Gestational hemodilution as a putative risk factor for postpartum depression: A large-scale nationwide longitudinal cohort study.

BACKGROUND: While anemia during pregnancy has been linked to increased postpartum depression (PPD) risk, longitudinal studies on the association between gestational hemodilution, represented by decreased hematocrit (Hct) during the transition from the 1st to 2nd trimester, and PPD risk, are scarce. The current study aimed to investigate this association in a nationwide cohort over the perinatal period. METHODS: This retrospective cohort study included 104,715 women who gave birth between January 2008 and December 2015. The cohort was followed up for new-onset PPD during the year post birth and gestational hemodilution was assessed by the change in Hct levels (Δ: 2nd-1st trimester). The cohort was divided into three hemodilution groupings: maximal and minimal 10 % of mothers and intermediate 80 %. Multivariable regression analyses were performed to estimate the association between gestational hemodilution and PPD, adjusting for confounders. RESULTS: Among the full cohort, 2.2 % (n = 2263) met the definition of new-onset PPD. Mothers with greater hemodilution had higher rates of PPD: 2.7 % (n = 269) in the maximal hemodilution group, 2.1 % (n = 1783) in the intermediate and 1.9 % (n = 211) in the minimal hemodilution group (p < 0.001). The maximal hemodilution group had higher rates of pre-gestational psychiatric disorders (p < 0.001) and higher adjusted risk for PPD [OR = 1.18, 95 % CI (1.04, 1.35)]. LIMITATIONS: Data on iron levels and supplementation were unavailable, thus it could not be adjusted for in the analysis. CONCLUSIONS: Women in the top 10th percentile of gestational hemodilution may be at risk for PPD, justifying monitoring of gestational Hct as a biomarker for PPD.

Association of Celiac Serology Normalization With the Risk of Hypothyroidism: A Cohort Study.

INTRODUCTION: We evaluated whether persistent-positive celiac serology is associated with the risk of hypothyroidism. METHODS: We extracted a cohort of subjects aged 1-80 years with a positive IgA anti-tissue transglutaminase between January 1, 2008, and December 31, 2012, and a repeat anti-tissue transglutaminase test within 6-36 months from a large population-based electronic medical record database. Based on serology tests, we categorized the pediatric (age <21 years) and adult cohorts into normalized or persistent-positive serology groups. All subjects were followed up for incident diagnosis of hypothyroidism from the last serology date up to December 31, 2017. Hazard ratio (HR) along 95% confidence intervals (CIs) were prepared to evaluate the association of celiac serology group with a diagnosis of hypothyroidism, crude, and adjusted for age, sex, and diagnosis of type 1 diabetes mellitus. RESULTS: Among the pediatric cohort (n = 2,687), during a median follow-up of 64 months (interquartile range 48-80), 2.3% (16/681) of the persistent-positive serology group and 1.0% (20/2,006) of the normalized serology group developed hypothyroidism (HR 2.07 [95% CI 1.07-4.44], adjHR 1.77 [95% CI 0.91-3.46]). The rate among the pediatric cohort with an established diagnosis of celiac disease was 3.4% (10/486) vs 1.0% (5/481), HR 2.83 (0.96-8.32). In the adult cohort (n = 1,286), 4.5% (20/442) of the persistent-positive group and 3.9% (33/811) of the normalized serology group developed hypothyroidism (HR 1.13 [95% CI 0.65-1.97]). DISCUSSION: In this retrospective, age-stratified analysis, we report that persistent-positive serology may be associated with the risk of hypothyroidism among the pediatric population. Prospective cohorts are needed to validate our findings.

Association of Renin-Angiotensin-Aldosterone Inhibitors with COVID-19 Infection and Disease Severity among Individuals with Hypertension.

