Chromosomal abnormalities and neurological outcomes in fetal cerebral ventriculomegaly: a retrospective cohort analysis.

INTRODUCTION: This study investigated the incidences of chromosomal abnormalities and the neurological outcomes according to the degree of fetal cerebral ventriculomegaly. METHODS: All women with antenatal ultrasound diagnosis of fetal cerebral ventriculomegaly were retrospectively identified from two maternal-fetal medicine units in Hong Kong from January 2014 to December 2018. Degrees of fetal ventriculomegaly were classified as mild (10-11.9 mm), moderate (12-14.9 mm), or severe (≥15 mm). Genetic investigation results were reviewed, including conventional karyotyping and chromosomal microarray analysis (CMA); correlations between chromosomal abnormalities and the degree of fetal ventriculomegaly were explored. The neurological outcomes of subsequent live births were analysed to identify factors associated with developmental delay. RESULTS: Of 84 cases (ie, pregnant women and their fetuses) included, 46 (54.8%) exhibited isolated fetal ventriculomegaly, 55 (65.5%) had mild cerebral ventriculomegaly, and 29 (34.5%) had moderate or severe cerebral ventriculomegaly. Overall, 20% (14/70) of cases had chromosomal abnormalities. Moreover, 12% (3/25) of mild isolated ventriculomegaly cases had abnormal karyotype or CMA results. The CMA provided an incremental diagnostic yield of 8.6% (6/70), compared with conventional karyotyping; 4.3% exhibited pathogenic variants and 4.3% exhibited variants of uncertain significance. Among the 53 live births in the cohort, fewer cases of mild isolated ventriculomegaly were associated with developmental delay than more severe isolated ventriculomegaly (9.7% vs 41.7%, P<0.03). CONCLUSIONS: Chromosomal microarray analysis testing should be offered to all women with fetal cerebral ventriculomegaly, including women with isolated mild ventriculomegaly. The incidence of developmental delay after birth increases with the degree of prenatal cerebral ventriculomegaly.

Hypoxia is an effective stimulus for vesicular release of ATP from human umbilical vein endothelial cells.

INTRODUCTION: Hypoxia induces dilatation of the umbilical vein by releasing autocoids from endothelium; prostaglandins (PGs), adenosine and nitric oxide (NO) have been implicated. ATP is vasoactive, thus we tested whether hypoxia releases ATP from primary Human Umbilical Vein Endothelial Cells (HUVEC). METHODS: HUVEC were grown on inserts under no-flow conditions. ATP was assayed by luciferin-luciferase and visualised by quinacrine labeling. Intracellular Ca(2+) ([Ca(2+)]i) was imaged with Fura-2. RESULTS: ATP release occurred constitutively and was increased by hypoxia (PO2: 150-8 mmHg), ∼10-fold more from apical, than basolateral surface. Constitutive ATP release was decreased, while hypoxia-induced release was abolished by brefeldin or monensin A, inhibitors of vesicular transport, and LY294002 or Y27632, inhibitors of phosphoinositide 3-kinases (PI3K) and Rho-associated protein kinase (ROCK). ATP release was unaffected by NO donor, but increased by calcium ionophore, by >60-fold from apical, but <25% from basolateral surface. Hypoxia induced a small increase in [Ca(2+)]i compared with ATP (10 µM); hypoxia inhibited the ATP response. Quinacrine-ATP fluorescent loci in the perinuclear space, were diminished by hypoxia and monensin, whereas brefeldin A increased fluorescence intensity, consistent with inhibition of anterograde transport. DISCUSSION: Hypoxia within the physiological range releases ATP from HUVEC, particularly from apical/adluminal surfaces by exocytosis, via an increase in [Ca(2+)]i, PI3K and ROCK, independently of NO. We propose that hypoxia releases ATP at concentrations sufficient to induce umbilical vein dilation via PGs and NO and improve fetal blood flow, but curbs amplification of ATP release by autocrine actions of ATP, so limiting its pro-inflammatory effects.

Does gestational diabetes mellitus affect respiratory outcome in late-preterm infants?

