Understanding the influence of cytokines in intrauterine hepatitis B transmission: A cross-sectional study in China.

Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.

Intrauterine transmission of SARS-CoV-2 to and prenatal ultrasound abnormal findings in the fetus of a pregnant woman with mild COVID-19.

BACKGROUND: Whether intrauterine transmission of COVID-19 occurs remains uncertain, and it remains unclear whether the disease affects fetuses. We present a case of intrauterine transmission of SARS-CoV-2 infection and the prenatal ultrasonographic findings of the fetus in a pregnant woman with mild COVID-19. CASE PRESENTATION: A 30-year-old woman was admitted to our hospital for ultrasound examination in January 2023 at 26+ 3 weeks' gestation. Twenty-one days prior, her COVID-19 nucleic acid test was positive, and she had mild symptoms, including fever (38.3 °C), headache, chills, ankle pain and cough. After receiving symptomatic treatment, she fully recovered. Prenatal ultrasound revealed that the placenta was diffusely distributed with punctate echogenic foci, hepatomegaly, and the volume of bilateral lungs decreased significantly, with enhanced echo. In addition, we found that the surface of the fetal brain demonstrated widened gyri with a flattened surface. The prenatal MRI confirmed these fetal abnormalities. Amniotic fluid was tested for SARS-CoV-2, and the sample tested was positive for the virus. After careful consideration, the pregnant woman decided to terminate the pregnancy. CONCLUSION: The intrauterine transmission of COVID-19 is certain. Moreover, the intrauterine transmission of COVID-19 may cause abnormalities in various organs of the fetus.

Intrauterine Transmission of SARS-CoV-2.

We documented fetal death associated with intrauterine transmission of severe acute respiratory syndrome coronavirus 2. We found chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrate in muscle in the placenta and fetal tissue. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission.

The metabolic and immunological characteristics of pregnant women with COVID-19 and their neonates.

Our aim was to investigate whether SARS-CoV-2 infection raised high risks of late pregnancy complications, and posed health problems in fetuses and neonates. We analyzed the data of COVID-19 pregnant women with COVID-19 during late pregnancy and their neonates. Eleven out of 16 (69%) pregnant women with COVID-19 had ++ or +++ of ketone body in urine. The blood uric acid of pregnant patients was 334 µmol/L (IQR, 269-452). D-dimer and FDP in pregnant patients were 3.32 mg/L (IQR, 2.18-4.21) and 9.6 mg/L (IQR, 5.9-12.4). Results of blood samples collected at birth showed that 16 neonates had leukocytes (15.7 × 109/L (IQR, 13.7-17.2)), neutrophils (11.1 × 109/L (IQR, 9.2-13.2)), CK (401 U/L (IQR, 382-647)), and LDH (445 U/L (IQR, 417-559)). Twenty-four hours after birth, a neonate from COVID-19 woman had fever and positive of SARS-CoV-2 gene. Another woman had strongly positive for SARS-CoV-2 gene (+++) for 4 weeks, and delivered one neonate who had SARS-CoV-2 IgM (46 AU/mL) and IgG (140 AU/mL) on day 1 after birth. In the third trimester, COVID-19 infection in pregnant patients raised high risks of ketonuria, hypercoagulable state, and hyperfibrinolysis, which may lead to severe complications. COVID-19 increased the inflammatory responses of placenta, and fetuses and neonates had potential organ dysregulation and coagulation disorders. There was a potential intrauterine transmission while pregnant women had high titer of SARS-CoV-2, but it is necessary to detect SARS-CoV-2 in the blood cord, placenta, and amniotic fluid to further confirm intrauterine infection of fetuses.

Expression of S100 proteins is associated with HBV intrauterine transmission.

