"An update on the approach to treatment of Sjogren's Disease in pregnancy".

BACKGROUND: Women with Sjögren's Disease are more likely to experience pregnancy complications compared to their counterparts without the disease. Attention to detail and familiarity with the most recent research and guidelines in this field are required to achieve optimal maternal and fetal outcomes. Such complications include pregnancy induced hypertension, fetal growth restriction, thromboembolic events, and preterm delivery. Among the most life-threatening sequela of maternal Sjogren's Disease is fetal autoimmune congenital heart block (ACHB), which has high potential to cause intrauterine fetal death, neonatal mortality, developmental delay, and other long-term pediatric complications. Currently, surveillance with weekly echocardiograms and obstetric sonograms in the second trimester are recommended to screen for ACHB with the goal of early detection and intervention before progression from first- or second- of heart block to complete heart block. OBJECTIVE: We describe a case of maternal Sjogren's Disease, which prompted us to raise questions regarding the optimal frequency of obtaining fetal echocardiograms, and the ideal management in case a prolonged PR interval was to be found. We use this case to provide a springboard for discussion on updated antenatal management strategies for ACHB prevention. METHODS: To conduct this analysis, we searched PubMed for articles published over the last 10 years, with attention focused on articles written since 2016. Additionally, updated guidelines by other specialties such as Rheumatology, Cardiology and Pediatrics on this issue were reviewed. RESULTS: Thorough search of the literature yielded several meta-analyses concurring that the mothers with Sjogren's Disease had increased rates of premature birth, pregnancy induced hypertension, increased risks of delivering infants with intrauterine growth restriction (IUGR), with the most life-threatening risk being that of congenital heart block. Literature supporting prophylactic hydroxychloroquine and the use of steroids to reverse or halt the progression of congenital heart block at the time of diagnoses appeared at the forefront of search results. CONCLUSION: Pregnant women with SS have an increased risk for complications such as intrauterine growth restriction, thromboembolic events, pregnancy-induced hypertension, preterm delivery, and cesarean delivery and should prioritize obtaining pre- or peri-conceptional counseling. In women with anti SSA/SSB antibodies, a medication regimen should be considered with the object of decreasing the concentration of these antibodies, and hence decrease the risks of ACHB. Current literature supports the inclusion of hydroxychloroquine for this purpose, even prior to conception. Although the most recent studies recommend against prophylactic use of steroids, their potential to prevent progression to complete block should be weighed against their potential negative effects. Short and long-term treatment with corticosteroids has been associated with increased maternal risk of infection, weight gain, osteonecrosis, hypertension and bone mineral density disorders. Intrauterine growth restriction, oligohydramnios, and adrenal suppression have been among the fetal risks associated with steroids while improved infant survival or decreased need for pacing have not been demonstrated. Management of these pregnancies is complex and should include a multidisciplinary approach involving a maternal-fetal medicine sub-specialist, a rheumatologist, a pediatrician, a neonatologist, and the patient herself with her family in a model of shared decision-making.

Embryonic, Fetal, and Neonatal Complications in Infants of Diabetic Mothers: Insights from the Cincinnati Diabetes in Pregnancy Program Project Grant.

This study aimed to review how the Cincinnati Diabetes in Pregnancy Program Project Grant (PPG) contributed to the understanding and treatment of neonatal complications in infants of diabetic mothers (IDMs). This is a retrospective review of all PPG work on glycemic control at different pregnancy time points and its association with embryonic, fetal, and neonatal complications, such as congenital malformations (CMs), intrauterine growth restriction, macrosomia, hypoglycemia, respiratory distress syndrome (RDS), asphyxia, and polycythemia. We found that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal hypoglycemic episodes or insulin therapy, are independent risk factors for major CMs. A suggestive association of major CMs with maternal Magnesium deficiency was also observed. Poor glycemic control during late embryogenesis and early fetal development was associated with an increased risk of minor CMs. We described a biphasic pattern of fetal growth whereby early growth delay was followed by enhanced fetal growth associated with neonatal macrosomia. Macrosomia was associated with poorer glycemic control in the third trimester and an increased risk of birth trauma. Macrosomia was also correlated with animal-origin insulin concentrations in cord blood, demonstrating that insulin bound to antibodies can cross the placenta and may affect the fetus. We also showed that neonatal hypoglycemia was significantly associated with third-trimester glycemic control, in addition to hyperglycemia occurring during labor. With modern management and adequate prenatal care, IDMs are no longer at increased risk for RDS. Perinatal asphyxia was associated with increased proteinuria appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. Polycythemia in IDMs is prevalent and correlates with proxy measurements of fetal hypoxemia (nucleated red blood cells at delivery) and poorer glycemic control in late pregnancy. The PPG in its various phases revealed the important role of glycemic control at nearly every stage of pregnancy including labor. KEY POINTS: · Poor glycemic control during embryogenesis is a major risk factor for CMs.. · Magnesium deficiency might contribute to major malformations.. · Macrosomia is associated with poor glycemic control in the third trimester.. · Strict glycemic control reduces fetal and neonatal morbidity in pregnancies with insulin-dependent diabetes mellitus..

