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OBJECTIVE: To evaluate longitudinal changes in cervical length (CL) and mean cervical shear wave elastography (CSWE) score in women with a singleton or twin pregnancy who undergo spontaneous preterm birth (sPTB) compared with those who deliver at term. METHODS: This was a prospective longitudinal study of unselected women with a singleton or twin pregnancy attending a dedicated research clinic for screening for sPTB at four timepoints during pregnancy: 11 + 0 to 15 + 6 weeks, 16 + 0 to 20 + 6 weeks, 21 + 0 to 24 + 6 weeks and 28 + 0 to 32 + 6 weeks. At each visit, a transvaginal ultrasound scan was conducted to measure the CL and the CSWE scores in six regions of interest (ROI) (inner, middle and external parts of anterior and posterior cervical lips). The mean CSWE score from the six ROIs was calculated for analysis. Log10 transformation was applied to data to produce a Gaussian distribution prior to statistical analysis. A multilevel mixed-effects analysis was performed to compare longitudinally CL and CSWE between the sPTB and term-delivery groups. RESULTS: The final cohort consisted of 1264 women, including 1143 singleton pregnancies, of which 57 (5.0%) were complicated by sPTB, and 121 twin pregnancies, of which 33 (27.3%) were complicated by sPTB. Compared to those who delivered at term, women with sPTB had a lower CL across gestation when controlling for history of cervical surgery, number of fetuses, gestational age (GA) at cervical assessment and the interaction between GA at cervical assessment and sPTB (P < 0.001). Specifically, CL in the sPTB group was significantly lower at 21 + 0 to 24 + 6 weeks (P = 0.039) and 28 + 0 to 32 + 6 weeks (P < 0.001). Twin pregnancies had significantly greater CL throughout pregnancy compared with singleton pregnancies (regression coefficient, 0.01864; P < 0.001). After adjusting for maternal age, weight, height, body mass index and GA at cervical assessment, CSWE score in the sPTB group was significantly lower compared with that in the term-delivery group across gestation (P = 0.013). However, on analysis of individual visits, CSWE score in the sPTB group was significantly lower than that in the term-delivery group only at 11 + 0 to 15 + 6 weeks (P = 0.036). There was no difference in CSWE score between singleton and twin pregnancies throughout gestation (regression coefficient, -0.00128; P = 0.937). CONCLUSIONS: Women with sPTB have a shorter and softer cervix across gestation compared with those who deliver at term. A shorter cervix in the sPTB group is observed from the late second trimester onwards, while lower cervical stiffness in the sPTB group is observed primarily in the first trimester. CL is significantly lower in singleton pregnancies compared with twin pregnancies, while cervical stiffness does not differ between the two. Our findings indicate that the cervix tends to undergo a softening process prior to shortening in sPTB cases. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Medida do Comprimento Cervical , Colo do Útero , Técnicas de Imagem por Elasticidade , Gravidez de Gêmeos , Nascimento Prematuro , Humanos , Feminino , Gravidez , Técnicas de Imagem por Elasticidade/métodos , Estudos Longitudinais , Estudos Prospectivos , Adulto , Colo do Útero/diagnóstico por imagem , Medida do Comprimento Cervical/métodos , Idade Gestacional , Ultrassonografia Pré-Natal/métodos , Ultrassonografia Pré-Natal/estatística & dados numéricosRESUMO
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.
