Impact of Immune Effect to Different Dosage Hepatitis B Virus Vaccine in Premature Infants

doi:10.3877/cma.j.issn.1673-5250.2012.03.008

Objective

To investigate the strong or weak impact of immune response to different pregnant week premature infants in different dosage hepatitis B virus vaccine and the level changes of immune response rate, anti- hepatitis b surface(HBs) titer, Immunoglobulin (IgG, IgM, IgA) and complement (C)3, C4.

Methods

From April 2009 to October 2010, 270 case of premature and 100 cases of healthy full-term infants were recruited in the newborn department. Those cases were divided into 4 groups: <30 pregnant weeks (group Ⅰ, n=90), pregnant weeks from 30 to 33 weeks (group Ⅱ, n=90); pregnant weeks from 34 to 36 (group Ⅲ, n=90); pregnant weeks >37 weeks (control group, n=100). Then every group was sub-divided into group A(5 μg HB Vaccine) and group B (10 μg HB Vaccine) according to inoculation dose, the time of inoculation is at the 0, 1st and 6th month after birth. The anti-HBs titers, concentration of immunoglobulin (IgG, IgM, IgA) and complement (C3, C4) after four months from the third inoculation were examined. The newborns were injected 200 IU HBIG in 12 hours after the birth if his mother was hepatitis B virus carrier. Strong or weak response rates of hepatitis B vaccine in each group and the differences of seroconversion rate were compared. The changes of strong and weak response in immunoglobulin levels were analyzed.

Results

No obvious local and systemic reaction was found in all groups and all tests were finished successfully. No significant differences of anti-HBs titer were found among group of Ⅰ-A, Ⅱ-A, Ⅲ-A and control group A (P>0.05), also among groupⅠ-B, Ⅱ-B, Ⅲ-B and control group B (P> 0.05). Statistically significant differences of anti-HBs strong response percentage were found amongⅠ-A, Ⅱ-A, Ⅲ-A and control group A (P<0.05); also among groupⅠ-B, Ⅱ-B, Ⅲ-B and control group B (P<0.05). Immunoglobulin (IgG, IgM, IgA) and complement (C3, C4) changes: Ⅰ, Ⅱ, Ⅲ and control groups were compared in A, and B groups, IgM, IgA, C3 strong response level significantly higher than no (weak) response level of premature infants (P<0.05); Group B of hepatitis B vaccine seroconversion rate was significantly higher than that of group A (P<0.05).

Conclusions

Premature infants with hepatitis B vaccine after birth did not find any adverse reaction, and the antibody levels generate better. Stronger response percentage of premature infants is lower than that of full-term infants, especially <30 pregnant-week premature infants. High-dose hepatitis B vaccine can improve the strong response percentage of premature hepatitis B vaccination. Premature infants with strong responses have better humoral immune function than infants without or weak response.

Key words: premature infant, hepatitis B vaccine, dosage, immune effect

表1 Ⅰ，Ⅱ，Ⅲ组和对照组婴儿出生体重、孕龄、随访年龄、性别比较(±s)

Table 1 Comparison of birth weight, pregnant weeks, follow－up age, and gender among four groups (±s)

组别	n	出生体重(g)	胎龄(孕周)	随访年龄(个月)	性别(男∶女)
Ⅰ组	90	1621±130	29.7±1.3	11.7±3.5	47∶43
Ⅱ组	90	1814±101	32.5±1.5	11.0±3.9	45∶45
Ⅲ组	90	2127±120	35.5±1.5	10.6±3.6	45∶45
对照组	100	3387±104	38.6±1.0	10.4±3.0	58∶42
F	?	4691.94	782.92	2.49	1.6616
P	?	<0.01	<0.01	>0.05	>0.05

表1 Ⅰ，Ⅱ，Ⅲ组和对照组婴儿出生体重、孕龄、随访年龄、性别比较(±s)

Table 1 Comparison of birth weight, pregnant weeks, follow－up age, and gender among four groups (±s)

