OS054. Differential strain sensitivities to ischemia/reperfusion in two mouse models of fetal growth restriction.

INTRODUCTION: Uterine ischemia/reperfusion (I/R) in rodents is a common model for the study of fetal growth restriction (FGR). It has been observed that different strains of mice vary in their response to uterine I/R. OBJECTIVES: Our objective was to characterize fetal and placental growth, and uterine and placental inflammation, in pregnant mice from 2 strains (C3H/HeOuJ and C57BL/6J), in response to different uterine I/R modalities. METHODS: Timed-pregnant mice (6-8 in each experimental group) were subjected to unilateral uterine I/R by either total flow restriction (TFR,right ovarian and uterine arterial clamping,5 or 30min) or partial flow restriction (PFR,right ovarian artery clamping,30min), or to sham-operation, on the 14th (for C57 mice) or 15th (for C3H mice) day of gestation. Four days later, fetal and placental weights and fetal loss were evaluated, and myeloperoxidase (MPO) activity was assayed in uterine and placental tissues. Data were analyzed by ANOVA with p<0.05 considered significant. RESULTS: In C3H/HeOuJ mice, TFR/30 min induced significantly (p<0.05) lower fetal and placental weights, and higher MPO activity in both uterus and placenta, compared to sham-operated controls. PFR/30min produced fetal but not placental growth restriction in the C3H mice. In contrast, C57BL/6J mice exhibited much greater sensitivity to uterine I/R: TFR/5 min was adequate to induce FGR in the C57 mice, which was equivalent in proportion to FGR caused by TFR/30min in C3H. C57 mice also exhibited significantly greater fetal loss and higher uterine, but not placental, MPO activity in response to I/R compared to sham-operated controls. CONCLUSION: Reliable FGR can be induced in different strains of mice by uterine I/R through adjustment of intensity, duration, and gestation day of the challenge. Mice of different strains have different tolerance to uterine I/R. These strain disparities would lend themselves to identifying the role of mouse strain-specific genetic determinants which form the bases for the observed differences in sensitivity to I/R-induced FGR.

Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction.

The vasoactive mediators nitric oxide and endothelin are both produced in and active in the uterine and placental vasculature. Inhibition of nitric oxide synthase (NOS) results in fetal growth restriction. Endothelin (ET-1) is upregulated in the setting of NOS inhibition. Our purpose was to determine the impact of ET-1 on uterine and placental perfusion in the pregnant rat treated with a NOS inhibitor. Timed-pregnant Sprague-Dawley rats were treated with L-NAME (2.5 mg/kg/h), with and without A-127722 (10 mg/kg/day), or their respective vehicles, for 1, 4, or 7 days beginning on day 14 of gestation. Blood flow to various organs was determined by microsphere infusion. Maternal and fetal plasma nitrate/nitrite (NOx) was determined by fluorometric assay. Uterine and placental perfusion was significantly decreased by NOS inhibition and was restored to normal by ETA antagonism at 1 and 4 days of infusion but not at 7 days. Maternal plasma NOx, but not fetal plasma NOx, was significantly decreased by NOS inhibition alone. ETA antagonism in combination with NOS inhibition significantly lowered fetal plasma NOx. These results indicate that ET-1 is an important regulator of uterine and placental perfusion in the NOS inhibition model of fetal growth restriction. Our results also suggest that maternal administration of L-NAME does not result in significant transport of L-NAME across the placenta, but that addition of an ETA antagonist results in increased placental perfusion, allowing L-NAME greater access to the fetal compartment.

Influence of ET(B) receptor antagonism on pregnancy outcome in rats.

