Indications for caesarean sections at ≥34 weeks among nulliparous women and differential composite maternal and neonatal morbidity.

OBJECTIVE: To compare composite maternal and neonatal morbidities (CMM, CNM) among nulliparous women with primary indications for caesarean section (CS) as acute clinical emergency (group I; ACE), non-reassuring fetal heart rate (group II) and arrest disorder (group III). DESIGN: A multicentre prospective study. SETTING: Nineteen academic centres in the USA, with deliveries in 1999-2002. POPULATION: Nulliparous women (n = 9829) that had CS. METHODS: Nulliparous women undergoing CS for three categories of indications were compared using logistic regression model, adjusted for five variables. MAIN OUTCOME MEASURES: CMM was defined as the presence of any of the following: intrapartum or postpartum transfusion, uterine rupture, hysterectomy, cystotomy, ureteral or bowel injury or death; CNM was defined as the presence of any of the following: umbilical arterial pH <7.00, neonatal seizure, cardiac, hepatic, renal dysfunction, hypoxic ischaemic encephalopathy or neonatal death. RESULTS: The primary reasons for CS were ACE in 1% (group I, n = 114) non-reassuring FHR in 29% (group II; n = 2822) and failed induction/dystocia in the remaining 70% (group III; n = 6893). The overall risks of CMM and CNM were 2.5% (95% confidence intervals, CI, 2.2-2.8%) and 1.9% (95% CI 1.7-2.2), respectively. The risk of CMM was higher in group I than in group II (RR 4.1, 95% CI 3.1, 5.3), and group III (RR 3.2, 95% CI 2.7, 3.7). The risk of CNM was also higher in group I than in group II (RR 2.8, 95% CI 2.3, 3.4) and group III (RR 14.1, 95% CI 10.7, 18.7). CONCLUSIONS: Nulliparous women who have acute clinically emergent caesarean sections are at the highest risks of both composite maternal and neonatal morbidity and mortality.

The impact of route of delivery and presentation on twin neonatal and infant mortality: a population-based study in the USA, 1995-97.

OBJECTIVE: We examined whether the route of delivery for near-term (> or = 34 weeks' gestation) twins, as candidates for vaginal delivery, affected neonatal and infant mortality rates. We further evaluated whether these mortality rates were modified by fetal presentation. METHODS: A population-based retrospective cohort study based on the matched multiple births data in the USA (1995-97) was performed. Analyses were restricted to non-malformed liveborn twins delivered at (> or = 34 weeks' gestation. Twins with breech-breech and breech-vertex presentations were excluded, since they are not candidates for vaginal delivery. Neonatal mortality rates (death within the first 27 days) and post-neonatal mortality rates (death between 28 and 365 days) per 1000 twin live births, by route of delivery and fetal presentation, were derived. The associations between neonatal mortality, post-neonatal mortality and the route of delivery for vertex-breech versus vertex-vertex presentations were expressed based on relative risks (RR) and 95% confidence intervals (CI) derived from logistic regression models based on the method of generalized estimating equations. RESULTS: Of the 177,622 twins analyzed, 87% (n = 154,531) presented as vertex-vertex. Fifty-five per cent (n = 97,692) of twins were both delivered vaginally, 41% (n = 72,825) were both delivered by Cesarean section and, of the remaining 4% (n = 7,105), the first twin was delivered vaginally and the second by Cesarean section. Twins with vertex-breech presentations delivered by Cesarean-cesarean sections, as well as those with vertex-vertex presentations delivered vaginally, had the lowest neonatal mortality rate (1.6 per 1000 live births). The highest neonatal mortality rate in the vertex-breech pairs occurred with vaginal-Cesarean deliveries (2.7 per 1000 live births). Among twins with vertex-vertex presentations, twins delivered via the vaginal-Cesarean route experienced the highest neonatal mortality (3.8 per 1000 live births). The RR for neonatal mortality in this group was 2.24 (95% CI 1.35, 3.72) compared with twins both delivered vaginally. CONCLUSION: Route of delivery and fetal presentation both confer an impact on twin infant mortality rates. Strategies to reduce discordant routes in complicated vaginal deliveries may lead to improved neonatal survival.

