The Effect of City-Level Sugar-Sweetened Beverage Taxes on Longitudinal HbA1c and Incident Diabetes in Adults With Prediabetes.

OBJECTIVE: Prediabetes, which is a condition characterized by higher-than-normal blood glucose levels that are under the threshold for diabetes, impacts over one-third of U.S. adults. Excise taxes on sugar-sweetened beverages (SSBs) are a proposed policy intervention to lower population consumption of SSBs and generate revenue to support health-related programs, thus potentially delaying or preventing the development of diabetes in individuals with prediabetes. We leveraged data from Kaiser Permanente in California to examine the impact of SSB taxes in California on individual-level mean HbA1c levels and rates of incident diabetes. RESEARCH DESIGN AND METHODS: We compared two outcomes, mean HbA1c levels and rates of incident diabetes, among a matched cohort of adults with prediabetes who lived and did not live in SSB excise tax cities, using outcomes collected in the 6 years prior and 4 years following SSB tax implementation. We used multivariable linear mixed effects models to analyze longitudinal mean HbA1c and discrete-time survival models for incident diabetes. RESULTS: We included 68,658 adults in the analysis. In adjusted models, longitudinal mean HbA1c (percent) was 0.007 (95% CI 0.002, 0.011) units higher in the tax cities compared with controls; while the estimated difference was statistically significant, it was not clinically significant (HbA1c < 0.5%). There was no significant difference in the risk of incident diabetes between individuals living in tax and control cities. CONCLUSIONS: We found no clinically significant association between SSB taxes and either longitudinal mean HbA1c or incident diabetes among adults with prediabetes in the 4 years following SSB tax implementation.

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.

Pregnancy post-bariatric surgery: Improved outcomes with telephonic nutritional management program.

BACKGROUND: Pregnancies post-bariatric surgery are increasingly common. It is important to understand how to manage prenatal care in this high-risk population to optimize perinatal outcomes. OBJECTIVE: To determine among pregnancies post-bariatric surgery whether participation in a telephonic nutritional management program was associated with improved perinatal outcomes and nutritional adequacy. STUDY DESIGN: Retrospective cohort study of pregnancies post-bariatric surgery from 2012 to 2018. Participation in a telephonic management program with nutritional counseling, monitoring and nutritional supplement adjustment. Modified Poisson Regression estimated the relative risk using propensity score methods to account for baseline differences between the patients who participated in the program and patients who did not. RESULTS: 1575 pregnancies occurred post-bariatric surgery, of which 1142 (72.5 % of pregnancies) participated in the telephonic nutritional management program. Participants in the program were less likely than non-participants to have a preterm birth (aRR 0.48, 95 % CI 0.35-0.67), preeclampsia (aRR 0.43, 95 % CI (0.27-0.69)), gestational hypertension (aRR 0.62, 95 % CI 0.41-0.93), and to have neonates admitted to a Level 2 or 3 (aRR 0.61, 95 % CI0.39-0.94; aRR 0.66, 95 % CI 0.45-0.97, respectively), after adjusting for the propensity score to account for baseline differences. Risk of cesarean delivery, gestational weight gain, glucose intolerance and birthweight did not differ by participation. Among 593 pregnancies with nutritional labs available, participants in the telephonic program were less likely to have nutritional inadequacy in late pregnancy (aRR 0.91, 95 % CI 0.88-0.94). CONCLUSION: Participation in a telephonic nutritional management program post-bariatric surgery was associated with improved perinatal outcomes and nutritional adequacy.

Rates of malignancies among patients with moderate to severe atopic dermatitis: a retrospective cohort study.

