Bradycardia-to-delivery interval and fetal outcomes in umbilical cord prolapse.

INTRODUCTION: Umbilical cord prolapse is a major obstetric emergency associated with significant perinatal complications. However, there is no consensus on the optimal decision-to-delivery interval, as many previous studies have shown poor correlation between the interval and umbilical cord arterial blood gas or perinatal outcomes. We aim to investigate whether bradycardia-to-delivery or decision-to-delivery interval was related to poor cord arterial pH or adverse perinatal outcome in umbilical cord prolapse. MATERIAL AND METHODS: This was a retrospective study conducted at a university tertiary obstetric unit in Hong Kong. All women with singleton pregnancy complicated by cord prolapse during labor between 1995 and 2018 were included. Women were categorized into three groups. Group 1: persistent bradycardia; Group 2: any type of decelerations without bradycardia; and Group 3: normal fetal heart rate. The main outcome was cord arterial blood gas results of the newborns in different groups. Maternal demographic data and perinatal outcomes were reviewed. Correlation analysis between cord arterial blood gas result and time intervals including bradycardia-to-delivery, deceleration-to-delivery, and decision-to-delivery were performed for the different groups with Spearman test. RESULTS: There were 34, 30, and 50 women in Groups 1, 2, and 3, respectively. Cord arterial pH and base excess did not correlate with decision-to-delivery interval in any of the groups, but they were inversely correlated with bradycardia-to-delivery interval in Group 1 (Spearman's ρ = -.349; P = .043 and Spearman's ρ = -.558; P = .001, respectively). The cord arterial pH drops at 0.009 per minute with bradycardia-to-delivery interval in Group 1 (95% CI 0.0180-0.0003). The risk of significant acidosis (pH < 7) was 80% when bradycardia-to-delivery interval was >20 minutes, and 17.2% when the interval was <20 minutes. CONCLUSIONS: There is significant correlation between bradycardia-to-delivery interval and cord arterial pH in umbilical cord prolapse with fetal bradycardia but not in cases with decelerations or normal heart rate. The drop of cord arterial pH is rapid and urgent delivery is essential in such situations.

First Report of a Novel Deletion Due to εγδß-Thalassemia in a Chinese Family.

A fetus of Chinese descent presented with ultrasound features of anemia at 20 weeks' gestation. Father had low a mean corpuscular volume (MCV) level. Multiplex gap-polymerase chain reaction (gap-PCR) excluded common α-thalassemia (α-thal) deletions and mutations and PCR sequencing of the α1- and α2-globin genes were negative. The fetus had a normal karyotype. Array comparative genomic hybridization (aCGH) showed a single copy loss of 189.87 kb in chromosome 11p15.4, involving the whole ß-globin gene cluster, inherited from the father. Multiplex ligation-dependent probe amplification (MLPA) confirmed the deletion included the ε-globin gene, confirming the diagnosis of heterozygous (εγδß)0-thalassemia [(εγδß)0-thal], also inherited from the father. The fetus had a worsening anemic condition in utero and required a transfusion at 26 weeks' gestation, raising the hemoglobin (Hb) level from 5.3 to 12.6g/dL. A cesarean-section was subsequently performed at 32 weeks' gestation because of reduced fetal movements, and a 1650g baby girl with good Apgar scores was delivered. Hemoglobin at birth was 12.8g/dL, gradually dropping to 6.8 g/dL, requiring three neonatal transfusions. Her condition gradually stabilized after 2 months with Hb stable at 8.0 g/dL. Family screening by MLPA showed that the paternal grandmother carried the same deletion. The deletion in this case is distinct and is the reported first case. The deletion transmitted across three successive generations with great phenotypic variation. The final adult phenotype of (εγδß)0-thal is usually mild, therefore, with accurate prenatal diagnosis this condition is salvageable by in utero and early neonatal transfusions, preventing adverse pregnancy and neonatal outcomes.

Systematic Selection of Reference Genes for the Normalization of Circulating RNA Transcripts in Pregnant Women Based on RNA-Seq Data.

