Using big data to analyze the vaccination status of children with congenital heart disease in Yinzhou District, China

ABSTRACT

Congenital heart disease (CHD) represents a significant population warranting particular attention concerning vaccination coverage. To comprehend the vaccination status of CHD within Yinzhou District, Ningbo City, China, and to facilitate the formulation of preventive, control, and immunization strategies against vaccine-preventable diseases in children with congenital heart conditions. Using the China Yinzhou Electronic Health Record Study (CHERRY) database, we analyzed the vaccination coverage of children with CHD born between January 1, 2016 and September 20, 2021, and analyzed the influencing factors associated with the level of vaccination coverage. This study involved 762 children diagnosed with CHD at the age of 12 months, revealing that 86.74% of these children had received at least one dose of the National Immunization Program (NIP) vaccines. The coverage for non-NIP vaccines, such as the rotavirus vaccine, influenza vaccine, Influenza Haemophilus influenzae Type b (Hib) Conjugate Vaccine, 13-valent pneumococcal conjugate vaccine (PCV13), and inactivated enterovirus type 71 vaccine (EV71), stood at 27.30%, 7.74%, 63.25%, 33.76%, and 34.51%, respectively. The completion coverage for the entire vaccination schedule were 27.30%, 5.51%, 55.77%, 34.25%, and 25.59%, respectively. There was a statistically significant correlation between vaccination coverage in classification of diagnostic medical institutions and the types of diagnosed diseases. Compared to their typically developing counterparts, 12-month-old children afflicted with CHD exhibit a slightly diminished vaccination coverage, alongside a discernible inclination toward delayed vaccination. Notably, the determination to undergo vaccinations seems predominantly influenced by the classification of diagnostic medical institutions. In practical terms, proactive measures involving early diagnosis, comprehensive health assessments, and timely interventions ought to be implemented to enhance vaccination rates while prioritizing safety.

KEYWORDS:

• Congenital heart disease (CHD)
• NIP vaccines
• non-NIP vaccines
• vaccination coverage

Introduction

Congenital Heart Disease (CHD) encompasses cardiovascular anomalies resulting from irregularities in the development of the heart and associated blood vessels during fetal gestation. This condition is one of the prevalent congenital ailments affecting pediatric populations.¹ The elevated prevalence of CHD predominantly is manifested in developing nations across Africa and Asia, whereas the incidence remains comparatively lower in developed countries.² A study assesses the burden of congenital diseases in 38 OECD (Organization for Economic Co-operation and Development) countries from 1990 to 2019.³ The total number of prevalent cases of CHD increased from 1,469,128 to 1,590,654. In contrast, the number of CHD-related deaths decreased from 37,291 to 13,886, resulting in a 60% decrease in the age-standardized mortality rate. Prior research has indicated an approximate incidence rate of CHD in European and American nations to be around 0.9%, while in China, it ranges from 0.6% to 0.9%.⁴ Annually, an estimated 150,000 to 200,000 new cases of CHD among newborns occur in China.⁵ A study on CHD among newborns in China presents meta-analysis results, indicating that the national incidence rate of neonatal CHD was 0.49% from 2015 to 2019. This rate has increased by approximately 0.11% to 0.41% by 2021.⁶ Furthermore, the prevalence of CHD in Zhejiang Province is notably lower than the national average in China, with Ningbo City recording a prevalence rate of approximately 0.67%.⁷

Among the reported confirmed cases, approximately half of them requiring cardiac surgery or catheter intervention treatment.^8,9 This subset accounts for about 26.7% of all monitored birth defects in China, and ranking CHD as the foremost among such birth defects.¹⁰ The pathological and physiological mechanisms of CHD are diverse, with the fundamental feature being abnormal cardiac structure. Among these, the prevalent types of CHD include atrial septal defects, ventricular septal defects, patent ductus arteriosus, and tetralogy of Fallot.¹¹ Pediatric patients diagnosed with CHD exhibit heightened vulnerability to infectious diseases due to potential cardiopulmonary impairments, consequently facing an increased risk of developing additional illnesses or complications following an infection. Moreover, when infected, these individuals may experience more severe symptoms compared to their healthy counterparts.¹² The treatment modalities for CHD encompass surgical intervention, procedures, pharmacological therapy, or a combination of these methods. Through prompt and efficacious intervention, a majority of patients can achieve recovery to a standard level of daily functioning, typically without significant lingering effects or sequelae.

The National Immunization Program (NIP) serves as a public health intervention aimed at protecting public health through large-scale vaccination of the population. Vaccination plays a vital role in preventing infections among children with CHD. Advancements in medical technology have notably increased the identification of congenital diseases, particularly through heart disease screening initiatives. The World Health Organization (WHO) recommends that not only the majority of children with CHD not be excluded from vaccination, but they should also receive timely immunization for protection. Research studies have underscored the positive efficacy and safety of vaccinating children with CHD.¹³ In recent years, investigations have been undertaken regarding vaccination coverage among children with CHD in specific regions, highlighting widespread challenges such as low vaccination coverage, delayed immunization, or instances of refused vaccinations. Notably, there remains a lack of reports detailing the vaccination status of children with CHD under the age of one year in China. Using big data, this study analyzes the current vaccination status of children with CHD, aiming to provide a reference for the development of prevention, control, and immunization strategies against vaccine-preventable diseases in this population.

Methods

Data source

As part of the CHinese Electronic health Records Research in Yinzhou (CHERRY) project,¹⁴ data were compiled for children born between January 1st, 2016, and September 20th, 2021. Through the linkage of records using ICD-10（International Classification of Diseases, 10th Revision） coding, we identified and screened children with CHD. Additionally, leveraging the unique and encoded identifiers of the survey subjects, we connected and consolidated relevant management databases within the Yinzhou regional public health integrated platform. We first gather the baseline information of children with CHD, which includes their date of birth, gender, residential address, and household registration address and diagnostic data for the children, which includes the name of the diagnosed disease, the age at diagnosis, and the diagnosing institution from outpatient and inpatient medical records at the hospital. Additionally, we collect their vaccination history, including the vaccine names, vaccination dates, and doses administered, in the vaccination database of the big data platform for Yinzhou District, Ningbo City. Subsequently, we associate it with unique and encoded identifiers and perform data deduplication. In order to ensure a slow observation period of 12 months, children under the age of 12 months were excluded from the observation period. We will initially align the diagnostic, baseline, and vaccination data pertaining to CHD according to coding. Subsequently, we will identify children diagnosed with CHD within their first 12 months of age. Finally, we will export this matched information for further analysis and reference purposes. These processes are detailed in Figure 1.

