Association Between Neighborhood Deprivation in Early Pregnancy and Gestational Diabetes Mellitus.

OBJECTIVE: To evaluate whether having a pregnancy in a deprived neighborhood was associated with an increased risk of gestational diabetes mellitus (GDM) compared with having a pregnancy in the least-deprived neighborhoods. METHODS: This was a retrospective observational cohort study of pregnant individuals within Kaiser Permanente Northern California from 2011 to 2018 with residential history from prepregnancy through 24 weeks of gestation and clinical data from prepregnancy through delivery. The primary outcome was a diagnosis of GDM. Neighborhood deprivation was characterized with an index aggregating multiple indicators of Census tract-level sociodemographic information. Mediation analysis using inverse odds ratio weighting estimated the mediation effects of prepregnancy body mass index (BMI), gestational weight gain, smoking tobacco, and illegal drug use before GDM diagnosis. RESULTS: Overall, 214,375 pregnant individuals were included, and 11.3% had a diagnosis of GDM. Gestational diabetes prevalence increased with neighborhood deprivation from 10.0% in the lowest Neighborhood Deprivation Index quintile to 12.7% in the highest quintile. Compared with pregnant individuals in the least deprived neighborhoods (quintile 1), pregnant individuals in quintiles 2-5 had elevated risk of GDM (relative risk [95% CI]) when adjusted for maternal age, parity, insurance type, and residential history (quintile 2, 1.17 [1.10-1.23]; quintile 3, 1.38 [1.30-1.46]; quintile 4, 1.54 [1.45-1.63]; quintile 5, 1.71 [1.62-1.82]). There was a dose-response relationship between relative risk of GDM and increasing quintile of neighborhood deprivation (P for trend <.001). Prepregnancy BMI mediated 45.8% (95% CI, 40.9-50.7%) of the association. Other potential mediators were found to mediate a small if not negligible proportion of this association (2.4-3.6%). CONCLUSION: Neighborhood deprivation was associated with GDM, and a considerable proportion of this relationship was mediated by prepregnancy BMI.

Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes.

OBJECTIVE: Metformin is the most common treatment for type 2 diabetes (T2D). However, there have been no pharmacogenomic studies for T2D in which a population of color was used in the discovery analysis. This study sought to identify genomic variants associated with metformin response in African American patients with diabetes. RESEARCH DESIGN AND METHODS: Patients in the discovery set were adult, African American participants from the Diabetes Multi-omic Investigation of Drug Response (DIAMOND), a cohort study of patients with T2D from a health system serving southeast Michigan. DIAMOND participants had genome-wide genotype data and longitudinal electronic records of laboratory results and medication fills. The genome-wide discovery analysis identified polymorphisms correlated to changes in glycated hemoglobin (HbA1c) levels among individuals on metformin monotherapy. Lead associations were assessed for replication in an independent cohort of African American participants from Kaiser Permanente Northern California (KPNC) and in European American participants from DIAMOND. RESULTS: The discovery set consisted of 447 African American participants, whereas the replication sets included 353 African American KPNC participants and 466 European American DIAMOND participants. The primary analysis identified a variant, rs143276236, in the gene ARFGEF3, which met the threshold for genome-wide significance, replicated in KPNC African Americans, and was still significant in the meta-analysis (P = 1.17 × 10-9). None of the significant discovery variants replicated in European Americans DIAMOND participants. CONCLUSIONS: We identified a novel and biologically plausible genetic variant associated with a change in HbA1c levels among African American patients on metformin monotherapy. These results highlight the importance of diversity in pharmacogenomic studies.

Mediating Effects of Cardiometabolic Risk Factors on the Association Between Maternal Race-Ethnicity and Cesarean Delivery Among Low-Risk Women.

