Endocervical hyaluronan and ultrasound-indicated cerclage.

OBJECTIVE: To investigate whether, at the time of ultrasound-indicated cerclage, the endocervical concentration of hyaluronan (HA), 27-kDa heat shock protein (HSP-27) and/or interleukin-8 (IL-8) would predict pregnancy outcome. METHODS: Endocervical samples, obtained from 40 women undergoing ultrasound-indicated cerclage at 15 + 3 to 25 + 0 weeks' gestation, were assayed by enzyme-linked immunosorbent assay for HA, HSP-27 and IL-8. All subjects had a cervical length of < 1.5 cm or dramatic cervical length change on serial endovaginal ultrasound, no uterine contractions or tenderness, no fever and intact membranes and underwent a modified Shirodkar cerclage. RESULTS: The median HA level was 10.0 ng/mL in the 12 women who delivered at < 37 weeks' gestation as opposed to 39.7 ng/mL in the 28 women delivering at 37-41 weeks (P = 0.017). Median HSP-27 and IL-8 concentrations were not significantly different in these groups. CONCLUSION: A higher endocervical HA level at the time of ultrasound-indicated cerclage is associated with a longer interval before birth.

Association of sex of the fetus in isolated fetal choroid plexus cysts.

We sought to determine if an association exists between sex of the fetus and the finding of isolated fetal choroid plexus cysts. Of 131 fetuses, 62 were male (47.3%) and 69 were female (52.7%). No statistically significant differences were found in the maternal demographic parameters studied (age, race, gravidity, parity, sonogram timing) or descriptive cyst information obtained (location, number, dimensions, resolution), although bilaterality was more common in male fetuses. The determination that isolated choroid plexus cysts are seen equally frequently in male and female fetuses adds to basic information about such a common sonographic finding.

Characterization and prognostic significance of variable decelerations in the second stage of labor.

The characteristics of variable decelerations (VD) in the second stage of labor and the relationship between the number, frequency, or severity and neonatal outcome have not been studied. We have analyzed the characteristics of VD in the second stage of labor and their prognostic significance in the prediction of Apgar scores. In this descriptive study, fetal heart tracings containing VD from 250 singleton, vaginal deliveries between June 1994 and July 1996 were reviewed blinded to outcome information. Excluded were: (1) deliveries at <36 weeks, (2) uninterpretable tracing, (3) absence of VD in second stage of labor, and (4) absence of exam establishing beginning of second stage of labor. VD characteristics evaluated: shape (U, V, W); anterior and posterior "shoulders"; slow return to baseline (< or = 30-degree curve); cumulative depth of VD per 10 min, second stage oxytocin dose. Outcome information collected: method of delivery, birth weight and Apgar scores. Statistical analysis included regression and analysis of variance (ANOVA). The mean maternal age was 32+/-5 years and gestational age 39+/-1.3 week. In the second stage of labor, the mean oxytocin dose was 3+/-5 mu/min, length of the second stage 65+/-57 min, total number of VD averaged 21+/-17 and uterine contractions 26+/-22 per patient. The percentage of VD <100 bpm was 50+/-27%, VD <70 bpm 13+/-20%, anterior shoulders 76+/-30%, posterior shoulders 75+/-30% and slow return to baseline 12+/-17%. The number of VD significantly increased with the length of the second stage of labor (r=0.85, p <0.001). The total number and percentage of VD <70 bpm were inversely correlated with 5-min Apgar score (p=0.038, 0.015 respectively). The sum of the depth of VD/length of second stage as well as the percentage of VD with anterior and/or posterior shoulders and slow return to baseline were not significantly related to Apgar scores (p=0.08, 0.72, 0.73, 0.99, respectively). Patients with a higher percentage of decelerations with slow return to baseline had a higher rate of operative vaginal deliveries (20 vs. 11 %, p=0.002); but no significant differences in Apgar scores compared with those with spontaneous delivery (p=0.9). Second stage VD <70 bpm were significantly associated with lower 5-min Apgar scores. Although the presence of VD with a slow return to baseline was significantly associated with operative delivery, there was no difference in 5-min Apgar scores.

