Developmental medicine and child neurology, 2018
Cerebral palsy after assisted reproductive technology: a cohort study
Author affiliations
- The Kids Research Institute Australia ROR
Developmental medicine and child neurology, 2018
Goldsmith S, Mcintyre S, Badawi N, Hansen M
To calculate the birth prevalence of cerebral palsy (CP) after assisted reproductive technology (ART) and compare the clinical outcomes of children with CP after ART or natural conception. This cohort study used linked CP and ART register data from live births in Western Australia (1994-2002). Birth prevalence was calculated and data analysed using descriptive statistics and logistic regression. It was adjusted for confounding variables and stratified by plurality and gestational age. In total, 211 660 live births were included; prevalence of CP was increased in children born after ART (7.2/1000 live births compared with naturally conceived births, 2.5/1000). Odds of CP were doubled for singletons; when stratified by gestational age odds were only increased in the under 32-week group. Prevalence of CP was increased in ART (9.9/1000 live births) and naturally conceived twins (8.4/1000 live births). Clinical outcomes were similar between ART and naturally conceived children. The birth prevalence of CP is increased two-fold after ART. After stratification for gestational age and plurality, residual risk remains in singletons born very preterm. Birth prevalence of CP will be tracked over time to identify any impact of changes to clinical practice. In Western Australia, assisted reproductive technology (ART) increases birth prevalence of cerebral palsy (CP), mediated mostly by preterm and multiple births. Preterm birth alone does not account for the doubled odds of CP for ART singletons born very preterm. Clinical outcomes are similar between ART and naturally conceived children with CP.
Kahn LG et al., 2026 · JAMA Network Open
Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, This cohort study was conducted among mother-child dyads in the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) Cohort, with infants conceived between 1998 and 2022. Associations of subfecundity and infertility treatment with neurodevelopmental outcomes were assessed among children ages 2 to 10 years. Data were analyzed from May 14, 2025, to March 31, 2026. Subfecundity was defined as prior consultation for, treatment of, or diagnosis of infertility for either partner; at least 2 prior miscarriages; or ever having had unprotected heterosexual intercourse for 12 months without conceiving. Infertility treatment was categorized as in vitro fertilization (IVF) or non-IVF treatment. Harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist yielded continuous raw scores for externalizing and internalizing problems. The total raw Social Responsiveness Scale (SRS) score quantified autism-like symptoms. Caregivers reported physician diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Among 15 382 mother-infant dyads, there were 14 191 unique maternal participants (mean [SD] age at delivery, 30.9 [5.33] years; 8780 parous participants [57.1%]). ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively. In generalized linear models, subfecundity was associated with higher externalizing problem and SRS scores among all pregnancies (externalizing problems: b = 0.47 [95% CI, 0.14-0.81]; SRS score: b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing problems: b = 0.45 [95% CI, 0.07-0.83]; SRS score: b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity had higher odds of ASD (overall: odds ratio [OR], 1.27 [95% CI, 1.03-1.57]; natural conceptions: OR, 1.31 [95% CI, 1.04-1.64]). Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived via natural conception with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) or without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). There were no significant associations for IVF treatment. In this large US cohort study, subfecundity was associated with elevated scores for caregiver-reported symptoms of behavioral problems and higher odds of ASD diagnosis, independent of infertility treatment. Non-IVF treatment was associated with ADHD, warranting further research into specific indications for treatment that may increase risk of offspring neurodevelopmental problems.
Oakley LL et al., 2025 · Human reproduction (Oxford, England)
Does the risk of childhood cancer following ARTs vary by sex? In this registry-based study, some childhood cancers showed positive sex- and age-specific associations in children conceived using certain ART modalities, which were not evident in overall combined analyses. The relationship between ART and risk of childhood cancer has shown diverse outcomes in prior research. Studies examining whether there are sex differences in childhood cancer risk after ART conception are lacking. This registry-based cohort study included all children born in Norway between 1984 and 2022 (n = 2 255 025), followed until 31 December 2023. Children were identified via the Medical Birth Registry of Norway, and information was extracted on whether they were conceived via ART (defined as IVF/ICSI). Of the 2 255 025 children included in the study, 53 694 were ART-conceived. Birth records were linked to the Cancer Registry of Norway. Childhood cancer was defined as a cancer diagnosis according to the International Classification of Childhood Cancer Third Edition (ICCC-3) before the age of 18 years. Cox regression models were used to estimate the age- and sex-specific risk of cancer for ART-conceived children compared to children not conceived via ART. Among all children, 0.25% had a cancer diagnosis before the age of 18 years. The cumulative incidence of cancer was higher in children conceived by ART (IVF/ICSI) than in those not conceived via ART (21.5 vs 17.5 per 100 000 person-years, P = 0.04), and especially higher in boys conceived with ICSI or after cryopreserved embryo transfer. When combining all age groups, both sexes and all cancer types, there was little evidence of increased cancer risk with ART (adjusted hazard ratio (aHR) 1.13, 95% CI 0.94-1.36). However, differences were found when stratifying by age and sex. From age 5-9 years, ART-conceived children had a higher overall risk of cancer (aHR 1.53, 95% CI 1.06-2.20), with a slightly higher estimate in boys (aHR 1.73, 95% CI 1.09-2.74), than in girls (aHR 1.28, 95% CI 0.70-2.33). The risk was not higher up to age 5 years, or after age 10 years. In combined analyses, there was no overall increased risk after ICSI. When stratifying by sex, a higher risk was seen after ICSI for boys (aHR 1.69, 95% CI 1.18-2.42), but not for girls (aHR 0.65, 95% CI 0.37-1.16). The combined risk after cryopreservation (aHR 1.42, 95% CI 0.95-2.13) was driven by a higher risk in boys (aHR 1.79, 95% CI 1.09-2.94), while no evidence of an association was found in girls (aHR 1.01, 95% CI 0.50-2.03). No increased risk was seen with IVF or after fresh transfer for either boys or girls. Childhood cancer is a rare outcome, and some analyses of cancer subtypes were likely underpowered. Results from this large registry-based study suggest that addressing age- and sex-specific differences in the risk of childhood cancer following ART conception reveals increased risks for certain groups. Our findings require further study with consideration of possible underlying sex-specific mechanisms related to ART and different childhood cancers. This work was funded by: the Research Council of Norway through its Centres of Excellence Funding Scheme (project number 262700); the Norwegian Cancer Association (project number 244291); and the Norwegian Institute of Public Health. The funding agencies had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. The authors declare no conflict of interests. N/A.