RNA transcripts circulating in peripheral blood represent an important source of non-invasive biomarkers. To accurately quantify the levels of circulating transcripts, one needs to normalize the data with internal control reference genes, which are detected at relatively constant levels across blood samples. A few reference gene candidates have to be selected from transcriptome data before the validation of their stable expression by reverse-transcription quantitative polymerase chain reaction. However, there is a lack of transcriptome, let alone whole-transcriptome, data from maternal blood. To overcome this shortfall, we performed RNA-sequencing on blood samples from women presenting with preterm labor. The coefficient of variation (CV) of expression levels was calculated. Of 11,215 exons detected in the maternal blood whole-transcriptome, a panel of 395 genes, including PPP1R15B, EXOC8, ACTB, and TPT1, were identified to comprise exons with considerably less variable expression level (CV, 7.75-17.7%) than any GAPDH exon (minimum CV, 27.3%). Upon validation, the selected genes from this panel remained more stably expressed than GAPDH in maternal blood. This panel is over-represented with genes involved with the actin cytoskeleton, macromolecular complex, and integrin signaling. This groundwork provides a starting point for systematically selecting reference gene candidates for normalizing the levels of circulating RNA transcripts in maternal blood.

Factors influencing the career interest of medical graduates in obstetrics and gynaecology in Hong Kong: a cross-sectional questionnaire survey.

INTRODUCTION: The trend of declining interest of medical graduates in pursuing obstetrics and gynaecology as a career has been observed in many overseas studies. This study aimed to evaluate the career interest of the most recent medical graduates in Hong Kong, especially their level of interest in obstetrics and gynaecology, and to identify key influential factors for career choice and career interest in obstetrics and gynaecology. METHODS: All medical graduates from the Chinese University of Hong Kong and the University of Hong Kong who attended the pre-internship lectures in June 2015 were invited to participate in this cross-sectional questionnaire survey. The main outcome measures were the level of career interest in obstetrics and gynaecology, the first three choices of specialty as a career, key influential factors for career choice, and key influential factors for career interest in obstetrics and gynaecology. RESULTS: Overall, 73.7% of 323 new medical graduates participated in the study and 233 questionnaires were analysed. The median score (out of 10) for the level of career interest in obstetrics and gynaecology was 3. There were 37 (16.2%) participants in whom obstetrics and gynaecology was among their first three choices, of whom 29 (78.4%) were female. Obstetrics and gynaecology ranked as the eighth most popular career choice. By factor analysis, the strongest key influential factor for career interest in obstetrics and gynaecology was clerkship experience (variance explained 28.9%) and the strongest key influential factor for career choice was working style (variance explained 26.4%). CONCLUSIONS: The study confirmed a low level of career interest in obstetrics and gynaecology among medical graduates and a decreasing popularity of the specialty as a career choice. The three key influential factors for career interest in obstetrics and gynaecology and career choice were working style, clerkship experience, and career prospects.

Characteristics of Maternal Mortality Missed by Vital Statistics in Hong Kong, 2000-2019.

Importance: Reducing maternal mortality is a global objective. The maternal mortality ratio (MMR) is low in Hong Kong, China, but there has been no local confidential enquiry into maternal death, and underreporting is likely. Objective: To determine the causes and timing of maternal death in Hong Kong and identify deaths and their causes that were missed by the Hong Kong vital statistics database. Design, Setting, and Participants: This cross-sectional study was conducted among all 8 public maternity hospitals in Hong Kong. Maternal deaths were identified using prespecified search criteria, including a registered delivery episode between 2000 to 2019 and a registered death episode within 365 days after delivery. Cases as reported by the vital statistics were then compared with the deaths found in the hospital-based cohort. Data were analyzed from June to July 2022. Main Outcomes and Measures: The outcomes of interest were maternal mortality, defined as death during pregnancy or within 42 days after ending the pregnancy, and late maternal death, defined as death more than 42 days but less than 1 year after end of the pregnancy. Results: A total of 173 maternal deaths (median [IQR] age at childbirth, 33 [29-36] years) were found, including 74 maternal mortality events (45 direct deaths and 29 indirect deaths) and 99 late maternal deaths. Of 173 maternal deaths, 66 women (38.2%) of individuals had preexisting medical conditions. For maternal mortality, the MMR ranged from 1.63 to 16.78 deaths per 100 000 live births. Suicide was the leading cause of direct death (15 of 45 deaths [33.3%]). Stroke and cancer deaths were the most common causes of indirect death (8 of 29 deaths [27.6%] each). A total of 63 individuals (85.1%) died during the postpartum period. In the theme-based approach analysis, the leading causes of death were suicide (15 of 74 deaths [20.3%]) and hypertensive disorders (10 of 74 deaths [13.5%]). The vital statistics in Hong Kong missed 67 maternal mortality events (90.5%). All suicides and amniotic fluid embolisms, 90.0% of hypertensive disorders, 50.0% of obstetric hemorrhages, and 96.6% of indirect deaths were missed by the vital statistics. The late maternal death ratio ranged from 0 to 16.36 deaths per 100 000 live births. The leading causes of late maternal death were cancer (40 of 99 deaths [40.4%]) and suicide (22 of 99 deaths [22.2%]). Conclusions and Relevance: In this cross-sectional study of maternal mortality in Hong Kong, suicide and hypertensive disorder were the dominant causes of death. The current vital statistics methods were unable to capture most of the maternal mortality events found in this hospital-based cohort. Adding a pregnancy checkbox to death certificates and setting up a confidential enquiry into maternal death could be possible solutions to reveal the hidden deaths.

