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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. Evidence‐based clinical algorithms may help support respectful, high quality intrapartum care. [Correction added on 23 August 2024, after first online publication: The Abstract has been updated to structure layout in this version.] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease therapy. Here, we present two cases of fetal hyperthyroidism with maternal hypothyroidism and review the assessment and intrauterine therapy for fetal hyperthyroidism. Both women were referred at 22+ and 23+ weeks of gestation with abnormal ultrasound findings, including fetal heart enlargement, pericardial effusion, and fetal tachycardia. Both women had a history of Graves disease while in a state of hypothyroidism with a high titer of TRAb. A sonographic examination showed a diffusely enlarged fetal thyroid with abundant blood flow. Invasive prenatal testing revealed no significant chromosomal aberration. Low fetal serum TSH and high TRAb levels were detected in the cord blood. Fetal hyperthyroidism was considered, and maternal oral methimazole (MMI) was administered as intrauterine therapy, with the slowing of fetal tachycardia, a reduction in fetal heart enlargement, and thyroid hyperemia. During therapy, maternal thyroid function was monitored, and the dosage of maternal levothyroxine was adjusted accordingly. Both women delivered spontaneously at 36+ weeks of gestation, and neonatal hyperthyroidism was confirmed in both newborns. After methimazole and propranolol drug treatment with levothyroxine for 8 and 12 months, both babies became euthyroid with normal growth and development. [ABSTRACT FROM AUTHOR]

BACKGROUND The establishment of maternal–fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal–fetal interface and their associations with pathological processes. OBJECTIVE AND RATIONALE This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal–fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal–fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed. SEARCH METHODS A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal–fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included. OUTCOMES The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal–fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal–fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal–fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groundwork for further exploration of glycans in reproductive biology under both physiological and pathological conditions. WIDER IMPLICATIONS A deep understanding of the functions of glycan structures would provide insights into the molecular mechanisms underlying their involvement in the physiological and pathological regulation of early pregnancy. Glycans may also potentially serve as novel early predictive markers and therapeutic targets for repeated implantation failure, pregnancy loss, and other pregnancy complications. [ABSTRACT FROM AUTHOR]

Pregnancy involves a wide range of adaptations in the maternal body. Maternal immune tolerance toward the foreign fetus is critical for a successful pregnancy. Decidual macrophages are the primary antigen-presenting and phagocytic cells responsible for antigen presentation and apoptotic cell removal. Their phenotype changes dynamically during pregnancy. Placenta-derived exosomes are small vesicles carrying active biological molecules such as microRNAs, proteins, and lipids. The placenta-derived exosomes have been implicated in endothelial cell activation, smooth muscle cell migration, and T-cell apoptosis, but it is unknown whether placenta-derived exosomes would affect the development and functions of decidual macrophages. In this study, we reported that placenta-derived exosomes stimulated macrophage polarization into alternatively activated (M2) macrophages. Mechanistically, miRNA-30d-5p from the placenta-derived exosomes induced macrophage polarization to the M2 phenotype by targeting histone deacetylase 9. Furthermore, the conditioned medium of placenta-derived exosome–treated macrophages promoted trophoblast migration and invasion. By contrast, the conditioned medium impaired the ability of endothelial cell tube formation and migration. Placenta-derived exosome–treated macrophages had no impact on T-cell proliferation. Together, we demonstrated that placenta-derived exosomes polarize macrophages to acquire a decidua-like macrophage phenotype to modulate trophoblast and endothelial cell functions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fetal structural congenital abnormalities (SCAs) complicate 2–3% of all pregnancies. Whole-exome sequencing (WES) has been increasingly adopted prenatally when karyotyping and chromosomal microarray do not yield a diagnosis. This is a retrospective cohort study of 104 fetuses with SCAs identified on antenatal ultrasound in Hong Kong, where whole exome sequencing is performed. Molecular diagnosis was obtained in 25 of the 104 fetuses (24%). The highest diagnostic rate was found in fetuses with multiple SCAs (29.2%), particularly those with involvement of the cardiac and musculoskeletal systems. Variants of uncertain significance were detected in 8 out of the 104 fetuses (7.7%). Our study shows the utility of WES in the prenatal setting, and the extended use of the technology would be recommended in addition to conventional genetic workup. [ABSTRACT FROM AUTHOR]

