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.

Relationship between viral load and pregnancy outcomes among hepatitis B carriers.

OBJECTIVE: Pregnant hepatitis B carriers may have a higher risk of adverse pregnancy outcomes. Current evidences are conflicting regarding the relationship between hepatitis B virus (HBV) and various pregnancy complications, owing to the inclusion of women with different viral activity. This study is to evaluate the relationship between hepatitis B e antigen (HBeAg) status/HBV DNA level and pregnancy outcomes among pregnant hepatitis B carriers in Hong Kong. MATERIALS AND METHODS: This was a retrospective analysis of a prospective multicenter observational study carried out in Hong Kong between 2014 and 2016. Pregnant HBV carriers were recruited. HBeAg was tested. HBV DNA level was quantified at 28-30 weeks of gestation. The rates of gestational diabetes mellitus (GDM), gestational hypertension, pre-eclampsia, preterm prelabour rupture of membranes (PPROM), preterm birth, low birth weight (LBW), macrosomia and mode of delivery were recorded. RESULTS: 679 pregnancies were analyzed. 23.3% of women were seropositive for HBeAg. The mean viral load (SD) at 28-30 weeks of gestation was 3.6 (2.5) log10IU/ml. No statistically significant differences were found in the rates of GDM, gestational hypertension, pre-eclampsia, PPROM, preterm birth, LBW, macrosomia and mode of delivery among women with different viral load levels (≤2 log10IU/ml, 2.01-6 log10IU/ml and >6 log10IU/ml). Positive maternal HBeAg status was not associated with pregnancy complications compared to seronegative women. CONCLUSION: Seropositive HBeAg status or a higher level of HBV DNA during pregnancy did not pose a significant negative impact to the pregnancy outcomes.

Prenatal ultrasonography of craniofacial abnormalities.

Craniofacial abnormalities are common. It is important to examine the fetal face and skull Epub ahead of print during prenatal ultrasound examinations because abnormalities of these structures may indicate the presence of other, more subtle anomalies, syndromes, chromosomal abnormalities, or even rarer conditions, such as infections or metabolic disorders. The prenatal diagnosis of craniofacial abnormalities remains difficult, especially in the first trimester. A systematic approach to the fetal skull and face can increase the detection rate. When an abnormality is found, it is important to perform a detailed scan to determine its severity and search for additional abnormalities. The use of 3-/4-dimensional ultrasound may be useful in the assessment of cleft palate and craniosynostosis. Fetal magnetic resonance imaging can facilitate the evaluation of the palate, micrognathia, cranial sutures, brain, and other fetal structures. Invasive prenatal diagnostic techniques are indicated to exclude chromosomal abnormalities. Molecular analysis for some syndromes is feasible if the family history is suggestive.

The effect of rupture of membranes and labour on the risk of hepatitis B vertical transmission: Prospective multicentre observational study.

OBJECTIVE: To evaluate the effect of rupture of membranes and labour on the risk of hepatitis B virus (HBV) vertical transmission. STUDY DESIGN: A prospective multicentre observational study was carried out in Hong Kong between 2014-2016. Pregnant HBV carriers were recruited. The duration of rupture of membranes, labour and mode of delivery were collected prospectively. HBV DNA was examined at 28-30 weeks of gestation. All newborns received standard HBV vaccination and immunoglobulin. Hepatitis B surface antigen of infants was tested at 9-12 months of age. RESULTS: 641 pregnancies were recruited and analyzed. No statistically significant difference was found in gravida, parity, gestational age at delivery, mode of delivery, duration of rupture of membranes, duration of labour, preterm delivery, preterm rupture of membranes or birth weight (p > 0.05). Subgroup analysis in viral load > 7log10IU/ml and 8log10IU/ml also did not find a significant association between duration of rupture of membranes and labour with immunoprophylaxis failure. CONCLUSIONS: Duration of rupture of membranes and labour would not affect the risk of HBV vertical transmission in infants following standard HBV vaccination and hepatitis B immunoglobulin administration.

Prenatal sonography of placental abscess and prolonged antibiotic treatment for Serratia marcescens bacteremia.

Termination of pregnancy is indicated for Serratia marcescens bacteremia, a major cause of mortality. Our present case was highly challenging because the patient wished to continue with her pregnancy, and the ultrasonography showed features of a placental abscess. Although the outcomes were good after prolonged antibiotic treatment, this was an exceptional case.

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10.

BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings.