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Research Question: Are children born after assisted reproductive technology (ART) at higher risk of developing Langerhans cell histiocytosis (LCH)?, Design: Records of children born after ART recorded by the UK Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine the number of children developing LCH. Calculated person-years at risk were used in conjunction with the incidence of LCH in the general population to determine the expected number of cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardized incidence ratio (SIR) was derived as the ratio of observed to expected cases. Exact 95% CI were calculated., Results: In total, 118,155 children born after ART contributed 796,633 person-years follow-up (average follow-up 6.74 years). Eight cases of LCH were identified, compared with 3.75 cases expected (SIR 2.135, 95% CI 0.92-4.21; P = 0.074). Significantly more cases were associated with intracytoplasmic sperm injection (ICSI) (SIR 4.02, 95% CI 1.31-9.39) and male factor infertility (SIR 5.41, 95% CI 1.47-13.84). Most cases of LCH had single-system disease (n = 6)., Conclusions: This study found that significantly more cases of LCH were identified in children born after ICSI and in children whose parents had male factor infertility. A non-significant excess of cases in children born after ART was identified. Absolute excess risk was small. Given the rarity of LCH and the small number of cases included in this large cohort, further studies into the risk of LCH in children born after ART are indicated., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although in vitro fertilization has been associated with an increased risk for hypertensive disorders of pregnancy, the association of risk with in vitro fertilization treatment parameters is unclear., Objective: To evaluate risk for hypertensive disorders of pregnancy by maternal fertility status and in vitro fertilization treatment parameters., Materials and Methods: Women in 8 states who underwent in vitro fertilization resulting in a live birth during 2004-2013 were linked to their infant's birth certificates. A 10:1 sample of births from non-in vitro fertilization deliveries were selected for comparison. Those with an indication of infertility treatment on the birth certificate were categorized as subfertile and omitted from the study population; all others were categorized as fertile. The in vitro fertilization pregnancies were additionally categorized by oocyte source (autologous versus donor) and embryo state (fresh versus thawed). Both the fertile and in vitro fertilization births were limited to singletons only, and the in vitro fertilization pregnancies were limited to those using partner sperm. Hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) were identified from the birth certificate, modeled using logistic regression, and reported as adjusted odds ratios and 95% confidence intervals. For analyses of in vitro fertilization pregnancies from autologous oocytes-fresh embryos, the reference group was fertile women (subgroup analysis 1). For analyses within the in vitro fertilization group, the reference group was autologous oocytes-fresh embryos (subgroup analysis 2)., Results: The study population included 1,465,893 pregnancies (1,382,311 births to fertile women and 83,582 births to in vitro fertilization-treated women). Compared to fertile women, in vitro fertilization-treated women with autologous-fresh cycles were not at increased risk for hypertensive disorders of pregnancy (adjusted odds ratio, 1.04; 95% confidence interval, 0.99, 1.08). Among in vitro fertilization births (subgroup analysis 2), the risk for hypertensive disorders of pregnancy was increased for the autologous-thawed (adjusted odds ratio, 1.30; 95% confidence interval, 1.20, 1.40); donor-fresh (adjusted oddds ratio, 1.92; 95% confidence interval, 1.71, 2.15); and donor-thawed (adjusted odds ratio, 1.70; 95% confidence interval, 1.47, 1.96) groups. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results. When stratified by <34 weeks (early-onset hypertensive disorders of pregnancy) versus ≥34 weeks (late-onset hypertensive disorders of pregnancy), only the donor-fresh group had an increased risk of early-onset hypertensive disorders of pregnancy, but the risks for all other oocyte source-embryo state groups compared to autologous-fresh were increased for late-onset hypertensive disorders of pregnancy., Conclusion: The risk for hypertensive disorders of pregnancy is increased for in vitro fertilization-treated women in pregnancies conceived via frozen embryo transfer (with both autologous or donor oocyte) and fresh donor oocyte embryo transfer. No increase in risk was seen with autologous oocyte-fresh embryo transfers in vitro fertilization cycles. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Study Question: Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population?, Summary Answer: This study showed no overall increased risk of childhood cancer in individuals born after donor ART., What Is Known Already: Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date., Study Design, Size, Duration: This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years)., Participants/materials, Setting, Methods: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles., Main Results and the Role of Chance: In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25-37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight., Limitations Reasons for Caution: Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available., Wider Implications of the Findings: This is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed., Study Funding/competing Interest(s): This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests., Trial Registration Number: N/A., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Background: Accurate population-based data are needed on the incidence of cancer in children born after assisted conception., Methods: We linked data on all children born in Britain between 1992 and 2008 after assisted conception without donor involvement with data from the United Kingdom National Registry of Childhood Tumours to determine the number of children in whom cancer developed before 15 years of age. Cohort cancer rates were compared with population-based rates in Britain over the same period, with stratification for potential mediating and moderating factors, including sex, age at diagnosis, birth weight, singleton versus multiple birth, parity, parental age, type of assisted conception, and cause of parental infertility., Results: The cohort consisted of 106,013 children born after assisted conception (700,705 person-years of observation). The average duration of follow-up was 6.6 years. Overall, 108 cancers were identified, as compared with 109.7 expected cancers (standardized incidence ratio, 0.98; 95% confidence interval [CI], 0.81 to 1.19; P=0.87). Assisted conception was not associated with an increased risk of leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, or renal or germ-cell tumors. It was associated with an increased risk of hepatoblastoma (standardized incidence ratio, 3.64; 95% CI, 1.34 to 7.93; P=0.02; absolute excess risk, 6.21 cases per 1 million person-years) and rhabdomyosarcoma (standardized incidence ratio, 2.62; 95% CI, 1.26 to 4.82; P=0.02; absolute excess risk, 8.82 cases per 1 million person-years), with hepatoblastoma developing in 6 children and rhabdomyosarcoma in 10 children. The excess risk of hepatoblastoma was associated with low birth weight., Conclusions: There was no increase in the overall risk of cancer among British children born after assisted conception during the 17-year study period. Increased risks of hepatoblastoma and rhabdomyosarcoma were detected, but the absolute risks were small. (Funded by Cancer Research UK and others.).