Maternal age and risk of fetal death in singleton gestations: USA, 1995-2000.

OBJECTIVE: To determine the magnitude of risk for fetal death among singleton pregnancies in relation to maternal age, and to compare the risks with other common indications for fetal testing. STUDY DESIGN: We performed a retrospective cohort analysis of singleton births delivered between 1995 and 2000 using the US linked birth/infant death data. Gestational age at < 24 weeks and fetuses with anomalies were excluded. Fetal death rates at > or = 24 and > or = 32 weeks were calculated among women aged 15-19, 20-24, 25-29, 30-34, 35-39, 40-44 and 45-49 years, as well as for other common indications for testing: chronic and pregnancy-induced hypertension, diabetes and small-for-gestational age (SGA). The association between maternal age and fetal deaths was derived after adjusting for potential confounders through multivariable logistic regression models. Relative risks (RR) and 95% confidence intervals (CI) were derived from these models after adjusting for the effects of gravidity, race, marital status, prenatal care, education, smoking and placental abruption. RESULTS: Among the 21,610,873 singleton births delivered at > or = 24 weeks, fetal deaths occurred in 58,580 (2.7 per 1000). Births to young (15-19 years) and older (> or = 35 years) women comprised 12.6% and 11.4%, respectively. Compared with women aged 20-24 years, young women did not experience an increased risk of fetal death. However, increasing rates of fetal death at > or = 24 and at > or = 32 weeks were seen with increasing maternal age. The RR for fetal death at > or = 24 and at > or = 32 weeks among women 35-39 years were 1.21 and 1.31, respectively, while the RRs were 1.62 and 1.67 among women aged 40-44 years. Women 45-49 years were 2.40-fold (95% CI 1.77, 3.27) and 2.38-fold (95% CI 1.64, 3.46) as likely to deliver a stillborn fetus at > or = 24 weeks and > or = 32 weeks, respectively. RRs for fetal death at > or = 24 and > or = 32 weeks for hypertensive disease, diabetes, and SGA ranged between 1.46 and 4.95. CONCLUSION: Fetal deaths are increased among older women (> or = 35 years). Fetal testing in women of advanced maternal age may be beneficial.

Relationship among placenta previa, fetal growth restriction, and preterm delivery: a population-based study.

OBJECTIVE: To examine the independent contributions of prematurity and fetal growth restriction to low birth weight among women with placenta previa. METHODS: A population-based, retrospective cohort study of singleton live births in New Jersey (1989-93) was performed. Mother-infant pairs (n = 544,734) were identified from linked birth certificate and maternal and infant hospital discharge summary data. Women diagnosed with previa were included only if they were delivered by cesarean. Fetal growth, defined as gestational age-specific observed-to-expected mean birth weight, and preterm delivery (before 37 completed weeks) were examined in relation to previa. Severe and moderate categories of fetal smallness and large for gestational age were defined as observed-to-expected birth weight ratios below 0.75, 0.75-0.85, and over 1.15, respectively, all of which were compared with appropriately grown infants (observed-to-expected birth weight ratio 0.86-1.15). RESULTS: Placenta previa was recorded in 5.0 per 1000 pregnancies (n = 2744). After controlling for maternal age, education, parity, smoking, alcohol and illicit drug use, adequacy of prenatal care, maternal race, as well as obstetric complications, previa was associated with severe (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.25, 1.50) and moderate fetal smallness (OR 1.24, 95% CI 1.17, 1.32) births. Preterm delivery was also more common among women with previa. Adjusted OR of delivery between 20-23 weeks was 1.81 (95% CI 1.24, 2.63), and 2.90 (95% CI 2.46, 3.42) for delivery between 24-27 weeks. OR for delivery by each week between 28 and 36 weeks ranged between 2.7 and 4.0. Approximately 12% of preterm delivery and 3.7% of growth restriction were attributable to placenta previa. CONCLUSION: The association between low birth weight and placenta previa is chiefly due to preterm delivery and to a lesser extent with fetal growth restriction. The risk of fetal smallness is increased slightly among women with previa, but this association may be of little clinical significance.

Placental abruption among singleton and twin births in the United States: risk factor profiles.

