Febrile seizures following measles and varicella vaccines in young children in Australia

BackgroundFebrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age.MethodsAll FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11–23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk.ResultsThere were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5–12 days post receipt of MMR1 at 12 months (RI = 1.9 [95% CI: 1.3–2.9]), but not after VV at 18 months (RI = 0.6 [95% CI: 0.3–1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11–23 months (95% CI = 7–49 cases per 100,000) or 1 per 4167 doses.ConclusionsOur study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013.     

Similar relative risks of seizures following measles containing vaccination in children born preterm compared to full-term without previous seizures or seizure-related disorders

Background

Febrile seizures are associated with the first dose of measles-containing vaccines and the risk increases with chronologic age during the second year of life. We used the Vaccine Safety Datalink (VSD) to determine if the relative increase in risk of seizures following receipt of measles-containing vaccine differs by gestational age at birth.

Beliefs about causes of autism and vaccine hesitancy among parents of children with autism spectrum disorder

Vaccine hesitancy may be more common among parents of children with autism spectrum disorder (ASD). We examined factors associated with ASD-specific vaccine hesitancy among caregivers of children with ASD who participated in the SPARK study (Simons Foundation Powering Autism Research for Knowledge). 225 participants completed an online survey containing the Parent Attitudes About Childhood Vaccines (PACV) questionnaire (measure of vaccine hesitancy) and the Illness Perception Questionnaire revised for parents of children with ASD (IPQ-R-ASD; measure of parents’ views about ASD). 65 participants (28.8%) were vaccine hesitant (PACV score ≥ 50); children of vaccine-hesitant parents (VHPs) were less likely to be first born (n = 27, 41.5%), had greater ASD-symptom severity (mean Social Communication Questionnaire score = 23.9, SD = 6.9), and were more likely to have experienced developmental regression (n = 27, 50.9%) or plateau (n = 37, 69.8%). Compared to non-hesitant parents, VHPs significantly more often endorsed accident/injury, deterioration of the child’s immune system, diet, environmental pollution, general stress, parents’ negative views, parents’ behaviors/decisions, parents’ emotional state, and vaccines as causes for ASD. VHPs also had higher scores on the Personal Control, Treatment Control, Illness Coherence, and Emotional Representations subscales of the IPQ-R than did non-hesitant parents. In the final model, ASD-related vaccine hesitancy was significantly associated with higher scores on the Emotional Representations subscale (OR = 1.13, p = 0.10), agreement with deterioration of the child’s immunity as a cause of ASD (OR = 12.47, p < 0.001), the child not having achieved fluent speech (OR = 2.67, p = 0.17), and the child experiencing a developmental plateau (OR = 3.89, p = 0.002). Findings suggest that a combination of child functioning and developmental history, as well as parents’ negative views about and their sense of control over ASD, influence vaccine hesitancy among parents of children with ASD.     

芜湖市学龄前儿童孤独症谱系障碍患病现状及影响因素研究

目的 探讨2～6岁学龄前儿童孤独症谱系障碍(ASDs)患病现状及其影响因素.方法 以2019年1-12月在安徽省芜湖市某医院参加健康体检的2～6岁学龄前儿童作为研究对象.以问卷调查的方法收集数据,描述ASDs患病情况,并分析芜湖市学龄前儿童ASDs的影响因素.结果 共对13482名儿童完成调查,完整回答调查问卷的共有1...     

