The hemodynamic effects of maternal hypo- and hyperoxygenation in healthy term pregnancies

OBJECTIVE: To evaluate the hemodynamic effects of maternal hypo- and hyperoxygenation in normal term pregnancy. METHODS: Ten healthy women between 35-41 weeks' gestation were exposed to 10% oxygen in inspired air for 10 minutes and, after a 5-minute recovery period, to a stepwise increase in oxygenation with 50 and 100% oxygen for 10 minutes. Maternal ventilation, hemodynamics, and oxygenation were assessed noninvasively, and maternal and fetal vascular responses were assessed with pulsed-wave color Doppler velocimetry. Computerized cardiotocography was used for fetal heart rate (FHR) analysis. RESULTS: Substantial maternal hypoxia was achieved and accompanied by a statistically significant rise in the maternal heart rate (from 89 +/- 11 to 104 +/- 16 beats per minute) and systolic blood pressure (from 123 +/- 13 to 131 +/- 13 mmHg). Doppler measurements demonstrated a statistically significant decline in the pulsatility index (PI) of the maternal internal carotid artery (from 1.8 +/- 0.3 to 1.5 +/- 0.4) and an increase in the uterine artery PI (from 0.60 +/- 0.12 to 0.72 +/- 0.13). Baseline FHR, heart rate variability, and Doppler velocimetry in the umbilical artery and the middle cerebral artery showed no statistically significant changes. Hyperoxia did not cause changes in the maternal circulation, but the FHR decreased significantly (from 142 +/- 12 to 133 +/- 11 beats per minute). CONCLUSION: Acute short-term hypoxia modifies the maternal circulation, suggesting redistribution of maternal blood flow, but exerts no detectable effects on the healthy fetus. Maternal hyperoxygenation induces no apparent adverse effects.     

Fetal response to voluntary maternal hyperventilation. A preliminary report

Maternal hyperventilation can cause transient reduction in fetal oxygen tension. Fifty women with normal and high-risk pregnancies, between the 32nd and 43rd week, were voluntarily hyperventilated; in 33, fetal heart rate (FHR) acceleration or transient tachycardia were observed (reactive FHR). Of the 33 pregnancies the outcome was good in 30 (91%) as judged by the absence of perinatal death, no fetal distress in labor and no intrauterine growth retardation (IUGR). In 14 patients in whom there was no FHR response to maternal hyperventilation (non-reactive FHR), the outcome of pregnancy was significantly worse; one infant died neonatally, 10 were either chronically (IUGR), or acutely distressed. Only in 3 was the outcome good (21%). The study showed that there is good correlation between a "reactive" FHR and favorable neonatal outcome, and between a "non-reactive" FHR and an unfavorable neonatal outcome.     

Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia

Preeclampsia (PE) is a hypertensive disorder, which develops in late pregnancy and is usually associated with placental hypoxia and dysfunction. We have recently demonstrated that leptin is a novel placenta-derived hormone in humans and suggested its significance in human pregnancy (see Ref. 19). To explore the changes in the leptin production in placenta in PE, we measured the plasma leptin level and placental leptin messenger RNA expression in pregnant women with PE. Plasma leptin levels in preeclamptic women were elevated significantly, compared with gestational age- and body mass index-matched normal pregnant women (P < 0.0001). Plasma leptin levels in the severe PE group were significantly higher than those in the mild PE group (P < 0.0001). Plasma leptin levels in preeclamptic women were reduced, soon after the placental delivery, to those expected for their body mass indices. Northern blot analysis revealed that leptin messenger RNA levels are increased in the placentas from preeclamptic women, compared with normal pregnant women. Leptin secretion was increased significantly in a human trophoblastic cell line (BeWo cells) cultured under hypoxic conditions (5% O2), compared with those cultured under standard conditions (20% O2; P < 0.01). The present study demonstrated that placental production of leptin is augmented in severe PE, probably because of placental hypoxia, thereby suggesting the possible significance of leptin as a marker of placental hypoxia in severe PE.     

