27. Categorical variables were analyzed using chi-square tests. Student t test and Mann-Whitney U test were applied to analyze the differences in continuous variables, as appropriate. RESULTS: A total of 1375 twin deliveries and 142,659 singleton deliveries met the inclusion criteria. Duration of the active phase of labor was significantly longer in twin labors than in singleton labors in both nulliparous and multiparous parturients; the 95th percentile duration was 2 hours longer in nulliparous twin labors and >3.5 hours longer in multiparous twin labors than in singleton labors. The cervical dilation progression rate was significantly slower in twin deliveries than in singleton deliveries with a mean rate in twin deliveries of 1.89 cm/h (95th percentile, 0.51 cm/h) and a mean rate of 2.48 cm/h (95th percentile, 0.73 cm/h) in singleton deliveries (P<.001). In addition, epidural use further slowed labor progression in twin deliveries. The second stage of labor was also markedly longer in twin deliveries, both in nulliparous and multiparous women (95th percentile, 3.04 vs 2.83 hours, P=.002). CONCLUSION: Twin labors are characterized by a slower progression of the active phase and second stage of labor compared with singleton labors in nulliparous and multiparous parturients. Epidural analgesia further slows labor progression in twin labors. Implementation of these findings in clinical management might lower cesarean delivery rates among cases with protracted labor in twin gestations.

First pregnancy risk factors and future gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) affect about 17% of all pregnancies and is associated with significant short- and long-term health consequences for the mother and her offspring. Early diagnosis and prompt interventions may reduce these adverse outcomes. We aimed to identify first pregnancy characteristics as risk factors for GDM in subsequent pregnancy. MATERIALS AND METHODS: A population-based nested case-control study was conducted in a large tertiary hospital. The study population included all women with two singleton consecutive pregnancies and deliveries, without GDM in the first pregnancy. Characteristics and complications of the first pregnancy were compared among cases and controls. A multivariable logistic regression model was used to study the association between pregnancy complications (in the first pregnancy) and GDM in the subsequent pregnancy, while adjusting for confounding variables. RESULTS: A total of 38,750 women were included in the study, of them 1.9% (n = 728) had GDM in their second pregnancy. Mothers with GDM in their second pregnancy were more likely to have the following first pregnancy complications: hypertensive disorders, perinatal mortality, maternal obesity and fetal macrosomia. Results remained significant after adjustment for maternal age and inter-pregnancy interval. Having either one of the complications increased the risk for GDM by 2.33 (adjusted OR = 2.33; 95% CI 1.93-2.82) while a combination of two complications increased GDM risk by 5.38 (adjusted OR = 5.38; 95% CI 2.85-10.17). CONCLUSIONS: First pregnancy without GDM complicated by hypertensive disorders, perinatal mortality, maternal obesity and fetal macrosomia was associated with an increased risk for GDM in the subsequent pregnancy. Women with these complications may benefit from early detection of GDM in their subsequent pregnancy.

Relaparotomy post-cesarean delivery: characteristics and risk factors.

PURPOSE: Relaparotomy following cesarean delivery (CD) is performed at a rate of 0.2-1% of CD. The objective of the present study was to identify risk factors for relaparotomy following CD, and to examine whether there is a difference in the risk of relaparotomy between CD performed during different hours of the day. METHODS: A retrospective study on all CD over 10 years compared pregnancies that underwent laparotomy within 1 week following CD to those that did not. RESULTS: Sixty-four patients underwent relaparotomy out of 24,239 CDs (0.26%). In univariate analysis, relaparotomy was significantly associated with pregnancies following assisted-reproductive-technologies odds ratio (OR) 95% confidence interval (CI) 3.15 (1.90-5.22), hypertensive disorders of pregnancy OR 3.05 (1.62-5.72), twin pregnancies OR 95% CI 3.78 (2.21-6.48), preterm deliveries OR 95% CI 2.44 (1.46-4.10), placenta previa OR 95% CI 6.41(2.55-16.09) and urgent CD 1.74 (1.06-2.86), especially during the second-stage of labor OR 95% CI 2.73 (1.34-5.54). The time of day of CD did not influence the rate of relaparotomy. In a multivariable-regression analysis, the adjusted odds ratio for relaparotomy was 10.24 in CD due to placenta previa, and 5.28 in CD performed at the second-stage of delivery. At relaparotomy, active bleeding was found in 50 patients (78.1%), nearly half received packed cells, 12.5% developed consumptive coagulopathy, and 17.2% needed hospitalization in the intensive care unit. 6.3% underwent a second relaparotomy, mainly due to bleeding. CONCLUSION: Placenta previa, and urgent CDs mainly those performed at the second stage of labor are risk factors for relaparotomy after CD.