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Líquido Amniótico , Atresia Biliar , Vesícula Biliar , Idade Gestacional , gama-Glutamiltransferase , Humanos , gama-Glutamiltransferase/sangue , Feminino , Gravidez , Estudos Retrospectivos , Valores de Referência , Líquido Amniótico/química , Atresia Biliar/diagnóstico , Atresia Biliar/sangue , Valor Preditivo dos Testes , Adulto , Diagnóstico Pré-Natal/métodosRESUMO
INTRODUCTION: Because there have been changes in the management of macrosomic pregnancies and shoulder dystocia in the past decade, this study was conducted to compare the incidences of shoulder dystocia and perinatal outcomes between the periods of 2000-2009 and 2010-2019. METHODS: This retrospective study was conducted in a tertiary obstetric unit. All cases of shoulder dystocia were identified using the hospital's electronic database. The incidences, maternal and fetal characteristics, obstetric management methods, and perinatal outcomes were compared between the two study periods. RESULTS: The overall incidence of shoulder dystocia decreased from 0.23% (134/58 326) in 2000-2009 to 0.16% (108/65 683) in 2010-2019 (P=0.009), mainly because of the overall decline in the proportion of babies with macrosomia (from 3.3% to 2.3%; P<0.001). The improved success rates of the McRoberts' manoeuvre (from 31.3% to 47.2%; P=0.012) and posterior arm extraction (from 52.9% to 92.3%; P=0.042) allowed a greater proportion of affected babies to be delivered within 2 minutes (from 59.0% to 79.6%; P=0.003). These changes led to a significant reduction in the proportion of fetuses with low Apgar scores: <5 at 1 minute of life (from 13.4% to 5.6%; P=0.042) and <7 at 5 minutes of life (from 11.9% to 4.6%; P=0.045). CONCLUSION: More proactive management of macrosomic pregnancies and enhanced training in the acute management of shoulder dystocia led to significant improvements in shoulder dystocia incidence and perinatal outcomes from 2000-2009 to 2010-2019.
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Distocia , Distocia do Ombro , Gravidez , Feminino , Humanos , Parto Obstétrico , Distocia/epidemiologia , Distocia/terapia , Distocia/etiologia , Incidência , Distocia do Ombro/epidemiologia , Distocia do Ombro/terapia , Estudos Retrospectivos , Hong Kong/epidemiologia , OmbroRESUMO
Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. INTRODUCTION: As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. METHODS: 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). RESULTS: Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1-3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively). CONCLUSION: AIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.
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Escoliose , Adolescente , Densidade Óssea , Remodelação Óssea , Criança , Osso Cortical , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Escoliose/diagnóstico por imagemRESUMO
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.
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Pré-Eclâmpsia , Proteína Plasmática A Associada à Gravidez , Biomarcadores , Feminino , Humanos , Recém-Nascido , Fator de Crescimento Placentário , Gravidez , Primeiro Trimestre da Gravidez , Fluxo Pulsátil , Artéria Uterina/diagnóstico por imagemRESUMO
OBJECTIVE: The diagnostic yield for congenital heart defects (CHD) with routine genetic testing is around 10%-20% when considering pathogenic CNVs or aneuploidies as positive findings. This is a pilot study to investigate the utility of genome sequencing (GS) for prenatal diagnosis of CHD. METHODS: Genome sequencing (GS, 30X) was performed on 13 trios with CHD for which karyotyping and/or chromosomal microarray results were non-diagnostic. RESULTS: Trio GS provided a diagnosis for 4/13 (30.8%) fetuses with complex CHDs and other structural anomalies. Findings included pathogenic or likely pathogenic variants in DNAH5, COL4A1, PTPN11, and KRAS. Of the nine cases without a genetic etiology by GS, we had outcome follow-up data on eight. For five of them (60%), the parents chose to keep the pregnancy. A balanced translocation [46,XX,t(14; 22)(q32.33; q13.31)mat] was detected in a trio with biallelic DNAH5 mutations, which together explained the recurrent fetal situs inversus and dextrocardia that was presumably due to de novo Phelan-McDermid syndrome. A secondary finding of a BRCA2 variant and carrier status of HBB, USH2A, HBA1/HBA2 were detected in the cohort. CONCLUSIONS: GS expands the diagnostic scope of mutation types over conventional testing, revealing the genetic etiology for fetal heart anomalies. Patients without a known genetic abnormality indicated by GS likely opted to keep pregnancy especially if the heart defect could be surgically repaired. We provide evidence to support the application of GS for fetuses with CHD.
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Doenças Fetais , Cardiopatias Congênitas , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Feminino , Coração Fetal , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Projetos Piloto , Gravidez , Diagnóstico Pré-Natal/métodosRESUMO
BACKGROUND: Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents' view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. OBJECTIVE: To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. METHODS: A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0-3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. RESULTS: Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an "opt-out" approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. CONCLUSION: Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.