Background: While racial-ethnic disparities in cesarean delivery rates among nulliparous women delivering a term singleton in the vertex position (NTSV) exist, it remains unclear the extent to which potentially modifiable maternal cardiometabolic risk factors (obesity, maternal hyperglycemia and hypertensive disorders) underlie these disparities. We examined race-ethnicity and risk of NTSV cesarean deliveries and whether the associations were mediated by maternal cardiometabolic risk factors. Materials and Methods: A cohort study of 62,048 NTSV deliveries in Kaiser Permanente Northern California. The outcome was cesarean delivery. Results: Black, Asian, and Hispanic women were at increased risk of having a NTSV cesarean delivery compared with White women (relative risks and 95% confidence intervals: 1.37 [1.28-1.45]; 1.11 [1.07-1.16]; 1.12 [1.07-1.16], respectively), independent of established risk factors and prenatal care utilization. The extent to which cardiometabolic risk factors mediated the associations between race-ethnicity (each group vs. White, in separate analyses) and NTSV cesarean delivery varied by race-ethnicity. Maternal overweight/obesity (body mass index ≥25.0) mediated the association between Black and Hispanic race-ethnicity and NTSV cesarean delivery (21.1% [15.8-26.4] and 24.7% [14.6-34.8, respectively), but not for Asian race. Maternal hyperglycemia (gestational diabetes mellitus or preexisting diabetes) mediated the association between Asian and Hispanic race and NTSV cesarean delivery (18.5% [9.8-27.2] and 9.8% [5.0-14.7], respectively), but not for Black race. Hypertensive disorders mediated 3.2% (0.70-5.8) of the association between Black race and cesarean delivery, but not for other race-ethnicities. Conclusion: Black, Asian, and Hispanic women are at increased risk for NTSV cesarean deliveries. Maternal cardiometabolic risk factors only partially mediate the associations between race-ethnicity and NSTV cesarean deliveries.

A Pre-Pregnancy Biomarker Risk Score Improves Prediction of Future Gestational Diabetes.

CONTEXT: Previous studies have not examined the ability of multiple preconception biomarkers, considered together, to improve prediction of gestational diabetes mellitus (GDM). OBJECTIVE: To develop a preconception biomarker risk score and assess its association with subsequent GDM. DESIGN: A nested case-control study among a cohort of women with serum collected as part of a health examination (1984 to 1996) and subsequent pregnancy (1984 to 2009). Biomarkers associated with GDM were dichotomized into high/low risk. SETTING: Integrated health care system. PARTICIPANTS: Two controls were matched to each GDM case (n = 256 cases) on year and age at examination, age at pregnancy, and number of pregnancies between examination and index pregnancy. MAIN OUTCOME MEASURE: GDM. RESULTS: High-risk levels of sex hormone-binding globulin (SHBG; <44.2 nM), glucose (>90 mg/dL), total adiponectin (<7.2 µg/mL), and homeostasis model assessment-estimated insulin resistance (>3.9) were independently associated with 2.34 [95% confidence interval (CI): 1.50, 3.63], 2.03 (95% CI: 1.29, 3.19), 1.83 (95% CI: 1.16, 2.90), and 1.67 (95% CI: 1.07, 2.62) times the odds of GDM and included in the biomarker risk score. For each unit increase in the biomarker risk score, odds of GDM were 1.94 times greater (95% CI: 1.59, 2.36). A biomarker risk score including only SHBG and glucose was sufficient to improve prediction beyond established risk factors (age, race/ethnicity, body mass index, family history of diabetes, previous GDM; area under the curve = 0.73 vs 0.67, P = 0.002). CONCLUSIONS: The improved, predictive ability of the biomarker risk score beyond established risk factors suggests clinical use of the biomarker risk score in identifying women at risk for GDM before conception for targeted prevention strategies.

A cohort study of maternal cardiometabolic risk factors and primary cesarean delivery in an integrated health system.

BACKGROUND: Maternal cardiometabolic risk factors (i.e., hyperglycemia, pre-existing hypertension and high body mass index) impact fetal growth and risk of having a cesarean delivery. However, the independent and joint contribution of maternal cardiometabolic risk factors to primary cesarean section is unclear. We aimed to elucidate the degree to which maternal cardiometabolic risk factors contribute to primary cesarean deliveries and whether associations vary by infant size at birth in an integrated health system. METHODS: A cohort study of 185,045 singleton livebirths from 2001 to 2010. Poisson regression with robust standard errors provided crude and adjusted relative risks (RR) and 95% confidence intervals (CIs) for cesarean delivery risk associated with risk factors. We then estimated the proportion of cesarean sections that could be prevented if the cardiometabolic risk factor in pregnant women were eliminated (the population-attributable risk [PAR]). RESULTS: In a single multivariable model, maternal cardiometabolic risk factors were independently associated with cesarean delivery: RR (95% CI) abnormal glucose screening 1.04 (1.01-1.08); gestational diabetes 1.18 (1.11-1.18) and pre-existing diabetes 1.60 (1.49-1.71); pre-existing hypertension 1.16 (1.10-1.23); overweight 1.27 (1.24-1.30); obese class I 1.46 (1.42-1.51); obese class II 1.73 (1.67-1.80); and obese class III 1.97 (1.88-2.07); adjusting for established risk factors, medical facility and year. The associations between maternal cardiometabolic risk factors and primary cesarean delivery remained among infants with appropriate weights for gestational age. The PARs were 17.4% for overweight/obesity, 7.0% for maternal hyperglycemia, 2.0% for pre-existing hypertension and 20.5% for any cardiometabolic risk factor. CONCLUSIONS: Maternal cardiometabolic risk factors were independently associated with risk of primary cesarean delivery, even among women delivering infants born at an appropriate size for gestational age. Effective strategies to increase the proportion of women entering pregnancy at an optimal weight with normal blood pressure and glucose before pregnancy could potentially eliminate up to 20% of cesarean deliveries.

