Trends in the Prenatal Detection of Major Congenital Heart Disease in Alberta From 2008-2018.

OBJECTIVE: The effect of expanded obstetrical ultrasound cardiac views on the diagnosis of fetal congenital heart disease (CHD) has not been fully examined at a population level. We hypothesized there has been a significant increase in the prenatal detection of CHD in Alberta, particularly for CHD associated with cardiac outflow tract and 3-vessel view abnormalities. METHODS: Using provincial databases, we retrospectively identified all fetuses and infants diagnosed between 2008 and 2018 in Alberta with major CHD requiring surgical intervention within the first postnatal year. We evaluated individual lesions and categorized CHDs into the following groups based on the obstetrical ultrasound cardiac views required for detection: (1) 4-chamber view (e.g., hypoplastic left heart syndrome, Ebstein's anomaly, single ventricle); (2) outflow tract view (e.g., tetralogy of Fallot, d-transposition, truncus arteriosus); (3) 3-vessel or other non-standard cardiac views (e.g., coarctation, anomalous pulmonary veins); and (4) isolated ventricular septal defects using any view. RESULTS: Of 1405 cases of major CHD, 814 (58%) were prenatally diagnosed. Over the study period, prenatal detection increased in all groups, with the greatest increase observed for groups 1 and 2 (75%-88%; P = 0.008 and 56%-79%; P = 0.0002, respectively). Although rates of prenatal detection also increased for groups 3 and 4 (27%-43%; P = 0.007 and 13%-30%; P = 0.04, respectively), fewer than half of the cases in each group were detected prenatally, even in more recent years. CONCLUSIONS: While rates of prenatal detection of CHD have significantly improved during the past decade, many defects with abnormal 3-vessel and non-standard views, as well as isolated ventricular septal defects, still go undetected.

Social determinants of health and adverse maternal and birth outcomes in adolescent pregnancies: A systematic review and meta-analysis.

BACKGROUND: Adverse outcomes in adolescent pregnancies have been attributed to both biological immaturity and social determinants of health (SDOH). The present systematic review evaluated the evidence on the association between SDOH and adverse maternal and birth outcomes in adolescent mothers. METHODS: Comprehensive literature searches were conducted to identify observational studies evaluating the relationship between SDOH and adverse adolescent pregnancy outcomes. Study selection, risk of bias appraisal, and data extraction of study characteristics were independently performed by two reviewers. Pooled odds ratios (pOR) with 95% confidence intervals (95% CI) were calculated to assess the association between SDOH and adverse birth outcomes. RESULTS: Thirty-one studies met the inclusion criteria. The most frequently evaluated SDOH was race while the most commonly reported maternal and birth outcomes were caesarean section and preterm birth (PTB), respectively. The risk of bias of included studies was fair on the Newcastle-Ottawa Scale. Meta-analyses of retrospective cohort studies showed that, compared to White adolescent mothers, African American teens had increased odds of PTB (pOR 1.67; 95% CI 1.59, 1.75) and low birthweight (pOR 1.53; 95% CI 1.45, 1.62). Rural residence was consistently linked with PTB while low maternal socio-economic (SES) and illiteracy were found to increase the risk of adolescent maternal mortality and LBW infants. CONCLUSION: Social determinants of health contribute to the risk of adverse pregnancy outcomes in adolescent mothers. African American race, rural residence, inadequate education, and low SES are markers for poor pregnancy outcomes in adolescent mothers. Further research needs to be done to understand the underlying causal pathways to inequalities in adolescent pregnancy outcomes.

Maternal Area of Residence, Socioeconomic Status, and Risk of Adverse Maternal and Birth Outcomes in Adolescent Mothers.

