Assessment of costs and benefits of management of gestational diabetes mellitus.

The purpose of this pilot study was to perform a cost-identification analysis of care for gestational diabetes mellitus (GDM) by determining the direct costs of the diagnostic procedures and treatment used for the outpatient management of GDM (program input costs) and the direct costs of maternal hospitalization after diagnosis of GDM, delivery of the baby, and newborn care (outcome costs). Reimbursed average charges in the Northern California (NoCal) managed care market in 1996 were used to establish the direct costs, and the direct costs were then applied to the elements of care and pregnancy outcomes of three GDM management programs in NoCal, Southern California (SoCal), and New England (NewEng), using prospectively collected data. Reimbursed amounts for the detailed elements of GDM management (program input costs) are presented in the categories of diagnosis of GDM, diabetes treatment supplies, doctor's office visits, office visits to ancillary providers, and fetal surveillance. Program input costs per patient were $817 for diet-treated and $1,838 for insulin-treated women in NoCal, and were estimated to be $882 for diet-treated and $1,425 for insulin-treated women in NewEng. Program input costs for women requiring insulin treatment who were randomized to premeal or postprandial blood glucose testing (N Engl J Med 333:1237, 1995) in SoCal were estimated to be $3,596 per patient for the premeal group and $3,770 per patient for the postprandial group. Reimbursed amounts for health care expenditures related to pregnancy outcomes are detailed in the categories of hospital and physician charges for maternal antepartum hospitalization ($1,864 for 2 days), vaginal delivery with 50% use of epidural anesthesia ($4,050), cesarean section ($5,932), and neonatal intensive care ($9,130 for 4 days). Outcome costs per patient were $5,792 for diet-treated and $6,462 for insulin-treated women in NoCal. Outcome costs per patient were estimated to be $6,096 for diet-treated and $11,216 for insulin-treated women in NewEng, and $8,013 for the premeal blood glucose group and $7,495 for the postprandial blood glucose group in SoCal (both groups required insulin treatment). Incremental cost-effectiveness of postprandial monitoring in the SoCal controlled trial was $35 per patient in input costs per cesarean section averted and $25 per patient in input costs per neonatal intensive care unit day prevented. The benefit-to-cost ratio of the difference in input and outcome costs was 2.98 in favor of postprandial monitoring in the SoCal study. Cost analysis should be included in clinical trials of the management of GDM.

Chronological supplement to the Carcinogenic Potency Database: standardized results of animal bioassays published through December 1982.

This paper is a chronological supplement to our earlier publication, "A Carcinogenic Potency Database of the Standardized Results of Animal Bioassays." We report here results of carcinogenesis bioassays published in Technical Reports of the National Cancer Institute/National Toxicology Program between July 1980 and December 1982, and the general literature between July 1981 and December 1982. This supplement includes results of 280 long-term, chronic experiments of 114 test compounds, and reports the same information about each experiment in the same plot format as the earlier paper: e.g., the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 and its statistical significance, dose response, author's opinion about carcinogenicity, and literature reference. While a number of appendices are provided to facilitate use of this supplement, we have not duplicated here the material published earlier. Instead, we refer the reader to the earlier publications (Peto et al. and Gold et al.) for a thorough description of the numerical index of carcinogenic potency (TD50), a guide to the plot of the database, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. For 44 of the 114 chemicals reported in this second plot, results of earlier experiments are also given in the first plot; since only 1981-1982 results are reported here, the first plot is required for these repeated compounds. In this paper we also give corrections for errors that appeared in the earlier publication.

A carcinogenic potency database of the standardized results of animal bioassays.

The preceding paper described our numerical index of carcinogenic potency, the TD50 and the statistical procedures adopted for estimating it from experimental data. This paper presents the Carcinogenic Potency Database, which includes results of about 3000 long-term, chronic experiments of 770 test compounds. Part II is a discussion of the sources of our data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Part III is a guide to the plot of results presented in Part IV. A number of appendices are provided to facilitate use of the database. The plot includes information about chronic cancer tests in mammals, such as dose and other aspects of experimental protocol, histopathology and tumor incidence, TD50 and its statistical significance, dose response, author's opinion and literature reference. The plot readily permits comparisons of carcinogenic potency and many other aspects of cancer tests; it also provides quantitative information about negative tests. The range of carcinogenic potency is over 10 million-fold.

The effects of carbohydrate restriction in patients with diet-controlled gestational diabetes.

