Impact of Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus on Offspring Cardiovascular Health in Early Adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), influence maternal cardiovascular heath (CVH) long after pregnancy, but their relationship to offspring CVH following in utero exposure remains uncertain. OBJECTIVE: To examine associations of HDP or GDM with offspring CVH in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study from 2000 to 2006 and the HAPO Follow-Up Study from 2013 to 2016. This analysis included 3,317 mother-child dyads from 10 field centers, comprising 70.8% of HAPO Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures were having any HDP or GDM compared with not having HDP or GDM, respectively (reference). The outcome was offspring CVH at ages 10 to 14 years, based on four metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The outcome was primarily defined as having at least one CVH metric that was non-ideal versus all ideal (reference), and secondarily as the number of non-ideal CVH metrics: at least one intermediate metric, one poor metric, or at least two poor metrics versus all ideal (reference). Modified Poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3,317 maternal-child dyads, the median (IQR) ages were 30.4 (25.6, 33.9) years for pregnant individuals and 11.6 (10.9, 12.3) years for children. During pregnancy, 10.4% of individuals developed HDP and 14.6% developed GDM. At follow-up, 55.5% of offspring had at least one non-ideal CVH metric. In adjusted models, having HDP (aRR 1.14; 95% CI 1.04, 1.25) or having GDM (aRR 1.10; 95% CI 1.02, 1.19) was associated with greater risk that offspring developed less-than-ideal CVH at ages 10 to 14 years. The above associations strengthened in magnitude as the severity of adverse CVH metrics increased (i.e., with the outcome measured as >1 intermediate, 1 poor, and >2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSONS: In this multi-national prospective cohort, pregnant individuals who experienced either HDP and GDM were at significantly increased risk of having offspring with worse CVH in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Reflections on the Multicenter Randomized Trial of Treatment for Mild Gestational Diabetes.

After the 2006 hyperglycemia and adverse pregnancy outcomes study, which confirmed the relationship between maternal glycemia and pregnancy outcomes, the debate remained on whether treatment benefited gestational diabetes mellitus (GDM). Nonetheless, practitioners continued to universally screen for and treat women identified as GDM. To assess the benefits and harms of screening and treatment of GDM, the National Institute of Child Health and Human Development Maternal and Fetal Medicine Unit Network designed and conducted a well-designed randomized controlled trial in women with mild GDM. The trial established that treatment of GDM resulted in a significant reduction in several important perinatal and maternal outcomes.

Rural-urban disparities in pregestational and gestational diabetes in pregnancy: Serial, cross-sectional analysis of over 12 million pregnancies.

OBJECTIVE: To compare trends in pregestational (DM) and gestational diabetes (GDM) in pregnancy in rural and urban areas in the USA, because pregnant women living in rural areas face unique challenges that contribute to rural-urban disparities in adverse pregnancy outcomes. DESIGN: Serial, cross-sectional analysis. SETTING: US National Center for Health Statistics (NCHS) Natality Files from 2011 to 2019. POPULATION: A total of 12 401 888 singleton live births to nulliparous women aged 15-44 years. METHODS: We calculated the frequency (95% confidence interval [CI]) per 1000 live births, the mean annual percentage change (APC), and unadjusted and age-adjusted rate ratios (aRR) of DM and GDM in rural compared with urban maternal residence (reference) per the NCHS Urban-Rural Classification Scheme overall, and by delivery year, reported race and ethnicity, and US region (effect measure modification). MAIN OUTCOME MEASURES: The outcomes (modelled separately) were diagnoses of DM and GDM. RESULTS: From 2011 to 2019, there were increases in both the frequency (per 1000 live births; mean APC, 95% CI per year) of DM and GDM in rural areas (DM: 7.6 to 10.4 per 1000 live births; APC 2.8%, 95% CI 2.2%-3.4%; and GDM: 41.4 to 58.7 per 1000 live births; APC 3.1%, 95% CI 2.6%-3.6%) and urban areas (DM: 6.1 to 8.4 per 1000 live births; APC 3.3%, 95% CI 2.2%-4.4%; and GDM: 40.8 to 61.2 per 1000 live births; APC 3.9%, 95% CI 3.3%-4.6%). Individuals living in rural areas were at higher risk of DM (aRR 1.48, 95% CI 1.45%-1.51%) and GDM versus those in urban areas (aRR 1.17, 95% CI 1.16%-1.18%). The increased risk was similar each year for DM (interaction p = 0.8), but widened over time for GDM (interaction p < 0.01). The rural-urban disparity for DM was wider for individuals who identified as Hispanic race/ethnicity and in the South and West (interaction p < 0.01 for all); and for GDM the rural-urban disparity was generally wider for similar factors (i.e. Hispanic race/ethnicity, and in the South; interaction p < 0.05 for all). CONCLUSIONS: The frequency of DM and GDM increased in both rural and urban areas of the USA from 2011 to 2019 among nulliparous pregnant women. Significant rural-urban disparities existed for DM and GDM, and increased over time for GDM. These rural-urban disparities were generally worse among those of Hispanic race/ethnicity and in women who lived in the South. These findings have implications for delivering equitable diabetes care in pregnancy in rural US communities.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

