The Safety of Histamine 2 (H2) Blockers in Pregnancy: A Meta-analysis

Heartburn and acid reflux increase the severity of nausea and vomiting of pregnancy, and may lead to more serious medical conditions. The fetal safety of histamine 2 (H2) blockers, the most common antireflux medication, during pregnancy needs to be determined. The aim herein is to determine the fetal safety of H2 blockers during pregnancy through systematic review. All original research assessing the safety of H2 blockers in pregnancy was sought. Data included congenital malformations, spontaneous abortions, preterm delivery, and small for gestational age. A random-effects model combined results. With data from 2,398 exposed and 119,892 nonexposed to H2 blockers, overall odds ratio was 1.14 [0.89, 1.45]. Further analysis revealed no increased risks for spontaneous abortions, preterm delivery, and small for gestational age with odds ratios and 95% confidence intervals (CIs) of 0.62 [0.36–1.05], 1.17 [0.94, 1.147], and 0.28 [0.06, 1.22], respectively. H2 blockers can be used safely in pregnancy.     

Preterm Infants with Paroxysmal Supraventricular Tachycardia: Presentation, Response to Therapy, and Outcome

Objectives: We investigated the clinical course of preterm infants with paroxysmal supraventricular tachycardia in comparison to their term counterparts. Background: Paroxysmal supraventricular tachycardia (PSVT) is the most common arrhythmia in childhood. It is known to cause significant morbidity and rarely mortality, most commonly in infants. Yet, there is minimal information in the literature on preterm infants with PSVT. Methods: Retrospective review of 40 infants, 26 term and 14 preterm, less than three months of age who presented with PSVT from January 1990 to January 1999. We compared the severity of first clinical presentation, in-hospital response to long-term medications, and outcome after discharge. Results: Symptomatic severity on presentation was not different between preterm and term infants. Preterm infants required fewer medication trials (p=0.01) and had no recurrences after discharge in contrast with 43% recurrence in the term infants (p<0.0001). No preterm infants had Wolff-Parkinson-White syndrome (WPW) in contrast to 42% of term infants (p=0.003). Term infants with WPW were more symptomatic (p=0.01), required more medications (p=0.004), but had a similar recurrence frequency as terms infants without WPW (p=0.95). Excluding infants with WPW, preterm infants were more severely symptomatic (p=0.02), yet no longer was there a difference in response to first medication trial (p=0.30). Conclusions: We found that preterm infants with PSVT are as severely symptomatic on presentation, require fewer medications for adequate in-hospital control, and have fewer recurrences than their term counterparts. Unexpectedly, preterm infants did not present with WPW. The presence of WPW only in the term infants may account for differences in the clinical course between preterm and term infants.     

Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery

Ureaplasma urealyticum is the microorganism most frequently isolated from the amniotic fluid of women in preterm labor. The relationship between intra-amniotic U. urealyticum in healthy second-trimester pregnant women and subsequent pregnancy outcome was investigated. Transabdominal amniotic fluid obtained from 254 asymptomatic women at 15-17 weeks' gestation were tested by polymerase chain reaction (PCR). U. urealyticum was identified in 29 subjects (11.4%). A subsequent preterm labor occurred in 17 U. urealyticum-positive women (58.6%), compared with 10 (4.4%) U. urealyticum-negative women (P<.0001). Preterm birth was documented in 7 (24.1%) U. urealyticum-positive women compared with only 1 U. urealyticum-negative woman (0.4%) (P<.0001). U. urealyticum-positive women also had a higher prevalence of preterm labor in a prior pregnancy (20.7%) than did the negative women (2.7%; P=.0008). PCR testing of second-trimester amniotic fluid for U. urealyticum can identify women at risk for subsequent preterm labor and delivery.     

