Assessing the impact of medically assisted reproduction on autism spectrum disorder risk.

PURPOSE: Techniques of medically assisted reproduction interact with the embryo at crucial developmental stages, yet their impact on the fetus and subsequent child's health remains unclear. Given rising infertility rates and more frequent use of fertility treatments, we aimed to investigate if these methods heighten the risk of autism spectrum disorder (ASD) in children. METHODS: A population-based cohort study was conducted at Soroka University Medical Center, a tertiary referral hospital, encompassing singleton births. The incidence of ASD in offspring, incorporating either hospital or community-based diagnoses, was compared in relation to the conception method. To examine the cumulative incidence of ASD, a Kaplan-Meier survival curve was utilized. Cox proportional hazards model was employed to adjust for confounders. RESULTS: Among 115,081 pregnancies, 0.5% involved ovulation induction (OI) and 1.7% in vitro fertilization (IVF), with the rest conceived naturally. Fertility treatments were more common in older patients and linked to more diabetes, hypertensive disorders, preterm, and cesarean deliveries. Out of 767 ASD diagnoses, offspring from OI and IVF had higher initial ASD rates (2.1% and 1.3%) than natural conceptions (0.6%). In a Cox model accounting for maternal age, ethnicity, and gender, neither OI nor IVF was significantly associated with ASD. The adjusted hazard ratios were 0.83 (95% CI 0.48-1.43) for OI and 1.34 (95% CI 0.91-1.99) for IVF. When considering fertility treatments combined, the association with ASD remained non-significant (aHR 1.11, 95% CI 0.80-1.54, p = 0.52). CONCLUSION: Fertility treatments, including OI and IVF, do not exhibit a significant association with heightened ASD risk in offspring.

Second-versus first-born twin: comparison of short- and long-term outcomes.

PURPOSE: An ancient description of the competition between twins for first breath is found in the biblical story of Jacob and Esau (Genesis 25:26) when Jacob pulled his older brother's heel in the hope of becoming firstborn but to no avail. In this study, we sought to evaluate the short and long-term outcomes of twin pairs, comparing between the second- and first-born twin. METHODS: A population-based cohort study, including dichorionic twin deliveries occurring between the years 1991 and 2021 at Soroka University Medical Center. A General estimation equation (GEE) was applied to adjust for confounders. The incidence of offspring's hospitalizations due to various medical conditions was compared. Kaplan-Meier survival analyses compared cumulative morbidity. Cox proportional hazards models were used to control for confounders. RESULTS: 5507 twin deliveries met the inclusion criteria. Second-born twins had higher rates of cesarean deliveries, statistically significant in the GEE multivariable analysis. More first-twin fetuses were experiencing non-reassuring fetal heart rate patterns, although other obstetrical outcomes as well as mortality rates were comparable between groups. Second twins weighed lower than their older sibling (mean difference 33 g) and were more frequently SGA and low birthweight (1500-2500 g); (p < 0.05). Later during childhood, offspring of twin deliveries experienced notable morbidity due to infectious (23.8-24.1%), respiratory (10.5-10.9%), neurological (7.0-7.8%) and cardiovascular pathologies (1.7-1.9%) during childhood, that was unaffected by birth order. CONCLUSION: Other than birthweight differences, the birth order of dichorionic twins is not associated with adverse neonatal health indices, nor does it predict excess risk for morbidity during childhood.

Long-term neurological outcomes of offspring misdiagnosed with fetal growth restriction.