Figure 1. Flow diagram of the study design.

Alternative vaccination

Following the guidelines outlined in the “National Immunization Program for Children and Immunization Procedures and Instructions (2016 Edition)” as released by the National Health and Family Planning Commission,¹⁵ the administration of non-NIP vaccines containing components of the immunization program by the vaccine recipient can be considered an equivalent alternative immunization.

The NIP vaccines analyzed in this study included Hepatitis B vaccine (HepB), Bacillus Calmette-Guérin vaccine (BCG), Poliomyelitis vaccine (PV), Diphtheria Tetanus Pertussis (DPT) vaccine, Measles, Mumps and Rubella vaccine (MMR), Japanese encephalitis vaccine (JE), Meningococcal vaccine (MenV), Hepatitis A vaccine (HepA). And non-NIP vaccines included Rotavirus vaccine (RV), influenza vaccine, Haemophilus influenzae Type b (Hib) vaccine, Conjugate Vaccine, 13-valent pneumococcal conjugate vaccine (PCV13), and inactivated enterovirus type 71 vaccine (EV71). This information is presented in detail in Table 1.

Table 1. Alternative vaccine types.

Vaccine Name	Vaccines containing the respective components
PV	Inactivated poliovirus vaccine (IPV)
	Oral poliovirus vaccine (OPV)
	Diphtheria, Tetanus, Pertussis, Inactivated Polio Vaccine, Haemophilus influenzae type b vaccine
DPT	Diphtheria Tetanus Pertussis vaccine (DPT)
	Haemophilus influenzae type b and Diphtheria-Tetanus-acellular Pertussis combination vaccine
JE^a	Japanese Encephalitis Vaccine
	Inactivated Japanese Encephalitis Vaccine
Menv	A meningococcal polysaccharide vaccine
	C meningococcal conjugate vaccine
	AC meningococcal Hib combination vaccine
MMR	Leprosy vaccine
	Measles-mumps-rubella vaccine
RV	Oral rotavirus live vaccine
	Oral pentavalent reassortant rotavirus attenuated vaccin
Hib^b	Haemophilus Influenzae Type b Conjugate Vaccine
	Bivalent Influenza Haemophilus influenzae Type b (Hib) Conjugate Vaccine and Acellular Pertussis (DTaP) Vaccine
	AC meningococcal Hib combination vaccine

^aAccording to the national immunization program, it is recommended that children receive either one dose of live attenuated Japanese encephalitis vaccine or two doses of inactivated Japanese encephalitis vaccine at 8 months of age. This study posits that completing the two-dose regimen of inactivated Japanese encephalitis vaccine is equivalent to receiving one dose of live attenuated Japanese encephalitis vaccine for the purposes of analysis and evaluation.

^bAccording to the national immunization program guidelines, it is recommended that children receive either a single dose of oral rotavirus live vaccine or a three-dose series of oral pentavalent reassortant rotavirus vaccine to complete the vaccination schedule.

Statistical analysis

The investigation enrolled children born between January 1, 2016, to September 20, 2021, segmenting the vaccine coverage into three distinct intervals. These divisions included the vaccination coverage for children at 12 months old, extending from January 1, 2016, to September 20, 2020; encompassing children at 12 and 24 months old between January 1, 2016, and September 20, 2019; and spanning children at 12, 24, and 36 months old within the time frame of January 1, 2016, to September 20, 2018.

Vaccine coverage, also known as immunization coverage or vaccination coverage, refers to the proportion of a population that has received a specific vaccine or series of vaccines within a given time frame. It is a critical indicator of the effectiveness of vaccination programs in preventing the spread of vaccine-preventable diseases. Vaccine coverage is typically expressed as a percentage and is calculated using the following formula^16,17: Vaccination coverage of a vaccine dose (%) = number of persons actually vaccinated for that vaccine dose/number of persons who should be vaccinated for that vaccine dose × 100%. Total NIP vaccination coverage (%) = (Number of individuals who received the actual 14 doses of NIP vaccines/Number of individuals expected to receive the 14 doses of NIP vaccines) × 100%.

The process of data organization and subsequent statistical analyses were conducted utilizing the Python 3.9 software (developed by Guido van Rossum, originated in the Netherlands.). Chi-square tests will be conducted to examine the correlation between the first dose of vaccination, completion of vaccination, and the following variables: gender, household registration, the age (in months) when diagnosed with CHD, grading of diagnostic medical institutions, and the types of diagnosed diseases. The chi-square tests will be two-tailed with a significance level of α = 0.05.

Results

Study population

Table 2 shows the baseline characteristics of children with CHD born from January 1,2016 to September 202,021. A total of 762 children were enrolled in this study conducted within the Yinzhou District of Ningbo. Among these participants, 402 (52.76%) were males, while 360 (47.24%) were females. The distribution of births across the years 2016 to 2020 was 124(16.27%), 146(19.16%), 169(22.18%), 272(35.70%), and 51(6.69%), respectively. Furthermore, 506 children (66.40%) were registered in households within Zhejiang Province, whereas 256 children (33.60%) were registered in households outside Zhejiang Province. The numbers of infants aged less than 3 months, more than 3 months, more than 6 months, and more than 9 months but less than 12 months were 307 (40.29%), 258 (33.86%), 143 (18.76%), 54 (7.09%), correspondingly. The number of children who received their initial diagnosis of CHD at municipal hospitals, district hospitals, and township hospitals was 547 (71.78%), 114 (13.25%), and 101 (13.26%), respectively. The diagnoses of CHD, patent ductus arteriosus, heart disease, and other diseases (including pulmonary valve stenosis, congenital heart ear malformations, congenital heart valve defects, heart enlargement, right heart, paroxysmal supraventricular tachycardia, and paroxysmal heart rhythm disorders) were 602 (79.01%), 101 (13.25%), and 59 (7.74%), respectively, as shown in Table 2.