Trimester-Specific Gestational Weight Gain and Infant Size for Gestational Age.

Gestational weight gain is known to influence fetal growth. However, it is unclear whether the associations between gestational weight gain and fetal growth vary by trimester. In a diverse cohort of 8,977 women who delivered a singleton between 2011 and 2013, we evaluated the associations between trimester-specific gestational weight gain and infant size for gestational age. Gestational weight gain was categorized per the 2009 Institute of Medicine (IOM) recommendations; meeting the recommendations was the referent. Large for gestational age and small for gestational age were defined as birthweight > 90th percentile or <10th percentile, respectively, based on a national reference standard birthweight distribution. Logistic regression models estimated the odds of having a large or small for gestational age versus an appropriate for gestational age infant. Only gestational weight gain exceeding the IOM recommendations in the 2nd and 3rd trimesters independently increased the odds of delivering a large for gestational age infant (Odds Ratio (95% Confidence Interval): 1st: 1.17 [0.94, 1.44], 2nd: 1.47 [1.13, 1.92], 3rd: 1.70 [1.30, 2.22]). Gestational weight gain below the IOM recommendations increased the likelihood of having a small for gestational age infant in the 2nd trimester only (1.76 [1.23, 2.52]). There was effect modification, and gestational weight gain below the IOM recommendations increased the likelihood of having a small for gestational age infant in the 2nd trimester and only among women with a pre-pregnancy body mass index from 18.5-24.9 kg/m2 (2.06 [1.35, 3.15]). These findings indicate that gestational weight gain during the 2nd and 3rd trimesters is more strongly associated with infant growth. Interventions to achieve appropriate gestational weight gain may optimize infant size at birth.

Prepregnancy Adverse Lipid Profile and Subsequent Risk of Gestational Diabetes.

CONTEXT: Lower low-density lipoprotein (LDL) peak diameter and a predominance of small, dense LDL are associated with type 2 diabetes, but it is unclear whether they are a risk factor for gestational diabetes mellitus (GDM). OBJECTIVE: To evaluate whether prepregnancy lipid profile predicts the development of GDM during pregnancy. DESIGN: A nested case-control study among women who participated in a multiphasic health exam, where blood was collected and stored between 1984 and 1996, and who then had a subsequent pregnancy between 1984 and 2009. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Cases were 254 women who developed GDM. Two controls were selected for each case and matched for year of blood draw, age at baseline, age at pregnancy, and number of intervening pregnancies. MAIN OUTCOME MEASURES: Prepregnancy LDL peak diameter and prepregnancy lipid subfraction concentrations grouped according to size, and the odds of developing GDM. RESULTS: Women in the lowest quartiles of LDL peak diameter and high-density lipoprotein had increased odds of GDM compared with women in the highest quartiles (odds ratio [95% CI], 2.60 [1.37-4.94] and 1.98 [1.01-3.86], respectively), in multivariable adjusted models. Being in the highest quartile of small and very small LDL subfractions also increased the odds of GDM (2.61 [1.35-5.03] and 2.44 [1.22-4.85], respectively). CONCLUSIONS: Lower LDL peak diameter size and high-density lipoprotein levels and higher levels of small and very small LDL subfraction groups were present years before pregnancy in women who developed GDM. A prepregnancy atherogenic lipid profile may help identify women at risk of GDM to target for prevention.

Pregravid liver enzyme levels and risk of gestational diabetes mellitus during a subsequent pregnancy.

