Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.

Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Pneumococcal vaccination during pregnancy for preventing infant infection.

BACKGROUND: Each year at least one million children worldwide die of pneumococcal infections. The development of bacterial resistance to antimicrobials adds to the difficulty of treatment of diseases and emphasizes the need for a preventive approach. Newborn vaccination schedules could substantially reduce the impact of pneumococcal disease in immunized children, but does not have an effect on the morbidity and mortality of infants less than three months of age. Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal disease during the first months of life before the pneumococcal vaccine administered to the infant starts to produce protection. OBJECTIVES: To assess the effect of pneumococcal vaccination during pregnancy for preventing infant infection. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966 to June 2004), EMBASE (January 1985 to June 2004), and reference lists of articles. SELECTION CRITERIA: Randomized controlled trials in pregnant women comparing pneumococcal vaccine with placebo or doing nothing or with another vaccine to prevent infant infections. DATA COLLECTION AND ANALYSIS: Two authors independently assessed methodological quality and extracted data using a data collection form. Study authors were contacted for additional information. MAIN RESULTS: Three trials (280 participants) were included. There was no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (one trial, 149 pregnancies, relative risk (RR) 0.51; 95% confidence interval (CI) 0.18 to 1.41). Although the data suggest an effect in reducing pneumococcal colonisation in infants by 16 months of age (one trial, 56 pregnancies, RR 0.33; 95% CI 0.11 to 0.98), there was no evidence of this effect in infants at two months of age (RR 0.28; 95% CI 0.02 to 5.11) or by seven months of age (RR 0.32; 95% CI 0.08 to 1.29). AUTHORS' CONCLUSIONS: There is insufficient evidence to support whether pneumococcal vaccination during pregnancy could reduce infant infections.

Prophylactic oral betamimetics for reducing preterm birth in women with a twin pregnancy.

BACKGROUND: Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction frequency or delay preterm birth in singleton pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a twin pregnancy is unproven. OBJECTIVES: To assess the effects of prophylactic oral betamimetics administered to women with twin pregnancies. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (May 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966 to May 2004), EMBASE (January 1985 to May 2004), and reference lists. SELECTION CRITERIA: Randomized controlled trials in twin pregnancies comparing oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth. DATA COLLECTION AND ANALYSIS: Standard methods of The Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Trials were independently assessed for methodological quality by at least two authors, who extracted data using a data collection form. MAIN RESULTS: Five trials (344 twin pregnancies) were included. All trials compared oral betamimetics to placebo. Betamimetics reduced the incidence of preterm labour (one trial, 50 twin pregnancies, relative risk (RR) 0.40; 95% confidence interval (CI) 0.19 to 0.86). However, betamimetics did not reduce preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10) or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50). Mean neonatal birthweight in the betamimetic group was significantly higher than in the placebo group (three trials, 478 neonates, weighted mean difference 111.2 grams; 95% CI 22.2 to 200.2). Nevertheless, there was no evidence of an effect of betamimetics in reduction of low birthweight (two trials, 366 neonates, RR 1.19; 95% CI 0.77 to 1.85) or small-for-gestational age neonates (two trials, 178 neonates, RR 0.92; 95% CI 0.52 to 1.65). Two trials (388 neonates) showed that betamimetics significantly reduced the incidence of respiratory distress syndrome but the difference was not significant when the analysis was adjusted for correlation of babies from twins. Three trials (452 neonates) showed no evidence of an effect of betamimetics in reducing neonatal mortality (RR 0.80; 95% CI 0.35 to 1.82). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.

Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV).