OBJECTIVE: To determine the effect of endothelin-B (ET(B))-selective receptor antagonism on pregnancy outcome in normal rats. METHODS: ET(B) receptor antagonist (A-192621; 5.0, 10.0, and 15.0 mg/kg per day) or vehicle was infused subcutaneously for 7 days by osmotic pump. Infusion was begun on day 14 of a 22-day gestation. Nonpregnant animals were treated similarly, and blood pressure (BP) responses and plasma antagonist levels were compared to those in pregnant animals. Mean arterial pressure (MAP) was measured on days 1, 4, and 7 of the infusion. Plasma ET(B) antagonist levels were measured on day 7 of infusion. On gestational day 21, fetal and placental weights and viability were evaluated at hysterotomy. Data were analyzed by analysis of variance and are presented as mean +/- standard error of the mean. RESULTS: Fetal and placental weights were significantly lower at doses of 10 and 15 mg/kg per day of the ET(B) antagonist compared with vehicle-treated controls (P <.001); these effects were less severe at 15 than at 10 mg/kg per day despite a fourfold higher plasma level of antagonist. Mean arterial pressure was significantly higher at 10 and 15 mg/kg per day compared with controls, but only on infusion day 1 (P <.05). In contrast, MAPs for nonpregnant rats were elevated throughout the infusion at all doses of the ET(B) antagonist (P <.05). CONCLUSIONS: ET(B) receptor antagonism inhibited fetal growth and increased maternal MAP in a dose-dependent manner, although the effect on BP was not sustained in pregnant animals. ET(B) receptor antagonism is detrimental to pregnancy outcome in the rat.

Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats.

OBJECTIVE: To determine the role of endothelin (ET) in fetal and placental growth in rats with and without long-term nitric oxide synthase (NOS) inhibition. METHODS: Pregnant rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline and with one of three ET receptor antagonists or vehicle. The antagonists included A-182086 (nonselective) as well as A-127722 and FR-139317 (both ET(A) selective). Treatment was begun on day 14 of gestation. On gestational day 21, a hysterotomy was done. Litter size was recorded, and viability and fetal and placental weights were determined. Results were analyzed by analysis of variance or by a Kruskal-Wallis nonparametric analysis. RESULTS: In the absence of L-NAME, fetal and placental weights were not affected by ET(A)-selective antagonism but were significantly decreased by nonselective receptor antagonism (P <.001 and P <.05 for fetal and placental weights, respectively). Infusion of L-NAME resulted in fetal and placental growth restriction (P <.001). In the setting of L-NAME infusion, fetal and placental weights were increased by the ET(A)-selective antagonists (P <.01) but not by the nonselective antagonist, compared with weights from animals treated with L-NAME alone. There were more fetal deaths with L-NAME treatment (P <.05), but their occurrence was not significantly affected by any of the ET receptor antagonists. CONCLUSIONS: Endothelin-A antagonism alone did not affect fetal or placental growth, whereas combined ET(A) plus ET(B) antagonism produced fetal and placental growth restriction. In the setting of long-term NOS inhibition, ET(A)-selective antagonism improved fetal and placental growth, whereas antagonism of both ET(A) and ET(B) receptors did not. Endothelin contributes to NOS inhibition-induced growth restriction acting through the ET(A) receptor.

Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity.

OBJECTIVE: To compare lamellar body counts with the lecithin/sphingomyelin ratio and phosphatidylglycerol analysis in terms of assessment of risk of respiratory distress syndrome (RDS). METHODS: Lamellar body counts, lecithin-sphingomyelin ratios (L/Ss), and phosphatidylglycerol levels were assessed in 1611 amniotic fluid samples obtained at four clinical sites from pregnant women whose fetuses were at risk for RDS. Cases in which delivery occurred within 72 hours of sample collection (n = 833) were analyzed. Specific cutoffs for predicting the likelihood of RDS for both the lamellar body count and the L/S had been derived previously at each of the clinical sites based on receiver operating characteristic curves using unrelated samples, whereas phosphatidylglycerol was reported as either mature (present) or immature (absent). Standard clinical and radiographic criteria were used to diagnose RDS, and the diagnosis was confirmed by review of newborn records. RESULTS: One hundred (12.0%) of the 833 infants delivered within 72 hours of sample collection developed RDS. The negative predictive value of the lamellar body count (97.7%) was similar to that of the L/S (96.8%) and slightly better than that of phosphatidylglycerol analysis (94.7%) (P =.048). The lamellar body count performed as well as phospholipid analysis irrespective of gestational age or patient population. CONCLUSION: The lamellar body count compares favorably with traditional phospholipid analysis as an assay for assessment of fetal lung maturity. Lamellar body counts are preferable because they are faster, more objective, less labor intensive, less technique dependent, and less expensive and because they can be performed with equipment available in every hospital laboratory.

