Association between risk of infant death and birth-weight z scores according to gestational age: A nationwide study using the Finnish Medical Birth Register.

OBJECTIVE: To investigate the association between infant mortality and birth weight using estimated fetal weight (EFW) versus birth-weight charts, by gestational age (GA). METHODS: This nationwide population-based study used data from the Finnish Medical Birth Register from 2006 to 2016 on non-malformed singleton live births at 24-41+6 weeks of gestation (N = 563 630). The outcome was death in the first year of life. Mortality risks by birth-weight z score, defined as a continuous variable using Marsál's EFW and Sankilampi's birth-weight charts, were assessed using generalized additive models by GA (24-27+6, 28-31+6, 32-36+6, 37-38+6, 39-41+6 weeks). We calculated z score thresholds associated with a two- and three-fold increased risk of infant death compared with newborns with a birth weight between 0 and 0.675 standard deviations. RESULTS: The z score thresholds (with corresponding centiles in parentheses) associated with a two-fold increase in infant mortality were: -3.43 (<0.1) at 24-27+6 weeks, -3.46 (<0.1) at 28-31+6 weeks, -1.29 (9.9) at 32-36+6 weeks, -1.18 (11.9) at 37-38+6 weeks, and - 1.34 (9.0) at 39-41+6 weeks according to the EFW chart. These values were - 2.43 (0.8), -2.62 (0.4), -1.34 (9.0), -1.37 (8.5), and - 1.43 (7.6) according to the birth-weight chart. CONCLUSION: The association between birth weight and infant mortality varies by GA whichever chart is used, suggesting that different thresholds for the screening of growth anomalies could be used across GA to identify high-risk newborns.

Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden.

AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.

Risk of Psychosis Among Individuals Who Have Presented to Hospital With Self-harm: A Prospective Nationwide Register Study in Sweden.

BACKGROUND AND HYPOTHESIS: Recent research showed that young people who presented to hospital with self-harm in Finland had a significantly elevated risk of later psychosis. We investigated the prospective relationship between hospital presentation for self-harm and risk of psychosis in an unprecedentedly large national Swedish cohort. STUDY DESIGN: We used inpatient and outpatient healthcare registers to identify all individuals born between 1981 and 1993 who were alive and living in Sweden on their 12th birthday and who presented to hospital one or more times with self-harm. We compared them with a matched cohort, followed up for up to 20 years, and compared the cumulative incidence of psychotic disorders. Furthermore, we examined whether the strength of the relationship between hospital presentation for self-harm and later psychosis changed over time by examining for cohort effects. STUDY RESULTS: In total, 28 908 (2.0%) individuals presented to hospital with self-harm without prior psychosis diagnosis during the follow-up. For individuals who presented to hospital with self-harm, the cumulative incidence of diagnosed psychosis was 20.7% at 20 years follow-up (hazard radio = 13.9, 95% CI 13.3-14.6, P-value <5 × 10-308). There was no evidence of a dilution of the effect over time: while the incidence of hospital self-harm presentation increased, this did not result in an attenuation over time of the strength of the relationship between hospital self-harm presentation and subsequent psychosis. CONCLUSIONS: Individuals who present to hospital with self-harm in their teens and 20s represent an important risk group for psychosis prediction and prevention.

Maternal Diabetes and Overweight and Congenital Heart Defects in Offspring.

