Suzanne L. Lubarsky

Late Postpartum Eclampsia Revisited

Objective: To describe the clinical and neurologic findings in patients with late postpartum eclampsia (convulsions beginning more than 48 hours, but less than 4 weeks, after delivery). Methods: This study evaluated all patients with the diagnosis of late postpartum eclampsia managed at our institution between August 1977 and July 1992. Results: There were 54 cases of late postpartum eclampsia among a total of 334 cases of eclampsia during the study period. Late postpartum eclampsia constituted 56% of total postpartum eclampsia and 16% of all cases of eclampsia. Convulsions began from postpartum days 3‐23 (mean 6). Thirty women (56%) had been identified as preeclamptic before their convulsions. A history of either severe headache or visual disturbances before convulsion was elicited in 83% of the patients. During the study period, eight women not included in the study group had late postpartum seizures attributed to other causes. Conclusions: Severe headache or visual disturbance frequently antedates late postpartum eclampsia. Only eight of 62 patients with late postpartum seizures had identifiable etiologies other than eclampsia. (Obstet Gynecol 1994;83:502‐5)

Uterine rupture associated with the use of misoprostol in the gravid patient with a previous cesarean section

OBJECTIVE Our purpose is to report our experience with uterine rupture in patients undergoing a trial of labor after previous cesarean delivery in which labor was induced with misoprostol. The literature on the use of misoprostol in the setting of previous cesarean section is reviewed. STUDY DESIGN This report was based on case reports, a computerized search of medical records, and literature review. RESULTS Uterine rupture occurred in 5 of 89 patients with previous cesarean delivery who had labor induced with misoprostol. The uterine rupture rate for patients attempting vaginal birth after cesarean section was significantly higher in those who received misoprostol, 5.6%, than in those who did not, 0.2% (1/423, P =.0001). Review of the literature reveals insufficient data to support the use of misoprostol in the patient with a previous cesarean delivery. CONCLUSION Misoprostol may increase the risk of uterine rupture in the patient with a scarred uterus. Carefully controlled studies of the risks and benefits of misoprostol are necessary before its widespread use in this setting.

The diagnosis and classification of gestational diabetes mellitus: Is it time to change our tune?

OBJECTIVE This study was designed to determine the impact on our population of adopting the Carpenter and Coustan criteria for gestational diabetes mellitus in place of the currently used National Diabetes Data Group criteria, to review the evidence supporting replacement of the National Diabetes Data Group criteria with the Carpenter and Coustan criteria, and to propose analogous diagnostic criteria for diabetes in pregnant and nonpregnant women. STUDY DESIGN The National Diabetes Data Group criteria and the proposed Carpenter and Coustan criteria were both used to retrospectively review medical records of patients screened for gestational diabetes mellitus during 1995 and 1996 in the Kaiser Permanente Northwest Division. Computerized search was performed on automated data systems and software was used for statistical analyses. A MEDLINE review of relevant literature was conducted. RESULTS Of 8857 pregnant women screened for gestational diabetes in 1995 and 1996, 284 (3.21%) met the National Diabetes Data Group criteria, whereas 438 (4.95%) met the Carpenter and Coustan criteria. We estimate that in our population use of the Carpenter and Coustan criteria in 1996 could at best have reduced the prevalence of infants weighing >/=4000 g from 17.1% to 16.9% and the prevalence of infants weighing >/=4500 g from 2.95% to 2.91%. CONCLUSIONS Replacing the National Diabetes Data Group criteria with the Carpenter and Coustan criteria would increase by 54% the number of pregnant women with a diagnosis of gestational diabetes mellitus and would also increase costs, while only minimally affecting prevalence of infant macrosomia. The medical literature does not provide compelling evidence for adopting the Carpenter and Coustan criteria. Standardization of both measurement of venous plasma glucose level and diagnostic criteria for gestational diabetes mellitus is an important goal. Parallel criteria for diagnosis and classification of diabetes mellitus in pregnant and nonpregnant women should be developed.

The effect of chronic nitric oxide synthesis inhibition on blood pressure and angiotensin II responsiveness in the pregnant rat

