Objective
We sought to determine rates of maternal postpartum hepatitis B virus (HBV) follow-up with a HBV specialist and identify factors associated with poor follow-up, as prior research has focused on infant outcomes and not maternal care.
Study Design
We conducted a retrospective review of data from Partners HealthCare system, the largest health care system in Massachusetts, and identified women with chronic HBV who delivered from 2002 through 2012.
Results
We identified 291 women (mean age 31.5 years, 51% Asian) with incident HBV during pregnancy. In all, 47% had postpartum follow-up with a HBV specialist, but only 19% also had appropriate laboratory tests (hepatitis B e antigen [HBeAg], hepatitis B e antibody, HBV DNA, and ALT) within 1 year of their HBV diagnosis. Mothers with HBV follow-up were more likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001), a positive HBeAg (20% vs 8%, P = .004), and elevated AST values (17% vs 8%, P = .02). On multivariable logistic regression analysis, a mother who had a PCP (odds ratio, 2.50; 95% confidence interval, 1.37–4.59) or positive HBeAg (odds ratio, 4.45; 95% confidence interval, 1.64–12.06) had a greater likelihood of having HBV follow-up.
Conclusion
Only 19% of HBV-infected mothers met care guidelines 1 year after being diagnosed with HBV. Inadequate postpartum HBV care affects women of all races/ethnicities. Women who had a PCP as well as those who were HBeAg positive were more likely to be referred for postpartum follow-up with a HBV specialist, suggesting that providers might be referring patients when they perceive HBV to be more serious or complex.
Chronic hepatitis B virus (HBV) infection affects an estimated 2.2 million people in the United States and 350 million people globally, resulting in approximately 1 million deaths annually worldwide from decompensated cirrhosis and hepatocellular carcinoma (HCC). Prophylaxis to prevent vertical transmission from mothers to infants is highly effective and critical to controlling the spread of chronic HBV infection. Thus, screening pregnant women for active HBV infection is standard of care and applied almost universally throughout the United States. Although mothers are also subject to future risk from untreated HBV, little research has focused on maternal postpartum care and outcomes following prenatal diagnosis of HBV.
According to the American Congress of Obstetricians and Gynecologists (ACOG) and American Association for the Study of Liver Diseases (AASLD), appropriate HBV care includes referral to a physician experienced in the management of chronic liver disease, typically a gastroenterologist/hepatologist or infectious disease specialist, for routine liver disease monitoring and HCC surveillance. However, our recent study of a single New York City medical center found that <10% of mothers with a positive hepatitis B surface antigen (HBsAg) test during pregnancy received appropriate HBV care postpartum. These mothers and their close contacts are at risk for developing future complications of HBV, including cirrhosis and HCC, which can be prevented by existing antiviral therapies. To further highlight this concern, 1 mother from our cohort died from metastatic HCC shortly after delivering a healthy infant. Postpartum HBV care is essential not only for maternal health, but also as a public health measure to prevent HBV transmission to subsequent children as well as close contacts through HBV screening and immunization.
Our prior study was limited to a single New York City medical center with a predominantly Latino population and may not be generalizable to other patient populations, and we are unaware of other research addressing postpartum care for HBV. In the current study, we sought to determine rates of postpartum HBV specialty clinic follow-up and identify factors associated with poor follow-up in the Partners HealthCare system, the largest health care system in Massachusetts. We hypothesized that poor HBV follow-up would be a prevalent problem among all women.
Materials and Methods
We conducted a retrospective chart review of data from the Partners HealthCare system, a not-for-profit, integrated health care system, which is comprised of several hospitals, community health centers, numerous other health-related services, and >60,000 employees. The 2 founding institutions, Brigham and Women’s Hospital (BWH) and Massachusetts General Hospital (MGH), serve as major teaching affiliates for Harvard Medical School, and perform most of the deliveries at Partners HealthCare, approximately 8000 and 3500 deliveries a year, respectively, accounting for approximately 40% of all deliveries in Boston.
We identified women who delivered at 1 of 2 Partners HealthCare–affiliated hospitals, BWH or MGH, from 2002 through 2012 using the Partners Research Patient Data Registry, a centralized electronic data repository of >4 million patients that includes >1 billion diagnoses, medications, laboratory results, procedures, demographic, and visit entries. Pregnancy and delivery status was identified using International Classification of Diseases, Ninth Revision and diagnosis-related group delivery codes. We then searched for evidence of active HBV infection, which we defined as the presence of a positive HBsAg laboratory test. We included in our analysis women in whom active HBV infection was confirmed by either 2 positive tests for HBsAg at least 6 months apart, or a single positive HBsAg result in conjunction with a negative core IgM, which is in agreement with AASLD and the Centers for Disease Control and Prevention (CDC) definitions of HBV. In rare cases, we used clinician judgment to determine whether the patient had HBV infection, such as in the case of a suspected S gene escape mutant. We excluded patients who had established HBV specialty care prior to their first pregnancy within the data set (index pregnancy).
