Maternal infection during pregnancy may be a risk factor for epilepsy in offspring. Use of antibiotics is a valid marker of infection.
To examine the relationship between maternal infection during pregnancy and risk of childhood epilepsy we conducted a historical cohort study of singletons born in northern Denmark from 1998 through 2008 who survived ≥29 days. We used population-based medical databases to ascertain maternal use of antibiotics or hospital contacts with infection during pregnancy, as well as first-time hospital contacts with a diagnosis of epilepsy among offspring. We compared incidence rates (IR) of epilepsy among children of mothers with and without infection during pregnancy. We examined the outcome according to trimester of exposure, type of antibiotic, and total number of prescriptions, using Poisson regression to estimate incidence rate ratios (IRRs) while adjusting for covariates. Among 191 383 children in the cohort, 948 (0.5%) were hospitalised or had an outpatient visit for epilepsy during follow-up, yielding an IR of 91 per 100 000 person-years (PY). The five-year cumulative incidence of epilepsy was 4.5 per 1000 children. Among children exposed prenatally to maternal infection, the IR was 117 per 100 000 PY, with an adjusted IRR of 1.40 (95% confidence interval (CI): 1.22–1.61), compared with unexposed children. The association was unaffected by trimester of exposure, antibiotic type, or prescription count.
Prenatal exposure to maternal infection is associated with an increased risk of epilepsy in childhood. The similarity of estimates across types of antibiotics suggests that processes common to all infections underlie this outcome, rather than specific pathogens or drugs.
To assess the risk of developing Type-1 diabetes among children who were exposed to maternal bereavement during the prenatal or 1-year preconception period.
We identified N = 1,548,746 singleton births born in Denmark between January 1st 1979 through December 31st 2004, and their next of kin. Altogether, 39,857 children were exposed to bereavement during their prenatal life. The main outcome of interest was hospitalization for type-1 diabetes (ICD 8: 249; ICD 10: E10).
We found the strongest association for type-1 diabetes among children exposed to traumatic father or sibling deaths (aIRR: 2.03, 1.22–3.38); the association was mainly seen for girls (aIRR: 2.91, 1.61–5.26).
We found evidence to suggest that female fetuses exposed to severe prenatal stress are at increased risk for developing type-1 diabetes.
The etiology of type-2 diabetes is only partly known, and a possible role of prenatal stress in programming offspring for insulin resistance has been suggested by animal models. Previously, we found an association between prenatal stress and type-1 diabetes. Here we examine the association between prenatal exposure to maternal bereavement during preconception and pregnancy and development of type-2 diabetes in the off-spring.
We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1st 1979 through December 31st 2008 (N = 1,878,246), and linked them to their parents, grandparents, and siblings. We categorized children as exposed to bereavement during prenatal life if their mothers lost an elder child, husband or parent during the period from one year before conception to the child’s birth. We identified 45,302 children exposed to maternal bereavement; the remaining children were included in the unexposed cohort. The outcome of interest was diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from birth using log-linear poisson regression models and used person-years as the offset variable. All models were adjusted for maternal residence, income, education, marital status, sibling order, calendar year, sex, and parents’ history of diabetes at the time of pregnancy.
We found children exposed to bereavement during their prenatal life were more likely to have a type-2 diabetes diagnosis later in life (aIRR: 1.31, 1.01–1.69). These findings were most pronounced when bereavement was caused by death of an elder child (aIRR: 1.51, 0.94–2.44). Results also indicated the second trimester of pregnancy to be the most sensitive period of bereavement exposure (aIRR:2.08, 1.15–3.76).
Our data suggests that fetal exposure to maternal bereavement during preconception and the prenatal period may increase the risk for developing type-2 diabetes in childhood and young adulthood.
Experimental animal studies and one population-based study have suggested an increased risk for adverse neurodevelopmental outcome after prenatal exposure to SSRIs. We describe the methods and design of a population-based study examining the association between prenatal SSRI exposure and neurodevelopment until age 14.
