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Few studies have investigated the offspring of women with anorexia nervosa (AN). The aim of this study was to examine perinatal status, mental and physical health in the offspring of mothers with a history of AN. Fifty-one individuals with adolescent-onset AN and 51 matched controls (COMP) have been followed prospectively. Presently, 30 years after AN onset, at a mean age of 44 years, female participants who had given birth (nAN = 40, nCOMP = 40) were interviewed regarding psychiatric health in their offspring using the Developmental and Well-Being Assessment and the MINI International Neuropsychiatric Interview. In addition, information on the offspring's perinatal status, psychiatric- and physical health was obtained from the Swedish Medical Birth Register and The Swedish National Patient Register. Data regarding mental and physical health were available for 83 and 86 offspring in the AN and COMP groups, respectively. At birth, all of weight, length, head circumference and ponderal index were significantly reduced in the offspring of mothers with a history of AN. In adolescence, parental interviews indicated an overrepresentation of current psychiatric diagnoses in the offspring of mothers with AN. Compared with the offspring in the COMP group, endocrinological, immune and metabolic disorders were much more common in the offspring of the AN group. In conclusion, a history of AN increases the risk of worse perinatal outcome of the offspring. Later on, in childhood and adolescence, psychiatric and physical morbidity may be overrepresented in the offspring of women with AN. [ABSTRACT FROM AUTHOR]

Background: Genetically informed studies have provided mixed findings as to what extent parental substance misuse is associated with offspring substance misuse and antisocial behavior due to shared environmental and genetic factors. Methods: We linked data from nationwide registries for a cohort of 2 476 198 offspring born in Sweden 1958–1995 and their parents. Substance misuse was defined as International Classification of Diseases diagnoses of alcohol/drug use disorders or alcohol/drug-related criminal convictions. Quantitative genetic offspring-of-siblings analyses in offspring of monozygotic and dizygotic twin, full-sibling, and half-sibling parents were conducted. Results: Both maternal and paternal substance misuse were robustly associated with offspring substance misuse [maternal adjusted hazard ratio (aHR) = 1.83 (95% confidence interval (CI) 1.80–1.87); paternal aHR = 1.96 (1.94–1.98)] and criminal convictions [maternal aHR = 1.56 (1.54–1.58); paternal aHR = 1.66 (1.64–1.67)]. Additive genetic effects explained 42% (95% CI 25–56%) and 46% (36–55%) of the variance in maternal and paternal substance misuse, respectively, and between 36 and 44% of the variance in substance misuse and criminality in offspring. The associations between parental substance misuse and offspring outcomes were mostly due to additive genetic effects, which explained 54–85% of the parent-offspring covariance. However, both nuclear and extended family environmental factors also contributed to the associations, especially with offspring substance misuse. Conclusions: Our findings from a large offspring-of-siblings study indicate that shared genetic influences mostly explain the associations between parental substance misuse and both offspring substance misuse and criminality, but we also found evidence for the contribution of environmental factors shared by members of nuclear and extended families. [ABSTRACT FROM AUTHOR]

With the improvement of treatments, a growing number of survivors with childhood or adolescent central nervous system (CNS) tumor are parenting their own children. We aimed to explore the risk of somatic diseases among children of these survivors compared to population controls. Children of survivors with CNS tumor below age of 20 were identified between 1973 and 2014 by combining the several Swedish registers. Five children without parental CNS tumor were matched randomly to generate the population comparisons. Relative risk (RR) and absolute excess risk (AER) were calculated for overall somatic diseases, and hazard ratio (HR) was calculated for specific type of somatic diseases. A total of 2231 somatic disease diagnoses were identified in children of survivors with a cumulative incidence rate of 94.77 per 1000 person‐years, whereas the rate was 92.79 in matched comparisons thus resulting in an overall RR of 1.02 (95% CI = 0.98‐1.07) and AER of 1.98 (95% CI = −2.06, 6.13). Specifically, five of 1364 children of survivors had CNS tumor with an incidence rate of 0.21 per 1000 person‐year, whereas the rate was 0.04 in children of matched children, generating a HR of 4.91 (95% CI = 1.42‐16.96). Children of male survivors were at a statistically increased risk of malignancy, as well as infectious and parasitic diseases. In conclusion, no significantly higher risk of overall somatic diseases was found in children of survivors with CNS tumor before the age of 20, but children with a paternal diagnosis of CNS tumor had significantly increased risk of malignancies and infectious and parasitic diseases. What's new? Survivors of central nervous system (CNS) tumors are at higher risk of experiencing late adverse effects on reproductive function. However, it remains unknown if the tumor or related treatments subsequently affect the physical health of their offspring. This population‐based study did not find an association of parental CNS tutors in childhood or adolescence with the risk of overall somatic diseases in the offspring. Nonetheless, an increased risk was observed in preterm born children, and children of male survivors had an increased risk of malignancies and infectious and parasitic diseases, calling for a tailored surveillance strategy. [ABSTRACT FROM AUTHOR]

