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Social-emotional problems occurring early in life can place children at future risk of adverse health, social and economic outcomes. Determinants of social-emotional problems are multi-layered and originate from different contexts surrounding children, though few studies consider them simultaneously. We adopted a holistic approach by using Bronfenbrenner's process-person-context-time model as a structuring device. We aimed to assess what characteristics of families and children from pregnancy, over birth, and up to 3 years of age are associated with social-emotional problems in boys and girls. This study used regional data from the Salut Programme, a universal health promotion programme implemented in Antenatal and Child Health Care, and data from national Swedish registers. The study population included 6033 3-year-olds and their parents during the period 2010–2018. Distinct logistic regression models for boys and girls were used to assess associations between the family social context, parents' lifestyle, parent's mental health, children's birth characteristics, and indicators of proximal processes (the independent variables); and children's social-emotional problems as measured by the parent-completed Ages and Stages Questionnaire: Social-Emotional between 33 and 41 months of age (the outcome). Overall, a less favourable family social context, detrimental lifestyle of the parents during pregnancy, and parents' mental illness from pregnancy onwards were associated with higher odds of social-emotional problems in 3-year-olds. Higher screentime and infrequent shared book-reading were associated with higher odds of social-emotional problems. The multifaceted determinants of children's social-emotional problems imply that many diverse targets for intervention exist. Additionally, this study suggests that Bronfenbrenner's process-person-context-time theoretical framework could be relevant for public health research and policy.

Background Abnormal birth weight – small for gestational age (SGA) and large for gestational age (LGA) – are important indicators for newborn health. Due to changes in lifestyle in recent decades, it is essential to keep up-to-date with the latest information on maternal factors linked to abnormal birth weight. The aim of this study is to investigate SGA and LGA in relation to maternal individual, lifestyle and socioeconomic characteristics. . Methods This is a register-based cross-sectional study. Self-reported data from Sweden’s Salut Programme maternal questionnaires (2010–2014) were linked with records in the Swedish Medical Birth Register (MBR). The analytical sample comprised 5089 singleton live births. A Swedish standard method using ultrasound-based sex-specific reference curves defines the abnormality of birth weight in MBR. Univariable and multivariable logistic regressions were used to examine crude and adjusted associations between abnormal birth weights and maternal individual, lifestyle and socioeconomic characteristics. A sensitivity analysis, using alternative definitions of SGA and LGA under the percentile method, was undertaken. Results In multivariable logistic regression, maternal age and parity were associated with LGA (aOR = 1.05, CI = 1.00, 1.09) and (aOR = 1.31, CI = 1.09, 1.58). Maternal overweight and obesity were strongly associated with LGA (aOR = 2.28, CI = 1.47, 3.54) and (aOR = 4.55, CI = 2.85, 7.26), respectively. As parity increased, the odds of delivering SGA babies decreased (aOR = 0.59, CI = 0.42, 0.81) and preterm deliveries were associated with SGA (aOR = 9.46, CI = 5.67, 15.79). The well-known maternal determinants of abnormal birthweight, such as unhealthy lifestyles and poor socioeconomic factors, were not statistically significant in this Swedish setting. Conclusions The main findings suggest that multiparity, maternal pre-pregnancy overweight and obesity are strong determinants for LGA babies. Public health interventions should address modifiable risk factors, especially maternal overweight and obesity. These findings suggest that overweight and obesity is an emerging public health threat for newborn health. This might also result in the intergenerational transfer of overweight and obesity. These are important messages for public health policy and decision making.

BACKGROUND: Social-emotional ability is important for overall health and wellbeing in early childhood. Recognizing preschool children in need of extra support, especially those living in unfavourable conditions, can have immediate positive effects on their health and benefit their wellbeing in the long-term. OBJECTIVES: The aim of this study is to investigate whether there are social inequalities in preschool children's social-emotional problems, and whether inequalities differ between boys and girls. METHOD: This study utilized repeated measures from cross-sectional population-based surveys of three-year old children (2014-2018). The final study population comprised of 9,099 children which was 61% of all the eligible children in Västerbotten County during the study period. The Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) 36-month interval was used to measure children's social-emotional ability. Social inequalities were studied with respect to parents' income, education, and place of birth, for which data was obtained from Statistics Sweden. Multiple logistic and ordered regressions were used. RESULTS: Among 3-year-olds, social-emotional problems were more common in the most vulnerable social groups, i.e. parents in the lowest income quintile (OR: 1.45, p

Aim Several countries, such as Norway and Sweden, have not implemented universal varicella vaccination. We present data for Norway and Sweden that were generated by a paediatric multi-country Phase III study over a 10-year period. This assessed the efficacy, antibody persistence and safety of two varicella vaccines containing the same Oka-strain. Methods This was an observer-blind, controlled trial conducted in 10 European countries. Children aged 12-22 months (n=5803) were randomised 3:3:1 and vaccinated between 1 September 2005 and 10 May 2006. The two-dose group received two tetravalent measles-mumps-rubella-varicella vaccine doses. The one-dose group received one monovalent varicella vaccine dose after a measles-mumps-rubella vaccine dose. Control group participants received two measles-mumps-rubella vaccine doses. Main study outcomes were vaccine efficacy against confirmed varicella cases and incidence of adverse events. Results Vaccine efficacy in the two-dose group was ≥92.1% in both Norwegian and Swedish children compared to 72.3% in Norway and 58.0% in Sweden in the one-dose group. Incidences of adverse events and serious adverse events were similar in the Norwegian and Swedish study populations. Conclusion Consistent with overall study results, high efficacy against varicella and acceptable safety profiles of the two varicella vaccines were observed in Norwegian and Swedish populations. These findings highlight the benefits of varicella vaccines, particularly when administered as a two-dose schedule.