上海市公立幼儿园4～6岁儿童孤独谱系障碍现况调查

目的 了解上海市公立幼儿园4～6岁儿童中孤独谱系障碍(ASD)的患病情况。方法 随机选取松江区与徐汇区为代表,以普查方式,采用克氏孤独症行为量表、社会交往问卷、高功能ASD筛查问卷,对调查区域的公立幼儿园中所有10 385名4～6岁儿童进行筛查,对筛查阳性者采用孤独症诊断访谈量表与DSM-5进行诊断。结果 在9 665份有效问卷中,共9名患儿确诊为ASD,男女性别比为8 : 1,时点患病率为0.93‰,ADI-R评估结果与DSM-5的诊断一致。其中2名患儿没有就诊记录,“语言”相关问题为家长选择就医的首要主诉,“社会交往质的障碍”为确诊患儿最显著的症状。结论 上海市学龄前儿童孤独谱系障碍的时点患病率较低,可能与一些患儿未入园有关。     

Estimating the number of US children susceptible to measles resulting from COVID-19-related vaccination coverage declines

Measles elimination hinges on vaccination coverage remaining above 95% to retain sufficient community protection. Recent declines in routine measles vaccinations due to the COVID-19 pandemic coupled with prior models indicating the country was close to the 92% herd immunity benchmark are a cause for concern. We evaluated population-level measles susceptibility in the US, including sensitivity analyses accounting for pandemic-related impacts on immunization. We estimated the number of children aged 0–18 currently susceptible to measles and modeled susceptibility proportions in decreased vaccination scenarios. Participants were respondents to the NIS-Teen survey between 2008 and 2017 that also had provider-verified vaccination documentation. The exposure of interest was vaccination with a measles-containing vaccine (MCV), and the age at which they were vaccinated for all doses given. Using age at vaccination, we estimated age-based probabilities of vaccination and modeled population levels of MCV immunization and immunity vs. susceptibility. Currently, 9,145,026 children (13.1%) are estimated to be susceptible to measles. With pandemic level vaccination rates, 15,165,221 children (21.7%) will be susceptible to measles if no attempt at catch-up is made, or 9,454,436 children (13.5%) if catch-up vaccinations mitigate the decline by 2–3%. Models based on increased vaccine hesitancy also show increased susceptibility at national levels, with a 10% increase in hesitancy nationally resulting in 14,925,481 children (21.37%) susceptible to measles, irrespective of pandemic vaccination levels. Current levels of measles immunity remain below herd immunity thresholds. If pandemic-era reductions in childhood immunization are not rectified, population-level immunity to measles is likely to decline further.     

The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: the first case-control study in Asia

Objective

The aim of this study was to investigate the relationship between autism spectrum disorder (ASD) and general vaccinations, including measles–mumps–rubella (MMR) vaccine, in Japanese subjects, a population with high genetic homogeneity.

Patients and methods

A case–control study was performed. Cases (n = 189) were diagnosed with ASD, while controls (n = 224) were volunteers from general schools, matched by sex and birth year to cases. Vaccination history and prenatal, perinatal, and neonatal factors from the Maternal and Child Health handbook, which was part of each subject's file, were examined. To determine the relationship between potential risk factors and ASD, crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and the differences in mean values of the quantitative variables between cases and controls were analyzed using an unpaired t-test. Moreover, MMR vaccination and the effect of the number of vaccine injections were investigated using a conditional multiple regression model.

Results

For MMR vaccination, the OR was 1.04 (95% CI, 0.65–1.68), and no significant differences were found for the other vaccines. For all of the prenatal, perinatal and neonatal factors, there were no significant differences between cases and controls. Furthermore, regarding the presence of ASD, MMR vaccination and the number of vaccine injections had ORs of 1.10 (95% CI, 0.64–1.90) and 1.10 (95% CI, 0.95–1.26), respectively, in the conditional multiple regression model; no significant differences were found.

Conclusions

In this study, there were not any convincing evidences that MMR vaccination and increasing the number of vaccine injections were associated with an increased risk of ASD in a genetically homogeneous population. Therefore, these findings indicate that there is no basis for avoiding vaccination out of concern for ASD.     

