Search

Objective: To determine the risk of long-term cardiovascular disease (CVD) among children born following in vitro fertilization (IVF) and compared with spontaneous pregnancies., Study Design: A population-based cohort study including all singleton deliveries occurring between 1991and 2014 at a tertiary medical center was performed. Hospitalizations up to the age of 18 years involving CVD were evaluated in children delivered following IVF, ovulation induction, and spontaneous pregnancies. CVD included valvular disorders, hypertension, arrhythmias, rheumatic disease, cardiomyopathy, ischemic heart disease, and heart failure. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence, and a Cox regression model controlled for confounders., Results: During the study period, 242 187 singleton deliveries met the inclusion criteria; 1.1% following IVF (n = 2603), and 0.7% following ovulation induction (n = 1721). Hospitalizations up to the age of 18 years involving CVD (n = 1503) were comparable in children delivered following IVF (0.6%), ovulation induction (0.7%), and spontaneous pregnancies (0.6%; P = .884). No significant difference in the cumulative incidence of CVD was noted between the groups (log rank P = .781). Controlling for maternal age, gestational age, birthweight, maternal diabetes, and hypertensive disorders in pregnancy, fertility treatment was not noted as a risk factor for long-term pediatric CVD (IVF adjusted hazard ratio 1.05, 95% CI 0.63-1.74, P = .86; ovulation induction adjusted hazard ratio 0.97, CI 95% 0.55-1.71, P = .92)., Conclusions: Singletons conceived via fertility treatments do not appear to be at an increased risk of long-term pediatric CVD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We aimed to evaluate the association between advanced maternal age and the long-term health of the offspring., Methods: In this population-based cohort study, hospitalizations of offspring up to the age of 18 years were compared according to maternal age. The incidence of long-term hospitalizations of the offspring due to cardiovascular, endocrine, neurological, hematological, respiratory and gastro-intestinal morbidities was evaluated. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence. Cox regression models were performed to control for confounders., Results: During the study period, 202,709 deliveries were included, of which 26,287 (12.9%) were in women aged 35-39 years, and 6,718 (3.3%) in women aged 40-50 years. Children born to older mothers did not have a significantly different cumulative incidence of long-term pediatric morbidities evaluated, as compared with the comparison group, using Kaplan-Meier survival analyses. In the Cox regression analyses, advanced maternal age did not exhibit an independent association with long-term morbidities of the offspring., Conclusion: Despite the association of advanced maternal age with adverse maternal and immediate neonatal outcomes, there does not seem to be an association with the long-term morbidity of the offspring., (© 2018 S. Karger AG, Basel.)

Objective: To evaluate the long-term pediatric neurological morbidity of children born to mothers who reported smoking during pregnancy as compared with children born to non-smoking mothers., 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 neurological morbidities were evaluated according to a predefined set of ICD-9 codes, including autism, development and movement disorders, cerebral palsy and more. A Kaplan-Meier survival 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, 242,342 deliveries met the inclusion criteria. Of them, 2861 (1.2%) were children of smoking mothers. Neurological-related hospitalizations were significantly higher in children born to smoking mothers, as compared with the non-smoking group (5.3% vs. 3.1%, p < 0.01). Specifically, these children had higher rates of movement, eating and developmental disorders as well as attention deficit hyperactive disorder. The Kaplan-Meier survival curve demonstrated a significant higher cumulative incidence of neurological-related hospitalizations in the smoking group (log rank p < 0.01). Using a Cox proportional hazards model, controlling for potential confounders, maternal tobacco use was found to be independently associated with long-term neurological morbidity of the offspring (adjusted HR = 1.58, CI 1.33-1.89, p value < 0.01)., Conclusion: Maternal smoking during pregnancy is an independent risk factor for long-term neurological morbidity of the offspring., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the association between maternal asthma and perinatal outcome., Study Design: In this retrospective population-based cohort study, all pregnancies between 1991 and 2014 in a tertiary medical center, were included. Multiple pregnancies and congenital malformations were excluded. Pregnancy course and outcomes were compared between women with and without asthma, and multivariable generalized estimating equations were used to control for confounders., Results: During the study period, 243,363 deliveries met the inclusion criteria, 1.35% of which (n = 3283) occurred in women diagnosed with asthma. Multiple perinatal complications were found to be associated with maternal asthma, including hypertensive disorders, preterm delivery, and cesarean delivery. However, no significant differences between the groups were noted in neonatal outcomes, including perinatal mortality rates and low Apgar scores. In the regression model, maternal asthma was noted as an independent risk factor for preterm delivery, hypertensive disorders of pregnancy, and cesarean delivery (aOR = 1.21, 95%CI 1.1-1.4, p = .007; aOR = 1.35, 95%CI 1.2-1.6, p < .001; and aOR = 1.27, 95%CI 1.2-1.4, p < .001, respectively) while controlling for multiple confounders., Conclusions: Maternal asthma is associated with an increased risk for adverse pregnancy outcome. This association remains significant while controlling for variables considered to coexist with maternal asthma. Nevertheless, perinatal outcome is generally favorable.

Objective: The objective of this study is to investigate whether an abnormal birthweight at term, either small for gestational age (SGA, < 5th centile for gestational age) or large for gestational age (LGA, > 95th centile for gestational age), is a risk factor for perinatal complications as compared with birthweight appropriate for gestational age (AGA)., Methods: A population-based retrospective cohort analysis of all singleton pregnancies delivered between 1991 and 2014 at Soroka Medical Center. Congenital malformations and multiple pregnancies were excluded. A multivariable generalized estimating equation regression model was used to control for maternal clusters and other confounders., Results: During the study period, 228,242 births met the inclusion criteria, of them 91% were AGA (n = 207,652), 4.7% SGA, and 4.3% LGA. SGA significantly increased the risk for perinatal mortality (aOR 5.6, 95%CI 4.5-6.8) and low 5-min Apgar scores (aOR 2.2, 95%CI 2.0-2.4), while LGA did not. SGA and LGA were both significant risk factors for cesarean delivery. LGA was significantly associated with shoulder dystocia and post-partum hemorrhage (aOR =13.6, 95%CI 10.9-17.0, and aOR 1.7, 95%CI 1.2-2.6, respectively)., Conclusions: Extreme birthweights at term are significantly associated with adverse maternal and neonatal outcomes. As opposed to SGA, LGA is not independently associated with perinatal mortality.

Objective: Maternal anemia (Hemoglobin, <11 mg/dl) has been shown to affect fetal growth and pregnancy outcome. We aimed to study a possible association between maternal anemia and the risk for neurological morbidity in the offspring, during a follow-up period of up to 18 years., Study Design: A population-based cohort analysis was performed at the Soroka University Medical Center (SUMC), a single regional tertiary center comparing total and specific subtypes of neurological morbidities associated with hospitalizations among children stratified by three maternal post-partum hemoglobin categories: ≥11 mg/dl (no anemia); 11.0 mg/dl > Hb ≥ 7 mg/dl (mild-to-moderate anemia) and <7 mg/dl (severe anemia). Data on pregnancy course and outcome, and later offspring hospitalizations, were compared between the three study groups. All singleton deliveries between the years 1991-2014 were included in the analysis, and congenital malformations were excluded. A Kaplan-Meier survival curve was used to compare cumulative hospitalization incidence based on maternal anemia status, and a Weibull survival multivariable hazard model was constructed to adjust for confounding variables., Results: The study population included 217,358 deliveries of which 50.6% were in mothers who were not anemic, 49.0% in mothers with moderate anemia and 0.4% in mothers with severe anemia. During the follow up period (0-18 years, median 10.22 years), 2.1% of offspring were hospitalized with a neurological diagnoses. Neurological hospitalization incidence decreased from 2.95/1000 person years, in the severe anemia group, to 2.32/1000 person years and 2.01/1000 person years, among the mild-to-moderate and no anemia groups, respectively (p = 0.007). The association between maternal anemia and offspring long-term pediatric neurological morbidity remained significant in a Weibull hazards model controlled for gestational age, delivery mode, SGA and insufficient prenatal care (adjusted HR 1.55; 1.05-2.31 and adjusted HR 1.13; 1.06-1.20; among the severe and mild-to-moderate anemia, vs. no anemia, respectively)., Conclusion: Children born to anemic mothers are at an increased risk for pediatric neurological-related hospitalizations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate whether delivery of small for gestational age (SGA) neonate poses a risk for subsequent long-term ophthalmic morbidity., Methods: In this population-based study, all deliveries between 1991 and 2014 were included. Congenital malformations and multiple gestations were excluded from the analysis. Offspring were defined as either SGA (weight below the 5th percentile for gestational age) or non-SGA. Comparison was performed regarding the incidence of long-term ophthalmic morbidity in a cohort of neonates who were born SGA and those who were not. Ophthalmic morbidity was documented during any encounter with the hospital for a period of up to 18 years after delivery. Ophthalmic morbidity included infections of the eye or the adnexa, inflammation of any cause requiring admission, visual disturbances, and other hospital admissions carrying an ICD-9 code of ophthalmic designation. A Cox proportional hazards model was used to estimate the adjusted hazards ratio (HR) for ophthalmic morbidity During the study period, 243,682 deliveries met the inclusion criteria, of which 11,290 (4.63%) were defined as SGA., Results: During the follow-up period, SGA neonates had higher rates of ophthalmic-related hospitalizations (1.2% versus 1.0%; OR = 1.22, 95% CI 1.02-1.46; p = 0.026). In a Cox proportional hazards model, adjusted for confounders such as maternal age, gestational age at delivery, child birth year, low 5 min Apgar scores (< 7), gestational diabetes, maternal hypertensive disorders, placental abruption and placenta previa, SGA neonate was independently associated with subsequent long-term ophthalmic morbidity (adjusted HR = 1.22; 95% CI 1.02-1.47; p = 0.024)., Conclusion: Delivery of an SGA neonate is an independent risk factor for long-term ophthalmic morbidity.