Maternal hepatitis B or C status and the long-term risk of gastrointestinal morbidity for offspring: A population-based cohort study.

BACKGROUND: More than 360 million people have chronic hepatitis B or C (HBV/HCV) infection worldwide, many of which are women at childbearing age. While the risk of perinatal HBV/HCV has been well established, the long-term implications on offspring health, have been less studied. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term gastrointestinal (GI) morbidities in offspring. AIMS & METHODS: A population-based cohort analysis compared the risk for long-term childhood GI morbidities in children born to HBV/HCV carrier mothers vs the risk in those who were born to noncarriers. Childhood GI morbidities were predefined based on ICD-9 codes, as recorded in hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. A Kaplan-Meier survival curve was constructed to compare the cumulative GI morbidities over time, and a Cox proportional hazards model was used to control for confounders. RESULTS: During the study period (1991-2014), 242 342 newborns met the inclusion criteria: 771 (0.3%) were born to HBV/HCV mothers and 241 571 (99.7%) were not. The median follow-up was 10.51 years (0-18 years). Offspring to HBV/HCV mothers had a higher incidence of GI diseases (9.3% vs 5.4%, OR = 1.82; 95% CI 1.43-2.32; Kaplan-Meier log-rank = 0.001). The increased risk remained significant in the Cox proportional hazards models, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 2.26, 95% CI: 1.79-2.85; P < .001). CONCLUSION: Maternal HBV or HCV carrier status is an independent risk factor for long-term the GI morbidity of offspring.

Maternal diabetes following gestational diabetes: Does multiple gestation multiply the risk?

OBJECTIVE: To assess whether the risk for future diabetes is higher among women diagnosed with gestational diabetes (GD) during twin versus singleton gestations. METHOD: A retrospective cohort study was performed including all women who delivered at a tertiary medical center between the years 1991 and 2021 and had at least one GD diagnosis. The first GD diagnosis per women was defined as the index pregnancy. Women diagnosed with GD during multiple gestations were compared with women diagnosed with GD during singleton gestations. The outcomes included first hemoglobin A1C (Hba1C) level > 6.4 mg/dL post partum, and the highest level measured during the follow-up period of up to 30 years. Multivariable logistic and Cox proportional analysis were used to compare the risk between the two groups while adjusting for confounding variables. RESULTS: The current study included 13 770 mothers, with 458 patients (3.3%) diagnosed with GD during twin gestations and 13 312 (96.7%) during singleton gestations. The mean follow-up was 12.25 ± 9.3 years. Mothers of both groups did not differ in age at index pregnancy; however, mothers of twins were more likely to conceive following fertility treatments. Incidence of diabetes and prediabetes (defined as Hba1C > 6.4 and >5.7, respectively) were lower among the twin-gestation group, both during the 6-month postpartum period (for diabetes: 15.5% vs 22.1%; odds ratio [OR], 0.65 [95% confidence interval (CI), 0.46-0.91]) and during the long-term follow-up (for diabetes: 31.8% vs 40.7%; OR, 0.68 [95% CI, 0.52-0.88]). These results remained significant in the multivariable analysis, while accounting for age, ethnicity, and fertility treatments. CONCLUSION: GD diagnosis during multiple versus singleton gestations is associated with a lower risk for future diabetes.

Long term respiratory morbidity of cesarean-delivered second twin compared to their vaginally-delivered sibling: A retrospective population-based cohort study.

