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The percentage of people without children over their lifetime is approximately 25% in men and 20% in women. Individual diseases have been linked to childlessness, mostly in women, yet we lack a comprehensive picture of the effect of early-life diseases on lifetime childlessness. We examined all individuals born in 1956-1968 (men) and 1956-1973 (women) in Finland (n = 1,035,928) and Sweden (n = 1,509,092) to the completion of their reproductive lifespan in 2018. Leveraging nationwide registers, we associated sociodemographic and reproductive information with 414 diseases across 16 categories, using a population and matched-pair case-control design of siblings discordant for childlessness (71,524 full sisters and 77,622 full brothers). The strongest associations were mental-behavioural disorders (particularly among men), congenital anomalies and endocrine-nutritional-metabolic disorders (strongest among women). We identified new associations for inflammatory and autoimmune diseases. Associations were dependent on age at onset and mediated by singlehood and education. This evidence can be used to understand how disease contributes to involuntary childlessness.

Objectives: To study sexually transmitted Chlamydia trachomatis infections (STCTs), teenage pregnancies, and payment defaults in individuals born preterm as proxies for engaging in risk-taking behavior. Study design: Our population-based register-linkage study included all 191 705 children alive at 10 years (8492 preterm [4.4%]) born without malformations in Finland between January 1987 and September 1990 as each mother’s first child within the cohort. They were followed until young adulthood. We used Cox regression to assess the hazards of STCTs, teenage pregnancies, payment defaults, criminal offending, and substance abuse by gestational age. Gestational age was considered both as a continuous and categorical (extremely, very, moderately, late preterm, early term, post term, and full term as reference) exposure. Results: A linear dose-response relationship existed between gestational age and STCT and teenage pregnancy; adjusted hazard for STCT decreased by 1.6% (95% CI, 0.7%‐2.6%), and for teenage pregnancy by 3.3% (95% CI, 1.9%‐4.8%) per each week decrease in gestational age. Those born extremely preterm (23‐27 completed weeks) had a 51% (95% CI, 31%‐83%) lower risk for criminal offending than their full-term born counterparts, and those born very preterm (range, 28‐31 weeks) had a 28% (95% CI, 7%‐53%) higher hazard for payment defaults than those born at full term. Gestational age was not associated with substance abuse. Conclusions: The lower risk-taking that characterizes people born preterm seems to generalize to sexual and to some extent criminal behavior. Those born very preterm are, however, more likely to experience payment defaults.

STUDY QUESTION: Are genetic disorders and congenital malformations associated with premature ovarian insufficiency (POI)? SUMMARY ANSWER: A wide range of genetic disorder and congenital malformation diagnoses are associated with POI, especially early onset POI. WHAT IS KNOWN ALREADY: POI is known to be associated with some genetic disorders, such as Turner syndrome and Fragile X premutation. Multiple genetic syndromes, such as ataxia teleangiectasia and galactosemia, have also been associated with an increased risk of POI, and many of these genetic syndromes manifest with various congenital malformations. In previous studies, a genetic aetiology has been found for 7–15% of POI cases. STUDY DESIGN, SIZE, DURATION: This population-based study included 5011 women diagnosed with POI in 1988–2017. The data were collected from various national registries and covers women with POI nationwide. PARTICIPANTS/MATERIALS, SETTING, METHODS: We identified 5011 women diagnosed with POI from 1988 to 2017 from the drug reimbursement registry of the Social Insurance Institution of Finland. Women with surgical POI (bilateral oophorectomy for benign indications) were not included. We selected four population controls per woman with POI matched by month and year of birth and municipality of residence. Diagnostic codes for genetic disorders and congenital malformations (GD/CM) for the cases and controls were searched from the Hospital Discharge Register. Binary logistic regression was used to compare the odds for GD/CM among cases and controls. To minimize bias, for the statistical analyses, we excluded diagnoses which were reported <2 years prior to the index date. MAIN RESULTS AND THE ROLE OF CHANCE: Of the women with POI, 15.9% (n = 797) had at least one diagnostic code for GD or CM. The odds ratio (OR) for Turner syndrome was 275 (95% CI 68.1–1110), and for other sex chromosome abnormalities, it was 12.7 (95% CI 4.1–39.1). For autosomal single gene disorders, the OR was 16

