Interferon therapy in primary care.

Interferons are proteins produced by human blood cells in response to stimulation (viral infection). The natural roles of interferons are host defense and modulation of the immune system. Therapeutic uses are based on these roles. Interferon-alpha has been widely used for malignancies, skin conditions, viral infections, and myeloproliferative disorders. Interferon-beta is a standard treatment for relapsing multiple sclerosis. Interferon-gamma therapy is currently used for chronic granulomatous disease and skin lesions (human papilloma virus related and keloids), but further research is ongoing. Side effects of interferon therapy are common and limit utility. Flulike symptoms are reported by more than 75% and depression by 10-40% of interferon users. Severe adverse effects are less common but may be life threatening, including autoimmune diseases, thrombotic-thrombocytopenic purpura, and acute renal failure. Limited use of interferon therapy during pregnancy has been described, with successful maternal and neonatal outcomes. Use of interferon therapy during early pregnancy is not an indication for termination.

A comparison of glyburide and insulin in women with gestational diabetes mellitus.

BACKGROUND: Women with gestational diabetes mellitus are rarely treated with a sulfonylurea drug, because of concern about teratogenicity and neonatal hypoglycemia. There is little information about the efficacy of these drugs in this group of women. METHODS: We studied 404 women with singleton pregnancies and gestational diabetes that required treatment. The women were randomly assigned between 11 and 33 weeks of gestation to receive glyburide or insulin according to an intensified treatment protocol. The primary end point was achievement of the desired level of glycemic control. Secondary end points included maternal and neonatal complications. RESULTS: The mean (+/-SD) pretreatment blood glucose concentration as measured at home for one week was 114+/-19 mg per deciliter (6.4+/-1.1 mmol per liter) in the glyburide group and 116+/-22 mg per deciliter (6.5+/-1.2 mmol per liter) in the insulin group (P=0.33). The mean concentrations during treatment were 105+/-16 mg per deciliter (5.9+/-0.9 mmol per liter) in the glyburide group and 105+/-18 mg per deciliter (5.9+/-1.0 mmol per liter) in the insulin group (P=0.99). Eight women in the glyburide group (4 percent) required insulin therapy. There were no significant differences between the glyburide and insulin groups in the percentage of infants who were large for gestational age (12 percent and 13 percent, respectively); who had macrosomia, defined as a birth weight of 4000 g or more (7 percent and 4 percent); who had lung complications (8 percent and 6 percent); who had hypoglycemia (9 percent and 6 percent); who were admitted to a neonatal intensive care unit (6 percent and 7 percent); or who had fetal anomalies (2 percent and 2 percent). The cord-serum insulin concentrations were similar in the two groups, and glyburide was not detected in the cord serum of any infant in the glyburide group. CONCLUSIONS: In women with gestational diabetes, glyburide is a clinically effective alternative to insulin therapy.

Electronic fetal monitoring: what's reassuring?

BACKGROUND: To determine which combinations of fetal heart rate pattern abnormalities are associated with normal outcome in term pregnancies. METHODS: A cohort of 2200 consecutive deliveries was examined and the fetal heart rate tracings analyzed. Singleton, term patients without chorioamnionitis or serious malformations were used to perform logistic regression analysis to select those FHR patterns associated with increased risk for Apgar<7 and cord pH<7.15, or immediate adverse outcome. RESULTS: Patients having no fetal heart rate abnormalities, mild variable decelerations, decreased variability, mild bradycardia, or accelerations present, constituted 84% of all fetal heart rate tracings. These tracings alone, or in combination, predicted 5 minute Apgar score> or =7 in 99.7%, cord pH> or =7.15 in 96.9% and no adverse neonatal sequelae in 96.2% of cases. Accelerations were reassuring regardless of FHR pattern. When these patterns were not present, non-reassuring tracings, the risk for immediate adverse outcome increased 50%. The non-reassuring tracings were both without accelerations and had tachycardia, prolonged bradycardia, severe variable or late decelerations, or a combination of these patterns. This increased risk was independent of the risk of confounders: i.e. thick meconium (1.8-fold), prolonged second stage of labor (>50 min., 1.5-fold), maternal disease (e.g. kidney, respiratory, 3-fold), or hypertensive disease (1.9-fold). CONCLUSIONS: The great majority of fetal heart rate pattern abnormalities can be considered reassuring as they are within normal variations of a healthy fetus. The non-reassuring ones identify infants that truly require further evaluation by fetal scalp, vibroacoustic stimulation, or fetal scalp blood sampling.

