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

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

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

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

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

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

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

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

Twins vs singletons-Long-term health outcomes.

INTRODUCTION: Multiple gestations are a risk factor for most pregnancy complications. The current study aimed to study whether offspring born after twin pregnancies are at increased risk for long-term health complications. MATERIAL AND METHODS: A retrospective cohort study was conducted in a large medical center, including all offspring born between the years 1991-2021, which were followed-up until 18 years of age. Hospital-based diagnoses of the offspring were categorized into main groups of morbidities: cardiac, respiratory, infectious, neurological, malignancy, and metabolic. Incidence of hospitalization with diagnoses from each main group was compared between twins and singletons, as well as time to first hospitalization. Cox proportional hazard models were used to study the association between twins vs singletons and hospitalizations by grouped morbidities, while adjusting for maternal age, ethnicity and gender, besides maternal recurrence in the cohort. RESULTS: A total of 369 478 offspring were included in the analysis; of these 11 986 (3.2%) were twins and 357 492 (96.8%) were singletons. Twins were more likely to be delivered preterm (odds ratio = 17.65, 95% CI: 16.74-18.60), by cesarean delivery and following infertility treatments. Incidence of hospitalizations with all morbidity groups was slightly, some significantly, higher among twins, including cardiac: 1.9% vs 1.5%, respiratory; 8.4% vs 7.1%, neurological: 7.7% vs 7.4%, infectious: 26.0% vs 24.1%, and malignancies: 0.7% vs 0.4%. The risk remained higher in the multivariable analyses (adjusted hazard ratios ranging between 1.09-1.75). When stratifying by gestational age at delivery, the risk for most morbidities was lower among twins vs singletons born in similar gestational ages. CONCLUSIONS: Twins as compared to singletons are at increased risk for most morbidities due to their risk of being born earlier.

Perinatal outcome and long-term hospitalization of triplets according to birth order.

PURPOSE: The association between birth order and adverse perinatal outcomes has been well studied in twin pregnancies. However, little is known about the differences in immediate perinatal outcomes as well as long-term hospitalization of the offspring in triplet pregnancies according to their birth order. As such, we aimed to assess the differences in immediate perinatal outcomes and long-term hospitalizations among triplets by their birth order. METHODS: In a retrospective hospital-based cohort study, immediate perinatal outcomes and long-term hospitalizations were compared among triplet siblings according to their birth order. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. The study groups were followed until 18 years of age for cardiovascular, respiratory, neurological, and infection-related hospitalizations. Generalized estimation equation (GEE) models were used to control for confounders. Kaplan-Meier survival curves were used to compare cumulative long-term hospitalization incidences and Cox proportional hazards models were performed to control for confounders. RESULTS: The study included 117 triplet deliveries. Rates of small for gestational age (SGA) infants increased linearly by birth order (6.0%, 7.7%, and 15.4% for the first, second, and third siblings, respectively; p-value for trends = 0.035). Using a GEE model controlling for maternal age, being born third in a triplet pregnancy was independently associated with SGA (third vs. first sibling, adjusted OR 3.0, 95% CI 1.38-6.59, p = 0.005). No significant differences in cardiovascular, respiratory, neurological, and infection-related hospitalizations were noted among the first, second, and third siblings. Likewise, using Kaplan-Meier survival analyses, no significant differences in the cumulative incidence of long-term pediatric hospitalizations were noted between the siblings. In Cox proportional hazards models, controlling for weight and gender, birth order in a triplet pregnancy did not exhibit an association with long-term hospitalizations of the offspring. CONCLUSION: Despite the association between birth order and SGA, birth order in triplets does not seem to have an impact on the risk for long-term offspring hospitalization.

Trend and risk Factors for Severe Peripartum Maternal morbidity - a population-based Cohort Study.

