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Background: The prevalence of chronic hypertension in women of reproductive age is on the rise mainly due to delayed childbearing. Maternal chronic hypertension, prevailing prior to conception or manifesting within the early gestational period, poses a substantial risk for the development of preeclampsia with adverse maternal and fetal outcomes, specifically as a result of placental dysfunction. We aimed to investigate whether chronic hypertension is associated with placenta-mediated complications regardless of the development of preeclampsia in pregnancy., Methods: This was a population-based, retrospective cohort study from 'Soroka' university medical center (SUMC) in Israel, of women who gave birth between 1991 and 2021, comparing placenta-mediated complications (including fetal growth restriction (FGR), placental abruption, preterm delivery, and perinatal mortality) in women with and without chronic hypertension. Generalized estimating equation (GEE) models were used for each outcome to control for possible confounding factors., Results: A total of 356,356 deliveries met the study's inclusion criteria. Of them, 3949 (1.1%) deliveries were of mothers with chronic hypertension. Women with chronic hypertension had significantly higher rates of all placenta-mediated complications investigated in this study. The GEE models adjusting for preeclampsia and other confounding factors affirmed that chronic hypertension is independently associated with all the studied placental complications except placental abruption., Conclusions: Chronic hypertension in pregnancy is associated with placenta-mediated complications, regardless of preeclampsia. Therefore, early diagnosis of chronic hypertension is warranted in order to provide adequate pregnancy follow-up and close monitoring for placental complications, especially in an era of advanced maternal age.

Background : Chorioamnionitis during labor exposes the fetus to an intrauterine state that may alter the future immune response and may expose the offspring to future susceptibility to infectious disease. We evaluated the long-term pediatric infectious morbidity of children born at term to mothers who have chorioamnionitis during labor. Methods: This was a population-based cohort analysis including only term singleton deliveries at a regional tertiary hospital between the years 1991 and 2021. Offspring to mothers with and without a diagnosis of chorioamnionitis during labor were compared. Offspring hospitalizations up to the age of 18 years involving infectious morbidity were evaluated using the Kaplan-Meier survival curve and a Cox regression model to control possible confounders. Results: A total of 331,598 deliveries were included, 988 (0.3%) of which were of mothers diagnosed with chorioamnionitis during labor. All infectious morbidity rates included in the analysis were comparable between groups. The Kaplan-Meier survival curves were similar for both groups (log-rank = 0.881) and the multivariable analysis ascertained that chorioamnionitis during labor was not a risk factor for offspring's long-term infectious morbidity (HR 0.929, 95%CI 0.818-1.054, p = 0.254). Conclusions: In our cohort, term chorioamnionitis during labor was not associated with a higher risk of pediatric hospitalization due to infections. The infectious/inflammatory state during labor did not expose nor increase the susceptibility of the term offspring to future infectious morbidity.

Background: Controversy exists in the literature regarding the possible association between infertility treatments in singleton pregnancies and long-term risk for childhood malignancy. Data regarding infertility treatments in twins and long-term childhood malignancies are scarce. Objective: We sought to investigate whether twins conceived following infertility treatments are at an increased risk for childhood malignancy. Study design: A population-based retrospective cohort study, comparing the risk for future childhood malignancy in twins conceived by infertility treatments (in vitro fertilization and ovulation induction) and those who were conceived spontaneously. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. A Kaplan-Meier survival curve was used to compare the cumulative incidence of childhood malignancies, and a Cox proportional hazards model was constructed to control for confounders. Results : During the study period, 11,986 twins met the inclusion criteria; 2910 (24.3%) were born following infertility treatments. No statistically significant differences were noted between the groups comparing the rate (per 1000) of childhood malignancies (2.0 in the infertility treatments group vs. 2.2 in the comparison group, OR 1.04, 95% CI 0.41-2.62; p = 0.93). Likewise, the cumulative incidence over time was comparable between the groups (log-rank test, p = 0.87). In a Cox regression model, controlling for maternal and gestational age, no significant differences in childhood malignancies were noted between the groups (adjusted HR = 0.82, 95% CI 0.49-1.39, p = 0.47). Conclusions: In our population, twins conceived following infertility treatments are not at an increased risk for childhood malignancies.

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.