OBJECTIVE: Adolescent pregnancy is a significant public health issue in Canada. Current evidence highlights the individual role of social determinants of health such as maternal residence and socioeconomic status (SES) on teen pregnancy outcomes. This study evaluated the joint association between residence/SES and adverse adolescent pregnancy outcomes. METHODS: This was a population-based retrospective cohort study of all singleton, live deliveries (2010-2015) from women aged 15 to 19 who were registered in the Alberta Perinatal Health Program. Information on maternal residence and SES was extracted from the Pampalon Material Deprivation Index data set. The study categorized mothers into four risk dyads: rural/high SES, rural/low SES, urban/high SES, and urban/low SES. Adjusted odds ratios (ORs) of adverse pregnancy outcomes were calculated in logistic regression models (Canadian Task Force Classification II-2). RESULTS: A total of 9606 births from adolescent mothers were evaluated. Thirty percent of adolescent mothers were classified as urban/high SES; 27% were urban/low SES; 7% were rural/high SES; and 36% were placed in the rural/low SES category. Compared with urban/high SES mothers, rural/low SES mothers had increased odds of postpartum hemorrhage (OR 1.57; 95% confidence interval [CI] 1.41-1.74), operative vaginal delivery (OR 1.37; 95% CI 1.18-1.60), Caesarean section (OR 1.39; 95% CI 1.19-1.62), large for gestational age infants (OR 1.39; 95% CI 1.16-1.66), low birth weight (OR 1.11; 95% CI 1.07-1.65), and preterm birth (OR 1.48; 95% CI 1.17-1.87). CONCLUSION: Rural pregnant adolescents of low SES have the highest odds for adverse pregnancy outcomes. Social determinants of health that affect adolescent pregnancies need further examination to identify high-risk subgroups and understand pathways to health disparities in this vulnerable population.

Relationship Between Interpregnancy Interval and Adverse Perinatal and Neonatal Outcomes in Northern Alberta.

BACKGROUND: Birth outcomes are known to be associated with birth spacing, but there are population differences. The purpose of this study was to examine the association between interpregnancy intervals and perinatal and neonatal outcomes in a Canadian population during the era of mandatory folate fortification of food. METHODS: We conducted a study of 46 243 women who had two consecutive singleton births in northern Alberta between 1999 and 2007, using a linked provincial dataset. Perinatal outcomes of interest were preterm birth, low birth weight (LBW), small for gestational age, and perinatal death. Neonatal outcomes were low Apgar score, low arterial blood gas pH, need for neonatal resuscitation or admission to NICU, and neonatal death. Multivariable logistic regression was used to control for maternal demographic and obstetrical characteristics. RESULTS: The risk of preterm birth was increased for multiple interpregnancy intervals: for an interval of 0 to 5 months, the adjusted odds ratio (aOR) was 1.37 (95% CI 1.18 to 1.59), for 6 to 11 months the aOR was 1.18 (95% CI 1.04 to 1.34), for 24 to 35 months the aOR was 1.16 (95% CI 1.02 to 1.31), and for 36+ months the aOR was 1.36 (95% CI 1.20 to 1.53), compared with the reference interval of 12 to 17 months. The risk of LBW was increased with interpregnancy intervals of 0 to 5 months (aOR 1.48; 95% CI 1.23 to 1.80), 6 to 11 months (aOR 1.21; 95% CI 1.03 to 1.42), 24 to 35 months (aOR 1.21; 95% CI 1.03 to 1.41) and 36+ months (aOR 1.48; 95% CI 1.27 to 1.73). The risk of SGA was increased with intervals 0 to 5 months (aOR 1.29; 95% CI 1.09 to 1.52), 24 to 35 months (aOR 1.15; 95% CI 1.01 to 1.31), and 36+ months (aOR 1.26; 95% CI 1.11 to 1.44). The risk of perinatal death was increased with an interval of 36+ months (aOR 1.60; 95% CI 1.06 to 2.43). Similar associations were also observed for neonatal outcomes. CONCLUSION: This study suggests that both short and long interpregnancy intervals are associated with adverse perinatal and neonatal outcomes, and it provides risk estimates for a Canadian population in the era of folate fortification of food.

