The risk of Type 1 diabetes in children born after ART: a Nordic cohort study from the CoNARTaS group.

STUDY QUESTION: Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART? SUMMARY ANSWER: The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment. WHAT IS KNOWN ALREADY: ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life. STUDY DESIGN SIZE DURATION: A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994-2014), Finland (1990-2014), and Norway (1984-2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively. PARTICIPANTS/MATERIALS SETTING METHODS: The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984-1990, 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found, except for the youngest cohort of children born 2011-2015 where ART was associated with a higher risk of DM1. We found no significant differences in risk of DM1 when comparing children born after IVF versus ICSI or fresh versus frozen embryo transfer, but with only few cases in each group. LIMITATIONS REASONS FOR CAUTION: The main limitation of the study is the relatively short follow-up time. The incidence rate of DM1 peaks during ages 10-14 years, hence a longer follow-up would benefit all analyses and, in particular, the subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS: Overall, our findings are reassuring especially considering the concomitantly increasing number of children born from ART and the increasing incidence of DM1 globally. STUDY FUNDING/COMPETING INTERESTS: This Nordic registry study has been supported by the Nordic Trial Alliance/NORDFORSK and Rigshospitalets Research Foundation. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. None of the authors has any conflicts of interest to declare regarding this study. TRIAL REGISTRATION NUMBER: ISRCTN11780826.

Surgically confirmed endometriosis in adolescents in Finland-A register-based cross-sectional cohort study.

INTRODUCTION: Increasing awareness of endometriosis in adolescents requires data on the nature of the disease and its management. Our objective was to investigate the subtypes of surgically confirmed endometriosis in adolescents (aged <20 years) and trends in the incidence rates and endometriosis-related procedures during the study period, 1987-2012. MATERIAL AND METHODS: In this register-based cohort study, we identified 526 adolescents receiving their initial surgical diagnosis of endometriosis between 1987 and 2012 from the Finnish Hospital Discharge Register. The age-specific incidence rate of surgically confirmed endometriosis was calculated by dividing the number of adolescents during specific periods by person-years. We calculated the relative differences in incidence rates between the periods using crude incidence ratios. RESULTS: Adolescents were divided into three age groups, <17, 17-18, and 19 years, which comprised 8.2% (43/526), 39.7% (209/526), and 52.1% (274/526) of the study cohort, respectively. Peritoneal endometriosis and ovarian endometriosis were the most common types (379/526 [72%] and 119/526 [23%], respectively). The incidence rate of surgically confirmed endometriosis per 100 000 person-years varied from 5.63 (95% confidence interval [CI] 4.24-7.33) to 11.42 (95% CI 9.64-13.44). The incidence rate in 2001-2005 was significantly higher and was 1.6- to 2.0-fold that of the periods 1987-1990 and 2006-2012, respectively. Comparing the periods in which International Classification of Diseases, Ninth Revision (ICD-9; 1987-1995) and Tenth Revision (ICD-10; 1996-2012) codes were used, the use of laparoscopy (78.2% vs 88.9%), day surgery (10.3% vs 31.6%), and procedures for ovarian (18.8% vs 34.1%) and deep (0.6% vs 10.8%) endometriosis increased. The types of endometriosis and procedures did not differ between the age groups. CONCLUSIONS: Peritoneal endometriosis was the most common type of endometriosis overall and by age group. During the 26-year period, the incidence rate of initial surgical diagnosis of endometriosis peaked in 2001-2005 and decreased thereafter. The proportion of procedures performed for ovarian and deep endometriosis increased, as did the use of laparoscopy and day surgery.

Ideal Cardiovascular Health and Vascular Phenotype Associations in Mothers with Obesity and Their Six-Year-Old Children.

