Umbilical cord nucleated red blood cell counts: normal values and the effect of labor.

OBJECTIVE: To determine the umbilical cord blood nucleated red blood cell (UC-nRBC) count in uncomplicated pregnancies delivered by elective cesarean section or delivered vaginally. METHODS: A total of 57-term singleton pregnancies were studied: 33 with elective cesarean sections and 24 with vaginal deliveries. UC-nRBC was analyzed for its nucleated red blood cell counts. A logarithmic transformation of the data was used for statistical analysis. RESULTS: The mean+/-standard deviation (s.d.) for nucleated red blood cell per 100 white blood cells (nRBC/100WBC) from the elective cesarean section group was 7.8+/-7.4. The vaginal delivery group had a mean value of 9.3+/-10.5, which was not significantly different. A value of 22 nRBC/100WBC defined the upper 95% confidence limit. The correlation between absolute nRBC and nRBC/100 WBC was 0.97. CONCLUSION: Although chronic hypoxia is associated with elevated nRBC, the stress of uncomplicated labor does not change the level. This adds credence to its use as a marker for hypoxia preceding labor and delivery.

A prospective study of vaginal pH as a predictor of preterm delivery.

OBJECTIVE: To test the usefulness of vaginal pH determinations in the prediction of the risk of preterm delivery at or before 36 weeks of gestation. METHODS: This was a prospective study of asymptomatic pregnant women. Vaginal pH was determined using pH paper in a sterile speculum examination during prenatal visits. Patients were followed to delivery and hospital records were reviewed to extract obstetric information. A total of 308 women agreed to participate and met the criteria for enrolment. Preterm delivery was defined as delivery at or prior to 36 weeks of gestation. Abnormal pH was defined as a pH of > 5.0. RESULTS: Abnormal vaginal pH was associated with increased risk of preterm delivery, (OR 3.3, 95% CI 1.15, 9.2; p = 0.02). In the first trimester, an abnormal vaginal pH was not associated with preterm delivery (p = 0.3). After the first trimester, a vaginal pH of 5.0 or greater was associated with increased risk of preterm delivery (OR 9.6, 95% CI 2.0, 45.5; p = 0.001) as well as delivering an infant of less than 2500 g (OR 3.1, 95% CI 1.2, 7.8; p = 0.015). History of a previous preterm delivery was associated with increased risk of preterm delivery (OR 6.2, 95% CI 1.6, 23.7; p = 0.02). A logistic regression model used to control for a history of preterm delivery and race showed abnormal vaginal pH to remain as an independent predictor of preterm delivery (p = 0.01). CONCLUSIONS: High vaginal pH (> or = 5.0) identified women at risk for preterm delivery.

Fetal abdominal circumference measurements of 35 and 38 cm as predictors of macrosomia. A risk factor for shoulder dystocia.

OBJECTIVE: To determine if ultrasound measurements of fetal abdominal circumference (AC) can be used to predict macrosomic infants. STUDY DESIGN: Using a computer database, 1,996 women at > or = 36 weeks' gestation, delivering a singleton infant and having an ultrasound examination within one week of delivery were studied. Fetal AC was evaluated to determine if it was useful in predicting the birth of a macrosomic infant, > 4,000 or > 4,500 g. RESULTS: AC predicted infants > 4,500 g better than those > 4,000 g. Almost all macrosomic infants > 4,500 g had an AC of > or = 35 cm (68/69, or 99%), but many nonmacrosomic infants were also in this group (683). AC of > or = 38 cm occurred in 99 infants, and 37 of the 69 (53.6%) weighing > 4,500 g were identified. Most infants (78%) with AC > or = 38 cm weighed > 4,000 g. CONCLUSION: Fetal AC was very helpful in identifying potential macrosomic infants. If AC was < 35 cm, the risk of infant birth weights > 4,500 g was < 1%. If AC was > or = 38 cm, the risk was 37% (37/99), and > 50% of these infants were identified (37/69, or 53.6%).

Histologic chorioamnionitis is associated with fetal growth restriction in term and preterm infants.

