Maternal hepatitis B virus carrier status and pregnancy outcomes: a prospective cohort study

Cui et al. BMC Pregnancy and Childbirth (2016) 16:87 DOI 10.1186/s12884-016-0884-1 RESEARCH ARTICLE Open Access Maternal hepatitis B virus carrier status and pregnancy outcomes: a prospective cohort study Ai-Ming Cui1†, Xiao-Yan Cheng1†, Jian-Guo Shao2†, Hai-Bo Li3, Xu-Lin Wang4, Yi Shen4, Li-Jing Mao1, Sheng Zhang4, Hai-Yun Liu1, Lei Zhang5 and Gang Qin2,4* Abstract Background: Infection with hepatitis B virus (HBV) in pregnant women may be a threat for both mothers and fetuses. This study was performed to explore the impact of maternal HBV carrier status on pregnancy outcomes. Methods: We conducted a prospective cohort study at the Obstetrics & Gynecology Hospital of Nantong University between January 1, 2012 and September 30, 2015. A consecutive sample of 21,004 pregnant women, 513 asymptomatic HBV carriers and 20,491 non-HBV controls, was included in this study. The main outcomes of interest were selected pregnancy outcomes including miscarriage, stillbirth, preterm birth (PTB), gestational diabetes (GDM), intrahepatic cholestasis of pregnancy (ICP), preterm premature rupture of the membrane (PPROM), low birth weight (LBW), small for gestational age (SGA) and Apgar scores. The incidence of adverse pregnancy outcomes between asymptomatic HBV carriers and non-HBV controls were compared using the chi-square test and logistic regression. P values were two sided, and P <0.05 was considered to indicate statistical significance. Results: The incidences of stillbirth, PTB, GDM, ICP, PPROM, LBW, and SGA were similar between the HBV carrier and non-HBV groups. The proportion of miscarriage was significantly higher among the HBV carriers than the controls (9.36 % vs 5.70 %; P <0.001). After using multivariate modelling to adjust for possible socio-demographical variables and obstetric complications, women with HBV carrier status were still more likely to have miscarriage (adjusted OR 1.71, 95 % CI 1.23–2.38). In addition, the incidences of other maternal and neonatal outcomes were similar between the two groups. Conclusion: Maternal HBV carrier status may be an independent risk factor for miscarriage and careful surveillance is warranted. Keywords: Pregnancy, Hepatitis B virus infection, Miscarriage Background Hepatitis B virus (HBV) infection is one of the most common health problems worldwide. The prevalence of HBV infection among women of childbearing age may be as high as 2–8 % in China [1, 2], whereas in the USA it is only 0.4 % [3]. Most pregnant women with HBV infection are chronic carriers, indicated by positive * Correspondence: † Equal contributors 2 Center for Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, China 4 Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, 9 Se-Yuan Road, Nantong, Jiangsu 226000, China Full list of author information is available at the end of the article serum hepatitis B surface antigen (HBsAg) status. HBsAg expression has also been found in cells of the ovarian follicle or placental capillary endothelium [4]. Intrauterine infection and vertical transmission of HBV is a fundamental reason why there are so many chronic HBV carriers in China. The overall estimated rates of immunoprophylaxis failure for infants with HBsAgpositive and HBeAg-positive mothers were 4.87 and 9.66 % respectively [5]. Although HBV carrier status is relatively common among pregnant women, especially in highly endemic countries such as China, there is a paucity of data regarding the impact of maternal HBV infection on the © 2016 Cui et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Cui et al. BMC Pregnancy and Childbirth (2016) 16:87 risk for adverse pregnancy outcomes. The limited studies on this issue have always yielded conflicting results [6–15]. Due to this dearth of information, we undertook this hospital-based prospective cohort study, which seeks to examine the association of HBV carrier status with pregnancy outcomes. Methods Study design and participant population We conducted a prospective cohort study at the Obstetrics & Gynecology Hospital of Nantong University, China between January 1, 2012 and September 30, 2015. All pregnant women who visited the tertiary teaching hospital were screened and recruited through 2012 to 2014. Data on maternal characteristics (age, education, medical history) were taken from questionnaires completed by women after their first antenatal visit. Body mass index (BMI) was classified according to the WHO classification: underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) or obesity (≥30 kg/m2) [16]. As part of standard prenatal care at our hospital, all women are screened in the first trimester of pregnancy for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), IgG antibodies against HCV and HIV, syphilis tests with the treponema pallidum particle agglutination assay (TP-PA) and RPR, specific IgM antibodies against toxoplasma, rubella virus, CMV and HSV-1/2. All enrolled participants fulfilled the following criteria: (i) normal alanine transaminase (ALT) at study entry; (ii) no evidence of hepatitis C virus (HCV) infection (antiHCV negative), (iii) absence of human immunodeficiency virus (HIV) infection (anti-HIV negative) and active syphilis infection (rapid plasma reagin test/RPR negative); (iv) absence of IgM antibodies against toxoplasma (TOX), rubella virus (RV), cytomegalovirus (CMV), herpes simplex virus (HSV-1/2); (v) exclusion of other liver diseases such as alcoholic liver diseases (ALDs), nonalcoholic fatty liver diseases (NAFLDs) or autoimmune liver diseases (AILDs); (vi) absence of preexisting chronic diseases such as diabetes mellitus, hypertension, or heart diseases. HBV carriers were defined as: HBsAg positivity >6 months confirmed by previous medical history, and persistently normal levels of ALT before and at study entry. In addition, HBV carriers were excluded if they had received antiviral treatment within the previous year. A total of 24,713 pregnant women were reviewed and screened in their first trimester of pregnancy at the Obstetrics & Gynecology Hospital of Nantong University, China. Of these, 3382 were excluded: due to abnormal ALT or other liver diseases (HCV infection, ALDs, NAFLDs, or AILDs) in 1065 subjects; due to other infection (HIV infection, active syphilis infection, positivity of Page 2 of 8 anti-TOX IgM, a (...truncated)