Importance: Maternal diabetes and overweight or obesity are known to be associated with increased risk of congenital heart defects (CHDs) in offspring, but there are no large studies analyzing outcomes associated with these factors in 1 model. Objective: To investigate the association of maternal diabetes and overweight or obesity with CHDs among offspring in 1 model. Design, Setting, and Participants: This nationwide, population-based register study was conducted in a birth cohort from Finland consisting of all children born between 2006 and 2016 (620 751 individuals) and their mothers. Data were analyzed from January 2022 until November 2023. Exposures: Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obesity (≥30), was assessed. Maternal diabetes status, classified as no diabetes, type 1 diabetes (T1D), type 2 or other diabetes, and gestational diabetes, was assessed. Main Outcomes and Measures: Odds ratios (ORs) of isolated CHDs in children were found. In addition, 9 anatomical CHD subgroups were studied. Results: Of 620 751 children (316 802 males [51.0%]; 573 259 mothers aged 20-40 years [92.3%]) born in Finland during the study period, 10 254 children (1.7%) had an isolated CHD. Maternal T1D was associated with increased odds of having a child with any CHD (OR, 3.77 [95% CI, 3.26-4.36]) and 6 of 9 CHD subgroups (OR range, 3.28 [95% CI, 1.55-6.95] for other septal defects to 7.39 [95% CI, 3.00-18.21] for transposition of great arteries) compared with no maternal diabetes. Maternal overweight was associated with left ventricular outflow tract obstruction (OR, 1.28 [95% CI, 1.10-1.49]) and ventricular septal defects (OR, 0.92 [95% CI, 0.86-0.98]), and obesity was associated with complex defects (OR, 2.70 [95% CI, 1.14-6.43]) and right outflow tract obstruction (OR, 1.31 [95% CI, 1.09-1.58]) compared with normal maternal BMI. Conclusions and Relevance: This study found that maternal T1D was associated with increased risk for most types of CHD in offspring, while obesity and overweight were associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. These different risk profiles of T1D and overweight and obesity may suggest distinct underlying teratogenic mechanisms.

Fruit, berry, and vegetable consumption and the risk of islet autoimmunity and type 1 diabetes in children-the Type 1 Diabetes Prediction and Prevention birth cohort study.

BACKGROUND: Prospective studies investigating the association among fruit, berry, and vegetable consumption and the risk of islet autoimmunity (IA) and type 1 diabetes (T1D) are few. OBJECTIVES: In this cohort study, we explored whether the consumption of fruits, berries, and vegetables is associated with the IA and T1D development in genetically susceptible children. METHODS: Food consumption data in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) cohort study were available from 5674 children born between September 1996 and September 2004 in the Oulu and Tampere University Hospitals. Diet was assessed with 3-d food records at the age of 3 and 6 mo and annually from 1 to 6 y. The association between food consumption and the risk of IA and T1D was analyzed using joint models adjusted for energy intake, sex, human leukocyte antigen (HLA) genotype, and a family history of diabetes. RESULTS: During the 6-y follow-up, 247 children (4.4%) developed IA and 94 (1.7%) T1D. Furthermore, 64 of 505 children with at least 1 repeatedly positive autoantibody (12.7%) progressed from islet autoantibody positivity to T1D. The consumption of cruciferous vegetables was associated with decreased risk of IA [hazard ratio (HR): 0.83; 95% credible intervals (CI): 0.72, 0.95, per 1 g/MJ increase in consumption] and the consumption of berries with decreased risk of T1D (0.60; 0.47, 0.89). The consumption of banana was associated with increased risk of IA (1.08; 1.04, 1.12) and T1D (1.11; 1.01, 1.21). Only the association between banana and IA remain significant after multiple testing correction. CONCLUSIONS: In children genetically at risk for T1D, the consumption of cruciferous vegetables was associated with decreased risk of IA and consumption of berries with decreased risk of T1D. In addition, the consumption of banana was associated with increased risk of IA and T1D.

Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study.

BACKGROUND: Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10-18 years). METHODS: We used population-wide data from Finland (1 187 610 adolescents born 1987-2006) and Norway (555 431 adolescents born 1998-2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23-27 weeks (extremely preterm), 28-31 weeks (very preterm), 32-33 weeks (moderately preterm), 34-36 weeks (late preterm), 37-38 weeks (early term), 39-41 weeks (term, reference category) and 42-44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10-18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence. FINDINGS: Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19-2·39) for two health outcomes (PAF 9·0%; 8·3-9·6), and 4·22 (3·66-4·87) for four health outcomes (PAF 22·7%; 19·4-25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose-response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets. INTERPRETATION: Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10-18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care. FUNDING: European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.

