Amniotic fluid gamma-glutamyl transferase for prediction of biliary atresia in cases of non-visualisation of the fetal gallbladder: a retrospective study using a validated analytical platform and local reference range.

INTRODUCTION: The level of amniotic fluid gamma-glutamyl transferase (AFGGT) may help identify biliary atresia (BA) in cases of non-visualisation of the fetal gallbladder (NVFGB). This study aimed to validate a serum/plasma matrix-based gamma-glutamyl transferase (GGT) assay for amniotic fluid (AF) samples, establish a local gestational age-specific AFGGT reference range, and evaluate the efficacy of AFGGT for predicting fetal BA in pregnancies with NVFGB using the constructed reference range. METHODS: The analytical performance of a serum/plasma matrix-based GGT assay on AF samples was evaluated using a Cobas c502 analyser. Amniotic fluid gamma-glutamyl transferase levels in confirmed euploid singleton pregnancies (16+0 to 22+6 weeks of gestation) were determined using the same analyser to establish a local gestational age-specific reference range (the 2.5th to 97.5th percentiles). This local reference range was used to determine the positive predictive value (PPV) and negative predictive value (NPV) of AFGGT level <2.5th percentile for identifying fetal BA in euploid pregnancies with NVFGB. RESULTS: The serum/plasma matrix-based GGT assay was able to reliably and accurately determine GGT levels in AF samples. Using the constructed local gestational age-specific AFGGT reference range, the NPV and PPV of AFGGT level <2.5th percentile for predicting fetal BA in pregnancies with NVFGB were 100% and 25% (95% confidence interval=0, 53), respectively. CONCLUSION: In pregnancies with NVFGB, AFGGT level ≥2.5th percentile likely excludes fetal BA. Although AFGGT level <2.5th percentile is not diagnostic of fetal BA, fetuses with AFGGT below this level should be referred for early postnatal investigation.

Impact of replacing or adding pregnancy-associated plasma protein-A at 11-13 weeks on screening for preterm pre-eclampsia.

OBJECTIVE: To assess whether pregnancy-associated plasma protein-A (PAPP-A) alters or provides equivalent screening performance as placental growth factor (PlGF) when screening for preterm pre-eclampsia (PE) at 11-13 weeks of gestation. METHODS: This was a secondary analysis of a non-intervention screening study of 6546 singleton pregnancies that were screened prospectively for preterm PE in the first trimester between December 2016 and June 2018. Patient-specific risks for preterm PE were estimated by maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), PlGF and PAPP-A. A competing-risks model with biomarkers expressed as multiples of the median was used. All women and clinicians were blinded to the risk for preterm PE. The performance of screening for preterm PE using PlGF vs PAPP-A vs both PAPP-A and PlGF was assessed by comparing areas under the receiver-operating-characteristics (AUC) curves. McNemar's test was used to compare detection rate at a fixed false-positive rate (FPR) of 10%. RESULTS: PlGF and PAPP-A were measured in 6546 women, of whom 37 developed preterm PE. The AUC and detection rate at 10% FPR using PlGF in combination with maternal history, MAP and UtA-PI were 0.854 and 59.46%, respectively. The respective values were 0.813 and 51.35% when replacing PlGF with PAPP-A and 0.855 and 59.46% when using both PAPP-A and PlGF. Statistically non-significant differences were noted in AUC when replacing PlGF with PAPP-A (ΔAUC, 0.04; P = 0.095) and when using both PAPP-A and PlGF (ΔAUC, 0.002; P = 0.423). However, on an individual case basis, screening using PlGF in conjunction with maternal history, MAP and UtA-PI identified three (8.1%) additional pregnancies that developed preterm PE and that were not identified when replacing PlGF with PAPP-A. Screening using PAPP-A in addition to maternal history and other biomarkers did not identify any additional pregnancies. CONCLUSION: On an individual case basis, adoption of a screening strategy that uses PAPP-A instead of PlGF results in reduced detection of preterm PE, consistent with previous literature. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Non-visualisation of fetal gallbladder in a Chinese cohort.

