Absorption of dietary and supplemental folate in women with prior pregnancies with neural tube defects and controls.

BACKGROUND: The Public Health Service of the United States recommends that all women capable of childbearing consume .4 mg (400 microg) folic acid per day to decrease the risk of having a pregnancy affected by a neural tube defect such as spina bifida or anencephaly. Three strategies are available to women to achieve this goal: use of dietary supplements; use of fortified foods; and/or increased intake of naturally occurring folate from foods. Identification of the most effective vehicle for delivery of folate to all women is critical in order to prevent these devastating congenital defects. OBJECTIVE: To investigate the difference in response to an oral load of folate both from naturally occurring food sources and synthetic supplements among women with prior pregnancies affected by neural tube defects and controls. METHODS: We compared the absorption of test doses of 400 microg pteroylglutamic acid (unconjugated or synthetic folic acid found in supplements) and 400 microg pteroylpolyglutamic acid (conjugated or food folate) in 10 women with a history of neural tube defect affected pregnancies and eight controls with normal birth outcomes. The folate test dose was given as either 32 fluid ounces of orange juice or a folic acid single supplement pill. All participants received each test dose at separate clinic visits. The response to each test dose was measured by constructing an area under the curve (AUC) from the serum folate levels at 1, 2 and 3 hours post dose and applying a t-test to compare within and between cases and controls. We also compared red cell folate, vitamin B12, zinc and homocysteine between cases and controls. RESULTS: Within group comparisons showed that the area under the curve was significantly greater for the pteroylglutamic acid dose compared to the pteroylpolyglutamic acid dose for both cases and controls (p=0.02 and p=0.03, respectively). In a between group comparison, control women had a greater serum folate response to both forms of the vitamin compared to the case women, but the difference reached statistical significance only for the pteroylglutamic acid dose (p=0.02). Other measured nutrients differed between cases and controls, but did not reach statistical significance. CONCLUSION: We conclude that for all women synthetic folic acid as supplements or fortified foods may be the best way to increase acute folate levels in the blood, and thus delivery to the developing embryo. Further, since case women had a diminished response to both forms of the vitamin, and some case women had almost no response, we speculate that women with prior affected pregnancies may need a larger dose of folate to elicit a plasma response equivalent to the general population.

Maternal smoking during pregnancy and the risk of congenital urinary tract anomalies.

To study maternal smoking during pregnancy and the risk of congenital urinary tract anomalies, we interviewed mothers of 118 affected infants born to residents of western Washington State during 1990 and 1991 and mothers of 369 control infants randomly selected from those without birth defects delivered during those years in five hospitals in King County, Washington. Maternal smoking was associated with an increased risk of congenital urinary tract anomalies in offspring (adjusted odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.2, 4.5). This risk was higher among light smokers (1-1000 cigarettes during the pregnancy) (OR = 3.7; 95% CI = 1.7, 8.6) than among heavy smokers (OR = 1.4; 95% CI = 0.6, 3.3). Our results corroborate previous findings and support the hypothesis of a causal relation.

A population-based case-control study of risk factors for breech presentation.

OBJECTIVE: We evaluated relationships between breech presentation and infant, maternal, and pregnancy characteristics of singleton births. STUDY DESIGN: A population-based case-control study (3588 breech cases, 8183 controls) was conducted with data from the 1987 to 1988 Washington State birth certificate. RESULTS: Low birth weight, short gestational age, primiparity, and older maternal age were associated with increased risk of breech birth, and after we controlled for these factors, the following were also associated with breech birth: hydrocephalus, established maternal diabetes, congenital malformation of the infant, smoking during pregnancy, and late or no prenatal care. In addition, black and Filipino women had decreased risk of breech presentation compared with white women. CONCLUSION: Several different maternal and infant characteristics appear to increase risk of breech birth, suggesting that there may be several different biologic mechanisms leading to breech presentation.

Recent changes in delivery site of low-birth-weight infants in Washington: impact on birth weight-specific mortality.