Functional insulin therapy and pregnancy

Pregnant type-I diabetic women have to be treated in an experienced diabetes center where optimal cooperation and exchange of knowledge between obstetrician, diabetologist and neonatologist is guaranteed. Given optimal preconceptional metabolic control and thorough guidance throughout pregnancy maternal and fetal risk of type-I diabetic patients without severe diabetic late complications is similar to that of healthy pregnant women. "Near-normoglycemic" metabolic control and meticulous prevention of severe and long-standing hypoglycemic episodes can be achieved throughout pregnancy by functional insulin therapy employing a basis-bolus regime of insulin administration with frequent blood glucose self control (more than 6 times a day). Non-compliant diabetic patients and those with severe diabetic late complications represent a high-risk group for complications in pregnancy. To avoid such risks special care and preconceptional information is mandatory.     

Changes in maternal cardiovascular parameter during tocolysis and in the dorsal position shock syndrome (author's transl)

Maternal circulatory parameters and fetal heart rate were measured in 25 healthy pregnant women in the last trimenon during treatment with Fenoterol, Fenoterol in combination with Verapamil and Verapamil alone. Dosages were used in accordance with the tocolytic guidelines from Weidinger and Wiest. We were able to demonstrate that the betamimetic Fenoterol alone and in combination with the Ca++-antagonist Verapamil strongly increases the maternal heart rate an the maternal cardiac output whereas the peripheral resistance decreases accordingly. The average blood pressure stayed leveled, so that a decreased uterine blood flow cannot be assumed under betamimetics from the maternal cardiovascular point of view. However, there are indications for an increased placental blood flow during tocolysis. The betamimetic drug show no significant effect on the fetal heart rate. Additional application of the Ca++-antagonist Verapamil during tocolysis with Fenoterol (in dosages usually used for tocolysis) doesn't change cardiovascular reactions caused by Fenoterol. Change in position from supine to left lateral position caused a short term increase in the maternal cardiac output even noted in pregnant women without a clinically observed cavasyndrom. These changes of maternal cardiac output are comparable with those in orthostatic stress situations.     

The effects of host carbogen (95% oxygen/5% carbon dioxide) breathing on metabolic characteristics of Morris hepatoma 9618a

Characteristics of the tumour metabolic profile play a role in both the tumour-host interaction and in resistance to treatment. Because carbogen (95% oxygen/5% carbon dioxide) breathing can both increase sensitivity to radiation and improve chemotherapeutic efficacy, we have studied its effects on the metabolic characteristics of Morris hepatoma 9618a. Host carbogen breathing increased both arterial blood pCO2 and pO2, but decreased blood pH. A fourfold increase in tumour pO2 (measured polarographically) and a twofold increase in image intensity [measured by gradient recalled echo magnetic resonance (MR) imaging sensitive to changes in oxy/deoxyhaemoglobin] were observed. No changes were seen in blood flow measured by laser Doppler flowmetry. Tumour intracellular pH remained neutral, whereas extracellular pH decreased significantly (P < 0.01). Nucleoside triphosphate/inorganic phosphate (NTP/Pi), tissue and plasma glucose increased twofold and lactate decreased in both intra- and extracellular compartments, suggesting a change to a more oxidative metabolism. The improvement in energy status of the tumour was reflected in changes in tissue ions, including Na+, through ionic equilibria. The findings suggest that the metabolic profile of hepatoma 9618a is defined partly by intrinsic tumour properties caused by transformation and partly by tissue hypoxia, but that it can respond to environmental changes induced by carbogen with implications for improvements in therapeutic efficacy.     

