Improving blood product management in placenta accreta patients with severe bleeding: institutional experience.

BACKGROUND: Placenta accrete spectrum (PAS) is a significant risk factor for postpartum hemorrhage and effective blood product management is critical in ensuring patient safety. In PAS patients undergoing cesarean section (CS) blood transfusion management guided by the combined clinical experience of the anesthesiologist and surgeon with point-of-care coagulation testing appears safe and effective. We describe and evaluate our experience and identify potential areas for improvement with blood product management in this patient population. METHODS: A retrospective chart review of peri-operative demographic, anesthetic, and obstetric data was conducted for all patients with PAS undergoing CS between 2012 and 2018 at our center. To facilitate a practical evaluation of blood product management, we divided patients into two groups based on the severity of bleeding. RESULTS: A total of 221 parturients with PAS underwent CS, with 133 in group 1 requiring excessive amounts of transfusion and 88 in group 2 requiring management similar to other uncomplicated CS cases. There were no deaths or instances of disseminated intravascular coagulation, and intensive care unit admission occurred in five cases (2.2%). Patients in group 1 had higher mean nadir values of intra-operative hemoglobin and platelet count. We observed a high rate of missing data for peri-operative measurement of lactate and fibrinogen, PAS grade documentation, and temperature monitoring. CONCLUSION: Given no significant morbidity or mortality, clinical judgment in experienced centers appears safe for the management of PAS patients undergoing CS. The adoption of an institutional protocol and point-of-care coagulation testing could decrease over-transfusion and associated complications.

Cephalic extraction versus breech extraction in second-stage caesarean section: a retrospective study.

OBJECTIVE: Our primary objective was to compare maternal and neonatal outcomes based on the attempted mode of extraction. Our secondary objective was to compare the outcomes based on the actual mode of extraction. DESIGN: A retrospective cohort study at a single tertiary centre between the years 2011 and 2019. SETTING: The study included 1028 cases of term pregnancies in vertex presentation that were delivered by caesarean section at the second stage of delivery. POPULATION: Patients were grouped according to the attempted mode of extraction: attempted cephalic extraction (674) and breech extraction (354). A subgroup analysis was conducted, comparing successful cephalic extraction (615), failed cephalic extraction (59) and breech extraction (354). METHODS: Both maternal and neonatal complication rates were compared between the groups. RESULTS: There were significantly more uterine incision extensions (27.4 versus 11.9%, P < 0.001) and increased need for blood transfusion (10.7 versus 6.2%, P = 0.018) in the cephalic extraction compared with the breech extraction group. The highest rate of uterine incision extensions (45.8%) and need for blood transfusion (22%) was in the subgroup of failed cephalic extraction. The rate of adverse neonatal outcomes was comparable between the two groups. However, in the subgroup of failed cephalic extraction, there were higher rates of low 1-minute Apgar scores, NICU hospitalisation and limb fractures compared with successful cephalic extractions and breech extractions (P = 0.016, 0.01, <0.001, respectively). CONCLUSIONS: Breech extraction in second-stage caesarean section is associated with fewer maternal complications compared wiith attempted cephalic extraction without increasing neonatal complication rates. TWEETABLE ABSTRACT: In breech versus cephalic extraction, breech extraction was found to have better outcomes in second-stage caesarean section.

Development and validation of a machine-learning model for prediction of shoulder dystocia.

