Prenatal sonographic features can accurately determine parental origin in triploid pregnancies.

OBJECTIVE: To describe the prenatal sonographic features and maternal biochemical markers in triploid pregnancies and to assess whether prenatal phenotype can determine genetic origin. METHODS: We performed a retrospective multicenter cohort study that included all triploid pregnancies diagnosed between 2000 and 2018 in two Fetal Medicine Units in Amsterdam. Fetal growth, presence of structural anomalies, extra-fetal anomalies, and maternal biochemical markers were retrieved. Asymmetrical intrauterine growth restriction was diagnosed when the head-to-abdominal circumference (HC/AC) ratio was >95th centile. Parental origin was analyzed via molecular genotyping in 46 cases (38.3%). RESULTS: One hundred and twenty triploid pregnancies were identified, of which 86 cases (71.6%) were detected before 18 weeks of gestation. Triploidy of maternal origin was found in 32 cases (69.6%) and was associated with asymmetrical growth restriction, a thin placenta, and low pregnancy-associated plasma protein A and free beta-human chorionic gonadotrophin (ß-hCG) levels. Triploidy of paternal origin was found in 14 cases (30.4%) and was associated with an increased nuchal translucency, placental molar changes, and a high free ß-hCG. Prospective prediction of the parental origin of the triploidy was made in 30 of the 46 cases based on phenotypical ultrasound presentation, and it was correct in all cases. CONCLUSION: Asymmetrical growth restriction with severe HC/AC discrepancy is pathognomonic of maternal triploidy. Placental molar changes indicate a paternal triploidy. Moreover, triploidy can present with an abnormal first trimester combined test, with serum levels on the extreme end. When available results of maternal serum markers can support the diagnosis of parental origin of the triploidy, an accurate assessment of the parental origin based on prenatal sonographic features is possible, making DNA analysis redundant.

Economic evaluation of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis: a cost-minimization analysis.

PURPOSE: To assess the cost-effectiveness of Multiplex Ligation-dependent Probe Amplification (MLPA, P095 kit) compared to karyotyping. METHODS: A cost-minimization analysis alongside a nationwide prospective clinical study of 4,585 women undergoing amniocentesis on behalf of their age (≥36 years), an increased risk following first trimester prenatal screening or parental anxiety. RESULTS: Diagnostic accuracy of MLPA (P095 kit) was comparable to karyotyping (1.0 95% CI 0.999-1.0). Health-related quality of life did not differ between the strategies (summary physical health: mean difference 0.31, p = 0.82; summary mental health: mean difference 1.91, p = 0.22). Short-term costs were lower for MLPA: mean difference 315.68 (bootstrap 95% CI 315.63-315.74; -44.4%). The long-term costs were slightly higher for MLPA: mean difference 76.42 (bootstrap 95% CI 71.32-81.52; +8.6%). Total costs were on average 240.13 (bootstrap 95% CI 235.02-245.23; -14.9%) lower in favor of MLPA. Cost differences were sensitive to proportion of terminated pregnancies, sample throughput, individual choice and performance of tests in one laboratory, but not to failure rate or the exclusion of polluted samples. CONCLUSION: From an economic perspective, MLPA is the preferred prenatal diagnostic strategy in women who undergo amniocentesis on behalf of their age, following prenatal screening or parental anxiety.

Multiplex ligation-dependent probe amplification versus karyotyping in prenatal diagnosis: the M.A.K.E. study.

BACKGROUND: In the past 30 years karyotyping was the gold standard for prenatal diagnosis of chromosomal aberrations in the fetus. Traditional karyotyping (TKT) has a high accuracy and reliability. However, it is labor intensive, the results take 14-21 days, the costs are high and unwanted findings such as abnormalities with unknown clinical relevance are not uncommon. These disadvantages challenged the practice of karyotyping. Multiplex ligation-dependent probe amplification (MLPA) is a new molecular genetic technique in prenatal diagnosis. Previous preclinical evidence suggests equivalence of MLPA and traditional karyotyping (TKT) regarding test performance. METHODS/DESIGN: The proposed study is a multicentre diagnostic substitute study among pregnant women, who choose to have amniocentesis for the indication advanced maternal age and/or increased risk following prenatal screening test. In all subjects, both MLPA and karyotyping will be performed on the amniotic fluid sample. The primary outcome is diagnostic accuracy. Secondary outcomes will be maternal quality of life, women's preferences and costs. Analysis will be intention to treat and per protocol analysis. Quality of life analysis will be carried out within the study population. The study aims to include 4500 women. DISCUSSION: The study results are expected to help decide whether MLPA can replace traditional karyotyping for 'low-risk' pregnancies in terms of diagnostic accuracy, quality of life and women's preferences. This will be the first clinical study to report on all relevant aspects of the potential replacement. TRIAL REGISTRATION: The protocol is registered in the clinical trial register number ISRCTN47252164.