Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.

BACKGROUND: Preeclampsia affects approximately 3% of all pregnancies and is a major cause of maternal and perinatal morbidity and death. In the last decade, extensive research has been devoted to early screening for preeclampsia with the aim of reducing the prevalence of the disease through pharmacologic intervention in the high-risk group starting from the first trimester of pregnancy. OBJECTIVE: The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history (maternal factors) and biomarkers. STUDY DESIGN: The data for this study were derived from prospective screening for adverse obstetric outcomes in women who attended for their routine first hospital visit at 11-13 weeks gestation in 2 maternity hospitals in England. We screened 35,948 singleton pregnancies that included 1058 pregnancies (2.9%) that experienced preeclampsia. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A, and placental growth factor multiple of the median values. Five-fold cross validation was used to assess the performance of screening for preeclampsia that delivered at <37 weeks gestation (preterm-preeclampsia) and ≥37 weeks gestation (term-preeclampsia) by models that combined maternal factors with individual biomarkers and their combination with screening by maternal factors alone. RESULTS: In pregnancies that experienced preeclampsia, the values of uterine artery pulsatility index and mean arterial pressure were increased, and the values of serum pregnancy-associated plasma protein-A and placental growth factor were decreased. For all biomarkers, the deviation from normal was greater for early than late preeclampsia; therefore, the performance of screening was related inversely to the gestational age at which delivery became necessary for maternal and/or fetal indications. Combined screening by maternal factors, uterine artery pulsatility index, mean arterial pressure, and placental growth factor predicted 75% (95% confidence interval, 70-80%) of preterm-preeclampsia and 47% (95% confidence interval, 44-51%) of term-preeclampsia, at a false-positive rate of 10%; inclusion of pregnancy-associated plasma protein-A did not improve the performance of screening. Such detection rates are superior to the respective values of 49% (95% confidence interval, 43-55%) and 38% (34-41%) that were achieved by screening with maternal factors alone. CONCLUSION: Combination of maternal factors and biomarkers provides effective first-trimester screening for preterm-preeclampsia.

Competing risks model in screening for preeclampsia by maternal characteristics and medical history.

OBJECTIVE: The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history. STUDY DESIGN: This was a screening study of 120,492 singleton pregnancies at 11-13 weeks' gestation, including 2704 pregnancies (2.2%) that experienced preeclampsia. A survival-time model for the gestational age at delivery with preeclampsia was developed from variables of maternal characteristics and history. This approach assumes that, if the pregnancy was to continue indefinitely, all women would experience preeclampsia and that whether they do so or not before a specified gestational age depends on competition between delivery before or after development of preeclampsia. A 5-fold cross validation study was conducted to compare the performance of the new model with the National Institute for Health and Clinical Excellence (NICE) guidelines. RESULTS: In the new model, increased risk for preeclampsia, with a consequent shift in the Gaussian distribution of the gestational age at delivery with preeclampsia to the left, is provided by advancing maternal age, increasing weight, Afro-Caribbean and South Asian racial origin, medical history of chronic hypertension, diabetes mellitus and systemic lupus erythematosus or antiphospholipid syndrome, family history and personal history of preeclampsia, and conception by in vitro fertilization. The risk for preeclampsia decreases with increasing maternal height and in parous women with no previous preeclampsia; in the latter, the protective effect, which is related inversely to the interpregnancy interval, persists beyond 15 years. At a screen-positive rate of 11%, as defined by NICE, the new model predicted 40%, 48%, and 54% of cases of total preeclampsia and preeclampsia requiring delivery at <37 and <34 weeks' gestation, respectively, which were significantly higher than the respective values of 35%, 40%, and 44% achieved by application of NICE guidelines. CONCLUSION: A new model that is based on maternal characteristics and medical history has been developed for the estimation of patient-specific risks for preeclampsia. Such estimation of the a priori risk for preeclampsia is an essential first step in the use of Bayes theorem to combine maternal factors with biomarkers for the continuing development of more effective methods of screening for the disease.