OBJECTIVES: To develop a machine-learning (ML) model for prediction of shoulder dystocia (ShD) and to externally validate the model's predictive accuracy and potential clinical efficacy in optimizing the use of Cesarean delivery in the context of suspected macrosomia. METHODS: We used electronic health records (EHR) from the Sheba Medical Center in Israel to develop the model (derivation cohort) and EHR from the University of California San Francisco Medical Center to validate the model's accuracy and clinical efficacy (validation cohort). Subsequent to application of inclusion and exclusion criteria, the derivation cohort included 686 singleton vaginal deliveries, of which 131 were complicated by ShD, and the validation cohort included 2584 deliveries, of which 31 were complicated by ShD. For each of these deliveries, we collected maternal and neonatal delivery outcomes coupled with maternal demographics, obstetric clinical data and sonographic fetal biometry. Biometric measurements and their derived estimated fetal weight were adjusted (aEFW) according to gestational age at delivery. A ML pipeline was utilized to develop the model. RESULTS: In the derivation cohort, the ML model provided significantly better prediction than did the current clinical paradigm based on fetal weight and maternal diabetes: using nested cross-validation, the area under the receiver-operating-characteristics curve (AUC) of the model was 0.793 ± 0.041, outperforming aEFW combined with diabetes (AUC = 0.745 ± 0.044, P = 1e-16 ). The following risk modifiers had a positive beta that was > 0.02, i.e. they increased the risk of ShD: aEFW (beta = 0.164), pregestational diabetes (beta = 0.047), prior ShD (beta = 0.04), female fetal sex (beta = 0.04) and adjusted abdominal circumference (beta = 0.03). The following risk modifiers had a negative beta that was < -0.02, i.e. they were protective of ShD: adjusted biparietal diameter (beta = -0.08) and maternal height (beta = -0.03). In the validation cohort, the model outperformed aEFW combined with diabetes (AUC = 0.866 vs 0.784, P = 0.00007). Additionally, in the validation cohort, among the subgroup of 273 women carrying a fetus with aEFW ≥ 4000 g, the aEFW had no predictive power (AUC = 0.548), and the model performed significantly better (0.775, P = 0.0002). A risk-score threshold of 0.5 stratified 42.9% of deliveries to the high-risk group, which included 90.9% of ShD cases and all cases accompanied by maternal or newborn complications. A more specific threshold of 0.7 stratified only 27.5% of the deliveries to the high-risk group, which included 63.6% of ShD cases and all those accompanied by newborn complications. CONCLUSION: We developed a ML model for prediction of ShD and, in a different cohort, externally validated its performance. The model predicted ShD better than did estimated fetal weight either alone or combined with maternal diabetes, and was able to stratify the risk of ShD and neonatal injury in the context of suspected macrosomia. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Disparity in fetal growth between twin and singleton gestation: the role of adipokines.

OBJECTIVE: Twin pregnancies are characterized by unique pattern of attenuated fetal weight gain during late gestation compared with singleton gestation. The mechanism(s) responsible for regulating twin growth has not yet elucidated. Leptin and adiponectin are two adipocytokines implicated in metabolism and energy balance of fetuses, newborns and adults. Moreover, these hormones have been suggested to play a role in fetal growth. The objective of the study was to determine cord blood adiponectin and leptin in twins and singletons, with and without growth impairment. STUDY DESIGN: This was a case-control study. It included two groups of newborns, matched for gestational age and birth weight percentile: singleton (n=60 newborns) and twins (n=44 newborns). Adiponectin and leptin were determined in cord blood, and compared between the groups according to clinical and demographic characteristics. Non-parametric and parametric statistical methods were employed. RESULTS: Median adiponectin and leptin concentrations were lower in twins vs singletons (P<0.001 for both comparisons). Among small for gestational age newborns (SGA), median concentration of adiponectin (P=0.04), but not leptin (P=0.1), was lower in twins compared to singletons. In pooled analysis (singleton plus twins), cord blood adiponectin and leptin were strongly correlated with gestational age (P<0.001 and P=0.005, respectively) and birth weight (P<0.001 and P<0.001, respectively). Regression analysis revealed that plurality (P=0.02) was significantly and independently associated with cord blood adiponectin concentrations, after adjustment for confounding variables. Similar regression in which leptin was the independent variable revealed that only birth weight (P=0.01) was significantly and independently associated with cord blood leptin concentrations. CONCLUSIONS: Twin pregnancies are associated with lower cord blood concentrations of adiponectin and leptin compared with singleton gestations. However, only cord blood adiponectin, but not leptin, was lower in SGA neonates. Collectively, these data suggest that adiponectin may be implicated in the mechanism accounting for the growth disparity between twins and singletons.

