Nerea Maiz

Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A

To derive a model and examine the performance of first‐trimester combined screening by maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A).

First-Trimester Prediction of Hypertensive Disorders in Pregnancy

This study aimed to establish a method of screening for pregnancy hypertension by a combination of maternal variables, including mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor in early pregnancy. The base-cohort population constituted of 7797 singleton pregnancies, including 34 case subjects who developed preeclampsia (PE) requiring delivery before 34 weeks (early PE) and 123 with late PE, 136 with gestational hypertension, and 7504 cases subjects (96.3%) who were unaffected by PE or gestational hypertension. Maternal history, uterine artery pulsatility index, mean arterial pressure, and pregnancy-associated plasma protein-A were recorded in all of the cases in the base cohort, but placental growth factor was measured only in the case-control population of 209 cases who developed hypertensive disorders and 418 controls. In each case the measured mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor were converted to a multiple of the expected median (MoM) after correction for maternal characteristics found to affect the measurements in the unaffected group. Early PE and late PE were associated with increased mean arterial pressure (1.15 MoM and 1.08 MoM) and uterine artery pulsatility index (1.53 MoM and 1.23 MoM) and decreased pregnancy-associated plasma protein-A (0.53 MoM and 0.93 MoM) and placental growth factor (0.61 MoM and 0.83 MoM). Logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. It was estimated that, with the algorithm for early PE, 93.1%, 35.7%, and 18.3% of early PE, late PE, and gestational hypertension, respectively, could be detected with a 5% false-positive rate and that 1 in 5 pregnancies classified as being screen positive would develop pregnancy hypertension. This method of screening is far superior to the traditional approach, which relies entirely on maternal history.

First‐trimester maternal serum pregnancy‐associated plasma protein‐A and pre‐eclampsia

To examine the relationship between low maternal serum pregnancy‐associated plasma protein‐A (PAPP‐A) and uterine artery pulsatility index (UtA‐PI) at 11 + 0 to 13 + 6 weeks with subsequent development of pre‐eclampsia (PE).

Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free β-hCG and pregnancy-associated plasma protein-A

BACKGROUND A beneficial consequence of screening for trisomy 21 is the early diagnosis of trisomies 18 and 13. Our objective was to examine the performance of first-trimester screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency (NT) thickness, fetal heart rate (FHR) and maternal serum-free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A). METHODS Prospective screening for trisomy 21 by maternal age, fetal NT, free beta-hCG and PAPP-A at 11(+0)-13(+6) weeks in singleton pregnancies, including 56 376 normal cases, 395 with trisomy 21, 122 with trisomy 18 and 61 with trisomy 13. Risk algorithms were developed for the calculation of patient-specific risks for each of the three trisomies based on maternal age, NT, FHR, free beta-hCG and PAPP-A. Detection (DR) and false positive rates (FPR) were calculated and adjusted according to the maternal age distribution of pregnancies in England and Wales in 2000-2002. RESULTS The DR and FPR were 90% and 3%, respectively, for trisomy 21, 91% and 0.2% for trisomy 18 and 87% and 0.2% for trisomy 13. When screen positivity was defined by an FPR of 3% on the risk for trisomy 21 in conjunction with an FPR of 0.2% on the maximum of the risks for trisomies 13 and 18, the overall FPR was 3.1% and the DRs of trisomies 21, 18 and 13 were 91%, 97% and 94%, respectively. CONCLUSIONS As a side effect of first-trimester screening for trisomy 21, approximately 95% of trisomy 13 and 18 fetuses can be detected with an 0.1% increase in the FPR.

Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation.

To investigate the performance of first‐trimester screening for aneuploidies by including assessment of ductus venosus flow in the combined test of maternal age, fetal nuchal translucency thickness, fetal heart rate, and serum free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A.

Hypertensive disorders in pregnancy: screening by uterine artery Doppler at 11–13 weeks

To examine the performance of screening for hypertensive disorders in pregnancy by a combination of the maternal factor‐derived a‐priori risk with the uterine artery (UtA) pulsatility index (PI) and to determine whether it is best in such screening to use the mean PI of the two arteries, the highest PI or the lowest PI.

Contribution of fetal tricuspid regurgitation in first-trimester screening for major cardiac defects.

OBJECTIVE: To estimate the potential value of fetal assessment for tricuspid regurgitation at 11–13 weeks of gestation in the prediction of major cardiac defects. METHODS: We screened for aneuploidies by measuring fetal nuchal translucency thickness as well as assessing blood flow across the tricuspid valve for evidence of tricuspid regurgitation and in the ductus venosus for evidence of reversed A-wave at 11 0/7 to13 6/7 weeks of gestation. The estimated performance of different combinations of increased fetal nuchal translucency, tricuspid regurgitation, and ductus venosus reversed A-wave in screening for major cardiac defects was examined. RESULTS: The study population of euploid fetuses included 85 cases with major cardiac defects and 40,905 with no cardiac defects. Fetal nuchal translucency above the 95th percentile, tricuspid regurgitation, or ductus venosus reversed A-wave was observed in 30 (35.3%), 28 (32.9%), and 24 (28.2%) of the fetuses with cardiac defects, respectively, and in 1,956 (4.8%), 516 (1.3%), and 856 (2.1%) of those without cardiac defects. Any one of the three markers was found in 49 of the fetuses with cardiac defects (57.6%, 95% confidence interval [CI] 47.0–67.6%) and in 3,265 of those without cardiac defects (8.0%, 95% CI 7.7–8.2%). CONCLUSION: Assessment of flow across the tricuspid valve improves the performance of screening for major cardiac defects by fetal nuchal translucency and ductus venosus flow. LEVEL OF EVIDENCE: II