Group B streptococcus infection rate unchanged by gestational diabetes.

OBJECTIVE: Group B streptococcal colonization in pregnancy has been associated with adverse perinatal outcomes, including intra-amniotic infection, postpartum endometritis, and neonatal sepsis. We sought to determine whether gestational diabetes increases the risk of maternal and neonatal morbidity from group B streptococcal colonization. METHODS: Gestational diabetic and nondiabetic women who underwent vaginal or anogenital culture for group B streptococcus colonization in pregnancy were followed up for pregnancy outcome. Antibiotic prophylaxis was not routinely given. Major perinatal morbidity included intraamniotic infection, endometritis, and neonatal sepsis. Potential confounding variables included induction of labor, cesarean delivery, prematurity, maternal antibiotic use, and prolonged rupture of membranes. RESULTS: We compared 446 gestational diabetic women to 1,046 nondiabetic women for outcome. Overall, 12% were colonized with group B streptococcus, with no difference in colonization rates between gestational diabetic (12%) and nondiabetic (12%) women. There were no differences in intraamniotic infection rates between gestational diabetic and nondiabetic women, whether group B streptococcus positive (16% compared with 13%) or group B streptococcus negative (10% compared with 11%). Likewise, endometritis did not differ (6-9%) regardless of diabetes or group B streptococcus status. Neonatal sepsis was higher in group B streptococcus-positive women overall (3% compared with 1%, odds ratio 3.71, 95% confidence interval 1.23, 10.81), but did not differ between diabetic and nondiabetic pregnancies. CONCLUSION: Gestational diabetes does not alter the perinatal morbidity associated with group B streptococcal colonization in pregnancy.

Delayed appearance of pulmonary maturation markers is associated with poor glucose control in diabetic pregnancies.

Fetuses born after pregnancies complicated by diabetes display delayed pulmonary maturation as measured by the delayed appearance of biochemical indicators of pulmonary maturity (phosphatidylglycerol, lecithin/sphingomyelin ratio) and by the occurrence of hyaline membrane disease even in term gestations. We tested the hypothesis that poor maternal glycemic control is associated with delayed appearance of the biochemical markers of fetal pulmonary maturation. Consecutive diabetic pregnancies with documentation of maternal glycemic control and amniotic fluid analysis for PG were analyzed. Maternal glycemic control was defined as good if the mean blood glucose was < or = 5.8 mmol/L (105 mg/dl) and poor if > 5.8 mmol/L. The presence of amniotic fluid phosphatidylglycerol was considered an indicator of lung maturity. Hyaline membrane disease was defined by the criteria of Corbet et al. [J Pediatr 118:277-284, 1991]. A total of 621 diabetic pregnancies were analyzed (261 good glycemic control, 360 poor glycemic control). Phosphatidylglycerol was absent in 21% of good glycemic control vs. 31% of poor glycemic control pregnancies (P < 0.05). When stratified by gestational age, the risk of absence of phosphatidylglycerol was significantly higher in the poor glycemic control group (O.R. 1.83, 1.19-2.84). At 36-37.9 weeks, poor glycemic control pregnancies had significantly higher rates of absent phosphatidylglycerol (37% vs. 22%, O.R. 2.04, 1.1-3.9). All cases of hyaline membrane disease beyond 32 weeks gestation occurred in poor glycemic control pregnancies. There were no cases of hyaline membrane disease beyond 37.0 weeks gestation. We conclude that poorly controlled maternal glucose levels are associated with delayed appearance of phosphatidylglycerol in diabetic pregnancies. However, after 37.0 weeks of gestation, no significant neonatal pulmonary disease occurred.

Induction of labor in the nineties: conquering the unfavorable cervix.