BACKGROUND: The association between use of renin-angiotensin-aldosterone (RAAS) inhibitors and both SARS-CoV-2 infection and the development of severe COVID-19 has been presented in the recent medical literature with inconsistent results. OBJECTIVES: To assess the association between RAAS inhibitor use and two outcomes: infection with SARS-CoV-2 (Model 1) and severe COVID-19 among those infected (Model 2). METHODS: We accessed used electronic health records of individuals from Israel who were receiving anti-hypertensive medications for this retrospective study. For Model 1 we used a case-control design. For Model 2 we used a cohort design. In both models, inverse probability weighting adjusted for identified confounders as part of doubly robust outcome regression. RESULTS: We tested 38,554 individuals for SARS-CoV-2 who had hypertension and were being treated with medication; 691 had a positive test result. Among those with a positive test, 119 developed severe illness. There was no association between RAAS inhibitor use and a positive test. Use of RAAS inhibitors was associated with a decreased risk for severe COVID-19 (adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.29-0.77) compared with users of non-RAAS anti-hypertensive medication. The association remained significant when use of angiotensin-converting-enzyme inhibitors (adjusted OR 0.46, 95%CI 0.27-0.77) and angiotensin II receptor blockers (adjusted OR 0.39, 95%CI 0.16-0.95) were analyzed separately. CONCLUSIONS: Among individuals with hypertension using RAAS inhibitors, we found a lower risk of severe disease compared to those using non-RAAS anti-hypertensive medications. This finding suggests that RAAS inhibitors may have a protective effect on COVID-19 severity among individuals with medically treated hypertension.

Using population-level incidence of hepatitis C virus and immigration status for data-driven screening policies: a case study in Israel.

BACKGROUND: Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis. METHODS: Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined. RESULTS: Of the 2 029 501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively). DISCUSSION: In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases.

A multi-country investigation of influenza vaccine coverage in pregnant individuals, 2010-2016.

BACKGROUND: Many countries recommend influenza vaccination during pregnancy. Despite this recommendation, influenza vaccine among pregnant individuals remains under-utilized and uptake varies by country. Factors associated with influenza vaccine uptake during pregnancy may also vary across countries. METHODS: As members of the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), five sites from four countries (Australia, Canada, Israel, and the United States) retrospectively identified cohorts of individuals aged 18-50 years who were pregnant during pre-defined influenza seasons. Influenza vaccine coverage estimates were calculated for the 2010-11 through 2015-16 northern hemisphere and the 2012 through 2015 southern hemisphere influenza seasons, by site. Sites used electronic health records, administrative data, and immunization registries to collect information on pregnancy, health history, demographics, and vaccination status. Each season, vaccination coverage was calculated as the percentage of individuals who received influenza vaccine among the individuals in the cohort that season. Characteristics were compared between those vaccinated and unvaccinated, by site. RESULTS: More than two million pregnancies were identified over the study period. Influenza vaccination coverage ranged from 5% to 58% across sites and seasons. Coverage increased consistently over the study period at three of the five sites (Western Australia, Alberta, and Israel), and was highest in all seasons at the United States study site (39-58%). Associations with vaccination varied by country and across seasons; where available, parity >0, presence of a high-risk medical condition, and urban residence were consistently associated with increased likelihood of vaccination. CONCLUSIONS: Though increasing, uptake of influenza vaccine among pregnant individuals remains lower than recommended. Coverage varied substantially by country, suggesting an ongoing need for targeted strategies to improve influenza vaccine uptake in this population.

Diagnoses and Health Care Utilization for After-Hours Telemedicine Versus Primary Care Visits.

OBJECTIVE: The use of a nation-wide, pediatricians online (PO) after-hours telemedicine service has been offered in Israel for more than a decade. We sought to compare PO visits with those to the primary care pediatrician (PCP). METHODS: This is a retrospective cross-sectional study using Israel's largest health care provider database. We included children aged 0 to 18 years using either PO or PCP between 2015 and 2018. We compared the baseline characteristics, matching by socioeconomic status, chronic illness, and diagnosis, and compared their admission rates, laboratory testing, and medication prescription. RESULTS: During this study period there were 262,541 PO visits and a random 10% sample of PCP visits which yielded 1,813,103 visits. Users of PO were more likely to have a higher socioeconomic status (43% vs 28.9%), fever (13.3% vs 4.4%) and less likely to have acute respiratory conditions (8.8% vs 16.7%). Users of PO had higher rates of emergency department admissions (2.9% vs 0.4%), hospital admissions (0.9% vs 0.2%), and lower rates of laboratory testing (3.7% vs 7.4%) and medication prescription (42.0% vs 52.0%) within 24 hours. All differences were statistically significant (P < .005). CONCLUSIONS: Our pediatric telemedicine service operating after-hours has been found to be feasible, and widely used, for a myriad of clinical conditions. Significant differences exist between PO and PCP visit characteristics and outcomes. However, it remained unclear whether these differences reflect the difference in the patient population or whether they are the result of the different clinical services. Further research is warranted to clarify this matter.

