Adverse obstetric and neonatal outcomes associated with maternal schizophrenia-spectrum disorders and prenatal antipsychotic use: a meta-analysis of 37,214,330 pregnancy deliveries and propensity-score weighted population-based cohort study assessing confounder dependency of risk estimates.

Studies demonstrated increased obstetric and neonatal complications in women with schizophrenia-spectrum disorder (SSD), but most inadequately addressed confounders and rarely considered antipsychotic effects. We conducted a meta-analysis and a population-based cohort study evaluating associations of adverse obstetric/neonatal outcomes with SSD and prenatal antipsychotic use. In the meta-analysis, we searched four databases from inception to October-31-2023 and generated pooled risk estimates using random-effect models. In the cohort study, we identified women aged 15-50 years with SSD-diagnosis from electronic-heath-record database of public healthcare-services who delivered first/singleton children between 2003 and 2018 in Hong Kong. Propensity-score weighted regression-analyses incorporating important confounders including maternal pre-existing and gestational morbidities, substance/alcohol abuse, and psychotropic use, were performed to assess risk of adverse obstetric/neonatal outcomes in SSD-women versus non-SSD-women, and subsequently treated-SSD and untreated-SSD subgroups to disentangle effects of SSD from antipsychotic exposure. The meta-analysis (studies = 18, women = 37,214,330, including 42,926 SSD-women) found significant associations of SSD with 12 of 17 analyzed negative obstetric/neonatal outcomes (with pooled relative risk ranged:1.12-2.10), including placental complications, induced labor, Caesarean delivery, fetal distress, stillbirth, preterm birth, small-for-gestational-age, low birth weight, low APGAR scores, neonatal and post-neonatal deaths. However, the cohort study (466,358 women, including 804 SSD-women) revealed that elevated risk of most study outcomes in unadjusted-models were markedly-attenuated or became non-significant in propensity-score weighted adjusted-models, except index-delivery hospitalization ≥7 days (odds ratio [OR] = 1.76 [95% CI = 1.33-2.34]), preterm birth (OR = 1.48 [95% CI = 1.09-2.00]) and neonatal special-care admission (OR = 1.65 [95% CI = 1.35-2.01]). Apart from higher neonatal special-care admission in treated-SSD than untreated-SSD women (OR = 1.75 [95% CI = 1.23-2.52]), no significant between-group differences emerged in other outcomes. In sum, elevated risk of most obstetric/neonatal complications reported in SSD-women might largely be explained by maternal physical comorbidities, substance/alcohol use disorders and other confounders. Interventions targeting modifiable maternal risk factors should be incorporated in prenatal care for SSD-women to minimize avoidable adverse outcomes.

Clinical algorithms for the monitoring and management of spontaneous, uncomplicated labour and childbirth.

AIM: To develop evidence-based clinical algorithms for the assessment and management of spontaneous, uncomplicated labour and vaginal birth. POPULATION: Pregnant women at any stage of labour, with singleton, term pregnancies considered to be at low risk of developing complications. SETTING: Health facilities in low- and middle-income countries. SEARCH STRATEGY: We searched for relevant published algorithms, guidelines, systematic reviews and primary research studies on Cochrane Library, PubMed, and Google on terms related to spontaneous, uncomplicated labour and childbirth up to 01 June 2023. CASE SCENARIOS: Three case scenarios were developed to cover assessments and management for spontaneous, uncomplicated first, second and third stage of labour. The algorithms provide pathways for definition, assessments, diagnosis, and links to other algorithms in this series for management of complications. CONCLUSIONS: We have developed three clinical algorithms to support evidence-based decision making during spontaneous, uncomplicated labour and vaginal birth. These algorithms may help guide health care staff to institute respectful care, appropriate interventions where needed, and potentially reduce the unnecessary use of interventions during labour and childbirth.

Medulla Tetrapanacis water extract alleviates inflammation and infection by regulating macrophage polarization through MAPK signaling pathway.

