Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study.

Background: In the coBRIM phase III trial, the addition of cobimetinib, an MEK inhibitor, to vemurafenib, a BRAF inhibitor, significantly improved progression-free survival [hazard ratio (HR), 0.58; P < 0.0001] and overall survival (HR, 0.70; P = 0.005) in advanced BRAF-mutated melanoma. Here, we report on the incidence, course, and management of key adverse events (AEs) in the coBRIM study. Patients and methods: Patients were randomly assigned 1:1 to receive vemurafenib (960 mg twice a day) and either cobimetinib (60 mg once a day, 21 days on/7 days off) or placebo. In addition to standard safety evaluations, patients underwent regular ophthalmic, cardiac, and dermatologic surveillance examinations. Results: Of 495 patients recruited to the study, 493 patients received treatment and constituted the safety population (cobimetinib combined with vemurafenib, 247; vemurafenib, 246). At data cut-off (30 September 2015), median follow-up was 18.5 months. Nearly every patient experienced an AE. In patients who received cobimetinib combined with vemurafenib, the frequency of grade ≥3 AEs was higher than in patients who received vemurafenib alone (75% versus 61%). Most AEs, including grade ≥3 AEs, occurred within the first treatment cycle. After the first cycle (28 days), the incidence of common AEs (rash, diarrhoea, photosensitivity, elevated creatine phosphokinase, serous retinopathy, pyrexia, and liver laboratory abnormalities) decreased substantially over time. Most AEs were managed conservatively by supportive care measures, dose modifications of study treatment, and, occasionally, permanent treatment discontinuation. Conclusions: These data indicate that most AEs arising from treatment with cobimetinib combined with vemurafenib generally occur early in the treatment course, are mild or moderate and are manageable by patient monitoring, dose modification and supportive care. ClinicalTrials.gov: NCT01689519.

European ancestry decreases the risk of early onset, severe lupus nephritis in a single center, multiethnic pediatric lupus inception cohort.

PURPOSE: To determine whether pediatric SLE patients without European ancestry are at higher risk for development of severe lupus nephritis (ISN/RPS class III, IV or V). METHODS: Ninety-eight of 101 patients with pediatric SLE (age <18 years at diagnosis) were enrolled. Race/ethnicity of four grandparents, socioeconomic status (SES) and language proficiency were collected. The primary outcome was time to development of severe lupus nephritis. RESULTS: Based on patient report of four grandparent ancestry, 29% had at least one grandparent of European ancestry (14% had all four grandparents of European ancestry). Patients without European ancestry were 46% Hispanic, 47% Asian, and 3% African American. In the entire 98 patient cohort, 12% had ≥3 different ancestries. Patients without European ancestry had significantly lower SES levels and English proficiency. There was no significant difference between patients with or without European ancestry in duration of SLE, age of onset, and lag time between symptoms and diagnosis. Patients with at least one grandparent of European ancestry had a decreased risk of developing severe lupus nephritis, which remained significant after controlling for age, gender, SES and English proficiency (hazard ratio 0.4, 95% confidence interval 0.2-0.9). CONCLUSION: This study demonstrates that presence of at least one grandparent of European ancestry decreases the risk of severe lupus nephritis, a finding that is not explained by measurable socioeconomic differences and language barriers.

Bax, Bak and mitochondrial oxidants are involved in hypoxia-reoxygenation-induced apoptosis in human placenta.

Although apoptosis is prominent in placental cells in pregnancy complications such as preeclampsia, the cause is unknown. We surmised that hypoxia-reoxygenation (HR) is the mechanism and hypothesized that mitochondrial oxidants and Bcl-2 proteins cause HR-induced placental apoptosis. Our goal was studying expression of five Bcl-2 proteins--Bcl-2, Bcl-xL, Bax, Bak, Bad--and testing effects of diazoxide and cyclosporine A on oxidative stress and apoptosis in villous tissues subjected to HR. Term human placentas were obtained from normal pregnancies following elective caesarean deliveries. Villous tissues were subjected to "repetitive HR" (one hour at 2% O(2) then one hour at 8% O(2), alternatively, for a total of 6h) or "prolonged HR" (3h at 2% O(2) then 3h of 8% O(2)). Samples maintained at 2% and 8% O(2) served as hypoxic and normoxic controls, respectively. Prolonged HR caused the most severe villous apoptotic changes, increased the expression of Bax and Bak mRNA and protein and reduced the expression of Bcl-2 mRNA. Pre-administration of diazoxide and cyclosporine A reduced TUNEL-positive nuclei and levels of nitrotyrosine and 4-hydroxy-2-nonenol after prolonged HR. Thus, duration of hypoxia and reoxygenation is important in determining severity of HR-induced apoptosis in placenta. These apoptotic changes are closely associated with Bax and Bak effects and oxidative stress in mitochondria.