Study Question: Is maternal polycystic ovary syndrome (PCOS) associated with increased risks for a broad spectrum of psychiatric and mild neurodevelopmental disorders in offspring?Summary Answer: Maternal PCOS and/or anovulatory infertility is independently, and jointly with maternal obesity, perinatal problems, cesarean delivery and gestational diabetes, associated with increased risks in offspring for almost all groups of psychiatric and mild neurodevelopmental disorders with onset in childhood or adolescence.What Is Known Already: Maternal PCOS was previously associated with autism spectrum disorder, attention-deficit/hyperactivity disorders and possibly developmental delay in offspring. Few studies have investigated the association between maternal PCOS and other psychiatric and neurodevelopmental disorders in offspring.Study Design, Size, Duration: This was a population-based cohort study in Finland including all live births between 1996 and 2014 (n = 1 105 997). After excluding births to mothers with symptoms similar to PCOS, a total of 1 097 753 births by 590 939 mothers remained. Children were followed up until 31 December 2018, i.e. up to the age of 22 years.Participants/materials, Setting, Methods: National registries were used to link data of the included births and their mothers. Data from 24 682 (2.2%) children born to mothers with PCOS were compared with 1 073 071 (97.8%) children born to mothers without PCOS. Cox proportional hazards modeling was used to evaluate the hazard ratio (HR) and 95% CI for the risk of neuropsychiatric disorders in relation to maternal PCOS. Stratified analyses were performed to test the independent role of PCOS and the joint effects of PCOS with maternal obesity, perinatal problems, cesarean delivery, gestational diabetes and use of fertility treatment. The analysis was adjusted for maternal age, country of birth, marriage status at birth, smoking, parity, psychiatric disorders, prescription of psychotropic N05/N06 during pregnancy and systemic inflammatory diseases when applicable.Main Results and the Role Of Chance: A total of 105 409 (9.8%) children were diagnosed with a neurodevelopmental or psychiatric disorder. Firstly, maternal PCOS was associated with any psychiatric diagnosis (HR 1.32; 95% CI 1.27-1.38) in offspring. Particularly, the risk was increased for sleeping disorders (HR 1.46; 95% CI 1.27-1.67), attention-deficit/hyperactivity disorders and conduct disorders (HR 1.42; 95% CI 1.33-1.52), tic disorders (HR 1.42; 95% CI 1.21-1.68), intellectual disabilities (HR 1.41; 95% CI 1.24-1.60), autism spectrum disorder (HR 1.40; 95% CI 1.26-1.57), specific developmental disorders (HR 1.37; 95% CI 1.30-1.43), eating disorders (HR 1.36; 95% CI 1.15-1.61), anxiety disorders (HR 1.33; 95% CI 1.26-1.41), mood disorders (HR 1.27; 95% CI 1.18-1.35) and other behavioral and emotional disorders (ICD-10 F98, HR 1.49; 95% CI 1.39-1.59). In short, there was no significant difference between sexes. The results were robust when restricting the analyses to the first-born children or births to mothers without psychiatric diagnosis or purchase of psychotropic medication. Secondly, stratified analysis according to maternal BMI showed that the risk of any neuropsychiatric disorder was increased in offspring to normal-weight mothers with PCOS (HR 1.20; 95% CI 1.09-1.32), and markedly higher in those to severely obese mothers with PCOS (HR 2.11; 95% CI 1.76-2.53) compared to offspring to normal-weight mothers without PCOS. When excluding perinatal problems, mothers with PCOS were still associated with increased risks of any neuropsychiatric disorders in offspring (HR 1.28; 95% CI 1.22-1.34) compared to mothers without PCOS. However, an additional increase was observed for PCOS in combination with perinatal problems (HR 1.99; 95% CI 1.84-2.16). Likewise, excluding cases with maternal gestational diabetes (HR 1.30; 95% CI 1.25-1.36), cesarean delivery (HR 1.29; 95% CI 1.23-1.35) or fertility treatment (HR 1.31; 95% CI 1.25-1.36) did not eliminate the associations.Limitations, Reasons For Caution: The register-based prevalence of PCOS was lower than previously reported, suggesting that this study may capture the most severe cases. To combine anovulatory infertility with PCOS diagnosis as PCOS exposure might introduce diagnostic bias. It was not feasible to distinguish between subtypes of PCOS. Furthermore, familial factors might confound the association between maternal PCOS and neuropsychiatric disorders in offspring. Maternal BMI was available for birth cohort 2004-2014 only and there was no information on gestational weight gain.Wider Implications Of the Findings: This study provides further evidence that maternal PCOS and/or anovulatory infertility, independently and jointly with maternal obesity, perinatal problems, gestational diabetes and cesarean delivery, implies a broad range of adverse effects on offspring neurodevelopment. These findings may potentially help in counseling and managing pregnancies.Study Funding/competing Interest(s): This study was supported by the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C and C.L.), THL Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. was supported by the China Scholarship Council during her training in Karolinska Institute. L.K. was supported by the China Scholarship Council for his PhD study in Karolinska Institute. The authors have no competing interests to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: With the increased number of cancer survivors, it is necessary to explore the effect of cancer and its treatments on pregnancy outcomes, such as preterm birth, which seriously endangers the health of offspring. We aimed to explore the risk of being born preterm among offspring of cancer survivors. Materials and Methods: This is a retrospective cohort study. All singleton live births between 1973 and 2014 in Sweden with information of birth outcomes were retrieved from the Swedish Medical Birth Register. By linking to several Swedish registers, we identified all parents of children and parental cancer diagnosis. Logistic regression was used to estimate odds ratios and 95% confidence intervals. Results: As compared to the children without parental cancer, the risk of being born preterm was significantly higher among children of overall female cancer survivors born after cancer diagnosis with an adjusted OR of 1.48 (95 CI% = 1.39–1.59), in particular those diagnosed with childhood cancer and cancer in female genital organs. Besides, the risk might continuously decline with time at the first 8 years after maternal diagnosis. A higher risk of being born preterm was found among offspring of male survivors diagnosed with central nervous system cancer (Adjusted OR = 1.26, 95% CI = 1.04–1.53). Conclusions: Our study provides evidence for a higher risk of being born preterm among children of female cancer survivors and male survivors with central nervous system tumor, as well as indicates that the effect on female reproductive system from cancer and related-treatments might decline with time. [ABSTRACT FROM AUTHOR]

