Cohort Profile: The Finnish Gestational Diabetes (FinnGeDi) Study

The Finnish Gestational Diabetes (FinnGeDi) study is a multicentre study that considered Finnish women who gave birth in 2009–12, as well as their children and the children’s fathers. The study period was after the introduction of new Finnish national comprehensive screening guidelines for gestational diabetes mellitus (GDM).1 The study consisted of two arms: a prospective clinical, genetic case-control arm and a national register-based arm which also includes data on children’s siblings and grandparents. The FinnGeDi study was initiated to study different aspects of GDM as diagnosed by comprehensive screening, which was expected to increase the prevalence of GDM by identifying previously undiagnosed cases.2 GDM is characterized by carbohydrate intolerance and/or hyperglycaemia—with its onset or first recognition during pregnancy, which is not overt type 1 diabetes nor type 2 diabetes (T2D).3 GDM affects 10–30% of all pregnancies,4 recurs in 30–84% of women5 and is becoming more common worldwide.6 It is frequently the first manifestation of an increased risk of diabetes, as up to two-thirds of women with a history of GDM are estimated to develop subsequent T2D.7–9 Women with a history of GDM also have an increased risk for other metabolic and cardiovascular diseases.9,10 Exposure to maternal hyperglycaemia also impacts on the fetus: in addition to short-term consequences—that is, macrosomia and neonatal hypoglycaemia11—children born from GDM pregnancies are at increased risk of later T2D, metabolic syndrome, cardiovascular disease and cognitive impairment.12–14 GDM represents a part of a continuum of maternal hyperglycaemia.2,11 There are no unanimously accepted international criteria for diagnosis or screening,15 and guidelines vary considerably even between high-income countries.15–17 Typically, GDM is diagnosed by an oral glucose tolerance test (OGTT), which may be performed only in women whose characteristics indicate an increased risk (risk-factor-based screening) or in all or most pregnant women (universal or comprehensive screening).15 The FinnGeDi study was established after the national Finnish Current Cure Guidelines were introduced in 2008 and comprehensive screening was recommended to replace the previous risk-factor-based screening.1 The study was expected to identify new GDM cases in women without previous risk factors and result in a higher GDM prevalence.2 The study aimed to identify potential genetic and epigenetic biomarkers of GDM and assess putative risk factors and clinical characteristics of GDM, enabling the characterization of clinically identifiable and mechanistically meaningful subgroups of the disorder. The short- and long-term health of the mother and child are to be followed up—that is, evaluating the consequences of GDM. Furthermore, the incidence, distribution and consequences of GDM are to be assessed in different socioeconomic and demographic groups and across generations. To approach these questions from different perspectives, two arms were included in the FinnGeDi study: (i) a multicentre case-control arm including questionnaires, medical data, Medical Birth Register (MBR) data and DNA samples from pregnant women with and without GDM, their children and the children’s fathers; and (ii) the register-based arm using the MBR and other Finnish comprehensive national registers. The study headquarters and database are located at the National Institute for Health and Welfare (Finland), which is the primary research institution of the study in addition to Oulu University Hospital. The study is funded by the Academy of Finland and private foundations. The cohort includes two arms: a case-control arm and a register-based arm. The prospectively collected case-control cohort consists of 1146 pregnant women with GDM and 1066 women without GDM, their children from the index pregnancy and the children’s fathers. The flow chart of the study population is presented in Figure 1. Women with GDM were recruited from delivery units as they came to give birth, and the next consenting woman without GDM was recruited as a control. The women were recruited between 1 February 2009 and 31 December 2012 at two tertiary-level hospitals (Oulu University Hospital and Helsinki University Hospital), which serve as secondary-level hospitals for their region, and five secondary-level hospitals (in Jyväskylä, Pori, Kajaani, Seinäjoki and Lappeenranta). All the hospitals serve a specific geographical area. Women with pre-pregnancy diabetes mellitus (DM) and multiple pregnancies were excluded from the study. Women and their spouses (the fathers of the children) signed informed consent to the use of the growth and developmental data of their children and to contact with the family later for follow-up studies. Blood samples (leukocyte DNA) were drawn from both parents and from the umbilical cord after delivery. Plasma from the umbilical