Van Duijne H et al., 2025 · Human Reproduction
Abstract Do children conceived by assisted reproductive technology (ART) have increased overall or cause-specific mortality risk through adolescence, compared with children not conceived by ART? Reassuringly, after median follow-up of 17 years, overall and cause-specific mortality risk was not increased in ART-conceived children compared with non-ART-conceived children. More than 10 million children worldwide have been born as a result of ART. While there is evidence of increased risk of perinatal mortality and perinatal complications among babies born after ART, little is known about overall and cause-specific mortality risk in children and adolescents. Since the proportion of children born after ART has increased dramatically in recent decades, it is important from a public health perspective to investigate overall and cause-specific mortality in ART-offspring, particularly up to adolescence and young adulthood. Study design, size, duration Data were used from the OMEGA cohort, a historical nationwide cohort with prospective follow-up in The Netherlands. Children of women who were treated in one of the 13 IVF clinics or 2 regional fertility centers during 1983-2011 were included. Of 83,413 live-born children, 47,870 were ART-conceived and 35,543 were not ART-conceived (conceived naturally with or without ovarian stimulation among subfertile couples). Participants/materials, setting, Data on type of fertility treatment and maternal risk factors were available from maternal medical records and the Dutch Perinatal Registry. Complete information on date and cause of death was ascertained through Statistics Netherlands through 2019. The mortality risk in ART children was compared with the mortality risk in non-ART children, using Cox regression analysis (adjusted hazard ratios [HRs]) and with mortality risk in children from the general Dutch population, calculating standardized mortality ratios (SMRs). Main Median age at end of follow-up was 17.5 years (IQR=12.1-24.3) and was shorter in ART-conceived children (16.0 years) than in non-ART children (19.8 years). In total, 718 children died, 399 in the ART group and 319 in the non-ART group, median age of death was 0.02 (IQR=0.00-0.40) and 0.14 years (IQR=0.00-15.93), respectively. Overall mortality risk was not increased in ART-conceived children compared with children of subfertile couples not conceived by ART (HR = 1.02, 95%CI=0.87-1.20), also not for IVF and ICSI specifically (HR = 1.08, 95%CI=0.91-1.28; HR = 0.90, 95%CI=0.71-1.12, respectively). However, for IVF-conceived children, mortality risk was increased in the first 6 months of life (<6 months: HR = 1.23, 95%CI=1.00-1.51) compared with children not conceived by ART. IVF-conceived children were at increased risk of death due to perinatal complications compared with non-ART children (HR = 1.29, 95%CI=1.02-1.65). For ICSI-conceived children, no increased risks were observed. Risks of overall mortality in children aged ≥6 months were non-significantly decreased (>6 months: HR = 0.81, 95%CI=0.61-1.08; HR = 0.81, 95%CI=0.59-1.10; HR = 0.83, 95%CI=0.50-1.36). Overall mortality risk among ART-children was increased compared with mortality incidence in the general population (SMR=1.19, 95%CI=1.08-1.32), mainly driven by excess deaths due to conditions originating in the perinatal period (SMR=2.01, 95%CI=1.76-2.30). No other increased cause-specific mortality risks were observed. Limitations, Despite the large cohort and long-term follow-up, the absolute number of deaths was small, which limited the power to detect differences in some subgroups. In addition, results are largely based on ART treatment protocols used until 2011, consequently, it is uncertain how study results generalize to more contemporary ART treatment. These results contribute to knowledge about long-term health risks in ART-offspring. Reassuringly, long-term mortality up to the age of 24 years among ART-conceived children was similar to mortality in non-ART children and the general population. This knowledge is important for ART children, future parents considering ART, and physicians. No
Rios P et al., 2024 · JAMA network open
Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations. To assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally. For this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023. Use of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI). The risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth. This study included 8 526 306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years). The findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.