Medulla Tetrapanacis (MT) is a commonly used herb to promote lactation and manage mastitis in lactating mothers. However, its anti-inflammatory and anti-bacterial effects are currently unknown. We hypothesized that MT water extract possesses anti-inflammatory and anti-bacterial effects by modulating macrophage polarization to reduce the release of inflammatory mediators and phagocytosis via inactivation of MAPKs pathways. The chemical composition of the MT water extract was analyzed by UPLC-Orbitrap-mass spectrometry. The anti-inflammatory and anti-bacterial properties of the MT water extract were examined using LPS-stimulated inflammation and Staphylococcus aureus infection model in RAW 264.7 cells, respectively. The underlying mechanism of action of the MT water extract was also investigated. We identified eight compounds by UPLC-Orbitrap-mass spectrometry that are abundant within the MT water extract. MT water extract significantly suppressed LPS-induced nitric oxide, TNF-α and IL-6 secretion in RAW 264.7 cells which was accompanied by the promotion of macrophage polarization from pro-inflammatory towards anti-inflammatory phenotypes. MT water extract significantly suppressed the LPS-induced MAPK activation. Finally, MT water extract decreased the phagocytic capacity of the RAW 264.7 cells against S. aureus infection. MT water extract could suppress LPS-induced inflammation by promoting macrophages towards an anti-inflammatory phenotype. In addition, MT also inhibited the growth of S. aureus.

A prospective, double-blinded cohort study using quantitative fetal fibronectin testing in symptomatic women for the prediction of spontaneous preterm delivery.

BACKGROUND: Spontaneous preterm birth (PTB) affects 6.5% of deliveries in Hong Kong. Quantitative fetal fibronectin (fFN) is under-utilised as a test for PTB prediction in Hong Kong. Our objective was to evaluate the effectiveness of quantitative fFN in predicting spontaneous PTB in women with symptoms of threatened preterm labour (TPTL) in our population. METHODS: A prospective, double-blinded cohort study of women with a singleton gestation and TPTL symptoms presenting to a tertiary hospital in Hong Kong between 24 + 0 to 33 + 6 weeks was performed from 1st October 2020 and 31st October 2021. Women with vaginal bleeding, ruptured membranes, and cervical dilation > 3 cm were excluded. The primary outcome was to test the characteristics of quantitative fFN in predicting spontaneous PTB < 37 weeks. Secondary outcome was to investigate the relationship between fFN value and time to PTB. Test characteristics of quantitative fFN at different thresholds were evaluated. RESULTS: 48 women with TPTL were recruited. All had fFN testing at admission with the results being concealed from the obstetrician managing the patient. 10 mothers had PTB (< 37 weeks' gestation). 7/48 (15%) had a subsequent PTB within 14 days from testing and 5 (10%) delivered within 48 h. The negative predictive value (NPV) of predicting delivery within 14 days was 97.3% and 100% when using a cut-off of < 50ng/ml and < 10ng/ml respectively. Using > 200 ng/ml as cut-off can also reliably predict delivery within 48 h - 7 days with positive predictive value PPV of 100%; as well as PTB before 37 weeks. CONCLUSIONS: Quantitative fFN has predictive value for spontaneous PTB prediction in symptomatic women in a Hong Kong population. fFN concentration could help clinicians rule out PTB and avoid unnecessary interventions and hospitalisation.

Perceptions and Challenges of Telehealth Obstetric Clinics Among Pregnant Women in Hong Kong: Cross-Sectional Questionnaire Study.

