Risk of borderline ovarian tumors after fertility treatment - Results from a Danish cohort of infertile women.

OBJECTIVE: Results from previous studies examining the association between fertility treatment and borderline ovarian tumors are inconsistent. The aim of this study was to investigate the association between fertility treatment and borderline ovarian tumors in a cohort of infertile women. METHODS: This cohort study was based on the Danish Infertility Cohort and included all infertile women aged 20-45 years living in Denmark between 1 January 1995 and 31 December 2017 (n = 146,891). Information on use of fertility drugs, borderline ovarian tumors and cancer diagnoses, covariates, emigration, and vital status was obtained by linkage to national registers. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) with adjustment for potential confounders for overall borderline ovarian tumors and for serous- and mucinous borderline ovarian tumors separately. RESULTS: During a median 11.3 years of follow-up, 144 women developed a borderline ovarian tumor. No marked associations between ever use of clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators, human chorionic gonadotropin or progesterone and borderline ovarian tumors were observed, neither overall nor for serous and mucinous borderline ovarian tumors analysed separately. Further, no clear associations with borderline ovarian tumors were found according to cumulative dose, time since first use or parity status for any fertility drugs. CONCLUSIONS: No marked associations between use of fertility drugs and borderline ovarian tumors were observed. However, the cohort's relatively young age at end of follow-up emphasizes the importance of extending the follow-up period for women who have used fertility drugs.

Association Between Maternal Hormonal Contraception Use and Central Nervous System Tumors in Children.

Importance: The incidence of central nervous system (CNS) tumors in children appears to be increasing, yet few risk factors are established. There is limited information regarding whether maternal hormonal contraception use increases this risk. Objective: To examine the association between maternal hormonal contraception use and CNS tumors in children (<20 years). Design, Setting, and Participants: In this nationwide cohort study based on population-based registry data, 1 185 063 children born in Denmark between January 1, 1996, and December 31, 2014, were followed up for a diagnosis of a CNS tumor (final follow-up on December 31, 2018). Exposures: Maternal hormonal contraception use was analyzed according to any use, regimen (combined/progestin only), and route of administration (oral/nonoral), categorized as recent use (≤3 months before start and during pregnancy), previous use (>3 months before start of pregnancy), and no use. For injections, implants, and intrauterine devices that are used for a different time period, the categorization was appropriately altered. Main Outcomes and Measures: Hazard ratio (HR) and incidence rate difference (IRD) of CNS tumors diagnosed at younger than 20 years. Results: After 15 335 990 person-years of follow-up (mean follow-up, 12.9 years), 725 children were diagnosed with a CNS tumor. The mean age at diagnosis was 7 years, and 342 (47.2%) of the diagnosed children were female. The adjusted incidence rate of CNS tumors per 100 000 person-years was 5.0 for children born to mothers with recent hormonal contraception use (n = 136 022), 4.5 for children born to mothers with previous use (n = 778 843), and 5.3 for children born to mothers with no use (n = 270 198). The corresponding HRs were 0.95 ([95% CI, 0.74-1.23]; 84 children with CNS tumors; IRD, -0.3 [95% CI, -1.6 to 1.0]) for recent use and 0.86 ([95% CI, 0.72-1.02]; 421 children with CNS tumors; IRD, -0.8 [95% CI, -1.7 to 0.0]) for previous use, compared with no use. No statistically significant associations were found for recent or previous use of oral combined, nonoral combined, oral progestin only, or nonoral products compared with no use of hormonal contraception. Conclusions and Relevance: Among Danish children, there was no statistically significant association between any maternal hormonal contraception use and CNS tumor risk.

Maternal Medication Use and Childhood Cancer in Offspring-Systematic Review and Considerations for Researchers.