For the included women, we obtained from the Research Patient Data Registry information on sociodemographic characteristics including age race/ethnicity, marital status, insurance type (commercial compared to noncommercial, including Medicaid, Medicare, subsidized insurance, self-pay, and safety net coverage), and English as the primary language. We also collected information on clinical characteristics that might be associated with postpartum follow-up rates, which included comorbidities (coinfection with hepatitis C virus [HCV], human immunodeficiency virus [HIV]), viral hepatitis serologies, and laboratory indicators of possible active liver disease (alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin, international normalized ratio [INR], creatinine, platelet count, albumin, hemoglobin, alpha-fetoprotein). When available, postpartum liver biopsy, laboratory, and imaging results were collected. The primary outcome was first-time referral for postpartum HBV follow-up with either a gastroenterology/hepatology or infectious disease specialist during which HBV management was addressed in the outpatient provider note.
In bivariate analyses, to compare differences between patients with and without postpartum HBV follow-up, we used the t test for continuous characteristics, such as for age and most laboratory data, including total bilirubin, INR, creatinine, platelets, albumin, and hemoglobin. We used χ 2 or Fisher exact test for categorical data, such as race/ethnicity, marital status, insurance type, English as the primary language, presence of comorbidities (HCV, HIV), and for certain laboratory data that we converted into categories, such as elevated ALT. We used characteristics that were found to be significant on bivariate analyses ( P < .05) that might affect referral practices and clinically relevant demographics selected a priori, which included race/ethnicity, commercial insurance status, and English as self-reported primary language, in a multivariable logistic regression model to identify independent predictors of postpartum care, reported as odds ratios (OR) and 95% confidence intervals (CIs). We conducted all statistical analyses using software (SPSS Statistics, version 21; IBM Corp, Armonk, NY).
This project was reviewed and approved by the Partners HealthCare Institutional Review Board.
Results
From 2002 through 2012, a total of 339 women with chronic HBV delivered at Partners HealthCare. A total of 14% (48/339) had documented HBV specialty follow-up before their index pregnancy and so were excluded from the analysis, resulting in a total study population of 291 mothers, among whom we had longitudinal data for median follow-up of 3.3 years (interquartile range [IQR], 6.8). In all, 51% were Asian and the mean age was 31.5 (SD 5.6) years. Most women (69%) had only 1 pregnancy during the study period. A majority indicated English as their primary language (76%) and carried some form of commercial health insurance (54%). Of mothers, 54% were hepatitis B e antibody (HBeAb) positive. In all, 44% (127/291) had all of the laboratory tests recommended by AASLD for HBV management, including hepatitis B e antigen (HBeAg), HBeAb, HBV DNA, and ALT, of which, 39% (50/127) were chronic inactive carriers, characterized by HBeAg negative/HBeAb positive low (<2000 IU/mL) or undetectable HBV DNA levels and normal ALT. The interval from the time of the initial positive HBsAg finding until follow-up laboratory testing varied according to type of test checked: ALT a median of 2.1 weeks (IQR 6.5), HBeAg had a median delay of 3.3 weeks (IQR 13.4), and HBV DNA a median of 8.1 weeks (IQR 131.3). One mother was coinfected with HIV and none had HCV. Only 71% of women underwent HIV testing despite recommendations supporting universal screening during pregnancy by the CDC and ACOG in 2006. Women who delivered on or before the 2006 recommendations had a greater proportion of missing HIV tests when compared to women who delivered after (38% vs 16%, respectively, P < .0001). None of the patients had evidence for development of HCC and none died within the study period.
Of mothers, 47% (137/291) had postpartum HBV specialty care, 39% (53/137) of whom were seen during pregnancy. The vast majority (95%) were seen by a gastroenterologist/hepatologist, while the rest were seen by an infectious disease specialist. When comparing women with and without postpartum HBV follow-up ( Table 1 ), mothers with HBV follow-up were almost twice as likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001) and, as expected, more likely to have appropriate adjunctive laboratory testing performed including hepatitis A virus antibody, HBeAg, HBeAb, DNA level, and HCV antibody. A larger proportion of mothers with HBV follow-up were HBeAg positive (20% vs 8%, P = .004) and had elevated AST values (17% vs 8%, P = .02). While there was no difference in median DNA levels between groups during the index pregnancy, mothers who had HBV follow-up had higher median peak DNA levels with continued monitoring (5320 IU [IQR 114,746] vs 305 IU [IQR 2971], P = .002). Mothers with follow-up were more likely to have an HIV antibody checked and a slightly lower mean creatinine, but the difference was not clinically relevant. Other laboratory results (hemoglobin, platelet count, total bilirubin, albumin, INR) were not different between groups (data not shown).