Daily versus Alternate-Day Iron Supplementation for Pregnant Women with Iron Deficiency Anemia: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the most effective regimen to raise hemoglobin (Hb) by comparing alternate-day dosing of iron to daily dosing in pregnant women with iron deficiency anemia. STUDY DESIGN: Women with Hb < 11.0 g/dL and ferritin ≤ 25 µg/L between 120/7 and 340/7 weeks' gestation were recruited. A total of 88 patients were randomized using block randomization with 1:1 allocation to receive either 1 tablet of 325 mg ferrous sulfate on consecutive days or 2 tablets every other day. The primary outcome, the change in Hb after 6 weeks of treatment was assessed using an analysis of covariance to adjust for baseline level. Secondary outcomes included change in ferritin, hepcidin, side effects, and compliance. Patients completed a questionnaire to assess for adverse symptoms and adherence was monitored by installing a pill reminder app on smartphones of patients. RESULTS: A total of 88 patients were consented. The daily iron group had a greater proportion of nulliparous women (40 vs. 7%). Most patients (98%) had mild anemia (Hb: 9-10.9 g/dL) at recruitment, with a median gestational age of 28.1 weeks (interquartile range [IQR]: 25.6, 30.9) and median duration of treatment of 42 days (IQR: 35, 45). At 6 weeks, the daily iron group had a mean increase in Hb of 0.8 ± 0.9 g/dL, whereas the alternate-day iron group had a mean increase of 0.5 ± 1.0 g/dL (baseline adjusted difference of means: -0.3 [95% confidence interval: -0.7, 0.1], p = 0.15). Frequency of adverse effects attributable to iron were similar between groups. Patient self-reported compliance to treatment was also similar between groups. Among those that used the app, compliance was higher among the daily group compared with the alternate daily group (median: 95.5% [IQR: 75, 100] vs. 85% [IQR: 40, 92]), although this difference was not statistically significant (p = 0.07). CONCLUSION: This trial suggests that there are no significant differences between alternate-day iron supplementation and daily iron supplementation for treating iron deficiency anemia. KEY POINTS: · Intermittent iron provides no additional benefit compared to daily iron in the treatment of anemia.. · Patient compliance to treatment was similar between the groups.. · The frequency of side effects was not significantly different between the groups..

Hypoglycemia in Prospective Multicenter Study of Pregnancies with Pre-Existing Type 1 Diabetes on Sensor-Augmented Pump Therapy: The LOIS-P Study.

Background: Pregnancies in type 1 diabetes are high risk, and data in the United States are limited regarding continuous glucose monitoring (CGM)-based hypoglycemia throughout pregnancy while on sensor-augmented insulin pump therapy. Materials and Methods: Pregnant women with type 1 diabetes in the LOIS-P Study (Longitudinal Observation of Insulin use and glucose Sensor metrics in Pregnant women with type 1 diabetes using continuous glucose monitors and insulin pumps) were enrolled before 17 weeks gestation at three U.S. centers and we used their personal insulin pump and a study Dexcom G6 CGM. We analyzed data of 25 pregnant women for CGM hypoglycemia based on international consensus guidelines for percentage time <63 and 54 mg/dL, hypoglycemic events and prolonged hypoglycemia events for 24-h, daytime, and overnight periods, and severe hypoglycemia (SH) episodes. Results: For a 24-h period, biweekly median percentage of time <63 mg/dL ranged from 0.8% at biweek 4-5 to 3.7% at biweek 14-15 with high variability throughout pregnancy. Median percentage of time <63 and 54 mg/dL was higher overnight than daytime (P < 0.01). Hypoglycemic events occurred throughout the pregnancy, ranged 1-4 events per 2 weeks, significantly decreased after the 20th week, and occurred predominantly during daytime (P < 0.01). For overnight period, hypoglycemia and events were more concentrated from 12 to 3 am. Seven prolonged hypoglycemia events without any associated SH occurred in four participants (16%), primarily overnight. Three participants experienced a single episode of SH. Conclusions: Our results suggest a higher overall risk of hypoglycemia throughout pregnancy during the overnight period with continued daytime risk of hypoglycemic events in pregnancies complicated by type 1 diabetes.