组别	n	出生体重(g)	胎龄(孕周)	随访年龄(个月)	性别(男∶女)
Ⅰ组	90	1621±130	29.7±1.3	11.7±3.5	47∶43
Ⅱ组	90	1814±101	32.5±1.5	11.0±3.9	45∶45
Ⅲ组	90	2127±120	35.5±1.5	10.6±3.6	45∶45
对照组	100	3387±104	38.6±1.0	10.4±3.0	58∶42
F	?	4691.94	782.92	2.49	1.6616
P	?	<0.01	<0.01	>0.05	>0.05

表2 A组婴儿抗－HBsAb滴度、强应答率及抗体阳转率比较[n(%)]

Table 2 Comparison of anti－HBsAb titer, percentage of strong response and positive conversion rate in infants of group A [n(%)]

组别	n	抗－HBsAb滴度(±s)	弱(无)应答率	强应答率	抗体阳转率
Ⅰ组A	45	521±362	23(51.1)	22(48.9)	25(55.6)
Ⅱ组A	45	571±376	18(40.0)	27(60.0)	31(68.9)
Ⅲ组A	45	571±376	18(40.0)	27(60.0)	31(68.9)
对照组A	50	701±292	10(20.0)	40(80.0)	43(86.0)

表2 A组婴儿抗－HBsAb滴度、强应答率及抗体阳转率比较[n(%)]

Table 2 Comparison of anti－HBsAb titer, percentage of strong response and positive conversion rate in infants of group A [n(%)]

组别	n	抗－HBsAb滴度(±s)	弱(无)应答率	强应答率	抗体阳转率
Ⅰ组A	45	521±362	23(51.1)	22(48.9)	25(55.6)
Ⅱ组A	45	571±376	18(40.0)	27(60.0)	31(68.9)
Ⅲ组A	45	571±376	18(40.0)	27(60.0)	31(68.9)
对照组A	50	701±292	10(20.0)	40(80.0)	43(86.0)

表3 B组婴儿抗－HBsAb滴度、强应答率及抗体阳转率比较[n(%)]

Table 3 Comparison of anti－HBsAb titer, strong response percentage and positive conversion rate in group B infants [n(%)]

组别	n	抗－HBsAb滴度(±s)	弱(无)应答率	强应答率	抗体阳转率
Ⅰ组B	45	569±357	15(33.3)	30(66.7)	35(77.8)
Ⅱ组B	45	591±363	10(22.2)	35(77.8)	39(86.7)
Ⅲ组B	45	693±399	7(15.6)	38(84.4)	41(91.1)
对照组B	50	731±289	5(10.0)	45(90.0)	49(98.0)

表3 B组婴儿抗－HBsAb滴度、强应答率及抗体阳转率比较[n(%)]

Table 3 Comparison of anti－HBsAb titer, strong response percentage and positive conversion rate in group B infants [n(%)]

组别	n	抗－HBsAb滴度(±s)	弱(无)应答率	强应答率	抗体阳转率
Ⅰ组B	45	569±357	15(33.3)	30(66.7)	35(77.8)
Ⅱ组B	45	591±363	10(22.2)	35(77.8)	39(86.7)
Ⅲ组B	45	693±399	7(15.6)	38(84.4)	41(91.1)
对照组B	50	731±289	5(10.0)	45(90.0)	49(98.0)

表4 不同孕龄早产儿和不同接种剂量对免疫球蛋白及补体的影响[±s，n(%)]

Table 4 Effects on immunoglobulin and complement in premature infant of different gestational age and in different vaccine doses [±s，n(%)]