PURPOSE: The mechanisms underlying HBV intrauterine transmission remain unknown. In this study, we explored the mechanism of HBV intrauterine transmission by iTRAQ proteomics analysis. METHODS: iTRAQ technology was applied to perform comparative proteomics studies on six HBV+/+ neonates and six HBV+/- neonates whose mothers and fathers were HBsAg positive and paternal HBsAg negative, respectively. The data obtained from the mass spectrometer were analyzed using MASCOT ( https://matrixscience.com ) to qualitatively and quantitatively compare the differentially expressed proteins in the two groups. Gene Ontology and KEGG pathway analyses were performed to analyze the differentially expressed proteins. The expressions of HBV intrauterine transmission-related proteins in serum samples and corresponding placental tissues were further verified by immunohistochemistry and Western Blot. Then, the human trophoblast cell line (Swan71) infected with HBV was used to analyze the potential mechanisms of HBV intrauterine transmission under the mediation of differential proteins. RESULTS: A total of 35 differentially expressed proteins, including 17 up-regulated proteins and 18 down-regulated proteins, were identified by comparing serum protein expression levels in HBV+/+ and HBV+/- neonates. The differentially expressed proteins were mainly related to RAGE receptor binding, NF-kappa B transcription factor activity, innate immune response, defense response to bacterium, and the signaling pathway in pathogenic microorganism infection. The expressions of S100A8/9/12 in HBV+/+ maternal placenta tissue were significantly increased. The expressions of S100A8/9/12 proteins in Swan71 cells were significantly increased after HBV infection. CONCLUSION: High expression of S100 proteins may be associated with the intrauterine-transplacental transmission of HBV.

Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface.

Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. IMPORTANCE: In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fetal compartment via efficient replication within the maternal decidual aspect of the placenta, coinhabited by maternal and fetal cells. The identified distinct placental tissue innate immune responses and damage pathways could provide a mechanistic basis for some of the placental developmental abnormalities associated with ZIKV infection. The findings in the unique model of the human decidua should pave the way to future studies examining the interaction of ZIKV with decidual immune cells and to evaluation of therapeutic interventions aimed at the earliest stages of transmission.

Intrauterine HPV transmission: a systematic review of the literature.

PURPOSE: To evaluate the percentage of intrauterine vertical human papillomavirus (HPV) transmission among HPV-positive mothers and the relative risk of intrauterine vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women. METHODS: This systematic review was made according to the PRISMA statement. We searched PubMed and Scopus and the final articles were selected by two reviewers. Data from the selected articles were plotted, and the pooled percentage of antenatal vertical HPV transmission among HPV-positive mothers as well as the pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women were calculated. RESULTS: 9 studies including 421 HPV-positive mothers and their offsprings were selected from 434 potential papers. Following meta-analysis, the pooled percentage of antenatal vertical HPV transmission was 4.936% (95% CI 1.651-9.849), with moderate heterogeneity between the studies (I2 = 72.22%). The pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women was 0.912, with no statistical significance (95% CI 0.226-3.674) and homogeneity between the studies (I2 = 24.48%).

Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study.

Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up.

Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus.

Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti-microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human ß-defensin-3 (HBD-3), apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV-seronegative pregnant women (controls), 7 HBV-seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV-seropositive pregnant women with non-infected infants (non-infected group). The expression of HBD-3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD-3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD-3 and A3G were higher in non-infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD-3, A3G, and MBL by Swan 71. It may be concluded HBV up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of HBV.

Evaluation of neonatal Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in HBV intrauterine transmission susceptibility.

To investigate whether single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV) intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A femoral venous blood sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence quantitative PCR assay. Our results showed that when adjusting for maternal HBeAg, maternal HBV DNA and mode of delivery, allele 'T' for SNP c.1377C/T was significantly associated with HBV intrauterine transmission susceptibility [adjusted OR (aOR) 0.55, 95% confidence interval (CI) 0.34-0.91, P = 0.020] and the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0.28, 95% CI 0.09-0.91, P = 0.033). Allele 'A' for SNP G2848A was significantly associated with HBV intrauterine transmission susceptibility (aOR 0.62, 95% CI 0.39-1.00, P = 0.048) and the GA genotype protected neonates from HBV intrauterine transmission (aOR 0.45, 95% CI 0.22-0.93, P = 0.031). The TLR3 (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine transmission susceptibility, although the reduction in risk to HBV intrauterine transmission is modest and the biological mechanism of the observed association merits further investigation.

Possibility of intrauterine transmission from mother to fetus/newborn: Systematic review and meta-analysis of diagnostic methods to detect SARS-CoV-2 infection.