Parental severe mental illness (SMI) may affect offspring physical health outcomes in multiple ways. Offspring of parents with SMI are at higher risk of developing mental illness. The impact of parental SMI on offspring’s cardiometabolic health and mortality by diseases and medical conditions is still poorly understood. This study aimed to examine cardiometabolic morbidity in middle-aged offspring of parents with SMI. The following cardiometabolic disorders were used as outcome measures: diabetes mellitus, hypertension, hyperlipidaemia, coronary artery disease, obesity and cerebrovascular disorders. The study also examined cardiometabolic risk factors including glucose levels, lipid levels, insulin levels and insulin resistance. Another aim of the study was to investigate mortality by diseases and medical conditions in offspring of parents with SMI. The follow-up time was 49 years. The study determined if the risk of mortality by diseases and medical conditions increased among offspring of individuals with SMI compared to a comparison group. The hypothesis was that offspring of people with severe mental disorders have increased cardiometabolic morbidity risk and mortality risk by diseases and medical conditions. The study was prospective with data from both clinical examination and registers. Participants were from unselected population-based birth cohort: The Northern Finland Birth Cohort 1966 (n=12,231). Offspring of parents with SMI had increased cardiometabolic morbidity risk. Male offspring had elevated risk of coronary artery disease, hyperlipidaemia, obesity and hypertension. Offspring of parents with SMI had increased risk for obesity, especially offspring of mothers with SMI. Female offspring of parents with SMI had partly increased risk for disturbances in cardiometabolic risk factors. They had increased risk for higher glucose level and waist circumference. Offspring of parents with SMI had no increased risk for mortality by diseases and medical, Tiivistelmä Vanhempien vakava mielenterveyden häiriö (SMI) voi vaikuttaa jälkeläisten fyysiseen terveyteen monin eri tavoin. Vakavaa mielenterveydenhäiriötä sairastavien vanhempien jälkeläisillä on suurempi riski sairastua psykiatrisiin sairauksiin. Vanhempien vakavan mielenterveyden häiriön vaikutus jälkeläisten kardiometaboliseen terveyteen ja tautikuolleisuuteen on kuitenkin heikosti ymmärretty. Tämän tutkimuksen tavoitteena oli tutkia vakavaa mielenterveyden häiriötä sairastavien vanhempien keski-ikäisten jälkeläisten kardiometabolista sairastavuutta. Seuraavia kardiometabolisia häiriöitä käytettiin tulosmuuttujina: diabetes mellitus, verenpainesairaudet, rasva-aineenvaihdunnan häiriöt, iskeemiset sydänsairaudet, lihavuus ja aivoverenkierron sairaudet. Tutkimuksessa tarkasteltiin myös kardiometabolisia riskitekijöitä, mukaan lukien glukoositaso, lipiditaso, insuliinitaso ja insuliiniresistenssi. Tutkimuksen tavoitteena oli selvittää myös vakavaa mielenterveyden häiriötä sairastavien vanhempien jälkeläisten tautikuolleisuutta. Seuranta-aika oli 49 vuotta. Hypoteesina oli, että vakavaa mielenterveydenhäiriötä sairastavien vanhempien jälkeläisillä on suurentunut kardiometabolisten sairauksien riski ja suurentunut kuolleisuusriski. Tutkimus oli prospektiivinen kliinisistä tutkimuksista ja rekistereistä saatuun dataan perustuva. Osallistujat olivat valikoimattomasta väestöpohjaisesta syntymäkohortista: Pohjois-Suomen syntymäkohortti 1966:sta (n=12,231). Vakavaa mielenterveyden häiriötä sairastavien vanhempien jälkeläisillä oli suurentunut riski kardiometabolisiin sairauksiin. Vakavaa mielenterveydenhäiriötä sairastavien vanhempien miespuoleisilla jälkeläisillä oli suurentunut iskeemisen sydänsairauden, hyperlipidemian, lihavuuden ja verenpainetaudin riski. Lihavuuden riski oli kohonnut vaikeaa mielenterveyden häiriötä sairastavien vanhempien jälkeläisillä, erityisesti äitien. Vakavaa mielenterveydenhäiriötä sairastavien vanhempien naispuoleisilla jälkeläisillä oli os