OBJECTIVE: To determine the effect of carbohydrate restriction on perinatal outcome in patients with diet-controlled gestational diabetes mellitus (GDM). METHODS: Women with diet-controlled GDM were divided non-randomly into two groups based on their dietary carbohydrate content: those with low dietary carbohydrate content (below 42%) and those with high dietary carbohydrate content (exceeding 45%). Subjects kept dietary accounts and were followed with daily fasting and postprandial glucose assessments. Subjects also were tested daily for urinary ketones. Glycosylated hemoglobin, mean fasting and postprandial glucose values, incidence of macrosomia and large for gestational age (LGA) infants, cesarean deliveries for cephalopelvic disproportion and macrosomia, and need for insulin therapy were compared between the groups. RESULTS: The two groups were identical in terms of demographic characteristics. Significant reductions in the postprandial glucose values were seen among subjects in the low-carbohydrate group (P < .04). Fewer subjects in the low-carbohydrate group required the addition of insulin for glucose control (P < .047; relative risk [RR] 0.14; 95% confidence interval [CI] 0.02, 1.00). The incidence of LGA infants was significantly lower in the low-carbohydrate group (P < .035; RR 0.22; 95% CI 0.05, 0.91). Subjects in the low carbohydrate group also had a lower rate of cesarean deliveries for cephalopelvic disproportion and macrosomia (P < .037; RR 0.15; 95% CI 0.04, 0.94). CONCLUSION: Carbohydrate restriction in patients with diet-controlled GDM results in improved glycemic control, less need for insulin therapy, a decrease in the incidence LGA infants, and a decrease in cesarean deliveries for cephalopelvic disproportion and macrosomia.

Term early-onset neonatal seizures: obstetric characteristics, etiologic classifications, and perinatal care.

OBJECTIVE: To describe obstetric characteristics and etiologic classifications and assess perinatal care in term neonates with early-onset seizures. METHODS: We performed a retrospective review of neonatal and obstetric records of neonates delivered at term with a diagnosis of early-onset seizures between January 1981 and December 1992 at Long Beach Memorial Medical Center. Data regarding obstetric characteristics and etiologic classifications of the seizures were abstracted from the medical records. Lack of antepartum testing in high-risk patients, delayed intervention with nonreassuring antepartum or intrapartum fetal heart rate patterns, birth trauma, and failure to use prophylactic antibiotics or treat infection were the criteria used for identifying seizures that were potentially preventable. RESULTS: Forty term neonates had early-onset seizures out of 60,712 live births (0.07%). These seizures were attributed to hypoxic events in 15 neonates (37.5%), cerebral malformations in seven (17.5%), cerebral infarcts in seven (17.5%), intracranial hemorrhage in five (12.5%), infection in three, and an unknown etiology in three. Twenty-three neonates had 5-minute Apgar scores of 7 or greater (cerebral malformations excluded). Seven of these neonates (30%) had cerebral infarcts. A review of all records identified nine cases (22.5%) of the early-onset seizures as potentially preventable. CONCLUSION: The majority of the term early-onset neonatal seizures identified did not appear to be preventable. Many of the neonates with 5-minute Apgar scores of 7 or greater had cerebral infarcts.

Labor and delivery management of the multiple gestation.

Labor and delivery management of multiple gestations remains controversial. The authors review issues relating to the management of labor and the administration of anesthesia in twin gestations. A comprehensive review of published data pertaining to delivery route planning for twins using fetal presentation, gestational age, and estimated fetal weight is presented. Individualization of intrapartum care in twin gestations is imperative.

Cervical assessment: visual or digital?

Our hypothesis for this study was that visual cervical assessment is not equivalent to digital assessment in patients with uterine contractions. We compared visual with digital cervical examinations done on 133 gravid women evaluated in the labor and delivery department because of uterine contractions. Patients at 27 weeks' gestation or more, subjectively in early labor, were prospectively entered into the study. Cervical dilatation and effacement were determined by two separate examiners blinded to each other's assessment, one by digital examination and the other by visual examination, in random order no more than 5 minutes apart. Eight of 133 patients were excluded from data analysis because of inability to visualize the cervix during speculum examination. Data analysis was done with correlation coefficient and the Bland and Altman test for agreement of two clinical measurements. Visual examination only underestimated actual cervical dilation by 0.60 cm (95% confidence interval [CI] 0.58 to 0.62 cm) and the limits of agreement were -2.06 cm (95% CI -2.02 to -2.09 cm) to 3.25 cm (95% CI 3.21 to 3.29 cm). Similarly, visual assessment underestimated effacement by 14.2% (95% CI 13.7% to 14.6%) and the limits of agreement were -41.3% (95% CI -40.5% to 42.0%) to 69.9% (95% CI 68.8% to 70.4%). In conclusion, cervical assessment in patients with uterine contractions who are thought to be in labor by visual speculum examination is not equivalent to that by digital examination. This difference seems to only be clinically significant if the cervix is more than 3 cm dilated.

