First‐trimester screening for trisomies in pregnancies with vanishing twin

Abstract

Objectives To examine multiples of the median (MoM) values of serum free beta‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first‐trimester combined screening for trisomy. Methods This was a retrospective study comparing maternal serum free β‐hCG and PAPP‐A levels at 11–13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing‐twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling. Results First, in pregnancies with a vanishing twin, median free β‐hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985–1.016 vs 0.995; 95% CI, 0.948–1.044; P = 0.849). Second, PAPP‐A MoM was higher in vanishing‐twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985–1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080–1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105–1.249; P < 0.0001). Third, in vanishing‐twin pregnancies with a dead embryo, PAPP‐A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first‐trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false‐positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β‐hCG and to 91% with the addition of serum PAPP‐A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP‐A for the interval between estimated gestational age at embryonic demise and blood sampling. Conclusions First‐trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β‐hCG, as in singleton pregnancy, without the use of serum PAPP‐A. Alternatively, PAPP‐A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Screening for aneuploidy in twins

“…Some studies of vanishing twin pregnancies have suggested that NT combined with beta-hCG with or without PAPP-A can be considered for aneuploidy screening. 59,60 cfDNA from a vanishing twin may be present in the maternal circulation and may lead to a false-positive or false-negative result for an interval up to 15 weeks after ultrasound identification. 61 Although, 1 study suggested that delaying testing until 14 weeks in vanishing twin pregnancy improves accuracy because of fading of contaminating DNA, 62 cfDNA testing is not currently recommended in the presence of a vanishing twin sac as the persistence of cfDNA from a cotwin demise is unknown.…”

Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and meta‐analysis

“…If cfDNA testing is adopted as a first-line method of screening for trisomy in twin pregnancy, it is still imperative that women should be offered an 11-14-week scan for, first, accurate dating of pregnancy from the crown-rump length of the largest twin, second, diagnosis of chorionicity, which is the main determinant of a wide range of adverse outcomes 34 , third, measurement of fetal nuchal translucency thickness and assessment of intertwin discordance in crown-rump length, which have a strong influence on adverse pregnancy outcome 35,36 , fourth, diagnosis of a vanishing twin, because this would preclude the use of cfDNA testing for at least 16 weeks after the estimated time of fetal demise 37,38 , fifth, early diagnosis of major fetal abnormalities 39 , sixth, to determine the presence of major defects, such as holoprosencephaly or exomphalos, in which case an invasive test with microarray rather than cfDNA testing would be the appropriate pregnancy management 40 , seventh, early screening for preterm pre-eclampsia, which is 8-9-times more common in twins than in singleton pregnancies 41,42 , and, eighth, measurement of cervical length, because, if this is short, prophylactic use of vaginal progesterone could substantially reduce the risk of preterm birth 43 .…”

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis

“…This was a multicenter cohort study of women with twin pregnancy from eight fetal medicine units in the UK, Spain, Italy, Bulgaria and Portugal, in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar 5 . At 11-13 weeks, we recorded maternal demographic characteristics and carried out ultrasound examination for, first, determination of gestational age from the measurement of CRL of the larger twin 13 , second, determination of chorionicity from the number of placentae and the presence or absence of the lambda sign at the intertwin membrane-placental junction 14 , third, exclusion of vanishing twin 15 , fourth, diagnosis of major fetal abnormalities 16 , fifth, assessment of intertwin discordance in CRL (difference between the two fetuses expressed as a percentage of the larger one), because a large discordance is associated with adverse pregnancy outcome 10 , and, sixth, measurement of NT in each fetus for assessment of risk for trisomy and determination of whether the NT in one or both fetuses was ≥ 95 th percentile of our reference range for CRL 17 , because high NT is associated with adverse pregnancy outcome 11 . In most, but not all, pregnancies, maternal serum free β-human chorionic gonadotropin (β-hCG) and PAPP-A were measured using automated machines (DelfiaXpress system, PerkinElmer Life and Analytical Sciences, Waltham, MA, USA; Brahms Kryptor system, Thermo Fisher Scientific, Berlin, Germany; or Cobas e411 system, Roche Diagnostics, Penzberg, Germany) and the values were expressed as multiples of the median (MoM) after adjustment for maternal weight, height, racial origin, parity, smoking status, method of conception and machine used for the measurement 18,19 .…”