BACKGROUND: Both gestational diabetes mellitus (GDM) and late-preterm delivery at 34-36 weeks' gestation are independently associated with neonatal respiratory complications, but it is unknown whether their combination increases further its risk. We therefore appraised the independent effect of GDM on the respiratory outcome of late-preterm infants. METHODS: In a retrospective cohort study, respiratory outcome of 911 infants delivered at 34-36 weeks' gestation between 1 January 2009 and 30 August 2012 from mothers with GDM (study group, n=130) was compared with infants delivered at the same gestation by mothers without GDM (control group, n=781). RESULTS: The study group had significantly higher incidence of transient tachypnoea of newborn (TTN, p=0.02) and air leak (p=0.012), and required more respiratory support, including oxygen, continuous positive airway pressure (CPAP), mechanical ventilation and neonatal intensive care, with a longer length of hospital stay, but not duration on respiratory support. On logistic regression analysis, GDM is an independent risk factor for TTN (aOR=1.5, 95% C.I.1.0-2.4), CPAP (aOR=2.37, 95% C.I. 1.05-4.89), mechanical ventilation (aOR=4.02 95% C.I. 1.57-10.32) and neonatal intensive care (aOR 1.83, 95% C.I. 1.05-3.87). CONCLUSIONS: Our results demonstrated an independent effect of GDM on the risk of severe respiratory complications in late-preterm infants. Additional close monitoring and timely intervention are necessary in the management of these infants.

Diagnostic challenges of human brucellosis in Hong Kong: a case series in two regional hospitals.

A retrospective analysis of six patients diagnosed with brucellosis in two regional hospitals was carried out. The epidemiological, clinical, and laboratory features were studied. All patients had exposure history. Three patients presented with musculoskeletal symptoms, while three had predominantly genitourinary symptoms. One patient did not have fever at presentation. All patients were diagnosed by positive blood culture of Brucella melitensis, and the diagnosis was not suspected for all except one patient at presentation. Given the inferior sensitivity of blood culture to serology, human brucellosis may be underdiagnosed, especially when the index of suspicion is low.

A role for receptor-operated Ca2+ entry in human pulmonary artery smooth muscle cells in response to hypoxia.

Hypoxic pulmonary vasoconstriction (HPV) is an important homeostatic mechanism in which increases of [Ca2+]i are primary events. In this study, primary cultured, human pulmonary artery smooth muscle cells (hPASMC) were used to examine the role of TRPC channels in mediating [Ca2+]i elevations during hypoxia. Hypoxia (PO2) about 20 mm Hg) evoked a transient [Ca2+]i elevation that was reduced by removal of extracellular calcium. Nifedipine and verapamil, blockers of voltage-gated calcium channels (VGCCs), attenuated the hypoxia-induced [Ca2+)]i elevation by about 30%, suggesting the presence of alternate Ca2+ entry pathways. Expression of TRPC1 and TRPC6 in hPASMC were found by RT-PCR and confirmed by Western blot analysis. Antagonists for TRPC, 2APB and SKF96365, significantly reduced hypoxia-induced [Ca2+]i elevation by almost 60%. Both TRPC6 and TRPC1 were knocked down by siRNA, the loss of TRPC6 decreased hypoxic response down to 21% of control, whereas the knockdown of TRPC1 reduced the hypoxia response to 85%, suggesting that TRPC6 might play a central role in mediating hypoxia response in hPASMC. However, blockade of PLC pathway caused only small inhibition of the hypoxia response. In contrast, AICAR, the agonist of AMP-activated kinase (AMPK), induced a gradual [Ca2+]i elevation, whereas compound C, an antagonist of AMPK, almost abolished the hypoxia response. However, co-immunoprecipitation revealed that AMPKalpha was not colocalized with TRPC6. Our data supports a role for TRPC6 in mediation of the [Ca2+]i elevation in response to hypoxia in hPASMC and suggests that this response may be linked to cellular energy status via an activation of AMPK.