(1) Background: Due to the global escalation in the prevalence of obesity, bariatric surgeries have become a popular solution in many western countries. The aim of the current study was to compare offspring health and the obesity of women before and after undergoing bariatric surgeries. (2) Methods: A retrospective population-based study was performed, including all singleton deliveries which occurred at a tertiary medical center between the years 1991-2021. Among women who had bariatric surgeries, the health of the offspring born before and after the surgery were compared. The offspring were followed up until the age of 18 years, and their hospitalization records were summarized. The incidence of hospitalization with either endocrine, cardiac, respiratory, neurologic, or infectious diagnoses were compared between the groups, as well as offspring obesity. Multivariable Cox proportional models were used to match between siblings and to address confounding variables, including maternal age, gestational age at delivery, fertility treatment, smoking and pregnancy hypertensive disorders. (3) Results: The study population included 3074 deliveries of women who underwent bariatric surgeries (1586 were before and 1488 after the surgery). Offspring born after maternal bariatric surgeries were at a comparable risk for most morbidities, besides endocrine-related morbidities (3.1% vs. 5.0%, OR = 1.61; 1.1-2.35) and obesity (2.5% vs. 4.1%, OR = 1.63; 1.08-2.48). The risk for these morbidities was higher among the offspring of mothers after, vs. before, the surgery, despite adjustment for maternal age and other confounding variables. (4) Conclusions: While bariatric surgeries are considered an effective treatment for obesity, it seems to have less of an effect on the offspring of women who underwent such surgeries. Other persistent factors are most likely associated with the offspring's risk for morbidities, especially endocrine morbidities and obesity, which remain even though the mother underwent bariatric surgeries.

Objective: We opted to investigate whether fetal growth restriction (FGR) in dichorionic-diamniotic twins is a risk factor for long-term cardiovascular morbidity in offspring. Study design: A population-based retrospective cohort study, comparing long-term cardiovascular morbidity among FGR and non-FGR twins, born between the years 1991 and 2021 in a tertiary medical center. Study groups were followed until 18 years of age (6570 days) for cardiovascular-related morbidity. A Kaplan-Meier survival curve compared the cumulative cardiovascular morbidity. A Cox proportional hazard model assisted with adjusting for confounders. Results: In this study, 4222 dichorionic-diamniotic twins were included; 116 were complicated with FGR and demonstrated a significantly higher rate of long-term cardiovascular morbidity (4.4% vs. 1.3%, OR = 3.4, 95% CI 1.35-8.78, p = 0.006). The cumulative incidence of long-term cardiovascular morbidity was significantly higher among FGR twins (Kaplan-Meier Log rank test p = 0.007). A Cox proportional-hazard model found an independent association between FGR and long-term cardiovascular morbidity, when adjusted for both birth order and gender (adjusted HR 3.3, 95% CI 1.31-8.19, p = 0.011). Conclusions: FGR in dichorionic-diamniotic twins is independently associated with an increased risk for long-term cardiovascular morbidity in offspring. Therefore, increased surveillance may be beneficial., Competing Interests: The authors declare no conflict of interest.

Sparse and conflicting data exist regarding the normal partogram of grand-multiparous (GMP, defined as parity of 6+) parturients. Customized partograms may potentially lower cesarean delivery rates for protraction disorders in this population. In this study, we aim to construct a normal labor curve of GMP women and compare it to the multiparous (MP, defined as parity of 2-5) partogram. We conducted a multicenter retrospective cohort analysis of deliveries between the years 2003 and 2019. Eligible parturients were the trials of labor of singletons ≥37 + 0 weeks in cephalic presentation with ≥2 documented cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, preterm labor, major fetal anomalies, and fetal demise. GMP comprised the study group while the MP counterparts were the control group. A total of 78,292 deliveries met the inclusion criteria, comprising 10,532 GMP and 67,760 MP parturients. Our data revealed that during the first stage of labor, cervical dilation progressed at similar rates in MPs and GMPs, while head descent was a few minutes faster in GMPs compared to MPs, regardless of epidural anesthesia. The second stage of labor was faster in GMPs compared to MPs; the 95th percentile of the second stage duration of GMPs (48 min duration) was 43 min less than that of MPs (91 min duration). These findings remained similar among deliveries with and without epidural analgesia or labor induction. We conclude that GMPs' and MPs' cervical dilation progression in the active phase of labor was similar, and the second stage of labor was shorter in GMPs, regardless of epidural use. Thus, GMPs' uterus function during labor corresponds, and possibly surpasses, that of MPs. These findings indicate that health providers can use the standard partogram of the active phase of labor when caring for GMP parturients.

