Physiological subtypes of gestational glucose intolerance and risk of adverse pregnancy outcomes.

BACKGROUND: Women with gestational glucose intolerance, defined as an abnormal initial gestational diabetes mellitus screening test, are at risk of adverse pregnancy outcomes even if they do not have gestational diabetes mellitus. Previously, we defined the physiological subtypes of gestational diabetes mellitus based on the primary underlying physiology leading to hyperglycemia and found that women with different subtypes had differential risks of adverse outcomes. Physiological subclassification has not yet been applied to women with gestational glucose intolerance. OBJECTIVE: We defined the physiological subtypes of gestational glucose intolerance based on the presence of insulin resistance, insulin deficiency, or mixed pathophysiology and aimed to determine whether these subtypes are at differential risks of adverse outcomes. We hypothesized that women with the insulin-resistant subtype of gestational glucose intolerance would have the greatest risk of adverse pregnancy outcomes. STUDY DESIGN: In a hospital-based cohort study, we studied women with gestational glucose intolerance (glucose loading test 1-hour glucose, ≥140 mg/dL; n=236) and normal glucose tolerance (glucose loading test 1-hour glucose, <140 mg/dL; n=1472). We applied homeostasis model assessment to fasting glucose and insulin levels at 16 to 20 weeks' gestation to assess insulin resistance and deficiency and used these measures to classify women with gestational glucose intolerance into subtypes. We compared odds of adverse outcomes (large for gestational age birthweight, neonatal intensive care unit admission, pregnancy-related hypertension, and cesarean delivery) in each subtype to odds in women with normal glucose tolerance using logistic regression with adjustment for age, race and ethnicity, marital status, and body mass index. RESULTS: Of women with gestational glucose intolerance (12% with gestational diabetes mellitus), 115 (49%) had the insulin-resistant subtype, 70 (27%) had the insulin-deficient subtype, 40 (17%) had the mixed pathophysiology subtype, and 11 (5%) were uncategorized. We found increased odds of large for gestational age birthweight (primary outcome) in women with the insulin-resistant subtype compared with women with normal glucose tolerance (odds ratio, 2.35; 95% confidence interval, 1.43-3.88; P=.001; adjusted odds ratio, 1.74; 95% confidence interval, 1.02-3.48; P=.04). The odds of large for gestational age birthweight in women with the insulin-deficient subtype were increased only after adjustment for covariates (odds ratio, 1.69; 95% confidence interval, 0.84-3.38; P=.14; adjusted odds ratio, 2.05; 95% confidence interval, 1.01-4.19; P=.048). Among secondary outcomes, there was a trend toward increased odds of neonatal intensive care unit admission in the insulin-resistant subtype in an unadjusted model (odds ratio, 2.09; 95% confidence interval, 0.99-4.40; P=.05); this finding was driven by an increased risk of neonatal intensive care unit admission in women with the insulin-resistant subtype and a body mass index of <25 kg/m2. Infants of women with other subtypes did not have increased odds of neonatal intensive care unit admission. The odds of pregnancy-related hypertension in women with the insulin-resistant subtype were increased (odds ratio, 2.09; 95% confidence interval, 1.31-3.33; P=.002; adjusted odds ratio, 1.77; 95% confidence interval, 1.07-2.92; P=.03) compared with women with normal glucose tolerance; other subtypes did not have increased odds of pregnancy-related hypertension. There was no difference in cesarean delivery rates in nulliparous women across subtypes. CONCLUSION: Insulin-resistant gestational glucose intolerance is a high-risk subtype for adverse pregnancy outcomes. Delineating physiological subtypes may provide opportunities for a more personalized approach to gestational glucose intolerance.

Congenital thrombotic thrombocytopenic purpura (TTP) with placental abruption despite maternal improvement: a case report.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare but serious complication in pregnancy that places the mother and fetus at high risk for morbidity and mortality. This case illustrates novel pregnancy complications associated with this rare medical condition. CASE PRESENTATION: A 31-year-old G3P0020 at 28 weeks and 1 day was admitted with severe thrombocytopenia and was ultimately diagnosed with TTP. With therapeutic plasma exchange (TPE), maternal status improved. At 28 weeks 6 days, however, non-reassuring fetal testing prompted cesarean delivery with placental abruption noted intraoperatively. Pathology examination confirmed placental abruption and also revealed multiple placental infarcts. CONCLUSION: While medical management of TTP can significantly improve the health of the mother, this case highlights the potential role of TTP in abruption and other placental pathology and thus, the need for close fetal surveillance throughout an affected pregnancy.