First-trimester maternal plasma cell-free fetal DNA and preeclampsia

OBJECTIVE The purpose of this study was to determine whether, in pregnancies that experience preeclampsia, plasma cell-free fetal DNA (cffDNA) at 11-13 weeks of gestation is increased and whether this increase is related to the uterine artery pulsatility index (PI). STUDY DESIGN Plasma cffDNA and uterine artery PI were measured in 44 cases with preeclampsia, which included 11 cases that required delivery at <34 weeks of gestation and 176 normal control subjects. All fetuses were male, and cffDNA was assessed by amplification of the DYS14 gene. The association between cffDNA and uterine artery PI was assessed by regression analysis. RESULTS Median cffDNA was higher in early preeclampsia (median, 95.5 genome equivalents/mL; interquartile range, 72.7-140.9 genome equivalents/mL), but not late preeclampsia (median, 50.8 genome equivalents/mL; interquartile range, 25.0-103.8 genome equivalents/mL), than control subjects (median, 51.5 genome equivalents/mL; interquartile range, 31.1-84.9 genome equivalents/mL). There was a significant association between cffDNA and uterine artery PI (P = .038) but not in the control subjects (P = .174). CONCLUSION The increase in plasma cffDNA in pregnancies that experience preeclampsia is associated with the degree of impairment in placental perfusion.

Ductus Venosus Doppler at 11 to 13 Weeks of Gestation in the Prediction of Outcome in Twin Pregnancies

OBJECTIVE: To examine the independent contribution of abnormal flow in the ductus venosus at 11 to 13 weeks of gestation in the prediction of adverse pregnancy outcome in relation to chorionicity. METHODS: This was a prospective study in 516 dichorionic and 179 monochorionic twin pregnancies in which the fetal ductus venosus flow was assessed at 11 0/7 to 13 6/7 weeks of gestation. The prevalence of reversed a-wave in the fetal ductus venosus was compared between monochorionic and dichorionic pregnancies and between those with and without pregnancy complications. Comparisons between each of the pregnancy outcomes and the normal outcome group and between monochorionic and dichorionic pregnancies were made using the Mann-Whitney U-test for continuous variables and the χ2 test and Fisher exact test for categorical variables. RESULTS: The prevalence of reversed a-wave in at least one of the fetuses was significantly higher in monochorionic than in dichorionic pregnancies (18.4% compared with 8.3%, P<.001) and in pregnancies complicated by miscarriage (28.6%, P=.005), fetal aneuploidy (70.0%, P<.001), and twin–twin transfusion syndrome (38.5%, P<.001) compared with the pregnancies with two healthy live births (7.7%). Pregnancy outcome was normal in 33 of the 43 (76.7%) dichorionic and in 14 of the 33 (42.4%) monochorionic twins with reversed a-wave in at least one of the fetuses. CONCLUSION: In twins, reversed a-wave in the ductus venosus at 11 to 13 weeks of gestation is associated with increased risk for aneuploidies, miscarriage, and development of severe twin–twin transfusion syndrome. However, in about 75% of dichorionic twins and 40% of monochorionic twins with reversed a-wave, the pregnancy outcome is normal. LEVEL OF EVIDENCE: II

Contribution of ductus venosus Doppler in first-trimester screening for major cardiac defects.

Objective: To determine whether assessment of ductus venosus flow at 11–13 weeks’ gestation improves the detection rate of cardiac defects achieved by screening with nuchal translucency (NT) thickness. Methods: Prospective first-trimester screening for aneuploidies, including measurement of fetal NT and assessment of ductus venosus flow. The performance of different combinations of increased fetal NT and abnormal blood flow in the ductus venosus in screening for major cardiac defects was examined. Results: The study population of euploid fetuses included 85 cases with major cardiac defects and 40,905 with no cardiac defects. The fetal NT was above the 95th and above the 99th centile in 30 (35.3%) and 18 (21.2%) of the fetuses with cardiac defects, respectively, and in 1,956 (4.8%) and 290 (0.7%) of those without cardiac defects, respectively. Reversed a-wave was observed in 24 (28.2%) of the fetuses with cardiac defects and in 856 (2.1%) of those with no cardiac defects. Specialist fetal echocardiography for cases with NT above the 99th centile and those with reversed a-wave, irrespective of NT, would detect 38.8% of major cardiac defects at an overall false- positive rate of 2.7%. Conclusions: Assessment of ductus venosus flow improves the performance of NT screening for cardiac defects.