Contexte : Bien qu'il soit reconnu que les issues de grossesse sont associées aux intervalles intergrossesses, certaines différences sont constatées d'une population à l'autre. Cette étude avait pour objectif d'examiner l'association entre les intervalles intergrossesses et les issues périnatales et néonatales au sein d'une population canadienne, au cours des années suivant la décision qui a rendu obligatoire l'enrichissement des aliments en folate. Méthodes : Nous avons mené une étude auprès de 46 243 femmes qui ont mené deux grossesses monofœtales consécutives à terme dans le nord de l'Alberta entre 1999 et 2007, en utilisant un ensemble de données liées provinciales. L'accouchement préterme, le faible poids de naissance (FPN), l'hypotrophie fœtale et le décès périnatal ont été les issues périnatales sur lesquelles nous nous sommes penchés. Pour ce qui est des issues néonatales, nous nous sommes penchés sur le faible indice d'Apgar, le faible pH mis au jour par gazométrie du sang artériel, la nécessité de procéder à une réanimation néonatale ou à une admission à l'UNSI et le décès néonatal. Une régression logistique multivariée a été utilisée pour neutraliser l'effet des caractéristiques démographiques et obstétricales maternelles. Résultats : Nous avons constaté que de multiples intervalles intergrossesses ont été marqués par une hausse du risque d'accouchement préterme : un intervalle de 0 à 5 mois était associé à un rapport de cotes corrigé (RCc) de 1,37 (IC à 95 %, 1,18 - 1,59), un intervalle de 6 à 11 mois était associé à un RCc de 1,18 (IC à 95 %, 1,04 - 1,34), un intervalle de 24 à 35 mois était associé à un RCc de 1,16 (IC à 95 %, 1,02 - 1,31) et un intervalle de plus de 36 mois était associé à un RCc de 1,36 (IC à 95 %, 1,20 - 1,53), par comparaison avec l'intervalle de référence (de 12 à 17 mois). Le risque de FPN a connu une hausse dans le cas des intervalles intergrossesses de 0 à 5 mois (RCc, 1,48; IC à 95 %, 1,23 - 1,80), de 6 à 11 mois (RCc, 1,21; IC à 95 %, 1,03 - 1,42), de 24 à 35 mois (RCc, 1,21; IC à 95 %, 1,03 - 1,41) et de plus de 36 mois (RCc, 1,48; IC à 95 %, 1,27 - 1,73). Le risque d'hypotrophie fœtale a connu une hausse dans le cas des intervalles intergrossesses de 0 à 5 mois (RCc, 1,29; IC à 95 %, 1,09 - 1,52), de 24 à 35 mois (RCc, 1,15; IC à 95 %, 1,01 - 1,31) et de plus de 36 mois (RCc, 1,26; IC à 95 %, 1,11 - 1,44). Le risque de décès périnatal a connu une hausse dans le cas de l'intervalle intergrossesse de plus de 36 mois (RCc, 1,60; IC à 95 %, 1,06 - 2,43). Des associations semblables ont également été constatées pour ce qui est des issues néonatales. Conclusion : Cette étude laisse entendre que les intervalles intergrossesses tant courts que longs sont associés à des issues indésirables périnatales et néonatales, et elle offre des estimations du risque pour une population canadienne au cours des années suivant la décision qui a rendu obligatoire l'enrichissement des aliments en folate.

Relationship between interpregnancy interval and congenital anomalies.

OBJECTIVE: To assess the association between interpregnancy intervals and congenital anomalies. STUDY DESIGN: A retrospective cohort study on women who had 2 consecutive singleton births from 1999-2007 was conducted using a linked dataset from the Alberta Perinatal Health Program, the Alberta Congenital Anomalies Surveillance System, and the Alberta Health and Wellness Database. Interpregnancy interval was calculated as the interval between 2 consecutive deliveries minus the gestational age of the second infant. The primary outcome of congenital anomaly was defined using the International Classification of Diseases. Maternal demographic and obstetric characteristics and interpregnancy intervals were included in multivariable logistic regression models for congenital anomalies. RESULTS: The study included 46,243 women, and the overall rate of congenital anomalies was 2.2%. Both short and long interpregnancy intervals were associated with congenital anomalies. The lowest rate was for the 12-17 months category (1.9%, reference category), and increased rates were seen for both short intervals (2.5% for 0-5 months; adjusted odds ratio, 1.32; 95% confidence interval, 1.01-1.72) and long intervals (2.3% for 24-35 months; adjusted odds ratio, 1.25; 95% confidence interval, 1.02-1.52). Statistically significant associations were also observed for folate independent anomalies, but not for folate dependent anomalies. CONCLUSION: The risk of congenital anomalies appears to increase with both short and long interpregnancy intervals. This study supports the limited existing studies in the literature, further explores the types of anomalies affected, and has implications for further research and prenatal risk assessment.

