Performance of the Dexcom G7 Continuous Glucose Monitoring System in Pregnant Women with Diabetes.

Background: We evaluated accuracy and safety of a seventh-generation real-time continuous glucose monitoring (CGM) system during pregnancy. Materials and Methods: Evaluable data for accuracy analysis were obtained from 96 G7 sensors (Dexcom, Inc.) worn by 96 of 105 enrolled pregnant women with type 1 (n = 59), type 2 (n = 21), or gestational diabetes (n = 25). CGM values were compared with arterialized venous glucose values from the YSI comparator instrument during 6-h clinic sessions at different time points throughout the sensors' 10-day wear period. The primary endpoint was the proportion of CGM values in the 70-180 mg/dL range within 15% of comparator glucose values. Secondary endpoints included the proportion of CGM values within 20% or 20 mg/dL of comparator values ≥ or <100 mg/dL, respectively (the %20/20 agreement rate). Results: Of the 1739 pairs with CGM in the 70-180 mg/dL range, 83.2% were within 15% of comparator values. The lower bound of the 95% confidence interval was 79.8%. Of the 2102 pairs with CGM values in the 40-400 mg/dL range, the %20/20 agreement rate was 92.5%. Of the 1659 pairs with comparator values in the 63-140 mg/dL range, the %20/20 agreement rate was 92.3%. The %20/20 agreement rates on days 1, 4 and 7, and 10 were 78.6%, 96.3%, and 97.3%, respectively. Consensus error grid analysis showed 99.8% of pairs in the clinically acceptable A and B zones. There were no serious adverse events. The sensors' 10-day survival rate was 90.3%. Conclusion: The G7 system is accurate and safe during pregnancies complicated by diabetes and does not require confirmatory fingerstick testing. Clinical Trial Registration: clinicaltrials.gov NCT04905628.

Perinatal Stressors and Consequences for Neonates with Critical Congenital Heart Disease.

INTRODUCTION: The prenatal diagnosis of congenital heart disease (CHD) is a traumatic event that can cause expectant parents to experience anxiety, depression, and toxic stress. Prenatal exposure to stress may impact neonatal postoperative outcomes. In addition, expectant parents may have other psychosocial stressors that may compound maternal stress. We investigated the relationship between stress in pregnancies complicated by prenatally diagnosed CHD and their neonatal outcomes. METHODS: A pilot retrospective cohort study of pregnancies with prenatally diagnosed critical CHD (2019-2021) was performed. The collected data included pregnancy characteristics and neonatal and postoperative outcomes (including the need for exogenous corticosteroid treatment (ECT)). In order to quantify prenatal stressors, a composite prenatal stress score (PSS) was established and utilized. RESULTS: In total, 41 maternal-fetal dyads were evaluated. Thirteen (32%) neonates had single-ventricle anatomy. The need for ECT after CHD surgery was associated with higher pregnant patient PSS (p = 0.01). PSS did not correlate with birthweight, infection, or hypoglycemia in the neonatal period. CONCLUSIONS: Prenatal stress is multifactorial; higher PSS is correlates with post-bypass ECT, suggesting that a stressful intrauterine environment may be associated with worse neonatal postoperative outcomes.

Adverse Perinatal and Neonatal Outcomes among Adolescent Pregnancies in the United States.

