Confined placental mosaicism, IUGR, and adverse pregnancy outcome: A controlled retrospective U.K. collaborative survey

Abstract

In a retrospective collaborative study involving 21 U.K. laboratories and 11,775 CVS prenatal diagnostic procedures, a total of 73 cases of confined placental mosaicism (CPM) were identified among the 8004 first-trimester referrals because of advanced maternal age, a previous child with a numerical chromosome abnormality, or a family history of the same. Data were collected on subsequent cytogenetic follow-up and pregnancy outcome for each case and a referral matched control. Comparison with the control population failed to demonstrate a marked increase in adverse pregnancy outcome in the CPM group, but a significant increase in both low and high birth weight infants was recorded. In a parallel study, 7 out of 108 cases, referred for prenatal diagnosis because of ultrasound detection of isolated intrauterine growth retardation (IUGR) in the second or third trimester, were shown to have a chromosome abnormality restricted to the extraembryonic tissues. These included cases of CPM involving trisomy 9 and del(13)(q13), neither of which has previously been reported in association with IUGR.

Correlation of Confined Placental Mosaicism with Fetal Intrauterine Growth Retardation

“…There are only few reported cases of placental mosaicism and uniparental disomy for chromosome 9. The association of IUGR with CPM 9 was reported in the study of Wolstenholme et al [11] and Appelman et al [40]. Wilkinson et al [41] reported a prenatally diagnosed case of maternal UPD 9 associated with CPM 9.…”

“…A significantly higher risk for adverse outcome including fetal loss and intrauterine growth retardation (IUGR) has been noted among pregnancies complicated by CPM [1,[9][10][11]. The results of cytogenetic studies on term placentas in growth-restricted fetuses showed conflicting results.…”

“…There are few reported cases of growth-retarded fetuses with mosaic placenta and aneuploid cell line including partial monosomy. Wolstenholme et al [11] detected one fetus with del(13)(q13) delivered at 32 weeks of pregnancy with a birth weight of 700 g. The newborn had abnormal ears and generalized edema and died at 28 days. In our group of growth-retarded fetuses, pregnancy with placental partial monosomy del(16)(p11) ended with intrauterine fetal death.…”

Chromosomal Mosaicisms during Prenatal Diagnosis

“…Though the procedure provides early diagnosis of genetic outcome as compared with amniocentesis, a chromosomal mosaicism of pseudonature is a daunting challenge which usually results in amniocentesis as a follow-up procedure. True mosaicism occurred in about 0.2% of the cases while confined placental mosaicism (CPM) has been encountered in about 2% of the cases [3,4]. CPM has been associated with spontaneous fetal loss [5].…”

Somatic genomic variations in extra-embryonic tissues

“…Alternatively, a trisomic blastocyst may be rescued by chromosome loss within the embryo, leaving the extraembryonic lineages and thus the placenta trisomic [24][25][26]. Approximately 20% of pregnancies complicated by idiopathic intrauterine growth restriction are associated with CPM [27][28][29]. About 5% of conceptions with trisomy 13 or 18 develop trophoblast-confined mosaicism and continue their intrauterine development into the third trimester [30].…”