Lamellar body counts: a consensus on protocol.

Lamellar bodies, concentrically layered "packages" of phospholipid that represent the storage form of surfactant, can be counted in the platelet channel of most electronic cell counters. The lamellar body count has been used for more than a decade and performs as well as traditional phospholipid analysis as an assay for evaluating fetal lung maturity. It is preferable to phospholipid analysis because it is rapid, objective, and inexpensive and can be performed in any hospital laboratory. The current methodologies for specimen preparation vary widely among laboratories, most notably with respect to centrifugation, resulting in differences in maturity cutoffs used. Our goal was to establish a consensus regarding a standardized methodology for the lamellar body count. Institutions that previously had published their results with lamellar body counts were invited to contribute. The consensus of the four participating institutions includes the following: centrifugation is not a necessary step and should be abandoned, maturity is suggested by a count of 50,000/microL or greater, and immaturity is suggested by a count of 15,000/microL or lower. As the lamellar body count gains wider acceptance as a primary assay for assessing fetal lung maturity, the test must be performed uniformly and accurately, given the implications of acting on a falsely negative test resulting from improper methodology.

Comparison of active phase labor between triplet, twin, and singleton gestations.

OBJECTIVE: To characterize the active phase of labor in triplet pregnancies and compare it with gestational age-matched twins and singletons. METHODS: Active phase rates were calculated beginning at 5 cm of dilation for women with triplet gestations longer than 24 weeks who labored and reached the second stage. Twin and singleton cohorts that also completed the first stage of labor were matched for gestational age at delivery (+/-1 week), parity, and epidural use. Intrapartum variables included oxytocin use (induction or augmentation, duration of infusion, and maximum dosage), cervical dilation at membrane rupture, and active phase dilation rate. RESULTS: Thirty-two triplet pregnancies met inclusion criteria between January 1994 and September 1998 and were each compared with twin and singleton cases in a 1:2 ratio. Triplet and twin active phase rates, while similar (1.8 versus 1.7 cm/hour, respectively), were significantly lower than the mean singleton dilation rate (2.3 cm/hour, P =.02). No other intrapartum variables differed between the three groups. Despite controlling for gestational age at delivery, mean birth weights were significantly higher in singletons and correspondingly lower in twins and triplets (2,493 versus 2,112 and 1,968 g, respectively; P =.001). An analysis of active phase dilation rates as a function of the cumulative birth weight per pregnancy demonstrated an inverse correlation, with slower progress in active labor associated with increasing total fetal weight (R = -.24; P =.002). CONCLUSIONS: Triplet and twin active phase dilation proceeds at a slower rate than that observed in singleton pregnancies. The rate of active phase dilation is inversely correlated to total fetal weight.

Endothelin and blood pressure regulation in the female rat: studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension.

OBJECTIVE: To evaluate the role of endothelin (ET) in blood pressure regulation in normal pregnant and nonpregnant rats and with nitric oxide synthase (NOS) inhibition. METHODS: Pregnant and nonpregnant Sprague-Dawley rats were treated for 7 days with an ET(A)-selective (A-127722 or FR-139317), ET(B)-selective (A-192621), or ET(A)/ET(B) nonselective (A-182086) endothelin receptor antagonist, and/or with the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 2. 5 mg/kg/h). In pregnant rats, the ET antagonists and L-NAME were administered from gestational day 14 through day 21 (term = 22 days). All rats received indwelling arterial catheters for blood pressure measurement. Mean arterial pressures were recorded on infusion days 1, 4, and 7 and these data were compared by analysis of variance among experimental groups with p < 0.05 considered significant. RESULTS: The ET(A) receptor antagonism lowered blood pressure in both pregnant and nonpregnant rats (p < 0.05), whereas ET(B) antagonism resulted in hypertension (p < 0.001). ET(B) antagonism-induced hypertension was attenuated by pregnancy (p < 0. 001). Hypertension was induced in all rats treated with L-NAME (p < 0.001). Endothelin receptor antagonism, regardless of specificity, did not ameliorate L-NAME-induced hypertension in pregnant or nonpregnant female rats. The only observed effect of ET(A) antagonism on NOS inhibition-induced hypertension was the prevention of a continued rise at infusion day 7 in nonpregnant rats. CONCLUSIONS: Endothelin, acting via both the ET(A) and ET(B) receptors, contributes to blood pressure homeostasis in pregnant and nonpregnant rats. Endothelin receptor antagonism does not ameliorate NOS-inhibition-induced hypertension in pregnant rats.

