Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations.

CONTEXT: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. CASE: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. CONCLUSIONS: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated.

Treatment of gestational diabetes mellitus: glyburide compared to subcutaneous insulin therapy and associated perinatal outcomes.

OBJECTIVE: To examine perinatal outcomes in women with gestational diabetes mellitus treated with glyburide compared to insulin injections. STUDY DESIGN: This is a retrospective cohort study of women diagnosed with gestational diabetes mellitus (GDM) who required pharmaceutical therapy and were enrolled in the Sweet Success California Diabetes and Pregnancy Program between 2001 and 2004, a California state-wide program. Women managed with glyburide were compared to women treated with insulin injections. Perinatal outcomes were compared using chi-square test and multivariable logistic regression models; statistical significance was indicated by p < 0.05 and 95% confidence intervals (CI). RESULTS: Among the 10,682 women with GDM who required medical therapy and met study criteria, 2073 (19.4%) received glyburide and 8609 (80.6%) received subcutaneous insulin injections. Compared to insulin therapy and controlling for confounders, oral hypoglycemic treatment was associated with increased risk of birthweight >4000 g (aOR = 1.29; 95% CI [1.03-1.64]), and admission to the intensive care nursery (aOR = 1.46 [1.07-2.00]). CONCLUSION: Neonates born to women with gestational diabetes managed on glyburide, and were more likely to be macrosomic and to be admitted to the intensive care unit compared to those treated with insulin injections. These findings should be examined in a large, prospective trial.

50-Gram glucose challenge test: is it indicative of outcomes in women without gestational diabetes mellitus?

OBJECTIVE: To examine whether the 50-gram glucose challenge test (GCT) is associated with perinatal outcomes in women without gestational diabetes mellitus (GDM). METHODS: This is a retrospective cohort study of 13,789 women who received the GCT and did not have a diagnosis of GDM at the University of California, San Francisco UCSF. GCT values were categorized and examined as predictors of perinatal morbidity using chi-square test and multivariable logistic regression analyses adjusting for maternal characteristics. RESULTS: In women with an elevated GCT but without GDM, the odds of preeclampsia, cesarean delivery, and elevated birth weight were increased. The odds of large-for-gestational age status were increased with aOR 2.0 (95% CI 1.38-2.90) in the 160-179 mg/dl group. The odds of shoulder dystocia was increased with aOR 3.35 (CI 1.03-10.88) in the ≥180 mg/dl group. CONCLUSION: In women without GDM, elevated 50-gram GCT values were associated with higher odds of perinatal morbidity. These findings further support evidence that impaired glucose tolerance is a continuum with possible associated adverse outcomes even at mild ranges; additional research is required to investigate appropriate interventions for women with abnormal screens for GDM.

Perinatal outcomes in patients with gestational diabetes mellitus by race/ethnicity.

OBJECTIVE: To determine if racial/ethnic differences exist in perinatal outcomes in women with gestational diabetes mellitus (GDM). METHODS: This is a retrospective cohort study of singleton pregnancies with GDM cared for by the Sweet Success: California Diabetes and Pregnancy Program (CDAPP) between 2001 and 2004 at inpatient obstetric and neonatal services in California. There were a total of 26,411 women with gestational diabetes who were subgrouped by four races/ethnicities: Caucasian, African-American, Latina, and Asian. The chi-squared test was used to compare the dichotomous outcomes and p<0.05 was used to indicate statistical significance. Multivariable logistic regression analyses were performed to control for potential confounders. Perinatal outcomes, including severity of GDM, cesarean delivery (CD), birthweight, preterm birth, intrauterine fetal demise (IUFD) and neonatal intensive care unit (NICU) admission were compared. RESULTS: Compared to Caucasians, African-Americans had higher odds of primary CD [aOR=1.29, 95% CI (1.05?1.59)] while lower odds were seen in Latinas [aOR=0.84, 95% CI (0.75-0.94)] and Asians [aOR=0.86, 95% CI (0.77-0.96)]. Asians had lower odds [aOR=0.58 (95% CI 0.48-0.70)] of birthweight >4000 g. African-Americans had highest odds of IUFD [aOR=5.93 95% CI (1.73-20.29)]. There were no differences in NICU admission. CONCLUSION: Perinatal outcomes in women diagnosed with GDM differ by racial/ethnic group. Such variation can be used to individually counsel women with GDM.

Carpenter-Coustan criteria compared with the national diabetes data group thresholds for gestational diabetes mellitus.