Fetal gender screening by ultrasound at 11 to 13(+6) weeks.

BACKGROUND: To survey the accuracy of fetal gender determination during first trimester screening and scan for congenital anomalies. METHODS: A prospective observational study was performed on 496 singleton pregnancies at the first trimester ultrasound screening. The doctor was a certified sonographer of first trimester screening by the Fetal Medicine Foundation(FMF). Ultrasound examination was performed on a GE Voluson 730 Pro, transabdominally, between 11 and 13(+6) weeks. Both transverse and mid-sagittal planes of a section of the fetal genital tubercle were performed to identify the gender. The subsequent gender at birth was obtained from karyotyping reports or hospital birth records. RESULTS: During the study, 496 patients requested gender information at the time of first trimester screening. Of the patients it was possible to determine gender (441 out of 496), the scan achieved an overall success rate of 91.8% in correctly identifying gender. The success rate for correctly identifying fetal gender (where identification was possible) increased with gestational age, from 71.9% at 11 weeks, 92% at 12 weeks, and 98.3% at 13 weeks, respectively, where gestational age was calculated from the crown-rump length in conjunction with menstrual or ovulation dating (p<0.001). Of the 55 cases where no identification of gender was possible, 39 were in the 11-week gestational age group, representing 40.6% of this category. The overall fetal gender accuracy rate for male fetus was slightly better than female (92.5 versus 91.2%), but was not statistically significant. CONCLUSIONS: This study demonstrated that the gestational age of the fetus has a material effect on the accuracy rate of gender determination. At 12 weeks and over, the average success rate for correctly identifying gender, where gender identification was possible, was 94.8%, with the accuracy at 13 weeks of 98.3% approaching that achieved by invasive testing. Fetal gender identification at 11

Tumour necrosis factor-alpha converting enzyme in human gestational tissues from pregnancies complicated by chorioamnionitis.

Chorioamnionitis increases the risk of preterm labour and is associated with adverse neonatal outcomes including cerebral palsy. Tumour necrosis factor-alpha (TNF-alpha) derived from the gestational tissues (placenta, fetal membranes and maternal decidua) is thought to play a pivotal role in the induction of cytokine response in chorioamnionitis. Tumour necrosis factor-alpha converting enzyme (TACE) is essential for the release of TNF-alpha. Our aim was to determine whether the expression of TACE is increased in human gestational tissues from pregnancies complicated by chorioamnionitis, and whether lipopolysaccharide (LPS) causes increased expression of TACE in the human gestational tissues in vitro. The immunostaining of TACE was generally more intense, in particular in the syncytiotrophoblast and stromal cells, in villous samples from pregnancies complicated by chorioamnionitis than those from normal pregnancies. Increased immunoreactivity of TACE was also noted in the amnion and choriodecidua. In parallel, there was an increased infiltration of monocytes/macrophages within the villous stroma and choriodecidua. As a complement to our in vivo findings, LPS significantly increased the levels of mRNA and protein of TACE in a dose-dependent response in villous and fetal membrane explant cultures. Together, our results imply a potential role of TACE in the pathogenesis of chorioamnionitis.

The influence of image magnification in first-trimester screening for Down syndrome by fetal nuchal translucency in Asians.