Table 2. Sociodemographic characteristics of children in our study(n = 762).

indicators	the number of children	proportion (%)
The birth year
2016	124	16.27
2017	146	19.16
2018	169	22.18
2019	272	35.70
2020	51	6.69
Gender
Male	402	52.76
Female	360	47.24
Household registration
Zhejiang Province	506	66.40
Outside Zhejiang province	256	33.60
The age (in months) when diagnosed with CHD
0~	307	40.29
3~	258	33.86
6~	143	18.76
9 ~12	54	7.09
Grading of diagnostic medical institutions
Municipal hospitals	114	14.96
District hospitals	547	71.78
Township hospitals	101	13.26
The types of diagnosed diseases
CHD	101	13.25
Patent ductus arteriosus	602	79.01
Heart disease and other diseases*	59	7.74

*Other CHD conditions include pulmonary valve stenosis, congenital heart valve abnormalities, atrial septal defect, heart enlargement, right-sided heart, paroxysmal supraventricular tachycardia, and paroxysmal ventricular tachycardia.

Vaccination coverage of children with CHD at 12 months

NIP vaccines of CHD children

Among children with CHD, the coverage of the first NIP vaccines at 12 months of age was 86.74%. A total of 755 children received the first dose of HepB, with a vaccination coverage of 99.08%. Among these, 698 children (92.45%) received the vaccine before being diagnosed with CHD. Moreover, 547 children successfully completed the three-dose immunization program for HepB, with a completion coverage of 71.78%. Of these, 109 children (19.93%) received the vaccine before being diagnosed with CHD. A total of 597 children received BCG, with a vaccination coverage of 78.35%. Among them, 516 children (86.43%) received the vaccine before being diagnosed with CHD. Seven hundred and twenty-nine children received the first dose of PV, resulting in a vaccination coverage of 95.67%. Among them, 465 children (63.79%) received the vaccine before being diagnosed with CHD. Additionally, 668 children completed the three-dose immunization program for PV, achieving a completion coverage of 87.66%. Of these, 233 children (34.88%) received the vaccine before being diagnosed with CHD. Six hundred and seventeen children received JE, including 408 children who received the attenuated vaccine and 209 children who received the inactivated vaccine, resulting in a vaccination coverage of 80.97%. Furthermore, 664 children received the first dose of MenV, achieving a vaccination coverage of 87.14%. Among these, 137 children (20.63%) received the vaccine before being diagnosed with CHD. Five hundred and fifty-nine children received the second dose of MenV, achieving a vaccination coverage of 73.36%. `18 children received the first dose of DPT, resulting in a vaccination coverage of 94.23%. Data availability by vaccine is displayed in Table 3.

Table 3. The vaccination coverage for children with congenital heart disease aged 12 months (n = 762).

Vaccine	Vaccine doses	The number of vaccinated children	The number of vaccinated children before diagnosis	The number of vaccinated children after diagnosis	The number of unvaccinated children	Vaccination coverage (%)
HepB	HepB_1	755	698	57	7	99.08
	HepB_2	704	479	225	58	92.39
	HepB_3	547	109	438	215	71.78
BCG	BCG	597	516	81	165	78.35
PV	PV_1	729	465	264	33	95.67
	PV_2	706	321	385	56	92.65
	PV_3	668	233	435	94	87.66
MR	MR	654	74	580	108	85.83
JE	JE_1	617	60	557	145	80.97
	JE_2	–	–	–	–	–
MenV	MenV_1	664	137	527	98	87.14
	MenV_2	559	48	511	203	73.36
DTP	DTP_1	718	388	330	44	94.23
	DTP_2	694	276	418	68	91.08
	DTP_3	641	194	447	121	84.12
	DTP_4	–	–	–	–	–
HepA	HepA	–	–	–	–	–
Var	Var	–	–	–	–	–
RV	AR	208	46	162	554	27.30
Influenza vaccine	Influ_1	59	4	55	703	7.74
	Influ_2	42	3	39	720	5.51
Hib	Hib_1	482	277	205	280	63.25
	Hib_2	462	181	281	300	60.63
	Hib_3	425	122	303	337	55.77
	Hib_4	–	–	–	–	–
PCV13	PCV13_1	287	184	103	475	37.66
	PCV13_2	275	126	149	487	36.09
	PCV13_3	261	88	173	501	34.25
EV71	EV71_1	263	13	250	499	34.51
	EV71_2	195	7	188	567	25.59

*CHD: congenital heart disease; HepB_1: the first dose of hepatitis B vaccine; HepB_2: the second dose of hepatitis B vaccine; HepB_3: the third dose of hepatitis B vaccine; BCG: BCG vaccine; PV_1: the first dose of poliovirus vaccine; PV_2: the second dose of poliovirus vaccine; PV_3: the third dose of poliovirus vaccine; MMR: measles, mumps and rubella vaccine; JE_1: the first dose of Japanese encephalitis vaccine; JE_2: the second dose of Japanese encephalitis vaccine; MenV_1: the first dose of meningococcal vaccine; MenV_2: the second dose of meningococcal vaccine; DTP_1: the first dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_2: the second dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_3: the third dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine. RV: Rotavirus vaccine; Influ_1: First dose of influenza vaccine; Influ_2: Second dose of influenza vaccine; Hib_1: First dose of Haemophilus influenzae type b vaccine; Hib_3: Third dose of Haemophilus influenzae type b vaccine; PCV13_1: First dose of 13-valent pneumococcal conjugate vaccine; PCV13_2: Second dose of 13-valent pneumococcal conjugate vaccine; EV71_1: First dose of inactivated enterovirus 71 vaccine; EV71_2: Second dose of inactivated enterovirus 71 vaccine.

