Prognosis for pregnancies with trisomy 16 confined to the placenta: A Danish cohort study

Abstract

Objective To evaluate the risk of adverse pregnancy outcome when trisomy 16 confined to the placenta is diagnosed and to identify possible prognostic markers for adverse outcomes in these pregnancies. Method Registered cases (n = 49) of trisomy 16 diagnosed prenatally in Denmark from 1990 to 2013 were included. Results Twenty‐five of the pregnancies intended to be continued had confined placental trisomy 16 mosaicism (CPM16). Adverse pregnancy outcome was seen in 17 CPM16 pregnancies (68%), ranging from mild small for gestational age (SGA) to fetal malformations and intrauterine demise. For cases ascertained by combined first trimester screening, the median concentration of pregnancy associated plasma protein A (PAPP‐A) was 0.17 MoM (IQR: 0.11 MoM). Adverse pregnancy outcome showed a trend toward an association with a high frequency of trisomic cells. Eight children (32%) were born at term with a normal birth weight and no malformations. Conclusion The risk of adverse pregnancy outcome in case of CPM16 is correlated to ascertainment by combined first trimester screening and tends to be associated with a high frequency of trisomic cells in the placenta. We recommend that variables including ascertainment, the frequency of trisomic cells, and the maternal serum concentration of PAPP‐A are taken into consideration when evaluating the prognosis in CPM16 while acknowledging that these factors are strongly correlated.

Prevalence of mosaicism in uncultured chorionic villus samples after chromosomal microarray and clinical outcome in pregnancies affected by confined placental mosaicism

“…Regarding pregnancy outcome, we found that low PAPP‐A MoM is an important predictor for adverse clinical outcome in pregnancies affected by CPM as reported previously . This underlines that PAPP‐A provides additional information of clinical importance beyond PAPP‐As predictive abilities of t21.…”

“…CPM for whole chromosomes has been related to a high perinatal loss rate and unfavorable outcome . To our knowledge, pregnancy outcome after CPM for CNVs has only been scarcely studied .…”

“…However, the risk of low‐level TFM cannot be eliminated . Furthermore, counseling remains challenging as even aberrations confined to the placenta (confined placental mosaicism, CPM) may cause dysfunction of the placenta leading to intrauterine growth restriction and other complications …”

Rare autosomal trisomies: comparison of detection through cell‐free DNA analysis and direct chromosome preparation of chorionic villus samples

“…Most, but not all, of these abnormalities were CPM. The significance of CPM with trisomy 16 is now recognized, but the consequences of other RATs remain controversial. The need to understand the clinical implications of RATs in cytotrophoblasts has become urgent because of the introduction of genome‐wide cfDNA testing that also detects these abnormalities.…”

Genetic syndromes associated with isolated fetal growth restriction

“…This aneuploidy is estimated to complicate more than 1% of all clinically recognized pregnancies, including miscarriages, stillbirths and live births. When trisomy 16 is assumed to be confined to the placenta (CPM16) in an ongoing pregnancy, counseling of the expectant parents is challenging, as CPM16 has been associated with a normal outcome in 20‐36% of the cases while the frequency of SGA is 43‐58%, fetal/child malformations 20‐22%, preeclampsia 16‐24% and prematurity 32‐37%. Moreover, several imprinted genes have been described on chromosome 16 and maternal uniparental disomy may be associated with FGR and other obstetric complications (even though not all publications support this hypothesis‐ see below in Epigenetic changes section).…”