Incidence of neonatal sepsis after universal antenatal culture-based screening of group B streptococcus and intrapartum antibiotics: A multicentre retrospective cohort study.

OBJECTIVE: To compare the incidences of early and late-onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E. coli) before and after implementation of universal screening and intrapartum antibiotics prophylaxis (IAP). DESIGN: Retrospective cohort study. SETTING: Eight public hospitals and 31 Maternal and Child Health Centres (in Hong Kong. POPULATION: 460 552 women attending routine antenatal service from 2009 to 2020. METHODS: Universal culture-based GBS screening has been offered to eligible women since 2012. Total births, GBS screening tests, maternal GBS colonisation and neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database. MAIN OUTCOME MEASURES: Maternal GBS colonisation rate, early- and late-onset neonatal sepsis (including GBS and E. coli). RESULTS: Of 318 740 women with universal culture-based screening, 63 767 women (20.0%) screened positive. After implementation of GBS screening and IAP, the incidence of early-onset neonatal sepsis decreased (3.25 versus 2.26 per 1000 live births, p < 0.05), including those caused by GBS (1.03 versus 0.26 per 1000 live births, p < 0.05). Segmented regression showed that change in early-onse GBS sepsis incidence after screening was the only significant variable in the outcome trend. There was no significant evidence of increase in incidence of late-onset neonatal sepsis including those caused by GBS. CONCLUSIONS: Universal culture-based GBS screening and IAP were associated with reduction in early-onset neonatal sepsis including GBS disease. Although an increase in incidence of late-onset neonatal sepsis including those caused by GBS cannot be totally ruled out, we did not identify significant evidence that this occurred.

Imaging of placental circulations by 4D sonography with high-definition flow and spatiotemporal image correlation technology.

Conventionally, two- and three- dimensional color Doppler ultrasonography are used to examine the placental vascularization, but there are limitations in the examinations. In this report, spatiotemporal image correlation (STIC) volume acquisition in high-definition flow, displayed in glass-body mode was used to study the placental vascularization in eight pregnancies. At 20 weeks' gestation, STIC technique allowed visualization of blood flow in the intraplacental branches of the umbilical artery (IPB) and the spiral artery jets in a cardiac cycle. In particular, blood flow from a mega jet penetrating more than half of the placental thickness was demonstrated. Small blood flow from a tertiary order branch of the IPB traversing the placenta and sharply diminishing into the uterine wall was also demonstrated. There were differences in the IPB pattern between normal pregnancies and pregnancies at risk of fetal growth restriction/pre-eclampsia. There were also differences in the appearance of IPB between 20- and 33-weeks' gestation. The results of this report support that it is feasible to use STIC technology to study the placental vascularization. This novel application of STIC technology can increase the understanding of the complex vascularization.

Imaging of fetal precordial venous system by four-dimensional ultrasound with spatiotemporal image correlation technology.

Despite the use of two- and three- dimensional color Doppler ultrasonography, the prenatal sonographic evaluation of precordial venous system remains difficult. Spatiotemporal image correlation (STIC) technology has been well described for the assessment of the fetal heart, but not of precordial venous system. As demonstrated in this report, it is feasible to use four-dimensional ultrasound with STIC rendered volume in glass-body mode and tomographic ultrasound imaging to image this system including the connection and drainage of the ductus venosus, hepatic veins and inferior vena cava to the fetal heart. This novel approach can increase the understanding of this venous system.

Hypomanic symptoms in early pregnancy: prevalence and associated factors.

