Date Published: April 24, 2019
Publisher: Public Library of Science
Author(s): Vatthanaphone Latthaphasavang, Philippe Vanhems, Nicole Ngo-Giang-Huong, Philavanh Sibounlang, Phimpha Paboriboune, Laurent Malato, Valy Keoluangkhot, Syvilay Thammasack, Nicolas Salvadori, Woottichai Khamduang, Nicolas Steenkeste, Christian Trépo, Paul Dény, Gonzague Jourdain, Pierre Roques.
Mother-to-child transmission of hepatitis B virus (HBV) is the main cause of new infections worldwide. We aimed at assessing the percentage of infants successfully immunized in two major hospitals in Vientiane, Lao PDR where HB immune globulin (HBIg) is not available.
We studied a prospective cohort of chronically HBV infected pregnant women and their infants until 6 months post-partum from January 2015 to March 2017. All infants received HB vaccine at birth and 6, 10 and 14 weeks thereafter, and HBV status was assessed at 6 months of age. HBV surface gene sequencing was performed in infected mother-infant pairs.
Of 153 mothers with HB surface antigen (HBsAg), 60 (39%) had detectable serum HBe antigen (HBeAg). HBeAg positive pregnant women were younger than those negative (median age 26 versus 28 years; p = 0.02) and had a significantly higher HBV viral load at delivery (median 8.0 versus 4.0 log10 IU/mL, p <0.001). Among the 120 infants assessed at 6 months of age, 5 (4%) were positive for HBsAg and had detectable HBV viral load by polymerase chain reaction. All were born to mothers with HBeAg and viral load >8.5 log10 IU/mL. However, only four (3.3%, 95% CI 0.5% to 7.0%) had a virus strain closely related to their mother’s strain. HBV surface gene mutations were detected in 4 of the 5 infected infants. Anti-HBs antibody levels were below 10 IU/L in 10 (9%) uninfected infants at 6 months of age.
Mother-to-child transmission occurred less frequently than expected without the use of HBIg. Adding HBIg and/or maternal antiviral prophylaxis may have prevented some of these infections. The observation of unsatisfactory levels of anti-HBs antibodies in 9% of the uninfected infants at 6 months highlights the need for improvement of the universal immunization procedures.
An estimated 257 million people are chronically infected with hepatitis B virus (HBV) worldwide . Mother-to-child transmission accounts for the majority of new chronic HBV carriers, especially in Asia. HBV can be transmitted in utero, during delivery or during infancy and later [2–4]. About 80–90% of infants infected at birth will develop chronic HBV infection, and 20–30% of adults who are HBV-chronically infected will experience serious complications including liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and liver-related death . HBV Genotypes B and C are common in South-East Asia. Perinatal exposure plays a key role in viral transmission . Combination of hepatitis B immunoglobin at birth and vaccine is highly effective: with this strategy, several studies have observed that more than 85% of infants born to HBV-infected mothers were not infected with HBV [6–12].
The proportion of women with HBeAg (39%) among HBsAg positive women was similar to that reported in recent studies in Asia [11,12]. Of 141 infants born to 140 HBV chronically infected mothers in this study, 120 were assessed for HBV infection at six months of age and, of those 120 infants, 5 (4%) were found infected. As in many settings in the world, newborns had no access to HB immune globulin. As expected, all 5 infected infants were born to a mother who tested positive for HBeAg during pregnancy. The infection rate among infants born to HBeAg positive mothers was similar to that reported in most studies where infants received HBIg, i.e. from 7% to 11% [11,22–24], though two recent studies reported low rates of transmission: 2% in Thailand  and 4.5% in Hong Kong . The relatively low risk of transmission observed in our study could be related to the short duration between birth and first administration of HB vaccine, the lack of invasive procedures, the low percentage of cesarean sections, or sampling variations.
In this first study describing HBV perinatal transmission in Lao PDR, we observed a relatively low rate of MTCT considering the lack of HBIg. Maternal antiviral treatment may have prevented four infections acquired from the mothers. However, one infant was infected by a virus unrelated to her mother’s virus, strongly suggesting immunization failure, and 10 uninfected infants had unsatisfactory levels of anti-HBs antibodies at 6 months. This supports the need for more intensive measures to prevent mother-to-child transmission through the use of immune globulin and/or maternal antiviral prophylaxis, but also the need for improvement of the universal immunization procedures.