Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes.

OBJECTIVE: Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. DESIGN: Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. SETTING: Antenatal clinics. POPULATION: Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). METHODS: Maternal serum levels of sRAGE (total circulating pool), N(ε)-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. MAIN OUTCOME MEASURES: Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE-). RESULTS: In DM PE+ versus DM PE-, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE:hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE:AGE and sRAGE:CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. CONCLUSIONS: In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM.

Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women.

AIMS/HYPOTHESIS: Elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), a soluble form of vascular endothelial growth factor receptor, and endoglin, a co-receptor for TGFbeta1, confer high risk of pre-eclampsia in healthy pregnant women. In this multicentre prospective study, we determined levels of these and related factors in pregnant women with type 1 diabetes, a condition associated with a fourfold increase in pre-eclampsia. METHODS: Maternal serum sFlt1, endoglin, placental growth factor (PlGF) and pigment epithelial derived factor were measured in 151 type 1 diabetic and 24 healthy non-diabetic women at each trimester and at term. RESULTS: Approximately 22% of the diabetic women developed pre-eclampsia, primarily after their third trimester visit. In women with pre-eclampsia (diabetic pre-eclampsia, n = 26) vs those without hypertensive complications (diabetic normotensive, n = 95), significant changes in angiogenic factors were observed, predominantly in the early third trimester and prior to clinical manifestation of pre-eclampsia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic pre-eclampsia vs type 1 diabetic normotensive women at the third trimester visit (p < 0.05) and the normal rise of PlGF during pregnancy was blunted (p < 0.05). Among type 1 diabetic women, third trimester sFlt1 and PlGF were inversely related (r(2) = 42%, p < 0.0001). Endoglin levels were increased significantly in the diabetic group as a whole vs the non-diabetic group (p < 0.0001). CONCLUSIONS/INTERPRETATION: Higher sFlt1 levels, a blunted PlGF rise and an elevated sFlt1/PlGF ratio are predictive of pre-eclampsia in pregnant women with type 1 diabetes. Elevated endoglin levels in women with type 1 diabetes may confer a predisposition to pre-eclampsia and may contribute to the high incidence of pre-eclampsia in this patient group.

The preterm prediction study: can low-risk women destined for spontaneous preterm birth be identified?

OBJECTIVE: Half of all preterm births occur in women without clinical risk factors. Our goal was to assess fetal fibronectin assay, Bishop score, and cervical ultrasonography as screening tests to predict which low-risk pregnancies will end in preterm birth. STUDY DESIGN: We performed a secondary analysis of data collected at 22 to 24 weeks' gestation from low-risk subjects enrolled in the Preterm Prediction Study, an observational study of risk factors for preterm birth conducted by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Analysis was limited to primigravid women and to women who did not have a history of preterm birth or spontaneous pregnancy loss at <20 weeks' gestation. Bishop score (> or =4), fetal fibronectin level (> or =50 ng/mL), and cervical length (< or =25 mm) at 24 weeks' gestation were evaluated alone and in sequence as tests to predict spontaneous delivery before 35 weeks' gestation. RESULTS: Of the 2929 subjects enrolled in the original study, 2197 (1207 primigravid women and 900 low-risk multiparous women) met criteria for this analysis. There were 64 spontaneous births before 35 weeks' gestation (3.04%). All three tests were significantly related to birth before 35 weeks' gestation (high Bishop score: relative risk, 3.6; 95% confidence interval, 2.1-6.3; fetal fibronectin detection: relative risk, 8.2; 95% confidence interval, 4.8-13.9; short cervical length: relative risk, 6.9; 95% confidence interval, 4.3-11.1). However, the sensitivities of the tests alone were low (23.4% for high Bishop score, 23.4% for fetal fibronectin detection, and 39.1% for short cervix), as were the sensitivities for Bishop score followed by cervical ultrasonography (14.1%) and fetal fibronectin assay followed by cervical scan (15.6%). CONCLUSION: In the setting of low-risk pregnancy, fetal fibronectin assay and cervical ultrasonography have low sensitivity for preterm birth before 35 weeks' gestation. Sequential screening with Bishop score or fetal fibronectin assay followed by cervical ultrasonography further decreased sensitivity to only 15% among low-risk women.

