The clinical value of gas-liquid chromatography in the detection of intra-amniotic microbial invasion

Short-chain organic acids are byproducts of bacterial metabolism, and their detection by gas-liquid chromatography (GLC) in amniotic fluid has been proposed as a rapid, sensitive, and specific method for the diagnosis of infection. This study was conducted to determine whether GLC analysis of amniotic fluid would be helpful in a population of women in whom the Gram stain examination was negative. Amniotic fluid was retrieved by transabdominal amniocentesis from three groups of patients. Group 1 (negative control) contained 14 women with term pregnancies without clinical and microbiologic evidence of infection of the amniotic cavity; group 2 (positive control) included 17 women with a positive Gram stain examination and culture of amniotic fluid; group 3 (study group) comprised 25 women at risk for intra-amniotic infection who had a negative Gram stain of amniotic fluid. None of the patients in group 1 and 16 of 17 patients (94.1%) in group 2 had pathologic short-chain organic acids in the amniotic fluid. Seven of the 25 patients in group 3 had a positive amniotic fluid culture and only two had an abnormal GLC pattern. Of the remaining 18 patients with negative amniotic fluid cultures, eight had abnormal GLC results. In group 3, the sensitivity of GLC was 28.5% and the specificity was 55.5%. Gas-liquid chromatographic analysis of amniotic fluid has limited clinical value in the prediction of amniotic fluid culture when the Gram stain examination is negative.     

Amniotic fluid volume as a risk factor in preterm premature rupture of the membranes

During a prospective study evaluating the expectant management of preterm (26 to 34 weeks) premature rupture of membranes (PROM), the authors compared maternal and neonatal outcome of 17 patients with a marked reduction in amniotic fluid volume with 22 subjects having identifiable pockets of amniotic fluid after membrane rupture. The results demonstrated no significant differences in maternal age, gravidity, cervical dilatation, incidence of labor on admission, use of tocolytics, steroid usage, interval from membrane rupture to delivery, or cesarean section rate. The gestational age at which PROM occurred (31.4 +/- 1.9 versus 29.8 +/- 2.2 weeks) was significantly (P less than .05) more advanced in the adequate fluid patients when compared with the reduced fluid group. Clinical amnionitis was a far more common occurrence in the reduced fluid patients when compared with the adequate fluid group (47 versus 14%, respectively, P less than .05) as was postpartum endometritis (59 versus 18%, P less than .05). The incidence of overt neonatal sepsis was similar between the adequate fluid (14%) and reduced fluid (18%) patients. These results suggest that when a marked reduction in amniotic fluid after PROM is identified, patients are at a three-times greater risk for antepartum amnionitis and postpartum endometritis.     

A comparison of amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy

OBJECTIVE: Our purpose was to determine whether there are differences in the timing of the appearance of various amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy. STUDY DESIGN: A case-control study of 295 subjects with diabetes and 590 control subjects was performed by use of gestational age-matched amniocentesis specimens analyzed for lecithin/sphingomyelin (L/S) ratio, phosphatidylinositol (PI), and phosphatidylglycerol (PG) composition. Diabetic subjects were stratified according to type of diabetes, degree of blood glucose control, and birth percentile of the neonate. RESULTS: There was no difference in L/S ratios over gestational age by type of diabetes or quality of glycemic control. Women with preexisting diabetes had significantly higher PI levels at 33 to 35 weeks' gestation, which became similar to levels of control subjects after 36 weeks, whereas patients with gestational diabetes mellitus and control subjects had similar PI levels throughout. In diabetic subjects, the onset of production of PG was delayed from 35.9 +/- 1.1 weeks (controls) to 38.7 +/- 0.9 weeks (overt diabetics) and 37.3 +/- 1.0 weeks for gestational diabetes mellitus (P <.001). The delay in PG synthesis was not related to infant sex, level of maternal glucose control, or fetal macrosomia. CONCLUSIONS: Fetal pulmonary maturation, as evidenced by the onset of PG production in the amniotic fluid, is delayed in diabetic pregnancy by 1 to 1.5 weeks. This delay appears to be associated with an early and sustained elevation in amniotic fluid PI levels at 32 to 34 weeks.     