Feasibility of Closed-Loop Insulin Delivery with a Pregnancy-Specific Zone Model Predictive Control Algorithm.

Objective: Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). Research Design and Methods: Pregnant women with T1D from 14 to 32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a 2-day multicenter supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63 and 140 mg/dL compared with participants' 1-week run-in period. Early (2-h) postprandial glucose control was also evaluated. Results: Eleven participants completed the study (age: 30.6 ± 4.1 years; gestational age: 20.7 ± 3.5 weeks; weight: 76.5 ± 15.3 kg; hemoglobin A1c: 5.6% ± 0.5% at enrollment). No serious adverse events occurred. Compared with the 1-week run-in, there was an increased percentage of time in 63-140 mg/dL during supervised CLC (CLC: 81.5%, run-in: 64%, P = 0.007) with less time >140 mg/dL (CLC: 16.5%, run-in: 30.8%, P = 0.029) and time <63 mg/dL (CLC: 2.0%, run-in:5.2%, P = 0.039). There was also less time <54 mg/dL (CLC: 0.7%, run-in:1.6%, P = 0.030) and >180 mg/dL (CLC: 4.9%, run-in: 13.1%, P = 0.032). Overnight glucose control was comparable, except for less time >250 mg/dL (CLC: 0%, run-in:3.9%, P = 0.030) and lower glucose standard deviation (CLC: 23.8 mg/dL, run-in:42.8 mg/dL, P = 0.007) during CLC. Conclusion: In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy (NCT04492566).

Anthropometric models to estimate fat mass at 3 days, 15 and 54 weeks.

BACKGROUND: Currently available infant body composition measurement methods are impractical for routine clinical use. The study developed anthropometric equations (AEs) to estimate fat mass (FM, kg) during the first year using air displacement plethysmography (PEA POD® Infant Body Composition System) and Infant quantitative magnetic resonance (Infant-QMR) as criterion methods. METHODS: Multi-ethnic full-term infants (n = 191) were measured at 3 days, 15 and 54 weeks. Sex, race/ethnicity, gestational age, age (days), weight-kg (W), length-cm (L), head circumferences-cm (HC), skinfold thicknesses mm [triceps (TRI), thigh (THI), subscapular (SCP), and iliac (IL)], and FM by PEA POD® and Infant-QMR were collected. Stepwise linear regression determined the model that best predicted FM. RESULTS: Weight, length, head circumference, and skinfolds of triceps, thigh, and subscapular, but not iliac, significantly predicted FM throughout infancy in both the Infant-QMR and PEA POD models. Sex had an interaction effect at 3 days and 15 weeks for both the models. The coefficient of determination [R2 ] and root mean square error were 0.87 (66 g) at 3 days, 0.92 (153 g) at 15 weeks, and 0.82 (278 g) at 54 weeks for the Infant-QMR models; 0.77 (80 g) at 3 days and 0.82 (195 g) at 15 weeks for the PEA POD models respectively. CONCLUSIONS: Both PEA POD and Infant-QMR derived models predict FM using skinfolds, weight, head circumference, and length with acceptable R2 and residual patterns.

Longitudinal Observation of Insulin Use and Glucose Sensor Metrics in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitors and Insulin Pumps: The LOIS-P Study.