Several studies have reported vertical transmission of SARS-CoV-2; however, information regarding intrauterine transmission based on diagnostic methods to detect SARS-CoV-2 infection is scarce. A systematic review and meta-analysis was conducted to identify and explore the studies that attempt to ascertain the possibility of intrauterine transmission of SARS-CoV-2 infection according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement. The results demonstrate that SARS-CoV-2 can be transmitted intrauterine, as detected by clinical manifestations (1.00, 95 % CI: 1.00 - 1.00, 0.51, 95 % CI: 0.22 - 0.80), imaging (0.50, 95 % CI: 0.24 - 0.76, 0.03, 95 % CI: 0.00 - 0.17), molecular (1. 00, 95 % CI: 1.00 - 1.00, 0.92, 95 % CI: 0.77 - 1.00), immunological (0.32, 95 % CI: 0.10 - 0.57, 0.34, 95 % CI: 0.11 - 0.61), and histological approaches (0.79, 95 % CI: 0.52 - 0.98) in maternal and fetal/neonatal specimens, respectively. The possibility of intrauterine transmission of SARS-CoV-2 from mother to fetus/newborn was 41 % (95 % CI 0.37 - 0.45). We might confirm/verify the intrauterine transmission of SARS-CoCV-2 from mother to fetus/newborn.

Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission.

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.

A case report: Hypoxic ischemic encephalopathy & pneumonia in a neonate after SARS-CoV-2 intrauterine transmission.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is primarily transmitted via respiratory droplet or aerosol route. However, there is mounting evidence for intrauterine transmission. We report on a late preterm infant with suspected intrauterine acquisition of SARS-CoV-2 who experienced birth depression, hypoxic ischemic encephalopathy, multisystem organ involvement, and late onset COVID-19 pneumonia [22].

COVID-19 and Pregnancy.

Pregnancy seems to be a risk factor for severe disease with COVID-19. Although SARS-CoV-2 intrauterine transmission seems to be rare, most studies show COVID-19 during pregnancy increases the risk for pregnancy complications, with higher risk among those with severe disease compared with those mildly affected. Studies suggest that COVID-19 vaccination during pregnancy is safe and effective. Antibodies to SARS-CoV-2 have been found in umbilical cord blood and breast milk following maternal vaccination, which might provide protection to the infant. However, vaccination rates during pregnancy remain low. Studies are needed to understand ways to address SARS-CoV-2 vaccine hesitancy among pregnant persons.

Detection and isolation of small ruminant lentivirus in the amniotic fluid of goats.

The objective of this study was to verify the presence of small ruminant lentivirus in the amniotic fluid of goats using molecular tests and viral isolation by cocultivation in the amniotic fluid of naturally infected goats. The study analyzed eight goats: seven were small ruminant lentivirus-positive and one was negative. The amniotic fluid was collected from each of the eight animals during cesarean section at 147 days of pregnancy. Cocultivation was undertaken using secondary goat nictitating membrane cell cultures obtained by explant from a small ruminant lentivirus-negative calf followed by trypsinization and sub-cultivation of the cells for 63 days. During this period, five supernatant collections were performed for DNA extraction and subsequent nested polymerase chain reaction. DNA was extracted from the amniotic fluid after 3 h of cellular sedimentation, from which a sample of 600 µL was taken from the sediment and another 600 µL sample from the supernatant. After DNA extraction, nested polymerase chain reaction was performed. Of the eight goats, 62.5 % (05/08) were small ruminant lentivirus-positive, with 43.75 % (07/16) of the total samples positive when considering the two repetitions (supernatant and cell sediment). Moreover, positivity was confirmed by small ruminant lentivirus pro-viral DNA amplification in the cell supernatant throughout the cocultivation period. Small ruminant lentivirus were present in the amniotic fluid samples from the naturally infected goats indicating an intrauterine transmission route. Moreover, this biological fluid can be adopted for the diagnosis of these lentiviruse because it is an important risk factor related to intrauterine transmission.

Quantitative HBsAg and Qualitative HBeAg Predicts Intrauterine Placental Infection and Umbilical Blood Cord in Pregnant Women.