Purpose: We aimed to evaluate the effect of traffic-related noise (TRN), environmental noise (EN) and traffic-related air pollution (TRAP) on preeclampsia. Methods: We followed 285 pregnant women from Maternal and Child Health Clinics who reported exposure to TRN on a scale from 0 (absence of EN) to 10 (high level of EN). EN was measured using a portable dosimeter, and NOx was calculated using the AERMOD pollutant dispersion model. Results: Using a multiple logistic regression model, adjusted for maternal age, BMI, number of births, fetal sex and maternal chronic illness, TRN (score ≥ 6 vs. score < 6) and TRAP (NOx ≥ 300 µ/m3 vs. NOx < 300 µ/m3) were noted as independent risk factors for preeclampsia, with OR = 3.07 (95% CI 0.97; 9.70, p = 0.056) and OR = 3.43 (95% CI 1.20; 9.87, p = 0.022), respectively. Joint exposure to TRN and TRAP was associated with a significant and independent risk for preeclampsia (OR of 4.11 (95% CI 1.31; 12.94, p = 0.016). Conclusions: In our population, traffic-related noise and ambient TRAP were risk factors for preeclampsia.

Objective: To investigate whether there is a linear association between the degree of prematurity and the risk for long-term ophthalmic morbidity among preterm infants. Study design: A population-based, retrospective cohort study, which included all singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. All infants were divided into four groups according to gestational age categories: extremely preterm births, very preterm births, moderate to late preterm births and term deliveries (reference group). Hospitalizations of offspring up to 18 years of age involving ophthalmic morbidity were evaluated. Survival curves compared cumulative hospitalizations and regression models controlled for confounding variables. Results: During the study period, 243,363 deliveries met the inclusion criteria. Ophthalmic-related hospitalization rates were lower among children born at term (0.9%) as compared with extremely preterm (3.6%), very preterm (2%), and moderate to late preterm (1.4%) born offspring (p < 0.01; using the chi-square test for trends). The survival curve demonstrated significantly different hospitalization rates between the gestational ages (p < 0.001). The regression demonstrated an independent risk for ophthalmic morbidity among extremely preterm born offspring (adjusted hazard ratio 3.8, confidence interval 1.6−9.2, p < 0.01), as well as very preterm and moderate to late preterm (adjusted hazard ratio 2.2 and 1.5, respectively) as compared with term deliveries. Conclusions: The risk for long-term ophthalmic-related hospitalization of preterm offspring gradually decreases as the gestational age increases.

(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.

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.

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.

(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.

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.

Survivors of the 2003 SARS epidemic were found to have higher rates of adverse mental conditions. This study aimed to assess cognitive function in women delivering during the COVID-19 pandemic, as compared to women who delivered before the COVID-19 pandemic. A cohort study was performed during the immediate postpartum period of women delivering singletons at term. Cognitive function was assessed using an objective neurocognitive test (Symbol Digit Modalities Test SDMT90, SDMT4) and a subjective self-estimation questionnaire (Attention Function Index AFI). The exposed group was recruited during the COVID-19 outbreak in Israel (May 2020), whereas the comparison group consisted of women delivering at the same medical center before the COVID-19 pandemic (2016-2017). Multivariable regression models were constructed to control potential confounders. There were 79 parturients recruited during the COVID-19 pandemic and compared with 123 women who delivered before the COVID-19 pandemic. Women delivering during the COVID-19 pandemic scored lower in the subjective AFI test compared to the unexposed group (70.0 ± 15.4 vs. 75.1 ± 14.7, p = 0.018). However, no significant difference was found in the objective SDMT tests scores. These results remained similar in the multivariable regression models when controlling for maternal age, ethnicity and time from admission to assessment, for AFI, SDMT90 and SDMT4 scores ( p = 0.014; p = 0.734; p = 0.786; respectively). While no significant difference was found in objective tests, our findings propose that the exposure to the COVID-19 pandemic is independently associated with a significant decrease in subjective maternal cognitive function during the immediate postpartum period.

