Jon Hyett

ENDOSCOPIC LASER COAGULATION IN THE MANAGEMENT OF SEVERE TWIN-TO-TWIN TRANSFUSION SYNDROME

Objective To assess the clinical effectiveness of endoscopic laser coagulation of placental vessels in the

Obstetric outcome after threatened miscarriage with and without a hematoma on ultrasound

OBJECTIVE To examine the effect of threatened miscarriage on second-trimester maternal serum α-fetoprotein (MSAFP) levels and pregnancy outcome; and to study the significance of ultrasound evidence of an intrauterine hematoma on pregnancy outcome in these patients. METHODS A retrospective, case–control study was performed on 144 women presenting with bleeding in the first trimester and 144 age-matched control subjects who attended for routine dating scans during the same time scale. The presence or absence of an intrauterine hematoma, MSAFP, and pregnancy outcomes were recorded. RESULTS The incidence of adverse pregnancy outcome was significantly (P = .02) higher in women with a history of first-trimester threatened miscarriage than in the control group. The relative risk (RR) of an adverse pregnancy outcome for the study group was 2.22 (95% confidence interval [CI] 1.12, 4.39) compared with the control group. The RR of delivering a baby of less than 1000 g was 4.43 (95% CI 0.5, 39.2) in women with first-trimester threatened miscarriage. This was independent of the presence of an intrauterine hematoma. The RR of MSAFP being raised to more than 2.5 multiples of the median (MoM) in the study group was 6.25 (95% CI 0.77, 50.6). There was no difference between women with threatened miscarriage who had or did not have ultrasound evidence of an intrauterine hematoma. CONCLUSION Threatened miscarriage in the first trimester is associated with an increased incidence of adverse pregnancy outcome, independently of the presence of an intra-uterine hematoma. Higher MSAFP in threatened miscarriage suggests a direct placental injury even in the absence of a hematoma.

Non‐invasive first trimester determination of fetal gender: a new approach for prenatal diagnosis of haemophilia

Ten carriers of haemophilia referred for prenatal diagnosis were offered first trimester non‐invasive fetal gender determination by ultrasound and analysis of free fetal DNA (ffDNA) in maternal plasma in an attempt to reduce the need for an invasive diagnostic procedure in female pregnancies. Although repeat testing was required in three cases, fetal gender was determined correctly in all cases (four females, six males) at a median gestation of 12+3 (11+2 to 14+1) using both methods. In all cases of a female fetus, the mothers opted not to have invasive testing. Both methods provide a reliable option of avoiding invasive testing in female pregnancies.

Fetal heart rate and umbilico-placental Doppler flow velocity waveforms in early pregnancies with a chromosomal abnormality and/or an increased nuchal translucency thickness

Fetal heart rate, umbilical artery pulsatility index, end-diastolic flow, nuchal translucency thickness and placental thickness were recorded in 250 women with a viable singleton pregnancy undergoing chorionic villous sampling for fetal karyotyping at 11-14 weeks of gestation. The fetal karyotype was normal in 210 cases and abnormal in 40, including 21 with trisomy 21, 13 with trisomy 18, three with triploidy, two with monosomy X and one with trisomy 13. A total of 52 fetuses with a normal karyotype had a nuchal translucency > or = 3 mm and were considered separately. There was a stable and significant increase in the mean fetal heart rate in trisomy 21 pregnancies compared to controls. No significant difference was found for the other variables between the groups. In chromosomally normal fetuses with an increased nuchal thickness, the development of fetal heart rate and compliance of the umbilico-placental circulation were within the normal ranges. Some fetuses with trisomy 18 or triploidy had an increased resistance to blood flow in the umbilical artery, which was probably due to abnormal placental development.

Procedure-related complications of rapid amniodrainage in the treatment of polyhydramnios.

To investigate the procedure‐related complications of rapid amniodrainage in the treatment of polyhydramnios.

Evolution of sonographic findings in a fetus with agenesis of the urethra, vagina, and rectum.

In a 12‐week gestation fetus, routine ultrasound examination suggested dilated loops of bowel. Repeat scans at 13 and 15 weeks showed normal growth but persistence of bowel dilatation. At 20 weeks there was megacystis, hyperechogenic bowel, ascites, and oligohydramnios. The diagnosis of cloacal abnormality was suspected and the parents chose to have pregnancy termination. Post‐mortem examination demonstrated female pseudohermaphroditism with agenesis of the urethra, vagina, and rectum.