Children born at early term (37 0/7 to 38 6/7 weeks' gestation) are at an increased risk for long-term respiratory, cardiovascular, neurological, and developmental morbidities as compared with children born at full term (39 0/7 to 40 6/7 weeks' gestation). In this population-based cohort analysis, we sought to evaluate the long-term hematological morbidity of early-term born children. The cohort consisted of 223,242 term singleton deliveries. Hospitalizations of the offspring up to 18 years of age involving hematological morbidity were evaluated, including hereditary and acquired anemias, immunodeficiency disorders, coagulation disorders, white blood cell disorders, cytopenias, polycythemia, and myelodysplastic syndrome. Hematological hospitalizations were significantly more common in children delivered at early term as compared with those born at later gestational ages. A Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of hematological-related hospitalizations in the early-term born group (logrank p < 0.001). Using a Cox regression model, early-term delivery was found to be an independent risk factor for childhood hematological morbidity with an adjusted hazard ratio of 1.15 (95%CI 1.01-1.30, p=0.027).Conclusion: Early-term delivery appears to be independently associated with pediatric long-term hematological morbidity of the offspring. What is Known? • It has been shown that children born at early term are at increased risk for short-term adverse outcomes including perinatal mortality. • Early-term infants are also at increased risk for long-term morbidity, mainly respiratory. What is New? • Early-term delivery is also independently associated with long-term hematological morbidity of the offspring.

Objective: To examine the association between routine blood tests during pregnancy and future risk of cardiovascular morbidity., Methods: The present case-control study was conducted among women who delivered at a teaching hospital in Israel between January 1, 2000, and December 31, 2012. The cohort comprised women who were subsequently hospitalized owing to cardiovascular morbidity (case group) and age-matched non-hospitalized women (control group). Blood levels of creatinine, glucose, potassium, urea, and uric acid were measured during pregnancy. Only women with at least one test result available for all five measurements were included. The relationship between upper quartile blood test values and cardiovascular hospitalization was assessed., Results: The study included 4115 women (212 in the case group and 3903 in the control group). Three measures were associated with a future risk of cardiovascular morbidity requiring hospitalization: creatinine (hazard ratio [HR] 1.86, 95% confidence interval [CI] 1.37-2.53; P<0.001); potassium (HR 1.48, 95% CI 1.09-2.01; P=0.013), and urea (HR 1.60, 95% CI 1.17-2.19; P=0.003). The number of blood test results in the upper quartile also increased such risk. The HRs for two tests and at least three tests were 1.65 (95% CI 1.06-2.56; P=0.026) and 3.32 (95% CI 2.19-5.04; P<0.001), respectively., Conclusions: Future cardiovascular morbidity was predicted by routine blood tests during pregnancy., (© 2018 International Federation of Gynecology and Obstetrics.)

Maternal morbidity is associated with cesarean deliveries. However, new evidence suggests that short- and long-term neonatal morbidity is also associated. This includes respiratory morbidity with conflicting results. To determine whether mode of delivery has an impact on the long-term risk for respiratory morbidity in the offspring, a population-based cohort analysis was conducted including all singleton term deliveries occurring between 1991 and 2014 at a single tertiary medical center. A comparison was performed between children delivered via elective cesarean delivery (CD) and those delivered vaginally. Multiple gestations and fetuses with congenital malformations were excluded from the analysis as were all cases of urgent CDs. Pediatric hospitalizations involving respiratory morbidity of offspring up to the age of 18 years were evaluated. A Kaplan-Meier survival curve was used to compare cumulative respiratory morbidity incidence and a Cox regression model to control for confounders. During the study period, 132,054 term deliveries met the inclusion criteria; 8.9% were via elective CDs (n = 11,746) and 91.1% (n = 120,308) were vaginal deliveries. Hospitalizations of the offspring involving respiratory morbidity were significantly more common in offspring delivered by CDs (5.2 vs. 4.3% in vaginal deliveries, p < 0.001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory morbidity in the elective CD group (log rank p < 0.001). In a Cox proportional hazards model, while controlling for maternal age, gestational age, and birthweight, CD exhibited a significant and independent association with long-term respiratory morbidity of the offspring (adjusted hazard ratio = 1.22 (CI, 1.12-1.33), p < 0.001).Conclusion: Elective cesarean delivery at term is a significant risk factor for long-term pediatric respiratory morbidity of the offspring. What is Known: • Cesarean delivery is a major surgery with known possible complications. • Cesarean delivery has possible immediate complications for the newborn including respiratory complications. What is New: • Our study shows more long term respiratory morbidity in the CD group including asthma and obstructive sleep apnea. • Different possible explanations have been proposed including exposure to maternal flora during vaginal delivery and the stress hormones secreted during contractions and delivery.

Objective: Anemia is associated with increased cardiovascular morbidity in the general population. Anemia is common during pregnancy. We examined the association between anemia at the very early postpartum period and long-term atherosclerotic-related morbidity., Patients and Methods: A retrospective study including women who gave birth between 1988 and 2013 was conducted. The women were divided into two groups according to hemoglobin (Hb) value on the first day after delivery: Hb <10 g/dL and Hb ≥10 g/dL. We examined the rates of hospitalization due to atherosclerotic-related morbidity, which were classified into minor and major events. The follow-up period was from the index birth until either hospitalization or the end of study period. Survival estimates were calculated by Kaplan-Meier survival analysis. Cox proportional hazards models were used to evaluate whether Hb <10 gr/dL is an independent risk factor for long-term atherosclerotic events., Results: The study population included 30,088 (37.40%) women with Hb <10 g/dL and 50,354 (63%) women with Hb ≥10 g/dL at the index birth. The hospitalization incidence density was higher in the Hb <10 g/dL group versus the Hb ≥10 g/dL group, for total atherosclerotic- related hospitalizations (4.35 vs. 3.76, p < 0.001), and hospitalization for major events (1.83 vs. 1.51, p < 0.001) and minor events (2.60 vs. 2.31, p < 0.001). In Cox proportional hazards models, it was demonstrated that Hb <10 g/dL was independently associated with total hospitalizations (HR 1.13; CI: 1.04-1.24 p = 0.004) and hospitalizations for major events (HR 1.16; CI: 1.01-1.34 p = 0.034) Conclusions: Hb <10 g/dL at the very early postpartum period might be a marker for long-term atherosclerotic-related morbidity.