Body mass index trajectories among people with obesity and association with mortality: Evidence from a large Israeli database.

OBJECTIVE: Previous studies using longitudinal weight data to characterize obesity are based on populations of limited size and mostly include individuals of all body mass index (BMI) levels, without focusing on weight changes among people with obesity. This study aimed to identify BMI trajectories over 5 years in a large population with obesity, and to determine the trajectories' association with mortality. METHODS: For inclusion, individuals aged 30-74 years at index date (1 January 2013) with continuous membership in Clalit Health Services from 2008 to 2012 were required to have ≥1 BMI measurement per year in ≥3 calendar years during this period, of which at least one was ≥30 kg/m2. Latent class analysis was used to generate BMI trajectories over 5 years (2008-2012). Cox proportional hazards models were used to assess the association between BMI trajectories and all-cause mortality during follow-up (2013-2017). RESULTS: In total, 367,141 individuals met all inclusion criteria. Mean age was 57.2 years; 41% were men. The optimal model was a quadratic model with four classes of BMI clusters. Most individuals (90.0%) had stable high BMI over time. Individuals in this cluster had significantly lower mortality than individuals in the other trajectory clusters (p < 0.01), including clusters of people with dynamic weight trajectories. CONCLUSIONS: The results of the current study show that people with stable high weight had the lowest mortality of all four BMI trajectories identified. These findings help to expand the scientific understanding of the impact that weight trajectories have on health outcomes, while demonstrating the challenges of discerning the cumulative effects of obesity and weight change, and suggest that dynamic historical measures of BMI should be considered when assessing patients' future risk of obesity-related morbidity and mortality, and when choosing a treatment strategy.

Development and validation of a machine learning-based postpartum depression prediction model: A nationwide cohort study.

BACKGROUND: Currently, postpartum depression (PPD) screening is mainly based on self-report symptom-based assessment, with lack of an objective, integrative tool which identifies women at increased risk, before the emergent of PPD. We developed and validated a machine learning-based PPD prediction model utilizing electronic health record (EHR) data, and identified novel PPD predictors. METHODS: A nationwide longitudinal cohort that included 214,359 births between January 2008 and December 2015, divided into model training and validation sets, was constructed utilizing Israel largest health maintenance organization's EHR-database. PPD was defined as new diagnosis of a depressive episode or antidepressant prescription within the first year postpartum. A gradient-boosted decision tree algorithm was applied to EHR-derived sociodemographic, clinical, and obstetric features. RESULTS: Among the birth cohort, 1.9% (n = 4104) met the case definition of new-onset PPD. In the validation set, the prediction model achieved an area under the curve (AUC) of 0.712 (95% confidence interval, 0.690-0.733), with a sensitivity of 0.349 and a specificity of 0.905 at the 90th percentile risk threshold, identifying PPDs at a rate more than three times higher than the overall set (positive and negative predictive values were 0.074 and 0.985, respectively). The model's strongest predictors included both well-recognized (e.g., past depression) and less-recognized (differing patterns of blood tests) PPD risk factors. CONCLUSIONS: Machine learning-based models incorporating EHR-derived predictors, could augment symptom-based screening practice by identifying the high-risk population at greatest need for preventive intervention, before development of PPD.

Prediction of Childhood Obesity from Nationwide Health Records.