OBJECTIVE: The aim of this prospective study was to evaluate the impact of image magnification in the measurements of crown-rump length (CRL) and nuchal translucency (NT) thickness for first-trimester Down syndrome screening in Asians. METHODS: Ultrasound measurements of NT and CRL were performed in 561 consecutive Taiwanese unaffected fetuses and 11 cases of Down syndrome fetuses between 12 and 14 weeks of gestation. All sonographic images were measured by one qualified examiner to prospectively undergo first-trimester NT screening for Down syndrome. Fetal CRL and NT thickness were measured on three separated images including the original image, regular image, and the magnified image. RESULTS: A significant mean difference (0.59 +/- 4.24 mm) of CRL was found between measurements on the original and regular image (p < 0.001). There was a significant mean difference of NT thickness measurements between the regular and magnified image (0.12 +/- 0.25 mm, p < 0.001). Seven out of the 11 cases (63.6%) of Down syndrome with NT thickness > or =2.5 mm was measured on three separated images. A significantly reduced incidence of NT thickness > or =2.5 mm on the magnified image was noted than those of the original and regular image measurements in unaffected cases (p < 0.001). Either using the assessing method by the 95th centile cutoff value of NT thickness or combined risk, our results could achieve observed detection rate of 63.6% measured on three separated images. CONCLUSIONS: Our data indicate that the image magnification could reduce the false-positive rate by using a fixed cutoff value of NT thickness, but would have no influence on the results when using the assessing method either by the 95th centile cutoff value of NT thickness or the combined risk. In order to place the caliper more accurately, a magnified image should be recommended as a standard image in the measurements of the NT thickness.

Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome.

OBJECTIVES: To compare early second-trimester maternal serum placenta growth factor concentrations in Down syndrome pregnancies and those in normal pregnancies. METHODS: A case-control study was performed to evaluate the maternal serum placenta growth factor concentrations in 36 Down syndrome and 320 normal pregnancies with matched gestational age during the second trimester. For the detection of serum concentrations of placenta growth factor, a quantitative sandwich enzyme immunoassay technique (R & D Systems Inc., Minneapolis, Minnesota, USA) was performed. RESULTS: Using a multiple linear regression model, maternal serum placenta growth factor level was associated with gestational age (p<0.001) and the existence of Down syndrome pregnancy (p<0.001). After converting maternal serum placenta growth factor concentrations of each analyte to multiples of the appropriate gestational median (MoM), placenta growth factor MoM (p<0.001) was revealed to be an independent variable for Down syndrome pregnancies after adjusting for the effects of maternal age (p<0.001), free beta-hCG (p<0.001) and AFP (p=0.014) by multivariate logistic regression analysis. CONCLUSIONS: Maternal serum placenta growth factor concentration was elevated in Down syndrome pregnancies during the early second trimester. Placenta growth factor might be a novel marker for maternal serum Down syndrome screening.

Growth of endothelial cells on different concentrations of Gly-Arg-Gly-Asp photochemically grafted in polyethylene glycol modified polyurethane.

To improve endothelial cell adhesion and growth on the surface of polyethylene glycol modified polyurethane (PU-PEG), cell adhesive peptide Gly-Arg-Gly-Asp (GRGD) was photochemically grafted to the surface. The surface grafted GRGD-N-Succinimidyl-6-[4'-azido-2'-nitrophenylamino]hexanoate (SANPAH) on a PU-PEG surface was performed by adsorption and subsequent ultraviolet irradiation. Fourier transform infrared spectra (FTIR) and electron spectroscopy for chemical analysis (ESCA) confirmed the GRGD grafted to form a PU-PEG-GRGD surface. The composition fraction of nitrogen calculated from ESCA analysis for the PU-PEG-GRGD surface was well correlated with the concentration of GRGD to be immobilized. Human umbilical vein endothelial cells (ECs) were well adhered and growing on the PU-PEG-GRGD surface. Moreover, the viability of ECs growing on PU-PEG-GRGD surfaces, analyzed by MTT test, was also well correlated with the GRGD concentrations immobilized on the surface. With photochemical techniques, we could manipulate different contents of GRGD to form multiple regions of PU-PEG-GRGD surface that could enhance the growth of ECs on the surface, and the enhancement efficiency was well correlated with GRGD contents.

Prediction of pregnancy rate of in vitro fertilization and embryo transfer in women aged 40 and over with basal uterine artery pulsatility index.