Study Question: Do children born after assisted reproductive technology (ART) have an increased risk of developing type 1 diabetes?Summary Answer: Children born after ART were found to have an increased risk of type 1 diabetes in the unadjusted analysis, while after adjustment this association was only significant in children born after frozen embryo transfer.What Is Known Already?: Some studies raise concerns as to whether fertility treatments may influence long-term morbidity in children born after ART. Elevated blood pressure and altered glucose metabolism have been found after ART in a few studies.Study Design, Size, Duration: A register-based national cohort study that included all children born in Sweden between 1985 and 2015-in total, 3 138 540 children-was carried out.Participants/material, Setting, Methods: The study was population-based and all live-born singleton children born after ART (n = 47 938) or spontaneous conception (SC) (n = 3 090 602) were included. The ART cohort comprised 36 727 children born after fresh embryo transfer and 11 211 children born after frozen embryo transfer. Several national registries were used together with data from Statistics Sweden.Main Results and the Role Of Chance: In total, 202 children born after ART and 17 916 children born after SC developed type 1 diabetes, corresponding to 43.4 and 35.5 per 100 000 person-years at risk (hazard ratio [HR] 1.23; 95% confidence interval [CI], 1.07 to 1.42). Mean follow-up was 9.7 (SD 6.4) years for ART children and 16.3 (SD 9.2) years for SC children. After adjustment for calendar year of birth, HR for type 1 diabetes was 1.13; 95% CI, 0.98-1.30. After further adjustment for sex, maternal age, country of birth, educational level, smoking and parental diabetes, HR was 1.07; 95% CI, 0.93-1.23. In subgroup analyses, an association was found between frozen embryo transfer and type 1 diabetes (adjusted HR 1.52; 95% CI, 1.08-2.14 and 1.41; 95% CI, 1.05-1.89 for frozen versus fresh and frozen versus SC, respectively). When comparing intracytoplasmic sperm injection to in vitro fertilization, no difference was found (adjusted HR 1.08; 95% CI, 0.77-1.51).Limitations, Reasons For Caution: Limitations were the missing data and residual confounding caused by unknown confounders. Furthermore, the control group consisted of all children not conceived by ART and not non-ART children from subfertile mothers. The study was also performed in only singletons and not in the total ART population.Wider Implications Of the Findings: Type 1 diabetes is a serious disease, affecting human life in several ways, including risk of serious complications, reduced life span and a life-long treatment. Our results are generally reassuring, showing no increase in diabetes in ART children compared to children born after SC after adjustment for relevant confounders. The observation of an association between children born after frozen embryo transfer and type 1 diabetes, although based on subgroup analyses with a limited number of children and modest in size, is however a reason for concern.Study Funding/competing Interest(s): This study was funded by Nordforsk 71450, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement 70940, and the Hjalmar Svensson Foundation. The authors have no competing interests.Trial Registration Number: ISRCTN 11780826. [ABSTRACT FROM AUTHOR]