(B) First trimester serum CD147 levels of the normotensive and PE pregnant women were measured by ELISA (normotensive N = 52, PE N = 26, early-onset PE = 8, late-onset PE N = 18). * P < .05 gl CD147 has an unusual transmembrane domain characterised by a single-charged glutamic acid in the hydrophobic transmembrane region, which promotes protein-protein interactions.4 CD147 is a component of two receptor complexes (Figure 3F; Table S2) on the plasma membrane of human EVCT. Dear Editor, Trophoblastic CD147, also known as basigin (BSG), regulates the differentiation and spiral artery remodelling functions of extravillous trophoblasts (EVCTs), and its deficiency contributes to the pathophysiology of preeclampsia (PE). Dysregulation of the CD147 complex confers defective placental development: A pathogenesis of early-onset preeclampsia. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Key points: What's already known about this topic? The anomalies associated with Kabuki syndrome (KS) may be detectable on routine fetal ultrasound. What does this study add?This study provides comprehensive information on the prenatal manifestations of KS. Although the prenatal ultrasound findings are not specific for KS, recognition of the fetal abnormalities should alert clinicians to consider discussion regarding targeted fetal genetic testing using the KS panel or exome sequencing and provision of appropriate counselling to explain the findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Preterm birth accounts for 75% of perinatal deaths and more than 50% of long-term neurological disabilities. For a singleton pregnancy, progesterone treatment is effective in prevention of preterm birth in women with an asymptomatic short cervix or a history of preterm birth. However, a large proportion of preterm births still is not currently preventable. The aim of this study is to determine whether early universal use of oral progesterone before 14 + 0 weeks of gestation can prevent preterm birth better than universal screening of cervical length at 18 + 0 to 23 + 6 weeks of gestation, followed by progesterone treatment in those with a short cervix in singleton pregnancy.Methods: This is a multicenter, randomized, double-blind, placebo-controlled trial registered with ClinicalTrials.gov on 12 February 2018. Eligible consecutive pregnant women with singleton gestation attending antenatal outpatient clinics will be recruited after receiving counseling and signing the written consent form. Transvaginal cervical length measurement will be performed at recruitment (before 14 + 0 weeks of gestation) and between 18 + 0 and 23 + 6 weeks of gestation. After randomization, women will be randomly assigned to either the treatment group (oral dydrogesterone 10 mg three times daily) or the placebo group, and medication will be started before 14 + 0 weeks of gestation. Assigned groups will be unblinded if the cervical length is ≤ 25 mm between 18 + 0 and 23 + 6 weeks of gestation, and the management option for short cervix will be discussed (oral progesterone, vaginal progesterone, or cervical cerclage). The primary outcome is preterm birth before 37 + 0 weeks of gestation.Discussion: Progesterone is used extensively in part of the in vitro fertilization program as luteal phase support, and it is not associated with teratogenicity. Universal progesterone supplementation may be a better approach to prevent preterm birth. This large, multicenter, randomized, double-blind, placebo-controlled trial will provide the best evidence, leading to the best strategy for the prevention of preterm birth.Trial Registration: ClinicalTrials.gov, NCT03428685. Registered on 12 February 2018. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Miscarriage is a common complication of pregnancy occurring in 15-20 % of all clinically recognized pregnancies. Currently, there is still no good scientific evidence to support the routine use of progestogens for the treatment of threatened miscarriage because the existing studies were not large enough to show a significant difference and some of them were not randomized or double-blind.Methods: This is a double-blind, randomized controlled trial. A total of 400 patients presenting with first-trimester threatened miscarriage will be enrolled. They will be randomized to take dydrogesterone 40 mg per os, followed by 10 mg per os three times a day or placebo until twelve completed weeks of gestation or 1 week after the bleeding has stopped, whichever is longer. The primary outcome is the percentage of miscarriage before 20 weeks of gestation.Discussion: We postulate that the dydrogesterone therapy will significantly reduce the risk of miscarriage in women with threatened miscarriage.Trial Registration: This study is registered at ClinicalTrials.gov, NCT02128685 . Registered on 29 April 2014. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 25-year-old multiparous woman who was presented with enlarged nuchal translucency at weeks and 6 days of gestation and was diagnosed with non-immune hydrops fetalis (NIFH). Topics mention including the Trisomy 21, transient abnormal myelopoiesis and transient leukaemia.

We suggested using maternal age and body mass index to identify HBV carriers at higher risk of elevated HBV DNA.[2] Using a high-throughput platform to quantify hepatitis B surface antigen (HBsAg) level might be another option in resource-limited settings. 1 Vyas AK, Singh AK, Mishra N, Kumar A. Timing of hepatitis B virus DNA quantification and treatment approach during pregnancy. [Extracted from the article]