Trial of labour in twin pregnancies: a retrospective cohort study.

OBJECTIVE: To assess the success rate of vaginal delivery among women with twin pregnancies; the Twin Birth Study has shown that vaginal delivery and caesarean section are equally safe for twin delivery but >40% of the planned vaginal delivery group delivered by caesarean section. DESIGN: A retrospective cohort study. SETTING: A tertiary medical centre. POPULATION: A total of 2194 women with twin pregnancies not complicated with very low birthweight. METHODS: Planned mode of delivery was documented in the woman's electronic record upon entering the delivery room. Information regarding maternal age at delivery, parity, gestational age, presentation, previous history of caesarean delivery, birthweight and Apgar score was collected from the obstetric electronic charts. MAIN OUTCOME MEASURED: Rate of vaginal twin delivery. RESULTS: Of the 2194 women included, 1311 twin pregnancies had planned caesarean delivery and 883 underwent a trial of labour. Of the 883 women who underwent a trial of labour, the rate of vaginal delivery was 86.9%, whereas the rates of caesarean delivery and combined vaginal-caesarean delivery were 11.1% and 2.0%, respectively. Presentation of second twin, gestational age and maternal age did affect the chances of success. Nulliparity [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.4-4.05], Foley induction of labour (OR 2.33, 95% CI 1.38-3.91) and body mass index >30 kg/m(2) (OR 1.76, 95% CI 1.03-3) were independent risk factors for caesarean delivery. CONCLUSIONS: The rate of vaginal delivery among women with twin pregnancies who undergo labour can be high, especially in women who laboured spontaneously and have delivered before. TWEETABLE ABSTRACT: The rate of vaginal delivery of twins can be high, especially in women who have delivered before.

Diffusion MRI findings in monochorionic twin pregnancies after intrauterine fetal death.

BACKGROUND AND PURPOSE: Monochorionic twin pregnancies complicated by the IUFD of 1 twin are associated with substantial morbidity to the survivor twin. The aim of this study was to determine whether fetal sonography, T2 MR imaging, and DWI can diagnose acute cerebral lesions in the survivor of an MC twin pregnancy shortly after fetal death of the co-twin. MATERIALS AND METHODS: During the study period (2007-2010) 34 cases of single IUFD were evaluated. Group A included 6 cases complicated by spontaneous IUFD. Group B had 10 cases of fetal death shortly after treatment of severe TTTS. These were compared with group C, with 18 pregnancies treated by selective termination due to severe complications in MC pregnancies. RESULTS: Altogether 9/34 patients had abnormal prenatal cerebral findings. In group A, in 2/6 of pregnancies with spontaneous death, MR imaging showed findings of severe cerebral infarct, while cerebral damage was not evident by sonography. In another case, the surviving fetus was found to be hydropic on sonography, while MR imaging findings were normal. In group B, in 1/10 cases, cerebral infarct was demonstrated only by DWI. In 2 other cases, sonographic findings were normal, but MR imaging showed germinal matrix bleeding. In group C, in 1/18 cases, only DWI showed bilateral cerebral ischemia. In 2 other cases, MR imaging findings suggested germinal matrix bleeding and focal changes in the basal ganglia. In both cases, fetal sonographic findings were normal. CONCLUSIONS: In our study, early manifestations of cerebral ischemia in monochorionic twin pregnancies were better diagnosed with MR imaging, especially with DWI.

Fetal thymus size as a predictor of chorioamnionitis in women with preterm premature rupture of membranes.