BACKGROUND: The incidence of chlorioamnionitis occurs in between 8 to 12 women for every 1000 live births and 96% of the cases of chlorioamnionitis are due to ascending infection. Following spontaneous vaginal delivery, 1% to 4% of women develop postpartum endometritis. The incidence of neonatal sepsis is 0.5% to 1% of all infants born. Maternal vaginal bacteria are the main agents for these infections. It is reasonable to speculate that prevention of maternal and neonatal infections might be possible by washing the vagina and cervix with an antibacterial agent for all women during labour. Chlorhexidine belongs to the class of compounds known as the bis-biguanides. Chlorhexidine has antibacterial action against a wide range of aerobic and anaerobic bacteria, including those implicated in peripartal infections. OBJECTIVES: To evaluate the effectiveness and side-effects of chlorhexidine vaginal douching during labour in reducing maternal and neonatal infections (excluding Group B Streptococcal and HIV). SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (from 1966 to 2002), EMBASE (from 1980 to 2002), CINAHL (from 1982 to 2002) and LILACS (from 1982 to 2002). SELECTION CRITERIA: Randomized or quasi-randomized trials comparing chlorhexidine vaginal douching during labour with placebo or other vaginal disinfectant to prevent (reduce) maternal and neonatal infections (excluding Group B Streptococcal and HIV). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality, extracted and entered the data into the RevMan software and interpreted the data. A third reviewer analysed and interpreted the data. The fourth reviewer also interpreted the data. MAIN RESULTS: Three studies (3012 participants) were included. There was no evidence of an effect of vaginal chlorhexidine during labour in preventing maternal and neonatal infections. Although the data suggest a trend in reducing postpartum endometritis, the difference was not statistically significant (relative risk 0.83; 95% confidence interval 0.61 to 1.13). REVIEWERS' CONCLUSIONS: There is no evidence to support the use of vaginal chlorhexidine during labour in preventing maternal and neonatal infections. There is a need for a well-designed randomized controlled trial using appropriate concentration and volume of vaginal chlorhexidine irrigation solution and with adequate sample size.

The international infections in pregnancy study: group B streptococcal colonization in pregnant women.

BACKGROUND: Heavy colonization with group B streptococcus (GBS) has been associated with increased risk of preterm birth and neonatal sepsis; the burden of neonatal GBS disease varies geographically. To determine whether variation in heavy colonization and GBS serotypes could contribute to geographic differences in disease burden, we assessed the prevalence of heavy colonization and the distribution of serotypes in asymptomatic pregnant women in multiple countries. METHODS: Cervical, lower vaginal and urine samples were collected from women attending seven prenatal clinics in six countries. Light colonization was defined as GBS isolation from Lim broth only; heavy colonization was isolation from urine or sheep blood agar plates. Isolates were serotyped using capillary precipitation. RESULTS: GBS was present in 11.3% of 1308 participants (range 7.1-21.7%); 5.0% were heavily colonized (0.4-18.8%) and 6.4% were lightly colonized (2.9-8.0%). Serotypes III and V were most common (both 17.2%). Serotypes VII and VIII were found in one study center. CONCLUSIONS: The prevalence of heavy colonization and GBS serotypes varied significantly among our study centers. Whether this variation could in part explain geographic differences in neonatal morbidity and mortality is a hypothesis that needs further study.

Birthweight-specific neonatal mortality in developing countries and obstetric practices.

OBJECTIVES: To evaluate birthweight-specific neonatal mortality and perinatal interventions in major medical centers in developed and developing countries. METHODS: A survey was developed and electronically mailed to 13 medical centers participating in the Global Network for Perinatal and Reproductive Health (GNPRH). The ability of a center to provide requested data was assessed. The mortality rates and use of specific perinatal interventions in centers in developing countries were compared with developed countries. RESULTS: Nine centers in developing countries responded to the survey, and three centers in developed countries were used for comparison. Data collection was highly variable. Most developing country centers were able to provide data by birthweight but not by gestational age. The differences in mortality rates between developing and developed countries were more pronounced at lower gestational ages and birthweights. A difference was found in perinatal interventions between developing and developed countries. In the former, viability was generally considered 28 weeks, and the gestational age at which cesarean sections were usually performed for the sake of the fetus at preterm gestations varied from 26 to 37 weeks. Most centers did not routinely induce for pPROM; only five out of nine centers used antibiotics to prolong latency. Most centers used tocolysis beginning at 26-28 weeks through 32-37 weeks, and a variety of tocolytic agents were used. Most centers routinely used corticosteroids for preterm infants, and all centers employed repeat weekly steroid dosing if undelivered. CONCLUSIONS: Despite the fact that the GNPRH centers included in this study represent some of the best health care available in these countries, they lag far behind centers in developed countries in neonatal mortality rates and their use of various obstetric practices. Furthermore, incomplete and inconsistent data collection complicates the evaluation of the factors contributing to high neonatal mortality rates.

Oral misoprostol is rapidly absorbed in postpartum women at term.

