Navigating a 'Perfect Storm' on the Path to Prevention of Type 2 Diabetes Mellitus After Gestational Diabetes: Lessons from Patient and Provider Narratives.

Objectives Complications of pregnancy such as gestational diabetes mellitus (GDM) forewarn future chronic illness and disability, and demonstrate the need for a life course approach to prevention. Our study had two aims: (1) to elucidate how experiences reported by patients and providers converge to facilitate or impede follow-up care after GDM, and (2) to elicit recommendations for system-level changes to enhance prevention across key care transitions. Methods We conducted in-depth interviews with 30 GDM patients and 29 providers of maternity, specialty and primary care in an urban safety hospital network, and used a three-tiered thematic analysis to interpret their narratives. Results Findings reveal that a 'perfect storm' gathers on the path to prevention across stages of care. At diagnosis, patients feel profound anxiety about the debilitating effects of type 2 diabetes mellitus in their communities, providers choose reassurance over risk communication, and both focus primarily on the birth of a healthy baby. Providers report that clinical teams often lack coordination, and confuse patients with a barrage of often-inconsistent advice. In the postpartum period, providers juggle competing clinical priorities and mothers juggle overwhelming demands; for both, the recommended 2-h oral glucose tolerance test is too arduous for women and providers to do as prescribed. Finally, the transition from maternity to primary care is complicated by communication barriers between clinicians and patients, and between maternity and primary care providers. Conclusions for Practice Respondents propose systems innovations to open communication between provider specialties in order to bridge the chasm between reproductive care and life course prevention.

Onset of T2DM after gestational diabetes: What the prevention paradox tells us about risk.

This study investigates the effect of severity of gestational diabetes (GDM) on likelihood of post-delivery glucose testing and early onset Type 2 diabetes (T2DM). We asked if clinical focus on relative risk (RR), i.e. greater probability of T2DM onset in a higher-severity group, contributes to missed opportunities for prevention among women with lower-severity GDM. A sample of 12,622 continuously-insured women with GDM (2006-2015) was drawn from a large national dataset (OptumLabs® Data Warehouse) and followed for 3-years post-delivery. Higher-severity GDM was defined as addition of hypoglycemic therapy to standard of care for GDM. We found that women with higher-severity (n = 2627) were twice as likely as lower-severity women (n = 9995) to obtain glucose testing post-delivery. Moreover, 357 (13.6%) of the higher-severity women developed T2DM by year-3 vs. 600 (6.0%) lower-severity women. In an analysis of the population attributable fraction (PAF), defined as the contribution of excess risk to population prevalence, lower-severity women contributed more cases to diabetes rates than higher-risk women (PAF 79% vs. 21%), despite an increased RR in the higher-severity group (13.6% vs. 6.0%, RR 2.26, 95%CI 2.00, 2.56). Projecting out to the 327,950 U.S. deliveries in 2014, we estimate that 9277 higher-severity women (13.6%) and 15,584 lower-severity women (6.0%), will have developed T2DM by 2018. These data demonstrate that lower-severity GDM contributes substantially to the diabetes epidemic. Greater awareness of clinical and cost implications of gaps in follow-up for lower-severity GDM may strengthen the likelihood of post-delivery testing and primary care referral, and thus reinforce the path to prevention.

Effect of Immediate Referral vs a Brief Problem-solving Intervention for Screen-Detected Peripartum Depression: A Randomized Clinical Trial.