OBJECTIVE: To determine the efficacy, safety, and duration of induced labor using an integrative approach (prostaglandin, amniotomy, oxytocin) and to depict these findings graphically. METHODS: Five hundred ninety-seven pregnancies requiring induction of labor between October 1993 and May 1995 were analyzed prospectively. Patients were categorized by Bishop score at entry and by parity for comparison of success of induction, maternal and fetal complications, and duration of labor. RESULTS: The women who had a Bishop score at entry of 3 or less had significantly higher rates of failed induction (9.4 versus 0.7%, P < .01) and of cesarean delivery (29 versus 15.4%, P < .01) than those with a Bishop score above 3. Compared with spontaneous labor, the rates of cesarean delivery in induced labor remained significantly elevated. Complications of induction were infrequent, regardless of Bishop score. The time from initiation of induction to achievement of active phase was significantly longer in women with lower Bishop scores. CONCLUSION: Regardless of cervical status and parity, vaginal delivery can be anticipated in the majority of patients undergoing labor induction. The induction characteristics described may assist in the management of induced labor.

Chemotherapeutic induction of labour. A rational approach.

Induction of labour, defined as stimulation of uterine contractions before the spontaneous onset of labour, is indicated when the condition of the mother or fetus precludes awaiting the onset of spontaneous labour. In current medical practice, induction of labour comprises 2 phases: cervical priming and induction of contractions. Although numerous agents have been used for cervical priming, the current standard of care is the use of intracervical or intravaginal prostaglandin E2. The only drug currently used for induction of contractions is intravenous oxytocin. While many protocols are deemed acceptable, when required, the use of cervical priming, amniotomy and intravenous oxytocin are advocated. Utilising this approach, rapid delivery can be obtained in the majority of women.

Preeclampsia: is induction of labor more successful?

OBJECTIVE: To test the hypothesis that preeclamptic women are more readily inducible than are nonpreeclamptic women, regardless of cervical condition. METHODS: One hundred eighty-three preeclamptic women and 461 nonpreeclamptic women requiring labor induction were studied prospectively. Patients were categorized by Bishop score, parity, gestational age, and method of induction. Outcome variables were success of induction and cesarean delivery rates. RESULTS: Failed induction was significantly more common in the preeclamptic group (8.2% versus 1.7%; odds ratio [OR] 5.06; 95% confidence interval [CI] 1.97, 13.28), as was cesarean delivery (28% versus 16%; OR 2.09; 95% CI 1.36, 3.18). When controlled by logistic regression for Bishop score, parity, method of induction, epidural anesthesia, macrosomia, and gestational age, a fourfold higher risk of failed induction and a twofold higher risk of cesarean delivery were found in the preeclamptic group. CONCLUSIONS: Induction of labor in preeclamptic women has a higher risk of failure and consequently of cesarean delivery than in nonpreeclamptic women. The vast majority of patients achieve vaginal delivery.

Perinatal outcome in growth-restricted fetuses: do hypertensive and normotensive pregnancies differ?

OBJECTIVE: To test the hypothesis that fetal growth restriction (FGR) associated with a maternal hypertensive disorder results in worse perinatal outcome than FGR in pregnancies without maternal hypertension. METHODS: All consecutive, singleton, nondiabetic, small for gestational age (SGA) deliveries (birth weight at or below the tenth percentile for gestational age) in a 15-year computerized data base were analyzed for pregnancy outcome. Perinatal outcome was compared after stratification by presence or absence of hypertensive disorders and by gestational age at delivery. RESULTS: Eleven thousand two hundred twenty-seven SGA pregnancies were analyzed. The morbidity and mortality profiles differed between hypertensive and normotensive pregnancies delivered preterm and those delivered at term. Perinatal mortality was significantly higher in the normotensive than in the hypertensive group in preterm deliveries (30.3 versus 18.7%, odds ratio [OR] 1.9 [confidence interval (CI) 1.3-2.9]). At term, hypertensive pregnancies demonstrated significantly higher mortality than normotensive pregnancies (4.6 versus 1.9%, OR 2.42 [95% CI 1.7-3.4]). In both preterm and term gestations, cesarean rates were significantly higher in hypertensive pregnancies than in normotensive pregnancies. Using logistic regression analysis, hypertension was independently associated with a 39% reduction in risk of perinatal mortality preterm, compared with a twofold increased risk of perinatal mortality at term. CONCLUSION: Before term, FGR in normotensive women resulted in significantly higher perinatal mortality than FGR in hypertensive women. In contrast, at term, FGR in pregnancies complicated by hypertension had poorer perinatal outcomes than FGR in normotensive women.