BACKGROUND: Offspring born via cesarean delivery (CD) may be more prone to develope long-term respiratory diseases, compared to those delivered vaginally (VD). In this study, we compared the rates of respiratory diseases between first twins VD and second twins delivered via CD. METHODS: This was a retrospective database study. All twin deliveries encompassed at the Soroka University Medical Center, a large tertiary hospital in southern Israel, between 1991 and 2020, in which the first twin was VD and the second via CD were included. Respiratory diseases included respiratory tract diseases such as bronchiolitis and bronchial asthma. The cumulative incidence of respiratory diseases was compared between the twins using Kaplan-Meier survival analysis and multivariable Cox models to adjust for confounding variables. RESULTS: A total of 395,408 deliveries occurred during the study period, with 13,402 (3.4%) of all deliveries being twins. Of these, 184 (1.4%) were first twins VD and second twins delivered via CD. The second CD twin was more likely to have a non-reassuring fetal heart rate pattern and an Apgar score less than 7 at 5 min. No other differences were found between the siblings. The incidence of long-term respiratory diseases was not statistically different between the CD and VD siblings (7.6% vs. 9.4%, respectively; OR = 0.54; 95% CI: 0.23-1.26). Similarly, the cumulative incidence of respiratory diseases was not statistically different (Kaplan-Meier, log-rank, p = .59), and in the multivariable analysis which adjusted for birthweight and fetal distress during delivery (adjusted hazard ratio = 1.06; 95% CI: 0.43-26.25). CONCLUSIONS: While the immediate outcomes for the CD twin were slightly worse compared to the VD twin, there was no difference in long-term respiratory diseases between the siblings.

The association between normal 50-g glucose challenge test results and risk for future metabolic morbidities: A retrospective cohort study.

OBJECTIVE: To study the association between normal glucose challenge test (GCT) results during pregnancy and the incidence of future maternal metabolic morbidities. METHOD: This was a population-based retrospective cohort study conducted between the years 2005 and 2020. The study included all women aged 17-55 years who underwent GCT as part of the routine prenatal care at the Central District of Clalit Health Services, Israel. The highest GCT result per woman was categorized into five study groups: <120 (reference), 120-129, 130-139, 140-149, and ≥150 mg/dL. Adjusted hazard ratios of the study groups for metabolic morbidities were calculated with Cox proportional survival analysis models. RESULTS: Among a total of 77 568 women participants, 53%, 12.3%, and 10.3% had normal GCT results of <120, 120-129, and 130-139 mg/dL, respectively. During the study period of 6.07 ± 4.35 years, 13 151 (17.0%) cases of metabolic morbidities were documented. High-normal GCT results of 120-129 and 130-139 mg/dL were significantly associated with increased risk for future metabolic morbidity compared with <120 mg/dL (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.08-1.22 and aHR 1.32, 95% CI 1.24-1.41, respectively). CONCLUSION: Although GCT is only recommended as a screening tool for gestational diabetes mellitus, high results, even within the normal range, may point to maternal increased risk for future metabolic morbidity.

Maternal hepatitis B or C carrier status and long-term risk for offspring neurological morbidity: a population-based cohort study.

Hepatitis B and hepatitis C (HBV/HCV) are important global public health concerns. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term offspring neurological hospitalisations. A population-based cohort analysis compared the risk for long-term childhood neurological hospitalisations in offspring born to HBV/HCV carrier vs. non-carrier mothers in a large tertiary medical centre between 1991 and 2014. Childhood neurological diseases, such as cerebral palsy, movement disorders or developmental disorders, were pre-defined based on ICD-9 codes as recorded in hospital medical files. Offspring with congenital malformations and multiple gestations were excluded from the study. A Kaplan-Meier survival curve was constructed to compare cumulative neurological hospitalisations over time, and a Cox proportional hazards model was used to control for confounders. During the study period (1991-2014), 243,682 newborns met the inclusion criteria, and 777 (0.3%) newborns were born to HBV/HCV mothers. The median follow-up was 10.51 years (0-18 years). The offspring from HBV/HCV mothers had higher incidence of neurological hospitalisations (4.5 vs. 3.1%, hazard ratio (HR) = 1.91, 95% CI 1.37-2.67). Similarly, the cumulative incidence of neurological hospitalisations was higher in children born to HBV/HCV carrier mothers (Kaplan-Meier survival curve log-rank test p < 0.001). The increased risk remained significant in a Cox proportional hazards model, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 1.40, 1.01-1.95, p = 0.049). We conclude that maternal HBV or HCV carrier status is an independent risk factor for the long-term neurological hospitalisation of offspring regardless of gestational age and other adverse perinatal outcomes.

The association between an oral glucose tolerance test performed at term pregnancy and obstetric outcomes.