OBJECTIVE: To examine perinatal outcomes in women who would meet the diagnostic criteria for gestational diabetes mellitus (GDM) according to the Carpenter and Coustan but not by the National Diabetes Data Group (NDDG) thresholds. METHODS: This is a retrospective cohort study of women screened for GDM between January 1988 and December 2001. During the study period, only women who were diagnosed with GDM by the NDDG criteria received counseling and treatment. Women diagnosed with GDM according to the Carpenter and Coustan thresholds but not by the NDDG criteria were compared with women without GDM by either criteria. Perinatal outcomes were examined using chi test and multivariable logistic regression analyses. RESULTS: Among the 14,693 women screened for GDM, 753 (5.1%) would have GDM diagnosed by the Carpenter and Coustan criteria and 480 (3.3%) by the NDDG criteria only, giving 273 (1.9%) women as the study group. Compared with women without GDM, women with GDM by the Carpenter and Coustan but not by the NDDG criteria had higher odds of cesarean delivery (OR 1.44, 95% confidence interval [CI] 1.01-2.07), operative vaginal delivery (OR 1.72, 95% CI 1.20-2.46), birth weight greater than 4,500 g (OR 4.47, 95% CI 2.26-8.86), and shoulder dystocia (OR 2.24, 95% CI 1.03-4.88). CONCLUSION: Women diagnosed with GDM by the Carpenter and Coustan criteria but not by the NDDG criteria had higher risk of operative deliveries, macrosomia, and shoulder dystocia. We recommend using the Carpenter and Coustan diagnostic thresholds for GDM, because these diagnostic criteria are more sensitive than the NDDG criteria. LEVEL OF EVIDENCE: II.

Glucose challenge test: screening threshold for gestational diabetes mellitus and associated outcomes.

OBJECTIVE: To examine whether women with an 1-hour 50-g glucose challenge test (GCT) for gestational diabetes mellitus (GDM) between 120 and 140 mg/dL and >or=140 mg/dL are at risk of perinatal complications. STUDY DESIGN: A retrospective cohort study of women with singleton pregnancies screened for GDM between 1988 and 2001 with a 1-hour 50-g GCT. Values of GCT were stratified into four subgroups: <120, 120-129, 130-139, and >or=140 mg/dL. Perinatal outcomes were compared using the Chi-square test and multivariable logistic regression analysis. RESULTS: There were 13 901 women meeting the study criteria. Compared to women with a GCT of <120 mg/dL, women with a GCT of 130-139 mg/dL and >or=140 mg/dL were more likely to have preeclampsia and operative vaginal or cesarean deliveries. Neonates born to women with a GCT of 130-139 mg/dL also had higher odds of having a 5-minute Apgar score <7 (odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.01-2.29), shoulder dystocia (OR = 2.02, 95% CI 1.16-2.55), birth trauma (OR = 1.47, 95% CI 1.06-2.02), and composite morbidity (OR = 1.25, 95% CI 1.03-1.51). Women with a GCT of >or=140 mg/dL had higher odds of macrosomia (OR = 1.32, 95% CI 1.13-1.54) and shoulder dystocia (OR = 1.68, 95% CI 1.11-2.55). CONCLUSION: Women with GCT results of 130-139 mg/dL appear to be at increased risk for perinatal morbidity. Thus, utilizing a diagnostic test in women with a GCT above 130 mg/dL should be considered.

Screening or diagnostic: markedly elevated glucose loading test and perinatal outcomes.

OBJECTIVE: To determine the diagnostic value of markedly elevated 50-g glucose loading test results (>or=200 mg/dL) and associated perinatal outcomes. METHOD: This was a retrospective cohort study of 14 771 pregnancies screened for gestational diabetes mellitus (GDM) between 1988 and 2001. The positive predictive value of the 50-g oral glucose loading test (GLT) results as measured by plasma glucose value was examined. Perinatal outcomes were assessed for women with GLT results >or=200 mg/dL compared to GLT <200 mg/dL, stratified by the diagnosis of GDM. Statistical comparisons were made using the Chi-square test and Student's t-test and potential confounding factors were controlled for using multivariable logistic regression analyses. A p value <0.05 and 95% confidence intervals were used to indicate statistical significance. RESULTS: The positive predictive values for a GDM diagnosis were 62% for GLT results between 180 and 189 mg/dL, 79% for those between 200 and 209 mg/dL, and 100% for GLT results >or=230 mg/dL. Compared to women with a GLT result <200 mg/dL, among women not diagnosed with GDM but with a GLT >or=200 mg/dL the adjusted odds ratio (aOR) for cesarean delivery was 4.18 (95% confidence intervals, 1.15-15.2). These women also had higher aORs for preterm delivery <32 weeks (aOR = 8.05 (1.02-63.6)), shoulder dystocia (aOR = 15.14 (1.64-140)), and their neonates were more likely to have a 5-minute Apgar score <7 (aOR = 6.41 (1.23-33.3)). For women diagnosed with GDM and with a GLT >or=200 mg/dL, the aOR for cesarean delivery was also elevated compared to those with a GLT <200 mg/dL (aOR = 2.24 (1.19-4.21)). CONCLUSION: A GLT value of >or=200 mg/dL is not absolutely diagnostic for gestational diabetes but is associated with unfavorable perinatal outcomes.