Non-NIP vaccines for CHD children

A total of 208 children completed the vaccination for the RV, achieving in a vaccination coverage of 27.30%. The number of children who completed the first and second doses of influenza vaccine was 59 and 42, respectively, resulting in vaccination coverage of 7.74% and 5.51%. Moreover, the number of children who completed the first, second, and third doses of Hib was 482, 462, and 425, with vaccination coverage of 63.25%, 60.63%, and 55.77%, respectively. The number of children who completed the first, second, and third doses of PCV13 was 287, 275, and 261, resulting in vaccination coverage of 37.66%, 36.09%, and 34.25%, respectively. Additionally, the number of children who received the first and second doses of EV71 was 263 and 195, achieving vaccination coverage of 34.51% and 25.59%, respectively (Table 3).

Vaccination coverage of children with CHD at 24 months

NIP vaccines of CHD children

A total of 647 children were enrolled to analyze the vaccination coverage at 24 months of age. The first-dose vaccination coverage for HepB, BCG, PV, MMR, JE, MenV, DTP, and HepA were 99.85%, 92.89%, 97.84%, 92.27%, 89.49%, 93.51%, 97.22%, and 71.10%, respectively. The third doses of HepB, PV, and DTP, were inoculated to 88.72%, 94.28%, and 92.43% of the children, respectively. The second doses of JE and MenV were given to 8.19% and 86.09% of the children, respectively (Table 4).

Table 4. The vaccination coverage for children with congenital heart disease aged 24 months (n = 647).

Vaccine	Vaccine doses	Vaccination coverage at 12 months of age(%)			Vaccination coverage at 24 months of age(%)
		The number of vaccinated children	The number of unvaccinated children	Vaccination coverage (%)	The number of vaccinated children	The number of unvaccinated children	Vaccination coverage (%)
HepB	HepB_1	642	5	99.23	646	1	99.85
	HepB_2	618	29	95.52	631	16	97.53
	HepB_3	543	104	83.93	574	73	88.72
BCG	BCG	576	71	89.03	601	46	92.89
PV	PV_1	617	30	95.36	633	14	97.84
	PV_2	605	42	93.51	626	21	96.75
	PV_3	580	67	89.64	610	37	94.28
MR	MR	569	78	87.94	597	50	92.27
JE	JE_1	532	115	82.23	579	68	89.49
	JE_2	–	–	–	53	594	8.19
MenV	MenV_1	572	75	88.41	605	42	93.51
	MenV_2	482	165	74.50	557	90	86.09
DTP	DTP_1	609	38	94.13	629	18	97.22
	DTP_2	592	55	91.50	617	30	95.36
	DTP_3	555	92	85.78	598	49	92.43
	DTP_4	–	–	–	459	188	70.94
HepA	HepA	–	–	–	460	187	71.10
Var	Var	46	601	7.11	513	134	79.29
RV	RV	169	478	26.12	198	449	30.60
Influenza vaccine	Influ_1	51	596	7.88	120	527	18.55
	Influ_2	38	609	5.87	109	538	16.85
Hib	Hib_1	405	242	62.60	452	195	69.86
	Hib_2	390	257	60.28	399	248	61.67
	Hib_3	363	284	56.11	380	267	58.73
	Hib_4	–	–	–	299	348	46.21
PCV13	PCV13_1	222	425	34.31	235	412	36.32
	PCV13_2	216	431	33.38	224	423	34.62
	PCV13_3	210	437	32.46	213	434	32.92
EV71	EV71_1	200	447	30.91	321	326	49.61
	EV71_2	136	511	21.02	301	346	46.52

*CHD: congenital heart disease; HepB_1: the first dose of hepatitis B vaccine; HepB_2: the second dose of hepatitis B vaccine; HepB_3: the third dose of hepatitis B vaccine; BCG: BCG vaccine; PV_1: the first dose of poliovirus vaccine; PV_2: the second dose of poliovirus vaccine; PV_3: the third dose of poliovirus vaccine; MMR: measles, mumps and rubella vaccine; JE_1: the first dose of Japanese encephalitis vaccine; JE_2: the second dose of Japanese encephalitis vaccine; MenV_1: the first dose of meningococcal vaccine; MenV_2: the second dose of meningococcal vaccine; DTP_1: the first dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_2: the second dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_3: the third dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine. RV: Rotavirus vaccine; Influ_1: First dose of influenza vaccine; Influ_2: Second dose of influenza vaccine; Hib_1: First dose of Haemophilus influenzae type b vaccine; Hib_3: Third dose of Haemophilus influenzae type b vaccine; PCV13_1: First dose of 13-valent pneumococcal conjugate vaccine; PCV13_2: Second dose of 13-valent pneumococcal conjugate vaccine; EV71_1: First dose of inactivated enterovirus 71 vaccine; EV71_2: Second dose of inactivated enterovirus 71 vaccine.

Non-NIP vaccines of CHD children

The first-dose vaccination coverage for Var, RV, influenza vaccine, Hib, PCV13 and EV71 were 79.29%, 30.60%, 18.55%, 69.86%, 36.32 and 49.61%, respectively. The second doses of influenza, Hib, and EV71 vaccine were administered to 16.85%, 61.67%, and 46.52% of the children, respectively. Moreover, the third doses of PCV13 were given to 32.92% of the children (Table 4).

Vaccination coverage of children with CHD at 36 months

NIP vaccines of CHD children

A total of 647 children were enrolled to analyze the vaccination coverage at 24 months of age. The first-dose vaccination coverage for HepB, BCG, PV, MMR, JE, MenV, DTP, and HepA were 100%, 97.86%, 98.66%, 89.57%, 95.19%, 95.45%, 98.13% and 84.49%, respectively. Moreover, the third doses of HepB, PV, and DTP were inoculated to 95.45%, 96.52% and 95.72% of the children, respectively. Additionally, the second doses of JE and MenV were given to 83.16% and 91.98% of the children, respectively (Table 5).

Table 5. The vaccination coverage for children with congenital heart disease aged 36 months (n = 374).