The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial.

OBJECTIVE: Delayed cord clamping has been shown to decrease the need for transfusion in preterm neonates, but may delay resuscitation. The aim of this study was to determine whether umbilical cord milking compared with immediate cord clamping in extremely preterm deliveries reduces the need for neonatal red blood cell transfusion. STUDY DESIGN: Women admitted to a tertiary care center and expected to deliver between 24 to 28 completed weeks of gestation were randomized to cord milking before clamping or immediate cord clamping. The primary outcome was the risk of neonatal transfusion, reported as risk ratio (RR) and 95% confidence interval (CI). RESULT: Of 113 women who were enrolled and randomized, 56 were assigned to cord milking with 36 remaining eligible and completing the study and 57 were assigned to the control group with 39 remaining eligible and completing the study. Albeit not statistically significant, neonates in the cord milking group were less likely to require transfusion compared with those in the control group (RR: 0.86; 95% CI: 0.73 to 1.0). Neonates whose cords were milked had higher hematocrits at birth (P=0.004) and were less likely to develop an intraventricular hemorrhage (P=0.0195). CONCLUSION: Milking the umbilical cord of a preterm neonate is an easy intervention with the potential to improve perinatal outcomes. Our results suggest that milking of the cord increases the neonate's initial hematocrit and may lessen the need for transfusion in the neonatal period. The observed reduction in the incidence of intraventricular hemorrhage may have important long-term implications that warrant further study.

Prediction of an abnormal karyotype in fetuses with omphalocele.

The aim of this study was to assess the value of ultrasonographic evaluation in predicting abnormal karyotypes in fetuses with omphalocele. Forty fetuses with antenatally diagnosed omphalocele and available karyotype results were reviewed. Ultrasound evaluation included herniation contents and size, and the detection of other anomalies. Nine of 40 consecutive fetuses had abnormal karyotypes: trisomy 18 (n = 5), trisomy 13 (n = 3), 47,XXX (n = 1). Only 1/25 with an extracorporeal liver versus 8/15 with an intracorporeal liver had abnormal chromosomes [P = 0.0006, RR = 0.14 (0.02 < RR < 0.9)]. Small defects (< 3 cm) were associated with abnormal karyotypes [P = 0.01, RR = 4.7 (1.4 < RR < 15.6)]. Finding concurrent malformations was highly associated with chromosomal anomalies [P = 0.00004, RR = 4.4 (2.3 < RR < 8.5)]. The presence of associated malformations, an intracorporeal liver, and a small herniation size are highly suggestive of an associated abnormal karyotype.

Aplasia cutis congenita: a rare cause of elevated alpha-fetoprotein levels.

We present a catastrophic case of aplasia cutis congenita from a pregnancy complicated by elevated maternal serum and amniotic fluid alpha-fetoprotein levels and a positive acetylcholinesterase. Delivery occurred at 27 weeks 1 day after premature rupture of membranes with chorioamnionitis. The neonate lacked > 90% of its skin and died.

Gestational diabetes: does the presence of risk factors influence perinatal outcome?

OBJECTIVE: Our purpose was to determine whether gestational diabetics with risk factors for gestational diabetes have worse glucose tolerance and poorer birth outcomes than those without risk factors. STUDY DESIGN: We conducted a nonconcurrent cohort study of gestational diabetics identified by universal screening and delivered from Jan. 1, 1990, to Dec. 31, 1992. Multiple gestations and patients with chronic medical conditions were excluded. The following risk factors for gestational diabetes mellitus were abstracted: obesity (> 80 kg), family history of diabetes, previous gestational diabetes mellitus, and previous macrosomic, stillborn, or anomalous fetus. Patients with one or more risk factors were compared with those without risk factors. A group of low-risk nondiabetic patients served as controls. The incidences of A2 diabetes mellitus, cesarean section, neonatal macrosomia, and shoulder dystocia were the outcome variables of interest. RESULTS: Selective screening would have failed to detect 43% of gestational diabetics. Twenty-eight percent of the missed gestational diabetics would have required insulin (class A2). When compared with controls, patients with gestational diabetes mellitus were at increased risk for macrosomia (26% vs 11%, p < 0.01), cesarean section (37% vs 15%, p < 0.01), and shoulder dystocia (9% vs 2%, p < 0.05). Patients with and without risk factors did not differ in mean maternal age, gestational age at delivery, birth weight, incidence of requiring insulin, macrosomia, or cesarean delivery. The similarities between those with and without risk factors remained after stratification by maternal age (> or = 30 years). CONCLUSION: Gestational diabetics are at increased risk for adverse birth outcomes compared with low-risk controls. Class A2 diabetes mellitus and fetal macrosomia with its attendant risks are equally prevalent among patients with and without risk factors for gestational diabetes mellitus. Because > 40% of cases will be missed with selective screening, universal screening should be favored for detection of gestational diabetes mellitus.

