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(1) Background: We aimed to study whether a low 5 min Apgar score is associated with pediatric neurological morbidities throughout childhood. (2) Methods: A population-based retrospective cohort study was conducted. The exposed group was defined as offspring with a 5 min Apgar score <7, and the remaining offspring served as the comparison group. The primary outcome was defined as pediatric hospitalizations with any neurological morbidity. Multivariable survival models were used to evaluate the association between the exposure and outcome while adjusting for potential confounders. Additional models were used to study this association separately among term- and preterm-born offspring. (3) Results: The study population included 349,385 singletons born between the years 1991 and 2021, 0.6% (n = 2030) of whom had a 5 min Apgar score <7 (exposed). The cohort was followed for up to 18 years (median ~ 10.6). The incidence of neurological morbidity-related hospitalizations was higher among the exposed group versus the unexposed group (11.3% versus 7.5%, hazard ratio = 1.84; 95%CI 1.58−2.13). A low 5 min Apgar score remained a significant risk factor for neurological hospitalizations after adjusting for preterm delivery, maternal age, hypertension during pregnancy, gestational diabetes mellitus, chorioamnionitis, and delivery mode (adjusted hazard ratio = 1.61; 95%CI 1.39−1.87). However, after modeling term and preterm offspring separately, a low 5 min Apgar score was independently associated with neurological hospitalizations only among offspring born at term (adjusted hazard ratio = 1.16; 95%CI 0.87−1.55 and 1.70; 95%CI 1.42−2.02 for preterm and term offspring, respectively). (4) Conclusions: A low 5 min Apgar score is independently associated with childhood neurological morbidity, specifically among term-born offspring. Although not designed to identify risk for long-term health complications, Apgar scores may be a marker of risk for short- and long-term neurological morbidities among term newborns.

Objective: This study investigates the risk for long-term respiratory hospitalizations of offspring born small for gestational age (SGA) at term., Study Design: A retrospective population-based cohort analysis was performed to examine the risk of long-term respiratory hospitalizations between SGA compared to appropriate for gestational age (AGA) newborns. The analysis included all term singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations, multiple gestation, cases of perinatal mortality and large for gestational age (LGA) were excluded. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence up to the age of 18 years, and a Cox hazards regression model was used to control for confounders., Results: During the study period 216,671 deliveries met the inclusion criteria; of them 4.8% (n = 10,450) were diagnosed as SGA neonates. During the follow-up period, the rate of hospitalization due to respiratory morbidity was significantly higher in the SGA group as compared to the AGA group (5.2% vs. 4.7%, OR = 1.13, 95% confidence interval [CI] = 1.03-1.24, p = 0.011). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory morbidity in the SGA group (log-rank p = 0.026). In the Cox hazards regression model, controlled for relevant clinical confounders, SGA was found to be an independent risk factor for long-term pediatric respiratory morbidity (adjusted hazard ratio [HR] = 1.1, 95% CI = 1.001-1.19, p = 0.049)., Conclusion: Being delivered SGA at term is an independent long-term risk factor for pediatric respiratory hospitalization., (© 2021 Wiley Periodicals LLC.)

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.

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Uterine rupture during labor is a life-threatening event associated with high morbidity for both mother and fetus. While the immediate maternal and neonatal outcomes of uterine rupture are well established, less is known regarding the long-term respiratory morbidity of offspring which survived uterine rupture., Aim: To assess whether a history of uterine rupture at birth, is associated with an increased risk for future offspring respiratory morbidity., Materials and Methods: In this population-based retrospective cohort study, all singleton deliveries between 1991 and 2014 were included. Known offspring chromosomal or congenital anomalies and cases of perinatal mortality were excluded from the analysis. The incidence of hospitalizations with respiratory morbidities, predefined in a set of ICD-9 codes, was compared between offspring delivered with or without uterine rupture. Cox proportional hazards models were conducted, to control for each confounder separately., Results: During the study period 238,622 deliveries met the inclusion criteria, of those 127 (0.053%) were complicated by uterine rupture. Rates of respiratory related hospitalizations were 7.1 and 4.9%, among offspring delivered with or without uterine rupture, respectively ( p  = .22), and in the Kaplan- Meier survival curves, no significant differences were found between the groups (log rank test p  = .241). While using Cox proportional hazards models and controlling for each confounder separately, uterine rupture was not found to be an independent risk factor for long-term respiratory morbidity of the offspring., Conclusion: Uterine rupture was not found as an independent risk factor for offspring long-term respiratory morbidity. The limited number of cases in the exposed group, could only demonstrate a trend with no significance, and therefore further investigation is required.

Objective: To identify risk factors in first pregnancy for perinatal mortality in the subsequent pregnancy., Methods: A retrospective population-based nested case-control study was conducted, including all women with two first singleton consecutive deliveries. Women with perinatal mortality in their first pregnancy were excluded, and cases with perinatal mortality in the second pregnancy were compared with controls who delivered a live birth. Characteristics and complications of the first pregnancy were compared between the groups using multivariable logistic models., Results: A total of 43 043 women were included in the study, 385 (0.9%) were cases. Cases, as compared with controls (live births), were younger (22.62 ± 4.0 vs 23.22 ± 4.0 years), with shorter inter-pregnancy interval (1.38 ± 1.55 vs 1.56 ± 1.53 years), and were more likely to have the following complications in their first pregnancy: severe pre-eclampsia (3.4% vs 1.7%), small for gestational age (12.5% vs 8.0%), preterm delivery (17.7% vs 7.8%), and congenital or chromosomal malformations (9.6% vs 5.9%). In multivariable analysis the risk for perinatal mortality was greater with each additional complication (adjused odds ratio [aOR] 1.64, 95% confidence interval [CI] 1.30-2.07, P < 0.001; aOR 2.55, 95% CI 1.61-4.04, P < 0.001; aOR 7.88, 95% CI 3.81-16.29, P < 0.001 for one, two, and three or more complications, compared with no complications, respectively)., Conclusion: Complications in first pregnancy ending with live birth are associated with increased risk for perinatal mortality in a subsequent pregnancy., (© 2021 International Federation of Gynecology and Obstetrics.)

Respiratory morbidity is a hallmark complication of prematurity. Children born preterm are exposed to both short- and long-term respiratory morbidity. This study aimed to investigate whether a critical gestational age threshold exists for significant long-term respiratory morbidity. A 23-year, population-based cohort analysis was performed comparing singleton deliveries at a single tertiary medical center. A comparison of four gestational age groups was performed according to the WHO classification: term (≥37.0 weeks, reference group), moderate to late preterm (32.0-36.6 weeks), very preterm (28.0-31.6 weeks) and extremely preterm (24.0-27.6 weeks). Hospitalizations of the offspring up to the age of 18 years involving respiratory morbidities were evaluated. A Kaplan-Meier survival curve was used to compare cumulative hospitalization incidence between the groups. A Cox proportional hazards model was used to control for confounders and time to event. Overall, 220,563 singleton deliveries were included: 93.6% term deliveries, 6% moderate to late preterm, 0.4% very preterm and 0.1% extremely preterm. Hospitalizations involving respiratory morbidity were significantly higher in children born preterm (12.7% in extremely preterm children, 11.7% in very preterm, 7.0% in late preterm vs. 4.7% in term, p < 0.001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory-related hospitalizations in the preterm groups (log-rank, p < 0.001). In the Cox regression model, delivery before 32 weeks had twice the risk of long-term respiratory morbidity. Searching for a specific gestational age threshold, the slope for hospitalization rate was attenuated beyond 30 weeks' gestation. In our population, it seems that 30 weeks' gestation may be the critical threshold for long-term respiratory morbidity of the offspring, as the risk for long-term respiratory-related hospitalization seems to be attenuated beyond this point until term.