BACKGROUND: Integrating telehealth in an obstetric care model is important to prepare for possible infection outbreaks that require social distancing and limit in-person consultations. To ensure the successful implementation of obstetric telehealth in Hong Kong, it is essential to understand and address pregnant women's concerns. OBJECTIVE: This study aimed to assess pregnant women's attitudes, concerns, and perceptions regarding telehealth obstetric clinic services in Hong Kong. METHODS: We conducted a prospective cross-sectional questionnaire study at Queen Mary Hospital between November 2021 and August 2022. Utilizing a 5-point rating scale, the questionnaire aimed to capture pregnant women's preferences, expectations, feasibility perceptions, and privacy concerns related to telehealth clinic services. We used statistical analyses, including chi-square tests and multinomial logistic regression, to compare questionnaire responses and investigate the association between advancing gestation and attitudes toward telehealth clinics. RESULTS: The study included 664 participants distributed across different pregnancy stages: 269 (40.5%) before 18 gestational weeks, 198 (29.8%) between 24 and 31 weeks, and 197 (29.7%) after delivery. Among them, 49.8% (329/664) favored face-to-face consultations over telehealth clinics, and only 7.3% (48/664) believed the opposite. Additionally, 24.2% (161/664) agreed that telehealth clinics should be launched for obstetric services. However, the overall preference for telehealth clinics was <20% for routine prenatal checkups (81/664, 12.2%) and addressing pregnancy-related concerns, such as vaginal bleeding (76/664, 11.5%), vaginal discharge (128/664, 19.4%), reduced fetal movement (64/664, 9.7%), uterine contractions (62/664, 9.4%), and suspected leakage of amniotic fluid (54/664, 8.2%). Conversely, 76.4% (507/664) preferred telehealth clinics to in-person visits for prenatal education talks, prenatal and postpartum exercise, and addressing breastfeeding problems. Participants were more comfortable with telehealth clinic tasks for tasks like explaining pregnancy exam results (418/664, 63.1%), self-administering urinary dipsticks at home (373/664, 56.4%), medical history-taking (341/664, 51.5%), and self-monitoring blood pressure using an electronic machine (282/664, 42.8%). %). During the postpartum period, compared to before 18 weeks of gestation, significantly more participants agreed that telehealth clinics could be an option for assessing physical symptoms such as vaginal bleeding (aOR 2.105, 95% CI 1.448-3.059), reduced fetal movement (aOR 1.575, 95% CI 1.058-2.345), uterine contractions (aOR 2.906, 95% CI 1.945-4.342), suspected leakage of amniotic fluid (aOR 2.609, 95% CI 1.721-3.954), fever (aOR 1.526, 95% CI 1.109-2.100), and flu-like symptoms (aOR 1.412, 95% CI 1.030-1.936). They were also more confident with measuring the symphysis-fundal height, arranging further investigations, and making diagnoses with the doctor via the telehealth clinic. The main perceived public health advantage of telehealth clinics was the shorter traveling and waiting time (526/664, 79.2%), while the main concern was legal issues from wrong diagnosis and treatment (511/664, 77.4%). CONCLUSIONS: Face-to-face consultation remained the preferred mode of consultation among the participants. However, telehealth clinics could be an alternative for services that do not require physical examination or contact. An increased acceptance of and confidence in telehealth was found with advancing gestation and after delivery. Enforcing stricter laws and guidelines could facilitate the implementation of telehealth clinics and increase confidence in their use among pregnant women for obstetric care.

Clinical presentation, investigation, underlying causes, and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage.

AIM: To evaluate the causes of miscarriage and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage. METHODS: Retrospective analysis of 170 consecutive second trimester miscarriages between 14 + 0 and 23 + 6 weeks recorded in the Clinical Data Analysis and Reporting System from 2012 to 2021. Cases were excluded if miscarriages occurred before 14 + 0 weeks of gestation, data were incomplete, or passage of the fetus happened before the clinical assessment. Cases were classified with a stepwise approach into three phenotypic groups including silent miscarriages (ST-SM), rupture of membranes (ST-ROM), and inevitable miscarriages (ST-IM) depending on the fetal heart pulsation and leakage of liquor at presentation. Clinical investigation of the underlying causes and the outcome of the subsequent pregnancy was then reviewed. RESULTS: There were 97 cases of ST-SM, 21 cases of ST-ROM, and 52 cases of ST-IM. Placental histology and karyotype examination were more likely to yield significant results in the cases of ST-ROM and ST-SM (p < 0.05). The phenotypic examination identified different underlying causes including fetal anomaly, suspected cervical insufficiency, diabetes mellitus, and unknown causes (p < 0.001). Sixty-four cases achieved a subsequent pregnancy. Although women with history of ST-ROM and ST-IM received more cervical length monitoring and cervical cerclage than those with ST-SM (66.7% vs. 44.4% vs. 7.5%, p = 0.0002; and 16.7% vs. 22.2% vs. 2.5%, p = 0.031, respectively), the risk of recurrent second trimester miscarriage was higher in ST-ROM and ST-IM than in ST-SM (16.7% vs. 0%, p = 0.018). CONCLUSION: The classification can differentiate different second trimester miscarriage phenotypes, which offers essential information to guide investigation panels of the underlying cause of miscarriages, and the prognosis and management of subsequent pregnancy. Future researches focused on second trimester miscarriage should report their findings according to different phenotypes.

