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We aimed to study the association between fetal gender in twin pregnancies and the risk for childhood infectious morbidity of the offspring.A population-based cohort analysis was performed comparing total and subtypes of infectious related pediatric hospitalizations among males versus females offspring of twin pregnancies. The analysis included all dichorionic twins born between the years 1991-2021. A Kaplan-Meier survival curve was used to compare the cumulative infectious morbidity incidence, and a Cox proportional hazards model was constructed to adjust for confounders.The study population included 4222 newborns (2111 males and 2111 females). Males had higher rates of infectious-related hospitalizations using a Cox proportional hazards model, an independent association was shown between male gender and infectious related hospitalizations of the offspring (Adjusted HR = 1.2, 95% CI: 1.1-1.4; p 0.001).Male gender in twin pregnancies is associated with an increased risk for long-term pediatric infectious morbidity.

Maternal condyloma acuminata infection may be vertically transmitted to the offspring during pregnancy and childbirth. Our study aimed to investigate the possible impact of maternal condyloma acuminata infection in pregnancy on offspring respiratory and infectious morbidity.A population-based cohort analysis including all singleton deliveries occurring between 1991 and 2014 at a tertiary medical center. Long-term infectious and respiratory morbidities were compared between children with and without exposure to maternal condyloma infection during pregnancy. A Kaplan-Meier survival curve was used to compare cumulative hospitalization rate and a Cox regression analyses to control for confounders.No significant differences were found in total respiratory and infectious related hospitalizations between the study groups. The survival curves demonstrated no difference in the cumulative incidence between the two groups in both respiratory hospitalizations (log-rank, p = 0.18) and infectious hospitalizations (log-rank, p = 0.95). Cox multivariable analyses demonstrated that exposure to maternal condyloma infection during pregnancy is not a risk factor for neither infectious (aHR 0.91, [CI] 0.49-1.69) nor respiratory (aHR 0.37, [CI] 0.09-1.51) morbidity during childhood and adolescence.Exposure to maternal condyloma infection during pregnancy does not appear to be an independent risk factor for later respiratory or infectious morbidity throughout childhood and adolescence.

To study the association between phototherapy for the treatment of neonatal jaundice and the risk of childhood neoplasms.This population-based retrospective cohort study included all infants born at ≥32 weeks of gestation at a single medical center between 1988 and 2018. The incidence of neoplastic diseases was compared between infants exposed to phototherapy and those unexposed. Kaplan-Meier curves and log-rank tests were used for cumulative incidence comparison, and multivariable Cox and Weibull survival analysis were used to adjust for confounding or clinically significant variables.The study population included 342 172 infants, of whom 18 797 (5.5%) were exposed to phototherapy. The median duration of follow-up was 9.5 years (range, birth to 18 years). Phototherapy was associated with a significantly increased risk for childhood malignancies and benign tumors (preterm birth and maternal age-adjusted hazard ratio, 1.89 [95% CI, 1.35-2.67] for malignancies and 1.27 [95% CI, 1.02-1.57] for benign tumors) Specifically, phototherapy was associated with hematopoietic cancers and leukemia (hazard ratio, 2.29 [95% CI, 1.48-3.54; P .01] for hematopoietic cancers and 2.51 [95% CI, 1.52-4.14; P .001] for leukemia), but not with solid tumors and lymphoma.Phototherapy may be associated with a slightly increased childhood risk of neoplasm. It is important to strictly follow phototherapy treatment guidelines to minimize unnecessary exposure.

(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.

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

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

OBJECTIVE To examine whether early-term delivery impacts on the long-term ophthalmic health of offspring. METHODS A retrospective population-based cohort study was conducted, including all singleton deliveries (1991-2014) occurring at a tertiary medical center. Gestational age was divided into: early prematurity, late prematurity, and early, full, late, and post term. Hospitalizations of offspring up to 18 years of age involving ophthalmic morbidity were evaluated. Survival curves compared cumulative hospitalizations and regression models controlled for confounders. RESULTS During the study period, 243 363 deliveries met the inclusion criteria. Ophthalmic-related hospitalization rates were lower among early-term born children (1.0%) as compared with early- (2.2%) and late-preterm (1.3%) born children, but higher than those in full- (0.9%), late- (0.8%), and post-term (0.8%) born offspring (P

To determine whether abdominal (open) vs. laparoscopic myomectomy affects the obstetrical outcomes of subsequent pregnancies.A retrospective cohort study was conducted at a tertiary university medi...