Small-for-gestational-age (SGA) is defined as a birth weight below the 10th or below the 5th percentile for a specific gestational age and sex. Previous studies have demonstrated an association between SGA neonates and long-term pediatric morbidity. In this research, we aim to evaluate the possible association between small-for-gestational-age (SGA) and long-term pediatric neurological morbidity. A population-based retrospective cohort analysis was performed, comparing the risk of long-term neurological morbidities in SGA and non-SGA newborns delivered between the years 1991 to 2014 at a single regional medical center. The neurological morbidities included hospitalizations as recorded in hospital records. Neurological hospitalization rate was significantly higher in the SGA group (3.7% vs. 3.1%, OR = 1.2, 95% CI 1.1-1.3, p < 0.001). A significant association was noted between neonates born SGA and developmental disorders (0.2% vs. 0.1%, OR = 2.5, 95% CI 1.7-3.8, p < 0.001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of neurological morbidity in the SGA group (log-rank p < 0.001). In the Cox proportional hazards model, which controlled for various Confounders, SGA was found to be an independent risk factor for long-term neurological morbidity (adjusted hazard ratio (HR) = 1.18, 95% CI 1.07-1.31, p < 0. 001). In conclusion, we found that SGA newborns are at an increased risk for long-term pediatric neurological morbidity., Competing Interests: The authors report no conflicts of interest.

In this study, we sought to ascertain a relationship between gestational age at birth and infectious morbidity of the offspring via population-based cohort analysis comparing the long-term incidence of infectious morbidity in infants born preterm and stratified by extremity of prematurity (extreme preterm birth: 24 + 0-27 + 6, very preterm birth: 28 + 0-31 + 6, moderate to late preterm birth: 32 + 0-36 + 6 weeks of gestation, and term deliveries). Infectious morbidity included hospitalizations involving a predefined set of International Classification of Diseases 9 (ICD9) codes, as recorded in hospital records. A Kaplan-Meier survival curve compared cumulative incidence of infectious-related morbidity. A Cox proportional hazards model controlled for confounders and time to event. The study included 220,594 patients: 125 (0.1%) extreme preterm births, 784 (0.4%) very preterm births, 13,323 (6.0%) moderate to late preterm births, and 206,362 term deliveries. Offspring born preterm had significantly more infection-related hospitalizations (18.4%, 19.8%, 14.9%, and 11.0% for the aforementioned stratification, respectively, p < 0.001). Multivariate analysis found being born very or late to moderate preterm was independently associated with long-term infectious morbidity (adjusted hazard ratio (aHR) 1.5, 95% confidence interval (CI) 1.27-1.77 and aHR 1.23, 95% CI 1.17-1.3, respectively, p < 0.001). A comparable risk of long-term infectious morbidity was found in the two groups of premature births prior to 32 weeks gestation. In our population, a cutoff from 32 weeks and below demarks a significant increase in the risk of long-term infectious morbidity of the offspring.

Objective: To evaluate the perinatal outcome of women with tuberculosis and to assess a possible association between maternal tuberculosis and long-term infectious morbidity of the offspring., Study Design: Perinatal outcome and long-term infectious morbidity of offspring of mothers with and without tuberculosis were assessed. The study groups were followed until 18 years of age tracking infectious-related morbidity and infectious-related hospitalizations and then compared. For perinatal outcome, generalized estimation equation models were used. A Kaplan-Meier survival curve was used to compare cumulative incidence of long-term infectious morbidity. A Cox proportional hazards model was conducted to control for confounders., Results: During the study period, 243,682 deliveries were included, of which 46 (0.018%) occurred in women with tuberculosis. Maternal tuberculosis was found to be independently associated with placental abruption, cesarean deliveries, and very low birth weight. However, offspring born to mothers with tuberculosis did not demonstrate higher rates of infectious-related morbidity. Maternal tuberculosis was not noted as an independent risk factor for long-term infectious morbidity of the offspring., Conclusion: In our study, maternal tuberculosis was found to be independently associated with adverse perinatal outcomes. However, higher risk for long-term infectious morbidity of the offspring was not demonstrated. Careful surveillance of these women is required.

