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.

Intravenous immunoglobulin in the management of severe early onset red blood cell alloimmunisation.

Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case-control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti-D or anti-K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti-D in 17 women and anti-K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8-53.2, p = 0.0013) and improved perinatal survival (eight of eight vs. none of six, p = 0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early-onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.

Implementation of Public Funded Genome Sequencing in Evaluation of Fetal Structural Anomalies.

With the advancements in prenatal diagnostics, genome sequencing is now incorporated into clinical use to maximize the diagnostic yield following uninformative conventional tests (karyotype and chromosomal microarray analysis). Hong Kong started publicly funded prenatal genomic sequencing as a sequential test in the investigation of fetal structural anomalies in April 2021. The objective of the study was to evaluate the clinical performance and usefulness of this new service over one year. We established a web-based multidisciplinary team to facilitate case selection among the expert members. We retrospectively analyzed the fetal phenotypes, test results, turnaround time and clinical impact in the first 15 whole exome sequencing and 14 whole genome sequencing. Overall, the molecular diagnostic rate was 37.9% (11/29). De novo autosomal dominant disorders accounted for 72.7% (8/11), inherited autosomal recessive disorders for 18.2% (2/11), and inherited X-linked disorders for 9.1% (1/11). The median turnaround time for ongoing pregnancy was 19.5 days (range, 13-31 days). Our study showed an overall clinical impact of 55.2% (16/29), which influenced reproductive decision-making in four cases, guided perinatal management in two cases and helped future family planning in ten cases. In conclusion, our findings support the important role of genome sequencing services in the prenatal diagnosis of fetal structural anomalies in a population setting. It is important to adopt a multidisciplinary team approach to support the comprehensive genetic service.

Prenatal presentation in two fetuses with features of Beckwith Wiedemann syndrome-An unexpected diagnosis of androgenetic chimera and its clinical implications.

Beckwith Wiedemann Syndrome (BWS, OMIM 130650) is an imprinting disorder that may present antenatally with a constellation of sonographic features namely polyhydramnios, macrosomia, macroglossia, omphalocele, placental mesenchymal dysplasia, cardiomegaly, nephromegaly, fetal hydrops, and other rare anomalies. Paternal uniparental disomy in chromosome 11p15 imprinting region accounts for 20% of all BWS, and 8% among those were due to genome-wide paternal uniparental disomy (GWpUPD). GWpUPD is a rare condition and usually results in prenatal lethality. The 31 liveborns reported in the literature demonstrate female predominance in surviving GWpUPD. Here, we reported two prenatal cases which initially presented with features suggestive of BWS, which subsequently were confirmed to have GWpUPD. Further trio SNP genotyping analysis using SNP-based chromosomal microarray revealed androgenetic biparental chimera as the underlying cause. Finally, we highlighted the importance of recognizing GWpUPD as a possible cause in a fetus presenting with BWS phenotype, as it carried a different disease prognosis, tumor predisposition, manifestations of other imprinting disorders, and possibility in unmasking autosomal recessive disorders from the paternal alleles.

Adaptive risk prediction system with incremental and transfer learning.

Currently, popular methods for prenatal risk assessment of fetal aneuploidies are based on multivariate probabilistic modelling, that are built on decades of scientific research and large-scale multi-center clinical studies. These static models that are deployed to screening labs are rarely updated or adapted to local population characteristics. In this article, we propose an adaptive risk prediction system or ARPS, which considers these changing characteristics and automatically deploys updated risk models. 8 years of real-life Down syndrome screening data was used to firstly develop a distribution shift detection method that captures significant changes in the patient population and secondly a probabilistic risk modelling system that adapts to new data when these changes are detected. Various candidate systems that utilize transfer -and incremental learning that implement different levels of plasticity were tested. Distribution shift detection using a windowed approach provides a computationally less expensive alternative to fitting models at every data block step while not sacrificing performance. This was possible when utilizing transfer learning. Deploying an ARPS to a lab requires careful consideration of the parameters regarding the distribution shift detection and model updating, as they are affected by lab throughput and the incidence of the screened rare disorder. When this is done, ARPS could be also utilized for other population screening problems. We demonstrate with a large real-life dataset that our best performing novel Incremental-Learning-Population-to-Population-Transfer-Learning design can achieve on par prediction performance without human intervention, when compared to a deployed risk screening algorithm that has been manually updated over several years.