OBJECTIVE: Our aim was to evaluate associations between chorioamnionitis and fetal growth restriction in infants enrolled in the Collaborative Perinatal Project. STUDY DESIGN: A total of 2579 nonanomalous, singleton infants delivered at 28 to 44 weeks' gestation with chorioamnionitis were matched 1:3 for ethnicity, gestational age, parity, and maternal cigarette use (all of which were correlated with both chorioamnionitis and markers of fetal growth restriction) with 7732 control infants. Moderate or marked leukocytic infiltrates of the placenta defined chorioamnionitis. Birth weight, length, head circumference, weight/length ratio, ponderal index, and birth weight/head circumference ratio in the lowest 5th percentile were markers of fetal growth restriction. Placental weight and the birth weight/placental weight ratio were also evaluated. RESULTS: Compared with data on matched control infants, histologic chorioamnionitis was associated with all markers of fetal growth restriction and with low birth weight/placental weight ratios (odds ratios, 1.3-1.7). The strongest associations were found at 28 to 32 weeks' gestation (odds ratios, 2.2-11). Attributable risks for several markers of fetal growth restriction exceeded 50% in infants born at <33 weeks' gestation. CONCLUSION: Histologic chorioamnionitis is associated with multiple markers of fetal growth restriction, with stronger associations noted in prematurity.

Use of methergine for the prevention of postoperative endometritis in non-elective cesarean section patients.

OBJECTIVE: Methergine increases constriction of uterine musculature which may facilitate sloughing of endometrial debris, close uterine vessels, and prevent post-cesarean endometritis. The objective of this study was to evaluate the efficacy of methergine in preventing endometritis in patients undergoing non-elective cesarean section delivery. METHODS: Eighty patients undergoing non-elective cesarean section were enrolled in a prospective randomized clinical trial of methergine (41) versus no methergine (39) administration during the postpartum period. The hospital records were abstracted after discharge to compare the postpartum course. RESULTS: There were no significant demographic differences between the two groups. The women receiving methergine had a significant reduction in the rate of postoperative endometritis (10% vs. 36%, P < 0.005). In addition, the mean postoperative hemoglobin was significantly higher in the methergine treated group (P < 0.001). CONCLUSIONS: The use of methergine postpartum in women undergoing non-elective cesarean sections significantly reduces the incidence of postoperative endometritis and blood loss.

Fetal erythropoietin levels in pregnancies complicated by meconium passage: does meconium suggest fetal hypoxia?

OBJECTIVE: We sought to determine whether umbilical cord plasma erythropoietin levels were different in deliveries complicated by meconium passage and to determine whether this response is influenced by gestational age. STUDY DESIGN: Fetal erythropoietin levels were measured in 203 appropriately grown neonates at 37 to 43 weeks of gestation; among those, 70 had passed meconium. RESULTS: Meconium passage in the entire population was associated with elevated fetal erythropoietin levels (68 vs 31 mIU/mL; P <.001). Cord blood gases, pH, base deficit, and PO (2), as well as the 1- and 5-minute Apgar scores, were not different between the meconium and no-meconium groups. Gestational age and birth weights were significantly higher in the meconium group. Stepwise multiple regression analysis with meconium and gestational age used as the independent variables showed both meconium and gestational age to be independently associated with fetal erythropoietin levels (r = 0.356, F = 14.5; meconium, P <.001; gestational age, P <.01). CONCLUSIONS: These results suggest that meconium passage can be associated with chronic fetal hypoxia as demonstrated by elevated fetal erythropoietin levels, independent of gestational age.

Human uterine leiomyomata express higher levels of peroxisome proliferator-activated receptor gamma, retinoid X receptor alpha, and all-trans retinoic acid than myometrium.

Uterine leiomyomata are the main indication for a hysterectomy in the United States and occur in 25% of women >35 years. Because uterine leiomyomata can form when ovariectomized guinea pigs are exposed to estradiol and retinoic acids, we tested whether human leiomyomata had high levels of retinoic acids and related nuclear receptors. Compared with normal human myometrium, leiomyomata had 3- to 5-fold higher levels of peroxisome proliferator-activated receptor gamma (PPARgamma), retinoid X receptor alpha proteins, and all-trans retinoic acid, but only during the follicular phase of the menstrual cycle. 9-cis Retinoic acid was undetectable in either leiomyomata or myometrium. PPARgamma mRNA levels were lower in leiomyomata than myometrium, but only during the luteal phase of the cycle. A PPARgamma agonist, troglitazone, was given to guinea pigs along with estradiol and all-trans retinoic acid and produced the largest leiomyomata seen to date in this model. By contrast, no tumors formed when troglitazone was given alone or with estradiol or when troglitazone was given with estradiol and 9-cis retinoic acid. New therapies for human leiomyomata may emerge by combining antagonists for PPARgamma and retinoid X receptor alpha with selective estrogen receptor modulators.

Macrosomia prediction using ultrasound fetal abdominal circumference of 35 centimeters or more.