Purpose: To investigate whether patients with a history of recurrent pregnancy loss (RPL) have an increased risk for future female malignancies., Methods: A retrospective population-based study compared the incidence of long-term female malignancies in a cohort of women with and without a history of RPL (2 or more consecutive pregnancy losses). Deliveries occurred between the years 1988 and 2013, with a mean follow-up duration of 12 years. Women with known malignancies before the index pregnancy were excluded from the analysis. Female malignancies were divided according to specific type including ovary, breast, uterine and uterine cervix. Kaplan-Meier survival curve was used to estimate the cumulative incidence of malignancies. Cox proportional hazards model was used to determine the adjusted hazard ratios (HR) for female malignancy after controlling for confounders., Results: During the study period, 106,265 patients met the inclusion criteria; 6.6% (n = 7052) of patients had a diagnosis of RPL. During the follow-up period, patients with RPL had a significantly increased risk of being diagnosed with female malignancies as a group, while individually there was an increased risk of breast and uterine cervix cancer. Using a Kaplan-Meier survival curve, patients with a history of RPL had a significantly higher cumulative incidence of female malignancies. Using a Cox proportional hazards model, adjusted for confounders such as smoking, parity, and diabetes mellitus, a history of RPL remained independently associated with female malignancies (adjusted HR 1.4; P = 0.003)., Conclusions: RPL is independently associated with long-term female malignancies. Patients with a history of RPL may benefit from counseling and screening for breast and uterine cervix cancer in particular.

Aims: The prevalence of gestational diabetes mellitus (GDM) has been increasing worldwide. We aimed to study the effect of GDM on the risk for childhood cardiovascular morbidity of the offspring., Methods: A population-based cohort analysis was performed comparing total and different subtypes of cardiovascular related pediatric diagnoses among offspring of mothers with GDM vs. offspring of mothers with no diabetes. The analysis included all singletons born between the years 1991-2014. Cardiovascular related morbidities included hospitalizations involving a pre-defined set of ICD-9 codes. Mothers with pregestational diabetes, Infants with congenital malformations, multiple gestations, and perinatal deaths were excluded from the analysis. A Cox proportional hazards model was constructed to adjust for confounders., Results: The study population included 216197 newborns which met the inclusion criteria; among them 4.4% (9460) were born to mothers with GDM controlled by diet and exercise (GDM A1) and 0.3% (724) were born to mothers with GDM requiring oral treatment or insulin (GDM A2). A significant association was noted between GDM and the rate of cardiovascular related hospitalizations (0.97 for GDM A2 vs. 0.57 for GDM A1 vs. 0.33 for no GDM, respectively; p < 0.001). The association remained significant and independent for GDM A1 only while adjusting for relevant confounders [adjusted HR = 1.6 (1.2-2.2); p value 0.001]., Conclusions: A significant association is noted between the GDM and the rate of cardiovascular hospitalizations of the offspring. However, in our population GDM A1 is an independent risk factor for pediatric cardiovascular morbidity of the offspring.

Background: Gestational diabetes mellitus (GDM) is a worldwide public health problem. Few studies investigated the association of intra uterine exposure to GDM and long-term endocrine morbidity of offspring., Objective: To assess whether in utero exposure to GDM increases the risk for long-term endocrine morbidity of the offspring., Methods: A retrospective cohort study was conducted including all singleton born to women who delivered between 1988 and 2014. All births occurred in a tertiary medical center. Data were collected from the computerized perinatal database of the obstetrics and gynecology department and the computerized hospitalization database. The exposure variables were: diet-controlled GDM (GDMA1) and treated GDM (GDMA2). Multivariate generalized estimating equation (GEE) logistic regression model analysis was used to control for confounders and for maternal clusters., Results: During the study period 231,271 deliveries met the inclusion criteria, of which 12,642 deliveries (5.4%) were diagnosed with GDM. During the follow-up period, children exposed in utero to GDM had a higher rate of long- term hospitalizations with diagnoses of endocrine morbidity (such as diabetes mellitus and obesity) compared to those unexposed. Using a GEE model, controlling for confounders such as maternal age, follow up-time, obesity and birthweight, in-utero exposure to GDMA1 (adjusted OR = 2.1; 95% CI 1.7-2.7; P < 0.001) and especially to GDMA2 (adjusted OR = 3.1; 95% CI 2.2-4.4, P < 0.001) were found as risk factors for long-term endocrine disease during childhood., Conclusion: Exposure to GDM is a risk factor for long-term endocrine morbidity in the offspring., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to investigate whether maternal bronchial asthma increases the risk for long-term respiratory morbidity of the offspring., Study Design: A population-based cohort study compared the incidence of long-term pediatric hospitalizations due to respiratory disease of the offspring of mothers with and without bronchial asthma. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Congenital malformations as well as multiple pregnancies were excluded. Kaplan-Meier's survival curve was used to estimate cumulative incidence of respiratory morbidity. A multivariate generalized estimating equation (GEE) logistic regression model analysis was used to control for confounders., Results: During the study period, 253,808 deliveries met the inclusion criteria; of which 1.3% were born to mothers with bronchial asthma ( n  = 3,411). During the follow-up period, children born to women with bronchial asthma had a significantly higher rate of long-term respiratory morbidity (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.3-1.7; p  < 0.001). Specifically, the rate of childhood asthma was higher among offspring of mothers with asthma (OR = 2.3; 95% CI = 1.8-2.9; p  < 0.001). Children born to women with asthma had higher cumulative incidence of respiratory morbidity, using a Kaplan-Meier's survival curve (log-rank test; p  < 0.001). Using two multivariable GEE logistic regression models, controlling for the time to event, maternal age, and gestational age at delivery, maternal bronchial asthma was found to be an independent risk factor for long-term respiratory disease of the offspring (adjusted OR = 1.6; 95% CI = 1.4-1.9; p  < 0.001), and specifically for bronchial asthma (adjusted OR = 2.5; 95% CI = 1.9-3.1; p  < 0.001)., Conclusion: Maternal bronchial asthma is an independent risk factor for long-term respiratory morbidity of the offspring., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate the association between newborn gender and the risk for later pediatric respiratory morbidity., Study Design: A population based cohort analysis was performed by comparing the risk of long-term respiratory morbidity (until 18 years of age) according to gender. Respiratory morbidity included hospitalizations involving pneumonia, asthma, bronchitis, bronchiolitis, upper respiratory tract infection (URTI), influenza, and bronchiectasis. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan-Meier survival curves were constructed to compare cumulative respiratory morbidity. A Cox proportional hazards model controlled for confounders., Results: During the study period 240 953 newborns met the inclusion criteria. Among them, 118 113 were females (49.0%) and 122 840 were males (51.0%). During the 18 years of follow-up, 13 719 (5.7%) different newborns were hospitalized with respiratory related morbidity. Males had significantly higher rates of respiratory morbidity as compared with females (6.4% vs 4.9% respectively, P < 0.001, OR 1.32, 95% CI 1.28-1.37). Specifically, pneumonia, bronchitis, asthma, bronchiolitis, and URTI were significantly more common in males. Males exhibited higher total cumulative respiratory morbidity (log rank P < 0.001), as well as higher cumulative morbidity in several sub-categories. These sub-categories included pneumonia, bronchitis, asthma, bronchiolitis, and URTI (P < 0.05 in all). The Cox regression model demonstrated male gender to be an independent risk factor for pediatric respiratory morbidity while adjusting for gestational age, birthweight, and other confounders (HR 1.29, 95% CI 1.25-1.34, P < 0.001)., Conclusions: Males are at an increased risk for pediatric respiratory morbidity, independent of obstetrical characteristics such as gestational age and birthweight., (© 2018 Wiley Periodicals, Inc.)