The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our objective was to determine the relative importance of demographic characteristics, clinical risk factors, and ancillary screening tests in the prediction of preterm birth as a result of premature rupture of membranes. STUDY DESIGN: A total of 2929 women were evaluated in 10 centers at 23 to 24 weeks' gestation. Demographic and clinical characteristics were ascertained. Cervicovaginal fetal fibronectin and bacterial vaginosis were evaluated. Cervical length was measured by vaginal ultrasonography. Patients were evaluated for spontaneous preterm birth caused by preterm premature rupture of membranes at <37 and <35 weeks' gestation. Multivariate analyses were performed separately for nulliparous women and multiparous women. RESULTS: Premature rupture of membranes at <37 weeks' gestation complicated 4.5% of pregnancies, accounting for 32.6% of preterm births. Univariate analysis revealed low body mass index, pulmonary disease, contractions within 2 weeks, short cervix (

Preterm prediction study: is socioeconomic status a risk factor for bacterial vaginosis in Black or in White women?

Bacterial vaginosis (BV), an important risk factor for preterm birth, is a more common infection in Black compared with White pregnant women. Because Black women in the United States are more likely to have lower measures of socioeconomic status (SES), this study examined the hypothesis that BV is associated with low SES. The project evaluated data from the Preterm Prediction Study of 2,929 women prospectively followed during their pregnancies. The women, who were screened for BV at 24 and 28 weeks of gestation, underwent a structured interview to evaluate demographic factors, SES, home and work environment, drug or alcohol use, and prior medical history. Black women in the study had many measures of lower SES compared with the White women, and reported less use of tobacco, alcohol and drugs. In neither the Black nor White women was an association found between BV and measures of SES (with the sole exception of "absence of a home telephone"). Most measures of SES do not explain the difference in rates of BV in Black and in White pregnant women.

The preterm prediction study: effect of gestational age and cause of preterm birth on subsequent obstetric outcome. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: We sought to evaluate the association between prior spontaneous preterm delivery and subsequent pregnancy outcome. STUDY DESIGN: A total of 1711 multiparous women with singleton gestations were prospectively evaluated at 23 to 24 weeks' gestation. Prior pregnancies were coded for the presence or absence of a prior spontaneous preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest prior delivery (13-22, 23-27, 28-34, and 35-36 weeks' gestation) was recorded. Current gestations were categorized as spontaneous preterm delivery at <28, <30, <32, <35, or <37 weeks' gestation. The risk of spontaneous preterm delivery in the current gestation was determined on the basis of the occurrence, gestational age, and cause of the earliest prior spontaneous preterm delivery. RESULTS: The incidences of spontaneous preterm delivery before 28, 30, 32, 35, and 37 weeks' gestation were 0.8%, 1.1%, 1.9%, 5.1%, and 11.9%, respectively. Those with a prior spontaneous preterm delivery carried a 2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those with no prior spontaneous preterm delivery (21. 7% vs 8.8%; P

Cesarean delivery rates in the United States. The 1990s.

The increase in CS rates in the United States in the 1970s and 1980s and the gradual decrease in the 1990s have been the focus of considerable attention because of the increased maternal morbidity and cost associated with the procedure without apparent impact on infant mortality. Focused efforts to reduce CS have resulted in a modest decrease the rate of primary CS and a marked increase in VBAC. Considerable variation in CS rates exists among regions in the United States and among states within those regions. The states with the higher CS rates are clustered in the South and Northeast regions of the United States, whereas rates tend to be lower in the West and Midwest. This variation cannot be explained by standard demographic risk factors and is likely related to local culture and mode of practice. Patient case mix should also be taken into account when comparing CS rates. Accounting for differences risk may help highlight differences in mode of practice and thus identify opportunities for improvement. Several reports from hospitals and communities of education and peer review programs have resulted in a significant reduction in their CS rates without increasing perinatal or maternal morbidity and mortality. A common theme in these reports of successful strategies to decrease the CS rate safely is the importance of physician motivation to make a change.

A randomized clinical trial of prostaglandin E2 intracervical gel and a slow release vaginal pessary for preinduction cervical ripening.

OBJECTIVE: Our purpose was to compare the efficacy of 2 different prostaglandin E2 delivery methods for preinduction cervical ripening. STUDY DESIGN: Ninety patients admitted for labor induction with a Bishop score <8 were randomized to either 0.5 mg prostaglandin E2 intracervical gel (Prepidil) every 6 hours for 2 doses or 10 mg prostaglandin E2 slow release vaginal pessary (Cervidil). Oxytocin induction was begun after 12 hours. It was estimated that enrollment of 90 women would be required to identify a 30% difference in the percent delivered in <24 hours (1 - beta = .80, alpha = .05). Data were analyzed with use of chi2 analysis or the Student t test. RESULTS: There were 45 subjects in each treatment arm. The percent delivered by 24 hours was 53% with intracervical gel and 63% with vaginal pessary (P = .28). Mean change in Bishop score was 1.8 +/- 1.9 for the intracervical gel versus 3.2 +/- 3.1 for the vaginal pessary (P = .01). No difference was demonstrated in mean time to delivery, 28.3 versus 24.0 hours (P = .19) or percent requiring cesarean section. CONCLUSION: Preinduction cervical ripening with a slow release prostaglandin E2 vaginal pessary resulted in greater change in Bishop score than with intracervical prostaglandin E2. There was a trend toward shorter time to delivery with the pessary. There was no statistically significant difference in percent delivered in <24 hours.

Neonatal mortality for very low birth weight deliveries in South Carolina by level of hospital perinatal service.

OBJECTIVE: The purpose of this study was to determine whether neonatal mortality rates for very low birth weight (500 to 1499 g) infants born in South Carolina differ by level of perinatal services available at the hospital of birth. STUDY DESIGN: Linked live birth certificates and infant death certificates for 1993 through 1995 were used. Birth weight-specific neonatal mortality rates among 2375 very low birth weight infants were estimated and analyzed by race and by level of perinatal services at the hospital of birth. Rates were compared with chi2 analysis. RESULTS: Seventy-eight percent of very low birth weight deliveries occurred in level III hospitals. The overall neonatal mortality rate was 178 deaths/1000 very low birth weight live births. Neonatal mortality rates, adjusted for birth weight and race, were significantly higher (P < .05) for infants born in level I hospitals (267 deaths/1000 live births), all level II hospitals (232 deaths/1000 live births), and level II hospitals with neonatologists (213 deaths/1000 live births) than for infants born in level III centers (146 deaths/1000 live births). CONCLUSION: Very low birth weight infants are more likely to survive if born in level III hospitals than in level I or II facilities, with or without neonatologists. Obstetric providers should support public health efforts and perinatal health systems to ensure that all women have access to a strong system of risk-appropriate perinatal care.