Fetal circulation and malaria

OBJECTIVE: To quantity the fetal vascular changes during flare-up, and to evaluate the sensitivity and the specificity of Doppler indices for the prediction of acute fetal distress at the end of the pregnancy. METHOD: Every day of flare-up the umbilical resistance (Rp), cerebral resistance (Rc), cerebro-placental ratio (CPR = Rc/Rp), and hypoxia index (HI = delta % CPR x crisis duration) were calculated. RESULTS: Twenty-three pregnancies were investigated at St Laurent du Maroni Hospital (French Guiana). During flare-ups the Doppler placental resistance increased (placental disorder), cerebral resistance decreased (vasodilation), CPR decreased (flow redistribution toward the brain), and HI increased. An abnormal CPR (< 1) was associated with abnormal fetal heart rate (FHR) in 61.5% of the cases, a CPR > 1 was associated with a normal FHR in 80% of the cases. (sensitivity: 80%, specificity 61%). A CPR < 1 was associated with one of the abnormalities (abnormal FHR, cesarean section, abnormal Apgar) in 71% of the cases, a CPR > 1 was associated with normal delivery in 55% of the cases (sensitivity: 71.4%, Specificity 55%). A HI higher than 150 was associated with abnormal FHR in 75% of the cases, a HI < 150 was associated with normal FHR in 90% of the cases (sensitivity: 89%, specificity: 77%). Lastly the combination (HI > 150 + CPR < 1) was associated with abnormal FHR in 80% of the cases, 1 or 2 of these parameters were associated with normal FHR in 84.6% of the cases (sensitivity: 80%, specificity: 84%). The minimum CPR and the HI during malaria flare-up can be used to predict acute fetal distress at delivery.     

Posttraumatic stress disorder among female juvenile offenders

OBJECTIVE: To assess cardiorespiratory, tissue oxygen and hepatic nicotine adenine dinucleotide hydride (NADH) responses to graded hypoxia. DESIGN: Prospective, controlled, randomized study. SETTING: University laboratory. ANIMALS AND INTERVENTIONS: 18 anaesthetised Sprague-Dawley rats spontaneously breathing either 21% (controls), 12.5% or 10% inspired oxygen concentrations (6 rats per group). MEASUREMENTS AND RESULTS: All animals in the 21 and 12.5% O2 groups survived the 3-h study period, compared to only 1 in the 10% O2 group. In this latter group, mean arterial pressure and renal blood flow fell immediately with hypoxaemia, whereas aortic blood flow was maintained until the preterminal stages. Critical cellular hypoxia was suggested by an increasingly severe base deficit, an initial rise then a preterminal fall in hepatic NADH intensity and premature death in all but 1 animal. Hepatic NADH fluorescence intensity was unchanged in control animals but showed a progressive rise in the 12.5% O2 group, accompanied by a small though static increase in arterial base deficit. No significant differences were seen in arterial and tissue partial pressure of oxygen between the 12.5 and 10% O2 groups. CONCLUSIONS: This study demonstrates major differences in cardiorespiratory, hepatic NADH and outcome responses to small variations in the degree of hypoxic hypoxia. The fall in NADH fluorescence intensity presages impending death and is likely to reflect failure of cellular metabolic processes.     

Carbon monoxide: effects on oxygenation of the fetus in utero

The partial pressure of oxygen in fetal blood decreases in proportion to the carboxyhemoglobin concentrations in fetal and maternal blood. Because fetal oxygen tensions normally equal 20 to 30 percent of the values for adults, this reduction can result in severe hypoxia of vital tissues. Decreases in oxygen tension may be a factor in the lower birth weights of infants born to women who smoke or are exposed to severe air pollution.     

Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.     

The determination of human placental lactogen (HPL) for hormonal supervision in late pregnancy

In the serum of 145 women between the 34th and 42nd weeks of pregnancy, 209 radioimmunological determinations of human placental lactogen were made, using the Pharmacia, Uppsala, Sweden, HCS Phadebas Test. Following the determination of normal HPL levels in late pregnancy, the HPL values of high-risk pregnancies were investigated in relation to normal values and compared with the clinical pattern. A satisfactory relation was found between low HPL levels and fetal growth retardation. To some extent the HPL data can also be used in monitoring severe EPH-gestosis and postmaturity. Light cases of gestosis and pregnancies involving Rh-incompatibility do not affect HPL production. The clinical findings regarding HPL levels should not be overestimated in attempting to diagnose placental insufficiency.     