First-trimester maternal factors and biomarker screening for preeclampsia.

Preeclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. PE can be subdivided into early onset PE with delivery <34 weeks' gestation and late onset PE with delivery ≥34 weeks. Early onset PE is associated with a higher incidence of adverse outcome. This review illustrates that effective screening for the development of early onset PE can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, mean arterial pressure, uterine artery Doppler, maternal serum pregnancy-associated plasma protein-A and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%.

Maternal serum placental growth factor isoforms 1 and 2 at 11-13, 20-24 and 30-34 weeks' gestation in late-onset pre-eclampsia and small for gestational age neonates.

OBJECTIVE: To compare the maternal serum concentrations of placental growth factor (PlGF)-1 and PlGF-2 in the first, second and third trimesters in normal pregnancies and in those complicated by pre-eclampsia (PE) or the delivery of small for gestational age (SGA) neonates after 37 weeks. METHODS: Serum PlGF-1 and PlGF-2 were measured at 11-13, 20-24 and 30-34 weeks' gestation in 50 cases of PE, 99 cases of SGA and 298 controls. The values of PlGF-1 and PlGF-2 at 11-13 weeks were expressed as multiples of the median (MoM) after adjustment for maternal characteristics. The distributions of PlGF-1 and PlGF-2 in cases and controls at 20-24 and 30-34 weeks were converted to MoM of the values at 11-13 weeks and compared. RESULTS: Serum PlGF-1 and PlGF-2 levels were highly correlated and both increased with gestational age. At 30-34 weeks, the median MoM values for PlGF-1 and PlGF-2 in the late PE (4.2 and 4.3) and late SGA (7.2 and 6.0) groups were significantly lower than in the controls (12.8 and 9.9). Combining the two isoforms did not improve the prediction of late PE and late SGA provided by PlGF-1 alone. CONCLUSIONS: The performances of serum PlGF-1 and PlGF-2 in the prediction of late PE and late SGA are similar.

Maternal serum placental growth factor (PlGF) isoforms 1 and 2 at 11-13 weeks' gestation in normal and pathological pregnancies.

OBJECTIVE: To compare the maternal serum concentration of placental growth factor-1 (PlGF-1) and PlGF-2 at 11-13 weeks' gestation in normal pregnancies and in those complicated by preeclampsia (PE), delivery of small for gestational age (SGA) neonates and fetal trisomies 21, 18 and 13. METHODS: Serum PlGF-1 and PlGF-2 were measured in 270 pathological pregnancies (PE, n = 80; SGA, n = 80; trisomy 21, n = 44; trisomy 18, n = 38; trisomy 13, n = 28) and 590 normal controls. The values were expressed as multiple of the median (MoM) after adjustment for maternal characteristics and corrected for adverse pregnancy outcomes and the median MoM values in each pathological pregnancy were compared to the normal group. RESULTS: There were significant contributions to PlGF-1 and PlGF-2 from gestational age, smoking and racial origin. In addition, there were significant contributions to PlGF-1 from parity and method of conception. The median MoM of PlGF-1 and PlGF-2 was significantly decreased in PE (0.783 and 0.916 MoM), SGA (0.891 and 0.851 MoM), trisomy 21 (0.609 and 0.749 MoM), trisomy 18 (0.529 and 0.730 MoM) and trisomy 13 (0.373 and 0.699 MoM). CONCLUSIONS: In pathological pregnancies, except SGA, the decrease in serum PlGF-1 at 11-13 weeks' gestation is more marked than the decrease in PlGF-2.

Optimal method and timing of intrauterine intervention in twin reversed arterial perfusion sequence: case study and meta-analysis.

