Associations between the Safe Prevention of Primary Cesarean Delivery Care Consensus and Maternal/Neonatal Outcomes.

OBJECTIVE: This study aimed to compare cesarean delivery (CD) rates and maternal/neonatal outcomes before and after the 2014 ACOG/SMFM Obstetric Care Consensus for Safe Prevention of Primary CD. STUDY DESIGN: This retrospective study compared unscheduled CD rates and outcomes of singleton, cephalic, term pregnancies at a tertiary-care teaching maternity hospital. Births 5 years before (March 2009-February 2014) and after (June 2014-May 2019) release of the consensus were included. Chi-square and t-test were used to compare outcomes and logistic regression to adjust for confounders. RESULTS: In this study, 44,001 pregnancies were included, 20,887 before and 23,114 after the consensus. Unscheduled CD rates increased after the consensus (12.9 vs. 14.3%, p < 0.001); however, there was no difference after adjustment (adjusted odds ratio [aOR], 0.97; 95% confidence interval [CI], 0.91-1.03). Vaginal birth after cesarean (VBAC) deliveries increased among multiparas (4.8 vs. 7.2%, p < 0.001), which remained significant after adjustment (aOR, 1.51; 95% CI, 1.37-1.66). Postpartum hemorrhage, blood transfusion, and chorioamnionitis were modestly increased, while third-degree perineal lacerations decreased. Uterine rupture and neonatal outcomes were unchanged after adjustment. CONCLUSION: At our tertiary-care maternity hospital, the Safe Prevention of Primary CD Care Consensus was not associated with a change in unscheduled CD, though VBAC deliveries increased. We did not demonstrate improved neonatal outcomes and showed increased maternal morbidity that warrants further study. KEY POINTS: · Consensus did not change unscheduled cesarean rates.. · Consensus associated with increased hemorrhage.. · Institutional outcomes can assist implementing changes..

The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

Second trimester prediction of gestational diabetes: maternal analytes as an additional screening tool.

OBJECTIVES: Early diagnosis of gestational diabetes can lead to greater optimization of glucose control. We evaluated associations between maternal serum analytes (alpha-fetoprotein [AFP], free beta-human chorionic gonadotropin [beta-hCG], inhibin, and estriol) and the development of gestational diabetes mellitus (GDM). METHODS: This retrospective cohort study identified single-ton pregnancies with available second trimester serum analytes between 2009 and 2017. GDM was identified by ICD-9 and -10 codes. We examined the associations between analyte levels and GDM and to adjust for potential confounders routinely collected during genetic serum screening (maternal age, BMI, and race) using logistic regression. Optimal logistic regression predictive modeling for GDM was then performed using the analyte levels and the above mentioned potential confounders. The performance of the model was assessed by receiver operator curves. RESULTS: Out of 5,709 patients, 660 (11.6%) were diagnosed with GDM. Increasing AFP and estriol were associated with decreasing risk of GDM, aOR 0.76 [95% CI 0.60-0.95] and aOR 0.67 [95% CI 0.50-0.89] respectively. Increasing beta-hCG was associated with a decreasing risk for GDM(aOR 0.84 [95% CI 0.73-0.97]). There was no association with inhibin. The most predictive GDM predictive model included beta-hCG and estriol in addition to the clinical variables of age, BMI, and race (area under the curve (AUC 0.75), buy this was not statistically different than using clinical variables alone (AUC 0.74) (p=0.26). CONCLUSIONS: Increasing second trimester AFP, beta-hCG, and estriol are associated with decreasing risks of GDM, though do not improve the predictive ability for GDM when added to clinical risk factors of age, BMI, and race.

Academic clinical learning environment in obstetrics and gynecology during the COVID-19 pandemic: responses and lessons learned.