Doppler study of the fetal cardiac function in prolonged pregnancies

OBJECTIVE: To evaluate the association between fetal cardiac function and amniotic fluid index (AFI) in postterm fetuses, and to determine if changes in fetal cardiac function precede the occurrence of nonreassuring intrapartum fetal heart rate (FHR) patterns. METHODS: Forty-five otherwise low-risk pregnant women between 41 and 43 weeks' gestation were studied longitudinally. Gestational age was confirmed in all patients by ultrasound before 20 weeks' gestation. Each subject had two or three tests performed every 3-4 days, including a non-stress test, a biophysical profile, and Doppler studies of the aortic and pulmonic outflow tracts. Aortic and pulmonic artery flow velocity waveforms were recorded slightly distal to the valves. Peak velocity, velocity time integral, and heart rate were calculated from the flow velocity waveforms we obtained. The change in AFI and aortic and pulmonic peak velocity and [velocity time integral] x [heart rate] were calculated for each fetus. RESULTS: Labor was induced at 42 weeks' gestation in 20 patients, and 17 entered labor spontaneously. Changes in AFI, observed during the follow-up period, correlated significantly with changes in aortic peak velocity (r = 0.54, P < .01) and with aortic outflow [velocity time integral] x [heart rate] (r = 0.60, P < .001) but not with pulmonic peak velocity and [velocity time integral] x [heart rate]. The decrease in aortic peak velocity and aortic and pulmonic [velocity time integral] x [heart rate] was significantly higher (P < .01) in eight fetuses that developed a nonreassuring intrapartum FHR (reduced FHR variability, late decelerations, and severe variable decelerations) than in those who had an uneventful labor. CONCLUSION: In prolonged pregnancies, cardiac function deteriorates in fetuses that develop a nonreassuring intrapartum FHR, and the changes in the left cardiac function correlate with changes in AFI.     

Immunohistochemical demonstration of c-myc oncogene product in middle ear cholesteatoma

Oxygen consumption at intermittent mandatory ventilation (IMV) rates of 10 and 20 breaths per minute was evaluated to determine whether a higher IMV rate in mechanically ventilated premature infants with apnea and respiratory insufficiency would reduce metabolic expenditure. Ten studies were performed in seven infants, with three infants studied twice after a trial of failed elective extubation. The mean birth weight was 952 +/- 183 kg (SD), and the mean postnatal age was 12 +/- 8 days (SD). Mean oxygen consumption per kilogram of body weight was not significantly related to pulmonary resistance, dynamic lung compliance, or resistive work of breathing. Mean oxygen consumption was not altered at the different IMV rates. The oxygen consumption difference at the two IMV rates was not significantly related to dynamic lung compliance, resistance, or work of breathing. These results demonstrate that mechanically dependent premature infants without bronchopulmonary dysplasia do not have significant alteration in oxygen consumption with changes in IMV. This finding suggests that there is no potential metabolic energy balance benefit in use of moderately higher IMV rates to achieve improved growth rates in this population of infants.     

Fetal heart rate characteristics at 25 to 28 weeks' gestation

The objective of this article is to define normative fetal heart rate (FHR) tracing characteristics between 25-28 weeks' gestation in a low-risk population with normal pregnancy outcomes and to determine which criteria best determine FHR reactivity. Continuous FHR tracings were reviewed from 188 low-risk women participating in a trial of the Mammary Stimulation Test (MST) at 25-28 weeks' gestation. A reactive tracing required the presence of > or =two accelerations in 20 min. Different acceleration criteria were evaluated based upon the width of the acceleration (short vs. long) and the amplitude of the acceleration (10 vs. 15 bpm). Seventy-one percent of the FHR tracings were reactive using the higher amplitude (15 bpm), short criteria. This number increased significantly to 92% when the lower amplitude (10 bpm), short criteria were used (p <0.01). As gestational age advanced, there was a trend toward increased reactivity irrespective of which criteria were used, but these differences were not significant. Reducing the acceleration amplitude criteria to 10 bpm in preterm pregnancies will maximize the number of reactive nonstress tests. This is advantageous because it would improve test specificity and decrease the false-positive rate. Our findings need to be prospectively validated in a high-risk population.     