Fetal but not maternal serum cytokine levels correlate with histologic acute placental inflammation.

Our objective was to determine if placental histologic acute inflammation is related to maternal and fetal serum cytokine levels in preterm labor, using a data set previously constructed blinded to histopathologic information. To this goal in 1992, 32 consecutive patients at 20-36 weeks with progressive labor and tocolytic failure were recruited. Maternal serum sampled during the active phase of labor, and fetal (umbilical vein) serum were assayed by ELISA for levels of soluble interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptor (IL-2 R), and interleukin 6 (IL-6) (T-Cell Diagnostics). Acute placental inflammation was scored by two groups blinded to clinical data, and the average scores analyzed for relationships to serum cytokine levels. Weighted kappa values, reflecting interobserver agreement in scoring of acute inflammation, were: amnion 0.84; choriodecidua 0.84; umbilical cord 0.85; and chorionic plate 0.73. Fetal levels of IL-1 beta and IL-2 R were higher with grade 3-4 acute amnionitis than with grades 0-2 (p = 0.022 and p = 0.023). Fetal levels of all three cytokines were higher in grade 3-4 umbilical vasculitis (IL-1 beta p = 0.008, IL-2 R p = 0.01, and IL-6 p = 0.03). In contrast, maternal serum cytokine levels were not associated with presence or severity of histologic evidence of acute placental inflammation. Histologic acute inflammation was not related to duration of labor, interval from membrane rupture to delivery, and presence or duration of antibiotic therapy. We conclude that fetal serum, but not maternal serum cytokine levels, are correlated with histologic evidence of acute placental inflammation, and may reflect a predominant placental origin of the cytokines.

Elevated amniotic fluid interleukin-6 levels during the early second trimester are associated with greater risk of subsequent preterm delivery.

PROBLEM: Subclinical intra-amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin-6 (IL-6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm. METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL-6 at 14-20 weeks in a group of women subsequently delivering at < or = 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL-6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one-way ANOVA after log-transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis. RESULTS: There was an inverse correlation between AF IL-6 levels at 15-20 weeks and gestational age at delivery (r = -0.16, P = 0.03). Women delivering at < or = 34 weeks had significantly higher median AF IL-6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at > or = 37 weeks. Logistic regression analysis showed that IL-6 was independently associated with PTD at < or = 34 weeks after controlling for race and birth weight centiles (P = 0.039). CONCLUSIONS: AF IL-6 at 15-20 weeks can identify patients at risk for PTD at < or = 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester.

Midtrimester amniotic fluid tumor necrosis factor-alpha does not predict small-for-gestational-age infants.

PROBLEM: To evaluate the independent ability of midtrimester amniotic fluid tumor necrosis factor-alpha (TNF-alpha) in the prediction of small-for-gestational-age (SGA) infants. METHOD OF STUDY: In this case-control study, patients delivering a SGA infant were matched with controls based on GA at delivery, maternal age, race, and parity. Patients with immune disease, chronic hypertension, diabetes, asthma, congenital hearts disease, multiple gestation, and fetal anomalies were excluded. Amniotic fluid samples were immunoassayed for TNF-alpha. Potential confounding variables evaluated were maternal serum alpha-fetoprotein level, smoking history, pregnancy induced hypertension, and neonatal gender. Statistical analysis included Fisher's exact test and ANOVA after log transformation with P < 0.05 considered significant. RESULTS: Eighteen patients delivered SGA neonates and were matched with 41 controls. No significant differences were identified in the confounding variables between patients with SGA neonates and controls. Amniotic fluid TNF-alpha levels were not significantly different between patients subsequently delivering SGA neonates and controls [median 7.63 (range 0.25-16.1) pg/mL versus 9.39 (0.25-66.9) pg/mL, P = 0.8]. CONCLUSIONS: Midtrimester amniotic fluid TNF-alpha levels are not predictive of SGA neonates when compared with controls matched for gestational age at delivery.