The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: We sought to estimate the risk of spontaneous preterm birth in parous women by use of obstetric history, fetal fibronectin, and sonographic cervical length. STUDY DESIGN: The probability of spontaneous preterm birth before 35 weeks' gestation was estimated from a logistic regression model with data from 1282 parous women analyzed according to gestational age at the most recent prior delivery (prior preterm birth at 18 to 26 weeks, 27 to 31 weeks, 32 to 36 weeks, and > or = 37 weeks' gestation), fetal fibronectin status (positive = > or = 50 ng/dl), and cervical length by percentile groups (< or = 10th = < or = 25 nm, 10th to 50th = 26 to 35 mm, and > 50th = > 35 mm) measured at 22 to 24 weeks' gestation. Fibronectin and cervical length results were blinded for clinical care. RESULTS: Among fetal fibronectin positive women with a prior preterm birth, the estimated recurrence risk of preterm birth < 35 weeks' gestation was approximately 65% when the cervix was < or = 25 mm, 45% when the cervix was 26 to 35 mm, and 25% when the cervix was > 35 mm at 24 weeks' gestation. For fetal fibronectin negative women with a prior preterm birth, the recurrence risk was 25% when the cervix was < or = 25 mm, 14% when the cervix was 26 to 35 mm, and 7% when the cervix was > 35 mm. The risk of preterm birth was increased among women with a history of preterm delivery but was not influenced by the gestational age at delivery of the most recent preterm birth. CONCLUSION: The recurrence risk of spontaneous preterm birth varies widely according to fetal fibronectin and cervical length. Cervical length and fetal fibronectin results had distinct and significant effects on the recurrence risk of preterm birth. Predicted recurrence risk is increased by twofold to fourfold in women with a positive compared with a negative fetal fibronectin, and it increases as cervical length shortens in both fetal fibronectin-positive and fetal fibronectin-negative women. These data may be useful to care for women with a history of preterm birth and to design studies to prevent recurrent premature delivery.

Fetal anomaly detection by second-trimester ultrasonography in a tertiary center.

OBJECTIVE: Our purpose was to determine the relative accuracy of indicated versus screening second-trimester ultrasonography for detection of fetal anomalies and to assess the cost effectiveness of anomaly screening. STUDY DESIGN: The study population consisted of 2031 pregnant women with singleton gestations who prospectively underwent ultrasonographic scanning between 15 and 22 weeks and received complete obstetric care at the Medical University of South Carolina between July 1, 1993, and June 30, 1996. Patients were divided into two groups: (1) indicated and (2) screening. The cost of screening ultrasonography was compared with the cost of newborn care for selected anomalous fetuses. RESULTS: Forty-seven fetuses (2.3%) were diagnosed by ultrasonography as having a major anomaly: 8.6% in the indicated group and 0.68% in the screening group (p=0.001). The sensitivity for detecting the anomalous fetus was 75.0% overall: 89.7% in the indicated group and 47.6% in the screening group (p=0.001). Of the 47 patients diagnosed with fetal anomalies, 11 (23.4%) chose pregnancy termination; of the 35 (74.5%) live-born anomalous infants, 29 (82.9%) were discharged alive. Projected newborn cost savings offset the cost of routine midtrimester screening. CONCLUSIONS: Detection of anomalous fetuses was significantly better in the indicated compared with the screening group. Nevertheless, routine ultrasonographic screening appeared cost-effective in our population.

The preterm prediction study: risk factors for indicated preterm births. Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development.

OBJECTIVE: Preterm births occur for many different reasons. Most efforts to identify risk factors for preterm births either ignore cause and consider preterm births as a single entity or examine risk factors for spontaneous preterm births. We performed this study to examine risk factors for indicated preterm births, which constitute more than one quarter of all preterm births. STUDY DESIGN: The study included 2929 women evaluated at 24 weeks' gestation at 10 centers. Information was gathered about demographic factors, socioeconomic status, home and work environments, drug and alcohol use, and medical history. In addition vaginal samples were evaluated for fetal fibronectin and bacterial vaginosis and cervical length was measured by transvaginal ultrasonography. Associations with indicated preterm birth were evaluated by univariate tests and by multivariable analysis with logistic regression. RESULTS: Of the women studied at 24 weeks' gestation 15.3% were delivered of their infants at <37 weeks' gestation. Of these deliveries, 27.7% were indicated preterm births. Risk factors in the final multivariable model were, in order of decreasing odds ratios, mullerian duct abnormality (odds ratio 7.02), proteinuria at <24 weeks' gestation (odds ratio 5.85), history of chronic hypertension (odds ratio 4.06), history of previous indicated preterm birth (odds ratio 2.79), history of lung disease (odds ratio 2.52), previous spontaneous preterm birth (odds ratio 2.45), age >30 years (odds ratio 2.42), black ethnicity (odds ratio 1.56), and working during pregnancy (odds ratio 1.49). Alcohol use in pregnancy was actually associated with a lower risk of indicated preterm birth (odds ratio 0.35). CONCLUSION: The risk factors found in this analysis tend to be different from those associated with spontaneous preterm birth.