Aims: Assessing the value of oral glucose tolerance test performed at term pregnancy in identifying obstetric complications. Methods: Retrospective cohort study of women with a normal 50 g glucose challenge test who also had an oral glucose tolerance test at term (defined as at or after 37 weeks of gestation). Comparison between the pathological and normal oral glucose tolerance test groups was performed. Results: The mean glucose in the glucose challenge test of women in the normal oral glucose tolerance test (n = 256) group was lower than that in the pathological oral glucose tolerance test (N = 16) group (105 ± 17 mg/dl (5.8 ± 0.9 mmol/l) vs 117 ± 13 mg/dl (6.5 ± 0.7 mmol/l), p = 0.007). Relevant obstetrical complications did not differ significantly between the groups. Of note, in the pathological oral glucose tolerance test group only one woman delivered a macrosomic infant. Conclusions: A pathological oral glucose tolerance test performed at term was unable to identify women at risk for impaired glucose metabolism-related obstetric complications and is therefore of limited clinical value and seems to be unjustified.

Prenatal maternal COVID-19 vaccination and pregnancy outcomes.

BACKGROUND: Prenatal maternal physiological changes may cause severe COVID-19 among pregnant women. The Pfizer-BioNTech COVID-19 vaccine (BNT162b2 mRNA) has been shown to be highly effective and it is recommended for individuals aged ≥16 years, including pregnant women, although the vaccine has not been tested on the latter. OBJECTIVE: To study the association between prenatal Pfizer-BioNTech COVID-19 vaccination, pregnancy course and outcomes. STUDY DESIGN: A retrospective cohort study was performed, including all women who delivered between January and June 2021 at Soroka University Medical Center, the largest birth center in Israel. Excluded were women diagnosed with COVID-19 in the past, multiple gestations or unknown vaccination status. Pregnancy, delivery and newborn complications were compared between women who received 1 or 2-dose vaccines during pregnancy and unvaccinated women. Multivariable models were used to adjust for background characteristics. RESULTS: A total of 4,399 women participated in this study, 913 (20.8%) of which were vaccinated during pregnancy. All vaccinations occurred during second or third trimesters. As compared to the unvaccinated women, vaccinated women were older, more likely to conceive following fertility treatments, to have sufficient prenatal care, and of higher socioeconomic position. In both crude and multivariable analyses, no differences were found between the groups in pregnancy, delivery and newborn complications, including gestational age at delivery, incidence of small for gestational age and newborn respiratory complications. CONCLUSIONS: Prenatal maternal COVID-19 vaccine has no adverse effects on pregnancy course and outcomes. These findings may help pregnant women and health care providers to make informed decision regarding vaccination.

Prenatal particulate matter exposure and Intrauterine Fetal Death.

BACKGROUND: Intrauterine Fetal Death (IUFD) is a rare and tragic pregnancy complication. The main causes for IUFD are largely unknown. Particulate Matter (PM)2.5 exposure has been suggested as an IUFD risk factor. OBJECTIVES: To study the association between maternal PM2.5 levels and IUFD risk, to address ethnicity as a possible effect modifier, and to identify a prenatal period during which PM2.5 is most harmful regarding IUFD risk. METHODS: This is a retrospective cohort study, which included pregnant women at the Soroka University Medical Center between the years 2003-2017. Estimated PM2.5 levels were calculated per residence, using a hybrid model incorporating daily satellite remote sensing data at a 1 km spatial resolution. Multiple gestations, fetuses with congenital malformations or chromosomal abnormalities were excluded. Mean PM2.5 level was calculated per trimester, the entire pregnancy and the last gestational week. Analyses were also performed separately for the two ethnic groups in the study: Jews and Bedouin-Arabs. Multivariable analysis were applied to study the association between PM2.5 exposure at the different periods and IUFD risk. RESULTS: The study included 87,887 pregnancies, 444 (0.5%) ended with IUFD. Mean PM2.5 levels ranged between 18.18 and 22.32 µm. First trimester and entire pregnancy PM2.5 levels were significantly associated with increased IUFD risk among Jewish women only. In a multivariable model, for every 10 µg/m3 unit increase in PM2.5 the risk for IUFD increases by 2.98 (95%CI 1.50-5.90) and by 3.61 (95%CI 1.32-9.85) during first trimester and the entire pregnancy, respectively, while adjusting for maternal age, smoking, socioeconomic score and season. CONCLUSIONS: In this retrospective cohort an association was found between PM2.5 levels and IUFD among Jewish women only. These results strengthen the importance of addressing this effect modifier when studying air pollution effects on human health.

Pregnant women may be sweeter in the summer: Seasonal changes in glucose challenge tests results. A population-based study.

