B. Serra

Initial experience with non-invasive prenatal testing of cell-free DNA for major chromosomal anomalies in a clinical setting

Abstract Objective: To evaluate non-invasive prenatal testing (NIPT) of cell-free DNA (cfDNA) as a screening method for major chromosomal anomalies (CA) in a clinical setting. Methods: From January to December 2013, Panorama™ test or Harmony™ prenatal test were offered as advanced NIPT, in addition to first-trimester combined screening in singleton pregnancies. Results: The cohort included 333 pregnant women with a mean maternal age (MA) of 37 years who underwent testing at a mean gestational age of 14.6 weeks. Eighty-four percent were low-risk pregnancies. Results were provided in 97.3% of patients at a mean reporting time of 12.9 calendar days. Repeat sampling was performed in six cases and results were obtained in five of them. No results were provided in four cases. Four cases of Down syndrome were detected and there was one discordant result of Turner syndrome. We found no statistical differences between commercial tests except in reporting time, fetal fraction and MA. The cfDNA fraction was statistically associated with test type, maternal weight, BMI and log βhCG levels. Conclusions: NIPT has the potential to be a highly effective screening method for major CA in a clinical setting.

Prenatal invasive testing: a 13-year single institution experience

Abstract Objectives: To analyze trends in screening and invasive prenatal diagnosis over a 13-year period in relation to changes in the national prenatal screening policy. Methods: Fetal karyotypes obtained following 11 045 prenatal invasive procedures between January 1999 and December 2011 were retrospectively reviewed. Referral indications were classified as medical and non-medical (anxiety). The number of tests per relevant chromosomal abnormalities (CA) detected in both groups adjusted for indication was calculated. Results: A total of 414 CA were detected (3.8%), 355 of which were considered clinically significant. The percentage of invasive procedures has declined from 49% to 12%, although cases referred by anxiety have increased from 22% to 55%. A total of 3129 invasive procedures did not have any medical indication (28%) and 13 relevant CA (0.42%) were found in this group. In this low-risk series, the index “number of invasive testing needed to detect 1 relevant CA” adjusted for indication was 241. Conclusions: Changes in our national prenatal policy through this 13-year period show an increasing efficiency of prenatal detection of CA. However, despite the intensifying screening policies, low-risk pregnant women show a growing demand for prenatal invasive testing and a baseline risk for cytogenetic abnormality of 1/241.

The study of fetal neurobehavior in twins in all three trimesters of pregnancy

Abstract Aim: The aim was to assess the onset and the frequencies of the first intertwin contacts by four-dimensional ultrasound (4D US) in the 1st trimester of pregnancy. In the second part of the study, fetal behavior and Kurjak Antenatal Neurodevelopmental Test (KANET) score of twins compared to singletons in the 2nd and the 3rd trimesters was assessed. Patients and methods: Transvaginal 4D assessment was performed in 20 women in the 1st trimester between 56 and 69 postmenstrual days (PMD), while trans-abdominal approach was performed from 70 PMD onwards and at weekly intervals until 112 PMD. Fetal behavior was assessed by 4D UD US between 28 and 36 gestational weeks in 49 twin pregnancies. Results: The first intertwin contacts appeared at 61 PMD, while complex body movements appeared at 68 PMD. The complexity of intertwin contacts increased from 84 PMD. With increasing gestational age, a higher frequency of movements was observed. The number of abnormal, borderline, and normal KANET scores between singletons and twins was not statistically significant. Scores for isolated eye blinking, mouthing, grimacing, hand to head movement, finger movements, Gestalt perception and general movements differed significantly in twins and singletons. Conclusions: Two types of activities were observed: spontaneous and reactive. Although twins showed less activity and different behavioral pattern than singletons, a considerable proportion of overall motility was due to intertwin contacts.

Rapid aneuploidy testing versus traditional karyotyping in amniocentesis for certain referral indications.