INTRODUCTION: The objective of this study was to define the optimal method and timing of intervention in twin reversed arterial perfusion (TRAP) sequence. MATERIAL AND METHODS: During a period of 20 years (1993-2013), we performed endoscopic laser coagulation of umbilical cord vessels or intrafetal laser in 67 pregnancies with TRAP sequence. These data were combined with those reported in the literature to determine the survival rate of the pump twin for different methods and timing of interventions. RESULTS: A variety of techniques were used to interrupt the blood supply to the acardiac twin. Most procedures were performed at or after 16 weeks, and with most methods the survival rate of the pump twin was about 80%. Good results were also obtained for triplet pregnancies. In 18 of 30 cases (60%) diagnosed at 11-14 weeks, there was spontaneous cessation of flow in the acardiac twin before planned intervention at 16-18 weeks, and in 11 of these (61.1%) the pump twin died or suffered brain damage. In 103 pregnancies treated by intrafetal laser at 12-27 weeks, there was no correlation between gestational age at treatment and survival rate, but there was an inverse association between gestational age at treatment and gestational age at birth. DISCUSSION: In TRAP sequence, survival may be improved by elective intervention at 12-14 weeks.

Prediction of preeclampsia by mean arterial pressure at 11-13 and 20-24 weeks' gestation.

OBJECTIVES: To assess the performance of screening for preeclampsia (PE) by mean arterial pressure (MAP) at 11-13 and at 20-24 weeks' gestation. METHODS: MAP was measured at 11-13 and 20-24 weeks in 17,383 singleton pregnancies, including 70 with early PE, requiring delivery <34 weeks' gestation, 143 with preterm PE, delivering <37 weeks and 537 with total PE. MAP was expressed as multiple of the median (MoM) after adjustment for maternal characteristics and corrected for adverse pregnancy outcomes. The performance of screening for PE by maternal characteristics and MAP MoM at 11-13 weeks (MAP-1), MAP MoM at 20-24 weeks (MAP-2) and their combination was evaluated. RESULTS: In screening by maternal characteristics and MAP-1, at a false-positive rate (FPR) of 10%, the detection rates (DR) of early PE, preterm PE and total PE were 74.3, 62.9 and 49.3%, respectively; the DR at FPR of 5% were 52.9, 42.7 and 35.8%. In screening by MAP-1 and MAP-2 the DR at FPR of 10%, were 84.3, 65.7 and 52.5%; the DR at FPR of 5% were 60.0, 49.7 and 37.6%, respectively. CONCLUSIONS: Performance of screening for PE by MAP is best when measurements are taken at both 11-13 and 20-24 weeks' gestation than at only one of these gestational ranges.

Competing risk model in screening for preeclampsia by mean arterial pressure and uterine artery pulsatility index at 30-33 weeks' gestation.

OBJECTIVE: To assess risk for preeclampsia (PE) based on maternal characteristics, mean arterial pressure (MAP) and uterine artery pulsatility index (Ut-PI) at 30-33 weeks' gestation. METHODS: Screening study in singleton pregnancies including 2,140 that subsequently developed PE and 83,615 that were unaffected by PE, gestational hypertension or delivery of small-for-gestational-age neonates (normal group). We developed a survival time model for the time of delivery for PE by combination of maternal characteristics and history with MAP and Ut-PI multiple of the median (MoM) values (biophysical test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE and 13,878 of the normal group. The detection rate of PE requiring delivery within 4, 6 and 8 weeks of the visit was estimated. RESULTS: In pregnancies with PE the log10 MoM values of MAP and Ut-PI were inversely related to gestational age at delivery. Biophysical testing detected 90, 65 and 53% of PE with delivery within 4, 6 and 8 weeks of the visit, at a fixed false-positive rate of 5%. INTERPRETATION: Testing by maternal characteristics, Ut-PI and MAP at 30-33 weeks could identify 90% of pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Competing risks model in screening for preeclampsia by biophysical and biochemical markers at 30-33 weeks' gestation.

