Comparative effectiveness trial of metformin versus insulin for the treatment of gestational diabetes in the USA: clinical trial protocol for the multicentre DECIDE study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use. METHODS AND ANALYSIS: In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org. ETHICS AND DISSEMINATION: The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT06445946.

Diabetic Ketoacidosis and Adverse Outcomes Among Pregnant Individuals With Pregestational Diabetes in the United States, 2010-2020.

OBJECTIVE: To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA. METHODS: We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations. RESULTS: Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, -1.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n=485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n=285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations. CONCLUSION: The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods.

Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) - a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health.

PURPOSE: Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health. PARTICIPANTS: Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at <15 weeks of gestation from Boston, Massachusetts area hospitals. Participants completed ≤4 prenatal study visits (median: 12, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks), during which we collected biospecimens, health histories, demographic and behavioural data, and vitals and anthropometric measurements. Participants completed a postpartum fasting 2-hour 75 g oral glucose tolerance test. Clinical data were abstracted from electronic medical records. Ongoing (as of 2024) extended post-pregnancy follow-up visits occur annually following similar data collection protocols. FINDINGS TO DATE: We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight. FUTURE PLANS: Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study.

Risk of Neonatal Hypoglycemia in Infants of Mothers With Gestational Glucose Intolerance.

OBJECTIVE: To examine the relationship between gestational glucose intolerance (GGI) and neonatal hypoglycemia. RESEARCH DESIGN AND METHODS: This was a secondary analysis of 8,262 mother-infant dyads, with delivery at two hospitals between 2014 and 2023. We categorized maternal glycemic status as normal glucose tolerance (NGT), GGI, or gestational diabetes mellitus (GDM). We defined NGT according to a normal glucose load test result, GGI according to an abnormal glucose load test result with zero (GGI-0) or one (GGI-1) abnormal value on the 100-g oral glucose tolerance test, and GDM according to an abnormal glucose load test result with two or more abnormal values on the glucose tolerance test. Neonatal hypoglycemia was defined according to blood glucose <45 mg/dL or ICD-9 or ICD-10 diagnosis of neonatal hypoglycemia. We used logistic regression analysis to determine associations between maternal glucose tolerance category and neonatal hypoglycemia and conducted a sensitivity analysis using Δ-adjusted multiple imputation, assuming for unscreened infants a rate of neonatal hypoglycemia as high as 33%. RESULTS: Of infants, 12% had neonatal hypoglycemia. In adjusted models, infants born to mothers with GGI-0 had 1.28 (95% 1.12, 1.65), GGI-1 1.58 (95% CI 1.11, 2.25), and GDM 4.90 (95% CI 3.81, 6.29) times higher odds of neonatal hypoglycemia in comparison with infants born to mothers with NGT. Associations in sensitivity analyses were consistent with the primary analysis. CONCLUSIONS: GGI is associated with increased risk of neonatal hypoglycemia. Future research should include examination of these associations in a cohort with more complete neonatal blood glucose ascertainment and determination of the clinical significance of these findings on long-term child health.

Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes.

Reduced insulin sensitivity (insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM). We conducted transcriptomic profiling of 434 human placentas and identified a positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~26 weeks gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which, together with high gene expression levels in our placenta samples, suggests a placental or decidual source. Higher circulating IGFBP1 levels were associated with greater insulin sensitivity (lesser insulin resistance) at ~26 weeks gestation in the same cohort and in two additional pregnancy cohorts. In addition, low circulating IGFBP1 levels in early pregnancy predicted subsequent GDM diagnosis in two cohorts of pregnant women. These results implicate IGFBP1 in the glycemic physiology of pregnancy and suggest a role for placental IGFBP1 deficiency in GDM pathogenesis.

The simultaneous occurrence of gestational diabetes and hypertensive disorders of pregnancy affects fetal growth and neonatal morbidity.

BACKGROUND: Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present. OBJECTIVE: We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy. STUDY DESIGN: In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission). RESULTS: The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy compared with unaffected pregnancies (adjusted odds ratio, 0.72 [95% confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001). CONCLUSION: Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity.

Metabolomic and genetic architecture of gestational diabetes subtypes.