Abstract Objective. (1) To determine the suitability of replacing full karyotype analysis with quantitative fluorescent polymerase chain reaction (QF-PCR) for prenatal diagnosis in amniotic fluid samples obtained by amniocentesis. (2) To evaluate an indication-based classification of cases at risk of missing clinically relevant chromosomal disorders by QF-PCR. Methods. We reviewed all fetal karyotypes obtained by amniocentesis between January 2004 and December 2008. We compared the cytogenetic findings obtained through conventional karyotype with those that would have been theoretically obtained using QF-PCR. Results. Of the 4007 karyotypes obtained, 110 abnormal karyotypes were found (2.8%). Out of these, 30 (27%) were chromosomal abnormalities (CA) which would not have been detected by PCR alone. These included 16 cases (53%) predicted to confer no increased risk, 9 (30%) predicted to have a low risk, and 5 (17%) with an uncertain or high risk of fetal abnormality. A policy of QF-PCR alone would have identified 80 of 85 (94%) clinically significant CA. When QF-PCR shows a normal result, the overall residual risk is 0.75% for any CA and 0.12% for a clinical significant CA. Conclusion. In our population, a policy of QF-PCR alone would miss 0.12% clinically relevant CA. QF-PCR directed to common aneuploidies can be considered as an economically and clinically acceptable prenatal diagnosis policy, offering full karyotype only for specific indications.

Fatal alloimmune thrombocytopenia due to anti-HLA alloimmunization in a twin pregnancy: A very infrequent complication of assisted reproduction

The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Platelets express the HLA-A and B antigens on their membrane and some studies report that maternal anti-HLA class I antibody can also cause FNAIT. We report here a very unusual case of a first twin pregnancy produced in vitro by oocyte and semen donation where the mother developed markedly elevated HLA antibodies, in the absence of anti-platelet or anti-neutrophil antibodies, that provoked in one of the twins a profound thrombocytopenia and intracranial hemorrhage and a mild thrombocytopenia and neutropenia in the second twin lasting until the fourth month of life. In addition, anti-D alloimmunization provoked hemolytic disease of the newborn with intrauterus anemia detected in the first twin and post-natal anemia in the second twin that required red blood cell transfusion and phototherapy. We hypothesize that the complete HLA-incompatible twin pregnancy due to the oocyte donation might have contributed to the severity of the clinical manifestations.

Prenatal Diagnosis of Chromosome Abnormalities: A 13-Year Institution Experience

Objective: To analyze trends in screening and invasive prenatal diagnosis of chromosome abnormalities (CA) over a 13-year period and correlate them to changes in the national prenatal screening policy. Methods: We retrospectively reviewed Down syndrome (DS) screening tests and fetal karyotypes obtained by prenatal invasive testing (IT) in our fetal medicine unit between January 1999 and December 2011. Results: A total of 24,226 prenatal screening tests for DS and 11,045 invasive procedures have been analyzed. Over a 13-year period, utilization of non-invasive screening methods has significantly increased from 57% to 89%. The percentage of invasive procedures has declined from 49% to 12%, although the percentage of IT performed for maternal anxiety has increased from 22% to 55%. The percentage of detected CA increased from 2.5% to 5.9%. Overall, 31 invasive procedures are needed to diagnose 1 abnormal case, being 23 procedures in medical indications and 241 procedures in non-medical indications. Conclusions: Our experience on screening and invasive prenatal diagnostic practice shows a decrease of the number of IT, with a parallel decline in medical indications. There is an increasing efficiency of prenatal screening program to detect CA. Despite the increasing screening policies, our population shows a growing request for prenatal IT. The a priori low risk population shows a not negligible residual risk for relevant CA. This observation challenges the current prenatal screening strategy focused on DS; showing that the residual risk is higher than the current cut-off used to indicate an invasive technique.