Background: Type 2 diabetes and dyslipidemias co-occur frequently with severe mental illnesses (SMI). However, less is known about serum insulin and lipid levels and prevalence of Insulin Resistance (IR) in offspring with familial risk for SMI. Method: The Northern Finland Birth Cohort 1966 consists of 12,068 mothers, 11,068 fathers, and 12,231 children from the two northernmost provinces in Finland. At age 46 they participated in clinical examination including measurements of glucose, lipids, and IR and answered a questionnaire including information about their nutrition and physical activity. The information on parental SMI was obtained from the Hospital Discharge Register. Parents with SMI were those who had been treated in hospital for any psychiatric disorder during 1969–1982 (ICD-8 codes 290–315). The final study group included 334 (7.3 %) offspring who had a parent with SMI and 4249 (92.7 %) offspring in the comparison group. Results: We did not find increased risk for disturbances in lipid levels, insulin levels, or IR levels between the study group (offspring of either parent with SMI) compared with the comparison group. All offspring, especially female offspring of either parent with SMI, had an increased risk for higher glucose levels and waist circumference. The results remained the same after excluding offspring with SMI. Conclusion: Our findings suggest that offspring of parents with SMI, especially female offspring, have partly increased risk for disturbances in cardiometabolic risk factors. Disturbances in glucose metabolism may have an effect via familial risk of severe mental illness.

Attendance in special education (SE) is more common among individuals born preterm than among those born at term. Less is known about school grades of those born preterm in mainstream education (ME), and how these grades predict later educational attainment. This population-based register-linkage study assessed (1) attendance in SE, and then focused on those in ME by assessing (2) school grades at 16 year, (3) completed educational level at 25 year, and (4) school grades as predictors for completed education by gestational age (GA) with full-term birth (39–41 completed weeks) as reference. The sample comprised 223,744 individuals (10,521 preterm, 4.7%) born in Finland (1/1987–9/1990). Of the sample, 4.9% attended SE. Those born preterm had up to 5.5-fold rates for SE. In ME, those born extremely preterm (EPT) had marginally lower mathematics grades compared with full-term counterparts, whilst those born late preterm or early term had slightly higher grades. Those born EPT or very preterm had lower physical education grades in ME. However, the minor differences in school grades according to GA appear not to translate into educational differences in young adulthood. The associations between school grades at 16 year and completed education at 25 year did not vary by GA.

Aims: In most population-based epidemiological follow-up studies the aim is not to intervene in the life of the participants. Although the idea is not to intervene, being a member of the longitudinal follow-up study and studies conducted during follow-up may affect the target population. A population-based study including mental health enquiries might reduce the unmet need for psychiatric treatment by motivating people to seek treatment for their psychiatric ill-health. We examined the use of psychiatric care services in the population born in the year 1966 in Northern Finland, of whom 96.3% are participants in the prospective Northern Finland Birth Cohort 1966 (NFBC1966). Methods: As a study cohort we used people born in 1966 in Northern Finland (n = 11 447). The comparison cohort included all the people born in the years 1965 and 1967 in the same geographical area (n = 23 339). The follow-up period was from age 10 to 50 years. The outcome measure was the use of psychiatric care services, which was analysed using Cox Proportional Hazard regression and Zero-Truncated Negative Binomial Regression. Results: People born in 1966 in Northern Finland did not differ from those born in 1965 and 1967 in terms of the outcome measure. Conclusions: We found no association between participation in an epidemiological follow-up study and the use of psychiatric care services. The NFBC1966 may be regarded as a representative at the population level in terms of psychiatric outcomes despite the personal follow-up of the birth cohort. The associations of participation in epidemiological follow-up studies have previously been under-examined, and the results need to be replicated.