Normal values for human umbilical venous and amniotic fluid pressures and their alteration by fetal disease

Umbilical venous and amniotic fluid pressures were measured in 68 human pregnancies at the time that cordocentesis was performed. Normal umbilical venous pressure was unrelated to gestational age and remained within a tight range (5.3 +/- 2.3 mm Hg, mean +/- SD). Fetuses with an elevated umbilical venous pressure had disorders consistent with either hepatomegaly or congestive heart failure. Umbilical venous pressure was significantly increased before treatment in two fetuses with immune hydrops; it rapidly declined with treatment. Neither gestational age nor umbilical venous pressure was significantly different in the groups that received and did not receive pancuronium. There was a strong relationship between amniotic fluid pressure and gestational age in normal pregnancy (r = 0.54, p less than 0.0001). Women with hydramnios had amniotic fluid pressures greater than control subjects (p = 0.0007). This investigation documents normal human amniotic fluid and fetal umbilical venous pressures. These measurements are altered by disease and may prove to be of diagnostic and therapeutic value in the future.     

Amnionitis with Ureaplasma urealyticum or other microbes leads to increased morbidity and prolonged hospitalization in very low birth weight infants

OBJECTIVE: To investigate the influence of culture proven intrauterine infection on preterm morbidity and to test the effect of antimicrobial treatment. METHODS: Retrospective cohort study conducted between October 1997 and February 2001 in patients with preterm premature rupture of membranes or preterm labor. Vaginal swabs were sampled and amniocentesis for microbiologic culture of the amniotic fluid was performed. Patients with Ureaplasma urealyticum in the amniotic fluid were treated with josamycin. Infants were followed post partum according to birth weight, gestational age, APGAR score and infant morbidity. RESULTS: In 49 eligible patients, 40% of cultures were positive, 22% for Ureaplasma urealyticum, 12% for other bacteria and 6% for candida. Children of mothers with positive amniotic fluid cultures had significantly lower gestational ages (26+4 weeks for Ureaplasma urealyticum [p=0.04] and 25+5 weeks for other microorganisms [p=0.0017] versus 28+6 weeks for mothers with negative amniotic fluid cultures) and lower birth weights (975 g [n.s.] and 828 g [p=0.0072] versus 1,041 g) but were appropriate for their gestational ages. 33.3% and 66.7% versus 24% of the children were mechanically ventilated [n.s.], duration of mechanical ventilation was 5.3 [p=0.02] and 10.1 days [p=0.04] versus 1.4 days, and prevalence of chronic lung disease was 38% and 33% versus 11% [n.s.]. Prevalence of severe intraventricular hemorrhage (12.5% [n.s.] and 33% [p=0.04] versus 3.4%) and nosocomial infections (50% for both groups of positive cultures versus 10.3% for negative cultures, p=0.02 and 0.03, respectively) was higher and median length of stay was significantly longer (121 [p=0.02] and 107 days [p=0.03] versus 60 days) in these patients. Maternal positive vaginal swab cultures were not associated with any of the above-mentioned factors. In none of the patients treated with macrolids for proven Ureaplasma urealyticum amnionitis could the microbes be eradicated. CONCLUSION: Maternal positive amniotic fluid cultures have been associated with lower gestational age and lower birth weight. Rate of infant morbidity was higher and length of stay was significantly longer in this group. Positive vaginal swabs were not predictive for infant morbidity. Treatment of mothers showing positive amniotic fluid cultures with macrolids was not effective.     

Inhibition of group B streptococci by amniotic fluid from patients with intra-amniotic infection and from control subjects

This study describes the inhibition of group B streptococci by amniotic fluid from 50 patients with intra-amniotic infection and 50 matched, noninfected control subjects. Patients were matched for gestational age, time from rupture of membranes to delivery, and time from rupture of membranes to collection of the sample of fluid. Study patients had the clinical diagnosis of intra-amniotic infection and greater than or equal to 10(2) colony-forming units of a high-virulence organism per milliliter. None of the control patients became infected or received antibiotics. We collected the amniotic fluid in the study patients prior to antibiotic therapy. A comparison of bacterial growth in the amniotic fluid versus the amniotic fluid plus phosphate showed that only eight (16%) of the intra-amniotic infection samples of fluid were inhibitory, whereas 18 (36%) of the control samples of fluid were inhibitory (X2 = 5.20, p less than 0.02). However, a comparison of group B streptococci growth in amniotic fluid and Todd-Hewitt broth did not show a statistically significant difference. We conclude that the amniotic fluid bacterial inhibitory assay with group B streptococci is technically more difficult to perform and interpret.     