The authors performed a population-based epidemiologic study to evaluate and contrast risk factor profiles for placental abruption among singleton and twin gestations. Data were derived from linked US birth/infant death files for 1995 and 1996, comprising 7,465,858 singleton births and 193,266 twin births. The authors also evaluated effect modification between smoking and hypertension and the effect of a dose-response relation with number of cigarettes smoked daily on abruption risk. Abruption was recorded in 5.9 per 1,000 singleton births and 12.2 per 1,000 twin births. Risk factors for abruption among singleton and twin births, respectively, included preterm premature rupture of membranes (adjusted relative risks (RRs) = 4.89 and 2.01), eclampsia (RRs = 3.58 and 1.67), anemia (RRs = 2.23 and 2.33), hydramnios (RRs = 2.04 and 1.66), renal disorders (RRs = 1.54 and 2.56), and intrapartum fever (>100 degrees F) (RRs = 1.17 and 1.69). Chronic hypertension (RR = 2.38) and pregnancy-induced hypertension (RR = 2.34) were risk factors for abruption in singleton births but not in twin births. Number of cigarettes smoked daily demonstrated a dose-response trend for abruption risk in singletons and twins. Abruption was more likely to occur among smokers with chronic hypertension (RRs = 4.66 and 3.15) and eclampsia (RRs = 6.28 and 5.08). The authors conclude that abruption is twice as likely to occur in twins as in singletons with differing risk factor profiles. This suggests that abruption in twins may result from different pathophysiologic processes.

Outcome of prenatally diagnosed mild unilateral cerebral ventriculomegaly.

The objective of this study was to determine the frequency of prenatally diagnosed unilateral cerebral ventriculomegaly and also to assess neonatal outcome in infants with this prenatal diagnosis. A computerized ultrasonography database identified fetuses with isolated and nonisolated unilateral cerebral ventriculomegaly from October 1994 to June 1999. The Denver II Developmental Screening Test was used to assess developmental skills. Unilateral cerebral ventriculomegaly was diagnosed in 15 of 21,172 (1 per 1,411) pregnancies. The width of the enlarged lateral ventricle ranged from 1.0 to 1.9 cm. In 10 (67%) of 15 cases unilateral cerebral ventriculomegaly was an isolated finding. Eight of the 14 infants who were born at 36 weeks' gestation or later had postnatal cranial imaging, and ventricular asymmetry was confirmed in 5 (63%). One infant with an arachnoid cyst and cerebral palsy died at 2 years of age. The remaining 11 infants in whom developmental milestones were assessed had age-appropriate skills. Unilateral fetal ventriculomegaly is usually an isolated finding and when isolated has little measurable effect on developmental outcome.

Efficacy of screening for fetal Down syndrome in the United States from 1974 to 1997.

OBJECTIVE: To estimate the 16-week prevalence of Down syndrome in the United States from 1974 to 1997 and to determine the efficacy of maternal age cutoffs and triple screens for detecting it antenatally. METHODS: Using natality statistics for the United States from 1974 to 1997 of maternal-age-specific live births to women 13-49 years old, we evaluated advanced maternal age (35-49 years at delivery) and the triple serum test (maternal serum alpha-fetoprotein, hCG, and unconjugated estriol) as screening tests for Down syndrome. Efficacy was evaluated using sensitivity, false-positive rate, positive predictive value, and likelihood ratio (likelihood ratio = sensitivity/false-positive rate). RESULTS: In 1974, the estimated second-trimester prevalence of Down syndrome was one in 740, but by 1997 that had increased to one in 504. The proportion of Down syndrome fetuses at 16 weeks' gestation in women 35-49 years old increased from 28.5% in 1974 to 47.3% in 1997. However, live births to women 35-49 years old increased more rapidly from 4.7% in 1974 to 12.6% in 1997. The likelihood ratio for maternal age to identify an affected pregnancy decreased during the study period and was substantially lower than that using the serum test. CONCLUSION: A maternal age cutoff of 35 years in the 1990s resulted in high false-positive rates and was less efficacious based on likelihood ratio and positive predictive value. Serum testing of all pregnant women would reduce the number of amniocenteses and decrease procedure-related losses.

Hepatic hemangioendothelioma: prenatal sonographic findings and evolution of the lesion.