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..

Association between glycemic control and group B streptococcus colonization among pregnant individuals with pregestational diabetes.

PROBLEM: Pregestational diabetes increases the risk of group B streptococcus (GBS) colonization in pregnancy. Whether glycemic control is associated with differences in this risk is unknown. We examined the association between glycemic control and GBS colonization among pregnant individuals with pregestational diabetes. METHOD OF STUDY: A retrospective cohort of pregnant individuals with pregestational diabetes at a tertiary care center. The exposure was glycemic control, measured as hemoglobin A1c (A1c) at >20 weeks and assessed categorically at thresholds of <6.5% and <6.0%, and secondarily, as a continuous percentage. The outcome was maternal GBS colonization. Multivariable logistic regression was used and adjusted for age, parity, race, and ethnicity as a social determinant, body mass index, type of diabetes, and gestational age at A1c assessment. RESULTS: Among 305 individuals (33% Type 1, 67% type 2), 45.0% (n = 140) were colonized with GBS. Individuals with an A1c < 6.5% were half as likely to be colonized with GBS compared with those with a A1c ≥ 6.5% (38.8% vs. 53.9%; adjusted odds ratio, AOR: 0.55; 95% CI: 0.33-0.91). Results were unchanged at an A1c threshold of <6.0% (35.7% vs. 48.5%; AOR: 0.60; 95% CI: 0.36-0.98). Individuals with a higher A1c as a continuous measure (%) were more likely to be colonized (AOR: 1.57 per 1%; 95% CI: 1.25-1.97). CONCLUSIONS: Pregnant individuals with pregestational diabetes with worse glycemic control were at an increased risk of GBS colonization. Further study is needed to understand if improved glycemic control leads to lower risk of GBS colonization.

Racial and ethnic differences in the association between pregnancy dysglycemia and cardiometabolic risk factors 10-14 years' postpartum in the HAPO follow-up study.

Associations between pregnancy dysglycemia and subsequent maternal cardiometabolic factors 10-14 years postpartum were largely similar across self-identified racial and ethnic groups among birthing people in the U.S. enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-up Study.

Association between community-level political affiliation and peripartum vaccination.