Rapid aneuploidy testing (knowing less) versus traditional karyotyping (knowing more) for advanced maternal age: what would be missed, who should decide?

OBJECTIVES: The application of rapid aneuploidy testing as a stand-alone approach in prenatal diagnosis is much debated. The major criticism of this targeted approach is that it will not detect other chromosomal abnormalities that will be picked up by traditional karyotyping. This study aimed to study the nature of such chromosomal abnormalities and whether parents would choose to terminate affected pregnancies. DESIGN: Retrospective study on a cytogenetic database. SETTING: Eight public hospitals in Hong Kong. PARTICIPANTS: The karyotype results of 19 517 amniotic fluid cultures performed for advanced maternal age (>or=35 years) from 1997 to 2002 were classified according to whether they were detectable by rapid aneuploidy testing. The outcomes of pregnancies with abnormal karyotypes were reviewed from patient records. RESULTS: In all, 333 (1.7%) amniotic fluid cultures yielded abnormal karyotypes; 175 (52.6%) of these were detected by rapid aneuploidy testing, and included trisomy 21 (n=94, 28.2%), trisomy 18 or 13 (n=21, 6.3%), and sex chromosome abnormalities (n=60, 18.0%). The other 158 (47.4%) chromosomal abnormalities were not detectable by rapid aneuploidy testing, of which 63 (18.9%) were regarded to be of potential clinical significance and 95 (28.5%) of no clinical significance. Pregnancy outcomes in 327/333 (98.2%) of these patients were retrieved. In total, 143 (42.9%) of these pregnancies were terminated: 93/94 (98.9%) for trisomy 21, 20/21 (95.2%) for trisomy 18 or 13, 19/60 (31.7%) for sex chromosome abnormalities, and 11/63 (17.5%) for other chromosomal abnormalities with potential clinical significance. There were no terminations in the 95 pregnancies in which karyotyping results were regarded to be of no clinical significance. CONCLUSIONS: 'Knowing less' by the rapid aneuploidy stand-alone testing could miss about half of all chromosomal abnormalities detectable by amniocentesis performed for advanced maternal age. Findings from two fifths of the latter were of potential clinical significance, and the parents chose to terminate one out of six of the corresponding pregnancies. If both techniques are available, parents could have enhanced autonomy to choose.

Ex-utero intrapartum treatment: a controlled approach to the management of anticipated airway problems in the newborn.

Airway problems in an unborn foetus that may cause obstruction can be safely managed using an ex-utero intrapartum technique. Advanced technology now allows many congenital airway problems to be diagnosed in the prenatal period. Careful prenatal planning of an ex-utero intrapartum treatment allows safe airway control while the foetus remains on uteroplacental support. It avoids the need for emergent intervention of an acutely obstructed airway in a neonate that often has disastrous consequences.

Evaluation of a peptide-based enzyme immunoassay for anti-SARS coronavirus IgG antibody.

High throughput assays for anti-SARS-CoV IgG antibody detection are need for large-scale epidemiologic studies. The performance of a microplate enzyme immunoassay, DETECT-SARS was evaluated for the detection of anti-SARS-CoV IgG antibody. This assay is based on synthetic peptides derived from the nucleocapsid and spike proteins. The results showed that the assay provided a high degree of sensitivity (95.9%) for convalescent serum samples. The level of specificity was close to 90%, and did not show significant variation among different control groups. The high degree of sensitivity together with the high-throughput nature makes it advantageous as a screening assay for studies where handling of a large number of specimens is required.

Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus.