OBJECTIVES: Our purpose was to ascertain whether the proportion of low-birth-weight infants delivered in Washington at tertiary hospitals changed between 1980 and 1991 and whether mortality differed by level of birth hospital. STUDY DESIGN: A retrospective cohort study was performed of 500 to 2499 gm infants born to Washington residents between 1980 and 1991 (n = 43,228). RESULTS: Overall, the percentage of low-birth-weight infants born at tertiary centers rose from 1980 to 1982 through 1986 to 1988 and subsequently declined significantly. Among infants weighing < 2000 gm nontertiary delivery was associated with greater potentially preventable mortality (500 to 999 gm, relative risk 1.5, 95% confidence interval 1.3 to 1.8; 1000 to 1499 gm, relative risk 2.1, 95% confidence interval 1.3 to 3.3; 1500 to 1999 gm, relative risk 1.6, 95% confidence interval 1.0 to 2.6). Nontertiary delivery of 2000 to 2499 gm infants was associated with lower overall mortality (relative risk 0.5, 95% confidence interval 0.3 to 0.8), but higher-risk deliveries in this birth weight range were apparently concentrated at tertiary hospitals. CONCLUSIONS: In light of the apparent benefit of tertiary center birth for infants weighing < 2000 gm, the possible erosion of effective regionalized perinatal care networks should be monitored closely.

Risk factors for preeclampsia in twin pregnancies: a population-based cohort study.

OBJECTIVE: To evaluate in twin pregnancies the characteristics parity, race, smoking, and age, known to be risk factors for preeclampsia in non-twin pregnancies. METHODS: All twin pregnancies (3407) and approximately twice as many singletons (8287) were assembled using Washington state birth certificates from the period 1984-1988. RESULTS: In singleton pregnancies, preeclampsia was more common in women who were younger, black, poor, nulliparous, and nonsmokers. In twin pregnancies, similar associations were found, but were only statistically significant for age, race, and parity. There were no significant differences in the risk factors between twin and singleton women. Logistic regression showed that twin pregnancy carries a relative risk (RR) of 3.5 (95% confidence interval [CI] 3.0-4.2), nulliparity an RR of 4.0 (95% CI 3.3-4.8), and black race an RR of 1.8 (95% CI 1.2-2.6) for preeclampsia. In each case, this risk is independent of the other risk factors. CONCLUSION: Twin pregnancy carries nearly a fourfold increased risk of preeclampsia, independent of race and parity, and the risk of a nulliparous twin pregnancy is 14 times that of a parous singleton pregnancy. Risk factors in a singleton pregnancy act similarly in a twin pregnancy. Thus, any pathophysiologic model for preeclampsia needs to account for the risk twin pregnancy poses as well as other risk factors, such as parity and race.

Periconceptional multivitamin use in relation to the risk of congenital urinary tract anomalies.

To study the relation of maternal periconceptional vitamin use to the risk of a congenital urinary tract anomaly (CUTA), we conducted a case-control study using the Washington State Birth Defect Registry. We identified CUTA cases with no known chromosomal abnormality in seven counties in western Washington State occurring between January 1, 1990, and December 31, 1991. We randomly selected a sample, as controls, of all infants delivered in five large hospitals in King County who did not have a birth defect and who were born in the same year as the cases. About 55% of all infants in King County and a smaller proportion of infants in the other six counties are delivered in these five hospitals. We interviewed mothers of 118 cases and 369 controls to obtain information about their vitamin use during the pregnancy and during the year before the conception. After adjustment for maternal race, family income, county of maternal residence, and birth year, we found that women who used multivitamins during the first trimester had only 15% the risk of bearing a child with a CUTA compared with women who did not take vitamins [odds ratio (OR) = 0.15; 95% confidence interval (CI) = 0.05-0.43]. The reduction was smaller for use restricted to the second or third trimesters (OR = 0.31; 95% CI = 0.09-1.02). Among women who used vitamins during the first trimester, vitamin use before conception was not associated with any further reduction in the risk, nor did there appear to be an association with the amount or brand of vitamin used.(ABSTRACT TRUNCATED AT 250 WORDS)

A longitudinal study of maternal serum human chorionic gonadotropin levels during pregnancy.