Intrapartum fetal death is devastating for both parents and medical caregivers. The purpose of this study was to evaluate the risk factors for intrapartum fetal death, which often influence management in subsequent pregnancies.This population-based cohort study included all singleton deliveries between the years 1991-2016 at Soroka University Medical Center. Trends over the years, risk factors for intrapartum fetal death and the effect of day of the week were examined. A generalized estimation equation (GEE) model was used to control for confounders.During the study period 344,536 deliveries were recorded, of which 251 (0.1%) suffered intrapartum fetal death. Rates did not change significantly over the years (p = 0.130, using the chi-square test for trends). Preterm delivery, placental abruption, uterine rupture, shoulder dystocia, congenital malformations, severe preeclampsia and fetal malpresentation were significantly more common in pregnancies complicated by intrapartum death. Using a GEE model; shoulder dystocia (aOR 23.8, 95% CI 9.9-57.3, p 0.005), uterine rupture (aOR 19.0, 95% CI 7.0-51.4, p 0.05), preterm delivery (aOR 11.9, 95% CI 8.6-16.5, p 0.001), placental abruption (aOR 6.2, 95% CI 4.1-9.4, p 0.001), fetal malpresentation (aOR 3.6, 95% CI 2.6-4.9, p 0.005) and congenital malformations (aOR 2.6, 95% CI 1.9-3.5, p 0.05) were all independent risk factors for intrapartum fetal death. Weekend deliveries were not at increased risk of intrapartum fetal death.Several risk factors were identified for intrapartum fetal death, with shoulder dystocia demonstrating the highest risk. Unfortunately most factors are neither preventable nor predictable and interventions to decrease the rate of intrapartum fetal death remain elusive.

To evaluate the association between prenatal maternal anemia (hemoglobin, Hb 11 g/dl) and long-term respiratory morbidity of the offspring.A retrospective population-based cohort analysis was performed at a single tertiary medical center. We include all singletons born between 1991-2014 and discharged alive. Offspring with congenital malformations were excluded. The 3 study groups were defined on maternal Hb levels on discharge: severe anemia ( 7.0 g/dl), mild to moderate anemia (7.0-11.0 g/dl) and unexposed (≥ 11.0 g/dl). Offspring respiratory morbidity was predefined on ICD-9 codes and recruited from the hospitalized medical records. A Kaplan-Meier survival curve was formed to compare the cumulative hospitalization and a multivariable Cox survival analysis was used to control for cofounders (gestational age, maternal age, diabetes, hypertensive disorders, post-partum hemorrhage and transfusion of blood products).214,305 deliveries met the inclusion criteria: 807 (0.3%) mothers had severe anemia, 105,196 (49.1%) mothers had mild-moderate anemia, and the remaining were not anemic (108,302, 50.5%). Respiratory hospitalization was significantly higher among the offspring born to anemic mothers (6.2%; 5.3% and 5.1%; p = 0.020, in the study groups). However, association between maternal anemia and respiratory-related hospitalization remained significant only among the mild-moderate anemic group (adjusted Cox hazard ratio = 1.1; 95% CI 1.05-1.14; p 0.01). The Kaplan-Meier survival analysis showed significant higher total respiratory hospitalizations in offspring according to maternal anemia status (Log Rank p-value = .001).Maternal anemia was associated with long-term respiratory morbidity of the offspring.