INTRODUCTION: Non-visualisation of fetal gallbladder (NVFGB) is associated with chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis in Caucasian fetuses. We investigated the outcomes of fetuses with NVFGB in a Chinese cohort. METHODS: This retrospective analysis included cases of NVFGB among Chinese pregnant women at five public fetal medicine clinics in Hong Kong from 2012 to 2019. We compared the incidences of subsequent gallbladder visualisation, chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis between cases of isolated NVFGB and cases of non-isolated NVFGB. RESULTS: Among 19 cases of NVFGB detected at a median gestational age of 21.3 weeks (interquartile range, 20.0-22.3 weeks), 10 (52.6%) were isolated and nine (47.4%) were non-isolated. Eleven (58.0%) cases had transient non-visualisation, four (21.0%) had gallbladder agenesis, three (15.8%) had chromosomal abnormalities (trisomy 18, trisomy 21, and 22q11.2 microduplication), one (5.2%) had biliary atresia, and none had cystic fibrosis. The incidence of serious conditions was significantly higher in the non-isolated group than in the isolated group (44.4% vs 0%; P=0.029); all three cases with chromosomal abnormalities and the only case of biliary atresia were in the non-isolated group, while all four cases with gallbladder agenesis were in the isolated group. The incidences of transient non-visualisation were similar (55.6% vs 60.0%; P=1.000). CONCLUSION: Isolated NVFGB is often transient or related to gallbladder agenesis. While investigations for chromosomal abnormalities and biliary atresia are reasonable in cases of NVFGB, testing for cystic fibrosis may be unnecessary in Chinese fetuses unless the NVFGB is associated with consistent ultrasound features, significant family history, or consanguinity.

Outcome of radiofrequency ablation for selective fetal reduction before vs at or after 16 gestational weeks in complicated monochorionic pregnancy.

OBJECTIVE: To investigate whether gestational age at intervention (< or ≥ 16 weeks) and other factors affect the risk of loss of the cotwin after selective fetal reduction using radiofrequency ablation (RFA) in monochorionic (MC) pregnancy. METHODS: This was a single-center retrospective analysis of 63 consecutive RFA procedures performed at our institution from January 2011 to October 2019 for selective fetal reduction in complicated MC pregnancies. Indications for RFA were twin reversed arterial perfusion sequence (13 cases), twin-to-twin transfusion syndrome (12 cases), twin anemia-polycythemia sequence (two cases), selective fetal growth restriction (10 cases), discordant anomalies (17 cases) and multifetal pregnancy reduction in triplets or quadruplets with a MC pair (nine cases). Twenty-six (41.3%) of these procedures were performed before and 37 (58.7%) after 16 weeks. Potential factors that could affect the risk of loss of the cotwin, including gestational age at RFA, order of multiple pregnancy, amnionicity, indication for RFA and number of ablation cycles, were assessed first by univariate analysis and then by multivariate analysis. RESULTS: There were 17 (27.0%) cotwin losses. Ablation cycles numbering four or more was the only factor among those investigated to be associated with loss of the cotwin after RFA (P = 0.035; odds ratio, 5.21), while the indication for RFA, order of multiple pregnancy, amnionicity and gestational age at RFA had no effect. Comparing RFA performed at < 16 vs ≥ 16 weeks, there was no difference in the rate of cotwin loss (23.1% vs 29.7%; P = 0.558) or preterm prelabor rupture of the membranes before 34 weeks (7.7% vs 5.4%; P = 0.853), or in the median gestational age at delivery (36.2 vs 37.3 weeks; P = 0.706). CONCLUSIONS: RFA is a promising tool for early selective fetal reduction in MC pregnancy before 16 weeks. Four or more ablation cycles is a major risk factor for cotwin loss. Careful assessment pre- and post-RFA, together with proficient operative skills to minimize the number of ablation cycles, are the mainstay to ensure that this procedure is effective and safe. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

First trimester screening for pre-eclampsia in Chinese pregnancies: case-control study.

OBJECTIVE: To assess the potential of screening for pre-eclampsia (PE) in a Chinese population. DESIGN: Case-control study. SETTING: Teaching hospital in Hong Kong. POPULATION: A total of 3330 women having a viable singleton pregnancy attending first-trimester Down-syndrome screening. METHODS: Mean arterial pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF) were measured. Screening markers were transformed to multiples of the gestational median (MoM) and adjusted for maternal and pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were compared with published expected values. PE screening performance was assessed using area under receiver operating curves (AUROC). MAIN OUTCOME MEASURES: PE detection rate. RESULTS: A total of 30 (0.9%) women developed either early (<34 weeks) or late (≥34 weeks) onset PE. MAP was dependent on maternal BMI, UtA-PI on fetal crown rump length, uterine artery peak systolic velocity (UtA-PSV) on maternal age and gestation, and PlGF on gestation in non-PE pregnancies. MoM distributions determined using published Fetal Medicine Foundation models deviated significantly from one for both MAP (P < 0.0001) and PI (P < 0.0001), but not PlGF (P = 0.52) in non-PE pregnancies, whilst PlGF MoM distributions in those who developed early as opposed to late onset PE were significantly higher (P = <0.05). AUROC for any PE using multiple markers was 0.72 (95% CI: 0.64-0.81) with detection rates of 72 and 55% for early and late PE, respectively, for a 10% false positive rate. CONCLUSION: Detection rates for PE in our Chinese population were lower than the expected 90-95% even after adjusting MoM for local women's characteristics. FUNDING: General Research Fund (Project number 470513). TWEETABLE ABSTRACT: Pre-eclampsia screening in the Chinese population had detection rates lower than previously published results.