BACKGROUND: Political affiliation has been associated with vaccine uptake, but whether this association holds in pregnancy, when individuals are recommended to receive multiple vaccinations, remains to be studied. OBJECTIVE: This study aimed to examine the association between community-level political affiliation and vaccinations for tetanus, diphtheria, and pertussis; influenza; and COVID-19 in pregnant and postpartum individuals. STUDY DESIGN: A survey was conducted about tetanus, diphtheria, and pertussis and influenza vaccinations in early 2021, with a follow-up survey of COVID-19 vaccination among the same individuals at a tertiary care academic medical center in the Midwest. Geocoded residential addresses were linked at the census tract to the Environmental Systems Research Institute 2021 Market Potential Index, which ranks a community in comparison to the US national average. The exposure for this analysis was community-level political affiliation, defined by the Market Potential Index as very conservative, somewhat conservative, centrist, somewhat liberal, and very liberal (reference). The outcomes were self-reported vaccinations for tetanus, diphtheria, and pertussis; influenza; and COVID-19 in the peripartum period. Modified Poisson regression was used and adjusted for age, employment, trimester at assessment, and medical comorbidities. RESULTS: Of 438 assessed individuals, 37% lived in a community characterized by very liberal political affiliation, 11% as somewhat liberal, 18% as centrist, 12% as somewhat conservative, and 21% as very conservative. Overall, 72% and 58% of individuals reported receiving tetanus, diphtheria, and pertussis and influenza vaccinations, respectively. Of the 279 individuals who responded to the follow-up survey, 53% reported receiving COVID-19 vaccination. Individuals living in a community characterized by very conservative political affiliation were less likely to report vaccinations for tetanus, diphtheria, and pertussis (64% vs 72%; adjusted risk ratio, 0.83; 95% confidence interval, 0.69-0.99); influenza (49% vs 58%; adjusted risk ratio, 0.79; 95% confidence interval, 0.62-1.00); and COVID-19 (35% vs 53%; adjusted risk ratio, 0.65; 95% confidence interval, 0.44-0.96) than those in a community characterized by very liberal political affiliation. Individuals living in a community characterized by centrist political affiliation were less likely to report vaccinations for tetanus, diphtheria, and pertussis (63% vs 72%; adjusted risk ratio, 0.82; 95% confidence interval, 0.68-0.99) and influenza (44% vs 58%; adjusted risk ratio, 0.70; 95% confidence interval, 0.54-0.92) than those in a community characterized by very liberal political affiliation. CONCLUSION: Compared with pregnant and postpartum individuals living in communities characterized by very liberal political beliefs, those living in communities characterized by very conservative political beliefs were less likely to report vaccinations for tetanus, diphtheria, and pertussis; influenza; and COVID-19, and those in communities characterized by centrist political beliefs were less likely to report vaccinations for tetanus, diphtheria, and pertussis and influenza. Increasing vaccine uptake in the peripartum period may need to consider engaging an individual's broader sociopolitical milieu.

Hypertensive Disorders of Pregnancy and Long-Term Maternal Cardiovascular and Metabolic Biomarkers.

OBJECTIVE: This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers. STUDY DESIGN: Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic ß-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy. RESULTS: Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: -0.24, 95% confidence interval: -0.44, -0.03). There were no differences between gestational hypertension and no HDP. CONCLUSION: In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum. KEY POINTS: · Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.. · Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.. · Longitudinal studies with postpartum interventions after preeclampsia are needed..

Disparities in Continuous Glucose Monitoring Use Among Women of Reproductive Age with Type 1 Diabetes in the T1D Exchange.

We identified characteristics associated with continuous glucose monitoring (CGM) use in women of reproductive age with type 1 diabetes (T1D) in the T1D Exchange clinic registry from 2015 to 2018. Among 6643 assessed women, the frequency of CGM increased from 2015 to 2018 (20.6% vs. 30.0%; adjusted odds ratios [aOR]: 1.72; confidence interval [95% CI]: 1.51-1.95) and was more likely with recent pregnancy (45.3% vs. 25.8%; aOR: 1.63; 95% CI: 1.23-2.16). Non-Hispanic Black and Hispanic race and ethnicity, younger age, lower educational attainment, lower income, and Medicaid insurance were associated with lower odds of CGM. The use of CGM was associated with lower odds of diabetic ketoacidosis and lower hemoglobin A1c without any difference in the odds of symptomatic severe hypoglycemia. In conclusion, although CGM use was associated with better glycemic control, the majority of reproductive-age women still did not use it. Those who did not use CGM were more likely to be those at greatest risk of adverse pregnancy outcomes.

Association between Diabetes in Pregnancy and Shoulder Dystocia by Infant Birth Weight in an Era of Cesarean Delivery for Suspected Macrosomia.

OBJECTIVE: We estimated the association between diabetes and shoulder dystocia by infant birth weight subgroups (<4,000, 4,000-4,500, and >4,500 g) in an era of prophylactic cesarean delivery for suspected macrosomia. STUDY DESIGN: A secondary analysis from the National Institute of Child Health and Human Development U.S. Consortium for Safe Labor of deliveries at ≥24 weeks with a nonanomalous, singleton fetus with vertex presentation undergoing a trial of labor. The exposure was either pregestational or gestational diabetes compared with no diabetes. The primary outcome was shoulder dystocia and secondarily, birth trauma with a shoulder dystocia. We calculated adjusted risk ratios (aRRs) with modified Poison's regression between diabetes and shoulder dystocia and the number needed to treat (NNT) to prevent a shoulder dystocia with cesarean delivery. RESULTS: Among 167,589 assessed deliveries (6% with diabetes), pregnant individuals with diabetes had a higher risk of shoulder dystocia at birth weight <4,000 g (aRR: 1.95; 95% confidence interval [CI]: 1.66-2.31) and 4,000 to 4,500 g (aRR: 1.57; 95% CI: 1.24-1.99), albeit not significantly at birth weight >4,500 g (aRR: 1.26; 95% CI: 0.87-1.82) versus those without diabetes. The risk of birth trauma with shoulder dystocia was higher with diabetes (aRR: 2.29; 95% CI: 1.54-3.45). The NNT to prevent a shoulder dystocia with diabetes was 11 and 6 at ≥4,000 and >4,500 g, versus without diabetes, 17 and 8 at ≥4,000 and >4,500 g, respectively. CONCLUSION: Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered. Guidelines providing the option of cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights. KEY POINTS: · >Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered.. · Cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights.. · These findings can inform delivery planning for providers and pregnant individuals with diabetes..