Objective: To know the correlation between quantitative Hepatitis B surface Antigen (HbsAg) and maternal Hepatitis B Envelope Antigen (HbeAg) with hepatitis B intrauterine transmission via placental infection. Hepatitis B in pregnancy causes a mother to child transmission (MTCT) via transplacental route started with placental infection. HBV DNA viral load and HBeAg are the independent risk factors for MTCT, but it rarely available in developing country. Materials and methods: A cross-sectional study in 33 pregnant women with HbsAg positive in 4 referral hospital in East Java, Indonesia. Quantitative HBS Ag and HBeAg) status were determined serologically from a peripheral venous blood sample. Placental Hepatitis B infection was detected by immunohistochemistry of HBsAg from placental tissues. The intrauterine transmission was diagnosed by positive HBsAg in cord blood sampling after deliveries. Results: Serum quantitative HBsAg level has a good sensitivity and spesificity to predict placental infection (90% and 83%), with a cut off value of 3.14 Log10 IU/mL (AUC 0.87; 95% CI: 0.74-0.99). Quantitative HBsAg level also has a good sensitivity and spesificity to predict HBV transmission in umbilical blood cord (81.8% and 95.5%) with a cut off value of 3.62 log10 IU/ml (AUC: 0.925, 95% CI: 0.813-1; p = 0.000). Placental infection is significantly related with intrauterine transmission with OR 4.6 (95% CI 2.29-9.4; p = 0.002). Conclusion: The study reveals that maternal serum quantitative HBsAg level can be used as an alternative test to substitute HBeAg or HBV DNA as a marker to predict the placental infection and intrauterine transmission, especially in low-middle income countries.

[Relationship between mutations of HBV basal core promoter region in HBsAg-positive mothers and intrauterine transmission].

Objective: To analyze the relationship between maternal mutations in basal core promoter region of hepatitis B virus (HBV) genotype C and intrauterine transmission. Methods: We collected information on general demographic characteristics and process of delivery among 399 pairs of consecutive HBsAg-positive mothers and their neonates, from the Third People's Hospital of Taiyuan in Shanxi province, China. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Electro-chemiluminescence immuno-assay (ECLIA) kits were used to detect both maternal and neonatal HBV DNA and serological markers in the peripheral blood. From 113 mothers with HBV DNA load ≥10(6) IU/ml, we selected 22 mothers whose neonates were with intrauterine transmission and randomly selected the same number of mothers whose neonates were without intrauterine transmission, as controls. The whole-length HBV DNA were extracted, amplified, cloned, sequenced and genotyped. Finally, a total of 39 mothers with genotype C of HBV were selected for mutation analysis. Results: Thirty-nine cases of genotype C (88.63%) were finally included in the study, with 19 cases in the intrauterine transmission group and 20 cases as controls. Rates of A1762T/G1764A double mutations were significantly different between the intrauterine transmission group and the control group (7.53% vs. 27.72%, P<0.001). Results from the multivariate analysis showed that the A1762T/G1764A double mutations had reduced the risk of intrauterine transmission (aOR=0.065, 95%CI: 0.006-0.746, P=0.028). Maternal A1762T/G1764A double mutations appeared to be possibly associated with neonatal HBeAg (P=0.050). Conclusion: A1762T/G1764A double mutations of HBV DNA from the genotype C of those HBsAg-positive mothers could reduced the risk of HBV intrauterine transmission during pregnancy.

[Important role of study on intrauterine transmission of HBV in prevention and control of hepatitis B].

The new research of intrauterine transmission of HBV includes intrauterine dominant infection and occult infection. Intrauterine dominant infection of HBV is the traditional intrauterine infection. Although intrauterine infection of HBV has been studied for decades, the intervention effects on HBV infection are very limited. As a result, mother to child transmission has become the main route of the transmission of HBV. With the development of science and technology, people's understand of intrauterine occult infection of HBV has been deepened, and the definition of intrauterine transmission of HBV has been further completed and expanded. The study of intrauterine occult infection of HBV will play an important role in prevention and control of hepatitis B in China through filling in a gap in the field of prevention and control of vertical transmission of HBV, exploring new research perspective and providing guideline for related decision-making.

[Epidemiology study of intrauterine transmission of HBV in HBsAg-positive parturients in Xi'an].