Purpose: The current study was aimed to assess whether maternal epilepsy is linked to long-term neurological morbidity of the offspring, and to examine whether maternal epilepsy is associated with adverse pregnancy outcomes., Methods: A population-based cohort study was conducted comparing perinatal outcomes of women with and without epilepsy, including long-term neurological morbidity of the offspring. Both the exposed and unexposed groups were followed up to 18 years of age for neurological-related morbidity. To assess perinatal outcomes of women with epilepsy, generalized estimation equation (GEE) models were used to control for confounders. To compare the cumulative incidence of long-term neurological morbidity a Kaplan-Meier survival curve was used. A Cox proportional hazards model was built to control for confounders., Results: During the study period, 243,682 deliveries met the inclusion criteria; 711 (0.29%) were of mothers with epilepsy. Maternal epilepsy was noted as an independent risk factor for preterm delivery, cesarean delivery, and low birth weight using GEE models controlling for maternal age and parity. Offspring born to mothers with epilepsy had higher rates of long-term neurological morbidity (Kaplan-Meier log-rank test, p < 0.001). A Cox proportional hazards model, controlled for maternal age, hypertensive disorders, gestational age, and diabetes mellitus, demonstrated that being born to a mother with epilepsy was an independent risk factor for long-term neurological morbidity of the offspring (adjusted HR 2.7, 95% CI 2.12-3.56, p < 0.001)., Conclusions: The pregnancy of epileptic women is independently associated with the adverse perinatal outcome as well as a higher risk for long-term neurological morbidity of the offspring., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Research using artificial intelligence (AI) in medicine is expected to significantly influence the practice of medicine and the delivery of health care in the near future. However, for successful deployment, the results must be transported across health care facilities. We present a cross-facilities application of an AI model that predicts the need for an emergency caesarean during birth. The transported model showed benefit; however, there can be challenges associated with interfacility variation in reporting practices., (©Joshua Guedalia, Michal Lipschuetz, Sarah M Cohen, Yishai Sompolinsky, Asnat Walfisch, Eyal Sheiner, Ruslan Sergienko, Joshua Rosenbloom, Ron Unger, Simcha Yagel, Hila Hochler. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.12.2021.)

Objective: To examine whether smoking during pregnancy is correlated with long-term ophthalmic complications of the offspring., Study Design: A population-based cohort analysis was performed comparing all deliveries of mothers who reported smoking during pregnancy and non-smoking mothers between 1991 and 2014 at a single tertiary medical center. Hospitalizations of the offspring up to the age of 18 years involving ophthalmic morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan-Meier curve was used to compare cumulative hospitalization rate in exposed and unexposed offspring and a Cox proportional hazards model was used to control for confounders., Results: During the study period, 243,680 deliveries met the inclusion criteria. Of them, 2965 (1.2%) were children of smoking mothers. Ophthalmic-related hospitalizations were significantly higher in children born to smoking mothers, as compared with the non-smoking group (1.4% vs. 0.1%, p < 0.01). Specifically, these hospitalizations were due to higher rates of visual disturbance rate and ophthalmic infections. The Kaplan-Meier curve demonstrated a significant higher cumulative incidence of ophthalmic-related hospitalizations in the smoking group (log rank p < 0.001). Using a Cox proportional hazards model, controlling for potential confounders, maternal tobacco use was found to be independently associated with long-term ophthalmic morbidity of the offspring (adjusted HR = 1.51, CI 1.11-2.04)., Conclusion: Maternal smoking during pregnancy is an independent risk factor for long-term ophthalmic morbidity of the offspring. These results are in line with many recent studies that strongly support maternal smoking cessation during pregnancy due to high offspring morbidity risk., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To evaluate whether an association exists between maternal anemia and offspring failure to thrive (FTT) during childhood., Methods: A population-based cohort analysis was performed, comparing the risk for FTT among children (up to 18 years old) based on maternal hemoglobin (Hb) levels, upon postpartum discharge. Maternal Hb levels were categorized into 3 levels: <9.0 (moderate-severe anemia), 9.0-11.0 (mild anemia), and ≥11.0 g/dL (no anemia). FTT diagnosis was based on hospital records. All singletons born between 1991 and 2014 and discharged alive without congenital malformations were included. A survival curve was constructed to compare the cumulative FTT incidence, and a Weibull parametric survival analysis to assess the independent association between maternal anemia and offspring FTT while controlling for confounders., Results: Of the 214,305 included deliveries, 22,071 parturients (10.3%) were discharged with Hb <9.00; 83,932 (39.2%) with Hb between 9.0-11.0; and 108,302 (50.5%) with Hb ≥11.0 g/dL. FTT rates were 1.3% ( n  = 287), 1.2% ( n  = 967), and 1.1% ( n  = 1141) in the same groups, respectively ( p  = .003). The survival curve demonstrated a significantly higher cumulative incidence of FTT diagnosis in the moderate-severe maternal anemia group ( p  < .001). In the Weibull analysis, constructed for newborns with appropriate birthweight, both groups of maternal anemia were found to be independently associated with FTT related hospitalizations (mild anemia aHR, 1.1; 95%CI 1.002-1.219; p  = .045, moderate-severe anemia aHR, 1.321; 95%CI, 1.141-1.529; p  < .001)., Conclusion: Maternal anemia is independently associated with long-term FTT in offspring, with increasing FTT rates proportional to anemia severity.

Objective: This study aimed to investigate the possible impact of meconium-stained amniotic fluid (MSAF) on the occurrence of neurological-related hospitalizations throughout childhood and adolescence., Study Design: In this population-based cohort analysis, all singleton deliveries occurring between 1991 and 2014 at the Soroka University Medical center were included and the long-term neurological-related hospitalizations were compared between children with and without MSAF during their delivery. A Kaplan-Meier survival analysis was constructed for the evaluation of cumulative hospitalization rate due to neurological morbidity over the 18 years of follow-up, and a Cox proportional hazards model was used to study the independent association between MSAF and childhood neurological morbidity while controlling for potential confounders., Results: During the study period, 243,725 deliveries met the inclusion criteria; 35,897 of the cohort (15%) constituted the exposed group (MSAF), while the rest of the cohort ( n  = 207,828) constituted the unexposed group (no MSAF). A total of 7,543 hospitalizations due to neurological-related morbidity were documented with a rate of 3.2% (1,152) in children exposed to MSAF as compared with 3.1% (6,391) in the unexposed group (OR 1.1, 95% confidence interval 0.9-1.1, p  = 0.149). The survival curve showed a comparable cumulative hospitalization rate in the MSAF-exposed group compared with the unexposed group (log rank p  = 0.349). The Cox analysis, controlled for gestational diabetes and hypertension, gestational and maternal ages, demonstrated MSAF exposure not to be an independent risk factor for neurological-related hospitalizations during childhood (adjusted hazard ratio = 1.03, 0.96-1.09)., Conclusion: Fetal exposure to MSAF, at any gestational age, does not appear to be an independent risk factor for later neurological-related hospitalizations throughout childhood and adolescence., Key Points: · MSAF is associated with several short-term complications such as low Apgar scores.. · The long-term implications of MSAF exposure are yet to be clearly defined.. · Fetal exposure to MSAF is not a risk factor for neurological morbidity throughout childhood.., Competing Interests: None declared., (Thieme. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan-Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan-Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80-1.18; adjusted HR 1.01, 95% CI 0.83-1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.