AIMS: A 1-hour, 50-gram glucose challenge test (GCT) is the first step in the diagnosis of gestational diabetes mellitus (GDM). Seasonal fluctuations in fasting glucose levels and GCT results were previously described. We sought to investigate seasonal changes in GCT results in a large cohort. METHODS: GCT results were analyzed of all women insured at the Central District of Clalit Health Services (the largest health maintenance organization in Israel), between the years 2005 and 2016. RESULTS: A total of 101,359 GCT results were analyzed. Mean GCT was 110 ±â€¯28.9 mg/dL, and 14.5% (n = 14,652) were pathological. Both the mean and the incidence of pathological GCT were lowest in the winter, followed by spring, fall, and summer, (p for trend < 0.001). The difference in mean GCT between winter and summer was 7.82 ±â€¯0.24 mg/dL (95% CI, 7.35-8.29). After adjustment for BMI and age, having a GCT in the winter was independently associated with the lowest risk for pathological GCT, as compared to all other seasons. CONCLUSIONS: Seasonal changes in GCT results should be studied further in additional regions, and if found, the cutoff threshold for abnormal GCT should be re-examined and adapted to local weather conditions and seasonal variability.

The association between anogenital distance, reproductive and general health in adult females- a prospective cohort of 17 years.

BACKGROUND: Studies have suggested an association between prenatal hormonal environment and anogenital distance (AGD). We aimed to study the association between AGD and health characteristics in adult women. METHODS: In this prospective cohort AGD was measured in 300 parturients during the years 2000-2001. In December 2017, study participants` hospital records were abstracted and medical diagnoses grouped into major categories, including gynecological, cardiovascular, and other. Associations between AGD and the morbidities categories were evaluated using multivariable survival models, which adjusted for confounding variables. RESULTS: Participants were 44.3 ±â€¯5.4 years old with mean AGD 40.3 mm (±10.7 mm). Women with below vs. above mean AGD were more likely to develop gynecological morbidities (39.9% vs. 27.1%, adjusted Hazard ratio 1.82; 95%CI 1.08-3.06). CONCLUSIONS: Women with short AGD are at increased risk for gynecological morbidities. AGD should be studied further, and may possibly be used for screening of women at risk for these conditions.

Pregnant Women Become Sweeter: A Population-Based Study of Trends in Glucose Challenge Test Results Over a Decade.

Background: Glucose challenge tests (GCTs) are widely used to screen for gestational diabetes mellitus. Women with high normal GCT results may be at increased risk for immediate obstetric complications and future diabetes. We analyzed the ∼10-year trend in mean GCT results and incidence of high normal (125-140 mg/dL) and abnormal GCT results (>140 mg/dL) in a large cohort of women in Israel. Materials and Methods: Data on all GCTs performed between 2005 and 2016 were gathered from the computerized database of the Central District of Clalit Health Services, the largest Health Maintenance Organization in Israel. Trends over time were studied by time series analysis, and a multivariable logistic model was constructed to study the risk for abnormal results, while adjusting for maternal age and body mass index (BMI). Results: Altogether 101,359 GCTs were analyzed. Over the study period, mean maternal age increased from 28.7 ± 5.1 to 30.1 ± 5.1 years and mean GCT results from 101.7 to 114.6 mg/dL (p < 0.001, for both), whereas the incidence of women with abnormal GCT (>140 mg/dL) increased from 10.6% to 18.1% (p < 0.001) and of those with high normal GCT (>125 mg/dL) from 20.2% to 31.3% (p < 0.001). A multivariable logistic model revealed that later years were associated with an increased risk for abnormal GCT result, while adjusting for maternal age and BMI (adjusted odds ratio = 1.07; 95% confidence interval 1.07-1.08). Conclusions: Over ∼10 years, mean GCT results and high GCT incidence have significantly increased. These findings are in line with the worldwide diabetes epidemic and demonstrate the worsening in glucose metabolism also in relatively young women.

Fertility treatments and offspring pediatric infectious morbidities: results of a population-based cohort with a median follow-up of 10 years.