OBJECTIVE: To determine if birth weights greater than 4000 g can be predicted by ultrasound measurements of abdominal circumferences. METHODS: In 1996, 254 newborns delivered at Tampa General Hospital weighed at least 4000 g, 84 of whom had ultrasound examinations within 2 weeks of delivery. Those were compared with 84 neonates with recent ultrasounds who weighed less than 4000 g. Data were abstracted retrospectively from maternal medical records. RESULTS: The best linear predictor of birth weight was ultrasound measurement of abdominal circumference (AC), which had a correlation coefficient of 0.95. An AC measurement of 35 cm or more predicted 93% of macrosomic infants. Among 177 macrosomic infants born vaginally, 23 (13%) had shoulder dystocia. In that group, induction of labor was associated with a greater than three-fold increase in risk of shoulder dystocia (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.4, 8.2; P < .01). Labor augmentation was not associated with increased risk of shoulder dystocia. CONCLUSION: Abdominal circumference measurements were useful in screening for suspected macrosomia. An AC measurement of 35 cm or more identified more than 90% of macrosomic infants who were at risk for shoulder dystocia. Induction of labor in macrosomic patients increased the risk of shoulder dystocia.

Fetal erythropoietin levels in growth-restricted and appropriately grown neonates with and without abnormal fetal heart rate tracings: a comparison with cord blood gases and Apgar scores.

OBJECTIVE: To determine if umbilical cord plasma erythropoietin (EPO) levels in combination with cord blood gases and Apgar scores can distinguish between subacute and chronic uteroplacental insufficiency. METHODS: A total of 184 neonates delivered between 1993 and 1997 at Tampa General Hospital were studied. Cord plasma EPO levels, cord blood gases, and Apgar scores were determined prospectively and compared in four subgroups that were defined based on the presence or absence of fetal growth restriction (FGR; chronic fetal hypoxia), abnormal fetal heart rate tracings during labor (FHR; subacute/acute fetal hypoxia), or both. RESULTS: Both growth-restricted and appropriately grown newborns with abnormal intrapartum FHR tracing had elevated umbilical cord plasma EPO (183.5 and 135.2 mIU/ml, respectively; normal = 20.7 mIU/ml) and base deficit, whereas pH, Po2, and 1-minute and 5-minute Apgar scores were significantly lower, compared with appropriately grown newborns with a normal intrapartum course. Among newborns with normal heart rate tracings and FGR, the mean plasma EPO levels were elevated (89.5 mIU/ml), whereas the other parameters were not different from normal. CONCLUSION: Our findings suggest that, although cord blood gases and Apgar scores may reflect subacute and acute events, they are not good predictors of chronic uteroplacental insufficiency. The supplemental use of umbilical cord plasma EPO levels may improve our ability to identify chronic uteroplacental insufficiency.

Effects of raloxifene in a guinea pig model for leiomyomas.

OBJECTIVE: Chronic exposure of oophorectomized guinea pigs to 17beta-estradiol causes leiomyoma formation. Our aims were to determine whether these leiomyomas can become estradiol independent after exposure to estradiol and if raloxifene inhibits leiomyoma growth when given concomitantly with estradiol. STUDY DESIGN: To induce leiomyoma development, 6 oophorectomized animals received two estradiol implants for 140 days. Next, the estradiol implants were replaced with empty implants in 3 animals, whereas the other 3 received 2 new estradiol implants and raloxifene given per os 10 mg/kg per day for 60 days. Tumor size was monitored biweekly by ultrasonography. RESULTS: On estradiol removal, abdominal wall leiomyomas regressed within 15 to 30 days; when estradiol implants were reintroduced, leiomyomas redeveloped. Within 30 days on raloxifene, all abdominal leiomyomas (n = 9) regressed as determined by ultrasonography and verified at laparotomy. Serum raloxifene and estradiol levels were 432 +/- 46 pg/mL and 78 +/- 13 pg/mL (mean +/- SEM, n = 3), respectively, after 60 days of treatment. CONCLUSIONS: Leiomyomas did not become estradiol independent, even after long exposure to estradiol; ultrasonography allowed frequent, noninvasive assessment of leiomyoma size, and raloxifene rapidly regressed leiomyomas in this animal model.

The effects of Betamethasone on white blood cells during pregnancy with PPROM.