BACKGROUND: Heredity and family-shared lifestyle contribute to cardiovascular risk, but the magnitude of their influence on arterial structure and function in early childhood is unknown. We aimed to assess associations between child and maternal ideal cardiovascular health, maternal subclinical atherosclerosis, and child arterial phenotype. METHODS: Cross-sectional analysis of 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL) longitudinal cohort was done at child age 6.1 ± 0.5 years with assessments of ideal cardiovascular health (BMI, blood pressure, fasting glucose, total cholesterol, diet quality, physical activity, smoking), body composition, very-high frequency ultrasound of carotid arteries (25 and 35 MHz), and pulse wave velocity. RESULTS: We found no association between child and maternal ideal cardiovascular health but report evidence of particular metrics correlations: total cholesterol (r=0.24, P=0.003), BMI (r=0.17, P=0.02), diastolic blood pressure (r=0.15, P=0.03), and diet quality (r=0.22, P=0.002). Child arterial phenotype was not associated with child or maternal ideal cardiovascular health. In the multivariable regression explanatory model adjusted for child sex, age, systolic blood pressure, lean body mass, and body fat percentage, child carotid intima-media thickness was independently associated only with maternal carotid intima-media thickness (0.1 mm increase [95% CI 0.05, 0.21, P=0.001] for each 1 mm increase in maternal carotid intima-media thickness). Children of mothers with subclinical atherosclerosis had decreased carotid artery distensibility (1.1 ± 0.2 vs 1.2 ± 0.2%/10 mmHg, P=0.01) and trend toward increased carotid intima-media thickness (0.37 ± 0.04 vs 0.35 ± 0.04 mm, P=0.06). CONCLUSION: Ideal Cardiovascular Health metrics are heterogeneously associated in mother-child pairs in early childhood. We found no evidence of child or maternal Ideal Cardiovascular Health effect on child arterial phenotype. Maternal carotid intima-media thickness predicts child carotid intima-media thickness, but the underlying mechanisms remain unclear. Maternal subclinical atherosclerosis is associated with local carotid arterial stiffness in early childhood.

No effect of gestational diabetes or pre-gestational obesity on 6-year offspring left ventricular function-RADIEL study follow-up.

AIMS: We aimed to investigate associations between pre-pregnancy obesity, gestational diabetes (GDM), offspring body composition, and left ventricular diastolic and systolic function in early childhood. METHODS: This is an observational study, including 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL; 96 with GDM, 128 with pre-pregnancy obesity) with follow-up from gestation to 6-year postpartum. Follow-up included dyads anthropometrics, body composition, blood pressure, and child left ventricular function with comprehensive echocardiography (conventional and strain imaging). RESULTS: Offspring left ventricular diastolic and systolic function was not associated with gestational glucose concentrations, GDM, or pregravida obesity. Child body fat percentage correlated with maternal pre-pregnancy BMI in the setting of maternal obesity (r = 0.23, P = 0.009). After adjusting for child lean body mass, age, sex, systolic BP, resting HR, maternal lean body mass, pre-gestational BMI, and GDM status, child left atrial volume increased by 0.3 ml (95% CI 0.1, 0.5) for each 1% increase in child body fat percentage. CONCLUSIONS: No evidence of foetal cardiac programming related to GDM or maternal pre-pregnancy obesity was observed in early childhood. Maternal pre-pregnancy obesity is associated with early weight gain. Child adiposity in early childhood is independently associated with increased left atrial volume, but its implications for long-term left ventricle diastolic function and cardiovascular health remain unknown.

Risk of preterm birth in primiparous women with exposure to antidepressant medication before pregnancy and/or during pregnancy - impact of body mass index.

INTRODUCTION: Preterm birth is a major cause of infant mortality. It is unknown whether body mass index (BMI) influences the risk of preterm birth in women, who prenatally use antidepressants. MATERIALS AND METHODS: The study cohort (N = 6920) consists of all primiparous European born women without previously diagnosed diabetes from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data on births, pre-pregnancy BMI and purchases of antidepressants from 12 months before conception until delivery were obtained from Finnish National Registers. RESULTS: Of the primiparous women, 9.9% used antidepressants. The overall prevalence of preterm birth was 5.2%. In women with a pre-pregnancy BMI <18.5 kg/m2, the Odds Ratio (OR) for preterm birth among antidepressant users compared with those who were non-users was 1.91 (95% confidence intervals [CI] 0.40 to 9.15, adjusted for age, smoking, education, use of fertility treatments and number of previous pregnancies) while in women with a pre-pregnancy BMI ≥30 kg/m2, the OR was 0.53 (95% CI 0.21-1.36), respectively. DISCUSSION: Primiparous women using antidepressants, who were underweight before conception should be closely monitored and provided tailored care in a maternity clinic to minimize the risk of preterm birth. Key messages In primiparous women, one in ten used antidepressant medications before pregnancy and/or during pregnancy. In primiparous women, the prevalence of preterm birth was 5%. Underweight primiparous women using antidepressants should be closely monitored and provided tailored care in a maternity clinic.