OBJECTIVE: Liver enzymes are independent predictors of type 2 diabetes. Although liver fat content correlates with features of insulin resistance, a risk factor for developing gestational diabetes mellitus (GDM), the relationship between liver enzymes and GDM is unclear. The objective of this study was to assess whether pregravid liver enzyme levels are associated with subsequent risk of GDM. RESEARCH DESIGN AND METHODS: A nested case-control study was conducted among women who participated in the Kaiser Permanente Northern California multiphasic health checkup (1984-1996) and had a subsequent pregnancy (1984-2009). Case patients were 256 women who developed GDM. Two control subjects were selected for each case patient and matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies. RESULTS: Being in the highest quartile versus the lowest quartile of γ-glutamyl transferase (GGT) levels was associated with a twofold increased risk of subsequent GDM (odds ratio 1.97 [95% CI 1.14-3.42]), after adjusting for race/ethnicity, prepregnancy BMI, family history of diabetes, and alcohol use. This result was attenuated after adjusting for homeostasis model assessment of insulin resistance (HOMA-IR), fasting status, and rate of gestational weight gain. There was significant interaction between GGT and HOMA-IR; the association with GGT was found among women in the highest tertile of HOMA-IR. Aspartate aminotransferase and alanine aminotransferase were not associated with increased GDM risk. CONCLUSIONS: Pregravid GGT level, but not alanine aminotransferase or aspartate aminotransferase level, predicted the subsequent risk of GDM. Markers of liver fat accumulation, such as GGT level, are present years before pregnancy and may help to identify women at increased risk for subsequent GDM.

Maternal gestational weight gain and offspring risk for childhood overweight or obesity.

OBJECTIVE: The objective of the study was to evaluate the association between gestational weight gain, per the 2009 Institute of Medicine (IOM) recommendations, and offspring overweight/obesity at 2-5 years of age. STUDY DESIGN: This was a prospective cohort study of 4145 women who completed a health survey (2007-2009) and subsequently delivered a singleton at Kaiser Permanente Northern California (2007-2010). Childhood overweight/obesity was defined as a body mass index (BMI) z-score of the 85th percentile or greater of the Centers for Disease Control and Prevention child growth standards. Gestational weight gain was categorized according to the 2009 IOM recommendations. Logistic regression was used; meeting the IOM recommendations was the referent. RESULTS: Exceeding the IOM recommendations was associated with a 46% increase in odds of having an overweight/obese child (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.17-1.83), after adjusting for maternal prepregnancy BMI, race/ethnicity, age at delivery, education, child age, birthweight, gestational age at delivery, gestational diabetes, parity, infant sex, total metabolic equivalents, and dietary pattern. The OR (95% CI) for childhood overweight/obesity among women gaining below the IOM recommendations was 1.23 (0.88-1.71). The associations between gaining outside the IOM recommendations and childhood obesity were stronger among women with a normal prepregnancy BMI (OR, 1.63; 95% CI, 1.03-2.57) (below); OR, 1.79; 95% CI, 1.32-2.43) (exceeded). CONCLUSION: Gestational weight gain outside the IOM recommendations is associated with increased odds of childhood overweight/obesity, independent of several potential confounders and mediators. Gestational weight gain had a greater impact on childhood overweight/obesity among normal-weight women, suggesting that the effect may be independent of genetic predictors of obesity.

Risk of large-for-gestational-age newborns in women with gestational diabetes by race and ethnicity and body mass index categories.

OBJECTIVE: To compare the prevalence of large-for-gestational-age (LGA) newborns across categories of body mass index (BMI) in five racial and ethnic groups. METHODS: This cohort study examined 7,468 women with gestational diabetes mellitus (GDM) who delivered a live newborn between 1995 and 2006 at Kaiser Permanente Northern California. The racial and ethnic groups were non-Hispanic white, African American, Hispanic, Asian, and Filipina. The BMI was classified using the World Health Organization International guidelines (normal, 18.50-24.99; overweight, 25.00-29.99; obese, 30.00-34.99; obese class II, 35.00 or higher). Having an LGA newborn was defined as birth weight more than 90th percentile for the study population's race or ethnicity and gestational age--specific birth weight distribution. Logistic regression was used to estimate odds of having an LGA newborn by BMI and race and ethnicity. RESULTS: Overall prevalence of LGA newborns was highest in African American women (25.1%), lowest in Asians (13.9%), and intermediate among Hispanic (17.3%), white (16.4%), and Filipina women (15.3%). The highest increased risk of LGA newborns was observed among women with class II obesity in most racial and ethnic groups, and African American and Asian women with class II obesity had a four-fold increased risk of LGA newborns compared with women of normal weight in the same racial and ethnic group. CONCLUSIONS: African American women with GDM have a greater risk of LGA newborns at a lower BMI than other racial and ethnic groups. Clinicians should be aware that among women with GDM, there may be significant racial and ethnic differences in the risk of LGA newborns by BMI threshold.