组别		n	IgG(g/L)	IgM(mg/L)	IgA(mg/L)	C3(g/L)	C4(g/L)	抗体阳转率
Ⅰ组A		45	?	?	?	?	?	?
?	强应答	15	6.53±1.67	133.8±23.7	6.93±0.72	0.94±0.14	0.22±0.06	25(55.6)
?	弱(无)应答	30	6.46±1.45	100.4±13.8	5.72±0.52	0.43±0.15	0.19±0.04	?
Ⅰ组B		45	?	?	?	?	?	?
?	强应答	23	6.61±1.61	135.3±24.4	7.15±0.77	1.00±0.13	0.24±0.07	35(7.8)
?	弱(无)应答	22	6.59±1.58	105.4±14.4	5.82±0.79	0.47±0.13	0.20±0.05	?
Ⅱ组A		45	?	?	?	?	?	?
?	强应答	18	6.73±1.55	130.7±27.1	7.51±0.75	0.97±0.19	0.23±0.04	25(68.9)
?	弱(无)应答	27	6.68±1.58	110.3±15.7	6.41±0.71	0.47±0.16	0.21±0.03	?
Ⅱ组B		45	?	?	?	?	?	?
?	强应答	26	6.83±1.70	143.2±28.2	7.87±0.82	1.07±0.20	0.25±0.06	39(86.7)
?	弱(无)应答	19	6.71±1.64	113.3±17.3	6.51±0. 84	0.47±0.13	0.23±0.05	?
Ⅲ组A		45	?	?	?	?	?	?
?	强应答	21	7.61±1.75	149.7±36.3	8.54±0.93	1.24±0.25	0.29±0.09	25(75.6)
?	弱(无)应答	24	7.54±1.73	115.3±25.7	7.11±0.90	0.73±0.21	0.28±0.08	?
Ⅲ组B		45	?	?	?	?	?	?
?	强应答	28	7.66±1.77	159.2±37.2	8.72±0.94	1.25±0.29	0.31±0.07	39(91.1)
?	弱(无)应答	17	7.55±1.74	120.3±25.9	7.17±0.94	0.78±0.22	0.29±0.09	?

表4 不同孕龄早产儿和不同接种剂量对免疫球蛋白及补体的影响[±s，n(%)]

Table 4 Effects on immunoglobulin and complement in premature infant of different gestational age and in different vaccine doses [±s，n(%)]

组别		n	IgG(g/L)	IgM(mg/L)	IgA(mg/L)	C3(g/L)	C4(g/L)	抗体阳转率
Ⅰ组A		45	?	?	?	?	?	?
?	强应答	15	6.53±1.67	133.8±23.7	6.93±0.72	0.94±0.14	0.22±0.06	25(55.6)
?	弱(无)应答	30	6.46±1.45	100.4±13.8	5.72±0.52	0.43±0.15	0.19±0.04	?
Ⅰ组B		45	?	?	?	?	?	?
?	强应答	23	6.61±1.61	135.3±24.4	7.15±0.77	1.00±0.13	0.24±0.07	35(7.8)
?	弱(无)应答	22	6.59±1.58	105.4±14.4	5.82±0.79	0.47±0.13	0.20±0.05	?
Ⅱ组A		45	?	?	?	?	?	?
?	强应答	18	6.73±1.55	130.7±27.1	7.51±0.75	0.97±0.19	0.23±0.04	25(68.9)
?	弱(无)应答	27	6.68±1.58	110.3±15.7	6.41±0.71	0.47±0.16	0.21±0.03	?
Ⅱ组B		45	?	?	?	?	?	?
?	强应答	26	6.83±1.70	143.2±28.2	7.87±0.82	1.07±0.20	0.25±0.06	39(86.7)
?	弱(无)应答	19	6.71±1.64	113.3±17.3	6.51±0. 84	0.47±0.13	0.23±0.05	?
Ⅲ组A		45	?	?	?	?	?	?
?	强应答	21	7.61±1.75	149.7±36.3	8.54±0.93	1.24±0.25	0.29±0.09	25(75.6)
?	弱(无)应答	24	7.54±1.73	115.3±25.7	7.11±0.90	0.73±0.21	0.28±0.08	?
Ⅲ组B		45	?	?	?	?	?	?
?	强应答	28	7.66±1.77	159.2±37.2	8.72±0.94	1.25±0.29	0.31±0.07	39(91.1)
?	弱(无)应答	17	7.55±1.74	120.3±25.9	7.17±0.94	0.78±0.22	0.29±0.09	?