AIMS/HYPOTHESIS: Physiological gestational diabetes mellitus (GDM) subtypes that may confer different risks for adverse pregnancy outcomes have been defined. The aim of this study was to characterise the metabolome and genetic architecture of GDM subtypes to address the hypothesis that they differ between GDM subtypes. METHODS: This was a cross-sectional study of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study who underwent an OGTT at approximately 28 weeks' gestation. GDM was defined retrospectively using International Association of Diabetes and Pregnancy Study Groups/WHO criteria, and classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity) or insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion). Metabolomic analyses were performed on fasting and 1 h serum samples in 3463 individuals (576 with GDM). Genome-wide genotype data were obtained for 8067 individuals (1323 with GDM). RESULTS: Regression analyses demonstrated striking differences between the metabolomes for insulin-deficient or insulin-resistant GDM compared to those with normal glucose tolerance. After adjustment for covariates, 33 fasting metabolites, including 22 medium- and long-chain acylcarnitines, were uniquely associated with insulin-deficient GDM; 23 metabolites, including the branched-chain amino acids and their metabolites, were uniquely associated with insulin-resistant GDM; two metabolites (glycerol and 2-hydroxybutyrate) were associated with the same direction of association with both subtypes. Subtype differences were also observed 1 h after a glucose load. In genome-wide association studies, variants within MTNR1B (rs10830963, p=3.43×10-18, OR 1.55) and GCKR (rs1260326, p=5.17×10-13, OR 1.43) were associated with GDM. Variants in GCKR (rs1260326, p=1.36×10-13, OR 1.60) and MTNR1B (rs10830963, p=1.22×10-9, OR 1.49) demonstrated genome-wide significant association with insulin-resistant GDM; there were no significant associations with insulin-deficient GDM. The lead SNP in GCKR, rs1260326, was associated with the levels of eight of the 25 fasting metabolites that were associated with insulin-resistant GDM and ten of 41 1 h metabolites that were associated with insulin-resistant GDM. CONCLUSIONS/INTERPRETATION: This study demonstrates that physiological GDM subtypes differ in their metabolome and genetic architecture. These findings require replication in additional cohorts, but suggest that these differences may contribute to subtype-related adverse pregnancy outcomes.

Estimating Glycemia From HbA1c and CGM: Analysis of Accuracy and Sources of Discrepancy.

OBJECTIVE: To examine the accuracy of different periods of continuous glucose monitoring (CGM), hemoglobin A1c (HbA1c), and their combination for estimating mean glycemia over 90 days (AG90). RESEARCH DESIGN AND METHODS: We retrospectively studied 985 CGM periods of 90 days with <10% missing data from 315 adults (86% of whom had type 1 diabetes) with paired HbA1c measurements. The impact of mean red blood cell age as a proxy for nonglycemic effects on HbA1c was estimated using published theoretical models and in comparison with empirical data. Given the lack of a gold standard measurement for AG90, we applied correction methods to generate a reference (eAG90) that we used to assess accuracy for HbA1c and CGM. RESULTS: Using 14 days of CGM at the end of the 90-day period resulted in a mean absolute error (95th percentile) of 14 (34) mg/dL when compared with eAG90. Nonglycemic effects on HbA1c led to a mean absolute error for average glucose calculated from HbA1c of 12 (29) mg/dL. Combining 14 days of CGM with HbA1c reduced the error to 10 (26) mg/dL. Mismatches between CGM and HbA1c >40 mg/dL occurred more than 5% of the time. CONCLUSIONS: The accuracy of estimates of eAG90 from limited periods of CGM can be improved by averaging with an HbA1c-based estimate or extending the monitoring period beyond ∼26 days. Large mismatches between eAG90 estimated from CGM and HbA1c are not unusual and may persist due to stable nonglycemic factors.

Higher Maternal Body Mass Index Is Associated With Lower Placental Expression of EPYC: A Genome-Wide Transcriptomic Study.

CONTEXT: Elevated body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. The placental transcriptome may elucidate molecular mechanisms underlying these associations. OBJECTIVE: We examined the association of first-trimester maternal BMI with the placental transcriptome in the Gen3G prospective cohort. METHODS: We enrolled participants at 5 to 16 weeks of gestation and measured height and weight. We collected placenta samples at delivery. We performed whole-genome RNA sequencing using Illumina HiSeq 4000 and aligned RNA sequences based on the GTEx v8 pipeline. We conducted differential gene expression analysis of over 15 000 genes from 450 placental samples and reported the change in normalized gene expression per 1-unit increase in log2 BMI (kg/m2) as a continuous variable using Limma Voom. We adjusted models for maternal age, fetal sex, gestational age at delivery, gravidity, and surrogate variables accounting for technical variability. We compared participants with BMI of 18.5 to 24.9 mg/kg2 (N = 257) vs those with obesity (BMI ≥30 kg/m2, N = 82) in secondary analyses. RESULTS: Participants' mean ± SD age was 28.2 ± 4.4 years and BMI was 25.4 ± 5.5 kg/m2 in early pregnancy. Higher maternal BMI was associated with lower placental expression of EPYC (slope = -1.94, false discovery rate [FDR]-adjusted P = 7.3 × 10-6 for continuous BMI; log2 fold change = -1.35, FDR-adjusted P = 3.4 × 10-3 for BMI ≥30 vs BMI 18.5-24.9 kg/m2) and with higher placental expression of IGFBP6, CHRDL1, and CXCL13 after adjustment for covariates and accounting for multiple testing (FDR < 0.05). CONCLUSION: Our genome-wide transcriptomic study revealed novel genes potentially implicated in placental biologic response to higher maternal BMI in early pregnancy.

