A case of confined placental mosaicism with double trisomy associated with stillbirth L.R. Goodfellow a, * , G. Batra b , V. Hall c , E. McHale d , A.E.P. Heazell a a Maternal and Fetal Health Research Centre, Manchester Academic Health Sciences Centre, 5th floor (Research), St Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK b Department of Paediatric and Perinatal Pathology, Central Manchester University Hospitals Foundation Trust, Manchester, UK c Department of Obstetrics and Gynaecology, Macclesfield District General Hospital, Macclesfield, UK d Department of Cytogenetics, Central Manchester University Hospitals Foundation Trust, Manchester, UK article info Article history: Accepted 13 June 2011 Keywords: Placenta Stillbirth Confined placental mosaicism Cytogenetics Placental mesenchymal dysplasia abstract We present a case of stillbirth in which the fetus was well grown and karyotypically normal, but the placenta was morphologically abnormal and had confined placental mosaicism (CPM) for a double trisomy of chromosomes 12 and 15. A compilation of published cases of CPM reveals that whilst approximately 80% of pregnancies progress normally, there is an association with abnormal placental morphology, intrauterine growth restriction, fetal abnormalities and stillbirth. This case highlights the potential adverse effects of CPM and the benefit of placental examination in determining the cause of stillbirth. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Stillbirth affects 1 in 200 pregnancies in the developed world. Modern classification systems identify placental pathology as a cause in 26e70% of stillbirths [1]. This frequently represents infarction or inflammatory pathologies [2]. However, rarer causes of placental dysfunction may also result in stillbirth. Here, we present a case of stillbirth with abnormal placental morphology in which confined placental mosaicism (CPM) was identified. 2. Case report A 34 year old Caucasian woman presented in her third preg- nancy at 13 weeks gestation. She was healthy and had a history of a spontaneous first trimester miscarriage and a normal delivery of a live born male at term. The father was 34 years old, Caucasian, healthy, and no biological relation to the mother. First and second trimester assessments, including Down’s syndrome screening and ultrasounds, were normal. At 32 weeks and 4 days gestation she presented with absent fetal movements for 24 h. There was no history of abdominal pain or vaginal bleeding. A diagnosis of fetal death in utero was made. Following induction of labor a stillborn male infant weighing 2.02 kg (58th centile) was born. There were no external congenital malformations or dysmorphic features. Post mortem revealed a left-sided diaphragmatic hernia, with the pleural cavity containing a substantial loop of small intestine and the spleen. The left lung weight was smaller than expected, in keeping with the restricted left pleural space. Organ weights of the heart, liver, kidneys, spleen, adrenals and brain were below that expected for gestation. However, all were anatomically and histo- logically normal. The remaining alimentary, endocrine, musculo- skeletal and genitourinary systems were normal in shape, position and size. Review of the images of the second trimester USS by a consultant obstetrician (VH) failed to show the diaphragmatic hernia, suggesting it had developed later in gestation. Placental weight was 451 g, (just below 50th centile [3]). Examination of eight placental biopsies showed approximately 50% of large stem villi had excessive stromal tissue (Fig. 1A), placental mesenchymal dysplasia was considered but it was not felt to be typical. Arteries within stem and intermediate villi were exces- sively muscularised (Arrows, Fig. 1B) but without features of fetal thrombotic vasculopathy, specifically there was no evidence of haemorrhagic endovasculitis, intimal cushions or occlusive thrombi. Terminal villi showed normal development of vasculo- syncytial membranes (Fig. 1C). Analysis of cultured placental membrane and villus samples showed a male karyotype with trisomy for both chromosome 12 and chromosome 15 (Fig. 1D). No evidence of mosaicism was detected in 56 cells from the mesen- chymal core, which originates from the inner cell mass. Cytocell 12 and 15 centromere probes were used to perform fluorescence in situ hybridization studies (FISH) on 40 uncultured fetal skin * Corresponding author. Tel.: þ44 161 276 5460. E-mail address: laurargoodfellow@doctors.org.uk (L.R. Goodfellow). Contents lists available at ScienceDirect Placenta journal homepage: www.elsevier.com/locate/placenta 0143-4004/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2011.06.008 Placenta 32 (2011) 699e703