Glucometer analysis of one-hour glucose challenge samples.

OBJECTIVE: Our purpose was to explore a cost-saving measure for diabetes screening by using glucometer testing on venous whole blood obtained after a 1-hour glucose challenge test. Glucometer results falling above an upper threshold would predict abnormal plasma values and mandate a glucose tolerance test; results below the lower threshold would predict normal plasma values and avoid further testing. Results between the thresholds would require traditional plasma analysis. STUDY DESIGN: We performed a prospective cohort study on 222 consecutive pregnant women. A standard 50 gm glucose screen was performed with venous blood drawn at 1 hour. We immediately removed a drop of whole blood from the venous sample and analyzed it on a portable glucometer, Accu-Chek III. The remaining sample was submitted immediately for routine plasma analysis. All values were obtained on the same glucometer, which was calibrated daily in our clinic laboratory. Regression analysis was performed on 129 samples to select the two thresholds. The selected thresholds were then applied prospectively to the next 93 consecutive samples for validation. RESULTS: Excellent correlation (r = 0.9045) exists between the glucometer and laboratory values. Glucometer threshold values of 110 mg/dl and 155 mg/dl were selected because they predicted plasma values < 135 mg/dl or > 135 mg/dl with 95% certainty, respectively. Prospectively, the thresholds were completely accurate in classifying the values. CONCLUSION: Venous whole blood assayed by glucometer can reliably predict an elevated or normal automated plasma glucose value. By applying thresholds, three fourths of all patients can immediately receive reassuring information, whereas the patients with poorest glucose tolerance are immediately identified and diagnostic testing is scheduled. Additionally, our model reduces the number of automated laboratory studies by 80% and reduces the cost of diabetic screening.

Vitamin and mineral supplement prior to and during pregnancy.

Vitamin and mineral supplementation during pregnancy is a common practice in the United States, but is often unnecessary. An assessment of dietary practices is recommended for all women to evaluate the need for improved diet or vitamin and mineral supplementation. Most women do not receive enough folic acid from dietary sources and should take a folic acid supplement in the preconception period to minimize their risk of neural tube defect. Iron supplementation is recommended in the second and third trimester. A multivitamin and mineral supplement is recommended during pregnancy for women who do not ordinarily consume an adequate diet and for women in high-risk categories, such as multifetal gestation, heavy cigarette smokers, and alcohol and drug abusers.

