Idit Segal

Fertility treatments and pediatric neoplasms of the offspring: results of a population-based cohort with a median follow-up of 10 years

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

Cesarean Delivery and Childhood Malignancies: A Single-Center, Population-Based Cohort Study

&NA; Rising rates of cesarean deliveries worldwide prompt the evaluation of long‐term morbidity to the offspring. In this retrospective cohort study, we evaluated whether cesarean delivery influences the development of childhood malignancies. We identified an association of cesarean delivery with acute lymphoblastic leukemia in children, suggesting prudence in the recommendation of cesarean delivery for nonmedically indicated cases.

Small for gestational age as an independent risk factor for long-term pediatric gastrointestinal morbidity of the offspring

Abstract Objective: The concept of neonatal programming has begun to emerge as an important component of adult health. Scarce data exist regarding perinatal risk factors for long-term gastrointestinal (GI) morbidity of the offspring. We aimed to evaluate the association between birthweight (BW) at term and long-term pediatric GI morbidity. Study design: A population-based cohort analysis was performed, comparing the risk of long-term GI morbidity (up to the age of 18 years) in children delivered at term according to their BW. The study included all term deliveries occurring between 1991 and 2014 at a single regional tertiary medical center. Multiple gestations and fetuses with congenital malformations were excluded. BW was subdivided into: small for gestational age (small for gestational age (SGA) – BW ≤ 5th centile), appropriate for gestational age (AGA −5th centile < BW < 95th centile), and large for gestational age (LGA – BW ≥95th centile). Hospitalizations up to the age of 18 years involving GI morbidity were evaluated, using a predefined set of ICD-9 codes, as recorded in the hospital files. A Kaplan–Meier survival curve was used to compare cumulative GI morbidity incidence. A Cox proportional hazards model was constructed to control for confounders. Results: During the study period, 225,600 term singleton deliveries met the inclusion criteria. Of them, 4.6% (n = 10,415) were SGA and 4.3% (n = 9796) were LGA. During the 18-years follow-up period, 11,791 (5.2%) children were hospitalized with GI morbidity. Hospitalizations were significantly more common in the SGA group, as compared with the AGA and LGA groups (6.6 versus 5.2 versus 4.5%, respectively, p < .001) Specifically, inflammatory bowel disease, celiac, hernia, hepatitis, and cholecystitis, were more common in the SGA group. The Kaplan–Meier survival curve demonstrated a significantly higher cumulative incidence of gastrointestinal morbidity in the SGA group (log rank p < .001). In the Cox proportional hazards model, controlled for relevant clinical confounders, SGA BW was found to be an independent risk factor for long-term GI morbidity (adjusted HR = 1.23, 95%CI 1.14–1.33, p < .001). Conclusions: SGA offspring are at an increased and independent risk for long-term pediatric GI morbidity.

Long-Term Cardiovascular Morbidity in Children Born Following Fertility Treatment

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

Elective Cesarean Delivery at Term and the Long-Term Risk for Neurological Morbidity of the Offspring

Objective The studys objective was to determine whether mode of delivery has an impact on the long‐term risk for neurologic morbidity of the offspring. Materials and Methods This population‐based cohort analysis included all term singleton deliveries between 1991 and 2014. The study population was divided into two study group: elective cesarean deliveries (CD) versus vaginal deliveries (VD). Urgent cesarean deliveries, pregnancy, and delivery complications including preeclampsia and gestational diabetes were excluded. The evaluation of cumulative neurological hospitalization rate over time was performed with a Kaplan‐Meier survival analysis and Cox proportional hazards models were used to study the independent association between mode of delivery and neurological morbidity while controlling for potential confounders. Results During the study period 132,054 deliveries met the inclusion criteria, 11,746 CD (8.9%), and 120,308 (91.1%) VD. A total of 3,626 neurological hospitalizations were documented with 2.70% (3,244) in the VD group as compared with 3.25% (382) in the CD group. The survival curves showed higher cumulative hospitalization rates in the CD as compared with the VD group (p ≤ 0.001). The Cox analysis demonstrated CD to be an independent risk factor for pediatric neurological hospitalizations (p < 0.001). Conclusion Term elective CD is an independent risk factor for neurological morbidity of the offspring.

Low Apgar scores in term newborns and long-term gastro-intestinal morbidity: a population-based cohort study with up to 18 years of follow-up

Abstract Introduction: Low Apgar scores (<7) measured at age 5 minutes can predict short-term infant morbidity and mortality. Although an association exists between low Apgar scores and neuropsychological disorders, other childhood disorders were not thoroughly studied. We aimed to study the possible association between low 5-minute Apgar scores in term newborns and their long-term childhood gastrointestinal (GI) morbidity. Methods: A population-based cohort analysis was performed comparing total and different subtypes of GI-related pediatric hospitalizations among newborns with normal (≥7) and low (<7) 5-minute Apgar scores. The analysis included all term singletons born between the years 1999 and 2014 at a single tertiary regional medical center. Infants with congenital malformations, multiple gestations, and all perinatal deaths were excluded from the analysis. GI-related morbidities included hospitalizations involving a predefined set of ICD-9 codes, as recorded in the hospital computerized files. A Kaplan–Meier survival curve was constructed to compare the cumulative GI morbidity, and a Cox proportional hazards model was used to adjust for confounders. Results: The study population, including 223 244 term singletons, was followed for an average of 10.02 ± 6.0 years (0–18 years, median 10.25) following discharge from birth hospitalization. Low 5-minute Apgar scores were recorded in 585 (0.3%) newborns. Incidence of GI-related hospitalizations was higher among the low versus the normal 5-minute Apgar score group (7.4 versus 5.2%; 8.6/1000 person years (PY) versus 5.2/1000 PY, respectively; p = .02; odds ratio =1.66, 95%CI 1.36–1.96). The association remained significant and independent while adjusting for gestational age, fetal weight, offspring gender, maternal age, maternal smoking, hypertension, and diabetes (Adjusted HR =1.57, 95%CI 1.16–2.12, p = .003). Conclusions: Low 5 minutes Apgar score is associated with an increased risk for long-term pediatric GI morbidity of the offspring. Our results suggest that Apgar scores can be used as a possible predictor for long-term pediatric morbidities and thus may necessitate appropriate surveillance in this vulnerable group of children.