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To better understand the role of neuroendocrinological regulation in adolescent mental health, stress reactivity needs to be analyzed through both the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Accordingly, this study examined how adolescents' internalizing and externalizing mental health symptoms are associated with their salivary alpha-amylase and cortisol levels, responses, and coordination (symmetry versus asymmetry). We utilized a developmentally salient stress task of mother-adolescent conflict discussion. Eighty 18-20-year-old late adolescents (55% girls) participated in a home laboratory assessment involving a 10-min conflict discussion with their mothers. Five adolescent saliva samples were collected to measure alpha-amylase and cortisol levels before, immediately after, and in 10-min intervals following the conflict discussion, to indicate stress reactivity. Adolescents had reported their internalizing (depression, anxiety, somatization) and externalizing (inattention, hyperactivity, anger control problems) symptoms 1 year earlier as part of a prospective family study. Internalizing symptoms were associated with adolescents' high baseline cortisol levels, but not with cortisol responses or alpha-amylase levels or responses. In contrast, externalizing symptoms were associated with blunted alpha-amylase responses. Neither internalizing nor externalizing symptoms were associated with asymmetry between alpha-amylase and cortisol reactivity. The mother-adolescent conflict discussion was relevant as a stress stimulus to induce neuroendocrinological stress responses in adolescents. The nature of mental health problems was important for stress reactivity, yet, we found no evidence about mental health problems being related to endocrinological asymmetry in adolescents.

STUDY QUESTION To what extent can hypertensive disorders in pregnancy (HDP) explain the higher risk of preterm birth following frozen embryo transfer (frozen-ET) and fresh embryo transfer (fresh-ET) in ART compared with naturally conceived pregnancies? SUMMARY ANSWER HDP did not contribute to the higher risk of preterm birth in pregnancies after fresh-ET but mediated 20.7% of the association between frozen-ET and preterm birth. WHAT IS KNOWN ALREADY Risk of preterm birth is higher after ART compared to natural conception. However, there is also a higher risk of HDP in pregnancies after ART compared to natural conception, in particular after frozen-ET. HDP increases the risk of both spontaneous and medically indicated preterm birth. It is not known to what extent the higher risk of preterm birth in ART-conceived pregnancies is mediated through HDP. STUDY DESIGN, SIZE, DURATION This registry-based cohort study included singleton pregnancies from the Committee of Nordic ART and Safety (CoNARTaS) cohort from Denmark (1994–2014), Norway (1988–2015), and Sweden (1988–2015). The analysis included 78 300 singletons born after fresh-ET, 18 037 after frozen-ET, and 4 426 682 after natural conception. The exposure was ART conception with either frozen-ET or fresh-ET versus natural conception. The main mediator of interest was any of the following HDP: gestational hypertension, preeclampsia, eclampsia, or chronic hypertension with superimposed preeclampsia. The main outcome was any preterm birth, defined as delivery <37 weeks of gestation. Secondary outcomes were spontaneous and medically indicated preterm birth, and different severities of preterm birth based on the gestational age threshold. PARTICIPANTS/MATERIALS, SETTING, METHODS We linked data from the national Medical Birth Registries, ART registries/databases, and the National Patient Registries in each country using the unique national identity number of the mother. Criteria for inclusion were singleton pregnancies with birth order 1–4 in women aged ≥20 years at delivery. We used logistic regression to estimate odds ratios (ORs) with 95% CIs of preterm birth and decomposed the total effect into direct and mediated (indirect) effects to estimate the proportion mediated by HDP. Main models included adjustment for the year of delivery, maternal age, parity, and country. MAIN RESULTS AND THE ROLE OF CHANCE Pregnancies following frozen-ET had a higher risk of any preterm birth compared to natural conception (occurrence 6.6% vs 5.0%, total effect OR 1.29, 95% CI 1.21–1.37) and 20.7% of the association was mediated by HDP (mediated effect OR 1.05, 95% CI 1.04–1.05). The mediation occurred primarily in medically indicated preterm births. Pregnancies following fresh-ET also had a higher risk of any preterm birth compared to naturally conceived pregnancies (occurrence 8.1% vs 5.0%, total effect OR 1.49, 95% CI: 1.45–1.53), but none of this could be mediated by HDP (mediated effect OR 1.00, 95%CI 1.00–1.00, proportion mediated 0.5%). Sensitivity analyses with extra confounder adjustment for body mass index and smoking, and restriction to primiparous women, were consistent with our main findings. Furthermore, the results were not driven by differences in ART procedures (intracytoplasmic sperm injection, culture duration, or the number of embryos transferred). LIMITATIONS, REASONS FOR CAUTION Although we could adjust for some important confounders, we cannot exclude residual confounding, particularly from factors associated with infertility. WIDER IMPLICATIONS OF THE FINDINGS This population-based mediation analysis suggests that some of the higher risk of preterm birth after ART treatment may be explained by the higher risk of HDP after frozen-ET. If causality is established, investigations into preventive strategies such as prophylactic aspirin in pregnancies after frozen-ET may be warranted. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by NordForsk (project number: 71450), the Nordic Federation of Obstetrics and Gynaecology (project numbers NF13041, NF15058, NF16026, and NF17043), the Norwegian University of Science and Technology (project number 81850092), an ESHRE Grant for research in reproductive medicine (grant number 2022-2), and the Research Council of Norway's Centres of Excellence funding scheme (project number 262700). D.A.L.'s and A.E.'s contribution to this work was supported by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreements No 101021566) and the UK Medical Research Council (MC_UU_00032/05). D.A.L. has received support from Roche Diagnostics and Medtronic Ltd for research unrelated to that presented here. Pinborg declares grants from Gedeon Richter, Ferring, Cryos, and Merck, consulting fees from IBSA, Ferring, Gedeon Richter, Cryos, and Merck, payments from Gedeon Richter, Ferring, Merck, and Organon,travel support from Gedeon Richter. All other authors declare no conflicts of interest related to this work. TRIAL REGISTRATION NUMBER ISRCTN 35879. [ABSTRACT FROM AUTHOR]