Background: Early life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre- and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months. Methods: We included 1387 mother–child dyads from the prospective, population-based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web-based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician-diagnosed asthma; parents (n = 1025) reported physician-diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions. Results: Prenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01–3.26) but not in the adjusted analyses (aOR 1.58, 0.82–3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95–2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47–3.11), asthma (aOR 2.35, 1.32–4.19), and eczema (aOR 1.49, 1.07–2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25–0.83) but not with food allergy nor sensitization to inhalants. Conclusion: Pre- and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.

Bacterial meningitis is known to cause hearing impairments and neurologic deficits; however, less is known regarding psychiatric disabilities. In this study, we assessed psychiatric disabilities and other long-term consequences of childhood bacterial meningitis.From a previously validated dataset, we selected children having had bacterial meningitis. We then reviewed medical records and child health records from discharge onwards to identify disabilities. We calculated the occurrence of disabilities with a 95% confidence interval (CI), and we used a χ test to assess possible individual risk factors associated with occurrence of disabilities.Of the 80 children included in this study, permanent disabilities not attributed to preexisting diseases were noted in 56% (CI: 45-67) during the mean observation period of 19 years and 2 months. Psychiatric disease was diagnosed in 30% (CI: 21-41), and another 5% (CI: 2-13) were under ongoing investigations for symptoms of psychiatric disease. Hearing impairments affected at least 30% (CI: 20-40), and neurologic deficits affected at least 23% (CI: 15-34). While other disabilities were often detected within the first year, psychiatric disabilities were detected after a mean time period of 14 years (CI: 11:1-16:11). Although some associations were noted, no individual risk factor was able to predict the occurrence of disabilities.Psychiatric disabilities affect more than one-third of survivors and are among the most common long-term consequence of childhood bacterial meningitis. Late discovery and predictive difficulties call for a revision of current guidelines to include a specific long-term strategy for detecting psychiatric disabilities.

ObjectiveTo examine the association between perinatal factors and hospitalisations for sepsis and bacterial meningitis in early childhood (from 28 days to 2 years of age).DesignA population‐based cohort study. The Swedish Medical Birth Register was combined with the National Inpatient Register, the Cause of Death Register, the Total Population Register and the Longitudinal integration database for health insurance and labour market studies. Associations between perinatal factors and hospitalisations were examined using negative binomial regression models.SettingSweden.Participants1 406 547 children born in Sweden between 1997 and 2013.Main outcome measuresHospital admissions for sepsis and bacterial meningitis recorded between 28 days and 2 years of life.ResultsGestational age was inversely associated with severe infections, that is, extreme prematurity was strongly associated with an increased risk of sepsis, adjusted incidence rate ratio (aIRR) 10.37 (95% CI 6.78 to 15.86) and meningitis aIRR 6.22 (95% CI 2.28 to 16.94). The presence of congenital malformation was associated with sepsis aIRR 3.89 (95% CI 3.17 to 4.77) and meningitis aIRR 1.69 (95% CI 1.09 to 2.62). Moreover, children born small or large for gestational age were more likely to be hospitalised for sepsis and children exposed to maternal smoking were more likely to be hospitalised for meningitis.ConclusionsPrematurity and several other perinatal factors were associated with an increased risk of severe infections in young children. Therefore, clinical guidelines for risk assessment of infections in young children should consider perinatal factors.

Concerns have been raised that an overconsumption of baby food fruit pouches among toddlers might increase the risk of childhood obesity. This study aimed to quantify the consumption of fruit pouches and other fruit containing food products and to explore potential correlations between the consumption of these products and body-mass index z-score (BMIz) at 18 months, taking other predictive factors into consideration. The study was based on 1499 children and one-month-recall food frequency questionnaires from the Swedish population-based birth cohort NorthPop. Anthropometric outcome data were retrieved from child health care records. BMIz at 18 months of age was correlated to maternal BMI and gestational weight gain and inversely correlated to fruit juice consumption and breastfeeding. BMIz at 18 months of age was not correlated to consumption of fruit pouches, sugar-sweetened beverages, whole fruit or milk cereal drink. Overweight at 18 months of age was correlated to maternal BMI and inversely correlated to breastfeeding duration. To our knowledge, this is the first study that investigates possible associations between baby food fruit pouch consumption and overweight in toddlers. We found that moderate fruit pouch consumption is not associated with excess weight at 18 months of age.