We investigated whether maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status increases the risk for long-term oncologic morbidity of their offspring up to the age of 18 years. A population-based cohort study was conducted, including all singleton deliveries between the years 1991 and 2014 at a tertiary medical center. Our study included: HBV carriers ( n  = 588), HCV carriers ( n  = 183) and non-carriers ( n  = 241,570. No significant differences regarding oncologic morbidity were found between offspring of HBV carriers (0.2%), HCV carriers (0%) and non-carriers (0.6%; p  = 0.216, respectively). To conclude: maternal HBV or HCV carrier status is not a risk factor for long-term oncologic morbidity of the offspring.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We sought to explore whether maternal pre-pregnancy obesity is an independent risk factor for offspring respiratory morbidity during childhood., Methods: A population-based retrospective cohort analysis comparing childhood respiratory morbidity incidence in offspring to mothers with pre-pregnancy obesity (BMI ≥ 30 kg/m 2 ) and those who had lower BMI was conducted. Respiratory diagnoses were pre-defined based on ICD-9 codes. The study population comprises of all deliveries that took place at the Soroka University Medical Center (SUMC), the sole tertiary hospital in the Negev (Southern Israel), between the years 1991-2014. A Kaplan-Meier survival curve was used for cumulative respiratory morbidity incidences over time and a Cox proportional hazards model was constructed to control for confounders., Results: During the study period, 242,342 infants met the inclusion criteria; out of which 3290 were born to mothers with a diagnosis of pre-pregnancy obesity. Offspring to mothers with pre-pregnancy obesity had a significant higher risk for obstructive sleep apnea (OR 1.43, 95% CI 1.002-2.046) as well as a higher total risk for hospitalizations due to childhood respiratory morbidity (OR 1.21, 95% CI 1.041-1.398). The cumulative respiratory morbidity incidence over time was significantly higher in the maternal pre-pregnancy obesity group (p = 0.044). Controlling for maternal age, gestational diabetes mellitus, hypertensive disorders and gestational age, pre-pregnancy obesity remained an independent risk factor for offspring respiratory morbidity (adjusted HR = 1.175, 95% CI 1.018-1.357)., Conclusion: Maternal pre-pregnancy obesity may create an environment leading to an increased risk for long-term offspring respiratory morbidity, and specifically obstructive sleep apnea., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate perinatal outcomes and long-term neurological morbidity of offspring to mothers with a history of ectopic pregnancy., Methods: In this retrospective study, perinatal outcomes and long-term neurological morbidity of offspring were assessed among mothers with a history of ectopic pregnancy, either medically or surgically treated. The study groups were followed until 18 years of age for neurological-related morbidity. For perinatal outcomes, generalized estimated equation (GEE) models were used to control for confounders. A Kaplan-Meier survival curve was used to compare cumulative neurological morbidity incidence and Cox proportional hazards model was conducted to control for confounders., Results: A total of 243,682 mothers were included; 1424 mothers (0.58%) had a previous ectopic pregnancy, of which 25.6% (n = 365) were treated medically, and 74.3% (n = 1059) were treated surgically. Using GEE models, controlling for confounders, both surgically and medically treated ectopic pregnancies were noted as independent risk factors for preterm delivery in the subsequent pregnancies. Maternal history of surgically treated ectopic pregnancy was also independently associated with cesarean delivery. Offspring to mothers with previous ectopic pregnancy had comparable rates of long-term neurological morbidity. In the Cox proportional hazards model, controlling for confounders, being born to a mother with a history of previous ectopic pregnancy was not found to be independently associated with long-term neurological morbidity of offspring., Conclusions: Maternal history of ectopic pregnancy is independently associated with preterm delivery. However, offspring of mothers with a history of ectopic pregnancy are not at an increased risk for long-term neurological morbidity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Tobacco consumption in the form of cigarette smoking is one of the most prevalent controllable risk factors for adverse health outcomes and is a known reproductive toxin. We aimed to study the effect of maternal cigarette smoking during pregnancy on the risk of long-term gastrointestinal (GI) morbidity of their offspring. A population-based cohort analysis was performed comparing long-term GI-related hospitalizations among offspring of smoking mothers compared with offspring of non-smoking mothers up to the age of 18. The analysis included all singletons born between the years 1999-2014 at a single tertiary medical center. A Kaplan-Meier survival curve was used to compare the cumulative GI morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 242,342 children who met the inclusion criteria, 2861(1.2 %) of them were born to smokers. Offspring of smoking mothers were found to have higher rates of GI-related hospitalizations (7.2 % vs. 5.4 %, p < 0.01). Furthermore, the cumulative incidence of long-term GI morbidity was higher compared with those born to non-smoking mothers (log-rank p < 0.01). Specifically, an increased risk for inflammatory bowel disease was noted (OR = 1.48, 95 % CI 1.2-1.8, P < 0.01). Using a Cox proportional hazards model, controlling for confounders including maternal age, ethnicity, maternal diabetes mellitus and hypertensive disorders of pregnancy, birth weight, prematurity and mode of delivery, the association between maternal smoking during pregnancy and long-term GI morbidity of the offspring remained significant (adjusted HR = 1.54, 95 % CI 1.3-1.8, P < 0.01). In-utero exposure to maternal smoking is associated with an increased risk for long-term GI morbidity of the offspring., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this study, we investigate if children born following assisted reproduction technologies (ARTs) are at an increased risk for long-term ophthalmic complications. For this purpose, a population-based cohort analysis was conducted which included all deliveries between 1991 and 2014 at a single tertiary medical center. Offspring were classified relative to conception method as ART or spontaneous pregnancies. Offspring hospitalizations up to the age of 18 years involving ophthalmic morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan-Meier survival curve was used to compare cumulative hospitalization rates in exposed (ART) and unexposed offspring (spontaneous), and a Cox proportional hazards model was used to control for potential confounders. A total of 243,682 deliveries were included in the study. In that, 1.8% of the deliveries (4364) were of mothers who underwent fertility treatments and 98.2% (239,318) were conceived spontaneously. Offspring born to mothers who underwent fertility treatments had a significantly higher hospitalization rate involving ophthalmic morbidity, as compared to spontaneously conceived offspring (1.2% vs. 1.0%, p = 0.04). The Kaplan-Meier survival curve pointed to a significantly higher cumulative incidence of ophthalmic morbidity following ART (log rank p = 0.02). Cox proportional hazards model was adjusted for maternal age, preterm delivery, maternal hypertensive disorders, diabetes, and mode of delivery which demonstrated ART as an independent risk factor for long-term pediatric ophthalmic morbidity (adjusted hazard ratio = 1.37, CI 1.04-1.80, p-value = 0.02). We concluded that ART is an independent risk factor for long-term ophthalmic morbidity of the offspring.