OBJECTIVES: While the rates of maternal mortality in developed countries have remained low in recent years, rates of severe maternal morbidity (SMM) are still increasing in high income countries. As a result, SMM is currently used as a measure of maternity care level. The aim of this study was to investigate the prevalence and risk factors of SMM surrounding childbirth. METHODS: A nested case-control study was performed between the years 2013-2018. SMM was defined as peripartum hospitalization involving intensive care unit (ICU). A comparison was conducted between parturient with SMM to those without, randomly matched for delivery mode and date of birth in a 1:1 ratio. Multivariable logistic regression models were used to evaluate the independent association between SMM and different maternal and pregnancy characteristics. RESULTS: During the study period, 96,017 live births took place, of which 144 (1.5 per 1,000 live births-0.15%) involved SMM with ICU admissions. Parturient with SMM were more likely to have a history of 2 or more pregnancy losses (18.2% vs. 8.3%, p = 0.004), deliver preterm (48.9% vs. 8.8%, p < 0.001), and suffer from placenta previa (11.9% vs. 1.5%, p < 0.001), and/or placenta accreta (9.7% vs. 1.5%, p = 0.003). Several significant and independent risk factors for SMM were noted in the multivariable regression models: preterm delivery, history of ≥ 2 pregnancy losses, grand-multiparity, Jewish ethnicity, and abnormal placentation (previa or accreta). CONCLUSIONS FOR PRACTICE: SMM rates in our cohort were lower than reported in developed countries. An independent association exists between peripartum maternal ICU admissions and several demographic and clinical risk factors, including preterm birth and abnormal placentation.

The Association between Ovarian Hyperstimulation Syndrome and Pregnancy Complications following Fertility Treatments.

OBJECTIVE: This study was aimed to assess the association between ovarian hyperstimulation syndrome (OHSS) and pregnancy complications among women who conceived following fertility treatment. STUDY DESIGN: A retrospective population-based cohort study, including all singleton deliveries of patients conceived following ovulation induction (OI) or in vitro fertilization (IVF) between 1988 and 2016, was conducted. All births occurred in a single tertiary medical center. A comparison was performed between deliveries of women who had experienced OHSS at early gestation and subsequently had a pregnancy and women without OHSS. Women lacking prenatal care, multiple gestations, and stillbirths were excluded from the analyses. A multivariable logistic regression model was used to control for confounders. RESULTS: During the study period, 351,373 deliveries met the inclusion criteria, of which 6,748 were deliveries of infants who were conceived by either IVF or OI. Of this study population, 105 cases (1.6%) composed the exposed group, that is, women who had experienced OHSS with a subsequent live birth. In the multivariate analyses, after controlling for confounders, OHSS was not found as an independent risk factor for preeclampsia, gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), preterm delivery (both <37 and <34 weeks), low birth weight (LBW), very LBW (VLBW), small for gestational age (SGA), and caesarean delivery. In a subanalysis conducted solely on the IVF population, similar results were found, aside from the association between OHSS and preterm delivery before 34 weeks of gestation which was statistically significant (adjusted odds ratio [AOR] = 2.3 95% confidence interval [CI]: 1.0-5.3, p = 0.049). CONCLUSION: In our population, OHSS was not found as a risk factor for adverse pregnancy and perinatal outcome. In IVF patients, OHSS is a risk factor for preterm delivery before 34 weeks of gestation. KEY POINTS: · OHSS is not a risk factor for pregnancy complications.. · Complications investigated were preeclampsia, GDM, prematurity, and others.. · In IVF patients, OHSS is a risk factor for preterm delivery..

Maternal anemia and long-term respiratory morbidity of the offspring-Results of a population-based cohort.

PURPOSE: To evaluate the association between prenatal maternal anemia (hemoglobin, Hb < 11 g/dl) and long-term respiratory morbidity of the offspring. METHODS: 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). RESULTS: 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). CONCLUSION: Maternal anemia was associated with long-term respiratory morbidity of the offspring.