Natural history of infants with vitamin D deficiency in Hong Kong.

BACKGROUND AND OBJECTIVES: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD. METHODS AND STUDY DESIGN: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected. RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L). CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Biallelic TMEM260 variants cause truncus arteriosus, with or without renal defects.

Only two families have been reported with biallelic TMEM260 variants segregating with structural heart defects and renal anomalies syndrome (SHDRA). With a combination of genome, exome sequencing and RNA studies, we identified eight individuals from five families with biallelic TMEM260 variants. Variants included one multi-exon deletion, four nonsense/frameshifts, two splicing changes and one missense change. Together with the published cases, analysis of clinical data revealed ventricular septal defects (12/12), mostly secondary to truncus arteriosus (10/12), elevated creatinine levels (6/12), horse-shoe kidneys (1/12) and renal cysts (1/12) in patients. Three pregnancies were terminated on detection of severe congenital anomalies. Six patients died between the ages of 6 weeks and 5 years. Using a range of stringencies, carrier frequency for SHDRA was estimated at 0.0007-0.007 across ancestries. In conclusion, this study confirms the genetic basis of SHDRA, expands its known mutational spectrum and clarifies its clinical features. We demonstrate that SHDRA is a severe condition associated with substantial mortality in early childhood and characterised by congenital cardiac malformations with a variable renal phenotype.

Human placental exosomes induce maternal systemic immune tolerance by reprogramming circulating monocytes.

BACKGROUND: The maternal immune system needs to tolerate the semi-allogeneic fetus in pregnancy. The adaptation occurs locally at the maternal-fetal interface as well as systemically through the maternal circulation. Failure to tolerate the paternal antigens may result in pregnancy complications, such as pregnancy loss and pre-eclampsia. However, the mechanism that regulates maternal immune tolerance, especially at the systemic level, is still an enigma. Here we report that the first-trimester placenta-derived exosomes (pEXOs) contribute to maternal immune tolerance by reprogramming the circulating monocytes. RESULTS: pEXOs predominantly target monocytes and pEXO-educated monocytes exhibit an immunosuppressive phenotype as demonstrated by reduced expression of marker genes for monocyte activation, T-cell activation and antigen-process/presentation at the transcriptomic level. They also have a greater propensity towards M2 polarization when compared to the monocytes without pEXO treatment. The inclusion of pEXOs in a monocyte-T-cell coculture model significantly reduces proliferation of the T helper cells and cytotoxic T cells and elevates the expansion of regulatory T cells. By integrating the microRNAome of pEXO and the transcriptomes of pEXO-educated monocytes as well as various immune cell functional assays, we demonstrate that the pEXO-derived microRNA miR-29a-3p promotes the expression of programmed cell death ligand-1, a well-known surface receptor that suppresses the adaptive immune system, by down-regulation of phosphatase and tensin homolog in monocytes. CONCLUSIONS: This is the first report to show how human pEXO directly regulates monocyte functions and its molecular mechanism during early pregnancy. The results uncover the importance of pEXO in regulating the maternal systemic immune response during early pregnancy by reprogramming circulating monocytes. The study provides the basis for understanding the regulation of maternal immune tolerance to the fetal allograft.

Knowledge, perception and expectation of management of hepatitis B infection among pregnant hepatitis B carriers in Hong Kong.