OBJECTIVE: Fetal growth restriction (FGR) is a major determinant of adverse short- and long-term perinatal outcomes. The current definition of FGR (estimated fetal weight measurement < 10th percentile) may lead, at times, to a false diagnosis of fetuses that are eventually born appropriate for gestational age (AGA). Our objective was to investigate the potential association between a misdiagnosis of antepartum fetal growth restriction and long-term neurological outcomes in offspring. STUDY DESIGN: A population-based cohort analysis was performed including deliveries between the years 1991-2020 in a tertiary medical center. We compared neurological hospitalization during childhood among AGA infants falsely diagnosed as FGR versus AGA infants without a false FGR diagnosis. A Kaplan-Meier survival curve was used to assess cumulative morbidity and a Cox proportional hazards model was employed to control for confounders. RESULTS: During the study period, 324,620 AGA infants met the inclusion criteria; 3249 of them were falsely classified as FGR. These offspring had higher rates of hospitalizations due to various neurological conditions, as compared to those without an FGR diagnosis (OR 1.431, 95% CI 1.278-1.608; P < 0.001). In addition, cumulative hospitalization incidence was elevated in the FGR group (log-rank P-value < 0.001). When controlling for confounders, a false FGR diagnosis remained independently associated with long-term neurological morbidities (adjusted HR 1.086, 95% CI 1.003-1.177, P = 0.043). CONCLUSION: Misdiagnosis of FGR in the antepartum period is associated with an increased risk for offspring long-term neurological morbidities.

Examining the relationship between autism spectrum disorder in children whose mother had labour epidural analgesia for their birth: A retrospective cohort study.

BACKGROUND: Controversy exists regarding the association between autism spectrum disorder (ASD) in children whose mother had labour epidural analgesia for their birth, as the few existing investigations have reported mixed findings. OBJECTIVE: This study aims to evaluate the possibility of an association in our heterogeneous population. DESIGN: A retrospective population-based cohort study. SETTING: Vaginal deliveries that took place between the years 2005 and 2017 at Soroka University Medical Center, a tertiary referral hospital in Israel, and a follow-up on the incidence of ASD in the children. PATIENTS: A hundred and thirty-nine thousand, nine hundred and eighty-one labouring patients and their offspring. MAIN OUTCOME MEASURES: The incidence of children diagnosed with ASD (both hospital and community-based diagnoses) was compared based on whether their mothers had received labour epidural analgesia during their labour. A Kaplan-Meier survival curve compared cumulative incidence of ASD. A Cox proportional hazards model was used to control for relevant confounders. RESULTS: Labour epidural analgesia was administered to 33 315 women. Epidural analgesia was more common among high-risk pregnancy groups (including pregnancies complicated with diabetes mellitus, hypertensive disorders, intrauterine growth restriction, and oligohydramnios; P  < 0.001). In a Cox proportional hazards model, the association between epidural analgesia during labour and ASD in the children lost statistical significance following adjustment for confounders such as maternal age, gestational age, hypertensive disorders, diabetes mellitus, and ethnicity [adjusted hazard ratio = 1.13, 95% confidence interval (CI), 0.96 to 1.34, P  = 0.152]. CONCLUSION: In our population, after adjusting for confounders, epidural analgesia is not independently associated with autism spectrum disorder in the children. These findings enhance our knowledge regarding the safety of epidural analgesia and enable patients to make informed decisions about their pain relief techniques during labour.

Association Between Mode of Delivery of the Breech Fetus and Hospitalizations Due to Inflammatory Bowel Disease During Childhood.

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<0.001 and P=0.004, respectively). Using a Weibull parametric while controlling for relevant confounders, cesarean delivery emerged as an independent risk factor for long-term IBD-related morbidity of the offspring delivered in breech presentation (adjusted hazard ratio=3.18, 95% confidence interval: 1.47-6.87, P=0.003). CONCLUSION: Cesarean delivery is associated with higher rates of hospitalizations due to IBD and total GI morbidity during childhood in term singleton in breech presentation.

Shoulder Dystocia during Delivery and Long-Term Neurological Morbidity of the Offspring.