OBJECTIVES Our purpose was to determine whether blockade of inducible or endothelial nitric oxide synthesis prevents maternal vasodilation and blunting of angiotensin II responsiveness in the pregnant rat. STUDY DESIGN Pregnant and nonpregnant rats were given (1) drinking water alone (untreated), (2) drinking water containing the inducible nitric oxide synthase inhibitor aminoguanidine (0.5 gm/L), or (3) drinking water containing the nonselective nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (0.5 gm/L) from postmating days 5 to 21. On days 7, 14, and 20, 24-hour urinary nitrate-nitrite excretion, urine protein concentration, hematocrit, mean arterial blood pressure, and pressor responses to angiotensin II (12.5 to 200 ng/kg) were measured. On day 21 litter size, fetal weight, and fetal mortality were determined. RESULTS Urinary nitrate-nitrite excretion was increased, and hematocrit and blood pressure were decreased by day 20 of pregnancy. Angiotensin II pressor responses were decreased on days 14 and 20 of pregnancy. Aminoguanidine slightly decreased nitrate-nitrite excretion in pregnant, but not nonpregnant rats, and abolished the late pregnancy increase. Aminoguanidine did not affect hematocrit, blood pressure, or angiotensin II responsiveness in either pregnant or nonpregnant rats. N omega-nitro-L-arginine methyl ester greatly reduced nitrate-nitrite excretion and induced hypertension in both nonpregnant and pregnant rats, but on day 20 blood pressure of the pregnant rats was significantly lower than that of the nonpregnant rats. N omega-nitro-L-arginine methyl ester increased angiotensin II responsiveness on days 14 and 20 only in the pregnant rats. N omega-nitro-L-arginine methyl ester, but not aminoguanidine, increased fetal mortality and decreased fetal weight. CONCLUSIONS Inducible nitric oxide synthesis accounts for increased nitrate-nitrite excretion during pregnancy. Endothelium-derived nitric oxide may attenuate angiotensin II responsiveness but does not cause vasodilation and the fall in blood pressure during the last week of gestation.

CHRONIC NITRIC OXIDE SYNTHESIS INHIBITION DOES NOT PREVENT PREGNANCY VASODILATION IN THE RAT

Objective: To determine if blockade of endothelium-derived nitric oxide synthesis from the day after embryo implantation to the day before parturition prevents maternal systemic vasodilation in the rat.Methods: Timed-pregnant and age-matched nonpregnant Wistar-Kyoto rats were administered the nonselective nitric oxide synthase inhibitor Nw-nitro-L-arginine methyl ester (15 mg/rat/day, s.c.) or saline vehicle (untreated) for 14 days using osmotic minipumps. On the last day of treatment (day 20 of gestation in the pregnant rats), plasma total nitrate/nitrite concentration, mean arterial blood pressure, and heart rate were measured. Cardiac output and organ blood flows were then measured using radioactive-labeled microspheres for the calculation of total systemic and organ/tissue vascular conductances, respectively.Results: Chronic blockade of nitric oxide synthesis decreased plasma nitrate/nitrite concentration >90% and induced hypertension with decreased cardiac output and organ blood flows in both nonpreg...

Evidence of a Nonendothelial Source of Nitric Oxide in the Isolated Perfused Hindlimb Vasculature of the Pregnant Rat

OBJECTIVE This study was undertaken to further elucidate the roles of the vascular endothelium and nitric oxide (NO) in the regulation of vascular tone and constrictor responsiveness in pregnancy. METHODS The perfusion pressure-flow relationship was measured in isolated, perfused, norepinephrine-constricted (1) endothelium-intact, (2) endothelium-denuded, and (3) N omega-nitro-L-arginine methyl ester (L-NAME)-treated hindlimbs from nonpregnant and term-pregnant rates. RESULTS Baseline perfusion pressure at a flow rate of 2 mL/min was similar (approximately 20 min Hg) in all hindlimbs. Norepinephrine (0.5 muM) increased perfusion pressure in both nonpregnant (+21.6 +/- 2.4 mm Hg) and pregnant (+13.6 +/- 0.9 mm Hg) endothelium-intact rat hindlimbs. In nonpregnant rat hindlimbs, endothelium removal and L-NAME increased norepinephrine vasoconstriction similarly (+44.3 +/- 4.0 mm Hg and +46.4 +/- 8.6 mm Hg, respectively). In pregnant-rat hindlimbs, L-NAME increased norepinephrine vasoconstriction by 43.5 +/- 10.8 mm Hg, similar to that in nonpregnant-rat hindlimbs, but endothelium removal only increased norepinephrine vasoconstriction by 28.0 +/- 2.2 mm Hg. Perfusion pressure increased linearly as the flow rate was increased from 2 to 4 mL/min, and the slope of the regression line of the endothelium-intact pregnant-rat hindlimbs (7.0 +/- 0.6) was slightly, but not significantly, lower than that of the nonpregnant-rat hindlimbs (9.6 +/- 0.9). Endothelium removal increased the slopes of the regression lines, but that of pregnant-rat hindlimbs (12.8 +/- 1.6) was significantly lower (p < or = 0.05) than that of the nonpregnant-rat hindlimbs (23.8 +/- 1.8). L-NAME caused a similar increase in the pressure-flow slopes of nonpregnant-rat (36.5 +/- 3.4) and pregnant-rat (32.1 +/- 5.3) hindlimbs. CONCLUSIONS These results suggest that nonendothelial nitric oxide production may be increased in the hindlimb resistance vasculature of the pregnant rat, which may play a role in the normal pregnancy blunting of constrictor responsiveness and reduction of vascular resistance.