cord sample was frozen and stored at –80°C. The parents completed background questionnaires—including information on family and medical history and lifestyle factors (i.e. physical activity, diet and smoking). Maternal welfare clinical and hospital records were reviewed to confirm GDM diagnosis, and detailed information on the women’s medical and obstetric history, pregnancy complications and outcomes, laboratory measurements and the newborns’ health was obtained. These data were combined with the MBR data. For each delivery in Finland, a structured form for the MBR is completed by the health personnel at the delivery hospital within 7 days after delivery. It included data on key obstetric, perinatal and neonatal outcomes. The MBR was completed using data compiled by the Population Register Centre on live births and by Statistics Finland on stillbirths and infant deaths. Available data, including blood samples, are described in detail in Tables 1 and 2. Flow chart of women in the case-control arm. GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test. Flow chart of women in the case-control arm. GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test. Number of available samples and data in the case-control arm DNA duo: DNA samples from mother and child; GDM n = 971 (84.7%)/control n = 927 (87.0%). DNA trio: DNA samples from mother, father and child; GDM n = 846 (73.8%)/control n = 833 (78.1%). GDM, gestational diabetes mellitus. Number of available samples and data in the case-control arm DNA duo: DNA samples from mother and child; GDM n = 971 (84.7%)/control n = 927 (87.0%). DNA trio: DNA samples from mother, father and child; GDM n = 846 (73.8%)/control n = 833 (78.1%). GDM, gestational diabetes mellitus. Description of the data sources for both study arms Index pregnancy and delivery data OGTT values Delivery data Primary health care data (growth, development, health) Baseline Follow-up Case-control Register-based Baseline Follow-up Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S Case-control Register-based Diagnoses Procedures Hospitalization Baseline Follow-up Case-control Register-based Follow-up (from 2011a) Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/G Case-control Register-based Case-control Register-based Case-control Register-based Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Case-control Register-based Case-control Register-based Index pregnancy and delivery data OGTT values Delivery data Primary health care data (growth, development, health) Baseline Follow-up Case-control Register-based Baseline Follow-up Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S Case-control Register-based Diagnoses Procedures Hospitalization Baseline Follow-up Case-control Register-based Follow-up (from 2011a) Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/G Case-control Register-based Case-control Register-based Case-control Register-based Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Case-control Register-based Case-control Register-based Mo, index mother; Fa, index father; C, index child; S, siblings of the index child; G, grandparents of the index child; OGTT, oral glucose tolerance test Year when register was established. Description of the data sources for both study arms Index pregnancy and delivery data OGTT values Delivery data Primary health care data (growth, development, health) Baseline Follow-up Case-control Register-based Baseline Follow-up Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S Case-control Register-based Diagnoses Procedures Hospitalization Baseline Follow-up Case-control Register-based Follow-up (from 2011a) Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/G Case-control Register-based Case-control Register-based Case-control Register-based Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Case-control Register-based Case-control Register-based Index pregnancy and delivery data OGTT values Delivery data Primary health care data (growth, development, health) Baseline Follow-up Case-control Register-based Baseline Follow-up Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S Case-control Register-based Diagnoses Procedures Hospitalization Baseline Follow-up Case-control Register-based Follow-up (from 2011a) Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/G Case-control Register-based Case-control Register-based Case-control Register-based Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Baseline Follow-up Mo/Fa/C Mo/Fa/C/S/G Case-control Register-based Case-control Register-based Case-control Register-based Mo, index mother; Fa, index father; C, index child; S, siblings of the index child; G, grandparents of the index child; OGTT, oral glucose tolerance test Year when register was established. The diagnosis of GDM was based on an abnormal OGTT result during pregnancy. According to the Finnish Current Care guidelines introduced in 2008, a 75 g 2-h OGTT was recommended to be performed between the 24th and 28th