We describe a case of hepatic hemangioendothelioma that was first suspected based on prenatal sonographic findings at 19 weeks' menstrual age. At 16 weeks, the patient presented with a markedly elevated maternal serum alpha-fetoprotein level. Serial sonographic examinations revealed that the fetus had cardiomegaly, hepatomegaly with a hepatic mass and dilated intrahepatic vessels, a single umbilical artery, and a placental chorioangioma. Arteriovenous shunting within the hepatic mass was seen using color Doppler and pulsed Doppler sonography. An enlarged artery arising from the abdominal aorta supplying the mass was demonstrated. Postnatal physical examination and radiologic studies supported the diagnosis of hepatic hemangioendothelioma. The evolution in the sonographic appearance of this hepatic lesion in utero over a 17-week period is described.

Fetal Down syndrome screening: a cost effectiveness analysis of alternative screening programs.

OBJECTIVE: To compare the efficacy and cost effectiveness of different screening programs for fetal Down syndrome (DS). METHODS: Screening tools evaluated included maternal age, triple screening (TS), and ultrasound (U/S) for fetal markers of DS. Sensitivities used were TS: 55% <35 years, 80% > or = 35 years; U/S: 70%. Average regional fees used were TS: $80, U/S: $200, amniocentesis (AM): $1,000. Five screening programs were evaluated: 1) <35 years, no screening; > or = 35 years, AM; 2) <35 years, TS with AM for screen-positive subjects; > or = 35 years, AM; 3) all patients, TS with AM for screen-positive subjects; 4) <35 years, TS followed by U/S for screen-positive women, AM for women with fetal markers of DS on U/S; > or = 35 years TS with AM for screen-positive subjects; 5) all women, TS followed by U/S for screen-positive women, AM for women with fetal markers of DS on U/S. The sensitivity, total cost, cost/case DS detected (Cost/DS), AM losses, and residual risk (RR, undetected DS fetuses/women not receiving AM) were calculated for each screening program. Population analysis was performed using 1988 IL delivery statistics. RESULTS: It was estimated that 260 cases of DS would occur in the population of 167,654 women (8.4% > or = 35 years at delivery). Sensitivity for programs 1-5 was 30, 69, 62, 51, and 36 percent, respectively, and cost/DS was 181,000, 203,000, 162,000, 151,000, and 194,000 dollars, respectively. CONCLUSIONS: DS screening incorporating TS in all patients with program #4 and without program #3 selective U/S in women <35 years yield the best combination of sensitivity and cost effectiveness while minimizing the number of AM-related losses.

Economic evaluation of prenatal carrier screening for fragile X syndrome.

OBJECTIVE: The objective of this study was to conduct an economic evaluation of routine prenatal carrier testing for fragile X syndrome. METHODS: This economic analysis was conducted from the societal perspective. A cost-benefit equation was developed based on the premise that the cost of routinely offering prenatal carrier testing for fragile X syndrome should be at least equal to, or less than, the cost of the current practice of not offering such testing. Sensitivity analyses included key assumptions regarding therapeutic abortion rates (50-100%) and patient screening acceptance rates (50-80%). RESULTS: A policy of routinely offering prenatal carrier testing for fragile X syndrome may be beneficial only if the cost per screening test is less than $120 during the first year of the screening program, or less than $240 when the program reaches its full maturity. Given the current cost per screening test of $250, prenatal screening for carrier status for fragile X syndrome carries the potential for annual losses of approximately $10 to $195 million in the United States. In addition, approximately 46-115 fetal lives may be lost due to invasive genetic procedures. CONCLUSIONS: Prenatal screening for fragile X syndrome may be economically beneficial only if the cost of the prenatal screening test for carrier identification is considerably less than the current cost.

Maternal chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis.