PURPOSE: The purpose was to determine the effect of basal uterine perfusion on the pregnancy rates of in vitro fertilization and embryo transfer (IVF-ET) in women aged 40 and above. METHODS: A total of 47 patient aged 40 and over underwent IVF-ET. The conception cycles and the nonconception cycles were compared. RESULTS: Of the 47 patients, 4 patients were pregnant (8.5%). The mean age, basal follicle stimulating hormone (FSH), basal estradiol (E2) level, antral follicle count (AFC), number of ampoules of gonadotropin used, E2 levels and endometrial thickness on the day of human chorionic gonadotropin (hCG) administration, number of retrieved and fertilized oocytes, and number of transferred embryos were not statistically significant between the conception and nonconception cycles. However, the basal uterine artery pulsatility index (UA PI) was significantly lower in the conception cycles (P < 0.001). The receiver operating characteristics (ROC) curve analysis for basal FSH, AFC, and basal UA PI in predicting the pregnancy rate of IVF in patients aged > or = 40 were demonstrated. The best prediction rate was achieved by a pulsatility index cutoff of < 2.0 for a receptive uterus. CONCLUSIONS: Increased uterine perfusion in the early follicular phase enhanced the pregnancy rate of IVF in women aged 40 and above. It is therefore essential that patients aged > or = 40 with poor basal uterine perfusion should be identified early in the early follicular phase of the menstrual cycle to apply appropriate intervention to improve the uterine circulation for the subsequent chance of pregnancy.

Maternal serum screening for down syndrome by using alpha-fetoprotein and human chorionic gonadotropin in an asian population. a prospective study.

The purpose of the present study is to evaluate the efficacy of second-trimester maternal serum screening program by using alpha-fetoprotein (AFP) and total human chorionic gonadotropin (hCG) in an Asian population. During June 1994 to July 1998, we conducted a prospective study of serum screening protocol for Down syndrome. The cut-off point for a positive result in this analysis was a risk of >/=1/270. A total of 17,742 pregnant women with singleton pregnancy were screened, and 1,153 (6.5%) had positive result. Sixteen of the 17,742 pregnancies had Down syndrome, and 10 of them had positive result. The positive rate and detective rate for Down syndrome were 6.5 and 62.5%, respectively. However, the detective rate will reduce to 47.6% after being adjusted by age-specific risk. It is indicated that the double-marker test using AFP and total hCG is an effective screen strategy for second-trimester detection of Down syndrome in Asian women.

Maternal serum screening for down syndrome in pregnancies conceived by intra-uterine insemination.

The purpose of our study was to assess the influence of intra-uterine insemination (IUI) on the results of maternal serum Down syndrome screening. 43 women with IUI pregnancies and 4507 healthy women who conceived were studied. Ovulation in IUI pregnancies was induced by clomiphene and/or human menopausal gonadotrophin (hMG). Maternal serum levels of free beta-human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) were measured for Down syndrome screening. It was considered screen-positive when the risk of Down syndrome was 1 in 270 or greater in the second trimester. The value of maternal serum AFP was significantly lower in the IUI group (median=0.760 MoM) than in the control group (median=1.050 MoM). However, the value of free beta-hCG was not significantly different between the two groups. The positive rate of maternal serum Down syndrome in IUI pregnancies was similar to that of the control group. Our results indicate that IUI pregnancy may be associated with a lower level of AFP, although the mechanism for this difference remains unknown.

Maternal urine alpha-fetoprotein concentrations between 14 and 21 weeks of gestation.

BACKGROUND: The aim of this study was to ascertain the normal range of the midtrimester maternal urine alpha-fetoprotein (AFP) concentrations in Taiwanese pregnancies. METHODS: AFP was measured in the urine samples, obtained before genetic amniocentesis, from 268 women with normal singleton pregnancies between 14 and 21 weeks of gestation. Week-specific median values for urine AFP/creatinine (Cr) were calculated by weighted linear regression after log transformation and the data were converted to units in the multiple of the median (MoM). The gestational age in all cases was determined by ultrasound parameters. RESULTS: The levels of urine AFP and AFP/Cr increased gradually with advancing gestational age. The AFP/Cr MoM values of singleton pregnancies after log transformation showed a normal distribution with a mean (standard deviation) of 0.0071 (0.3228). The median, 10th and 90th centiles of AFP/Cr were 0.98, 0.43 and 3.61 MoM, respectively. Of the pregnant Taiwanese women studied, 4.9% (13/268) and 16% (43/268) had urine AFP/Cr MoM levels less than 0.31 MoM and 0.5 MoM respectively. CONCLUSION: The establishment of a reference range which allows for gestational differences in AFP/Cr levels is essential for further antenatal testing.

Second-trimester maternal urine human chorionic gonadotrophin beta-core fragment concentrations in Asian pregnancies with fetal chromosomal abnormalities.