Timing of labor induction after premature rupture of membranes between 32 and 36 weeks' gestation.

OBJECTIVE: The objective was to determine a consensus gestational age for labor induction after premature rupture of membranes between 32 and 36 weeks' gestation on the basis of the relative frequencies of adverse neonatal outcomes. STUDY DESIGN: A retrospective review was undertaken of all patients with premature rupture of membranes between 32 and 36 weeks' gestation. These patients were managed expectantly whenever possible. Neonatal outcomes were stratified by gestational age at rupture of membranes. RESULTS: Two hundred thirty-six patients with rupture of membranes between 32 and 36 weeks' gestation were managed expectantly. Prolongation of pregnancy by >/=1 week was infrequent in all cases, particularly if membrane rupture occurred after 34 weeks' gestation. Reductions in the neonatal length of stay and the incidence of hyperbilirubinemia were observed at 34 weeks' gestation with respect to younger gestational ages. No perinatal deaths occurred among the study cases. CONCLUSIONS: A "break point" in neonatal morbidity was observed at 34 weeks' gestation, which supports induction of labor at this gestational age. The short latencies observed limit the potential benefits of expectant management.

Pregnancy in the chronically hypertensive patient.

The majority of patients with mild chronic hypertension have successful pregnancy outcomes. Most perinatal morbidity is secondary to superimposed preeclampsia. Antihypertensive therapy does not appear to significantly affect pregnancy outcome, nor the incidence of superimposed preeclampsia in mild chronic hypertensives. The maternal and fetal risks are considerably higher for severe chronic hypertension and for those patients with target organ disease. These patients ideally should be counseled regarding their risks prior to pregnancy. Antihypertensive therapy should be instituted at diastolic pressures greater than or equal to 100 mm Hg.

Endothelin-1-induced placental and fetal growth restriction in the rat.

The objective of this study was to evaluate the effect of increased circulating endothelin on fetal and placental growth in the rat. Indwelling arterial and venous catheters were placed on day 14 of a 22-day gestation in timed-pregnant Sprague-Dawley rats. Saline, 0.2 nmol/kg/h endothelin, or 0.5 nmol/kg/h endothelin was continuously infused from day 15 through 21 in randomly assigned animals (n = 12 in each group). Maternal arterial blood pressure and serum endothelin levels were evaluated on days 15, 18, and 21 of gestation. On day 21, pregnancy outcome data including fetal and placental weights, litter size, and the occurrence of stillbirths were ascertained, and fetal blood was obtained for serum endothelin levels. All data were compared among the three groups, and statistical significance was determined by analysis of variance. Endothelin infusion resulted in a dose-dependent decrease in fetal and placental weights when compared to saline-treated pregnancies. A significant increase in maternal arterial blood pressure was noted only in the 0.5 nmol/kg/h endothelin group. Fetal and placental growth restriction occurred in the absence of maternal hypertension in the 0.2 nmol/kg/h group. These results demonstrate that endothelin infusion causes restriction of fetal and placental growth, even in the absence of maternal hypertension.

Endothelin receptor A antagonism prevents hypoxia-induced intrauterine growth restriction in the rat.