Methods and design
This is a cohort study of national registers in Finland: the Medical Birth Register, the Register of Congenital Malformations, the Hospital Discharge Register including inpatient and outpatient data, the Drug Reimbursement Register, and the Population Register. The total study population includes 845,345 women and their live-born, singleton offspring aged 14 or younger and born during Jan 1st 1996-Dec 31st 2010. We will compare the prevalence of psychiatric and neurodevelopmental outcomes in offspring exposed prenatally to SSRIs to offspring exposed to prenatal depression and unexposed to SSRIs. Associations between exposure and outcome are assessed by statistical methods including specific modeling to account for correlated outcomes within families and differences in duration of follow-up between the exposure groups. Descriptive results. Of all pregnant women with pregnancy ending in delivery (n = 859,359), 1.9% used SSRIs. The prevalence of diagnosed depression and depression-related psychiatric disorders within one year before or during pregnancy was 1.7%. The cumulative incidence of registered psychiatric or neurodevelopmental disorders was 6.9% in 2010 among all offspring born during the study period (age range 0–14 years).
The study has the potential for significant public health importance in providing information on prenatal exposure to SSRIs and long-term neurodevelopment.
SSRI; Pregnancy; Neurodevelopment
We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost a close relative during pregnancy or within 1 year before the pregnancy and they were included in the exposed group. The exposed children had a risk of febrile seizures similar to that of the unexposed children (hazard ratio (HR) 1.00, 95% CI 0.94–1.06). The HRs did not differ according to the nature or timing of bereavement. Our data do not suggest any causal link between exposure to prenatal stress and febrile seizures in childhood.
Prenatal stress; Bereavement; Febrile seizures; Fetal programming; Longitudinal study
OBJECTIVE: To investigate whether prenatal growth affects the risk of development of childhood onset insulin dependent (type I) diabetes mellitus. DESIGN: Population based case-control study. SETTING: Data from a nationwide childhood diabetes case register were linked with data from the nationwide Swedish Medical Birth Registry. SUBJECTS: Data from a total of 4584 diabetic children born after 1973 and diagnosed with diabetes from 1978 to 1992 were studied. For each child with insulin dependent diabetes three control children were randomly selected from among all infants born in the same year and at the same hospital as the proband. MAIN OUTCOME MEASURES: Birth weight, gestation, maternal age and parity, number of previous spontaneous abortions, and sex specific birth weight by gestational week expressed as multiples of the standard deviation (SD). RESULTS: There was a clear trend in the odds ratio for childhood onset diabetes according to SD of birth weight. The odds ratio (95% confidence interval) for small for gestational age after stratification for maternal age, parity, smoking habits, and maternal diabetes was 0.81 (0.65 to 0.99) and for large for gestational age after similar stratification was 1.20 (1.02 to 1.42). CONCLUSIONS: Intrauterine conditions that affect prenatal growth seem also to affect the risk of development of childhood diabetes in the way previously described for postnatal growth: a poor growth decreases and an excess growth increases the risk. The mechanism for this association is unclear.
It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population–based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age.
We followed 65,212 children born in Denmark from 1970–1989 who underwent health examinations from 7 to 13 years of age in public or private schools in Copenhagen. We identified 459 children as exposed to prenatal stress, defined by being born to mothers who were bereaved by death of a close family member from one year before pregnancy until birth of the child. We compared the prevalence of overweight between the exposed and the unexposed. Body mass index (BMI) values and prevalence of overweight were higher in the exposed children, but not significantly so until from 10 years of age and onwards, as compared with the unexposed children. For example, the adjusted odds ratio (OR) for overweight was 1.68 (95% confidence interval [CI] 1.08–2.61) at 12 years of age and 1.63 (95% CI 1.00–2.61) at 13 years of age. The highest ORs were observed when the death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI 1.71–6.42 at age 12, and OR 2.31, 95% CI 1.08–4.97 at age 13).
Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood.
The aetiology of childhood cancer remains largely unknown but recent research indicates that uterine environment plays an important role. We aimed to examine the association between the Apgar score at 5 min after birth and the risk of childhood cancer.
Nationwide population-based cohort study.
Nationwide register data in Denmark and Sweden.
All live-born singletons born in Denmark from 1978 to 2006 (N=1 771 615) and in Sweden from 1973 to 2006 (N=3 319 573). Children were followed up from birth to 14 years of age.
Main outcome measures
Rates and HRs for all childhood cancers and for specific childhood cancers.