Predicting High-Risk Fetal Cardiac Disease Anticipated to Need Immediate Postnatal Stabilization and Intervention with Planned Pediatric Cardiac Operating Room Delivery.

BACKGROUND: Distances between delivery and cardiac services can make the care of fetuses with cardiac disease at risk of acute cardiorespiratory instability at birth a challenge. In 2013 we implemented a fetal echocardiography-based algorithm targeting fetuses considered high risk for acute cardiorespiratory instability at ≤2 hours of birth for delivery in our pediatric cardiac operating room of our children's hospital, and, herein, examine our experience. METHODS AND RESULTS: We reviewed maternal and postnatal medical records of all fetuses with cardiac disease encountered January 2013 to March 2022 considered high risk for acute cardiorespiratory instability. Secondary analysis was performed including all fetuses with diagnoses of d-transposition of the great arteries/intact ventricular septum (d-TGA/IVS) and hypoplastic left heart syndrome (HLHS) encountered over the study period. Forty fetuses were considered high risk for acute cardiorespiratory instability: 15 with d-TGA/IVS and 7 with HLHS with restrictive atrial septum, 4 with absent pulmonary valve syndrome, 3 with obstructed anomalous pulmonary veins, 2 with severe Ebstein anomaly, 2 with thoracic/intracardiac tumors, and 7 others. Pediatric cardiac operating room delivery occurred for 33 but not for 7 (5 with d-TGA/IVS, 2 with HLHS with restrictive atrial septum). For high-risk cases, fetal echocardiography had a positive predictive value of 50% for intervention/extracorporeal membrane oxygenation/death at ≤2 hours and 70% at ≤24 hours. Of "low-risk" cases, 6/46 with d-TGA/IVS and 0/45 with HLHS required intervention at ≤2 hours. Fetal echocardiography for predicting intervention/extracorporeal membrane oxygenation/death at ≤2 hours had a sensitivity of 67%, specificity 93%, and positive and negative predictive values of 80% and 87%, respectively, for d-TGA/IVS, and 100%, 95%, 71%, and 100% for HLHS, respectively. CONCLUSIONS: Fetal echocardiography can predict the need for urgent intervention in a majority with d-TGA/IVS and HLHS and in half of the entire spectrum of high-risk cardiac disease.

Successful outcome with intrauterine transfusion in non-immune hydrops fetalis secondary to congenital syphilis.

BACKGROUND: Congenital syphilis is rare, but the incidence has increased over the last few years in Alberta. Previous reports of fetal hydrops secondary to syphilis are few and have not demonstrated the application of middle cerebral artery peak systolic velocity (MCA PSV) to monitor for fetal anemia, or reported successful management with intrauterine transfusion. CASE: A 17-year-old primigravida at 28 weeks' gestational age with positive syphilis serology and fetal hydrops was treated with high-dose intravenous penicillin. An elevated MCA PSV suggested fetal anemia. Successful intrauterine cordocentesis and transfusion of packed red blood cells led to resolution of fetal hydrops. The fetus delivered spontaneously at 35 weeks' gestation with no clinical signs of congenital syphilis. CONCLUSION: Syphilitic hydrops may be successfully managed with high dose intravenous penicillin, measurement of MCA PSV, and intrauterine transfusion.

Changes in maternal characteristics and obstetric practice and recent increases in primary cesarean delivery.

OBJECTIVE: To estimate the contribution of changes in maternal characteristics (namely, age, parity, prepregnancy weight, weight gain in pregnancy, smoking status) and obstetric practice (namely, labor induction, epidural anesthesia, delivery by an obstetrician, midpelvic forceps delivery) to recent increases in primary cesarean delivery rates. METHODS: We studied all deliveries in Nova Scotia, Canada, between 1988 and 2000 after excluding women who had a previous cesarean delivery (n = 127,564). Logistic regression was used to study the effect of changes in maternal characteristics and obstetric practice on primary cesarean delivery rates. The effect of changes in midpelvic forceps delivery was examined through ecologic Poisson regression. RESULTS: Primary cesarean delivery rates increased from 13.4% of deliveries in 1988 to 17.5% in 2000. This was due to increases in cesarean deliveries for dystocia (14% increase), breech (24% increase), suspected fetal distress (21% increase), hypertension (47% increase), and miscellaneous indications (73% increase). Adjustment for maternal characteristics reduced the temporal increase in primary cesarean delivery rates between 1988-1991 and 1998-2000 from 21% (95% confidence interval [CI] 16%, 25%) to 2% (95% CI -2%, 7%). Additional adjustment for obstetric practice factors further reduced period effects. Midpelvic forceps delivery was significantly and negatively associated with primary cesarean delivery (P =.001). CONCLUSION: Recent increases in primary cesarean delivery rates are a consequence of changes in maternal characteristics. Obstetric practice, which has altered due to changes in maternal characteristics and concerns related to fetal and maternal safety, has also contributed to increases in primary cesarean delivery.