Vaccine	Vaccine doses	Vaccination coverage at 12 months of age(%)			Vaccination coverage at 24 months of age(%)			Vaccination coverage at 36 months of age(%)
		The number of vaccinated children	The number of unvaccinated children	Vaccination coverage (%)	The number of vaccinated children	The number of unvaccinated children	Vaccination coverage (%)	The number of vaccinated children	The number of unvaccinated children	Vaccination coverage (%)
HepB	HepB_1	371	3	99.20	373	1	99.73	374	0	100
	HepB_2	360	14	96.26	371	3	99.20	373	1	99.73
	HepB_3	331	43	88.50	355	19	94.92	357	17	95.45
BCG	BCG	343	31	91.71	363	11	97.06	366	8	97.86
PV	PV_1	355	19	94.92	367	7	98.13	369	5	98.66
	PV_2	347	27	92.78	362	12	96.79	365	9	97.59
	PV_3	335	39	89.57	358	16	95.72	361	13	96.52
MR	MR	19	355	5.08	332	42	88.77	335	39	89.57
JE	JE_1	316	58	84.49	349	25	93.32	356	18	95.19
	JE_2	14	360	3.74	67	307	17.91	311	63	83.16
MenV	MenV_1	332	42	88.77	355	19	94.92	357	17	95.45
	MenV_2	290	84	77.54	344	30	91.98	344	30	91.98
DTP	DTP_1	351	23	93.85	364	10	97.33	367	7	98.13
	DTP_2	340	34	90.91	358	16	95.72	364	10	97.33
	DTP_3	322	52	86.10	352	22	94.12	358	16	95.72
	DTP_4	–	–	–	306	68	81.82	322	52	86.10
HepA	HepA	–	–	–	191	183	51.07	316	58	84.49
Var	Var	40	334	10.70	331	43	88.50	340	34	90.91
RV	RV	68	306	18.18	91	283	24.33	100	274	26.74
Influenza vaccine	Influ_1	35	339	9.36	75	299	20.05	96	278	25.67
	Influ_2	26	348	6.95	70	304	18.72	88	286	23.53
Hib	Hib_1	217	157	58.02	257	117	68.72	259	115	69.25
	Hib_2	207	167	55.35	214	160	57.22	214	160	57.22
	Hib_3	191	183	51.07	203	171	54.28	203	171	54.28
	Hib_4	–	–	–	176	198	47.06	185	189	49.47
PCV13	PCV13_1	73	301	19.52	73	301	19.52	74	300	19.79
	PCV13_2	72	302	19.25	72	302	19.25	72	302	19.25
	PCV13_3	70	304	18.72	71	303	18.98	71	303	18.98
EV71	EV71_1	88	286	23.53	169	205	45.19	194	180	51.87
	EV71_2	54	320	14.44	159	215	42.51	187	187	50.00

*CHD: congenital heart disease; HepB_1: the first dose of hepatitis B vaccine; HepB_2: the second dose of hepatitis B vaccine; HepB_3: the third dose of hepatitis B vaccine; BCG: BCG vaccine; PV_1: the first dose of poliovirus vaccine; PV_2: the second dose of poliovirus vaccine; PV_3: the third dose of poliovirus vaccine; MMR: measles, mumps and rubella vaccine; JE_1: the first dose of Japanese encephalitis vaccine; JE_2: the second dose of Japanese encephalitis vaccine; MenV_1: the first dose of meningococcal vaccine; MenV_2: the second dose of meningococcal vaccine; DTP_1: the first dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_2: the second dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_3: the third dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine. RV: Rotavirus vaccine; Influ_1: First dose of influenza vaccine; Influ_2: Second dose of influenza vaccine; Hib_1: First dose of Haemophilus influenzae type b vaccine; Hib_3: Third dose of Haemophilus influenzae type b vaccine; PCV13_1: First dose of 13-valent pneumococcal conjugate vaccine; PCV13_2: Second dose of 13-valent pneumococcal conjugate vaccine; EV71_1: First dose of inactivated enterovirus 71 vaccine; EV71_2: Second dose of inactivated enterovirus 71 vaccine.

Non-NIP vaccines of CHD children

The first-dose vaccination coverage for Var, RV, influenza vaccine, Hib, PCV13 and EV71 were 84.49%, 26.74%, 25.67%, 69.25%, 19.79% and 51.87%, respectively. The second doses of influenza, Hib, and EV71 vaccines were administered to 23.53%, 57.22% and 50.00% of the children, respectively. The third doses of PCV13 were given to 18.98% of the children (Table 5).

Factors affecting vaccination coverage for CHD children

Factors affecting vaccination coverage of NIP vaccines

There was no statistically significant difference between whether children with CHD were vaccinated against NIP vaccines and gender. However, a statistically significant difference was observed between vaccinating MMR and the age at CHD diagnosis. Furthermore, there was a statistically significant difference in vaccinating MMR, JE, MenV based on Household registration. Additionally, a statistically significant difference was observed between vaccinating the third dose of HepB and BCG and the types of diagnosed diseases. Additionally, the decision to inoculate the third dose of HepB, BCG, PV, MMR and MenV showed statistically different related to the classification of diagnostic institutions (Table 6).

Table 6. Univariate analysis of NIPs coverage of children with congenital heart disease within 12 months of age(n = 762).