Cancer is an important cause of childhood mortality, yet the etiology is largely unknown. A combination of pre- and postnatal factors is thought to be implicated, including maternal medication use. We aimed to provide: 1) a systematic review of peer-reviewed publications on associations between maternal medication use and childhood cancer, with a focus on study design and methodology; and 2) suggestions for how to increase transparency, limit potential biases, and improve comparability in studies on maternal medication use and childhood cancer. We conducted a systematic search in the PubMed, Embase, Scopus, Cochrane, and Web of Science databases to June 8, 2020. Altogether, 112 studies were identified. The reviewed studies were heterogeneous in study design, exposure, and outcome classification. In 21 studies (19%), the outcome was any childhood cancer. Of the 91 papers that reported on specific types of cancer, 62% did not report the cancer classification system. The most frequently investigated medication groups were sex hormones (46 studies, excluding fertility medications), and antiinfectives (37 studies). Suggestions for strengthening future pharmacoepidemiologic studies on maternal medication use and childhood cancer relate to choice of cancer classification system, exposure windows, and methods for identification of, and control for, potential confounders.

The impact of childhood cancer on parental working status and income in Denmark: Patterns over time and determinants of adverse changes.

Having a child with cancer may affect the socioeconomic situation of the parents. We aimed to assess the impact of childhood cancer on parental working status and income and to identify determinants of adverse changes after the child's cancer diagnosis by calendar period. We conducted a nationwide cohort study using Danish registry data. Parents of children diagnosed with cancer in 1982-2014 (n = 12,418) were matched with comparison parents of cancer-free children (n = 125,014). We analysed annual working status (working/not working) and annual disposable income (lowest quintile/not lowest quintile) of case and comparison parents over a period of 10 years after diagnosis by calendar period (1982-1999 vs. 2000-2014). Logistic regression models were used to identify determinants of adverse changes after diagnosis. Mothers of children diagnosed in 1982-1999 were more likely not working or having a low income than comparison mothers up to 10 years after diagnosis. This risk of not working or low income was lower in mothers of children diagnosed in 2000-2014 compared to 1982-1999 in the first years after diagnosis (pinteraction < 0.05). We observed no consistent patterns among fathers. Low parental education, diagnosis of lymphoid leukaemia and younger age of the child at diagnosis were the main determinants of adverse changes in working status or income after diagnosis. Childhood cancer adversely interfered with parents' socioeconomic situation in the earlier calendar period, particularly among mothers. The absence of such an effect in more recent years emphasises the supportive role of a countries' welfare system alongside the general advances in childhood cancer treatment.

The impact of childhood cancer on parental separation, divorce, and family planning in Denmark.

BACKGROUND: Childhood cancer is a devastating experience for the family. The objective of the current study was to assess the impact of having a child with cancer on parental separation, divorce, and future family planning among families residing in Denmark. METHODS: The authors conducted a nationwide cohort study using Danish registry data. Parents of children diagnosed with cancer between 1982 and 2014 (7066 children and 12,418 case parents) were matched with 10 comparison parents of cancer-free children per case parent (69,993 children and 125,014 comparison parents). We used discrete-time Cox regression models to compare the risk of separation (end of cohabitation) and divorce between case and comparison parents, and to identify risk factors for separation and divorce among case parents only. Descriptive statistics were used to compare family planning between case and comparison parents. RESULTS: Case parents were found to have a slightly lower risk of separation (hazard ratio, 0.96; 95% confidence interval, 0.93-0.99) and divorce (hazard ratio, 0.92; 95% confidence interval, 0.87-0.97) than comparison parents. The authors found that case parents who were aged <45 years, with short education (an International Standard Classification of Education code indicating early childhood education, primary education, and lower secondary education), and who were unemployed were at an increased risk of separation and divorce. Moreover, the parents of children diagnosed with cancer at a young age (aged <15 years) were more likely to separate or divorce. No differences with regard to the total number of children and time to a next child after the cancer diagnosis were observed between case and comparison parents. CONCLUSIONS: Having a child with cancer was not associated with an overall adverse impact on parents' risk of separation or divorce and future family planning. These encouraging findings should be communicated to parents to support them along their child's cancer trajectory.

Risk of febrile seizures among children conceived following fertility treatment: A cohort study.