Given that the perinatal period is a time of increased risk for pregnant women to manifest mental health problems, the identification of antenatal hypomanic symptoms is particularly important. However, data on antenatal hypomanic symptoms is lacking. The present study was aimed at filling this research gap by investigating the prevalence of hypomanic symptoms, including the "active-elated" and "irritable/risk-taking" sides of hypomanic symptoms at the first trimester, and examining their associations with anxiety and depressive symptoms at the following time points: the first trimester, the second trimester, and up to 6-week postpartum. A prospective longitudinal design with a quantitative approach was adopted. A consecutive sample of 229 pregnant Chinese women in Hong Kong was assessed. Hypomanic symptoms were assessed with the Hypomania Checklist-32 (HCL-32). Of the sample, 43.6% had elevated levels of hypomanic symptoms in the first trimester. Multiple regression analysis showed that after adjusting for potential confounding factors, irritable/risk-taking symptoms were independently associated with higher anxiety symptoms in the first and second trimesters and in the 6-week postpartum period. Primary healthcare practitioners should be made aware of antenatal hypomanic symptoms in pregnant women to facilitate early identification and intervention for anxiety and depression to improve the well-being of both mothers and infants.

Prospective risk of stillbirth and neonatal complications for monochorionic diamniotic and dichorionic diamniotic twins after 24 weeks of gestation.

INTRODUCTION: Our study compared the prospective risks of intrauterine fetal death (IUFD), neonatal death (NND), perinatal death (PND), and neonatal morbidities in monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies. METHODS: This retrospective cohort study included twin pregnancies who had antenatal care and delivery in a public hospital from 2011 to 2018. Exclusion criteria included monoamnionicity, one/both twin miscarriage, twin-twin transfusion syndrome, or lethal congenital abnormalities. All twins were managed in multiple pregnancy clinic with standardized protocols. Gestational age-specific IUFD, NND, PND, and neonatal morbidity rates were compared according to chorionicity. RESULTS: Three hundred seventy-eight MCDA and 1282 DCDA twins were included. MCDA twins had higher risks of PND (1.9% vs. 0.7% in DCDA twins, p = 0.05), composite neonatal morbidity (p = 0.01), preterm delivery (p < 0.01), and low birth weight (p < 0.01). The prospective risk of IUFD was 0.6% and 0.4% for MCDA and DCDA twins, respectively after 34 weeks' gestation. No NND occurred among deliveries after 30 weeks. The risk of neonatal morbidity of MCDA twins fell from 22.7% at 34 weeks to 2.7% at 37 weeks (p < 0.01). For DCDA twins, the risk of morbidity fell insignificantly from 36 to 38 weeks (4.0% vs. 3.4%, p = 0.60). Logistic regression analysis suggested that the increased risk of perinatal morbidities was related to the higher rate of preterm delivery in MCDA twins rather than chorionicity. CONCLUSION: With close fetal monitoring, the risk of late IUFD in twin pregnancies without major complications is low. Perinatal morbidity can be minimized by avoiding late preterm deliveries in twin pregnancies.

Cost-effectiveness analysis of chromosomal microarray as a primary test for prenatal diagnosis in Hong Kong.

BACKGROUND: Chromosomal microarray (CMA) has been shown to be cost-effective over karyotyping in invasive prenatal diagnosis for pregnancies with fetal ultrasound anomalies. Yet, information regarding preceding and subsequent tests must be considered as a whole before the true cost-effectiveness can emerge. Currently in Hong Kong, karyotyping is offered free as the standard prenatal test while genome-wide array comparative genome hybridization (aCGH), a form of CMA, is self-financed. A new algorithm was proposed to use aCGH following quantitative fluorescent polymerase chain reaction (QF-PCR) as primary test instead of karyotyping. This study aims to evaluate the cost-effectiveness of the proposed algorithm versus the current algorithm for prenatal diagnosis in Hong Kong. METHODS: Between November 2014 and February 2016, 129 pregnant women who required invasive prenatal diagnosis at two public hospitals in Hong Kong were prospectively recruited. The proposed algorithm was performed for all participants in this demonstration study. For the cost-effectiveness analysis, cost and outcome (diagnostic rate) data were compared with that of a hypothetical scenario representing the current algorithm. Further analysis was performed to incorporate women's willingness-to-pay for the aCGH test. Impact of government subsidies on the aCGH test was explored as a sensitivity analysis. RESULTS: The proposed algorithm dominated the current algorithm for prenatal diagnosis. Both algorithms were equally effective but the proposed algorithm was significantly cheaper (p ≤ 0.05). Taking into account women's willingness-to-pay for an aCGH test, the proposed algorithm was more effective and less costly than the current algorithm. When the government subsidy reaches 100%, the maximum number of diagnoses could be made. CONCLUSION: By switching to the proposed algorithm, cost saving can be achieved whilst maximizing the diagnostic rate for invasive prenatal diagnosis. It is recommended to implement aCGH as a primary test following QF-PCR to replace the majority of karyotyping for prenatal diagnosis in Hong Kong.

