Nicole Woodrow

ABNORMAL CERVICAL CYTOLOGY IN PREGNANCY : EXPERIENCE OF 811 CASES

Summary: This paper reviews our hospitals experience spanning 15 years and involving 811 women referred with abnormal cervical cytology in pregnancy. It supports the safety and accuracy of managing dysplasia in pregnancy with colposcopy, directed punch biopsy and deferral of treatment until the postpartum period. The histologically‐proven progression in pregnancy to a higher grade of dysplasia postpartum was 7%. None of the women are known to have developed microinvasive or invasive cancer between antenatal assessment and postpartum review. Of these 811 women, 16% were lost to follow‐up, 1 of whom subsequently represented 4 years later with invasive cervical cancer.

Meeting the challenge of interpreting high‐resolution single nucleotide polymorphism array data in prenatal diagnosis: does increased diagnostic power outweigh the dilemma of rare variants?

Several studies have already shown the superiority of chromosomal microarray analysis (CMA) compared with conventional karyotyping for prenatal investigation of fetal ultrasound abnormality. This study used very high‐resolution single nucleotide polymorphism (SNP) arrays to determine the impact on detection rates of all clinical categories of copy number variations (CNVs), and address the issue of interpreting and communicating findings of uncertain or unknown clinical significance, which are to be expected at higher frequency when using very high‐resolution CMA.

Mid‐trimester Ultrasound Diagnosis of Isolated Talipes Equinovarus: Accuracy and Outcome for Infants

Summary: Seventeen fetuses were diagnosed with isolated congenital talipes equinovarus (CTEV) on mid‐trimester ultrasound at the Royal Womens Hospital, Melbourne, between January, 1992 and December 1995. Sixteen of the 17 cases had an amniocentesis performed and all karyotypes were normal. The remaining case was phenotypically normal, except for a clubfoot. None of the pregnancies was complicated by any of the recognized intrauterine environmental causes of CTEV. Four of the babies were delivered prematurely and all survived the neonatal period. Six (35%) infants did not have CTEV at birth, although 2 had postural varus feet. Nine of the 11 infants who did have CTEV at birth were treated within days of birth with plaster of Paris for periods of 6 to 12 weeks. Two infants required no further treatment, 5 required orthotics and 2 required surgery. The other 2 infants with CTEV at birth were treated with orthotics at 8 weeks of age. All infants were considered to have an excellent result at the 2 year follow‐up. Seven (41%) of the prospective parents received antenatal counselling by an orthopaedic surgeon and the lack of study on outcome following an ultrasound diagnosis of CTEV was the impetus for our work.

Differential Gene Expression in Menstrual Endometrium From Women With Self-Reported Heavy Menstrual Bleeding

Heavy menstrual bleeding (HMB) is a significant social and public health issue for menstruating women. Development of targeted treatments has been limited by poor understanding of local mechanisms underlying HMB. We aimed to determine how gene expression differs in menstrual phase endometrium from women with HMB. Menstrual phase endometrial biopsies were collected from women with (n = 7) and without (n = 10) HMB (regular menstrual cycles, no known pelvic pathology), as well as women with uterine fibroids (n = 7, n = 4 had HMB). Biopsies were analyzed using Illumina Sentrix Human HT12 arrays and data analyzed using “Remove Unwanted Variation-inverse”. Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery v6.7 were used to identify gene pathways, functional gene clusters, and upstream regulators specific to the clinical groupings. Individual genes of interest were examined using quantitative polymerase chain reaction. In total, 829 genes were differentially expressed in one or more comparisons. Significant canonical pathways and gene clusters enriched in controls relative to both HMB and fibroid groups suggest the mechanisms responsible for HMB include modifications of the endometrial inflammatory or infection response. In contrast, differentially expressed genes in women with fibroids suggest modifications of hemoglobin, antigen processing, and the major histocompatibility complex (class II, beta chain) activity. In conclusion, HMB associated with fibroids may be regulated by different endometrial mechanisms from HMB in women without fibroids and from normal menstrual bleeding. These novel data provide numerous testable hypotheses that will advance our understanding of the mechanisms responsible for HMB.

Molecular Karyotyping: A Revolutionary Concept in Prenatal Diagnosis

The ‘standard of care’ for chromosome testing has recently changed. For the last 30 years it has involved chromosome testing using microscope analysis. New technology using ‘DNA chips’, i.e. molecular karyotyping or microarray has now become available and is routinely offered to pregnant women undergoing invasive testing for an ultrasound detected fetal abnormality. Women who choose to take advantage of this technology undergo extensive counselling in a multidisciplinary setting regarding the possible implications of an abnormal result. They are advised that there are some molecular changes which are known to be harmless and will not be reported. They are also counselled that some molecular changes will be reported but their clinical significance is uncertain. This article reviews the current evidence-based role of molecular karyotyping in routine clinical practice in the setting of ultrasound detected fetal abnormality.

OP05.02: Single umbilical artery: is it a risk factor in multiple pregnancies?

Objectives: To examine the association between a single umbilical artery (SUA) and perinatal outcomes in multiple pregnancies in an Australian tertiary referral centre. Methods: Multiple pregnancies with at least one fetus diagnosed with a SUA at the midtrimester scan between August 2003 and January 2011 were included in the study. All patients have undergone detailed morphology ultrasound examination at our unit. Colour Doppler was used to visualize the umbilical arteries adjacent to the fetal bladder and in a section of a free loop of cord. The diagnosis of a SUA was confirmed on histopathologic examination of placentae and umbilical cords. Results: Twenty-six fetuses with a SUA were identified in the study period and complete follow-up data were available for 22 cases. In all pregnancies included in the study only one of the fetuses of each multiple pregnancy had a SUA. Of the 22 fetuses comprising the study population, 13 were dichorionic twins, 5 MCDA twins, 1 MCMA twin and 3 triplets. Fifteen (68%) cases were isolated, i.e., no chromosomal or structural fetal anomalies were present. In 7 fetuses (32%) with a SUA there were structural anomalies and just one of them had a chromosomal abnormality (trisomy 18). Eight cases (36%) of fetal growth restriction (3 with structural anomalies) and 2 cases of twin-to-twin transfusion syndrome were detected. In terms of perinatal mortality there were 2 intrauterine fetal deaths and 2 neonatal deaths (18%), 1 selective termination (triplets to twins) and 1 cord ligation in a monochorionic twin with multiple abnormalities. The mean gestational age of delivery was 31 weeks with preterm delivery before 34 weeks happening in 15 cases (68%). Seven (32%) patients had a normal vaginal delivery and 15 (68%) a caesarean section. The mean birth weight was 1505 g in the cases of a SUA and 1643 g in the fetuses with 3 vessel cords. Conclusions: Our study shows that multiple pregnancies with at least one fetus with a SUA are at increased risk for adverse perinatal outcomes.