Background: In this study we sought to ascertain a critical threshold of the degree of prematurity and long-term digestive morbidity of the offspring., Methods: A population-based cohort analysis was conducted, comparing long-term incidence of digestive morbidity in infants born preterm. Cases were divided into four groups according to the extremity of prematurity. Digestive morbidity included hospitalizations involving a predefined set of ICD9 codes. A Kaplan-Meier survival curve was constructed to compare cumulative incidence of digestive morbidity. A Cox proportional hazards model was used to control for confounders., Results: During the study period 220,563 patients met the inclusion criteria. Offspring born preterm had significantly more hospitalizations due to digestive morbidity compared to term offspring. The Kaplan-Meier survival curve demonstrated significant higher cumulative incidence of long-term digestive morbidity of the offspring with decreasing gestational age (Log rank p < 0.001). The risk was highest at 28 weeks gestation. Using a Cox proportional hazards model, being born at very and moderate to late preterm birth was independently associated with long-term digestive morbidity., Conclusion: Preterm delivery is an independent risk factor for long-term digestive morbidity of the offspring. In our population, 28 weeks gestation is the critical cut-off for pronounced digestive morbidity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Gestational diabetes mellitus (GDM) results in an increased risk for maternal and neonatal complications in singletons. In twin pregnancies, however, scarce data exist regarding its implications., Objective: To investigate whether a diagnosis of GDM in twin gestation poses a risk for subsequent maternal long-term cardiovascular morbidity., Study Design: A population-based cohort study was conducted, comparing the incidence of cardiovascular morbidity within a group of women with and without a diagnosis of GDM who delivered twins in a tertiary medical center, between the years 1991 and 2014. Mothers with pregestational diabetes mellitus, triplet or higher-order multiples, patients lacking prenatal care, patients with known cardiovascular morbidities prior to or during the current pregnancy and fetal malformations or/and chromosomal abnormalities were excluded. Kaplan-Meier's survival curve was used to estimate the cumulative incidence of cardiovascular-related hospitalizations, and a Cox proportional hazards model was used to estimate the adjusted HRs for cardiovascular morbidity., Results: Of 4256 twin deliveries that met the inclusion criteria, 336 (7.9%) occurred in patients that were diagnosed with GDM. During a follow-up period of more than 10 years, with a median of 3431 (0-9172) days in total, patients with GDM had higher rates of simple cardiovascular events as compared to women without diagnosis of GDM (incidence = 7, 2.1%. OR = 2.7, 95% confidence interval (CI) 1.17-6.12, p  = .03). Total cardiovascular hospitalizations were comparable between the groups. There was no difference between the two groups in the rate of complex cardiovascular events, noninvasive or invasive cardiac diagnostic procedures. In a Cox proportional hazards model, which is adjusted for maternal age, ethnicity, hypertensive disorders, and fertility treatments, GDM in twin pregnancies was not found to be associated with long-term cardiovascular morbidity (adjusted HR 1.41, 95% CI 0.77-2.58, p  = .26)., Conclusions: While GDM during twin pregnancy might be associated with long-term maternal simple cardiovascular events, the complex, as well as the total morbidities, are comparable to patients without GDM.

Purpose: Sexual violence is a global health problem. We aimed to evaluate the association between self-reported history of sexual violence and parturients' health behaviors, focusing on routine gynecological care, and mental well-being., Methods: This was a retrospective questionnaire-based study, including mothers of newborns delivered at the "Soroka" University Medical Center (SUMC). Participants were asked to complete three validated questionnaires, including: screening for sexual violence history (SES), post-traumatic stress disorder (PDS) and post-partum depression (EPDS). Additionally, a demographic, pregnancy and gynecological history data questionnaire was completed, and medical record summarized. Multiple analyses were performed, comparing background and outcome variables across the different SES severity levels. Multivariable regression models were constructed, while adjusting for confounding variables., Results: The study included 210 women. Of them, 26.3% (n = 57) reported unwanted sexual encounter, 23% (n = 50) reported coercion, 1.8% (n = 4) assault and attempted rape, and 1.4% (n = 3) reported rape. A significant association was found between sexual violence history and neglected gynecological care, positive EPDS screening, and reporting experiencing sexual trauma. Several multivariable regression models were constructed, to assess independent associations between sexual violence history and gynecological health-care characteristics, as well as EPDS score. Sexual violence history was found to be independently and significantly associated with a negative relationship with the gynecologist, avoidance of gynecological care, sub-optimal routine gynecological follow-up, and seeking a gynecologist for acute symptoms (adjusted OR = 0.356; 95% CI 0.169-0.749, adjusted OR = 0.369; 95% CI 0.170-0.804, adjusted OR = 2.255; 95% CI 1.187-4.283, and adjusted OR = 2.113; 95% CI 1.085-4.111, respectively), as well as with the risk of post-partum depression (adjusted OR = 4.46; 95% CI 2.03-9.81). All models adjusted for maternal age and ethnicity., Conclusion: Sexual violence history is extremely common among post-partum women. It is independently associated with post-partum depression, neglected gynecological care, a negative relationship with the gynecologist, and with reporting of experiencing sexual trauma. Identifying populations at risk and taking active measures, may reduce distress and improve emotional well-being and family function., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: Meconium stained amniotic fluid (MSAF) is a well-established risk factor for neonatal short-term respiratory complications. Little is known regarding the long-term morbidity. We investigated the possible association between MSAF and offspring respiratory morbidity., Methods: A population-based, cohort study of singleton deliveries occurring between 1991 and 2014 at a sole regional tertiary medical center was performed. Incidence of offspring respiratory related hospitalizations up to the age of 18 years were evaluated and compared to unexposed offspring. A Kaplan-Meier survival curve was used to compare cumulative respiratory morbidity incidence, and a Cox proportional hazards model was used to control for confounders., Results: During the study period 242,342 deliveries met the inclusion criteria. Of them, 14.7% (n = 35,609) were complicated with MSAF. Incidence of respiratory-related hospitalizations was significantly lower in children exposed to MSAF as compared to the unexposed group (4.5% vs. 4.9%, respectively; p < .01). Specifically, hospitalizations involving pneumonitis were significantly less common among the MSAF group (odds ratio, 0.35; 95% confidence interval [95% CI], 0.13-0.96; p = .03). The Kaplan-Meier survival curve demonstrated significantly lower total cumulative respiratory morbidity rates in the MSAF exposed group (log rank p < .01). In the Cox model, controlled for clinically relevant confounders, MSAF exhibited an independent and significant protective effect on long-term childhood respiratory morbidity (aHR, 0.91; 95% CI, 0.86-0.96; p < .01)., Conclusions: Fetal exposure to MSAF during labor appears to be associated with lower rates of long-term respiratory related hospitalizations in the offspring. Changes in offspring microbiome, as well as functional and anatomical modulations possibly resulting from MSAF exposure, might offer a plausible explanation of our findings., (© 2021 Wiley Periodicals LLC.)