OBJECTIVE: The purpose of this study was to determine whether elevated levels of umbilical vein IL-6 would be a better marker for early neonatal sepsis than the clinical signs of maternal chorioamnionitis. METHODS: Patients delivering preterm because of spontaneous preterm labor or premature rupture of the membranes were evaluated for clinical signs of chorioamnionitis, which was defined as a temperature of > or =100.4 degrees F along with > or =2 of the following: significant maternal tachycardia (> or = 120 bpm), fetal tachycardia (> or =160 bpm), purulent discharge, uterine tenderness, and leukocytosis (WBC > or =18,000 cells/mm3). Umbilical vein blood was assayed for interleukin-6. An elevated interleukin-6 level was determined to be 25 pg/mL. Infants were evaluated for evidence of early neonatal sepsis. The abilities of clinical chorioamnionitis and interleukin-6 levels > or =25 pg/mL to predict early neonatal sepsis were compared. RESULTS: There were 28 patients delivering 14 (50%) neonates with evidence for early neonatal sepsis. The incidence of suspected neonatal sepsis in women with and without clinical chorioamnionitis was 6/10 (60%) vs. 8/18 (44.4%), P = 0.43. Using receiver operator characteristic curves, the best cutoff for interleukin-6 was found to be 25 pg/mL. The compared sensitivity, specificity, and positive and negative predictive values of clinical chorioamnionitis vs. interleukin-6 levels > or =25 pg/mL for predicting early neonatal sepsis were 42.9% vs. 92.9%, 71.4% vs. 92.9%, 60% vs. 92.9%, and 55.6% vs. 92.9%, respectively. CONCLUSIONS: Elevated umbilical vein levels of interleukin-6 predict those preterm infants with early sepsis better than the presence of clinical chorioamnionitis.

Incidence of placental abruption in relation to cigarette smoking and hypertensive disorders during pregnancy: a meta-analysis of observational studies.

OBJECTIVE: To systematically review the literature and summarize the relationship between cigarette smoking and placental abruption, and to evaluate the joint influences of smoking and hypertensive disorders (chronic hypertension and preeclampsia) on the subsequent development of abruption. DATA SOURCES: We reviewed studies identified through a MEDLINE literature search between 1966 and 1997 and through studies cited in the references of published reports. METHODS OF STUDY SELECTION: A total of 13 observational (seven case-control and six cohort) studies were identified which included a total of 1,358,083 pregnancies. We excluded case reports on placental abruption, and restricted the literature search to studies published in English. A meta-analysis was performed by computing pooled odds ratios based on random-effects models describing the association between placental abruption, smoking, and hypertensive disorders. Potential sources of heterogeneity among these studies were explored in detail. TABULATION, INTEGRATION, AND RESULTS: The overall incidence of placental abruption was 0.64% (8724 of 1,358,623). Smoking was associated with a 90% increase in the risk of placental abruption (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.8, 2.0). This pattern was consistent by study design (case-control compared with cohort studies) and smoking prevalence (low compared with high prevalence, defined as less than 30% compared with 30% or more, respectively). However, the association was significantly (p < .001) stronger among the seven studies conducted outside the United States (OR 2.1, 95% CI 2.0, 2.2), compared with the six studies conducted in the United States (OR 1.6, 95% CI 1.5, 1.8). Pooled population attributable risk percentage for each stratum ranged between 15% and 25%, implying that 15-25% of placental abruption episodes are attributable to cigarette smoking. Data on the dose-response relationship between number of cigarettes smoked per day and the risk of abruption indicate that the OR increased with increasing number of cigarettes smoked. Furthermore, a meta-analysis of the joint effects of smoking and hypertension during pregnancy on the development of abruption identified two published studies, including 102,609 pregnancies. In the presence of smoking, the risk of abruption was further increased due to chronic hypertension, mild or severe preeclampsia, or chronic hypertension with superimposed preeclampsia. CONCLUSION: Our meta-analyses showed an increased risk for placental abruption in relation to both cigarette smoking and hypertensive disorders during pregnancy. Because cigarette smoking is a modifiable risk factor, and hypertensive disorders are potentially treatable if diagnosed early in pregnancy, patient education, smoking cessation programs, and early prenatal care may be important factors in the prevention of placental abruption.

Pregnancy outcomes in women treated with elective versus ultrasound-indicated cervical cerclage.