OBJECTIVE: To evaluate body mass index (BMI) acceleration patterns in children and to develop a prediction model targeted to identify children at high risk for obesity before the critical time window in which the largest increase in BMI percentile occurs. STUDY DESIGN: We analyzed electronic health records of children from Israel's largest healthcare provider from 2002 to 2018. Data included demographics, anthropometric measurements, medications, diagnoses, and laboratory tests of children and their families. Obesity was defined as BMI ≥95th percentile for age and sex. To identify the time window in which the largest annual increases in BMI z score occurs during early childhood, we first analyzed childhood BMI acceleration patterns among 417 915 adolescents. Next, we devised a model targeted to identify children at high risk before this time window, predicting obesity at 5-6 years of age based on data from the first 2 years of life of 132 262 children. RESULTS: Retrospective BMI analysis revealed that among adolescents with obesity, the greatest acceleration in BMI z score occurred between 2 and 4 years of age. Our model, validated temporally and geographically, accurately predicted obesity at 5-6 years old (area under the receiver operating characteristic curve of 0.803). Discrimination results on subpopulations demonstrated its robustness across the pediatric population. The model's most influential predictors included anthropometric measurements of the child and family. Other impactful predictors included ancestry and pregnancy glucose. CONCLUSIONS: Rapid rise in the prevalence of childhood obesity warrant the development of better prevention strategies. Our model may allow an accurate identification of children at high risk of obesity.

Choosing Wisely: Determining performance of unjustified imaging in a large healthcare system.

AIMS: The Choosing Wisely Campaign identifies procedures and treatments that lack clinical justification for routine use according to expert opinion and evidence-based medicine. This study describes the rates and features of two such examples over a 10-year period. METHODS: This is a cross-sectional rolling cohort study between 2008 and 2017 in Clalit Health Services, the largest healthcare delivery system in Israel, with seven main hospitals and over 4.5 million members nationwide. All adult members who visited a Clalit Emergency Department (ED), and all children members who visited a Clalit ED for abdominal pain or appendicitis were eligible to be included in this study. Our measures were routine chest radiograph (CXR) in the context of pre-admission assessment for adults and abdominal computed tomography (CT) to rule out appendicitis for children. RESULTS: Of the 3 689 869 adult visits without a clinical indication for a CXR, 9.1% or 337 058 of them received a chest radiograph. Of the 35 973 children visits for presumed appendicitis, 7.2% of them had no imaging performed, 82.3% had an ultrasound (US), 6.9% had an US followed by a CT, and 3.6% or 1293 of them received a CT. There were several independent risk factors such as BMI, hospital, sex, year and diagnosis that are associated with having imaging that is not clinically indicated. CONCLUSIONS: Overall, this study found that diagnostic imaging practices are applied inconsistently by hospital and by population. Intervention efforts should be focused on subpopulations at greatest risk to further reduce exposure to such imaging.

Validating reported cause of death using integrated electronic health records from a nation-wide database.

BACKGROUND: To compare the underlying cause of death reported by the Israeli Central Bureau of Statistics (CBS) with diagnoses in the electronic health records (EHR) of a fully integrated payer/provider healthcare system. METHODS: Underlying cause of death was obtained from the CBS for deaths occurring during 2009-2012 of all Clalit Health Service members in Israel. The final cohort consisted of members who had complete medical records. The frequency of a supportive diagnosis in the EHR was reported for 10 leading causes of death (malignancies, heart disease, cerebrovascular disease, diabetes, kidney disease, septicemia, accidents, chronic lower respiratory disease, dementia and pneumonia and influenza). RESULTS: Of the 45 680 members included in the study, the majority of deaths had at least one diagnosis in the EHR that could support the cause of death. The lowest frequency of supportive diagnosis was for septicemia (52.2%) and the highest was for malignancies (94.3%). Sensitivity analysis did not suggest an alternative explanation for the missing documentation. CONCLUSIONS: The underlying cause of death coded by the CBS is often supported by diagnoses in Clalit's EHR. Exceptions are septicemia or accidents that cannot be anticipated from a patient's EHR, and dementia which may be under-reported.

The relationship between inpatient hyperglycaemia and mortality is modified by baseline glycaemic status.