OBJECTIVE: The study aimed to evaluate risk factors and implications of shoulder dystocia (SD) on the neurological outcome of successfully delivered offspring. STUDY DESIGN: This is a cohort analysis including 207,571 deliveries. Risk factors for SD were evaluated using general estimation equation multivariable analyses. Offspring hospitalization incidence up to age 18 years due to neurological conditions was compared between both groups. Kaplan-Meyer curve was used to assess the cumulative hospitalization incidence. Cox proportional hazards model was used to control for confounders. RESULTS: SD complicated 0.2% (n = 353) of deliveries included in the study (n = 207,571). Risk factors for SD were fetal macrosomia, maternal diabetes mellitus, male gender, and advanced maternal age (p < 0.05 for all). Higher perinatal mortality was observed among SD cases (2.8 vs. 0.4%, p < 0.001). In most of the investigated neurological conditions no significant differences were found between the groups. Comparable rates of cumulative neurological-related hospitalization were observed (log rank p-value = 0.342) as well as lack of association between SD and neurological hospitalization (adjusted HR = 0.73; 95% CI 0.36-1.47; p = 0.381) when controlled for gestational age. CONCLUSION: Risk factors for SD are macrosomia, diabetes mellitus, male gender, and advanced maternal age. SD is not associated with long-term neurological morbidity of the offspring.

Respiratory morbidity among offspring misclassified as growth restricted.

OBJECTIVE: An ultrasound-based diagnosis implies that some fetuses suspected to be growth-restricted (FGR) are discovered at birth to be appropriately grown (appropriate for gestational age [AGA] birth weight, between the 10th and 90th percentile). These fetuses may thus be exposed to unnecessary medical interventions, including early labor induction. In this study, we have evaluated the long-term respiratory health of offspring misclassified as FGR. STUDY DESIGN: A population-based cohort analysis was conducted, including deliveries of AGA singletons between 1991 and 2021 at a tertiary referral hospital. Incidence of morbidity due to various respiratory conditions was compared between AGA offspring with prenatal diagnosis of FGR, and those without a false diagnosis of FGR. The Kaplan-Meier approach was used to estimate cumulative morbidity incidence. The stratified Cox proportional-hazards model was used to control for confounders. RESULTS: A total of 324,620 deliveries of AGA newborns were included in the analyses; 3249 of them (1.0%) were misclassified prenatally as FGR. The FGR subgroup delivered at an earlier gestational age (36.7 vs. 39.1 weeks, p < .001) and had more than 25% higher incidence of respiratory-related morbidity during childhood (33.2% vs. 26.5%), specifically related to asthma and obstructive sleep apnea (p < .001 for all). A higher cumulative morbidity rate due to respiratory conditions was observed in the Kaplan-Meier survival curve (log-rank p value < .001). This association between FGR and respiratory morbidity was independent of preterm delivery, maternal age, cesarean delivery, and child's birth year (adjusted hazard ratio = 1.14, 95% confidence interval: 1.07-1.21, p < .001), using a Cox proportional hazards model. CONCLUSION: AGA newborns misclassified as FGR, are at an increased risk for long-term respiratory morbidity during childhood and adolescence.

The future of patient education: A study on AI-driven responses to urinary incontinence inquiries.

OBJECTIVE: To evaluate the effectiveness of ChatGPT in providing insights into common urinary incontinence concerns within urogynecology. By analyzing the model's responses against established benchmarks of accuracy, completeness, and safety, the study aimed to quantify its usefulness for informing patients and aiding healthcare providers. METHODS: An expert-driven questionnaire was developed, inviting urogynecologists worldwide to assess ChatGPT's answers to 10 carefully selected questions on urinary incontinence (UI). These assessments focused on the accuracy of the responses, their comprehensiveness, and whether they raised any safety issues. Subsequent statistical analyses determined the average consensus among experts and identified the proportion of responses receiving favorable evaluations (a score of 4 or higher). RESULTS: Of 50 urogynecologists that were approached worldwide, 37 responded, offering insights into ChatGPT's responses on UI. The overall feedback averaged a score of 4.0, indicating a positive acceptance. Accuracy scores averaged 3.9 with 71% rated favorably, whereas comprehensiveness scored slightly higher at 4 with 74% favorable ratings. Safety assessments also averaged 4 with 74% favorable responses. CONCLUSION: This investigation underlines ChatGPT's favorable performance across the evaluated domains of accuracy, comprehensiveness, and safety within the context of UI queries. However, despite this broadly positive reception, the study also signals a clear avenue for improvement, particularly in the precision of the provided information. Refining ChatGPT's accuracy and ensuring the delivery of more pinpointed responses are essential steps forward, aiming to bolster its utility as a comprehensive educational resource for patients and a supportive tool for healthcare practitioners.