Maternal drug allergy has been associated with altered immune status and an inflammatory environment, which may affect the risk of future infectious diseases in the offspring.We aimed to evaluate perinatal outcomes and long-term infectious hospitalization in the offspring of women with documented drug allergy.The study was conducted at the Soroka University Medical Center (SUMC), a tertiary medical center. For perinatal outcomes, generalized estimation equation (GEE) models were used controlling for maternal age, maternal diabetes mellitus, smoking, and hypertensive disorders. The study groups were followed until 18 years of age for infectious-related hospitalizations. A Kaplan-Meier survival curve was used to compare the cumulative incidence of long-term infectious hospitalizations. A Cox proportional hazards model was conducted to control for confounders.During the study period, 243 682 deliveries met the inclusion criteria, of which 9756 (4.0%) occurred in women with documented drug allergy. Using GEE, maternal drug allergy was found to be a significant independent risk factor for hypertensive disorders, diabetes mellitus, intra-uterine growth restriction (IUGR), and preterm delivery. Offspring also had significantly higher rates of long-term infectious hospitalizations. Kaplan-Meier survival curves demonstrated significantly higher cumulative incidence rates of infectious hospitalization (log-rank p .001). In a Cox proportional hazards model, being born to a mother with documented drug allergy was independently associated with infectious hospitalization of the offspring in the long term.Maternal documented drug allergy is independently associated with an adverse perinatal outcome such as IUGR and preterm delivery and increased risk of long-term infectious hospitalization of the offspring.

To identify first pregnancy risk factors for placental abruption in subsequent pregnancy.In a population-based nested case-control study, cases were defined as women with placental abruption in their second pregnancy, and controls as women without abruption. A total of 43 328 women were included in the study, 0.4% (n = 186) of second pregnancies had placental abruption. Multivariable logistic models were used to study the association between first pregnancy complications and placental abruption in subsequent pregnancy.Having either small for gestational age, preterm delivery, pre-eclampsia or cesarean delivery during first pregnancy were independently associated with increased risk for placental abruption, and the risk was higher with any additional complication (age adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI] 1.46-2.74; aOR 3.61, 95% CI 2.23-5.86; and aOR 3.86, 95% CI 1.56-9.56, for one, two, and three or more complications, respectively).First pregnancy may serve as a window of opportunity to identify women at risk for future placental abruption.

Objective To study the association among fertility treatments, treatment protocol, and offspring neoplasm risk up to the age of 18 years. Design A population-based retrospective cohort. Setting Soroka University Medical Center (SUMC), the single tertiary medical center and in vitro fertilization (IVF) unit in southern Israel. Patient(s) All offspring born at the SUMC between the years 1995 and 2018 after IVF treatment (the exposed group) and offspring conceived spontaneously (the unexposed group). Intervention(s) The study was performed at the SUMC, the single tertiary medical center and IVF unit in southern Israel. The exposed and unexposed were matched with a ratio of 1:4, based on maternal age and calendar month of delivery. Data collection included a summary of the couple’s medical records, delivery data, and offspring neoplasm diagnoses. Main Outcome Measure(s) Offspring neoplasm of any kind and time to diagnosis in each of the groups. Result(s) A total of 1,583 exposed and 5,874 offspring were included in the study. The incidences of offspring benign neoplasm were 14 (0.9%) versus 21 (0.4%), and the incidences of malignancies were 17 (1.1%) versus 29 (0.5%) among offspring of the IVF and spontaneous groups, respectively. The association between mode of conception and offspring neoplasm risk remained significant after adjusting for confounders, including mode of delivery and pregnancy complications such as hypertensive disorder, gestational diabetes mellitus, and preterm delivery compared with spontaneously conceived offspring. Among the IVF group, the increased risk for neoplasm was found among offspring who were transferred as fresh embryos, at an earlier stage of development (cleavage stage), or after three or more aspirated oocytes. Conclusion(s) IVF treatment is associated with offspring neoplasm risk; specifically, the risk was greater among offspring who were returned as fresh embryos, at an earlier embryotic stage (cleavage stage), or after three or more aspirated oocytes.