Course, risk factors, and adverse outcomes of disordered eating in pregnancy.

OBJECTIVE: Although eating disorders in pregnancy have been studied extensively, little research attention has been given to disordered eating. The objectives of the present study were to determine the prevalence and levels of disordered eating in the perinatal period, and to identify risk factors and adverse outcomes of disordered eating during pregnancy. METHOD: A prospective longitudinal design with a quantitative approach was adopted. A consecutive sample of 1,470 Chinese pregnant women from hospitals in Hong Kong was assessed using standardized instruments at five time points from the first trimester to 6 months postpartum. RESULTS: The levels of disordered eating changed significantly across trimesters. Higher levels of disordered eating in pregnancy were significantly associated with higher levels of disordered eating at 6 weeks and 6 months postpartum, greater anxiety and depressive symptoms, lower 1-min Apgar scores, and abnormal birth weight. DISCUSSION: The present study pointed to the need for more research and clinical attention to antenatal disordered eating given that it is associated with anxiety, depression, postpartum disordered eating and obstetric outcomes.

The effect of a telephone-based cognitive behavioral therapy on quality of life: a randomized controlled trial.

Health-related quality of life (HRQoL) has emerged as a major public health concern in perinatal care. The purpose of this study was to examine the effect of telephone-based cognitive behavioral therapy (T-CBT) on HRQoL among Chinese mothers at risk of postnatal depression at 6 weeks and 6 months postpartum. A multi-center randomized controlled trial was conducted at the postnatal units of three regional hospitals. Three hundred and ninety-seven women at risk of postnatal depression were recruited and were randomly assigned to the T-CBT (n = 197) or usual care (n = 200). Assessment was conducted at baseline, 6 weeks and 6 months postpartum for HRQoL. Women in the T-CBT experienced greater improvement in the physical component of HRQoL from baseline to 6 weeks and 6 months postpartum than the usual care group. At 6 months postpartum, the T-CBT group also experienced better HRQoL in the mental component of HRQoL than the usual care group. The T-CBT appears to be feasible and effective in improving HRQoL in women at risk of postnatal depression in the primary care practice.

The Effect of Telephone-Based Cognitive-Behavioral Therapy on Postnatal Depression: A Randomized Controlled Trial.

BACKGROUND: Cognitive-behavioral therapy (CBT) is one of the most effective interventions for postnatal depression. However, few studies have evaluated the effect of CBT delivered via telephone for newborn mothers. The purpose of this study was to evaluate the efficacy of telephone-based CBT for postnatal depression at 6 weeks and 6 months postpartum. METHODS: A multisite randomized controlled trial was conducted in the postnatal units at 3 regional hospitals in Hong Kong. A total of 397 women with an Edinburgh Postnatal Depression Scale (EPDS) score ≥10 on the second or third day postpartum were randomized to receive telephone-based CBT (n = 197) or standard care (n = 200). Primary outcome was the total EPDS score. A cutoff score of 9/10 on the EPDS was used to define women at risk of postnatal depression. RESULTS: Telephone-based CBT was associated with significantly lower depressive symptoms compared with standard care, when assessed at 6 weeks postpartum in the subgroups of mothers with minor depression (EPDS 10-12; difference = 1.90, 95% CI: 0.72-3.08; p = 0.002) and major depression (EPDS ≥13; difference = 5.00, 95% CI: 3.12-6.88; p < 0.001). The effect was sustained at 6 months postpartum in the subgroup with minor depression (difference = 1.20, 95% CI: 0.09-2.32; p = 0.034) but not significant in the subgroup with major depression (difference = 1.69, 95% CI: -0.10-3.47; p = 0.064). The proportion of women who satisfied our definition of postnatal depression was significantly lower in the intervention group at 6 weeks (difference = 23.3%, 95% CI: 13.7-33.0%; p < 0.001) and 6 months postpartum (difference = 11.4%, 95% CI: 1.9-20.8%; p = 0.019). CONCLUSIONS: Telephone-based CBT produced a significantly greater reduction in depressive symptoms than standard care during the postpartum period.