Background: Suboptimal glycemic control is associated with maternal and neonatal morbidity and mortality in pregnancy complicated by type 1 diabetes (T1D). Prospective analysis of continuous glucose monitoring (CGM) metrics, insulin pump settings, and insulin delivery can better characterize the changes in glycemic levels and insulin use throughout pregnancy with T1D. Materials and Methods: Prescribed parameters, insulin delivery, carbohydrate intake, and CGM data for 25 pregnant women with T1D from three U.S. sites were collected. Participants enrolled before 17 weeks gestation and used personal insulin pumps and study CGM. Mean daily total, basal, and bolus insulin doses (units/kg), CGM time in range (TIR: 63-140 mg/dL), and pump-entered carbohydrates were analyzed for every 2-week gestational interval. Linear mixed-effects regression models were used to evaluate changes across gestational ages compared to 12-14 weeks. Results: Basal insulin was higher during weeks 6-12 and 24-40. Daily bolus and total insulin were higher during weeks 20-40. Pump parameters were adjusted to intensify insulin therapy from 22 weeks onward. Average TIR across pregnancy was 59% ± 14%. Between 18 and 30 weeks, TIR was significantly lower, and time above range was significantly higher compared to the reference biweek. Time below target was lower between 22 and 34 weeks. Seven participants achieved >70% recommended TIR for pregnancy. Participants with maternal complications or infant neonatal intensive care unit admissions had lower TIR. Conclusion: While insulin dosing changed significantly with advancing gestation, most participants did not achieve >70% TIR. Customized anticipatory pump setting adjustments and automated systems aimed toward the designated TIR are needed to improve outcomes for this population. NCT03761615.

No sustained effects of an intervention to prevent excessive GWG on offspring fat and lean mass at 54 weeks: Yet a greater head circumference persists.

BACKGROUND: LIFT (Lifestyle Intervention for Two) trial found that intervening in women with overweight and obesity through promoting healthy diet and physical activity to control gestational weight gain (GWG) resulted in neonates with greater weight, lean mass and head circumference and similar fat mass at birth. Whether these neonate outcomes are sustained at 1-year was the focus of this investigation. METHODS: Measures included body composition by PEA POD air displacement plethysmography (ADP) and Echo Infant quantitative magnetic resonance (QMR) and head circumference at birth (n = 169), 14 (n = 136) and 54 weeks (n = 137). Differences in fat and lean mass between lifestyle intervention (LI) and Usual care (UC) groups were examined using ANCOVA adjusting for maternal age and BMI, GWG, offspring sex and age. RESULTS: Compared to UC, LI infants had similar weight (112 ± 131 g; P = .40), fat mass (14 ± 80 g; P = .86), lean mass (100 ± 63 g; P = .12) at 14 weeks and similar weight (168 ± 183 g; P = .36), fat mass (148 ± 124 g; P = .24), lean mass (117 ± 92 g; P = .21) at 54 weeks. Head circumference was greater in LI at 54 weeks (0.46 ± 2.1 cm P = .03). CONCLUSIONS: Greater lean mass observed at birth in LI offspring was not sustained at 14 and 54 weeks, whereas the greater head circumference in LI offspring persisted at 54 weeks.

Increased Visceral Adipose Tissue Without Weight Retention at 59 Weeks Postpartum.

OBJECTIVE: This study aimed to determine whether controlling maternal gestational weight gain (GWG) influences adipose tissue distribution at 1 year postpartum. METHODS: Women with overweight or obesity (n = 210, BMI ≥ 25 or ≥ 30) were randomized to a lifestyle intervention (LI) designed to control GWG or to usual obstetrical care (UC). Measures included anthropometry, whole-body magnetic resonance imaging for visceral (VAT), intermuscular, and subcutaneous adipose tissue, and cardiometabolic risk factors in pregnancy (15 and 35 weeks) and after delivery (15 and 59 weeks). RESULTS: Baseline (15 weeks) characteristics were similar (mean [SD]: age, 33.8 [4.3] years; weight, 81.9 [13.7] kg; BMI, 30.4 [4.5]; gestational age at randomization, 14.9 [0.8] weeks). LI had less GWG (1.79 kg; P = 0.003) and subcutaneous adipose tissue gain at 35 weeks gestation (P < 0.01). UC postpartum weight (2.92 kg) was higher at 15 weeks but not different from baseline or LI at 59 weeks postpartum. Postpartum VAT increased from baseline in LI by 0.23 kg at 15 weeks and 0.55 kg at 59 weeks; in UC, it increased by 0.34 kg at 15 and 59 weeks. Intermuscular adipose tissue remained elevated in LI (0.22 kg) at 59 weeks. VAT was associated with several cardiometabolic risk factors at 59 weeks. CONCLUSIONS: Despite no weight retention at 59 weeks postpartum, women had increased VAT by ~30%. Postpartum modifiable behaviors are warranted to lower the risk of VAT retention.