OBJECTIVE: Emerging evidence indicates that chorioamnionitis is associated with a significant decrease in thymic size at birth in very low birth weight (VLBW) preterm infants. The aim of this study was to determine whether decreased fetal thymus size is associated with histological or clinical chorioamnionitis in patients with preterm premature rupture of membranes (PROM). METHODS: Twenty-one patients between 24 and 35 weeks of gestation with preterm PROM were included. Serial ultrasound examinations were performed during the latency period, and measurements of the fetal thymus size were obtained. Small thymus was defined as a thymus perimeter < or = 5th percentile according to a fetal thymus nomogram, which was based on measurements of 403 fetuses. Diagnosis of chorioamnionitis was made using neonatal clinical parameters and histological examinations of the placentas. RESULTS: In our study 13 patients presented with thymus size below the 5th percentile. Among the 13 patients with small thymus, nine (69%) had clinical or histological findings consistent with the diagnosis of chorioamnionitis. All eight women with a normal-sized thymus had no evidence of clinical or histological chorioamnionitis. Fetal thymus perimeter < or = 5th percentile yielded a sensitivity of 100%, specificity of 66.7%, a positive predictive value of 69% and a negative predictive value of 100% for identifying chorioamnionitis in patients with preterm PROM. CONCLUSIONS: Fetal thymus size is decreased in women with preterm PROM and chorioamnionitis. Measurement of the fetal thymus might allow an early diagnosis of chorioamnionitis in cases of preterm PROM. Normal thymus size might be used to rule out latent intrauterine infection.

Maternal serum adiponectin levels during human pregnancy.

OBJECTIVE: Pregnancy is a unique situation characterized by insulin resistance. The role of adiponectin, an insulin-sensitizing hormone, has not been completely clarified during pregnancy. The aim of this cross-sectional study was to evaluate adiponectin levels during pregnancy and postpartum. STUDY DESIGN: Adiponectin and leptin levels were tested in 80 pregnant women, 20 in each trimester (mean gestational age 10.5+/-1.9; 19.3+/-4.9; 39.3+/-0.8 weeks,) as well as 4 days postpartum. RESULTS: Adiponectin levels during first (13.3+/-3.6 micro g/ml), second (12.6+/-4.4 micro g/ml) and third trimester (11.2+/-3.7 micro g/ml) did not differ and were significantly higher than postpartum levels (8.8+/-2.1 micro g/ml; P<0.0001, P<0.004 and P<0.02, respectively). CONCLUSION: Despite increased insulin resistance during pregnancy, no significant alterations in adiponectin levels were observed. This may imply that the regulation of adiponectin during gestation is altered. The elevated gestational adiponectin levels are consistent with increased 'adiponectin resistance' during pregnancy.

One or two hours postprandial glucose measurements: are they the same?

OBJECTIVE: This study was undertaken to compare the rate of abnormal glucose levels measured after 1 hour (>140 mg%) with those measured after 2 hours (>120 mg%) postprandially in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Sixty-eight women were included in this study. All had GDM based on the criteria of Carpenter-Coustan. Women with fasting glucose levels of 105 mg% or more were excluded from the study. All women were initially treated by diet. All women measured daily capillary blood glucose levels when fasting as well as 1 hour and 2 hours postprandially for 1 week, immediately after diagnosis of GDM. Glucose levels were obtained by memory-based glucometers. All women were followed in a specialized gestational-diabetes clinic throughout the pregnancy. Insulin therapy was started on an individual basis according to common clinical criteria. Epidemiologic and perinatal data were collected from medical charts. RESULTS: The average age of the women was 30.8 +/- 5.4 years. Thirty-five percent of participants were primipara. The mean gestational age at diagnosis was 28.8 +/- 5.4 weeks. Glucose measurements included 618 readings during fasting and 2730 either 1 hour or 2 hours postprandial. Rates of abnormal glucose (>95 mg% when fasting; >140 mg% 1 hour or >120 mg% 2 hours after each meal) per person were the following: fasting, 27.1% abnormal glucose measurements; postbreakfast, 22.4% abnormal levels after 1 and 8.5% after 2 hours (P < .01); postlunch, 16.4% abnormal levels after 1 hour and 18.2% after 2 hours (not significant); postdinner, 16.3% abnormal levels after 1 hour and 30.1% after 2 hours (P < .01). CONCLUSION: The rate of abnormal values was 2.5-fold greater 1 hour postbreakfast than 2 hours postbreakfast, in contrast to an opposite ratio of a 2-fold increase in the rate of abnormal values 2 hours postdinner versus 1 hour postdinner. Therefore, differential measurement (1 hour after breakfast and 2 hours after dinner) might impose stricter criteria for controlling blood glucose levels. Further clinical research should explore whether differential measurements might reduce the rate of diabetes-associated complications.

Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus.

We have determined prehepatic insulin secretion rates (ISRs) in seven patients with gestational diabetes mellitus (GDM) and in eight age- and weight-matched nondiabetic pregnant women during late gestation (third trimester) and again postpartum. Plasma glucose concentrations were raised to approximately 8.9 mM with iv glucose (hyperglycemic clamping), and ISRs were determined by deconvolution of peripheral C-peptide concentrations using C-peptide kinetic parameters that were obtained in every patient during late gestation and again postpartum. Plasma insulin levels were measured by RIA with an antibody with minimal (<0.2%) cross-reactivity with proinsulin. During late gestation, women with GDM were more insulin resistant than nondiabetic controls and had significantly lower ISRs (689 vs. 849 pmol/min, P < 0.05) and glucose uptake rates (30.6 vs. 49.4 micromol/kg.min, P < 0.05) in response to hyperglycemia. Postpartum, ISRs and insulin resistance decreased in women with GDM and controls (ISR by 43% and 43%, respectively, and insulin resistance by 75% and 118%, respectively), and both groups had similar ISRs (352 vs. 408 pmol/min, nonsignificant). Women with GDM, however, continued to be more insulin resistant than controls. In summary, patients with GDM during late pregnancy not only had severe deficiencies in ISR but, in addition, were more insulin resistant than controls. Postpartum, insulin resistance and ISRs (and plasma insulin levels) improved in both groups, and ISRs (and plasma insulin levels) were no longer significantly different in patients with GDM and controls. Insulin resistance, however, remained higher in women with GDM, and their glucose uptake remained lower. We concluded that the women with GDM had a major ss-cell defect that made it impossible for them to compensate for their increased level of insulin resistance, which occurred during late pregnancy.

Segmentary fetal branch pulmonary artery blood flow velocimetry: in utero Doppler study.

OBJECTIVE: To evaluate changes in human, fetal segmentary, pulmonary artery blood flow velocimetry throughout pregnancy. DESIGN: Ninety-nine women with a singleton, low-risk gestation between 14 and 37 weeks of pregnancy were selected to participate in a prospective, cross-sectional study. All fetuses were evaluated using power and color Doppler ultrasound. Flow velocity waveforms at three sites of the right pulmonary artery were obtained. The pulsatility index (PI) was calculated in the proximal, mid and distal segment of the pulmonary artery. Mean values and 95% confidence interval (CI) for each segment were determined in correlation with gestational age. RESULTS: A full study that included Doppler measurements of all three segments of the pulmonary artery was completed on 99 fetuses. The highest mean PI of 2.36 was obtained in the proximal segment of the right pulmonary artery (CI = 2.29-2.42), whereas in the mid and distal segments the mean PI decreased significantly to 1.57 (CI = 1.53-1.61) and 1.02 (CI = 1.0-1.0) (P < 0.001), respectively. Throughout gestation, the mean PI measurements in the proximal, middle and distal segments of the branch pulmonary artery increased slightly, but without statistical significance (r = 0.274, 0.248, 0.047), respectively; (P > 0.5). CONCLUSIONS: The data obtained suggests that pulmonary circulation maintains stable vascular resistance during gestation in the human fetus. However, the PI obtained from the separate segments of the branch pulmonary artery is unique and each differs from the other, reflecting the proximity to the heart and the peripheral impedance at each location.

Fuel metabolism during pregnancy.