A total of 8087 children received a cancer diagnosis (1.6 per 1000). Compared to children with a 5-min Apgar score of 9–10, children with a score of 0–5 had a 46% higher risk of cancer (adjusted HR 1.46, 95% CI 1.15 to 1.89). The potential effect of low Apgar score on overall cancer risk was mostly confined to children diagnosed before 6 months of age. Children with an Apgar score of 0–5 had higher risks for several specific childhood cancers including Wilms’ tumour (HR 4.33, 95% CI 2.42 to 7.73).
A low 5 min Apgar score was associated with a higher risk of childhood cancers diagnosed shortly after birth. Our data suggest that environmental factors operating before or during delivery may play a role on the development of several specific childhood cancers.
Oncology; Epidemiology; Paediatric oncology; Preventive Medicine
To examine the influence of parental age at delivery and birth order on subsequent risk of childhood diabetes.
Prospective population based family study.
Area formerly administered by the Oxford Regional Health Authority.
1375 families in which one child or more had diabetes. Of 3221 offspring, 1431 had diabetes (median age at diagnosis 10.5 years, range 0.4-28.5) and 1790 remained non-diabetic at a median age of 16.1 years.
Main outcome measures
Disease free survival and hazard ratios for the development of type 1 diabetes in all offspring, assessed by Cox proportional hazard regression.
Maternal age at delivery was strongly related to risk of type 1 diabetes in the offspring; risk increased by 25% (95% confidence interval 17% to 34%) for each five year band of maternal age, so that maternal age at delivery of 45 years or more was associated with a relative risk of 3.11 (2.07 to 4.66) compared with a maternal age of less than 20 years. Paternal age was also associated with a 9% (3% to 16%) increase for each five year increase in paternal age. The relative risk of diabetes, adjusted for parental age at delivery and sex of offspring, decreased with increasing birth order; the overall effect was a 15% risk reduction (10% to 21%) per child born.
A strong association was found between increasing maternal age at delivery and risk of diabetes in the child. Risk was highest in firstborn children and decreased progressively with higher birth order. The fetal environment seems to have a strong influence on risk of type 1 diabetes in the child. The increase in maternal age at delivery in the United Kingdom over the past two decades could partly account for the increase in incidence of childhood diabetes over this period.
Recent findings suggest that maternal iron deficiency may increase the risk of schizophrenia-spectrum disorder in offspring. We initiated this study to determine whether maternal prepartum anemia influences offspring risk of schizophrenia. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Register. In a cohort of 1 115 752 Danish singleton births from 1978 to 1998, cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Cohort members were followed from their 10th birthday until onset of schizophrenia, death, or December 31, 2008, whichever came first. Adjusted for relevant confounders, cohort members whose mothers had received a diagnosis of anemia during pregnancy had a 1.60-fold (95% confidence interval = 1.16–2.15) increased risk of schizophrenia. Although the underlying mechanisms are unknown and independent replication is needed, our findings suggest that maternal iron deficiency increases offspring risk of schizophrenia.
Schizophrenia; epidemiology; risk factor; Denmark; maternal iron deficiency; follow-up; cohort
Recent studies have provided evidence that intrauterine exposure to maternal diabetes has lifelong effects on adult offspring, including increased risks of obesity, type 2 diabetes and cardiovascular disease. The aim of this study was to assess the relationship between exposure to maternal diabetes in utero and cardiovascular risk factors in healthy children and to investigate whether these associations are independent of maternal prepregnancy BMI and offspring attained BMI.
Data were from a retrospective cohort of children aged 6–13 years born during 1994–2002. Multiple linear regression was used to examine the associations between exposure and cardiovascular risk factors with adjustment for demographic factors and pubertal stage and additionally for maternal prepregnancy BMI and offspring attained BMI.
Ninety-nine offspring of diabetic pregnancies had significantly increased E-selectin, vascular adhesion molecule 1 (VCAM1), leptin, waist circumference, BMI and systolic blood pressure and decreased adiponectin levels compared with 422 offspring of non-diabetic pregnancies after adjustment for age, sex and race/ethnicity (p<0.05 for each risk factor). Additional adjustment for maternal prepregnancy BMI substantially attenuated group differences in the risk factors except for E-selectin, VCAM1 and waist circumference, which remained significantly higher in exposed children.