Background: Parents' low health literacy (HL) has negative impacts on child health. Parental interventions may improve parents' HL and thus impact child health positively. Objectives: This study aimed to gain knowledge about associations between parents' comprehensive HL (CHL) and child health after an extended postnatal home visiting program in Swedish multicultural, disadvantaged settings compared to parents receiving regular child healthcare (CHC). Materials and Methods: This quasi‐experimental study used a case–control sampling method to recruit first‐time parents through two CHC centres in Stockholm (2017–2020). Participants (N = 151) were interviewed twice through structured questionnaires when their child was <2 months and 15–18 months old. HLS‐EU‐Q16 assessed parents' CHL. Children's medical records (0–18 months) were reviewed regarding breastfeeding, children's exposure to smoking, language development and healthcare utilisation. Data were analysed with regression models and non‐parametric tests. Results: No significant association was found between parents' CHL and child health. However, significantly fewer unplanned visits to the CHC centre were observed among children (0–18 months) in the intervention group irrespective of CHL, compared with children to parents with improved CHL in the comparison group (F = 3.856, p = 0.011). Conclusions: Postnatal home visiting interventions practicing proportional universalism and family‐centred care may reduce unplanned visits within CHC in disadvantaged settings despite parents' CHL. Further studies with long‐term follow‐up are suggested to explore associations between parents' CHL and child health. Trial Registration: As a clinical study (not a clinical trial) with appropriate ethical permission with participants' consents, this study was retrospectively registered (18 February 2020) in the ISRCTN registry (ISRCTN10336603). [ABSTRACT FROM AUTHOR]

Abstract Background Health literacy (HL) is important for individuals in terms of knowledge and competence to make decisions about healthcare, health promotion and disease prevention. Migrants generally demonstrate lower HL levels compared to the majority populations. HL interventions among migrants are rarely studied. Thus, there is a need to find useful HL measurements for multicultural settings. The importance of understanding parents’ HL is related to their key role in providing and promoting the health of their children. This study aimed to add knowledge about the psychometric properties of the HLS-EU-Q16 instrument (Swedish version) among parents in Swedish multicultural settings. Methods A cross sectional design was used. Totally 193 first-time parents (N = 193) were recruited through two child healthcare centres in Stockholm. Parents were interviewed when their infants were

BackgroundThe aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception.Methods and findingsWe performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 person-years), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproductive method and of leukemia after FET were observed. The main limitation of this study is the small number of children with cancer in the FET group.ConclusionsChildren born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications.Trial registrationTrial registration number: ISRCTN 11780826.

