Pre-existing diabetes mellitus (DM) is a challenging pregnancy complication as poor glycemic control is associated with adverse maternal and fetal outcomes. In this study, we aimed to investigate DM-related knowledge, attitudes, preconception care practices, and contraceptive prevalence in women with DM.This descriptive cross-sectional survey was conducted among reproductive-aged Thai women receiving DM treatment at King Chulalongkorn Memorial Hospital between August 1, 2021, and June 30, 2022. Patients with DM who were not pregnant or trying to conceive and could be contacted via the phone were included and a validated self-administered questionnaire was distributed electronically.A total of 238 participants were included in the final analysis, yielding 69.4% response rates. The mean (standard deviation) score for knowledge of pregnancy planning and pregnancy-related risks was 6.8 (3.5) out of 15. Only about half of the participants had discussed pregnancy planning with their physicians. Multivariable analysis showed that younger age at DM diagnosis, non-Buddhism, married, higher education, and medical personnel were significantly associated with higher knowledge scores. Women aged > 45 years and those with higher practice scores had significantly higher adjusted odds of using highly effective contraception; the most common methods included male condoms and combined oral contraceptive pills. There was an unmet need for contraception in 9.5% of women with DM.Although highly effective contraception is safe for patients with DM, only about half of our participants used tier one or two contraceptives or had received consultation regarding preconception planning. There was a notable gap in care coordination among specialists; integrating reproductive healthcare into DM therapy would improve access to preconception care.© 2023. BioMed Central Ltd., part of Springer Nature.

It has been known for decades that diabetic women have somewhat decreased fertility and that their offspring have an increased risk of being born with developmental abnormalities. We review results from studies examining the impact of maternal hyperglycemia and diabetes on oocyte and early embryo development. We focus on the effects of the maternal milieu on metabolism, cell signaling and the regulation of glucose-transporter expression in the developing oocyte and embryo.Offspring of diabetic mothers have metabolic disease at higher rates than can be explained by genetic inheritance alone. Oocytes from hyperglycemic animals display several abnormalities and are of lower quality than oocytes from control animals. There appears to be a decrease in glucose transport in embryos exposed to a hyperglycemic environment, which may lead to programmed cell death.Maternal hyperglycemia and diabetes have detrimental effects on the developing embryo at several stages of development. Although the exact pathophysiology of the developmental defects seen in infants born to diabetic mothers remains unclear, the role of glucose transport and regulation seems to play a critical role in early growth and development.

Reproductive abnormalities in women with a history of childhood diabetes are believed to be partially attributed to hyperglycemia. Prolonged hyperglycemia can negatively affect ovarian function and fertility during reproductive life. To address this in an experimental setting, the present study used streptozotocin-induced hyperglycemic prepubertal mouse model. The impact of prolonged hyperglycemic exposure during prepubertal life on ovarian function, oocyte quality, and functional competence was assessed in adult mice. The ovarian reserve was not significantly altered; however, the in vitro maturation potential (P < 0.001), mitochondrial integrity (P < 0.01), and meiotic spindle assembly (P < 0.05-0.001) in oocytes were significantly affected in hyperglycemic animals in comparison to control groups. The results from the study suggest that prepubertal hyperglycemia can have adverse effects on the oocyte functional competence and spindle integrity during the reproductive phase of life. Because these changes can have a significant impact on the genetic integrity and developmental potential of the embryos and fetus, the observation warrants further research both in experimental and clinical settings.

Metabolic stress conditions are often characterized by upregulated lipolysis and subsequently increased serum free fatty acid (FFA) concentrations, leading to the uptake of FFAs by non-adipose tissues and impairment of their function. This phenomenon is known as lipotoxicity. The increased serum FFA concentrations are reflected in the ovarian follicular fluid, which can have harmful effects on oocyte development. Several studies using in vitro and in vivo mammalian models showed that altered oocyte metabolism, increased oxidative stress, and mitochondrial dysfunction are crucial mechanisms underlying this detrimental impact. Ultimately, this can impair offspring health through the persistence of defective mitochondria in the embryo, hampering epigenetic reprogramming and early development. In vitro and in vivo treatments to enhance oocyte mitochondrial function are increasingly being developed. This can help to improve pregnancy rates and safeguard offspring health in metabolically compromised individuals.