Objective: The study's objective was to determine whether mode of delivery has an impact on the long-term risk for neurologic morbidity of the offspring., Materials and Methods: This population-based cohort analysis included all term singleton deliveries between 1991 and 2014. The study population was divided into two study group: elective cesarean deliveries (CD) versus vaginal deliveries (VD). Urgent cesarean deliveries, pregnancy, and delivery complications including preeclampsia and gestational diabetes were excluded. The evaluation of cumulative neurological hospitalization rate over time was performed with a Kaplan-Meier survival analysis and Cox proportional hazards models were used to study the independent association between mode of delivery and neurological morbidity while controlling for potential confounders., Results: During the study period 132,054 deliveries met the inclusion criteria, 11,746 CD (8.9%), and 120,308 (91.1%) VD. A total of 3,626 neurological hospitalizations were documented with 2.70% (3,244) in the VD group as compared with 3.25% (382) in the CD group. The survival curves showed higher cumulative hospitalization rates in the CD as compared with the VD group ( p ≤ 0.001). The Cox analysis demonstrated CD to be an independent risk factor for pediatric neurological hospitalizations ( p  < 0.001)., Conclusion: Term elective CD is an independent risk factor for neurological morbidity of the offspring., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To investigate the association between episiotomy and perineal damage in the subsequent delivery., Study Design: A retrospective cohort study was conducted, comparing outcome of subsequent singleton deliveries of women with and without episiotomy in their first (index) delivery. Deliveries occurred between the years 1991-2015 in a tertiary medical center. Traumatic vaginal tears, multiple pregnancies, and cesarean deliveries (CD) in the index pregnancy were excluded from the analysis. Multiple logistic regression models were used to control for confounders., Results: During the study period, 43,066 women met the inclusion criteria; of them, 50.4% (n = 21,711) had subsequent delivery after episiotomy and 49.6% (n = 21,355) had subsequent delivery without episiotomy in the index pregnancy. Patients with episiotomy in the index birth higher rates of subsequent episiotomy (17.5 vs. 3.1%; P < 0.001; OR 1.9; 95% CI). In addition, the rates of the first and second degree perineal tears as well as the third and fourth degree perineal tears were significantly higher in patients following episiotomy (33.6 vs. 17.8%; P < 0.001, and 0.2 vs. 0.1%; P = 0.002, respectively). Nevertheless, there was no significant difference at the rates of CD and instrumental deliveries, between the groups. While adjusting for maternal age, ethnicity, birth weight, and vacuum delivery-the previous episiotomy was noted as an independent risk factor for recurrent episiotomy in the subsequent delivery (adjusted OR 6.7; 95% CI 6.2-7.3, P < 0.001). The results remained significant for term (adjusted OR 6.8; 95% CI 6.2-7.4, P < 0.001) as well as preterm deliveries (adjusted OR 4.5; 95% CI 3.3-6.3, P < 0.001) in two different models., Conclusion: Episiotomy is an independent risk factor for recurrent episiotomy in the subsequent delivery.

Introduction: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Regarding the offspring, little is known about the long-term complications. The objective of the current study is to assess whether in utero exposure to preeclampsia increases the risk of long-term cardiovascular morbidity in the offspring., Materials and Methods: A population-based cohort study compared the incidence of cardiovascular disease between singletons exposed and unexposed to preeclampsia. Deliveries occurred between 1991 and 2014 in a regional tertiary medical center. A Cox proportional hazard model was used to control for confounders., Results: During the study period 231,298 deliveries met the inclusion criteria; 4.1% of the births were to mothers diagnosed with preeclampsia, of which 3.2% with mild preeclampsia (n = 7286), 0.9% with severe preeclampsia (n = 2174) and 0.03% with eclampsia (n = 73). A significant linear association was noted between preeclampsia (no preeclampsia, mild preeclampsia, severe preeclampsia and eclampsia) and cardiovascular disease of the offspring (0.24%, vs. 0.33% vs. 0.51% vs. 2.73% respectively, p < 0.001 using the chi-square test for trends). In the offspring born at term, severe preeclampsia was found to be an independent risk factor for cardiovascular morbidity (adjusted HR = 2.32; 95% CI 1.15-4.67). In offspring born preterm, neither severe preeclampsia (adjusted HR = 1.36; 95% CI 0.53-3.48) nor mild preeclampsia (adjusted HR = 0.37; 95% CI 0.52-2.71) were associated with cardiovascular morbidity of the offspring., Conclusion: Exposure to severe maternal preeclampsia is an independent risk factor for long-term cardiovascular morbidity in the offspring born at term., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

In the past several decades, rates of delayed childbearing have increased, and as a result, maternal age has advanced. Our objective was to evaluate whether advanced maternal age is independently associated with an increased risk of childhood cancers in the offspring. A retrospective cohort study of women who delivered between the years 1991 and 2014 was conducted. Elderly parturients (≥ 35 years) were divided into two sub-categories: 35-39 and 40-50 years. The comparison group consisted of parturients aged 20-34 years. All hospitalizations of offspring up to the age of 18 years involving malignant morbidity were compared between the groups. A Kaplan-Meier survival curve was used to compare cumulative malignant morbidity incidence of the offspring. A Weibull regression model was used to control for confounders. During the study period, 201,738 deliveries met the inclusion criteria. Of them, 16.3% (n = 32,804) occurred in mothers aged 35 years or more (35-39 years old n = 26,145, 79.7%; 40-50 years old n = 6659, 20.3%). In the Weibull regression model, advanced maternal age exhibited no association with general malignant morbidity in the offspring up to 18 years of age (mothers aged 35-39: adjusted HR 1.06, 95% CI 0.76-1.48, p = 0.727; mothers aged 40-50: adjusted HR 0.73, 95% CI 0.36-1.46, p = 0.373). For leukemia, the regression model exhibited an independent association in maternal ages of 35-39 (adjusted HR 2.23, 95% CI 1.34-3.69, p = 0.002)., Conclusion: Advanced maternal age does not appear to raise the risk for future malignancy in the offspring up to the age 18 years. The specific nature of the association between maternal age and leukemia of the offspring necessitates further investigation. What is Known: • Advanced maternal age is associated with a marked elevation in the risk of different pregnancy complications and adverse pregnancy outcomes. What is New: • Advanced maternal age does not appear to raise the risk for future malignancy in the offspring up to the age 18 years. • Leukemia of the offspring may be associated with advanced maternal age although the specific nature of the association necessitates further investigation.

Aims: To assess the implications of gestational diabetes mellitus (GDM) on long-term respiratory related hospitalizations of the offspring., Methods: A population-based cohort analysis including singleton pregnancies delivered between the years 1991 to 2014 in a tertiary referral hospital was conducted. Incidence of hospitalizations (up to age 18 years) due to various respiratory diseases was compared between offspring of GDM-complicated pregnancies and normoglycemic pregnancies. Kaplan-Meyer curves were used to assess cumulative hospitalization incidence. Cox proportional hazards model was used to control for baseline selected confounders., Results: During the study period 216,197 deliveries met the inclusion criteria. Of those, 4.7% (n = 10,184) were complicated by GDM. In most of the investigated respiratory diseases, no significant differences were found between offspring of both groups. Nonetheless, obstructive sleep apnea-related hospitalization rate was higher among the GDM group, an association which proved to be independent of potential confounders with an adjusted hazard ratio of 1.26 (95% CI 1.02-1.55; p = 0.036)., Conclusion: Gestational diabetes mellitus does not appear to be associated with long-term respiratory hospitalizations of the offspring other than obstructive sleep apnea-related hospitalizations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Rising rates of cesarean deliveries worldwide prompt the evaluation of long-term morbidity to the offspring. In this retrospective cohort study, we evaluated whether cesarean delivery influences the development of childhood malignancies. We identified an association of cesarean delivery with acute lymphoblastic leukemia in children, suggesting prudence in the recommendation of cesarean delivery for nonmedically indicated cases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring., Methods: A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999-2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders., Results: The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5-2.9; p < 0.001; Kaplan-Meier log-rank test p < 0.001)., Conclusion: Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We aimed to investigate the effect of failed vacuum delivery leading to an emergency cesarean delivery on the long-term pediatric hematologic morbidity of the offspring., Study Design: In this population-based cohort study, the risk of long-term hematologic morbidity (up to the age of 18 y) was evaluated in children born following successful vacuum vaginal delivery, as compared with that of children born following a failed procedure leading to an emergent cesarean delivery. Multiple pregnancies and fetuses with congenital malformations were excluded. A Kaplan-Meier survival curve was constructed to compare cumulative pediatric hematologic morbidity, and a Cox proportional hazards model was used to control for confounders., Results: A total of 7978 neonates met the inclusion criteria. Vacuum delivery was successful in 7733 cases (96.9%), whereas it failed in 245 cases (3.1%). Total hematologic morbidity of the offspring up to 18 years of age was comparable between the groups (1.6% vs. 0.8%, P=0.8). The Kaplan-Meier survival curve showed no difference in the cumulative incidence of total hematologic morbidity (log rank, P=0.22). In the Cox regression model, failed vacuum delivery was not independently associated with long-term hematologic morbidity, as compared with a successful procedure, while adjusting for multiple confounders (adjusted hazards ratio [HR], 1.8; 95% confidence interval, 0.7-5.0; P=0.25)., Conclusions: Failed vacuum delivery does not seem to be associated with an increased risk for pediatric hematologic morbidity of the offspring up to 18 years of age.

