In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).

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(Abstracted from N Engl J Med 2016;374:2324–2334) Hepatitis B virus (HBV), a leading cause of cirrhosis and liver cancer, is a serious health threat, and prevention of HBV transmission is an important part of the strategy to alleviate infection and its outcomes. Hepatitis B virus can be vertically transmitted from mothers to fetuses during childbirth, and infants who are untreated can consequently develop chronic infection.

We evaluated the efficacy and safety of telbivudine (LdT, 600 mg/day) vs control patients (no treatment) in decreasing vertical transmission of HBV, in HBeAg-positive mothers (HBVDNA >6log(10) copies/mL). HBeAg-positive pregnant women either in the second or third trimester were recruited in a prospective, case-control, open-label study, at the Second Affiliated Hospital of the Southeast University, China (February 2008-December 2010). Efficacy (month 7: HBVDNA (+), HBsAg (+) infants) in either the overall group or the treated group and control group was analysed using student's t-test. Infants were followed for at least 1 year. 362 women received LdT (second trimester n = 257; third trimester n = 105) and 92 were untreated. Before delivery, the mean maternal HBVDNA was 2.73, 2.47, 3.34 and 7.94 log10 copies/mL in the overall, second and third trimester treated and control groups, respectively (P < 0.001). At birth, 11.8% of babies overall (43/365), 13.5% (35/259) of those treated in the second trimester, 7.5% of those treated in the third trimester (8/106) and 20.7% (19/92) of untreated infants were HBsAg positive. At month 7, none of the LdT-treated infant had detectable HBVDNA, while eight infants from control mothers were HBsAg positive. Vertical transmission was 0% in LdT treated and 9.3% (8/86) in the control groups (P < 0.001). No difference in the vertical transmission rate was found in mothers treated in the second or third trimester. LdT treatment was safe for mothers and infants, and no congenital deformities were reported.

Telbivudine, an FDA pregnancy category B drug, has been found to reduce hepatitis B virus (HBV) perinatal transmission with no safety concerns in infants aged up to 1 year. This study evaluated the long-term efficacy and safety of telbivudine in 214 infants born to 210 pregnant women with chronic hepatitis B infection who were treated with telbivudine during pregnancy (weeks 20-32 of gestation). The infants were followed for up to 5 years after birth. The efficacy endpoint was the rate of perinatal transmission, which was established by HBsAg and HBV DNA levels at 7 and 12 months. Safety endpoints included head circumference, weight, height, congenital abnormality and hospitalization rates. In addition, the Denver Developmental Screening Test was performed in 92 randomly selected infants. None of the 214 infants born to these women were infected with HBV, and all had effective serum hepatitis B surface antibody (HBsAb) levels. Compared with Chinese standard values, there were few differences in the infants' mean head circumference, weight, and height values. No birth defects were diagnosed, and the congenital abnormality rate was 0.934%. Serious adverse events requiring hospitalization occurred in 20 infants (9.35%). The qualified Denver Developmental Screening Test rate in 92 infants was 97.82%, which was comparable to a rate of 92% in normal Chinese children. Thus, treatment with telbivudine during the second or third trimesters of pregnancy safely blocked perinatal transmission of HBV. Infants born to telbivudine-treated mothers showed normal growth and development during long-term follow-up of up to 5 years.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial pneumonia. Compared with glycopeptide antibiotics, linezolid achieves higher lung epithelial lining fluid concentrations, which may have an advantage in treating nosocomial pneumonia patients. The objective of this study was to evaluate the efficacy and safety of linezolid versus vancomycin or teicoplanin for the treatment of nosocomial pneumonia. Data were obtained from the Cochrane Central Register of Controlled Trials and the EMBASE and MEDLINE databases. Randomised controlled studies involving the use of linezolid versus vancomycin or teicoplanin in nosocomial pneumonia patients were included in the study. Twelve linezolid trials were included. There was no statistically significant difference between the two groups in the treatment of nosocomial pneumonia regarding the clinical cure rate [relative risk (RR) = 1.08, 95 % confidence interval (CI) = 1.00-1.17, p = 0.06]. Linezolid was associated with better microbiological eradication rate in nosocomial pneumonia patients compared with glycopeptide antibiotics (RR = 1.16, 95 % CI = 1.03-1.31, p = 0.01). There were no differences in the all-cause mortality (RR = 0.95, 95 % CI = 0.83-1.09, p = 0.46) between the two groups. However, the risks of rash (RR = 0.41, 95 % CI = 0.24-0.71, p = 0.001) and renal dysfunction (RR = 0.41, 95 % CI = 0.27-0.64, p < 0.0001) were higher with glycopeptide antibiotics. Although linezolid was more effective in eradicating microbiology than glycopeptide antibiotics for nosocomial pneumonia patients, it did not demonstrate superiority in clinical cure. The incidences of renal dysfunction and rash are higher in the glycopeptide antibiotics group.

This study aimed to investigate the relationship between hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the ovary and vertical transmission of HBV. HBV DNA and HBV cccDNA were assayed in the ovaries of 33 pregnant women who were positive for HBV DNA. The HBVM (HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) level and the HBV DNA content in peripheral blood of infants were measured. The overall positive rate of HBV DNA and HBV cccDNA in samples was 51·52% (17/33). The intrauterine infection rate of the infants was 12·12% (4/33). When HBV DNA and HBV cccDNA were both positive, the intrauterine infection rate of infants was significantly higher than when they were both negative (P<0·05). Levels of HBV cccDNA and the rate of positive samples were significantly higher in mothers with infants with intrauterine infection than in those without (P<0·01 and P<0·05, respectively). HBV can infect the human ovary and may transmit to the filial generation via the ovum.

ObjectiveThe physical and neuromental development of infants remains uncertain after fetal exposure to tenofovir disoproxil fumarate (TDF) for the prevention of mother-to-child transmission of HBV. We aimed to investigate the safety of TDF therapy during the third trimester of pregnancy.DesignInfants from a previous randomised controlled trial were recruited for our long-term follow-up (LTFU) study. Mothers with chronic hepatitis B were randomised to receive TDF therapy or no treatment during the third trimester. Infants’ physical growth or malformation, bone mineral density (BMD) and neurodevelopment, as assessed using Bayley-III assessment, were examined at 192 weeks of age.ResultsOf 180 eligible infants, 176/180 (98%) were enrolled and 145/176 (82%) completed the LTFU (control group: 75; TDF-treated group: 70). In the TDF-treated group, the mean duration of fetal exposure to TDF was 8.57±0.53 weeks. Congenital malformation rates were similar between the two groups at week 192. The mean body weight of boys in the control and TDF-treated groups was significantly higher (19.84±3.46 kg vs. 18.47±2.34 kg; p=0.03) and within the normal range (18.48±2.35 kg vs. 17.80±2.50 kg; p=0.07), respectively, when compared with the national standard. Other prespecified outcomes (head circumference, height, BMD, and cognitive, motor, social–emotional, and adaptive behaviour measurements) were all comparable between the groups.ConclusionInfants with fetal exposure to TDF had normal physical growth, BMD and neurodevelopment at week 192. Our findings provide evidence on the long-term safety of infants after fetal exposure to maternal TDF therapy for preventing hepatitis B transmission.Trial registration numberNCT01488526.