Knowledge and future preference of Chinese women in a major public hospital in Hong Kong after undergoing non-invasive prenatal testing for positive aneuploidy screening: a questionnaire survey.

BACKGROUND: Despite the non-invasive nature of non-invasive prenatal testing (NIPT), there is still a need for a separate informed consent process before testing. The objectives of this study are to assess (a) knowledge and preferences of Chinese women in a major public hospital in Hong Kong who underwent NIPT, and (b) whether their knowledge and preferences differ depending on womens' characteristics and sources of information. METHODS: Setting: Prenatal diagnosis and counselling clinic. Between February 2012 and September 2013, a questionnaire survey was distributed to all women who underwent NIPT after positive aneuploidy screening. As a pilot study, ten knowledge questions were designed based on the rapid response statement on Prenatal Detection of Down Syndrome using Massively Parallel Sequencing from the International Society for Prenatal Diagnosis in 2011. The source of women's knowledge and their preferences were also evaluated. While conventional screening was publicly funded, NIPT was not. Differences between subgroups were compared using chi square tests and logistic regression analysis. RESULTS: Of 152 women who underwent NIPT, 135 (88.8%) completed their questionnaires. More than 90% of women recognised the possibility of false positive and false negative results. Slightly more than 70% of women knew the inferior sensitivity of NIPT compared to an invasive test, and the possibility of an uninformative test result, but were not aware of the complicated aspects of NIPT. Pregnant women with an advanced level of education or those who underwent NIPT before 15 weeks provided answers that was more accurate by around 10-20% in two to three knowledge questions than those without. These associations were confirmed by multivariate logistic regression analysis. The women received information on NIPT largely from their private doctors (47.4%) and web (41.5%). In their future pregnancies, more women would opt for NIPT (a self-financed item) after positive screening ('free' in a public hospital) (57.8%) than as a primary screening (30.4%). CONCLUSIONS: It is feasible to use a questionnaire based on the ISPD statement on NIPT to assess women's knowledge of the test. The Chinese women who underwent NIPT recognised the limitations, but did not understand the complicated aspects. More information should be provided by health care professionals in order to facilitate an informed choice by patients. More women preferred NIPT as a contingent test than as a primary screening probably because of its high cost.

Recommendations on routine mid-trimester anomaly scan.

The purpose of this paper is to discuss the minimal requirements of the routine mid-trimester anomaly scan in Asian countries after taking into account various factors, including local circumstances, medical practice, guidelines, and availability of experienced sonographers and high-resolution ultrasound machines, which affect the prenatal detection rate of fetal anomalies. In general, a routine mid-trimester anomaly scan includes the assessment of the number of fetuses, fetal cardiac activity, size, anatomy, liquor and placental location. The most controversial issue is which fetal structures should at least be examined. We discussed the requirements of a basic routine scan, as well as the optional views, which can be obtained if feasible to improve the detection of fetal, placental or maternal abnormalities. Routine anomaly scan remains a clinical challenge.

Application of Color Doppler with 3- and 4-Dimensional Ultrasonography in the Prenatal Evaluation of Fetal Extracardiac and Placental Abnormalities.

