Intrahepatic cholestasis of pregnancy and hepatitis B virus infection during pregnancy elevates the risks of small for gestational age and low birth weight infants
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摘要:
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，HBsAg）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。 -
关键词:
- HBV感染 /
- 妊娠期肝内胆汁淤积症 /
- 小于胎龄儿 /
- 低出生体重 /
- 交互作用
Abstract: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. -
表 1 研究对象一般特征分布[n(%)]
Table 1. Distribution of basic characteristics of the study population[n(%)]
一般特征 例数(n=6 364) 妊娠期HBV感染 P值a 妊娠期肝内胆汁淤积症 P值a 否(n=5 987) 是(n=377) 否(n=6 165) 是(n=199) 母亲年龄(岁) < 0.001 0.856 <25 1 068 976(91.39) 92(8.61) 1 034(96.82) 34(3.18) 25~ 3 036 2 882(94.93) 154(5.07) 2 938(96.77) 98(3.23) ≥30 2 260 2 129(94.20) 131(5.80) 2 193(97.04) 67(2.96) 家庭人均月收入(元) 0.105 0.016 <3 000 3 287 3 079(93.67) 208(6.33) 3 164(96.26) 123(3.74) ≥3 000 2 591 2 453(94.67) 138(5.33) 2 523(97.38) 68(2.62) 缺失值 486 455(93.62) 31(6.38) 478(98.35) 8(1.65) 文化程度 < 0.001 0.737 本科以下 2 515 2 319(92.21) 196(7.79) 2 434(96.78) 81(3.22) 本科及以上 3 778 3 602(95.34) 176(4.66) 3 662(96.93) 116(3.07) 缺失值 71 66(92.96) 5(7.04) 69(97.18) 2(2.82) 孕期是否工作 0.039 0.724 否 2 056 1 916(93.19) 140(6.81) 1 994(96.98) 62(3.02) 是 4 308 4 071(94.50) 237(5.50) 4 171(96.82) 137(3.18) 孕期吸烟(主动及被动) 0.014 0.138 否 5 181 4 892(94.42) 289(5.58) 5 027(97.03) 154(2.97) 是 1 183 1 095(92.56) 88(7.44) 1 138(96.20) 45(3.80) 孕期补充维生素 < 0.001 0.477 否 4 867 4 550(93.49) 317(6.51) 4 719(96.96) 148(3.04) 是 1 497 1 437(95.99) 60(4.01) 1 446(96.59) 51(3.41) 孕前BMI (kg/m2) 0.044 0.177 <18.5 1 373 1 303(94.90) 70(5.10) 1 321(96.21) 52(3.79) 18.5~ 4 315 4 038(93.58) 277(6.42) 4 192(97.15) 123(2.85) ≥24.0 676 646(95.56) 30(4.44) 652(96.45) 24(3.55) 孕期体重获得(kg) 0.298 < 0.001 <15.0 1 932 1 805(93.43) 127(6.57) 1 846(95.55) 86(4.45) 15.0~ 2 023 1 908(94.32) 115(5.68) 1 966(97.18) 57(2.82) >18.5 2 345 2 216(94.50) 129(5.50) 2 292(97.74) 53(2.26) 缺失值 64 58(90.63) 6(9.37) 61(95.31) 3(4.69) 妊娠期糖尿病 0.449 0.122 无 6 303 5 931(94.10) 372(5.90) 6 108(96.91) 195(3.09) 有 61 56(91.80) 5(8.20) 57(93.44) 4(6.56) 子痫前期及子娴 0.937 < 0.001 无 6 032 5 675(94.08) 357(5.92) 5 860(97.15) 172(2.85) 有 332 312(93.98) 20(6.02) 305(91.87) 27(8.13) 小于胎龄儿 0.025 0.116 否 5 878 5 541(94.27) 337(5.73) 5 700(96.97) 178(3.03) 是 486 446(91.77) 40(8.23) 465(95.68) 21(4.32) 出生体重 0.020 < 0.001 低出生低重儿 436 398(91.28) 38(8.72) 405(92.89) 31(7.11) 正常体重儿 5 504 5 184(94.19) 320(5.81) 5 340(97.02) 164(2.98) 巨大儿 424 405(95.52) 19(4.48) 420(99.06) 4(0.94) 注：a表示χ2检验时未包含缺失值。 
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表 2 妊娠期HBV感染及肝内胆汁淤积症对小于胎龄儿发生风险的影响
Table 2. Effects of HBV infection and intrahepatic cholestasis in pregnancy on the risk of small for gestational age
HBV感染 ICP 适于胎龄儿 小于胎龄儿 χ2值 P值 OR(95% CI)值a 小于胎龄儿(n=486) 否 否 4 568 432 1.00 是 否 265 33 1.002 0.317 0.91(0.58~1.45) 否 是 134 14 0.296 0.586 0.92(0.69~1.23) 是 是 28 7 2.197 0.138 1.25(0.93~1.67) 未足月小于胎龄儿(n=100) 否 否 4 568 90 1.00 是 否 265 3 1.447 0.229 0.47(0.14~1.59) 否 是 134 3 1.323 0.250 0.69(0.37~1.30) 是 是 28 4 7.185 0.007 1.76(1.16~2.65) 足月小于胎龄儿(n=386) 否 否 4 568 342 1.00 是 否 265 30 2.653 0.103 1.39(0.94~2.08) 否 是 134 11 0.013 0.910 0.98(0.72~1.35) 是 是 28 3 0.037 0.848 1.04(0.69~1.55) 注：a表示调整变量包括母亲年龄、家庭人均月收入、文化程度、孕期是否工作、孕期吸烟(包括被动吸烟)、孕期补充维生素及孕期体重获得。
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表 3 妊娠期HBV感染及肝内胆汁淤积症对低出生体重发生风险的影响
Table 3. Effects of HBV infection and intrahepatic cholestasis in pregnancy on the risk of Low birth weight
HBV感染 ICP 正常体重儿 低体重儿 χ2值 P值 OR (95% CI)值a 低出生体重儿(n=436) 否 否 5 043 380 1.00 是 否 297 25 0.144 0.704 0.91(0.58~1.45) 否 是 141 18 0.053 0.818 1.03(0.78~1.36) 是 是 23 13 23.147 <0.001 1.85(1.44~2.38) 未足月低出生体重儿(n=344) 否 否 5 043 301 1.00 是 否 297 18 0.468 0.494 0.83(0.48~1.42) 否 是 141 13 0.188 0.665 0.93(0.68~1.29) 是 是 23 12 24.449 <0.001 1.94(1.49~2.52) 足月低出生体重儿(n=92) 否 否 5 043 79 1.00 是 否 297 7 0.168 0.682 1.18(0.53~2.63) 否 是 141 5 1.113 0.291 1.29(0.80~2.09) 是 是 23 1 0.397 0.529 1.25(0.62~2.51) 注：a表示调整变量包括母亲年龄、家庭人均月收入、文化程度、孕期是否工作、孕期吸烟(包括被动吸烟)、孕期补充维生素、孕期体重获得及早产史
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