BACKGROUND: Studies have shown that fertility treatment in mothers is associated with neurological problems in children. However, knowledge about any association between maternal use of fertility treatment and febrile seizures in children is lacking. OBJECTIVE: To determine whether maternal use of fertility treatment is associated with febrile seizures in children. METHODS: All liveborn children in Denmark during 1996-2012 (n = 1 065 901) were linked with the Danish Infertility Cohort and the Danish national registers and were followed from one year of age until the first episode of a febrile seizure, death, emigration, loss to follow-up, or end of follow-up (December 2015). Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. RESULTS: Approximately 16% children (n = 172 140) were conceived by infertile women, and approximately 3% (n = 34 082) were diagnosed with febrile seizures during follow-up. Compared with children conceived by fertile women, children conceived following any fertility treatment (HR 1.11, 95% CI 1.06, 1.16), following specific fertility treatment, for example IVF (HR 1.15, 95% CI 1.05, 1.25), ICSI (HR 1.20, 95% CI 1.10, 1.32), and following fertility drugs (HR 1.06, 95% CI 1.00, 1.11) had slight increase in risk of febrile seizures, after adjusting for calendar year of birth, parental age, education, parity status, and maternal smoking during pregnancy. The associations were unchanged when children conceived naturally by infertile women were used as the reference group. CONCLUSIONS: Children conceived following fertility treatment had slightly increased relative risk for febrile seizures.

Incidence and time trends of childhood cancer in Denmark, 1943-2014.

Background: Surveillance of childhood cancer incidence is informative for etiologic research and health policy. However, high-quality data covering several decades of virtually complete cancer diagnosis in children is sparse.Methods: Incident cases of childhood cancer (0-19 years at diagnosis), classified according to Birch and Marsden's International Classification of Childhood Cancer, first edition (ICCC-1), were identified in the Danish Cancer Registry and used to calculate age-standardized incidence rates (ASRs) and estimated annual percentage change (EAPC) separately for 1943-1977 (early period) and 1977-2014 (recent period).Results: During 1943-2014, 15,184 childhood cancer cases were reported. The ASR for any cancer was 13.0 per 100 000 person-years in the early period (EAPC 0.55%; 95% CI 0.30-0.80) and 17.7 per 100 000 person-years in the recent period (EAPC 1.16%; 95% CI 0.96-1.36). In both periods, the increasing trend was seen in both boys (EAPC 0.69%; 95% CI 0.43-0.96/EAPC 0.96%; 95% CI 0.75-1.17) and girls (EAPC 0.37%; 95% CI -0.01-0.75/EAPC 1.41%; 95% CI 1.11-1.72) and in children aged 0-14 years (EAPC 0.53%; 95% CI 0.26-0.80/EAPC 0.86%; 95% CI 0.64-1.08) and 15-19 years (EAPC 0.60%; 95% CI 0.19-1.02/EAPC 1.97%; 95% CI 1.67-2.28). Increasing trends were observed for all main diagnostic groups.Conclusions: The incidence of childhood cancer in Denmark has increased since the 1940s, especially since 1977 and in older children. In recent years the increase has been most pronounced among girls.

Maternal use of hormonal contraception and risk of childhood ADHD: a nationwide population-based cohort study.

Although maternal use of hormones has been suspected of increasing the risk for childhood attention-deficit/hyperactivity disorder (ADHD), no study has examined hormonal contraception use in this context. We examined the association between maternal hormonal contraception use before or during pregnancy and ADHD risk in children. This nationwide population-based cohort study included 1,056,846 children born in Denmark between 1998 and 2014. Prescriptions for hormonal contraceptives redeemed by the mother was categorized as: no use, previous use (> 3 months before pregnancy), and recent use (≤ 3 months before or during pregnancy). Children were followed for ADHD, from birth until 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During 9,819,565 person-years of follow-up (median: 9.2), ADHD was diagnosed or a prescription for ADHD medication redeemed for 23,380 children (2.2%). The adjusted HR for ADHD was higher in children of mothers who had previously (HR 1.23; 95% CI 1.18-1.28) or recently (HR 1.30; 95% CI 1.24-1.37) used hormonal contraception than in those of mothers with no use. The highest estimates were seen for use of non-oral progestin products with HRs of 1.90 (95% CI 1.59-2.26) for previous use, 2.23 (95% CI 1.96-2.54) for recent use, and 3.10 (95% CI 1.62-5.91) for use during pregnancy. Maternal use of hormonal contraception was associated with an increased risk for ADHD in the offspring; more pronounced for non-oral progestin-only than other products.