OBJECTIVE: To determine if pregnant women with normal singletons will continue to have elevated serum human chorionic gonadotropin (hCG), given that they had an elevated serum hCG in the second trimester. METHODS: Nineteen women with second-trimester hCG levels > or = 2.0 multiples of the median, and 20 women with second-trimester hCG levels < 2.0 multiples of the median were the subjects of this investigation. All study participants had serum hCG levels repeated during the third trimester of pregnancy. We used a chi-square test and Student's t test for comparing categorical variables, and the means of continuous variables, respectively. RESULTS: Using the criterion of > or = 2.0 multiples of the median of the comparison group to define hCG elevation, women with elevated second-trimester hCG levels were women with normal second-trimester hCG levels (risk ratio = 3.9; 95% confidence interval 1.6-9.8; p < 0.001). Adjustment for potential confounders did not materially alter the association. CONCLUSION: Women with elevated hCG in the second trimester continued to have elevations in the third trimester. The persistence of elevated hCG levels in pregnancies uncomplicated by fetal anomalies should be evaluated as a clinical marker of adverse pregnancy outcomes.

Oral contraceptive use after conception in relation to the risk of congenital urinary tract anomalies.

The authors conducted a case-control study of the relation of OC use after conception to the occurrence of congenital urinary tract anomalies (CUTAs). Singleton CUTA cases with no known chromosomal abnormality from seven counties in western Washington State born during the period January 1, 1990-December 31, 1991 were identified through the Washington State Birth Defect Registry. Controls without birth defects were randomly selected from singleton births that occurred in the same year as the cases in five large hospitals in King County. Mothers of the 118 cases and 369 controls were interviewed to obtain their contraceptive history as well as other information. Mothers of nine cases (7.6%) and eight controls (2.2%) had taken OCs at some time during the pregnancy. After adjustment for birth year and county of maternal residence, OC use after conception was associated with an almost five-fold increased risk of having a baby with a CUTA [odds ratio (OR) = 4.8, 95 percent confidence interval (CI), 1.6-14.1] relative to no contraception at or after conception. Use of other contraceptive methods after conception was not related to the risk of CUTAs. OC use during the 3 or 6 months prior to the conception also was not associated with the risk of CUTAs. Further adjustment for sociodemographic factors, reproductive history, perinatal exposure to exogenous agents, and past OC use did not change the results, nor did restricting the analysis to residents of King County.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: A case-control study examined the relation of OC use after conception to the occurrence of congenital urinary tract anomalies (CUTAs). Singleton CUTA cases with no known chromosomal abnormality from 7 counties in western Washington state born during the period January 1, 1990-December 31, 1991 were identified through the Washington State Birth Defect Registry. Controls without birth defects were randomly selected from singleton births that occurred in the same year as the cases in 5 large hospitals in King County. Mothers of the 118 cases and 369 controls were interviewed to obtain their contraceptive history. Mothers of 9 cases (7.6%) and 8 controls (2.2%) had taken OCs at some time during the pregnancy. After adjustment for birth year and county of maternal residence, OC use after conception was associated with a 4.8-fold increased risk of having a baby with a CUTA [odds ratio (OR) = 4.8, 95% confidence interval (CI), 1.6-14.1) relative to no contraception at or after conception. The risk seemed to increase with increasing duration of OC use after their last menstruation: OR = 8.0 for women with longer than 4 weeks duration of use. Use of other contraceptive methods after conception was not related to the risk of CUTAs. OC use during the 3-6 months prior to conception was not associated with an increased risk of CUTAs in offspring relative to no OC use during the same period. Further adjustment for sociodemographic factors, reproductive history, perinatal exposure to exogenous agents, and past OC use did not change the results, nor did restricting the analysis to residents of King County. The cases exposed to prenatal OC use were slightly more likely to have megaloureter than were unexposed cases (4/9 vs. 27/109). These results are compatible with the hypothesis that oral contraceptive use after conception predisposes to the development of CUTAs in offspring; this hypothesis should be tested in other epidemiological studies of congenital malformations.