Mumps,measles and rubella vaccination in children with PFAPA syndrome

There is no published data regarding immunologic response to vaccinations in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis). The aim of this study was to evaluate mumps, measles and rubella immunity in children with PFAPA. 31 children with PFAPA syndrome and 22 healthy children (control group – CG) were recruited to the study. All children were previously vaccinated with one dose of MMR vaccine according to the Polish obligatory vaccination schedule. The patients from both groups were evaluated for anti-measles, anti-mumps and anti-rubella IgG antibodies concentrations (ELISA tests; the reference values for protective antibody levels were 150 IU/L, 16 RU/L and 11 IU/ml respectively). The percentage of patients with protective antibodies levels was as follows: measles – 93.55% of PFAPA and 95.45% of CG patients (p = 0.77); mumps – 74.19% of PFAPA and 95.45% of CG patients (p = 0.02); rubella – 80.65% of PFAPA and 90.9% of CG patients (p = 0.30). Conclusions: Children with PFAPA syndrome present a good response to the measles and rubella component of the MMR vaccine, however immunity against mumps after one dose of MMR may not be sufficient. Further investigation concerning immunity against vaccine-preventable diseases and the safety of vaccinations in children with periodic fever syndromes is required.     

Validation of febrile seizures identified in the Sentinel Post-Licensure Rapid Immunization Safety Monitoring Program

BackgroundThe Sentinel Initiative was established in 2008 to monitor the safety of FDA-regulated medical products. We evaluated the positive predictive value (PPV) of ICD-9 codes for post-vaccination febrile seizures to identify optimal algorithms for use in post-market safety surveillance.MethodsWe identified ICD-9 diagnosis codes for fever and seizures in the emergency department or inpatient setting after vaccinations of interest from July 1, 2010 to June 30, 2011. Medical record review was conducted to verify febrile seizure events.ResultsOf 216 potential febrile seizures identified with one or more seizure codes (the broadest algorithm), 152 were chart-confirmed (i.e., documentation of fever within 24 h of seizure or clinician diagnosis of febrile seizure; PPV 70%, 95% CI 64, 76%). Two codes specific for febrile seizures produced the highest PPV (PPV 91%, 95% CI 85, 95%) and accounted for 140 confirmed febrile seizures. In the absence of febrile seizure codes, other seizure codes yielded much lower PPVs, regardless of the presence of fever codes.ConclusionsOur results indicate that ICD-9 diagnosis codes in the inpatient and emergency department settings have high predictive value for identifying febrile seizures within the Sentinel Distributed Database. While the PPV of the algorithm based on any diagnosis code for seizure is moderate, the algorithm limited to febrile seizure codes has a high PPV (>90%) and captures the vast majority of confirmed cases identified by the broadest algorithm, suggesting that the narrower algorithm limited to febrile seizure codes may be preferred.     

Risk of febrile convulsions after MMRV vaccination in comparison to MMR or MMR+V vaccination

Background

In July 2006, Priorix-Tetra™, a combined measles-mumps-rubella-varicella (MMRV) vaccine, was licensed in Germany. Since a postlicensure study had shown a more than twofold elevated risk of febrile convulsions (FC) after first dose vaccination with the combined MMRV vaccine ProQuad^® compared to separately administered MMR and V vaccines (MMR+V), the Paul-Ehrlich-Institute, the German regulatory agency for vaccine licensing and safety, requested a study investigating the risk of FC for Priorix-Tetra™.

Methods

We performed a matched cohort study based on claims data of more than 17 million insurees in the German Pharmacoepidemiological Research Database. All children born between 01.01.2004 and 31.12.2008 who received a 1st dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V (combined group), respectively, by sex, age, month of vaccination and statutory health insurance. The primary outcome was defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis. The secondary outcome excluded only neurological conditions to provide a more comparable outcome definition to the one used in the ProQuad^® study. Numbers needed to harm (NNH), risk ratios and confounder adjusted odds ratios (ORs) with 95% CIs were estimated to compare the exposure groups.

Results

In the main risk period 5–12 days after immunization, the adjusted ORs of the primary endpoint for immunization with MMRV vaccine relative to the comparator vaccine indicated in brackets were 4.1 [95% CI 1.3–12.7; MMR], 3.5 [0.7–19.0; MMR+V], and 4.1 [1.5–11.1; MMR and MMR+V]. The corresponding ORs for the secondary outcome were 2.3 [1.4–3.9; MMR], 1.5 [0.8–2.9; MMR+V] and 2.4 [1.5–3.9; MMR and MMR+V].