Background: Neurological, visual and hearing deviations have been observed in the offspring of parents with schizophrenia. This study test whether children to parents hospitalized with schizophrenia have increased the likelihood of childhood neurological disorder. Methods: Among all parents in Sweden born 1950–1985 and with offspring born 1968–2002: 7107 children with a parent hospitalized for schizophrenia were compared to 172 982 children with no parents hospitalized for schizophrenia or major depression, as well as to 32 494 children with a parent hospitalized for major depression as a control population with another severe psychiatric outcome. We estimated relative risks (RR) and two-sided 95% confidence intervals calculated from Poisson regression. Results: Children to parents with schizophrenia were more likely than controls to have been hospitalized before the age of 10 with a diagnosis of cerebral palsy, RR = 1.76 (95% CI: 1.15–2.69); epilepsy, RR = 1.78 (95% CI: 1.33–2.40), combined neurological disease, RR = 1.33 (95% CI: 1.11–1.60) and certain diseases of the eye, RR = 1.92 (95% CI: 1.17–3.15) and ear, RR = 1.18 (95% CI: 1.05–1.32). Similar disease-risk-pattern was found for children to parents hospitalized with a diagnosis of major depression. A specific risk increase for strabismus RR = 1.21 (95%CI: 1.05–1.40) was found for off-spring with parental depression. Conclusions: Compared with children to healthy parents, children to parents with schizophrenia have increased risk of a variety of neurological disorders as well as visual and hearing disorders at an early age. The risk increase was not specific to schizophrenia but was also seen in children to parents with a diagnosis of major depression. [ABSTRACT FROM AUTHOR]

Background: With improvements in treatment of cancer, more men of fertile age are survivors of cancer. This study evaluates trends in birth rates among male cancer survivors and mortality rates of their offspring.Methods: From the Swedish Multi-generation Register and Cancer Register, we identified 84,752 men ≤70 years with a history of cancer, for which we calculated relative birth rates as compared to the background population(Standardized Birth Ratios, SBRs). We also identified 126,696 offspring of men who had cancer, and compared their risks of death to the background population(Standardized Mortality Ratio, SMRs). Independent factors associated with reduced birth rates and mortality rates were estimated with Poisson modelling.Results: Men with a history of cancer were 23 % less likely to father a child compared to the background population(SBR 0.77, 95 % Confidence Interval[CI] 0.75-0.79). Nulliparous men were significantly more likely to father a child after diagnosis (SBR 0.81, 95 % CI 0.79-0.83) compared to parous men (SBR 0.68, 95 % CI 0.66-0.74). Cancer site(prostate), onset of cancer during childhood or adolescence, parity status at diagnosis(parous), current age(>40 years) and a recent diagnosis were significant and independent predictors of a reduced probability of fathering a child after diagnosis. Of the 126,696 children born to men who have had a diagnosis of cancer, 2604(2.06 %) died during follow up. The overall mortality rate was similar to the background population(SMR of 1.00, 95 %CI 0.96-1.04) and was not affected by the timing of their birth in relation to father's cancer diagnosis.Conclusion: Male cancer survivors are less likely to father a child compared to the background population. This is influenced by cancer site, age of onset and parity status at diagnosis. However, their offspring are not at an increased risk of death. [ABSTRACT FROM AUTHOR]