AIMS: There is a well-established association between inpatient hyperglycaemia and mortality. However, evidence is inconsistent regarding whether this association is differential among those with and without type 2 diabetes mellitus (T2DM). Most studies are based on convenience samples or are unable to adjust for comorbidities. We examined whether the association between hyperglycaemia and 30-day mortality was modified by baseline glycaemic status. MATERIALS AND METHODS: This was a retrospective cohort study of 174,671 eligible hospitalized individuals between 2012 and 2015. Thirty-day mortality was assessed during the first inpatient stay up to 30 days post discharge. The adjusted association between hyperglycaemia and mortality was assessed with logistic regression models. Then, four interaction terms were entered into the model to assess if the association between hyperglycaemia and mortality differed by baseline glycaemic status. RESULTS: The multivariate model demonstrated a 2.18-fold risk of mortality associated with hyperglycaemia (odds ratio [OR] [95%CI]: 2.19 [2.08-2.31]). Adding the interaction terms between hyperglycaemia and baseline glycaemic status the ORs of 30-day mortality were 1.41 (1.25-1.60) in non-T2DM status, 1.32 (1.16-1.51) in pre-diabetes status and 1.30 (1.04-1.62) in unscreened status, as compared to T2DM status with hyperglycaemia. CONCLUSIONS: Hyperglycaemia is positively associated with mortality and both those without and with controlled T2DM are at highest risk. These findings may help medical staff identify potential increased risk of mortality upon hospital entry and discharge, and direct further research to assess how hyperglycaemia control and proactive deterioration prevention throughout the entire inpatient stay may prevent adverse outcomes.

Long-term effectiveness of the Diabetes Conversation Map™ Program on health outcomes: A case-control retrospective cohort study.

AIM: To evaluate the clinical and health behavioural outcomes of a large sample of participants from the Diabetes Conversation Map™ Program. DESIGN: A matched-case-control study that was performed on a retrospective cohort study. METHODS: Participants were 11,053 Clalit Health Services members with type 2 diabetes who enrolled in the Diabetes Conversation Map™ Program between January 2010 - April 2016. The matched-control group was formulated using sequential matching, by matching cases to controls at a ratio of 1:3, based on age, sex, and HbA1c level. The associations between the programme group and annual clinical and health behaviours were assessed between cases and controls at five time points using linear and Poisson regression analyses. RESULTS: The intervention group had significantly lower HbA1c, glucose, and low-density lipoprotein levels and more frequent glucose blood testing each year up to 36 month post-enrolment compared with the matched controls. Other outcomes were significantly different for shorter time periods, including higher high-density lipoprotein and lower triglyceride levels at 6- and 12-month follow-up and lower diastolic blood pressure and greater medication adherence at 6-month follow-up. CONCLUSIONS: Enrolment in the programme was associated with improved clinical and health behaviour outcomes for at least 6 months and most outcomes persisted for up to 36 months. IMPACT: This is the first study to evaluate the Diabetes Conversation Map™ Program with a large sample over long period of time. This nurse-led group intervention evaluation adds to the literature on health outcomes on the lives of patients with type 2 diabetes. STUDY REGISTRATION: This study was registered retrospectively to the Open Science Framework, the registration form can be found at: https://osf.io/63cse.

A comprehensive descriptive assessment of obesity related chronic morbidity and estimated annual cost burden from a population-based electronic health record database.