This person-oriented study aimed to identify adolescents’ hierarchical attachment profiles with parents and peers, and to analyze associations between the profiles and adolescent psychosocial adjustment. Participants were 449 Finnish 17–19-year-olds reporting their attachments to mother, father, best friend, and romantic partner and details on mental health (internalizing symptoms, inattention/hyperactivity, and anger control problems) and risk-taking behavior (substance use and sexual risk-taking). Attachment was measured with Experiences in Close Relationships – Relationship Structures (ECR-RS); internalizing, inattention/hyperactivity, and anger control problems with Self-Report of Personality — Adolescent (SRP—A) of the Behavior Assessment System for Children, third edition (BASC-3); substance use with the Consumption scale of the Alcohol Use Disorders Identification Test (AUDIT-C) and items from the Finnish School Health Promotion Study; and sexual risk-taking behavior with the Cognitive Appraisal of Risky Events (CARE). Latent profile analysis identified five attachment profiles: “All secure” (39%), “All insecure” (11%), “Parents insecure – Peers secure” (21%), “Parents secure – Friend insecure” (10%), and “Parents secure – Partner insecure” (19%). “All insecure” adolescents showed the highest and “All secure” adolescents the lowest levels of mental health problems and substance use. Further, parental attachment security seemed to specifically prevent substance use and anger control problems, while peer attachment security prevented internalizing problems. Our findings help both understand the organization of attachment hierarchies in adolescence and refine the role of specific attachment relationships in psychosocial adjustment, which can be important for clinical interventions in adolescence.

ObjectiveIn autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) defects in the autoimmune regulator gene lead to impaired immunotolerance. We explored the effects of immunodeficiency and endocrinopathies on gynecologic health in patients with APECED.DesignCross-sectional cohort study combined with longitudinal follow-up data.MethodsWe carried out a gynecologic evaluation, pelvic ultrasound, and laboratory and microbiologic assessment in 19 women with APECED. Retrospective data were collected from previous study visits and hospital records.ResultsThe study subjects’ median age was 42.6 years (range, 16.7-65.5). Sixteen patients (84%) had premature ovarian insufficiency, diagnosed at the median age of 16.5 years; 75% of them used currently either combined contraception or hormonal replacement therapy. In 76% of women, the morphology and size of the uterus were determined normal for age, menopausal status, and current hormonal therapy. Fifteen patients (79%) had primary adrenal insufficiency; three of them used dehydroepiandrosterone substitution. All androgen concentrations were under the detection limit in 11 patients (58%). Genital infections were detected in nine patients (47%); most of them were asymptomatic. Gynecologic C. albicans infection was detected in four patients (21%); one of the strains was resistant to azoles. Five patients (26%) had human papillomavirus infection, three of which were high-risk subtypes. Cervical cell atypia was detected in one patient. No correlation between genital infections and anti-cytokine autoantibodies was found.ConclusionsOvarian and adrenal insufficiencies manifested with very low androgen levels in over half of the patients. Asymptomatic genital infections, but not cervical cell atypia, were common in female patients with APECED.

BackgroundSome earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC).Methods and findingsThis was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (ConclusionsIn this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART.Trial registration numberISRCTN11780826.