A randomized study of antibiotic therapy in idiopathic preterm labor

A randomized study was undertaken to test the effects of antibiotics as an adjunct to established methods of tocolysis. One hundred fifty patients with cervical dilation of 1 cm or more and no clinically identifiable cause for preterm labor qualified for the study. Fifty-three (35%) received 500 mg ampicillin orally every 6 hours, 50 (33%) received 500 mg erythromycin orally every 6 hours, and 47 served as controls. Antibiotics were prescribed for 10 days, and the treatment was not altered by the results of cervical cultures. Of these 150 patients, 16 (11%) had positive amniotic fluid cultures. The pregnancies with positive amniotic fluid culture were characterized by significantly less time gained after admission (2.6 versus 28.7 days) and lower birth weight (1262 versus 2470 g) than in those with negative cultures. Histologic studies of the placenta revealed chorioamnionitis in 22 (16%) of 134 patients with negative amniotic fluid cultures; these pregnancies were associated with less time gained after admission (12.5 versus 31.9 days) and lower birth weight (1680 versus 2618 g) compared with pregnancies without histologic chorioamnionitis. In patients with similar gestational age and cervical dilation, the adjunctive use of antibiotic therapy resulted in a statistically significant delay from admission to delivery (30 versus 17 days). In cases of negative amniotic fluid cultures, cervical colonization with group B streptococcus and/or Gardnerella vaginalis increased the risk of prematurity, which improved significantly when ampicillin was given.     

母血羊水中IL—6和IL—8水平与绒毛膜羊膜炎关系的研究

目的 探讨白细胞介素－６（ＩＬ－６）和白细胞介素－８（ＩＬ－８）在监测胎早破中的作用。方法 采用酶联免疫吸附实验对４６例胎盘早破孕妇母血清,羊水中ＩＬ－６和ＩＬ－８水平进行监测,并以正常足月妊娠孕妇２０例做对照组。结果 胎膜早破孕妇母血清ＩＬ－６,ＩＬ－８和羊水中ＩＬ－６和ＩＬ－８水平均较正常足月妊娠组高。差异差异（Ｐ〈０．０１,Ｐ〈０．０５）;随着破膜时间延长母血ＩＬ－６、ＩＬ－８和羊水中ＩＬ－     

Qualitative amniotic fluid volume versus amniocentesis in predicting infection in preterm premature rupture of the membranes

Qualitative amniotic fluid volume assessment and amniocentesis were performed on admission in 54 patients who presented with premature rupture of the membranes and no clinical signs of infection or labor. Comparison of these two methods in predicting infection outcome--as reflected by the development of clinical amnionitis and/or neonatal sepsis--suggests them to have the same efficacy in predicting infection outcome in patients with premature rupture of the membranes. Qualitative amniotic fluid volume was found to have sensitivity 50%, specificity 92.8%, positive predictive value 66.6%, and negative predictive value 86.6%; amniocentesis was found to have sensitivity 58.3%, specificity 88%, positive predictive value 58.3%, and negative predictive value 88%. The use of ultrasonically estimated amniotic fluid volume could replace or be used in addition to amniocentesis in identifying patients with ruptured membranes at particular risk for developing infection.     

Second-trimester amniotic fluid interleukin-10 concentration predicts preterm delivery.

OBJECTIVE: Interleukin-6 (IL-6) is an inflammatory cytokine that has been shown to be elevated in the amniotic fluid of patients with preterm labor. On the other hand, interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to inhibit the synthesis of other cytokines. We hypothesized that amniotic fluid IL-10 in the early second trimester is low in patients who subsequently develop preterm labor, and because of its deficiency, excessive inflammatory responses associated with IL-6 elevation lead to preterm labor and delivery. STUDY DESIGN: Amniotic fluid IL-6 and IL-10 levels were measured in 96 women who underwent genetic amniocentesis between 15 and 23 weeks' gestation. Levels of IL-6 and IL-10 were measured by immunoassay and correlated with demographic and pregnancy outcome information. RESULTS: Fifteen patients delivered at or before 36 weeks and 81 patients delivered after 36 weeks. There was an inverse correlation between amniotic fluid IL-10 concentration and gestational age at delivery. Similarly, an inverse correlation also existed between amniotic fluid IL-6 concentration and gestational age at delivery. CONCLUSIONS: Both IL-10 and IL-6 levels in second-trimester amniotic fluid obtained at the time of genetic amniocentesis appeared to be higher in patients who subsequently developed preterm delivery. Therefore, low amniotic fluid IL-10 production during the second trimester does not seem to be an etiology for preterm labor.     