COVID-19 pandemic is changing profoundly the obstetrics and gynecology (OB/GYN) academic clinical learning environment in many different ways. Rapid developments affecting our learners, patients, faculty and staff require unprecedented collaboration and quick, deeply consequential readjustments, almost on a daily basis. We summarized here our experiences, opportunities, challenges and lessons learned and outline how to move forward. The COVID-19 pandemic taught us there is a clear need for collaboration in implementing the most current evidence-based medicine, rapidly assess and improve the everchanging healthcare environment by problem solving and "how to" instead of "should we" approach. In addition, as a community with very limited resources we have to rely heavily on internal expertise, ingenuity and innovation. The key points to succeed are efficient and timely communication, transparency in decision making and reengagement. As time continues to pass, it is certain that more lessons will emerge.

Maternal cardiovascular-related single nucleotide polymorphisms, genes, and pathways associated with early-onset preeclampsia.

INTRODUCTION: Preeclampsia is a medical condition complicated with hypertension and proteinuria during pregnancy. While preeclampsia affects approximately 5% of pregnancies, it remains without a cure. In addition, women who had preeclampsia during pregnancy have been reported to have an increased risk for cardiovascular disease later in life. However, the disease etiology and molecular mechanisms remain poorly understood. The paucity in the literature on preeclampsia associated maternal cardiovascular risk in different ethnic populations also present a need for more research. Therefore, the objective of this study was to identify cardiovascular/metabolic single nucleotide polymorphisms (SNPs), genes, and regulatory pathways associated with early-onset preeclampsia. MATERIALS AND METHODS: We compared maternal DNAs from 31 women with early-onset preeclampsia with those from a control group of 29 women without preeclampsia who delivered full-term normal birthweight infants. Women with multiple gestations and/or known medical disorders associated with preeclampsia (pregestational diabetes, chronic hypertension, renal disease, hyperthyroidism, and lupus) were excluded. The MetaboChip genotyping array with approximately 197,000 SNPs associated with metabolic and cardiovascular traits was used. Single nucleotide polymorphism analysis was performed using the SNPAssoc program in R. The Truncated Product Method was used to identify significantly associated genes. Ingenuity Pathway Analysis and Ingenuity Causal Network Analysis were used to identify significantly associated disease processes and regulatory gene networks respectively. RESULTS: The early-onset preeclampsia group included 45% Filipino, 26% White, 16% other Asian, and 13% Native Hawaiian and other Pacific Islanders, which did not differ from the control group. There were no SNPs associated with early-onset preeclampsia after correction for multiple comparisons. However, through gene-based tests, 68 genes and 23 cardiovascular disease-related processes were found to be significantly associated. Associated gene regulatory networks involved cellular movement, cardiovascular disease, and inflammatory disease. CONCLUSIONS: Multiple cardiovascular genes and diseases demonstrate associations with early-onset preeclampsia. This unfolds new areas of research regarding the genetic determinants of early-onset preeclampsia and their relation to future cardiovascular disease.

Delayed Appearance of a Traumatic Fetal Intracranial Hemorrhage.

BACKGROUND: Fetal intracranial injury is a potentially devastating sequelae of maternal trauma, but there is little guidance regarding fetal evaluation in this setting. CASE: A 23-year-old woman at 27-week gestation was admitted after a high-speed motor vehicle accident. The initial obstetrical ultrasound was unremarkable, but persistently minimal fetal heart rate variability was observed. Ultrasound on day 3 after the accident showed an intracranial hyperechogenic lesion and subdural fluid collection. The neonate, following an uneventful birth at 39 weeks, had seizures and abnormal muscle tone. MRI was consistent with in utero intracranial hemorrhage. CONCLUSION: Serial fetal imaging following maternal trauma, particularly when accompanied by abnormal fetal heart rate tracings, should be considered when fetal injury is a concern, even in the setting of a normal initial ultrasound.

Effect of dialysis on fetal heart rate: is inpatient admission for fetal monitoring necessary?