Maternal condyloma acuminata infection in pregnancy and offspring long-term respiratory and infectious outcome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Maternal term pruritus and long-term neuropsychiatric hospitalizations of the offspring.

PURPOSE: Pruritus during pregnancy is associated with adverse maternal, pregnancy, and neonatal outcomes. We opted to assess the association between term pruritus and long-term neuropsychiatric hospitalizations of the offspring. METHODS: In a population-based retrospective cohort study, the incidence of long-term neuropsychiatric hospitalizations was compared between offspring born to women with or without pruritus at term. Neuropsychiatric morbidity was assessed up to the age of 18 years according to ICD-9 codes associated with hospitalization of the offspring. A Kaplan-Meier survival curve was used to compare cumulative neuropsychiatric hospitalizations incidence and Cox proportional hazards models were used to control for confounders. The study included 226,918 deliveries of which 600 (0.26%) were in women with term pruritus. RESULTS: Offspring born to women with pruritus exhibited a higher rate of long-term neuropsychiatric hospitalizations, specifically due to developmental and neurodegenerative disorders. Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of long-term neuropsychiatric hospitalizations in offspring of women with pruritus. Using several Cox proportional hazards models, being born to a woman with pruritus was independently associated with an increased risk of long-term neuropsychiatric hospitalizations. CONCLUSIONS: Maternal term pruritus was found to be independently associated with long-term neuropsychiatric hospitalizations of the offspring.

Critical analysis of risk factors for intrapartum fetal death.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The association between emotion regulation and pain during the immediate postpartum period.

PURPOSE: The present study aims to investigate the association between emotion regulation difficulties and pain perception during the immediate postpartum period. METHODS: A cross-sectional study was performed in women during the immediate postpartum period. Women completed the Difficulties in Emotion Regulation Scale (DERS) questionnaire to measure difficulties in emotion regulation. A second analysis was conducted for the six subdomains of the DERS questionnaire. The visual analog scale (VAS) was used to measure pain intensity. The association between DERS scores and VAS score was assessed. Multivariable logistic regression models were constructed to control for potential confounders. RESULTS: A total of 150 women were included in the final analysis, of whom 112 (74.6%) delivered vaginally and 38 (25.4%) had a cesarean delivery. Higher DERS scores, indicating more difficulties in emotion regulation, were significantly associated with higher VAS scores regardless of mode of delivery. Likewise, higher emotion regulation scores in 5 of 6 subdomains were associated with higher VAS scores (p < 0.001). Using multivariate logistic regression models higher DERS scores were independently associated with higher VAS scores. CONCLUSION: Difficulties in emotion regulation are associated with higher pain perception during the immediate postpartum period. Interventions designed to improve emotion regulation may improve maternal well-being in the immediate postpartum period and possibly reduce use of pain medication.

Perinatal outcomes and long-term infectious morbidity of offspring born to mothers with familial Mediterranean fever.

PURPOSE: To investigate perinatal outcomes and long-term infectious morbidity in children of mothers with familial Mediterranean fever (FMF). METHODS: A population-based cohort study comparing perinatal outcomes and long-term infectious morbidity of offspring of mothers with and without FMF was conducted. All singleton deliveries between the years 1991-2021 in a tertiary medical center were included. The study groups were followed until 18 years of age for long-term infectious morbidity. A Kaplan-Meier survival curve was used to compare the cumulative incidence of long-term infectious morbidity, and generalized estimation equation (GEE) models as well as Cox proportional hazards models were constructed to control for confounders. RESULTS: During the study period, 356,356 deliveries met the inclusion criteria. 411 of them were women with FMF. The mean follow-up period interval was 9.7 years (SD = 6.2) in both study groups. Using GEE models, preterm delivery, cesarean delivery, and low birth weight were independently associated with maternal FMF. The total infectious-related hospitalization rate was significantly higher in offspring born to mothers with FMF compared to the comparison group (Kaplan-Meier survival curve, log-rank p < 0.001). Using a Cox proportional hazards model, controlling for gestational age, maternal age, diabetes mellitus, cesarean delivery, and hypertensive disorders, being born to a mother with FMF was found to be an independent risk factor for long-term infection-related hospitalization of the offspring. CONCLUSION: Maternal FMF was found to be independently associated with long-term infection-related hospitalization of the offspring. This positive correlation may reflect an intra-uterine pro-inflammatory environment which may result in the offspring's long-term susceptibility to infection.