The aim of this study was to investigate the second trimester concentrations of maternal urine human chorionic gonadotrophin beta-core fragment (HCGbetacf) in Asian pregnanci2es with fetal chromosomal abnormalities. HCGbetacf concentrations were analysed from 34 urine samples in chromosomally abnormal pregnancies, including 28 cases of Down's syndrome, one case of trisomy 18, and five cases of other chromosomal abnormalities (one mosaic deletion and four translocations), and in a cohort of 268 normal pregnancies receiving second trimester amniocentesis. Results were normalized to urine creatinine (Cr) concentration and converted to the multiple of the median (MOM) concentration for the appropriate gestation. The median HCGbetacf MOM concentrations of Down's syndrome pregnancies (12.89) was significantly higher than that of normal pregnancies (1. 06) (P < 0.00001). Wide variations of HCGbetacf concentrations were observed in other chromosomally abnormal pregnancies. There were 18 of 28 (64%) Down's syndrome cases but one of five (20%) other chromosomally abnormal cases with HCGbetacf concentrations above the 95th centile of the control values (8.22 MOM cut-off). These findings suggest that HCGbetacf could be a potential marker in urine screening for fetal Down's syndrome in Asians.

Urine free beta-human chorionic gonadotropin levels between 14 and 21 weeks of gestation in Taiwanese pregnancies.

BACKGROUND: The purpose of this study was to determine the reference range of maternal urine free beta-human chorionic gonadotropin (beta -hCG) concentrations between 14 and 21 weeks of gestation. METHODS: We measured the concentrations of urine free beta -hCG from 268 healthy singleton Taiwanese pregnancies between 14 and 21 weeks of gestation. Results were corrected for creatinine (Cr) concentration and converted to the multiple of the median (MOM) level for the appropriate gestation. Gestational ages of all cases were determined using ultrasound dating. RESULTS: The median levels of urine free beta -hCG and free beta-hCG/Cr had a downward trend in association with the increasing gestation age. The median, 5th, 10th, 90th and 95th centiles of free beta- hCG/Cr MOM values were 1.02, 0.20, 0.25, 2.32 and 3.38 MOM, respectively. Urine free beta- hCG/Cr MOM values showed a log Gaussian distribution with the mean and standard deviation (SD) distribution of -0.0657 and 0.3792, respectively. CONCLUSION: To allow for differences in free beta -hCG/Cr median values at various ages of gestation, establishment of the reference range is essential for further development of maternal urine screening for Down syndrome.

Urine free beta-hCG and total estriol for Down syndrome screening during the second trimester in an Asian population.

OBJECTIVE: To evaluate second-trimester free beta-hCG and total estriol (E3) in the maternal urine as markers for Down syndrome screening in an Asian population. METHODS: Free beta-hCG and total E3 were measured in the urine samples of 28 Taiwanese Down syndrome pregnancies and 268 unaffected singleton pregnancies at 14-25 weeks. Results were normalized to urine creatinine concentrations and converted to multiples of the median (MoM) levels. Gestational ages were estimated by ultrasound measurements. RESULTS: Median values of free beta-hCG, total E3, free beta-hCG to total E3 ratio, and the free beta-hCG to total E3 MoM ratio in Down syndrome pregnancies were 4.75 MoM, 0.66 MoM, 8.99 MoM, and 9.51, respectively. At a 5% false-positive rate, the observed detection rates were 36% (ten of 28) with total E3, 71% (20 of 28) with free beta-hCG, 68% (19 of 28) with free beta-hCG/total E3, and 71% (20 of 28) with free beta-hCG/total E3 MoM. When combined with maternal age, the expected detection rates were 65% with total E3, 71% with free beta-hCG, 76% with free beta-hCG/total E3, 80% with free beta-hCG/total E3 MoM, and 89% when combining free beta-hCG, total E3, and maternal age. CONCLUSION: Urine free beta-hCG and total E3 are useful markers for Down syndrome screening during the second trimester in Taiwanese women.

Antimicrobial efficacy of endoscopic disinfection procedures: a controlled, multifactorial investigation.