Lack of awareness regarding the risk of hepatitis B virus (HBV) infection and the interventions available during pregnancy among the pregnant carriers may influence their willingness and adherence to the management. This study assessed the knowledge, perception and expectation of HBV infection among pregnant HBV carriers in Hong Kong. A prospective multicentre cross-sectional questionnaire study was carried out between August 2019 and April 2021. The general knowledge on HBV, perception and expectation, and interventions to reduce vertical transmission were questioned. Obtaining ≥70% correct answers was defined as having sufficient knowledge. 422 (82.7%) were known carriers. Only 18.4% of women had sufficient overall knowledge. The correct answer rates and percentage of sufficient knowledge were statistically lower for HBV knowledge specific to pregnancy compared with general knowledge (42.5% vs. 58.5%, p < 0.001; 8.8% vs. 30.2%, p < 0.001 respectively). Multiple logistic regression showed higher education and receiving HBV medical care within a year prior to pregnancy were associated with sufficient overall (OR 3.46; 95% CI 2.05-5.83 and OR 2.76; 95% CI 1.62-4.7, p < 0.001), and general knowledge (OR 2.86; 95% CI 1.81-4.51 and OR 2.14; 95% CI 1.33-3.44, p < 0.05). 298 (58.4%), 357 (70.0%) and 150 (29.4%) women believed they should receive care by obstetrician, hepatologist or general practitioner respectively. 46.9% did not want to initiate antiviral treatment due to the cost, perceived teratogenicity and maternal side effects. The knowledge of HBV among pregnant carriers in Hong Kong was poor despite the majority of them being aware of their carrier status prior to the pregnancy.

Use of oral progestogen in women with threatened miscarriage in the first trimester: a randomized double-blind controlled trial.

STUDY QUESTION: Will use of oral progestogen in women with threatened miscarriage in the first trimester reduce the miscarriage rate when compared with placebo? SUMMARY ANSWER: Use of oral progestogen in women with threatened miscarriage in the first trimester did not reduce miscarriage before 20 weeks when compared with placebo. WHAT IS KNOWN ALREADY: Miscarriage is a common complication of pregnancy and occurs in 15-20% of clinically recognized pregnancies. Use of vaginal progestogens is not effective in reducing miscarriage but there is still no good evidence to support use of oral progestogen for the treatment of threatened miscarriage. STUDY DESIGN, SIZE, DURATION: This was a randomized double-blind controlled trial. A total of 406 women presenting with threatened miscarriage in the first trimester were recruited from 30 March 2016 to May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women attending Early Pregnancy Assessment Clinics because of vaginal bleeding during the first trimester were recruited and randomly assigned to use dydrogesterone 40 mg orally, followed by 10 mg orally three times a day or placebo until 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever was later. The primary outcome was the miscarriage rate before 20 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: The two groups of women had comparable age, BMI, number of previous miscarriages, gestation and ultrasound findings at presentation. The miscarriage rate before 20 weeks of gestation was similar in both groups, being 12.8% (26/203) in the progestogen group and 14.3% (29/203) in the placebo group (relative risk 0.897, 95% CI 0.548-1.467; P = 0.772). The live birth rate was 81.3% in the progestogen group versus 83.3% in the placebo group (P = 0.697). No significant differences were found between the two groups in terms of obstetric outcomes and side effects. LIMITATIONS, REASONS FOR CAUTION: The primary outcome was the miscarriage rate, rather than the live birth rate. Women were recruited from Early Pregnancy Assessment Clinics and those with heavy vaginal bleeding might be admitted into wards directly instead of attending Early Pregnancy Assessment Clinic. The severity of vaginal bleeding was subjectively graded by women themselves. The sample size was not adequate to demonstrate a smaller difference in the miscarriage rate between the progestogen and placebo groups. We did not exclude women with multiple pregnancy, which increased the risk of miscarriage although there was only one set of twin pregnancy in the placebo group. WIDER IMPLICATIONS OF THE FINDINGS: Use of oral progestogen is not recommended in women with threatened miscarriage in the first trimester. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Health and Medical Research Fund, HKSAR (reference number 12132341). All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov with an identifier NCT02128685. TRIAL REGISTRATION DATE: 1 May 2014. DATE OF FIRST PATIENT'S ENROLMENT: 30 March 2016.

Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature.

Schuurs-Hoeijmakers syndrome (SHS) is a rare syndrome involving a de novo variant in the PACS1 gene on chromosome 11q13. There are 36 individuals published in the literature so far, mostly diagnosed postnatally (34/36) after recognizing the typical facial features co-occurring with developmental delay, intellectual disability, and multiple malformations. Herein, we present one prenatal and 15 postnatal cases with the recurrent heterozygous pathogenic variant NM_018026.3:c.607C>T p.(Arg203Trp) in the PACS1 gene detected by exome sequencing. These 16 cases were identified by mining Centogene and the Hong Kong clinical genetic service databases. Collectively, the 49 postnatally diagnosed individuals present with typical facial features and developmental delay, while the three prenatally diagnosed individuals present with multiple congenital anomalies. In the current study, the use of exome sequencing as an unbiased diagnostic tool aided the diagnosis of SHS (pre- and postnatally). The identification of additional cases with SHS add to the current understanding of the clinical phenotype associated with pathogenic PACS1 variants. Databases combining clinical and genetic information are helpful for the study of rare diseases.