Differential changes in 15-hydroxyprostaglandin dehydrogenase and prostaglandin H synthase (types I and II) in human pregnant myometrium

Prostaglandins (PGs) play a key role in the onset of labor in many species and regulate uterine contractility and cervical dilatation. Therefore, the regulation of prostaglandin output by PG synthesizing (PGHS-I and PGHS-II) and metabolizing (PGDH) enzymes in the human myometrium may determine uterine activity patterns in human labor both at preterm and at term. We hypothesized that expression of PGHS isozymes and PGDH in myometrium from women at preterm and term labor would change to favor increased uterotonin (PG) production. Myometrial samples were obtained from the lower uterine segment during cesarean section deliveries from women presenting in preterm, no labor; preterm, labor; term, no labor; term, labor. Immunoreactive (ir-) PGHS and PGDH protein was localized using immunohistochemistry, and changes in protein levels were determined by Western blotting. Ir-PGHS-I and PGHS-II proteins were localized only to myocytes. Ir-PGDH was localized to myocytes in all samples of myometrium examined, but using dual immunofluorescence and immunohistochemistry, ir-PGDH was also detected in cells of the connective tissue. Levels of ir-PGHS-I and PGHS-II protein were not significantly different between no labor and labor tissues, either at preterm or at term. There was no significant effect of gestational age on levels of PGDH, PGHS-I, and PGHS-II protein, but there was a significant decrease in ir-PGDH protein levels in myometrium with labor both at preterm and at term. In addition, there was a decrease in PGDH activity in myometrium from women in labor, both at preterm and at term. Therefore, we conclude that PGDH, PGHS-I, and PGHS-II protein localize within the myocytes of the human pregnant myometrium. A decrease in PGDH protein and activity occurs in association with active labor and may contribute to the amount of bioactive PGs available to act within the human pregnant myometrium at that time.     

Melatonin prevents experimental preterm labor and increases offspring survival

Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra‐amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation‐associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS‐treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin‐treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS‐induced rises in uterine prostaglandin (PG) E₂, PGF_2α, and cyclooxygenase‐2 protein levels. In addition, melatonin prevented the LPS‐induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor‐alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival.     

Evaluation of psychopathology in patients with paroxysmal supraventricular tachycardia

BACKGROUND: A higher prevalence of anxiety- and depression-related symptoms are expected in patients with at least one somatic disease and who are on medications compared with the general population. OBJECTIVES: To determine if patients with paroxysmal supraventricular tachycardia (PSVT) show a higher prevalence of anxiety and depressive symptoms compared with a control population. The induction of depressive symptoms by beta-blockers or calcium channel blockers was also evaluated. METHODS: Twenty-five patients (17 women, eight men) with documented PSVT (atrioventricular re-entrant tachycardia or atrioventricular nodal re-entrant tachycardia) were evaluated by a battery of questionnaires and inventories, which provide information about the presence of symptoms of anxiety and/or depression. All patients were examined by a psychiatrist and completed the following five scales: Symptom Checklist-90, Hamilton Anxiety Scale, Hamilton Depression Rating Scale, Zung's Self-Rating Depression Scale and Beck Self-Assessment Depression Scale. RESULTS AND CONCLUSIONS: The majority of the evaluations (Hamilton Anxiety Scale, Beck Self-Assessment Depression Scale, Zung's Self-Rating Depression Scale), did not show a higher incidence of severe symptoms of depression in the group of patients with PSVT. However, the Hamilton Depression Rating Scale rated the symptoms of depression as significant, but the score was low enough to be considered nonsignificant. According to the Symptom Checklist-90, men perceived the presence of the cardiological disease more intensively and more negatively than women (P=0.1). Psychiatric history and therapy with psychopharmacological agents were comparable in both groups. It was noted that patients had sporadic contacts with a psychiatrist or a psychologist, but this was not directly associated with PSVT.     

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors,and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labor at term and preterm