Do growth-retarded premature infants have different rates of perinatal morbidity and mortality than appropriately grown premature infants?

OBJECTIVE: To determine if perinatal morbidity and mortality differ in growth-retarded, small for gestational age (SGA), premature infants and appropriate for gestational age (AGA) infants. METHODS: All consecutive, singleton, nondiabetic, preterm pregnancies delivered over a 15-year period were analyzed. Infants were categorized as SGA (at or below the tenth percentile) or AGA (11th to the 89th percentiles), then stratified by birth weight and gestational age categories. Perinatal morbidity and mortality were examined. RESULTS: We studied 4183 preterm deliveries, 1012 of them SGA and 3171 of them AGA. Overall, we found significantly higher rates of fetal and neonatal death in the SGA group. Stratification by gestational age revealed significantly higher rates of neonatal death for the SGA group compared with the AGA group in each gestational age category. Overall, comparison also revealed significantly higher rates of fetal heart rate abnormality in the SGA group but no difference in neonatal sepsis, birth trauma, cesarean delivery, hyaline membrane disease, or congenital anomalies. CONCLUSION: Growth-retarded premature infants have a significantly higher risk of morbidity and mortality, both before and after delivery, than do appropriately grown infants.

Low-dose versus high-dose oxytocin augmentation of labor--a randomized trial.

OBJECTIVE: Our purpose was to compare the efficacy and safety of low-dose versus high-dose oxytocin regimens in the augmentation of labor. STUDY DESIGN: Three hundred ten term pregnancies requiring augmentation of labor underwent randomization to receive either a low-dose or high-dose oxytocin augmentation regimen. Maternal demographics, labor-delivery data, and neonatal outcome were compared. RESULTS: The high-dose oxytocin group had a significantly lower cesarean section rate, regardless of parity (10.4% vs 25.7%, p < 0.001), with no differences in maternal complications and neonatal outcomes. The time needed to correct the labor abnormality was also significantly decreased (1.24 +/- 1.4 hours vs 3.12 +/- 1.6 hours, p < 0.001) in the high-dose group. CONCLUSIONS: The use of high-dose oxytocin regimen benefits both nulliparous and multiparous women requiring labor augmentation by significantly lowering both the time necessary to correct the labor abnormality and the need for cesarean section.

Are labor abnormalities more common in shoulder dystocia?

OBJECTIVE: Our objective was to determine the association between labor abnormalities and shoulder dystocia. STUDY DESIGN: All consecutive cases of shoulder dystocia from January 1986 to August 1994 were reviewed (n = 276). For purposes of comparison a control group of vaginally delivered patients was randomly selected in a 2:1 ratio (n = 600). Charts were reviewed for demographic information, labor and delivery events, and neonatal outcome. RESULTS: Labor abnormalities were comparable in the shoulder dystocia and control groups, both in the active phase and in the second stage. When patients with diabetes and those with macrosomic infants were analyzed separately, no significant differences in labor abnormalities were identified. The rate of operative vaginal delivery was significantly higher in the shoulder group, and one third of the operative deliveries were midpelvic. In addition, the induction rate was higher in the shoulder group. CONCLUSIONS: Our data suggest that labor abnormalities may not serve as clinical predictors for subsequent development of shoulder dystocia, thus emphasizing the unpredictability of this condition.

Munchausen's syndrome and the laboratory. Self-injection of human chorionic gonadotropin.