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Bancos de Espécimes Biológicos , Triagem Neonatal , Recém-Nascido , Criança , Feminino , Humanos , Triagem Neonatal/métodos , Hong Kong , Pais , MãesRESUMO
INTRODUCTION: Although the stillbirth rate is low in Hong Kong, up to 50% of stillbirths have unclassifiable causes and up to one third of stillbirths have unexplained causes. This retrospective study investigated the underlying causes of singleton stillbirths in Hong Kong. METHODS: This study examined the prevalences and causes of stillbirths in a university tertiary obstetric unit between 2000 and 2019. Medical records were reviewed for all singleton pregnancies complicated by stillbirths. Causes of stillbirth were determined via clinical assessments and laboratory findings, then compared between 2000-09 and 2010-19. RESULTS: Overall perinatal mortality significantly decreased by 16.7%, from 5.52/1000 in 2000-09 to 4.59/1000 in 2010-19; the singleton stillbirth rate slightly decreased (from 3.27/1000 to 2.91/1000). These changes were related to early prenatal diagnostic improvements concerning congenital malformations and genetic disorders. Pre-eclampsia prevalence among singleton pregnancies increased from 1.5% to 1.7% because of increasing maternal age; the stillbirth rate among patients with pre-eclampsia decreased from 2.5% to 1.4%. Foetal growth restriction of unknown cause contributed to 16% of all stillbirths; this prevalence did not change over time. Moreover, foetal growth restriction was not diagnosed during routine antenatal care in 43.5% of patients. Thirty-six percent of all stillbirths were unexplained. The prevalences of stillbirth associated with chorioamnionitis and placental abruption did not change over time. CONCLUSIONS: Causes of stillbirth in Hong Kong have changed in the past 20 years because of altered demographic characteristics and improved prenatal testing. Further improvements should focus on early foetal growth restriction detection and preeclampsia prevention.
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Pré-Eclâmpsia , Natimorto , Feminino , Hong Kong/epidemiologia , Humanos , Placenta , Pré-Eclâmpsia/epidemiologia , Gravidez , Estudos Retrospectivos , Natimorto/epidemiologiaRESUMO
INTRODUCTION: Because of the ageing population in Hong Kong, there is an increasing incidence of total knee arthroplasties (TKA) conducted in patients aged >80 years. METHODS: This retrospective case-control study enrolled all patients who were aged >80 years and underwent fast-track primary TKA between 2011 and 2015. Their outcomes were compared with the outcomes of a matched control group of younger patients who underwent fast-track TKA in the same period. RESULTS: In total, 220 patients were included in this study with a follow-up period of at least 2 years (mean=3.2 years; range, 2-5 years); 112 (51%) were octogenarians and 108 (49%) were non-octogenarians. Greater improvement in Knee Society Score was found in the octogenarian group at 1 year after surgery (46 ± 19 vs 39 ± 16, P=0.018). The incidence of complications was higher in the octogenarian group (15.2% vs 4.6%, P=0.009). There were no significant differences in the incidence of major complications, the rate of intensive care unit admission, or the 1-year mortality rate between the two groups. After adjustment for confounding factors, Charlson Comorbidity Index >5, history of major cerebrovascular accident, and history of peptic ulcer disease were predictive of complications after fast-track TKA (P=0.039, P=0.016, and P=0.007, respectively); octogenarian status was not predictive of complications. CONCLUSIONS: Octogenarians had greater improvement in Knee Society Score at 1 year after fast-track TKA, compared with non-octogenarians, but there were no significant differences in the incidences of mortality or major complications.
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Artroplastia do Joelho , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Estudos de Casos e Controles , Humanos , Incidência , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Multiple pregnancies have become more common, but their perinatal mortality rate remains higher than the rate among singleton pregnancies. This retrospective study investigated the prevalence and causes of perinatal mortality among multiple pregnancies in Hong Kong. METHODS: All multiple pregnancies in a university tertiary obstetric unit between 2000 and 2019 were reviewed, and the medical records of cases complicated by stillbirth and neonatal death were identified. The causes of perinatal mortality were determined based on clinical assessment and laboratory results, then compared between the first (2000-2009) and second (2010-2019) decades. RESULTS: The prevalence of multiple pregnancies increased from 1.41% in the first decade to 1.91% in the second decade (P<0.001). Compared with the first decade, the second decade had a lower stillbirth rate (14.72 vs 7.68 [both per 1000 births]; P=0.026), late neonatal death rate (4.78 vs 1.16 [both per 1000 livebirths]; P=0.030), and total mortality rate (25.32 vs 13.82 [both per 1000 births]; P=0.006). The decline in stillbirth rate was related to improvements in antenatal care and treatment. The decline in the late neonatal death rate was related to a reduction in preterm birth before 34 weeks (18.5% vs 15.2%; P=0.006), as well as an improvement in the mortality rate in the subgroup of 31-33 weeks (19.23 vs 0 [both per 1000 livebirths]; P=0.035). CONCLUSION: Although the prevalence of multiple pregnancies increased during the study period, the corresponding total perinatal mortality rate improved by 45.4%.
