Peter Skovbo

The Danish Fetal Medicine Database: establishment, organization and quality assessment of the first trimester screening program for trisomy 21 in Denmark 2008–2012

To describe the establishment and organization of the Danish Fetal Medicine Database and to report national results of first‐trimester combined screening for trisomy 21 in the 5‐year period 2008–2012.

Increased nuchal translucency, normal karyotype and infant development

To investigate whether chromosomally normal fetuses with a nuchal translucency (NT) ≥ 99th percentile (3.5 mm) in the first trimester have an increased risk of delayed development at 2 years of age.

ECEL1 mutation causes fetal arthrogryposis multiplex congenita

Arthrogryposis multiplex congenita (AMC) is a descriptor for the clinical finding of congenital fixation of multiple joints. We present a consanguineous healthy couple with two pregnancies described with AMC due to characteristic findings on ultrasonography of fixated knee extension and reduced fetal movement at the gestational age of 13 weeks + 2 days and 12 weeks + 4 days. Both pregnancies were terminated and postmortem examinations were performed. The postmortem examinations confirmed AMC and suggested a diagnosis of centronuclear myopathy (CNM) due to characteristic histological findings in muscle biopsies. Whole exome sequencing (WES) was performed on all four individuals and the outcome was filtered by application of multiple filtration parameters satisfying a recessive inheritance pattern. Only one gene, ECEL1, was predicted damaging and had previously been associated with neuromuscular disease or AMC. The variant found ECEL1 is a missense mutation in a highly conserved residue and was predicted pathogenic by prediction software. The finding expands the molecular basis of congenital contractures and the phenotypic spectrum of ECEL1 mutations. The histological pattern suggestive of CNM in the fetuses can expand the spectrum of genes causing CNM, as we propose that mutations in ECEL1 can cause CNM or a condition similar to this. Further investigation of this is needed and we advocate that future patients with similar clinical presentation or proven ECEL1 mutations are examined with muscle biopsy. Secondly, this study illustrates the great potential of the clinical application of WES in couples with recurrent abortions or stillborn neonates.

Associations between fetal HLA-G genotype and birth weight and placental weight in a large cohort of pregnant women – Possible implications for HLA diversity

Birth weight and placental weight are crucial parameters for the survival of fetuses and newborns in mammals. High variation in the MHC is important for an effective adaptive immune response. The maternal immune system must be controlled in relation to the semi-allogenic fetus. The immunoregulatory HLA/MHC class Ib gene, HLA-G, is strongly expressed on extravillous trophoblast cells. We investigated birth weight and placental weight of the newborns in mothers heterozygous for an HLA-G 14bp insertion (Ins)/deletion (Del) gene polymorphism. Separate analyses for pregnancies without preeclampsia (n=185), pregnancies complicated by preeclampsia (n=101), and both groups combined, were performed. Interestingly, we observed the highest mean birth weight and placental weight in homozygous 14bp Del/Del newborns, and the lowest in 14bp Ins/Ins newborns (P=0.008 and P=0.009). The 14bp Del/Del genotype is also associated with high expression of HLA-G on the trophoblast membrane. In theory, fetuses and newborns with intermediate weights and sizes would be an optimal compromise for both the fetus/father and the mother compared with very high and low weights. If such fetuses/newborns more often are heterozygous at the HLA-G gene locus, then newborns with two distinct HLA haplotypes are favored, leading to a higher degree of HLA diversity. The results of the study may indicate that a compromise between an intermediate birth weight and placental weight, induction of maternal tolerance by a fetal-derived non-polymorphic HLA class Ib molecule, and favoring of HLA heterozygous offspring, have evolved in humans.

OC02.03: Increased nuchal translucency, normal karyotype and infant development

C. B. Miltoft1, C. K. Ekelund1, B. M. Hansen2, A. Lando2, O. B. Petersen3, P. Skovbo4, F. S. Jorgensen5, L. Sperling6, H. Zingenberg7, A. Nikkila8, A. C. Shalmi9, I. Stornes10, V. Ersbak11, A. Tabor1 1Fetal Medicine and Ultrasound, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Neonatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 3Department of Obstetrics and Gynaecology, Aarhus University Hospital, Skejby, Aarhus, Denmark; 4Department of Obstetric and Gynaecology, Aalborg University Hospital, Aalborg, Denmark; 5Fetal Medicine Unit, Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark; 6Department of Obstetrics and Gynecology, Copenhagen University Hospital, Herlev, Copenhagen, Denmark; 7Department of Obstetrics and Gynecology, Copenhagen University Hospital, Glostrup, Copenhagen, Denmark; 8Department of Obstetrics and Gynecology, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark; 9Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hillerod, Copenhagen, Denmark; 10Department of Obstetrics and Gynecology, Randers Hospital, Randers, Denmark; 11Department of Obstetrics and Gynecology, Silkeborg Hospital, Silkeborg, Denmark

OC05.05: The Danish Fetal Medicine Database: establishment and quality assessment of first trimester screening for trisomy 21 in the period 2008–2010

Objectives: Prenatal screening for fetal aneuploidies is best achieved in the first trimester when there is no reliable screening test for spina bifida (SB). Early ultrasound features may be too complex to be of value in routine screening. We assessed the screening potential of simple and reproducible fetal biometric measurements at 11–14 weeks’. Methods: 34,951 unselected consecutive pregnancies including 18 subsequently found to have spina bifida. Another 28 cases of SB were referred for assessment. Each biometric measurement was expressed in multiples of the median for crown-rump length. Results: Biparietal diameter (BPD) was smaller in spina bifida (P < 0.0001). 22/44 (50%) cases with a spina bifida aperta had a BPD < 5th centile. BPD was independent of maternal adiposity and smoking status. Conclusions: Simple and reproducible BPD at 11–14 weeks gestation could detect half the cases of open fetal spina bifida by identifying 5% of pregnancies for expert scanning in the first trimester.

P11.01: Development and establishment of a national Danish fetal medicine database for quality surveillance and research

were rated to enable highly diagnostic confidence (82.9%), and produce better image quality for the near field image (94.3%), the far field image (88.6%), and overall (94.3%). Conclusions: The current study described an objective method of comparing image quality acquired using different sonographic technologies. Ultrasound transducer incorporated with PureWave Crystal technology produces significantly better image quality for diagnostic purpose.