Association of community walkability and glycemic control among pregnant individuals with pregestational diabetes mellitus.

BACKGROUND: Neighborhood walkability is a community-level social determinant of health that measures whether people who live in a neighborhood walk as a mode of transportation. Whether neighborhood walkability is associated with glycemic control among pregnant individuals with pregestational diabetes remains to be defined. OBJECTIVE: This study aimed to evaluate the association between community-level neighborhood walkability and glycemic control as measured by hemoglobin A1c (A1C) among pregnant individuals with pregestational diabetes. STUDY DESIGN: This was a retrospective analysis of pregnant individuals with pregestational diabetes enrolled in an integrated prenatal and diabetes care program from 2012 to 2016. Participant addresses were geocoded and linked at the census-tract level. The exposure was community walkability, defined by the US Environmental Protection Agency National Walkability Index (score range 1-20), which incorporates intersection density (design), proximity to transit stops (distance), and a mix of employment and household types (diversity). Individuals from neighborhoods that were the most walkable (score, 15.26-20.0) were compared with those from neighborhoods that were less walkable (score <15.26), as defined per national Environmental Protection Agency recommendations. The outcomes were glycemic control, including A1C <6.0% and <6.5%, measured both in early and late pregnancy, and mean change in A1C across pregnancy. Modified Poisson regression and linear regression were used, respectively, and adjusted for maternal age, body mass index at delivery, parity, race and ethnicity as a social determinant of health, insurance status, baseline A1C, gestational age at A1C measurement in early and late pregnancy, and diabetes type. RESULTS: Among 417 pregnant individuals (33% type 1, 67% type 2 diabetes mellitus), 10% were living in the most walkable communities. All 417 individuals underwent A1C assessment in early pregnancy (median gestational age, 9.7 weeks; interquartile range, 7.4-14.1), and 376 underwent another A1C assessment in late pregnancy (median gestational age, 30.4 weeks; interquartile range, 27.8-33.6). Pregnant individuals living in the most walkable communities were more likely to have an A1C <6.0% in early pregnancy (15% vs 8%; adjusted relative risk, 1.46; 95% confidence interval, 1.00-2.16), and an A1C <6.5% in late pregnancy compared with those living in less walkable communities (13% vs 9%; adjusted relative risk, 1.33; 95% confidence interval, 1.08-1.63). For individuals living in the most walkable communities, the median A1C was 7.5 (interquartile range, 6.0-9.4) in early pregnancy and 5.9 (interquartile range, 5.4-6.4) in late pregnancy. For those living in less walkable communities, the median A1C was 7.3 (interquartile range, 6.2-9.2) in early pregnancy and 6.2 (interquartile range, 5.6-7.1) in late pregnancy. Change in A1C across pregnancy was not associated with walkability. CONCLUSION: Pregnant individuals with pregestational diabetes mellitus living in more walkable communities had better glycemic control in both early and late pregnancy. Whether community-level interventions to enhance neighborhood walkability can improve glycemic control in pregnancy requires further study.

Trends in gestational diabetes mellitus among nulliparous pregnant individuals with singleton live births in the United States between 2011 to 2019: an age-period-cohort analysis.