Prenatal phenotype of Kabuki syndrome: A case series and literature review.

OBJECTIVES: Kabuki syndrome (KS) is a genetic disorder characterized by intellectual disability, facial dysmorphism and congenital anomalies. We aim to investigate the prenatal features of fetuses with KS and to provide a comprehensive review of the literature on prenatal sonographic abnormalities associated with KS. METHODS: We retrospectively reviewed the prenatal ultrasound findings of all mothers of children with molecularly confirmed KS in Hong Kong, between 1991 and 2019. We also performed systematic review of the literature to identify studies on the prenatal findings in KS. RESULTS: We identified 11 cases with KS with detectable fetal ultrasound findings ranging from no detectable abnormalities to a variety of non-specific findings including increased nuchal translucency, pleural effusion, cardiac anomalies, renal anomalies, intrauterine growth restriction, polyhydramnios, oligohydramnios and single umbilical artery. In combining our cases with the 77 cases published, 42 (50.6%) of them had more than one abnormal antenatal ultrasound finding. The most frequent ultrasound features observed were cardiac anomalies (49.4%), followed by polyhydramnios (28.9%), genitourinary anomalies (26.5%), single umbilical artery (15.7%), intrauterine growth restriction (14.5%) and hydrops fetalis/pleural effusion/ascites (12.0%). CONCLUSIONS: These cases demonstrate the prenatal phenotypic heterogeneity associated with KS. Although the ultrasound abnormalities are non-specific, KS should be considered in the differential diagnosis when these fetal findings following normal microarray analysis/karyotyping.

Effect of delayed interval delivery of remaining fetus(es) in multiple pregnancies on survival: a systematic review and meta-analysis.

BACKGROUND: The management of the pregnancy after delivery of the first fetus during a second-trimester miscarriage or very early preterm birth has not been well defined. OBJECTIVE: The objective of the study was to evaluate whether delayed interval delivery of the remaining fetus(es) in twins/triplets is associated with improved survival, when compared with immediate delivery, after miscarriage or very preterm birth of the first fetus in multiple pregnancy. DATA SOURCES: PubMed, MEDLINE, and Cochrane Library were systematically searched through January 2019. STUDY ELIGIBILITY CRITERIA (STUDY DESIGN, POPULATIONS, AND INTERVENTIONS): The following eligibility criteria applied: full-text original article; included at least 5 cases of delayed interval delivery for remaining fetus(es); and reported the survival rate of the first-born and the remaining fetus(es). STUDY APPRAISAL AND SYNTHESIS METHODS: K.W.C. and W.W. searched, screened, and reviewed the articles. The quality of the studies was assessed according to the Strengthening the Reporting of Observational studies in Epidemiology checklist. If possible, data were stratified for assigned chorionicity. Effect sizes were pooled through a meta-analysis. RESULTS: A total of 2295 published article and abstracts were identified. Only 16 studies met inclusion criteria. Meta-analysis of 492 pregnancies (432 twins [88%], 56 triplets [11%], 3 quadruplets and 1 quintuplets) showed that delayed interval delivery significantly improved the perinatal survival of remaining fetus(es) compared with the first born (odds ratio, 5.22, 95% confidence interval, 2.95-9.25, I2 = 53%), before 20+0 weeks (odds ratio, 6.32, 95% confidence interval, 1.99-20.13, I2 = 0%), between 20+0 and 23+6 weeks (odds ratio, 3.31, 95% confidence interval, 1.95-5.63, I2 = 0%), and after 24+0 weeks (odds ratio, 1.92, 95% confidence interval, 1.21-3.05, I2 = 0%), in dichorionic twin pregnancy (odds ratio, 14.89, 95% confidence interval, 6.19-35.84, I2 = 0%), and unselected triplet pregnancy (odds ratio, 2.33, 95% confidence interval, 1.02-5.32, I2 = 0%. ). Among the survivors, there were no significant differences in the short-term and long-term neonatal morbidities between the first-born and the remaining fetus(es). Serious maternal morbidity was reported in 39% of pregnancy after delayed interval delivery (71 of 183). In addition, 2 cases were managed by postpartum hysterectomy and 1 reported postoperative uterovaginal fistula. There were no recorded cases of maternal mortality. CONCLUSION: Delayed interval delivery when a fetus has delivered in a multiple pregnancy is an effective management option to increase the survival rate of the remaining fetus(es). About 39% of women may experience morbidity following this management option.