OBJECTIVES: Patients with atopic dermatitis (AD), also known as eczema, may be at an increased risk for malignancies compared with patients without AD; however, incidence rates (IRs) of malignancies in patients with moderate to severe AD are largely unknown. The objective of this study was to evaluate and compare IRs of malignancies in adults with moderate to severe AD (aged ≥18 years). DESIGN: Retrospective cohort study using data from a Kaiser Permanente Northern California (KPNC) cohort. AD severity classification was adjudicated with medical chart review. Covariates and stratification variables included age, sex and smoking status. SETTING: Data were obtained from the KPNC healthcare delivery system in northern California, USA. Cases of AD were defined by outpatient dermatologist-rendered codes and prescriptions of topical therapy or phototherapy (moderate) or systemic treatment (severe). PARTICIPANTS: KPNC health plan members with moderate or severe AD (2007-2018). PRIMARY AND SECONDARY OUTCOME MEASURES: Malignancy IRs and 95% CIs per 1000 person-years were calculated. RESULTS: 7050 KPNC health plan members with moderate and severe AD met eligibility criteria for inclusion. IRs (95% CI) were highest for non-melanoma skin cancer (NMSC) in patients with moderate and severe AD (4.6 (95% CI 3.9 to 5.5) and 5.9 (95% CI 3.8 to 9.2), respectively) and breast cancer (2.2 (95% CI 1.6 to 3.0) and 0.5 (95% CI 0.1 to 3.9), respectively). Except for breast cancer, which was only evaluated in women, malignancies were higher (with non-overlapping CIs) in patients with moderate and moderate to severe AD in men versus women for basal cell carcinoma and NMSC and in former versus never smokers for NMSC and squamous cell carcinoma. CONCLUSIONS: This study estimated IRs of malignancies in patients with moderate and severe AD and provides valuable information for dermatology clinicians and ongoing clinical trials in these populations.

Perinatal Outcomes After Bariatric Surgery Compared With a Matched Control Group.

OBJECTIVE: To evaluate perinatal outcomes associated with pregnancy after bariatric surgery within a large integrated health care system using propensity score matching. METHODS: We conducted a retrospective cohort study that evaluated perinatal outcomes in pregnant patients after bariatric surgery from January 2012 through December 2018. History of bariatric surgery was identified by using International Classification of Diseases codes and a clinical database. Primary outcomes were preterm birth (PTB), gestational hypertension, preeclampsia, impaired glucose tolerance or gestational diabetes, a large-for-gestational-age (LGA) or small-for-gestational-age (SGA) neonates, and cesarean birth. Propensity scores were estimated by using logistic regression that accounted for age at delivery, prepregnancy body mass index, year of delivery, parity, neighborhood deprivation index, race and ethnicity, insurance status, initiation of prenatal visit in the first trimester, smoking during pregnancy, chronic hypertension, and preexisting diabetes. Five patients in the control group were matched to each patient in the case group on linear propensity score, and modified Poisson regression was used to adjust for covariates. Sensitivity analyses by timing and type of surgery were performed. RESULTS: We identified a case cohort of 1,591 pregnancies in patients after bariatric surgery and a matched cohort of 7,955 pregnancies in patients who had not undergone bariatric surgery. Demographic characteristics were similar in both groups. In multivariate models, pregnancy after bariatric surgery was associated with a decreased risk of preeclampsia (7.5% vs 10.2%, adjusted relative risk [aRR] 0.72, 95% CI 0.60-0.86), gestational diabetes or impaired fasting glucose (23.5% vs 35.0%, aRR 0.73, 95% CI 0.66-0.80), and LGA (10.6% vs 19.9%, aRR 0.56, 95% CI 0.48-0.65) and an increased risk of SGA (10.9% vs 6.6%, aRR 1.51, 95% CI 1.28-1.78). No significant differences were observed in PTB, gestational hypertension and cesarean delivery. CONCLUSION: Pregnancy after bariatric surgery in a racially and ethnically diverse cohort of patients is associated with decreased risk of preeclampsia, gestational diabetes or impaired fasting glucose, and LGA neonates; it is also associated with an increased risk of SGA neonates compared with pregnant patients in a matched control group.

Rates of cardiovascular events among patients with moderate-to-severe atopic dermatitis in an integrated health care system: A retrospective cohort study.

