Faculty Bibliography

OBJECTIVE:Our purpose was to determine the incidence of placenta previa based on the available epidemiologic evidence and to quantify the risk of placenta previa based on the presence and number of cesarean deliveries and a history of spontaneous and induced abortion. STUDY DESIGN/METHODS:We reviewed studies on placenta previa published between 1950 and 1996 on the basis of a comprehensive literature search with use of MEDLINE and by identifying studies cited in the references of published reports. Studies were chosen for inclusion in the metaanalysis if the incidence of placenta previa and its cross-classification with either prior cesarean delivery or abortions (both spontaneous and induced) or both were available. We also extracted details about the study design (case-control or cohort study) and place where they were conducted (United States or other countries). Published case reports dealing with placenta previa and studies relating to abruptio placentae were excluded from this review. We also restricted the search to studies published in English. No attempts were made to locate any unpublished studies. Data from studies identified during the literature search were reviewed and abstracted by a single author. In case of discrepancies or when the information presented in a study was unclear, abstraction by a (blinded) second reviewer was sought to resolve the discrepancy. RESULTS:Data on the incidence of placenta previa and its associations with previous cesarean delivery and abortions were abstracted. Subgroup analyses were performed to identify potential sources of heterogeneity by study design and place where they were conducted. Statistical methods used for the metaanalysis included the fixed-effects logistic regression model, whereas potential sources of heterogeneity among studies were evaluated by fitting random-effects models. The tabulation of 36 studies identified a total of 3.7 million pregnant women, of whom 13,992 patients were diagnosed with placenta previa. The reported incidence of placenta previa ranged between 0.28% and 2.0%, or approximately 1 in 200 deliveries. Women with at least one prior cesarean delivery were 2.6 (95% confidence interval 2.3 to 3.0) times at greater risk for development of placenta previa in a subsequent pregnancy. The results varied by study design, with case-control studies showing a stronger relative risk (relative risk 3.8, 95% confidence interval 2.3 to 6.4) than cohort studies did (relative risk 2.4, 95% confidence interval 2.1 to 2.8). Four studies, encompassing 170,640 pregnant women, provided data on the number of previous cesarean deliveries. These studies showed a dose-response pattern for the risk of previa on the basis of the number of prior cesarean deliveries. Relative risks were 4.5 (95% confidence interval 3.6 to 5.5) for one, 7.4 (95% confidence interval 7.1 to 7.7) for two, 6.5 (95% confidence interval 3.6 to 11.6) for three, and 44.9 (95% confidence interval 13.5 to 149.5) for four or more prior cesarean deliveries. Women with a history of spontaneous or induced abortion had a relative risk of placenta previa of 1.6 (95% confidence interval 1.0 to 2.6) and 1.7 (95% confidence interval 1.0 to 2.9), respectively. Substantial heterogeneity in the results of the metaanalysis was noted among studies. CONCLUSION/CONCLUSIONS:There is a strong association between having a previous cesarean delivery, spontaneous or induced abortion, and the subsequent development of placenta previa. The risk increases with number of prior cesarean deliveries. Pregnant women with a history of cesarean delivery or abortion must be regarded as high risk for placenta previa and must be monitored carefully. This study provides yet another reason for reducing the rate of primary cesarean delivery and for advocating vaginal birth for women with prior cesarean delivery.