This article reviews carbohydrate and fat metabolism in both healthy pregnant women and women with gestational diabetes. Emphasis is placed on more recent investigations that have utilized stable, nonradioactive isotopes with insulin clamps to study gestational fuel metabolism. In early pregnancy, glucose-stimulated insulin secretion is increased, insulin sensitivity is unchanged or enhanced, and glucose tolerance is normal or slightly improved. Late gestation is characterized by accelerated fetal growth, rising concentrations of several diabetogenic hormones, and increased insulin resistance. The increased resistance reduces maternal glucose utilization, sparing carbohydrates for the rapidly growing fetus. The inhibitory effect of insulin on the rate of lipolysis is also significantly reduced during the third trimester of pregnancy. An earlier than normal switch from carbohydrate to fat utilization serves to promote the use of lipids as a maternal energy source. Women with gestational diabetes have been reported to have either comparable or increased insulin resistance during late gestation with several studies also demonstrating reduced insulin secretory capacity.

Effect of insulin on fat metabolism during and after normal pregnancy.

Whereas development of resistance to the action of insulin on glucose metabolism during gestation has been recognized, it is presently not known whether there is also resistance to the action of insulin on lipid metabolism. We have, therefore, examined the effect of physiological hyperinsulinemia (during euglycemic-hyperinsulinemic clamping) on free fatty acid (FFA) turnover in seven nondiabetic overweight or obese women during and after pregnancy. Basal rates of FFA release, oxidation, and reesterification and basal plasma FFA concentrations were not significantly different from each other during the 2nd and 3rd trimester of pregnancy and postpartum. During euglycemic-hyperinsulinemic (approximately 500 pmol/l) clamping, however, lipolysis was significantly less inhibited during the 3rd trimester (from 7.0 +/- 0.9 to 4.9 +/- 0.9 micromol x kg(-1) x min(-1), -30%) than during the 2nd trimester (from 8.4 +/- 0.6 to 4.1 +/- 0.9 micromol x kg(-1) x min(-1), -51%) and postpartum (from 8.5 +/- 1.1 to 4.2 +/- 0.6 micromol x kg(-1) x min(-1), -51%). Similarly, fat oxidation was not inhibited at all (from 3.5 +/- 0.3 to 3.8 +/- 0.5 micromol x kg(-1) x min(-1)) during the 3rd trimester but was suppressed by 51% (from 3.9 +/- 0.2 to 1.9 +/- 0.3 micromol x kg(-1) x min(-1)) during the 2nd trimester and by 38% (from 2.6 +/- 0.7 to 1.6 +/- 0.5 micromol x kg(-1) x min(-1) postpartum. These data demonstrated that resistance to the action of insulin on lipolysis and on fat oxidation developed during late gestation and disappeared postpartum.

Leptin in human pregnancy: the relationship with gestational hormones.

OBJECTIVES: The aims of the study were (1) to examine the relationship between leptin and placental hormones by measuring serial changes in serum levels of leptin during and after pregnancy and (2) to study the effects of several gestational hormones on leptin release from fully differentiated 3T3-L1 adipocyte cell cultures. STUDY DESIGN: Serum levels of leptin were measured throughout pregnancy and at 3 months post partum in 29 healthy women and were also measured in 18 healthy women at delivery by cesarean section and on postpartum day 3. In addition, 3T3-L1 mouse adipocytes were incubated for 24 hours in media containing various reproductive hormones and leptin production was measured. RESULTS: Serum leptin levels increased significantly (8.4 +/- 0.9 vs 13.5 +/- 1.5 ng/mL; P <.001) between the first 2 trimesters of pregnancy but not between the second and third trimesters. These changes in leptin did not correlate significantly with changes in body mass index. Leptin levels dropped significantly during the immediate postpartum period, from 34.1 +/- 4.9 at cesarean delivery to 7.3 +/- 1.4 ng/mL on postpartum day 3 (P <.001). Fasting insulin level did not correlate significantly with leptin level during pregnancy but did so during the postpartum period (r = 0.60; P <.05). Leptin secretion from 3T3-L1 adipocytes was increased significantly when cells were cultured with human chorionic gonadotropin (150%, P <.01) and also when they were cultured with estrogen (120%, P <.03). CONCLUSION: The data suggest that leptin production by adipose tissue is stimulated by several hormones of pregnancy, which may contribute to the increased leptin levels observed during gestation.

Is self-monitoring of blood glucose necessary in the management of gestational diabetes mellitus?