Intrapartum Maternal Fever and Long-Term Infectious Morbidity of the Offspring.

Maternal intrapartum fever can lead to various maternal and neonatal complications and is attributed to various etiologies including infectious and non-infectious processes. In this study, we evaluated whether intrapartum fever affects the offspring's tendency to long-term infectious morbidity. A population-based cohort analysis including deliveries between 1991 and 2021 was conducted. The incidence of hospitalizations of the offspring up to the age of 18 years, due to various infectious conditions, was compared between pregnancies complicated by intrapartum fever and those that were not. A Kaplan-Meier survival curve was used to assess cumulative hospitalization incidence. A Cox proportional hazards model was used to control for confounders. Overall, 538 of the 356,356 included pregnancies were complicated with fever. A higher rate of pediatric hospitalizations due to various infectious conditions was found among the exposed group, which was significant for viral, fungal and ENT infections (p < 0.05 for all). The total number of infectious-related hospitalizations was significantly higher (30.1% vs. 24.1%; OR = 1.36; p = 0.001), as was the cumulative incidence of hospitalizations. This association remained significant after controlling for confounders using a Cox proportional hazards model (adjusted HR = 1.21; 95% CI 1.04-1.41, p = 0.016). To conclude, fever diagnosed close to delivery may influence offspring susceptibility to pediatric infections.

Decreased fetal movements: Perinatal and long-term neurological outcomes.

BACKGROUND: While maternal perception of decreased fetal movements during advanced stages of pregnancy may be an indicator for adverse perinatal outcome, the long-term neurological outcome of offspring of affected pregnancies remains largely unknown. OBJECTIVE: To examine whether maternal complaint of decreased fetal movements is associated with adverse perinatal outcomes, and to assess the implications of decreased fetal movements on long-term neurological morbidity of the offspring. STUDY DESIGN: A single center cohort analysis including deliveries between the years 1991-2014 was conducted. The association between decreased fetal movements and adverse perinatal outcome was evaluated using a general estimation equation (GEE) multivariable analyses. Incidence of hospitalizations (up to age 18 years) due to various neurological conditions was compared between offspring of affected pregnancies, and those who were not, using a Kaplan-Meyer survival curve. A Cox proportional hazards model was used to control for confounders. RESULTS: 439 (0.18%) of 242,342 deliveries included in this study were accompanied by maternal complaint of decreased fetal movements. Perinatal outcome was comparable between the groups, with no cases of perinatal mortality observed among the exposed group. Total neurological-related hospitalization rate of the offspring, as well as hospitalizations due to movement disorders, were higher among the exposed group (Kaplan-Meyer log-rank test P < 0.05). This association between decreased fetal movements and increased long-term neurological hospitalization proved to be independent of potential confounders with an adjusted hazard ratio of 1.54 (95% CI 1.0-2.37). CONCLUSION: Maternal complaint of decreased fetal movements does not predict adverse perinatal outcome but is associated with an elevated risk for long-term neurological morbidity of the offspring.

Elevated cancer risk in Holocaust survivors residing in Israel: A retrospective cohort study.