Background: The aim of this study was to investigate whether patients with endometriosis who achieved pregnancy have a higher risk for pregnancy complications and adverse perinatal outcomes as compared to patients without endometriosis., Methods: The study compared obstetrical and perinatal outcomes of women with and without endometriosis who delivered between 1988-2013 at the Soroka University Medical Center. The study population included 504 deliveries divided into the following groups: 1) women with endometriosis (N.=35); and 2) without endometriosis (N.=467). Endometriosis was diagnosed by laparoscopy or laparotomy. Multiple logistic regression models were used to control for confounders., Results: No significant increase in obstetrical complications was noted in the endometriosis group, but significantly higher rates of cesarean sections. Perinatal outcomes were comparable between the groups., Conclusions: In our population, endometriosis was not found as a risk factor for obstetrical complications or adverse perinatal outcomes. Larger population based cohort studies are needed to clarify the relationship between endometriosis and adverse pregnancy outcomes.

Objective: To determine whether early term delivery (at 37 0/7 -38 6/7 weeks of gestation) is associated with long-term pediatric cardiovascular morbidity of the offspring., Study Design: A population-based cohort analysis was performed including all term deliveries occurring between 1991 and 2014 at a single tertiary medical center. Gestational age at delivery was subdivided into early term (37 0/7 -38 6/7 ), full term (39 0/7 -40 6/7 ), late term (41 0/7 -41 6/7 ) and post term (≥42 0/7 ) delivery. Hospitalizations of children up to the age of 18 years involving cardiovascular morbidity were evaluated, including structural valvular disease, hypertension, arrhythmias, rheumatic fever, ischemic heart disease, pulmonary heart disease, perimyoendocarditis, congestive heart failure, and others. Kaplan-Meier survival curves were used to compare cumulative hospitalization incidence between groups. A multivariable Weibull parametric model was used to control for confounders., Results: During the study period, 223 242 term singleton deliveries met the inclusion criteria. Of them, 24% (n = 53 501) occurred at early term. Hospitalizations involving cardiovascular morbidity were significantly more common in children delivered at early term (0.7%) as compared with those born at full (0.6%), late (0.6%), or post term (0.5%; P = .01). The survival curve demonstrated a significantly higher cumulative incidence of cardiovascular-related hospitalizations in the early term group (log-rank P <.001). In the Weibull model, early term delivery was found to be an independent risk factor for cardiovascular-related hospitalization as compared with full term delivery (adjusted HR, 1.16; 95% CI, 1.01-1.32; P = .02)., Conclusion: Early term delivery is independently associated with pediatric cardiovascular morbidity of the offspring as compared with offspring born at full term., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate risk factors and pregnancy outcome of spontaneous vs in-vitro fertilization (IVF) twins complicated with preeclampsia., Study Design: A retrospective population-based cohort study comparing maternal and neonatal outcome in IVF vs spontaneously conceived twins was conducted. Deliveries occurred in a tertiary medical center between the years 1988 and 2010. Women who conceived after ovulation induction and those with chronic hypertension were excluded from the study. Multiple logistic regression models were used to control for confounders., Results: The study population included 4428 twin pregnancies, of these 314 (7.1%) had preeclampsia; 64 (20.3%) were IVF twins and 250 (79.7%) were spontaneous twins. Preeclampsia was more common in IVF compare to spontaneous twins (13.8 vs 7.6%, OR = 1.81, CI = 1.50-2.17, P < 0.001). The mothers of IVF twins were significantly older, and were more likely to be nulliparous. The rate of cesarean delivery was higher among IVF twins. The mean gestational age at delivery and the mean birth weight were significantly lower in IVF twins. While controlling for confounders using a multivariate analysis, IVF was found as an independent risk factor for preterm delivery in twin pregnancies with preeclampsia. However, there was no difference in the perinatal mortality or 5 min Apgar scores < 7 between the two groups., Conclusion: Preeclampsia is more common in IVF twins compared to spontaneous twin pregnancies. IVF twins with preeclampsia are at an increased risk for cesarean delivery, preterm delivery and low birth weight.

Background: Although concerns have been raised regarding the long-term health risks of offspring conceived following fertility treatments, limited information is available regarding their health status beyond the neonatal period. We aimed to evaluate the risk of long-term eruptive dermatological morbidity among children born following fertility treatments as compared to those conceived spontaneously., Methods: A population-based cohort study was conducted, including all singleton deliveries occurring between the years 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations and multiple gestations were excluded. Children delivered following fertility treatment pregnancies and spontaneous pregnancies were compared. Hospitalizations of the offspring up to the age of 18 years involving cutaneous eruptions were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence and a Cox regression model to control for confounders., Results: During the study period, 242,187 singleton deliveries met the inclusion criteria, 1.8% of which were following fertility treatments (n = 4324). Eruptive dermatological morbidity of the offspring up to the age of 18 years was significantly more common in the fertility treatment group (1.5%) as compared to spontaneous pregnancies (1.1%; P = 0.023). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of eruptive dermatological morbidity following fertility treatments (log-rank P = 0.007). Using the Cox regression model, while controlling for multiple confounders, fertility treatment was noted as an independent risk factor for long-term pediatric eruptive dermatological morbidity (adjusted HR = 1.43, CI 1.12-1.83, P = 0.004)., Conclusion: Singletons conceived via fertility treatments appear to be at an increased risk for long-term eruptive dermatological morbidity., (© 2018 The International Society of Dermatology.)

Problem: Recurrent pregnancy loss (RPL) potentially involves an abnormal maternal inflammatory response. We investigated whether children of mothers with a history of RPL are at an increased risk for childhood gastrointestinal (GI) morbidity, with a specific focus on inflammatory bowel diseases (IBD)., Method of Study: A population-based cohort analysis comparing the risk for long-term GI morbidity in children born to mothers with and without a history of RPL. Gastrointestinal (GI) morbidity included hospitalizations involving a pre-defined set of ICD-9 codes., Results: During the study period, 242 186 newborns met the inclusion criteria; 5% of which were offspring to mothers with a history of RPL. Gastrointestinal morbidity was significantly more common in the RPL group (6.6% vs 5.3%). Specifically, offspring to mothers with a history of RPL had significantly higher rates of IBD (2.1% vs 1.7%)., Conclusion: Maternal history of RPL is associated with an increased risk for pediatric GI morbidity in the offspring., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients' preferences in choosing obstetricians/gynecologists are widely investigated, but studies among traditional populations are lacking. Bedouins comprise a traditional Arab Muslim society in the Arabian Peninsula (Saudi Arabia), The Levant (Syria, Jordan and Israel) and North Africa (Egypt). Most of the Bedouins in Israel populate several villages, mostly in the southern part of the country. This cross-sectional study compared 200 Bedouin and 200 Jewish women who responded to an anonymous questionnaire. Queried on gender alone, more Bedouin responders preferred female obstetricians/gynecologists (59.5 vs. 33% Jewish responders, p value <0.0001). Bedouin women preferred a female obstetrician/gynecologist for intimate procedures [feeling more comfortable (66.3%) and believing that females were more gentle (50%)]. However, they and the Jewish participants ranked ability, experience and knowledge as the top 3 qualities of an obstetrician/gynecologist, putting reputation in 4th place and gender in 5th place. Bedouin women strongly preferred female obstetricians/gynecologists, although professional skills were an important factor in their choice of caregiver. The ideal obstetrician/gynecologist for Bedouin women would be a skilled, knowledgeable, and experienced female.