A woman presented to our emergency center after self-injection of human chorionic gonadotropin in an attempt to gain admission to the hospital. Her initial urine pregnancy test (an assay for beta-hCG) was negative. Subsequent blood samples received from the patient the same day revealed markedly elevated beta-hCG levels, suggesting possible laboratory error. Although the patient's sonogram was negative for an intrauterine pregnancy, an ectopic pregnancy could not be ruled out and the patient was taken to surgery, where no evidence of pregnancy was found. Retrospective evaluation of the patient's medical history revealed that she had 30 previous surgical procedures, for which most were performed for alleged gynecological reasons. The authors suggest that this case of Munchausen's syndrome illustrates one of the more interesting solutions for a "laboratory error."

Meconium-stained amniotic fluid: increased risk for adverse neonatal outcome.

OBJECTIVE: To determine the risk of adverse neonatal outcome associated with meconium-stained amniotic fluid independent of that related to antepartum or intrapartum abnormalities. METHODS: A cohort of 2200 consecutive deliveries was examined and the fetal heart rate (FHR) tracings analyzed independently. Singleton term pregnancies without fatal malformations were stratified by the consistency of meconium and compared. RESULTS: Moderate or thick meconium increased the risk for adverse outcome more than threefold (relative risk 3.2, 95% confidence interval 2.0-5.2). This risk was independent of fetal heart tracing abnormalities or maternal hypertensive, kidney, or heart disease. CONCLUSION: Thick meconium alone should alert the physician to a high-risk fetal condition. This phenomenon requires continuous FHR monitoring and reassurance of fetal well-being by acid-base assessment or the equivalent, regardless of maternal disease status or the presence of abnormal FHR tracings.

The effect of clinical chorioamnionitis on cord blood gas at term.

OBJECTIVE: We sought to determine the effect of clinical chorioamnionitis on cord blood gas values in term pregnancies not complicated by any other disease. STUDY DESIGN: 2200 consecutive deliveries were studied. Following exclusion of twins, non-viable malformations and stillbirths, as well as mothers with high-risk pregnancy diseases--i.e. hypertension, diabetes, preterm labor, third-trimester bleeding, IUGR, postdates, oligohydramnios, i.v. drug abused, decreased fetal movement, maternal viral infection, UTI or pneumonia (n = 897)--two groups of patients remained: term pregnancies complicated only by clinical chorioamnionitis (n = 81) and uncomplicated term pregnancies (n = 1246). RESULTS: Evaluation of mean cord blood gas values revealed a significant difference in pH, PO2, PCO2 and BE values, with the infants of mothers with clinical chorioamnionitis having lower pH values (7.23 +/- 0.07 vs. 7.28 +/- 0.07). However, evaluating the independent effect of chorioamnionitis on arterial cord blood pH (using a logistic regression model) showed that clinical chorioamnionitis, by itself, did not contribute to this change in arterial cord blood pH. CONCLUSION: Chorioamnionitis was neither the explanation nor the cause for differences in arterial cord blood pH found between the two groups in our study. In cases of chorioamnionitis, these differences were attributed to other factors, such as length of labor, mode of delivery, method of delivery and presence of meconium.

Intensified versus conventional management of gestational diabetes.

OBJECTIVE: We tested the hypothesis that intensified management of gestational diabetes mellitus on the basis of stringent glycemic control, verified glucose data, and adherence to an established criterion for insulin initiation results in near normoglycemia control and reduction of adverse outcomes. STUDY DESIGN: A prospective, population-based study compared the effect on perinatal outcome of conventional (n = 1316) and intensified (n = 1145) management. Group assignment was based on availability of memory-based reflectance meters at entry to the program. A contemporaneous randomized control group (nondiabetic, n = 4922) was selected. RESULTS: The diabetic groups were comparable in demographic characteristics and in factors associated with higher risk for adverse pregnancy outcome, such as previous macrosomia, previous gestational diabetes mellitus, and family history of diabetes. The control group was younger, less obese, and had a lower rate of previous macrosomia. The intensified management group had rates of macrosomia, cesarean section, metabolic complications, shoulder dystocia, stillbirth, neonatal intensive care unit days, and respiratory complications lower than those in the conventional management group and comparable to those of the nondiabetic controls. Other maternal complication rates, such as for preeclampsia, chronic hypertension, and infection, were similar for the three groups. Mean blood glucose levels were a good predictor of perinatal outcome. Gestational age at delivery, previous history of macrosomia, and overall mean blood glucose levels were the only significant predictors of birth weight percentile in both diabetic groups (logistic regression). CONCLUSION: The intensified management approach is significantly associated with enhanced perinatal outcome. This management strategy clarifies the relationship between glycemic control and neonatal outcome.