OBJECTIVE: To assess the risk for preeclampsia (PE) by maternal characteristics, uterine artery pulsatility index (Ut-PI), mean arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 30-33 weeks' gestation. METHODS: This was a screening study in singleton pregnancies including 2,140 that developed PE and 83,615 that were unaffected by PE. We developed a survival time model for the time of delivery for PE by combining maternal characteristics and history with Ut-PI, MAP, PlGF and sFlt-1 multiple of the median (MoM) values (combined test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE, and 13,878 unaffected pregnancies and data on PlGF and sFlt-1 were available in 118 cases of PE and 3,734 unaffected pregnancies. Modelled detection rate of all PE and PE requiring delivery within 4 and 6 weeks of the visit was estimated. RESULTS: Screening by the combined test would detect 66, 98 and 86% of all PE and PE requiring delivery within 4 and 6 weeks of the visit, respectively, at a false positive rate of 5%. INTERPRETATION: Screening by biophysical and biochemical testing at 30-33 weeks could identify most pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Competing risks model in screening for preeclampsia by serum placental growth factor and soluble fms-like tyrosine kinase-1 at 30-33 weeks' gestation.

OBJECTIVE: To assess the risk for preeclampsia (PE) by maternal characteristics, serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 30-33 weeks' gestation. METHODS: This was a screening study in singleton pregnancies including 2,140 that subsequently developed PE and 83,615 that were unaffected by PE, gestational hypertension or delivery of small-for-gestational-age neonates (normal group). We developed a survival time model for the time of delivery for PE by combination of maternal characteristics and history with PlGF and sFlt-1 multiple of the median (MoM) values (biochemical test). Data on third-trimester PlGF and sFlt-1 were available in 118 cases of PE and 3,734 of normal group. The detection rate (DR) of PE requiring delivery within 4, 6 and 8 weeks of the visit was estimated. RESULTS: In pregnancies with PE, the log10 MoM values of PlGF and sFlt-1 were linearly related to gestational age at delivery. Screening by the biochemical test detected 100, 76, and 62% of PE with delivery within 4, 6 and 8 weeks of the visit, at a fixed false-positive rate of 5%. INTERPRETATION: Testing by PlGF and sFlt-1 at 30-33 weeks could identify all pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Maternal serum cytokines at 30-33 weeks in the prediction of preeclampsia.

OBJECTIVE: The aim of this case-control study at 30-33 weeks, a few days or weeks before the clinical onset of preeclampsia (PE), was to assess whether serum concentrations of cytokines differ between patients who are destined to develop PE and those with uncomplicated pregnancies. METHODS: A panel of cytokines was measured using Luminex technology at 30-33 weeks' gestation in 39 cases that developed PE at or after 34 weeks and 117 unaffected controls. RESULTS: The serum concentrations of most analysed cytokines were no different in women who developed PE than in controls. The proportions of women with detectable concentrations of MIP-1α and IL-8 were significantly lower in those with PE than in the controls (MIP-1α: 14/39 vs 76/117, P = 0.003; IL-8:13/39 vs 83/117, P < 0.0001). The median maternal serum concentration of IL-1ß was significantly lower in the PE cases than in the controls (0.38 pg/mL, range 0.01-0.92, vs 0.60 pg/mL, range 0.02-3.54, P = 0.005). CONCLUSION: Our findings do not lend support to the hypothesis that systemic inflammation precedes the onset of PE or that cytokines are good markers for such inflammation and certainly the panel of cytokines we examined does not provide useful prediction of subsequent development of PE.

Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy.