Prospective birth cohort studies are longitudinal research studies that follow a group of individuals from birth throughout their lifespan, collecting data on various factors over time. The data collection methods may include clinical examinations, questionnaires, tests, interviews, and linkage to existing data, enabling the examination of multiple risk factors and potential interactions between them. The follow-up procedures raise a question about whether intensive follow-up could affect the study population in any way. This study focuses on the association between participation in longitudinal follow-up studies and the use of psychiatric care services and cardiometabolic disorders in two prospective birth cohort studies, the Northern Finland Birth Cohort 1966 (NFBC1966) and the Northern Finland Birth Cohort 1986 (NFBC1986). The hypothesis is that participation in the NFBC studies may increase the use of psychiatric healthcare services and reduce suicidal behaviour, and that cohort participants may live healthier lives and have fewer cardiometabolic disorders than comparison cohorts. In addition, we explored the changes in the incidences of hospital-treated psychiatric disorders in five large Finnish birth cohorts of individuals born between 1966 and 1997. The results show somewhat inconsistent effects of participation in the NFBC1966 and NFBC1986 studies. Female participants of NFBC1966 had a significantly younger onset of several cardiometabolic disorders, while female participants of NFBC1986 used less psychiatric care services and male participants of NFBC1986 had a decreased risk for several cardiometabolic disorders. In addition, the incidence of hospital-treated psychiatric disorders increased over the decades in the five birth cohorts in Finland, which is somewhat opposite to the Finnish psychiatric health policy plan. It is important to note that the cohort participants of NFBC1986 are still relatively young, and an accurate assessment of the diff, Tiivistelmä Prospektiiviset syntymäkohorttitutkimukset ovat pitkittäistutkimuksia, joissa tutkimusväestöä seurataan syntymästä lähtien läpi elämän keräämällä tietoja eri tekijöistä ajan kuluessa. Tietoja voidaan kerätä kliinisillä tutkimuksilla, kyselyillä ja haastatteluilla, mikä mahdollistaa useiden riskitekijöiden ja niiden mahdollisten vuorovaikutusten tutkimisen. Prospektiivisten syntymäkohorttien pitkä seuranta herättää kysymyksen, voiko intensiivinen seuranta vaikuttaa tutkimusväestöön millään tavalla. Tämä tutkimus keskittyy pitkittäisseurantaan osallistumisen ja psykiatristen terveydenhuoltopalveluiden käytön sekä kardiometabolisten häiriöiden väliseen yhteyteen kahdessa prospektiivisessa syntymäkohorttitutkimuksessa, Pohjois-Suomen syntymäkohortti 1966:ssa (NFBC1966) ja Pohjois-Suomen syntymäkohortti 1986:ssa (NFBC1986). Hypoteesina on, että osallistuminen NFBC-tutkimuksiin saattaa lisätä psykiatristen terveydenhuoltopalveluiden käyttöä ja vähentää itsemurhakäyttäytymistä, sekä se, että kohortin osallistujat saattavat elää terveellisemmin ja kärsiä vähemmän kardiometabolisista häiriöistä kuin vertailukohortit. Lisäksi tutkitaan sairaalassa hoidettujen psykiatristen häiriöiden esiintyvyyden muutoksia viidessä suuressa suomalaisessa syntymäkohortissa, joiden osallistujat ovat syntyneet vuosien 1966 ja 1997 välillä. Tulokset osoittavat jonkin verran epäjohdonmukaisia vaikutuksia NFBC1966- ja NFBC1986-syntymäkohortteihin osallistumisella. NFBC1966:n naisosallistujilla oli tilastollisesti merkitsevästi nuorempi sairastumisikä kardiometabolisiin sairauksiin, NFBC1986:n naisosallistujat käyttivät vähemmän psykiatrisia hoitopalveluita ja NFBC1986:n miesosallistujilla oli pienentynyt riski sairastua kardiometabolisiin sairauksiin vertailukohorttiin verrattuna. Lisäksi sairaalassa hoidettujen psykiatristen häiriöiden esiintyvyys kasvoi viimeisten vuosikymmenten aikana viidessä syntymäkohortissa Suomessa, mikä on jonkin verran ristiriidassa Suomen psykiatrisen tervey