Relationship between human immunodeficiency virus-1 RNA identification in placenta and perinatal transmission.

OBJECTIVES: The objectives of this study were to identify human immunodeficiency virus (HIV)-associated nucleic acids in placenta with 35S RNA in situ hybridization and to correlate the presence of virus with perinatal HIV transmission. STUDY DESIGN: Blood from nine mother-infant pairs was collected for CD4+ lymphocyte count and p24 antigen analysis. Placental specimens were obtained for in situ hybridization, viral culture, and hematoxylin-eosin histologic analysis. Neonatal infection was diagnosed by p24 antigen analysis, polymerase chain reaction, and viral culture. Pediatric follow-up was obtained by personal communication and review of chart records. RESULTS: Three of 10 placentas from nine HIV-positive pregnant women (one set of twins) were found to contain evidence of HIV infection by RNA in situ hybridization. Maternal age, gravidity, parity, previous number of terminations, duration HIV-seropositive, maternal CD4+ at delivery, and neonatal cord CD4+ count were similar in those whose placentas contained virus versus those in whom virus was not identified. The incidence of histologic changes was similar in the HIV-positive and negative placentas from seropositive subjects and was similar to the incidence of histologic changes in placentas from known seronegative subjects. Placental culture failed to demonstrate the presence of virus in vitro. Of the three placentas that had positive in situ hybridization, two infants became HIV-positive. CONCLUSIONS: 35S RNA in situ hybridization identified the presence of nucleic acids in syncytiotrophoblasts from formalin-fixed, paraffin-embedded placentas. This technique is a useful tool to screen placentas at birth for HIV-RNA to judge the likelihood of perinatal HIV transmission.

Angiogenin: a marker for preterm delivery in midtrimester amniotic fluid.

OBJECTIVE: Neovascularization is a response of tissue to ischemic damage. Placental ischemia is thought to underlie a significant portion of preterm deliveries. Our objective was to evaluate whether angiogenin, a potent inducer of neovascularization, is increased in midtrimester amniotic fluid of patients destined to be delivered preterm. STUDY DESIGN: We designed a case-control study of singleton gestations undergoing midtrimester amniocentesis for standard genetic indications. Inclusion criteria were (1) pregnancy outcome information available, (2) gestational age at amniocentesis 15 to 20 weeks, (3) no evidence of fetal structural or chromosomal anomalies, and (4) absence of conditions associated with preterm delivery. Amniotic fluid angiogenin levels were measured by immunoassay and normalized by natural log transformation for statistical analysis. RESULTS: Eleven patients with preterm deliveries were matched with 33 controls. Amniotic fluid angiogenin levels were significantly higher in patients with preterm deliveries compared with controls (median 30.1 ng/ml [range 13.6 to 71.0 ng/ml] vs 17.8 ng/ml [7.8 to 43.3 ng/ml], p = 0.002). Demographic data were not significantly different. The association between angiogenin levels and preterm delivery persisted after small-for-gestational-age neonates were excluded (p = 0.02). Receiver-operator characteristic curve analysis showed that an angiogenin level of 31.0 ng/ml was the optimal cutoff point for prediction of preterm delivery (sensitivity 45.5%, specificity 91.0%, p = 0.03, odds ratio 6.0). CONCLUSIONS: Midtrimester amniotic fluid angiogenin levels are elevated in patients with preterm delivery. This supports the theory that preexisting intrauterine ischemia and inflammation are important risk factors for preterm delivery and may be already present in the early midtrimester.

Evaluation of early second trimester maternal serum creatine kinase isoenzyme BB as a marker of poor pregnancy outcome.