Genome-Wide Cell-Free DNA Test for Fetal Chromosomal Abnormalities and Variants: Unrestricted Versus Restricted Reporting.

This study aimed to compare the screening performance of genome-wide cfDNA testing for chromosomal abnormalities between two periods where additional findings were reported and not reported. Data were obtained from consecutive pregnant women with a singleton pregnancy at ≥10 weeks who requested cfDNA testing during 2015-2019. The performance of screening of the cfDNA test was determined by calculating the concordance rate, detection rate, and false-positive rate. Data from 3981 women were included. The no-result rates were similar between the two reporting periods (2.04% vs. 2.08%). Concordance rates for trisomy 21 and 18 were 100% and 100%, respectively. There were two cases tested high risk for trisomy 13, with a concordance rate of 0%. In total, 12 cases were high risk for any sex chromosome aneuploidy with an overall concordance of 75%, and 15 cases tested high risk for any rare autosomal trisomy, with a 13.3% concordance rate. The detection rates for trisomy 21 and 18 were 100% and 100%, respectively. For any SCA, the detection rate was 90%. For the two reporting periods, the combined false-positive rates were 0.93% and 0.17%, which were significantly different (p = 0.002). Restricting the reporting of additional findings from genome-wide cfDNA analysis has reduced the false-positive rate but without a reduction in the no-result rate.

Maternal height and risk of hypertensive disorders in pregnancy.

PURPOSE: The relationship between maternal height and gestational hypertensive disorders was examined in a cohort of Chinese gravidae managed in 1997-2013 to clarify the association between short stature with preeclampsia (PE) and gestational hypertension (GH). MATERIALS AND METHODS: Retrospective study of 87 290 gravidae categorized by their height into four quartile groups. The impact of short stature, defined as height in the lowest quartile, on incidence of PE and GH was studied in relation to the presence of risk factors. The independent role of short stature was determined by regression analysis. RESULTS: The 25th, 50th, and 75th percentile values of height were 154 cm, 158 cm, and 161 cm respectively. The incidence of PE, but not GH, was inversely correlated with height (p = .025). Short stature altered the impact of parity status, advanced age, high body mass index, infant gender, and medical history, on incidence of PE but not GH. On regression analysis, short stature increased risk of PE (adjusted RR 1.134, 95%CI 1.005-1.279) but reduced GH (adjusted RR 0.836, 95%CI 0.718-0.974). CONCLUSIONS: Maternal short stature should be defined according to distribution in a specific ethnic group, and it exerts a significant but opposite effect on the incidence of PE versus GH.

Prior abortion history and pregnancy hypertensive disorders in primiparous gravidae.

OBJECTIVES: To explore the relationship between prior abortion history with incidence of pregnancy hypertensive disorders (PHD), including gestational hypertension (GH) and pre-eclampsia (PE), to determine whether the secular increases in GH and PE in developed countries could be related in part to the decreased incidence of abortion. STUDY DESIGN: A single center retrospective cohort study on primiparous Chinese gravidae managed in 1997-2015 in our hospital. MAIN OUTCOME MEASURES: The occurrence of PHD, GH and PE with respect to the presence or otherwise of prior abortions, with the analysis stratified for risk factors that include advanced age, high body mass index (BMI), history of medical disorders, birth before 34 weeks, and maternal hepatitis B virus (HBV) infection and rubella non-immunity which have been shown to influence the occurrence of PHD in our population. RESULTS: The 23,698 (39.3%) of the 60,335 gravidae in the cohort with ≥ one prior abortion had higher incidence of advanced age, HBV infection, rubella non-immunity, and high BMI, but lower incidence of PHD, GH, PE and birth before 34 weeks gestation. The difference in the incidence of GH and PE between gravidae having one versus those with two or more abortions was minimal, and the effect of abortion on PHD was influenced by the other risk factors. On regression analysis, prior abortion reduced PHD (aRR 0.761, 95% CI 0.684-0.846), GH (aRR 0.660, 95% CI 0.563-0.773), and PE (aRR 0.857, 95% CI 0.745-0.987). CONCLUSIONS: Prior abortion reduces the subsequent development of GH and PE in primiparous women.