Gestational age at birth and hospitalisations for infections among individuals aged 0-50 years in Norway: a longitudinal, register-based, cohort study.

Background: Preterm birth is associated with increased risk of childhood infections. Whether this risk persists into adulthood is unknown and limited information is available on risk patterns across the full range of gestational ages. Methods: In this longitudinal, register-based, cohort study, we linked individual-level data on all individuals born in Norway (January 01, 1967-December 31, 2016) to nationwide hospital data (January 01, 2008-December 31, 2017). Gestational age was categorised as 23-27, 28-31, 32-33, 34-36, 37-38, 39-41, and 42-44 completed weeks. The analyses were stratified by age at follow-up: 0-11 months and 1-5, 6-14, 15-29, and 30-50 years. The primary outcome was hospitalisation due to any infectious disease, with major infectious disease groups as secondary outcomes. Adjusted hospitalisation rate ratios (RRs) for any infection and infectious disease groups were estimated using negative binomial regression. Models were adjusted for year of birth, maternal age at birth, parity, and sex, and included an offset parameter adjusted for person-time at risk. Findings: Among 2,695,830 individuals with 313,940 hospitalisations for infections, we found a pattern of higher hospitalisation risk in lower gestational age groups, which was the strongest in childhood but still evident in adulthood. Comparing those born very preterm (28-31) and late preterm (34-36) to full-term (39-41 weeks), RRs (95% confidence interval) for hospitalisation for any infectious disease at ages 1-5 were 3.3 (3.0-3.7) and 1.7 (1.6-1.8), respectively. At 30-50 years, the corresponding estimates were 1.4 (1.2-1.7) and 1.2 (1.1-1.3). The patterns were similar for the infectious disease groups, including bacterial and viral infections, respiratory tract infections (RTIs), and infections not attributable to RTIs. Interpretation: Increasing risk of hospitalisations for infections in lower gestational age groups was most prominent in children but still evident in adolescents and adults. Possible mechanisms and groups that could benefit from vaccinations and other prevention strategies should be investigated. Funding: St. Olav's University Hospital and Norwegian University of Science and Technology, Norwegian Research Council, Liaison Committee for education, research and innovation in Central Norway, European Commission, Academy of Finland, Sigrid Jusélius Foundation, Foundation for Pediatric Research, and Signe and Ane Gyllenberg Foundation.

Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries.

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.

Longitudinal consumption of fruits and vegetables and risk of asthma by 5 years of age.

BACKGROUND: Fruit and vegetable consumption has been linked to a decreased risk of asthma, but prospective evidence on longitudinal consumption in childhood is scarce. We aimed to investigate the association between fruit and vegetable consumption in childhood and the risk of asthma by the age of 5 years, and to explore the role of processing of fruits and vegetables in the Finnish Type 1 Diabetes Prediction and Prevention Allergy Study. METHODS: Child's food consumption was assessed by 3-day food records completed at the age of 3 and 6 months, and 1, 2, 3, 4, and 5 years, and asthma and allergies by a validated modified version of the ISAAC questionnaire at the age of 5 years. Consumption of processed and unprocessed fruits and vegetables was calculated. Joint models with a current value association structure for longitudinal and time-to-event data were used for statistical analyses. RESULTS: Of the 3053 children, 184 (6%) developed asthma by the age of 5 years. The risk of asthma was not associated with the consumption of all fruits and vegetables together (HR 1.00, 95%CI 0.99-1.01 per consumption of 1 g/MJ, adjusted for energy and other covariates), or with most subgroups. Weak inverse associations were seen between all leafy vegetables and asthma (HR = 0.87, 0.77-0.99), and unprocessed vegetables and nonatopic asthma (HR = 0.90, 95% CI 0.81-0.98). CONCLUSION: Total consumption of fruits and vegetables in childhood was not associated with the development of asthma by the age of 5 years. Weak inverse associations found for vegetables need to be confirmed or rejected in future studies.