BACKGROUND: The rate of gestational diabetes mellitus has increased over the past decade. An age, period, and cohort epidemiologic analysis can be used to understand how and why disease trends have changed over time. OBJECTIVE: This study aimed to estimate the associations of age (at delivery), period (delivery year), and cohort (birth year) of the pregnant individual with trends in the incidence of gestational diabetes mellitus in the United States. STUDY DESIGN: We conducted an age, period, and cohort analysis of nulliparous pregnant adults aged 18 to 44 years with singleton live births from the National Vital Statistics System from 2011 to 2019. Generalized linear mixed models were used to calculate the adjusted rate ratios for the incidence of gestational diabetes mellitus for each 3-year maternal age span, period, and cohort group compared with the reference group for each. We repeated the analyses with stratification according to self-reported racial and ethnic group (non-Hispanic Asian-Pacific Islander, non-Hispanic Black, Hispanic, and non-Hispanic White) because of differences in the incidence of and risk factors for gestational diabetes mellitus by race and ethnicity. RESULTS: Among 11,897,766 pregnant individuals, 5.2% had gestational diabetes mellitus. The incidence of gestational diabetes mellitus was higher with increasing 3-year maternal age span, among those in the more recent delivery period, and among the younger birth cohort. For example, individuals aged 42 to 44 years at delivery had a 5-fold higher risk for gestational diabetes mellitus than those aged 18 to 20 years (adjusted rate ratio, 5.57; 95% confidence interval, 5.43-5.72) after adjusting for cohort and period. Individuals who delivered between 2017 and 2019 were at higher risk for gestational diabetes mellitus than those who delivered between 2011 and 2013 (adjusted rate ratio, 1.24; 95% confidence interval, 1.23-1.25) after adjusting for age and cohort. Individuals born between 1999 and 2001 had a 3-fold higher risk for gestational diabetes mellitus than those born between 1969 and 1971 (adjusted rate ratio, 3.12; 95% confidence interval, 2.87-3.39) after adjusting for age and period. Similar age, period, and cohort effects were observed for the assessed racial and ethnic groups, with the greatest period effects observed among Asian and Pacific Islander individuals. CONCLUSION: Period and birth cohort effects have contributed to the rising incidence of gestational diabetes mellitus in the United States from 2011 to 2019.

Long-Term Maternal Metabolic and Cardiovascular Phenotypes after a Pregnancy Complicated by Mild Gestational Diabetes Mellitus or Obesity.

OBJECTIVE: The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. STUDY DESIGN: This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. RESULTS: Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, -0.24 and -0.15; 95% confidence intervals [CIs], -0.36 to -0.12 and -0.28 to -0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, -0.11; 95% CI, -0.19 to -0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, -0.42; 95% CI, -0.52 to -0.32), but not other biomarkers. CONCLUSION: Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. KEY POINTS: · Mild GDM increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Obesity increases the risk of insulin resistance 5 to 10 years postpartum but not pancreatic dysfunction.. · Neither mild GDM nor obesity increased the risk of cardiovascular dysfunction 5 to 10 years postpartum..

Association of community-level food insecurity and glycemic control among pregnant individuals with pregestational diabetes.

AIM: To evaluate whether pregnant individuals with pregestational diabetes who live in a food-insecure community have worse glycemic control compared to those who do not live in a food-insecure community. METHODS: A retrospective analysis of pregnant individuals with pregestational diabetes enrolled in a multidisciplinary prenatal and diabetes care program. The exposure was community-level food insecurity per the Food Access Research Atlas. The outcomes were hemoglobin A1c (A1c) < 6.0 % in early and late pregnancy, and an absolute decrease in A1c ≥ 2.0 % and mean change in A1c across pregnancy. RESULTS: Among 418 assessed pregnant individuals with pregestational diabetes, those living in a food-insecure community were less likely to have an A1c < 6.0 % in early pregnancy compared to those living in a community without food insecurity [16 % vs. 30 %; adjusted risk ratio (aRR): 0.55; 95 % CI: 0.33-0.92]. Individuals living in a food-insecure community were more likely to achieve a decrease in A1c ≥ 2.0 % [35 % vs. 21 %; aRR: 1.55; 95 % CI: 1.06-2.28] and a larger mean decrease in A1c across pregnancy [mean: 1.46 vs. 1.00; adjusted beta: 0.47; 95 % CI: 0.06-0.87)]. CONCLUSIONS: Pregnant individuals with pregestational diabetes who lived in a food-insecure community were less likely to enter pregnancy with glycemic control, but were more likely to have a reduction in A1c and achieve similar A1c status compared to those who lived in a community without food insecurity. Whether interventions that address food insecurity improve glycemic control and consequent perinatal outcomes remains to be studied.

A Comparison of Vaginal and Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth.

