To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling.Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples.Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands.753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing.Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection.Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%.Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.
Abstract Background Previous studies have shown evidence of hypoxemia and hypercapnia during cardiopulmonary exercise test (CPET) evaluation in children with congenital central hypoventilation syndrome (CCHS). However, there are no longitudinal studies which compared CPET findings to polysomnogram (PSG) or PHOX2B mutation, to date. Objectives To describe the longitudinal CPET findings in a cohort of children with CCHS and correlate the findings to the PSG results. Methods This retrospective study was conducted in children with CCHS followed in the Long‐term Ventilation Program at SickKids, Toronto, Canada between September, 2013 and January, 2020. CCHS genetic mutation, age of diagnosis, ventilatory support, family history, disease associations of CCHS, CPETs, and PSG parameters were recorded and analyzed. Results A total of nine patients with CCHS (46 CPETs and 46 PSGs) were enrolled. Four (44.4%) children had polyalanine repeat mutations. The mean ( SD ) age at the time of diagnosis and duration of ventilatory usage were 3.2 ± 3.4 years and 11.5 ± 2.8 years, respectively. All abnormal CPETs had hypercapnia in at least 1 phase of the exercise test. Hypercapnia (12/46; 26.1%) at peak of exercise was the most common abnormality. None of the children experienced an oxygen desaturation below 90%. End‐tidal CO 2 (PetCO 2 ) at rest and at peak exercise in the CPETs were significantly correlated with PSG TcCO 2 while PetCO 2 at anaerobic threshold was correlated with CO 2 in pre‐PSG capillary blood gas. Conclusion Nocturnal hypoventilation may impact the CPET results in CCHS children. Serial CPETs should be considered standard clinical care for all CCHS children.
a hydatidiform mole and phenotypically normal fetus.We report a case of placental mesenchymal dysplasia concomitant with fetal lymphangioma.On the basis of the detailed ultrasonography and MRI appearances, the fetal intra-abdominal lymphangioma and placental abnormalities suggestive of molar changes were observed at 28 weeks of gestation.A Cesarean section was carried out at 29 weeks of gestation because progression of the lesions and oligohydramnios with advancing gestation were observed.The placenta had mimicking partial moles, vesicle-like villi that diffusely occupied the area on the maternal surface of the placenta.Microscopic examination revealed enlarged stem villi which neither syncytiotrophoblast proliferation nor trophoblastic inclusions.The vesicle-like villi showed diploid cellular DNA contents.Molecular genetic analysis using the polymerase chain reaction amplification of polymorphic microsatellite markers confirmed genetic identity among the vesicle-like villi and her parents.The overall histologic and genetic findings were consistent with placental mesenchymal dysplasia.
Abstract Introduction: This study aimed to compare the pregnancy and perinatal outcomes of women with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy. Methods: Women who delivered in an obstetric unit from March 2022 to October 2022 were recruited. The history of vaccination and SARS-CoV-2 infection during pregnancy was recorded. The pregnancy and perinatal outcomes of women with and without SARS-CoV-2 infection were compared. Results: A total of 1015 women were recruited — 41.5% had SARS-CoV-2 infection during pregnancy and 25.2% were unvaccinated. The incidences of preeclampsia, gestational diabetes mellitus and caesarean section were similar between the two groups. There were more preterm deliveries (9.0% vs 5.1%, P = 0.01) and more late preterm deliveries of between 33 and 36 + 6 weeks (6.2% vs. 3.7%, P = 0.03) in the SARS-CoV-2 infection group. There were no statistically significant differences between the two groups in perinatal outcomes, including birthweight, incidence of small for gestational age, low Apgar scores, and neonatal intensive care or special care baby unit admissions. There were no differences in pregnancy and perinatal outcomes between women infected in the first/second trimester and those infected in the third trimester, except for lower mean birthweight (3180 g vs. 3292 g, P = 0.04). There were no major differences in pregnancy outcome between vaccinated and unvaccinated women. Conclusion: The pregnancy and perinatal outcomes of women who were infected with SARS-CoV-2 during gestation appear favourable.