Long term outcome of second twins born to mothers who attempted vaginal delivery a retrospective study.

OBJECTIVE: To evaluate mortality and long term neurodevelopmental outcomes of the second twins born to mothers who attempted vaginal delivery. STUDY DESIGN: Two hundred and twenty-seven eligible cases of second twin born to mothers who attempted vaginal delivery were identified retrospectively in a ten-year period. Information on adverse long term outcomes (a composite of mortality and neurodevelopmental disorders) were retrieved from their electronic medical record, and the risk factors were determined. RESULTS: The median follow-up duration was 8 years (range 4-13 years). Adverse composite long term outcomes were observed in 6.6% (15/227). Gestation at delivery < 32 week (p = 0.001) and inter-twin delivery interval of > 30 min (P = 0.000) were significantly associated with adverse long term outcomes of the second twin on multivariate analysis. Second twins in the combined vaginal- caesarean birth group had no significant increase in adverse outcomes compared to those in the vaginal-vaginal birth group. CONCLUSION: Adverse long term outcomes were uncommon among second twins born to mothers who attempted vaginal delivery. Adverse outcomes were associated with prematurity and inter-twin delivery interval of more than 30 min, but not with actual mode of delivery.

Health professionals' involvement and information provision in genetic counseling following prenatal diagnosis of sex chromosome aneuploidy in Hong Kong.

This study supports training in genetic counseling for obstetricians and adoption of a multidisciplinary approach in the counseling process following prenatal diagnosis of sex chromosome aneuploidy.

Body mass index at 11-13 weeks' gestation and pregnancy complications in a Southern Chinese population: a retrospective cohort study.

OBJECTIVE: To assess the association between body mass index (BMI) and adverse pregnancy outcomes. MATERIALS AND METHODS: A multicentre retrospective cohort study was conducted in three hospitals in Hong Kong including 67,248 women with singleton pregnancy at 11-13 weeks between 2010 and 2016. The relationship between maternal BMI and (1) miscarriage or stillbirth, (2) development of preeclampsia (PE), (3) gestational hypertension (GH), (4) development of gestational diabetes mellitus (GDM), (5) spontaneous preterm delivery (sPTD) <34 and <37 weeks, (6) delivery of a small for gestational age (SGA) or large for gestational age (LGA) neonate, (7) caesarean section (CS), and (8) postpartum haemorrhage (PPH) were examined after adjusting for confounding factors. RESULTS: The prevalence of maternal overweight (BMI 25-29.9 kg/m2) and obesity (BMI ≥30 kg/m2) were 13.2% and 2.9%, respectively. Women with a BMI ≥30 kg/m2 were nine times more likely to develop GH (95%CI 7.3-11.7), five times more likely to develop PE (95%CI 4.3-6.8) and GDM (95%CI 5.0-6.5) and 1.5-2 times more likely to deliver SGA/LGA neonate. sPTD, required delivery by CS and developed PPH, than those with a BMI of 18.5-22.9 kg/m2, and that maternal underweight (BMI <18.5 kg/m2) significantly reduced the risk of GDM, delivery by CS, and PPH. Increased risk of subsequent development of adverse outcomes was observed when BMI was ≥23.0 kg/m2. CONCLUSIONS: Maternal overweight and obesity are associated with an increased risk for subsequent development of various pregnancy complications. The need of increased awareness and health surveillance is essential when BMI ≥23 kg/m2.

Decision outcomes in women offered noninvasive prenatal test (NIPT) for positive Down screening results.