Maternal energy-adjusted fatty acid intake during pregnancy and the development of cows' milk allergy in the offspring.

Cows' milk allergy (CMA) is one of the earliest manifestations of allergic diseases. Early dietary factors, like maternal diet during pregnancy, may play a role in the development of allergic diseases in the offspring. We aimed to investigate the association between maternal intake of fatty acids during pregnancy and the risk of CMA in the offspring. Our study was conducted in a population-based cohort, the Finnish Type 1 Diabetes Prediction and Prevention study. We collected the maternal dietary data by a validated FFQ. We obtained the information on CMA in the study participants (n 448) from registers and from the parents. Dietary data and information on CMA were available for 4921 children. We used logistic regression in the analyses, and fatty acid intakes were energy adjusted. The maternal intake of SFA, MUFA, PUFA, n-3 PUFA, n-6 PUFA, trans fatty acids, ratio of n-3 PUFA to n-6 PUFA or ratio of linoleic acid to α-linolenic acid was not associated with the risk of CMA in the offspring when adjusted for perinatal factors, background factors, parental history of asthma or allergic rhinitis and infant animal contacts. The intake of α-linolenic acid was associated with a decreased risk (OR 0·72; 95 % CI 0·56, 0·93) of CMA in the offspring of mothers without a history of allergic rhinitis or asthma. In conclusion, the maternal intake of fatty acids during pregnancy is not associated with the risk of CMA in the offspring.

Preterm birth and the risk of chronic disease multimorbidity in adolescence and early adulthood: A population-based cohort study.

BACKGROUND: People who were born prematurely have high risks of many individual diseases and conditions in the early part of the life course. However, our knowledge of the burden of multiple diseases (multimorbidity) among prematurely born individuals is limited. We aimed to investigate the risk and patterns of chronic disease multimorbidity in adolescence and early adulthood among individuals born across the spectrum of gestational ages, comparing preterm and full-term born individuals. METHODS AND FINDINGS: We used individual-level data from linked nationwide registers to examine the associations of gestational age at birth with specialised healthcare records of ≥2 chronic diseases (multimorbidity) in adolescence (age 10-17 years) and early adulthood (age 18-30 years). Our study population comprised 951,116 individuals (50.2% females) born alive in Finland between 1st January 1987 and 31st December 2006, inclusive. All individuals were followed from age 10 years to the onset of multimorbidity, emigration, death, or 31 December 2016 (up to age 30 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for multimorbidity using flexible parametric survival models. During 6,417,903 person-years at risk (median follow-up: 7.9 years), 11,919 individuals (1.3%) had multimorbidity in adolescence (18.6 per 10,000 person-years). During 3,967,419 person-years at risk (median follow-up: 6.2 years), 15,664 individuals (1.7%) had multimorbidity in early adulthood (39.5 per 10,000 person-years). Adjusted HRs for adolescent multimorbidity, comparing preterm to full-term born individuals, were 1.29 (95% CI: 1.22 to 1.36) and 1.26 (95% CI: 1.18 to 1.35) in females and males, respectively. The associations of preterm birth with early adult multimorbidity were less marked, with the adjusted HRs indicating 1.18-fold risk in females (95% CI: 1.12 to 1.24) and 1.10-fold risk in males (95% CI: 1.04 to 1.17). We observed a consistent dose-response relationship between earlier gestational age at birth and increasing risks of both multimorbidity outcomes. Compared to full-term born males, those born at 37-38 weeks (early term) had a 1.06-fold risk of multimorbidity in adolescence (95% CI: 0.98 to 1.14) and this risk increased in a graded manner up to 6.85-fold (95% CI: 5.39 to 8.71) in those born at 23-27 weeks (extremely premature), independently of covariates. Among females, the same risks ranged from 1.16-fold (95% CI: 1.09 to 1.23) among those born at 37-38 weeks to 5.65-fold (95% CI: 4.45 to 7.18) among those born at 23-27 weeks. The corresponding risks of early adult multimorbidity were similar in direction but less marked in magnitude, with little difference in risks between males and females born at 36-37 weeks but up to 3-fold risks observed among those born at 23-27 weeks. CONCLUSIONS: Our findings indicate that an earlier gestational age at birth is associated with increased risks of chronic disease multimorbidity in the early part of the life course. There are currently no clinical guidelines for follow-up of prematurely born individuals beyond childhood, but these observations suggest that information on gestational age would be a useful characteristic to include in a medical history when assessing the risk of multiple chronic diseases in adolescent and young adult patients.