OBJECTIVE: To compare pregnancy outcomes in women at risk for pregnancy loss treated with elective versus ultrasound-indicated placement of cerclage. METHODS: A retrospective cohort study was performed on two groups of patients with singleton gestations. The first group consisted of women at risk for pregnancy loss who were treated with an elective cerclage, while the second group was managed conservatively and followed with serial transvaginal cervical sonography and transfundal pressure. An emergency cerclage was placed in women in the second group when the endocervical canal length shortened to < 20 mm, either spontaneously or in response to transfundal pressure. The two groups were compared with respect to maternal demographics, obstetric and gynecological history, and gestational age, both at time of cerclage placement and delivery. RESULTS: A total of 138 patients were identified. Eighty-one patients were treated with an elective cerclage and 57 with an ultrasound-indicated cerclage. Patients treated with elective cerclages were older (32 versus 27 years, p = 0.0003), more commonly white (56.8% versus 38.6%, p = 0.0380), less commonly nulliparous (23.5% versus 43.9%, p = 0.0063), and more often private patients (92.6% versus 28.1%, p < 0.0001). A history of previous treatment with cerclage (45.7% versus 10.5%, odds ratio (OR) 0.2, 95% confidence interval (CI) 0.1-0.4) and one prior midtrimester loss (53.1% versus 33.3%, OR 0.4, 95% CI 0.2-0.9) were also more common in the elective versus ultrasound-indicated cerclage group. However, there was no difference in the rates of previous preterm delivery, two midtrimester losses, two terminations of pregnancy, in utero diethylstilbestrol exposure, uterine anomalies, history of cone biopsy or parity. As expected, gestational age at placement of cerclage was significantly earlier in the elective group (13.0 versus 20.0 weeks, p < 0.0001). The median (range) gestational age at delivery (37 (15-41) versus 37 (17-41) weeks, p = 0.90), the number of early (< 25 weeks) losses (9.9% versus 8.8%, OR 1.6, 95% CI 0.3-7.9), and preterm deliveries (< 37 weeks) (35.8% versus 36.8%, OR 1.1, 95% CI 0.4-3.2) were similar in the elective and ultrasound-indicated cerclage patients, respectively. CONCLUSION: In patients at risk for pregnancy loss, placement of cervical cerclages in response to ultrasonographically detected shortening of the endocervical canal length is a medically acceptable alternative to the use of elective cerclage.

An economic evaluation of prenatal strategies for detection of trisomy 18.

OBJECTIVE: The objective of this study was to perform an economic evaluation of prenatal diagnostic strategies for women who are at increased risk for fetal trisomy 18 caused by either fetal choroid plexus cysts discovered in a conventional sonogram or an abnormal triple screen. STUDY DESIGN: The prevalence of trisomy 18 in the presence of second-trimester fetal choroid plexus cysts and also in the presence of abnormal triple screen were made on the basis of previously reported studies. A cost/benefit analysis and cost-effectiveness determination of 3 strategies were performed: (1) no prenatal diagnostic workup of at-risk patients, (2) universal genetic amniocentesis of all at-risk patients, and (3) universal second-trimester targeted genetic ultrasonography of all at-risk patients with amniocentesis (for fetal karyotyping) reserved only for those with abnormal ultrasonography results. RESULTS: The strategy of no prenatal diagnostic workup was the least expensive approach, costing $1,650,000 annually in the United States. The more costly approach was the strategy of universal amniocentesis for detecting fetal trisomy 18 in the presence of either second-trimester choroid plexus cysts or abnormal maternal serum screening, generating an annual cost of approximately $12 million and 40 fetal losses as a result of amniocenteses. The strategy of targeted genetic ultrasonography generated an annual cost of only $5 million and 8 fetal losses as a result of amniocenteses. CONCLUSIONS: Routine second-trimester amniocentesis in patients at increased risk for fetal trisomy 18 caused by either the presence of fetal choroid plexus cysts or abnormal triple screening is not justified from the cost/benefit point of view.

A cost-effectiveness analysis of prenatal carrier screening for cystic fibrosis.