Patients with versus without atopic dermatitis may have a greater risk of cardiovascular events, and the risk increases with severity of atopic dermatitis. The incidence of cardiovascular events in the population of patients with moderate-to-severe atopic dermatitis is largely unknown. This retrospective study evaluates incidence rates of cardiovascular events in patients aged ≥12 years with moderate-to-severe atopic dermatitis in a cohort of Kaiser Permanente Northern California health care system members without recognized risk factors for adverse events. Patients with moderate-to-severe atopic dermatitis, as defined by dermatologist-rendered code and prescription history between 2007 and 2018, were included. Major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolisms were identified via International Classification of Diseases codes. Stratification variables included age, sex, race, smoking history, and diabetes. Incidence rates per 1000 person-years were calculated by the number of patients with an incident event divided by the total person-years of observation. Among 8197 patients with moderate-to-severe atopic dermatitis, incidence rates per 1000 person-years (95% confidence interval) for major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolism were: 2.6 (2.1-3.2), 2.0 (1.5-2.5), 1.6 (1.2-2.1), and 0.7 (0.5-1.0), respectively. Incidence rates for all events were higher for older versus younger patients, patients with versus without diabetes, former smokers versus patients who had never smoked, and men versus women, except for pulmonary embolisms, which were higher in women. This study estimated the incidence of cardiovascular events in patients with moderate-to-severe atopic dermatitis and provides valuable information for clinicians.

A Web-Based mHealth Intervention With Telephone Support to Increase Physical Activity Among Pregnant Patients With Overweight or Obesity: Feasibility Randomized Controlled Trial.

BACKGROUND: Pregnant patients with overweight or obesity are at high risk for perinatal complications. Excess gestational weight gain (GWG) further exacerbates this risk. Mobile health (mHealth) lifestyle interventions that leverage technology to facilitate self-monitoring and provide just-in-time feedback may motivate behavior change to reduce excess GWG, reduce intervention costs, and increase scalability by improving access. OBJECTIVE: This study aimed to test the acceptability and feasibility of a pilot mHealth lifestyle intervention for pregnant patients with overweight or obesity to promote moderate intensity physical activity (PA), encourage guideline-concordant GWG, and inform the design of a larger pragmatic cluster randomized controlled trial. METHODS: We conducted a mixed methods acceptability and feasibility randomized controlled trial among pregnant patients with a prepregnancy BMI of 25 to 40 kg/m2. Patients with singletons at 8 to 15 weeks of gestation who were aged ≥21 years and had Wi-Fi access were recruited via email from 2 clinics within Kaiser Permanente Northern California and randomized to receive usual prenatal care or an mHealth lifestyle intervention. Participants in the intervention arm received wireless scales, access to an intervention website, activity trackers to receive automated feedback on weight gain and activity goals, and monthly calls from a lifestyle coach. Surveys and focus groups with intervention participants assessed intervention satisfaction and ways to improve the intervention. PA outcomes were self-assessed using the Pregnancy Physical Activity Questionnaire, and GWG was assessed using electronic health record data for both arms. RESULTS: Overall, 33 patients were randomly assigned to the intervention arm, and 35 patients were randomly assigned to the usual care arm. All participants in the intervention arm weighed themselves at least once a week, compared with 20% (7/35) of the participants in the usual care arm. Participants in the intervention arm wore the activity tracker 6.4 days per week and weighed themselves 5.3 times per week, and 88% (29/33) of them rated the program "good to excellent." Focus groups found that participants desired more nutrition-related support to help them manage GWG and would have preferred an app instead of a website. Participants in the intervention arm had a 23.46 metabolic equivalent of task hours greater change in total PA per week and a 247.2-minute greater change in moderate intensity PA per week in unadjusted models, but these effects were attenuated in adjusted models (change in total PA: 15.55 metabolic equivalent of task hours per week; change in moderate intensity PA: 199.6 minutes per week). We found no difference in total GWG (mean difference 1.14 kg) compared with usual care. CONCLUSIONS: The pilot mHealth lifestyle intervention was feasible, highly acceptable, and promoted self-monitoring. Refined interventions are needed to effectively affect PA and GWG among pregnant patients with overweight or obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03936283; https://clinicaltrials.gov/ct2/show/NCT03936283.

Contribution of maternal cardiometabolic risk factors to racial-ethnicity disparities in preterm birth subtypes.