Compared with unexposed children, healthy offspring exposed to maternal diabetes in utero have a worse cardiovascular risk profile. In particular, offspring have substantially increased levels of circulating cellular adhesion molecules, which are biomarkers of adverse endothelium perturbation and may be related to the earliest preclinical stages of atherosclerosis and diabetes.
Adipokines; Adiposity; Blood pressure; Cardiovascular risk factors in children; Developmental origins of health and disease; Endothelial cell adhesion molecules; Gestational diabetes; Intrauterine exposure to maternal diabetes; Lipids; Pregnancy
The presence of diabetes mellitus poses a challenge in the treatment of patients with acute myocardial infarction (AMI). We aimed to evaluate the sex-specific outcomes of diabetic and non-diabetic patients with AMI who have undergone percutaneous coronary intervention (PCI).
Data of the Estonian Myocardial Infarction Registry for years 2006–2009 were linked with the Health Insurance Fund database and the Population Registry. Hazard ratios (HRs) with the 95% confidence intervals (CIs) for the primary composite outcome (non-fatal AMI, revascularization, or death whichever occurred first) and for the secondary outcome (all cause mortality) were calculated comparing diabetic with non-diabetic patients by sex.
In the final study population (n = 1652), 14.6% of the men and 24.0% of the women had diabetes. Overall, the diabetics had higher rates of cardiovascular risk factors, co-morbidities, and 3–4 vessel disease among both men and women (p < 0.01). Among women, the diabetic patients were younger, they presented later and less often with typical symptoms of chest pain than the non-diabetics (p < 0.01). Women with diabetes received aspirin and reperfusion for ST-segment elevation AMI less often than those without diabetes (p < 0.01). During a follow-up of over two years, in multivariate analysis, diabetes was associated with worse outcomes only in women: the adjusted HR for the primary outcome 1.44 (95% CI 1.05 − 1.96) and for the secondary outcome 1.83 (95% CI 1.17 − 2.89). These results were largely driven by a high (12.0%) mortality during hospitalization of diabetic women.
Diabetic women with AMI who have undergone PCI are a high-risk group warranting special attention in treatment strategies, especially during hospitalization. There is a need to improve the expertise to detect AMI earlier, decrease disparities in management, and find targeted PCI strategies with adjunctive antithrombotic regimes in women with diabetes.
Diabetes mellitus; Sex; Acute myocardial infarction; Percutaneous coronary intervention; Mortality; Outcome
To test whether depression is associated with an increased risk of incident diabetic foot ulcers.
The Pathways Epidemiologic Study is a population-based prospective cohort study of 4839 patients with diabetes in 2000–2007. The present analysis included 3474 adults with type 2 diabetes and no prior diabetic foot ulcers or amputations. Mean follow-up was 4.1 years. Major and minor depression assessed by the Patient Health Questionnaire-9 (PHQ-9) were the exposures of interest. The outcome of interest was incident diabetic foot ulcers. We computed the hazard ratio (HR) and 95% CI for incident diabetic foot ulcers, comparing patients with major and minor depression to those without depression and adjusting for sociodemographic characteristics, medical comorbidity, glycosylated hemoglobin (HbA1c), diabetes duration, insulin use, number of diabetes complications, body mass index, smoking status, and foot self-care. Sensitivity analyses also adjusted for peripheral neuropathy and peripheral arterial disease as defined by diagnosis codes.
Compared to patients without depression, patients with major depression by PHQ-9 had a two-fold increase in the risk of incident diabetic foot ulcers (adjusted HR 2.00, 95% CI: 1.24, 3.25). There was no statistically significant association between minor depression by PHQ-9 and incident diabetic foot ulcers (adjusted HR 1.37, 95% CI: 0.77, 2.44).
Major depression by PHQ-9 is associated with a two-fold higher risk of incident diabetic foot ulcers. Future studies of this association should include better measures of peripheral neuropathy and peripheral arterial disease, which are possible confounders and/or mediators.
diabetes; depression; foot ulcers; complications
A depressed Apgar score at 5 minutes is a marker for perinatal insults, including neurologic damage. We examined the association between 5-minute Apgar score and the risk of epilepsy hospitalization in childhood.