Long-term effects of a preconception lifestyle intervention on cardiometabolic health of overweight and obese women.

BACKGROUND: The global prevalence of obesity in women keeps increasing. The preconception period may be a window of opportunity to improve lifestyle, reduce obesity and improve cardiometabolic health. This study assessed the effect of a preconception lifestyle intervention on long-term cardiometabolic health in two randomized controlled trials (RCTs). METHODS: Participants of the LIFEstyle and RADIEL preconception lifestyle intervention studies with a baseline body mass index (BMI) ≥29 kg/m2 were eligible for this follow-up study. Both studies randomized between a lifestyle intervention targeting physical activity, diet and behaviour modification or usual care. We assessed cardiometabolic health 6 years after randomization. RESULTS: In the LIFEstyle study (n = 111) and RADIEL study (n = 39), no statistically significant differences between the intervention and control groups were found for body composition, blood pressure, arterial stiffness, fasting glucose, homeostasis model assessment of insulin resistance, HbA1c, lipids and high sensitive C-reactive protein levels 6 years after randomization. Participants of the LIFEstyle study who successfully lost ≥5% bodyweight or reached a BMI <29 kg/m2 during the intervention (n = 22, [44%]) had lower weight (-8.1 kg; 99% CI [-16.6 to -0.9]), BMI (-3.3 kg/m2; [-6.5 to -0.8]), waist circumference (-8.2 cm; [-15.3 to -1.3]), fasting glucose (-0.5 mmol/L; [-1.1 to -0.0]), HbA1c (-4.1 mmol/mol; [-9.1 to -0.8]), and higher HDL-C (0.3 mmol/L; [0.1-0.5]) compared with controls. CONCLUSION: We found no evidence of improved cardiometabolic health 6 years after a preconception lifestyle intervention among overweight and obese women in two RCTs. Women who successfully lost weight during the intervention had better cardiometabolic health 6 years later, emphasizing the potential of successful preconception lifestyle improvement.

Body surface area at birth and later risk for gestational diabetes mellitus among primiparous women.

AIMS: To assess the relationship between body surface area (BSA) at birth and future risk for gestational diabetes mellitus (GDM). METHODS: This is an observational cohort study from Vantaa, Finland. The cohort included 1548 Finnish primiparous women, aged 15-28 years, without pre-existing diabetes, who gave birth 2009-2015. All women were born full-term and had complete information about their birth weight and length, from the Finnish Medical Birth Register. Additional data for the study were provided by individual patient health records and Statistics Finland. Study participants were divided into five levels (I-V) according to BSA at birth, based on normal distribution. RESULTS: There was an inverse association between BSA at birth and risk for GDM (p = 0.015 for linearity, after adjustments for age, educational attainment, pre-pregnancy BMI and smoking). The odds ratio (OR) for GDM in level V, with the largest BSA at birth, compared with level I, with the smallest BSA at birth, was 0.43 [95% confidence interval (CI) 0.22-0.83]; adjusted for age, educational attainment, pre-pregnancy body mass index and smoking. The OR for GDM was 0.8 (95% CI 0.68-0.95, p = 0.009) for each one standard deviation increase in BSA at birth, adjusted for the same confounders. BSA at birth correlated with adult anthropometry: correlation coefficients were r = 0.16 (95% CI 0.11-0.21) for weight, r = 0.31 (95% CI 0.26-0.35) for height, and r = 0.06 (95% CI 0.01-0.11) for BMI. CONCLUSIONS: Body surface area at birth is inversely associated with future risk for GDM in primiparous women.

Effect of lifestyle counselling on health-related quality of life in women at high risk for gestational diabetes.