BACKGROUND: Human infection with an avian influenza A virus (subtype H5N1) was reported recently in Hong Kong. We describe the clinical presentation of the first 12 patients and options for rapid viral diagnosis. METHODS: Case notes of 12 patients with virus-culture-confirmed influenza A H5N1 infection were analysed. The clinical presentation and risk factors associated with severe disease were defined and the results of methods for rapid virus diagnosis were compared. FINDINGS: Patients ranged from 1 to 60 years of age. Clinical presentation was that of an influenza-like illness with evidence of pneumonia in seven patients. All seven patients older than 13 years had severe disease (four deaths), whereas children 5 years or younger had mild symptoms with the exception of one who died with Reye's syndrome associated with intake of aspirin. Gastrointestinal manifestations, raised liver enzymes, renal failure unrelated to rhabdomyolysis, and pancytopenia were unusually prominent. Factors associated with severe disease included older age, delay in hospitalisation, lower-respiratory-tract involvement, and a low total peripheral white blood cell count or lymphopenia at admission. An H5-specific reverse-transcription PCR assay (RT-PCR) was useful for rapid detection of virus directly in respiratory specimens. A commercially available enzyme immunoassay was more sensitive than direct immunofluorescence for rapid viral diagnosis. Direct immunofluorescence with an H5-specific monoclonal antibody pool was useful for rapid exclusion of H5-subtype infection. INTERPRETATION: Avian Influenza A H5N1 virus causes human influenza-like illness with a high rate of complications in adults admitted to hospital. Rapid H5-subtype-specific laboratory diagnosis can be made by RT-PCR applied directly to clinical specimens.

Neurological disorders in pregnancy.

Pregnant women can present with a wide variety of neurological conditions. Patient data from 1 January 1985 through 31 December 1994 for all deliveries at the Tsan Yuk and Queen Mary hospitals were reviewed to determine the local frequency of various neurological conditions during pregnancy. Conditions including epilepsy, eclampsia, facial nerve palsy, pituitary tumour, cerebrovascular disorders, myasthenia gravis, multiple sclerosis, and non-pituitary intracranial tumours were encountered, in descending order of frequency. The limitations of this retrospective analysis are acknowledged. This paper reviews the current concepts of these conditions and outlines appropriate management.

Cervical priming with oral misoprostol in pre-labor rupture of membranes at term.

OBJECTIVE: To investigate the effectiveness of oral misoprostol as a cervical priming agent for patients presenting with pre-labor rupture of membranes at term. METHODS: Eighty patients presenting with pre-labor rupture of membranes at term were randomized to receive either 200 micrograms of misoprostol or 50 mg of vitamin B6 orally 1 hour after admission. Labor was induced with intravenous oxytocin infusion 12 hours after oral medication if the patient did not go into labor. We compared the induction rate, duration of labor, mode of delivery, and leaking-to-delivery interval in the two groups. RESULTS: The cervical score was significantly improved and the induction rate was also reduced in the misoprostol group when compared with the control group. The interval from recruitment to onset of labor, duration of labor, and the interval from recruitment to delivery were significantly shorter in the misoprostol group. The mode of delivery and the perinatal outcome were similar for the two groups. CONCLUSION: Oral misoprostol is an effective agent for cervical priming and labor induction in patients with pre-labor rupture of membranes at term.

Comparative evaluation of macrodilution and alamar colorimetric microdilution broth methods for antifungal susceptibility testing of yeast isolates.

A comparative evaluation of the macrodilution method and the Alamar colorimetric method for the susceptibility testing of amphotericin B, fluconazole, and flucytosine was conducted with 134 pathogenic yeasts. The clinical isolates included 28 Candida albicans, 17 Candida tropicalis, 15 Candida parapsilosis, 12 Candida krusei, 10 Candida lusitaniae, 9 Candida guilliermondii, 18 Torulopsis glabrata, and 25 Cryptococcus neoformans isolates. The macrodilution method was performed and interpreted according to the recommendations of the National Committee for Clinical Laboratory Standards (document M27-P), and the Alamar colorimetric method was performed according to the manufacturer's instructions. For the Alamar colorimetric method, MICs were determined at 24 and 48 h of incubation for Candida species and T. glabrata and at 48 and 72 h of incubation for C. neoformans. The overall agreement within +/- 1 dilution for Candida species and T. glabrata against the three antifungal agents was generally good, with the values for amphotericin B, fluconazole, and flucytosine being 85.3, 77.9, and 86.2%, respectively, at the 24-h readings and 69.3, 65.2, and 97.2%, respectively, at the 48-h readings. Most disagreement was noted with fluconazole against C. tropicalis and T. glabrata. Our studies indicate that determination of MICs at 24 h by the Alamar colorimetric method is a valid alternate method for testing amphotericin B, fluconazole, and flucytosine against Candida species but not for testing fluconazole against C. tropicalis and T. glabrata. For flucytosine, much better agreement can be demonstrated against Candida species and T. glabrata at the 48-h readings by the Alamar method. Excellent agreement within +/- dilution can also be observed for amphotericin B, fluconazole, and flucytosine (80, 96, and 96%, respectively) against c. neoformans when the MICs were determined at 72 h by the Alamar method.