Buttock necrosis after hypogastric artery embolization for postpartum hemorrhage

Abstract Background: Uterine or hypogastric artery embolization is a useful alternative to hysterectomy in the treatment of postpartum hemorrhage. Case: Puerpera requiring a bilateral hypogastric artery embolization for postpartum hemorrhage after cesarean section in a term twin pregnancy. Unexpected unilateral buttock necrosis appeared 5 days later. Treatment consisted of debridement, the use of vacuum-assisted closure therapy and skin grafting. Conclusion: Buttock necrosis is a rare complication after hypogastric artery embolization in the treatment of postpartum hemorrhage.

PP067. Third trimester prediction of late PE.

INTRODUCTION It is well known that a multiparametric model including epidemiological maternal factors, uterine Doppler and biochemical parameters could be useful at 1st and 2nd Trimester for the prediction of early PE (<34 weeks of gestation) but less accurate for late PE (⩾34 weeks of gestation). Different physiopathologies have been suggested for these two entities. A new approach based in a 3rd trimester screening has been suggested for the predicton of late PE. OBJECTIVES To define the prediction capacity of maternal characteristics at 3rd trimester for late PE. MATERIAL AND METHODS 4724 pregnancies followed up and delivered in our centre from July 2010 to December 2012 were included in a cross sectional study. Out of these, 59 cases developed a late preeclampsia (1.2%). Controls were gestations with no diagnosis of PE nor gestational hypertension. All patients made a 3rd trimester visit at 31-33 weeks, where systolic and diastolic blood pressure and the absolute weight gain since the beginning of pregnancy were measured. Parity, maternal age and body mass index at the beginning of the pregnancy were also recorded. A multivariate logistic regression analysis was made to define the predictive capacity of these variables for late PE. RESULTS MAP was significantly higher in those patients who developped PE (78.8 vs 88.8 mmHg, p<0.05). Although cases had a higher BMI at first visit ( BMI 25.9 vs 23, p<0.05), the total weight gain during pregnancy up to the 3rd trimester was similar among groups (9.3 vs 10.3kg, p>0.05). The mean GA at delivery of cases was 38 (range 35-41 weeks) and of controls 39.1 (range 34-42 weeks). In a multivariate logistic regression analysis, MAP and BMI were independent and significant predictors of late PE at 3rd Trimester. The model including BMI and MAP has an AUC of 0.76 (0.683-0.837). CONCLUSIONS A 3rd trimester screening could be useful in the prediction of late-onset PE.

OP31.01: Prediction of intrauterine growth restriction by combination of first and second trimester biochemistry markers used in prenatal screening of Down syndrome

Objectives: Preterm birth is a main contributor for neurodevelopmental impairment in affected infants. The study aimed to evaluate long-term neurodevelopmental outcome of twins following preterm delivery between 2003 and 2008. Methods: Neurodevelopmental outcome of monochorionic (MC) and dichorionic (DC) twins, who were born between 24+0 weeks and 33+6 weeks at the Medical University of Graz, was analyzed retrospectively. Primary outcome was neurodevelopmental impairment at the age of two years. Secondary outcome were pregnancy complications. Results: The population consisted of 264 children (132 twin pregnancies), 94 (71%) were DC and 38 (29%) MC. The most frequent complications (30%) in each group were preterm rupture of membranes and preterm labor. Mean gestational age at delivery was 30+4 and 31+0 weeks for MC and DC twins, respectively. In the MC group 38 (84%) of 66 children had an uneventful outcome, while 7 (16%) had neurodevelopmental impairment [1 (2%) mild, 6 (13%) severe]. 114 (83%) of 138 DC children were healthy, whereas 24 (17%) presented neurologic delay [11 (8%) mild, 4 (3%) moderate, 9 (7%) severe]. Conclusions: The rates for neurodevelopmental impairment of MC and DC twins were comparable. However, severe problems occurred more often in MC twins.

OC05.03: Ductus venosus in Down's syndrome screening: which is the strategy of choice?

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.