Objectives: One of the most common indications for intrapartum cesarean delivery (CD) is nonreassuring fetal heart rate (NRFHR) patterns. We aimed to study the long-term effect of CD due to NRFHR on the risk for subsequent childhood infectious morbidity-related hospitalizations of the offspring., Study Design: A population-based cohort study was performed, comparing total and different subtypes of infectious morbidity-related pediatric hospitalizations among offspring born by CD due to NRFHR versus labor dystocia (failure of labor to progress during the 1st or 2nd stage). The analysis included all singletons born between the years 1999-2014 at a single tertiary regional medical center. Infectious-related morbidities included hospitalizations involving a predefined set of International Classification of Diseases, 9th revision codes, as recorded in hospital computerized files. Infants with congenital malformations, multiple gestations, vaginal deliveries and vacuum failure were excluded from the analysis. Perinatal mortality cases were excluded from the long-term analysis. A Kaplan-Meier survival curve was used to compare the cumulative morbidity, and a Cox proportional hazards model was constructed to adjust for confounders., Results: The study population included 9956 newborns who met inclusion criteria; among them, 5810 (58%) were born by CD due to NRFHR, and 4146 (42%) were born via CD following labor dystocia with normal fetal heart rate (comparison group). Offspring born following NRFHR had higher rates of infectious morbidity-related hospitalizations (11.4% vs. 9.1%; odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P < 0.01; Kaplan-Meier survival curve P < 0.01). The association remained significant and independent while adjusting for gestational age, maternal age and comorbidities, using a Cox proportional hazards model (adjusted hazard ratio, 1.3; 95% confidence interval, 1.2-1.4; P < 0.01)., Conclusions: In our population, CD due to NRFHR is a risk factor for pediatric infectious morbidity-related hospitalizations of the offspring., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: β-Thalassemia has been shown to be associated with adverse short-term perinatal outcomes including low birth weight and preterm labor. The aim of this study was to assess whether in-utero exposure of maternal β-thalassemia minor is a risk factor for offspring hematological morbidity., Study Design: A population-based retrospective cohort study was conducted, including all infants born between the years 1991-2014 at a tertiary medical center. Long-term hospitalizations with hematologic morbidities were compared between offspring of mothers with or without β-thalassemia minor. Multiple gestations, perinatal mortality, chromosomal disorders and congenital malformations were excluded. Both study groups were followed until 18 years of age for hospitalization with hematological morbidities. Kaplan-Meier survival curve was used to compare the cumulative hematological morbidity incidence between both groups, and a Cox proportional hazard model was used to control for confounders., Results: During the study period, 243,682 deliveries met the inclusion criteria, of them 0.3% (n = 677) were of mothers with β-thalassemia minor. Among offspring to thalassemic versus non-thalassemic mothers, hospitalization rates involving hematological morbidity, were higher (3.3% vs. 0.7%, p < 0.001) a finding that was consistent with the Kaplan-Meier survival curve (log rank p < 0.001). Using Cox regression model, which adjusted for maternal age, SGA, gestational age and birth weight, maternal β-thalassemia minor was found to be an independent risk factor for long-term offspring hematological (aHR = 5.54; 95% CI 3.63-8.44, p < 0.001, 5.56; 95% CI 3.65-8.47, p < 0.001, and 5.49; 95% CI 3.60-8.36, p < 0.001, respectively)., Conclusion: Prenatal maternal β-thalassemia minor is independently associated with offspring long-term hematological morbidity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Our hospital used to perform cesarean delivery under general anesthesia rather than neuraxial anesthesia, mostly because of patient refusal of members of the conservative Bedouin society. According to recommendations implemented by the Israeli Obstetric Anesthesia Society, which were implemented due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, we increased the rate of neuraxial anesthesia among deliveries., Objectives: To compare the rates of neuraxial anesthesia in our cesarean population before and during SARS-CoV-2 pandemic., Methods: We included consecutive women undergoing an elective cesarean delivery from two time periods: pre-SARS-CoV-2 pandemic (15 February 2019 to 14 April 2019) and during the SARS-CoV-2 pandemic (15 February 2020 to 15 April 2020). We collected demographic data, details about cesarean delivery, and anesthesia complications., Results: We included 413 parturients undergoing consecutive elective cesarean delivery identified during the study periods: 205 before the SARS-CoV-2 pandemic and 208 during SARS-CoV-2 pandemic. We found a statistically significant difference in neuraxial anesthesia rates between the groups: before the pandemic (92/205, 44.8%) and during (165/208, 79.3%; P < 0.0001)., Conclusions: We demonstrated that patient and provider education about neuraxial anesthesia can increase its utilization. The addition of a trained obstetric anesthesiologist to the team may have facilitated this transition.

Problem: Celiac disease is an autoimmune disease, patients with celiac have increased risk for infections, and offspring of celiac mothers have increased morbidity. The aim of the study was to assess long-term infectious morbidity among offspring of pregnant women with celiac disease., Method of Study: A population-based cohort study was conducted, including all singleton deliveries between the years 1991-2014 at a tertiary medical center. The offsprings were subdivided into two groups: offsprings of mothers with and without celiac disease. Data on demographics, maternal, perinatal, and long-term hospitalizations for infectious morbidity were compared between the two groups., Results: During the study period there were 210 (0.09%) deliveries of mothers with celiac, and they were compared to 242170 (99.91%) deliveries of non-celiac mothers. Cumulative infectious morbidity was significantly higher in offspring of mothers with celiac compared to offspring of mothers without celiac (Kaplan-Meier, log-rank p = .004). Specifically, among the offspring of mothers with celiac significantly higher rates of bacteremia was noted (1.0% vs. 0.1%; p = .001), and infections of the central nervous system (1% vs. 0.2%; p = .028). In the Cox multivariable model which accounted for confounding variables, being born to mothers with celiac disease was associated with significantly increased risk for long-term infectious morbidity of the offspring (adjusted HR = 1.6, 95% CI 1.165-2.357, p = .005)., Conclusions: Maternal celiac disease is an independent risk factor for long-term infectious morbidity for the offspring., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Pregnancies of women with systemic lupus erythematosus (SLE) are associated with preterm delivery. As preterm delivery is associated with long-term neurological morbidity, we opted to evaluate the long-term neurologic outcomes of offspring born to mothers with SLE regardless of gestational age., Methods: Perinatal outcomes and long-term neurological disease of children of women with and without SLE during pregnancy were evaluated. Children of women with and without SLE were followed until 18 years of age for neurological diseases. Generalized estimating equation (GEE) models were used to assess perinatal outcomes. To compare cumulative neurological morbidity incidence a Kaplan-Meier survival curve was used, and a Cox proportional hazards model was used to control for confounders., Result: A total of 243,682 deliveries were included, of which 100 (0.041%) were of women with SLE. Using a GEE model, maternal SLE was noted as an independent risk factor for preterm delivery. The cumulative incidence of long-term neurological disease was not found to be significantly higher when using the Kaplan Meier survival curves and maternal SLE was not found to be associated with long-term neurological disease of the offspring when a Cox model was used., Conclusion: Despite the association of SLE with preterm delivery, no difference in long-term neurological disease was found among children of women with or without SLE.

