Association of spontaneous abortion and lifestyle with diabetes mellitus in women: a cross-sectional study in UK Biobank.

Spontaneous abortion has been associated with higher risk of type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM), while the evidence remains equivocal. This study aimed to examine the association between spontaneous abortion and the risk of T2DM and GDM, and assesses whether lifestyle factors modified this association. This cross-sectional study used data from the UK Biobank, recruiting 170 599 ever-pregnant women from 22 assessment centers in England, Scotland, and Wales between 2006 and 2010. History of spontaneous abortion was self-reported and was confirmed by using medical records, categorized as none, 1, 2, or ≥3 spontaneous abortions. The primary outcomes, T2DM and GDM, were ascertained from medical records using ICD-10 codes. Multivariable logistic regression was performed to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for sociodemographic and health factors (e.g., age, ethnicity, cancer, chronic hypertension), reproductive factors (e.g., use of oral contraceptives, use of hormone treatment, hypertensive disorders of pregnancy), and lifestyle score. The lifestyle score was constructed based on smoking status, alcohol intake, physical activity, television viewing time, sleep duration, and diet quality. Effect modification by lifestyle score was assessed using multiplicative interaction terms in the regression models. Among 170 599 ever-pregnant women (mean [SD] age, 56.4 [8.0] years), a history of spontaneous abortion was associated with higher odds of T2DM (OR 1.17, 95% CI 1.10-1.24) and GDM (OR 1.38, 95% CI 1.20-1.60). The odds were higher for recurrent spontaneous abortions (for T2DM: ORs were 1.33 [95% CI 1.14-1.56] for three or more spontaneous abortions, 1.07 [95% CI 0.93-1.23] for two, and 1.09 [95% CI 1.01-1.17] for one compared with none; for GDM: the corresponding ORs were 2.01 [95% CI 1.48-2.71], 1.21 [95% CI 0.90-1.64], and 1.20 [95% CI 1.01-1.42], respectively). The odds of T2DM and GDM higher with less healthy lifestyle behaviors in both categories of spontaneous abortion, although no significant interactions between spontaneous abortion and lifestyle score were observed (P-interaction>0.05). Spontaneous abortion was associated with higher odds of T2DM and GDM, with a stronger association observed in women who experienced recurrent spontaneous abortions. It is imperative to integrate reproductive history into routine diabetes risk assessment, particularly for women with a history of multiple spontaneous abortions.

Liu S ，Chen Y ，Zhang A ，Chen X ，Yuan L ，Song B ... -  《BMC Pregnancy and Childbirth》

Dietary supplementation with myo-inositol in women during pregnancy for treating gestational diabetes.

Brown J ，Crawford TJ ，Alsweiler J ，Crowther CA ... -  《Cochrane Database of Systematic Reviews》

Antioxidants for female subfertility.

M.G. Showell, R. Mackenzie‐Proctor, V. Jordan, and R.J. Hart, “Antioxidants for Female Subfertility,” Cochrane Database of Systematic Reviews, no. 8 (2020): CD007807, https://doi.org/10.1002/14651858.CD007807.pub4 This Editorial Note is for the above article, published online on August 27, 2020, in Cochrane Library (cochranelibrary.com), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with Cochrane. The Editorial note has been agreed due to concerns discovered by the Cochrane managing editor regarding the retraction of six studies in the Review (Badawy et al. 2006, 10.1016/j.fertnstert.2006.02.097; El Refaeey et al. 2014, 10.1016/j.rbmo.2014.03.011; El Sharkwy & Abd El Aziz 2019a, https://doi.org/10.1002/ijgo.12902; Gerli et al. 2007, https://doi.org/10.26355/eurrev_202309_33752, full text: https://europepmc.org/article/MED/18074942; Ismail et al. 2014, http://dx.doi.org/10.1016/j.ejogrb.2014.06.008; Hashemi et al. 2017, https://doi.org/10.1080/14767058.2017.1372413). In addition, expressions of concern have been published for two studies (Jamilian et al. 2018, https://doi.org/10.1007/s12011-017-1236-3; Zadeh Modarres 2018, https://doi.org/10.1007/s12011-017-1148-2). The retracted studies will be moved to the Excluded Studies table, and their impact on the review findings will be investigated and acted on accordingly in a future update. Initial checks indicate that removal of the six retracted studies did not make an appreciable difference to the results. Likewise, the studies for which Expressions of Concern were issued will be moved to the Awaiting classification table; they did not report any review outcomes, so removal will have no impact on the review findings. A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. We searched the following databases (from their inception to September 2019), with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers. We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We included 63 trials involving 7760 women. Investigators compared oral antioxidants, including: combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I2 = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I2 = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I2 = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I2 = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I2 = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I2 = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. In this review, there was low- to very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.

Showell MG ，Mackenzie-Proctor R ，Jordan V ，Hart RJ ... -  《Cochrane Database of Systematic Reviews》

Antioxidants for female subfertility.

Showell MG ，Mackenzie-Proctor R ，Jordan V ，Hart RJ ... -  《Cochrane Database of Systematic Reviews》

Unhealthful plant-based diet associates with frailty risk predominantly in men with low income from the UK Biobank cohort.

Plant-based diets (PBD) are generally promoted as beneficial for health. However, whether this is also the case at older ages, when energy deficits, muscle loss and frailty affect health, is unclear. Research has shown that among older adults, particularly in men, a healthful PBD is associated with a lower frailty risk. This relation was however, not studied in the context of socio-economic status (SES), a major factor influencing the risk of frailty. Therefore, we aim to assess whether plant-based diets associate with frailty risk at older ages and whether this association is moderated by sex and income in a large population-based dataset. We investigated baseline data from the UK Biobank cohort study (UKB) cross-sectionally (n = 73 180, mean age = 55.48 ± 7.87). We applied a plant-based diet index [range 17-85], differentiating between a healthful (hPDI) and unhealthful plant-based diet (uPDI). Frailty was assessed by the Fried frailty phenotype and categorized into 0-4 symptoms of frailty. Average annual household income was divided into three categories: low (<18.000 £), medium (18.000-52.000 £) and high (>52.000 £). We applied an ordinal logistic regression model with frailty as the categorical outcome and PDI as continuous predictor while adjusting for age, sex, ethnicity, education, BMI and UKB assessment center. Secondly, we included an interaction term (PDI*sex*income). To identify subgroups driving any interactions, we stratified by sex and subsequently by income group to determine the effect of PDI in subgroups while additionally adjusting for lifestyle factors. A 10-unit increase in hPDI was associated with 3.4% lower odds for frailty (OR = 0.966, 95%CI [0.946, 0.987]), whereas a 10-unit increase in uPDI was associated with 7.7% greater odds for frailty (OR = 1.077, 95%CI [1.054, 1.101]). The association between uPDI and frailty was moderated by income and sex (uPDI*income*sex, p = 0.002), whereas no such moderation was found for hPDI (p = 0.602). Subsequent stratification reveals a significant effect of uPDI on frailty particularly among men with low income (OR = 1.177, 95% CI [1.069, 1.298]), but not for women. This association in men largely persisted after adjustment for additional lifestyle factors (OR = 1.119, 95%CI [0.995, 1.258]). We observed that adherence to an unhealthful plant-based diet was associated with a higher risk for frailty. This relation was especially observed for men with lower incomes and not explained by other lifestyle factors. While future research may investigate more specific determinants of health and diet behavior in men of low household income, this group in particular may profit from diet intervention improving diet quality.

Schorr K ，Rodriguez-Girondo M ，den Berg NV ，de Groot LC ，Slagboom PE ，Beekman M ... -  《-》