Maternal type 1 diabetes and relative protection against offspring transmission.

Type 1 diabetes is around twice as common in the offspring of men with type 1 diabetes than in the offspring of women with type 1 diabetes, but the reasons for this difference are unclear. This Review summarises the evidence on the rate of transmission of type 1 diabetes to the offspring of affected fathers compared with affected mothers. The findings of nine major studies are presented, describing the magnitude of the effect observed and the relative strengths and weaknesses of these studies. This Review also explores possible underlying mechanisms for this effect, such as genetic mechanisms (eg, the selective loss of fetuses with high-risk genes in mothers with type 1 diabetes, preferential transmission of susceptibility genes from fathers, and parent-of-origin effects influencing gene expression), environmental exposures (eg, exposure to maternal hyperglycaemia, exogenous insulin exposure, and transplacental antibody transfer), and maternal microchimerism. Understanding why type 1 diabetes is more common in the offspring of men versus women with type 1 diabetes will help in the identification of individuals at high risk of the disease and can pave the way in the development of interventions that mimic the protective elements of maternal type 1 diabetes to reduce the risk of disease in individuals at high risk.

Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.

CONTEXT: Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy. OBJECTIVE: We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status. METHODS: We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset. RESULTS: Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole. CONCLUSION: The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.

Long-term health outcomes in young women with polycystic ovary syndrome: A narrative review.

Polycystic ovary syndrome (PCOS) has long been recognized as a common disorder in young women leading to reproductive and cutaneous sequelae. However, the associated health risks are now known to extend beyond these familiar manifestations to a range of longer-term comorbidities. Here we review the evidence for an association of PCOS with adverse long-term health outcomes, discussing the pathophysiological mechanisms involved in addition to opportunities for therapeutic intervention. Cross-sectional and longitudinal studies point to an increased risk of type 2 diabetes, hypertension and dyslipidaemia, with recent data confirming that these translate to an increased risk of cardiovascular events independently of obesity. Obstructive sleep apnoea, nonalcoholic fatty liver disease and endometrial cancer are also more prevalent, while mental health disorders, notably anxiety and depression, are common but under-appreciated associations. Uncertainties remain as to whether these risks are apparent in all patients with PCOS or are confined to particular subtypes, whether risks persist post-menopausally and how risk may be affected by ethnicity. Further work is also needed in establishing if systematic screening and targeted intervention can lead to improved outcomes. Until such data are available, clinicians managing women with PCOS should counsel patients on long-term health risks and invest in strategies that limit progression to metabolic and non-metabolic morbidities.

Pregnancy in teenagers diagnosed with type 1 diabetes mellitus in childhood: a national population-based e-cohort study.

AIMS/HYPOTHESIS: The aim of this study was to describe the characteristics and outcomes of pregnancies in a national cohort of teenage (<20 years) and young adult women (≥20 years) with and without childhood-onset (<15 years) type 1 diabetes. We hypothesised that, owing to poor glycaemic control during the teenage years, pregnancy outcomes would be poorer in teenage mothers with type 1 diabetes than young adult mothers with type 1 diabetes and mothers without diabetes. METHODS: The Brecon Register of childhood-onset type 1 diabetes diagnosed in Wales since 1995 was linked to population-based datasets in the Secure Anonymised Information Linkage (SAIL) Databank, creating an electronic cohort (e-cohort) of legal births (live or stillbirths beyond 24 weeks' gestation) to women aged less than 35 years between 1995 and 2013 in Wales. Teenage pregnancy rates were calculated based on the number of females in the same birth cohort in Wales. Pregnancy outcomes, including pre-eclampsia, preterm birth, low birthweight, macrosomia, congenital malformations, stillbirths and hospital admissions during the first year of life, were obtained from electronic records for the whole Welsh population. We used logistic and negative binomial regression to compare outcomes among teenage and young adult mothers with and without type 1 diabetes. RESULTS: A total of 197,796 births were eligible for inclusion, including 330 to girls and women with childhood-onset type 1 diabetes, of whom 68 were teenagers (age 14-19 years, mean 17.9 years) and 262 were young adults (age 20-32 years, mean 24.0 years). The mean duration of diabetes was 14.3 years (9.7 years for teenagers; 15.5 years for young adults). Pregnancy rates were lower in teenagers with type 1 diabetes than in teenagers without diabetes (mean annual teenage pregnancy rate between 1999 and 2013: 8.6 vs 18.0 per 1000 teenage girls, respectively; p < 0.001). In the background population, teenage pregnancy was associated with deprivation (p < 0.001), but this was not the case for individuals with type 1 diabetes (p = 0.85). Glycaemic control was poor in teenage and young adult mothers with type 1 diabetes (mean HbA1c based on closest value to conception: 81.3 and 80.2 mmol/mol [9.6% and 9.5%], respectively, p = 0.78). Glycaemic control improved during pregnancy in both groups but to a greater degree in young adults, who had significantly better glycaemic control than teenagers by the third trimester (mean HbA1c: 54.0 vs 67.4 mmol/mol [7.1% vs 8.3%], p = 0.01). All adverse outcomes were more common among mothers with type 1 diabetes than mothers without diabetes. Among those with type 1 diabetes, hospital admissions during the first year of life were more common among babies of teenage vs young adult mothers (adjusted OR 5.91 [95% CI 2.63, 13.25]). Other outcomes were no worse among teenage mothers with type 1 diabetes than among young adult mothers with diabetes. CONCLUSIONS/INTERPRETATION: Teenage girls with childhood-onset type 1 diabetes in Wales are less likely to have children than teenage girls without diabetes. Teenage pregnancy in girls with type 1 diabetes, unlike in the background population, is not associated with social deprivation. In our cohort, glycaemic control was poor in both teenage and young adult mothers with type 1 diabetes. Pregnancy outcomes were comparable between teenage and young adult mothers with type 1 diabetes, but hospital admissions during the first year of life were five times more common among babies of teenage mothers with type 1 diabetes than those of young adult mothers with diabetes.

Seasonal pattern of incidence and outcome of Acute Kidney Injury: A national study of Welsh AKI electronic alerts.

OBJECTIVES: To identify any seasonal variation in the occurrence of, and outcome following Acute Kidney Injury. METHODS: The study utilised the biochemistry based AKI electronic (e)-alert system established across the Welsh National Health Service to collect data on all AKI episodes to identify changes in incidence and outcome over one calendar year (1st October 2015 and the 30th September 2016). RESULTS: There were total of 48 457 incident AKI alerts. The highest proportion of AKI episodes was seen in the quarter of January to March (26.2%), and the lowest in the quarter of October to December (23.3%, P < .001). The same trend was seen for both community-acquired and hospital-acquired AKI sub-sets. Overall 90 day mortality for all AKI was 27.3%. In contrast with the seasonal trend in AKI occurrence, 90 day mortality after the incident AKI alert was significantly higher in the quarters of January to March and October to December compared with the quarters of April to June and July to September (P < .001) consistent with excess winter mortality reported for likely underlying diseases which precipitate AKI. CONCLUSIONS: In summary we report for the first time in a large national cohort, a seasonal variation in the incidence and outcomes of AKI. The results demonstrate distinct trends in the incidence and outcome of AKI.