OBJECTIVE: This study aimed to examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). STUDY DESIGN: This retrospective cohort study included singleton pregnancies among women with a history of spontaneous PTB who received prenatal care at a single tertiary center from 2011 to 2016. Pregnancies were excluded if progesterone was not initiated prior to 24 weeks or the fetus had a major congenital anomaly. The primary outcome was PTB <37 weeks. A priori, noninferiority was to be established if the upper bound of the adjusted two-sided 90% confidence interval (CI) for the difference in PTB fell below 9%. Inverse probability of treatment weighting (IPTW) was used to carefully control for confounding associated with choice of treatment and PTB. Adjusted differences in PTB proportions were estimated via IPTW regression, with standard errors adjustment for multiple pregnancies per woman. Secondary outcomes included PTB <34 and <28 weeks, spontaneous PTB, neonatal intensive care unit admission, and gestational age at delivery. RESULTS: Among 858 pregnancies, 41% (n = 353) received vaginal progesterone and 59% (n = 505) were given 17OHP-C. Vaginal progesterone use was more common later in the study period, and among women who established prenatal care later, had prior PTBs at later gestational ages, and whose race/ethnicity was neither non-Hispanic white nor non-Hispanic Black. Vaginal progesterone did not meet noninferiority criteria compared with 17-OHPC in examining PTB <37 weeks, with an IPTW adjusted difference of 3.4% (90% CI: -3.5, 10.3). For secondary outcomes, IPTW adjusted differences between treatment groups were generally small and CIs were wide. CONCLUSION: We could not conclude noninferiority of vaginal progesterone to 17OHP-C; however, women and providers may be willing to accept a larger difference (>9%) when considering the cost and availability of vaginal progesterone versus 17OHP-C. A well-designed randomized trial is needed. KEY POINTS: · Vaginal progesterone is not noninferior to 17OHP-C.. · PTB risk may be 10% higher with vaginal progesterone.. · Associations did not differ based on obesity status..

Oral Glucose Tolerance Test in Pregnancy and Subsequent Maternal Hypertension.

OBJECTIVE: The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life. STUDY DESIGN: This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM (n = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n = 430). Participants were assessed at a median of 7 (IQR 6-8) years after their index pregnancy, and trained staff measured their blood pressure (systolic blood pressure [SBP]; diastolic blood pressure [DBP]). The association between values and the shape of the glucose curve during OGTT in the index pregnancy and the primary outcome defined as elevated BP (SBP ≥120, DBP ≥80 mm Hg, or receiving anti-HTN medications), and secondary outcome defined as stage 1 or higher (SBP ≥130, DBP ≥80 mm Hg, or receiving anti-HTN medications) at follow-up were evaluated using multivariable regression, adjusting for maternal age, body mass index, and pregnancy-associated hypertension during the index pregnancy. RESULTS: There was no association between fasting, 1-hour OGTT, and the outcomes. However, the 2-hour OGTT value was positively associated (adjusted odds ratio [aRR] per 10-unit increase 1.04, 95% CI 1.01-1.08), and the 3-hour was inversely associated (aRR per 10-unit increase 0.96, 95% CI 0.93-0.99) with the primary outcome. When the shape of the OGTT curve was evaluated, a monophasic OGTT response (peak at 1 hour followed by a decline in glucose) was associated with increased risk of elevated BP (41.3vs. 23.5%, aRR 1.66, 95% CI 1.17-2.35) and stage 1 HTN or higher (28.5 vs. 14.7%, aRR 1.83, 95% CI 1.15-2.92), compared with a biphasic OGTT response. CONCLUSION: Among persons with mild GDM or lesser degrees of glucose intolerance, the shape of the OGTT curve during pregnancy may help identify women who are at risk of HTN later in life, with biphasic shape to be associated with lower risk. KEY POINTS: · The shape of the Oral Glucose Tolerance Test curve may help identify patients who are at risk of having elevated BP or HTN 5 to 10 years following pregnancy.. · The 2-hour Oral Glucose Tolerance Test values is positively associated with elevated BP 5 to 10 years following pregnancy.. · This supports the concept of pregnancy as a window to future health and represents a potential novel biomarker for maternal cardiovascular health screening..

Impact of excessive gestational weight gain on exclusive breastfeeding among women with Type 1 and Type 2 diabetes and obesity.