Using color Doppler flow imaging or high-definition flow imaging with three-dimensional volume or spatio-temporal image correlation (STIC) in the glass-body mode allows displaying both gray-scale and color information of the heart cycle-related flow events and vessel spatial relationship. Conventionally, STIC in the glass-body mode has been used to examine the fetal heart and assess heart defects. Recently, a novel application of STIC in the visualization of abdominal precordial veins and intraplacental vascularization in singleton pregnancies has been reported. The aim of this present review is to discuss the use of color Doppler with three- and four-dimensional ultrasonography in the evaluation of extracardiac, placental, umbilical cord and twin abnormalities with examples. The glass-body mode is complementary to conventional 2D ultrasonography. Further studies are required to investigate use of the glass-body mode in the assessment of intraplacental vascularization in singleton and twin pregnancies.

Diagnostic Yield of Exome Sequencing in Fetuses with Sonographic Features of Skeletal Dysplasias but Normal Karyotype or Chromosomal Microarray Analysis: A Systematic Review.

Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing has rapidly revolutionized molecular diagnostic approaches in fetuses with structural anomalies. This review studies the additional diagnostic yield of prenatal exome sequencing in fetuses with prenatal sonographic features of skeletal dysplasias. This was a systematic review by searching PubMed for studies published between 2013 and July 2022 that identified the diagnostic yield of exome sequencing after normal karyotype or chromosomal microarray analysis (CMA) for cases with suspected fetal skeletal dysplasias based on prenatal ultrasound. We identified 10 out of 85 studies representing 226 fetuses. The pooled additional diagnostic yield was 69.0%. The majority of the molecular diagnoses involved de novo variants (72%), while 8.7% of cases were due to inherited variants. The incremental diagnostic yield of exome sequencing over CMA was 67.4% for isolated short long bones and 77.2% for non-isolated cases. Among phenotypic subgroup analyses, features with the highest additional diagnostic yield were an abnormal skull (83.3%) and a small chest (82.5%). Prenatal exome sequencing should be considered for cases with suspected fetal skeletal dysplasias with or without a negative karyotype or CMA results. Certain sonographic features, including an abnormal skull and small chest, may indicate a potentially higher diagnostic yield.

Outcome of twin pregnancies after amniocentesis.

AIM: The aim of this study was to assess the miscarriage and fetal loss rates of twin pregnancies after amniocentesis. MATERIAL AND METHODS: The outcome of 140 twin pregnancies that had amniocentesis performed from 1997 to 2006 was reviewed. RESULTS: Among 140 twin pregnancies with amniocentesis, 35 were excluded (fetuses with structural anomalies, post-selective feticide, abnormal fetal karyotype, twin-twin transfusion syndrome [TTTS], termination of pregnancy, and unknown outcome). For the remaining 105 twin pregnancies, 102 had live births of all fetuses. One dichorionic twin had silent miscarriage of one fetus at 23 weeks. Another dichorionic twin had intrauterine death of one fetus at unknown gestation. One patient had preterm delivery at 32 weeks with neonatal death of one twin due to severe intrauterine growth restriction. The miscarriage rate (one or both fetuses) for twins before 24 weeks was 0.96% (1/105), the pregnancy loss (one or both fetuses) within 4 weeks of amniocentesis was 0.96% (1/105). The total fetal loss rate was 0.96% (2/210) for twins. CONCLUSION: Our cohort showed a low fetal loss rate after amniocentesis for uncomplicated twin pregnancies.

Update on Color Flow Imaging in Obstetrics.

Color flow imaging (CFI), being non-invasive, is commonly used in obstetrics to study the fetal and placental circulations. The conventional CFI modes include color Doppler flow imaging (CDFI) and power Doppler imaging (PDI). In recent years, there is increasing use of new modes, including high-definition flow imaging (HDFI), radiant flow, microvascular flow imaging (MVFI), and three-/four-dimensional rendering in glass-body mode. Compared to CDFI, HDFI can show a higher resolution and sensitivity and allow the detection of slower flows. MVFI increases the sensitivity to fine or low-flow vessels while producing little or no motion artifacts. Radiant flow shows the blood flow with a sense of depth and reduces blood overflow. Glass-body mode, showing both gray-scale and color-flow information, can demonstrate the heart-cycle-related flow events and the vessel spatial relationship. In this review, the characteristics and applications of the various CFI modes in obstetrics are discussed. In particular, how these new technologies are integrated in detailed diagnostic and early morphology scans is presented.