Cow's milk allergy in infancy and later development of type 1 diabetes-nationwide case-cohort study.

BAKGROUND: It is suggested that early intake of cow's milk could be a risk factor for type 1 diabetes (T1DM). Further, the different immunological background, gives a suggestion of an inverse relationship for the occurrence of these diseases. The aim of this study was to explore the association between cow's milk allergy (CMA) and the risk of T1DM in a register-based case-cohort study. METHODS: Data were obtained from Finnish nationwide health registers. The study included all children born in Finland between January 01, 1986 and December 31, 2008 and diagnosed with T1DM before the age of 16 years (n = 7754). A 10% random sample from each birth year cohort was selected as a reference cohort (n = 137,798). T1DM, CMA, and asthma were defined based on valid special reimbursements for the costs of drugs/special formulas needed in the treatment of the diseases. Child's sex, birth decade, asthma, maternal diabetes and asthma, smoking during pregnancy, and previous deliveries were considered as confounding factors. Time-dependent, weighted Cox regression was applied for statistical analyses. RESULTS: Children with CMA had an increased risk of developing T1DM in fully adjusted model (HR = 1.17; 95% CI 1.02-1.34), but the association was no longer observed when including the use of special infant formulas in the definition of CMA in the sensitivity analysis (HR = 1.11; 95% CI 0.92-1.32). CMA was associated with an increased risk of T1DM in children without asthma (HR = 1.27; 95%CI 1.10-1.47), but not in children with asthma (HR = 0.80; 95% CI 0.92-1.27). CONCLUSION: Children with CMA may have an increased risk of T1DM.

Maternal antioxidant intake during pregnancy and the development of cows' milk allergy in the offspring.

Cows' milk allergy (CMA) is the most common food allergy in young children, and it is often the first manifestation of atopic diseases. Accordingly, very early environmental factors, such as maternal diet during pregnancy, may play a role in the development of CMA, but the evidence is limited. The aim of this study was to investigate the association between maternal intake of antioxidant nutrients during pregnancy and the subsequent development of CMA in the offspring in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Maternal dietary information during pregnancy was collected with a detailed, validated FFQ. The maternal dietary information and the information on putative confounding factors were available for 4403 children. Information on diagnosed CMA (n 448) was obtained from a medical registry and queried from the parents up to child's age of 3 years. The Finnish food composition database was used to calculate the average daily intake of nutrients. Logistic regression was applied for statistical analyses, and the nutrient intakes were adjusted for energy intake. OR are presented per 1 sd increment of the particular nutrient intake. Maternal total and dietary intake of ß-carotene was associated with an increased risk of CMA in the offspring when adjusted for the putative confounding factors (total OR 1·10, 95 % CI 1·02, 1·20; dietary OR 1·10; 95 % CI 1·01, 1·19). Using dietary supplements containing antioxidants in addition to a balanced diet may not confer any additional benefits.

The risk of complications in second pregnancy by maternal BMI: The role of first-pregnancy complications, pregestational diabetes and chronic hypertension.