Objective: Higher rates of mental disorders, specifically depression, were found among affected people in previous epidemiological studies taken after disasters. The aim of the current study was to assess risk for depression among pregnant women hospitalized during the "coronavirus disease 2019" (COVID-19) pandemic, as compared to women hospitalized before the COVID-19 pandemic., Study Design: A cross-sectional study was performed among women hospitalized in the high-risk pregnancy units of the Soroka University Medical Center (SUMC). All participating women completed the Edinburgh Postnatal Depression Scale (EPDS), and the results were compared between women hospitalized during the COVID-19 strict isolation period (19 March 2020 and 26 May 2020) and women hospitalized before the COVID-19 pandemic. Multivariable logistic regression models were constructed to control for potential confounders., Results: Women hospitalized during the COVID-19 strict isolation period ( n = 84) had a comparable risk of having a high (>10) EPDS score as compared to women hospitalized before the COVID-19 pandemic ( n = 279; 25.0% vs. 29.0%, p = 0.498). These results remained similar in the multivariable logistic regression model, while controlling for maternal age, ethnicity and known mood disorder (adjusted odds ratio (OR) 1.0, 95% CI 0.52-1.93, p = 0.985)., Conclusion: Women hospitalized at the high-risk pregnancy unit during the COVID-19 strict isolation period were not at increased risk for depression, as compared to women hospitalized before the COVID-19 pandemic.

The Chernobyl accident in 1986 spread ionizing radiation over extensive areas of Belarus and Ukraine, leading to adverse health effects in exposed children. More than 30 years later, exposed children have grown and became parents themselves. This retrospective study from Israel was aimed to evaluate whether Chernobyl-exposed women are at higher risk for adverse reproductive outcomes. Exposed immigrants were identified as high or low exposure based on Caesium-137 soil contamination levels registered in the town they lived in. The exposed group was age matched with three comparison groups: non-exposed immigrant women from the Former Soviet Union (FSU) excluding Belarus and the Ukraine, immigrants from other countries (Non FSU) and Israeli-born women at a ratio of 1:10. Chernobyl-exposed women were more likely to be nulliparous and have fewer children (2.1 + 0.8 vs. 3.1 + 1.8, p < 0.001), were more likely to undergo fertility treatments (8.8% vs. 5.8%, adjusted OR = 1.8, 95%CI 1.04-3.2, p = 0.036), and were also more likely to have anemia after delivery (49.4% vs. 36.6%, OR = 1.7, 95%CI 1.2-2.3, p = 0.001), compared to women in the combined comparison groups. The overall fertility of Chernobyl-exposed women seems to be reduced as reflected by the lower number of children and their greater need for fertility treatments.

Objective: The aim of this study was to evaluate the association between large for gestational age (LGA) at birth and future risk of childhood neoplasm., Study Design: a population-based cohort to compare the long-term risk (up to the age of 18 years) of childhood neoplasms (benign and malignant) in children that were born LGA vs. those that were appropriate for gestational age (AGA), between the years 1991-2014. Childhood neoplasms diagnosis were defined according to international classification of disease 9 (ICD-9) codes recorded medical files. Kaplan-Meier survival curves were used in order to compare cumulative incidence of oncological morbidity over the study period. The Cox proportional hazards model was used to control for confounders., Results: 231,344 infants met the inclusion criteria; out of those 10,369 were diagnosed LGA at birth. Children that were LGA at birth had a higher incidence of leukemia (OR 2.25, 95%CI 1.08-4.65, p = 0.025) as well as kidney tumors (OR = 4.7, 95%CI = 1.02-21.9, p = 0.028). In addition, cumulative incidence over time of childhood malignancies, leukemia, and kidney tumors were significantly higher in LGA children (Log Rank = 0.010, 0.021, and 0.028, respectively). In a Cox regression model controlling for other perinatal confounders, LGA at birth remained independently associated with an increased risk for childhood malignancy (adjusted HR 1.51, 95%CI 1.02-2.23, p = 0.039)., Conclusion: LGA at birth is associated with increased long-term risk for childhood malignancy and specifically leukemia and kidney tumors. This possible link may help to improve current knowledge regarding potential exposures that are associated with childhood cancer development.