Association Between Fertility Treatment and Cancer Risk in Children.

Importance: An increasing number of children worldwide are born after the use of fertility treatment, although it remains unclear whether the treatment affects the risk of childhood cancer and whether any associations observed are due to the use of specific drugs, the use of specific procedures, or the underlying infertility. Objective: To examine the association between different types of fertility treatments and cancer risk in children. Design, Setting, and Participants: A retrospective cohort study based on Danish population-based registry data and the Danish Infertility Cohort (individual record linkage) that included 1 085 172 children born in Denmark between January 1, 1996, and December 31, 2012, linked with parental information. There were a total of 2217 children diagnosed with cancer (follow-up occurred during 1996-2015). Exposures: Maternal fertility treatment during the index pregnancy, including the use of fertility drugs (clomiphene [n = 33 835], gonadotropins [n = 57 136], gonadotropin-releasing hormone analogs [n = 38 653], human chorionic gonadotropin [n = 68 181], progesterone [n = 41 628], and estrogen [n = 16 948]) and assisted reproductive technology (in vitro fertilization [n = 19 448], intracytoplasmic sperm injection [n = 13 417], and frozen embryo transfer [n = 3356]). Each exposure was examined separately and compared with children born to fertile women. Main Outcomes and Measures: Hazard ratios and incidence rate differences for childhood cancer. Results: After 12.2 million person-years of follow-up (mean, 11.3 years), the incidence rate of childhood cancer was 17.5 per 100 000 for children born to fertile women (n = 910 291) and 44.4 per 100 000 for children born after the use of frozen embryo transfer (n = 3356). Compared with children born to fertile women, the use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancer cases; hazard ratio, 2.43 [95% CI, 1.44 to 4.11]; incidence rate difference, 26.9 [95% CI, 2.8 to 51.0] per 100 000), mainly due to an increased risk of leukemia (5 cancer cases; incidence rate, 14.4 per 100 000; hazard ratio, 2.87 [95% CI, 1.19 to 6.93]; incidence rate difference, 10.1 [95% CI, -4.0 to 24.2] per 100 000) and sympathetic nervous system tumors (<5 cancer cases; hazard ratio, 7.82 [95% CI, 2.47 to 24.70]). There were no statistically significant associations with the use of the other types of fertility treatment examined. Conclusions and Relevance: Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined.

Maternal use of hormonal contraception and risk of childhood leukaemia: a nationwide, population-based cohort study.

BACKGROUND: Maternal hormonal contraception has been suspected of being linked to an increased risk of childhood cancer. The aim of this study was to assess the association between maternal use of hormonal contraception and diagnosis of leukaemia in their children. METHODS: In this cohort study, we followed a nationwide cohort of 1 185 157 liveborn children between 1996 and 2014 listed in the Danish Medical Birth Registry and identified those diagnosed with leukaemia in the Danish Cancer Registry. Redeemed prescriptions from the Danish National Prescription Registry provided information about maternal hormonal contraceptive use, categorised as: no use (never used contraception before birth; reference category), previous use (>3 months before start of pregnancy), and recent use (≤3 months before and during pregnancy). We also calculated risk estimates separately for maternal hormonal contraceptive use during pregnancy. The primary outcome of interest was a diagnosis of any leukaemia in the children. Secondary outcomes were diagnoses of lymphoid leukaemia and non-lymphoid leukaemia. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% CIs for risk of leukaemia in children. The Data Protection Agency registration number for this study is 2017-41-5221. FINDINGS: Between Jan 1, 1996, and Dec 31, 2014, the 1 185 157 liveborn children accumulated 11 114 290 person-years of follow-up (median 9·3 years, IQR 4·6-14·2), during which 606 children were diagnosed with leukaemia (465 with lymphoid leukaemia and 141 with non-lymphoid leukaemia). Children born to women with recent use of any type of hormonal contraception were at higher risk for any leukaemia than children of women who never used contraception (HR 1·46, 95% CI 1·09-1·96; p=0·011); and for exposure during pregancy the risk was 1·78 (0·95-3·31; p=0·070). No association was found between timing of use and risk for lymphoid leukaemia (HR 1·23, 95% CI 0·97-1·57, p=0·089, for previous use and 1·27, 0·90-1·80, p=0·167, for recent use); however, the HRs for non-lymphoid leukaemia were 2·17 (1·22-3·87; p=0·008) for recent use and 3·87 (1·48-10·15; p=0·006) for use during pregnancy. Hormonal contraception use close to or during pregnancy might have resulted in one additional case of leukaemia per about 50 000 exposed children, or 25 cases during the 9-year study period. INTERPRETATION: Our findings suggest the maternal hormonal use affects non-lymphoid leukaemia development in children. Since almost no risk factors have been established for childhood leukaemia, these findings suggest an important direction for future research into its causes and prevention. FUNDING: The Danish Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation.