The current study was aimed to assess whether maternal epilepsy is linked to long-term neurological morbidity of the offspring, and to examine whether maternal epilepsy is associated with adverse pregnancy outcomes. A population-based cohort study was conducted comparing perinatal outcomes of women with and without epilepsy, including long-term neurological morbidity of the offspring. Both the exposed and unexposed groups were followed up to 18 years of age for neurological-related morbidity. To assess perinatal outcomes of women with epilepsy, generalized estimation equation (GEE) models were used to control for confounders. To compare the cumulative incidence of long-term neurological morbidity a Kaplan–Meier survival curve was used. A Cox proportional hazards model was built to control for confounders. During the study period, 243,682 deliveries met the inclusion criteria; 711 (0.29%) were of mothers with epilepsy. Maternal epilepsy was noted as an independent risk factor for preterm delivery, cesarean delivery, and low birth weight using GEE models controlling for maternal age and parity. Offspring born to mothers with epilepsy had higher rates of long-term neurological morbidity (Kaplan–Meier log-rank test, p

We sought to explore whether maternal pre-pregnancy obesity is an independent risk factor for offspring respiratory morbidity during childhood. A population-based retrospective cohort analysis comparing childhood respiratory morbidity incidence in offspring to mothers with pre-pregnancy obesity (BMI ≥ 30 kg/m2) and those who had lower BMI was conducted. Respiratory diagnoses were pre-defined based on ICD-9 codes. The study population comprises of all deliveries that took place at the Soroka University Medical Center (SUMC), the sole tertiary hospital in the Negev (Southern Israel), between the years 1991–2014. A Kaplan–Meier survival curve was used for cumulative respiratory morbidity incidences over time and a Cox proportional hazards model was constructed to control for confounders. During the study period, 242,342 infants met the inclusion criteria; out of which 3290 were born to mothers with a diagnosis of pre-pregnancy obesity. Offspring to mothers with pre-pregnancy obesity had a significant higher risk for obstructive sleep apnea (OR 1.43, 95% CI 1.002–2.046) as well as a higher total risk for hospitalizations due to childhood respiratory morbidity (OR 1.21, 95% CI 1.041–1.398). The cumulative respiratory morbidity incidence over time was significantly higher in the maternal pre-pregnancy obesity group (p = 0.044). Controlling for maternal age, gestational diabetes mellitus, hypertensive disorders and gestational age, pre-pregnancy obesity remained an independent risk factor for offspring respiratory morbidity (adjusted HR = 1.175, 95% CI 1.018–1.357). Maternal pre-pregnancy obesity may create an environment leading to an increased risk for long-term offspring respiratory morbidity, and specifically obstructive sleep apnea.

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.

In this study we sought to ascertain a critical threshold of the degree of prematurity and long-term digestive morbidity of the offspring. A population-based cohort analysis was conducted, comparing long-term incidence of digestive morbidity in infants born preterm. Cases were divided into four groups according to the extremity of prematurity. Digestive morbidity included hospitalizations involving a predefined set of ICD9 codes. A Kaplan–Meier survival curve was constructed to compare cumulative incidence of digestive morbidity. A Cox proportional hazards model was used to control for confounders. During the study period 220,563 patients met the inclusion criteria. Offspring born preterm had significantly more hospitalizations due to digestive morbidity compared to term offspring. The Kaplan–Meier survival curve demonstrated significant higher cumulative incidence of long-term digestive morbidity of the offspring with decreasing gestational age (Log rank p