A preliminary study of cutaneous blood flow associated with postpartum use of oral misoprostol.

OBJECTIVE: To evaluate cutaneous blood flow, as identified by Doppler fluximetry, to understand the etiology of shivering associated with the postpartum use of oral misoprostol. METHODS: Eligible participants were recruited from a group of women who were enrolled in an ongoing randomized trial comparing 400 microg of oral misoprostol to 5 IU of intravenous oxytocin for postpartum hemorrhage prophylaxis. The laser Doppler fluximeter was used to noninvasively measure changes in peripheral tissue perfusion (flux). A skin probe attached to the upper arm recorded flux and skin temperature. Baseline levels were obtained before delivery and for 30 minutes postpartum (maximum flux) after the women received the study drug. Continuous variables were analyzed with Student t-test or paired t-test, with the Wilcoxon signed rank test used for non-parametric ordinal data. Categoric data were analyzed with the chi-square test or Fisher's exact test. RESULTS: Sixteen women were enrolled, and 10 women had a vaginal delivery and received the study drugs. Among these 10 women, a significant difference between baseline and maximum flux levels was demonstrated for both women treated with oxytocin (P = .04) and for those treated with misoprostol (P = .04). Women treated with oxytocin also had a significant change in skin temperature (P = .04). Maximum flux levels were not significantly different between the women receiving misoprostol compared with those receiving oxytocin (P = .42). CONCLUSIONS: Shivering associated with oral misoprostol may not be due to a resetting of the hypothalamic thermoregulatory centre. Further study is needed to determine whether shivering associated with oral misoprostol is dose-dependent or related to locally mediated phenomena.

Maternal serum screening: practice patterns of physicians in Newfoundland.

OBJECTIVE: To compare the utilization of the second trimester maternal serum screen (MSS) of a-fetoprotein, human chorionic gonadotrophin, and unconjugated estriol, in Newfoundland, by practice location, training, and gender. METHODS: Four hundred eighteen anonymous self-reported questionnaires were mailed out to all practising family physicians, general practitioners, and obstetricians in Newfoundland, who were identified through the provincial medical board. The survey included questions on demographic characteristics, provision of antenatal care, gestational age at which MSS is ordered, reasons for offering or not offering MSS, and the use of routine antenatal ultrasound. Categorical data were analyzed using chi-square and Fisher exact tests, as appropriate. RESULTS: Overall, 63% of physicians responded to the survey. Forty percent of respondents had an urban practice. Female physicians, regardless of specialty, were more likely to offer MSS to their patients (89% vs. 78%; P = 0.04), whereas family physicians and obstetricians were more likely to offer screening than general practitioners (85% vs. 83% vs. 25%; P = 0.02). Among physicians offering MSS, 54% offered it only to women 35 years and older. Practice location did not affect whether a woman was offered MSS (P = 0.41). Twenty-five percent of family physicians offering MSS did not offer it at the appropriate gestational age of 15 to 20 weeks. Ninety-four percent of pregnant women were routinely offered an ultrasound during pregnancy. CONCLUSION: The utilization of MSS in Newfoundland is affected by physician training and gender, but not by practice location. Further education of physicians is required to ensure appropriate use and timing of this screening test.

A case of alloimmune thrombocytopenia, hemorrhagic anemia-induced fetal hydrops, maternal mirror syndrome, and human chorionic gonadotropin-induced thyrotoxicosis.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin-induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.

Management of pregnancy-associated thrombotic thrombocytopenia purpura.