Objective Investigate the effects of maternal gestational diabetes mellitus ( GDM) on height, weight, and body mass index ( BMI) in offspring compared both to their siblings and to age-specific BMI reference values in Sweden. Their parents present BMI was also investigated. Methods The growth of 232 offspring to 110 women with at least one pregnancy with GDM, were studied up to 12 yr of age. Height and weight of children were collected from Health Care Centres and compared to age-specific reference values in Sweden. Self-reported height and weight of the parents were collected at follow-up. Results For boys, weight was higher at birth and at 8-10 yr of age, giving a higher BMI at 7-10 yr of age. Girls had an accelerated height growth at all ages, combined with an increased weight of varying degree resulting in higher BMI at birth and at 4-12 yr of age. A similar pattern was observed in siblings born after a normal pregnancy. Median BMI of mothers at follow-up was 25.4 (18.3-59.5 n = 105) and 26.5 (18.6-38.1 n = 90) for fathers. Conclusions Children born to mothers with prior GDM have a higher risk of overweight and obesity later in life. This is most likely due to life style habits rather than intrauterine factors, as the same BMI pattern was found in siblings born after a normal pregnancy. However, the design of the study could not rule out the role of genetic factors. Priority should be given to early life style intervention in these families. [ABSTRACT FROM AUTHOR]

Restricted fetal growth and young maternal age have been associated with increased risk of suicidal behaviour later in life. Research investigating the independent and interacting effects of these risk factors with parental mental health and socio-economic status is scarce. A case-control study was effected through record linkage between Swedish registers. Individuals born 1973-1983 who were hospitalized due to a suicide attempt (n = 17,159) or committed suicide (n = 1,407) were matched to ≤10 controls by sex, month and county of birth. Controlling for parental conditions, significantly increased odds ratios (OR) for suicide attempt were found for low birth weight (OR = 1.12, 95 % CI 1.01-1.25), short birth length (OR = 1.15, 95 % CI 1.08-1.22), short and light for gestational age (OR = 1.23, 95 % CI: 1.10-1.38), short but not light for gestational age (OR = 1.18, 95 % CI: 1.09, 1.29), teenage motherhood (OR = 1.66, 95 % CI 1.53-1.80), young fatherhood (OR = 1.33, 95 % CI 1.27-1.39) and multiparity (OR = 1.40, 95 % CI 1.31-1.50). For completed suicide, increased odds ratios were found for low birth weight (OR = 1.65, 95 % CI 1.16-2.35), teenage motherhood (OR = 1.44, 95 % CI 1.09-1.90) and young fatherhood (OR = 1.20, 95 % CI 1.02-1.41). There was a synergy effect between teenage motherhood and parental psychiatric inpatient care with regard to suicide attempt in offspring [synergy index = 1.53 (95 % CI 1.27-1.84)]. Low birth weight and length, and short and light for gestational age may increase the risk of subsequent suicidal behaviour, and more research is needed to investigate underlying mechanisms. Public health implications from this study include measures to improve pre- and perinatal parental mental health, particularly in teenage pregnancies. [ABSTRACT FROM AUTHOR]

BackgroundOffspring of patients with schizophrenia exhibit poorer school performance compared with offspring of non-schizophrenic parents. We aimed to elucidate the mechanisms behind this association.MethodWe linked longitudinal national population registers in Sweden and compared school performance among offspring of schizophrenic parents with offspring of non-schizophrenic parents (1 439 215 individuals with final grades from compulsory school 1988–2006). To investigate the mechanisms, we studied offspring of schizophrenic patients and controls within the same extended families. We investigated genetic effects by stratifying analyses of parent–child associations according to genetic relatedness (half-cousins, full cousins and half-siblings). Environmental effects were investigated by comparing school performance of offspring of schizophrenic fathers and of schizophrenic mothers, respectively, and by stratifying the analyses according to environmental relatedness while controlling genetic relatedness (paternal and maternal half-cousins, paternal and maternal half-siblings).ResultsOffspring of parents with schizophrenia had poorer overall school performance than unrelated offspring of non-schizophrenic parents (−0.31 s.d.). Variability in genetic relatedness greatly moderated the strength of the within-family association (β=−0.23 within exposure-discordant half-cousins, β=−0.13 within exposure-discordant full cousins, β=0.04 within exposure-discordant half-siblings), while no evidence was found that the environment affected offspring school performance.ConclusionsGenetic factors account for poorer school performance in children of parents with schizophrenia. This supports that cognitive deficits found in individuals with schizophrenia and their relatives might be genetically inherited. Early detection of prodromal signs and impaired functioning of offspring of patients with schizophrenia could lead to earlier and better tailored interventions. [ABSTRACT FROM PUBLISHER]

