Prenatal sonographic features can accurately determine parental origin in triploid pregnancies

Abstract

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 (β-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 β-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.

Figure 1

A, CRL measurements (n = 24) of triploidies plotted against a reference curve. B, Figure 1B AC measurements (n = 77) of triploidies plotted against a reference curve. C, Figure 1C HC/AC ratio measurements (n = 71) of triploidies plotted against a reference curve. Open dots represent the cases with placental molar changes on ultrasound

Figure 2

Triploidy of paternal origin at 12.5 weeks of gestation, referred because of an abnormal combined test with high levels of β‐hCG *** (7.6 MoM). Normal growth (A and B), dilated fossa posterior (B), micrognathia (A and B) increased Nuchal Translucency (C) and a partial hydatidiform mole (D)

Figure 3

Triploidy of paternal origin at 19.6 weeks of gestation with symmetrical growth restriction, holoproscencephaly (A and B), an omphalocele (C), and a partial hydatidiform mole (D)

Figure 4

Triploidy of maternal origin at 12.2 weeks of gestation, referred because of an abnormal combined test with low pregnancy‐associated plasma protein A (0.050 MoM). On ultrasound notable asymmetrical growth restriction; severe head‐to‐abdominal circumference discrepancy (A,B,C,D)

Figure 5

Triploidy of maternal origin at 19.2 weeks of gestation with notable asymmetrical growth restriction; severe head‐to‐abdominal circumference discrepancy (A,B,C), micrognathia (B,C), and a small placenta (A)