OBJECTIVE: To determine the rate of bioavailability of oral misoprostol in the tablet and a new capsule form in women with term pregnancies in the postpartum period. METHODS: Twenty-seven women received 400 microg of misoprostol orally after delivery of the fetal vertex in either the standard tablet form or crushed in methylcellulose capsules prepared in our pharmacy. Serum levels of misoprostol free acid, the principal metabolite, were measured at 5-, 15- and 30-min intervals after administration of the medication. The pharmacokinetics of the tablet and capsule groups were then compared. RESULTS: Twenty patients were included in the analysis. At 5 min, there was a trend towards a statistically significant difference in the concentration of misoprostol acid in the tablet group (89 pg/ml) versus the capsule group (20 pg/ml) (p = 0.007). No significant difference in plasma concentration was noted in the two groups at 15 min (tablet group, 256 pg/ml; capsule group, 245 pg/ml; p = 0.85) or 30 min (tablet group, 381 pg/ml; capsule group, 455 pg/ml; p = 0.45). CONCLUSION: Oral misoprostol is rapidly absorbed and bioavailable in the postpartum period. Misoprostol may prove useful in postpartum management. The novel packaging of misoprostol in capsule form allows for double-blinded studies with similar pharmacokinetics to the standard tablet.

Subclinical myocardial injury in small-for-gestational-age neonates.

OBJECTIVE: Small-for-gestational-age (SGA) infants are at risk for premature death from cardiovascular disease (myocardial infarction and stroke), hypertension, and diabetes in adult life. Severe intrauterine growth restriction is often associated with subclinical cardiovascular abnormalities detectable during fetal echocardiography. The objective of this study was to determine whether SGA newborns have evidence of myocardial injury at birth. STUDY DESIGN: Cardiac troponin I, a specific marker of myocardial injury widely used for the diagnosis of myocardial infarction in adults, was determined in umbilical cord blood. Umbilical cord venous blood was obtained at the time of birth from 72 SGA newborns (birth weight below the 10th centile for gestational age) and 309 newborns whose birth weights were appropriate for gestational age (AGA). Cardiac troponin I was determined with a commercially available immunoassay (sensitivity 0.2 ng/ml) employed in clinical laboratories (Immulite 2000, Diagnostic Products Corp., Los Angeles, CA). RESULTS: Cardiac troponin I was not detectable in any of the blood samples from AGA infants. In contrast, 4.2% (3/72) of SGA infants had detectable cardiac troponin I in umbilical cord blood (Fisher's exact test, p = 0.007). CONCLUSION: A subgroup of SGA newborns undergoes myocardial injury before birth. This insult may predispose to the development of adult premature cardiovascular disease and death.

Elevated monocyte chemotactic protein-1 in amniotic fluid is a risk factor for pregnancy loss.

OBJECTIVE: Pregnancy loss after mid-trimester amniocentesis occurs in 0.5-1% of cases and is frequently attributed to the procedure. Accumulating evidence implicates a pre-existing, but clinically silent, intra-amniotic inflammation in the etiology of adverse pregnancy outcome after mid-trimester amniocentesis. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine produced by a wide variety of cells during the course of an inflammatory response. This study was designed to assess if the amniotic fluid concentration of this chemokine identifies patients at risk for spontaneous abortion and/or fetal death. METHOD: A retrospective case-control study of women who had a mid-trimester amniocentesis was designed. Cases (n = 10) consisted of patients who had a spontaneous pregnancy loss after the procedure, while the control group (n = 84) consisted of patients who had a normal pregnancy outcome after mid-trimester amniocentesis. MCP-1 was measured by a specific enzyme immunoassay (sensitivity, 18.3 pg/ml). The Kolmogorov-Smirnov test was utilized to assess normal distribution of the data. Logarithmic transformation was applied to achieve normality. Statistical analysis was performed using Student's t test. A receiver operating characteristic (ROC) curve analysis was used to select a cut-off to dichotomize amniotic fluid concentrations of MCP-1. RESULTS: MCP-1 was detectable in all amniotic fluid samples. Patients who had a mid-trimester amniocentesis and a subsequent pregnancy loss had a higher mean amniotic fluid log MCP-1 concentration than those with a normal pregnancy outcome (pregnancy loss, mean 2.95 +/- 0.19 pg/ml vs. normal outcome, mean 2.78 +/- 0.19 pg/ml; p = 0.01). A cut-off of > 765 pg/ml was selected by ROC curve analysis (area under the curve, 0.74; p = 0.01). An amniotic fluid concentration of MCP-1 above this level was strongly associated with pregnancy loss (odds ratio, 7.35; 95% confidence interval, 1.7-31.1), a sensitivity of 70%, and a specificity of 76%. CONCLUSION: A subset of women who had a pregnancy loss after a mid-trimester amniocentesis had higher concentrations of the chemokine MCP-1 than those who had a normal pregnancy outcome. Subclinical intra-amniotic inflammation is a risk factor for pregnancy loss after mid-trimester amniocentesis. This observation may have medicolegal and clinical implications. An elevated MCP-1 concentration in amniotic fluid of patients with a pregnancy loss after a mid-trimester amniocentesis indicates that a pathological condition was present at the time of the procedure.