Conclusions

This study in children younger than 5 years, 90% of them between 11 and 23 months, shows a risk of FC similar in magnitude for Priorix-Tetra™ as has previously been reported for ProQuad^® suggesting a class effect for these quadrivalent vaccines.     

Safety of pandemic H1N1 vaccines in children and adolescents

During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children.We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines.As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally.     

Vitamin A and vitamin D deficiencies exacerbate symptoms in children with autism spectrum disorders

Objectives: This study was designed to investigate the vitamin A (VA) and vitamin D (VD) levels in children with autism spectrum disorders (ASD) and to determine whether co-deficiency of VA and VD exacerbates clinical symptoms in autistic children.

Methods: The Autism Behavior Checklist, Childhood Autism Rating Scale (CARS), and Social Responsiveness Scale (SRS) were used to assess the symptoms of 332 children diagnosed as ASD. And the Gesell Developmental Scale (GDS) was used to evaluate neurodevelopment in children with ASD. Anthropometric measurement and questionnaire results were compared for all autistic children and 197 age- and gender-matched control children. Serum retinol levels were detected with high-performance liquid chromatography, and serum levels of 25-OH vitamin D were measured with an immunoassay method in the two groups.

Results: The Z_HA, Z_WA, and Z_BMIA of the children with ASD were significantly lower than those of the control children. Furthermore, higher proportions of children with picky eating, resistance to new foods, and eating problems were observed in the ASD group when compared with the control group. Serum retinol and 25-OH vitamin D levels in autistic children were significantly lower than those in the control children. Additionally, VA and VD co-deficiency impacts more on the symptoms and development in autistic children.

Conclusions: We found that children with autism have more VA and VD deficiencies than control children, and VA and VD co-deficiency may exacerbate the symptoms of children with ASD.     

孤独症谱系障碍儿童的早期诊断与识别

目的:探讨连云港市婴幼儿孤独症谱系障碍患病的早期诊断及识别方法。方法:采用随机分层整群抽样方法对连云港市8 532名0～3岁儿童进行横断面调查研究,用婴幼儿孤独症筛查表(CHAT)筛查出可疑儿童,进一步应用儿童孤独症家长评定量表(ABC)、儿童期孤独症评定量表(CARS)及美国精神障碍诊断和统计手册(DSM-IV)诊断依据进行确诊。结果:8 532名儿童中9名为孤独症阳性,阳性率为10.55/万,其中<1岁1例,1～2岁3例,2～3岁5例;男孩7例,女孩2例。结论:加强对孤独症谱系障碍患儿的早期识别能力,做到早期诊断孤独症患儿,对孤独症患儿的日后康复工作意义重大。     

Safety of simultaneous vaccination with COVID-19 vaccines in the Vaccine Safety Datalink