Vaccine coverage (%)	Sample size	HepB_1	HepB_2	HepB_3	BCG	PV_1	PV_2	PV_3	MR	JE	MenV_1	MenV_2	DTP_1	DTP_2	DTP_3
Gender
Male	402	99.00	92.04	71.89	78.61	96.27	53.40	87.06	84.33	79.10	87.81	71.89	94.78	91.54	83.58
Female	360	99.17	92.78	71.67	78.06	95.00	46.60	88.33	87.50	83.06	86.39	75.00	93.61	90.56	84.72
p value	–	.999	.805	.999	.923	.496	.261	.674	.250	.195	.633	.375	.594	.727	.741
Household registration
Zhejiang Province	506	99.21	93.08	74.11	78.46	96.05	93.28	88.34	88.74	84.19	88.14	78.26	95.06	91.70	85.57
Outside the province	256	98.83	91.02	67.19	78.12	94.92	91.41	86.33	80.08	74.61	85.16	63.67	92.58	89.84	81.25
p value	–	.905	.383	.055	.990	.594	.430	.496	.002	.002	.294	<.001	.222	.475	.150
Grading of diagnostic medical institutions
Municipal hospitals	114	99.27	92.50	68.92	75.50	97.07	93.78	88.30	85.37	81.54	87.75	73.49	95.25	92.14	84.64
District hospitals	547	99.12	92.98	81.58	85.09	94.74	92.98	89.47	92.98	85.09	89.47	82.46	94.74	92.11	87.72
Township hospitals	101	98.02	91.09	76.24	86.14	89.11	86.14	82.18	80.20	73.27	81.19	62.38	88.12	84.16	77.23
p value	–	.481	.856	.014	.010	.001	.025	.186	.023	.072	.140	.004	.018	.032	.090
The types of diagnosed diseases
CHD*	101	99.00	92.69	76.08	82.23	95.02	92.36	88.04	85.38	80.90	86.71	71.93	93.52	90.37	83.55
Patent ductus arteriosus	602	100	92.08	57.43	66.34	98.02	92.08	84.16	84.16	78.22	87.13	76.24	96.04	92.08	83.17
Heart disease and other diseases	59	98.31	89.83	52.54	59.32	98.31	96.61	89.83	93.22	86.44	91.53	83.05	98.31	96.61	91.53
p value	–	.505	.726	< .05	< .05	.228	.477	.477	.225	.439	.574	.143	.227	.256	.268
The age (in months) when diagnosed with CHD
0~	307	99.35	90.88	67.75	78.18	94.79	91.21	85.02	82.74	77.85	84.36	70.03	92.51	88.93	81.11
3~	258	99.61	94.19	71.71	79.84	96.90	94.19	89.92	85.27	80.62	88.37	74.03	95.74	92.25	85.27
6~	143	97.90	93.01	76.92	79.72	95.80	93.71	88.81	90.21	86.01	89.51	76.92	95.10	93.01	86.71
9 ~ 12	54	98.15	90.74	81.48	68.52	94.44	90.74	88.89	94.44	87.04	90.74	79.63	94.44	92.59	88.89
p value	–	.291	.481	.077	.310	.633	.501	.327	.045	.132	.284	.282	.399	.393	.264

*CHD: congenital heart disease; HepB_1: the first dose of hepatitis B vaccine; HepB_2: the second dose of hepatitis B vaccine; HepB_3: the third dose of hepatitis B vaccine; BCG: BCG vaccine; PV_1: the first dose of poliovirus vaccine; PV_2: the second dose of poliovirus vaccine; PV_3: the third dose of poliovirus vaccine; MMR: measles, mumps and rubella vaccine; JE_1: the first dose of Japanese encephalitis vaccine; JE_2: the second dose of Japanese encephalitis vaccine; MenV_1: the first dose of meningococcal vaccine; MenV_2: the second dose of meningococcal vaccine; DTP_1: the first dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_2: the second dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine; DTP_3: the third dose of Diphtheria-Tetanus-Pertussis (DTP) vaccine.

Factors affecting the vaccination coverage of non-NIP vaccines

This study analyzed the factors affecting the vaccination coverage of five non-NIP vaccines. No statistically significant difference was found in the administration of non-NIP vaccines based on gender. However, a statistically significant difference was found in the administration of RV based on the grading of diagnostic medical institutions. There was a statistically significant difference in the administration of the influenza vaccine based on the grading of the diagnosing institution. Additionally, a statistically significant difference was observed in whether Hib was inoculated based on household registration. There was a statistically significant difference in the administration of PCV13 based on household registration and the grading of the diagnosing institution. Additionally, a statistically significant difference was observed in the administration of EV71 vaccines based on the grading of the diagnosing institution (Table 7).

Table 7. Univariate analysis of non-NIPs coverage of children with congenital heart disease within 12 months of age(n = 762).

Vaccine coverage (%)	Sample size	RV	Influ_1	Influ_2	Hib_1	Hib_2	Hib_3	PCV13_1	PCV13_2	PCV13_3	EV71_1	EV71_2
Gender
Male	402	28.11	5.97	4.23	64.68	61.44	55.22	38.81	36.57	33.83	35.07	24.13
Female	360	26.11	9.72	6.94	61.67	59.72	56.39	36.39	35.56	34.72	33.89	27.22
p value	–	.539	.072	.138	.432	.681	.802	.540	.830	.855	.789	.371
Household registration
Zhejiang Province	506	29.45	7.91	6.32	71.34	68.97	63.64	47.04	44.86	42.89	35.38	27.47
Outside the province	256	22.66	7.42	3.91	47.27	44.14	40.23	19.14	18.75	17.19	32.81	21.88
p value	–	.074	.926	.225	<.001	<.001	<.001	<.001	<.001	<.001	.534	.113
Grading of diagnostic medical institutions
Municipal hospitals	114	28.52	5.48	4.02	62.16	59.96	55.03	41.13	38.94	36.38	37.11	28.15
District hospitals	547	21.05	8.77	7.02	66.67	64.04	58.77	33.33	33.33	33.33	28.95	21.05
Township hospitals	101	26.72	18.81	11.88	65.35	60.40	56.44	23.76	23.76	23.76	26.73	16.83
p value	–	.264	<.001	.005	.593	.720	.757	.002	.011	.048	.052	.027
The types of diagnosed diseases
CHD*	101	25.25	7.64	5.48	63.29	60.47	55.48	35.88	34.55	32.56	31.89	22.76
Patent ductus arteriosus	602	36.63	8.91	5.94	65.35	62.38	56.44	45.54	41.58	41.58	42.57	34.65
Heart disease and other diseases*	59	30.50	6.78	5.08	59.32	59.32	57.63	42.37	42.37	38.98	47.46	38.98
p value	–	.055	.870	.972	.747	.915	.941	.132	.229	.152	.011	.002
The age (in months) when diagnosed with CHD
0~	307	28.66	5.86	3.91	63.84	61.24	55.37	39.41	37.46	34.85	35.50	27.04
3~	258	25.97	8.53	5.81	62.40	60.47	56.98	36.43	34.50	33.72	30.62	22.87
6~	143	32.17	10.49	8.39	64.34	61.54	55.94	37.76	37.76	34.97	41.26	27.97
9 ~ 12	54	11.11	7.41	5.56	61.11	55.56	51.85	33.33	31.48	31.48	29.63	24.07
p value	–	.026	.353	.280	.959	.877	.917	.802	.752	.960	.150	.608

*CHD: congenital heart disease; RV: Rotavirus vaccine; Influ_1: First dose of influenza vaccine; Influ_2: Second dose of influenza vaccine; Hib_1: First dose of Haemophilus influenzae type b vaccine; Hib_3: Third dose of Haemophilus influenzae type b vaccine; PCV13_1: First dose of 13-valent pneumococcal conjugate vaccine; PCV13_2: Second dose of 13-valent pneumococcal conjugate vaccine; EV71_1: First dose of inactivated enterovirus 71 vaccine; EV71_2: Second dose of inactivated enterovirus 71 vaccine.