OBJECTIVE: Despite a downward trend in recent years, adolescent pregnancies in the United States remain higher than any other western country. Adolescent pregnancies have been inconsistently associated with adverse perinatal outcomes. The objective of this study is to investigate the association between adolescent pregnancies and adverse perinatal and neonatal outcomes in the United States. STUDY DESIGN: This is a retrospective cohort study of singleton births in the United States from 2014 to 2020 using national vital statistics data. Perinatal outcomes included gestational diabetes, gestational hypertension, preterm delivery <37 weeks (preterm birth [PTB]), cesarean delivery (CD), chorioamnionitis, small for gestational age (SGA), large for gestational age (LGA), and neonatal composite outcome. Chi-square tests were used to compare outcomes among adolescent (13-19 years) versus adult (20-29 years) pregnancies. Multivariable logistic regression models were used to examine association of adolescent pregnancies with perinatal outcomes. For each outcome, we utilized three models: unadjusted logistic regression, adjusted for demographics, and adjusted for demographics and medical comorbidities. Similar analyses were used to compare younger (13-17 years) and older (18-19 years) adolescent pregnancies to adults. RESULTS: In a cohort of 14,014,078 pregnancies, we found that adolescents were at an increased risk of PTB (adjusted odds ratio [aOR]: 1.12, 99% confidence interval (CI): 1.12-1.13) and SGA (aOR: 1.02, 99% CI: 1.01-1.03) compared with adult pregnancies. We also found that multiparous adolescents with a prior history of CD were at an increased risk of CD, compared with adults. For all other outcomes, adult pregnancies were at higher risk for adverse outcomes in the adjusted models. When comparing birth outcomes among adolescents, we found that older adolescents are at an increased risk of PTB, whereas younger adolescents are at an increased risk of both PTB and SGA. CONCLUSION: After adjusting for confounders, our study demonstrates adolescents have an increased risk of PTB and SGA, compared with adults. KEY POINTS: · Adolescents as a whole subgroup have an increased risk of PTB and SGA compared with adults.. · Younger adolescents have a risk of PTB and SGA, whereas older adolescents have a risk of PTB only.. · Adverse birth outcomes in adults are gestational diabetes, chorioamnionitis, LGA, and worse neonatal composite score..

Influence of Neighborhood Socioeconomic Status on Adverse Outcomes in Pregnancy.

PURPOSE: To evaluate whether ZIP-code level neighborhood socioeconomic status (SES) is associated with adverse pregnancy outcomes. METHODS: A retrospective study of 2009-2014 Oregon Health and Science University (OHSU) births with maternal ZIP codes in one of 89 Portland metropolitan area ZIP codes. Deliveries with ZIP codes outside of the Portland metro area were excluded. Deliveries were stratified by SES based on ZIP code median household income: low (below 10th percentile), medium (11th-89th percentile), and high (above 90th percentile). Univariate analysis and multivariable logistic regression with medium SES as the reference group evaluated perinatal outcomes and strength of association between SES and adverse events. RESULTS: This study included 8118 deliveries with 1654 (20%) classified as low SES, 5856 (72%) medium SES, and 608 (8%) high SES. The low SES group was more likely to be younger, have a higher maternal BMI, have increased tobacco use, identify as Hispanic or Black, and less likely to have private insurance. Low SES was associated with a significantly increased risk of preeclampsia (RR 1.23 95% CI 1.01-1.49), but this was no longer significant after adjusting for confounders (aRR 1.23 95% CI .971-1.55). High SES was negatively associated with gestational diabetes mellitus (GDM), even after adjusting for confounders (aRR 0.710, 95% CI 0.507-0.995). CONCLUSION: In the Portland metropolitan area, high SES was associated with a lower risk of GDM. Low SES was associated with a higher risk of preeclampsia before accounting for covariates. ZIP code-based risk assessment may be a useful indicator in detecting healthcare disparities.

Comprehensive Management of Type 2 Diabetes During Pregnancy.

This JAMA Insights Clinical Update discusses a comprehensive approach to treating pregnant patients with type 2 diabetes to reduce adverse perinatal and neonatal outcomes.

Medications for Managing Preexisting and Gestational Diabetes in Pregnancy.

Persons with gestational and pregestational diabetes during pregnancy may require pharmacologic agents to achieve pregnancy glycemic targets, and the available medications for use in pregnancy are limited. Insulin is the only FDA-approved medication for use in pregnancy and has the greatest evidence for safety and efficacy. Metformin and glyburide are the most commonly used oral agents in pregnancy. Understanding each medication's unique pharmacokinetics, potential side effects, fetal or childhood risks, gestational age of medication initiation and patient's diabetes care barriers are important aspects of shared decision-making and choosing a regimen that will achieve glycemic and pregnancy goals.