Increased uterine activity and fetal deterioration during maternal hyperthermia

The role of hyperthermia in the absence of infection has been investigated in the pregnant baboon. Twenty-three near term animals were used. Catheters were placed in maternal and fetal arteries and thermocouples implanted in maternal colon and fetal esophagus. Maternal temperature was raised to between 41 and 42 degrees Centigrade (C.), by applying external heat. The temperature gradient between fetus and mother (delta T F-M) was 0.47 degree C. under steady-state conditions with maternal temperature at 38 degrees C. and rose to 0.75 degree C. at 42 degrees C. Hyperthermia caused a twofold increase in uterine activity; a metabolic acidosis developed in the mother and a profound acidosis and hypoxia developed in the fetus. There was also a marked fall in blood pressure and an increase in heart rate in both mother and fetus; late deceleration of the fetal heart rate occurred at a higher oxygen level and pHa than has been observed under normothermic conditions.     

Risk factors associated with acute dental pain in children

We have previously shown that high altitude pulmonary edema-susceptible subjects (HAPE-S) have an accentuated pulmonary vascular response to hypoxia. In this study, we investigated the relationship between plasma endothelin-1 (ET-1) levels and the acute hypoxic pulmonary vascular response in HAPE-S and control subjects. In six HAPE-S and seven healthy subjects, we evaluated acceleration time/right ventricular ejection time (AcT/RVET) using Doppler echocardiography, and measured plasma ET-1 levels by radioimmunoassay (RIA) before and after 5 minutes of breathing 10% oxygen. The HAPE-S showed a significantly increased pulmonary vascular response to hypoxia compared with healthy subjects. However, no statistically significant changes of plasma ET-1 levels were observed before and after hypoxia in both groups. We conclude that the increased pulmonary vascular response to acute hypoxia in HAPE-S may not be related to ET-1 release.     

Changes in respiratory control during and after 48 h of isocapnic and poikilocapnic hypoxia in humans

Ventilatory acclimatization to hypoxia is associated with an increase in ventilation under conditions of acute hyperoxia (VEhyperoxia) and an increase in acute hypoxic ventilatory response (AHVR). This study compares 48-h exposures to isocapnic hypoxia (protocol I) with 48-h exposures to poikilocapnic hypoxia (protocol P) in 10 subjects to assess the importance of hypocapnic alkalosis in generating the changes observed in ventilatory acclimatization to hypoxia. During both hypoxic exposures, end-tidal PO2 was maintained at 60 Torr, with end-tidal PCO2 held at the subject's prehypoxic level (protocol I) or uncontrolled (protocol P). VEhyperoxia and AHVR were assessed regularly throughout the exposures. VEhyperoxia (P < 0.001, ANOVA) and AHVR (P < 0.001) increased during the hypoxic exposures, with no significant differences between protocols I and P. The increase in VEhyperoxia was associated with an increase in slope of the ventilation-end-tidal PCO2 response (P < 0.001) with no significant change in intercept. These results suggest that changes in respiratory control early in ventilatory acclimatization to hypoxia result from the effects of hypoxia per se and not the alkalosis normally accompanying hypoxia.     

Pre-mRNA processing enhancer (PPE) element increases the expression of an intronless thymidylate synthase gene but does not affect intron-dependent S phase regulation