The aim of this population-based study was to evaluate whether prenatal exposure to preeclampsia poses a risk for long-term ophthalmic morbidity. A population-based cohort analysis compared the risk of long-term ophthalmic morbidity among children who were prenatally exposed to preeclampsia and those who were not. The study population was composed of children who were born between the years 1991 and 2014 at a single tertiary medical center. Total ophthalmic hospitalization and time-to-event were both evaluated. A Kaplan-Meier survival curve was conducted to compare cumulative ophthalmic hospitalization incidence based on the severity of preeclampsia. Confounders were controlled using a Cox regression model. A total of 242,342 deliveries met the inclusion criteria, of which 7279 (3%) were diagnosed with mild preeclampsia and 2222 (0.92%) with severe preeclampsia or eclampsia. A significant association was found between severe preeclampsia or eclampsia and the risk of long-term vascular-associated ophthalmic morbidity in the offspring (no preeclampsia 0.3%, mild preeclampsia 0.2% and severe preeclampsia or eclampsia 0.5%, p = 0.008). This association persisted after controlling for maternal age and ethnicity (adjusted hazard ratio (HR) 1.861, 95% CI 1.051-3.295). In conclusion, within our population, prenatal exposure to severe preeclampsia or eclampsia was found to be a risk factor for long-term vascular-associated ophthalmic morbidity in the offspring.

Background: The incidence of preeclampsia, which may cause significant maternal and perinatal morbidity, has risen in recent years, therefore it is critical to identify women at risk for preeclampsia. We aimed to identify risk factors in the first pregnancy (not complicated by preeclampsia) for preeclampsia in the subsequent pregnancy., Methods: A retrospective population-based nested case-control study was conducted, including all women with first (P1) and second (P2) singleton consecutive deliveries. Women who had experienced preeclampsia in their first pregnancy were excluded. Cases were defined as women with preeclampsia in their second pregnancy, and were compared to the controls, defined as women without this diagnosis in second pregnancy. Characteristics and complications of the first pregnancy were compared between cases and controls, and multivariable regression models were used to study the association between pregnancy complications (in the first pregnancy) and preeclampsia (in the subsequent pregnancy), while adjusting for confounders., Results: A total of 40,673 women were included in the study, 1.5% of second pregnancies were diagnosed with preeclampsia ( n = 627, i.e., Cases). Cases, as compared to controls were older in their 1st pregnancy, with longer inter-pregnancy interval, and were more likely to have the following complications in their first pregnancy: preterm delivery (15.0% vs. 7.7%), low birthweight (17.9% vs. 10.3%), perinatal mortality (3.2% vs. 1.1%), and gestational diabetes (7.0% vs. 2.7%). In the multivariable model, adjusted for maternal age, obesity and inter-pregnancy interval, either one of these first pregnancy complications were independently associated with an increased risk for preeclampsia (adjusted OR for either of first pregnancy complication =1.73; 95% CI 1.37-2.14, <0.001), and the risk was greater for each additional complication (adjusted OR for ≥2 risk factors =3.54; 95% CI 2.28-5.52, p < 0.001)., Conclusions: Complications in first pregnancy, including preterm delivery, perinatal mortality and gestational diabetes, are risk factors for primary preeclampsia in second pregnancy. First pregnancy may serve as a window of opportunity to identify women at risk for future preeclampsia and other morbidities later in life.

This study aimed to investigate the long-term effect of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on offspring endocrine morbidity. A population-based cohort study included all singleton deliveries between the years 1991-2014 at the Soroka University Medical Center, Beer-Sheva, Southern Israel. The mothers were subdivided into three groups, HBV carriers, HCV carriers and non-carriers. Data regarding the long-term endocrine morbidity of their offspring were compared between the groups. The study included 242,905 (99.7%) non-carrying mothers, 591 (0.2%) mothers who were carriers for HBV and 186 (0.1%) mothers who were carriers for HCV. The Kaplan-Meier's survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with HCV (log-rank test, p  = 0.002). Specifically, higher rates of hypoglycemia were noted among the offspring born to mothers who were carriers of HCV (1.1%; p = 0.001) compared with the offspring of mothers who were either carriers of HBV (0.2%) or non-carriers (0.1%). A Cox regression model controlled for maternal age, gestational age, maternal diabetes, hypertensive disorders of pregnancy, found maternal HCV carrier status to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 5.05, 95% CI: 1.625-15.695, p = 0.005). Maternal HCV carrier status is an independent risk factor for long-term endocrine morbidity.