Does transvaginal ultrasound of the cervix predict preterm premature rupture of membranes in a high-risk population?

OBJECTIVES: To determine in patients with a cervical length < 25 mm on transvaginal ultrasound if the severity of cervical length shortening can be used to predict preterm premature rupture of membranes (PPROM) and the contribution of PPROM to preterm delivery in these patients. METHODS: We retrospectively reviewed asymptomatic singleton pregnancies between 14 and 24 weeks at high risk of preterm delivery by obstetric history and transvaginal cervical length < 25 mm. Cases developing subsequent PPROM were compared with controls for transvaginal sonographic cervical characteristics. RESULTS: Of 69 patients identified to have a cervical length < 25 mm, 27 (39%) had PPROM, and 42 (61%) did not. Mean +/- standard deviation (SD) cervical length was 12.7 +/- 8.7 mm and 17.0 +/- 7.6 mm in the two groups, respectively (P = 0.04). Mean +/- SD cervical funneling was 57.4 +/- 31.4% and 40.0 +/- 28.1%, respectively (P = 0.01). The characteristics most predictive of PPROM were: cervical length of < 10 mm (sensitivity, specificity, positive and negative predictive values of 33, 90, 69, and 68%, respectively; odds ratio, 4.8; 95% confidence interval, 1.3-17.5) and cervical funneling > 75% (sensitivity, specificity, positive and negative predictive values of 33, 93, 75 and 68%, respectively; odds ratio, 6.5; 95% confidence interval, 1.6-26.9). Stepwise logistic regression revealed cervical length to be a significant predictor of PPROM (odds ratio, 4.0; 95% confidence interval, 1.1-14.2). CONCLUSION: In patients at high risk for preterm delivery because of obstetric history and transvaginal sonographic cervical length < 25 mm, a cervical length < 10 mm and cervical funneling > 75% were most predictive of PPROM. PPROM was the major contributor to preterm delivery in these patients.

An international survey of practice variation in the use of antibiotic prophylaxis in cesarean section.

OBJECTIVE: To examine the use of antibiotic prophylaxis in cesarean section in different countries and in relation to a reference regimen. METHOD: Fifty consecutive cesarean sections performed in eight centers in five countries were surveyed. Data from each center were compared to a regimen recommended by the Cochrane Collaboration (one dose of ampicillin or cefazolin administered to all women shortly before the procedure or immediately after cord clamping) using logistic regression with adjustment for procedure type. RESULT: Prophylaxis was used widely, but only four centers administered prophylaxis to all women. Ampicillin and cefazolin were the principal antibiotics used, but broad-spectrum agents and multidrug regimens were also used commonly. Only two centers reliably administered the antibiotic at the appropriate time. The majority of women received only one dose of antibiotic in only three centers. CONCLUSION: The use of antibiotic prophylaxis in cesarean section was variable and often at odds with published recommendations.

Fetal cardiac development and hemodynamics in the first trimester.

OBJECTIVE: To describe fetal cardiac and hemodynamic development in the first trimester of pregnancy. SUBJECTS AND METHODS: Forty-eight pregnancies were prospectively studied with transvaginal ultrasound and color Doppler. Fetal heart rate and size were documented together with the presence of inflow and outflow wave-forms and valve signals. RESULTS: Heart rate and size showed a positive correlation with gestational age. At 6 weeks of gestation, 20% of the cardiac cycle was occupied by the isovolumic contraction time (ICT); the isovolumic relaxation time (IRT) occupied 16% and remained unchanged, while the ICT progressively shortened and was not measurable after 12 weeks. The peak inflow velocities had changed from monophasic to biphasic by 10 weeks of gestation. At 7 weeks of gestation, semilunar valves were detected in 10% of examinations and the atrioventricular valves in 3%. The detection rate for both valves at 12 weeks was > or = 90%. In pregnancies that miscarried, the detection rate for both was < 25%. CONCLUSIONS: The Doppler signals that characterize the heart during the first trimester suggest effective heart compliance by 12 weeks. Normal valve development can be inferred from non-invasive Doppler recordings.