Research has documented associations between family functioning and offspring psychosocial adjustment, but questions remain regarding whether these associations are partly due to confounding genetic factors and other environmental factors. The current study used a genetically informed approach, the Children of Twins design, to explore the associations between family functioning (family conflict, marital quality, and agreement about parenting) and offspring psychopathology. Participants were 867 twin pairs (388 monozygotic; 479 dizygotic) from the Twin and Offspring Study in Sweden, their spouses, and children (51.7% female; M = 15.75 years). The results suggested associations between exposure to family conflict (assessed by the mother, father, and child) and child adjustment were independent of genetic factors and other environmental factors. However, when family conflict was assessed using only children's reports, the results indicated that genetic factors also influenced these associations. In addition, the analyses indicated that exposure to low marital quality and agreement about parenting was associated with children's internalizing and externalizing problems and that genetic factors also contributed to the associations of marital quality and agreement about parenting with offspring externalizing problems. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our study was to investigate whether reproductive factors influence the risk of primary brain tumours (PBT) in offspring. Methods: Data on all deliveries in two Swedish counties from 1955 to 1990 were extracted from two birth registries. The follow-up period closed at the end of 1994, with subjects followed up to early middle age. Incidence rates of malignancy for 1958-1994 were obtained from the Swedish Cancer Registry. Standardised incidence ratios (SIR) and relative risks were calculated for astrocytomas, primitive neuroectodermal tumour, ependymoma and meningiomas in offspring. Results: Few associations were detected. High birth weight indicated an increased risk for astrocytomas grade I and II for all primary brain tumours, and the risk was close to significance for astrocytomas grade I-II (SIR = 3.64; CI = 0.98-9.31). For children under 15 years of age the risk for astrocytomas grade I and II was further increased (SIR = 4.44; CI = 1.19-11.38). Conclusions: A consistent pattern of non-association indicated a low impact of intrauterine environment on the future development of primary brain tumours in offspring up to early middle age. [ABSTRACT FROM AUTHOR]

Schizophrenia in the mother may imply an increased risk of adverse pregnancy outcome. However, inconclusive findings, unknown pathological mechanisms and possible confounding by social factors and smoking requests further explorations. The aim of this study were to (1) examine non-optimal pregnancy outcome using data from a population-based cohort, controlling for covariates known to influence fetal growth; and (2) perform separate analyses of women diagnosed before childbirth and women hospitalized for schizophrenia during pregnancy. The study sample comprised 2096 births by 1438 mothers diagnosed with schizophrenia (of whom 696 mothers were antenatal diagnosed and 188 admitted during pregnancy) and 1,555,975 births in the general population. We found significantly increased risks for stillbirth, infant death, preterm delivery, low birth weight, and small-for-gestational-age among the offspring of women with schizophrenia. Women with an episode of schizophrenia during pregnancy had the highest risks (e.g., low birth weight; OR 4.3, 95% CI 2.9–6.6 and stillbirth; OR 4.4, 95% CI 1.4–13.8). Controlling for a high incidence of smoking during pregnancy among schizophrenic women (51% vs. 24% in the normal population) and other maternal factors (single motherhood, maternal age, parity, maternal education, mothers'' country of birth and pregnancy-induced hypertensive diseases) in a multiple regression model, reduced the risk estimates markedly. However, the risks for adverse pregnancy outcomes were even after adjustments generally doubled for women with an episode of schizophrenia during pregnancy compared to women in the control group (e.g., low birth weight; OR 2.3, 95% CI 1.5–3.5, preterm delivery; OR 2.4, 95% CI 1.5–3.8 and stillbirth; OR 2.5, 95% CI 0.8–7.9). The risks for preterm delivery and low birth weight were significantly elevated throughout the analyses. We conclude that schizophrenia in the mother implies an increased risk for poor perinatal outcome, not fully explained by maternal factors, and a need to consider a common familial (probably genetic) vulnerability for pre- and perinatal stress and schizophrenia. [Copyright &y& Elsevier]

As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.