OBJECTIVE: To examine the cost-effectiveness of prenatal carrier screening for cystic fibrosis. METHODS: A cost-benefit equation was developed that was based on the hypothesis that the cost of prenatal diagnosis required to diagnose and prevent one case of cystic fibrosis should be equal to or less than the lifetime cost generated from the birth of a neonate with cystic fibrosis. The formula was adjusted because a woman's positive or negative carrier status remains unchanged, thus eliminating the need for testing in subsequent pregnancies. The formula was manipulated to identify the optimal cost per screening test, as well as the net cost savings per prenatally diagnosed case of cystic fibrosis for various racial or ethnic groups. Sensitivity analyses included some key assumptions regarding the cost per screening test ($50-150), patient screening acceptance rates (25-100%), and therapeutic abortion rates (50-100%). RESULTS: Assuming therapeutic abortion rates of 50-100%, the net savings per prenatally diagnosed case of cystic fibrosis are $58,369-$382,369 among whites. Given the previously reported patient screening acceptance rates of 50-78%, the overall annual cost savings in the United States for whites are $161-251 million. However, the screening program was not found to be cost-effective for blacks, Asians, or Hispanics. CONCLUSION: Under most assumptions and sensitivity analyses, a prenatal cystic fibrosis-carrier screening program appears to be cost-effective.

An economic evaluation of first-trimester genetic sonography for prenatal detection of Down syndrome.

OBJECTIVE: To determine 1) the diagnostic accuracy requirements of first-trimester genetic sonography from the cost-benefit point of view and 2) the economic impact of first-trimester genetic sonography for the United States on the basis of the accuracy of previously published studies. METHODS: A cost-benefit equation was developed on the basis of the hypothesis that the cost of chorionic villus sampling (CVS) in pregnant women with advanced maternal age (at least 35 years old) should be at least equal to the cost of genetic sonography with CVS used only for those with abnormal ultrasound results. The components of the equation included the diagnostic accuracy of genetic ultrasound (sensitivity and specificity for detecting Down syndrome), the costs of the CVS package and genetic ultrasound, and the lifetime cost of Down syndrome cases. RESULTS: First-trimester genetic sonography was found to be beneficial if the overall sensitivity for detecting Down syndrome was greater than 70%, and even then, the cost-benefit ratio depended on the corresponding false-positive rate. The required minimum ultrasound sensitivity varied according to the maternal age-specific prevalence of Down syndrome and ranged between 40% (for women 35 years old) to 96% (for women 44 years old). Of eight published cohorts using nuchal translucency thickness for genetic sonography, five had accuracies of genetic ultrasound compatible with net benefits. CONCLUSION: The benefits of first-trimester genetic sonography depend on its diagnostic accuracy. First-trimester genetic sonography has the potential for annual savings of 22 million dollars in the United States.

The association of placenta previa with history of cesarean delivery and abortion: a metaanalysis.

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: 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: 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.

PIP: To quantify the risk of placenta previa based on the presence and number of cesarean deliveries and a history of spontaneous and induced abortion, a meta-analysis was conducted of salient studies published in the world literature in 1950-96. Subgroup analyses were conducted to identify important sources of heterogeneity by study design and location. The tabulation of 36 studies identified a total of 3.7 million pregnant women, of whom 13,992 had placenta previa. The reported incidence of placenta previa in these studies ranged from 0.28% to 2.0%. Women with at least 1 cesarean section delivery were 2.6 times (95% confidence interval (CI), 2.3-3.0) more likely to develop placenta previa in a subsequent pregnancy. The relative risk of placenta previa was higher in case-control studies (3.8) than cohort studies (2.4). An analysis of four studies, encompassing 170,640 pregnant women, showed a dose-response pattern for the risk of placenta previa on the basis of the number of previous cesarean deliveries. The relative risks increased from 4.5 (95% CI, 3.6-5.5) for 1 prior cesarean delivery to 44.9 (95% CI, 13.5-149.5) for 4 or more previous cesareans. Women with a history of spontaneous abortion had a relative risk of placenta previa of 1.6 (95% CI, 1.0-2.6), while those with a history of induced abortion had a relative risk of 1.7 (95% CI, 1.0-2.9). These findings suggest that pregnant women with a history of cesarean delivery or abortion should be regarded as at high risk for placenta previa and monitored closely. They further underscore the importance of avoiding unnecessary cesarean deliveries and encouraging vaginal birth for women with prior cesarean delivery.

Value of umbilical artery and vein levels of interleukin-6 and soluble intracellular adhesion molecule-1 as predictors of neonatal hematologic indices and suspected early sepsis.

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.

Epidemiology of antepartum fetal testing.

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.