Objective: To evaluate the impact of inadequate prenatal care on long-term morbidity among the offspring of an ethnic minority population., Methods: A retrospective population-based cohort analysis was performed among all Bedouin women with singleton pregnancies who delivered in a tertiary medical center in Israel between January 1, 1991, and January 1, 2014. Morbidity was defined as pediatric hospitalization across six distinct disease categories before 18 years of age. The cumulative morbidity rates were compared for offspring born following pregnancies with either inadequate (<3 visits to prenatal care facility) or adequate prenatal care., Results: Overall, 127 396 neonates were included; 19 173 (15.0%) were born following inadequate prenatal care. Pediatric hospitalizations for all morbidities other than cardiovascular ones were less frequent among the inadequate prenatal care group than the adequate prenatal care group (P<0.05). Survival curves demonstrated a lowered cumulative incidence for all morbidities in the inadequate prenatal care group, with the exception of cardiovascular disease., Conclusion: Inadequate prenatal care correlated with reduced pediatric hospitalization rates among offspring, possibly owing to a lack of child healthcare service utilization within the Bedouin population., (© 2017 International Federation of Gynecology and Obstetrics.)

Purpose: To investigate whether children born with isolated single umbilical artery (iSUA) at term are at an increased risk for long-term pediatric hospitalizations due to respiratory morbidity., Methods: Design: a population-based cohort study compared the incidence of long-term, pediatric hospitalizations due to respiratory morbidity in children born with and without iSUA at term., Setting: Soroka University Medical Center., Participants: all singleton pregnancies of women who delivered between 1991 and 2013., Main Outcome Measure(s): hospitalization due to respiratory morbidity., Analyses: Kaplan-Meier survival curves were used to estimate cumulative incidence of respiratory morbidity. A Cox hazards model analysis was used to establish an independent association between iSUA and pediatric respiratory morbidity of the offspring while controlling for clinically relevant confounders., Results: The study included 232,281 deliveries. 0.3% were of newborns with iSUA (n = 766). Newborns with iSUA had a significantly higher rate of long-term respiratory morbidity compared to newborns without iSUA (7.6 vs 5.5%, p = 0.01). Using a Kaplan-Meier survival curve, newborns with iSUA had a significantly higher cumulative incidence of respiratory hospitalizations (log rank = 0.006). In the Cox model, while controlling for the maternal age, gestational age, and birthweight, iSUA at term was found to be an independent risk factor for long-term respiratory morbidity (adjusted HR = 1.39, 95% CI 1.08-1.81; p = 0.012)., Conclusion: Newborns with iSUA are at an increased risk for long-term respiratory morbidity.

To compare pregnancy outcomes of immigrants from Former-Soviet-Union (FSUI) and Ethiopia (EI) to those of Jewish-native-born Israelis (JNB), in context of universal health insurance. Birth outcomes of all singletons born in Soroka-University Medical-Center (1998-2011) of EI (n = 1,667) and FSUI (n = 12,920) were compared with those of JNB (n = 63,405). Low birthweight rate was significantly higher among EI (11.0 %) and slightly lower (7.0 %) among FSUI, compared to JNB (7.5 %). Preterm-delivery rates were similar to those of JNB. Both immigrant groups had significantly (p < 0.001) higher rates of perinatal mortality (PM) than JNB (21/1000 in EI, and 11/1000 in FSUI, compared to 9/1000). Using multivariable GEE models both immigrant groups had significantly increased risk for PM; however, EI had twice as much FSUI origin (OR 2.3, 95 % CI 1.6-3.4, and OR 1.3, 95 % CI 1.1-1.6, respectively). Universal health care insurance does not eliminate excess PM in immigrants, nor the gaps between immigrant groups.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Prematurity is known to be associated with high rates of endocrine and metabolic complications in the offspring. Offspring born early term (37-38 6/7 weeks' gestation) were also shown to exhibit long-term morbidity resembling that of late preterm, in several health categories., Objective: We aimed to determine whether early term delivery impacts on the long-term endocrine and metabolic health of the offspring., Study Design: A population-based cohort analysis was performed, including all term singleton deliveries occurring from 1991 through 2013 at a single regional tertiary medical center. Congenital malformations and multiple pregnancies were excluded. Gestational age upon delivery was subdivided into early term deliveries and deliveries occurring at full term and later (≥39 weeks' gestation, comparison group). Endocrine and metabolic morbidity (including diabetes, obesity, hypoglycemia, hyperlipidemia, and hypothyroidism) of the offspring, up to the age of 18 years, was evaluated according to hospitalization files. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence. A Weibull parametric survival model was used to control for time to event, siblings, and other confounders., Results: During the study period 225,260 term deliveries met the inclusion criteria. Of them, 24% (n = 54,073) occurred at early term. Endocrine and metabolic morbidity was significantly more common in the early term group (0.51% vs 0.41%, P = .003). Specifically, overweight and obesity were more common among the early term group (P = .002). Differences were more prominent among children >5 years, who exhibited higher rates of type 1 diabetes mellitus, as well as obesity, when born at early term (P < .05). The survival curves demonstrated higher cumulative incidence of total endocrine and metabolic morbidity in the early term group. Using the Weibull parametric survival model, while controlling for siblings, maternal diabetes, hypertension, labor induction, and Apgar score, early term delivery exhibited an independent association with long-term childhood endocrine and metabolic morbidity of the offspring (adjusted hazard ratio, 1.17; 95% confidence interval, 1.01-1.34) and more so for age >5 years (adjusted hazard ratio, 1.30; 95% confidence interval, 1.08-1.56)., Conclusion: Deliveries occurring at early term are associated with higher rates of long-term pediatric endocrine and metabolic morbidity of the offspring as compared with deliveries occurring at a later gestational age. This association may be due to absence of full maturity of the hormonal axis in early term neonates or, alternatively, suggest an underlying fetal endocrine dysfunction as the initial mechanism responsible for spontaneous early term delivery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Human and animal studies have found an association between prenatal androgen exposure and the anogenital distance (AGD). The aims of this study were to study the association between female AGD, reproductive health and background characteristics., Methods: This was a cross sectional study, in which AGD were measured in 300 pregnant women who were recruited early during the first stage of labor. Demographic and health characteristics were collected and studied in association with AGD measurements., Results: AGD presented with normal distribution (mean 40.3mm±10.7) and was positively associated with maternal age (beta=0.032, 95%CI 0.007-0.05, p=0.01) and negatively associated with infertility treatments (beta=-1.06, 95%CI -1.99 to -0.12, p=0.03). AGD was not associated with parity, ethnicity, height and other characteristics., Conclusions: Adult females AGD is associated with age and fertility problems. Adult female AGD, used as a marker of early life exposure to EDCs, is possibly associated with reproductive characteristics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To identify trends in preterm delivery (PTD) as well as seasonality, temporal variation and the effect of heat stress on its incidence., Materials and Methods: In this retrospective population-based study, we included all deliveries taking place at the Soroka University Medical Center between the years 1988-2012. A time series database was built including meteorological factors and the number of spontaneous versus induced PTDs for each day. Data were analyzed using time-series analyses., Results: During the study period, 263 709 deliveries occurred, 7.9% of which were preterm. Spontaneous PTD rate steadily decreased, while induced PTD rate increased. A significant annual and seasonal variation was noted in PTD incidence. A significant higher incidence of spontaneous PTD was demonstrated during the summer period with an incidence rate ratio (IRR) of 4.1 (95%CI: 3.1-5.5; p < 0.001). This trend was not significant for induced PTD. A significant linear association was noted between the heat-stress index and the rates of spontaneous (IRR = 1.07, 95%CI: 1.05-1.10; p < 0.001) but not induced PTDs., Conclusions: Spontaneous PTD is more common during the summer and its rate is declining steadily over the past decades. Increased outdoor temperature has a significant effect on the incidence of spontaneous, but not induced, PTD.

