Ching-Chang Tsai

Proteomic profiling reveals α1-antitrypsin, α1-microglobulin, and clusterin as preeclampsia-related serum proteins in pregnant women

OBJECTIVE Preeclampsia is a major cause of mortality in pregnant women but the underlying mechanism remains unclear to date. In this study, we attempted to identify candidate proteins that might be associated with preeclampsia in pregnant women by means of proteomics tools. MATERIALS AND METHODS Differentially expressed proteins in serum samples obtained from pregnant women with severe preeclampsia (n = 8) and control participants (n = 8) were identified using two-dimensional gel electrophoresis (2-DE) followed by peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Additional serum samples from 50 normal and 41 pregnant women with severe preeclampsia were analyzed by immunoassay for validation. RESULTS Ten protein spots were found to be upregulated significantly in women with severe preeclampsia. These protein spots had the peptide mass fingerprints matched to α1-antitrypsin, α1-microglobulin, clusterin, and haptoglobin. Immunoassays in an independent series of serum samples showed that serum α1-antitrypsin, α1-microglobulin, and clusterin levels of severe preeclampsia patients (n = 41) were significantly higher than those in the normal participants (n = 50; α1-antitrypsin 295.95 ± 50.94 mg/dL vs. 259.31 ± 33.90 mg/dL, p = 0.02; α1-microglobulin 0.029 ± 0.004 mg/mL vs. 0.020 ± 0.004 mg/mL, p < 0.0001; clusterin 77.6 ± 16.15 μg/dL vs. 67.6 ± 15.87 μg/dL, p < 0.05). CONCLUSION Identification of these proteins by proteomics analysis enables further understanding of the pathophysiology of preeclampsia. Further studies are warranted to investigate the role of these biomarkers in prediction of this disease.

High interleukin-16 concentrations in the early second trimester amniotic fluid: an independent predictive marker for preterm birth.

Objective: Infection is believed to be one of frequent and important causes of preterm labor. We attempted to evaluate whether the level of inflammatory markers, e.g. interleukin-16 (IL-16), interleukin-18 (IL-18), and ferritin, in amniotic fluid at early second trimester can predict preterm birth. Methods: Amniotic fluid (AF) samples were collected from 350 pregnant women who had trans-abdominal amniocentesis for genetic indications at 16 to 20 weeks of gestation. AF levels of IL-16, IL-18 and ferritin levels were measured by immunoassay and were correlated with pregnancy outcomes. Results: Among the 350 pregnant women, 58 (16.6%) had preterm birth (<37 weeks gestation). AF levels of IL-16, IL-18, and ferritin were significantly higher in pregnant women with subsequent preterm birth. Multivariate analyses showed that a quartile higher of AF IL-16 level was significantly associated with preterm birth (OR: 3.09, 95% CI 1.52–6.27, p = 0.002). A receiver operating characteristic analysis revealed that an IL-16 cutoff value of 105 pg/ml was a reliable predictor of preterm birth (sensitivity, 90.2%; specificity, 52.7%; negative predictive value, 84.3%). Conclusion: It is feasible to predict preterm birth by measuring the AF levels of IL-16 especially for the pregnant women requiring genetic amniocentesis during early second trimester.

Confined placental mosaicism of double trisomies 9 and 21: discrepancy between non‐invasive prenatal testing, chorionic villus sampling and postnatal confirmation