Importance: The US Preventive Services Task Force recommends screening adults for depression in settings with programs in place to ensure receipt of appropriate care. Best practices regarding how to ensure such care are unknown, particularly for pregnant and postpartum persons. Objective: To compare the effectiveness of 2 strategies for the initial management of screen-detected peripartum depressive symptoms. Design, Setting, and Participants: This randomized comparative effectiveness trial was performed from February 1, 2018, to June 30, 2020, at the prenatal clinic, postpartum unit, and pediatric clinic within an urban safety-net hospital. Participants included peripartum persons with positive depression screen results. Data were analyzed from July 6, 2020, to September 21, 2022, based on intention to treat. Interventions: Engagement-focused care coordination (EFCC), which used shared decision-making and motivational techniques to refer patients to outside mental health services, and problem-solving education (PSE), a brief cognitive-behavioral program delivered at the screening site. Main Outcomes and Measures: The primary outcome consisted of severity of depressive symptoms; secondary outcomes included severity of anxiety symptoms and engagement with care, each measured bimonthly over 12 months. Rates of symptom elevations were modeled using negative binomial regression; rates of symptom trajectories were modeled using treatment × time interactions. Results: Among the 230 participants (mean [SD] age, 29.8 [5.8] years), 125 (54.3%) were Black and 101 (43.9%) were Hispanic or Latina. At baseline, 117 participants (50.9%) reported at least moderately severe depressive symptoms (Quick Inventory of Depressive Symptomatology score ≥11), and 56 (24.3%) reported clinically significant anxiety symptoms (Beck Anxiety Inventory score ≥21). Across 6 assessment time points, the mean (SD) number of moderately severe depressive symptom episodes in EFCC was 2.2 (2.2), compared with 2.2 (2.1) in PSE, for an adjusted rate ratio (aRR) of 0.95 (95% CI, 0.77-1.17). The mean (SD) number of anxiety symptom elevations in EFCC was 1.1 (1.8), compared to 1.1 (1.6) in PSE, for an aRR of 0.98 (95% CI, 0.69-1.39). There were significant treatment × time interactions relative to mean depressive symptom scores (-0.34 [95% CI, -0.60 to -0.08]; P = .009 for interaction term), favoring EFCC. There were no differences in engagement with care. Conclusions and Relevance: In this randomized comparative effectiveness trial, there were no differences in depressive or anxiety symptom burden across comparators; however, the evidence suggested improved depressive symptom trajectory with immediate referral. Further work is necessary to guide approaches to management following depression screening for peripartum persons. Trial Registration: ClinicalTrials.gov Identifier: NCT03221556.

Mistreatment Experiences, Protective Workplace Systems, and Occupational Distress in Physicians.

Importance: Reducing physician occupational distress requires understanding workplace mistreatment, its relationship to occupational well-being, and how mistreatment differentially impacts physicians of diverse identities. Objectives: To assess the prevalence and sources of mistreatment among physicians and associations between mistreatment, occupational well-being, and physicians' perceptions of protective workplace systems. Design, Setting, and Participants: This survey study was administered in September and October 2020 to physicians at a large academic medical center. Statistical analysis was performed from May 2021 to February 2022. Main Outcomes and Measures: Primary measures were the Professional Fulfillment Index, a measure of intent to leave, and the Mistreatment, Protection, and Respect Measure (MPR). Main outcomes were the prevalence and sources of mistreatment. Secondary outcomes were the associations of mistreatment and perceptions of protective workplace systems with occupational well-being. Results: Of 1909 medical staff invited, 1505 (78.8%) completed the survey. Among respondents, 735 (48.8%) were women, 627 (47.1%) were men, and 143 (9.5%) did not share gender identity or chose "other"; 12 (0.8%) identified as African American or Black, 392 (26%) as Asian, 10 (0.7%) as multiracial, 736 (48.9%) as White, 63 (4.2%) as other, and 292 (19.4%) did not share race or ethnicity. Of the 1397 respondents who answered mistreatment questions, 327 (23.4%) reported experiencing mistreatment in the last 12 months. Patients and visitors were the most common source of mistreatment, reported by 232 physicians (16.6%). Women were more than twice as likely as men to experience mistreatment (31% [224 women] vs 15% [92 men]). On a scale of 0 to 10, mistreatment was associated with a 1.13 point increase in burnout (95% CI, 0.89 to 1.36), a 0.99-point decrease in professional fulfillment (95% CI, -1.24 to -0.73), and 129% higher odds of moderate or greater intent to leave (odds ratio, 2.29; 95% CI, 1.75 to 2.99). When compared with a perception that protective workplace systems are in place "to a very great extent," a perception that there are no protective workplace systems was associated with a 2.41-point increase in burnout (95% CI, 1.80 to 3.02), a 2.81-point lower professional fulfillment score (95% CI, -3.44 to -2.18), and 711% higher odds of intending to leave (odds ratio, 8.11; 95% CI, 3.67 to 18.35). Conclusions and Relevance: This survey study found that mistreatment was common among physicians, varied by gender, and was associated with occupational distress. Patients and visitors were the most frequent source, and perceptions of protective workplace systems were associated with better occupational well-being. These findings suggest that health care organizations should prioritize reducing workplace mistreatment.

Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort.

RATIONALE: Stress-elicited disruption of immunity begins in utero. OBJECTIVES: Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families). METHODS: Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age). MEASUREMENTS AND MAIN RESULTS: Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-alpha to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced IFN-gamma. CONCLUSIONS: Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.

Parental characteristics, somatic fetal growth, and season of birth influence innate and adaptive cord blood cytokine responses.

BACKGROUND: Immunologic responses at birth likely relate to subsequent risks for allergic diseases and wheezing in infancy; however, the influences of parental characteristics and prenatal factors on neonatal immune responses are incompletely understood. OBJECTIVE: This study investigates potential correlations between urban parental, prenatal, and perinatal factors on innate and adaptive stimuli-induced cytokine responses. METHODS: Five hundred sixty and 49 children of parents with and without allergic disease or asthma, respectively, were enrolled into a prospective birth cohort study (Urban Environment and Childhood Asthma). Cord blood mononuclear cells were incubated with innate and adaptive immune stimuli, and cytokine responses (ELISA) were compared with season of birth, parental characteristics, in utero stressors, and fetal growth. RESULTS: Many cytokine responses varied by season of birth, including 2-fold to 3-fold fluctuations with specific IFN-alpha and IFN-gamma responses. Birth weight was inversely associated with IFN-gamma responses to respiratory syncytial virus (R = -0.16), but positively associated with IL-8 responses to a variety of innate stimuli (R = 0.08-0.12). Respiratory syncytial virus-induced cytokine responses were 21% to 54% lower in children of mothers with asthma. Cytokine responses were generally lower in babies born to parents with allergy/asthma. CONCLUSIONS: Innate cytokine responses are associated with parental allergic or airway disease, somatic fetal growth, ethnicity, and season of birth. Collectively, these findings suggest that urban prenatal exposures and familial factors affect the development of the fetal immune system.

Congenital Zika syndrome arising from sexual transmission of Zika virus, a case report.

BACKGROUND: Sexual transmission of Zika virus is well documented and pregnant women are advised to abstain or use barrier protection if a sexual partner has risk for Zika infection. However, to date there has not been a documented case of the congenital Zika syndrome resulting from sexual transmission. CASE PRESENTATION: A 32 year-old woman who had not traveled to any area with local Zika transmission in years became pregnant via frozen embryo transfer. Her husband traveled to Haiti several times prior to embryo transfer and during the pregnancy. Neither partner was ever symptomatic. In her second trimester when recommendations were published by the Centers for Disease Control and Prevention (CDC) regarding prevention of sexual transmission during pregnancy she was counseled to abstain or use barrier protection with her partner. At delivery, the infant head circumference measured less than the first percentile. Placental samples were sent to the CDC and all were positive for Zika RNA by RT-PCR. Evaluation for other causes of microcephaly was negative. Consistent with the most up to date diagnostic parameters for congenital Zika, including viral infection of the placenta, the baby was diagnosed with congenital Zika syndrome. CONCLUSIONS: Transmission via sexual contact during assisted reproductive therapies (ART) and pregnancy can result in Zika fetopathy. This case supports recommendations to counsel women undergoing ART and pregnant women to use barrier protection with partners with Zika exposure regardless of their symptoms.

Interrupting the Pathway from Gestational Diabetes Mellitus to Type 2 Diabetes: The Role of Primary Care.

OBJECTIVE: Our objective was to describe patient-, provider-, and health systems-level factors associated with likelihood of obtaining guideline-recommended follow-up to prevent or mitigate early-onset type 2 diabetes after a birth complicated by gestational diabetes mellitus (GDM). METHODS: This study presents a retrospective cohort analysis of de-identified demographic and health care system characteristics, and clinical claims data for 12,622 women with GDM who were continuously enrolled in a large, national U.S. health plan from January 31, 2006, to September 30, 2012. Data were obtained from the OptumLabs Data Warehouse. We extracted 1) known predictors of follow-up (age, race, education, comorbidities, GDM severity); 2) novel factors that had potential as predictors (prepregnancy use of preventive measures and primary care, delivery hospital size); and 3) outcome variables (glucose testing within 1 and 3 years and primary care visit within 3 years after delivery). RESULTS: Asian ethnicity, higher education, GDM severity, and delivery in a larger hospital predicted greater likelihood of post-GDM follow-up. Women with a prepregnancy primary care visit of any type were two to three times more likely to receive postpartum glucose testing and primary care at 1 year, and 3.5 times more likely to have obtained testing and primary care at 3 years after delivery. CONCLUSIONS: A history of use of primary care services before a pregnancy complicated by GDM seems to enhance the likelihood of postdelivery surveillance and preventive care, and thus reduce the risk of undetected early-onset type 2 diabetes. An emphasis on promoting early primary care connections for women in their early reproductive years, in addition to its overall value, is a promising strategy for ensuring follow-up testing and care for women after complicated pregnancies that forewarn risk for later chronic illness. Health systems should focus on models of care that connect primary and reproductive/maternity care before, during, and long after pregnancies occur.