| Characteristic | Without HBV follow-up, n = 154 | With HBV follow-up, n = 137 | P value |
|---|---|---|---|
| Mean (SD), median (IQR), a or n (%) | |||
| Background data | |||
| Mean age, y | 31.8 (5.3) | 31.2 (6.0) | .44 |
| Race/ethnicity | .59 | ||
| White | 22/154 (14%) | 16/137 (12%) | |
| Asian | 73/154 (47%) | 76/137 (55%) | |
| Black | 46/154 (30%) | 32/137 (23%) | |
| Hispanic | 7/154 (5%) | 7/137 (5%) | |
| Other | 2/154 (1%) | 3/137 (2%) | |
| English as self-reported primary language | 118/154 (77%) | 102/137 (74%) | .58 |
| Not married | 40/154 (26%) | 42/137 (31%) | .43 |
| Commercial health insurance | 83/154 (54%) | 75/137 (55%) | .91 |
| >1 pregnancy during study period | 47/154 (31%) | 42/137 (31%) | 1.00 |
| Cesarean delivery at any pregnancy | 41/154 (27%) | 44/137 (32%) | .37 |
| Primary care physician within Partners HealthCare | 58/154 (38%) | 90/137 (66%) | < .0001 |
| Time from initial positive hepatitis B surface antigen until follow-up HBV-related laboratory testing, in median weeks | |||
| HBeAg | 3.3 (14.6) | 3.3 (11.5) | .66 |
| HBV DNA | 9.7 (146.4) | 7.4 (123.0) | .81 |
| ALT | 1.9 (7) | 2.4 (6.4) | .85 |
| Hepatitis laboratory data during and after pregnancy | |||
| HAV | |||
| Total antibody checked | 49/154 (32%) | 85/137 (62%) | < .001 |
| HAV antibody positive b | 36/49 (73%) | 67/85 (79%) | .53 |
| HBV | |||
| HBc IgM checked b | 54/154 (35%) | 61/137 (45%) | .12 |
| HBeAg checked | 113/154 (73%) | 129/137 (94%) | < .0001 |
| HBeAg positive | 9/113 (8%) | 28/129 (22%) | .004 |
| HBeAb checked | 79/154 (51%) | 108/137 (79) | < .0001 |
| HBeAb positive | 70/79 (89%) | 88/108 (81%) | .22 |
| DNA checked | 63/154 (41%) | 114/137 (83%) | < .0001 |
| Median initial DNA level | 413 (3980) | 1420 (37,960) | .054 |
| Median peak DNA level c | 643 (4200) | 5320 (114,746) | .002 |
| HBV chronic inactive carrier status | 19/38 (50%) | 31/89 (35%) | .118 |
| HCV antibody checked b | 100/154 (65%) | 119/137 (87%) | < .0001 |
| HIV antibody checked | 102/154 (66%) | 106/137 (77%) | .04 |
| HIV positive | 1/96 (1%) | 0/106 (0%) | |
| Laboratory data during index pregnancy | |||
| Liver enzymes | |||
| ALT checked | 134/154 (87%) | 121/137 (88%) | .86 |
| Elevated ALT | 15/134 (11%) | 22/121 (18%) | .15 |
| AST checked | 133/154 (86%) | 121/137 (88%) | .73 |
| Elevated AST | 10/133 (8%) | 21/121 (17%) | .02 |
a IQR = 3rd quartile – 1st quartile
b All women were HAV IgM, HBc IgM, and HCV antibody negative
c Peak DNA value at any time, including outside of index pregnancy.
On multivariable logistic regression analysis, whether a mother had a PCP in the Partners HealthCare system (OR, 2.50; 95% CI, 1.37–4.59; P = .003) or a positive HBeAg (OR, 4.45; 95% CI, 1.64–12.06; P = .003) ( Table 2 ) each predicted a greater likelihood of having postpartum specialist follow-up. Other characteristics including race/ethnicity, English as self-reported primary language, commercial insurance status, and elevated AST were not independent predictors of follow-up.
| Variable | Adjusted OR (95% CI) |
|---|---|
| Primary care physician within Partners HealthCare | 2.50 (1.37–4.59) |
| Race/ethnicity | |
| White | 1.0 (Ref) |
| Asian | 1.49 (0.59–3.77) |
| Black | 1.39 (0.52–3.74) |
| Hispanic | 1.35 (0.30–6.01) |
| Other | 2.82 (0.22–37.13) |
| English as self-reported primary language | 0.89 (0.43–1.84) |
| Commercial health insurance | 1.21 (0.66–2.24) |
| HBeAg positive | 4.45 (1.64–12.06) |
| Elevated AST | 1.06 (0.40–2.78) |
There was a median delay of 12.0 months (IQR 59.3) from the time of HBV diagnosis until postpartum HBV specialist follow-up. Although 47% of mothers had HBV specialist follow-up, only 19% (55/291) also had appropriate monitoring with AASLD-recommended laboratory tests evaluated within 1 year of the initial positive HBsAg, which includes HBeAg, HBeAb, HBV DNA, and ALT. Among mothers with HBV follow-up, adherence to yearly monitoring was low, ranging from 20-44% depending on the parameter being measured ( Table 3 ). Most mothers had mild HBV disease; 79% had never been treated with antiviral therapy (which consisted of lamivudine, entecavir, tenofovir, or interferon) and only 4 of 22 who underwent liver biopsy had moderate to severe fibrosis (equivalent Ishak ≥3/6) with only 1 biopsy that showed cirrhosis. Inflammation was mostly mild.