BACKGROUND: The aim of this study is to validate the Fetal Medicine Foundation (FMF) multiple logistic regression algorithm for prediction of risk of pre-eclampsia in an Australian population. This model, which predicts risk using the population rate of pre-eclampsia, a variety of demographic factors, mean maternal arterial blood pressure (MAP), uterine artery PI (UtA PI) and pregnancy-associated plasma protein A (PAPP-A), has been shown to predict early-onset pre-eclampsia (delivery prior to 34 weeks) in 95% of women at a 10% false-positive rate. METHODS: All women who attended first trimester screening at the Royal Prince Alfred Hospital had their body mass index (BMI), MAP and UtA PI assessed in addition to factors traditionally used to assess aneuploidy (including PAPP-A MoM). After delivery, risks of early-onset (delivery prior to 34 weeks) pre-eclampsia, late pre-eclampsia and gestational hypertension were calculated using the FMF risk algorithm. RESULTS: A total of 3099 women were screened and delivered locally. 3066 (98.9%) women had all data to perform pre-eclampsia screening available. This included 3014 (98.3%) women with a live birth, where risks of early pre-eclampsia were calculated. Twelve women were delivered before 34 weeks because of early pre-eclampsia with a prevalence of early pre-eclampsia of 1 in 256 pregnancies. Risks generated through the use of maternal history, MAP, UtA PI and PAPP-A detected 41.7 and 91.7% of early pre-eclampsia at a false-positive rate of 5 and 10%, respectively. CONCLUSIONS: This study shows that the FMF early pre-eclampsia algorithm is effective in an Australian population.

Uterine artery Doppler at 30-33 weeks' gestation in the prediction of preeclampsia.

OBJECTIVE: To investigate the potential value of measuring uterine artery pulsatility index (PI) at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. METHODS: Screening study in singleton pregnancies at 30-33 weeks' gestation including 4,294 cases that were unaffected by PE, gestational hypertension (GH) or delivery of small for gestational age neonates (normal group), 145 that subsequently developed PE, with 37 cases requiring delivery at 34-37 weeks (intermediate-PE) and 108 delivering at or after 38 weeks (late-PE) and 161 that developed GH. The a priori risks for intermediate- and late-PE from maternal demographic characteristics and medical history were derived by logistic regression analysis. The a posteriori risks were calculated by combining the a priori risks with the likelihood ratios for uterine artery PI, which were calculated from fitted bivariate gaussian distributions. RESULTS: In screening for PE by a combination of maternal characteristics and uterine artery PI, the estimated detection rates of intermediate- and late-PE, at a false-positive rate of 10%, were 70.3 and 54.6%, respectively. CONCLUSION: Combined testing by maternal characteristics and uterine artery PI at 30-33 weeks could effectively identify women at high risk for subsequent development of PE.

Maternal serum placental growth factor, pregnancy-associated plasma protein-a and free ß-human chorionic gonadotrophin at 30-33 weeks in the prediction of pre-eclampsia.

OBJECTIVE: To investigate the potential value of maternal serum concentrations of free ß-human chorionic gonadotrophin (ß-hCG), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 30-33 weeks of gestation in the prediction of pre-eclampsia (PE) developing at or after 34 weeks. METHODS: Serum free ß-hCG, PAPP-A and PlGF were measured at 11-13 and at 30-33 weeks of gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. The measured concentration of metabolites was converted into multiples of the unaffected median (MoM) and the MoM values in the PE and control groups were compared. RESULTS: At 11-13 weeks, serum PlGF and PAPP-A, but not free ß-hCG, were significantly lower in the PE group than in the controls (0.824, 0.748 and 0.857 vs. 1.000 MoM). At 30-33 weeks in the PE group, PlGF was reduced (0.356 MoM), free ß-hCG was increased (1.750 MoM), but PAPP-A was not significantly different (0.991 MoM) from control (1.000 MoM). In screening for PE at 30-33 weeks by a combination of maternal characteristics and serum PlGF, the estimated detection rates, at a false-positive rate of 10%, of intermediate PE (requiring delivery at 34-37 weeks) and late PE (with delivery after 37 weeks) were 85.7 and 52.8%, respectively. The performance of screening was not improved by the addition of free ß-hCG or the free ß-hCG/PlGF ratio. CONCLUSION: Screening by maternal characteristics and serum PlGF at 30-33 weeks could identify most pregnancies that will subsequently develop PE.

Combined screening for preeclampsia and small for gestational age at 11-13 weeks.