After Gestational Diabetes: Impact of Pregnancy Interval on Recurrence and Type 2 Diabetes.

The contribution of pregnancy interval after gestational diabetes (GDM) to type 2 diabetes (T2DM) onset is a poorly understood but potentially modifiable factor for T2DM prevention. The purpose of this study was to assess the impact of GDM recurrence and/or delivery interval on follow-up care and T2DM onset in a sample of continuously insured women with a term livebirth within 3 years of a GDM-affected delivery. This is a secondary analysis of a cohort of 12,622 women with GDM, 2006-2012, drawn from a national administrative data system (OptumLabs Data Warehouse). We followed 1091 women with GDM who had a subsequent delivery within 3 years of their index delivery. GDM recurred in 49.3% of subsequent pregnancies regardless of the interval to the next conception. Recurrence tripled the odds of early T2DM onset within 3 years of the second delivery. Women with GDM recurrence had greater likelihood of glucose testing in that 3-year interval, but not transition to primary care for continued monitoring, as required by both American Congress of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) guidelines. In multivariable analysis, we found a trend toward increased likelihood of T2DM onset for short interpregnancy intervals (≤1 year vs. 3 year, 0.08). Pregnancy interval may play a previously unrecognized role in progression to T2DM. T2DM onset after GDM can be prevented or mitigated, but many women in even this insured sample did not receive recommended follow-up monitoring and preventive care, even after a GDM recurrence. The postpartum visit may be an ideal time to inform patients about T2DM prevention opportunities, and discuss potential benefits of optimal spacing of future pregnancies.

Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples.

Preterm birth (PTB) affects one in six Black babies in the United States. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort. DNAm in maternal blood and/or cord blood was measured using the Illumina HumanMethylation450 BeadChip. We identified 45 DNAm loci in maternal blood associated with early sPTB, with a false discovery rate (FDR) <5%. Replication analyses confirmed sPTB associations for cg03915055 and cg06804705, located in the promoter regions of the CYTIP and LINC00114 genes, respectively. Both loci had comparable associations with early sPTB and early medically-indicated PTB, but attenuated associations with late sPTB. These associations could not be explained by cell composition, gestational complications, and/or nearby maternal genetic variants. Analyses in the newborns of the 110 Black women showed that cord blood methylation levels at both loci had no associations with PTB. The findings from this study underscore the role of maternal DNAm in PTB risk, and provide a set of maternal loci that may serve as biomarkers for PTB. Longitudinal studies are needed to clarify temporal relationships between maternal DNAm and PTB risk.

The Association of Maternal Asthma and Early Pregnancy Vitamin D with Risk of Preeclampsia: An Observation From Vitamin D Antenatal Asthma Reduction Trial (VDAART).