The telomere gestational clock: increasing short telomeres at term in the mouse.

BACKGROUND: The biologic mechanism(s) regulating the length of gestation are currently poorly understood. After peaking at the blastocyst stage, the average telomere lengths have been reported to shorten during the remainder of gestation in the placenta and fetal membranes in both human and mouse pregnancies, thereby providing a potential countdown biologic clock. These previous studies have reported changes in the average telomere lengths, whereas it has now been shown that the shortest telomeres, not the average telomere lengths, are the mediators of telomere dysfunction which limits cellular survival and results in aging. OBJECTIVE: These studies sought to assess for the first time a significant increase in short telomeres in the fetal membrane and placental tissue near the end of pregnancy in the mouse. STUDY DESIGN: Placental and fetal membrane tissues were harvested from timed-pregnant CD-1 mice on gestational days 14-18 prior to the onset of parturition. Telomere lengths were determined for 30 DNA samples (5 each for gestational days 14, 16, and 18 from placentas and fetal membranes) using a commercial high-throughput quantitative fluorescence in situ hybridization technique. Quantitative measurements of representative short telomeres (ie, 3 kb and 5 kb telomere fragments) were performed for 29-30 DNA samples (4-7 each for gestational days 14, 15, 16, 17, and 18 from placentas, fetal membranes, and maternal liver) using a real-time quantitative polymerase chain reaction modification of the classic telomere restriction fragment technique. RESULTS: The median telomere lengths of fetal membrane tissue decreased from gestational days 14-18 (18,705-16,364 kb) and were significantly shorter than telomeres in placental tissue (P < .05). Representative histograms for the distribution of telomere lengths in mouse fetal membranes (as shown in the Figure) confirm a curve skewed to the left (toward shorter telomere lengths).The relative quantity of the representative short telomeres (ie, 3 kb and 5 kb fragments) increased significantly as gestation progressed in both placenta and fetal membrane tissue. In gestational day 18 fetal membranes, the relative quantity of 3 kb and 5 kb telomeres increased 5.5-fold and 9.3-fold compared with gestational day 14 tissues (P < .05). In placental tissue the relative quantity of 3 kb and 5 kb telomeres increased 9.3-fold and 7.8-fold compared with gestational day 14 tissues (P < .05). Studies performed using adult liver tissue demonstrated little variation of the representative short telomeres and no significant difference between the nonpregnant and pregnant samples. CONCLUSION: These mouse studies have demonstrated that the distribution of telomere lengths in fetal membrane and placental tissues are skewed toward shorter lengths and that the quantity of representative short telomeres increase significantly prior to parturition. The telomere gestational clock is a novel hypothesis supported by several preliminary mouse studies and interesting associations in human pregnancies between maternal conditions and telomere lengths. (eg, stress, education, pollution, neighborhood quality, and race). As such, the current hypothesis generating study provides a foundation for future research regarding the potential role for a telomere-based biologic clock that determines gestational length in human and other mammalian pregnancies.

Evaluating the Obstetrical Implications of Antenatal Testing for Women with Morbid Obesity: Maternal and Fetal Outcomes of Increased Surveillance.