STUDY QUESTION: Do women with endometriosis have lower first live birth rate before surgical diagnosis than women without verified endometriosis? SUMMARY ANSWER: Compared to reference women, the incidence of first live birth was lower in women prior to surgical verification of endometriosis irrespective of the type of endometriosis. WHAT IS KNOWN ALREADY: Endometriosis is associated with pain and reduced fertility. The mechanism of infertility is partly explained by anatomical, endocrinological, and immunological changes. Over the past decades, the treatment of both endometriosis and infertility has evolved. Knowledge of fertility far before surgical diagnosis of endometriosis in large cohorts and of different types of endometriosis has been lacking. The diagnostic delay of endometriosis is long, 6–7 years. STUDY DESIGN, SIZE, DURATION: Retrospective population-based cohort study focused on the time period before the surgical verification of endometriosis. All women with surgical verification of endometriosis in 1998–2012 were identified from the Finnish Hospital Discharge Register and the reference cohort from the Central Population Register. Data on deliveries, gynecological care, and sociodemographic factors before the surgical diagnosis were gathered from Finnish national registers maintained by the Finnish Institute for Health and Welfare, the Digital and Population Data Services Agency, and Statistics Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women aged 15–49 years at the time of surgical verification of endometriosis (ICD-10: N80.1–N80.9) in Finland during 1998–2012 were identified (n = 21 620). Of them, we excluded women born in 1980–1999 due to the proximity of the surgical diagnosis (n = 3286) and women left without reference (n = 10) for the final endometriosis cohort of 18 324 women. From the final cohort, we selected sub-cohorts of women with isolated diagnosis of ovarian (n = 6384), peritoneal (n = 5789), and deep (n = 1267) endom

Background: Preterm birth affects lungs in several ways but few studies have follow-up until adulthood. We investigated the association of the entire spectrum of gestational ages with specialist care episodes for obstructive airway disease (asthma and chronic obstructive pulmonary disease (COPD)) at age 18–50 years. Methods: We used nationwide registry data on 706 717 people born 1987–1998 in Finland (4.8% preterm) and 1 669 528 born 1967–1999 in Norway (5.0% preterm). Care episodes of asthma and COPD were obtained from specialised healthcare registers, available in Finland for 2005–2016 and in Norway for 2008–2017. We used logistic regression to estimate odds ratios (ORs) for having a care episode with either disease outcome. Results: Odds of any obstructive airway disease in adulthood for those born at <28 or 28–31 completed weeks were 2–3-fold of those born full term (39–41 completed weeks), persisting after adjustments. For individuals born at 32–33, 34–36 or 37–38 weeks, the odds were 1.1- to 1.5-fold. Associations were similar in the Finnish and the Norwegian data and among people aged 18–29 and 30–50 years. For COPD at age 30–50 years, the OR was 7.44 (95% CI 3.49–15.85) for those born at <28 weeks, 3.18 (95% CI 2.23–4.54) for those born at 28–31 weeks and 2.32 (95% CI 1.72–3.12) for those born at 32–33 weeks. Bronchopulmonary dysplasia in infancy increased the odds further for those born at <28 and 28–31 weeks. Conclusion: Preterm birth is a risk factor for asthma and COPD in adulthood. The high odds of COPD call for diagnostic vigilance when adults born very preterm present with respiratory symptoms.

Background: We studied the association between participation in the longitudinal follow-up study and cardiometabolic disorders in two longitudinal studies which started prospectively in the antenatal period: the Northern Finland Cohort 1966 (NFBC1966) and the Northern Finland Birth Cohort 1986 (NFBC1986). Both birth cohorts have been followed up since birth with multiple follow-ups including questionnaires, and clinical examinations. Methods: The NFBC studies were compared to comparison cohorts of individuals who were born in the same area as the study cohorts, but in different years. The data for the comparison cohort were obtained from registers. The cumulative incidence rates of hospital-treated cardiometabolic disorders were calculated for study and comparison cohorts covering the age of 7–50 years in NFBC1966 and the age of 0–29 years in NFBC1986. Cardiometabolic-related causes of death were analysed in NFBC1966 and the comparison cohort from the age of 0–50 years. The analysed cardiometabolic disorders were diabetes mellitus, coronary artery disease, hyperlipidaemia, obesity, hypertension, and cerebrovascular disorders. The risk ratio (RR) with 95% confidence intervals (CI) was calculated by sex. Results: In NFBC1966, no differences in cumulative incidences of cardiometabolic disorders or cardiometabolic-related deaths compared to the comparison cohort were found. Male members of NFBC1986 had decreased risk of obesity (RR: 0.45, 95% CI: 0.27–0.75) and any cardiometabolic disorders (RR: 0.75, 95% CI: 0.59–0.95) compared to the comparison cohort. Conclusions: The results suggest that participation in the NFBC1986 may have a weak positive health effect among men. Agreement to follow-up studies focusing on diet, substance use, and physical activity, may slightly decrease the incident risk of cardiometabolic disorders in the study population.