Prenatal chromosomal microarray testing of fetuses with ultrasound structural anomalies: A prospective cohort study of over 1000 consecutive cases.

OBJECTIVE: Evaluate the diagnostic yield of prenatal submicroscopic chromosome anomalies using prenatal array comparative genomic hybridisation (aCGH). METHOD: Prospective cohort study conducted between March 2013 and June 2017 including fetuses where an elevated nuchal translucency (NT) or structural anomaly was identified on ultrasound and common aneuploidy testing was negative. aCGH was performed using an 8-plex oligonucleotide platform with a genome wide backbone resolution of greater than 200 kb and interpretation in line with American College of Medical Genetics guidance. RESULTS: One thousand one hundred twenty-nine fetuses were included; 371 fetuses with an increased NT (32.9%) and 758 with a structural anomaly (67.1%). The rate of pathogenic copy number variants (CNVs) and variant of uncertain significance (VUS) was 5.9% (n = 22) and 0.5% (n = 2) in the elevated NT group and 7.3% (n = 55) and 0.8% (n = 6) in the mid-trimester anomaly group. No pathogenic CNVs were identified in fetuses with an NT less than 4.0 mm. Multisystem and cardiac anomalies had the greatest yield of pathogenic CNV with a 22q11.2 microdeletion present in 40% (12/30). CONCLUSION: Prenatal aCGH is a useful diagnostic tool in the investigation of fetuses with a significantly elevated NT or structural anomaly. With time and experience, rates of pathogenic CNVs have increased, and VUS have reduced, supporting the prenatal application of increasingly high resolution aCGH platforms.

The Accuracy of Self-Screening of Group B Streptococcus in Pregnant Women-A Randomized Crossover Study.

OBJECTIVE: Universal screening of vaginal and rectal group B streptococcus (GBS) carriage in pregnant women is now recommended in many countries to identify at-risk pregnancies and reduce the risk of early-onset GBS disease in newborn infants. This study compared self-screening by pregnant women with screening by health care workers in a largely Chinese population. METHODS: A randomized crossover study was conducted in Hong Kong. All women attending the GBS screening visit at 35-37 weeks gestation between May and October 2015 were approached for recruitment. Consenting participants underwent both self-screening and screening by health care workers. Group 1 had health care worker screening swabs first, and group 2 had self-screening first. A positive GBS diagnosis was made if either swab was positive. The sensitivity of each approach was calculated by comparison with this gold standard. Acceptance of GBS self-screening and neonatal outcomes was analyzed (Canadian Task Force Classification I). RESULTS: Of the 672 women approached, 428 (63.7%) consented to the study. The prevalence of GBS was 19.7% (83 of 422). Sensitivities of self-screening and screening by health care workers were 61.4% (51 of 83) and 97.6% (81 of 83), respectively (P < 0.05). Women who used vaginal pessaries and non-Chinese women had a higher positive concordance rate with health care workers (P < 0.05). Neonatal outcomes of GBS-positive mothers were similar in the concordant and discordant groups. CONCLUSION: The sensitivity of self-screening of GBS in Hong Kong was lower than the sensitivity of screening by health care workers. Cultural difference needs to be considered when implementing self-screening in different populations.

Prevention of perinatal hepatitis B virus transmission.

