孕期HBV感染及肝内胆汁淤积症对小于胎龄儿与低出生体重的交互影响

目的探讨妊娠期乙型肝炎病毒(hepatitis B virus,HBV)感染及肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)对小于胎龄儿(small for gestational age infant,SGA)与低出生体重儿(low birth weight infant,LBW)发生风险的影响,并分析其交互效应。方法以2017年1月～2018年4月在某三甲医院建卡就诊并在本院分娩的孕妇为研究对象,采用化学发光法测定孕妇外周血乙型肝炎表面抗原(hepatitis B surface antigen,HBs Ag)及总胆汁酸。以Logistic回归模型分析HBV感染及ICP孕妇发生不良妊娠结局的风险,用相乘与相加模型分析其交互作用。结果在控制混杂因素后,与正常孕妇相比,孕期仅感染HBV或仅患有ICP均不增加SGA与LBW的发生风险,但孕期HBV感染合并ICP使未足月SGA和LBW的发生风险分别增加了76%(OR=1. 76,95%CI:1. 16～2. 65,P=0. 007)与85%(OR=1. 85,95%CI:1. 44～2. 38,P <0. 001);孕期HBV感染与ICP对未足月SGA[RERI(95%CI)=6. 54 (0. 14～12. 94),AP (95%CI)=0. 90%(0. 68%～1. 13%),S (95%CI)=7. 03(1. 38～42. 64)]和LBW [RERI (95%CI)=5. 69(0. 48～10. 90),AP (95%CI)=0. 76%(0. 55%～0. 97%),S (95%CI)=8. 02(1. 92～33. 43)]存在相乘与相加的交互作用,其发生风险分别是两因素单独存在风险之和的7. 03倍和8. 02倍。结论妊娠期HBV感染合并ICP增加了未足月SGA和LBW的发生风险,怀孕后积极防治HBV感染与ICP可降低SGA和LBW的出生。

Intrahepatic cholestasis of pregnancy and hepatitis B virus infection during pregnancy elevates the risks of small for gestational age and low birth weight infants

  Objective  To explore the impact of hepatitis B virus infection, intrahepatic cholestasis during pregnancy on the risk of small for gestational age (SGA) and low birth weight (LBW), and analyze the interaction effect.  Methods  The study was conducted from Jan 2017 to Apr 2018 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. The peripheral blood hepatitis B surface antigen (HBsAg) and total bile acids of pregnant women were determined by chemiluminescence method, unconditional Logistic regression models were used to estimate association between hepatitis B virus infection, intrahepatic cholestasis of pregnancy and the risk of neonate outcomes.  Results  After adjusting for confounding factors, compared to normal pregnant women, HBV infection alone or ICP alone during pregnancy did not increase the risk of SGA or LBW. The increased risk of born before term SGA (OR=1.76, 95% CI: 1.16-2.65, P=0.007) and LBW infants (OR=1.85, 95%CI: 1.44-2.38, P<0.001) were observed in pregnant women with HBV infection and ICP, the additive and multiplicative interaction were also observed for before term SGA[RERI (95% CI)=6.54(0.14-12.94), AP (95% CI)=0.90%(0.68%-1.13%), S (95% CI)=7.03(1.38-42.64)] and LBW[RERI (95% CI)=5.69(0.48-10.90), AP (95% CI)=0.76%(0.55%-0.97%), S (95% CI)=8.02(1.92-33.43)].  Conclusions  Our results suggest that pregnancy HBV infection combined with ICP increase the risk of SGA and LBW infants. These two risk factors had a synergistic effect.