In this first Asian study, the decision outcomes (decision conflict, decision regret, and anxiety) of 262 pregnant women offered noninvasive prenatal test (NIPT) for high-risk Down screening results were assessed. Decision conflict was experienced by 3.5% and level of decisional regret low (mean score 15.7, 95%CI 13.2-18.3). All 13 cases of decisional regret were NIPT acceptors. Elevated anxiety was experienced by 55.9% at the time of decision making about NIPT and persistent in 30.3%. Insufficient knowledge about NIPT was associated with elevated anxiety at decision making (p = .011) and with decisional regret (p = .016). Decisional regret was associated with prolonged anxiety (p = .010).

Pregnancy outcomes of women randomized to receive real versus placebo acupuncture on the day of fresh or frozen-thawed embryo transfer.

INTRODUCTION: Acupuncture is commonly used in various aspect of Western medicine in recent years including in-vitro fertilization (IVF) treatment. Although there are many clinical trials of acupuncture in IVF and the Cochrane meta-analysis did not find benefit of adjuvant acupuncture for IVF, there is no report on the pregnancy outcomes of women who had received acupuncture during their IVF treatment. OBJECTIVES: To compare the pregnancy outcomes of women randomized to receive real versus placebo acupuncture during their IVF treatment. METHODS: A retrospective chart review was performed on the 212 women with on-going pregnancies after receiving real or placebo acupuncture by sterile disposable stainless steel needles or Streitberger's placebo needles to the acupoints before and after the embryo transfer on the day of fresh or frozen-thawed embryo transfer. The pregnancy outcomes were obtained from the Hospital Authority Clinical Management System for deliveries in the public sector or from a self-returned questionnaire if those in the private sector. RESULTS: No significant differences were found between the demographics of the two groups including their age, gravida, parity and the duration of subfertility. Maternal adverse outcomes including gestational diabetes and hypertensive disorder were comparable for the real acupuncture group (35.3% and 4.4% respectively) and the placebo acupuncture group (39.7% and 5.5% respectively). None of the patients had placenta accreta. The preterm delivery (<37 weeks gestation) rate in the real acupuncture group (23/86, 26.7%) was similar to that in the placebo acupuncture group (25/97, 25.8%). No statistical significant difference was found in the mode of delivery. There were no significant differences between the two groups for Apgar scores and birthweight. CONCLUSION: Acupuncture during IVF treatment does not influence pregnancy outcomes.

Parental decisions following prenatal diagnosis of sex chromosome aneuploidy in Hong Kong.

AIM: According to the published work, pregnancy termination rates due to prenatal diagnosis of fetal sex chromosome aneuploidies (SCA) vary widely. Some potentially modifiable and non-modifiable factors have been reported to be associated with parental decision. This study aimed to evaluate the rate of pregnancy termination for fetal SCA and the factors influencing parents' decisions in Hong Kong. METHODS: This was a 21-year retrospective cohort study of parents' decisions following prenatal diagnosis of SCA. Univariate and multivariate analyses for the association between demographic factors, prenatal factors, or counseling provided and decision-making were conducted. RESULTS: The study included 399 pregnancies with prenatal diagnosis of SCA and the overall termination rate was 55.6% (91.7%, 48.0%, 23.4%, 4.8%, and 22.7% for 45,X, 47,XXY, 47,XXX, 47,XYY, and mosaicism, respectively). Pregnancies with ultrasound abnormalities were associated with higher termination rates than pregnancies with normal ultrasound findings (91.3% vs 28.3%, P < 0.0001). From multivariate regression analysis on 226 pregnancies with normal ultrasound examination, a higher likelihood to terminate was found in pregnancies affected by 45,X and 47,XXY (adjusted odds ratio, 4.72, P < 0.0001). Increased maternal age and history of infertility were associated with lower likelihood to terminate (adjusted odds ratio, 0.9, P = 0.012; and 5.12, P = 0.038, respectively). The pregnancy termination rate declined over time. CONCLUSION: A significant correlation was found between the termination of SCA-affected pregnancy and the presence of fetal sonographic abnormalities, type of SCA, maternal age, and presence of infertility.