Association of perinatal outcomes among pregnant patients with gestational diabetes receiving benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children.

BACKGROUND: Treatment of gestational diabetes mellitus has been demonstrated to improve perinatal outcomes. However, the role of the Special Supplemental Nutrition Program for Women, Infants, and Children in maternal and neonatal outcomes for qualifying patients with gestational diabetes mellitus is less understood. OBJECTIVE: The objective of this study is to observe the relationship of enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children with pregnancy outcomes in patients with gestational diabetes. STUDY DESIGN: This was a retrospective cohort study using National Vital Statistics Birth Data of pregnant persons diagnosed with gestational diabetes mellitus between 2014 and 2018. The study population was composed of patients who had Medicaid coverage for maternity care; patients with Medicaid are automatically qualified for the Special Supplemental Nutrition Program for Women, Infants, and Children. The study groups were defined as those who enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children vs those who did not enroll. In addition, maternal and neonatal outcomes for these groups were analyzed. Univariate and multivariable logistic regression analyses adjusted for significant covariates were performed. RESULTS: Of 460,377 pregnant persons with pregnancies complicated by gestational diabetes mellitus, 73% were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children, and 27% were not. Pregnant persons with gestational diabetes mellitus enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children had decreased odds of preterm delivery before 34 and 37 weeks of gestation. Although the Special Supplemental Nutrition Program for Women, Infants, and Children group had higher odds of large-for-gestational-age neonates and cesarean delivery, the overall rates of these outcomes in both cohorts were high. CONCLUSION: The Special Supplemental Nutrition Program for Women, Infants, and Children provides a resource for perinatal support, supplemental food, and nutritional education. The decrease in the rates of preterm deliveries in pregnant persons with gestational diabetes mellitus that enroll in the Special Supplemental Nutrition Program for Women, Infants, and Children, Infants, and Children relative to those that qualified for the program but did not enroll suggested that having access to available education and food sources may influence perinatal outcomes.

Association of interpregnancy interval and gestational diabetes mellitus.

OBJECTIVE: To evaluate the association between interpregnancy interval (IPI) and risk for gestational diabetes mellitus (GDM). METHODS: We conducted a retrospective cohort study among singleton, non-anomalous, live birth pregnancies of 5,705,812 pregnant individuals in the United States from 2016 to 2018. We examined IPI of 4-<6 months, 6-11 months, 12-17 months, 24-35 months, 36-47 months, 48-59 months, 60-71 months, and ≥72 months in comparison to the reference interval of 18-23 months in relation to risk for GDM. We used logistic regression to evaluate the association between IPI and risk for GDM. RESULTS: There is a significantly increased risk for GDM associated with IPIs of 6-11 months and 12-17 months compared to the reference of 18-23 months (adjusted Odds Ratio [aOR] 1.05, 95% CI: 1.03-1.07; aOR 1.02, 95% CI: 1.01-1.03). The risk for GDM is greater for longer IPIs (36-47 months aOR 1.10, 95% CI: 1.05-1.08; 48-59 months aOR 1.11, 95% CI: 1.09-1.13; 60-71 months aOR 1.14, 95% CI: 1.12-1.16; ≥72 months aOR 1.31, 95% CI: 1.30-1.33). CONCLUSION: Our findings support the growing evidence that shorter and longer IPI increase the risk of GDM in pregnant individuals. Screening guidelines for detection of GDM may need to be re-evaluated and updated to include longer IPIs (≥36 months) as a risk factor for earlier screening prior to current recommendation of 24 weeks gestational age.

Strategies for Prevention or Treatment of Tobacco and Cannabis Use Disorder.

Tobacco and cannabis use in pregnancy are associated with increased adverse perinatal and long-term offspring outcomes. Products for both have evolved with various forms available on the market, challenging accurate counseling of risks and quantification of tobacco and cannabis usage during the perinatal period. Health care providers are recommended to screen for any type of use, provide consistent messaging of harms of tobacco and cannabis use in pregnancy, and offer individualized interventions. The journey to cessation can be complicated by barriers and triggers, lack of social supports, and mental health challenges that should be addressed to prevent relapse and withdrawals.