To evaluate the impact of a universal screening strategy in the first trimester (including nuchal translucency, PAPP-A and β-HCG), introduced in all Hong Kong public hospitals during second half of 2010. Before July 2010, a prenatal screening or invasive test for Down syndrome was offered to women of 35 or above only. This was a cohort study in all eight public hospitals with an obstetric department with total annual deliveries of around 41,000, and two certified prenatal diagnostic laboratories in Hong Kong. All sonographers were trained. The numbers were extracted from the Down syndrome screening database; i.e. denominator was the number of women screened. The primary outcome was the number of Down syndrome diagnosed prenatally and postnatally, and the number of prenatal invasive procedures carried out. The secondary outcomes measured were the number of women screened, and false positive rate. Compared to the second half of 2009, the number of Down syndrome diagnosed prenatally was increased from 9 to 21 in the second half of 2010. The number of women screened was increased from 3,971 to 14,355. The proportion of first trimester screening test was increased from 51.0% to 84.9%. The false positive rate was decreased from 9.0 to 5.6%. In one laboratory, the ratio of chorionic villus to amniotic fluid samples was increased from 0.23 to 0.96. Like the experience in other countries, the introduction of a universal combined risk assessment during the first trimester at a public level in Hong Kong increased the prenatal detection of Down syndrome. The impact on the number of infants born with Down syndrome, and the number of prenatal invasive procedures will be evaluated after further data collection.
In recent years, training in emergency obstetric skills has moved from the traditional clinical teaching in the labour ward to specific, targeted skills and scenario-based courses utilising mannequins and simulators. Such changes have been necessary, largely as a result of the limitations of traditional clinical teaching when it comes to genuine patient encounters in an emergency situation. The range of simulations now available extends from simple pelvic models to sophisticated computer-based birth simulators. Evidence for the effectiveness of such simulated training is gradually emerging, and in general, transfer of knowledge, improvement of clinical skills and teamwork are all enhanced. However, unequivocal evidence that such teaching improves clinical outcomes is still lacking. Further prospective research on the impact of emergency obstetric training courses as a means of reducing adverse perinatal outcomes is warranted.
To evaluate the accuracy of 2D and 3D ultrasound (USG) in the diagnosis of facial clefts, and particularly in predicting the presence or absence of associated alveolar clefts (CA)/ palate clefts (CP) in the presence of lip clefts (CL). All cases of facial clefts diagnosed before 24 weeks from 2009 to 2013 in a single obstetric unit were reviewed. The findings from conventional 2D USG scanning and 3D USG imaging using the reversed face view, oblique face view or other modified techniques were compared with the findings at postnatal examination of the babies after birth or at pathological examination of the fetuses after termination of pregnancy. The degree of accuracy of prenatal predictions were determined. A total of 42 cases were analyzed. There were 35 unilateral and 6 bilateral lip clefts (CL), and 1 median cleft. Three cases involved one fetus of a monochrionic diamniotic twin pair, and one case involved one fetus of a dichorionic diamniotic twin pair. Associated structural abnormalities were detected by antenatal USG in 5 cases, and significant karyotype abnormalities were detected in 4. Termination of pregnancy was performed in 13 of the cases. There were 11 cases with CL only, 6 with CL + CA and 25 with CL + CP. There were 6 cases where prenatal USG over-diagnosed the severity of the cleft, while 3 cases had underdiagnoses, giving an overall accuracy of 80% (34/42). The most common discrepancy was in the over or under diagnosis of alveolar clefts, while 1 case of unilateral cleft was over-diagnosed as a bilateral cleft. When only the prenatal diagnostic accuracy of presence or absence of CP was calculated, the overall accuracy was 95% (40/42, association 0.90). The prediction of presence or absence of palate clefts was good, but the precise prediction of alveolar clefts was inferior. The limitations of such USG predictions should be explained to the mothers at the time of counselling.