Using records linked from population registries, we conducted a cohort study among singleton children born alive in the period 1978–2001 in North Jutland County, Denmark. The first hospital discharge diagnosis of epilepsy during the follow-up time was the main outcome. We followed each child for up to 12 years, calculated absolute risks and risk differences, and used a Poisson regression model to estimate risk ratios for epilepsy hospitalization. We adjusted risk ratio estimates for birth weight, gestational age, mode of delivery, birth presentation, mother's age at delivery, and birth defects.
One percent of the 131,853 eligible newborns had a 5-minute Apgar score <7. These children were more likely to be hospitalized with epilepsy during the follow-up than were children with an Apgar score of 7 or greater. The crude risk difference for epilepsy hospitalization was 2.5 cases per 100 (95% confidence interval [CI] 1.3 to 3.8). The risk difference estimates were greater in the presence of other perinatal risk factors. The adjusted risk ratio was 2.4 (95% CI 1.5 to 3.8). Half of the 12-year risk for epilepsy hospitalization in those with a depressed Apgar score occurred during the first year of life. The risk ratio during the first year of life was 4.9 (95% CI 2.0 to 12.3).
An Apgar score <7 at five minutes predicts an increase in the subsequent risk of epilepsy hospitalization. This association is amplified by other perinatal risk factors.
OBJECTIVES: To study the relative and absolute risks of main types of lung cancer in a cohort of asbestos cement workers from Denmark. METHOD: A cohort of 7887 men and 576 women employed between 1928 and 1984 was compiled from the personnel files of Danish Eternit Production. The cohort was followed up for deaths, emigrations, and incident cancer cases during the period 1943-90. The observed number of lung cancer cases in the cohort was compared with the expected number based on incidences for the Danish population. Internal comparison was made with Poisson modelling. RESULTS: A total of 226 lung cancer cases were observed (223 men and three women). The standardised incidence ratio (SIR) for all lung cancer among men was 1.7 (observed number 223, expected number 129.7, 95% confidence interval (95% CI) 1.5-2.0). The SIRs were raised for all main types of lung cancer; adenocarcinoma 2.6, squamous cell carcinoma 1.7, and anaplastic carcinoma 1.5. The higher SIR for adenocarcinomas was found particularly with a latency period of 25 years or more. Among the 93 excess lung cancer cases, 36 were squamous cell carcinomas and 32 were adenocarcinomas. CONCLUSION: Asbestos cement work is associated with an increased risk of lung cancer of all main types. During the first 25 years after the start of employment this excess risk is shared almost equally between the different histological types of lung cancer, but the risk of adenocarcinomas is clearly higher after this point.
BACKGROUND: For over 20 years the association between sarcoidosis and malignancy, particularly lymphoma and lung cancer, has been disputed with misclassification being the major concern. The aim of the present study was to analyse the incidence of malignancies in a cohort of patients with sarcoidosis by linkage to a nationwide population based cancer register. METHODS: The cohort comprised 254 patients followed for a median of 25 years until death, emigration, or 31 December 1992, whichever came first. The expected number of cancer cases was calculated using the annual age and sex specific cancer rates from the Danish Cancer Registry. RESULTS: Thirty six cancers were registered, three of which were misclassified as sarcoidosis, leaving 33 cancers compared with 23 expected (standardised incidence ratio (SIR) = 1.4; 95% CI 0.99 to 2.0). Five lung cancers were observed compared with 2.5 expected, yielding an SIR of 2.0 (95% CI 0.7 to 4.7). There was no incidence of lymphoma and only one case of leukaemia. There was a significant excess number of pharyngeal cancers based on two cases (SIR = 15.4; 95% CI 1.7 to 56). CONCLUSIONS: This study does not support the theory of an association between sarcoidosis and malignancy, and the main reason other studies have shown such an association is most likely to have been due to selection bias and misclassification.
Objective To develop and validate a new diabetes risk algorithm (the QDScore) for estimating 10 year risk of acquiring diagnosed type 2 diabetes over a 10 year time period in an ethnically and socioeconomically diverse population.
Design Prospective open cohort study using routinely collected data from 355 general practices in England and Wales to develop the score and from 176 separate practices to validate the score.
Participants 2 540 753 patients aged 25-79 in the derivation cohort, who contributed 16 436 135 person years of observation and of whom 78 081 had an incident diagnosis of type 2 diabetes; 1 232 832 patients (7 643 037 person years) in the validation cohort, with 37 535 incident cases of type 2 diabetes.