Objective: We evaluated the possible association between fetal gender and long-term pediatric neurological morbidity., Methods: We performed a population-based retrospective cohort analysis comparing the risk of long-term neurological morbidity (up to age 18 years) of children born during the years 1991 to 2013 according to their gender. Neurological morbidity evaluated included hospitalizations in childhood involving pervasive developmental disorder, obstructive sleep apnea, cerebral palsy, epilepsy, and infantile spasms and disorders of eating as recorded in the hospital files. Multiple pregnancies and fetal congenital malformations were excluded. Kaplan-Meier survival curves were constructed to compare the cumulative neurological morbidity over the study period. A Cox proportional hazards model was used to control for obstetrical confounders, including gestational age at birth, birth weight, and maternal factors., Results: During the study period, 240,953 newborns were included in the long-term analysis: 51.0% (n = 122,840) males and 49.0% (n = 118,113) females. Hospitalizations for neurological problems (up to age 18 years) were significantly more common in males compared with females (1.1% vs 0.8%, respectively, odds ratio 1.31, 95% confidence interval 1.2 to 1.4, P < 0.001). Specifically, pervasive developmental disorder and obstructive sleep apnea were found to be significantly more common in males, and cerebral palsy reached borderline significance (0.1% vs 0.04%, odds ratio 1.39, 95% confidence interval 0.9 to 1.9, P = 0.06). The Kaplan-Meier survival curves demonstrated males to have a significantly higher cumulative incidence of total neurological morbidity as well as of pervasive developmental disorder and obstructive sleep apnea (all log-rank test P values <0.001). In the Cox regression model, male gender exhibited an independent association with long-term neurological morbidity, while adjusting for birth weight, gestational age, and other confounding variables (adjusted hazard ratio 1.29, 95% confidence interval 1.2 to 1.4, P < 0.001)., Conclusion: Males are at an increased risk for pediatric neurological morbidity independent of gestational age at birth and birth weight., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate whether patients with a history of gestational diabetes mellitus (GDM) have an increased risk for long-term ophthalmic morbidity., Methods: Design a population-based study compared the incidence of long-term maternal ophthalmic morbidity in a cohort of women with and without a history of GDM. Setting Soroka University Medical Center., Participants: All singleton pregnancies of women who delivered between 1988 and 2013. Main outcome measure(s) Diagnosis of ophthalmic morbidity. Analyses A Kaplan-Meier survival curve was used to estimate cumulative incidence of ophthalmic morbidity. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HR) for ophthalmic morbidity., Results: During the study period, 104,751 deliveries met the inclusion criteria; 9.4% (n = 9888) of which occurred in patients with a diagnosis of GDM during at least one of their pregnancies. Patients with GDM had a significantly higher incidence of ophthalmic morbidity such as glaucoma, diabetic retinopathy, and retinal detachment compared with controls (0.1 vs. 0.02%, p < 0.001; 0.2 vs. 0.04%, p < 0.001; 0.2 vs. 0.1%, p < 0.001, respectively). Patients with concurrent GDM and preeclampsia had a significantly higher incidence of total ophthalmic complications compared to patients with GDM only (1 vs. 0.6%, respectively, p < 0.001). Using Kaplan-Meier survival curve, patients with a previous diagnosis of GDM had significantly higher cumulative incidence of ophthalmic morbidity (p < 0.001, log-rank test). In the Cox proportional hazards model, a history of GDM remained independently associated with ophthalmic morbidity (adjusted HR 2.0; 95% CI 1.5-2.8; p < 0.001)., Conclusions: GDM is an independent risk factor for long-term maternal ophthalmic morbidity.

Objective: To address risk factors and perinatal outcomes after vacuum-assisted delivery (VAD) due to non-progressive labor (NPL) 2nd stage, and to assess its impact on the subsequent delivery., Methods: A retrospective, population-based cohort study was conducted in a tertiary medical center. Maternal characteristics, and maternal and neonatal outcomes of singleton pregnancies that resulted in VAD due to NPL 2nd stage were compared to those that resulted in VAD due to other indications. Multiple logistic regression models were constructed., Results: Out of 202,462 singleton deliveries, 3.4% were delivered using VAD. Of these, 1928 VAD due to NPL 2nd stage and 4985 VAD due to other indications were identified. Independent risk factors for VAD due to NPL 2nd stage were identified: advanced gestational age, pre-eclampsia, and labor induction. VAD due to NPL 2nd stage in the index pregnancy was noted as an independent risk factor for NPL 1st stage and NPL 2nd stage during the subsequent pregnancy., Conclusion: VAD due to NPL 2nd stage results in adverse perinatal outcome in the index and subsequent pregnancies. VAD due to NPL 2nd stage in the index pregnancy is an independent risk factor for NPL 1st stage and NPL 2nd stage during the subsequent pregnancy.

Objective: To evaluate whether offspring of women with müllerian anomalies are at an increased risk for long-term pediatric morbidity., Study Design: A population-based cohort study compared the incidence of long-term (up to the age of 18 years for offspring) hospitalizations due to cardiovascular, endocrine, neurological, hematological, respiratory and urinary morbidity of offspring to mothers diagnosed with uterine anomalies. Deliveries occurred between the years 1991 and 2013 in a tertiary medical center. Multiple pregnancies, unknown gestational age, gestational age of less than 24 weeks, perinatal mortality, and fetuses with congenital malformations were excluded. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence. Survival analysis for clustered data was performed for each major-system pediatric hospitalization., Results: During the study period 253,808 deliveries met the inclusion criteria; 0.48% (n=1230) of which occurred in women diagnosed with müllerian anomalies. In the Kaplan-Meier survival curve, children born to mothers with müllerian anomalies did not have a significantly different cumulative incidence of any of the long-term pediatric morbidities, compared with the comparison group. In the multivariable survival analysis for clustered data, after adjustment of maternal clusters, maternal age, gestational age and birthweight, müllerian anomalies did not exhibit an independent association with long-term morbidities of the offspring., Conclusion: Müllerian anomalies do not appear to have an independent impact on long-term morbidity of the offspring., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To investigate whether women who had a preterm delivery (PTD) are at an increased risk of subsequent long term maternal kidney disease., Study Design: A population-based study compared the incidence of long-term maternal kidney disease in a cohort of women with and without previous PTD. Deliveries occurred during a 25 years period, with a mean follow-up duration of 11.2 years., Results: Of 99 338 deliveries of women, 16 364 (16.4%) occurred in patients who had at least one PTD. A significant dose response was found between the number of previous PTDs and the gestational age at birth of the PTDs and future risk for renal-related hospitalizations. Patients with either spontaneous or indicated PTD had higher rates of renal-related hospitalizations (0.2% versus 0.1% OR= 2.6; 95%CI: 1.7-3.9, p  <0.001 and 0.5% versus 0.2% OR 3.41; 95%CI: 1.7-6.5, p  < 0.001, respectively). In a Cox proportional hazards model, PTD was independently associated with long-term maternal renal-related hospitalizations., Conclusions: PTD is an independent risk factor for long-term maternal kidney disease.