Objective: To investigate the current status and influence factors of HBV intrauterine transmission (BIT) in HBsAg-positive parturients and understand the outcome of HBV transmission and response to hepatitis B vaccine immunization in children in Xi'an. Methods: An epidemiological survey was conducted in 341 HBsAg-positive parturients who gave birth in Northwest Women and Children Hospital of Shaanxi Province from January 2015 to January 2018. Serological tests were performed by using venous blood from 344 newborns within 24 hours after birth and at the age of 1 year old. A nested case-control study was conducted to analyze the infection rates of intrauterine dominate HBV infection (DBI) and intrauterine occult HBV infection (OBI) in BIT and their influencing factors in newborns. The epidemiological survey was conducted to collect the information about the outcome of HBV transmission and the positive rate of HBsAb in children at high-risk from August 2016 to October 2018. Results: The BIT rate was 46.51%(160/344) in HBsAg-positive parturients, the DBI rate was 8.14% (28/344), the OBI rate was 38.37% (132/344), and the odds ratio of DBI and BIT in neonates of HBeAg-positive parturients were respectively 2.60 (95%CI: 1.19-5.70) and 2.21 (95%CI: 1.36-3.61) times higher than that of HBeAg-negative parturients. The odds ratio of BIT in neonates with maternal peripheral blood HBV DNA load ≥200, ≥10(3) and>10(6) copies/ml were 1.99 (95%CI: 1.29-3.08), 1.73 (95%CI: 1.11-2.69) and 2.33 (95%CI: 1.33-4.10) times higher than those in neonates with maternal peripheral blood HBV DNA<200,<10(3), and ≤10(6) copies/ml respectively. The incidence of DBI in neonates of parturients with placenta previa was 14.07 times higher than that of parturients without placenta previa (95%CI: 1.23-160.76). The incidence of BIT in neonates of parturients who received no hepatitis B immunoglobulin during pregnancy was 1.60 times higher than that in neonates of those who received hepatitis B immunoglobulin (95%CI: 1.02-2.53). Follow-up results showed that HBsAg negative conversion was found in 9 of 14 children with DBI, and 24.17%(22/91) of children had OBI. The overall rate of immune response to hepatitis B vaccine was 69.23%(63/91). The immune response rate in children with OBI was only 59.09%(13/22). Conclusion: Newborns of HBsAg-positive parturients had high rate of OBI and lower rate of immune response to hepatitis B vaccine detected in follow-up, indicating a gap in hepatitis B prevention and control. HBV monitoring and intervention in HBsAg-positive women of childbearing age and hepatitis B antibody monitoring in children at high-risk are important measures to control infection source and protect susceptible population.

[Correlation study of IL-18 expression in HBsAg positive parturients in intrauterine transmission of HBV].

Objective: To investigate the expression of IL-18 in peripheral blood of HBsAg positive parturients in intrauterine transmission of HBV. Methods: A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B, real time PCR was used to detect HBV DNA, and flow liquid chip method was used to detect IL-18 levels in peripheral blood of parturients and newborns. Results: The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 8.42% (24/285), 40.00% (114/285) and 48.42% (138/285), respectively. The level of IL-18 in peripheral blood of HBsAg-negative parturients were significantly lower than those of HBsAg-positive parturients (P=0.001), non-HBV intrauterine transmission (NBIT) group (P=0.001) and OBI group (P<0.001). The level of IL-18 in HBeAg negative group was significantly lower than that in HBeAg positive group (P=0.023). When HBV DNA load was ≥10(3) copies/ml, the level of IL-18 was significantly higher than that in HBsAg-negative group (P<0.01). With the increase of HBV DNA load in maternal blood, the level of IL-18 increased (P=0.024). When HBV DNA load was 10(3)-10(6) copies/ml, the level of IL-18 in DBI group was significantly lower than that in NBIT group (P=0.022), and increased with the increase of HBV DNA load in maternal blood (P=0.016). With the increased severity of intrauterine transmission of HBV, the level of IL-18 in non-hepatitis B vaccine group decreased significantly (P=0.044). The level of IL-18 in non-hepatitis B vaccine group and immunoglobulin injection group was significantly higher than that in NBIT group (P<0.05). Multivariate analysis showed that the linear relationship between maternal HBeAg status and maternal IL-18 levels had statistical significance (P=0.01). Conclusions: IL-18 is a higher level balance regulator of Th1/Th2 immune network. Monitoring the level of IL-18 in HBsAg-positive parturients can be used not only for predicting the probability of DBI and OBI, but also as an intervention mean, especially for those who are HBeAg-positive and had HBV DNA load ≥10(3) copies/ml, to improve maternal cellular immune function, which is conducive to interrupting intrauterine transmission and providing a theoretical basis for the prevention and control of HBV intrauterine transmission.