Recurrent stillbirth. Significance and characteristics.

We sought to identify the significance of recurrent stillbirth and to determine the contributory etiologic factors for this phenomenon. Data were analyzed and retrospective chart review conducted for all stillbirths occurring during a 13-year period. Subjects were divided into two groups: those for whom the current stillbirth was the first and those who had had a previous stillbirth. The study included 48,479 consecutive multiparous women, of whom 403 had delivered stillborn infants (8.31/1,000 live births). For 34 of these subjects, this represented a recurrent stillbirth (84.36/1,000 live births). The recurrent-stillbirth group had a 10.15-fold higher risk for stillbirth. Additionally, this group had a twofold higher incidence of diabetes and hypertensive disease than did those women experiencing their first stillbirths; furthermore, the gestational age and birth weight of the stillborn infants were significantly lower in the recurrent-stillbirth group (P < .0004 and < .007, respectively). Such factors as socioeconomic class, chorioamnionitis and erythroblastosis fetalis, traditionally cited as contributing to repeated fetal loss, were not significant. Although recurrent stillbirth remains an unsolved problem, improving health care to specific groups within high-risk populations may reduce fetal loss.

Do tocolytic agents stop preterm labor? A critical and comprehensive review of efficacy and safety.

OBJECTIVE: Our aim was to determine the efficacy and safety of tocolytic agents currently used to treat premature labor. STUDY DESIGN: We carried out a comprehensive review of tocolytic agents in the treatment of premature labor. Three hundred twenty-eight studies published between 1933 and 1992 were analyzed. RESULTS: An analysis of randomized, placebo-controlled, clinical trials showed that magnesium sulfate is not better than placebo in the treatment of premature labor. beta-Adrenergic receptor agonists effectively stop premature labor for only 24 to 48 hours. Calcium channel blockers and oxytocin antagonists inhibit uterine contractions, but their role in stopping labor is undefined. Prostaglandin inhibitors appear to be effective in treating premature labor and have few adverse side effects. CONCLUSIONS: The only tocolytic drugs that might be effective are the prostaglandin inhibitors. Tocolytic agents should be used only between 24 and 32 completed weeks of gestation. Magnesium sulfate should not be used to treat premature labor. Oxytocin antagonists should be used only in experimental clinical trials. Calcium channel blockers and beta-adrenergic receptor agonists inhibit uterine contractions but do not prolong gestation for longer than 48 hours.

Glucose tolerance test periodicity as a descriptor of glucose tolerance abnormality.

The periodicity of the standard 100-g glucose tolerance test (GTT) was examined in a prospective study of 194 pregnant patients to determine how well gestational diabetes could be identified. A simplified formula, the GTT periodicity, was used to estimate the time for the GTT curve to return to the fasting level. One hundred one study subjects had all normal glucose values by the National Diabetes Data Group criteria (0-abnormal group), 47 had one value greater than normal (1-abnormal group), and 46 had more than one value abnormal or gestational diabetes. The 0-abnormal patients had a significantly shorter GTT periodicity than did 1-abnormal or gestational diabetic mothers (3.6 versus 4.8 versus 6.6 hours, respectively; P less than .04). Calculating the periodicity for the corresponding insulin excursions yielded significantly increasing values in a graduated fashion for each group (5.2 versus 6.9 versus 9.6 hours, respectively; P less than .05). Examination of the oscillation of the GTT curve about the fasting level allows a physiologic description of normal and abnormal glucose responses in pregnancy. Furthermore, our findings suggest that glucose and insulin periodicities are useful predictors of gestational diabetes in patients with positive screening.