表5 不同接种剂量对早产A组和早产B组婴儿免疫球蛋白及补体的影响比较[±s，n(%)]

Table 5 Comparision of immunoglobulin and complement in 270 premature infants[±s，n(%)]

组别		n	IgG(g/L)	IgM(mg/L)	IgA(mg/L)	C3(g/L)	C4(g/L)	抗体阳转率
早产A组		135	?	?	?	?	?	?
?	强应答	54	7.55±1.73	163.9±45.3	9.10±0.81	1.71±0.28	0.31±0.09	25(66.7)
?	弱(无)应答	81	7.51±1.64	115.0±24.4	7.19±0.93	0.75±0.23	0.29±0.08	?
早产B组		135	?	?	?	?	?	?
?	强应答	77	7.70±1.81	179.2±49.1	9.32±0.91	1.81±0.30	0.32±0.08	115(85.2)
?	弱(无)应答	58	7.48±1.71	123.1±27.3	7.27±0.93	0.86±0.27	0.30±0.09	?

表5 不同接种剂量对早产A组和早产B组婴儿免疫球蛋白及补体的影响比较[±s，n(%)]

Table 5 Comparision of immunoglobulin and complement in 270 premature infants[±s，n(%)]

组别		n	IgG(g/L)	IgM(mg/L)	IgA(mg/L)	C3(g/L)	C4(g/L)	抗体阳转率
早产A组		135	?	?	?	?	?	?
?	强应答	54	7.55±1.73	163.9±45.3	9.10±0.81	1.71±0.28	0.31±0.09	25(66.7)
?	弱(无)应答	81	7.51±1.64	115.0±24.4	7.19±0.93	0.75±0.23	0.29±0.08	?
早产B组		135	?	?	?	?	?	?
?	强应答	77	7.70±1.81	179.2±49.1	9.32±0.91	1.81±0.30	0.32±0.08	115(85.2)
?	弱(无)应答	58	7.48±1.71	123.1±27.3	7.27±0.93	0.86±0.27	0.30±0.09	?

表6 对照组不同接种剂量对免疫球蛋白及补体的影响[±s，n(%)]

Table 6 Effects on immunoglobulin and complement in different inoculation doses of control group [±s，n(%)]

组别		n	IgG(g/L)	IgM(mg/L)	IgA(mg/L)	C3(g/L)	C4(g/L)	抗体阳转率
对照组A		50	?	?	?	?	?	?
?	强应答	33	7.98±1.97	183.3±31.2	9.19±1.06	1.80±0.32	0.33±0.11	43(86.0)
?	弱(无)应答	17	7.88±1.86	121.3±27.8	7.31±0.91	1.17±0.26	0.30±0.09	?
对照组B		50	?	?	?	?	?	?
?	强应答	35	8.18±1.99	197.2±36.5	9.63±1.11	1.92±0.35	0.35±0.13	49(98.0)
?	弱(无)应答	15	7.97±1.95	122.1±28.2	7.34±0.93	1.19±0.27	0.32±0.093	?

表6 对照组不同接种剂量对免疫球蛋白及补体的影响[±s，n(%)]

Table 6 Effects on immunoglobulin and complement in different inoculation doses of control group [±s，n(%)]

组别		n	IgG(g/L)	IgM(mg/L)	IgA(mg/L)	C3(g/L)	C4(g/L)	抗体阳转率
对照组A		50	?	?	?	?	?	?
?	强应答	33	7.98±1.97	183.3±31.2	9.19±1.06	1.80±0.32	0.33±0.11	43(86.0)
?	弱(无)应答	17	7.88±1.86	121.3±27.8	7.31±0.91	1.17±0.26	0.30±0.09	?
对照组B		50	?	?	?	?	?	?
?	强应答	35	8.18±1.99	197.2±36.5	9.63±1.11	1.92±0.35	0.35±0.13	49(98.0)
?	弱(无)应答	15	7.97±1.95	122.1±28.2	7.34±0.93	1.19±0.27	0.32±0.093	?

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