There continues to be controversy regarding the role of blood glucose in the management of pregnant women with gestational diabetes mellitus (GDM), specifically with regard to the use of capillary versus venous samples, as well as the frequency and timing of blood glucose determinations. At the Third International Workshop Conference it was noted that "self-monitoring of capillary blood glucose has been useful in allowing the woman to participate in her own management," but its utility "in the mild GDM not requiring insulin, although reasonable and logical, has not been formally proved." This article reviews the existing evidence in the literature regarding the impact of self-monitoring of blood glucose on outcomes in pregnancies complicated by gestational diabetes. Data regarding the optimal timing, accuracy, costs, and psychosocial effects of self-monitored glucose determinations will also be explored.

Free fatty acids and insulin resistance during pregnancy.

The purpose of this study was to determine whether elevation of plasma free fatty acids (FFA) in early pregnancy would cause alterations in insulin-stimulated glucose disposal similar to those occurring in late gestation. Seven glucose-tolerant women underwent 4-h euglycemic hyperinsulinemic (1 mU/kg.min) clamping during the early second trimester of pregnancy (14-17 weeks) on 2 consecutive days, receiving either lipid (Liposyn II; 1.5 mL/min) and heparin (0.4 U/kg.min; L/H) or saline/glycerol (2.25 g/h; S/G) infusions. Rates of total body glucose disposal (6,6-2H2 glucose) and of carbohydrate and fat oxidation (indirect calorimetry) were determined at hourly intervals. Blood glucose was clamped at about 85 mg/dL. Plasma FFA increased from 290 +/- 50 to 1000 +/- 139 mumol/L during L/H infusion and decreased from 351 +/- 60 to 35 +/- 11 mumol/L during S/G infusion. L/H infusion inhibited insulin stimulation of total body glucose disposal by 28% compared with S/G infusion (from 6.7 +/- 0.7 to 4.9 +/- 0.6 mg/kg.min; P < 0.01). L/H infusion increased fat oxidation from 0.73 +/- 0.04 to 1.26 +/- 0.2 mg/kg.min (P < 0.05) and decreased carbohydrate oxidation from 2.0 +/- 0.2 to 1.6 +/- 0.2 mg/kg.min (P < 0.05). Endogenous glucose production decreased equally by approximately 70% during L/H and S/G infusions. These data showed that elevating plasma FFA levels during early pregnancy inhibits total body glucose uptake and oxidation. We conclude that elevation of plasma FFA can contribute to the peripheral insulin resistance commonly observed during late pregnancy.

Macrosomia does not predict overweight in late adolescence in infants of diabetic mothers.

OBJECTIVE: To determine the predictive value of macrosomia for overweight later in adult life in infants of diabetic mothers. DESIGN: Data from the computerized records of the Jerusalem Perinatal Study were matched to measurements made at age 17 obtained from the military draft medical examination records. PARTICIPANTS: 10,891 infants born in Jerusalem between November 1974 and February 1976. MAIN OUTCOME MEASURES: Macrosomia based on 90th percentile birth weight for gestational age and overweight defined as the 90th percentile for body mass index at age 17. RESULTS: Diabetes was diagnosed in 87 (0.8%) of the mothers. Thirty-one (35.6%) of the infants of the diabetic mothers were macrosomic compared to 1012 (9.4%) of the siblings of nondiabetic mothers (p < 0.001). At 17 years of age 10.3% vs. 9.4% of the siblings of diabetic vs. nondiabetic mothers were overweight (p > 0.05). The rate of adolescent overweight in macrosomic vs. nonmacrosomic subjects was 12.3% vs. 9.7% (p < 0.01) in siblings of nondiabetic mothers, and 16.1% vs. 7.1% (p > 0.05) for diabetic mothers. The sensitivity and specificity, in diabetic mothers, of macrosomia for overweight at age 17 was 44.4% and 66.7%, respectively. The positive and negative predictive value of macrosomia for overweight at age 17 was 16.1% and 92.9%, respectively. CONCLUSIONS: The risk of adolescent overweight was significantly increased among macrosomic infants, although this trend did not reach statistical significance in the smaller group of infants born to diabetic mothers. Macrosomia among infants of diabetic mothers had little predictive value for overweight in late adolescence.