gestational weeks in all women except those with a very low risk of developing GDM. For high-risk women, OGTT was recommended between 12 and 16 weeks of pregnancy, and if normal, a repeat test was recommended between 24 and 28 weeks. The detailed screening criteria are described in Table 3. The cut-off concentrations for venous plasma glucose were ≥5.3 mmol/l at baseline (fasting glucose), ≥10.0 mmol/l at 1 h after glucose intake or ≥8.6 mmol/l at 2 h after glucose intake. GDM diagnosis was set if one or more glucose concentrations exceeded the cut-off levels.1 Current Care Guideline 2007 for the screening of gestational diabetes mellitus using oral glucose tolerance test in Finland (Current Care Guideline: Gestational diabetes 2007)1 Previous GDM diagnosis Prepregnancy BMI ≥35 kg/m2 Glucosuria in early pregnancy Oral glucocorticoid medication Family history of T2D (parents, grandparents, siblings and children) Polycystic ovary sydrome Primiparous: age <25 years, pre-pregnancy BMI<25 kg/m2 and no family history of T2D Multiparous: age <40 years, pre-pregnancy BMI <25 kg/m2 and no previous GDM diagnosis or macrosomia Previous GDM diagnosis Prepregnancy BMI ≥35 kg/m2 Glucosuria in early pregnancy Oral glucocorticoid medication Family history of T2D (parents, grandparents, siblings and children) Polycystic ovary sydrome Primiparous: age <25 years, pre-pregnancy BMI<25 kg/m2 and no family history of T2D Multiparous: age <40 years, pre-pregnancy BMI <25 kg/m2 and no previous GDM diagnosis or macrosomia OGTT, oral glucose tolerance test; GDM, gestational diabetes mellitus; BMI, body mass index; T2D, type 2 diabetes mellitus. Current Care Guideline 2007 for the screening of gestational diabetes mellitus using oral glucose tolerance test in Finland (Current Care Guideline: Gestational diabetes 2007)1 Previous GDM diagnosis Prepregnancy BMI ≥35 kg/m2 Glucosuria in early pregnancy Oral glucocorticoid medication Family history of T2D (parents, grandparents, siblings and children) Polycystic ovary sydrome Primiparous: age <25 years, pre-pregnancy BMI<25 kg/m2 and no family history of T2D Multiparous: age <40 years, pre-pregnancy BMI <25 kg/m2 and no previous GDM diagnosis or macrosomia Previous GDM diagnosis Prepregnancy BMI ≥35 kg/m2 Glucosuria in early pregnancy Oral glucocorticoid medication Family history of T2D (parents, grandparents, siblings and children) Polycystic ovary sydrome Primiparous: age <25 years, pre-pregnancy BMI<25 kg/m2 and no family history of T2D Multiparous: age <40 years, pre-pregnancy BMI <25 kg/m2 and no previous GDM diagnosis or macrosomia OGTT, oral glucose tolerance test; GDM, gestational diabetes mellitus; BMI, body mass index; T2D, type 2 diabetes mellitus. Comparisons between women with or without GDM and their spouses are shown in Table 4. As expected, women with GDM were older, more often multiparous, had higher prepregnancy body mass index (BMI) values and often had chronic hypertension compared with controls. Less upper tertiary-level educated women were in the GDM group than in the control group. The groups were comparable in terms of smoking before and during pregnancy. The incidence of gestational hypertension and preeclampsia was higher in the women with GDM than in the controls. For preeclampsia, the difference remained significant even after adjustment for parity, maternal age and pre-pregnancy BMI. Women with GDM had more inductions of labour, caesarean sections and large-for-gestational-age (LGA) newborns than controls. The spouses of women with GDM were older and had higher BMI than those of the control group. The screening rates and glucose metabolism status of women with or without GDM are given in Supplementary Table 1, available as Supplementary data at IJE online. Maternal, neonatal and paternal characteristics of participants in the case-control arm Data are presented as mean ± SD or as number (percentages). GDM, gestational diabetes mellitus; BMI, body mass index; LGA, large for gestational age (birthweight ≥ 2 SD); SGA, small for gestational age (birthweight ≤2 SD). Unadjusted P-values based on Student’s t test or χ2 test. Adjusted P-values based on logistic regression. Adjusted for parity and mother’s age at birth. Difference of (self-reported) pre-pregnancy weight and weight at the last antenatal visit at 35 gestational weeks or later. Excess gestational weight gain based on Institute of Medicine 2009 criteria. Systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg detected before 20 weeks of gestation. Adjusted for parity, mother’s age at birth and pre-pregnancy BMI. Blood pressure ≥ 140/90 mmHg, no proteinuria. Blood pressure ≥ 140/90 mmHg and proteinuria (≥ 0.3 g/24 h or two ≥ 1+ readings on a dipstick). Adjusted for parity, mother’s age at birth, pre-pregnancy BMI, hypertensive pregnancy complications and induction of labour (yes/no). Adjusted for parity, mother’s age at birth, gestational weeks, pre-pregnancy BMI and hypertensive pregnancy