Serum and amniotic fluid lactic dehydrogenase in pregnant women

No significant differences were found when the serum and amniotic fluid total lactic dehydrogenase (LDH) and LDH isoenzymes in women with newborn infants involved by Rh hemolytic disease were compared with women with uninvolved infants. During the twenty-fourth to thirty-second weeks of gestation, the serum LDH 1 level was higher and the serum LDH 3 level was lower than levels of the nonpregnant control subjects. Serum LDH 3 levels were lower than those of the nonpregnant control subjects during the thirty-third to forty-second weeks of pregnancy. It was noted that there was an increase in amniotic fluid LDH 5 with increasing gestational age.     

Use of amniocentesis in preterm gestation with ruptured membranes

Sixty-one patients with preterm rupture of membranes were studied. Transabdominal amniocentesis was performed successfully in 42 patients (68.8%). Among these 42, 26 (61.9%) had a lecithin:sphingomyelin (L:S) ratio of 1.8 or greater and 16 (38.1%) demonstrated pulmonary immaturity. Amniotic fluid obtained from vaginal pooling was compared to fluid obtained transabdominally in seven patients and did not demonstrate any significant differences in L:S values. Gram stain and subsequent culturing of amniotic fluid obtained transabdominally was accomplished in 41 patients. Seven of the 41 patients (17.0%) had bacteria on Gram stain and/or subsequent amniotic fluid growth. All patients with either bacteria on Gram stain or a positive amniotic fluid culture developed clinical amnionitis or endometritis. Review of the neonatal morbidity and mortality in relation to gestational age of infants with preterm rupture of membranes suggests that: 1) In infants at less than 32 weeks' gestation, amniocentesis need not be done for pulmonary maturity as the morbidity of prematurity in this group is too high even in the presence of pulmonary maturity. 2) In infants at 32 to 34 weeks' gestation, amniocentesis for L:S ratio, Gram stain, and culture is helpful in selecting those in whom delivery should be instituted. 3) In infants at greater than 34 weeks' gestation, the neonatal morbidity is sufficiently reduced so that delivery should be considered except in cases of suspected delayed pulmonary maturation.     

Meconium-stained amniotic fluid across gestation and neonatal acid-base status

OBJECTIVE: To estimate whether the acid-base status of neonates born to women with meconium-stained amniotic fluid varies across gestation. METHODS: We carried out a retrospective cohort study of all pregnancies that were complicated by meconium-stained amniotic fluid in 2004. Cases were identified from a perinatal pathology database that contained data on all pregnancies complicated by meconium-stained amniotic fluid. Data abstracted from the charts included gestational age at delivery, umbilical arterial pH, birth weight, and the presence or absence of labor. Cases were stratified according to gestational age at delivery. The distribution of meconium-stained amniotic fluid across gestation was computed. The mean umbilical arterial pH values (with 95% confidence intervals) across gestation were assessed by analysis of variance. RESULTS: The mean umbilical arterial pH in women with meconium-stained amniotic fluid did not differ across gestation. The overall incidence of meconium-stained amniotic fluid was 12.0% (766 of 6,403 deliveries). The rates of meconium-stained amniotic fluid increased from 1.2% at 32 weeks to 100% at 42 weeks. CONCLUSION: The rising incidence of meconium-stained amniotic fluid with gestational age is consistent with the hypothesis that fetal maturation is a major etiologic factor in meconium passage. Also, the lack of variation of mean umbilical arterial pH across gestation suggests that fetal acidemia is not increased when meconium passage occurs earlier in pregnancy rather than at later gestational ages.     