Background: Children experience a higher risk of psychiatric problems when their parents are diagnosed with cancer. However, the psychological effect among offspring who are born after parental cancer diagnosed in childhood or adolescence is unknown. We aimed to investigate the risk of psychiatric disorders in children of survivors with childhood or adolescent central nervous system (CNS) tumors., Methods: By combining several nationwide Swedish registers, we identified all children who had at least one parent previously diagnosed with CNS tumor below the age of 20. Five children without parental CNS tumor were randomly selected for the matching. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence interval (CI)., Results: The incidence rate of psychiatric disorders was 8.46 per 1000 person-years in children of CNS tumor survivors, whereas the rate was 7.47 in the matched comparisons, yielding an adjusted HR of 1.10 (95% CI = 0.94, 1.28). Boys of survivors had a higher risk of psychiatric disorders (adjusted HR = 1.29, 95% CI = 1.04, 1.59). The risk of the specific types of psychiatric disorders in children of tumor survivors was comparable with that in the matched comparisons, except for mental retardation. Children of survivors experienced 2.36 times higher risk of mental retardation (95% CI = 1.21, 4.58), mainly of mild mental retardation (adjusted HR = 2.99, 95% CI = 1.40, 6.38)., Conclusion: Children of survivors with CNS tumor in early life did not experience a significantly increased risk of overall psychiatric disorders, with the exception of an elevated risk of mental retardation that was mainly mild., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Nonrandom mating has been shown for psychiatric diagnoses, with hypothesized-but not quantified-implications for offspring liability. This national cohort study enumerated the incidence of major psychiatric disorders among the offspring of parent pairs affected with schizophrenia (SCZ) and/or bipolar disorder (BIP) (i.e., dual-affected pairs)., Methods: Participants were all Swedish residents alive or born between 1968 and 2013 (n = 4,255,196 unique pairs and 8,343,951 offspring). Offspring with dual-affected, single-affected, and unaffected parents were followed (1973-2013) for incidence of broad psychiatric disorders. Primary outcomes included hazard ratio (HR) and cumulative incidence for SCZ and BIP in the offspring. Additional outcomes included any neuropsychiatric, anxiety, depressive, personality, or substance use disorders. Cumulative incidences of SCZ and BIP were used to inform heritability models for these disorders., Results: Hazards were highest within disorder (e.g., offspring of dual-SCZ pairs had sharply raised hazards for SCZ [HR = 55.3]); however, they were significantly raised for all diagnoses (HR range = 2.89-11.84). Incidences were significantly higher for the majority of outcomes, with 43.4% to 48.5% diagnosed with "any" disorder over follow-up. Risks were retained, with modest attenuations, for the offspring of heterotypic pairs. The estimated heritability of liability for SCZ (h 2  = 0.62, 95% confidence interval = 0.55-0.70) and BIP (h 2  = 0.52, 95% confidence interval = 0.46-0.58) did not differ significantly from estimates derived from single-affected parents., Conclusions: Risks for a broad spectrum of psychiatric diagnoses are significantly raised in the offspring of dual-affected parents, in line with expectations from a polygenic model of liability to disease risk. How these risks may contribute to population maintenance of these disorders is considered., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Pharmacotherapy is effective in reducing the core symptoms of attention-deficit/hyperactivity disorder (ADHD). We aimed to investigate the concurrent association between pharmacotherapy for ADHD in offspring and depression-related specialty care visits by the parents with a history of depression., Methods: Using data from a variety of Swedish national registers, we conducted a cohort study with 8-year follow-up of 5605 parents (3872 mothers and 1733 fathers) who had a history of depression and an offspring diagnosed with ADHD. The hazard rate for parental depression-related specialty care visits during exposed periods when the offspring was on medication for treatment of ADHD was compared with the hazard rate during unexposed periods when the offspring was off medication. Within-individual comparisons were employed to control for time-constant confounding factors., Results: Among mothers, the crude rates of depression-related specialty care visits during exposed and unexposed periods were 61.33 and 63.95 per 100 person-years, respectively. The corresponding rates among fathers were 49.23 and 54.65 per 100 person-years. When the same parent was compared with him or herself, fathers showed a decreased hazard rate for depression-related visits during exposed periods when the offspring was on medication for treatment of ADHD as compared to unexposed periods (hazard ratio, 0.79 [95% confidence interval, 0.70 to 0.90]). No statistically significant associations were observed in mothers., Conclusions: Among parents with a history of depression, pharmacotherapy for ADHD in offspring is concurrently associated with a decreased rate of depression-related specialty care visits in fathers but not in mothers. Future research with refined measures of parental depression and other time-varying familial factors is needed to better understand the mechanisms underlying the association.