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

BACKGROUND AND GOALS: While evidence suggests short-term benefits in neonatal morbidity and mortality from cesarean delivery of the fetus in breech presentation, the long-term implications for the offspring are less clear. To assess the implications of the mode of delivery on offspring's health, we have evaluated the long-term gastrointestinal (GI) morbidity of offspring with a breech presentation delivered in either way. MATERIALS AND METHODS: A population-based retrospective cohort study including singleton deliveries in breech presentation occurring between 1991 and 2014 at a tertiary referral hospital. Incidence of hospitalizations of the offspring up to the age of 18 years involving GI morbidity was compared between those delivered via cesarean section or vaginally. A Kaplan-Meier survival curve compared cumulative GI morbidity. A Weibull parametric survival model controlled for confounders while accounting for repeated occurrence of mothers and dependence among siblings. RESULTS: Overall, 86.9% (n=6376) of the 7337 fetuses in breech presentation, were delivered abdominally. Hospitalizations involving GI morbidity were higher in offspring delivered by cesarean section, specifically due to inflammatory bowel disease (IBD). Kaplan-Meier survival curve revealed the higher cumulative incidence of total GI morbidity and IBD specifically in the cesarean delivery group (P<0.001 and P=0.004, respectively). Using a Weibull parametric while controlling for relevant confounders, cesarean delivery emerged as an independent risk factor for long-term IBD-related morbidity of the offspring delivered in breech presentation (adjusted hazard ratio=3.18, 95% confidence interval: 1.47-6.87, P=0.003). CONCLUSION: Cesarean delivery is associated with higher rates of hospitalizations due to IBD and total GI morbidity during childhood in term singleton in breech presentation.

Maternal Anemia and Long-Term Offspring Infectious Morbidity.

OBJECTIVE: Anemia of pregnancy is a common condition associated with adverse obstetric outcomes. However, little is known about its long-term effect on the offspring. This study aimed to evaluate a possible association between anemia during pregnancy and the long-term incidence of infectious morbidity in the offspring. STUDY DESIGN: A large population-based retrospective study was conducted at the Soroka University Medical Center, the sole tertiary medical center in the south of Israel. The study included deliveries between the years 1991 and 2014 and compared long-term infectious morbidity of offspring of women with and without anemia during pregnancy (defined as hemoglobin level below 11 g/dL). The long-term incremental incidence of hospitalizations of offspring up to 18 years of age due to infectious morbidity was evaluated using Kaplan-Meier survival curves, while Cox's regression model was used to control for confounders. RESULTS: During the study period, 214,244 deliveries met the inclusion criteria, of which 110,775 (51.7%) newborns were born to mothers with anemia during pregnancy. The overall infectious-related hospitalization rate was significantly higher in children from the exposed group (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.04-1.10, p < 0.01). Kaplan-Meier survival curves showed a significantly higher cumulative incidence of hospitalizations due to infectious diseases as compared with children in the unexposed group (log-rank test, p < 0.01). The Cox model demonstrated a significant and independent association between maternal anemia and the long-term risk for hospitalization due to infectious diseases of the offspring (adjusted hazard ratio [aHR]: 1.09, 95% CI: 1.06-1.12, p < 0.01). CONCLUSION: Offspring of anemic mothers are at a greater risk for infectious-related hospitalizations in their first 18 years of life. KEY POINTS: · Anemia is highly common in pregnancy.. · Maternal anemia has multiple short-term implications.. · Our study shows anemia of pregnancy is independently associated with long-term offspring infectious morbidity..