Postovulatory aging oocytes usually feature diminished potential for fertilization and poor embryonic development due to enhanced oxidative damage to the subcellular organelles and macromolecules, which stands as a formidable obstacle in assisted reproductive technologies (ART). Here, we developed lipoic acid (LA) and polyethylene glycol (PEG)-modified CeO nanoparticles (LA-PEG-CeNPs) with biocompatibility, enzyme-like autocatalytic activity, and free radical scavenging capacity. We further investigated the LA-PEG-CeNPs effect in mouse postovulatory oocytes during in vitro aging. The results showed that LA-PEG-CeNPs dramatically reduced the accumulation of ROS in aging oocytes, improving mitochondrial dysfunction; they also down-regulated the pro-apoptotic activity by rectifying cellular caspase-3, cleaved caspase-3, and Bcl-2 levels. Consistently, this nanoenzyme prominently alleviated the proportion of abnormalities in spindle structure, chromosome alignment, microtubule stability, and filamentous actin (F-actin) distribution in aging oocytes, furthermore decreased oocyte fragmentation, and improved its ability of fertilization and development to blastocyst. Taken together, our finding suggests that LA-PEG-CeNPs can alleviate oxidative stress damage on oocyte quality during postovulatory aging, implying their potential value for clinical practice in assisted reproduction.

Diabetes-induced hyperglycemia has a direct damaging effect on ovarian function. Despite its deadly impact on ovaries, the mechanism of this condition has not been fully elucidated. Glucose transporters are involved in glucose uptake and utilization. Many transporters have been detected in the ovaries, but their roles in diabetes-induced ovarian impairment are still unclear. In this study, the goal is to analyze glucose transporter expression in the ovarian follicles of type 1 diabetes mellitus patients and determine their roles within ovarian function impairment. The ovarian function of a mouse model of type 1 diabetes mellitus was evaluated by observing its estrus cycle, follicular development, and ovulation. Subtypes of the glucose transporter (GLUT2, GLUT3, GLUT4, SGLT1, and SGLT2), adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK (Thr172) were found to be simultaneously present in follicle cells. Compared with nondiabetic control mice, the diabetic mice showed a dysregulated estrus cycle and a significantly higher number of abnormal ova. Furthermore, the expression of multiple glucose transporters was lower than that of phosphorylated AMPK. Phosphorylated AMPK possessed more follicular granulosa cells and oocytes of diabetic mice than in those of the control mice. These results suggest that diabetes-induced hyperglycemia reduces the capability of ovarian follicle cells by downregulating glucose transporter expression, causing decreased glucose uptake and energy deprivation. This impact can potentially impair egg maturation and ovulation.© 2019 by the Association of Clinical Scientists, Inc.