Outcome measures A Cox proportional hazards model was used to estimate effects of risk factors in the derivation cohort and to derive a risk equation in men and women. The predictive variables examined and included in the final model were self assigned ethnicity, age, sex, body mass index, smoking status, family history of diabetes, Townsend deprivation score, treated hypertension, cardiovascular disease, and current use of corticosteroids; the outcome of interest was incident diabetes recorded in general practice records. Measures of calibration and discrimination were calculated in the validation cohort.
Results A fourfold to fivefold variation in risk of type 2 diabetes existed between different ethnic groups. Compared with the white reference group, the adjusted hazard ratio was 4.07 (95% confidence interval 3.24 to 5.11) for Bangladeshi women, 4.53 (3.67 to 5.59) for Bangladeshi men, 2.15 (1.84 to 2.52) for Pakistani women, and 2.54 (2.20 to 2.93) for Pakistani men. Pakistani and Bangladeshi men had significantly higher hazard ratios than Indian men. Black African men and Chinese women had an increased risk compared with the corresponding white reference group. In the validation dataset, the model explained 51.53% (95% confidence interval 50.90 to 52.16) of the variation in women and 48.16% (47.52 to 48.80) of that in men. The risk score showed good discrimination, with a D statistic of 2.11 (95% confidence interval 2.08 to 2.14) in women and 1.97 (1.95 to 2.00) in men. The model was well calibrated.
Conclusions The QDScore is the first risk prediction algorithm to estimate the 10 year risk of diabetes on the basis of a prospective cohort study and including both social deprivation and ethnicity. The algorithm does not need laboratory tests and can be used in clinical settings and also by the public through a simple web calculator (www.qdscore.org).
Mixed-handedness, which may reflect atypical brain laterality, has been linked to a number of medical conditions as well as prenatal stress.
The aim of the study was to examine whether infertility or infertility treatment was associated with an increased risk of mixed-handedness in children.
Study design, subjects and outcome measures
We used data from three population-based birth cohorts in Denmark: the Aalborg-Odense Birth Cohort (1984-1987), the Aarhus Birth Cohort (1990-1992) and the Danish National Birth Cohort (1996-2002) (N=7728, 5720 and 29486, respectively). Data on time to pregnancy and infertility treatment was collected during pregnancy. Handedness was reported in a follow-up questionnaire when the children were at least 7 years old. Children were categorized as mixed-handed if the mothers reported that they used both hands equally.
Children born after infertility treatment, particularly intrauterine insemination, had a higher risk of being mixed-handed compared to children of fertile couples with a time to pregnancy ≤12 months (odds ratio 1.41, 95% confidence interval 1.09-1.82). Children of couples with unplanned pregnancies, particularly after an oral contraceptives failure, were also more likely to be mixed-handed. There was no association between a long waiting time to pregnancy and mixed-handedness in children.
Children born after infertility treatment, particularly intrauterine insemination, and children exposed to oral contraceptives during early gestation may have a higher risk of being mixed-handed.
Infertility; Infertility treatment; Mixed-handedness; Oral contraceptives; Time to pregnancy
The incidence of type 1 diabetes is increasing. Delivery by cesarean section is also more prevalent, and it is suggested that cesarean section is associated with type 1 diabetes risk. We examine associations between cesarean delivery, islet autoimmunity and type 1 diabetes, and genes involved in type 1 diabetes susceptibility.
RESEARCH DESIGN AND METHODS
Cesarean section was examined as a risk factor in 1,650 children born to a parent with type 1 diabetes and followed from birth for the development of islet autoantibodies and type 1 diabetes.
Children delivered by cesarean section (n = 495) had more than twofold higher risk for type 1 diabetes than children born by vaginal delivery (hazard ratio [HR] 2.5; 95% CI 1.4–4.3; P = 0.001). Cesarean section did not increase the risk for islet autoantibodies (P = 0.6) but was associated with a faster progression to diabetes after the appearance of autoimmunity (P = 0.015). Cesarean section–associated risk was independent of potential confounder variables (adjusted HR 2.7;1.5–5.0; P = 0.001) and observed in children with and without high-risk HLA genotypes. Interestingly, cesarean section appeared to interact with immune response genes, including CD25 and in particular the interferon-induced helicase 1 gene, where increased risk for type 1 diabetes was only seen in children who were delivered by cesarean section and had type 1 diabetes–susceptible IFIH1 genotypes (12-year risk, 9.1 vs. <3% for all other combinations; P < 0.0001).