OBJECTIVE: To combine a specific algorithm for small for gestational age (SGA) without preeclampsia (PE) and another algorithm for PE in the prediction of SGA and PE. METHODS: This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.3%) that subsequently developed PE, 3,168 (5.1%) that delivered SGA neonates and 57,458 that were unaffected by PE and SGA. We developed a prediction algorithm for SGA requiring delivery before 37 weeks' gestation (preterm-SGA) from maternal characteristics, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A and placental growth factor multiple of the median values. We then examined the performance of this algorithm individually and in combination with a previously reported algorithm for early-PE in the prediction of SGA and PE. RESULTS: When screen positivity was defined by risk cutoff of 1:200 using the algorithm for early-PE and the risk cutoff of 1:150 using the algorithm for preterm-SGA, the false positive rate was 10.9% and the detection rates of early-PE, late-PE, preterm-SGA and term-SGA were 95.3, 45.6, 55.5 and 44.3%, respectively. CONCLUSIONS: Effective first-trimester screening for early-PE and preterm-SGA can be provided by the combined use of the specific algorithms.

Systolic, diastolic and mean arterial pressure at 30-33 weeks in the prediction of preeclampsia.

OBJECTIVE: To investigate the potential value of measuring mean arterial pressure (MAP), systolic (sBP) and diastolic (dBP) blood pressure at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. METHODS: Screening study in singleton pregnancies at 30-33 weeks' gestation including 4,294 that were unaffected by PE, gestational hypertension (GH) or delivery of small-for-gestational-age neonates (normal group), 145 that subsequently developed PE [37 cases requiring delivery at 34-37 weeks (intermediate PE) and 108 delivering at or after 38 weeks (late PE)] and 161 that developed GH. The a priori risks for intermediate and late PE from maternal demographic characteristics and medical history were determined. The a posteriori risks were calculated by combining the a priori risks with the likelihood ratios for MAP, sBP and dBP, which were calculated from fitted bivariate gaussian distributions. RESULTS: The mean multiple of median MAP, sBP and dBP were significantly higher in the intermediate and late PE groups than in the normal group. In screening by a combination of maternal characteristics and MAP, the estimated detection rates of intermediate and late PE, at a false-positive rate of 10%, were 70.3 and 62.0%, respectively. The respective detection rates for sBP were 62.2 and 59.3% and for dBP were 62.2 and 57.4%. CONCLUSION: Combined testing by maternal characteristics and blood pressure at 30-33 weeks could effectively identify women at high risk for subsequent development of PE.

Maternal serum soluble endoglin at 30-33 weeks in the prediction of preeclampsia.

OBJECTIVE: To investigate the potential value of maternal serum concentration of soluble endoglin (sEng) at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. METHODS: Serum sEng was measured at 11-13 and at 30-33 weeks' gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. Regression analysis was used to determine which of the factors amongst the maternal characteristics were significant predictors of first- and third-trimester log10 sEng in the control group. The measured values of sEng were converted into multiples of the unaffected median (MoM) and the MoM values in the PE and controls were compared. RESULTS: The median sEng MoM at 30-33 weeks was significantly higher in the PE group (1.39, IQR 0.94-2.18) than in the controls (0.95, IQR 0.77-1.19), but at 11-13 weeks there was no significant difference between the groups. In screening by a combination of maternal characteristics and third-trimester sEng, the detection rates of intermediate- and late-PE, at a false-positive rate of 10%, were 64.3 and 50.0%, respectively. CONCLUSION: Screening by maternal characteristics and sEng at 30-33 weeks could identify most pregnancies that will subsequently develop PE.

Second-trimester screening for trisomy-21 using prefrontal space ratio.