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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.
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Atresia Biliar , Fibrose Cística , China , Aberrações Cromossômicas , Anormalidades Congênitas , Feminino , Feto , Vesícula Biliar/anormalidades , Vesícula Biliar/diagnóstico por imagem , Humanos , Lactente , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
INTRODUCTION: The global neonatal death (NND) rate has been declining in recent decades, but there are no comprehensive data concerning the characteristics of NNDs in Hong Kong. This study investigated the trends and aetiologies of NNDs among singleton pregnancies in Hong Kong. METHODS: This study included all cases of NND from singleton pregnancies in a tertiary hospital in Hong Kong between 2000 and 2019. The rates, clinical characteristics, and aetiologies of NND were compared between the first (2000-2009) and the second (2010-2019) decades. RESULTS: The NND rate decreased from 1.66/1000 livebirths (97 cases) in the first decade to 1.32/1000 livebirths (87 cases) in the second decade. Congenital or genetic abnormalities (82 cases) caused 44.6% of all NNDs. There was a significant reduction from 0.82/1000 livebirths in the first decade to 0.52/1000 livebirths in the second decade (P=0.037). Other causes of NND were prematurity (69 cases; 37.5%), sepsis (16 cases; 8.7%), hypoxic-ischaemic encephalopathy (15 cases; 8.2%), and sudden infant death syndrome (2 cases; 1.1%). Gestational age-specific neonatal mortality for moderately preterm neonates (31-33 weeks of gestation) significantly decreased from 34.73/1000 in 2000-2009 to 8.63/1000 in 2010-2019 (P=0.001), but there were no significant changes in neonatal mortality for other gestations. CONCLUSION: The NND rate in Hong Kong is among the lowest worldwide. Neonatal deaths in our centre declined over the past two decades, mainly because of improvements in the prenatal diagnosis and treatment of congenital or genetic abnormalities, as well as an improved survival rate among moderately preterm neonates.
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Mortalidade Infantil , Recém-Nascido Prematuro , Gravidez , Recém-Nascido , Lactente , Feminino , Humanos , Estudos Retrospectivos , Hong Kong/epidemiologiaRESUMO
STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.
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Oócitos , Indução da Ovulação , Animais , Células do Cúmulo , Feminino , Técnicas de Maturação in Vitro de Oócitos , Camundongos , Oogênese , Análise de Sequência de RNARESUMO
The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. INTRODUCTION: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. METHODS: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). CONCLUSION: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.
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Fraturas Ósseas , Deficiência de Vitamina D , Estudos de Casos e Controles , Criança , Estudos Transversais , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , VitaminasRESUMO
OBJECTIVE: To assess objectively the degree of fetal head elevation achieved by different maneuvers commonly used for managing umbilical cord prolapse. METHODS: This was a prospective observational study of pregnant women at term before elective Cesarean delivery. A baseline assessment of fetal head station was performed with the woman in the supine position, using transperineal ultrasound for measuring the parasagittal angle of progression (psAOP), head-symphysis distance (HSD) and head-perineum distance (HPD). The ultrasonographic measurements of fetal head station were repeated during different maneuvers, including elevation of the maternal buttocks using a wedge, knee-chest position, Trendelenburg position with a 15° tilt and filling the maternal urinary bladder with 100 mL, 300 mL and 500 mL of normal saline. The measurements obtained during the maneuvers were compared with the baseline measurements. RESULTS: Twenty pregnant women scheduled for elective Cesarean section at term were included in the study. When compared with baseline (median psAOP, 103.6°), the knee-chest position gave the strongest elevation effect, with the greatest reduction in psAOP (psAOP, 80.7°; P < 0.001), followed by filling the bladder with 500 mL (psAOP, 89.9°; P < 0.001) and 300 mL (psAOP, 94.4°; P < 0.001) of normal saline. Filling the maternal bladder with 100 mL of normal saline (psAOP, 96.1°; P = 0.001), the Trendelenburg position (psAOP, 96.8°; P = 0.014) and elevating the maternal buttocks (psAOP, 98.3°; P = 0.033) gave modest elevation effects. Similar findings were reported for HSD and HPD. The fetal head elevation effects of the knee-chest position, Trendelenburg position and elevation of the maternal buttocks were independent of the initial fetal head station, but that of bladder filling was greater when the initial head station was low. CONCLUSIONS: To elevate the fetal presenting part, the knee-chest position provides the best effect, followed by filling the maternal urinary bladder with 500 mL then 300 mL of fluid, respectively. Filling the bladder with 100 mL of fluid, the Trendelenburg position and elevation of the maternal buttocks have modest effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Feto/diagnóstico por imagem , Cabeça/embriologia , Apresentação no Trabalho de Parto , Posicionamento do Paciente/métodos , Ultrassonografia Pré-Natal/métodos , Adulto , Cesárea , Feminino , Feto/embriologia , Humanos , Períneo/diagnóstico por imagem , Gravidez , Período Pré-Operatório , Prolapso , Estudos Prospectivos , Nascimento a Termo/fisiologia , Cordão UmbilicalRESUMO
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.