Objectives Despite limited data, antenatal testing has been initiated in many institutions for women with morbid obesity given their increased risk of stillbirth. Therefore, our objective was to evaluate the obstetrical implications of antenatal testing in the morbidly obese population. Study Design We performed a retrospective cohort study of women undergoing antenatal testing from January 2011 through December 2012 who delivered at our institution. The exposed group was women undergoing antenatal testing with morbid obesity (body mass index [BMI] ≥ 40 kg/m(2)). This group was subdivided into two groups: group 1, which included women undergoing testing for morbid obesity alone, and group 2, which included women undergoing testing for morbid obesity with an additional medical comorbidity. The unexposed group (group 3) comprised nonmorbidly obese women (BMI < 35 kg/m(2)) undergoing antenatal testing for similar medical comorbidities. Our primary outcomes were induction of labor and gestational age at delivery. Results A total of 512 women met inclusion criteria. Group 1 had a lower induction rate as compared with groups 2 and 3 (22.2, 32.5, and 37.6%, respectively; p = 0.003). Additionally, women delivered at a later gestational age in group 1 (39.3 weeks [38.4-40.2]) compared with groups 2 (38.5 weeks [36.1-40.3]) or 3 (37.1 weeks [37.0-38.2]), p = 0.04. There were no significant differences in our secondary outcomes including rate of cesarean delivery (p = 0.11) or rate of nonreactive nonstress test (p = 0.4). Conclusions While it remains unknown whether antenatal testing decreases the stillbirth risk in morbidly obese women, this population does not appear to be at increased risk of induction of labor or delivery prior to 39 weeks secondary to testing. Future studies should evaluate neonatal implications and cost-effectiveness of antenatal testing in this group.

Antenatal testing in uncomplicated pregnancies: should testing be initiated after 40 or 41 weeks?

OBJECTIVE: This study aims to compare outcomes of antenatal testing in women who received testing between 40 weeks and 40+6 weeks versus those who received testing at ≥41 weeks. MATERIALS AND METHODS: This retrospective study included women without maternal comorbidities, who were referred for outpatient antenatal testing for gestational age ≥40 weeks. We compared women who received antenatal testing between 40 and 40+6 weeks (Group 1), to those who were only tested at ≥41 weeks (Group 2). RESULTS: A total of 827 Group 1 and 244 Group 2 pregnancies were evaluated. One-hundred and eighty-nine (18%) were sent to labor and delivery (L&D) for further evaluation. There were no significant differences between groups in terms of being sent or admitted to labor and delivery, the reason for which women were sent, induction of labor, mode of delivery, neonatal length of stay, or admission to intensive care. CONCLUSION: Pregnancies tested at 40 weeks were identified as abnormal and sent to L&D at the same rate as those tested at 41 weeks. Therefore, it may be reasonable to initiate fetal surveillance at the estimated date of delivery.

Maternal anemia is associated with adverse maternal and neonatal outcomes in Mbarara, Uganda.

PURPOSE: Maternal anemia is a significant risk factor for maternal morbidity and mortality, increasing risk of preterm birth, intrauterine growth restriction, stillbirth, and death. Moderate and severe anemia in pregnancy is defined as hemoglobin (Hb) <10 g/dl and Hb < 7 g/dl, respectively. We aimed to characterize the association of maternal anemia with maternal, neonatal, and placental outcomes in a resource-limited setting. METHODS: Data were collected from a prospective cohort of 352 pregnant women at a tertiary academic Ugandan hospital. One hundred and seventy-six (50%) of women were living with HIV. Hemoglobin was measured in labor, and placentas were collected postpartum. Maternal outcomes included mode of delivery, hemorrhage, blood transfusion, intensive care unit admission, and maternal mortality. Neonatal outcomes included gestational age at delivery, birthweight, stillbirth, and neonatal mortality. Placental descriptors included weight and thickness. Categorical variables were analyzed using Chi-squared and Fisher's exact tests. RESULTS: Hemoglobin < 10 g/dl, was present in 17/352 (5%) of women. Significantly more women with moderate or severe anemia were HIV-infected: 14/17 (82%) versus 162/335 (48%) (p = .006). Blood transfusions (2/17, 12% versus 5/335, 2%, p = .04) and neonatal deaths (2/17, 12% versus 9/335, 3%, p = .01) were more common in the anemia group. Placental thickness was lower in the anemia group (1.4 cm versus 1.7 cm, p = .04). CONCLUSIONS: Moderate and severe anemia was associated with maternal HIV infection, maternal blood transfusion, neonatal death, and decreased placental thickness. The overall rate of moderate and severe anemia among this cohort was lower than previously reported.

Longitudinal Changes in the Relationship Between Hemoglobin A1c and Glucose Tolerance Across Pregnancy and Postpartum.