OBJECTIVE: To study the association between mode of conception and offspring infectious morbidity risk. DESIGN: Population-based cohort study. SETTING: Regional university medical center. PATIENT(S): All singleton infants born between the years 1991 and 2014 and discharged alive from the hospital. INTERVENTION(S): Follow-up time in the study was calculated from birth to an event, defined as the first offspring hospitalization with any infectious morbidity. All infectious diagnoses were compared between the study groups, and a multivariable survival model was created to study the association between mode of conception and offspring pediatric hospitalization with infectious morbidity, and adjusting for confounding or clinically significant variables. MAIN OUTCOME MEASURE(S): First offspring pediatric hospitalization with infectious morbidity. RESULT(S): During the study period, 242,187 newborns met the inclusion criteria: 2,603 (1.1%) of which were conceived after undergoing IVF, 1,172 (0.7%) after ovulation induction (OI), and 237,863 (98.3%) were conceived spontaneously. Mothers receiving fertility treatments were older and with higher rates of preterm births and low birthweights. The hospitalizations rates per 1,000 person years of follow-up were 16.34/1,000 person years, 11.61/1,000 person years, and 10.19/1,000 person years, among the IVF, OI, and spontaneously conceived offspring, respectively. The adjusted hazard ratios were 1.26 (95% confidence interval 1.13-1.42) and 1.14 (95% confidence interval 1.00-1.38), for the IVF and OI compared with the spontaneously conceived offspring, respectively. The model adjusted for preterm delivery, birthweight, maternal age, hypertension, diabetes, and cesarean section. CONCLUSION(S): Higher risk for infectious morbidity was found among offspring conceived after fertility treatments compared with spontaneously conceived offspring.

DT56a (Femarelle): a natural selective estrogen receptor modulator (SERM).

A selective estrogen receptor modulator (SERM) is defined as a substance with dissimilar effects on different tissues: agonist in some and antagonists in others. The natural compound DT56a (Femarelle) was shown to activate estrogen receptors in human cultured female derived osteoblasts. It was also shown to relieve menopausal symptoms and to increase bone mineral density with no effect on sex steroid hormone levels and on the endometrial thickness. DT56a, similarly to estradiol-17beta (E2), stimulated the specific activity of creatine kinase (CK) in skeletal and vascular tissues of female rats, as a marker of estrogen receptor (ER) activation. However, in the uterus, CK was activated only by E2 but not by DT56a. In order to prove that DT56a is a SERM, we examined the mutual interaction between DT56a and E2, at supra physiological doses, in different tissues in both intact and ovariectomized female rats, as well as in human cultured vascular and bone cells. Administration of DT56a or E2 stimulated CK in all tissues tested, but when given simultaneously, in intact immature female rats, DT56a completely abolished E2 stimulation of CK in all organs except in the diaphyseal bone where the inhibition was partial. In ovariectomized female rats, DT56a abolished E2's stimulation of CK in diaphyseal bone, thymus, uterus and pituitary but caused a partial inhibition in aorta, left ventricle and epiphyseal cartilage. In human bone cells E2 stimulation of CK, of alkaline phosphatase (AP) activity and of DNA synthesis was completely abolished by DT56a in post-menopausal cells and partially inhibited in pre-menopausal cells. In human vascular cells, inhibition of DNA synthesis by E2 was completely abolished by DT56a and E2-induced CK was partially inhibited by DT56a. The results support the finding that DT56a is a SERM; it stimulated different parameters similar to E2, but when given simultaneously, at supra physiological doses, inhibited these E2's effects. Further investigations regarding intra and extra cellular mechanism of action of DT56a are currently performed.

Compliance to vaginal treatment-tablets versus cream: a retrospective 9 years study.

OBJECTIVE: Local estrogens are used for the treatment of genitourinary symptoms of menopause. The efficacy and adverse effects of both estrogen-containing vaginal tablets (VT) and estrogen-containing vaginal creams (VC)/gels are comparable. Our objective was to assess the compliance and adherence to treatment in a large population. METHODS: A retrospective study on women aged 40 to 89 was performed in the Central District of the "Clalit" Health Services between 2006 and 2014. Demographic data on all women and usage details were electronically recorded. Patients eligible for analysis used VT or VC for at least 4 consecutive months. RESULTS: A total of 2,269 patients used continuous monotherapy, of them 1,782 patients received treatment only with VC and 487 received treatment only with VT. Sixty-four percent of women treated with VT were treated for at least 4 months compared with 39% of women administered with VC (P < 0.000006). After 6 months of treatment, 83% of women with VT were asked for another prescription compared with 54% of women with VC (P < 0.001). The mean duration of treatment was 1,002 ±â€Š38 days for the VT-treated women, and 787 ±â€Š25 days for the VC-treated group (P < 0.000006). CONCLUSIONS: The present study showed superiority in the compliance and adherence of postmenopausal women to treatment with estrogen tablets over estrogen gel.