Greater Neonatal Fat-Free Mass and Similar Fat Mass Following a Randomized Trial to Control Excess Gestational Weight Gain.

OBJECTIVE: The objective of this study was to determine the effectiveness of controlling maternal gestational weight gain (GWG) in the second and third trimesters on neonate body composition. METHODS: Two hundred ten healthy women with overweight (25 > BMI < 30) or obesity (BMI ≥ 30) were randomly assigned to a lifestyle intervention (LI) program focused on controlling GWG through nutrition and activity behaviors or to usual obstetrical care (UC). Infant fat and fat-free mass (FFM) at birth were measured by using air displacement plethysmography (PEA POD) and by using quantitative magnetic resonance (QMR). RESULTS: At baseline, there were no between-group differences in maternal characteristics (mean [SD]): age: 33.8 (4.3) years, weight: 81.9 (13.7) kg, BMI: 30.4 (4.5), and gestational age at randomization: 14.9 (0.8) weeks. GWG was less in the LI group by 1.79 kg (P = 0.003) or 0.0501 kg/wk (P = 0.002). Compared with UC infants, LI infants had greater weight (131 ± 59 g P = 0.03), FFM (98 ± 45 g; P = 0.03) measured by PEA POD, and lean mass (105 ± 38 g; P = 0.006) measured by QMR. Fat mass and percent fat were not significantly different. CONCLUSIONS: Intervening in women with overweight and obesity through behaviors promoting healthy diet and physical activity to control GWG resulted in neonates with similar fat and greater FFM.

Misoprostol With Foley Bulb Compared With Misoprostol Alone for Cervical Ripening: A Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that cervical ripening using a combination of misoprostol and a transcervical Foley bulb leads to delivery within a shorter time compared with misoprostol alone. METHODS: This randomized controlled trial was offered to women admitted for cervical ripening. Inclusion criteria were gestational age 37 weeks or greater with intact membranes, singleton fetus, cephalic presentation, and Bishop score 6 or less. Exclusion criteria included, among others, prior uterine surgery, ruptured membranes, and any contraindication to vaginal delivery. Patients were randomized to cervical ripening using misoprostol and a transcervical Foley bulb simultaneously or misoprostol alone. Primary outcome was time from placement of the misoprostol to delivery. Secondary outcomes included time to active phase, time from active phase to delivery, cesarean delivery rate, uterine tachysystole, estimated blood loss, chorioamnionitis, cord pH, 5-minute Apgar score, and neonatal intensive care unit admission. Sample size calculation revealed that 94 participants were required in each group to detect a 3-hour difference with 80% power and α error of 0.05. Intention-to-treat analysis was performed. RESULTS: From September 2015 to July 2016, a total of 200 patients were randomized, 100 to each group. There were no differences between groups with respect to parity, body mass index, gestational age, Bishop score, birth weight, or indication for induction. Time to delivery was significantly shorter in the combined misoprostol-transcervical Foley group: 15.0 (11.0-21.8) hours (median [interquartile range]) vs 19.0 (14.0-27.3) hours in the misoprostol-only group (P=.001). This time difference remained significant after subanalysis by parity or after excluding cesarean deliveries. There was no difference between groups with respect to the rate or indication for cesarean delivery, estimated blood loss, rate of tachysystole, chorioamnionitis, or neonatal outcomes. CONCLUSION: Cervical ripening using misoprostol in combination with a transcervical Foley bulb is an effective method to shorten the course of labor compared with misoprostol alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02566005.

Current trends in the diagnosis and management of gestational diabetes mellitus in the United States.