INTRODUCTION: Maternal obesity is associated with an increased risk of several pregnancy complications. In the second pregnancy, previous pregnancy and other medical history provide additional information about individual morbidity risk. In this study, we assess the risk of pregnancy complications in the second pregnancy by maternal body mass index (BMI) and evaluate how first-pregnancy complications and preexisting conditions modify these associations. MATERIAL AND METHODS: We have used nationwide data on all women (n = 48 963) experiencing their first and second pregnancy between 2006 and 2013 in Finland. The associations between the full scale of maternal BMI and pregnancy complications (gestational diabetes, gestational hypertension and preeclampsia) were analyzed using logistic regression and restricted cubic spline regression models and interactions between BMI and first-pregnancy complications, pregestational diabetes or chronic hypertension were tested. RESULTS: The risk of pregnancy complications increased with adiposity. Unadjusted probability of second-pregnancy gestational diabetes with BMI of 25 kg/m2 was 56% and 8.4% among women with and without first-pregnancy gestational diabetes, respectively. The corresponding figures with BMI of 30 kg/m2 were 64% and 17%. Adjusted odds ratio (OR) (95% CI) for second-pregnancy gestational diabetes with BMI of 25 kg/m2 was 45 (34-59) and 3.3 (2.6-4.0) among women with and without first-pregnancy gestational diabetes, respectively, when compared with women with BMI of 20 kg/m2 and no first-pregnancy gestational diabetes. Adjusted OR (95% CI) for second-pregnancy gestational hypertension among women with BMI of 25 kg/m2 was 42 (26-66) and 2.3 (1.4-3.8) among women with and without first-pregnancy hypertensive disorder, respectively, when compared with women with BMI of 20 kg/m2 and no first-pregnancy hypertensive disorder. The risk of preeclampsia increased with adiposity independent of first-pregnancy complications. Pregestational diabetes or chronic hypertension did not modify the association between adiposity and any of the second-pregnancy complications. CONCLUSIONS: As maternal BMI increases, the risk of complications increases in the second pregnancy. The risk of gestational diabetes and hypertension is, however, highest among women with complications in the first pregnancy.

Perinatal factors and the risk of type 1 diabetes in childhood and adolescence-A register-based case-cohort study in Finland, years 1987 to 2009.

OBJECTIVES: Our aim was to clarify previously reported associations and to explore new ones between various maternal background and perinatal factors and the risk of type 1 diabetes in childhood. METHODS: We identified all children born 1 January 1987 to 31 December 2008 in Finland and diagnosed with type 1 diabetes by age 16 years or end of 2009 from the Special Reimbursement Register (n = 6862). A 10% random sample from each birth year cohort was selected as a reference cohort (n = 127 216). Information on perinatal factors was obtained from the Finnish Medical Birth Register. RESULTS: Maternal diabetes (hazard ratios [HR] = 6.43; 95% confidence interval [CI] 5.35, 7.73), maternal asthma (HR = 1.23; 95% CI 1.06, 1.43), child's high birth length for gestational age (HR = 1.35; 95% CI 1.22, 1.51 highest vs lowest quintile) and premature or early term birth (HR = 1.21; 95% CI 1.05, 1.39 gestational weeks 33-36 and HR = 1.17; 95% CI 1.09, 1.26 gestational weeks 37-38 vs gestational weeks 39-40) was associated with an increased risk of type 1 diabetes when adjusted for several potential confounders. Maternal smoking during pregnancy (HR = 0.72; 95% CI 0.66, 0.77), high number of previous live births (HR = 0.65; 95% CI 0.55, 0.76 ≥ 4 vs 0 live births), and the child being born small for gestational age (HR = 0.80; 95% CI 0.67, 0.96) was associated with a decreased risk of type 1 diabetes. CONCLUSIONS: Findings on maternal asthma and high birth length for gestational age increasing the risk of type 1 diabetes are novel and need to be confirmed. Our findings indicate that perinatal factors may play a role in the development of type 1 diabetes.

Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children: A Nationwide Case-Cohort Study.

Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995-2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled ß-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled ß-agonists might be at increased risk of type 1 diabetes.

The association between asthma and type 1 diabetes: a paediatric case-cohort study in Finland, years 1981-2009.

Background: The association between asthma and type 1 diabetes, two chronic, immune-mediated diseases, has been of longstanding interest, but the evidence is still conflicting. We examined this association in a large, nationwide case-cohort study among Finnish children, using a novel statistical approach. Methods: Among the initial cohort of all children born between 1 January 1981 and 31 December 2008, those who were diagnosed with asthma (n = 81 473) or type 1 diabetes (n = 9541) up to age 16 years by the end of 2009 were identified from the Central Drug Register maintained by the Social Insurance Institution of Finland. A 10% random sample from each initial birth year cohort was selected as a reference cohort (n = 171 138). The association between asthma and type 1 diabetes was studied using a multistate modelling approach to estimate transition rates between healthy and disease states since birth. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to represent the change in the transition rate between the disease states. Results: After adjusting for sex and birth decade, previous diagnosis of asthma increased the risk of subsequent type 1 diabetes by 41% (95% CI: 1.28, 1.54), whereas previous diagnosis of type 1 diabetes decreased the risk of subsequent asthma by 18% (95% CI: 0.69, 0.98). Conclusions: The findings of the present study imply that the association between the diseases is more complex than previously thought, and its direction depends on the sequential appearance of the diseases.

Risk of Pregnancy Complications in Relation to Maternal Prepregnancy Body Mass Index: Population-Based Study from Finland 2006-10.

BACKGROUND: Overweight and obesity are well-known risk factors for several pregnancy-related complications, but the nature of the association between maternal adiposity and these complications has been less studied. The objective of the present study was to examine the shape and the magnitude of the association between maternal prepregnancy body mass index and the risk of gestational diabetes, pre-eclampsia of different severity, gestational hypertension, and obstetric cholestasis among Finnish primiparae women. METHODS: Data on all primiparae women who delivered a singleton newborn in Finland between 2006 and 2010 were identified from the Finnish Medical Birth Register and the Finnish Hospital Discharge Register (n = 119 485). Associations were analysed using restricted cubic spline regression and logistic regression models. RESULTS: There was a nonlinear dose-dependent association between body mass index and the risk of gestational diabetes, pre-eclampsia, and gestational hypertension, and the risk was increased already among normal weight primiparae women. However, in the presence of pre-existing hypertension or diabetes body mass index was not associated with the risk of pre-eclampsia. CONCLUSIONS: Efforts to reduce prepregnancy overweight and obesity need to be intensified, and also, measures to better identify those normal weight women who are at increased risk of gestational diabetes, pre-eclampsia and gestational hypertension should be developed.

Mother's and offspring's use of antibiotics and infant allergy to cow's milk.

BACKGROUND: Evidence on the association between antibiotics and the risk of food allergies is limited. We explored the associations between mother's and offspring's use of antibiotics and the risk of cow's milk allergy in infancy. METHODS: We used a national registry to identify all children who were born in 1996-2004 in Finland and diagnosed with cow's milk allergy after 1 month of age by November 2005 (n = 15,672). For each case, we selected one control matched for birth date, sex, and hospital district. Information on antibiotic purchases and putative confounders was obtained from registries. The associations were analyzed using conditional logistic regression. RESULTS: Maternal use of antibiotics before and during pregnancy was associated with an increased risk of cow's milk allergy in the offspring (odds ratio = 1.26 [95% confidence interval = 1.20-1.33] and 1.21 [1.14-1.28], respectively, adjusting for putative confounders). The risk of cow's milk allergy increased with increasing number of child's antibiotics used from birth to diagnosis (test for trend P < 0.001). CONCLUSIONS: Both maternal and child's use of antibiotics were associated with an increased risk of cow's milk allergy. Future studies are needed to confirm these novel findings and to explore the potential biologic mechanisms behind the association.