We have studied TNF-related apoptosis-inducing ligand (TRAIL) and its membrane-bound (R1-R4) and soluble receptors [osteoprotegerin (OPG)] in gestational membranes to assess their significance in preterm parturition and premature rupture of membranes (PROM). TRAIL was detected by ELISA in extracts of term choriodecidual (but not amnion) tissues and explant-conditioned media. Concentrations of OPG (determined using ELISA) in gestational membranes were 20- to 50-fold greater than those of TRAIL. Median OPG concentrations in amniotic fluid (AF) at 15-17 wk gestation were similar to those at term before and during labor, whereas levels in pregnancies sampled preterm were significantly elevated. OPG levels in AF from women with preterm PROM were similar to those from women in preterm labor. In contrast, in pooled AF samples (n = 23-33), TRAIL concentrations at term with and without labor were elevated compared with samples from preterm deliveries. TRAIL-R3 and -R4 decoy receptors were detected in term amnion and choriodecidual extracts by immunoblotting and were localized by immunohistochemistry to amnion epithelial cells and chorionic trophoblasts. TRAIL (100 ng/ml) had little or no effect on amnion or choriodecidual cell viability or apoptosis, although these tissues responded to TNF-alpha with increased prostaglandin E(2) production. Our findings suggest that OPG is abundant in gestational membranes and, in concert with TRAIL decoy receptors, may protect resident cells of the fetal membranes against the proapoptotic effects of TRAIL and other related ligands during pregnancy.     

Coagulation and fibrinolysis in preeclampsia and neonates.

Coagulation and fibrinolysis were determined in 67 Indonesian women admitted to the University Hospitals for delivery in Medan. They were diagnosed to be at term gestation (mean 39.3 +/- 1.1 weeks) with moderate and severe preeclampsia (n=32) and in labor, and 8 had preterm labor (gestation mean 33.5 +/- 2.6 weeks). Twenty-seven normal pregnant women in labor (gestation mean 39.7 +/- 1.0 weeks) served as controls. Cord blood from 23 neonates from normal pregnancy and 31 neonates from preeclampsia was also evaluated. Preeclamptic women in labor showed further enhanced coagulation activation (F(1+2)) with raised urokinase-like plasminogen activator (u-PA) activity and reduced plasminogen activator inhibitor-2 (PAI-2) levels. In preterm preeclampsia, significantly reduced antithrombin III (ATIII) and PAI-2 levels with further elevated tissue-type PA (t-PA) antigen and plasminogen activator inhibitor-1 (PAI-1) antigen were seen compared to normal pregnancy. These would suggest a state of enhanced thrombin generation with elevated fibrinolytic/inhibitor proteins in preterm preeclampsia. The reduced PAI-2 levels seen in preeclampsia have been suggested to be associated with reduced placental function. Neonates born to mothers of either normal pregnancy or preeclampsia at term showed similar hemostatic changes with reduced fibrinogen, ATIII, t-PA, u-PA antigen, PAI-1 levels, and coagulation activation compared to their respective maternal plasma levels. No significant differences in hemostatic parameters studied between the neonates of both cohorts were seen, and this would suggest that the neonates were protected from the adverse effects of preeclampsia and their hemostatic system was physiologically balanced.     

Prospective study of systemic lupus erythematosus pregnancies

Different study designs have yielded different results on the effect of pregnancy on systemic lupus erythematosus (SLE) disease activity. Using the patient as her own control, and using nonpregnant SLE patients as controls, we have found flares to be more common in pregnancy. In SLE pregnancies followed prospectively at one center, we have found that preterm birth is the most frequent adverse event. Pregnancy loss occurred in 14%. Active SLE contributes to both preterm birth and to pregnancy loss. In addition, even in a first pregnancy, the presence of the lupus anticoagulant is associated with an increased risk of pregnancy loss.     

Different impacts of various tocolytic agents on increased risk of postoperative hemorrhage in preterm labor women undergoing Cesarean delivery: A population-based cohort study