Neonatal pulmonary hypoplasia and perinatal mortality in patients with midtrimester rupture of amniotic membranes--a critical analysis

OBJECTIVE: We sought to critically assess the risk factors for neonatal pulmonary hypoplasia and perinatal death in patients with preterm rupture of the amniotic membranes from 15 to 28 weeks' gestation. STUDY DESIGN: This was a prospective cohort study. The study patients had preterm rupture of the amniotic membranes at 15 to 28 weeks' gestation and were without fetal anomalies, multiple gestation, and oligohydramnios before rupture of the membranes. The amniotic fluid volume index was determined at admission and weekly afterward until delivery. RESULTS: The incidence of pulmonary hypoplasia was 12.9% (21/163). The overall perinatal mortality rate was 54% (88/163). Logistic regression analysis revealed the following: (1) Gestational age at rupture of the membranes, the latency period, and either the initial or the average amniotic fluid index have significant influence on the development of pulmonary hypoplasia; (2) gestational age at rupture of the membranes and latency period are significant factors in predicting perinatal death. CONCLUSIONS: In this large population of patients with rupture of membranes at 15 to 28 weeks' gestation, gestational age at rupture of the membranes, latency period, and amniotic fluid index were important independent predictors of neonatal pulmonary hypoplasia. In addition, gestational age at rupture of the membranes and latency period were important independent determinants of perinatal death. Expectant management of patients with preterm rupture of the amniotic membranes during this gestational age interval was associated with improved perinatal survival, even though it may increase the risk of pulmonary hypoplasia.     

Use of amniotic fluid analysis in the management of preterm rupture of the membranes

The management of preterm rupture of the membranes (PROM) must weigh the risks of respiratory distress from immediate delivery against those of expectant management. We divided 115 patients with PROM between 24 and 36 weeks of gestation into interventionist and expectant management groups on the basis of the amniotic fluid maturity. There was no difference between these groups with respect to gestational age and birth weight. Mature amniotic fluid was demonstrated in 41% of the patients. Interventionist management of infants with mature amniotic fluid irrespective of gestational age was associated with an improved outcome when compared to expectant management. Infants with PROM who can be shown to have mature amniotic fluid should be delivered promptly to avoid the small but real risks of expectant management.     

Amniotic fluid lipopolysaccharide-binding protein and soluble CD14 as mediators of the inflammatory response in preterm labor

OBJECTIVE: Our purpose was to determine the association of lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) with the proinflammatory response among women in preterm labor. The binding of lipopolysaccharide (LPS) with LBP and sCD14 activates macrophages at LPS concentrations up to 1000 times lower than required with LPS alone. LBP and sCD14 in amniotic fluid could explain the high concentrations of cytokines present in the amniotic fluid of culture-positive women and the presence of cytokines in the amniotic fluid of culture-negative women. STUDY DESIGN: A cohort of 169 afebrile women in preterm labor with intact membranes had amniotic fluid collected by transabdominal amniocentesis for culture and for LBP, sCD14, and interleukin 6 (IL-6) determinations by enzyme-linked immunosorbent assay. IL-6 levels of >2 ng/mL were considered elevated. Statistical analyses included analysis of variance, multiple comparisons with Bonferroni correction, and linear regression. RESULTS: All 169 amniotic fluid samples had measurable LBP and sCD14. Subjects were categorized by amniotic fluid culture results and IL-6 concentration into 3 groups: (1) positive amniotic fluid culture, (2) negative amniotic fluid culture, elevated IL-6 concentration, and (3) negative amniotic fluid culture, low IL-6 level. Geometric mean LBP and sCD14 levels differed significantly among groups such that levels were approximately twice as high among pregnancies with positive amniotic fluid culture or elevated IL-6 compared with those without evidence of inflammation (both P <.001). sCD14 was inversely associated with enrollment gestational age independent of amniotic fluid culture results and IL-6 concentrations. Among culture negative, low IL-6 pregnancies, sCD14 decreased 3.5% for each additional week of gestation (95% confidence interval [CI], 0.01%-6.4%; P =.02). LBP levels showed a similar trend in this group (P =.09). One hundred eleven subjects had detectable IL-6 levels. Among these subjects, IL-6 increased by 2.1-fold for every 10-fold increase in LBP (95% CI, 1.1-4.0; P =.02) and by 28.4-fold for every 10-fold increase in sCD14 (95% CI, 10.4-77.4; P <.001) with adjustment for gestational age by linear regression. CONCLUSIONS: LBP and sCD14 are present in amniotic fluid of preterm pregnancies and are linearly associated with amniotic fluid IL-6 concentrations. These molecules may amplify the cytokine response and thereby help explain the presence of cytokines in amniotic fluid when culturable quantities of microbes are absent.     