The Risk of Perinatal Mortality in Nulliparous Women Compared to Primiparous Women at Term.

OBJECTIVE: The aim of this study was to determine the rate of perinatal mortality among nulliparous women compared with primiparous women at term and further characterize the risk of stillbirth by each week of gestation. STUDY DESIGN: This is a retrospective cohort study of all term, singleton, nonanomalous births comparing perinatal mortality (stillbirth and neonatal death [NND]) between primiparous (parity = 1, with no history of abortion) and nulliparous (parity = 0) women who delivered in California between 2007 and 2011. Chi-squared tests and multivariable logistic regression analyses were performed to determine the frequencies and strength of association of perinatal mortality with parity, adjusting for maternal age, race, body mass index, pregestational diabetes, chronic hypertension, fetal sex, smoking status, and socioeconomic status. The risk of stillbirth at each gestational age at term was calculated using a pregnancies-at-risk life table method. A p-value less than 0.05 was used to indicate statistical significance. RESULTS: Of 1,317,761 total deliveries, 765,995 (58.1%) were to nulliparous women and 551,766 (41.9%) were to primiparous women with one prior birth. Nulliparous women had increased odds of stillbirth (adjusted odds ratio [aOR], 3.30; 95% confidence interval [CI], 2.93-3.72) and NND (aOR, 1.54; 95% CI, 1.19-1.98) compared with primiparous women. The risk of stillbirth in nulliparous women was greater at every gestational age between 370/7 and 410/7 weeks compared with primiparous women. Nulliparous women also had increased odds of small for gestational age infants at less than 10% birth weight (aOR, 1.76; 95% CI, 1.72-1.79), less than 5% birth weight (aOR, 1.91; 95% CI, 1.86-1.98), and less than 3% birth weight (aOR, 2.02; 95% CI, 1.93-2.11). CONCLUSION: Perinatal mortality is significantly greater in nulliparous women compared with primiparous women with term deliveries. These findings suggest that low-risk nulliparous women may require increased surveillance. There may be a role in improving maternal health by maximizing physiologic adaptation in nulliparous women. KEY POINTS: · Parity is associated with perinatal mortality.. · Perinatal mortality is significantly greater in nulliparous women compared with primiparous women.. · The risk of stillbirth in nulliparous women is greater at every gestational age compared with primiparous women..

Management of Women with Polycystic Ovary Syndrome During Pregnancy.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women and is associated with subfertility and adverse perinatal outcomes, which may include early pregnancy loss, gestational diabetes mellitus, hypertensive spectrum disorder, preterm birth, fetal growth disorders, and cesarean deliveries. The phenotypic heterogeneity, different diagnostic criteria, and PCOS-related conditions that women enter pregnancy with have limited evidenced-based studies and guidelines to reduce pregnancy complications among this high-risk population. This review summarizes the available evidence on the approach and management of women with PCOS preconception, prenatal, and postpartum.

Hyperglycemia and gestational diabetes suppress placental glycolysis and mitochondrial function and alter lipid processing.

The degree that maternal glycemia affects placental metabolism of trophoblast cell types [cytotrophoblast (CTB) and syncytiotrophoblast (SCT)] in pregnant persons with gestational diabetes mellitus (GDM) is unknown. We tested the hypotheses that (a) hyperglycemia suppresses the metabolic rates of CTB and SCT; and (b) low placental metabolic activity from GDM placentas is due to decreased oxygen consumption of CTB. Trophoblast cells isolated from GDM and non-GDM term placentas were cultured for 8-hour (CTB) and following syncytialization at 72-hour (SCT) in 5 mM of glucose or 25 mM of glucose. Oxygen consumption rates, glycolysis, ATP levels, and lipid droplet morphometries were determined in CTB and SCT. In CTB from GDM placentas compared to control CTB: (a) oxidative phosphorylation was decreased by 44% (41.8 vs 74.2 pmol O2 /min/100 ng DNA, P = .002); (b) ATP content was 39% lower (1.1 × 10-7 vs 1.8 × 10-7  nM/ng DNA, P = .046); and (c) lipid droplets were two times larger (31.0 vs 14.4 µm2 /cell, P < .001) and 1.7 times more numerous (13.5 vs 7.9 lipid droplets/cell, P < .001). Hyperglycemia suppressed CTB glycolysis by 55%-60% (mean difference 20.4 [GDM, P = .008] and 15.4 [non-GDM, P = .029] mpH/min/100 ng DNA). GDM SCT was not metabolically different from non-GDM SCT. However, GDM SCT had significantly decreased expression of genes associated with differentiation including hCG, GCM1, and syncytin-1. We conclude that suppressed metabolic activity by the GDM placenta is attributable to metabolic dysfunction of CTB, not SCT. Critical placental hormone expression and secretion are decreased in GDM trophoblasts.