The unpredictable nature of childbirth infrequently results in unplanned out-of-hospital birth, in a pre-hospital setting. We evaluated the perinatal and long-term outcome of children accidentally born out-of-hospital. This was a population-based analysis of singleton deliveries occurring at a single tertiary hospital. The maternal characteristics and pregnancy outcome of unplanned out-of-hospital births were compared with in-hospital attended deliveries. Long-term cumulative incidence of hospitalizations (up to 18 years) involving respiratory, neurological, endocrine or infectious morbidity were evaluated using Kaplan-Meier survival curves and Cox regression models were used to control for confounders. In total, 243,682 deliveries were included, and 1.5% ( n = 3580) were unplanned out-of-hospital births. Most occurred in multiparous women, and about a quarter of these women had inadequate prenatal care. Perinatal mortality rate was significantly higher for out-of-hospital births as compared with in-hospital births (OR = 2.9; 95% CI 2.2-3.8, p < 0.001). Kaplan-Meier survival curves demonstrated a significantly lower cumulative incidence of hospitalizations of children born out-of-hospital and the Cox models showed that hospitalization rates involving any of the above morbidities were significantly lower in children born out-of-hospital. While perinatal mortality was higher in unplanned out-of-hospital births, offspring born out-of-hospital showed a lower incidence of hospitalizations involving a variety of morbidities, possibly owing to under-utilization of healthcare services in this population., Competing Interests: The authors declare no conflict of interest.

The aim of this study was to evaluate perinatal outcome and long-term offspring gastrointestinal morbidity of women with celiac disease. Perinatal outcomes, as well as long-term gastrointestinal morbidity of offspring of mothers with and without celiac disease were assessed. The study groups were followed until 18 years of age for gastrointestinal-related morbidity. For perinatal outcomes, generalized estimation equation (GEE) models were used. A Kaplan-Meier survival curve was used to compare cumulative incidence of long-term gastrointestinal morbidity, and Cox proportional hazards models were constructed to control for confounders. During the study period, 243,682 deliveries met the inclusion criteria, of which 212 (0.08%) were to mothers with celiac disease. Using GEE models, maternal celiac disease was noted as an independent risk factor for low birth weight and cesarean delivery. Offspring born to mothers with celiac disease had higher rates of gastrointestinal related morbidity (Kaplan-Meier log rank test P < 0.001). Using a Cox proportional hazards model, being born to a mother with celiac disease was found to be an independent risk factor for long-term gastrointestinal morbidity of the offspring. Pregnancy of women with celiac disease is independently associated with adverse perinatal outcome as well as higher risk for long-term gastrointestinal morbidity of offspring., Competing Interests: The authors declare no conflict of interest.

Obesity is a leading cause of morbidity world-wide. Maternal obesity is associated with adverse perinatal outcomes. Furthermore, Obesity has been associated with increased susceptibility to infections. The purpose of this study was to evaluate long-term pediatric infectious morbidity of children born to obese mothers. This population-based cohort analysis compared deliveries of obese (maternal pre-pregnancy BMI ≥ 30 kg/m 2 ) and non-obese patients at a single tertiary medical center. Hospitalizations of the offspring up to the age of 18 years involving infectious morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan-Meier survival curve was used to compare cumulative hospitalization incidence between the groups and Cox proportional hazards model was used to control for possible confounders. 249,840 deliveries were included. Of them, 3399 were children of obese mothers. Hospitalizations involving infectious morbidity were significantly more common in children born to obese mothers compared with non-obese patients (12.5% vs. 11.0%, p < 0.01). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of infectious-related hospitalizations in the obese group (log rank p = 0.03). Using the Cox regression model, maternal obesity was found to be an independent risk factor for long-term infectious morbidity of the offspring (adjusted HR = 1.125, 95% CI 1.021-1.238, p = 0.017).