We hypothesized that maternal serum levels of the isoenzyme creatine kinase (CK)-BB, which is highly expressed in the placenta, may be elevated during the early second trimester in gestations destined to deliver prematurely or of a small-for-gestational-age infant (birthweight below 10th percentile). To test this hypothesis, we compared maternal serum CK-BB levels and percentage of CK-BB over total CK, in 69 normal pregnancies (delivering at term of appropriate-for-gestational-age infants) with those of 25 cases complicated by preterm delivery at < or = 34 weeks (n = 14), of a small-for-gestational-age infant (n = 8), or both (n = 3). No differences were present in maternal serum CK BB levels between normal and complicated pregnancies. Moreover, no correlation was found between gestational age at delivery and CK BB levels (r = 0.03; p = 0.7).

L-arginine reverses the adverse pregnancy changes induced by nitric oxide synthase inhibition in the rat.

OBJECTIVE: Inhibition of nitric oxide synthase with N omega-nitro-L-arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome of hypertension, proteinuria, intrauterine growth restriction, and renal glomerular capillary endothelial lesions in pregnant rats. We attempted to reverse these changes with late-pregnancy administration of L-arginine. STUDY DESIGN: Sprague Dawley rats with timed pregnancies received infusions of either saline solution (n = 12) (group SC) or L-NAME (n = 12) (group LC) (160 mg/kg per day) on gestational day 10 through term. On gestational day 16 half of the saline solution group (group SA) and half of the L-NAME group (group LA) received L-arginine (21 mg/kg per day) through delivery. Systolic blood pressures were determined via tail cuff on days 10, 16, and 21. Pup weights were assessed at delivery, serum and urine were collected and analyzed for nitrites and nitrates, and renal tissue was processed for histologic examination. Data were analyzed with the one-way analysis of variance and the Newman-Keuls test for multiple comparisons. RESULTS: In the L-NAME-treated animals L-arginine significantly lowered systolic blood pressure at late pregnancy (125 +/- 2.42 vs 153 +/- 3.0 mm Hg) (p < 0.01), increased mean pup weight (5.6 +/- 0.11 gm in group LA vs. 5.0 +/- 0.02 gm in group LC) (p < 0.001), decreased the degree of proteinuria (2+ vs trace), and decreased the proportion of injured glomeruli (7% vs 64%) (p < 0.001). CONCLUSIONS: Lesions induced by chronic inhibition of endothelium-derived nitric oxide synthesis (hypertension, intrauterine growth restriction, proteinuria, renal glomerulus injury) are reversed by treatment with L-arginine. These findings lend support to the potential for use of nitric oxide donors in the treatment and prevention of preeclampsia.

Second-trimester amniotic fluid or maternal serum interleukin-10 levels and small for gestational age neonates.

OBJECTIVE: To evaluate if interleukin-10 levels in either early second-trimester amniotic fluid (AF) or maternal serum can be utilized as a predictor of the subsequent occurrence of small for gestational age (SGA) infants after controlling for gestational age at delivery. METHODS: We identified patients who underwent genetic amniocentesis for standard genetic indications or maternal blood sampling for maternal serum alpha-fetoprotein (MSAFP)/triple screen between January 1992 and February 1995 with available follow-up delivery data. Small for gestational age was defined as birth weight less than the tenth percentile for gestational age. Control patients were matched for gestational age at delivery, maternal age, race, and parity with at least two controls for each study patient. We excluded patients with maternal immune disease, chronic hypertension, diabetes, asthma, congenital heart disease, multiple gestation, and fetuses with structural or chromosomal anomalies. Second-trimester AF and serum samples were assayed for interleukin-10. Potential confounding variables considered were MSAFP level, smoking history, pregnancy-induced hypertension, and neonatal gender. The interleukin-10 levels were normalized using natural log transformation for statistical analysis. Statistical analysis included chi 2, Fisher exact test, and analysis of variance, with P < .05 considered significant. RESULTS. From the AF data base, 18 patients (6%) delivered SGA neonates and were matched with 46 controls. From the maternal serum data base, 13 patients (7%) delivered SGA neonates and were matched with 45 controls. Neither AF nor maternal serum interleukin-10 levels were significantly different in patients subsequently delivering SGA neonates compared with controls (AF: median 21.0 pg/mL. [range 13.8-27.6] versus 17.5 pg/mL. [range 8.9-362.12], P = .18; serum: median 15.7 pg/mL [range 9.9-73.5] versus 18.7 pg/mL [range 9.7-71.7], P = .60, respectively). No significant differences were identified in gestational age at sampling, maternal smoking history, pregnancy-induced hypertension, or elevated MSAFP in patients delivering SGA neonates compared with controls (P > .05 for each). As expected, birth weight was significantly lower in patients delivering SGA neonates compared with controls (P < .001). CONCLUSION: Second-trimester AF or maternal serum interleukin-10 levels are not predictive of subsequent delivery of SGA infants.