complications. Maternal, neonatal and paternal characteristics of participants in the case-control arm Data are presented as mean ± SD or as number (percentages). GDM, gestational diabetes mellitus; BMI, body mass index; LGA, large for gestational age (birthweight ≥ 2 SD); SGA, small for gestational age (birthweight ≤2 SD). Unadjusted P-values based on Student’s t test or χ2 test. Adjusted P-values based on logistic regression. Adjusted for parity and mother’s age at birth. Difference of (self-reported) pre-pregnancy weight and weight at the last antenatal visit at 35 gestational weeks or later. Excess gestational weight gain based on Institute of Medicine 2009 criteria. Systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg detected before 20 weeks of gestation. Adjusted for parity, mother’s age at birth and pre-pregnancy BMI. Blood pressure ≥ 140/90 mmHg, no proteinuria. Blood pressure ≥ 140/90 mmHg and proteinuria (≥ 0.3 g/24 h or two ≥ 1+ readings on a dipstick). Adjusted for parity, mother’s age at birth, pre-pregnancy BMI, hypertensive pregnancy complications and induction of labour (yes/no). Adjusted for parity, mother’s age at birth, gestational weeks, pre-pregnancy BMI and hypertensive pregnancy complications. The register-based arm includes all 59 057 singleton pregnancies in women who gave birth in Finland in 2009. They were identified through the MBR, which includes data on whether OGTT was ‘performed (yes/no)’ and ‘abnormal OGTTs (yes)’, if ‘insulin treatment was begun during pregnancy (yes)’ and ‘ICD-10 diagnosis codes of GDM’. The accuracy of different variables and their combinations to identify GDM cases was checked against laboratory-verified OGTT results. In addition, data from the Finnish Care Register for Health Care (HILMO, former Hospital Discharge Register) were tested to identify whether it improved the accuracy of MBR variables (Supplementary Data 1, available as Supplementary data at IJE online). Based on these results, the accuracy of all three MBR variables mentioned above without HILMO variables was found to be 94.3%, and they were used to identify GDM cases from register data. In 2009, a total of 6583 women (11.1%) were reported to have GDM according to an ‘abnormal OGTT finding’ and/or ‘insulin initiation during pregnancy’ and/or ‘ICD-10 diagnosis codes of GDM’ (ICD-10 code ‘O24.4’ or ‘O24.9’). Women with type 1 diabetes and T2D (n = 449), women with unclear diagnosis codes (n = 2) and the latter pregnancy of women with two pregnancies in 2009 (n=19) were excluded. All other women were chosen to serve as controls (n =52 004) (Figure 2). Comparison of the baseline clinical characteristics of women with GDM and controls is shown in Supplementary Table 2A, available as Supplementary data at IJE online. OGTT-verified controls (n=19 227) were found to have more background risk factors of GDM than controls without OGTT results (n=32 777) (Supplementary Table 2B, available as Supplementary data at IJE online). Women recognized as having GDM through the MBR variable ‘ICD-10 diagnosis code of GDM’ had higher parity than women who were recorded to have ‘abnormal OGTT’ and/or ‘insulin initiation during pregnancy’ in the MBR (Supplementary Table 2C, available as Supplementary data at IJE online). Flow chart of women in the register-based arm according to the Medical Birth Register 2009. Number of women (% of all 59 057 singleton pregnancies). DM, diabetes; OGTT, oral glucose tolerance test; GDM, gestational diabetes mellitus. Flow chart of women in the register-based arm according to the Medical Birth Register 2009. Number of women (% of all 59 057 singleton pregnancies). DM, diabetes; OGTT, oral glucose tolerance test; GDM, gestational diabetes mellitus. The children born in 2009 serve as index children for the identification of their siblings, fathers and grandparents. By using the unique personal identification code allocated to each citizen and permanent resident of Finland, data from various national registers (including data on, for example, hospital discharges and diagnoses, reimbursement for drugs, congenital anomalies, cancer diagnoses, time and causes of deaths, social welfare benefits, educational degrees and occupation and matriculation examination scores) can be linked to all family members (Table 2). According to Finnish legislation, a register study does not require permission from the study participants if they are not contacted due to the study. As the MBR does not include numerical OGTT data, these data were obtained from hospital laboratory databases for a subpopulation of 4954 women with singleton pregnancies, who delivered in 2009 in six out of seven study hospitals, with a total of 15 000 births per year. These data were also used to validate the register data (Supplementary Figure 1, available as Supplementary data at IJE online). In the case-control arm, the questionnaires, medical data from hospital records and baseline register data were collected at the