BACKGROUND: The growing prevalence of obesity and its complications pose a huge burden on the individual and health care systems worldwide. This study presents the frequency of multiple prevalent co-morbidities and estimated annual cost burden by body mass index (BMI) groups, age, and sex among the Israeli adult population to provide policy makers with further evidence to appropriately target interventions. METHODS: This cross-sectional study utilized population-based electronic medical records from the largest payer-provider health fund in Israel. The population included individuals ≥25 years as of 01/01/2014. A new approach assessing body system-related morbidity (BSRM) prevalence was assessed along with estimated annual cost burden for the year 2015 and presented across BMI group, age, and sex via heat maps. RESULTS: Among 1,756,791 adults, 65% had an elevated BMI (BMI > 25 kg/m2). Heat map analysis demonstrated a higher multi-BSRM prevalence and relative estimated annual cost burden among participants with obesity in all age groups. There was a notably higher multi-BSRM prevalence among men and women aged 25-29 with class III obesity (26 and 30%, respectively) compared to the corresponding BMI groups between 18·5- < 25 kg/m2 (5 and 9%, respectively). Healthcare costs were 1·72 times higher among men aged 25-29 with class III obesity and 2·75 times among women aged 25-29 with class III obesity compared to those of healthy weight. CONCLUSIONS: The detailed analysis describes the uneven distribution of burdens across BMI groups, age, and sex allowing policy makers to identify sub-populations for targeted interventions.

An international cohort study of birth outcomes associated with hospitalized acute respiratory infection during pregnancy.

OBJECTIVES: Findings during the 2009 pandemic suggest severe maternal infection with pandemic influenza had adverse perinatal health consequences. Limited data exist evaluating the perinatal health effects of severe seasonal influenza and non-influenza infections during pregnancy. METHODS: A retrospective cohort of pregnant women from Australia, Canada, Israel, and the United States was established using birth records to identify pregnancies and birth outcomes and hospital and laboratory testing records to identify influenza and non-influenza associated acute respiratory or febrile illness (ARFI) hospitalizations. ARFI hospitalized women were matched to non-hospitalized women (1:4) by country and season of conception. Log-binomial regression was used to estimate the relative risk (aRR) of preterm birth (PTB), small-for-gestational-age (SGA), and low birthweight (LBW) birth, adjusting for pre-existing medical conditions, maternal age, and parity. RESULTS: 950 pregnant women hospitalized with an ARFI were matched with 3,800 non-hospitalized pregnant women. Compared to non-hospitalized women, risk of PTB was greater among women hospitalized with influenza-associated ARFI (aRR: 1.57; 95% CI: 1.15-2.15) and non-influenza ARFI (aRR: 2.78; 95% CI: 2.12-3.65). Similar results were observed for LBW; there were no associations with SGA birth. CONCLUSIONS: ARFI hospitalization during pregnancy was associated with increased risk of PTB and LBW.

Prediction of gestational diabetes based on nationwide electronic health records.

Gestational diabetes mellitus (GDM) poses increased risk of short- and long-term complications for mother and offspring1-4. GDM is typically diagnosed at 24-28 weeks of gestation, but earlier detection is desirable as this may prevent or considerably reduce the risk of adverse pregnancy outcomes5,6. Here we used a machine-learning approach to predict GDM on retrospective data of 588,622 pregnancies in Israel for which comprehensive electronic health records were available. Our models predict GDM with high accuracy even at pregnancy initiation (area under the receiver operating curve (auROC) = 0.85), substantially outperforming a baseline risk score (auROC = 0.68). We validated our results on both a future validation set and a geographical validation set from the most populated city in Israel, Jerusalem, thereby emulating real-world performance. Interrogating our model, we uncovered previously unreported risk factors, including results of previous pregnancy glucose challenge tests. Finally, we devised a simpler model based on just nine questions that a patient could answer, with only a modest reduction in accuracy (auROC = 0.80). Overall, our models may allow early-stage intervention in high-risk women, as well as a cost-effective screening approach that could avoid the need for glucose tolerance tests by identifying low-risk women. Future prospective studies and studies on additional populations are needed to assess the real-world clinical utility of the model.

Maternal age and cardiovascular and metabolic disease outcomes: a retrospective cohort study using data from population-based electronic medical records.