The quality of parenting shapes the development of children’s emotion regulation. However, the relative importance of parenting in different developmental stages, indicative of sensitive periods, has rarely been studied. Therefore, we formulated four hypothetical developmental timing models to test the stage-specific effects of mothering and fathering in terms of parental autonomy and intimacy in infancy, middle childhood, and late adolescence on adolescents’ emotion regulation. The emotion regulation included reappraisal, suppression, and rumination. We hypothesized that both mothering and fathering in each developmental stage contribute unique effects to adolescents’ emotion regulation patterns. The participants were 885 families followed from pregnancy to late adolescence. This preregistered study used data at the children’s ages of 1 year, 7 to 8 years, and 18 years. At each measurement point, maternal and paternal autonomy and intimacy were assessed with self- and partner reports using the Subjective Family Picture Test. At the age of 18 years, adolescents’ reappraisal and suppression were assessed using the Emotion Regulation Questionnaire and rumination using the Cognitive Emotion Regulation Questionnaire. Stage-specific effects were tested comparing structural equation models. Against our hypotheses, the results showed no effects of mothering or fathering in infancy, middle childhood, or late adolescence on adolescents’ emotion regulation patterns. The results were consistent irrespective of both the reporter (i.e., self or partner) and the parental dimension (i.e., autonomy or intimacy). In addition to our main results, there were relatively low agreement between the parents in each other’s parenting and descriptive discontinuity of parenting across time (i.e., configural measurement invariance). Overall, we found no support for the stage-specific effects of parent-reported parenting in infancy, middle childhood, or late adolescence on adolescents’ emotion regulation. Instead, our findings might reflect the high developmental plasticity of emotion regulation from infancy to late adolescence.

BackgroundCompared to naturally conceived children, adverse perinatal outcomes are more common among children born after assisted reproductive technology with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET). However, most previous studies could not adequately control for family confounding factors such as subfertility. We compared birth size and duration of pregnancy among infants born after fresh-ET or frozen-ET versus natural conception, using a within-sibship design to account for confounding by maternal factors.Methods and findingsThis registry-based cohort study with nationwide data from Denmark (1994-2014), Norway (1988-2015), and Sweden (1988-2015) consisted of 4,510,790 live-born singletons, 4,414,703 from natural conception, 78,095 from fresh-ET, and 17,990 from frozen-ET. We identified 33,056 offspring sibling groups with the same mother, conceived by at least 2 different conception methods. Outcomes were mean birthweight, small and large for gestational age, mean gestational age, preterm (ConclusionsWe found that infants conceived by fresh-ET had lower birthweight and increased odds of small for gestational age, and those conceived by frozen-ET had higher birthweight and increased odds of large for gestational age. Conception by either fresh-ET or frozen-ET was associated with increased odds of preterm birth. That these findings were observed within siblings, as well as in conventional multivariable population analyses, reduces the likelihood that they are explained by confounding or selection bias.Trial registrationClinicalTrials.gov ISRCTN11780826.

A father's mental health is important for family well-being, but research is scarce on paternal symptoms during the transition to fatherhood. This study identified fathers' latent mental health trajectory classes from the pre- to postnatal period and examined their associations with early fathering experiences. It further analysed, whether a family's infertility history was associated with mental health trajectory classes and moderated their effects on fathering experiences. Finnish fathers (N = 773) reported psychological distress (General Health Questionnaire; GHQ-36) and depressive symptoms (Beck Depression Inventory; BDI-13) in pregnancy (T1), and at 2 months (T2) and 12 months (T3) postpartum. They further reported their fathering experience (Parenting Stress Index; PSI-36) at T2 and T3. Results revealed five paternal mental health trajectory classes, differing in timing and course of symptoms across the pre- and postpartum: stable low (79%) and moderate increasing (9%) levels of symptoms, and prenatal (5%), early fatherhood (3%) and heterogeneous high levels of (4%) problems. The trajectory classes were associated with fathering experiences within parental, interactive and child domains, across the child's first year. The stable low levels of symptoms-class showed the most positive experiences and the heterogeneous high levels of problems-class the most negative ones; mental health problems in the early fatherhood-class reported negative fathering experience, but only when the child was 2 months old. A family's infertility history neither showed any significant association with trajectory classes nor moderated their impact on early fathering, supporting the growing evidence that infertility treatments do not place an additional burden on early fatherhood.