OBJECTIVE: To determine the effects of Betamethasone injections on maternal white blood cell counts. STUDY DESIGN: Thirteen pregnant women without fever or clinical infection and with premature rupture of the membranes at less than 34 weeks gestation were studied. No subject had labor during the week of study. Daily complete blood counts were done before and on days one and two after two 12 mg intramuscular injections of Betamethasone given 24 hours apart. RESULTS: The steroid injections produced a significant increase in total white counts from 9.8 +/- 5.0 to 14.2 +/- 0.7 x 10(3) cells/cc. There was a significant increase in polymorphonucleocytes and a decrease in lymphocytes and monocytes. CONCLUSION: The use of Betamethasone injections to mature fetal lungs results in a leukocytosis, but total white cell counts remain less than 20 x 10(3) cells/cc.

Urine protein dipstick measurements. A screen for a standard, 24-hour urine collection.

OBJECTIVE: To determine if the sum of urine protein dipstick values recorded during every void can be used to screen for patients who need a standard, 24-hour urine collection for determination of protein excretion. STUDY DESIGN: Thirty inpatient and 17 outpatient pregnant women undergoing 24-hour urine collection for protein concentration were enrolled. The volume, dipstick protein values and time of void were recorded. The 24-hour quantitative analysis of protein excretion performed by the laboratory was compared to the 24-hour sum of the products of each voided volume and dipstick value (dipstick factor). RESULTS: The dipstick factor significantly correlated with the total 24-hour protein excretion (correlation coefficient 0.84, P < 1 x 10(-7)). A dipstick factor of > or = 300 mg, indicated proteinuria with a sensitivity of 96%, specificity of 90%, positive predictive value of 92% and negative predictive value of 95%. Separately, we found differences in the amount of protein excretion when the 24-hour period was divided into six 4-hour periods, using analysis of variance. Paired t test analysis of the mean protein excretion from 16:00 to 04:00 showed significantly higher results than did the protein excretion from 04:01 to 16:00 (1,197 +/- 356 mg vs. 674 +/- 158 mg, P < .0001). CONCLUSION: The sum of dipstick factors in a 24-hour period is a reliable screening test for identifying patients who need the standard laboratory test for proteinuria.

Elevated umbilical cord plasma erythropoietin levels in prolonged pregnancies.

OBJECTIVE: To determine if umbilical cord plasma erythropoietin levels are elevated in pregnancies that continue beyond their expected date for delivery. METHODS: Erythropoietin was measured using an enzyme-linked immunosorbent assay in 124 appropriately grown newborns delivered from 37-43 weeks' gestation. Each woman had an uncomplicated labor and delivery course without evidence of fetal stress or meconium. The comparison was made between pregnancies ending at 37-40 weeks' gestation and those at 41-43 weeks' gestation. RESULTS: There was no difference between the two groups in cord blood gases or Apgar scores at 1 and 5 minutes. Cord plasma erythropoietin levels were significantly higher in pregnancies delivered after 41 completed weeks' gestation (41 or more weeks: 48.0+/-7.1 mIU/mL, n=45 versus 37-40 weeks: 26.1+/-4.2 mIU/mL, n=79, P < .001). When compared with pregnancies delivered between 37 and 40 weeks, erythropoietin levels were significantly elevated in pregnancies delivered at either 41, 42, or 43 weeks' gestation. CONCLUSION: In pregnancies reaching 41 weeks and beyond, cord plasma erythropoietin levels are significantly increased, indicating altered fetal oxygenation in some of these pregnancies. These results support the current practice of close fetal surveillance of prolonged pregnancies.

Umbilical cord plasma erythropoietin levels in pregnancies complicated by maternal smoking.

OBJECTIVE: Our goal was to determine whether maternal smoking was associated with elevated umbilical cord erythropoietin, a marker for chronic hypoxia. STUDY DESIGN: Plasma erythropoietin levels were measured in umbilical cord plasma of 222 newborns. There were 48 mothers who smoked and 174 nonsmokers. RESULTS: When all pregnancies were included, mean cord plasma erythropoietin levels were significantly higher in the smokers (78.0 +/- 15.3 mIU/ml) compared with the nonsmoking group (35.2 +/- 4.0 mIU/ml; p < 0.005). Regression analysis showed a significant positive correlation between the number of cigarettes smoked per day and cord plasma erythropoietin levels (r = 0.26, p < 0.0001). Smoking was associated with a significantly elevated risk (relative risk = 2.6, 95% confidence interval 1.7 to 10.9, p < 0.005) of fetal growth restriction. When pregnancies with fetal growth restriction were excluded from the analysis, the difference between the two groups remained significant (smokers 81.3 +/- 18.6, n = 38; nonsmokers 24.3 +/- 1.4, n = 164; p < 0.03). CONCLUSIONS: These results illustrate that smoking during pregnancy is associated with fetal growth restriction and significantly elevated umbilical cord erythropoietin levels.