Thomas J. Benedetti

Maternal complications of parenteral β-sympathomimetic therapy for premature labor

Abstract A diverse number of serious maternal complications associated with β-sympathomimetic treatment are now being recognized. Physicians and nurses using these drugs should be aware of the potential life-threatening complications. New guidelines for prevention of complications and avoidance of unnecessary treatment are suggested.

Hemodynamic observations in severe preeclampsia complicated by pulmonary edema.

Ten patients with severe preeclampsia complicated by pulmonary edema were studied with invasive hemodynamic monitoring. Eight of 10 patients developed pulmonary edema during the postpartum period. Five patients had alterations in the colloid osmotic pressure--pulmonary artery wedge pressure gradient related to elevations in the pulmonary artery wedge pressure and a reduction in the colloid osmotic pressure. Three patients had hemodynamic findings consistent with pulmonary capillary leak. Two patients had evidence of left ventricular failure. In three of the patients, the central venous pressure was significantly lower than the simultaneously determined pulmonary artery wedge pressure during the acute phase of the pulmonary edema.

CESAREAN SECTION BEFORE THE ONSET OF LABOR AND SUBSEQUENT MOTOR FUNCTION IN INFANTS WITH MENINGOMYELOCELE DIAGNOSED ANTENATALLY

Methods. To assess the effect of labor and type of delivery on the level of motor function in fetuses with uncomplicated meningomyelocele, we identified 200 cases of this disorder, accounting for 95 percent of the cases that occurred in the state of Washington during our 10-year study period. We compared the outcomes of 47 infants delivered by cesarean section before labor began, 35 delivered by cesarean section after a period of labor, and 78 who were delivered vaginally (another 40 were ineligible for the study)

Antepartum pneumonia in pregnancy

Thirty-nine patients satisfying criteria for antepartum pneumonia in pregnancy were retrospectively reviewed. Twenty-one patients had culture-proved bacterial pneumonias. Streptococcus pneumoniae was the most common organism isolated (13/39). Significant anemia (hemoglobin less than or equal to 10 gm) was present in 49% of patients (19/37) on admission. In the patients presenting in the second and third trimesters (25 to 36 weeks) of pregnancy, 85% (11/13) were delivered at term. The perinatal mortality rate for the entire group was 40/1,000. There were no maternal deaths.

Prediction of Infant Birth Weight by GDM Screening Tests: Importance of plasma triglyceride

OBJECTIVE We measured plasma glucose, GHb, GPro, IRI and TG at 24–28-wk gestation to determine the extent of elevations in GDM and relationships to glucose intolerance and infant macrosomia. RESEARCH DESIGN AND METHODS Plasma samples were obtained 1 h after ingestion of 50 g glucose after an overnight fast in 521 randomly selected negative screenees, 264 positive screenees with GTT−, and 96 positive screenees with GTT+ (GDM). RESULTS Screening test values in GDM subjects exceeded the GTT− group, whose values exceeded those of negative screenees: glucose, 9.6*, 8.7*, 6.3 mM; GHb, 5.2*, 4.9*, 4.7%; GPro, 3.1*, 3.0*, 2.8%; IRI, 791*, 662*, 410 pM; and TG, 2.3*, 1.9, 1.9 mM, (*P < 0.005 vs. negative screenees). TG was the only test elevated in the GDM but not in the GTT− groups. Screening test values correlated with GTT values in the following order (strongest to weakest): glucose* > TG* > GHb* > IRI > GPro (*statistical significance). Plasma TG was the only screening test significantly associated with birth weight corrected for gestational age (birth-weight ratio) (r = 0.09–0.16) (P < 0.05 to < 0.01) and was of the same order as 1- and 2-h GTT associations with birth weight (r = 0.13 and 0.14, respectively) (P < 0.05 to < 0.01). Plots of TG/birth-weight ratio increased linearly to the 80–90th TG percentile in negative screenees and GTT− subjects. GDM subjects followed this trend but with more variation. Above the 90th percentile for TGs, birth-weight ratio trended lower, significantly so when the groups were combined (P < 0.05). In multivariate analysis, TG was associated with birth-weight ratio even when maternal prepregnancy weight and pregnancy weight gain associations with TG and birth-weight ratio were controlled (P < 0.019). CONCLUSIONS Of the five screening tests evaluated, all were elevated in GDM, but TG is the best discriminator of GDM from the GTT− group, and it is the only test significantly related to birth-weight ratio—and to glucose intolerance besides glucose itself. The TG association with birth weight is not explained fully by maternal weight. The results suggest that plasma TG may be a physiological contributor to infant birth weight. Further evaluation of plasma TG in GDM screening is justified, but GHb, GPro, and IRI appear to hold less promise.