Discussion

Endorsed by the World Health Assembly in 2012, the Global Vaccine Action Plan 2011–2020 (GVAP) calls on all countries to achieve a national coverage of at least 90% with all vaccines included in the country’s national immunization schedule by 2020.¹⁸ Since the inception of the National Immunization Program in 1978, the Childhood Immunization Program has evolved into a crucial cornerstone of public health services in China. Aligned with the objectives outlined in the State Council’s “13th Five-Year Plan for Health and Healthcare” in 2016, the primary developmental target was established: achieving a vaccination coverage of over 90% among eligible children under the national immunization program at the township (town, street) level.¹⁹ There is presently no pertinent study on the vaccination coverage of CHD in China. Therefore, the vaccination coverage in this study can only be compared with that of healthy children. Between 2016 to 2019, the reported vaccination coverage for all doses of vaccines included in the national immunization program exceeded 97%.²⁰ In the years 2020 and 2021, the total reported immunization coverage for age-appropriate children receiving vaccines through the national immunization program was 99.20% and 99.27%, respectively.²¹ This study revealed that the coverage of NIP vaccines for children with CHD within 12 months of age was 86.74%, which falls below the national standard of 90%. The vaccination coverage for Var and EV71 vaccines aligns with the Chinese average for non-NIP vaccines. However, the coverage for other vaccines slightly surpasses the average observed in the rest of China. Household registration and the grading of diagnostic medical institutions appear to be the primary influencers on vaccination coverage.

A study from the United States and Canada demonstrated²² that 75.4% of healthcare workers advocated on-time vaccination for children with CHD. However, a notable delay in vaccination was observed for those with Brugada syndrome. Vaccination coverage varies among different vaccines for children with CHD, and delays in vaccination are commonly noted. As per the NIP vaccines, the completion of vaccination coverage among children with CHD at 12 months of age is lower than the vaccination rate for the general children.²¹ The absence of clear definition and classification of CHD in numerous vaccination instructions, along with the lack of corresponding clinical trials, introduces uncertainty regarding whether CHD should be considered a contraindication for specific vaccines. This uncertainty frequently leads vaccinators to hesitate in recommend relevant vaccines. Furthermore, parents of children, worried about the safety and effectiveness of vaccines, may refuse to inoculate. Previous literature addresses the reasons for delaying vaccination in children with CHD and the safety of vaccination in this population.⁹ In a questionnaire survey conducted among parents in Ningbo, Zhejiang Province, China, it was found that the primary reasons for delaying vaccination included vaccination clinics refusing to provide vaccines (77.6%), parents’ concerns about vaccine safety (19.0%), and parents’ doubts about the efficacy of vaccines after using certain medications (3.4%). Of the children with CHD, 83.7% received vaccines in accordance with the national guidelines, 14.4% were advised to delay specific vaccines, and 1.9% experienced delayed in all vaccinations. The incidence of adverse reactions to vaccination, as per the vaccination schedule is approximately 33.5 per 100,000, and with no reports of serious adverse reactions.

As of the end of 2020, the HepB vaccine has been implemented in 190 countries, and the global coverage rate for three doses of the HepB vaccine has reached 83%.²³ In a community in Beijing, the coverage rates for HepB and BCG vaccine for children with CHD were 72.9% and 85.7%, respectively.¹³ In this study, the completion coverage of HepB and BCG vaccines at 12 months of age were 71.78% and 78.35%, respectively, aligning with the findings of previous studies. However, the coverage at 36 months of age reached 100% for HepB and 97.86% for BCG, resembling the rates observed in normal children. It’s noteworthy that HepB and BCG vaccinations are recommended to be completed within 24 hours of birth. Most children were diagnosed with CHD around 3 months of age. Out of these cases, 698 (92.45%) and 516 (86.43%) children had received the first dose of HepB and BCG vaccinations, respectively, before their disease diagnosis. The safety of vaccines administered to such children was to be no different from that of normal children. However, the coverage rate for the BCG vaccine by 12 months of age stood at 78.35%, notably rising to 97.86% by 36 months of age, showcasing a considerable delay in comparison to the HepB vaccine.^24–27 The reasons for this delay may include: 1) The absence of a mandatory recommendation for BCG vaccine administration at birth, as the first dose of the HepB vaccine must be given within 24 hours after birth, emerging as an independent risk factor for delayed vaccination; 2) the low timeliness might be attributed to each vial of BCG vaccine containing 10 doses, leading most immunization clinics to provide BCG vaccine administration services once a week to reduce vaccine waste. Over the past five years, the average loss rate of BCG vaccine in Zhejiang Province was 80%, the highest among all expanded immunization program vaccines. 3) The uncertainty surrounding the protective effect and safety of the BCG vaccine stems from its limited protection against tuberculous meningitis and biliary tuberculosis, excluding community-acquired tuberculosis. Additionally, the BCG vaccine is associated with relatively high rates of adverse events. These factors have contributed to many parents hesitating when it comes to their children receiving the BCG vaccine.