PURPOSE: Chronic hepatitis B virus (HBV) infection remains endemic and continues to cause significant morbidity and mortality. It is a global health issue and the World Health Organization aims to eradicate HBV by 2030. Since vertical transmission accounts for the majority of chronic HBV infection, pregnancy offers an excellent opportunity to achieve complete HBV eradication by providing effective immunization of the offspring. METHODS: We reviewed recent publications identified from PubMed database using a combination of the relevant keywords for HBV, pregnancy, vertical transmission, immunoprophylaxis failure and antiviral treatment. RESULTS: We summarized the evidence of factors associated with, and measures to reduce and prevent maternal to child transmission, including the use of antiviral treatment during pregnancy to prevent immunoprophylaxis failure. Evidence suggested that highly viremia mother can be offered antenatal antiviral treatment to prevent immunoprophylaxis failure. We elaborated the viral load threshold to start maternal antiviral treatment and the importance of timely neonatal vaccination. A clinical algorithm to manage HBV carriers during pregnancy was proposed. CONCLUSION: Eradication of HBV is achievable with optimal management of HBV carriers, especially during pregnancy by interruption of vertical transmission. Routine antenatal screening and neonatal immunoprophylaxis remain the key measures to reduce the global HBV burden, and additional antenatal antiviral treatment could further minimize the chance of persistent infection in newborns.

Isolated Ascites in a Monochorionic Twin after Fetoscopic Laser Ablation Is Not Necessarily Secondary to Recurrence or Anaemia: Bowel Complications in Twin-to-Twin Transfusion Syndrome after Fetoscopic Laser Ablation.

BACKGROUND/PURPOSE: We report a case study of jejunal atresia and the results of a systematic literature review of all reported cases of bowel complications occurring after fetoscopic laser ablation (FLA) for the treatment of twin-to-twin transfusion syndrome (TTTS). METHODS: A systematic literature review was performed of bowel complications after FLA for TTTS according to PRISMA guidelines. RESULTS: There are 11 published cases of small bowel atresia, 5 cases of necrotising enterocolitis (NEC), and 2 cases with foetal bowel perforations. Recipient twins were more likely to be affected by small bowel atresia (7 recipient and 4 donor cases) and NEC (3 recipient and 2 donor twins). Prenatal ultrasonographic abnormalities were demonstrated in 7 out of 9 cases with bowel atresia and in both cases of bowel perforation. The overall survival rate for neonates with bowel complications after FLA is 72%, but is much lower for co-twins at 22%. The survival rates for jejunoileal atresia and NEC are 91 and 40%, respectively. CONCLUSIONS: It is uncertain as to whether these bowel anomalies are due to bowel ischaemia associated with TTTS, the treatment with FLA, or a combination of both. Cases with prenatal abdominal ultrasonographic abnormalities after FLA should have close prenatal and postnatal assessment to detect bowel complications.

Prenatal Diagnosis, Management, and Outcome of Fetal Subdural Haematoma: A Case Report and Systematic Review.

BACKGROUND: Fetal subdural haematoma (SDH) is associated with poor prognosis. OBJECTIVE: The conflicting evidence from the literature presents a challenge in prenatal counselling. We present a case study and systematic review of the literature for the management and outcome of fetal SDH. METHODS: Systematic search of electronic database. RESULTS: A total 45 cases were extracted from 39 papers. Prenatal ultrasonographic features were intracranial echogenicity (42%), lateral ventriculomegaly (38%), presence of an intracranial mass (31%), macrocephaly (24%), midline deviation of cerebral falx (20%), and intracranial fluid collection (11%). Further secondary features were noted including reversed diastolic flow in the middle cerebral artery (11%), echogenic bowel (4%), hydrops fetalis (2%), and elevated middle cerebral artery peak systolic velocity (2%) (all highly likely to be associated with fetal anaemia). The rates of termination of pregnancy, stillbirth, and neonatal death were 18% (8/45), 16% (7/45), and 11% (5/45), respectively. Overall, therefore, the fetal and perinatal mortality was 32% (12/37). Amongst the 24 survivors with available neurological outcome, 42% (10/24) and 58% (14/24) had abnormal and normal neurological outcome, respectively. Underlying aetiology of fetal SDH was not identified in 47% (21/45). Fetal SDH with an identifiable underlying aetiology was the only factor associated with a higher chance of normal neurological outcome when compared to fetal SDH without a detectable cause (78.5 vs. 21.4%, p = 0.035). CONCLUSIONS: Stillbirth and neonatal death occurred in a significant proportion of fetal SDH. 58% of survivors had normal neurological outcome, and better prognosis was seen in SDH with identifiable underlying aetiology.