OBJECTIVE: Our purpose was to compare various noninvasive stress techniques for their ability to elicit ultrasonographic cervical changes and to determine their efficacy in detecting ultrasonographic cervical incompetence. STUDY DESIGN: Eighty-nine patients at risk for pregnancy loss and preterm birth underwent ultrasonographic evaluation of the cervix at least twice between 15 and 24 weeks of gestation. With use of a transvaginal probe, the funnel width, funnel length, and endocervical canal length were measured in millimeters with the patient in the supine position. These measurements were repeated after three stress tests: transfundal pressure, coughing, and standing. The difference between the baseline measurements and those obtained after the stress tests were determined. A positive response to stress was defined as any decrease in endocervical canal length accompanied by an increase in funnel width and length. Improvement was defined by any increase in endocervical canal length accompanied by a decrease in funnel width and length. Cervical incompetence was defined as the presence of progressive cervical changes on ultrasonographic examinations with final endocervical canal length measurements below 26 mm. Results are reported as median (range). RESULTS: The number of positive cervical responses to transfundal pressure (19%, 17/89) was significantly greater than to coughing (3.3%, 3/89) and standing (9.0%, 8/89). The status of the cervix improved with standing in three cases, whereas this was not seen with transfundal pressure or coughing. There was no case where there was a positive response to standing or coughing and not to transfundal pressure. When the changes in funnel width and length and endocervical canal length as a result of transfundal pressure and standing in the 17 cases that responded to transfundal pressure, transfundal pressure resulted in a significantly greater increase in funnel width and length and a decrease in endocervical canal length. The efficacy of transfundal pressure in detecting the cervix that had subsequent progressive changes on ultrasonography was as follows: sensitivity 83.3%, specificity 97.2%, and positive and negative predictive values 88.2% and 95.8%, respectively. The efficacy of coughing was sensitivity 16.7%, specificity 100%, and positive and negative predictive values 100% and 85.5%, respectively. The efficacy of standing was sensitivity 33.3%, specificity 97.2%, and positive and negative predictive values 75% and 85.2%, respectively. Similar results were obtained when the analysis was confined to 37 patients who had a prior history of a midtrimester miscarriage. CONCLUSION: Transfundal pressure was the most effective technique in eliciting cervical changes during the active assessment of the cervix during pregnancy and the most sensitive in detecting the cervix that had progressive second-trimester cervical shortening during pregnancy, compared with coughing or standing position

OBJECTIVE: To determine the utilization rate of second-trimester genetic sonogram and its role in influencing the decision for amniocentesis in women at increased risk for fetal trisomy 21. METHODS: From November 1, 1993, to December 31, 1996, a second-trimester genetic sonogram or only genetic amniocentesis (as a first choice) were offered to pregnant women referred to our institution who were at increased risk for fetal trisomy 21. RESULTS: During the study period, 2089 women were referred to our unit for genetic prenatal diagnosis; of these, 1426 (68%) chose only genetic amniocentesis, and 663 (32%) chose a genetic sonogram as their first option. The yearly utilization rates of genetic sonogram were two of 477 or 0.4% for 1993, 82 of 495 or 16.6% for 1994, 251 of 523 or 48.0% for 1995, and 328 of 594 or 55.2% for 1996. Adjusting for potential confounders, multivariable logistic regression analysis showed that the most important factors associated with the women's decision to undergo genetic amniocentesis were three or more ultrasound markers present (relative risk [RR] 189.5, 95% confidence interval [CI] 37.1, 980.0), two ultrasound markers present (RR 47.2, 95% CI 9.8, 267.8), one ultrasound marker present (RR 12.7, 95% CI 5.5, 29.7), and abnormal serum biochemistry (RR 3.0, 95% CI 1.0, 8.9). CONCLUSION: The increasing utilization trend, in conjunction with the fact that an abnormal sonogram was the most influential factor in women's decision to undergo genetic amniocentesis, suggests that genetic sonogram services for detection of trisomy 21 should be added to the armamentarium of all prenatal diagnostic centers

This study was designed to evaluate the relationship of suspected early neonatal sepsis to umbilical artery and vein levels of interleukin-6 (IL-6) and soluble intracellular adhesion molecule-1 (sICAM-1). Umbilical artery and vein samples from 17 preterm and 6 term pregnancies were assayed for IL-6 (pg/ml) and sICAM-1 (ng/ml). Neonates were categorized as having probable or suspected sepsis vs. no sepsis within 3 days of birth. Levels of IL-6 and sICAM-1 were evaluated based on sepsis status. Neonatal hematologic parameters were correlated with umbilical artery (ua) and vein (uv) levels of IL-6 and sICAM-1. Sensitivity, specificity, positive and negative predictive values for detecting neonates having probable or suspected early sepsis were calculated. There were significant differences of IL-6 levels between suspected sepsis and no infants in the umbilical artery (P < 0.002) and vein (P < 0.0001). The sensitivity, specificity, positive and negative predictive values for detection of suspected early neonatal sepsis using umbilical artery IL-6 levels > 7 pg/ml were 88.5%, 66.6%, 58.8%, 91%, and for umbilical vein levels > 7 pg/ml these values were 88.5%, 93.3%, 88.5%, and 93.3%. Umbilical artery and vein IL-6 levels correlated with both absolute band counts and immature/total neutrophil ratios. sICAM-1 levels were not affected by designated sepsis status. Umbilical cord blood IL-6 (but not sICAM-1) is potentially useful as a marker for suspected early neonatal sepsis.