OBJECTIVE: Pregnant patients receiving hemodialysis (HD) have long hospital stays for the purpose of electronic fetal monitoring (EFM) during HD, which allows for monitoring of fetal well-being. However, more frequent dialysis allows for smaller fluid shifts, preventing maternal hypotension. Our aim was to determine differences in rates of EFM abnormalities during HD versus non-stress testing (NST) off dialysis for gravid women with renal failure. METHODS: Retrospective cohort study over a 13-year period (2000-2013) identified five patients with renal failure in pregnancy. EFM tracings were reviewed during HD (cases) and routine inpatient NST off HD (controls). Standardized nomenclature was used to identify EFM abnormalities. The rate of abnormalities per hour of EFM was calculated. Kruskal-Wallis test was used and statistical significance was set at p < 0.05. RESULTS: There were no significant differences in late decelerations (p = 0.2) between cases and controls. Significantly fewer variable decelerations (p = 0.01) and contractions (p ≤0.001) were noted during dialysis compared to controls. Significantly more prolonged decelerations (p = 0.02) were noted during HD compared to controls. CONCLUSION: There may be no fetal benefit of EFM during HD for gravid women with renal disease attributed to hypertensive and diabetic nephropathy. There may be cost savings by shifting HD to the outpatient setting.

Systemic and placental α-klotho: Effects of preeclampsia in the last trimester of gestation.

INTRODUCTION: α-klotho is an anti-aging protein, potentially important in preeclampsia (PE). Produced by kidney, brain and placenta, and by mRNA splicing is both a full-length membrane-bound and a truncated soluble protein in the circulation. The membrane-bound protein is an obligate co-receptor for fibroblast growth factor 23 (FGF23) and its action on receptor (FGFR), but ADAM proteinases also cause its shedding. The aims of this study were to investigate levels of maternal plasma, placental, and fetal membrane α-Klotho and their association with placental accelerated villous maturation (AVM) in PE. In addition, placental and membrane levels of ADAM17 and FGFR were measured in the same patients. METHODS: Maternal blood, placenta and fetal membranes from 61 women (31 with PE and 30 controls) between 32 and 40 weeks gestation were collected. Plasma α-klotho was measured by ELISA, and quantitative immunohistochemistry used for α-klotho, ADAM17 and FGFR1 in tissues. Placental AVM was histologically assessed. RESULTS: Maternal plasma levels of α-Klotho were higher in PE compared to controls (p = 0.01) and patients with the highest levels had significantly less AVM (p = 0.03). α-Klotho, ADAM17, and FGFR were all present in syncytiotrophoblast and cytotrophoblast of membranes. Between 32 and 40 weeks gestation, all placental levels decreased in controls respectively (p = 0.04, p = 0.004, p = 0.05), but not in PE. Fetal membrane levels were unchanged. DISCUSSION: Maternal plasma α-Klotho was increased in PE and its levels associated with reduced placental AVM. Changes in placental α-Klotho, ADAM17, and FGFR suggest their involvement in the pathophysiology of PE.

A Priori Attitudes Predict Amniocentesis Uptake in Women of Advanced Maternal Age: A Pilot Study.

Amniocentesis is an invasive procedure performed during pregnancy to determine, among other things, whether the fetus has Down syndrome. It is often preceded by screening, which gives a probabilistic risk assessment. Thus, ample information is conveyed to women with the goal to inform their decisions. This study examined the factors that predict amniocentesis uptake among pregnant women of advanced maternal age (older than 35 years old at the time of childbirth). Participants filled out a questionnaire regarding risk estimates, demographics, and attitudes on screening and pregnancy termination before their first genetic counseling appointment and were followed up to 24 weeks of gestation. Findings show that women's decisions are not always informed by screening results or having a medical indication. Psychological factors measured at the beginning of pregnancy: amniocentesis risk tolerance, pregnancy termination tolerance, and age risk perception affected amniocentesis uptake. Although most women thought that screening for Down syndrome risk would inform their decision, they later stated other reasons for screening, such as preparing for the possibility of a child with special needs. Findings suggest that women's decisions regarding amniocentesis are driven not only by medical factors, but also by a priori attitudes. The authors believe that these should be addressed in the dialogue on women's informed use of prenatal tests.