Preinduction prostaglandin E2 gel prior to induction of labor in women with a previous cesarean section.

The objective of the study was to evaluate the efficacy and safety of preinduction cervical ripening with 0.5 mg of intracervical prostaglandin E2 (PGE2) gel in women with a previous cesarean section. A retrospective cohort study design was used to compare 117 women with one previous cesarean section (VBACS) with 354 nulliparas. Both groups received preinduction cervical ripening treatment with intracervical PGE2 gel. Student's t and chi 2 tests were used to evaluate group differences. Mantel-Haenszel summary risk ratios and 95% confidence intervals were examined in order to assess the relative risk of cesarian section delivery after adjusting for potential confounders. The mean numbers of PGE2 gel applications were 2.4 and 2.5 for VBACS and controls, respectively (p < 0.05). Thirty-nine percent of VBACS entered labor spontaneously as compared with 33% of nulliparas. Mean duration of ruptured membranes (8.2 vs. 12.1 h) and length of labor (20.1 vs. 28.5 h) were reduced among VBACS as compared with controls (p < 0.05). Overall, VBACS had a higher cesarean section rate as compared with controls (49.6 vs. 31.9%; adjusted relative risk = 1.6, 95% confidence interval 1.2-2.1). There were no differences in the occurrence of maternal and fetal morbidity. Overall, the efficacy and safety of 0.5 mg PGE2 gel administered for preinduction cervical ripening in VBACS is comparable to that observed in nulliparas.

Maternal serum CA 125 levels in the diagnosis of abruptio placentae.

OBJECTIVE: To evaluate measurements of maternal serum CA 125 for the diagnosis of abruptio placentae. METHODS: This investigation was conducted at Swedish Medical Center/Seattle from December 1991 through April 1992. During the study period, we identified 21 consecutive patients with a clinical diagnosis of abruptio placentae. In addition, we enrolled two groups of patients whose pregnancies were not complicated by placental abruption (28 preterm controls and 53 term controls). RESULTS: Mean maternal serum levels of CA 125 were significantly higher among women with abruptio placentae (40.6 +/- 29.6 U/mL) than among preterm controls (26.6 +/- 17.2 U/mL) or term controls (22.0 +/- 11.4 U/mL). Using a positive threshold of 35 U/mL, the sensitivity and specificity of maternal serum CA 125 for abruptio placentae were 42.9% (95% confidence interval [CI] 21.7-64.1) and 92.5% (95% CI 85.4-99.6), respectively. CONCLUSIONS: These findings support an earlier report documenting higher mean maternal serum levels of CA 125 among women with pregnancies complicated by abruptio placentae than in control subjects. However, measurement of maternal serum CA 125 does not appear to be a useful marker for the diagnosis of abruptio placentae. At present, clinical diagnosis of abruptio placentae, with the aid of ultrasonography to rule out other causes of late gestational hemorrhage, should be considered the most sensitive and specific method of detecting this pregnancy complication.

Elevated second-trimester human chorionic gonadotropin and subsequent pregnancy-induced hypertension.

OBJECTIVE: Pregnancy-induced hypertension is believed to be a disorder of the vascular endothelium, possibly focused in the placenta. Markers such as cellular fibronectin appear early in patients in whom pregnancy-induced hypertension develops. We hypothesized that patients with elevated second-trimester levels of human chorionic gonadotropin would have an increased risk for pregnancy-induced hypertension. STUDY DESIGN: We conducted a cohort study, using a database of patients undergoing second-trimester serum screening for Down syndrome and who were delivered at our institution between January 1990 and August 1991. We included all 180 women with human chorionic gonadotropin levels > or = 2.0 multiples of the median. A sequential sample of 369 women with levels < 2.0 multiples of the median served as the referent group. Standard American College of Obstetricians and Gynecologists definitions of pregnancy-induced hypertension and proteinuria were used. RESULTS: Patients with elevated human chorionic gonadotropin levels were at increased risk for pregnancy-induced hypertension (risk ratio 1.7, 95% confidence interval 1.2 to 2.4) and proteinuric pregnancy-induced hypertension (risk ratio 5.1, 95% confidence interval 1.6 to 16.2). Adjusting for potential confounding factors did not alter these associations. CONCLUSIONS: Patients with elevated human chorionic gonadotropin appear to be at higher risk of pregnancy-induced hypertension and proteinuric pregnancy-induced hypertension. Second-trimester human chorionic gonadotropin levels should be further investigated as a potential marker for pregnancy-induced hypertension.