Patient choice and the randomized controlled trial

There are now many large series reporting the effectiveness of nuchal translucency (NT) screening for the detection of trisomy 21 in the literature, but to date there has been no randomized controlled trial comparing this screening option to more traditional approaches. The first large multicenter study reporting screening by a combination of maternal age (MA) and NT at 10–14 weeks’ gestation demonstrated that 77% of trisomy 21 fetuses could be detected for a 5% false-positive rate1. This compared favorably with a program of screening by MA alone, which had previously been shown to have a 30% detection rate for the same 5% false-positive rate2. This, and subsequent interventional studies, have been criticized for inflating detection rates, as they include some trisomy 21 fetuses that would have been spontaneously lost during the course of pregnancy. In reality, the proportion of trisomic fetuses aborting between 12 and 16 weeks of pregnancy, when screening by MA or with biochemical markers occurs, is small, and these fetuses would not exclusively have had increased NT3,4. An alternative method of studying the effectiveness of NT screening is through an observational study where NT is assessed but not reported. These studies are, however, subject to their own bias, as there is frequently insufficient time and energy spent training staff to measure NT correctly and other clinical priorities may override the need to complete the scan. Consequently, observation trials frequently report higher failure rates of NT measurement and lower detection rates for NT screening. One observational study gave sonographers written instructions on how to measure NT but there was no practical training or attempt to standardize measurement. There were large variations between centers in measurement of NT and the sensitivity of screening; for a 5% false-positive rate, the detection rate was 31% (range 0–100%)5. In another study of 47 053 women, NT was not measured in 4228 patients as they did not attend at a suitable gestation, sonographers were unable to obtain a measurement in 3416 pregnancies and image review deemed a further 3881 scans to be of unacceptable quality6. Consequently, NT was only successfully measured in 77% of pregnancies and the sensitivity of the test was described as being poor (38% for 5% false-positive rate). Randomized controlled trials have been shown to be the most rigorous way of comparing two treatment options and have had a significant impact on clinical practice through the development of evidence-based medicine7. This technique aims to remove systematic bias through randomization and, where feasible, blinding both clinicians and patients to the process. In this issue of the journal, Saltvedt et al. report the effect of screening 39 572 women randomized to trisomy 21 screening policies based either on NT assessment or on MA8. Women with a previous history of trisomy 21 or with other abnormalities noted at the time of the anomaly scan were also offered invasive testing. The trial aimed to determine whether NT screening led to a reduction in the number of liveborn infants with trisomy 21. A secondary outcome measure was the number of invasive tests performed to detect one trisomic fetus. The trial design addressed the potential bias of ‘the learning curve’ by ensuring that all 72 midwives and doctors involved in the study were trained in the standardized assessment of NT prior to starting the study. As the women were recruited and randomized at the same gestation in both arms of the study, and the mean gestation of invasive testing was the same in the two groups, the bias of intrauterine lethality was minimized, although it was unfortunate that spontaneous fetal losses were not routinely karyotyped. In the trial, NT detected 77% of trisomy 21 pregnancies for a false-positive rate of 5% and MA detected 58% of pregnancies for a false-positive rate of 18%. The same detection rates as described in previous interventional studies. There were 28% more trisomy 21 fetuses in the NT group, but this was not statistically significant. There was a significant difference in the proportion of liveborn trisomy 21 fetuses: 10 (18%) of 55 in the NT group and 16 (37%) of 43 in the MA group (χ2: P < 0.05), but no significant difference in the prevalence of trisomy 21 fetuses in all live births; 10 in 19 796 in the NT group vs. 16 in 19 776 in the MA group (χ2 test: P = 0.24). One trisomy 21 fetus was diagnosed for every 38 invasive tests performed in the NT group compared to 1 : 85 in the MA group. On face value, the trial shows that although NT assessment improves the detection rate for trisomy 21 and has a better positive predictive value for screening, it does not reduce the live-birth prevalence of Down syndrome compared to more traditional screening techniques. The results are, however, compromised by the effect of bias introduced by patient choice. During recruitment, 20% of women considered to be eligible for the trial chose not to participate, despite the fact that they were not restricted to acting on the results of the screening they were randomized to, and they could also request and act on other screening tests (second-trimester serum biochemistry) if they wished. Only 32% of the invasive tests performed in the NT group were performed for an indication proposed in the study

OP01.13: Non-invasive prenatal diagnosis of fetal sex using free fetal DNA in the maternal circulation—changing obstetric management

brachiocephalic trunk. In the fetus it can be detected in the threevessel-trachea view using color Doppler. Preliminary results showed a prevalence of this vessel in 1.5% of the normal population but in one third of fetuses with Trisomy 21. The aim of the present study was to find out the prevalence of this vascular variant in fetuses with chromosomal anomalies. Patients: In the 20 months study fetuses with abnormal karyotype and a documented course of the right subclavian artery (RSA) were included in the evaluation. In the last 12 months cases at 11–14 weeks scan were attempted to be included in the study as well. Results: A total of 47 fetuses could be assessed and an ARSA was found in 16 cases (34%) 7 being before 14 weeks. Following distribution was found: In Trisomy-21 4/14 (28.5%), in Trisomy-18 5/9 (55.5%), in Trisomy 13 2/4 (50%), in Turner-S. 3/7 (43%), in 1/7 (14%) with del22q.11 (but in 1/3 with left aortic arch) and in 1/6 miscellaneous, including a case with del.4p-. In only one case with T21 (mat.age 31y) it was besides an echogenic focus the only sign detected on ultrasound. In the remaining fetuses additional soft markers or malformations were found. Conclusions: An ARSA is a common finding in chromosomal anomalies and could be used as an additional soft marker not only in DS screening but also in other chromosomal anomalies. Its detection, possible already at early fetal echocardiography, increases the risk of a chromosomal anomaly. Further studies are needed to confirm these observations.

Can intra-uterine mortality be reduced in Nd-YAG laser treatment of Twin-Twin Transfusion Syndrome? An analysis

Recent studies have shown that laser therapy can reduce the mortality and morbidity associated with Twin-Twin Transfusion Syndrome in the second trimester of pregnancy. The purpose of this paper is to analyse current treatment strategies using laser surgery, and to suggest ways in which fetal mortality may be further reduced.