The pattern of cervical smear abnormalities in marginalised women in Hong Kong.

INTRODUCTION: "Ripple Action" and "WE Stand" are projects co-organised by the Hong Kong Women Doctors Association. The two projects organise free cervical screening for low-income women, new immigrants from Mainland China, and ethnic minority women. The objective of this study was to analyse the pattern of cervical smear abnormalities in these marginalised women. METHODS: The study group consisted of 1189 marginalised women who participated in a free cervical screening campaign, including 324 low-income local Chinese, 540 new immigrants from Mainland China, and 325 ethnic minority women. The comparison group consisted of 1141 local Chinese who attended a well women clinic. The prevalence of cervical smear abnormalities was compared using Chi squared test. RESULTS: In the study group, 42.6% of women had never had a cervical smear. Compared with the comparison group, they had a significantly higher prevalence of cervical smear abnormalities (13.7% vs 1.4%; P<0.001), including atypical smear (10.8% vs 0.5%; P<0.001), low-grade lesion (1.8% vs 0.8%; P=0.036), and high-grade lesion (1.1% vs 0.1%; P=0.002). Logistic regression analysis showed that the strongest predictors for abnormal cervical smear were being South Asian (odds ratio=11.859; 95% confidence interval, 4.635-30.341), South-East Asian (6.484; 3.192-13.171), or new immigrant from Mainland China (6.253; 2.463-15.877). CONCLUSIONS: Marginalised women had a significantly higher prevalence of cervical smear abnormality than the general population and almost half had never had a cervical smear before. Outreach strategies are needed to enrol this population into screening programmes.

Pancreatic cystic lesions and guidelines: a review.

No abstract available.

Intrapleural injection of OK-432 as the primary in-utero treatment for fetal chylothorax.

Chylothorax is a rare congenital condition associated with significant perinatal mortality and morbidity. Previous treatments with repeated thoracocentesis or thoracoamniotic shunting were technically demanding, and associated with significant procedure-related complications and neonatal complications. Here we report the first successful case in Hong Kong treated by a simple and effective intervention, namely pleurodesis with OK-432, in a fetus presenting at 20 weeks of gestation with bilateral pleural effusion.

A novel way of visualizing the ductal and aortic arches by real-time three-dimensional ultrasound with live xPlane imaging.

OBJECTIVE: To describe a novel method of visualizing the ductal and aortic arches by real-time three-dimensional echocardiography with live xPlane imaging. METHODS: Live xPlane imaging was used to display the ductal- and aortic-arch views in 107 women with singleton pregnancies, including seven cases with suspected congenital heart defects (CHDs). The three vessels and trachea (3VT) view was obtained in such an orientation that either the pulmonary artery or the aorta was parallel to the direction of the ultrasound beam. The xPlane reference line was then placed across the targeted vessel, which in a normal case would provide an image of the corresponding arch view as a dual-image display. RESULTS: Once the 3VT view had been obtained, live xPlane imaging showed the aortic and ductal arches in all 100 normal cases. In seven cases with suspected CHD, the 3VT view was abnormal in five cases and normal in the other two. However, the ductal-arch view demonstrated by live xPlane imaging was abnormal in five cases of conotruncal anomalies and normal in two cases in which conotruncal anomalies were excluded. CHDs were confirmed at autopsy following termination of pregnancy in five cases and on postnatal echocardiography in one case. The heart was found postnatally to be normal in one case of suspected CHD; in this case live xPlane imaging showed that the observed abnormal 3VT view was caused by a tortuous course of the thoracic aorta associated with an abnormal diaphragm. CONCLUSION: Live xPlane imaging is a novel and relatively simple method of visualizing the ductal- and aortic-arch views, and may potentially be a useful tool in the screening of fetal conotruncal and aortic-arch anomalies.