Tocolytic agents, commonly used for inhibiting preterm labor, pose the risk of uterine atony, leading to postpartum hemorrhage. This study elucidated the effects of different tocolytic agents on postoperative hemorrhage among women in preterm labor undergoing Cesarean delivery (CD). Data from Taiwan National Health Insurance Research Database were analyzed. The risk (adjusted hazard ratio [aHR] and 95% confidence intervals [CI]) of postoperative hemorrhage in CD women with preterm labor diagnosis using tocolytic agents (Tocolysis group) comparing to CD women not using tocolytic agents (Control group) were determined. Impacts of different tocolytic agents in this regard were also investigated. Our data revealed that the incidence (11.7% vs 2.6%, P < .001) and risk (aHR: 1.21, 95% CI: 1.12–1.31, P < .001) of postoperative hemorrhage were significantly higher in the Tocolysis group (n = 15,317) than in the Control group (n = 244,096). Ritodrine was the most frequently used tocolytic agent (80.5%), followed by combination therapy (using more than one tocolytic agents) (8.5%), magnesium sulfate (MgSO₄, 4.6%), calcium channel blockers (3.8%), betamimetics other than ritodrine (1.9%), prostaglandin synthase inhibitors (0.5%), and nitrates (0.1%). Barring those using calcium channel blockers and combination therapy, the use of MgSO₄ (aHR: 1.43, P = .001), betamimetics other than ritodrine (aHR: 1.71, P < .001), prostaglandin synthase inhibitors (aHR: 2.67, P < .001) and nitrates (aHR: 3.30, P = .001) was associated with higher risks of postoperative hemorrhage compared with ritodrine. In conclusion, CD women with preterm labor diagnosis using tocolytic agents exhibit an increased risk of postoperative hemorrhage and that this risk varies with the use of different tocolytic agents.     

Bacterial vaginosis complicating pregnancy and gynecologic surgery

Bacterial vaginosis, the most commonly diagnosed vaginitis, has traditionally been regarded as a benign condition. However, recent evidence suggests association with preclinical miscarriage, early pregnancy loss, preterm labor, low birth weight infants, gynecologic surgical infections, and postabortal pelvic inflammatory diseases. Since studies show significant reduction in preterm labor and postabortal endometritis with treatment, it is recommended that bacterial vaginosis in high-risk women for preterm labor and women who undergo surgical abortion be treated regardless of symptoms. No treatment is recommended, however, for asymptomatic low-risk women.     

善得定中止阵发性室上性心动过速机制和疗效的探讨

为探讨善得定中止阵发性室上性心动过速(室上速)的机制和疗效,本文采用膜片钳全细胞记录方法观察生长激素抑制因子(SS)对心室肌细胞L型钙通道的作用;窦性心律、室上速时静注善得定,观察A-H间期及中止室上速的方式、效果。结果显示SS对心室肌细胞L型钙通道均有明显抑制作用;静注善得定后A-H间期延长,14例室上速中8例(57.1％)以房室结顺向传导阻滞方式转复为窦性心律。表明善得定中止室上速疗效肯定,副作用小,但容易复发。     

Successful Pregnancies in Two Women with Hypoplastic Left Heart Syndrome

Objective. Hypoplastic left heart syndrome (HLHS) is a relatively common complex congenital heart defect. Prior to development of staged reconstruction (i.e., Norwood procedure), HLHS was almost universally fatal within months of birth. Early survivors of the Norwood procedure are now reaching reproductive age. We report successful pregnancies in two such women. Patients. The first patient was a 20-year-old woman transferred from a community hospital at 33 3/7 weeks gestation because of preterm labor, suspected preeclampsia, and mild chronic hypoxemia. She had normal systemic ventricular shortening without significant valvar regurgitation but severe neoaortic dilatation. A fetal ultrasound demonstrated intrauterine growth restriction. An urgent Cesarean section was performed at 33 6/7 weeks gestation, given breech position and intractable preterm labor. The second patient, a 23-year-old woman followed at this institution through pregnancy, presented with preterm labor at 36 weeks gestation. Her systemic ventricular shortening was normal, with mild tricuspid regurgitation but without neoaortic dilation or regurgitation. She developed active labor at 36 3/6 weeks, and had a spontaneous vaginal delivery of a small for gestational age infant. Both women tolerated labor and childbirth without complication. Neither infant had evidence of structural heart disease on fetal echocardiography or physical examination. Conclusions. These cases, the first reported successful pregnancies in mothers with HLHS, highlight the challenges of pregnancy among women with complex congenital heart disease in general and raise several considerations specific to HLHS.     

Activity and expression of soluble and particulate guanylate cyclases in myometrium from nonpregnant and pregnant women: down-regulation of soluble guanylate cyclase at term.