OBJECTIVE: Our purpose was to investigate the hypothesis that endothelin plays a critical role in maternal hypoxia-induced intrauterine growth restriction. STUDY DESIGN: Chronic indwelling venous and arterial catheters were placed on day 17 of a 22-day gestation in timed-pregnant Sprague-Dawley rats. Twelve rats were infused with saline solution and 12 with 6 mg/kg per day FR139317, an endothelin receptor A-specific antagonist. For gestational days 18 to 21 half the rats in each infusion group were housed in a normoxic environment and the other half in a hypoxic (14% oxygen) environment. On day 21 an arterial blood gas level was determined, the rats were then anesthetized, and a hysterotomy was performed. The weight of each pup and its corresponding placenta was recorded. Statistical significance was determined by analysis of variance. RESULTS: Among the rats receiving saline solution infusions, fetal weights were 20% less and placental weights were 11% less for those housed in a hypoxic environment compared with those housed in a normoxic environment (p < 0.003). Among the rats receiving FR139317 infusions, fetal and placental weights were not significantly different for those in a hypoxic environment compared with those in a normoxic environment. The fetal and placental weights for the rats receiving FR139317 infusion in hypoxic or normoxic environments were similar to those receiving saline solution in a normoxic environment. CONCLUSIONS: Endothelin plays a critical role in hypoxia-induced intrauterine growth restriction. Infusion of an endothelin antagonist prevents the intrauterine growth restriction caused by chronic hypoxia.

Congenital diaphragmatic hernia. In utero therapy and ethical considerations.

Despite advances in neonatal medicine, the mortality rate for congenital diaphragmatic hernia remains high. The results of work in animal models suggest that this anomaly may be amenable to in utero surgical correction. In this article, the natural history of congenital diaphragmatic hernia in humans is reviewed, and the development of antenatal management strategies is traced. The ethical issues surrounding the management of fetuses with diaphragmatic hernias are also discussed. The ground-breaking nature of the development of strategies for management of congenital diaphragmatic hernia underscores the importance of establishing scientific and ethical guidelines for future endeavors with in utero therapy.

Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered before 30 weeks' gestation.

OBJECTIVE: To determine if an additive effect exists between antenatal corticosteroid administration and postnatal surfactant therapy in the prevention of respiratory distress syndrome (RDS) in preterm infants. METHODS: A randomized, double-blind trial was conducted from April 1990 to June 1994, in which dexamethasone (5 mg every 12 hours for a total of four doses) or saline was given to women at risk for delivery at 24-29 weeks' gestation. At birth, prophylactic surfactant was administered to all study infants. Main outcome measures were RDS occurrence and severity. Secondary clinical end points included bronchopulmonary dysplasia, pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, retinopathy, intraventricular hemorrhage, and death. RESULTS: Seventy-five of the 124 randomized subjects delivered 96 infants within the studied gestational age range (dexamethasone, n = 54; placebo, n = 42). Similar maternal demographics and obstetric complications were noted between study groups. A greater population of infants were delivered from multi-fetal gestations in the dexamethasone cohort (26 of 54 versus 12 of 42 newborns; P = .05). There were no significant differences in the occurrence or severity of RDS between the dexamethasone and placebo infants (none or mild, 67 versus 67%; moderate, 24 versus 26%; severe, 9 versus 7%, respectively), or differences in any of the secondary clinical outcomes. The study size was sufficient to exclude a 50% reduction in RDS incidence as a consequence of dexamethasone exposure. An analysis restricted to singletons (dexamethasone, n = 28; placebo, n = 30) revealed similar overall occurrence of intraventricular hemorrhage (12 of 28 versus ten of 30; P = .63), but significantly fewer grade 3 and 4 intraventricular hemorrhages in dexamethasone-exposed neonates (two of 12 versus six of ten; P = .048). CONCLUSION: Antenatal dexamethasone does not appear to decrease the incidence or severity of RDS in surfactant-treated infants delivered at 24-29 weeks' gestation, but may be associated with reduced severity of intraventricular hemorrhages in surfactant-treated singletons in this gestational age range.

Amniotic fluid lamellar body count: a rapid and reliable fetal lung maturity test.