We opted to investigate whether a critical threshold exists for long-term pediatric neurological morbidity, and cerebral palsy (CP), in preterm delivery, via a population-based cohort analysis. Four study groups were classified according to their gestational age at birth: 24-27.6, 28-31.6, 32-36.6 weeks and term deliveries, evaluating the incidence of long-term hospitalizations of the offspring due to neurological morbidity. Cox proportional hazard models were performed to control for confounders. A Kaplan-Meier survival curve was used to compare the cumulative neurological morbidity incidence for each group. A total of 220,563 deliveries were included: 0.1% (118) occurred at 24-27.6 weeks of gestation, 0.4% (776) occurred at 28-31.6 weeks of gestation, 6% (13,308) occurred at 32-36.6 weeks of gestation and 93% (206,361) at term. In a Cox model, while adjusting for confounders, delivery before 25 weeks had a 3.9-fold risk for long-term neurological morbidity (adjusted HR (hazard ratio) = 3.9, 95% CI (confidence interval) 2.3-6.6; p < 0.001). The Kaplan-Meier survival curve demonstrated a linear association between long-term neurological morbidity and decreasing gestational age. In a second Cox model, adjusted for confounders, infants born before 25 weeks of gestation had increased rates of CP (adjusted HR = 62.495% CI 25.6-152.4; p <&nbsp;0.001). In our population, the critical cut-off for long-term neurological complications is delivery before 25 weeks gestation.

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Adverse effects of preterm birth have a direct correlation with the degree of prematurity, in which infants who are born extremely preterm (24-28 weeks gestation) have the worst outcomes. We sought to determine prominent risk factors for extreme PTB and whether these factors varied between various sub-populations with known risk factors such as previous PTB and multiple gestations. A population-based retrospective cohort study was conducted. Risk factors were examined in cases of extreme PTB in the general population, as well as various sub-groups: singleton and multiple gestations, women with a previous PTB, and women with indicated or induced PTB. A total of 334,415 deliveries were included, of which 1155 (0.35%) were in the extreme PTB group. Placenta previa (OR = 5.8, 95%CI 4.14-8.34, p < 0.001), multiple gestations (OR = 7.7, 95% CI 6.58-9.04, p < 0.001), and placental abruption (OR = 20.6, 95%CI 17.00-24.96, p < 0.001) were the strongest risk factors for extreme PTB. In sub-populations (multiple gestations, women with previous PTB and indicated PTBs), risk factors included placental abruption and previa, lack of prenatal care, and recurrent pregnancy loss. Singleton extreme PTB risk factors included nulliparity, lack of prenatal care, and placental abruption. Placental abruption was the strongest risk factor for extreme preterm birth in all groups, and risk factors did not differ significantly between sub-populations.

Introduction: Interpregnancy interval (IPI) is defined as the period between a live birth and the conception of a subsequent fetus. Both short (IPI < 6 months) and long IPI (IPI > 60 months) have been shown to increase the risk for adverse perinatal outcomes, some of which, are known risk factors for obstructive sleep apnea syndrome (OSAS) in the offspring., Aims: To study the association between IPI and risk for offspring OSAS, during a follow-up period of up to 18 years., Study Design: Population-based cohort., Subjects: In this population-based cohort analysis, all singleton live births, born to a mother with at least one previous birth occurring between 1991 and 2014, were included. Congenital malformations were excluded., Materials and Methods: Hospitalizations of the offspring due to OSAS diagnosis up to 18 years of age, were evaluated according to IPI length. Intermediate IPI (6-60 months) was considered as the reference. A Kaplan-Meier survival curve and a Cox hazards regression model were used to compare the incidence of OSAS between the groups, and to adjust for confounding variables., Results: The study population included 144,397 deliveries, of which 13.1% (n = 18,947) were followed by short IPI, 7.9% (n = 11,438) and 79.0% (n = 114,012) were followed by long and intermediate IPI, respectively. OSAS hospitalization rates were significantly higher among the long IPI group compared to intermediate and short IPIs (0.9%; 0.7% and 0.6%, respectively, p = .001). The association between long IPI and offspring pediatric OSAS remained significant after controlling for preterm delivery, maternal diabetes, and smoking, and mode of delivery, (adjusted HR = 1.45; 95% CI, 1.17-1.80)., Conclusions: Children born following long IPI are at increased risk for pediatric OSAS., (© 2020 Wiley Periodicals LLC.)

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/m 3 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., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objective: This study aimed to determine whether isolated single umbilical artery (iSUA), even absent identifiable genitourinary (GU) abnormalities, increases the risk of GU infection during childhood., Study Design: Retrospective population-based comparison of fetuses with iSUA versus normal three-vessel cords. Fetuses with growth restriction, prematurity, multiple gestations, and anatomical or chromosomal anomalies were excluded. The primary outcome was hospital-associated GU infection during the first 18 years of life. Kaplan-Meier's survival curves were used to assess cumulative risk; Cox's multivariable models were used to adjust for confounders., Results: Among 227,599 term singleton deliveries, children with iSUA ( n  = 729) had a higher incidence (1.8 vs. 0.6%, p  < 0.001) and cumulative incidence (log-rank test, p  < 0.001) of hospital-associated GU infection. The Cox's models confirmed these findings (hazard ratio: >2.82, confidence interval: 1.63-4.87 in composite models)., Conclusion: iSUA represents an independent risk factor for GU infection. Urinary tract imaging may be warranted., Competing Interests: None declared., (Thieme. All rights reserved.)

(1) Background: Preterm deliveries (PTD, <37 gestational weeks) which occur in 5-18% of deliveries across the world, are associated with immediate and long-term offspring morbidity, as well as high costs to health systems. Our aim was to identify risk factors during the first pregnancy ending at term for PTD in the subsequent pregnancy. (2) Methods: A retrospective population- based nested case-control study was conducted, including all women with two first singleton consecutive deliveries. Women with PTD in the first pregnancy were excluded. Characteristics and complications of the first pregnancy were compared among cases, defined as women with PTD in their second pregnancy, and the controls, defined as women delivering at term in their second pregnancy. A multivariable logistic regression model was used to study the association between pregnancy complications (in the first pregnancy) and PTD (in the subsequent pregnancy), while adjusting for maternal age and the interpregnancy interval. (3) Results: A total of 39,780 women were included in the study, 5.2% ( n = 2088) had PTD in their second pregnancy. Women with PTD, as compared to controls (i.e., delivered at term in second pregnancy), were more likely to have the following complications in their first pregnancy: perinatal mortality (0.4% vs. 1.0%), small for gestational age (12.4% vs. 8.1%), and preeclampsia (7.6% vs. 5.7%). In the multivariable model, after adjusting for maternal age, interpregnancy interval and co-morbidities, having any one of these first pregnancy complications was independently associated with an increased risk for PTD (adjusted OR = 1.44; 95%CI 1.28-1.62), and the risk was greater if two or more complications were diagnosed (adjusted OR = 2.09; 95%CI 1.47-3.00). These complications were also risk factors for early PTD (<34 gestational weeks), PTD with a systematic infectious disease in the background, and possibly with spontaneous PTD. (4) Conclusions: First pregnancy complications are associated with an increased risk for PTD in the subsequent pregnancy. First pregnancy, although ending at term, may serve as a window of opportunity to identify women at risk for future PTD.