The family environment shapes children's social information processing and emotion regulation. Yet, the long-term effects of early family systems have rarely been studied. This study investigated how family system types predict children's attentional biases toward facial expressions at the age of 10 years. The participants were 79 children from Cohesive, Disengaged, Enmeshed, and Authoritarian family types based on marital and parental relationship trajectories from pregnancy to the age of 12 months. A dot-probe task was used to assess children's emotional attention biases toward threatening (angry) and affiliative (happy) faces at the early (500 ms) and late (1250 ms) stages of processing. Situational priming was applied to activate children's sense of danger or safety. Results showed that children from Cohesive families had an early-stage attentional bias toward threat, whereas children from Enmeshed families had a late-stage bias toward threat. Children from Disengaged families had an early-stage attentional bias toward threat, but showed in addition a late-stage bias away from emotional faces (i.e., both angry and happy). Children from Authoritarian families, in turn, showed a late-stage attentional bias toward emotional faces. Situational priming did not moderate the effects of family system types on children's attentional biases. The findings confirm the influence of early family systems on the attentional biases, suggesting differences in the emotion regulation strategies children have developed to adapt to their family environments.

Abstract Background To improve prerequisites for better health development among children growing up in multicultural suburbs in Stockholm County, where poorer health is displayed in several aspects including child health, early support was initiated for first-time parents in one of the suburbs. An extended postnatal home visiting program during the child’s first 15 months was offered to families with first-time mothers during 2013–2014 and consisted of six home visits by a child health care nurse and a parental advisor from social services. Almost all invited families (94%) participated in the program and the program evaluation. Fathers’ participation in two or more home visits within the program was 53%. The aim of this study was to explore the experiences of fathers participating in the program, with respect to their role as a first-time parent from a resilience perspective. Methods In-depth interviews were conducted with nine fathers. Constructivist grounded theory (GT) was applied in the analysis. Results The fathers’ experiences formed the core category of the study, ‘striving for stability in living conditions’, as well as three categories: ‘everyday life conditions’, ‘adjustment to fatherhood in Sweden’ and ‘channels of support’. The fathers perceived that the home visiting program strengthened their parental confidence and increased their knowledge of societal services and local resources for their family. Conclusions In terms of resilience, the extended postnatal home visiting program benefitted the interviewed migrant fathers on an individual level by meeting part of their need for support regarding knowledge and parental confidence; on a structural level the program helped fathers gain information about available societal services and resources in their local area. Trial registration The study was retrospectively registered (11 August 2016) in the ISRCTN registry (ISRCTN11832097 DOI: https://doi.org/10.1186/ISRCTN11832097).

The sudden outbreak of the COVID-19 pandemic and the ensuing restrictive measures to combat infections led to a significant change in working life and social work within working communities. Workers had to switch to telecommuting quickly, which also affected the interactions between co-workers. In this research, we examined Finnish social workers’ experiences of their work communities during the first wave of the COVID-19 pandemic. We explored (1) how the restrictive measures affected social workers’ work communities and (2) what types of factors promoted and challenged the cohesion of social networks and mutual trust between colleagues. The conceptual framework was based on social capital theory, in which social relations are seen as a resource of a community. The data utilised in the study were social workers’ diaries (n = 33) written from mid-March until the end of May 2020. The data were analysed by a qualitative content analysis. The results highlight how the multilocation of work, fear of viral infection and varying attitudes towards the viral outbreak affected the interactions between colleagues in the early stages of the pandemic, increasing tensions and feelings of social distance between co-workers. The common professional value and knowledge base of social work, as well as remote work practices developed during the first wave of the COVID-19 pandemic, supported interactions between colleagues. Although remote interaction options were developed, they could not, however, fully replace the advantages of face-to-face interactions and everyday informal encounters between colleagues, the importance of which is essential for developing and maintaining the social capital of work communities.