The authors estimated the prevalence of heart malformation during the first year of life, using five data sets with varying degrees of completeness from two English regional health authorities. These areas covered a total population of 6,872,000. Analysis was carried out using capture-recapture methods, including log-linear modeling, on data collected between June 1993 and August 1994. A large number of cases in the community were unrecorded by any of the current sources of information. In South East Thames, where an antenatal training screening program for detecting heart malformations had been implemented in the late 1980s, the estimated prevalence rate varied from 5.5 per 1,000 births (95% confidence interval (CI): 3.5, 10.8) to 9.0 per 1,000 births (95% CI: 6.4, 14.2), depending on the assumptions in the model and the number of sources used in the analysis. In the Wessex region, which did not have a formal training program, prevalence was lower and varied little, from 4.3 per 1,000 (95% CI: 3.4, 6.0) to 5.1 per 1,000 (95% CI: 4.0, 7.2), according to assumptions. These two estimates were reasonable rates in comparison with reports in the literature. This analysis was helpful in demonstrating that the training program designed to identify severe heart malformations during the antenatal period in one of these regions had no lasting impact on prevalence.

Objectives: Analysis of incidence and characteristics of congenital abdominal wall defects, with special reference to the differences between the incidence of gastroschisis and exomphalos (omphalocele)., Design: Retrospective analysis using data from the Office of Population Censuses and Surveys (recoded to differentiate exomphalos and gastroschisis) and the National Congenital Malformation Notification Scheme., Setting: England and Wales, 1987 to 1993., Results: 1043 congenital anterior abdominal wall defects were notified within the seven year study period. Of these, 539 were classified as gastroschisis, 448 as exomphalos, 19 as "prune belly syndrome," and 37 as "unclassified." Gastroschisis doubled in incidence from 0.65 in 1987 to 1.35 per 10,000 total births in 1991, with little further change; the incidence of exomphalos decreased from 1.13 to 0.77 per 10000 births. The overall incidence of notified congenital abdominal wall defects was 2.15 per 10000 total births. Gastroschisis was associated with a lower overall maternal age than exomphalos and with a significantly lower proportion of additional reported congenital malformations (5.0%) than in the cohort with exomphalos (27.4%) (odds ratio 0.14, 95% confidence interval 0.09 to 0.22; P < 0.001). The sex ratio of the two cohorts was the same. The incidence of gastroschisis and exomphalos was higher in the northern regions of England than in the south east of the country., Conclusions: The national congenital malformation notification system showed an increasing trend in the incidence of fetuses born with gastroschisis and a progressive decreasing incidence of exomphalos in England and Wales between 1987 and 1993. Although the reasons for this are likely to be multifactorial, a true differential change seems likely. The observed increase in incidence of gastroschisis relative to exomphalos and the differentiation in maternal age have implications for resource management within the NHS and warrant further epidemiological monitoring. Regional differences may be due to a dietary or environmental factor, which requires further study.

The overall incidence of multiple births in England and Wales, which had been declining since the early 1950s, started to increase in the early 1980s in all age groups except for women under 20. This followed a rise in the incidence of triplet and higher order multiple births which had started in the late 1970s. Analyses of data for births between 1978 and 1983 showed that while stillbirth, perinatal, neonatal, and post-neonatal mortalities among multiple births fell considerably, they remained consistently higher than those for singleton births. Differences in the distribution of birth weight do not wholly explain these differences. Analyses of certified causes of stillbirth and death are difficult to interpret because a considerable proportion were attributed to 'multiple pregnancy'.