Estimation of fetal weight is important for clinical management. However, there are very few studies on the accuracy of ultrasound prediction of fetal weight in Chinese population. This study aims to determine the accuracy of sonographic prediction of fetal weight in Chinese population and the possible associated factors that affect its accuracy. A total of 200 Chinese patients who had prenatal ultrasound scan performed within 7 days of delivery were retrospectively reviewed. The accuracy of Hadlock1 formula and Shepard formula in prediction of fetal birthweight were compared. The possible factors that affect the accuracy were explored. Hadlock1 formula was found to be more accurate than Shepard formula. Hadlock1 formula had the mean percentage error (MPE) -4.33 with the mean absolute percentage error (MAPE) 7.35%. 71% of patients had estimated fetal weight within 10% of discrepancy from actual birthweight while 94.5% were within 15% of discrepancy. Shepard formula had the MPE 5.44 with the MAPE 7.5%. 66.5% of patients had estimated fetal weight within 10% of discrepancy from actual birthweight while 78.5 % were within 15% of discrepancy. For Hadlock1 formula, the MAPE was found to be significantly increased in patients with macrosomia (>4000 g) (p = 0.016) but not for Shepard formula (p = 0.248). For Hadlock1 formula, the MAPE was found to be significantly increased in patients with intrauterine growth restriction (p = 0.028) but it was significantly decreased in Shepard formula (p = 0.049). Maternal obesity, diabetes, pre-eclampsia, fetal presentation, placental location, liquor volume, rupture of membranes, fetal birth weight < 1500 g and fetal gender were found to have no significant impacts on the MAPE on both Hadlock1 and Shepard formula. Hadlock1 formula was overall more accurate than Shepard formula in estimation of fetal weight in Chinese population. However, Shepard formula was more accurate in predicting birthweight on intrauterine growth restricted fetuses and macrosomic fetuses.
The use of intrauterine balloon tamponade to manage postpartum hemorrhage is increasing. However, there is lack of studies on the menstrual and reproductive outcomes after such treatment. The purpose of this study is to explore the menstrual and reproductive outcomes for patients who had been managed by intrauterine balloon tamponade for severe postpartum hemorrhage in her index pregnancy.All patients who had delivered in United Christian Hospital from January 2011 to June 2016 with severe postpartum hemorrhage (PPH) (blood loss> = 1 L) were identified by the labour ward delivery registry and a comprehensive obstetric database. Patients who had intrauterine balloon tamponade inserted were compared with those managed solely by uterotonic agents as controls. Patients who had hysterectomy or additional procedures performed, such as compression sutures or uterine artery embolization were excluded from both groups. A questionnaire on menses, fertility and reproductive outcomes was mailed to both groups of patients. Those that had not replied within 4 weeks would receive a telephone survey.A total of 39 patients in the balloon tamponade group and 161 patients in the control group were recruited, which represented 87.0% of all eligible patients within the study period. The median follow up period was 45 months. All patients in the balloon tamponade group had return of menses after delivery. The majority of the patients (87.2%) in the balloon tamponade group had normal menstrual patterns in the 12 months after the index delivery as well as in the most recent 12 months. After excluding the patients with contraception, the subsequent pregnancy rate was 42.9% (9/21) in the balloon tamponade group compared to 45.9% (28/61) in the control group (p = 0.81). Among the 9 subsequent pregnancies in the balloon tamponade group, there were two miscarriages, one scar pregnancy, one induced abortion, while the remaining five were normal pregnancies with full term deliveries without intrauterine growth restriction. The majority of patients replied that they were satisfied with using Bakri balloon for PPH management in their index pregnancy.Intrauterine balloon tamponade for the management of severe PPH appeared to pose little adverse effects on subsequent menstrual and reproductive function.
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