Objective: We aimed to study the long-term effect of non-reassuring fetal heart rate (NRFHR) patterns on the risk for subsequent pediatric cardiovascular morbidity of the offspring., Study Design: A population based cohort study, comparing total and different subtypes of cardiovascular morbidity related pediatric hospitalizations among offspring born by caesarean delivery (CD) due to NRFHR versus labor dystocia (failure of labor to progress during the 1st or 2nd stage). The analysis included all singletons born between the years 1999-2014 at a single tertiary regional medical center. Cardiovascular related morbidities included hospitalizations involving a pre-defined set of ICD-9 codes, as recorded in hospital computerized files. Infants with congenital malformations, multiple gestations, vaginal deliveries and vacuum failure were excluded from the analysis. Perinatal mortality cases were excluded from the long-term analysis. A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity incidence, and a Cox proportional hazards model was used to adjust for confounders., Results: The study population included 9956 newborns who met inclusion criteria; among them, 5810 (58%) were born by CD due to NRFHR, and 4146 (42%) due to labor dystocia with normal FHR (comparison group). Rate of long- term cardiovascular related hospitalizations was comparable between both groups (0.8% vs. 0.7%, OR 0.9, 95% CI 0.6-1.4, p = 0.664; Kaplan-Meier survival curve p = 0.320(. Using a Cox proportional hazards model, controlling for gestational age, no association was found between NRFHR patterns and the risk for subsequent pediatric cardiovascular morbidity of the offspring (Adjusted HR = 0.8, 95% CI 0.5-1.3, p = 0.376)., Conclusion: In our population, NRFHR patterns do not affect the risk of long- term pediatric cardiovascular morbidity of the offspring., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

Purpose: The purpose of our study was to evaluate the effect of IPI on long-term neurological morbidity of the offspring., Methods: In this retrospective cohort study, 144,397 singleton infants born to multiparous mothers, between the years 1991 and 2014 in a tertiary medical center, were evaluated for different perinatal outcomes and were followed until 18 years of age for long-term neurological morbidity according to three IPI groups: Short IPI (< 6 months), long IPI (> 60 months) and intermediate IPI (6-60 months). We used a Kaplan-Meier survival curve to compare cumulative incidence of long-term neurological morbidity, and a Cox regression analysis to control for confounders such as gestational age, birth weight and maternal age., Results: Offspring born to mothers with long IPI had higher rates of neurological morbidity (3.62% among offspring born after long IPI vs. 3.18% and 3.19% among offspring born after short and intermediate IPI, respectively, p = 0.041). The cumulative incidence of long-term neurological morbidity was significantly higher in the long IPI group (Kaplan-Meier log-rank test p < 0.001). Being born after a long IPI was found to be an independent risk factor for long-term neurological morbidity of the offspring (adjusted hazard ratio 1.2; 95% confidence interval 1.1-1.4; p < 0.001)., Conclusion: Long IPI is independently associated with an increased risk of long-term neurological morbidity of the offspring.

Performing thyroid function tests (TFT) at 2 weeks of age in neonates of mothers with hypothyroidism, despite having a newborn screening program, is a debated approach. We examined whether there is an additional clinical benefit in TFT at 2 weeks of age in neonates born to mothers with hypothyroidism, in addition to the neonatal screening program. We performed a retrospective study which included all newborns of mothers with a diagnosis of hypothyroidism and gave birth in a single regional hospital between the years 2010 and 2016. Data were collected from a computerized medical record system of the hospital and the community clinics, and from Israel's national newborn screening program. Main outcome measure was results of serum TFT in comparison to the results of the neonatal screening test. There were 1392 newborns eligible according to the study criteria. Of these, 1033 underwent a newborn screening test, and serum TFT at least 2 weeks after birth. Eight babies with congenital hypothyroidism were detected independently by both the newborn screening program and at the TFT performed at 2 weeks of age.Conclusions: No added clinical benefit was found in retesting newborns of hypothyroid mothers for thyroid function in addition to the newborn screening program. What is Known • Performing thyroid function test 2 weeks after birth is a common practice in newborn to a mother with hypothyroidism. • Neonatal screening program for thyroid function is also done in these newborns. What is New • No newborn was found to have a normal newborn screening test but abnormal serum thyroid function test. • No added clinical benefit was found in retesting newborns of hypothyroid mothers for thyroid function in addition to the newborn screening program.

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., Competing Interests: None declared., (Thieme. All rights reserved.)

Major obstetrics and gynecology societies offer inconsistent recommendation regarding optimal delivery timing in uncomplicated dizygotic twins. We sought to investigate the impact of delivery timing within term gestation, in dizygotic twins, on the short- and long-term offspring morbidity. A prospectively analyzed cohort of dizygotic twin deliveries was conducted. All women delivered at a regional tertiary medical center, at term (≥37 0/7), between the years 1991 and 2014, were included. The primary exposure was delivery at 37 0/7-37 + 6/7 weeks, while delivery at ≥38 0/7 weeks' gestation was considered the reference. Neonatal short- and long-term outcomes according to hospitalizations of offspring up to 18 years of age due to cardiac, respiratory, hematological, neurological, and infectious morbidity were compared. Kaplan-Meier survival curves were used to compare cumulative incidences per each major-system hospitalization. Cox regression models were used to estimate the adjusted hazard ratios, while adjusting for variables with clinical importance. During the study period, 612 dizygotic twin deliveries met the inclusion criteria. Of them, 200 (31.3%) occurred at 37-37 6/7 weeks, and 412 (68.7%) occurred at ≥38 0/7 weeks' gestation. In the long-term analysis, rates of hospitalizations involving several major morbidity categories exhibited comparable rates in both groups. The Cox regression models did not demonstrate an independent association between gestational age within term and later major pediatric morbidity in offspring (total long-term morbidity: adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.29). Dizygotic twin deliveries occurring at different gestational ages within term do not appear to significantly impact on major short- and long-term outcomes.

Objective : To analyze preeclampsia as a risk factor for pediatric endocrine disease. Study Design : A population-based cohort analysis comparing the risk of endocrine morbidity of children born between 1991-2014 to mothers with and without preeclampsia. Results : The study included 253,808 deliveries. Exposed offspring had significantly more endocrine hospitalizations (0.7% vs 0.4%; p  < 0.001), specifically obesity (0.4% vs 0.2%,  p  < 0.001). While controlling for confounders, the exposed offspring had significantly more endocrine morbidity (OR 1.433 95% CI 1.115-1.841  p  = 0.005). Conclusion : Preeclampsia is an independent risk factor for long-term endocrine disease of the offspring, specifically obesity.