BACKGROUND: There are recognized racial-ethnic disparities in preterm birth and in maternal cardiometabolic risk factors likely linked to systemic racism. However, it is unclear the extent to which cardiometabolic risk factors contribute to the higher rates of preterm birth among minoritized populations. OBJECTIVE: This study aimed to evaluate racial-ethnic disparities in preterm birth subtypes and the role of maternal cardiometabolic risk factors as mediators of the association between maternal race-ethnicity and preterm birth subtypes. STUDY DESIGN: This was a retrospective cohort study of 295,210 singleton live births from 2011 to 2018. Preterm birth subtypes were defined as medically indicated and spontaneous preterm birth. Poisson regression with robust standard errors were used to provide estimates of the relative risks and 95% confidence intervals for preterm birth subtypes. Causal mediation analysis used logistic regression models to estimate the natural direct and natural indirect (mediated) effects of maternal cardiometabolic risk factors. RESULTS: Compared with White individuals, Black, Asian, and Hispanic individuals were at increased risk for having both medically indicated preterm birth (1.45, 1.30-1.61; 1.21, 1.12-1.31; and 1.13, 1.05-1.22, respectively) (risk ratios, 95% confidence intervals, respectively) and spontaneous preterm birth (1.20, 1.08-1.34; 1.34, 1.26-1.43; and 1.16, (1.08-1.23), independent of established risk factors. The extent to which cardiometabolic risk factors mediated the associations between race-ethnicity (each group vs White in separate analyses) and preterm birth subtypes varied by race-ethnicity. Hypertensive disorders mediated 30.1% of the association between Black race-ethnicity and medically indicated preterm birth, but it did not mediate the association for other racial-ethnic groups or for spontaneous preterm birth. Any glucose disorder in pregnancy was a mediator of medically indicated preterm birth and spontaneous preterm birth for Asian (65.8% and 13.9%, respectively) and Hispanic (17.3% and 11.9%) race-ethnicity but not for Black race-ethnicity. Overweight or obesity mediated the association between race-ethnicity and medically indicated preterm birth (15.5% among Black individuals and 25.1% among Hispanic individuals) and spontaneous preterm birth (10.7% among Hispanic individuals) but was not a mediator among Asian individuals. CONCLUSION: Black, Asian, and Hispanic individuals are at increased risk for preterm birth. Maternal cardiometabolic risk factors partially mediate the associations between race-ethnicity and preterm birth subtypes but the extent varies by race-ethnicity. These findings suggest that strategies that improve and diminish differences in cardiometabolic health between race-ethnicity populations may diminish disparities in preterm birth.

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.

Incidence and predictors of type 1 diabetes among younger adults aged 20-45 years: The diabetes in young adults (DiYA) study.

AIMS: To estimate incidence of type 1 diabetes (T1D) and to develop a T1D prediction model among young adults. METHODS: Adults 20-45 years newly-diagnosed with diabetes in 2017 were identified within Kaiser Permanente's healthcare systems in California and invited for diabetes autoantibody (DAA) testing. Multiple imputation was conducted to assign missing DAA status. The primary outcome for incidence rates (IR) and the prediction model was T1D defined by ≥1 positive DAA. RESULTS: Among 2,347,989 persons at risk, 7862 developed diabetes, 2063 had DAA measured, and 166 (8.0%) had ≥1 positive DAA. T1D IR (95% CI) per 100,000 person-years was 15.2 (10.2-20.1) for ages 20-29 and 38.2 (28.6-47.8) for ages 30-44 years. The age-standardized IRs were 32.5 (22.2-42.8) for men and 27.2 (21.0-34.5) for women. The age/sex-standardized IRs were 30.1 (23.5-36.8) overall; 41.4 (25.3-57.5) for Hispanics, 37.0 (11.6-62.4) for Blacks, 21.4 (14.3-28.6) for non-Hispanic Whites, and 19.4 (8.5-30.2) for Asians. Predictors of T1D among cases included female sex, younger age, lower BMI, insulin use and having T1D based on diagnostic codes. CONCLUSIONS: T1D may account for up to 8% of incident diabetes cases among young adults. Follow-up is needed to establish the clinical course of patients with one DAA at diagnosis.

Poor diet quality in pregnancy is associated with increased risk of excess fetal growth: a prospective multi-racial/ethnic cohort study.