Maternal type 1 diabetes (T1D) has been linked to preterm birth and other adverse pregnancy outcomes. How these risks vary with glycated hemoglobin (or hemoglobin A1c [HbA1c]) levels is unclear.To examine preterm birth risk according to periconceptional HbA1c levels in women with T1D.Population-based cohort study.Sweden, 2003 to 2014.2474 singletons born to women with T1D and 1 165 216 reference infants born to women without diabetes.Risk for preterm birth (<37 gestational weeks). Secondary outcomes were neonatal death, large for gestational age, macrosomia, infant birth injury, hypoglycemia, respiratory distress, 5-minute Apgar score less than 7, and stillbirth.Preterm birth occurred in 552 (22.3%) of 2474 infants born to mothers with T1D versus 54 287 (4.7%) in 1 165 216 infants born to mothers without diabetes. The incidence of preterm birth was 13.2% in women with a periconceptional HbA1c level below 6.5% (adjusted risk ratio [aRR] vs. women without T1D, 2.83 [95% CI, 2.28 to 3.52]), 20.6% in those with a level from 6.5% to less than 7.8% (aRR, 4.22 [CI, 3.74 to 4.75]), 28.3% in those with a level from 7.8% to less than 9.1% (aRR, 5.56 [CI, 4.84 to 6.38]), and 37.5% in those with a level of 9.1% or higher (aRR, 6.91 [CI, 5.85 to 8.17]). The corresponding aRRs for medically indicated preterm birth (n = 320) were 5.26 (CI, 3.83 to 7.22), 7.42 (CI, 6.21 to 8.86), 11.75 (CI, 9.72 to 14.20), and 17.51 (CI, 14.14 to 21.69), respectively. The corresponding aRRs for spontaneous preterm birth (n = 223) were 1.81 (CI, 1.31 to 2.52), 2.86 (CI, 2.38 to 3.44), 2.88 (CI, 2.23 to 3.71), and 2.80 (CI, 1.94 to 4.03), respectively. Increasing HbA1c levels were associated with the study's secondary outcomes: large for gestational age, hypoglycemia, respiratory distress, low Apgar score, neonatal death, and stillbirth.Because HbA1c levels were registered annually at routine visits, they were not available for all pregnant women with T1D.The risk for preterm birth was strongly linked to periconceptional HbA1c levels. Women with HbA1c levels consistent with recommended target levels also were at increased risk.Swedish Diabetes Foundation.

Offspring of diabetic mothers are susceptible to developing type 2 diabetes due to pancreatic islet dysfunction. However, the initiating molecular pathways leading to offspring pancreatic islet dysfunction are unknown. We hypothesized that maternal hyperglycemia alters offspring pancreatic islet transcriptome and negatively impacts offspring islet function. We employed an infusion model capable of inducing localized hyperglycemia in fetal rats residing in the left uterine horn, thus avoiding other factors involved in programming offspring pancreatic islet health. While maintaining euglycemia in maternal dams and right uterine horn control fetuses, hyperglycemic fetuses in the left uterine horn had higher serum insulin and pancreatic beta cell area. Upon completing infusion from GD20 to 22, RNA sequencing was performed on GD22 islets to identify the hyperglycemia-induced altered gene expression. Ingenuity pathway analysis of the altered transcriptome found that diabetes mellitus and inflammation/cell death pathways were enriched. Interestingly, the downregulated genes modulate more diverse biological processes, which includes responses to stimuli and developmental processes. Next, we performed ex and in vivo studies to evaluate islet cell viability and insulin secretory function in weanling and adult offspring. Pancreatic islets of weanlings exposed to late gestation hyperglycemia had decreased cell viability in basal state and glucose-induced insulin secretion. Lastly, adult offspring exposed to in utero hyperglycemia also exhibited glucose intolerance and insulin secretory dysfunction. Together, our results demonstrate that late gestational hyperglycemia alters the fetal pancreatic islet transcriptome and increases offspring susceptibility to developing pancreatic islet dysfunction.

We sought to determine the absolute risk of having a congenital anomaly in relation to periconceptional GHb concentration among women with prepregnancy diabetes.Two reviewers independently retrieved all cohort studies through a systematic literature search between January 1985 and May 2006. For each study, the absolute risk of having a pregnancy affected by a major or minor structural anomaly (diagnosed either antenatally or up to 28 days after conception) was calculated according to the number of SDs of GHb above the mean for nondiabetic, nonpregnant control subjects. A multilevel logistic-normal model was used to pool the data, which were expressed in tabular and graphic formats.In seven cohort studies, there were 117 anomalies among 1,977 pregnancies. At a periconceptional GHb concentration 0 SD above normal, the absolute risk of a pregnancy affected by a congenital anomaly was approximately 2% (95% CI 0.0-4.4). At 2 SD above normal, the risk was 3% (0.4-6.1), and at 8 SD it was approximately 10% (2.3-17.8). For each 1-SD unit increase in GHb, the associated risk of a congenital malformation increased by an odds ratio of 1.2 (95% CI 1.1-1.4). The risk in relation to A1C followed the same pattern.Using data from a limited number of published studies, a practical aid was developed to optimize use of the GHb and A1C concentrations for estimating the absolute risk of a congenital anomaly in the offspring of women with prepregnancy diabetes.