Applications of Advanced Ultrasound Technology in Obstetrics.

Over the years, there have been several improvements in ultrasound technologies including high-resolution ultrasonography, linear transducer, radiant flow, three-/four-dimensional (3D/4D) ultrasound, speckle tracking of the fetal heart, and artificial intelligence. The aims of this review are to evaluate the use of these advanced technologies in obstetrics in the midst of new guidelines on and new techniques of obstetric ultrasonography. In particular, whether these technologies can improve the diagnostic capability, functional analysis, workflow, and ergonomics of obstetric ultrasound examinations will be discussed.

Brief Advice, Nicotine Replacement Therapy Sampling, and Active Referral for Expectant Fathers Who Smoke Cigarettes: A Randomized Clinical Trial.

Importance: Pregnancy presents an opportunity to engage expectant fathers in smoking cessation, but evidence from randomized clinical trials is scarce. Objective: To evaluate the effectiveness of a proactive, combined intervention for smoking cessation in expectant fathers. Design, Setting, and Participants: This pragmatic randomized clinical trial in prenatal clinics in 7 public hospitals in Hong Kong proactively recruited and enrolled 1053 participants from October 10, 2018, to February 8, 2020. Included male adults were 18 years or older, smoked cigarettes daily in the past 3 months, had partners who were pregnant and nonsmoking in the past 30 days, and had a landline or mobile telephone number for follow-up. These participants were randomized to either the intervention group or the control group. The primary analyses used an intention-to-treat approach. Interventions: The intervention group received brief cessation advice, a 1-week free sample of nicotine replacement therapy (NRT), and active referral to a community-based smoking cessation service. The control group received only brief cessation advice with a leaflet on the hazards of perinatal exposure to tobacco smoke and the toll-free quitline telephone number. Main Outcomes and Measures: The primary outcome was biochemically validated tobacco abstinence at 6 months after intervention initiation defined by an exhaled carbon monoxide level of 3 parts per million or lower. The secondary outcomes included self-reported 24-week continuous abstinence at 6 months after intervention initiation as well as 7-day point prevalence abstinence, use of any NRT, and use of a smoking cessation service at 3 and 6 months after intervention initiation. Results: All 1053 randomized participants were male adults with a mean (SD) age of 33.8 (6.9) years. The retention rate at 6-month follow-up was 80.7%. The primary outcome of biochemically validated tobacco abstinence at 6 months after intervention initiation was significantly higher in the intervention group than in the control group (6.8% [36 of 527 participants] vs 3.6% [19 of 526]; odds ratio [OR], 1.96; 95% CI, 1.11-3.46; P = .02). The main secondary outcomes of self-reported 24-week continuous abstinence at 6 months (OR, 1.87; 95% CI, 1.08-3.23; P = .03) and 7-day point prevalence abstinence at 3 months (OR, 1.48; 95% CI, 1.05-2.09; P = .03) and 6 months (OR, 1.74; 95% CI, 1.29-2.34; P < .001) were also significantly higher in the intervention group. The intervention group had a significantly higher increase in perceived family harmony (score range, 0-10, with a higher score indicating a higher level of harmony) from baseline to 6 months (B = 0.28; 95% CI, 0.063-0.50; P = .01). Conclusions and Relevance: This trial found that combining brief advice with a 1-week sample of NRT and referral to smoking cessation programs nearly doubled the odds that expectant fathers who smoked would achieve validated abstinence compared with providing brief advice alone. The intervention was also effective in promoting family harmony. Trial Registration: ClinicalTrials.gov Identifier: NCT03671707.

Associations of body dissatisfaction with anxiety and depression in the pregnancy and postpartum periods: A longitudinal study.