BACKGROUND: Maternal asthma, uncontrolled asthma, and low vitamin D levels during pregnancy have been individually linked to increased risk of preeclampsia. OBJECTIVE: To investigate the association of history of physician-diagnosed asthma and uncontrolled asthma status during pregnancy with the risk of preeclampsia and the effects of early pregnancy vitamin D concentrations on this relationship. METHODS: A total of 816 subjects with available pregnancy outcome data and risk factors of interest were analyzed. A group of experienced obstetricians and gynecologists from 3 study centers validated the preeclampsia diagnoses. Vitamin D was measured using the DiaSorin method at 10 to 18 weeks of gestation. The Pregnancy-Asthma Control Test was used to assess asthma control during pregnancy. Criterion-based stepwise variable selection algorithm was applied to investigate the relationships of risk factors of interest (history of asthma diagnosis, uncontrolled asthma during pregnancy, and vitamin D) to preeclampsia. RESULTS: The incidence of preeclampsia was not related to the presence of asthma diagnosis (8.9% with vs 7.4% without). The adjusted odds of preeclampsia controlled for maternal serum 25-hydroxyvitamin D (25OHD) concentrations was higher for women with a higher proportion of uncontrolled asthma months per visit during pregnancy (adjusted odds ratio, 3.55; 95% CI, 1.15-13.0). Adjusting for asthma control status during pregnancy, an additional decrease in the associated preeclampsia risk by 7% was observed for a 10-unit (ng/mL) increase in early pregnancy 25OHD levels (adjusted odds ratio10-unit, 0.60; 95% CI, 0.43-0.82) as compared with the previous risk estimate of preeclampsia associated with low maternal 25OHD unadjusted for asthma control status. CONCLUSIONS: Uncontrolled asthma during pregnancy is associated with an increased risk of preeclampsia. Early pregnancy 25OHD contributes to the association of uncontrolled asthma status with preeclampsia.

Pregnancy outcomes in women with congenital heart disease.

BACKGROUND: Pregnant women with congenital heart disease are at increased risk for cardiac and neonatal complications, yet risk factors for adverse outcomes are not fully defined. METHODS AND RESULTS: Between January 1998 and September 2004, 90 pregnancies at age 27.7+/-6.1 years were followed in 53 women with congenital heart disease. Spontaneous abortions occurred in 11 pregnancies at 10.8+/-3.7 weeks, and 7 underwent elective pregnancy termination. There were no maternal deaths. Primary maternal cardiac events complicated 19.4% of ongoing pregnancies, with pulmonary edema in 16.7% and sustained arrhythmias in 2.8%. Univariate risk factors included prior history of heart failure (odds ratio [OR], 15.5), NYHA functional class > or =2 (OR, 5.4), and decreased subpulmonary ventricular ejection fraction (OR, 7.7). Independent predictors were decreased subpulmonary ventricular ejection fraction and/or severe pulmonary regurgitation (OR, 9.0) and smoking history (OR, 27.2). Adverse neonatal outcomes occurred in 27.8% of ongoing pregnancies and included preterm delivery (20.8%), small for gestational age (8.3%), respiratory distress syndrome (8.3%), intraventricular hemorrhage (1.4%), intrauterine fetal demise (2.8%), and neonatal death (1.4%). A subaortic ventricular outflow tract gradient >30 mm Hg independently predicted an adverse neonatal outcome (OR, 7.5). Cardiac risk assessment was improved by including decreased subpulmonary ventricular systolic function and/or severe pulmonary regurgitation (OR, 10.3) in a previously proposed risk index developed in pregnant women with acquired and congenital heart disease. CONCLUSIONS: Maternal cardiac and neonatal complication rates are considerable in pregnant women with congenital heart disease. Patients with impaired subpulmonary ventricular systolic function and/or severe pulmonary regurgitation are at increased risk for adverse cardiac outcomes.

Follow-up after gestational diabetes: a fixable gap in women's preventive healthcare.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a known harbinger of future type 2 diabetes mellitus (T2DM), hypertension, and cardiac disease. This population-based study was designed to identify gaps in follow-up care relevant to prevention of T2DM in a continuously insured sample of women diagnosed with GDM. RESEARCH DESIGN AND METHODS: We analyzed data spanning 2005-2015 from OptumLabs Data Warehouse, a comprehensive, longitudinal, real-world data asset with deidentified lives across claims and clinical information, to describe patterns of preventive care after GDM. Women with GDM were followed, from 1 year preconception through 3 years postdelivery to identify individual and healthcare systems characteristics, and report on GDM-related outcomes: postpartum glucose testing, transition to primary care for monitoring, GDM recurrence, and T2DM onset. RESULTS: Among 12 622 women with GDM, we found low rates of glucose monitoring in the recommended postpartum period (5.8%), at 1 year (21.8%), and at 3 years (51%). A minority had contact with primary care postdelivery (5.7% at 6 months, 13.2% at 1 year, 40.5% at 3 years). Despite increased population risk (GDM recurrence in 52.2% of repeat pregnancies, T2DM onset within 3 years in 7.6% of the sample), 70.1% of GDM-diagnosed women had neither glucose testing nor a primary care visit at 1 year and 32.7% had neither at 3 years. CONCLUSIONS: We found low rates of glucose testing and transition to primary care in this group of continuously insured women with GDM. Despite continuous insurance coverage, many women with a pregnancy complication that portends risk for future chronic illness fail to obtain follow-up testing and may have difficulty navigating between clinician specialties. Results point to a need for action to close the gap between obstetrics and primary care to ensure receipt of preventive monitoring as recommended by both the American Diabetes Association and the American Congress of Obstetricians and Gynecologists.

Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such 'missing heritability' may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10-8; empirical PG × E=1.2 × 10-8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10-9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.

Lost opportunities to prevent early onset type 2 diabetes mellitus after a pregnancy complicated by gestational diabetes.

OBJECTIVES: Gestational diabetes mellitus (GDM) greatly increases the risk of developing diabetes in the decade after delivery, but few women receive appropriately timed postpartum glucose testing (PPGT) or a referral to primary care (PC) for continued monitoring. This qualitative study was designed to identify barriers and facilitators to testing and referral from patient and providers' perspectives. METHODS: We interviewed patients and clinicians in depth about knowledge, values, priorities, challenges, and recommendations for increasing PPGT rates and PC linkage. Interviews were coded with NVIVO data analysis software, and analyzed using an implementation science framework. RESULTS: Women reported motivation to address GDM for the health of the fetus. Most women did not anticipate future diabetes for themselves, and focused on delivery outcomes rather than future health risks. Patients sought and received reassurance from clinicians, and were unlikely to discuss early onset following GDM or preventive measures. PPGT barriers described by patients included provider not mentioning the test or setting it up, transportation difficulties, work responsibilities, fatigue, concerns about fasting while breastfeeding, and timing of the test after discharge from obstetrics, and no referral to PC for follow-up. Practitioners described limited communication among multiple care providers during pregnancy and delivery, systems issues, and separation of obstetrics from PC. CONCLUSIONS: Patients' barriers to PPGT included low motivation for self-care, structural obstacles, and competing priorities. Providers reported the need to balance risk with reassurance, and identified systems failures related to test timing, limitations of electronic medical record systems (EMR), lack of referrals to PC, and inadequate communication between specialties. Prevention of early onset has great potential for medical cost savings and improvements in quality of life.

Early pregnancy vitamin D status and risk of preeclampsia.

BACKGROUND: Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia. METHODS: We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32-38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia. RESULTS: Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61-1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD <30 ng/ml) (adjusted odds ratio, 0.28; 95% CI, 0.10-0.96). Differential expression of 348 vitamin D-associated genes (158 upregulated) was found in peripheral blood of women who developed preeclampsia (FDR <0.05 in the Vitamin D Antenatal Asthma Reduction Trial [VDAART]; P < 0.05 in a replication cohort). Functional enrichment and network analyses of this vitamin D-associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses, including some nodes with a high degree of connectivity. CONCLUSIONS: Vitamin D supplementation initiated in weeks 10-18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia. TRIAL REGISTRATION: ClinicalTrials.gov NCT00920621. FUNDING: Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.

Changes in fetal position during labor and their association with epidural analgesia.

OBJECTIVE: To evaluate whether epidural analgesia is associated with a higher rate of abnormal fetal head position at delivery. METHODS: We conducted a prospective cohort study of 1,562 women to evaluate changes in fetal position during labor by using serial ultrasound examinations. Ultrasound examinations were performed at enrollment, epidural administration, 4 hours after the initial ultrasonography if epidural had not been administered, and late in labor (> 8 cm). Information about fetal head position at delivery was obtained from the provider. RESULTS: Regardless of fetal head position at enrollment (occiput transverse, occiput posterior, or occiput anterior), most fetuses were occiput anterior at delivery (enrollment position: occiput transverse 78%, occiput posterior 80%, occiput anterior 83%, P = .1). Final fetal position was established close to delivery. Of fetuses that were occiput posterior late in labor, only 20.7% were occiput posterior at delivery. Changes in fetal head position were common, and 36% of women had an occiput posterior fetus on at least one ultrasound examination. Women receiving epidural did not have more occiput posterior fetuses at the enrollment (23.4% epidural versus 26.0 no epidural, P = .9) or the epidural/4-hour ultrasound examination (24.9% epidural, 28.3% no epidural), but did have more occiput posterior fetuses at delivery (12.9% epidural versus 3.3% no epidural, P = .002); the association remained in a multivariate model (adjusted odds ratio 4.0, 95% confidence interval 1.4-11.1). CONCLUSION: Fetal position changes are common during labor, with the final fetal position established close to delivery. Our demonstration of a strong association of epidural with fetal occiput posterior position at delivery represents a mechanism that may contribute to the lower rate of spontaneous vaginal delivery consistently observed with epidural.