HCFA documentation guidelines and the need for discrete data: a golden opportunity for applied health informatics.

BACKGROUND: The medical community is shocked by the complexity of the documentation now required to support the Medicare billing codes. This situation represents an opportunity for Electronic Medical Records that use discrete data to become a central factor at the point of care by fulfilling these stringent documentation specifications. METHODS: This empirical study explores whether a discrete data EMR has the ability to generate automatically a report describing what billing code is consistent with the documentation recorded. We tested this hypothesis on HBOC Pathways SMR by attempting to create algorithms that reflected the HCFA guidelines. We validated this process using historical records from the Cleveland Clinic. RESULTS: All the data elements required by HCFA were available as discrete data. Using algorithms, the billing code consistent with the documentation of the health care encounter could be automatically generated. CONCLUSIONS: EMRs using discrete data can substantially reduce the burden placed on health care providers by HCFA's new documentation guidelines. This benefit creates a window of opportunity for health informatics to become an integral tool in the provision of health care. Using EMRs for billing purposes can help achieve the loftier goal of using EMRs for quality improvement.

Pregnancy outcomes among women with and without diabetic microvascular disease (White's classes B to FR) versus non-diabetic controls.

The objective of this paper is to evaluate the impact of contemporary management on the maternal and neonatal outcomes of pregnancies complicated by diabetes in women with microvascular disease versus women without microvascular disease. The study population consisted of two hundred and eighty-eight (288) pregnant women with pregestational diabetes and one hundred and fifty (150) healthy pregnant controls. Diabetic women were grouped according to the presence (n = 103) or absence of diabetic microvascular disease (n = 185). Data were collected regarding diabetes management, level of glycemic control, and the development of antenatal complications. Maternal and neonatal outcomes were compared among the three groups. Women in the diabetes groups were stratified according to mean blood glucose levels and glycosylated hemoglobin during each trimester. There was no significant difference found between the two diabetes groups in terms of preterm labor, polyhydramnios, pyelonephritis, and growth restriction. The only maternal complications that occurred with increased incidence among women with microvascular disease were acute hypertensive complications (51.6 vs. 32.9%; p<0.05). However, when the diabetes groups were compared to healthy controls, a significant difference was seen in all maternal and neonatal complications. Preterm delivery, polyhydramnios, and large-for-gestational-age (LGA) infants were associated with poor third-trimester metabolic control as compared with others in satisfactory metabolic controls: 30.8 vs. 11.4% for preterm delivery; 17.3 vs. 5.1% for polyhydramnios; 51.9 vs. 33.9% for LGA; p<0.05. Congenital malformations were associated with poor first-trimester glucose control (5.8 vs. 1.3% anomalies in well-controlled women). Furthermore, major congenital malformations were also significantly increased in the offspring of women with diabetic microvascular disease 6.8%, as compared to 1.69% in diabetic women without microvascular disease; p<0.01. The incidence of hypertensive complications did not differ between the two diabetic groups. Pregestational diabetic women with and without microvascular disease can be counseled to anticipate comparably favorable pregnancy outcomes, although maternal and neonatal complications may exceed that experienced by pregnant women without diabetes mellitus.

Longitudinal study of carbohydrate metabolism in healthy obese pregnant women.

OBJECTIVE: To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy. RESEARCH DESIGN AND METHODS: Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500-600 pmol/l) clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester (36.8 +/- 0.9) of pregnancy and again 15.6 +/- 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6-2H2]glucose) and oxidation (with indirect calorimetry) were measured. RESULTS: There were no significant changes with respect to the action of insulin on rates of glucose disappearance (GRd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (-28%, P < 0.05, compared with the second trimester and -40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (-39% compared with -79% at the second trimester and -77% postpartum, P < 0.01). CONCLUSIONS: Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterations were reversed after delivery and appeared to be adaptive mechanisms to cope with the increased demand for glucose of the growing fetus.