To study the association between peri-conceptional A1C and serious adverse pregnancy outcome (congenital malformations and perinatal mortality).Prospective data were collected in 933 singleton pregnancies complicated by type 1 diabetes.The risk of serious adverse outcome at different A1C levels was compared with the background population. The risk was significantly higher when peri-conceptional A1C exceeded 6.9%, and the risk tended to increase gradually with increasing A1C. Women with A1C exceeding 10.4% had a very high risk of 16%. Congenital malformation rate increased significantly at A1C above 10.4%, whereas perinatal mortality was increased even at A1C below 6.9%.These results support recent guidelines of preconceptional A1C levels <7% in women with type 1 diabetes.

To assess the association between first-trimester HbA(1c) (A1C) and the risk of adverse pregnancy outcomes in type 1 diabetic pregnancies.We identified all pregnant diabetic women in a Danish county from 1985 to 2003. A1C values from first trimester were collected, and pregnancy outcome was dichotomized as good (i.e., babies surviving the 1st month of life without major congenital abnormalities) and adverse (i.e., spontaneous and therapeutic abortion, stillbirth, neonatal death, or major congenital abnormalities detected within the 1st month). The prevalence of adverse outcomes was calculated according to quintiles of A1C. We computed receiver operating characteristic and lowess curve estimates and fitted logistic regression models to calculate prevalence odds ratio while adjusting for confounding by White class and smoking status.Of 573 pregnancies, 165 (29%) terminated with adverse outcomes. The prevalence of adverse outcomes varied sixfold from 12% (95% CI 7.2-17) in the lowest to 79% (60-91) in the highest quintile of A1C exposure. From A1C levels >7%, we found an almost linear association between A1C and risk of adverse outcome, whereby a 1% increase in A1C corresponded to 5.5% (3.8-7.3) increased risk of adverse outcome.Starting from a first-trimester A1C level slightly <7%, there is a dose-dependent association between A1C and the risk of adverse pregnancy outcome without indication of a plateau, below which the association no longer exits. A1C, however, seems to be of limited value in predicting outcome in the individual pregnancy.

Reduced oxygen during embryo culture in human ART prevents embryo oxidative stress. Oxidative stress is also the major mechanism by which maternal diabetes impairs embryonic development. This study employed induced hyperglycemia prepubertal mice to mimic childhood diabetes to understand the effects of varying oxygen tension during in vitro embryonic development. The oocytes were fertilized and cultured at low (≈5%) oxygen (LOT) or atmospheric (≈20%) oxygen tension (HOT) for up to 96 h. Embryo development, apoptosis in blastocysts, inner cell mass (ICM) outgrowth proliferation, and Hif1α expression were assessed. Though the oocyte quality and meiotic spindle were not affected, the fertilization rate (94.86 ± 1.18 vs. 85.17 ± 2.81), blastocyst rate (80.92 ± 2.92 vs. 69.32 ± 2.54), and ICM proliferation ability (51.04 ± 9.22 vs. 17.08 ± 3.05) of the hyperglycemic embryos were significantly higher in the LOT compared to the HOT group. On the other hand, blastocysts from the hyperglycemic group, cultured at HOT, had a 1.5-fold increase in apoptotic cells compared to the control and lower Hif1α transcripts in ICM outgrowths compared to the LOT. Increased susceptibility of embryos from hyperglycemic mice to higher oxygen tension warrants the need to individualize the conditions for embryo culture systems in ART clinics, particularly when an endogenous maternal pathology affects the ovarian environment.

Maternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.© 2024. The Author(s).

To assess the relationship between second and third trimester glycemic control and adverse outcomes in pregnant women with type 1 diabetes, as uncertainty exists about optimum glycemic targets.Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26 and 34 weeks' gestation were categorized into five groups, the lowest, <6.0% (42 mmol/mol), being the reference. Average pre- and postprandial results from an eight-point capillary glucose profile the previous day were categorized into five groups, the lowest (preprandial <5.0 mmol/L and postprandial <6.0 mmol/L) being the reference.An A1C of 6.0-6.4% (42-47 mmol/mol) at 26 weeks' gestation was associated with a significantly increased risk of large for gestational age (LGA) (odds ratio 1.7 [95% CI 1.0-3.0]) and an A1C of 6.5-6.9% (48-52 mmol/mol) with a significantly increased risk of preterm delivery (odds ratio 2.5 [95% CI 1.3-4.8]), pre-eclampsia (4.3 [1.7-10.8]), need for a neonatal glucose infusion (2.9 [1.5-5.6]), and a composite adverse outcome (3.2 [1.3-8.0]). These risks increased progressively with increasing A1C. Results were similar at 34 weeks' gestation. Glucose data showed less consistent trends, although the risk of a composite adverse outcome increased with preprandial glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3-8.0]).LGA increased significantly with an A1C ≥6.0 (42 mmol/mol) at 26 and 34 weeks' gestation and with other adverse outcomes with an A1C ≥6.5% (48 mmol/mol). The data suggest that there is clinical utility in regular measurement of A1C during pregnancy.© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

To implement and evaluate a regional prepregnancy care program in women with type 1 and type 2 diabetes.Prepregnancy care was promoted among patients and health professionals and delivered across 10 regional maternity units. A prospective cohort study of 680 pregnancies in women with type 1 and type 2 diabetes was performed. Primary outcomes were adverse pregnancy outcome (congenital malformation, stillbirth, or neonatal death), congenital malformation, and indicators of pregnancy preparation (5 mg folic acid, gestational age, and A1C). Comparisons were made with a historical cohort (n = 613 pregnancies) from the same units during 1999-2004.A total of 181 (27%) women attended, and 499 women (73%) did not attend prepregnancy care. Women with prepregnancy care presented earlier (6.7 vs. 7.7 weeks; P < 0.001), were more likely to take 5 mg preconception folic acid (88.2 vs. 26.7%; P < 0.0001) and had lower A1C levels (A1C 6.9 vs. 7.6%; P < 0.0001). They had fewer adverse pregnancy outcomes (1.3 vs. 7.8%; P = 0.009). Multivariate logistic regression confirmed that in addition to glycemic control, lack of prepregnancy care was independently associated with adverse outcome (odds ratio 0.2 [95% CI 0.05-0.89]; P = 0.03). Compared with 1999-2004, folic acid supplementation increased (40.7 vs. 32.5%; P = 0.006) and congenital malformations decreased (4.3 vs. 7.3%; P = 0.04).Regional prepregnancy care was associated with improved pregnancy preparation and reduced risk of adverse pregnancy outcome in type 1 and type 2 diabetes. Prepregnancy care had benefits beyond improved glycemic control and was a stronger predictor of pregnancy outcome than maternal obesity, ethnicity, or social disadvantage.

The rise in the global prevalence of diabetes, particularly among younger people, has led to an increase in the number of pregnant women with preexisting diabetes, many of whom have diabetes-related microvascular complications. We aimed to estimate the magnitude of the risks of adverse pregnancy outcomes or disease progression in this population.