Coffee, tea and caffeine consumption and risk of primary infertility in women: a Danish cohort study.

INTRODUCTION: The aim of this study was to investigate whether consumption of coffee, tea and caffeine affects the risk of primary infertility in women. MATERIAL AND METHODS: We selected nulliparous Danish women aged 20-29 years from a prospective cohort and retrieved information on coffee and tea consumption from a questionnaire and an interview at enrollment. We assessed the women's fertility by linkage to the Danish Infertility Cohort and retrieved information on children and vital status from the Civil Registration System. All 7574 women included for analysis were followed for primary infertility from the date of enrollment (1991-1993) until 31 December 2010. Analyses were performed with Cox proportional hazard models. RESULTS: During follow up, primary infertility was diagnosed in 822 women. Compared with never consumers, the risk of primary infertility among women who drank coffee or tea was not affected. The risk of primary infertility was neither associated with an increasing number of daily servings of coffee (hazard ratio 1.00; 95% confidence interval (CI), 0.97-1.03) or tea (hazard ratio 1.01; 95% CI, 0.99-1.03) in consumers only. Concerning total caffeine consumption (from coffee and tea), the risk of infertility was similar among consumers compared with never consumers. Finally, none of the additional daily 100 mg of caffeine affected the risk among consumers only (hazard ratio 1.00; 95% CI 0.98-1.02). CONCLUSIONS: In this population-based cohort study, not restricted to women seeking pregnancy, we found no association between coffee, tea or total caffeine consumption and the risk of primary infertility in women.

Maternal fertility problems and risk for transient neonatal diabetes mellitus.

AIMS: The study of imprinting disorders in the context of infertility and its treatment is important, as studies have indicated an increased risk. In this study, we evaluated the risk of transient neonatal diabetes mellitus (TNDM), defined here as diabetes mellitus presenting within the first six weeks of life, in children born to women with fertility problems. METHODS: This nationwide register-based cohort study comprised all 2,107,837 children born in Denmark between 1977 and 2010. Of these, 121,044 (5.7%) children were born to women with fertility problems. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal fertility status and the risk for TNDM. RESULTS: A total of 103 children developed TNDM during the follow-up period. Children born to women with fertility problems had an elevated risk for TNDM, after adjustment for birth year, maternal age at birth and parental history of diabetes, although this was not statistically significant (HR = 1.49; 95% CI 0.73-3.03). The risk of children born in the period 1994-2010 (a period with more comprehensive information on maternal fertility problems and with more invasive fertility treatment procedures) was increased almost twofold (HR = 1.92; 95% CI 0.92-4.00) but was still not statistically significant. CONCLUSIONS: Our results indicate that children born to women with fertility problems, particularly after 1993, may be at an elevated risk for TNDM. As the increased risks were not statistically significant, however, the finding may be due to chance.

Type 1 diabetes risk in children born to women with fertility problems: a cohort study in 1.5 million Danish children.