BACKGROUND: Pregnancy is a time of increasing vulnerability to the development of body dissatisfaction, anxiety, and depression. The present study aims to examine associations of body dissatisfaction with anxiety and depression at the following points: 6 months before pregnancy (retrospective report); in the first, second, and third trimesters of pregnancy; and up to 6 weeks postpartum. METHODS: A prospective longitudinal design with a quantitative approach was adopted. A consecutive sample of 1,371 Chinese pregnant women in Hong Kong was assessed using standardized instruments at four time points. RESULTS: A mixed-effects model with repeated measures revealed that body dissatisfaction and depression symptoms changed across different stages of pregnancy. Hierarchical multiple regressions showed that, after adjusting for the identified risk factors, body dissatisfaction before and during pregnancy were positively associated with antenatal anxiety and depression symptoms. Concurrent body dissatisfaction was positively associated with postpartum depression symptoms. LIMITATIONS: There was a high attrition rate in the follow-up assessments. Antenatal anxiety symptoms were assessed using the scale for general anxiety, which may not adequately capture the experience of anxiety among pregnant women. CONCLUSIONS: Primary healthcare practitioners should be made aware of body dissatisfaction among pregnant women in order to facilitate early intervention for anxiety and depression, because untreated psychological disturbance during pregnancy may persist into the postpartum period.

Brief cessation advice, nicotine replacement therapy sampling and active referral (BANSAR) for smoking expectant fathers: Study protocol for a multicentre, pragmatic randomised controlled trial.

BACKGROUND: Pregnancy presents a teachable moment to engage male smokers whose partners are pregnant in smoking cessation. Evidence on how to approach and help these smokers quit smoking in antenatal settings has remained scarce. This paper presents the rationale and study design of a trial which aims to evaluate the effectiveness of a brief intervention model for promoting smoking cessation in expectant fathers. METHODS: BANSAR is a pragmatic randomised controlled trial conducted in antenatal clinic in seven public hospitals in Hong Kong, China. An estimated 1148 fathers who smoke at least one cigarette daily and whose partners are pregnant and non-smoking will be randomised (1:1) to receive brief advice combined with 1-week sample of nicotine replacement therapy (NRT) and active referral to smoking cessation services, or brief advice only (usual care). Outcome will be assessed at 3 and 6 months after treatment initiation. The primary outcome is carbon monoxide-verified (<4 part per million) abstinence at 6 months post-treatment initiation. Secondary outcomes include self-reported 7-day point-prevalence abstinence and 24-week continuous abstinence, use of smoking cessation service and NRT and quit attempt, and smoking reduction, change in nicotine dependence and intention to quit in continuing smokers. COMMENT: This trial will provide real-world evidence on the effectiveness of a combined brief intervention model for smoking cessation in expectant fathers, an understudied population. The findings may be particularly relevant to low and middle-income countries, where male-to-female smoking ratios and birth rates tend to be higher than higher-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT03671707.

The KLHL40 c.1516A>C is a Chinese-specific founder mutation causing nemaline myopathy 8: Report of six patients with pre- and postnatal phenotypes.

BACKGROUND: Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. METHODS: We report six cases of nemaline myopathy 8 which involves the c.1516A>C variant, from five unrelated families of non-consanguineous southern Chinese. The pre- and postnatal phenotypes of these cases were reviewed with emphasis on prenatal clinical features. Genetic testing for the founder mutation was performed on three patients with homozygous mutations. RESULTS: Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet. Two pregnancies were terminated. Four live-born patients had postnatal features typical of nemaline myopathy 8. The length of survival ranged from 49 days to 17 months, with respiratory failure and infections being the principal causes of death. Haplotype analysis in three patients with homozygous mutation showed a shared haplotype block of 1.1727 cM spanning over the c.1516A>C variant, suggesting it is a southern Chinese-specific founder mutation. CONCLUSION: Analysis of the KLHL40 c.1516A>C variant should be considered in prenatal diagnosis of Chinese pregnant patients with suspected congenital neuromuscular disorders or with significant family history of congenital myopathies.