Tocolysis in advanced preterm labor: impact on neonatal outcome.

Chart review of 73 patients with 3.5 cm or more dilation, intact membranes, and regular contractions at less than 36 weeks. Forty-four (group A) received tocolysis with magnesium sulfate, and 13 of the 44 also received indomethacin. Twenty-nine (group B) received no tocolysis. Obstetric and neonatal outcomes were compared. Demographic factors and admission gestational age, cervical dilation, effacement, and uterine activity were similar. Twenty-one of the 44 in group A versus 3 of 29 in group B had delivery delayed by more than 48 hours (p = 0.002). Group A had a lower incidence of severe respiratory distress syndrome; 4 of 48 babies in group A versus 9 of 32 in group B (p = 0.04; RR = 0.47; confidence interval [CI], 0.2, 1.0). Tocolysis in advanced preterm labor delays delivery by more than 48 hours in 50% of patients. The neonatal benefits of aggressive tocolysis in cases with advanced cervical dilation may outweigh the potential maternal risks of tocolysis, particularly in the setting of extreme prematurity. Delay in delivery enabling steroid enhancement of pulmonary maturity reduces the severity of respiratory distress syndrome.

Preterm premature rupture of membranes and abruptio placentae: is there an association between these pregnancy complications?

OBJECTIVE: Our purpose was to determine whether the incidence of abruptio placentae is increased in pregnancies with preterm premature rupture of membranes and to assess whether certain clinical risk factors in this group predispose them to have abruptio placentae. STUDY DESIGN: A retrospective cohort study over a 2.5-year period was performed. The study group consisted of 756 singleton pregnancies between 20 and 36 weeks' gestation complicated by preterm premature rupture of membranes and managed expectantly. The control group consisted of 11,240 pregnancies not complicated by preterm premature rupture of membranes and delivered during the same time period. The incidence of abruptio placentae was compared between the two groups. The study group of patients with preterm premature rupture of membranes was further subdivided into cases with (n = 38) and without abruptio placentae (n = 718) and compared. Clinical factors such as admission amniotic fluid index, history of bleeding before or after rupture of membranes, incidence of intrapartum fetal distress, and low 5-minute Apgar scores (< 6), latency-to-delivery interval, gestational age and weight at delivery, and incidence of amnionitis and endometritis were compared. RESULTS: The incidence of abruptio placentae in the study group (38/756, 5%) was significantly higher than that in the control group (97/11, 240, 0.9%) (p < 0.001, odds ratio = confidence interval). Comparison of cases with preterm premature rupture of membranes with and without abruptio placentae demonstrated both groups to have a similar gestational age at delivery, birth weight, latency-to-delivery interval, amniotic fluid index, and infectious morbidity. The group with abruptio placentae had a significantly higher incidence of bleeding before rupture of membranes (six of 38, 15% vs eight of 718, 1%; p < 0.005) and of intrapartum fetal distress (18/38, 46% vs 49/718, 7%; p < 0.0009). CONCLUSIONS: Pregnancies complicated by preterm premature rupture of membranes that are managed expectantly are at significant risk for abruptio placentae. Preterm premature rupture of membranes in such cases is more often preceded by bleeding. These abruptions may predispose the patient to intrapartum fetal distress.

Pulmonary injury associated with appendicitis in pregnancy: who is at risk?