INTRODUCTION: While some studies have indicated that children born following fertility treatment are at an increased risk for insulin resistance and higher blood glucose levels, no study to date has investigated the risk of type 1 diabetes. In this large population-based cohort study we aim to assess the association between maternal fertility problems and the risk of type 1 diabetes in children. MATERIAL AND METHODS: Information on all children, born in Denmark from 1987 to 2010, was extracted from the Civil Registration System and linked with the Danish Infertility Cohort to identify maternal fertility status. Diabetes information was obtained from the National Patient Register and the Childhood Diabetes Register. A Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals. RESULTS: A total of 1 550 519 children made up the study cohort, of whom 110 393 (7.1%) were born to women with fertility problems. In all, 313 children born to women with fertility problems (0.36%) and 5176 children born to women without fertility problems (0.28%) were diagnosed with type 1 diabetes. The risk of type 1 diabetes was not affected by maternal fertility status (hazard ratio 1.01, 95% CI 0.90-1.13) when taking into account birth year, sex, history of parental diabetes, parental age and age at diagnosis. CONCLUSIONS: Our results showed no association between maternal fertility problems and risk of type 1 diabetes in children.

Maternal use of fertility drugs and risk of cancer in children--a nationwide population-based cohort study in Denmark.

Large population-based studies are needed to examine the effect of maternal use of fertility drugs on the risk of cancer in children, while taking into account the effect of the underlying infertility. A cohort of 123,322 children born in Denmark between 1964 and 2006 to 68,255 women who had been evaluated for infertility was established. We used a case-cohort design and calculated hazard ratios (HRs) for cancer in childhood (0-19 years) and in young adulthood (20-29 years) associated with maternal use of six groups of fertility drugs (clomiphene, gonadotropins [i.e., human menopausal gonadotropins and follicle-stimulating hormone], gonadotropin-releasing hormone analogs, human chorionic gonadotropins, progesterone and other fertility drugs). We found no statistically significant association between maternal use of fertility drugs and risk for overall cancer in childhood or young adulthood. However, with regard to specific cancers in childhood, our results showed that maternal use of progesterone before childbirth markedly increased the risks of their offspring for acute lymphocytic leukemia (any use: HR, 4.95; 95% CI, 1.69-14.54; ≥ three cycles of use: HR, 9.96; 95% CI, 2.63-37.77) and for sympathetic nervous system tumors (any use: HR, 5.79; 95% CI, 1.23-27.24; ≥ three cycles of use: HR, 8.51; 95% CI, 1.72-42.19). These findings show that maternal use of progesterone may increase the risk for specific cancers in the offspring. Additional large epidemiological studies are urgently needed to confirm our finding.

Hospital contact for mental disorders in survivors of childhood cancer and their siblings in Denmark: a population-based cohort study.

BACKGROUND: Survivors of childhood cancer are known to be at risk for long-term physical and mental effects. However, little is known about how cancers can affect mental health in the siblings of these patients. We aimed to assess the long-term risks of mental disorders in survivors of childhood cancer and their siblings. METHODS: Hospital contact for mental disorders was assessed in a population-based cohort of 7085 Danish children treated for cancer by contemporary protocols between 1975 and 2010 and in their 13 105 siblings by use of data from the Danish Psychiatric Central Research Registry. Hazard ratios (HRs) for first hospital contact were calculated using a Cox proportional hazards model. We compared these sibling and survivor cohorts with two population-based cohorts who were not childhood cancer survivors or siblings of survivors. FINDINGS: Survivors of childhood cancer were at increased risk of hospital contact for mental disorders, with HRs of 1·50 (95% CI 1·32-1·69) for males and 1·26 (1·10-1·44) for females. Children younger than 10 years at diagnosis had the highest risk, and increased risks were seen in survivors of CNS tumours, haematological malignancies, and solid tumours. Survivors had higher risk of neurodevelopmental, emotional, and behavioural disorders than population-based comparisons and siblings, and male survivors had higher risk for unipolar depression. Overall, siblings had no excess risk for mental disorders. However, our data suggest that siblings who were young at the time of cancer diagnosis of the survivor were at increased risk for mental disorders, whereas those older than 15 years at diagnosis were at a lower risk than the general population. INTERPRETATION: Childhood cancer survivors should be followed up for mental late effects, especially those diagnosed in young age. Further, clinicians should also be aware that siblings who were young at the time of cancer diagnosis might be at increased risk for mental health disorders.