OBJECTIVE: To evaluate the effect of narcotic and non-narcotic continuous epidural anesthesia on intrapartum fetal heart rate (FHR) tracings as measured by computer analysis. METHODS: We studied 37 women with uncomplicated pregnancies at term with reactive FHR tracings. The women were randomized to receive epidural anesthesia with either bupivicaine with fentanyl or bupivicaine alone. One-hour FHR tracings were obtained before epidural anesthesia. Thirty minutes after the initial bolus of the epidural a repeat computer analysis of 60-minute FHR tracing was obtained. Median values are reported for FHR parameters with statistical analysis performed by the Mann-Whitney U and Wilcoxon signed rank tests where appropriate. A power calculation was performed using a power of 90% to determine a required sample size of 28 patients. Statistical significance was set at P < .05. RESULTS: In early first stage of labor, there was no significant difference in pre- and postepidural anesthesia FHR baseline, accelerations of 10 and 15 beats per minute, episodes of high and low variation, and short- and long-term variation when using either narcotic or non-narcotic anesthetic agents. CONCLUSIONS: Thus, the clinician can consider the use of narcotic as well as non-narcotic continuous epidural anesthesia in the dosages used in our study with its attendant advantages without fear of obscuring the fetal heart rate tracing

OBJECTIVE: To investigate which second-trimester ultrasound markers for aneuploidy are the most diagnostically efficient in detecting fetal trisomy 21. METHODS: All second-trimester genetic sonograms performed since November 1, 1992 for women at increased risk for fetal trisomy 21 were analyzed retrospectively. Statistical analysis included descriptive statistics, the test of proportions, and univariate and multivariable logistic regression analysis using trisomy 21 as the dependent variable and ten aneuploidy ultrasound markers as independent variables. RESULTS: There were 581 normal fetuses, 23 with trisomy 21 and four with other chromosomal abnormalities. When one or more abnormal ultrasound markers were present, the sensitivity and false-positive rate for trisomy 21 were 87% and 13.4%, respectively. After adjusting for confounders, multivariate logistic regression analysis showed the best combination of ultrasound markers for detecting trisomy 21 to be nuchal fold thickening (relative risk [RR] 85.5; 95% confidence interval [CI] 20.4, 357.7), pyelectasis (RR 25.2; 95% CI 6.7, 95.0), and short humerus (RR 20.4; 95% CI 4.5, 92.1). The model combining these three ultrasound markers yielded a sensitivity of 87% and a false-positive rate of 6.7%. CONCLUSION: By using only three ultrasound markers (combination of nuchal fold thickening, pyelectasis, and short humerus) the false-positive rate is decreased from 13.4% to 6.7% without any compromise in the sensitivity (87%). The clinical usefulness of evaluating the various second-trimester ultrasound markers needs to be evaluated in prospective studies

The purpose of our study was to examine the relationship between insulin resistance and blood pressure during pregnancy and to determine to what extent insulin resistance is related to the subsequent development of pregnancy-induced hypertension. The study population consisted of 292 women who had serum insulin, glucose and insulin-glucose ratios determined at 26-28 weeks gestation in a fasting state and 1 hr after a 50-g oral glucose challenge. These were compared with blood pressures at 26-28 weeks gestation and in the late third trimester. A statistically significant correlation exists overall between (1) blood pressure at 26-28 weeks gestation and both fasting insulin and insulin-glucose ratios, as well as (2) systolic blood pressure at term and fasting insulin levels. However, when controlled for confounding variables including body mass index, race and age, no statistically significant relationship remained. The metabolic variables in patients with pregnancy-induced hypertension were not statistically different from the normotensive patients. In conclusion, this study demonstrates that insulin resistance and hyperinsulinemia are not major determinants of blood pressure during pregnancy.