Objective: To evaluate whether a woman's age at first birth is associated with cardiovascular risk and metabolic health outcomes (cardiometabolic outcomes) by age 45.Methods: This is a retrospective, population-based cohort study that uses electronic health record data from the largest health fund in Israel. Women aged 34-39 at baseline (2004-2006) free of chronic diseases were identified as nulliparous at baseline and were followed up to 10 years (through 2016). The cohort was divided into three groups based on their age at first birth: younger parturients (ages 35-39), older parturients (ages 40-44), and never had children. The percentage of adverse pregnancy events and cardiometabolic outcomes at age 45 were compared across these three groups as well as to women in the general population. Cardiovascular risk and metabolic health outcomes were defined as: Type 2 diabetes, obesity, hypertension, cardiovascular disease, and Framingham risk score.Methods and results: Out of a group of 126,121 women aged 34-39 at baseline, 9979 were nulliparous and free of comorbidities. Over the course of the follow-up, there were 952 younger parturients and 673 older parturients who had their first birth, and 8354 women who remained persistent nulliparous. While older parturients had more adverse pregnancy events, there was no difference in rates of cardiometabolic outcomes between the two parturient groups, and they both had lower rates than the persistent nulliparous and the general population.Conclusions: Parturients free of major chronic diseases who give birth at a later age do not have increased cardiometabolic outcomes in midlife as compared to a general population of women in a large retrospective cohort. Our results may support clinicians when counseling healthy women who are seeking advice regarding delaying their first pregnancy without a tradeoff on health outcomes.

High rates of serology testing for coeliac disease, and low rates of endoscopy in serologically positive children and adults in Israel: lessons from a large real-world database.

BACKGROUND: Although coeliac disease is common worldwide, little is known regarding screening patterns in unselected populations, and on real-life adherence to professional guidelines for coeliac disease diagnosis and management. OBJECTIVE: To explore current practices in the diagnosis and management of coeliac disease, using data from a large Health Maintenance Organization in Israel that covers 54% of the population. METHODS: A population-based electronic database of about 4.5 million individuals was reviewed during the period of 1 January 2008 to 31 December 2015. Rates and results of coeliac disease serology testing and endoscopy procedures were examined. Subgroup analysis was performed by age, sex, ethnicity and socioeconomic status. RESULTS: Coeliac disease serology cumulative testing rate was 17.1% and 8.9% in the paediatric and adult population, respectively. The cumulative incidence of positive coeliac disease serology was 0.45% in children and 0.17% in adults, and was associated with age, sex, ethnicity and socioeconomic status sub-groups (P-value < 0.01). Gastrointestinal endoscopies were not subsequently performed in 44.1% of children and 47.1% of adults with positive coeliac disease serology. Within the study period, 36% of children and 56% of adults never achieved coeliac disease serology normalization. CONCLUSION: In a large real-life database, screening for coeliac disease was common. However, confirmatory intestinal biopsies were under-utilized, and coeliac disease serology often remained positive over a long period time in both children and adults.

Association between prenatal exposure to a 1-month period of repeated rocket attacks and neuropsychiatric outcomes up through age 9: a retrospective cohort study.

Exposure to gestational stress is implicated in increased risk for neuropsychiatric disorders in offspring. We assessed association between prenatal exposure to a 1-month period of repeated rocket attacks during the 2006 Second Lebanon War in Northern Israel and emergence of childhood neuropsychiatric disorders from birth through 9 years of age. Children born to women who were pregnant during the war (N = 6999) were identified and compared to children in the same district born a year later (N = 7054), whose mothers were not exposed to rocket attacks during pregnancy. Multivariable regression models assessed risk for attention deficit hyperactivity disorder, autism, epilepsy, depression and/or anxiety, or any of these disorders (composite outcome) in offspring. Models controlled for multiple confounders including parents' demographics, parity, maternal use of psychotropic medications during pregnancy, post-partum depression and parental psychiatric history. Results show that exposed and comparison groups did not differ with respect to demographics, parity or psychiatric history. Exposed and comparison groups were similar with regard to gestational age and weight at birth. Multivariable models did not demonstrate an association between exposure to rocket attacks during pregnancy and neuropsychiatric outcomes by age 9. No interactions were found between exposure and gestational trimester at exposure or child's sex. Our findings suggest that in utero exposure to isolated, 1-month repeated rocket attacks on a civilian population was not associated with major neuropsychiatric outcomes in children by age 9. Future studies should evaluate whether this exposure is associated with psychiatric and/or other health-related outcomes later in life.