Fetal hyperechogenic bowel and Down's syndrome.

Hyperechogenic bowel was identified among 55 of 6781 (0.81%) fetuses prior to second-trimester genetic amniocentesis. Trisomy 21 was found in eight of the 55 (14.5%) fetuses identified with hyperechogenic bowel compared to 60 of 6726 (0.89%) fetuses with normal bowel echogenicity (p < 0.001). Hyperechogenic bowel carried a 16-fold greater risk for Down's syndrome than normal bowel echogenicity (relative risk 16.8, 95% confidence intervals 8.2-32.5). Chromosome abnormalities other than trisomy 21 were found in four additional fetuses with hyperechogenic bowel (two triploid and one each with 47,XXX; 45,X/47,XXX mosaicisim). Combining these four cases with the eight fetuses having trisomy 21, 21.8% (12 of 55) of fetuses with hyperechogenic bowel proved to have a chromosome abnormality. We conclude that hyperechogenic bowel is associated with chromosome abnormalities, particularly Down's syndrome, when detected during the second trimester.

Echogenic fetal bowel during the second trimester: clinical importance.

Clinical outcomes of 95 second-trimester fetuses prospectively considered to have echogenic bowel at ultrasound were compared with a control group of 110 consecutive second-trimester fetuses. Among the 95 fetuses in the study group, 64 (67%) had moderately echogenic (grade 2) or markedly echogenic (grade 3) bowel relative to the liver. Among the 110 fetuses in the control group, only two (1.8%) had moderately echogenic (grade 2) bowel; the rest (98.2%) had isoechoic (grade 0) or midly echogenic (grade 1) bowel relative to the liver. Adverse outcomes occurred in 45 of the 95 fetuses (47%) with echogenic bowel compared with eight of the 110 fetuses (7.27%) in the control group (P < .01; relative risk, 6.5; 95% confidence interval, 3.2, 13.1). Adverse outcomes included chromosomal abnormalities, intrauterine growth retardation, fetal demise, or other fetal anomalies. Within the study group, adverse outcomes occurred in 40 of the 64 fetuses (62%) with grade 2 or 3 bowel echogenicity, compared with five of the 31 fetuses (16%) with grade 1 echogenicity. Echogenic bowel is associated with an increased risk of adverse fetal outcome and this risk is confined primarily to grades 2 and 3 echogenicity.

An association between elevated levels of human chorionic gonadotropin in the midtrimester and adverse pregnancy outcome.