IntroductionSafety data on simultaneous vaccination (SV) with primary series monovalent COVID-19 vaccines and other vaccines are limited. We describe SV with primary series COVID-19 vaccines and assess 23 pre-specified health outcomes following SV among persons aged ≥5 years in the Vaccine Safety Datalink (VSD).MethodsWe utilized VSD’s COVID-19 vaccine surveillance data from December 11, 2020-May 21, 2022. Analyses assessed frequency of SV. Rate ratios (RRs) were estimated by Poisson regression when the number of outcomes was ≥5 across both doses, comparing outcome rates between COVID-19 vaccinees receiving SV and COVID-19 vaccinees receiving no SV in the 1–21 days following COVID-19 vaccine dose 1 and 1–42 days following dose 2 by SV type received (“All SV”, “Influenza SV”, “Non-influenza SV”).ResultsSV with COVID-19 vaccines was not common practice (dose 1: 0.7 % of 8,455,037 persons, dose 2: 0.3 % of 7,787,013 persons). The most frequent simultaneous vaccines were influenza, HPV, Tdap, and meningococcal. Outcomes following SV with COVID-19 vaccines were rare (total of 56 outcomes observed after dose 1 and dose 2). Overall rate of outcomes among COVID-19 vaccinees who received SV was not statistically significantly different than the rate among those who did not receive SV (6.5 vs. 6.8 per 10,000 persons). Statistically significant elevated RRs were observed for appendicitis (2.09; 95 % CI, 1.06–4.13) and convulsions/seizures (2.78; 95 % CI, 1.10–7.06) in the “All SV” group following dose 1, and for Bell’s palsy (2.82; 95 % CI, 1.14–6.97) in the “Influenza SV” group following dose 2.ConclusionCombined pre-specified health outcomes observed among persons who received SV with COVID-19 vaccine were rare and not statistically significantly different compared to persons who did not receive SV with COVID-19 vaccine. Statistically significant adjusted rate ratios were observed for some individual outcomes, but the number of outcomes was small and there was no adjustment for multiple testing.     

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children

Objectives: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited.

Methods: We performed a case–controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children.

Results: Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30?ng/ml) participated in the open label trial. They received vitamin D3 (300?IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span.

Conclusion: Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40?ng/ml.

Trial registration number: UMIN-CTR Study Design: trial Number: R000016846.     

海南省0~6岁儿童孤独症谱系障碍的现况调查及影响因素分析

目的 了解海南省0~6岁儿童孤独症谱系障碍的患病情况及其影响因素。方法 抽查海南省18个市（县）0~6岁儿童37 862人,采用儿童发育问题预警征象调查表筛查,再由专科医师现场诊断,采用一般描述统计、χ²检验、非条件logistic回归分析孤独症现况及影响因素。结果 共诊断235例孤独症儿童,总患病率为0.62%,其中男童为0.99%,女童为0.17%,男童高于女童（χ²=101.91,P=0.000）。随年龄增长孤独症患病率上升（χ²=288.62,P=0.000）。城市孤独症患病率高于其他地区,差异有统计学意义（χ²=114.77,P=0.000）。是否足月、新生儿窒息、父亲性格、父亲有嚼槟榔或吸烟习惯、母孕期总体情绪状态以及母亲人流史为孤独症的影响因素。结论 海南省0~6岁儿童孤独症谱系障碍的患病率居国内较高水平并受遗传因素、孕产过程、父母在孕前及孕期不良行为、习惯等综合因素的影响。     

孤独症谱系障碍婴幼儿早期筛查模式的探究

目的 分析Bayley婴幼儿发展量表第Ⅰ版(BSIDⅠ)联合改良版婴幼儿孤独症筛查量表(M-CHAT-R/F)筛查婴幼儿孤独症谱系障碍(ASD)的效果,为基层儿保系统开展ASD早期筛查提供临床数据依据。方法 采用前瞻性队列研究,选取2019年1—12月期间在义乌市妇幼保健院参与“0～3岁儿童早期发展风险和异常筛查项目”采用BSIDⅠ评估的6～12月龄婴儿为研究对象。采用2010年卫生部颁布《儿童孤独症诊疗康复指南》中婴儿期孤独症警示指标对6～12月龄阳性患儿进行BSIDⅠ评估。对认知发展指数(MDI)、运动发展指数(PDI)异常(MDI或PDI <80)的婴儿追踪随访,18月龄进行M-CHAT-R/F评估,后由专科医师进一步根据DSM-5进行ASD确诊。结果 纳入研究3 096例,警示指标阳性患儿535例,BSIDⅠ发育异常421例,占13.60%。18月龄时进行M-CHAT-R/F评估阳性共38例,初筛总阳性率为9.97%,最终确诊ASD 16例。将BSIDⅠMDI<80作为预测因子,其在ASD组与非ASD组筛查中具有统计学意义(χ²=10.28,P...