BACKGROUND: Nutritional perturbations during pregnancy may impact fetal and long-term childhood growth, although there are limited data on overall diet quality. We investigated whether diet quality, measured by the Healthy Eating Index-2010 (HEI-2010), during pregnancy was related to birthweight z-score (BWZ) and the clinically relevant birth outcomes of large- and small-for-gestational age (LGA and SGA). METHODS: In a prospective cohort of 2269 multi-racial/ethnic women from the Pregnancy Environment and Lifestyle Study (2014-2017), dietary intake was assessed by a food frequency questionnaire during early pregnancy. Offspring BWZ and LGA or SGA were derived based on gestational age-, sex-, and racial/ethnic-specific birthweight distributions. Multivariable linear and Poisson regression with robust standard errors were used. RESULTS: About 80% of women did not achieve good diet quality (HEI-2010 < 80). After adjusting for covariates, infants born to women in the lowest vs highest quartile of HEI-2010 (37.5-64.4 vs 78.7-94.2) had a 0.12 standard-deviation [95% confidence interval (CI) 0.01-0.23, P-for-trend = 0.023] greater BWZ and 1.76-fold (1.08-2.87, P-for-trend = 0.037) increased risk of LGA. No association was observed between HEI-2010 and SGA. Per-5-point substitution of the reversely coded empty calories component score with the whole grains component score in the HEI-2010 was related to a 25% (95% CI 0.66-0.86) lower risk of LGA. CONCLUSIONS: Poor diet quality in pregnancy was associated with higher birthweight and increased risk of LGA independent of maternal obesity and other covariates. Substitution of empty calories with whole grains may mitigate the risk of excess fetal growth. Our findings may inform potential prevention strategies and dietary guidelines for pregnant women.

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.

Validity of Self-Reported Pre-Pregnancy Weight and Body Mass Index Classification in an Integrated Health Care Delivery System.

BACKGROUND: Self-reported weight prior to pregnancy is prone to error. We utilised a measured pre-conceptional weight from the electronic health record (EHR) to investigate error in recalled pre-pregnancy body mass index (BMI) category and compared how associations between pre-pregnancy BMI and pregnancy outcomes varied by using the two measures. METHODS: We assessed differences in means, correlations, and categorisation of pre-pregnancy BMI for 5092 singleton pregnancies delivered between 2007 and 2013 in Kaiser Permanente Northern California. Associations between measured and self-reported BMI category and gestational diabetes, infant size for gestational age, and exceeding the Institute of Medicine gestational weight gain recommendations were assessed. RESULTS: Overall, the two measures assigned the same BMI category for 86.7% of women with higher risks of misclassification for overweight (Relative Risk (RR) 3.38, 95% Confidence Interval (CI) 2.79, 4.10), obese class I (RR 3.81, 95% CI 3.07, 4.75), and obese class II (RR 1.80, 95% CI 1.28, 2.55) women compared to normal weight women. However, associations between self-reported or measured BMI category and several pregnancy outcomes were similar. CONCLUSIONS: Despite misclassification, self-reported and measured pre-pregnancy weights were similarly associated with perinatal outcomes in this study population. Our results illustrate the value of the EHR for recording measured pre-pregnancy weight for use in research.

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.

Prepregnancy SHBG concentrations and risk for subsequently developing gestational diabetes mellitus.

OBJECTIVE: Lower levels of sex hormone-binding globulin (SHBG) have been associated with increased risk of diabetes among postmenopausal women; however, it is unclear whether they are associated with glucose intolerance in younger women. We examined whether SHBG concentrations, measured before pregnancy, are associated with risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up examination (1984-1996) and had a subsequent pregnancy (1984-2009). Eligible women were free of recognized diabetes. Case patients were 256 women in whom GDM developed. Two control subjects were selected for each case patient and were matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies. RESULTS: Compared with the highest quartile of SHBG concentrations, the odds of GDM increased with decreasing quartile (odds ratio 1.06 [95% CI 0.44-2.52]; 2.33 [1.07-5.09]; 4.06 [1.90-8.65]; P for trend < 0.001), after adjusting for family history of diabetes, prepregnancy BMI, race/ethnicity, alcohol use, prepregnancy weight changes, and homeostasis model assessment of insulin resistance. Having SHBG levels below the median (<64.5 nmol/L) and a BMI ≥25.0 kg/m(2) was associated with fivefold increased odds of GDM compared with normal-weight women with SHBG levels at or above the median (5.34 [3.00-9.49]). CONCLUSIONS: Low prepregnancy SHBG concentrations were associated with increased risk of GDM and might be useful in identifying women at risk for GDM for early prevention strategies.