The preterm prediction study: patterns of cervicovaginal fetal fibronectin as predictors of spontaneous preterm delivery. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to determine how various temporal patterns of fetal fibronectin positivity from 24 to 30 weeks predict subsequent fetal fibronectin test results and spontaneous preterm delivery. STUDY DESIGN: A total of 2929 women had vaginal and cervical fetal fibronectin tests obtained at least once at 24, 26, 28, or 30 weeks, and 1870 women had tests performed at all four gestational ages. Fetal fibronectin values > or = 50 ng/ml were considered positive. Various patterns of positive and negative tests were evaluated for prediction of (1) whether the next fetal fibronectin test would be positive or negative and (2) the percent of women with a spontaneous preterm delivery > or = 4 weeks after the last fetal fibronectin test at < 30, < 32, < 35, and < 37 weeks' gestational age. RESULTS: Women with previous negative test results had only a 3% chance of a subsequent positive test result; however, if the last test result was positive, 29% of the next tests were positive. Of the 1870 women with tests at 24, 26, 28, and 30 weeks, 89% had all negative results, 8.4% had one positive result, 1.8% had two positive results, and 0.8% had three or four positive results. The higher the percent of positive tests at 24 to 26 weeks, at 28 to 30 weeks, or at 24 to 30 weeks, the greater the risk of subsequent spontaneous preterm birth. As an example, the risk of spontaneous preterm birth at < 30 weeks for women with two negative fetal fibronectin test results at 24 and 26 weeks was 0.3% versus 16% for women with two positive results. CONCLUSION: The presence of a positive cervical or vaginal fetal fibronectin test result predicts subsequent positive fetal fibronectin positivity and subsequent spontaneous preterm birth. The greater the percent of positive results, the higher is the risk of spontaneous preterm birth. After a positive test result, two negative results are required before the risk of spontaneous preterm birth returns to baseline.

The preterm prediction study: a clinical risk assessment system.

OBJECTIVE: Our aims were to develop a risk assessment system for the prediction of spontaneous preterm delivery using clinical information available at 23 to 24 weeks' gestation and to determine the predictive value of such a system. STUDY DESIGN: A total of 2929 women were evaluated between 23 and 24 weeks' gestation at 10 centers. Demographic factors, socioeconomic status, home and work environment, drug and alcohol use, and medical history were evaluated. Information regarding symptoms, cultures, and treatments in the current pregnancy were ascertained. Anthropomorphic and cervical examinations were performed. Univariate analysis and multivariate logistic regression were performed in a random selection, constituting 85% of the study population. The derived risk assessment system was applied to the remaining 15% of the population to evaluate its validity. RESULTS: A total of 10.4% of women were delivered of preterm infants. The multivariate models for spontaneous preterm delivery were highly associated with spontaneous preterm delivery (p < 0.0001). A low body mass index (<19.8) and increasing Bishop scores were significantly associated with spontaneous preterm delivery in nulliparous and multiparous women. Black race, poor social environment, and work during pregnancy were associated with increased risk for nulliparous women. Prior obstetric outcome overshadowed socioeconomic risk factors in multiparous women with a twofold increase in the odds of spontaneous preterm delivery for each prior spontaneous preterm delivery. Current pregnancy symptoms, including vaginal bleeding, symptomatic contractions within 2 weeks, and acute or chronic lung disease were variably associated with spontaneous preterm delivery in nulliparous and multiparous women. When the system was applied to the remainder of the population, women defined to be at high risk for spontaneous preterm delivery (> or = 20% risk) carried a 3.8-fold (nulliparous women) and 3.3-fold (multiparous women) higher risk of spontaneous preterm delivery than those predicted to be at low risk. However, the risk assessment system identified a minority of women who had spontaneous preterm deliveries. The sensitivities were 24.2% and 18.2% and positive predictive values were 28.6% and 33.3%, respectively, for nulliparous and multiparous women. CONCLUSIONS: Although it is possible to develop a graded risk assessment system that includes factors that are highly associated with spontaneous preterm delivery in nulliparous and multiparous women, such a system does not identify most women who subsequently have a spontaneous preterm delivery. This system has investigational value as the basis for evaluating new technologies designed to identify at-risk subpopulations.

Prognostic significance of prior preterm twin delivery on subsequent singleton pregnancy.