OBJECTIVE: To characterize the relationship between hemoglobin A1c (HbA1c) levels and glucose tolerance across pregnancy and postpartum. DESIGN AND PARTICIPANTS: In a longitudinal study of pregnant women with gestational diabetes risk factors (N = 102), we performed oral glucose tolerance testing (OGTT) and HbA1c measurements at 10-15 weeks of gestation, 24-30 weeks of gestation (N = 73), and 6-24 weeks postpartum (N = 42). Complete blood counts were obtained from clinical records. We calculated HbA1c-estimated average glucose levels and compared them with mean OGTT glucose levels (average of fasting, 1- and 2-hour glucose levels). Linear mixed effects models were used to test for longitudinal changes in measurements. RESULTS: Mean OGTT glucose increased between 10-15 and 24-30 weeks of gestation (ß = 8.1 mg/dL, P = .001), while HbA1c decreased during the same time period (ß = -0.13%, P < .001). At 10-15 weeks of gestation and postpartum the discrepancy between mean OGTT glucose and HbA1c-estimated average glucose was minimal (mean [standard deviation]: 1.2 [20.5] mg/dL and 0.16 [18.1] mg/dL). At 24-30 weeks of gestation, the discrepancy widened (13.2 [17.9] mg/dL, ß = 12.7 mg/dL, P < .001, compared to 10-15 weeks of gestation, with mean OGTT glucose being higher than HbA1c-estimated average glucose). Lower hemoglobin at 24-30 weeks of gestation was associated with a greater discrepancy (ß = 6.4 mg/dL per 1 g/dL lower hemoglobin, P = .03 in an age- and gestational age-adjusted linear regression model). CONCLUSIONS: HbA1c accurately reflects glycemia in the 1st trimester, but underestimates glucose intolerance in the late 2nd trimester. Lower hemoglobin level is associated with greater underestimation. Accounting for gestational age and maternal hemoglobin may improve the clinical interpretation of HbA1c levels during pregnancy.

Management of the Cardiovascular Complications of Substance Use Disorders During Pregnancy.

PURPOSE OF REVIEW: Substance use disorder in pregnancy and subsequent cardiovascular complications are on the rise in the USA. The care of pregnant women with substance use disorder is complex, and requires a thorough understanding of mechanisms of action, pathophysiology, and cardiovascular response during pregnancy. The goal of this review is to provide information about the most common drugs of abuse in pregnancy and to recommend management guidelines. RECENT FINDINGS: Pregnant women with substance use disorder are at increased risk of significant cardiovascular complications, both as a direct effect of acute intoxication as well as the secondary risk from infection and cardiotoxicity associated with chronic use. This risk must be considered in the antepartum management, delivery, and postpartum periods. Understanding the increased cardiovascular risk of pregnant women with substance use disorder, as well as specific drug interactions, anesthesia considerations, best practices, and management considerations, is important for all clinicians caring for this population.

Implementation of designated bariatric surgery program leads to improved clinical outcomes.

BACKGROUND: Emphasis on the development of designated programs for bariatric surgery as a method of quality improvement has increased; however, the data on the effect of these programs on the clinical outcome are insufficient. The aim of the present study was to consider the effect of the implementation of a bariatric clinical program on patient outcomes in a high-volume academic setting. METHODS: We implemented a focused bariatric clinical program to establish common clinical pathways and improve the critical clinical processes. To evaluate the effect of this program, we studied outcome and quality indicators, such as caseload, average length of stay (ALOS), and mortality, readmission, and complication rates during the 6-year period since the introduction of the program. RESULTS: From June 2000 to June 2006 (financial year 2001-2006), 1886 Roux-en-Y gastric bypass procedures were performed at our institution, with 7 deaths (.37%). During this period, we observed a progressive decrease in the ALOS from 6.7 days in 2001 to 3.2 days in 2006, a significant reduction of the 30-day readmission rates from 15.7% in 2001 to 8.1% in 2006, and a reduction of the observed overall complication rate from 18.6% in 2001 to 4.8% in 2006. CONCLUSION: We observed a significant improvement in patient outcomes with the introduction of a designated bariatric surgery program. Additional studies of the validity of these quality indicators are needed to determine the true effect of these quality improvement programs.