The role of cGMP in the regulation of human myometrial smooth muscle contractility is at present unclear. cGMP can be synthesized by a cytoplasmic, soluble guanylate cyclase (sGC), which is stimulated by nitric oxide and carbon monoxide, and by particulate membrane-bound GC, which are activated by natriuretic peptides. The aim of this study was to determine whether sGC or pGC are present in nonpregnant and pregnant human myometrium, and whether the activity and expression of these enzymes and the cGMP content change during pregnancy and with labor. Myometrium was obtained from nonpregnant women (n = 12) and pregnant women who were preterm (25-34 wk gestation; n = 12), term (>38 wk) not in labor (n = 14), or term in active labor (n = 12). The cGMP content in myometrium obtained from preterm deliveries was significantly higher than that in tissue obtained from nonpregnant women and decreased at term, especially in laboring groups. Protein and mRNA for sGC, particulate GC-A, GC-B, and the clearance receptor were detected in human myometrium. cGMP in pregnant human myometrium, however, appears to be produced predominantly by sGC and possibly by GC-B, as GC-A was only weakly expressed. sGC activity was greater in myometrium from preterm (nonlabor) deliveries compared those taken at term (in labor), but was down-regulated compared with activity in nonpregnant myometrium. Neither atrial natriuretic peptide nor C-type natriuretic peptide (agonists for GC-A and GC-B, respectively) altered contractility in vitro of myometrium from women at term (not in labor). We conclude that the cGMP/guanylate cyclase system in human myometrium is gestationally regulated and potentially plays an important role in mediating quiescence during early pregnancy. A reduction in cGMP availability may contribute to the switch to contractile activity at term.     

Expression of prostaglandin I(2) synthase,but not prostaglandin E synthase,changes in myometrium of women at term pregnancy

Prostaglandins (PGs) act as potent uterotonins at the time of labor. Prostaglandin E synthase (PGES) is responsible for the formation of PGE(2), a uterotonin. PGI(2) is synthesized by the prostaglandin I synthase enzyme (PGIS) and contributes to relaxation in the lower uterine segment. We examined the expression of membrane-bound PGES and PGIS in myometrium from pregnant women during preterm and term labor. Tissues were collected from the lower uterine segment from preterm no labor, preterm labor, term no labor, and term labor patients and used for immunohistochemistry and Western blot analysis using specific antibodies. Immunoreactive (ir-) PGES and PGIS proteins were localized to the cytoplasm of myocytes of the myometrium and vascular smooth muscle cells. Ir-PGES was also detected in vascular endothelial cells. Western blot analyses revealed a predominant protein band of 180 kDa, and a second 16-kDa band for ir-PGES and 56-kDa band for ir-PGIS. There was no significant change in ir-PGES protein (180 or 16 kDa) or mRNA levels with preterm or term labor or gestational age. There was a significant decrease in PGIS mRNA and protein with advancing gestational age. We conclude that the gestational age decrease in the inhibitory PGIS is consistent with lessening of its influence in myometrium at the time of labor. The lack of change in PGES indicates that alterations at other points along the pathway of arachidonic acid metabolism may be of greater importance in affecting local changes in PGE(2).     

Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia

Paroxysmal supraventricular tachycardia (PSVT) is seen somewhat frequently in the emergency department but less frequently during pregnancy. Although verapamil is widely used as the drug of choice for PSVT with a narrow QRS complex in a hemodynamically stable patient, the acute IV use of verapamil during pregnancy has not been well studied. Only a limited number of case reports document its safety and efficacy in the treatment of maternal or fetal PSVT. In general, the use of medication during pregnancy requires careful assessment of both the maternal and fetal risks versus benefits and documentation of patient consent. Because it crosses the placenta, one of the major concerns with the acute use of IV verapamil centers around the drug's potential effect on fetal heart rate. The case we present describes the occurrence of PSVT on two separate occasions in a woman in the third trimester of pregnancy. In both episodes, as much as 10 mg IV verapamil was given with resulting successful conversion to normal sinus rhythm. Fetal heart monitoring during drug administration failed to show significant change in fetal heart rate.     