Maternal use of hormonal contraception and risk of childhood autism spectrum disorders: A Parental Exposures and Child Health (PECH) cohort study.

A recent hypothesis suggests that maternal hormonal contraception use has contributed to the increasing incidence of autism spectrum disorders (ASD). We used a nationwide population-based cohort (the PECH cohort) including 1,056,149 Danish children born in the period January 1, 1998, to December 31, 2014, to assess associations between maternal hormonal contraception use and childhood ASD (end of follow-up: December 31, 2017). Maternal hormonal contraception use was grouped as "recent use" (≤ 3 months before pregnancy start or during pregnancy), "previous use" (>3 months before pregnancy start) and "never use", except for few products. Incidence rate ratios (IRRs) were estimated using Poisson regression. During follow-up of nearly 12 million person-years, 19,996 children were diagnosed with ASD. A slightly higher IRR was observed for maternal recent use of any hormonal contraception, compared to previous use. This association was largely driven by the non-oral progestin-only products, and associations were especially seen for infantile autism and other/unspecified ASD. An increased IRR of infantile autism was also observed for recent use of the oral progestin-only products, compared to previous use. Our results suggest that maternal use of hormonal contraception may be associated with ASD risk in children, especially for the progestin-only products.

Increased risk for cancer among offspring of women with fertility problems.

Some studies have indicated that children born after fertility treatment have a potential risk for cancer, but the results are inconsistent. Furthermore, any negative effects of fertility treatment might be due to the underlying infertility rather than to the procedure itself. In the largest cohort study to date with information on fertility, we examined whether the offspring of women with fertility problems had a higher risk for cancer than offspring of women without fertility problems. The study cohort consisted of 2,830,054 offspring born in Denmark between 1964 and 2006. Of these, 125,844 were offspring of women evaluated for infertility. Cox regression models were used to estimate the possible effect of being the offspring of a woman evaluated for infertility on the risk for cancer. Analyses were performed separately for cancer during childhood (0-19 years) and cancer in young adulthood (>20 years). We found that offspring born to women with fertility problems had higher overall risks for cancer in childhood (hazard ratio (HR), 1.18; 95% confidence interval (CI), 1.05-1.32) and in young adulthood (HR, 1.22; 95% CI, 1.04-1.43) than offspring of women without fertility problems. Offspring of women with fertility problems had significantly increased risks for leukemia in childhood (HR, 1.30; 95% CI, 1.06-1.60) and for cancer of the endocrine glands in young adulthood (HR, 2.67; 95% CI, 1.35-5.29). These findings suggest that offspring born to mothers with fertility problems are at increased risk for cancer in both childhood and young adulthood. If real, our findings of an ∼18% overall increase in risk for cancer in childhood and an ∼22% overall increase in risk for cancer in young adulthood would mean about four additional cases of childhood cancer and about nine additional cases of cancer in young adults per 100,000 exposed offspring.

In Utero Exposure to Hormonal Contraception and Mortality in Offspring with and without Cancer: A Nationwide Cohort Study.

Approximately 400 million women of reproductive age use hormonal contraceptives worldwide. Eventually, pregnancy sometimes occurs due to irregular use. Use in early pregnancy is found to be associated with child morbidities including cancer, the main reason for disease-related death in children. Here, we add the missing piece about in utero exposure to hormonal contraception and mortality in offspring, including assessments of prognosis in children with cancer. In utero exposure to hormonal contraception may be associated with death since we found a hazard ratio (HR) of 1.22 (95% confidence interval (CI) 1.01-1.48) compared to children of mothers with previous use. The HRs were 1.22 (95% CI 0.99-1.13) for oral combined products and 2.92 (95% CI 1.21-7.04) for non-oral progestin-only products. A poorer prognosis was also found in exposed children with leukemia (3.62 (95% CI: 1.33-9.87)). If causal, hormonal contraception in pregnancy seems detrimental for offspring health and a marker of poorer prognosis in children with leukemia.