Maternal smoking during pregnancy causes reduction of fetal breathing movements, an effect attributed to nicotine in fetal blood. Nicotine is metabolized to cotinine which has a long plasma half-life and exhibits slow clearance across membrane barriers. It is also known to activate placental phospholipase-A2-like enzymes, resulting in formation of prostaglandins. Therefore, we studied transport of nicotine in isolated perfused cotyledon of normal human term placenta. The placental cotyledon was perfused with aerated (21% O2, 5% CO2) Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) containing 2% albumin on both maternal (230 ml, 15 ml/min, 35 mm Hg) and fetal (93 ml, 1.75 ml/min, 70 mm Hg) sides in a closed recirculating system. Nicotine (2 mg) was added to the maternal perfusate; perfusate samples (1 ml) were collected from both sides at regular intervals and analyzed for nicotine and cotinine by high-pressure liquid chromatography. This study gave the following results: (1) In about 60-80 min, 18.6% of the nicotine added to the maternal perfusate was transferred to the fetal perfusate, and the maternal/fetal concentration ratio reached 1.0. These results show rapid placental transfer of nicotine, consistent with its high lipid solubility. (2) Less than 1% is metabolized to cotinine in placenta. The ratio of cotinine concentrations in maternal and fetal perfusates reached 1.0 in about 40 min. These studies were also verified using 14C-nicotine. (3) Maximal reduction in fetal breathing movements occurs at about 30 min, and recovery occurs at 90 min after tobacco smoking by the mother. These observations agree with the rate of placental transfer of nicotine. (4) When nicotine was added on the fetal side, part of it was metabolized to cotinine. However, the maximal concentration of cotinine was twice higher on fetal than on maternal side. These observations suggest that accumulation of cotinine on fetal side may activate prostaglandin formation and trigger spontaneous abortions in pregnant smokers.     

Endocrine-metabolic response to acute starvation in human gestation

During a 72 hour fast in pregnant women, significant decrements in the maternal plasma glucose concentrations, accompanied by a significant increase in the plasma placental lactogen (hPL) concentration, occur. At the same time, utilization of glucogenic amino acids, principally alanine, takes place. The mean postprandial glucose concentration in pregnancy is significantly lower than that of comparable nonpregnant women (70.5 +/- 1.7 versus 79.5 +/- 1.3 mg. per 100 ml., p less than 0.001). There appears to be a significant sparing effect on the maternal plasma glucose concentration during acute fasting which may be mediated through hPL. Concentrations of amniotic fluid and fetal plasma glucose from women undergoing fasting decrease in a manner parallel to that of the mother. Fasting provokes a mean rise in plasma hPL of 33.2 per cent over basal levels. This rise is still evident 72 hours after refeeding, after which it gradually returns to pretest concentrations. The infusion of alanine or arginine to pregnant women at the end of the fast produced increments in the peripheral maternal glucose concentration. The response was much greater with alanine than with arginine, demonstrating the increased gluconeogenic potential of this amino acid. The increment in human growth hormone (hGH) following alanine infusion was significantly greater than that observed after arginine administration. Hypoaminoacidemia was present in nonpregnant and pregnant women in response to fasting, but the decline was greater in pregnancy. Acute fasting in the first half of gestation appears to produce significant alterations in carbohydrate metabolism evidenced by profound hypoglycemia, hypoinsulinemia, and hypoaminoacidemia. This maternal deficit can be reflected in fetal substrate concentrations. The effect of these changes on fetal growth and development is speculative at this time.     

Association of clinical intra-amniotic infection and meconium

The objective of this study was to determine the rate of intra-amniotic infection in patients with meconium-stained amniotic fluid compared to controls. With a retrospective case-controlled study design, we compared 100 pregnant women with meconium to 100 pregnant women without meconium for the development of intra-amniotic infection. Patients delivered between September 1 and December 31, 1990. Exclusion criteria were active infection prior to labor or antibiotic use within the 7 days prior to delivery. We diagnosed clinical intra-amniotic infection in patients with ruptured membranes by a maternal temperature 100.4 degrees F or higher and any two of the following: maternal or fetal tachycardia, uterine tenderness, white blood cell count 10,500 mm3 or more, or foul-smelling amniotic fluid. Demographic variables, labor characteristics, maternal infectious morbidity, and neonatal outcome were analyzed using the Wilcoxin rank test, chi-square test, or Fisher's exact test as appropriate. The rate of clinical intra-amniotic infection was significantly higher in women with meconium-stained amniotic fluid (8%) compared with women with no meconium (2%) (p = 0.05).