Objective  This study aims to evaluate the role of a family history of preterm delivery on the risk of preterm delivery in the next generation. Study Design  A retrospective population-based study was conducted. Perinatal information was gathered from 2,303 familial triads, composed of mothers (F 1 ), daughters (F 2 ), and children (F 3 ). All births occurred in the same regional medical center between the years 1991 and 2013. Statistical analysis using logistic regression was performed to define the risk of F 2 delivering a preterm baby (F 3 ) if she was born preterm herself, and then to define the risk of F 2 delivering preterm if her mother (F 1 ) gave birth preterm during any of her birthing events. Results  The risk for preterm delivery of the F 2 parturient was 34% greater if their mother (F 1 ) at any of her births had delivered preterm, controlling for parity, maternal age at delivery, and preeclampsia (adjusted odds ratio: 1.34, 95% confidence interval: -1.01 to 1.77; p  = 0.042). Conclusion  The family history of preterm delivery is an independent risk factor for preterm delivery. The family history includes the mother as well as one of the mother's sisters (F 2 generation) being born preterm., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Studies have questioned the long-term health effects of offspring conceived after fertility treatments., Methods: We aimed to evaluate whether an association exists between mode of conception (in vitro fertilization, ovulation induction, or spontaneous pregnancy) and neoplasm risk (both benign and malignant tumors) among the offspring; we observed the offspring for up to 18 years., Study Design: A population-based cohort analysis was performed that compared the risk for neoplasms among children (up to the age of 18 years) based on mode of conception. Neoplasm diagnoses were based on hospital records of the same single tertiary center in the region. All singletons born during from 1991-2013 and discharged alive were included in the study. Offspring with congenital malformations were excluded from the analysis. Kaplan-Meier survival curves were constructed to compare cumulative neoplasms incidence; multivariable survival analyses were used to control for confounders that included gestational age, pregnancy complications, and maternal factors., Results: During the study period, 242,187 newborn infants met the inclusion criteria: 2603 (1.1%) were conceived after in vitro fertilization; 1721 (0.7%) were conceived after ovulation induction treatments, and 237,863 (98.3%) were conceived spontaneously. During the follow-up period (median, 10.55 years), 1498 neoplasms(0.6%) were diagnosed. Incidence density rate for neoplasms was higher among children conceived either after in vitro fertilization (1.5/1000 person years) or ovulation induction treatments (1.0/1000 person years), as compared with naturally conceived children (0.59/1000 person years; Kaplan-Meier log rank, P<.001). The association between in vitro fertilization and total pediatric neoplasms and the association between any fertility treatments and malignancies remained significant; we controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age (adjusted hazard ratio, 2.48; 95% confidence interval, 1.71-3.50; and adjusted hazard ratio, 1.96; 95% confidence interval, 1.14-3.36, for all neoplasms and all malignancies, respectively)., Conclusion: Children conceived after fertility treatments are at an increased risk for pediatric neoplasms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the association between a history of prepregnancy obesity and a woman's future long-term risk for the development of female malignancies. A population-based study compared the incidence of long-term female malignancies in a cohort of consecutive women with and without a diagnosis of prepregnancy obesity. Deliveries occurred between the years 1988 and 2013, with a mean follow-up duration of 11.6 years. Women with known malignancies before the index pregnancy and known genetic predisposition for malignancy were excluded from the study. Female malignancies were divided according to specific type (ovary, uterine, breast, and uterine cervix). A Kaplan-Meier survival curve was used to estimate the cumulative incidence of malignancies. A Cox proportional hazards model was used to estimate the adjusted hazard ratios for female malignancy. During the study period, 106 251 deliveries fulfilled the inclusion criteria; 2.2% (n=2360) occurred in patients with a history of prepregnancy obesity. During the follow-up period, patients with prepregnancy obesity had a significantly increased risk for hospitalization because of female malignancies as a group and specifically ovarian and breast cancer. Using a Kaplan-Meier survival curve, patients with a previous diagnosis of prepregnancy obesity had a significantly higher cumulative incidence of female malignancies. Using a Cox proportional hazards model, adjusted for confounders such as gestational diabetes mellitus and maternal age, prepregnancy obesity remained independently associated with long-term risk for female malignancies (adjusted hazard ratio: 1.4; 95% confidence interval: 1.1-1.9; P=0.045). Prepregnancy obesity is an independent risk factor for long-term female malignancies such as ovarian and breast cancer.

Objective: To investigate whether patients with a history of gestational diabetes mellitus (GDM) have an increased future risk for female malignancies., Study Design: A population-based study compared the incidence of long-term female malignancies (ovary, uterine, breast, and uterine cervix) in a cohort of women with and without a diagnosis of GDM. Deliveries occurred between the years 1988-2013, with a mean follow-up duration of 12 years. Women with known malignancies prior to the index pregnancy were excluded. Kaplan-Meier survival curve was used to estimate cumulative incidence of malignancies. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HR) for female malignancy., Results: During the study period, 1,04,715 deliveries met the inclusion criteria; 9.4% (n = 9893) occurred in patients with a history of GDM in at least one of their pregnancies. During the follow-up period, patients with GDM had a significantly increased risk of being diagnosed with female malignancies, including ovarian, uterine, and breast cancer. Using a Kaplan-Meier survival curve, patients with a previous diagnosis of GDM had a significantly higher cumulative incidence of female malignancies. Using a Cox proportional hazards model, adjusted for confounders, such as parity, maternal age, and fertility treatments, a history of GDM remained independently associated with female malignancies (adjusted HR, 1.3; 95% CI 1.2-1.6; P = 0.001)., Conclusion: Patients with a history of GDM have an increased risk for future breast, ovarian, and uterine malignancies.

Background: Preterm delivery may affect the development of the upper airways resulting in a higher risk of obstructive sleep apnoea (OSA). We investigated whether children born at early term (37-38 6/7 weeks' gestation) are at an increased risk for childhood OSA as compared with those born later., Methods: In this population-based cohort analysis all singleton deliveries occurring between 1991-2013 at a single regional tertiary medical centre were included. Gestational age upon delivery was sub-divided into: early preterm (<33 6/7 weeks' gestation), late preterm (34-36 6/7), early term, full term (39-40 6/7), late term (41-41 6/7), and post term (>42 0/7). Incidence of OSA related hospitalizations of the offspring, up to the age of 18 years, was evaluated. A survival curve and a Cox model were used to assess the association., Results: During the study period 240 953 deliveries met the inclusion criteria. OSA hospitalization (n = 1320) rates decreased as gestational age increased from 1.1% in the early preterm group, 0.8% in late preterm, 0.7% at early term, 0.5% in full term, 0.4% in late term, to 0.3% in post term born children. In the Cox regression, early term delivery exhibited an increased risk for paediatric OSA (adjusted hazard ratio (HR) 1.3 95% Confidence interval (CI) 1.2, 1.5) while late and post term deliveries were associated with significantly lower OSA risk when compared with full term (HR 0.8 95% CI 0.6, 0.9 and HR 0.6 95% CI 0.4, 0.8, respectively)., Conclusions: Early term deliveries are associated with higher rates of paediatric OSA, which decrease gradually as gestational age advances., (© 2017 John Wiley & Sons Ltd.)

Objective: To determine whether fetal heart rate (FHR) monitoring categories during the 1st and 2nd stage of labor can predict arterial cord pH <7.2., Materials and Methods: A case control study was conducted including 653 consecutive term deliveries (37 weeks gestation and above) that were divided according to fetal pH ≤ 7.2 (n = 315) and fetal pH > 7.2 (n = 338). Deliveries occurred during the year 2013 in tertiary medical center, where arterial cord pH is routinely taken after birth. Intrapartum FHR monitoring categorization was defined according to the ACOG committee guidelines by two obstetricians. Multivariable models were constructed to control for confounders., Results: Variable decelerations, late decelerations and bradycardia during the 1st and 2nd stages of labor were significantly higher in group of deliveries ended in cord pH < 7.2 compared with group of deliveries ended in cord pH > 7.2. A significant association was observed between category 2 and 3 during the 1st stage of labor and pH ≤ 7.2. However, while controlling for FHR category 3 at the 2nd stage of labor, 1st stage categorization lost its association with pH <7.2, and only category 3 during the 2nd stage were noted as an independent risk factor for acidosis., Conclusion: FHR monitoring category 3 during the 2nd stage of labor is an independent predictor of fetal acidosis as expressed by arterial cord pH < 7.2.

Objective: Newborns exhibit the lowest immediate respiratory morbidity rates when born following 39 completed weeks of gestation. We sought to determine whether early-term delivery (37-38 + 6 weeks' gestation) impacts on long-term pediatric respiratory morbidity., Study Design: In this population-based prospective cohort analysis, all term singleton deliveries occurring between 1991 and 2013 at a single tertiary medical center were included. Gestational age upon delivery was sub-divided into: early (37-38 + 6 weeks' gestation), full (39-40 + 6 weeks' gestation), late (41-41 + 6 weeks' gestation), and post-term (>42 weeks) deliveries. The incidence of long-term hospitalizations (up to the age of 18 years) of the offspring due to a set of predefined respiratory morbidities was evaluated. Survival curves were used to compare cumulative morbidity incidence. A Cox hazards regression model was used to control for confounders., Results: During the study period, 229,142 term deliveries met the inclusion criteria. Of those, 24% (n = 55,202) occurred at early term. Hospitalizations up to the age of 18 years, as a result of complications in the respiratory system were significantly more common in the early-term group as compared with full and late-term delivery groups. In the Cox regression model, while controlling for multiple confounders, early-term delivery exhibited an independent association with long-term respiratory morbidity (adjusted HR = 1.24, CI 1.19-1.29, P < 0.001)., Conclusion: Deliveries occurring at early term are associated with higher rates of pediatric respiratory hospitalizations compared with full and late-term deliveries. Pediatr Pulmonol. 2017;52:198-204. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)