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.

Small for gestational age in twin pregnancies and the risk of offspring pediatric neurologic morbidity.

OBJECTIVES: Small for gestational age (SGA) singletons are at increased risk for neurodevelopmental abnormalities. Scarce data exist regarding the long-term implications of SGA in twins. We opted to study the association between SGA of one twin and long-term neurologic related morbidity in dichorionic diamniotic twins. STUDY DESIGN: A population-based retrospective cohort study including consecutive dichorionic diamniotic twins, born between the years 1991 and 2021 at a tertiary medical center was conducted. Total and subtypes of neurologic related pediatric hospitalizations among SGA versus non-SGA twins were compared. A Kaplan-Meier survival curve was used to compare the cumulative neurologic morbidity incidence, and a Cox proportional hazards model was constructed to adjust for confounders. RESULTS: The study population included 4222 newborns; 180 (4.3%) were SGA. Rate of long-term neurologic related hospitalizations was comparable between the two groups (8.7 vs. 8.0%, p = 0.755; Kaplan-Meier survival curve Log-rank p = 0.652). Using a Cox proportional hazards model, controlling for gender and birth order, no association was found between SGA and the risk for subsequent neurologic pediatric morbidity of the offspring (Adjusted HR = 1.0, 95% CI 0.6-1.8, p = 0.973). CONCLUSIONS: SGA is not associated with an increased risk for long-term pediatric neurologic morbidity in dichorionic diamniotic twins.

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.

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.

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.

Association Between Neonatal Phototherapy Exposure and Childhood Neoplasm.

OBJECTIVE: To study the association between phototherapy for the treatment of neonatal jaundice and the risk of childhood neoplasms. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Analysis of 10 urinary BTEX metabolites using LC-MS/MS.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are a group of volatile organic compounds that are ubiquitous in the environment due to numerous anthropogenic sources. Exposure to BTEX poses a health hazard by increasing the risk for damage to multiple organs, neurocognitive impairment and birth defects. Urinary BTEX metabolites are useful biomarkers for the evaluation of BTEX exposure, because of the ease of sampling and their longer physiological half-lives compared with parent compounds. A method that utilizes LC-MS/MS was developed and validated for simultaneously monitoring of 10 urinary BTEX metabolites. During the sample preparation an aliquot of urine was diluted with an equal volume of 1% formic acid; internal standard solution was added, and then the sample was centrifuged and analyzed. The analytes were separated on the Kinetex-F5 column by applying a linear gradient, consisting of 0.1% formic acid and methanol. The method was validated according to the FDA Bioanalytical Method Validation Guidance for Industry. The mean method's accuracies of the spiked matrix were 81-122%; the inter-day precision ranged from 4 to 20%; the limits of quantitation were 0.5-2 µg/L. The method was used for the evaluation of baseline levels of urinary BTEX metabolites in 87 firefighters.

Prediction of embryo implantation rate using a sole parameter of timing of starting blastulation.

A time-lapse monitoring system provides a complete picture of the dynamic embryonic development process and simultaneously supplies extensive morphokinetic data. The objective of this study was to investigate whether the use of the morphokinetic parameter of time of starting blastulation (tSB) can improve the implantation rate of day-5 transferred blastocyst selected based on morphological parameters. In this retrospective study we analyzed the morphokinetics of 196 day-5 transferred blastocysts, selected solely based on morphological parameters. The interval time from intracytoplasmic sperm injection (ICSI) to time of starting blastocyst formation (tSB) was calculated for each embryo. The overall implantation rate of transferred blastocyst, selected based only on morphological parameters, was 49.2%. Implantation rate, determined retrospectively, was significantly higher (58.8% versus 42.6%, P = 0.02) for embryos with a short interval time to tSB (78-95.9 h) compared with embryos with a longer timeframe (96-114 h). Time of expanded blastocyst (tEB) post-ICSI was also significantly associated with implantation; however, this parameter was not available for all the embryos at time of transfer. When we tested only high ranked KIDScore day-3 sub-group embryos, the implantation rate was significantly higher in short interval time embryos compared with longer interval time embryos (62.2% vs. 45.5%, respectively, P = 0.02).These observations emphasize the importance of the timing of starting blastulation over blastocyst morphological parameters and may provide a preferable criterion for good morphology day-5 blastocyst selection.

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..

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.

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 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.

Are morphokinetic parameters of embryo development associated with adverse perinatal outcomes following fresh blastocyst transfer?

RESEARCH QUESTION: Are obstetric and perinatal complications associated with morphokinetic parameters of embryo development? DESIGN: 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. RESULTS: 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. CONCLUSION: 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.