Increased incidence of childhood lymphoma in children with a history of small for gestational age at birth.

OBJECTIVE: The aim of this study was to evaluate whether children that were born small for gestational age (SGA) have an increased risk for childhood neoplasm. STUDY DESIGN: A population-based cohort analysis comparing the risk for long-term childhood neoplasms (benign and malignant) in children that were born SGA vs. those that were appropriate for gestational age (AGA), between the years1991-2014. Childhood neoplasms were predefined based on ICD-9 codes, as recorded in the hospital medical files. Kaplan-Meier survival curves were constructed to compare cumulative oncological morbidity in both groups over time. Cox proportional hazards model was used to control for confounders. RESULTS: During the study period 231,973 infants met the inclusion criteria; out of those 10,998 were born with a diagnosis of SGA. Children that were SGA at birth had higher incidence of lymphoma (OR 2.50, 95% CI 1.06-5.82; p value = 0.036). In addition, cumulative incidence over time of total childhood lymphoma was significantly higher in SGA children (Log Rank = 0.030). In a Cox regression model controlling for other perinatal confounders; SGA at birth remained independently associated with an increased risk for childhood lymphoma (adjusted HR 2.41, 95% CI 1.03-5.56, p value = 0.043). CONCLUSION: Being delivered SGA is associated with an increased long-term risk for childhood malignancy and specifically lymphoma.

Maternal epilepsy- perinatal outcome and long-term neurological morbidity of the offspring: a population-based cohort study.

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

Maternal Hepatitis B or Hepatitis C Virus Carrier Status is Not a Risk Factor for Long-Term Oncologic Morbidity of the Offspring: A Population-Based Cohort Study.

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.

Normal labor curve in twin gestation.

BACKGROUND: Failure to progress is one of the leading indications for cesarean delivery in trials of labor in twin gestations. However, assessment of labor progression in twin labors is managed according to singleton labor curves. OBJECTIVE: This study aimed to establish a partogram for twin deliveries that reflects normal and abnormal labor progression and customized labor curves for different subgroups of twin labors. STUDY DESIGN: This was a multicenter, retrospective cohort analysis of twin deliveries that were recorded in 3 tertiary medical centers between 2003 and 2017. Eligible parturients were those with twin gestations at ≥34 weeks' gestation with cephalic presentation of the presenting twin and ≥2 cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, major fetal anomalies, and fetal demise. The study group comprised twin gestations, whereas singleton gestations comprised the control group. Statistical analysis was performed using Python 3.7.3 and SPSS, version 27. Categorical variables were analyzed using chi-square tests. Student t test and Mann-Whitney U test were applied to analyze the differences in continuous variables, as appropriate. RESULTS: A total of 1375 twin deliveries and 142,659 singleton deliveries met the inclusion criteria. Duration of the active phase of labor was significantly longer in twin labors than in singleton labors in both nulliparous and multiparous parturients; the 95th percentile duration was 2 hours longer in nulliparous twin labors and >3.5 hours longer in multiparous twin labors than in singleton labors. The cervical dilation progression rate was significantly slower in twin deliveries than in singleton deliveries with a mean rate in twin deliveries of 1.89 cm/h (95th percentile, 0.51 cm/h) and a mean rate of 2.48 cm/h (95th percentile, 0.73 cm/h) in singleton deliveries (P<.001). In addition, epidural use further slowed labor progression in twin deliveries. The second stage of labor was also markedly longer in twin deliveries, both in nulliparous and multiparous women (95th percentile, 3.04 vs 2.83 hours, P=.002). CONCLUSION: Twin labors are characterized by a slower progression of the active phase and second stage of labor compared with singleton labors in nulliparous and multiparous parturients. Epidural analgesia further slows labor progression in twin labors. Implementation of these findings in clinical management might lower cesarean delivery rates among cases with protracted labor in twin gestations.