Thrombotic thrombocytopenia purpura (TTP) is an infrequent but serious disease. Pregnancy is a known risk factor for presentation or relapse of TTP. Difficulties in differentiating TTP from preeclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, and current treatment recommendations are discussed in this case report. A woman with previously treated and stable TTP had a relapse at 36 weeks' gestation. Careful surveillance led to an early diagnosis. Severe disease in the peripartum period was treated successfully with cryosupernatant plasma-based plasmapheresis and platelet transfusion, with good maternal and neonatal outcomes. Cryosupernatant plasma is a viable alternative to fresh frozen plasma for plasmapheresis for TTP and may offer some therapeutic and logistical advantages. Platelet transfusion can be undertaken safely if needed to prevent or treat significant hemorrhage.

Transvaginal ultrasonography to predict preterm birth in women with bicornuate or didelphus uterus.

OBJECTIVE: To estimate whether cervical length measured by transvaginal ultrasonography (TVUS) in women with uterine anomalies predicts spontaneous preterm birth (SPTB). METHODS: This retrospective cohort study compared women with a uterine anomaly who were pregnant with singleton gestations and delivered August 2000 to April 2008 to a low risk control group. Transvaginal ultrasonographic cervical lengths were measured 16-30 weeks gestation. Primary outcome was cervical length and SPTB less than 35 weeks and the primary exposure variable of interest was cervical length. Secondary outcomes were SPTB less than 37 weeks, less than 32 weeks, low birth weight, maternal and neonatal outcomes. Receiver operating characteristic curves were generated to identify the best cervical length cutoff. RESULTS: Women with a bicornuate uterus (N = 35) had shorter cervical length (3.46 cm) than the low risk control group (N = 122, 4.32 cm, p < 0.0001). Women with a bicornuate or didelphus uterus, compared with low risk women, had higher rates of SPTB less than 35 weeks (8.6% and 30.8% versus 0.8%, p = 0.0007), neonatal intensive care unit admission more than 24 h (26.5% and 41.7% versus 7.5%, p = 0.0021) and composite perinatal morbidity (32.4% and 69.2% versus 8.3%, p < 0.0001). Using a cutoff of 3.0 cm, TVUS cervical length in women with a bicornuate uterus predicted SPTB less than 35 weeks (positive predictive value [PPV] = 37.5% and negative predictive value [NPV] = 100%), birth weight less than 2500 g (PPV = 50.0% and NPV = 96.3%) and respiratory distress syndrome (PPV = 37.5% and NPV = 100%). CONCLUSION Women with a bicornuate uterus have shorter cervical lengths than low risk controls, and are at higher risk of SPTB less than 35 weeks. Transvaginal ultrasonographic cervical length predicts SPTB less than 35 weeks, low birth weight and perinatal morbidity in these women.

Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes.

OBJECTIVE: The study was undertaken to determine the risks of adverse obstetric outcomes in pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) and/or human chorionic gonadotropin (hCG) and to determine whether these risks vary by prepregnancy risk status. STUDY DESIGN: All women who underwent double-marker screening (MSAFP+hCG) between 1994 and 2000 and were delivered of an infant in Nova Scotia, Canada, during this period were identified from a hospital serum screening database and a provincial perinatal database. Patients with inaccurate dating, major structural anomalies, or chromosomal abnormalities were excluded. The primary outcomes studied were preeclampsia, abruptio placentae, fetal growth restriction, fetal death, and preterm birth. Women with medical or previous obstetric complications were designated high risk. Logistic regression, controlling for confounding factors, was used to estimate the relative risks (RRs) and 95% CI for elevated levels of MSAFP and/or hCG and each of the outcomes. RESULTS: Among the 14,374 women who met the study criteria, 5,789 were designated high risk. Except for abruptio placentae, unexplained elevated MSAFP or elevated hCG levels were independently associated with all the outcomes in both high- and low-risk women. Elevated screening values were associated with increased risk of abruptio placentae among low-risk women only. Particularly large RRs were seen for fetal death in both high- and low-risk women (RR=4.9, 95% CI 2.7-8.7 for elevated MSAFP or hCG in high- and low-risk women combined). CONCLUSION: Unexplained elevated levels of MSAFP and/or hCG are associated with an increased risk of most pregnancy complications. Increased antenatal surveillance of these patients is important regardless of prepregnancy risk status.