Mid-trimester prenatal sonographic diagnosis of a pericardial cyst.

Prenatal diagnosis of pericardial masses are infrequent and usually consist of intrapericardial teratomas or haemangiomas. We present the first report of prenatal diagnosis of a suspected pericardial cyst at 14 weeks' gestation which was subsequently confirmed by neonatal computed tomography.

Prenatal color and pulsed Doppler sonographic documentation of intrathoracic umbilical vein and ductus venosus, confirming extensive hepatic herniation in left congenital diaphragmatic hernia.

Prenatal sonographic diagnosis of an unusual case of a large left congenital diaphragmatic hernia is presented. The fetal stomach was located within the right thorax, posterior to the dextropositioned heart. Color and pulsed Doppler ultrasonography documented intrathoracic umbilical vein and ductus venosus vessels and respective waveforms, confirming extensive herniation of the left hepatic lobe.

Maternal and umbilical cord serum interleukin levels in preterm labor with clinical chorioamnionitis.

OBJECTIVE: Our purpose was to determine whether interleukin-1 beta, interleukin-6, and the soluble receptor for interleukin-2 levels in maternal and umbilical cord sera differed among patients with and without clinical chorioamnionitis delivered prematurely. STUDY DESIGN: Between February and November 1992, 32 women who were delivered between 20 and 36 weeks' gestation were enrolled in a prospective study to determine the levels of interleukin-1 beta, soluble interleukin-2 receptor, and interleukin-6 in maternal and umbilical cord serum. Cytokines were measured by enzyme-linked immunosorbent assay. Chorioamnionitis was identified by the presence of clinical markers in 12 patients. RESULTS: Soluble interleukin-2 receptor concentrations in maternal serum were significantly higher in women with clinical chorioamnionitis than in those without chorioamnionitis (median 400 U/ml, range 100 to 2100 U/ml vs median 275 U/ml, range 100 to 1300 U/ml, p < 0.04). Umbilical cord interleukin-6 concentrations were significantly higher in the presence of clinical chorioamnionitis than in the absence of chorioamnionitis (median 12.5 pg/ml, range 0 to 400 pg/ml vs median 0 pg/ml, range 0 to 25 pg/ml; p < 0.02). For patients with clinical chorioamnionitis there was a positive correlation between maternal and umbilical cord IL-2 receptor levels (r = 0.752, p < 0.01). No significant differences in maternal interleukin-1 beta or maternal interleukin-6 determinations were noted. Likewise, the umbilical cord interleukin-1 beta and IL-2 receptor concentrations were unchanged in the presence of clinical chorioamnionitis. CONCLUSIONS: This study demonstrates that for patients with preterm labor and clinical chorioamnionitis, maternal serum levels of IL-2 receptor, and umbilical cord serum levels of interleukin-6 are significantly increased compared with patients without chorioamnionitis.