Obstetric and neonatal outcomes associated with maternal hypothyroid disease.

OBJECTIVE: We sought to determine whether women with treated hypothyroid disease were more likely than women without thyroid disease to suffer adverse obstetric or neonatal outcomes or to deliver a child with a congenital anomaly. METHODS: Using an institutional database, we identified women with treated hypothyroid disease (n = 482) who delivered a baby at our institution during a 33-month period. We compared the occurrence of adverse obstetric or neonatal outcomes among these women to the occurrence among women without thyroid disease (n = 19,487). RESULTS: Women with treated hypothyroid disease were not at increased risk for delivering a baby with low birth- weight,fetal demise, or congenital anomaly compared to the control group. Women with treated hypothyroid disease were more likely to have chronic hypertension (2.3% vs. 1.2%, p = 0.03) and had an increased risk of pre-eclampsia (4.3% vs. 2.6%,p= 0.03) compared to women without thyroid disease. CONCLUSION: Women with treated hypothyroid disease are not at higher risk than the general population for adverse neonatal outcomes, but may be at increased risk for pre-eclampsia.

Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy.

Increased thromboembolic events occur in women with mechanical prosthetic valves during pregnancy, and selecting an effective and safe anticoagulant is still a challenge. Low molecular weight heparin (LMWH) is a promising alternative, but a recent warning and label change about its use in patients with mechanical prosthetic valves has caused confusion among physicians. The aim of the present study was to review the risks of maternal and fetal complications with mechanical heart valves treated with LMWH during pregnancy. We performed a review of the current medical literature through MEDLINE and EMBASE (1989 to 2004). Additional data sources included abstract proceedings, and reference lists of selected articles. Among 81 pregnancies in 75 women, the proportion of valve thrombosis was 8.64% (7/81; 95% CI, 2.52%-14.76%). The frequency of overall thromboembolic complication (TEC) was 12.35% (10/81; 95% CI, 5.19%-19.51%). Nine of ten patients with TEC received a fixed dose of LMWH and two of these received a fixed low dose of LMWH. Among 51 pregnancies whose anti-factor Xa levels were monitored, only one patient was reported to have a thromboembolic complication. The frequency of live births with LMWH was 87.65% (95%CI, 80.49%-94.81%). In pregnant women with mechanical heart valves, LMWH appears to be a suitable option to a vitamin K antagonist. The use of LMWH warrants monitoring and appropriate dose adjustments to maintain a 4-6 hr post-injection anti-factor Xa level at a minimum of 1.0 U/ml to decrease the incidence of TEC.

Association of rheumatologic disease with preeclampsia.

OBJECTIVE: To determine whether maternal rheumatologic disease is associated with an increased risk of adverse obstetric or neonatal outcomes. METHODS: Using an institutional database, we identified all women with diagnosed rheumatologic disease (n = 114) who delivered a baby at our institution during a 33-month period. We compared the incidence of adverse obstetric and neonatal outcomes among these women with the incidence among women without rheumatologic diseases (n = 18,534). RESULTS: Women with rheumatologic diseases were more likely to have preeclampsia than women without rheumatologic disease (8.8% versus 2.3%, P <.001) Women with rheumatologic diseases were also at increased risk of preterm delivery (15.2% versus 7.8%, P =.002) and small-for-gestational-age infants (8.0% versus 3.1%, P =.001) compared with women without rheumatologic disease. CONCLUSION: The finding that women with rheumatologic diseases are at increased risk of adverse obstetric outcomes suggests a need for heightened clinical vigilance and further research into the common pathophysiologic correlates. LEVEL OF EVIDENCE: II-2