School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study.

BACKGROUND: Conflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group. METHODS AND FINDINGS: This is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were -1.59 (95% CI -2.48 to -0.71, p < 0.001) between O-mT1D and O-BP and -0.78 (95% CI -1.48 to -0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D (p = 0.16). The study's limitation was no access to measures of glycemic control during pregnancy. CONCLUSIONS: O-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function.

National, clinical cohort study of late effects among survivors of acute lymphoblastic leukaemia: the ALL-STAR study protocol.

INTRODUCTION: More than 90% of patients diagnosed with childhood acute lymphoblastic leukaemia (ALL) today will survive. However, half of the survivors are expected to experience therapy-related chronic or late occurring adverse effects, reducing quality of life. Insight into underlying risk trajectories is warranted. The aim of this study is to establish a Nordic, national childhood ALL survivor cohort, to be investigated for the total somatic and psychosocial treatment-related burden as well as associated risk factors, allowing subsequent linkage to nation-wide public health registers. METHODS AND ANALYSIS: This population-based observational cohort study includes clinical follow-up of a retrospective childhood ALL survivor cohort (n=475), treated according to a common Nordic ALL protocol during 2008-2018 in Denmark. The study includes matched controls. Primary endpoints are the cumulative incidence and cumulative burden of 197 health conditions, assessed through self-report and proxy-report questionnaires, medical chart validation, and clinical examinations. Secondary endpoints include organ-specific outcome, including cardiovascular and pulmonary function, physical performance, neuropathy, metabolic disturbances, hepatic and pancreatic function, bone health, oral and dental health, kidney function, puberty and fertility, fatigue, and psychosocial outcome. Therapy exposure, acute toxicities, and host genome variants are explored as risk factors. ETHICS AND DISSEMINATION: The study is approved by the Regional Ethics Committee for the Capital Region in Denmark (H-18035090/H-20006359) and by the Danish Data Protection Agency (VD-2018-519). Results will be published in peer-reviewed journals and are expected to guide interventions that will ameliorate the burden of therapy without compromising the chance of cure.

Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes - Results from the EPICOM study.

AIMS/HYPOTHESIS: To investigate long-term consequences of diabetes during pregnancy, we determined adiponectin and leptin levels in adolescents born by women with type 1 diabetic (T1D) or non-diabetic mothers, and determined associations between adiponectin and leptin levels in adolescence and the magnitude of intrauterine hyperglycemia. RESEARCH DESIGN AND METHODS: We measured serum adiponectin and leptin and calculated leptin to adiponectin ratio (LAR) in 271 offspring of T1D women (index offspring) (13-20years), and 297 matched control offspring. Anthropometry included total body fat (TBF) by dual-energy X-ray absorptiometry and an oral glucose tolerance test. RESULTS: Adiponectin levels were lower in index females (-8.0% (95% CI; -13.9, -1.6)), but not in index males (0.4% (95% CI; -7.3, 8.6)). Leptin levels were approximately 30% higher in index than control offspring, irrespective of gender. In males, this was seen despite similar TBF in index and control offspring. LAR was increased in index offspring (both males and females) compared with control offspring. There were no association between offspring adiponectin and maternal HbA1c levels in pregnancy. Leptin and LAR seemed to be associated with third trimester HbA1c levels in females in unadjusted, but not adjusted analyses. CONCLUSION: Male and female offspring of women with T1D demonstrated increased serum leptin and LAR, whereas serum adiponectin was reduced in females only. These results suggest that abnormal regulation of adipokines is a consequence of being born to mothers with T1D. No direct association between maternal glycemic control and adiponectin and leptin levels or LAR in the adolescence was found. CLINICAL TRIAL REGISTRATION NUMBER: NCT01559181.

Influence of fetal growth velocity and smallness at birth on adrenal function in adolescence.

The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth weight <10 percentile). In 52 adolescent boys (17.5 years) we assessed circulating androgen levels (T, Δ(4)-adione, DHEAS), overnight serum cortisol profiles (every 20 min), ACTH stimulation test (250 µg i.v.) and analysis of 24-hour urinary adrenal steroid excretion. Urinary excretion of adrenal androgen and cortisol metabolites were significantly lower in the SGA compared to the AGA group. Basal morning cortisol levels were lower in adolescents born SGA compared to those born AGA (365 mmol/l, interquartile range (IQR) 284-413 vs. 445 mmol/l, IQR 377-495, p = 0.04), but overnight cortisol profiles (AUC) did not differ. The ACTH test showed equally stimulated levels of cortisol for those born SGA and AGA. There was no difference in serum testosterone, dehydroepiandrosterone sulfate and Δ(4)-adione levels between the SGA and AGA subjects. This suggests impaired excretion of adrenal androgen and cortisol metabolites in young men born SGA compared to AGA. In conclusion, this study demonstrated subtle changes in adolescent adrenal function associated with birth weight.