Prediction of preterm delivery with transvaginal ultrasonography of the cervix in patients with high-risk pregnancies: does cerclage prevent prematurity?

OBJECTIVES: We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes. STUDY DESIGN: Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospectively from 14 weeks' to 23 weeks 6 days' gestation with transvaginal ultrasonography of the cervix. The subgroup of patients with either a cervical length of <25 mm or funneling of >25% or both was offered McDonald salvage cerclage, which was performed at the discretion of the patient and the obstetrician. The 2 groups (with and without cerclage) were compared for the primary outcome of preterm delivery at <35 weeks' gestation. RESULTS: One hundred sixty-eight women were followed, including 97 (58%) with >/=1 prior 14- to 34-week preterm deliveries. Of 63 (37. 5%) patients identified as having cervical changes, 23 (37%) had preterm delivery; of 105 patients with no cervical changes, 8 (8%) had preterm delivery (relative risk, 4.8; 95% confidence interval, 2. 3-10.1). The sensitivity, specificity, and positive and negative predictive values of either a short cervix of <25 mm or funneling of >25% or both were 74%, 70%, 37%, and 92%, respectively. Of 63 pregnancies in which there were cervical changes, 39 underwent cerclage and 24 did not. These 2 groups were similar for demographic characteristics, risk factors, and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes (18.3 vs 21.2 weeks' gestation in the groups with and without cerclage, respectively; P <.001). Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage (odds ratio, 1.1; 95% confidence interval, 0.3-4.6). Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage, which was similar for all characteristics studied. The incidence of preterm delivery remained similar (27% vs 23%, respectively; P =.7), as did days from cervical changes to delivery (111 vs 96, respectively; P =.2). CONCLUSIONS: Transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation is a good predictor of preterm delivery in high-risk pregnancies. Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography.

Increased midtrimester amniotic fluid activin A: a risk factor for subsequent fetal death.

OBJECTIVE: The objective of this study was to determine whether concentrations of activin A and corticotropin-releasing factor in amniotic fluid can identify patients at risk of fetal death. STUDY DESIGN: A retrospective case-control study of women who have had a midtrimester amniocentesis was designed. Case subjects consisted of patients who had a spontaneous fetal death after the procedure, whereas the control group consisted of patients who had a normal pregnancy outcome after midtrimester amniocentesis. Dimeric activin A was measured by a specific 2-site enzyme immunoassay, and corticotropin-releasing factor was measured by a specific and sensitive radioimmunoassay after acidic extraction. Statistical analysis was performed with Mann-Whitney U test, Fisher's exact test, and chi2 tests and regression analysis. RESULTS: First, activin A was detectable in all amniotic fluid samples. Second, the concentration of activin A in amniotic fluid increased with advancing gestational age. Third, patients who subsequently had a fetal death had a higher median concentration of activin A than those with a normal pregnancy outcome (P <.01). Fourth, an amniotic fluid concentration of activin A greater than the 95th confidence interval for gestational age was found in 40% of patients who subsequently had a fetal death (odds ratio: 21.6; P <.005). Finally, the median concentration of corticotropin-releasing factor in amniotic fluid was not different in case subjects and control subjects. CONCLUSIONS: An elevated concentration of activin A in amniotic fluid identifies women at risk of fetal death.

Success rate of cytogenetic analysis at the time of second-trimester dilation and evacuation.