Glycated Albumin and Glycemia in Pregnancy and Postpartum: A Pilot Study.

OBJECTIVE: Percent glycated albumin (%GAlb) is a marker of glycemia over the past 2 to 3 weeks in nonpregnant individuals. Longitudinal changes in %GAlb extending throughout pregnancy and postpartum (PP) have not been described. We aimed to describe levels of %GAlb throughout pregnancy and PP and relationships with glycemia. STUDY DESIGN: Fifty women among those in the Study of Pregnancy Regulation of INsulin and Glucose cohort underwent 75-g oral glucose tolerance tests (OGTTs) at a mean of 13 weeks (V1) and 26 weeks (V2) of gestation and 11 weeks' PP. %GAlb was measured on frozen plasma samples. RESULTS: Total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 (ß = - 0.63% 95% CI [-0.8, -0.6] p < 0.001) and remained stable between V2 and PP (ß = - 0.04% [-0.3, 0.2] p = 0.78). Body mass index (BMI) was inversely related to %GAlb in pregnancy (V1: rho = - 0.5, p = 0.0001; V2 rho = - 0.4, p = 0.006), but not PP (rho = - 0.15, p = 0.31). The longitudinal changes in %GAlb persisted after adjusting for BMI. Neither glycemia measurements nor hemoglobin A1c were associated with %GAlb at any time point, and adjustments for BMI did not reveal additional associations. CONCLUSION: %GAlb decreases between early and late gestation and remains decreased PP, despite a PP increase in total albumin above early pregnancy values. Given the lack of correlation with OGTT values or A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women. KEY POINTS: · Changes in %GAlb extending to the postpartum period have not been described.. · %GAlb decreases in pregnancy and remains decreased postpartum, despite a postpartum increase in total albumin above early pregnancy values.. · Glycemia measurements nor A1c were associated with %GAlb at any time point, therefore, %GAlb is unlikely to be useful in assessing glycemia in pregnant or postpartum women..

Patient Priorities, Decisional Comfort, and Satisfaction with Metformin versus Insulin for the Treatment of Gestational Diabetes Mellitus.

OBJECTIVE: We compared patient priorities, decisional comfort, and satisfaction with treating gestational diabetes mellitus (GDM) with metformin versus insulin among pregnant individuals with GDM requiring pharmacotherapy. STUDY DESIGN: We conducted a cross-sectional study of patients' perspectives about GDM pharmacotherapy in an integrated prenatal and diabetes care program from October 19, 2022, to August 24, 2023. The exposure was metformin versus insulin as the initial medication decision. Outcomes included standardized measures of patient priorities, decisional comfort, and satisfaction about their medication decision. RESULTS: Among 144 assessed individuals, 60.4% were prescribed metformin and 39.6% were prescribed insulin. Minoritized individuals were more likely to receive metformin compared with non-Hispanic White individuals (34.9 vs. 17.5%; p = 0.03). Individuals who were willing to participate in a GDM pharmacotherapy clinical trial were more likely to receive insulin than those who were unwilling (30.4 vs. 19.5%; p = 0.02). Individuals receiving metformin were more likely to report prioritizing avoiding injections (62.4 vs. 19.3%; adjusted odds ratio [aOR]: 2.83; 95% confidence interval [CI]: 1.10-7.31), wanting to take a medication no more than twice daily (56.0 vs. 30.4%; aOR: 3.67; 95% CI: 1.56-8.67), and believing that both medications can equally prevent adverse pregnancy outcomes (70.9 vs. 52.6%; aOR: 2.67; 95% CI: 1.19-6.03). Conversely, they were less likely to report prioritizing a medication that crosses the placenta (39.1 vs. 82.5%; aOR: 0.09; 95% CI: 0.03-0.25) and needing supplemental insulin to achieve glycemic control (21.2 vs. 47.4%; aOR: 0.36; 95% CI: 0.15-0.90). Individuals reported similarly high (mean score > 80%) levels of decisional comfort, personal satisfaction with medication decision-making, and satisfaction about their conversation with their provider about their medication decision with metformin and insulin (p ≥ 0.05 for all). CONCLUSION: Individuals with GDM requiring pharmacotherapy reported high levels of decision comfort and satisfaction with both metformin and insulin, although they expressed different priorities in medication decision-making. These results can inform future patient-centered GDM treatment strategies. KEY POINTS: · Pregnant individuals with GDM requiring pharmacotherapy expressed a high level of decisional comfort and satisfaction with medication decision making.. · Individuals placed different priorities on deciding to take metformin versus insulin.. · These results can inform interventions aimed at delivering person-centered diabetes care in pregnancy that integrates patient autonomy and knowledge about treatment options..

Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. METHODS: Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). RESULTS: A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. CONCLUSIONS: Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Gestational Diabetes (GDM) is high blood sugar that develops during pregnancy and may cause complications. GDM diagnosis is centered on blood sugar levels. Despite everyone receiving standard treatment, the clinical outcomes may vary from one individual to another. This indicates a need to identify factors that may help GDM diagnosis and result in improved classification of those at greatest risk for complications. Here, we systematically analyzed all published evidence for potential markers that could identify those with GDM who have greater risk of complications. We find that high maternal weight is a risk factor for offspring born larger for their gestational age. Other promising markers were identified, but further analysis is needed before they can be applied in the clinic.

Supporting Our Physician Parents (SOPPort): A pilot program for parental wellness at the Massachusetts General Hospital.

Physician parents encounter unique challenges in balancing new parenthood with work responsibilities, especially upon their return from parental leave. We designed a pilot program that incorporated 1:1 parental coaching to expectant and new physician parents and provided stipends for lactation support and help at home. Additional initiatives included launching a virtual new parent group during the COVID-19 pandemic and starting an emergency backup pump supplies program. There was positive feedback for our Parental Wellness Program (PWP), which was used to secure expanded funding. Pilot results showed that our program had a meaningful impact on parental wellness, morale, productivity, and lactation efforts.

Sex-specific impact of maternal obesity on fetal placental macrophages and cord blood triglycerides.

INTRODUCTION: Maternal obesity is associated with increased risk of offspring obesity and cardiometabolic disease. Altered fetoplacental immune programming is a potential candidate mechanism. Differences in fetal placental macrophages, or Hofbauer cells (HBCs), have been observed in maternal obesity, and lipid metabolism is a key function of resident macrophages that may be deranged in inflammation/immune activation. We sought to test the following hypotheses: 1) maternal obesity is associated with altered HBC density and phenotype in the term placenta and 2) obesity-associated HBC changes are associated with altered placental lipid transport to the fetus. The impact of fetal sex was evaluated in all experiments. METHODS: We quantified the density and morphology of CD163-and CD68-positive HBCs in placental villi in 34 full-term pregnancies undergoing cesarean delivery (N = 15, maternal BMI ≥30 kg/m2; N = 19, BMI <30 kg/m2). Antibody-positive cells in terminal villi were detected and cell size and circularity analyzed using a semi-automated method for thresholding of bright-field microscopy images (ImageJ). Placental expression of lipid transporter genes was quantified using RTqPCR, and cord plasma triglycerides (TGs) were profiled using modified Wahlefeld method. The impact of maternal obesity and fetal sex on HBC features, lipid transporters, and cord TGs were evaluated by two-way ANOVA. Spearman correlations of cord TGs, HBC metrics and gene expression levels were calculated. RESULTS: Maternal obesity was associated with significantly increased density of HBCs, with male placentas most affected (fetal sex by maternal obesity interaction p = 0.04). CD163+ HBCs were larger and rounder in obesity-exposed male placentas. Sexually dimorphic expression of placental FATP4, FATP6, FABPPM, AMPKB1 and AMPKG and cord TGs was noted in maternal obesity, such that levels were higher in males and lower in females relative to sex-matched controls. Cord TGs were positively correlated with HBC density and FATP1 expression. DISCUSSION: Maternal obesity is associated with sex-specific alterations in HBC density and placental lipid transporter expression, which may impact umbilical cord blood TG levels and offspring cardiometabolic programming.

Gestational Glucose Intolerance and Birth Weight-Related Complications.

OBJECTIVE: To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight-related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. METHODS: In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight-related adverse pregnancy outcomes. RESULTS: Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23-1.49, P <.001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08-1.35, P <.001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52-2.08, P <.001). The odds of birth weight-related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. CONCLUSION: Gestational glucose intolerance in pregnancy is associated with birth weight-related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.

Gestational Diabetes and Long-Term Cardiometabolic Health.

This JAMA Insights discusses adverse long-term effects of gestational diabetes on the pregnant individual and the exposed fetus.