OBJECTIVE: Unexplained elevations in maternal serum alpha-fetoprotein in the midtrimester are associated with adverse pregnancy outcome. Recently it has also been suggested that elevations of maternal serum human chorionic gonadotropin in the second trimester may be associated with adverse pregnancy outcome. STUDY DESIGN: We conducted a cohort study of 460 women at Swedish Medical Center, Seattle, Washington, between Jan. 1, 1990, and Aug. 15, 1991, inclusive. Entry criteria for the cohort included (1) triple screen analysis (maternal serum alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol) between 15 and 18 weeks' gestation, (2) a risk for Down syndrome of more than one in 195 on the basis of triple screen analysis, (3) study group human chorionic gonadotropin > or = 2 multiples of the median and referent group < or = 2 multiples of the median, alpha-fetoprotein < or = 2 multiples of the median, unconjugated estriol > or = 0.5 multiples of the median, and (4) chromosomally normal single gestation without anomalies. Cumulative incidence risk ratios were estimated for each pregnancy outcome as a measure of the relative association with elevated human chorionic gonadotropin (> or = 2.0 multiples of the median) and adverse pregnancy outcome: low birth weight, < or = 2500 gm; preterm delivery, < 37 weeks' gestation; and small for gestational age, < or = 10th percentile. The Mantel extension test was used to evaluate any apparent linear trend in risk between level of human chorionic gonadotropin and adverse pregnancy outcome. RESULTS: Elevated human chorionic gonadotropin levels were associated with an increased risk for low birth weight (relative risk = 4.0), preterm delivery (relative risk = 2.8), and small for gestational age (relative risk = 1.8). The risk for each adverse outcome increased with increasing levels of human chorionic gonadotropin. CONCLUSIONS: Elevations of human chorionic gonadotropin in the midtrimester appear to be associated with adverse pregnancy outcome. The magnitude of the risk correlates with the level of human chorionic gonadotropin. This risk appears to be independent of the risk for adverse pregnancy outcome associated with unexplained elevations of maternal serum alpha-fetoprotein.

Induction of labor and risk of sudden infant death syndrome.

OBJECTIVE: To investigate whether induction of labor is related to the occurrence of sudden infant death syndrome (SIDS) using a population-based, case-control study. METHODS: Cases comprised infants born between 1984-1988 in Washington state who died of SIDS according to their death certificate (ICD-9-CM 798.0) (N = 728). For comparison, we randomly selected a group of infants born in these same years who did not die of SIDS (N = 3021). Information regarding the pregnancy, labor, delivery, and condition of the newborn was obtained from the infants' birth certificates. RESULTS: Among the indications for induction that were examined, we found a slightly elevated risk of SIDS associated with advanced gestational age (greater than 41 completed menstrual weeks) (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.0-1.8). A similar proportion of cases and controls had induced labors (OR 1.2, 95% CI 0.7-2.1). Although there was little or no apparent risk associated with induction among infants who had term gestations (37-41 completed menstrual weeks; OR 1.2, 95% CI 0.6-2.2), an increased risk was found among infants who had gestations of 42 weeks or greater (OR 3.0, 95% CI 0.7-12.5). We did not observe this trend with augmentation of labor. CONCLUSION: Our findings do not support an overall association between the methods used for induction of labor in the United States and the occurrence of SIDS. The elevated risk of SIDS observed in relation to induction of labor among infants who had post-term gestations raises the possibility that infants who do not spontaneously initiate labor may suffer some neuroregulatory or other abnormality involved in the pathogenesis of SIDS.

Humerus and femur length shortening in the detection of Down's syndrome.

OBJECTIVE: Our purpose was to determine the utility of screening for humerus and femur length shortening in prenatal detection of Down's syndrome (trisomy 21). STUDY DESIGN: On the basis of the biparietal diameter, predicted humerus and femur lengths were derived from a sample control group of 350 karyotypically normal fetuses. The regression formulas were prospectively applied to 45 consecutive fetuses with Down's syndrome and 942 fetuses with normal karyotypes. Ratios of measured humerus length/predicted humerus length and measured femur length/predicted femur length were calculated for each fetus. RESULTS: Eleven of 45 (24.4%) fetuses with Down's syndrome had short humerus (measured humerus length/predicted humerus length ratio of < or = 0.89), and 11 (24.4%) had short femur (measured femur length/predicted femur length ratio of < or = 0.91. In comparison, among 942 karyotypically normal fetuses only 43 (4.5%) showed short humerus and 44 (4.7%) showed short femur (p < 0.05). Fetuses with both short humerus and short femur carried an 11-fold greater risk of Down's syndrome (risk ratio = 11.1; 95% confidence interval = 5.0 to 25.0). CONCLUSION: Prenatal ultrasonographic detection of short humerus to short femur, or both significantly increase the risk of Down's syndrome; this information may be useful in screening programs.

A retrospective cohort study of seatbelt use and pregnancy outcome after a motor vehicle crash.