Vaccination coverage for Var among children with CHD aged 24 months and 36 months was 79.29% and 90.91%, respectively. These rates were considerably high than the average level in China,^18,28 comparable to the vaccination coverage in the United States,²⁹ and exceeded the vaccination coverage in Japan.³⁰ Var is a non-NIP vaccines in China, but Yinzhou District is in the immunization program vaccine management, resulting in significantly higher vaccination coverage compared to other non-NIP vaccines. Non-NIP vaccines are self-funded, and their coverage tends to correlate with the local economic level. Yinzhou District, being relatively economically developed, exhibits higher coverage of NIP vaccines NIP vaccines. RV had been introduced in 101 countries by 2018. Global coverage with the completed rotavirus series approximately quadrupled, increasing from 8% in 2010 to 35% in 2018.³¹ However, the RV coverage of 36-month-old children with CHD in Yinzhou District is 26.74%, which is lower than the national average level. Global coverage with 3 doses of the Hib vaccine is estimated at 76%. There is substantial variation between regions. The WHO European Region and South-East Asia Region are estimated to have 93% coverage and 91% coverage, respectively, while it is only 32% in the WHO Western Pacific Region.³² China’s vaccination coverage is about 55.9%,³³ while Yinzhou District’s vaccination coverage is 49.47%, which is lower than the national average. The EV71 vaccine coverage is higher than the typical vaccination coverage for children in China.¹⁶ The influenza vaccination coverage was 25.67%, exceeding the vaccination coverage in some provinces in China.³² The vaccination coverage of PCV13 for children under 2 y old in Ningbo was 14.26%, and the vaccination coverage in Yinzhou District was 18.98%, slightly higher than that of the Ningbo city area.³⁴

The vaccination rate for non-NIP vaccines is influenced by various factors, including the specific vaccine, parental willingness, and income level.³⁵ The analysis in this study found statistically significant disparities in the vaccination status of children with CHD based on the administration of non-NIP and the classification of household address and disease diagnosis institutions. Medical technology and health services in township hospitals are not as advanced as those in municipal, district and county hospitals. Untimely or unclear diagnosis leads to delayed medical interventions, which delays vaccination and reduces the vaccination coverage. In practice, offering early diagnosis, comprehensive health assessments and prompt treatment is essential to increase the vaccination rate and enhance the protective effect, all under the premise of safety.

The study of the electronic health records in Yinzhou, China, can provide disease and health-related information for 98% of the permanent residents in the area, accurately reflecting the real situation of CHD children’s vaccination in Yinzhou.¹⁴ This study is the first to assess the vaccination coverage of children with CHD in Yinzhou district at 12 months, 24 months and 36 months of age based on the national surveillance system Additionally, it analyzes the relevant factors that may affect the vaccination coverage. The data was analyzed using a big data platform, f employing a population-wide approach that distinguishes it from systematic reporting and monitoring data. This method provides a more comprehensive depiction of real-world conditions. Assessing the effectiveness of vaccination becomes challenging when coverage is either too low or too high in a population.³⁶ Through the analyzing of the vaccination status of all CHD children in Yinzhou, this study offers preliminary data support for evaluating the effectiveness of vaccination protection for CHD children in the future.

The National Health Care Commission has released the 2021 version of the National Immunization Program Schedule for Children with Vaccines.³⁷ In this version, CHD is not considered a contraindication to vaccination. Vaccinators are advised to make a comprehensive judgment on whether to vaccinate based on the clinician’s assessment of the child’s condition, growth and development status, the risks and benefits of vaccination, and the parents’ wishes. Children with CHD who are eligible for vaccination should be scheduled for vaccination in a timely manner so that children with CHD can receive vaccine protection as early as possible; if the criteria for vaccination are not met, the child should wait until his or her heart function is normalized after treatment (ejection fraction greater than 60%) and there are no comorbidities before receiving additional vaccination as appropriate. The United States, Canada, and Japan recommend that children with CHD follow the regular vaccination schedule. Additionally, for patients at high risk of CHD, pneumococcal and influenza vaccines are recommended to prevent complications from respiratory infections. In Australia, children with CHD are recommended to follow the regular vaccination schedule, with pneumococcal and Hib vaccines recommended until 6 months of age. In our country, we should also refer to the relevant foreign guidelines and develop a detailed vaccination strategy. Compared to typical children, those with CHD are more susceptible to various diseases and have a higher incidence and prevalence rate, making it even more important for them to receive vaccination in order to be protected by the vaccine. The current findings suggest that, in comparison to typically developing children, children with CHD show slightly lower vaccination coverage for certain vaccines. It is advisable to consider reference standards from other countries to establish vaccination criteria for various indicators, such as ultrasound (B-ultrasound) and blood routine parameters. Further refinement of the vaccination guidelines or recommendations for children with CHD should be made, with an emphasis on enhancing the comprehensive health assessment within specialized vaccination clinics.

CHD is a common heart disease in children, with complex causes involving genetics, environment, nutrition, and other factors. We aim to enhance routine immunization, ensure timely catch-up immunization, and promote standardized construction of vaccination clinics to improve the quality of vaccination management and strengthen monitoring and evaluation of immunization rates.

Conclusion

Between January 1, 2016, and September 20, 2021, the vaccination coverage for NIP vaccines among 12-month-old children with CHD in Yinzhou District, Ningbo City, China, consistently lagged behind the coverage among age-appropriate healthy children nationwide during the same period. Notably, there was a significant delay in vaccination within this specific population. However, for children aged 36 months, the majority achieved vaccination coverage of 90% or higher for most NIP vaccines. The vaccination coverage for non-NIP vaccines was not significantly lower than that for healthy children. There was no statistically significant difference in the vaccination of CHD children based on gender, but there were statistically significant differences in vaccination based on household registration, age at CHD diagnosis, grading of diagnostic medical institutions, and the types of diagnosed diseases.

It is emphasized that in practical work, there should be an earlier confirmation of CHD diagnosis, comprehensive health assessments, and timely treatment, all while ensuring safety. In the context of ensuring social public health, we cannot ignore the needs of this special group of patients with CHD. Improving vaccination coverage for patients with CHD will help reduce patients’ risk of contracting infectious diseases and improve their quality of life. It is important to confirm the diagnosis as early as possible, conduct comprehensive health assessments, provide timely treatment, and ensure safety while increasing the vaccination coverage. This will help reduce the risk of infectious diseases for patients with CHD and improve their quality of life.

Acknowledgments

Thank you to Zhijie An, Chao Ma, and Lance from the Chinese Center for Disease Control and Prevention for their knowledge and support for this article. Thank you to Guo Manyu from Jiading District Centre for Disease Control and Prevention, for her knowledge and support of this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Link to the dataset is provided in the Methods section.

Additional information

Funding

This study is supported by the National Natural Science Foundation of China [91846303], Ningbo Health Science and Technology Plan Project, China [2023Y60].