BACKGROUND: Adequate disinfection of endoscopes is essential to prevent environmental and patient-to-patient transmission of infectious agents, but data from controlled studies are limited. Moreover, there is controversy regarding current guidelines for disinfection. We compared the antimicrobial efficacy of several endoscopic disinfection procedures controlling for multiple factors that affect reprocessing. METHODS: A colonoscope was contaminated with 10(8) CFU/mL of Enterococcus faecalis as a standardized inoculum. The colonoscope was passed through 1 of 16 study arms (5 reps/arm for a total of 80 runs) that were controlled for all possible combinations of the following variables: manual precleaning; 10-, 20-, or 45-minute glutaraldehyde exposure; air or ethanol drying; or automated reprocessing with peracetic acid (liquid sterilization system). Suction accessory channels and air-water channels were harvested for microbiologic culture. RESULTS: Control runs (no cleaning or disinfection) recovered more than 5 x 10(7) CFU/mL from each sampling site. When each processing variable was isolated independent of other variables, the benefits of manual precleaning, longer soak times, and ethanol drying were apparent. When factors were combined, manual precleaning followed by 20- and 45-minute glutaraldehyde exposure and ethanol drying removed all test organisms, as did processing with the liquid sterilization system. CONCLUSION: Although the initial cost is higher, the automated liquid sterilization system provides effective sterilization and minimizes worker exposure. In units where chemical disinfection is used, our results suggest that manual precleaning followed by at least 20-minute glutaraldehyde exposure and ethanol rinse drying are sufficient to achieve complete disinfection.

Tumor vascular pattern and blood flow impedance in the differential diagnosis of leiomyoma and adenomyosis by color Doppler sonography.

PURPOSE: Our objective was to evaluate the differences between leiomyoma and adenomyosis by color Doppler sonography with new criteria. METHODS: A total of 78 patients with symptomatic uterine nodularities who were sonographically suspected to have leiomyoma or adenomyosis without other coexisting pathologic conditions was enrolled in the study. All patients underwent transvaginal color Doppler sonography (7.0-MHz vaginal probe) or transabdominal color Doppler sonography (5.0 MHz) during the early follicular phase. The morphology, tumor vascular pattern, and blood flow impedance of the uterine tumors were measured. All of the patients underwent surgery and the pathologic reports were used as references. RESULTS: The mean age was not statistically significant in patients with adenomyosis versus leiomyoma (P > 0.05). The morphologic criteria for adenomyosis and leiomyoma by sonography detected 79% of adenomyosis and 84% of leiomyoma. Adenomyosis had 87% randomly scattered vessels or intratumoral signals and 88% of leiomyomas showed peripheral scattered vessels or outer feeding vessels. Eighty-two percent of adenomyosis had a pulsitility index (PI) of arteries within or around uterine tumors > 1.17 and 84% of leiomyomas had a PI < or = 1.17. The reliability test of tumor vascular pattern and blood flow impedance were better than that of using morphological criteria alone. CONCLUSIONS: With the aid of color Doppler sonography, tumor vascular pattern and blood flow impedance of the arteries within or around uterine tumors could more accurately diagnose adenomyosis and leiomyoma in addition to the morphologic criteria on transvaginal sonography.

Risk factors for placenta accreta.

OBJECTIVE: To identify risk factors associated with placenta accreta in a large cohort study. METHODS: Data for this study came from the Taiwan Down Syndrome Screening Group, an ongoing project on feasibility of serum screening in an Asian population. Women who had serum screening for Down syndrome at 14-22 weeks' gestation using alpha-fetoprotein (AFP) and free beta-hCG between January 1994 and June 1997, and delivered in the same institution, were included (n = 10,672). Those who had multiple gestations (n = 200), overt diabetes (n = 11), or fetal malformations (n = 101) were excluded. If a woman was involved more than once, one randomly selected pregnancy was included in the analysis (n = 9349). Twenty-eight pregnancies were complicated by placenta accreta, diagnosed by clinical presentation (n = 26) or histologic confirmation (n = 2). Multiple logistic regression with adjustment for potentially confounding variables was used to identify independent risk factors for placenta accreta. RESULTS: Women who had placenta previa (odds ratio [OR] 54.2; 95% confidence interval [CI] 17.8, 165.5) and second-trimester serum levels of AFP and free beta-hCG greater than 2.5 multiples of the median (OR 8.3; 95% CI 1.8, 39.3 and OR 3.9; 95% CI 1.5, 9.9, respectively), and were 35 years and older (OR 3.2; 95% CI 1.1, 9.4) were at increased risk of having placenta accreta. CONCLUSION: Risk factors for placenta accreta include placenta previa, abnormally elevated second-trimester AFP and free beta-hCG levels, and advanced maternal age.