Increased false positive Down syndrome screening in women with sickle cell anemia.

OBJECTIVES: This study seeks to determine whether there is a higher rate of false positive serum screening for Down syndrome in women with sickle cell anemia and, if so, which markers contribute to the false positive screen. METHODS: This is a retrospective cohort study of women who had serum screening between 1998 and 2011. Subjects were women with sickle cell anemia (n = 13), and controls were African American women who did not have that disease (n = 91). The populations were compared using basic inferential statistics. RESULTS: The positive screen rate was 38.5% (5/13) in women with sickle cell anemia and 7.7% (7/91) in the control population (odds ratio 7.5, 95% confidence interval 1.6-35.8, P = 0.001). At the average age of the cases (25 years), the expected false positive rate is only 2%. The human chorionic gonadotrophin values were significantly higher in cases than controls (2.00 and 1.30 MoM, P = 0.017), whereas levels of other serum analytes were similar. None of the screen positive results were associated with a fetus or neonate affected by Down syndrome. CONCLUSIONS: The false positive Down syndrome serum screen rate is significantly higher in patients with sickle cell anemia than in African American women without that disease. The human chorionic gonadotrophin values were significantly higher in cases than controls, suggesting that placental factors may contribute to the elevated false positive rate. © 2015 John Wiley & Sons, Ltd.

Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia.

BACKGROUND: Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide epigenetic alterations occur in cord blood DNAs in association with EOPE and conducted a case control study to compare the genome-scale methylome differences in cord blood DNAs between 12 EOPE-associated and 8 normal births. RESULTS: Bioinformatics analysis of methylation data from the Infinium HumanMethylation450 BeadChip shows a genome-scale hypomethylation pattern in EOPE, with 51,486 hypomethylated CpG sites and 12,563 hypermethylated sites (adjusted P <0.05). A similar trend also exists in the proximal promoters (TSS200) associated with protein-coding genes. Using summary statistics on the CpG sites in TSS200 regions, promoters of 643 and 389 genes are hypomethylated and hypermethylated, respectively. Promoter-based differential methylation (DM) analysis reveals that genes in the farnesoid X receptor and liver X receptor (FXR/LXR) pathway are enriched, indicating dysfunction of lipid metabolism in cord blood cells. Additional biological functional alterations involve inflammation, cell growth, and hematological system development. A two-way ANOVA analysis among coupled cord blood and amniotic membrane samples shows that a group of genes involved in inflammation, lipid metabolism, and proliferation are persistently differentially methylated in both tissues, including IL12B, FAS, PIK31, and IGF1. CONCLUSIONS: These findings provide, for the first time, evidence of prominent genome-scale DNA methylation modifications in cord blood DNAs associated with EOPE. They may suggest a connection between inflammation and lipid dysregulation in EOPE-associated newborns and a higher risk of cardiovascular diseases later in adulthood.

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Genome-wide hypermethylation coupled with promoter hypomethylation in the chorioamniotic membranes of early onset pre-eclampsia.

Pre-eclampsia is the leading cause of fetal and maternal morbidity and mortality. Early onset pre-eclampsia (EOPE) is a disorder that has severe maternal and fetal outcomes, whilst its etiology is poorly understood. We hypothesize that epigenetics plays an important role to mediate the development of EOPE and conducted a case-control study to compare the genome-wide methylome difference between chorioamniotic membranes from 30 EOPE and 17 full-term pregnancies using the Infinium Human Methylation 450 BeadChip arrays. Bioinformatics analysis tested differential methylation (DM) at CpG site level, gene level, and pathway and network level. A striking genome-wide hypermethylation pattern coupled with hypomethylation in promoters was observed. Out of 385 184 CpG sites, 9995 showed DM (2.6%). Of those DM sites, 91.9% showed hypermethylation (9186 of 9995). Over 900 genes had DM associated with promoters. Promoter-based DM analysis revealed that genes in canonical cancer-related pathways such as Rac, Ras, PI3K/Akt, NFκB and ErBB4 were enriched, and represented biological functional alterations that involve cell cycle, apoptosis, cancer signaling and inflammation. A group of genes previously found to be up-regulated in pre-eclampsia, including GRB2, ATF3, NFKB2, as well as genes in proteasome subunits (PSMA1, PMSE1, PSMD1 and PMSD8), harbored hypomethylated promoters. Contrarily, a cluster of microRNAs, including mir-519a1, mir-301a, mir-487a, mir-185, mir-329, mir-194, mir-376a1, mir-486 and mir-744 were all hypermethylated in their promoters in the EOPE samples. These findings collectively reveal new avenues of research regarding the vast epigenetic modifications in EOPE.