Increased rates of adverse perinatal outcomes in women with gestational diabetes and depression.

OBJECTIVE: We sought to examine the impact of depression on adverse perinatal outcomes in women with Gestational Diabetes Mellitus (GDM). METHODS: We performed a retrospective cohort study comparing the rates of perinatal complications among singleton, nonanomalous births to women with GDM and the diagnosis of depression compared to GDM women without depression between 2007 and 2011 in California. Perinatal outcomes were analyzed using chi-square and multivariable logistic regression to compare frequencies of characteristics and outcomes and to determine the strength of association of depression and adverse perinatal outcomes among women with GDM. Statistical comparisons with a p-value of less than .05 and 95% CI that did not cross the null were considered statistically significant. RESULTS: Among the cohort of 170,572 women with GDM, 2090 (1.22%) were diagnosed with antenatal depression. Women with GDM and depression had significantly higher rates of preeclampsia (adjusted Odds Ratio [aOR] 1.28, 95% CI 1.11-1.49) and gestational hypertension (aOR 1.23, 95% CI 1.05-1.44). Women with GDM and depression also had higher rates of preterm delivery at <37, and <34 weeks gestational age (aOR 1.33, 95% CI 1.18-1.50 and 1.36, 95% CI 1.15-1.61, respectively). CONCLUSION: Women with GDM and a diagnosis of depression have higher rates of adverse perinatal outcomes than women with GDM alone. Identifying and managing depression among women with GDM has the potential to improve the care and health of this high-risk population.

Social Determinants of Placental Health and Future Disease Risks for Babies.

Birthweight is a well-known predictor of adult-onset chronic disease. The placenta plays a necessary role in regulating fetal growth and determining birth size. Maternal stressors that affect placental function and prenatal growth include maternal overnutrition and undernutrition, toxic social stress, and exposure to toxic chemicals. These stressors lead to increased vulnerability to disease within any population. This vulnerability arises from placental and fetal exposure to stressors during fetal life. The biological drivers linking various social determinants of health to compromised placental function and fetal development have been little studied.

Real-time microscopic assessment of fatty acid uptake kinetics in the human term placenta.

INTRODUCTION: The placenta employs an efficient and selective fatty acid transport system to supply lipids for fetal development. Disruptions in placental fatty acid transport lead to restricted fetal growth along with cardiovascular and neurologic deficits. Nevertheless, little is known about the molecular mechanisms involved in human placental fatty acid trafficking during the initial steps of uptake, or the importance of fatty acid chain length in determining uptake rates. METHODS: We employed BODIPY fluorophore conjugated fatty acid analogues of three chain lengths, medium (BODIPY-C5), long (BODIPY-C12), and very-long (BODIPY-C16), to study fatty acid uptake in isolated human trophoblast and explants using confocal microscopy. The three BODIPY-labeled fatty acids were added to freshly isolated explants and tracked for up to 30 min. Fatty acid uptake kinetics were quantified in trophoblast (cytotrophoblast and syncytiotrophoblast together) and the fetal capillary lumen. RESULTS: Long- (BODIPY-C12) and Very long-chain (BODIPY-C16) fatty acids accumulated more rapidly in the trophoblast layer than did medium-chain (BODIPY-C5) whereas BODIPY-C5 accumulated more rapidly in the fetal capillary than did the longer chain length fatty acids. The long-chain fatty acids, BODIPY-C12 and BODIPY-C16, are esterified and stored in lipid droplets in the cytotrophoblast layer, but medium-chain fatty acid, BODIPY-C5, is not. DISCUSSION: Fatty acids accumulate in trophoblast and fetal capillaries inversely according to their chain length. BODIPY-C5 accumulates in the fetal capillary in concentrations far greater than in the trophoblast, suggesting that medium-chain length BODIPY-labeled fatty acids are capable of being transported against a concentration gradient.