Confined placental mosaicism (CPM) is a prenatal condition of tissue-specific mosaicism in which a cytogenetic abnormality is confined to the placenta and is absent in the fetus1. Most CPM pregnancies are associated with good postnatal outcome but an impaired placenta may provide insufficient support for the pregnancy, leading to fetal complications such as intrauterine growth restriction (IUGR) or even intrauterine fetal demise (IUFD)2. Here we report an unusual case of a fetus with severe IUGR and oligohydramnios that was later diagnosed to have CPM of double trisomies 9 and 21, demonstrating the discrepancies between non-invasive prenatal testing (NIPT), chorionic villus sampling (CVS) and postnatal confirmation. A 40-year-old pregnant woman, gravida 2 para 1, was referred to our clinic at 32 weeks’ gestation because of oligohydramnios and severe IUGR. Prior to this visit, she had received regular prenatal care in mainland China and the pregnancy had been uneventful until the third trimester. The patient opted for NIPT (NIFTY-Extended test; BGI, Shenzhen, China) instead of CVS and amniocentesis due to her advanced age. The risks of fetal trisomies 13, 18 and 21 were low but trisomy 9 was suspected. A detailed ultrasound examination found nearly no amniotic fluid and severe IUGR; estimated fetal weight was 699 g, corresponding to 24 + 2 weeks’ gestation. As oligohydramnios made it difficult to identify fetal anatomy by ultrasound, magnetic resonance imaging (MRI) was performed subsequently. No significant anomaly was noted except oligohydramnios (Figure 1). Repeated NIPT with the genome-wide normalized score test3, performed by our laboratory, also indicated a high risk for trisomy 9 (P < 0.0001). Interphase fluorescence

Steatotic hepatocellular carcinomatosis mimicking malignant ovarian teratoma

to those confirmed on histopathological examination (Figure 1). The overall radiological and pathological features, including non-specific disorganization of the growth plates, were most suggestive of the short-rib polydactyly syndrome spectrum, an autosomal recessive group of disorders1. To the best of our knowledge, this is the first report of the use of postmortem imaging in the diagnosis of lethal skeletal dysplasia. The outstanding anatomical detail of not only the ossified bone, but also the growth plate zone, using postmortem MRI, suggests that this modality may become increasingly important and useful in the diagnosis of skeletal dysplasias, both preand postmortem, as increasing experience of their appearance is gained.

Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a Well Vaccinated Area

To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m2) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas.

Second-trimester placental volume and vascular indices in the prediction of small-for-gestational-age neonates.

Objective: To evaluate the ability of second-trimester placental volume and vascular indices to predict small-for-gestational-age (SGA) birth weight pregnancies. Material and Methods: Women with singleton pregnancies were prospectively evaluated at 17-20 weeks of gestation. Second-trimester placental volume and vascular indices were obtained and calculated using volume organ computer-aided analysis and three-dimensional (3D) power Doppler ultrasound. Participants were followed until delivery and their medical records were reviewed, including maternal age, parity and pregestational body weight and body height, as well as the gestational age, birth weight and gender of the fetus. Results: Of the 163 women with complete follow-up, 20 gave birth to SGA and 143 to appropriate-for-gestational-age (AGA) neonates. The mean second-trimester placental volume was significantly lower in the SGA than in the AGA group (170.6 ± 49.8 vs. 213.5 ± 75.8 cm3, p = 0.015). None of the vascular indices, including the vascularization index, flow index and vascularization flow index, differed significantly between the two groups. We also found that the optimum cutoff for placental volume at a gestational age of 17-18 weeks was 189.7 cm3. Discussion: Second-trimester placental volume was positively correlated with neonatal birth weight. Second-trimester placental volume measured on 3D ultrasound may be predictive of SGA neonates.

Prenatal sonographic appearance of Beare–Stevenson cutis gyrata syndrome

Background:  Beare first described a 2‐year‐old boy who had abnormal physical feature including hypertelorism, cutis gyratum, acanthosis nigrican, cleft palate, functional pyloric obstruction and abnormal genitalia. Ten cases of Beare–Stevenson cutis gyrata syndrome have been reported. Here, we present, the first case of antenatal ultrasound image of this rare syndrome. A 31‐year‐old Taiwanese, gravida 2, para 1, was referred for fetal evaluation at 32 weeks gestation because of polyhydramnios and fetal head anomaly. Conventional sonography revealed a single fetus with amniotic index of 27.3 cm, cover leaf skull, and a skin fold‐like umbilical cord. Three‐dimensional sonography of the face of the fetus showed, high wide forehead, ocular proptosis, and depressed nasal bridge. The patient delivered a male infant weighing 2980 g at 39 weeks gestation. Physical examination of the infant showed furrows of corrugated appearance of the skin, craniofacial anomalies, particularly craniosynosis, displaced ears, prominent umbilical stump and hypospadia. Computer tomography and magnetic resonance image were performed and revealed fronto‐ethmoid‐nasal, cephalocele, pansynostosis and frontal base defect.