Neonatal narcotic withdrawal in Hong Kong Chinese.

A retrospective case controlled study was carried out to study the neonatal characteristics, outcome and narcotic withdrawal syndrome in 51 neonates exposed to narcotic antenatally. The birth weight, head circumference and body length were significantly smaller in the study group while the incidence of prematurity (41%) and small-for-gestational age babies was increased (27.5%). Narcotic withdrawal occurred in 83% of narcotic exposed neonates. About half of them had onset of withdrawal symptoms within the first 24 hours. All of these newborns were treated by either phenobarbitone (45%), chlorpromazine (9.5%) or both (40.5%). The average duration of treatment was 15.7 days. There was one neonatal death due to in utero withdrawal and hypoxia, and another post-neonatal death due to sudden infant death. Neonatal jaundice, necrotising enterocolitis, clinical sepsis and congenital syphilis were more common in the drug-addicted group.

Umbilical artery Doppler velocimetry compared with fetal heart rate monitoring as a labor admission test.

A total of 155 patients admitted in early labor to the delivery unit of the University of Hong Kong were recruited into a study comparing the value of umbilical artery Doppler velocimetry and fetal heart rate (FHR) monitoring in early labor as an admission test. FHR monitoring for 30 min was recorded on admission, and umbilical A/B ratio was simultaneously performed. The FHR tracing was scored according to the Lyons score by a third independent observer after delivery. Outcome variables studied included small for gestational age (SGA), intrapartum FHR abnormalities, operative deliveries for fetal distress, umbilical cord pH, Apgar scores, admission into the special care baby unit, and a combination of the variables. It was found that at cut-off values of Lyons score < 7 and umbilical A/B ratio > 2.6 at term, about 19% of cases were abnormal for either tests, with only a few cases of overlap. Umbilical A/B ratio was found to be significantly correlated with SGA. The sensitivity and positive predictive values were, however, low. Both tests were relatively poor predictors for most of the outcome variables studied. Interestingly, FHR monitoring did not seem to have any advantage over Doppler velocimetry as a labor admission test. Further larger scale studies to evaluate their usefulness in medium and low risk populations are indicated.

Primary liver carcinoma complicating pregnancy.

Primary hepatic carcinoma complicating pregnancy has been sporadically reported in the literature. Its association with grossly raised serum alphafetoprotein values is of particular interest to obstetricians who perform routine maternal alphafetoprotein screening in the second trimester. A case with favourable maternal and fetal outcome is presented.

Narcotic addiction in pregnancy with adverse maternal and perinatal outcome.

A retrospective case controlled study was carried out on 51 Chinese gravidas who had abused narcotics and who were delivered in a teaching hospital in Hong Kong. Heroin was the most commonly abused drug. The number of patients who changed from heroin to methadone was small. The major antenatal complications were late antenatal booking (average 28 weeks), prematurity (41%), small for gestational age baby (27.5%), antepartum haemorrhage (13.7%) and high prevalence of venereal disease (23.5%). The babies born to drug addicted mothers were on average 629 g lighter at birth, 5 cm smaller in head circumference and 7 cm shorter in body length. Neonatal withdrawal symptoms occurred in 83% of all drug exposed neonates. The perinatal mortality rate was 19.6 per 1,000 total birth which was 2.5 times that of the control group. There was one maternal death in our series. Drug addiction in pregnancy poses a major risk to both mother and child.