Population-based biomarker screening and the development of severe preeclampsia in California.

OBJECTIVE: The purpose of this study was to examine the relationship between second-trimester maternal serum biomarkers and the development of early- and late-onset severe preeclampsia in euploid pregnancies. STUDY DESIGN: Included were 136,139 pregnancies that obtained second-trimester prenatal screening through the California Prenatal Screening Program with live births in 2006-2008. We identified severe preeclampsia diagnoses from hospital discharge records. We used log binomial regression to examine the association between abnormal second-trimester maternal serum biomarkers and the development of severe preeclampsia. RESULTS: Approximately 0.9% of all women (n = 1208) in our sample experienced severe preeclampsia; 329 women at <34 weeks' gestation and 879 women ≥34 weeks' gestation. High levels of alpha fetoprotein (AFP), human chorionic gonadotropin, inhibin (multiple of the median, ≥95th percentile), and low unconjugated estriol (multiple of the median, ≤5th percentile), were associated with severe preeclampsia (relative risk, 2.5-11.7). Biomarkers were more predictive of early-onset severe preeclampsia (relative risk, 3.8-11.7). One in 9.5 pregnancies with combined high AFP, inhibin, and low unconjugated estriol levels experienced severe early-onset preeclampsia compared with 1 in 680.5 pregnancies without any abnormal biomarkers. CONCLUSION: The risk of the development of severe preeclampsia increases for women with high second-trimester AFP, human chorionic gonadotropin, inhibin, and/or low unconjugated estriol; this is especially true for early-onset severe preeclampsia. When abnormal biomarkers co-occur, risk dramatically increases. Although the screening value of second-trimester biomarkers is low, abnormal biomarkers, especially when occurring in combination, appear to indicate placental dysfunction that is associated with the development of severe preeclampsia.

Obstetric, perinatal, and fetal outcomes in pregnancies with false-positive integrated screening results.

OBJECTIVE: To assess the risk of adverse obstetric, perinatal, and fetal outcomes for pregnant women participating in prenatal sequential integrated screening through the California Prenatal Screening Program who had a false-positive screening result. METHODS: Women who underwent first- and second-trimester prenatal integrated screening plus nuchal translucency measurement with outcome information available were included. Fetuses and neonates with chromosomal or neural tube defects were excluded. We compared the risk of adverse outcomes for all women with a positive screening result compared with a 10% random sample of women with a negative screening result. Logistic binomial regression was used to compare adverse outcomes in screen-positive compared with screen-negative women. RESULTS: We identified 9,051 screen-positive and 30,928 screen-negative pregnancies with outcome information available. Compared with screen-negative pregnancies, screen-positive women were more likely to be diagnosed with preeclampsia, placenta previa, or abruption (7.6% screen-positive, 3.8% screen-negative; relative risk 1.7, 95% confidence interval [CI] 1.6-1.8) or experience fetal loss before 20 weeks of gestation (1.9% screen-positive, 0.2% screen-negative; relative risk 3.5, 95% CI 3.2-3.8). Women with positive results for more than one screened condition were at substantially greater risk of fetal and neonatal mortality (relative risks 33.6-156.7, 95% CIs 21.8-194.4). CONCLUSION: Among pregnancies without chromosomal or neural tube defects, prenatal sequential integrated screening provides information regarding risk across a variety of adverse pregnancy outcomes.

Pregnancy outcome in anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder resulting in neurologic and psychiatric symptoms. Treatment is challenging in pregnancy, because little data exist to guide management. CASE: A 24-year-old woman with a known diagnosis of anti-NMDA receptor encephalitis using intravenous immunoglobulin therapy became pregnant. Her pregnancy was uncomplicated with no relapses. She delivered at 35 4/7 weeks of gestation after having preterm premature rupture of membranes. She had a relapse of symptoms after delivery. CONCLUSION: This patient with anti-NMDA receptor encephalitis had an uneventful pregnancy with overall good outcome; however, she experienced relapse soon after delivery. This disease may mimic other autoimmune diseases, with improvement during pregnancy and risk for relapse postpartum.

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Academic medical centers (AMCs) are pillars of the community; they provide health care, create jobs, educate biomedical professionals, and engage in research and innovation. To sustain their impact on human health, AMCs must improve the professional satisfaction of their faculty. Here, we describe ways to enhance recruitment, retention, creativity, and productivity of health science faculty.

Nighttime delivery and risk of neonatal encephalopathy.

OBJECTIVE: The objective of the study was to determine the relationship between nighttime delivery and neonatal encephalopathy (NE). STUDY DESIGN: The design of the study was a retrospective population-based cohort of 1,864,766 newborns at a gestation of 36 weeks or longer in California, 1999-2002. We determined the risk of NE associated with nighttime delivery (7:00 (PM) to 6:59 (AM)). RESULTS: Two thousand one hundred thirty-one patients had NE (incidence 1.1 per 1000 births). Nighttime delivery was associated with increased NE (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.03-1.20), birth asphyxia (OR, 1.18; 95% CI, 1.08-1.29), and neonatal seizures (OR, 1.17; 95% CI, 1.07-1.28). In adjusted analyses, nighttime delivery was an independent risk factor for NE (OR, 1.10; 95% CI, 1.01-1.21), as were severe intrauterine growth retardation (OR, 3.8; 95% CI, 3.1-4.8); no prenatal care (OR, 2.0; 95% CI, 1.4-2.9); primiparity (OR, 1.5; 95% CI, 1.4-1.7); advanced maternal age (OR, 1.3; 95% CI, 1.16-1.45); and infant male sex (OR, 1.3; 95% CI, 1.2-1.4). CONCLUSION: Future studies of time of delivery may generate new strategies to reduce the burden of NE.

Comparison of single versus multiple echogenic foci in the fetal heart regarding risk of aneuploidy.

OBJECTIVE: The purpose of this study was to investigate whether multiple echogenic cardiac foci (ECF) are associated with an increased risk of fetal trisomy 21 in our patient population. METHODS: During a span of 38 months, all women found to have an ECF on obstetric sonography were identified as study patients and grouped into single- and multiple-ECF groups. Age- and race-matched patients were identified as a control group. Fetal anatomic sonographic examinations were assessed for other markers of aneuploidy and major abnormalities. The baseline risk for trisomy 21 was assessed by maternal serum screening or age alone if no serum screening had been performed. Trisomy 21 was assessed by amniocentesis or clinically at birth. Both univariate and multivariate analyses were used to assess for associations with trisomy 21. RESULTS: Six of 71 patients (8.5%) with multiple ECF and 1 of 171 patients (0.6%) with a single ECF had trisomy 21. One of 242 control patients (0.4%) had trisomy 21. Logistic regression found multiple ECF (P < .008), the presence of a major finding or multiple minor findings (P = .0012), and a baseline risk for trisomy 21 of greater than 1 in 100 (P = .003) as independent associations with trisomy 21. CONCLUSIONS: Our results suggest that finding multiple ECF is a stronger predictor of trisomy 21 than what is described for a single ECF.