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

Are obstetric and perinatal complications associated with morphokinetic parameters of embryo development?This proof-of-concept pilot study included a retrospective analysis of embryo morphokinetic parameters of 85 live births following day 5 single blastocyst transfer. Kinetic variables included time interval (hours) from time of pronuclei fading (tPNf) to: time of 2 cells (tPNf-t2), 9 cells (tPNf-t9), morula (tPNf-tM), start of blastulation (tPNf-tSB), full blastocyst (tPNf-tB) and expanded blastocyst (tPNf-tEB). Multivariable logistic models were used to calculate the risk of perinatal complications after adjustment for confounders.The mean interval of tPNf-tSB was significantly longer for newborns with congenital anomalies compared with healthy newborns (79.49 ± 5.78 versus 71.7 ± 6.3, respectively, P = 0.01) and for embryos of women who had gestational diabetes mellitus compared with normoglycemic women (76.56 ± 7.55 versus 71.5 ± 6.13, respectively, P = 0.015). The mean interval of tPNf-t9 was significantly longer for low-birthweight newborns compared with normal weight (49.25 ± 5.54 versus 45.47 ± 4.77, respectively, P = 0.01). Preterm delivery was associated with several longer intervals of cell divisions compared with delivery at term (tPNf-t5: 28.76 ± 3.13 versus 26.64 ± 2.40, respectively, P = 0.01; tPNf-t6: 30.10 ± 3.05 versus 27.68 ± 2.30, respectively, P 0.001; tPNf-t7: 32.08 ± 4.11 versus 28.70 ± 2.67, respectively, P 0.001; tPNf-t8: 34.75 ± 4.95 versus 30.70 ± 4.10, respectively, P 0.001; tPNf-t9: 50.23 ± 5.87 versus 45.44 ± 4.67, respectively, P 0.001). For each of the outcomes, the association remained significant after adjusting for confounders.This study indicates that there may be a possible association between adverse perinatal outcomes and morphokinetic parameters. Larger studies are needed to establish this association.

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

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

Cesarean delivery (CD) has been recently suggested to be associated with offspring’s long-term health implications. We aimed to investigate the association between delivery mode and long-term infectious morbidity of the offspring while employing sibling matched analysis to maximize confounder control. A retrospective population-based cohort study was performed, which included all sibling deliveries occurring between 1991 and 2014 at a regional tertiary medical center. Offsprings were followed up until the age of 18 years. The study included 13,516 individuals (6758 sibling pairs): the first born was via vaginal delivery and the second via CD. Each siblings pair was considered a matched set, with the aim to perform a within-family analysis. A Kaplan–Meier survival curve was used to compare the cumulative infectious morbidity incidence and a multivariable Cox survival hazards regression model to control for confounders. Crude rates of total infectious hospitalizations were found to be significantly higher in the CD group (OR 1.25; 95% CI 1.12–1.40). Specifically, bronchiolitis (OR 2.02, 95% CI 1.56–2.63), otitis (OR 1.52, 95% CI 1.21–1.9), and gastroenteritis (OR 1.41, 95% CI 1.05–1.9) were all found to be significantly more common in the CD group. The survival curve demonstrated significantly higher cumulative infection-related hospitalization rates in the CD group (log-rank p

Objective This study aimed to investigate the possible impact of meconium-stained amniotic fluid (MSAF) on the occurrence of neurological-related hospitalizations throughout childhood and adolescence. Study Design In this population-based cohort analysis, all singleton deliveries occurring between 1991 and 2014 at the Soroka University Medical center were included and the long-term neurological-related hospitalizations were compared between children with and without MSAF during their delivery. A Kaplan-Meier survival analysis was constructed for the evaluation of cumulative hospitalization rate due to neurological morbidity over the 18 years of follow-up, and a Cox proportional hazards model was used to study the independent association between MSAF and childhood neurological morbidity while controlling for potential confounders. Results During the study period, 243,725 deliveries met the inclusion criteria; 35,897 of the cohort (15%) constituted the exposed group (MSAF), while the rest of the cohort (n = 207,828) constituted the unexposed group (no MSAF). A total of 7,543 hospitalizations due to neurological-related morbidity were documented with a rate of 3.2% (1,152) in children exposed to MSAF as compared with 3.1% (6,391) in the unexposed group (OR 1.1, 95% confidence interval 0.9–1.1, p = 0.149). The survival curve showed a comparable cumulative hospitalization rate in the MSAF-exposed group compared with the unexposed group (log rank p = 0.349). The Cox analysis, controlled for gestational diabetes and hypertension, gestational and maternal ages, demonstrated MSAF exposure not to be an independent risk factor for neurological-related hospitalizations during childhood (adjusted hazard ratio = 1.03, 0.96–1.09). Conclusion Fetal exposure to MSAF, at any gestational age, does not appear to be an independent risk factor for later neurological-related hospitalizations throughout childhood and adolescence. Key Points