Assuntos
Redução de Gravidez Multifetal , Gravidez Múltipla , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Complicações Pós-Operatórias , Gravidez , Resultado da Gravidez , Trimestres da Gravidez , Ablação por Radiofrequência , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the utility of expanded non-invasive prenatal screening (NIPS), compared with chromosomal microarray analysis (CMA), for the detection of chromosomal abnormalities in high-risk pregnancies. METHODS: This was a multicenter retrospective study of singleton pregnancies at high risk for chromosomal abnormality. Patients who underwent expanded NIPS and CMA sequentially during pregnancy from 2015 to 2019 were included in the analysis. Pregnancies with a positive result for sex chromosome aneuploidy were excluded as the full details could not be retrieved. The utility of expanded NIPS and CMA for detection of chromosomal abnormalities in this cohort was compared by assessing the concordance between the results. RESULTS: Of the 774 included high-risk pregnancies, 550 (71.1%) had a positive NIPS result, while a positive CMA result was detected in 308 (39.8%) cases. The rate of full or partial concordance between NIPS and CMA was 82.2%, 59.6% and 25.0% for trisomies 21, 18 and 13, respectively. For rare aneuploidies and segmental imbalances, NIPS and CMA results were fully or partially concordant in 7.5% and 33.3% of cases, respectively. Copy-number variants < 5 Mb were detected more often by CMA, with an incidence of 7.9% (61/774) compared with 3.1% (24/774) by NIPS. A genetic aberration was detected by CMA in 1 in 17 (5.8%) high-risk pregnancies that had a negative or non-reportable NIPS result. CONCLUSION: CMA allows for comprehensive detection of genome-wide chromosomal abnormalities in high-risk pregnancies. CMA should be offered instead of expanded NIPS for high-risk pregnancies. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.
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Aberrações Cromossômicas/embriologia , Transtornos Cromossômicos/diagnóstico , Análise em Microsséries/estatística & dados numéricos , Teste Pré-Natal não Invasivo/estatística & dados numéricos , Gravidez de Alto Risco/genética , Adulto , Transtornos Cromossômicos/embriologia , Feminino , Humanos , Análise em Microsséries/métodos , Teste Pré-Natal não Invasivo/métodos , Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: This study investigated the incidences of chromosomal abnormalities and the neurological outcomes according to the degree of fetal cerebral ventriculomegaly. METHODS: All women with antenatal ultrasound diagnosis of fetal cerebral ventriculomegaly were retrospectively identified from two maternal-fetal medicine units in Hong Kong from January 2014 to December 2018. Degrees of fetal ventriculomegaly were classified as mild (10-11.9 mm), moderate (12-14.9 mm), or severe (≥15 mm). Genetic investigation results were reviewed, including conventional karyotyping and chromosomal microarray analysis (CMA); correlations between chromosomal abnormalities and the degree of fetal ventriculomegaly were explored. The neurological outcomes of subsequent live births were analysed to identify factors associated with developmental delay. RESULTS: Of 84 cases (ie, pregnant women and their fetuses) included, 46 (54.8%) exhibited isolated fetal ventriculomegaly, 55 (65.5%) had mild cerebral ventriculomegaly, and 29 (34.5%) had moderate or severe cerebral ventriculomegaly. Overall, 20% (14/70) of cases had chromosomal abnormalities. Moreover, 12% (3/25) of mild isolated ventriculomegaly cases had abnormal karyotype or CMA results. The CMA provided an incremental diagnostic yield of 8.6% (6/70), compared with conventional karyotyping; 4.3% exhibited pathogenic variants and 4.3% exhibited variants of uncertain significance. Among the 53 live births in the cohort, fewer cases of mild isolated ventriculomegaly were associated with developmental delay than more severe isolated ventriculomegaly (9.7% vs 41.7%, P<0.03). CONCLUSIONS: Chromosomal microarray analysis testing should be offered to all women with fetal cerebral ventriculomegaly, including women with isolated mild ventriculomegaly. The incidence of developmental delay after birth increases with the degree of prenatal cerebral ventriculomegaly.