These findings suggest that type 1 diabetes risk modification by cesarean section may be linked to viral responses in the preclinical autoantibody-positive disease phase.
To study the influence of zygosity on the metabolic variables involved in the pathophysiology of type 2 diabetes.
Population based cross sectional study.
Odense University Hospital, Denmark.
125 monozygotic twin pairs and 178 dizygotic twin pairs of the same sex born between 1921 and 1940.
Main outcome measures
Clinical characteristics of monozygotic and dizygotic twins with or without a family history of type 2 diabetes.
Absolute prevalences of type 2 diabetes and impaired glucose tolerance according to the World Health Organisation criteria were similar in both the monozygotic and the dizygotic twins as were measurements of height, weight, body mass index, waist to hip ratio, and fasting plasma glucose and insulin concentrations. During the oral glucose tolerance test, monozygotic twins had a higher incremental plasma insulin area under the curve than dizygotic twins (10.05 (SD 0.68) v 9.89 (0.72) pmol/l×minutes, P<0.01) indicating insulin resistance. In twins with normal glucose tolerance and without first degree relatives or co-twins with type 2 diabetes or impaired glucose tolerance, both the glucose and insulin areas under the curve were higher among monozygotic twins (glucose 214.4 (88.3) v 189.8 (78.4) mmol/l×minutes, P<0.05; insulin 20 040 (14 865-32 554) v 17 625 (12 330-23 640) pmol/l×minutes, P=0.08).
Zygosity influences both plasma glucose and plasma insulin concentrations during an oral glucose tolerance test. This supports an intrauterine influence on glucose homeostasis and perhaps on insulin resistance in humans.
Key messagesZygosity affects glucose homeostasis and insulin resistance but has no influence on body weight and fat distributionDifferences in glucose metabolism between monozygotic and dizygotic twins are independent of a family history of type 2 diabetesThe validity of causal conclusions from classic twin studies may be questioned
Type 2 diabetes has been inconsistently associated with risk of atrial fibrillation (AF) in previous studies that have frequently been beset by methodological challenges.
Prospective cohort study.
The Atherosclerosis Risk in Communities Study.
Detailed medical histories were obtained on 13025 participants. Individuals were categorized as having no diabetes, pre-diabetes or diabetes based on the 2010 American Diabetes Association criteria at study baseline (1990–92).
Main Outcome Measures
Diagnoses of incident AF were obtained through 2007. Associations between type 2 diabetes and markers of glucose homeostasis with the incidence of AF were estimated using Cox proportional hazards models after adjusting for possible confounders.
Type 2 diabetes was associated with a significant increase in risk of AF (HR 1.35, 95% confidence interval [CI]: 1.14–1.60) after adjustment for confounders. There was no indication that individuals with pre-diabetes or those with undiagnosed diabetes were at increased risk of AF compared to those without diabetes. We observed a positive linear association between HbA1c and risk of AF in those with and without diabetes: 1.13 (1.07–1.20) and 1.05 (0.96–1.15) per 1% point increase, respectively. There was no association between fasting glucose or insulin (p>0.05) in those without diabetes but a significant association with fasting glucose in those with the condition (p=0.0002). Results were similar in whites and African Americans.
Diabetes, HbA1c level and poor glycemic control are independently associated with increased risk of AF, but the underlying mechanisms governing the relationship are unknown and warrant further investigation.
Atrial fibrillation; risk factors; macrovascular disease
We prospectively assessed the age- and sex-specific incidence and relative risk of malignant neoplasm of the pancreas in Taiwan’s diabetic population.
RESEARCH DESIGN AND METHODS
A total of 615,532 diabetic patients and 614,871 age- and sex-matched control subjects were linked to inpatient claims (2000–2006) to identify the admissions for malignant neoplasm of the pancreas (ICD-9: 157). The Cox proportional hazards regression model was used to estimate the age- and sex-specific relative risk of pancreatic neoplasm.