BACKGROUND: Pregestational diabetes, obesity and gestational weight gain (GWG) are associated with adverse perinatal outcomes, however, the influence of excessive GWG on lactation at discharge is less known. Our aim is to evaluate the impact of excessive GWG using the LifeCycle project guidelines on exclusive breastfeeding (EBF) and any BF rates at discharge among 171 women with Type 1 and 294 Type 2 diabetes and obesity who intended to BF. METHODS AND FINDINGS: Retrospective cohort study. Obesity was defined by BMI (kg/m2) as grade 1 (30-34.9), grade 2 (35-39.9) or grade 3 (≥40). GWG was categorized as adequate, inadequate or excessive according to the 2019 LifeCycle Project guidelines. Women with Type 1 were younger (30 vs 33y), primiparous (51 vs 32%), delivered earlier (37 vs 38w) than women with Type 2 andwere different in grade 1 (40 vs 26%), grade 3 obesity (19 vs 49%) and median GWG (15 vs 11kg). Of all 465 women with Type 1 and Type 2 combined, 365 (78%) who had excessive GWG and 100 (22%) who had non-excessive GWG showed similar EBF (27 vs 25%) and any BF (72 vs 72%) rates. Regression analysis showed that after adjusting for potential confounders excessive GWG was not a predictor of EBF or any BF at discharge. CONCLUSION: Type 1 and Type 2 diabetes, obesity and excessive GWG are associated with low EBF, however, excessive GWG is not an independent predictor of low EBF or any BF at discharge.

Trends in Active Treatment of Live-born Neonates Between 22 Weeks 0 Days and 25 Weeks 6 Days by Gestational Age and Maternal Race and Ethnicity in the US, 2014 to 2020.

Importance: Birth in the periviable period between 22 weeks 0 days and 25 weeks 6 days' gestation is a major source of neonatal morbidity and mortality, and the decision to initiate active life-saving treatment is challenging. Objective: To assess whether the frequency of active treatment among live-born neonates in the periviable period has changed over time and whether active treatment differed by gestational age at birth and race and ethnicity. Design, Setting, and Participants: Serial cross-sectional descriptive study using National Center for Health Statistics natality data from 2014 to 2020 for 61 908 singleton live births without clinical anomalies between 22 weeks 0 days and 25 weeks 6 days in the US. Exposures: Year of delivery, gestational age at birth, and race and ethnicity of the pregnant individual, stratified as non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White. Main Outcomes and Measures: Active treatment, determined by whether there was an attempt to treat the neonate and defined as a composite of surfactant therapy, immediate assisted ventilation at birth, assisted ventilation more than 6 hours in duration, and/or antibiotic therapy. Frequencies, mean annual percent change (APC), and adjusted risk ratios (aRRs) were estimated. Results: Of 26 986 716 live births, 61 908 (0.2%) were periviable live births included in this study: 5% were Asian/Pacific Islander, 37% Black, 24% Hispanic, and 34% White; and 14% were born at 22 weeks, 21% at 23 weeks, 30% at 24 weeks, and 34% at 25 weeks. Fifty-two percent of neonates received active treatment. From 2014 to 2020, the overall frequency (mean APC per year) of active treatment increased significantly (3.9% [95% CI, 3.0% to 4.9%]), as well as among all racial and ethnic subgroups (Asian/Pacific Islander: 3.4% [95% CI, 0.8% to 6.0%]); Black: 4.7% [95% CI, 3.4% to 5.9%]; Hispanic: 4.7% [95% CI, 3.4% to 5.9%]; and White: 3.1% [95% CI, 1.1% to 4.4%]) and among each gestational age range (22 weeks: 14.4% [95% CI, 11.1% to 17.7%] and 25 weeks: 2.9% [95% CI, 1.5% to 4.2%]). Compared with neonates born to White individuals (57.0%), neonates born to Asian/Pacific Islander (46.2%; risk difference [RD], -10.81 [95% CI, -12.75 to -8.88]; aRR, 0.82 [95% CI, [0.79-0.86]), Black (51.6%; RD, -5.42 [95% CI, -6.36 to -4.50]; aRR, 0.90 [95% CI, 0.89 to 0.92]), and Hispanic (48.0%; RD, -9.03 [95% CI, -10.07 to -7.99]; aRR, 0.83 [95% CI, 0.81 to 0.85]) individuals were significantly less likely to receive active treatment. Conclusions and Relevance: From 2014 to 2020 in the US, the frequency of active treatment among neonates born alive between 22 weeks 0 days and 25 weeks 6 days significantly increased, and there were differences in rates of active treatment by race and ethnicity.