Fetal meconium peritonitis after maternal hepatitis B: a case report and review of the literature

Abstract

Maternal hepatitis virus has rarely been implicated in fetal meconium peritonitis (FMP), and its underlying mechanism is largely unknown. We describe a case of FMP presumably caused by maternal chronic hepatitis B virus (HBV). A 29-year-old primigravid woman was referred to our hospital at 35 weeks of gestation for the disappearance of fetal movements. The maternal prenatal history included HBV for more than 10 years. Her HBV DNA level was suppressed (<20 IU/mL) and she was taking oral tenofovir disoproxil fumarate (300 mg/day). At 21⁺⁵ weeks, fetal ascites, echogenic bowel, and intra-abdominal calcifications were observed by abdominal ultrasound. These findings were confirmed by magnetic resonance imaging and were regarded as diagnostic for FMP. Cord blood and amniotic fluid were positive for hepatitis B e antigen and hepatitis B surface antigen. Ascites of the FMP was completely self-absorbed at 27⁺³ weeks. At 35 weeks of gestation, fetal movements had vanished and male stillbirth was induced. A histopathological examination of the placenta showed meconium uptake by macrophages in the amniochorionic membranes. Our findings suggest that maternal HBV can cross the placenta and induce FMP. Close surveillance may allow an early diagnosis of FMP and prevent fetal mortality.

Introduction

Fetal meconium peritonitis (FMP) is defined as sterile chemical peritonitis and is a rare phenomenon with an estimated incidence of 1 in 30,000 births. ¹ Several factors may be involved in the process of FMP, including genetic disorders, congenital defects, and infections.^2,3 There may be an association between maternal liver injury and subsequent FMP. Using the search terms “maternal hepatitis”, “maternal liver disease”, and “fetal meconium peritonitis” in MEDLINE for studies published up to November 2023, only six cases of FMP were identified after episodes of maternal hepatitis in the literature.^4–9 We recently encountered such a case of FMP that was presumably caused by maternal chronic hepatis B virus (HBV). Interestingly, ascites, which is a characteristic ultrasound manifestation of FMP, was self-absorbed without drainage.

Case presentation

A 29-year-old primigravid woman was referred at 35 weeks of gestation for the disappearance of fetal movements. The maternal prenatal history included HBV for more than 10 years. She was taking daily oral doses (300 mg) of tenofovir disoproxil fumarate for preconception and during pregnancy, and maintaining HBV DNA suppression at a low level (<20 IU/mL). Routine laboratory tests of alanine aminotransferase and aspartate aminotransferase concentrations were within the normal range. Serological studies for human immunodeficiency virus and TORCH (Toxoplasma gondii, other microorganisms, rubella virus, cytomegalovirus, and herpes simplex virus) tests were negative. Tests were also negative for cytomegalovirus, hepatitis A virus, hepatitis C virus, hepatitis E virus, and Epstein–Barr virus.

Two years before the current admission, serum liver tests showed an elevated fasting serum total bile acid concentration of 30.2 μmol/L (upper limit of normal: 10 μmol/L). Standard treatment with ursodeoxycholic acid was initiated and continued throughout the entire pregnancy, but total bile acid concentrations remained elevated (18.9–75.0 μmol/L).

At 21⁺⁵ weeks, abdominal ultrasound of the fetus showed fetal ascites, echogenic bowel (3.1 × 1.6 × 1.5 cm), and intra-abdominal calcifications (Figure 1(a)). No other major or minor malformation was detected. These ultrasound findings were confirmed by fetal magnetic resonance imaging (Figure 1(b)) and were regarded as diagnostic for FMP. The results of fetal karyotyping and whole-exome sequencing were normal. Cord blood and amniotic fluid were positive for hepatitis B e antigen and hepatitis B surface antigen, and negative for TORCH and common mutation of cystic fibrosis. An ultrasound scan was repeated every 2 weeks. Ascites was completely absorbed without drainage by paracentesis at 27⁺³ weeks, but the echogenic bowel and calcifications remained (Figure 1(c)). At 35 weeks of gestation, fetal movements had suddenly vanished, and a male stillbirth (weighing 3000 g) was obtained by the induction of labor. A histopathological examination of the placenta showed meconium uptake by macrophages in the amniochorionic membranes (Figure 2), chorionic plate, and umbilical cord. No post-mortem examination of the fetus was performed.

Figure 1.

Images suggest fetal meconium peritonitis. (a) Ultrasound signs of fetal ascites (i), echogenic bowel (ii), and calcification (iii) at 21⁺⁵ weeks of gestation. (b) Magnetic resonance imaging (original magnification  × 4) shows fetal ascites (i), echogenic bowel (ii), and calcification (iii) at 21⁺⁵ weeks of gestation and (c) ultrasound signs of echogenic bowel (i) and calcification (ii) at 27⁺³ weeks of gestation.