BACKGROUND: The incidence of gestational diabetes (GDM) is increasing and interventions to curb the detrimental effects of GDM are needed. We have previously reported that a combined diet and physical activity intervention has the potential to reduce GDM among high-risk women. It is also important to know whether the intervention affects health-related quality of life (HRQoL). METHODS: A total of 378 women at high risk for GDM were randomized into an intervention (lifestyle counselling four times during pregnancy, n=192), or a control group (n=186) before 20 gestational weeks. HRQoL was assessed with the 15D-instrument six times: once during each trimester and at six weeks, six months and 12 months postpartum. RESULTS: In this study population, the cumulative incidence of GDM was similar in the intervention and the control group (45.7 vs. 44.5%). There was no difference between the 15D scores of the control and intervention groups at any of the time points. CONCLUSIONS: Combined diet and physical activity intervention did not provide HRQoL benefits in the study. A high prevalence of GDM in both study groups may have confounded the effect of the intervention.

Effects of a Lifestyle Intervention During Pregnancy and First Postpartum Year: Findings From the RADIEL Study.

Context: Women with a history of gestational diabetes (GDM) have a sevenfold risk of developing type 2 diabetes. Objective: To assess the effects of a lifestyle intervention during pregnancy and first postpartum year on glucose regulation, weight retention, and metabolic characteristics among women at high GDM risk. Design: In the Finnish Gestational Diabetes Prevention study, trained study nurses provided lifestyle counseling in each trimester and 6 weeks, 6 months, and 12 months postpartum. Setting: Three maternity hospitals in the Helsinki area and one in Lappeenranta. Patients: In total, 269 women with previous GDM and/or a prepregnancy body mass index ≥30 kg/m2 were enrolled before 20 gestational weeks and allocated to either a control or an intervention group. This study includes the 200 participants who attended study visits 6 weeks and/or 12 months postpartum. Intervention: The lifestyle intervention followed Nordic diet recommendations and at least 150 minutes of moderate exercise was recommended weekly. Main Outcome Measure: The incidence of impaired glucose regulation (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) during the first postpartum year. Results: Impaired glucose regulation was present in 13.3% of the women in the control and in 2.7% in the intervention group [age-adjusted odds ratio, 0.18 (95% confidence interval, 0.05 to 0.65), P = 0.009] during the first postpartum year. There were no differences between the groups in weight retention, physical activity, or diet at 12 months postpartum. Conclusions: A lifestyle intervention during pregnancy and the first postpartum year successfully reduced the incidence of postpartum impairment in glucose regulation.

A randomized lifestyle intervention preventing gestational diabetes: effects on self-rated health from pregnancy to postpartum.

INTRODUCTION: The purpose was to examine the effects of a randomized lifestyle intervention on self-rated health from pregnancy to postpartum in participants at high risk for gestational diabetes mellitus. METHODS: We included 266 women with a history of gestational diabetes and/or prepregnancy BMI ≥30 kg/m2. The intervention group (n = 144) received individualized counseling on diet, physical activity, and weight management from trained nurses at six timepoints between the first trimester of pregnancy and 12 months postpartum, and met three times with a dietitian. The control group (n = 122) received standard antenatal care. We assessed self-rated health at the six timepoints by means of a single question with five response options ranging from good (1) to poor (5). Baseline-adjusted mean changes in self-rated health level were assessed with a mixed model for repeated measure methods. RESULTS: The mean (SD) for self-rated health at baseline was 1.8 (0.8) in the intervention group and 2.1 (0.9) in the control group (p = 0.006). Self-rated health varied over time (time effect p < 0.001) and was the poorest in the third trimester. The sample indicated that self-rated health improved in the intervention group and deteriorated in the control group from the first trimester to 12 months postpartum, but the difference between the groups did not reach statistical significance (group effect p = 0.064). DISCUSSION: The self-rated health level varied over time from the first trimester of pregnancy to 12 months postpartum in women at risk for gestational diabetes. Improving self-rated health among high-risk pregnant women through lifestyle intervention calls for further research.

Heterogeneity of maternal characteristics and impact on gestational diabetes (GDM) risk-Implications for universal GDM screening?