Drug allergy is associated with adverse short-term perinatal outcomes such as caesarian delivery and preterm delivery. The aim of the present study was to determine whether being born to a mother with known drug allergy increases the risk for long-term dermatological morbidity of the offspring. A population-based cohort study, comparing long-term dermatological morbidity of offspring to mothers with and without known drug allergy, was conducted. Dermatological morbidity was assessed up to the age of 18 years according to a predefined set of ICD-9 codes associated with hospitalization of the offspring. A Kaplan-Meier survival curve was used to compare cumulative incidence of long-term dermatological morbidity, and a Cox proportional hazards model was constructed to control of confounders. During the study period, 243,682 deliveries met the inclusion criteria, of them 4% (n = 9756) were of mothers with known drug allergy. Offspring born to mothers with known drug allergy had higher rates of long-term dermatological morbidity Likewise, the cumulative incidence of long-term dermatological morbidity was higher as compared with those without known drug allergy (Kaplan-Meier log-rank P = .021). Using a Cox proportional hazards model, controlling for confounders, being born to a mother with known drug allergy was found to be an independent risk factor for long-term dermatological morbidity of the offspring (adjusted HR 1.2, 95% CI 1.03-1.33, P = .016). Being born to a mother with known drug allergy is independently associated with higher risk for long-term dermatological morbidity of the offspring., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The objective of the study was to investigate whether maternal history of recurrent pregnancy loss (RPL) is associated with offspring childhood ophthalmic morbidity., Method: A hospital-based cohort analysis comparing long-term offspring ophthalmic morbidity in women with and without a history of RPL was performed. Ophthalmic morbidity included hospitalizations involving a pre-defined set of ICD-9 codes. Offspring with congenital anomalies, perinatal mortality cases, and multifetal pregnancies were excluded from the analysis. Cumulative morbidity incidence was compared using Kaplan-Meier survival curves, and the risk of long-term ophthalmic morbidity was assessed by Cox proportional hazards model after adjustment for confounders., Results: During the study period, 242,187 newborns met the inclusion criteria; 5% (12,182) of them were offspring born to mothers with a history of RPL. Ophthalmic morbidity was significantly more common in the RPL group (1.3% vs 0.9%, p < .001, Kaplan-Meier log-rank p < .001). Adjustment for confounders, such as maternal age, gestational age, hypertensive disorders, and maternal diabetes, using Cox regression found that being born to a mother with RPL was independently associated with long-term ophthalmic morbidity (adjusted HR 1.35, 95% CI 1.15-1.59, p < .001)., Conclusion: Being born to a mother with RPL is independently associated with an increased risk of ophthalmic morbidity., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: Drug allergies are increasingly common. Immunological factors, implicated in many neurological diseases, also influence an individual's susceptibility. We sought to ascertain a possible association between maternal drug allergy and long-term neurological-related hospitalizations in the offspring., Method of Study: This is a population-based cohort analysis, comparing the long-term risk of neurological-related hospitalization, involving a predefined set of ICD9 codes as recorded in hospital records, of children born to mothers with and without drug allergies. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Twin pregnancies, fetal malformations, and cases of perinatal mortality were excluded. A Kaplan-Meier survival curve was constructed to compare cumulative neurological hospitalizations. A Cox proportional hazards model was used to control for time to event., Results: The study included 242 342 patients, 9714 with known drug allergy (4%). Offspring born to mothers with drug allergies had significantly more neurological hospitalizations compared to controls (4.2% vs 3.1%; P ≤ .001; Kaplan-Meier log-rank test P ≤ .001), specifically for psychiatric disorders including eating disorders (0.3% vs 0.2%;P = .002), attention-deficit/hyperactivity disorder (0.124% vs 0.056%; P = .008), emotional disorders (0.8% vs 0.5%; P ≤ .001), and movement disorders (2.3% vs 1.8%; P = .002). While controlling for birth year, gestational age, maternal age, maternal diabetes, hypertensive disorders, and cesarean delivery, using a Cox proportional hazards model, maternal drug allergy was found to be an independent risk factor for neurological hospitalization of the offspring (adjusted HR 1.3, 95% CI 1.19-1.45 P < .001)., Conclusion: Being born to a mother with known drug allergy is an independent risk factor for long-term neurological hospitalization of the offspring., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Infectious diseases account for up to 43% of childhood hospitalizations. Given the magnitude of infection-related hospitalizations, we aimed to evaluate the effect of maternal smoking during pregnancy on the risk for long-term childhood infectious morbidity., Study Design: This is a population-based cohort analysis comparing the long-term risk for infectious diseases, in children born to mothers who smoked during pregnancy versus those who did not. Infectious diseases were predefined based on International Classification of Diseases, Ninth Revision codes. Deliveries occurred between the years 1991 and 2014., Results: A total of 246,854 newborns met the inclusion criteria; 2,986 (1.2%) were born to mothers who smoked during pregnancy. Offspring of smokers had significantly higher risk for several infectious diseases during childhood (upper respiratory tract, otitis, viral infections, and bronchitis) as well as increased risk for total infection-related hospitalizations (odds ratio = 1.5, 95% confidence interval [CI]: 1.3-1.7; p  = 0.001). Cumulative incidence of infection-related hospitalizations was significantly higher in offspring of smokers (log-rank test, p  = 0.001). Controlling for maternal age, diabetes, hypertensive disorders, and gestational age at index delivery, smoking remained an independent risk factor for infectious diseases during childhood (adjusted hazard ratio = 1.5, 95% CI: 1.3-1.6; p  = 0.001)., Conclusion: Intrauterine exposure to maternal smoking may create an environment leading to an increased future risk for long-term pediatric infectious morbidity of the offspring., Competing Interests: None declared., (Thieme. All rights reserved.)

We aimed to study both the short- and long-term neurological implications in offspring born with confirmed knotting of the umbilical cord-"true knot of cord". In this population based cohort study, a comparison of perinatal outcome and long-term neurological hospitalizations was performed on the basis of presence or absence of true knot of cord. A Kaplan-Meier survival curve was constructed to compare the cumulative incidence of neurological hospitalizations between the study groups. Multivariable regression models were used to assess the independent association between true knot of cord, perinatal mortality and long term neurological related hospitalizations, while controlling for potential confounders. The study included 243,639 newborns, of them 1.1% ( n = 2606) were diagnosed with true knot of the umbilical cord. Higher rates of intrauterine fetal demise (IUFD) were noted in the exposed group, a finding which remained significant in the multivariable generalized estimation equation, while controlling for confounders. The cumulative incidences of neurological hospitalizations over time were comparable between the groups. The Cox regression confirmed a lack of association between true knot of cord and total long term neurological related hospitalizations. While presence of true knot of the umbilical cord is associated with higher IUFD rates, in our population, however, its presence does not appear to impact the long term neurological health of exposed offspring.