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Aberrações Cromossômicas , Hidrocefalia , Estudos de Coortes , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/genética , Cariotipagem , Análise em Microsséries , Gravidez , Diagnóstico Pré-Natal , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
INTRODUCTION: The effect of massage for pain relief during labour has been controversial. This study investigated the efficacy of a programme combining intrapartum massage, controlled breathing, and visualisation for non-pharmacological pain relief during labour. METHODS: This randomised controlled trial was conducted in two public hospitals in Hong Kong. Participants were healthy low-risk nulliparous Chinese women ≥18 years old whose partners were available to learn massage technique. Recruitment was performed at 32 to 36 weeks of gestation; women were randomised to attend a 2-hour childbirth massage class at 36 weeks of gestation or to receive usual care. The primary outcome variable was the intrapartum use of epidural analgesia or intramuscular pethidine injection. RESULTS: In total, 233 and 246 women were randomised to the massage and control groups, respectively. The use of epidural analgesia or pethidine did not differ between the massage and control groups (12.0% vs 15.9%; P=0.226). Linear-by-linear analysis demonstrated a trend whereby fewer women used strong pharmacological pain relief in the massage group, and a greater proportion of women had analgesic-free labour (29.2% vs 21.5%; P=0.041). Cervical dilatation at the time of pethidine/epidural analgesia request was significantly greater in the massage group (3.8 ± 1.7 cm vs 2.3 ± 1.0 cm; P<0.001). CONCLUSION: The use of a massage programme appeared to modulate pain perception in labouring women, such that fewer women requested epidural analgesia and a shift was observed towards the use of weaker pain relief modalities; in particular, more women in the massage group were analgesic-free during labour.
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Analgesia Obstétrica , Dor do Parto , Adolescente , Feminino , Humanos , Dor do Parto/terapia , Massagem , Parto , Satisfação do Paciente , Gravidez , GestantesRESUMO
INTRODUCTION: To determine the carrier frequency and common mutations of Mendelian variants in Chinese couples using next-generation sequencing (NGS). METHODS: Preconception expanded carrier testing using NGS was offered to women who attended the subfertility clinic. The test was then offered to the partners of women who had positive screening results. Carrier frequency was calculated, and the results of the NGS panel were compared with those of a target panel. RESULTS: One hundred twenty-three women and 20 of their partners were screened. Overall, 84 (58.7%) individuals were identified to be carriers of at least one disease, and 68 (47.6%) were carriers after excluding thalassaemias. The most common diseases found were GJB2-related DFNB1 nonsyndromic hearing loss and deafness (1 in 4), alpha-thalassaemia (1 in 7), beta-thalassaemia (1 in 14), 21-hydroxylase deficient congenital adrenal hyperplasia (1 in 13), Pendred's syndrome (1 in 36), Krabbe's disease (1 in 48), and spinal muscular atrophy (1 in 48). Of the 43 identified variants, 29 (67.4%) were not included in the American College of Medical Genetics and Genomics or American College of Obstetrics and Gynecology guidelines. Excluding three couples with alpha-thalassaemia, six at-risk couples were identified. CONCLUSION: The carrier frequency of the investigated members of the Chinese population was 58.7% overall and 47.6% after excluding thalassaemias. This frequency is higher than previously reported. Expanded carrier screening using NGS should be provided to Chinese people to improve the detection rate of carrier status and allow optimal pregnancy planning.