The relation between amniotic fluid surfactant concentration in preterm labour and histological evidence of chorioamnionitis

Summary Concentration of amniotic fluid disaturated phosphatidylcholine (DSPC), factors related to cervical ripening, and histopathological evidence of chorioamnionitis were studied in 38 patients in preterm labour with intact membranes; all of them delivered spontaneously before 37 weeks. There was no correlation between the amniotic fluid DSPC level and gestational age at the time of amniocentesis. However, a significant inverse correlation was found between the amniotic fluid DSPC level and the interval between the onset of labour and delivery. The amniotic fluid DSPC level in cases with onset-delivery interval of <48h was significantly higher than that in cases with an onsetdelivery interval of 48h or more. The gestational age in the former group was significantly lower than in the latter (28.6 vs 32.0 weeks). The amniotic fluid DSPC level in the patients with chorioamnionitis was significantly higher than that in the patients without chorioamnionitis, although the gestational age did not differ between the two groups. All 3 infants with RDS were associated with cervical incompetence. Patients in preterm labour with chorioamnionitis may be refractory to tocolysis and have higher amniotic fluid surfactant levels.     

Effect of maternal-fetal disorders on lung maturation. I. Diabetes mellitus

Amniotic fluid for fetal lung maturity studies was obtained from 287 healthy and 198 diabetic women. Classes of diabetes were as follows: Class A, 111; Class B, 58; Class C, 13; Class D, 11; Class F, 4; and Class R, 1. The regression lines representing the relationship of amniotic fluid lecithin phosphorus concentration to gestational age at amniocentesis in each of the groups of diabetic patients were not statistically different from those of the control subjects. Each of the diabetic patients was then matched with a control subject of the same race, sex of newborn infant, and gestational age at amniocentesis. The regression lines of the nonhypertensive, hypertensive, and all diabetics were not different from those of their respective matched control subjects. Also there was no difference in the proportion of mature lecithin phosphorus concentrations at different weeks between diabetic and normal women. The absence of a significant influence of diabetes on fetal lung maturation is probably due to improvement in diabetic control resulting in normalization of the fetal metabolic environment.     

Second-trimester amniotic fluid interleukin-10 concentration predicts preterm delivery

Objective: Interleukin-6 (IL-6) is an inflammatory cytokine that has been shown to be elevated in the amniotic fluid of patients with preterm labor. On the other hand, interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to inhibit the synthesis of other cytokines. We hypothesized that amniotic fluid IL-10 in the early second trimester is low in patients who subsequently develop preterm labor, and because of its deficiency, excessive inflammatory responses associated with IL-6 elevation lead to preterm labor and delivery.

Study design: Amniotic fluid IL-6 and IL-10 levels were measured in 96 women who underwent genetic amniocentesis between 15 and 23 weeks' gestation. Levels of IL-6 and IL-10 were measured by immunoassay and correlated with demographic and pregnancy outcome information.

Results: Fifteen patients delivered at or before 36 weeks and 81 patients delivered after 36 weeks. There was an inverse correlation between amniotic fluid IL-10 concentration and gestational age at delivery. Similarly, an inverse correlation also existed between amniotic fluid IL-6 concentration and gestational age at delivery.

Conclusions: Both IL-10 and IL-6 levels in second-trimester amniotic fluid obtained at the time of genetic amniocentesis appeared to be higher in patients who subsequently developed preterm delivery. Therefore, low amniotic fluid IL-10 production during the second trimester does not seem to be an etiology for preterm labor.     

Physiological implications of the materno-fetal oxygen gradient in human early pregnancy

This study evaluates the role of the fetal fluid cavities on materno-fetal oxygen diffusion in early pregnancy. Oxygen tension (pO2) was recorded using a multiparameter sensor inserted inside the exocoelomic cavity (ECC) or in the amniotic cavity. There was no correlation between coelomic pO(2) and gestational age, but a negative correlation was found between amniotic pO(2) and gestational age. The mean (SEM) pO(2) was 19.5 mm Hg (1.83) in the ECC at 7-11 weeks and 15.4 mm Hg (1.36) in the amniotic cavity at 11-16 weeks. The volume of the ECC changed little between 7 and 10 weeks of gestation, indicating that coelomic pO(2) results from passive oxygen diffusion through the placenta and is an indicator of the overall pO(2) inside the gestational sac during the first trimester. By contrast, the amniotic cavity volume increases exponentially, whereas amniotic pO(2) decreases with gestational age, suggesting that the increase in uterine blood flow is not sufficient to compensate for the rapid increase in amniotic fluid volume during the first half of pregnancy.