Figure 2.

Meconium uptake by macrophages in the amniochorionic membranes (arrows; hematoxylin–eosin stain; original magnification,  × 200).

Ethics statement

Institutional review board approval was waived because of the retrospective nature of the study. Written informed consent was obtained from the patient for the publication of this case report. The reporting of this study conforms to the CARE guidelines. ¹⁰

Discussion

Although FMP is often complicated by genitourinary or gastrointestinal defects/infections, hepatitis virus infection still appears to be a contributor prior to or during pregnancy.^4–9 However, this finding needs to be proven by randomized, clinical trials. Therefore, there should be caution in extrapolating the cause of FMP to all maternal patients with hepatitis. Previous studies showed that hepatitis viruses could be transmitted in utero,^4,11 and sometimes their antigens/antibodies could not be detected in amniotic fluid or cord blood because of possible interference. In our case, hepatitis B e antigen and hepatitis B surface antigen were detected in the amniotic fluid and cord blood, which provided compelling evidence of intrauterine infection. ¹¹ Although the exact mechanism is unknown, case reports^4–9 (Table 1) have suggested a possible causal relationship between maternal hepatitis and FMP. Available evidence suggests that exposure to tenofovir disoproxil fumarate and ursodeoxycholic acid is not associated with an increased risk of meconium peritonitis.

Table 1.

Demographic data of patients with fetal meconium peritonitis after hepatitis.

Variable	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7
Age, years	23	35	21	29	28	26	29
Types of hepatitis	Hepatitis A	Hepatitis A	Hepatitis B	Hepatitis A	Autoimmune hepatitis	Drug-induced hepatitis	Hepatitis B
Gestational age at diagnosis of FMP, weeks	27	33	32	19.5	34	29	21+5
Ultrasound signs of FMP	Fetal ascites and polyhydramnios	Abdominal calcifications and ascites	Intraabdominal calcification	Polyhydramnios, abdominal calcifications, and ascites, resolved at 38 weeks	Polyhydramnios	Polyhydramnios	Ascites, echogenic bowel, and abdominal calcifications, resolved at 27+3 weeks
Cord blood	Hepatitis A IgG-positive	N/A	N/A	N/A	N/A	N/A	HBeAg- and HBsAg-positive
Delivery time, weeks	35	35	32	40	34	34	35
Fetal outcomes, delivery mode	Survived, vaginal	Survived, vaginal	Neonatal death on day 5, vaginal	Survived, vaginal	Survived, cesarean	Survived, cesarean	Stillbirth, vaginal
Location of bowel perforation	Distal ileum	Distal ileum	Bowel perforation could not be identified owing to diffuse adhesion within the abdominal cavity	None	Distal ileum	Ascending colon and distal transverse colon	N/A
Reference	4	5	6	7	8	9	Current report

FMP, fetal meconium peritonitis; IgG, immunoglobulin G; N/A, not available; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen.

Intra-abdominal calcification, polyhydramnios, and ascites were the predominant ultrasound features described in FMP cases, but some cases only presented with polyhydramnios and were eventually proven as pre-existing FMP by autopsy or laparotomy after birth (Table 1). Dynamic monitoring of ultrasound images could improve the efficacy of diagnosis of FMP and strengthen integrated perinatal management. ¹² Similar to other cases presented by Cho et al. ⁷ and Estroff et al., ¹³ prenatally diagnosed ascites in this case spontaneously resorbed during pregnancy. Perforation of the intestines appeared unlikely, but bowel perforation closing by itself (due to mild abdominal inflammation) could not be excluded. Although a fetal autopsy was refused in this case, meconium in phagocytes was found by a placental biopsy, providing a good alternative for confirmation of FMP.

Concern has been raised about the formation of ascites after HBV. There is speculation that ascitic fluid results from intrahepatic portal hypertension during regenerative change and infiltration by masses of inflammatory cells,^4,9 and vascular damage may also play a role in bowel ischemia and ascites. However, the exact mechanism of the effects of viral hepatitis on FMP need to be further clarified.

The outcome for cases of FMP is most favorable (Table 1) when fetuses are delivered in centers with pediatric surgery services, ¹⁴ but the survival rate may be overestimated owing to the high number of pregnancy terminations. In our case, sudden intrauterine fetal death occurred in the third trimester. Persistent total bile acid concentrations may contribute to stillbirth because of the lack of alternative possibilities, such as genetic disorders, placental abruption, and a twisted umbilical cord.

Conclusion

FMP involvement should be considered after maternal hepatitis infection after excluding other causes of meconium. Routine follow-up with ultrasound may be appropriate and improve fetal outcomes.