Compared with the control group, the diabetic patients had a significantly increased risk of pancreatic cancer (hazard ratio [HR] 1.54 [95% CI 1.39–1.71]). The higher and significant age-specific HRs were observed in diabetic men (1.91) and women (1.80) aged 45–65 years.
Middle-aged diabetic men and women were associated with the most increased risk of malignant neoplasm of the pancreas.
To determine the effect of Haemophilus influenzae type b vaccination and its timing on the risk of type 1 diabetes in Finnish children.
Cumulative incidence and relative risk of type 1 diabetes was compared among three birth cohorts of Finnish children: those born during the 24 months before the H influenzae type b vaccination trial, those in the trial cohort who were vaccinated at 3 months of age and later with a booster vaccine, and those in the trial cohort who were vaccinated at 24 months of age only. The probability of type 1 diabetes was estimated using regression analysis assuming that there were no losses to 10 year follow up and no competing risks.
Finland (total population 5 million and annual birth rate 1.3%).
128 936 children born from 1 October 1983 to 1 September 1985, and 116 352 children born from 1 October 1985 to 31 August 1987.
Main outcome measures
Probability of type 1 diabetes among children vaccinated with H influenzae type b and non-vaccinated children.
No statistically significant difference was found at any time during the 10 year follow up in the risk of type 1 diabetes between the children born before the vaccination period and those vaccinated at the age of 24 months only (relative risk 1.01). The difference in the risk between the cohort vaccinated first at the age of 3 months and the cohort vaccinated at the age of 24 months only was not statistically significant either (1.06).
It is unlikely that H influenzae type b vaccination or its timing cause type 1 diabetes in children.
Key messagesThe gradual increase in vaccination programmes does not permit any particular one to be pinpointed as being responsible for the increase in type 1 diabetes in FinlandThere is no difference in the risk of type 1 diabetes between children not vaccinated against H influenzae type b and those vaccinated at the age of 24 months onlyThe difference in risk between children vaccinated against H influenzae type b at the age of 3 months and those vaccinated at the age of 24 months was not statistically significantIt is very unlikely that H influenzae type b vaccination or its timing causes type 1 diabetes in Finnish children
To examine perinatal risk factors for the onset of Type 1 diabetes before 6 years of age, in a 2000–2005 Australian birth cohort.
Data from longitudinally linked delivery and hospital admission records (until June 2007) were analysed. Diabetes in mothers and children was identified from International Classification of Diseases 10 diagnosis codes in the hospital records.
There were 272 children admitted to hospital with a first diagnosis of diabetes out of 502 040 live births. Incidence for the infants born in 2000 was 16.0 per 100 000 person-years. Maternal Type 1 diabetes was a significant risk factor [crude relative risk (RR) 6.33], but maternal Type 2 diabetes and gestational diabetes were not significantly associated with diabetes in the child. Late preterm birth (34–36 weeks) (RR 1.64) and caesarean section (RR 1.30) increased the risk of a diabetes admission. Size-for-gestational-age was significantly associated with onset of diabetes (small-for-gestational age RR 0.48), but neither birth weight categories nor birth weight as a continuous variable were associated with risk of diabetes. Increasing maternal age was associated with an increased risk of diabetes in the child (RR 1.13 for each additional 5 years of age).
This study identified risk factors associated with onset of Type 1 diabetes before 6 years of age, in a recent birth cohort. Size-for-gestational-age had a consistent association with risk of early onset of Type 1 diabetes, small size being protective. Size-for-gestational-age measures should be preferred to birth weight thresholds when assessing risk of diabetes.
birthweight; Caesarean section; pregnancy; record linkage; Type 1 diabetes
Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis for patients at risk of transmitting an inherited disease such as myotonic dystrophy type 1(DM1) to their offspring. In this paper, the clinical application of preimplantation diagnosis for DM1 upon request to children born is described in a large cohort of risk couples. PGD could be offered to all 78 couples opting for PGD regardless of the triplet repeat size. The incidence of major complications was minimalised following a careful assessment in affected DM1 females anticipating possible cardiological, obstetrical and anaesthetical problems. A live-birth delivery rate per cycle with oocyte retrieval of 20% was the outcome. Forty-eight of the 49 children born are in good health and have normal psychomotor development.
preimplantation genetic diagnosis; myotonic dystrophy; counselling; child