Preeclampsia: A hyperdynamic disease model Thomas

Preeclampsia is a common disease and as such is a significant contributor to maternal and neonatal morbidity and mortality. Despite the ubiquity of the disease and its public health impact, no comprehensive mechanism has been established. Therapy has been limited to bed rest and premature delivery. The purpose of this article is to examine preeclampsia from a hemodynamic point of view and to advance a hypothesis of disease mechanism.

Hypocaloric diets and ketogenesis in the management of obese gestational diabetic women.

The extent to which given levels of caloric restriction will improve glycemic status but increase plasma ketone bodies in gestational diabetic women has received little attention. After reviewing the underlying physiology, we present data on two feeding studies investigating the question. In the first, a weight-maintaining approximately 2400-kcal/day diet was fed on a metabolic ward to 12 gestational diabetic women for 1 week. In the second week, subjects were randomized to a continuation of the 2400-kcal/day diet or to a 1200-kcal/day diet. Twenty-four-hour mean glucose levels remained unchanged in the control group but declined in the calorie-restricted group (6.7 mM or 121 mg/dl in week 1 vs 5.4 mM or 97.3 mg/dl in week 2) (p less than 0.01). Nine-hour overnight fasting plasma insulin also declined but oral glucose tolerance did not improve with caloric restriction. Fasting plasma beta-hydroxybutyrate rose in the calorie-restricted group, along with an increase in ketonuria, but not in the control group. A second study compared the impact of a 33% calorie-restricted diet or insulin to a full-calorie diet in a similar 2-week experimental design and measured hepatic glucose output and insulin sensitivity with dideuterated glucose before and during an insulin clamp. Diet in three subjects improved fasting and 24-hr mean glucose by 22 and 10%, respectively, whereas prophylactic insulin in three subjects produced 0 and 4% reductions, respectively. On average, ketonuria after a 9-hr fast declined to an equivalent degree with both treatments. Hepatic glucose output and insulin sensitivity were not statistically significantly altered by gestational diabetes or the therapeutic interventions compared to nondiabetic normal weight or obese pregnant controls. In conclusion, 50% caloric restriction improves glycemic status in obese women with gestational diabetes but is associated with an increase in ketonuria, which is of uncertain significance. An intermediate 33% level of caloric restriction (to 1600-1800 kcal daily) may be more appropriate in dietary management of obese woman with gestational diabetes mellitus and more effective than prophylactic insulin. Further studies are required to confirm these findings.

Metabolic Effects of 1200-kcal Diet in Obese Pregnant Women With Gestational Diabetes