OBJECTIVE: To evaluate the lamellar body count as a predictor of fetal lung maturity. METHODS: We conducted a prospective clinical outcome study. Amniocentesis was performed for evaluation of fetal lung maturity status within 72 hours of delivery in 130 patients. A lamellar body count was performed on each specimen, and a lecithin-sphingomyelin ratio and lung phospholipid profile were performed when possible (insufficient sample or contamination in eight cases). Each infant was evaluated for evidence of respiratory distress syndrome (RDS). RESULTS: A lamellar body count exceeding 30,000/microL predicted pulmonary maturity correctly in all cases (negative predictive value 1.00). All 16 cases of RDS had counts of 30,000/microL or less. If the lamellar body count was less than 10,000/microL, the positive predictive value for RDS was 67%, and the likelihood of a mature result from chromatographic phospholipid analysis was low (one of 14, 7%). Values between 10,000-30,000/microL indicated intermediate risk (four of 39, 10%) for developing RDS. Phospholipid analysis indicated fetal lung maturity in 35 of 39 (90%) cases with lamellar body counts in the intermediate risk range. CONCLUSIONS: The lamellar body count compares favorably with traditional phospholipid testing in the prediction of fetal lung maturity. Phospholipid analysis is not needed with lamellar body counts greater than 30,000/microL or less than 10,000/microL, but may be of benefit for values in the intermediate risk range. Advantages of this test include speed, objectivity, small sample volume required, and universal availability of instrumentation.

Causes of intrauterine growth restriction.

IUGR is a relatively common problem and a potential cause of significant perinatal morbidity and mortality. There are many possible causes of IUGR, and some cases may involve more than one (Table 1). Although an underlying cause may not always be identifiable, it it important to consider all of these factors because identification of the underlying cause of the IUGR may impact short-term management as well as long-term prognosis. The cornerstone of management for IUGR involves close antenatal surveillance with a well-timed delivery. Antenatal testing in the form of fetal heart rate monitoring, ultrasonographic evaluation, and, on occasion, umbilical blood sampling allows for ongoing surveillance of the growth-retarded fetus. Intrapartum management should include close fetal heart rate monitoring because the ability of the growth-restricted fetus to tolerate labor generally is low and the risk for acidosis is high. A pediatric team should attend the delivery because the risk of meconium aspiration and the frequency of low Apgar scores and metabolic disorders are high. The biochemical mediators reviewed in this article are not likely to be independent causative factors in IUGR; it is more likely they are important mediators of a pathologic process set in motion by other agents or insults. A better understanding of how these mediators contribute to the pathophysiology of IUGR will improve our understanding of this disorder and may allow for therapeutic interventions in the underlying pathophysiologic process.

Midtrimester Rh sensitization associated with circulating anticardiolipin antibodies and elevated maternal serum alpha-fetoprotein. A case report.

The incidence of antepartum Rh isoimmunization has been limited by third-trimester Rh immune globulin (RhIg) administration. Prophylactic failures are uncommon but can occur if sensitization takes place prior to the 28th week of gestation. We report a case of midtrimester Rh sensitization in an anticardiolipin antibody-positive primipara coincident with the discovery of an elevated maternal serum alpha-fetoprotein value, oligohydramnios and fetal growth retardation. This case suggests that fetal-maternal hemorrhage and subsequent sensitization may be facilitated by anticardiolipin antibody-induced placental damage. Prophylactic midtrimester RhIg administration might avoid sensitization in similar cases.

Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.

OBJECTIVE: We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome. STUDY DESIGN: Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished. RESULTS: Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth. CONCLUSIONS: The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.

Heparin therapy for congenital antithrombin III deficiency in pregnancy.

A patient with congenital antithrombin III deficiency and a history of thromboembolic events prior to pregnancy was successfully treated with subcutaneous heparin alone throughout two pregnancies. Although adjuvant antithrombin III infusions may have a role in the treatment of this disorder, especially in the peripartum period, there is no evidence that this approach is superior to heparin therapy alone. We present this case as further evidence that heparin therapy alone appears to be a safe and effective treatment for pregnant patients with this rare but serious disorder.