Prepregnancy cardiometabolic and inflammatory risk factors and subsequent risk of hypertensive disorders of pregnancy.

OBJECTIVE: The purpose of this study was to examine prepregnancy cardiometabolic and inflammatory markers and the subsequent risk of hypertensive disorders of pregnancy. STUDY DESIGN: This was a retrospective cohort study of 3380 women who took part in a comprehensive multiphasic health checkup (MHC) examination between 1984 and 1996 and who subsequently delivered at Kaiser Permanente Northern California. RESULTS: Two hundred five women were diagnosed with a hypertensive disorder of pregnancy. Prepregnancy measurements of overweight/obesity (body mass index, ≥25.0 kg/m(2)), prehypertension, and inflammation (leukocytes, ≥7.2 10(3)/µL) were associated independently with hypertensive disorder of pregnancy risk (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.3; OR, 2.1; 95% CI, 1.5-2.8; and OR, 1.6; 95% CI, 1.1-2.3, respectively). Being overweight/obese and having prehypertension before pregnancy was associated with a 3.5-fold increased risk of hypertensive disorder of pregnancy compared with women with normal levels of both risk factors. CONCLUSION: A prepregnancy cardiometabolic and inflammation risk profile may help clinicians identify high-risk women to target for early intervention or management of hypertensive disorder of pregnancy.

Gender differences in sexual behaviors of AD patients and their relationship to spousal caregiver well-being.

OBJECTIVES: Little is known about gender differences in sexuality among community-dwelling heterosexual couples in which one partner has Alzheimer's disease (AD). Few studies have examined gender differences in specific sexual behaviors or their associations with caregiver well-being. This study evaluated the impact of gender differences on intimacy and sexual satisfaction in marital relationships in which one partner has AD. METHOD: Baseline measures were collected from 162 AD patients and their partners enrolled in a multi-site study between 2001 and 2009 to evaluate gender differences in measures of intimacy, caregiver well-being, and patient sexual behaviors. RESULTS: While over 70% of all patients initiated physically intimate activities (i.e., kissing, hugging, and intercourse), most did not initiate intercourse specifically. Female caregivers reported higher levels of stress and depressive symptoms than male caregivers (p < 0.01). Satisfaction with intimacy was significantly associated with fewer stress and depressive symptoms in female caregivers (r = -0.29, p < 0.01). Caregiver gender, satisfaction with intimacy, and caring for a patient with mild AD were significant predictors of caregiver depressive symptoms (p's < 0.05). CONCLUSION: The majority of couples dealing with AD reported engaging in intimacy, suggesting its importance in the relationship. Female caregivers who reported less sexual satisfaction reported more frequent stress and depressive symptoms. Caregiver gender, satisfaction with intimacy, and the AD patient's level of cognitive functioning significantly contributed to caregiver well-being. Gender-specific therapies to address patient sexual difficulties and caregiver well-being could potentially maintain or improve the marital relationship.

The impact of dementia and mild memory impairment (MMI) on intimacy and sexuality in spousal relationships.

BACKGROUND: Sexuality and intimacy in couples in which one partner is affected by dementia has been widely researched. Few studies have explored these issues in couples where one partner is affected by mild memory impairment (MMI) or mild cognitive impairment (MCI). The objectives of this study were to (1) identify and contrast issues of intimacy and sexuality that spousal caregivers of persons with MMI and dementia may experience, and (2) identify future lines of research in this population. METHODS: Fourteen dementia and nine MMI spousal caregivers participated in focus groups conducted between 2008 and 2009 at the Stanford/VA Alzheimer's Research Center. Content analyses were conducted to identify themes. RESULTS: Five themes emerged: communication, marital cohesion, affectional expression, caregiver burden, and ambiguity concerning the future of the relationship. Dementia caregivers reported more difficulties with communication, cohesion, and perceptions of increased burden than their MMI counterparts. Both groups indicated reduced sexual expression due to physical limitations; substitute activities including hand-holding, massaging, and hugging were noted. Both groups reported difficulty anticipating the future of the relationship due to present stressors. While dementia caregivers could consider future romantic relationships with others, MMI caregivers were primarily able to consider future relationships only for companionship and emotional intimacy. CONCLUSION: Early therapeutic interventions may assist couples in modifying activities, behaviors, and expectations about the future of the relationship. Such modifications may help maintain relationship satisfaction, decrease burden, preserve quality of life, and delay time-to-placement. Extending time-to-placement could have cost savings implications for families and the healthcare system.