Prevention of early onset group B streptococcal disease by universal antenatal culture-based screening in all public hospitals in Hong Kong.

OBJECTIVES: To determine the prevalence of maternal colonization with group B streptococcus (GBS), and early onset GBS disease (EOGBSD) after implementation of universal screening. METHODS: This was a three-year retrospective cohort study on universal antenatal rectovaginal culture-based screening and intrapartum antimicrobial prophylaxis (IAP) to colonized women in the public sector in Hong Kong. Routinely collected data including maternal colonization and EOGBSD were retrieved. RESULTS: Of 113,989 GBS screening performed, 21.8% were positive. The colonization rate was higher in the public hospitals (higher risk) than in the Maternal and Child Health Centers (lower risk) (23.7% vs 18.1%, p < .001), while their false negative rates were not greater than expected. Majority of eligible women opted for screening, and colonized women received IAP. There were 29 cases of EOGBSD with clinical signs and a positive blood or cerebrospinal fluid culture. Compared to clinical risk-based screening, EOGBSD incidence decreased after universal screening (1 vs 0.24 per 1000 births, p < .001). Although EOGBSD occurred at a higher rate in preterm than term infants, 86.7% occurred in the latter, and were associated with a false negative screening result (41.3%), lack of screening (20.7%) or unavailability of a colonization result at labour (13.8%). CONCLUSIONS: Maternal GBS colonization rate was higher than previously reported, and varied with different risk populations. EOGBSD reduced after universal screening.

Prior pregnancy and antenatal rubella sero-negativity-evidence of persistent maternal immunologic alteration?

PROBLEM: It is unclear if the immunologic alterations induced by pregnancy could persist. METHOD OF STUDY: Antenatal rubella sero-negativity was correlated with gravidity, abortions and parity in 112 083 gravidae managed during 1997-2015, with further analysis stratified for factors known to influence rubella serology. RESULTS: The 10.2% sero-negative gravidae had different characteristics, and the incidence showed significant difference and positive trend (P<.001 for both) with gravidity, abortions and parity. The pattern remained consistent when analysis was stratified for advanced age, high body mass index and medical history, but was negated by hepatitis B virus infection except for abortions, and by high body mass index for parity. For gravidity 2-4, no difference in rubella sero-negativity was found between gravidae with all previous pregnancies ended in abortion vs delivery. CONCLUSION: Prior pregnancies diminished rubella immunity in a dose-dependent manner, which may be a reflection of the cumulative effect of pregnancy-associated maternal immunologic alteration.

Trends in preterm birth in singleton deliveries in a Hong Kong population.

OBJECTIVE: To examine trends in preterm birth and its relationship with perinatal mortality in Hong Kong. METHODS: In a retrospective cohort study, data were reviewed from singletons delivered between 1995 and 2011 at a university teaching hospital. Trends in preterm birth (between 24 and 36 weeks of pregnancy), perinatal mortality, and subtypes of preterm birth (spontaneous, iatrogenic, and following preterm premature rupture of membranes [PPROM]) were examined via linear regression. RESULTS: There were 103 364 singleton deliveries, of which 6722 (6.5%) occurred preterm, including 1835 (1.8%) early preterm births (24-33 weeks) and 4887 (4.7%) late preterm births (34-36 weeks). Frequency of preterm birth remained fairly consistent over the study period, but that of spontaneous preterm birth decreased by 25% (ß=-0.83; P<0.001), from 4.5% to 3.8%. Frequency of preterm birth following PPROM increased by 135% (ß=0.82; P<0.001), from 0.7% to 1.7%. The perinatal mortality rate decreased from 56.7 to 37.0 deaths per 1000 deliveries before 37 weeks (ß=-0.16; P=0.54). Early preterm birth contributed to 16.0% of all deaths. CONCLUSION: Although the overall rate of preterm birth in Hong Kong has remained constant, the frequencies of its subtypes have changed. Overall perinatal mortality is gradually decreasing, but early preterm birth remains a major contributor.