Background: Findings from animal and human studies indicate that anxiety and stress have a negative influence on the child and mother. The aim of this study was to explore the risk for having an anxiety diagnosis and the impact of the diagnosis in a three generational perspective., Methods: The information was retrieved from Swedish population-based registries. All women who gave birth between 1973 and 1977 (n 169,782), their daughters (n 244,152), and subsequently also the offspring of the daughters (n 381,953) were followed until 2013., Results: We found that 4% of the mothers and 6% of the grandmothers had been diagnosed with anxiety. Women who had mothers with an anxiety disorder were more than twice as likely to have an anxiety disorder themselves compared to all other women (OR = 2.20, 95% CI = 2.04-2.30). In the third generation, the children born to mothers with an anxiety disorder, the odds ratio of being diagnosed with anxiety was more than twice as high than for the rest of the population (OR = 2.54, 95% CI = 2.01-3.20). If both the mother and the grandmother had had an anxiety disorder the odds ratio for the child having a diagnosis of anxiety was three times higher (OR = 3.11, 95% CI = 2.04-4.75). Anxiety diagnosis in the two previous generations also increased the likelihood of the child having either more than two inpatient visits or more than 10 outpatient visits (OR = 2.64, 95% CI = 2.40-2.91 and OR = 2.21, 95% CI = 2.01-2.43, respectively)., Conclusions: The intergenerational effect on anxiety is high. In order to minimize the risk for further transmission of anxiety disorders, increased awareness and generous use of effective treatment regimes might be of importance.

Parents' antisocial behavior is associated with developmental risks for their offspring, but its effects on their children's cognitive ability are unknown. We used linked Swedish register data for a large sample of adolescent men (N = 1,177,173) and their parents to estimate associations between fathers' criminal-conviction status and sons' cognitive ability assessed at compulsory military conscription. Mechanisms behind the association were tested in children-of-siblings models across three types of sibling fathers with increasing genetic relatedness (half-siblings, full siblings, and monozygotic twins) and in quantitative genetic models. Sons whose fathers had a criminal conviction had lower cognitive ability than sons whose fathers had no conviction (any crime: Cohen's d = -0.28; violent crime: Cohen's d = -0.49). As models adjusted for more genetic factors, the association was gradually reduced and eventually eliminated. Nuclear-family environmental factors did not contribute to the association. Our results suggest that the association between men's antisocial behavior and their children's cognitive ability is not causal but is due mostly to underlying genetic factors., (© The Author(s) 2014.)

Objective: To investigate opinions on the acceptable number of donation offspring in a national cohort of oocyte and sperm donors., Design: A prospective follow-up study on a national cohort of gamete donors., Setting: Sweden., Methods: Study-specific questionnaire., Main Outcome Measures: Opinion on the acceptable number of offspring from one donor., Results: About half of both oocyte and sperm donors expressed an opinion that the number of offspring from one donor should be limited to between one and 10, and many donors reported having no firm opinion. When controlling for age, educational level, marital status and biological children, oocyte donors were four times more likely than sperm donors to support an upper limit of five offspring. For many sperm and oocyte donors the number of offspring resulting from their donations was unknown (43.2% oocyte, 47.1% sperm)., Conclusion: Oocyte donors have more restrictive opinions compared with sperm donors on the acceptable number of offspring from one donor. Donors perform a very humanitarian and societal act when donating their gametes. In the ambition to have safe and trustworthy clinics we need to have well known regulations to be able to recruit donors in the future., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To characterise early growth and neurocognitive development in children of mothers with a history of eating disorders (ED)., Design: A longitudinal cohort study., Setting: Child-care centres in Stockholm, Sweden., Population: Children born to mothers with previous ED (n = 47) (24 anorexia nervosa, 20 bulimia nervosa, 3 unspecified ED), and controls (n = 65)., Methods: Mean values and standard deviation scores of weight and height from birth to 5 years of age and head circumference up to 18 months of age were compared between groups. Neurocognitive development was studied at the age of 5 years by the validated parent questionnaire Five to Fifteen., Main Outcome Measures: Head growth and neurocognitive development., Results: We previously reported that mothers with a history of ED conceived infants with lower birthweight and head circumference than controls. At 3 months of age, body mass index (BMI) was no longer reduced but mean head circumferences of the children born to mothers with ED were smaller throughout the observation period. Similarly, the longitudinal results of the standard deviation scores of head circumference showed a significant overall group effect with lower levels in both subgroups of ED (anorexia nervosa and bulimia nervosa). The children of the ED mothers also had significantly higher Five to Fifteen scores than controls, reflecting difficulties in language skills. Head circumference at birth correlated with language skills in the children of mothers with ED., Conclusion: Children of mothers with previous ED demonstrated an early catch-up in BMI, but the average head circumference continued to be delayed until at least 18 months of age. The reduced head growth was related to delayed neurocognitive development., (© 2013 RCOG.)