OBJECTIVE: To assess current practice patterns among members of the Society for Maternal-Fetal Medicine (SMFM) with respect to the diagnosis and management of gestational diabetes mellitus (GDM). METHODS: A 38 question survey on GDM diagnosis and management was distributed to SMFM members. RESULTS: 2330 SMFM members were surveyed with a 40% response rate. Overall, 90.6% of respondents recommend a 2-step (versus a 1-step) diagnostic test. Cutoff values for the 1-h-50 g glucose challenge test vary from 130-140 mg/dL, but the majority (83%) adopts Carpenter Coustan criteria for the 3-h-100 g oral glucose tolerance test. The majority recommend glucose testing four times a day, with 55% preferring post-prandial testing at 2 h. Glyburide is used by 57% as a first-line agent, while 4% use metformin. Long-acting insulin analogs (glargine and/or detemir) are used by 46% and 33.6% of respondents, respectively. Antenatal testing is recommended by 38.7% for diet-controlled GDM compared to 98.7% for pharmacologically controlled GDM, with 56% starting by 34 weeks gestation. Most respondents recommend delivery of diet-controlled GDM at 40 weeks and pharmacologically controlled GDM at 39 weeks. Most (69%) offer elective cesarean section for an estimated fetal weight of >4500 g. CONCLUSIONS: There is significant variation in the diagnosis and management of GDM among SMFM members.

Troponins, heat shock proteins and glycogen phosphorylase BB in umbilical cord blood of complicated pregnancies.

PURPOSE OF THE STUDY: Heat shock proteins (Hsp) are evolutionary conserved molecules with a chaperone role in cell survival. We hypothesized that cord blood concentrations of molecules reflecting fetal cardiac muscle insult, including Hsp, troponins cTnI and cTnT, and glycol-phosphorylase BB (GP-BB) would be elevated in pregnancies complicated by gestational diabetes (GDM) or preeclampsia (PIH) compared to healthy controls. MATERIALS AND METHODS: Pregnant women admitted for delivery at >28 weeks were divided into four groups: healthy patients delivered vaginally (VAG), healthy patients delivered by c-section (CS), patients with PIH, and patients with GDM. Demographics, clinical characteristics, and cord blood concentrations of Hsp, troponins cTnI and cTnT, and GP-BB were compared between groups. Statistical analyses included t-test, Chi square, and Wilcoxon rank sum as appropriate. RESULTS: cTnI concentrations were significantly higher in the PIH group compared to the GDM and VAG groups and they were higher in the CS group compared to the VAG group. Concentrations of Hsp70 were higher in the GDM group compared to the VAG and CS groups. Concentration of GP-BB was higher in the PIH group compared to the VAG group. CONCLUSIONS: GP-BB and cTNI are the most sensitive markers for PIH-related fetal myocyte injury as is Hsp70 in pregnancies complicated by GDM.

Can a single preterm ultrasound accurately predict birth weight in gestational diabetes?

OBJECTIVE: To evaluate the accuracy of the gestation-adjusted projection method of birth weight prediction, as compared to near delivery ultrasound estimated fetal weight, in a gestational diabetic population. METHODS: A retrospective cohort was conducted including all women with gestational diabetes who had an ultrasound estimated fetal weight (EFW) between 34(0/7) and 36(6/7) weeks and an additional ultrasound EFW within 7 d of delivery at term. The gestation-adjusted projection (GAP) method was applied to the earlier sonogram, resulting in the GAP predicted birth weight. The GAP predicted weight and the term ultrasound EFW were compared to the actual birth weight. Absolute and percent birth weight errors were compared using paired t-tests. RESULTS: The mean absolute percent errors and mean absolute errors for the GAP method and term ultrasound were 7.7 ± 5.6% versus 7.1 ± 5.1% and 256 ± 184 g versus 236 ± 169 g respectively (p = 0.22 and p = 0.29). The sensitivity of predicting birth weight ≥4000 g was 22% for the GAP method and 28% for term ultrasound, with specificity reaching 97% for both the methods. CONCLUSION: The GAP method is as accurate as term ultrasound in predicting birth weight in gestational diabetes.

Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes.