OBJECTIVE: Our purpose was to determine risk factors for pulmonary injury in women with antepartum appendicitis. STUDY DESIGN: This case-control study included 49 patients with appendicitis during pregnancy. Patients who had pulmonary injury composed the study group (n = 9); the control subjects had no injury (n = 40). Records were abstracted for gestational age at surgery, type of anesthesia, presenting symptoms, findings on physical examination, vital signs, laboratory test results, use of tocolytics or antibiotics, and fluid management. Pulmonary injury was characterized by dyspnea, tachypnea, PaO2 < or = 70 mm Hg, and an abnormality on chest radiography. RESULTS: Pulmonary injury developed in nine study patients (18%) (adult respiratory distress syndrome, n = 2; pulmonary edema or infiltrates, n = 7) as a complication of appendicitis during pregnancy. All study group patients were at > 20 weeks' gestation compared with 27 of 40 (67%) control subjects (p = 0.05). Univariate analysis showed that fluid overload > or = 4 L, maximum respiratory rate > 24 breaths/min, maximum heart rate > 110 beats/min, maximum temperature > or = 100.4 degrees F, general anesthesia, and tocolytic use were significant (p < 0.005). By multivariate analysis with the use of stepwise logistic regression a model of fluid overload > or = 4 L, respiratory rate > 24 breaths/min, maximum temperature > or = 100.4 degrees F, and tocolytic usage would predict 99% of injury cases. CONCLUSIONS: Iatrogenic factors such as injudicious fluid management and tocolytic use can greatly increase the risk for pulmonary injury with antepartum appendicitis.

Naturally occurring insulin autoantibodies in neonates of normal pregnancies and their relationship to insulinemia and birth weight.

OBJECTIVE: The objectives of this study were to determine whether insulin autoantibodies are present in umbilical cord blood from normal pregnancies, determine whether cord blood insulin autoantibody levels correlate with respective maternal levels at delivery, determine whether cord blood insulin autoantibody levels are related to cord blood or maternal insulin levels, and to determine what relationship neonatal birth weight has with either cord blood insulin autoantibody and insulin levels or maternal insulin autoantibody and insulin levels. STUDY DESIGN: Paired umbilical cord and maternal serum samples were taken from 70 normal subjects at delivery. Measurements of serum insulin autoantibody (competitive charcoal radiobinding assay) and insulin (radioimmune inhibition assay) levels were performed. Multiple linear regression analysis and paired t tests were used for data analyses. RESULTS: Neonatal insulin autoantibody levels (120 nU/ml) were more than two times higher than maternal levels (49 nU/ml) (p < 0.001). No correlation was observed between neonatal and maternal insulin autoantibody levels (r = 0.14, p = 0.25). A positive correlation of both neonatal and maternal insulin with birth weight was observed (r = 0.28, p < 0.02; and r = 0.36, p < 0.01, respectively). CONCLUSIONS: These results suggest that the insulin autoantibody levels in fetal cord blood are not related to maternal levels in normal uncomplicated pregnancies. In addition, insulin levels in both maternal and neonatal circulations were positively correlated with increased birth weight in the normal pregnancies studied.

Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy.

BACKGROUND: The fetuses of women with gestational diabetes mellitus are at risk for macrosomia and its attendant complications. The best method of achieving euglycemia in these women and reducing morbidity in their infants is not known. We compared the efficacy of postprandial and preprandial monitoring in achieving glycemic control in women with gestational diabetes. METHODS: We studied 66 women with gestational diabetes mellitus who required insulin therapy at 30 weeks of gestation or earlier. The women were randomly assigned to have their diabetes managed according to the results of preprandial monitoring or postprandial monitoring (one hour after meals) of blood glucose concentrations. Both groups were also monitored with fasting blood glucose measurements. The goal of insulin therapy was a preprandial value of 60 to 105 mg per deciliter (3.3 to 5.9 mmol per liter) or a postprandial value of less than 140 mg per deciliter (7.8 mmol per liter). Obstetrical data and information on neonatal outcomes were collected. RESULTS: The prepregnancy weight, weight gain during pregnancy, gestational age at the diagnosis of diabetes and at delivery, degree of compliance with therapy, and degree of achievement of target blood glucose concentrations were similar in the two groups. The mean (+/- SD) change in the glycosylated hemoglobin value was greater in the group in which postprandial measurements were used (-3.0 +/- 2.2 percent vs. 0.6 +/- 1.6 percent, P < 0.001) and the infants' birth weight was lower (3469 +/- 668 vs. 3848 +/- 434 g, P = 0.01). Similarly, the infants born to the women in the postprandial-monitoring group had a lower rate of neonatal hypoglycemia (3 percent vs. 21 percent, P = 0.05), were less often large for gestational age (12 percent vs. 42 percent, P = 0.01) and were less often delivered by cesarean section because of cephalopelvic disproportion (12 percent vs. 36 percent, P = 0.04) than those in the preprandial-monitoring group. CONCLUSIONS: Adjustment of insulin therapy in women with gestational diabetes according to the results of postprandial, rather than preprandial, blood glucose values improves glycemic control and decreases the risk of neonatal hypoglycemia, macrosomia, and cesarean delivery.