OBJECTIVE: Our purpose was to determine whether preterm birth of twins is associated with an increased risk of preterm birth in a subsequent singleton pregnancy. STUDY DESIGN: The Medical University of South Carolina perinatal database was accessed to identify a cohort of patients who were delivered of twins followed by a singleton gestation (1981 to 1993). Maternal transports were excluded to minimize referral bias. Preterm birth was defined as < 37 weeks' gestation. Relative risks with 95% confidence intervals were calculated. RESULTS: One hundred forty-four patients were identified who were delivered of twins followed by a singleton gestation. Preterm delivery occurred in 86 (59.7%) of the twins and 21 (14.6%) of the subsequent singletons. Preterm birth of twins was associated with a significantly increased risk of preterm delivery in a subsequent singleton pregnancy (relative risk 2.87, 95% confidence interval 1.02 to 8.09). In the subset of women who were delivered of twins at < 30 weeks' gestation, 42% of the subsequent singletons were delivered preterm (relative risk 6.11, 95% confidence interval 2.07 to 18.02). The relative risk of preterm birth of a singleton after delivery of twins between 30 and 34 weeks' gestation was 3.63 (95% confidence interval 1.02 to 12.92). However, if the preceding twins delivered between 34 and 37 weeks' gestation, the relative risk of preterm birth of the subsequent singleton was not significantly increased (relative risk 1.42, 95% confidence interval 0.40 to 5.01). CONCLUSIONS: Preterm birth of twins before 34 weeks' gestation is associated with a significant risk for preterm delivery in a subsequent singleton pregnancy. The magnitude of risk increases with decreasing gestational age of the preceding twin delivery.

Randomized Clinical Trial of Azithromycin vs. Erythromycin for the Treatment of Chlamydia Cervicitis in Pregnancy.

OBJECTIVE: The purpose of this study was to prospectively test the null hypothesis that there is no difference in the clinical effectiveness of azithromycin and erythromycin for the treatment of chlamydia cervicitis in pregnancy. METHODS: All antepartum obstetrical patients underwent routine screening for chlamydia cervicitis using a DNA probe assay (Gen-Probe Pace, San Diego, CA). Women who tested positive for chlamydia cervicitis were prospectively randomized to receive either azithromycin 1 g orally at enrollment, or erythromycin 500 mg orally 4 times a day for 7 days. Sexual partners were referred to the county health department for evaluation and treatment. A test of cure was repeated in 2 weeks. RESULTS were analyzed by chi-square analysis and Fisher's exact test when indicated. RESULTS: One hundred forty women tested positive for chlamydia cervicitis and agreed to randomization. There were 4 (6.2%) treatment failures in the azithromycin group and 18 (27.7%) in the erythromycin group (P = 0.005). Gastrointestinal side effects were reported by 42 (65.5%) of the women taking erythromycin, but only 12 (19.4%) of those taking azithromycin (P < 0.002). Gastrointestinal side effects and resultant noncompliance were significantly related to treatment failure with erythromycin. CONCLUSIONS: The findings of this study support the conclusion that a single dose of azithromycin is a significantly more effective and better tolerated treatment regimen for chlamydia cervicitis in pregnancy than erythromycin which is currently recommended.

Predictive value of antepartum ultrasound examination for anomalies in twin gestations.

The purpose of this study was to evaluate the accuracy of antenatal ultrasonography in the detection of fetal anomalies among twin gestations cared for in a specialized antepartum twin clinic. A retrospective study was performed of 245 consecutive twin gestations followed in our twin clinic. The sensitivity, specificity and diagnostic indices of ultrasound to detect prenatal anomalies in the 490 infants delivered from July 1988 to October 1994 were determined. Fourteen infants had isolated congenital anomalies, and ten had multiple anomalies. The overall prevalence of congenital anomalies was 4.9%. Antepartum ultrasound examination had a sensitivity of 88% and a specificity of 100% for the detection of an anomalous infant, with a positive predictive value of 100% and a negative predictive value of 99%. The sensitivity of ultrasound for each individual anomaly within the cohort was 82%, with 100% specificity, 100% positive predictive value, and 98% negative predictive value. Our conclusions are that serial antepartum ultrasound examination of twins for congenital anomalies in our institution is very specific, with high positive and negative predictive values. The sensitivity, while also excellent, has limitations, which should be discussed with the patient.