OBJECTIVE: We sought to determine if insulin detemir (IDet) is noninferior to insulin neutral protamine Hagedorn (NPH) for the treatment of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) in pregnancy. STUDY DESIGN: We conducted a randomized, controlled noninferiority trial of women with GDM and T2DM who entered our Diabetes in Pregnancy Program from March 2013 through October 2014. Exclusion criteria were type 1 diabetes, age <18 years, and insulin allergy. Women who failed to achieve good glycemic control (GC) (mean blood glucose [BG] <100 mg/dL) on diet and/or hypoglycemic agents were randomized to receive either IDet or NPH, with short-acting insulin aspart added as needed. Patients were instructed to test BG 4 times a day (fasting and 2-hour postprandial). Targets of GC were fasting BG <90 mg/dL and postprandial BG <120 mg/dL, and insulin was adjusted as needed to achieve the targets. The primary outcome was overall mean BG during insulin treatment; secondary outcomes included overall mean postprandial and fasting BG, median number of weeks to achieve GC, percent of patients with overall GC, maternal weight gain, perinatal/neonatal outcomes, and number of hypoglycemic events. Power analysis (90% power) determined that 88 patients would need to be randomized, assuming a maximal acceptable difference in overall mean BG of 7 mg/dL (SD ± 10 mg/dL). A per protocol analysis was performed. RESULTS: In all, 105 women were randomized. Eighteen women were excluded leaving 87 participants for analysis (45 NPH, 42 IDet). Maternal characteristics were similar in both groups. The difference in the mean BG of the groups was 2.1 mg/dL with a 1-sided upper 95% confidence limit of 5.5 mg/dL (less than the maximal acceptable difference of 7 mg/dL; P = .2937). There was no significant difference in the primary outcome when an intent-to-treat analysis was performed or when the T2DM patients were excluded. The time to achieve GC was similar in both groups. There were no differences in perinatal outcomes and maternal weight gain among the groups. There were more hypoglycemic events per patient in the NPH group. CONCLUSION: IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy.

Glyburide transport across the human placenta.

OBJECTIVE: To estimate the magnitude of transplacental transfer of glyburide in women with gestational diabetes mellitus (GDM). METHODS: A prospective, observational study was conducted on women with GDM on glyburide therapy. On delivery admission, the glyburide dose and time of last dose were recorded. Immediately postdelivery, maternal and umbilical venous blood samples were obtained and the concentrations of glyburide were determined by high-performance liquid chromatography-mass spectrometry with a limit of detection of 0.25 ng/mL. RESULTS: Nineteen patient dyads were analyzed. The mean total daily maternal glyburide dose was 6.6±6.3 mg per day and the mean time between last dose and sampling was 13.3±6.5 hours. The mean maternal serum glyburide level at birth was 15.4±20.8 ng/mL, whereas the mean umbilical glyburide level was 7.5±8.2 ng/mL, which showed a statistical correlation (r=0.72, P<.01). There were statistically significant relationships between total maternal glyburide dose (1.25-20 mg per day) and maternal glyburide levels (0.93-70.71 ng/mL; r=0.46, P≤.01) and between total maternal glyburide dose and umbilical glyburide levels (0.95-32.41 ng/mL; r=0.43, P≤.01) However, we observed wide variability in maternal and umbilical glyburide levels at both extremes of the total glyburide dose. Seventy-nine percent of cord samples (15/19) had glyburide levels less than 10 ng/mL (the limit of detection reported in earlier studies) and 37% (7/19) were higher than the corresponding maternal samples. CONCLUSION: Transplacental transfer of glyburide is highly variable among patients, corroborating ex vivo placental perfusion studies showing a transport-mediated glyburide efflux from the fetal to the maternal circulation. In most neonates (79%), glyburide levels were below 10 ng/mL. LEVEL OF EVIDENCE: III.

The importance of fasting blood glucose in screening for gestational diabetes.

OBJECTIVE: To determine how well an isolated abnormal fasting blood glucose (FBG) value on the 1-step, 75-g, 2-hour glucose tolerance test (GTT) indicates significant gestational diabetes (GDM). METHODS: Retrospective cohort study, January 2011 to May 2012. Patients diagnosed by the 1-step method were assigned by their abnormal results to the isolated fasting (FBG), isolated 1-hour (1HBG), isolated 2-hour (2HBG), or multiple-value (≥2BG) group. Characteristics and outcomes were compared using ANOVA, Kruskal--Wallis, and Chi-squared tests. RESULTS: 324 patients were included. Compared to other groups, the FBG group (N = 23) had the highest incidence of requiring medical therapy (78.26%), mean body mass index (29.40 ± 6.20 kg/m(2)), and percentage of Black plus Hispanic women (60.87%). CONCLUSIONS: Seven percent of women were diagnosed with GDM by an isolated abnormal fasting BG and have significant disease. This group should not be missed; therefore, fasting BG should be integrated into all GDM screening.