Precision of umbilical artery Doppler studies. Intraobserver, interobserver, and biologic variability of fetal Doppler velocimetry.

The use of Doppler ultrasound to study fetal blood flow has become commonplace, despite the lack of detailed evaluation of the testing tool for precision. In evaluation of 25 patients, no significant intraobserver differences were found between readings on an individual waveform, nor were there significant differences between different observers on individual waveforms. Temporally separated waveforms within a 30-minute window gave the greatest variation. A multi-way analysis of variance noted significant differences in this category only. This study confirmed the precision of measurements by a single observer and between observers. Only biological alterations over time displayed significant variability.

The role of transvaginal ultrasound in a referral military hospital.

In an attempt to overcome some of the difficulties encountered with transabdominal ultrasonography we report on 55 patients who underwent 88 transvaginally directed sonograms. In 24 patients in whom a diagnosis of an early intrauterine pregnancy was made, the mean crow-rump length (CRL) was 10.7 mm (range, 3 to 27). In six patients (25%) the CRL was 5 mm or less. These data suggest that the use of transvaginally directed sonography may permit an earlier diagnosis of pregnancy than the abdominal approach does. This earlier diagnosis should allow the exclusion of ectopic pregnancy in many of the patients at risk for this disorder.

Cervical ripening. A retrospective experience with prostaglandin E2 "chips".

To improve the unfavorable cervix we instituted a policy of cervical ripening with "chips" of prostaglandin E2 suppositories. A standard, 20-mg suppository was cut into six equal parts, and one of the chips was inserted just inside the vaginal introitus every four to six hours. Repeat doses were utilized if no cervical change was evident and uterine activity was minimal. All the patients underwent continuous monitoring in the labor-and-delivery unit. Fifty patients with Bishop's scores of less than 4 underwent cervical ripening for a variety of obstetric indications. Forty-two patients (84%) achieved vaginal delivery. Three patients underwent cesarean delivery for fetal distress unrelated to hyperstimulation. Two additional patients experienced hyperstimulation; one of them required subcutaneous terbutaline. No other neonatal or maternal complications were encountered. Cervical ripening with prostaglandin chips may be a reasonable clinical alternative when one is faced with an obstetric indication for delivery in a patient with an unfavorable cervix.

Proliferation of group B streptococci in human amniotic fluid in vitro.

The group B Streptococcus is one of the most virulent organisms causing perinatal infection. Human amniotic fluid from the second and third trimesters was pooled and analyzed for electrolytes, protein, albumin, zinc, inorganic phosphorus, ferritin, lysozyme, and immunoglobulins. We inoculated replicates of specimens with known virulent strains of group B streptococci (893, 891, and 878) and Escherichia coli (C5) with Todd-Hewitt broth and normal saline solution used as controls. Group B streptococci strains 893 and 891 proliferated rapidly at rates similar to their rates in Todd-Hewitt Broth. Strain 878 grew at a rate slower than that of strains 893 and 891. The amniotic fluid specimens were similar with respect to factors reported as inhibitory to bacterial proliferation. Second- and third-trimester amniotic fluid supports the growth of group B streptococci as well as a culture medium optimized for bacterial growth. Strain-specific variance in group B streptococci growth rates in amniotic fluid may have clinical significance for those at risk for group B streptococci infection.

Update on external cephalic version performed at term.

External cephalic version under tocolysis at term was investigated during a prospective study at the Los Angeles County/University of Southern California Medical Center from October 1, 1979 to March 16, 1983. Two hundred twelve patients were considered for attempted version. Forty-one patients were excluded, and 23 patients as previously reported were randomized to the control group. The procedure was successful in 73% (108 of 148). Of the 102 successful versions observed until delivery (six lost to follow-up), 93% (95 of 102) presented in labor with a vertex presentation; seven fetuses reverted to abnormal lies. The cesarean section rate in the success group with a vertex presentation was 24% (23 of 95).