OBJECTIVE: The aim of this study was to determine the success rate of cytogenetic analysis from specimens obtained at the time of second-trimester termination of pregnancy by dilation and evacuation. STUDY DESIGN: All second-trimester dilation and evacuations performed by a single practitioner at a single institution from 1993 through 1995 were evaluated to pick out those patients in whom biopsy specimens were submitted for cytogenetic analysis. The main outcome studied was the ability to obtain karyotype results for these specimens. RESULTS: Cytogenetic studies were performed on 258 dilation and evacuation specimens with a median gestational age of 18 weeks (range 13-25 weeks). The indications for termination were fetal aneuploidy (n = 88, 34%), sonographically diagnosed fetal malformations (n = 82, 32%), intrauterine fetal death (n = 67, 26%), oligohydramnios or premature rupture of membranes (n = 16, 6%), and others (hematologic and metabolic disorders, n = 5, 2%). Successful karyotyping was achieved for 99% of specimens obtained at second-trimester dilation and evacuation, with 3 failures of growth (1% failure rate). The failures included a 14-week molar pregnancy, an 18-week fetus with Dandy-Walker malformation, and a 19-week intrauterine fetal death. Of the samples obtained in cases of intrauterine fetal death, 99% (66/67) provided adequate cytogenetic information. CONCLUSIONS: Karyotyping for abnormal second-trimester pregnancies and intrauterine fetal deaths at the time of a dilation and evacuation procedure has a success rate nearing 100%. In contrast to previous reports, our data indicate that it is unnecessary to perform pretermination invasive karyotyping in patients with abnormal second-trimester pregnancies or intrauterine fetal death who elect to undergo dilation and evacuation. Chromosome analysis at the time of termination of pregnancy by dilation and evacuation reduces patient discomfort, risk of infection, and cost while still providing reliable and vital cytogenetic information for future genetic counseling.

Perinatal bacterial infection: an update.

This article reviews the current trends in the evaluation and management of bacterial infection involving the uterus, placenta, membranes, amniotic fluid, and fetus occurring near the time of birth. The discussion includes information regarding risk, incidence, pathophysiology, bedside diagnosis, interventional options including antibiotics, corticosteroids, fetal monitoring, and delivery, and possible preventive measures which affect the outcome. The adequate evaluation and management of perinatal infection requires a team approach with obstetricians and pediatricians. Clinical screening is useful in developing the diagnosis, but amniotic fluid evaluation remains the proposed gold standard. The role of cytokines is becoming increasingly important, as is seen in the association of IL-6 with positive amniotic fluid cultures and periventricular leukomalacia. Prompt recognition and management of the pregnancy affected by infection can improve perinatal outcomes. A management protocol is presented to help structure the approach to suspected infection. Premature delivery due to perinatal infection may be preventable.

Cervical ultrasonography compared with manual examination as a predictor of preterm delivery.

OBJECTIVE: Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery. STUDY DESIGN: One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospectively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix. The primary outcome studied was preterm (< 35 weeks) delivery. RESULTS: Excluding six induced preterm deliveries, 96 pregnancies were analyzed. The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm (n = 17) and 31.3 mm in pregnancies delivered at term (n = 79) (p = 0.003); the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies, respectively (not significant). The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately (p < 0.0005). The 25th percentiles of ultrasonographic (25 mm) and manual (16 mm) cervical lengths showed relative risks for preterm delivery of 4.8 (95% confidence interval 2.1 to 11.1, p = 0.0004) and 2.0 (95% confidence interval 0.5 to 4.7, p = 0.1), respectively; sensitivity, specificity, and positive and negative predictive values were 59%, 85%, 45%, 91%, and 41%, 77%, 28%, and 86%, respectively. CONCLUSION: Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination. Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks' gestation.

Increase in prostaglandin bioavailability precedes the onset of human parturition.

The traditional paradigm that prostaglandins (PGS) are of central importance in the initiation of labor has been challenged. A group of investigators has recently reported that the amniotic fluid concentrations of PGE(2) and PGF(2 alpha) increase only late in the course of labor implying that "the accumulation of prostaglandins in amniotic fluid is an after-effect of labor and not indicative of a role of these compounds in the initiation of human parturition." The present study was conducted to determine whether amniotic fluid prostaglandin concentrations increase prior to the onset of human labor, the central question in this controversy. Three amniocenteses were performed in 17 women with intrahepatic cholestasis of pregnancy -- the first two prior to the onset of labor and the third during early spontaneous labor. PGE(2) and PGF(2 alpha) were measured with sensitive and specific radioimmunoassays. Amniotic fluid concentrations of PGE(2) and PGF(2 alpha) increased prior to the onset of spontaneous labor. An additional increase in the concentrations of PGE(2) and PGF(2 alpha) was found in samples obtained in early labor. We conclude that an increase in prostaglandin bioavailability precedes the onset of spontaneous human parturition.