OBJECTIVE: To investigate the potential value of prefrontal space ratio (PFSR) in second-trimester screening for trisomy-21. METHODS: A retrospective study utilizing stored midsagittal two-dimensional images of fetal profiles in 240 euploid and 45 trisomy-21 pregnancies at 16(+0)-23(+6) weeks' gestation. The vertical distance between the leading edge of the skull and that of the skin (D1) and the distance between the skull and the mandibulo-maxillary line (D2) were measured and the D1:D2 ratio (PFSR) was calculated. In euploid pregnancies, regression analysis was used to determine the association between D1, D2 and PFSR with gestational age (GA). D1 and D2 were expressed as delta (Δ) values with gestational age. ΔD1, ΔD2 and PFSR in cases and controls were compared. RESULTS: In trisomy-21, compared to controls, ΔD1 was increased (1.417 vs. 0.000 mm, p < 0.0001), ΔD2 was decreased (-0.842 vs. 0.000 mm, p = 0.003) and PFSR was increased (0.753 vs. 0.463, p < 0.0001). At a false-positive rate of 5%, the detection rates in screening by ΔD1, ΔD2 and PSFR were 80.0% (95% CI 65.4-90.4), 46.7% (95% CI 31.7-62.1) and 100.0% (95% CI 92.1-100.0), respectively. CONCLUSION: The PFSR is an effective marker in second-trimester screening for trisomy-21.

Prediction of preeclampsia by uterine artery Doppler at 20-24 weeks' gestation.

OBJECTIVES: To determine maternal characteristics affecting uterine artery pulsatility index (PI) in normal pregnancies at 20-24 weeks' gestation and examine in pregnancies with preeclampsia (PE) the relation between uterine artery PI multiple of the median (MoM) and severity of disease. METHODS: Uterine artery PI was measured at 20-24 weeks in 50,490 singleton pregnancies, including 1,442 (2.9%) that developed PE. Uterine artery PI was expressed as MoM after adjustment for maternal characteristics and corrected for adverse pregnancy outcomes. In PE, the correlation between uterine artery PI MoM with gestational age at delivery and birth weight Z-score was determined. RESULTS: In the normal group there were significant independent contributions to uterine artery PI from gestational age, racial origin and prior history of PE, and/or small for gestational age (SGA). In the PE group, there was an inverse significant association between uterine artery PI MoM and both gestational age at delivery and birth weight Z-score (p < 0.0001). Uterine artery PI was above the 95th percentile (1.509 MoM) in 72.7, 36.1 and 14.9% of cases of PE requiring delivery at <34, 34-37 and ≥38 weeks, respectively, and the percentages for PE with SGA were 80.2, 55.6 and 37.4%. CONCLUSIONS: In a normal pregnancy, uterine artery PI is affected by maternal characteristics, and in PE, uterine artery PI MoM is related to the severity of the disease.

Second-trimester uterine artery Doppler in the prediction of stillbirths.

OBJECTIVE: To examine the role of second-trimester uterine artery Doppler in the prediction of stillbirths. METHODS: Uterine artery pulsatility index (PI) was measured at 20-24 weeks' gestation in 65,819 singleton pregnancies. The PI was converted to multiples of median (MoM) and compared in live births and stillbirths. Regression analysis was used to determine the significance of association between log(10) uterine artery PI MoM and gestational age (GA) at delivery in cases of stillbirths. RESULTS: There were 306 (0.46%) stillbirths and in 159 (52.0%) of these there was pre-eclampsia (PE), placental abruption and/or birthweight below the 10th percentile (small for gestational age, SGA). In the stillbirths, the uterine artery PI MoM was significantly higher than in live births and was inversely associated with GA at delivery. The uterine artery PI MoM was above the 90th percentile in 80.6% of stillbirths with PE, abruption and/or SGA delivering at <32 weeks' gestation, in 41.9% at 33-36 weeks and in 34.3% at ≥37 weeks, and the respective percentages for stillbirths without PE, abruption or SGA were 15.8, 25.0 and 12.4%. CONCLUSION: Second-trimester uterine artery PI is effective in identifying early stillbirths in association with PE, abruption or SGA but not late deaths in the absence of PE, abruption or SGA.