Diabetic retinopathy (DR) may be worsened by pregnancy in pregnant women with preexisting type 1 diabetes (T1D) or type 2 diabetes (T2D). Conflicting findings from previous studies have resulted in inconsistencies in guidelines regarding DR management in pregnancy. Global estimates of DR prevalence and progression in pregnancy are therefore required to provide clearer information about the overall true burden of DR in this population.To estimate the prevalence of DR and its progression rate in pregnant women with preexisting T1D or T2D diagnosed before pregnancy.For this systematic review and meta-analysis, conducted from November 27, 2018, to June 29, 2021, a systematic literature search was conducted in MEDLINE/Ovid, Embase/Ovid, and Scopus databases to identify English-language articles that were published from inception through October 2020.Observational studies that reported on DR and its changes in pregnant women with preexisting T1D and T2D.Two independent reviewers extracted relevant data from each included study. Data were pooled using a random-effects model with the Freeman-Tukey double arcsine transformation. This study followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines.Prevalence of any DR, proliferative DR (PDR), and DR progression rates.A total of 18 observational studies involving 1464 pregnant women with T1D and 262 pregnant women with T2D were included in the analysis. The pooled prevalence of any DR and PDR in early pregnancy was 52.3 (95% CI, 41.9-62.6) and 6.1 (95% CI, 3.1-9.8) per 100 pregnancies, respectively. The pooled progression rate per 100 pregnancies for new DR development was 15.0 (95% CI, 9.9-20.8), worsened nonproliferative DR was 31.0 (95% CI, 23.2-39.2), progression from nonproliferative DR to PDR was 6.3 (95% CI, 3.3-10.0), and worsened PDR was 37.0 (95% CI, 21.2-54.0). DR progression rates per 100 pregnancies were similar between the T1D and T2D groups, except for the development of new DR (T1D groups: 15.8; 95% CI, 10.5-21.9; T2D groups: 9.0; 95% CI, 4.9-14.8). A global trend toward a lower DR progression rate was observed after the 1989 St Vincent Declaration.Results of this systematic review and meta-analysis suggest that women with T1D and T2D had a similar risk of DR progression during pregnancy. Despite improvements in the management of diabetes and diabetes during pregnancy, DR prevalence and progression in pregnant women with diabetes remains higher than the nonpregnant population with diabetes, highlighting the need to improve DR management in pregnancy.

Background Diets of the highest quality have been associated with a significantly lower risk of noncommunicable diseases.Objective It was the aim of this study to update a previous systematic review investigating the associations of diet quality as assessed by the Healthy Eating Index (HEI), Alternate Healthy Eating Index (AHEI), and Dietary Approaches to Stop Hypertension (DASH) score and multiple health outcomes. As an additional topic, the associations of these diet quality indices with all-cause mortality and cancer mortality among cancer survivors were also investigated.Design A literature search for prospective cohort studies that were published up to May 15, 2017 was performed using the electronic databases PubMed, Scopus, and Embase. Summary risk ratios (RRs) and 95% CIs were estimated using a random effects model for high vs low adherence categories.Results The updated review process showed 34 new reports (total number of reports evaluated = 68; including 1,670,179 participants). Diets of the highest quality, as assessed by the HEI, AHEI, and DASH score, resulted in a significant risk reduction for all-cause mortality (RR 0.78, 95% CI 0.77 to 0.80; I-2 = 59%; n = 13), cardiovascular disease (incidence or mortality) (RR 0.78, 95% CI 0.76 to 0.80; I-2 = 49%; n = 28), cancer (incidence or mortality) (RR 0.84, 95% CI 0.82 to 0.87; I-2 = 66%; n = 31), type 2 diabetes (RR 0.82, 95% CI 0.78 to 0.85; I-2 = 72%; n = 10), and neurodegenerative diseases (RR 0.85, 95% CI 0.74 to 0.98; I-2 = 51%; n = 5). Among cancer survivors, the association between diets for the highest quality resulted in a significant reduction in all-cause mortality (RR 0.88, 95% CI 0.81 to 0.95; I-2 = 38%; n = 7) and cancer mortality (RR 0.90, 95% CI 0.83 to 0.98; I-2 = 0%; n = 7).Conclusions In the updated meta-analyses, diets that score highly on the HEI, AHEI, and DASH were associated with a significant reduction in the risk of all-cause mortality, cardiovascular disease, cancer, type 2 diabetes, and neurodegenerative disease by 22%, 22%, 16%, 18%, and 15%, respectively. Moreover, high-quality diets were inversely associated with overall mortality and cancer mortality among cancer survivors.

Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes.To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome.This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022.Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery.The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy.Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group.Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation.ClinicalTrials.gov Identifier: NCT02932475.

The fetotoxic potential of prenatal exposure to angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) has been known for many years. Symptoms range from transient oligohydramnios to neonatal anuria and permanent renal damage, joint contractures, hypocalvaria, lung hypoplasia and intrauterine or neonatal death. This study aims to investigate the critical gestational time for renin-angiotensin system inhibitor (RAS-I)-induced fetopathy, to quantify the fetopathy risk and to evaluate factors associated with the occurrence and severity of fetopathy.Prospectively and retrospectively ascertained RAS-I exposed pregnancies from the databases of six teratology information services were analyzed.Eighty-nine pregnancies with ACE-I and 101 with ARB exposure beyond the first trimester were identified. Fifty-nine of these 190 pregnancies were classified as having evidence of RAS-I fetopathy. All pregnancies affected with fetopathy were exposed after 20 0/7 gestational weeks. Limited to prospectively enrolled cases with exposure at least 20 0/7 gestational weeks, the rate of fetopathy was 3.2% for ACE-I and 29.2% for ARB. The chance of recovery of amniotic fluid volume was higher with RAS-I discontinuation before 30 gestational weeks and with a longer exposure-free interval before delivery.Exposure to ARBs is associated with a higher fetopathy risk than exposure to ACE-Is. RAS-I should ideally be discontinued prior to pregnancy or immediately after recognition of pregnancy. Because symptoms may improve in cases of RAS-I-induced oligohydramnios, pregnancy should be maintained as long as there is fetal well being. Physicians and patients need to be alerted to the fetotoxic risks of RAS-I.

This study was undertaken to determine the frequencies of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes.This was a prospective observation of pregnancy outcomes among 462 women with pregestational diabetes mellitus (White classes B-F) and singleton pregnancies who were enrolled in a multicenter trial to compare low-dose aspirin with placebo for preeclampsia prevention. The main outcome measures were preeclampsia and neonatal outcomes.Among 462 women with pregestational diabetes, 92 (20%) had preeclampsia. Preeclampsia frequency rose significantly with increasing severity of diabetes according to White classification (class B, 11%; class C, 22%; class D, 21%; class R plus class F, 36%; P <.0001). Preeclampsia was also more common among women who had proteinuria at baseline (28% vs 18%; odds ratio, 1.75; 95% confidence interval, 1.02-3.01). Frequency of preterm delivery at <35 weeks' gestation rose greatly with increasing severity of diabetes (P =.0002). Women with proteinuria at baseline were significantly more likely to be delivered at <35 weeks' gestation (29% vs 13%; odds ratio, 2.6; 95% confidence interval, 1.5-4.6) and to have small-for-gestational-age infants (14% vs 3%; odds ratio, 5. 4; 95% confidence interval, 2.7-17.7), and they were less likely to have large-for-gestational-age infants (14% vs 40%; odds ratio, 0.2; 95% confidence interval, 0.1-0.5).Among women with pregestational diabetes mellitus, the frequency of preeclampsia rose with increasing severity of diabetes. Proteinuria early in pregnancy was associated with marked increases in adverse neonatal outcomes independent of preeclampsia development.