Association of a Health Care Provider Review Meeting With Cesarean Delivery Rates: A Quality Improvement Program.

OBJECTIVE: To examine the association of a quality improvement effort that was mediated through weekly review of all criteria for cesarean delivery on cesarean delivery prevalence and indications. METHODS: We conducted a retrospective cohort study using a natural experiment model that compared two timeframes, from 2009 to 2013, at a single institution. We introduced a weekly retrospective review conference to discuss all cesarean deliveries in 2010 that continued over time. The conferences were attended by obstetric care providers, anesthesiology, and labor and delivery nurses. Date of delivery was dichotomized by those delivering before July 1, 2010, and those delivering after. We included women with term singleton vertex gestations in our study population and then examined the rates of cesarean delivery by date of delivery. We then examined indications for the cesarean deliveries during the study period based on surgeon documentation. χ tests were used for statistical comparisons and a P value of <.05 was used to indicate statistical significance. RESULTS: There were 5,541 term singleton cephalic births during the study period. The rate of cesarean delivery declined significantly after our intervention in all women (22.2% vs 27.4%, P<.001) and nulliparous women (23.3% vs 30.9%, P<.001). The adjusted odds ratio of cesarean delivery in all women as related to time cohort is 0.68 (95% CI 0.58-0.79) and 0.56 (95% CI 0.44-0.70) in nulliparous women. We examined indications for the 1,315 cesarean deliveries during the study period by date of delivery. The indications of active-phase arrest, second-stage arrest, failed induction, repeat cesarean delivery, and maternal request decreased significantly between delivery cohorts in all women (P<.001) and in nulliparous women specifically (P<.001). Between delivery cohorts, we found that the prevalence of labored indications for cesarean delivery decreased more than nonlabored indications. CONCLUSION: Implementation of a weekly review conference was associated with a reduction in both overall cesarean delivery prevalence and labored indications at our institution.

A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes.

Use of oral agents to treat gestational diabetes mellitus remains controversial. Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress mitochondrial respiration, have epigenetic modifications on gene expression, mimic fetal nutrient restriction, and alter postnatal gluconeogenic responses. Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity, these properties raise important questions about developmental programming of metabolic disease in offspring. Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism. Two recent clinical randomized controlled trials in women with gestational diabetes mellitus or polycystic ovary syndrome provide evidence that metformin exposure in utero may produce a metabolic phenotype that increases childhood weight or obesity. These developmental programming effects challenge the conclusion that metformin is equivalent to insulin. Although the Society for Maternal-Fetal Medicine statement endorsed metformin over glyburide if oral agents are used, there are few studies directly comparing the 2 agents and it is not clear that metformin alone is superior to glyburide. Moreover, it should be noted that prior clinical studies have dosed glyburide in a manner inconsistent with its pharmacokinetic properties, resulting in poor glycemic control and high rates of maternal hypoglycemia. We concur with the American Diabetes Association and American Congress of Obstetricians and Gynecologists, which recommend insulin as the preferred agent, but we believe that it is premature to embrace metformin as equivalent to insulin or superior to glyburide. Due to the uncertainty of the long-term metabolic risks of either metformin or glyburide, we call for carefully controlled studies that optimize oral medication dosing according to their pharmacodynamic and pharmacokinetic properties in pregnancy, appropriately target medications based on individual patterns of hyperglycemia, and follow the offspring long-term for metabolic risk.