BACKGROUND: The purpose of this study was to examine the incidence of malignant diseases among Holocaust survivors in Israel compared with European and American immigrants who did not experience the Holocaust. METHODS: Study subjects included Holocaust survivors born in European countries under Nazi occupation before 1945, who immigrated to Israel after 1945 and were alive as of the year 2000. Living survivors were identified based on recognition criteria in accordance with the Holocaust Survivor Benefits Law. The comparison group consisted of Clalit enrollees who were born before 1945 in European countries not under Nazi occupation and were alive in 2000 or were born in any European country or America, immigrated to Israel before 1939 and were alive in 2000. The incidence of malignant diseases was compared in univariate and Poisson regression models analyses, controlling for age, smoking, obesity, diabetes and place of residence. RESULTS: The study included 294,543 Holocaust survivors, and the mean age at the beginning of follow-up was 74 ± 8.7 years; 43% males. In multivariable analyses, the rate ratio (RR) values for males and females were 1.9 and 1.3 for colon cancer, 1.9 and 1.4 for lung cancer, 1.6 and 1.4 for bladder cancer and 1.2 and 1.3 for melanoma, respectively. For prostate cancer in males, the RR was 1.4, while for breast cancer in females, it was 1.2. CONCLUSIONS: The incidence of malignant diseases among Holocaust survivors residing in Israel was higher than that among non-Holocaust survivors. These associations remained statistically significant in a multivariable analysis and were stronger for males.

Cardiovascular Morbidity and Risk Factors in Holocaust Survivors in Israel.

OBJECTIVES: To compare the prevalence of cardiovascular diseases and risk factors in Holocaust survivors with that of Jewish immigrants from Europe and America. DESIGN: Population-based, cross-sectional study. SETTING: Clalit, a large Israeli healthcare provider. PARTICIPANTS: Holocaust survivors (n=83,971) and a comparison group of Jewish individuals born in North or South America or European countries not under Nazi occupation or who immigrated to Israel before 1939 (n=16,058) (mean age 84±7, 61% female) MEASUREMENTS: Univariate and multivariable logistic regression analyses of cardiovascular diseases and risk factors. Matching the comparison group to Holocaust Survivors on propensity scores for exposure. RESULTS: The prevalence of ischemic heart disease (38.7% vs 31.3%), congestive heart failure (10.9% vs 9.1%), past stroke (15.7% vs 13.4%), and peripheral vascular disease (9.5% vs 7.9%) was higher in Holocaust survivors (p<.001 for all comparisons). Similar results were found for cardiovascular risk factors (diabetes mellitus (14.4% vs 13.6%), hypertension (89.3% vs 86.4%), dyslipidemia (75.9% vs 74.0%) (p<.001 for all comparisons). In multivariable analysis, matched on propensity scores and controlled for confounders, odds ratios for men and women were higher for diabetes (1.23, 1.55), dyslipidemia (1.53, 1.51), hypertension (1.56 , 1.94), stroke (1.18, 1.17), and ischemic heart disease (1.18, 1,40), but not congestive heart failure (0.95, 1.02). A Positive association was noted for peripheral vascular disease in males (1.20) but not females (0.96). CONCLUSION: Prevalence of cardiovascular diseases and risk factors was higher in Holocaust survivors. These associations were stronger in women in most cases.

Maternal gestational diabetes and long-term respiratory related hospitalizations of the offspring.

AIMS: To assess the implications of gestational diabetes mellitus (GDM) on long-term respiratory related hospitalizations of the offspring. METHODS: A population-based cohort analysis including singleton pregnancies delivered between the years 1991 to 2014 in a tertiary referral hospital was conducted. Incidence of hospitalizations (up to age 18 years) due to various respiratory diseases was compared between offspring of GDM-complicated pregnancies and normoglycemic pregnancies. Kaplan-Meyer curves were used to assess cumulative hospitalization incidence. Cox proportional hazards model was used to control for baseline selected confounders. RESULTS: During the study period 216,197 deliveries met the inclusion criteria. Of those, 4.7% (n = 10,184) were complicated by GDM. In most of the investigated respiratory diseases, no significant differences were found between offspring of both groups. Nonetheless, obstructive sleep apnea-related hospitalization rate was higher among the GDM group, an association which proved to be independent of potential confounders with an adjusted hazard ratio of 1.26 (95% CI 1.02-1.55; p = 0.036). CONCLUSION: Gestational diabetes mellitus does not appear to be associated with long-term respiratory hospitalizations of the offspring other than obstructive sleep apnea-related hospitalizations.