The effect of smoking during pregnancy on the incidence of low birth weight among Chinese parturients.

The incidence and effect of smoking in Chinese parturients are not well known. In a retrospective case-controlled study of 213 patients who smoked during pregnancy, it was found that the incidence of low birth-weight was doubled. On average the babies were smaller by 200 g, shorter by 1 cm and the head circumference was smaller by 0.3 cm. These anthropometric deficits may have significant long-term effects. Although the incidence of smoking in Chinese parturients is low (2%), the rising trend in recent years should prompt all physicians to advise expectant mothers to avoid smoking before and during pregnancy.

PIP: A retrospective case controlled study was conducted to ascertain the effects of smoking on pregnancy among 213 pregnant Chinese women. Cases were included from deliveries performed at Tsan Yuk Hospital, Hong Kong, between 1988 and 1990. 4 controls were matched for every case on the basis of age, parity, and year of delivery. Hospital incidence of smoking among pregnant women was 1.57%; there was .28% of heavy smokers among all pregnant women delivering at the hospital. The average number of cigarettes smoked per day was 9. The average age of smoker was 22.6 years. There were no statistically significant differences between controls and study participants for family income, education level, and occupational class. Small babies had been delivered in the past by 17 smoking mothers and by 13 mothers in the control group. Information on smoking, alcohol, and substance abuse was asked repeatedly on the first prenatal visit and thereafter. All were asked to stop smoking. 55% of the women provided data on the time of smoking cessation, of which 2.5% had stopped just before conception. 33% had stopped before 16 weeks, and 23% had stopped between 16 and 30 weeks. 11% stopped at 30-36 weeks, and 29.9% after 36 weeks. The remaining patients (45%) had stopped at some unknown point during the pregnancy. Study participants initiated prenatal care at a later stage of pregnancy (57%) compared with controls (23%). Body weight and prenatal weight gain were similar in both groups. There were no significant differences in prenatal complications or preterm labor between the 2 groups. The results of pregnancy outcome show that babies of smoking mothers weighed 200 gm less than babies of nonsmoking mothers. There were significantly more low birth weight babies (2500 gm) among smokers. The head circumference and supine body length were significantly smaller among the smokers. Apgar scores were similar, but the chances of being admitted to the special baby care unit were higher among smokers. Placental ratio was significantly higher in the study group.

Born before arrival--uncovering the hazards.

In a retrospective case controlled study the demographic background and outcome of 193 mothers whose babies were born before arrival at hospital was compared to that of a control group who delivered within the maternity units of 2 teaching hospitals in Hong Kong. Mothers who delivered before arrival at hospital were significantly more likely to be single, to have received no antenatal care, to have an unplanned pregnancy, low family income and to come from a socially disadvantaged group such as Vietnamese refugees and illegal immigrants from China. Lacerations to the genital tract, postnatal anaemia and blood transfusions were more common in the study group. Results of cervical cytology and rubella status were available in significantly fewer of these mothers. They were more likely to be ambivalent about contraception and less likely to attend the postnatal clinic. The perinatal mortality and morbidity was significantly increased.

A case controlled study of pregnancy complicated by severe maternal anaemia.

The perinatal outcome of 96 patients who had an antenatal haemoglobin value of less than 8.0 g/dl was compared with that of a similar number of controls who were matched for age and parity. Sixty-one patients (63%) had iron deficiency anaemia, 25 (26%) had alpha or beta thalassaemia minor, 7 (7.3%) had iron deficiency and thalassaemia trait, 2 had idiopathic pancytopenia and 1 had haemolytic anaemia due to systemic lupus erythematosus. Patients in the study group attended the antenatal booking clinic later, had less weight gain during pregnancy and their babies had lower birth-weights (2,984 g versus 3,177 g p less than 0.01) although there was no significant difference in the period of gestation at delivery. Six patients in the study group had placental abruption and another 2 patients had stillbirths but neither of these complications occurred in the control group. Although 37 patients (39%) in the study group received an antenatal blood transfusion, 53 (55%) of this group also had postnatal anaemia.