Reversible dilated cardiomyopathy associated with glucagonoma

An association between dilated cardiomyopathy and glucagonoma has not previously been described. A case of a 54 year old woman with tachycardia and congestive heart failure is described. Initial evaluation included an echocardiogram, which showed dilated cardiomyopathy with an ejection fraction of 15%. Coronary angiography and endomyocardial biopsy did not identify a secondary cause of her cardiomyopathy. She subsequently developed necrolytic migratory erythema, and imaging of her pancreas identified a pancreatic mass with a major increase of her serum glucagon concentration. Tachycardia persisted despite treatment with beta blockers. After resection of her tumour, her heart rate normalised and subsequently her heart returned to normal size and function. Glucagon is used to treat overdoses of beta blockers and calcium channel blockers, increasing heart rate by increasing myocardial cyclic AMP concentrations. Although rare, in the appropriate clinical setting, glucagonoma should be considered in the differential diagnosis for tachycardia and dilated cardiomyopathy.     

The utility of plasma CRH as a predictor of preterm delivery.

It has been suggested that CRH is a placental clock that controls the duration of pregnancy and that the timing of the rise in CRH may permit prediction of the onset of labor. We have performed a prospective longitudinal study, in 297 women, to examine the utility of a single second-trimester plasma CRH measurement to predict preterm delivery. Venous blood samples were taken at 4-weekly intervals, beginning at 16-20 wk gestation, until delivery for CRH and its binding protein. A time point at which a single plasma CRH test might give optimal data to predict preterm delivery was determined. Thirty-one subjects delivered prematurely (10.4%). Sampling for plasma CRH at 26 wk gestation seemed the optimal time point to maximize sensitivity and specificity of the test. The mean (+/- SD) plasma CRH in women at this gestation who eventually delivered after spontaneous labor within 1 wk of their due date (39-41 wk, n = 127) was 34.7 +/- 27.0 pM. A plasma CRH of more than 90 pM at 26 wk gestation had a sensitivity of 45% and a specificity of 94% for prediction of preterm delivery. The positive predictive value was 46.7%. Calculation of free CRH did not improve these figures. In conclusion, a single measurement of plasma CRH, toward the end of the second trimester, may identify a group at risk for preterm delivery, but over 50% of such deliveries will be unpredicted. These data do not support the routine clinical use of plasma CRH as a predictor of preterm labor.     

Plasma concentrations of prostaglandins during late human pregnancy: influence of normal and preterm labor.

Highly sensitive and specific RIA procedures have been used to measure prostaglandin concentrations in the peripheral circulation of late pregnant and parturient women. The concentrations of prostaglandin E (PGE) and prostaglandin F (PGF) in plasma samples assayed within 4 weeks of collection were not significantly different among the groups studied, the levels (mean +/- SEM, picograms per ml) were: late pregnancy (n = 13): PGE, 4.8 +/- 1.0; PGF, 6.2 +/- 0.5; early term labor (n = 5): PGE, 6.8 +/- 1.5; PGF, 7.9 +/- 0.7; late term labor (n = 5): PGE, 5.4 +/- 2.2; PGF, 12.4 +/- 3.5; and preterm labor (n = 7): PGE, 4.4 +/- 0.4; PGF, 6.9 +/- 1.4. The concentration of 13,14-dihydro-15-keto-prostaglandin F (PGFM) in late pregnancy was 59.0 +/- 7.8 pg/ml. During spontaneous term labor, the concentration of PGFM was significantly elevated (P less than 0.01) to 142.8 +/- 32.3 pg/ml in early labor and 282.7 +/- 55.3 pg/ml in late labor. The concentration of PGFM in plasma from patients in preterm labor (62.7 +/- 17.4 pg/ml) was not significantly different from that found during late pregnancy, but was significantly lower than levels found at term during early labor (P less than 0.05). The concentration of PGE increased significantly in frozen plasma samples stored for more than 4 weeks in all groups studied; the concentration of PGF was significantly elevated after storage only in the late pregnancy group (P less than 0.01). The plasma concentration of PGFM in all groups studied was unaffected by storage. It is concluded that measurement of PGFM concentrations is the most reliable method available of monitoring prostaglandins in the peripheral circulation and that great care must be exercised in the assay and interpretation of prostaglandin levels in human plasma.