Amniotic fluid abnormalities may be associated with adverse perinatal outcomes, some of which are endocrine related. To evaluate whether in utero exposure to amniotic fluid abnormalities is associated with long-term endocrine morbidity in the offspring. In this cohort study, the incidence of long-term endocrine disorders was compared between singletons exposed and non-exposed to oligohydramnios or polyhydramnios. During the study period, 195 943 newborns were included in the study, of them 2.0% (n = 4072) and 2.9% (n = 5684) were exposed to oligohydramnios and polyhydramnios, respectively. Long-term endocrine morbidity was higher among children exposed to isolated amniotic fluid disorders, as was also noted in the Kaplan–Meier survival curve (log-rank test p

BACKGROUND While the etiology in many cases of recurrent pregnancy loss (RPL) is unclear, recent evidence suggests possible immunological dysfunction, which is also implicated in the pathophysiology of many pediatric respiratory diseases. OBJECTIVE We sought to investigate whether maternal history of RPL is associated with long-term respiratory morbidity of the offspring. STUDY DESIGN A population based cohort analysis was performed comparing the risk of long-term respiratory morbidity (up to the age of 18 years) of children born to mothers with and without a history of RPL (defined as two or more losses). Respiratory morbidity included hospitalizations involving a predefined set of ICD-9 codes, as recorded in the hospital medical records. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. A Kaplan-Meier survival curve was constructed to compare cumulative respiratory morbidity, and a Cox proportional hazards model was used to control for confounders. RESULTS During the study period, 242 187 newborns met the inclusion criteria; 5% (n = 12 182) of which were offspring to mothers with a history of RPL. Respiratory morbidity was significantly more common in the exposed group (6.0% vs 4.8%, P

Objective Due to advances in medical care available for patients with congenital heart disease, these patients now have a longer life span. As a result, the number of pregnancies of mothers with congenital heart disease has increased. The purpose of the current study was to evaluate perinatal outcomes of women with congenital heart disease and to examine long-term cardiovascular morbidity of offspring to mothers with congenital heart disease. Materials and methods A population-based cohort analysis was performed including all singleton deliveries occurring between years 1991–2014 at Soroka University Medical Center. The primary exposure was defined as maternal congenital heart disease. Short-term perinatal outcomes as well as long-term cardiovascular related hospitalizations of the offspring up to the age of 18 years were compared between women with and without congenital heart disease. To compare perinatal outcomes between the two study groups, we conducted a Generalized Estimation Equation (GEE) model accounting for maternal age and multiple occurrence in the cohort, parity, fertility treatment, smoking and induction of labor. To compare cumulative long-term cardiovascular morbidity, we compared cardiovascular hospitalization incidence of offspring of mothers with and without congenital heart disease using Kaplan-Meier survival curve and Weibull regression analysis to control for maternal age, diabetes, smoking, hypertension, birth weight, and cesarean delivery. Results During the study period 243,313 deliveries met the inclusion criteria, of which 369 were of mothers with congenital heart disease. Maternal congenital heart disease was found to be an independent risk factor for low birth weight (adjusted OR = 1.5 CI 95 % 1.06–2.32, p=0.022) and cesarean delivery (adjusted OR = 1.4 CI 95 % 1.09–1.86, p = 0.008). Mothers with congenital heart disease also had higher risk for placental abruption, but it was not statistically significant (adjusted OR = 2.3 CI 95 % 0.87–6.16, p = 0.09). Long-term cardiovascular morbidity was comparable between the groups (Log rank p = 0.251; adjusted HR = 1.6 CI 95 % 0.62–4.42, p = 0.313). Conclusion In conclusion, pregnancies of women with congenital heart disease are at an increased risk for adverse short-term perinatal outcomes, such as low birth weight and cesarean delivery. However, we did not find an increase in long-term cardiovascular morbidity among offspring of these women; still this association cannot be ruled out.