Kristiina Rönö,1 Beata Stach-Lempinen,2 Johan Gunnar Eriksson,3,4 Maritta Pöyhönen-Alho,1 Miira Marjuska Klemetti,1,2,5 Risto Paavo Roine,6,7 Emilia Huvinen,1 Sture Andersson,8 Hannele Laivuori,6,9–11 Anita Valkama,3,4 Jelena Meinilä,3,4 Hannu Kautiainen,3,12 Aila Tiitinen,1 Saila Birgitta Koivusalo1 1Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Women’s Hospital, Helsinki, Finland; 2Department of Obstetrics and Gynecology, South Karelia Central Hospital, Lappeenranta, Finland; 3Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 4Public Health Research Program, Folkhälsan Research Center, Helsinki, Finland; 5Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 6Department of Health and Social Management, Research Centre for Comparative Effectiveness and Patient Safety, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Group Administration, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 8University of Helsinki and Helsinki University Hospital, Children’s Hospital, Pediatric Research Center, Helsinki, Finland; 9Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; 10Department of Obstetrics and Gynecology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; 11Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland; 12Department of General Practice and Primary Health Care, University of Eastern Finland, Kuopio, Finland Purpose: Lifestyle intervention studies performed during pregnancy have shown inconsistent results in relation to prevention of gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the effect of an intervention initiated already before pregnancy in prevention of GDM in high-risk women.Patients and methods: A randomized controlled trial was conducted in four Finnish maternity hospitals between the years 2008 and 2014. Altogether 228 high-risk women planning pregnancy were randomized to an intervention (n=116) or a control group (n=112). The risk factors were body mass index ≥30 kg/m2 (n=46), prior GDM (n=120), or both (n=62), without manifest diabetes at study inclusion. Trained study nurses provided individualized lifestyle counseling every 3 months in addition to a group session with a dietician. The control group received standard antenatal care. GDM was defined as one or more pathological glucose values in a 75 g 2-hour oral glucose tolerance test, performed between 12 and 16 weeks of gestation and if normal repeated between 24 and 28 weeks of gestation.Results: Within 12 months, 67% of the women (n=72) in the intervention group and 63% of the women (n=71) in the control group (p=0.84) became pregnant. The cumulative incidence of GDM among the women available for the final analyses was 60% (n=39/65) in the intervention group and 54% (n=34/63) in the control group (p=0.49). GDM was diagnosed already before 20 weeks of gestation in 60% (n=44/73) of the cases.Conclusion: The preconceptional lifestyle intervention applied in the present study did not reduce the incidence of GDM. Keywords: preconception, pregnancy, obesity, nutrition, physical activity

Abstract Background Assisted reproductive technology (ART) has been associated with low birth weight of fresh embryo transfer (FRESH) derived and increased birth weight of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on imprinted insulin-like growth factor 2 (IGF2)/H19 locus known to be important for normal growth. This locus is regulated by H19 imprinting control region (ICR) with seven binding sites for the methylation-sensitive zinc finger regulatory protein (CTCF). A polymorphism rs10732516 G/A in the sixth binding site for CTCF, associates with a genotype-specific trend to the DNA methylation. Due to this association, 62 couples with singleton pregnancies derived from FRESH (44 IVF/18 ICSI), 24 couples from FET (15 IVF/9 ICSI), and 157 couples with spontaneously conceived pregnancies as controls were recruited in Finland and Estonia for genotype-specific examination. DNA methylation levels at the H19 ICR, H19 DMR, and long interspersed nuclear elements in placental tissue were explored by MassARRAY EpiTYPER (n = 122). Allele-specific changes in the methylation level of H19 ICR in placental tissue (n = 26) and white blood cells (WBC, n = 8) were examined by bisulfite sequencing. Newborns’ (n = 243) anthropometrics was analyzed by using international growth standards. Results A consistent trend of genotype-specific decreased methylation level was observed in paternal allele of rs10732516 paternal A/maternal G genotype, but not in paternal G/maternal A genotype, at H19 ICR in ART placentas. This hypomethylation was not detected in WBCs. Also genotype-specific differences in FRESH-derived newborns’ birth weight and head circumference were observed (P = 0.04, P = 0.004, respectively): FRESH-derived newborns with G/G genotype were heavier (P = 0.04) and had larger head circumference (P = 0.002) compared to newborns with A/A genotype. Also, the placental weight and birth weight of controls, FRESH- and FET-derived newborns differed significantly in rs10732516 A/A genotype (P = 0.024, P = 0.006, respectively): the placentas and newborns of FET-derived pregnancies were heavier compared to FRESH-derived pregnancies (P = 0.02, P = 0.004, respectively). Conclusions The observed DNA methylation changes together with the phenotypic findings suggest that rs10732516 polymorphism associates with the effects of ART in a parent-of-origin manner. Therefore, this polymorphism should be considered when the effects of environmental factors on embryonic development are studied.