time of enrolment in 2009–12. The study enables longitudinal follow-up for both women and children by combining these data with data obtained from national registers. The development and growth data of the children will be collected later from child welfare clinic records. In the register-based arm, the register data from MBR and the OGTT results of the subpopulation of 4954 women were collected at baseline in 2009. The first follow-up for the both arms will be performed 7–10 years after the completion of the enrolment, and is planned to continue for decades. Permissions for the register follow-ups will be updated in 2024 and after that in 5-year periods. The linkage to registers is presented in Table 2. The case-control cohort provides a large dataset from questionnaires, hospital records and national registers, combined with DNA trio samples from parents and children to study novel genetic and epigenetic markers of GDM (Tables 1 and 2) The register-based arm provides data from MBR and other national registers including registers maintained by the National Institute of Health and Welfare, Statistics Finland, Population Register Centre and Social Insurance of Finland (Table 2). Index and their children are identified from MBR and the siblings and grandparents of the index children are identified from the Population Register The linkage of these registers provides data on and medical with their complications and socioeconomic of the index In the case-control arm, blood samples and data to study of GDM have collected and have The study will to epigenetic in other The results have not In of clinical data, women’s birth, pre-pregnancy age ≥35 years and family history of GDM or T2D were found to be risk factors for In the register-based arm, an on OGTT results after 24 weeks of pregnancy in the subpopulation of women The of the FinnGeDi cohort include prospective case-control samples from women, children and their fathers to study and of and the large and comprehensive databases of clinical, lifestyle and register data of women and with of longitudinal The use of different registers enables a of the socioeconomic and educational background which may the prevalence and consequences of GDM. The of data to the children’s grandparents will to the of on GDM. In the case-control arm, OGTT was performed in of the 1066 women in the control group. total of of those women without OGTT not the screening they were estimated to be at very low risk of developing GDM according to the national characteristics of the women without OGTT are detailed in Supplementary Table available as Supplementary data at IJE online. In the register-based arm, GDM status is based on register data, the of which to identify GDM as (Supplementary Data 1, available as Supplementary data at IJE online). In the of Finnish national registers, MBR, is and the In the control only of women were to have OGTT results (Figure 2). controls without OGTT results were found to have GDM risk factors than controls having OGTT results (Supplementary Table 2B, available as Supplementary data at IJE online). The use of comprehensive screening in an increase in the incidence of GDM during The screening increased from in to in and the prevalence of GDM increased from to women with GDM remained undiagnosed when study was to clinical data is by and to data is to permission from the For contact and study or Oulu University of and in a The FinnGeDi cohort was set up to a database combining detailed clinical data and DNA trio samples from mother, father and child to study and long-term consequences of GDM diagnosed using the new comprehensive screening The cohort is based at the National Institute for Health and Welfare The case-control cohort was recruited in and includes 1146 women with GDM and 1066 controls years, their children and the children’s fathers. The register-based cohort consists of Finnish a mother gave birth in 2009 (n = 59 057 singleton pregnancies). cohort includes 6583 women (11.1%) with GDM. The of data were blood samples from parents and clinical data from hospital and maternal welfare clinic register data from national registers and lifestyle and medical and family history data from Follow-up data will be performed 7–10 years after the of the for both and is planned to continue for decades. will include the linkage of baseline data to national example, hospital diagnoses, data on reimbursement for and of and time and causes of deaths. are updated The data be as due to national data The use of data study permission from all national may be to Supplementary data are available at IJE online. The study is funded by Academy of Finland, Diabetes for and Finnish Medical of Oulu University Hospital of Helsinki University Hospital Medical Oulu and National Institute for Health and Welfare is for with data and members and for data and research are for with are also to the in the hospitals for and

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.