OBJECTIVE: To study the incidence of gestational diabetes mellitus (GDM) in relation to phenotypic characteristics and gestational weight gain (GWG) among women at high risk for GDM. MATERIALS AND METHODS: This is a secondary analysis of a GDM prevention study (RADIEL), a randomized controlled trial conducted in Finland. 269 women with a history of GDM and/or a pre-pregnancy body mass index (BMI) ≥ 30 kg/m(2) were enrolled before 20 weeks of gestation and divided into four groups according to parity, BMI and previous history of GDM. The main outcome was incidence of GDM. RESULTS: There was a significant difference in incidence of GDM between the groups (p < 0.001). Women with a history of GDM and BMI <30 kg/m(2) showed the highest incidence (35.9%). At baseline they had fewer metabolic risk factors and by the second trimester they gained more weight. There was no interaction between GWG and GDM outcome and no significant difference in the prevalence of diabetes-associated antibodies. CONCLUSION: Despite a healthier metabolic profile at baseline the non-obese women with a history of GDM displayed a markedly higher cumulative incidence of GDM. GWG and the presence of diabetes-associated antibodies were not associated with GDM occurrence among these high-risk women. Key message Despite a healthier metabolic profile at baseline the non-obese women with previous gestational diabetes mellitus display a markedly higher cumulative incidence of gestational diabetes mellitus.

Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial.

OBJECTIVE: To assess whether gestational diabetes mellitus (GDM) can be prevented by a moderate lifestyle intervention in pregnant women who are at high risk for the disease. RESEARCH DESIGN AND METHODS: Two hundred ninety-three women with a history of GDM and/or a prepregnancy BMI of ≥30 kg/m(2) were enrolled in the study at <20 weeks of gestation and were randomly allocated to the intervention group (n = 155) or the control group (n = 138). Each subject in the intervention group received individualized counseling on diet, physical activity, and weight control from trained study nurses, and had one group meeting with a dietitian. The control group received standard antenatal care. The diagnosis of GDM was based on a 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. RESULTS: A total of 269 women were included in the analyses. The incidence of GDM was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40-0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM status, and the number of weeks of gestation). Gestational weight gain was lower in the intervention group (-0.58 kg [95% CI -1.12 to -0.04 kg]; adjusted P = 0.037). Women in the intervention group increased their leisure time physical activity more and improved their dietary quality compared with women in the control group. CONCLUSIONS: A moderate individualized lifestyle intervention reduced the incidence of GDM by 39% in high-risk pregnant women. These findings may have major health consequences for both the mother and the child.

Prevention of gestational diabetes through lifestyle intervention: study design and methods of a Finnish randomized controlled multicenter trial (RADIEL).

BACKGROUND: Maternal overweight, obesity and consequently the incidence of gestational diabetes are increasing rapidly worldwide. The objective of the study was to assess the efficacy and cost-effectiveness of a combined diet and physical activity intervention implemented before, during and after pregnancy in a primary health care setting for preventing gestational diabetes, later type 2 diabetes and other metabolic consequences. METHODS: RADIEL is a randomized controlled multi-center intervention trial in women at high risk for diabetes (a previous history of gestational diabetes or prepregnancy BMI ≥30 kg/m2). Participants planning pregnancy or in the first half of pregnancy were parallel-group randomized into an intervention arm which received lifestyle counseling and a control arm which received usual care given at their local antenatal clinics. All participants visited a study nurse every three months before and during pregnancy, and at 6 weeks, 6 and 12 months postpartum. Measurements and laboratory tests were performed on all participants with special focus on dietary and exercise habits and metabolic markers.Of the 728 women [mean age 32.5 years (SD 4.7); median parity 1 (range 0-9)] considered to be eligible for the study 235 were non-pregnant and 493 pregnant [mean gestational age 13 (range 6 to 18) weeks] at the time of enrollment. The proportion of nulliparous women was 29.8% (n = 217). Out of all participants, 79.6% of the non-pregnant and 40.4% of the pregnant women had previous gestational diabetes and 20.4% of the non-pregnant and 59.6% of the pregnant women were recruited because of a prepregnancy BMI ≥30 kg/m2. Mean BMI at first visit was 30.1 kg/m2 (SD 6.2) in the non-pregnant and 32.7 kg/m2 (SD 5.6) in the pregnant group. DISCUSSION: To our knowledge, this is the first randomized lifestyle intervention trial, which includes, besides the pregnancy period, both the prepregnancy and the postpartum period. This study design also provides an opportunity to focus upon the health of the next generation. The study is expected to produce novel information on the optimal timing and setting of interventions and for allocating resources to prevent obesity and diabetes in women of reproductive age.