OBJECTIVE:To assess intrauterine growth in a series of nine fetuses diagnosed with Beckwith-Wiedemann syndrome. METHODS:Infants confirmed postnatally to have Beckwith-Wiedemann syndrome were identified from records maintained in the Division of Clinical Genetics. Antenatal ultrasound and birth records were evaluated. Head circumference (HC), abdominal circumference (AC), and estimated fetal weight (EFW) were assigned percentiles based on gestational age. Newborn HC and birth weight were also assigned percentiles. Polyhydramnios was diagnosed using either amniotic fluid index or documented subjective assessment. RESULTS:Nine infants with Beckwith-Wiedemann syndrome had antenatal ultrasound examinations. Seven of these had more than one examination. Two infants were suspected to have Beckwith-Wiedemann syndrome in utero. Important ultrasound findings included omphalocele (four), enlarged liver and kidneys (one), and enlarged liver (one). Fetal tongue protrusion on ultrasound was not identified in any fetus. Six of nine fetuses (66%) with ultrasound examinations after 25 weeks' gestation had polyhydramnios. Evaluation of the fetal HC, AC, and EFW percentiles demonstrated that fetuses with Beckwith-Wiedemann syndrome may exhibit accelerated growth as early as 25-30 weeks' gestation, but may exceed the 90th percentile only after 36 weeks' gestation. CONCLUSIONS:Fetuses with omphalocele, polyhydramnios, and an AC less than the 90th percentile may have Beckwith-Wiedemann syndrome. Polyhydramnios and accelerated growth beginning between 25 and 36 weeks' gestation, even without omphalocele, should alert the physician to the possibility of Beckwith-Wiedemann syndrome.

Advances in perinatal and neonatal health care over the past few decades have resulted in a substantial reduction in perinatal mortality. Some of this improvement has been attributed to antepartum fetal surveillance techniques. The primary objective of antepartum fetal surveillance techniques is to avoid fetal deaths. An ideal secondary objective is to avoid neonatal complications related to intrauterine asphyxia. In this article, some of the difficulties in evaluating existing antepartum fetal surveillance techniques are highlighted. Some of the epidemiological methods for evaluating a screening test are reviewed and their importance discussed with reference to fetal testing procedures. Lastly, the possibility of considering indication-specific fetal testing to improve perinatal morbidity is examined.

OBJECTIVE: Our purpose was to observe the evolution of the endocervical canal length in women at risk for cervical incompetence after a positive response to transfundal pressure. STUDY DESIGN: Ten women at risk for cervical incompetence had a midtrimester cervical evaluation with transvaginal ultrasonography and transfundal pressure. With a transvaginal probe, the endocervical canal length was first measured. Transfundal pressure was then applied and the endocervical canal length was remeasured. All patients had a positive response to transfundal pressure as defined by a decrease in endocervical canal length after application of transfundal pressure. At the initial evaluation the digital examination of the cervix had revealed a closed and long cervix in all 10 cases. In 9 of the 10 patients repeat examinations were performed until the endocervical canal length progressively shortened to <10 mm or the digital examination revealed a dilated cervix. The endocervical canal lengths after application of transfundal pressure from the first and last examination were compared. One patient was lost to follow-up, but the obstetric outcome was available. RESULTS: The median time interval between the first and final examination was 7 (2 to 20) days in 9 of the patients. The median (range) gestational age at the first and final examination was 19.0 (15 to 22) weeks (n = 10) and 20.5 (18 to 24) weeks (n = 9), respectively. There was significant shortening of the endocervical canal length from the first to the last examination; 12.2 (4 to 20) mm (n = 10) versus 0.0 (0 to 9.5) mm (n = 9), p = 0.008. Six patients had membranes at the external cervical os before application of transfundal pressure at the last examination. The one patient lost to ultrasonographic follow-up had a pregnancy loss at 23 weeks of gestation, 6 weeks after a positive response to transfundal pressure. CONCLUSION: In patients at risk for cervical incompetence, shortening of the endocervical canal length in response to transfundal pressure requires treatment with a cervical cerclage because it is associated with progressive cervical changes over 1 to 3 weeks