Calorie restriction is widely used as a primary therapy for obese pregnant women with gestational diabetes. To better understand the metabolic consequences of marked calorie restriction, we performed a randomized prospective trial under metabolic ward conditions. Obese gestationally diabetic women were randomized to control (n = 5) and calorie-restricted (n = 7) groups. All patients consumed an ∼2400-kcal/day diet during the 1st wk of the study, and at the end of the 1st wk, metabolic features of the two groups were statistically indistinguishable. During the 2nd wk, the control group continued to consume ∼2400 kcal/day, whereas the calorie-restricted group consumed -1200 kcal/day. Twenty-four-hour mean glucose levels remained unchanged in the control group (6.7 ± 0.8 mM wk 1 vs. 6.8 ± 0.8 mM wk 2), although they dropped dramatically in the calorie-restricted group (6.7 ± 1.0 mM wk 1 vs. 5.4 ± 0.5 mM wk 2, P < 0.01). Fasting plasma insulin also declined in the calorierestricted group (265 ± 165 pM wk 1 vs. 145 ± 130 pM wk 2), resulting in a significant change between groups (P < 0.02). Surprisingly, fasting plasma glucose and glucose tolerance measured by the 3-h oral glucose tolerance test did not change within or between groups. Fasting levels of β-hydroxybutyrate rose in the calorie-restricted group (290 ± 240 μM wk 1 vs. 780 ± 30 μM wk 2) but not in the control group (P < 0.01). Finally, urine ketones increased significantly (P < 0.02) in the calorie-restricted group, whereas they remained absent in the control group. We conclude that diets in the range of ∼1200 kcal/day improve glycemic status in obese pregnant women with gestational diabetes but cause significant increases in ketonemia and ketonuria. Because the impact of maternal ketonemia and ketonuria on fetal well-being remains controversial, these changes are of concern. This level of calorie restriction appears unwise for general clinical usage. Further studies are needed to characterize the metabolic consequences of 1600- to 1800-kcal/day diets that have recently been reported to improve glycemic status without causing ketonuria or profound ketonemia.

Pharmacokinetics and pharmacodynamics of atenolol during pregnancy and postpartum

Preexisting hypertension complicates 5% of all pregnancies. The objective of this study was to evaluate steady‐state atenolol pharmacokinetics and pharmacodynamics (n = 17) during the second trimester (2nd T), third trimester (3rd T), and 3 months postpartum. Pregnancy as compared to 3 months postpartum (nonpregnant control) resulted in significant (P < .05) changes, including the following: 42% (2nd T) and 50% (3rd T) increase in creatinine clearance, 38% (2nd T) and 36% (3rd T) increase in atenolol renal clearance, 12% (2nd T) and 11% (3rd T) decrease in atenolol half‐life, 20% (2nd T) and 28% (3rd T) increase in cardiac output, 15% (2nd T) and 23% (3rd T) increase in resting heart rate, and 22% (2nd T) and 21% (3rd T) decrease in total peripheral resistance in subjects on steady‐state oral atenolol for treatment of hypertension in pregnancy. In conclusion, the renal clearance of atenolol along with creatinine clearance is increased during pregnancy. However, this does not translate into an increase in apparent oral clearance of atenolol, possibly related to the high variability in bioavailability. Atenolol administration did not appear to change the pattern of the increase in cardiac output and the decrease in total peripheral resistance, which normally occurs during pregnancy.

Risk factors and infant outcomes associated with umbilical cord prolapse: A population-based case-control study among births in Washington State

OBJECTIVE Our goal was to quantify the magnitude of risk associated with conditions resulting in umbilical cord prolapse and adverse infant outcome after cord prolapse. STUDY DESIGN This population-based case-control study used birth certificate data from 709 cases and 2407 randomly selected controls. Odds ratios were used as measures of association, with stratification performed to control for confounding. RESULTS Case infants were more likely to weigh < 2500 mg (odds ratio 4.8, 95% confidence interval 3.7 to 6.2) and to born prematurely (odds ratio 2.9, 95% confidence interval 2.2 to 3.7). Other risk factors were breech presentation (birth weight-adjusted odds ratio 2.5, 95% confidence interval 1.7 to 3.9) and being a second-born twin (odds ratio 5.0, 95% confidence interval 3.3 to 11.7). Subsequent adverse infant outcomes included an increased risk of mortality (relative risk 2.7, 95% confidence interval 1.9 to 4.0), with mortality being less likely to occur among cases delivered by cesarean section (relative risk 0.4, 95% confidence interval 0.2 to 0.6). CONCLUSIONS This study confirms previously suspected risk factors and supports clinical management of cord prolapse by cesarean section delivery.