To determine the effect of seatbelt use on pregnancy outcome we conducted a population-based retrospective cohort study of pregnant women (20 weeks' gestation or more) involved in motor vehicle collisions. Birth and fetal death certificates were obtained for 1243 restrained and 1349 unrestrained pregnant women involved in police-investigated motor vehicle crashes from 1980 through 1988. Unrestrained pregnant women drivers were 1.9 times more likely to have a low birth weight baby (95% confidence intervals = 1.2, 2.9) and 2.3 times more likely to give birth within 48 hours after the motor vehicle crash (95% confidence intervals = 1.1, 4.8) than restrained pregnant women drivers after adjusting for age and gestational age at crash. Although a trend for an increased risk of fetal deaths was observed among unrestrained women, too few fetal deaths occurred to accurately describe any association with restraint status. This study provides reassurance that the current recommendations on use of seatbelts by pregnant women are appropriate and should be continued.

A prospective evaluation of a second-trimester screening test for fetal Down syndrome using maternal serum alpha-fetoprotein, hCG, and unconjugated estriol.

OBJECTIVE: To test the efficacy of a screening protocol using a combination of maternal age plus three biochemical markers--maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3)--for the antenatal detection of fetal Down syndrome. METHODS: We conducted a prospective cohort study of 7718 women who underwent the triple-marker analysis between weeks 15-18 of pregnancy. A second-trimester risk for Down syndrome of 1:195 or greater was considered positive. Sensitivity, specificity, positive predictive value, and their 95% confidence intervals (CIs) were calculated. We evaluated test performance for various maternal age groups and screen-positive cutoffs, as well as the relative screening efficacies of maternal age and MSAFP, MSAFP plus hCG, and MSAFP, hCG, and unconjugated E3. RESULTS: Four hundred sixty-one of the 7718 women screened (6%) were identified as positive; 319 women chose amniocentesis, for an overall amniocentesis rate of 4.1%. Twenty of 22 pregnancies affected with Down syndrome were correctly identified, as were 7255 of 7696 unaffected pregnancies, yielding a sensitivity and specificity of 91% (95% CI 79-100%) and 94% (95% CI 93.8-94.8%), respectively. The use of maternal age plus all three analytes improved test performance compared with maternal age plus MSAFP and hCG, but either had a significantly improved detection rate compared with that for maternal age and MSAFP alone. CONCLUSION: The triple-marker screen appears to be an effective method of detecting Down syndrome pregnancies while maintaining an acceptable amniocentesis rate.

Low birth weight and preterm delivery in relation to early-gestation vaginal bleeding and elevated maternal serum alpha-fetoprotein.

OBJECTIVE: To determine whether early-gestation vaginal bleeding and elevated maternal serum alpha-fetoprotein (MSAFP) are independent risk factors for adverse infant outcomes. METHODS: We conducted a cohort study of 201 women with an elevated MSAFP (at least 2.0 multiples of the median [MOM]) and a second-trimester ultrasound evaluation at Swedish Hospital Medical Center between January 1989 and March 1991, and 211 women with MSAFP levels below 2.0 MOM who had also undergone ultrasound evaluations during the same period. RESULTS: Stratified analyses demonstrated that early-gestation bleeding and elevated MSAFP were independent risk factors for the delivery of both preterm and low birth weight infants. Compared with women with no history of early-gestation bleeding or elevated MSAFP, women with early-gestation bleeding alone had a relative risk (RR) of preterm delivery of 4.3 (95% confidence interval [CI] 1.5-12.1); non-bleeders with elevated MSAFP had an RR of 4.6 (95% CI 1.9-10.9). A combined history of early-gestation bleeding and elevated MSAFP was associated with an almost sixfold increased risk of preterm delivery (RR 5.8; 95% CI 2.2-15.6). Analyses restricted to women with normal-appearing appearing placentas by second-trimester ultrasound evaluations yielded similar results. CONCLUSIONS: These findings support an earlier report documenting the independence of early-gestation bleeding and elevated MSAFP as predictors of adverse infant outcomes.