Background: Knowing the individual child’s risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors. Methods: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure. Results: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p

Vaccine-preventable pathogens causing severe childhood infections include Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis. In this study conducted in a Swedish Arctic region, we evaluated the effects of general infant Hib and pneumococcal vaccination on invasive infectious diseases among children and assessed the need of meningococcal vaccination.We identified cases of bacterial meningitis and sepsis from diagnosis and laboratory registers in the Västerbotten Region, Sweden, during 1986-2015. We then reviewed medical records to confirm the diagnosis and extract data for assessing incidence changes, using an exploratory data analysis and a time-series analysis.Invasive Haemophilus disease declined by 89.1% (p 0.01), Haemophilus meningitis by 95.3% (p 0.01) and all-cause bacterial meningitis by 82.3% (p 0.01) in children aged 0 to four years following general infant Hib vaccination. Following pneumococcal vaccination, invasive pneumococcal disease declined by 84.7% (p 0.01), pneumococcal meningitis by 67.5% (p = 0.16) and all-cause bacterial meningitis by 48.0% (p = 0.23). Incidence of invasive meningococcal disease remained low during the study period.Remarkable sustained long-term declines of invasive infectious diseases in younger children occurred following infant Hib and pneumococcal vaccinations in this Swedish Arctic region. Despite not offering general infant meningococcal vaccination, incidence of invasive meningococcal disease remained low.

AIM: The aim of this study was to investigate mental health with respect to social-emotional problems among three-year-olds in relation to their gender, custody arrangements and place of residence. METHODS: A cross-sectional population-based design was used, encompassing 7,179 three-year-olds in northern Sweden during the period 2014-2017 from the regional Salut Register. Descriptive and comparative analyses were performed based on parents' responses on the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE), supplemented with items on gender, custody arrangement and place of residence. RESULTS: Parental-reported social-emotional problems were found in almost 10% of the children. Boys were reported to have more problems (12.3%) than girls (5.6%) (p

Introduction: The hexavalent vaccine DT3aP-HBV-IPV-Hib (Infanrix hexa, GSK) was first licensed in Europe in 2000. DT2aP-HBV-IPV-Hib (Hexyon/Hexacima/Hexaxim, Sanofi Pasteur), and DT5aP-HBV-IPV-Hib (Vaxelis, MCM Vaccine Company) were licensed in the EU in 2013 and 2016, respectively, based largely on studies demonstrating non-inferiority to DT3aP-HBV-IPV-Hib for immunogenicity and comparable reactogenicity profiles. Methods: We conducted a systematic literature review looking for direct head-to-head trials comparing DT2aP-HBV-IPV-Hib and DT5aP-HBV-IPV-Hib with DT3aP-HBV-IPV-Hib. The incidence of solicited local and systemic reactions following primary series administration of DT3aP-HBV-IPV-Hib or DT2aP-HBV-IPV-Hib were meta-analyzed. Results: A total of 317 unique records were retrieved from the search; nine met the predefined inclusion criteria; seven reported studies comparing DT3aP-HBV-IPV-Hib and DT2aP-HBV-IPV-Hib. Six trials assessing outcomes of the primary vaccination series were identified. Odds ratios and 95% confidence intervals (OR; 95%CI) were computed for DT3aP-HBV-IPV-Hib, using DT2aP-HBV-IPV-Hib as reference, for redness (0.72; 0.63–0.83), pain (0.74; 0.62–0.89), swelling (0.86; 0.74–0.99) at injection site, fever (0.67; 0.54–0.83), persistent crying (0.72; 0.61–0.84), drowsiness (0.82; 0.71–0.94), irritability (0.82; 0.69–0.98), anorexia (0.83; 0.72–0.95), and vomiting (0.96; 0.83–1.11). Conclusion: ORs of analyzed local and systemic solicited adverse reactions after primary vaccination with DT3aP-HBV-IPV-Hib appear to be slightly lower than with DT2aP-HBV-IPV-Hib.

Aim: A life-course immunisation approach is required to prevent and control pertussis. We aimed at reviewing pertussis incidence among infants in Denmark, Finland, Norway and Sweden, and at putting these data in the context of national surveillance systems and vaccination schedules. Methods: We collected 2014–2018 data on pertussis incidence, on pertussis vaccination schedules and on coverage of the third dose of the diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine from publicly available sources. We gathered opinions on national surveillance systems from public health and paediatrics experts of the relevant countries. Results: The pertussis vaccination schedules and coverage in infancy were similar across countries. All countries except Denmark recommended an additional booster vaccine dose for adolescents. None of the countries had maternal immunisation recommendation. Mean pertussis incidence in Denmark, Sweden and Finland was 168, 76 and 35 per 100,000 infant-years, respectively. Data were insufficient to derive a mean incidence in Norway. There were no systematic differences in the national surveillance systems across the countries. Conclusion: The higher mean pertussis incidence in Denmark may be explained by the lack of recommendations for adolescent pertussis booster vaccination. Further investigations are warranted.

ObjectiveTo examine the association between breastfeeding practice and hospitalisations for infectious diseases in early and later childhood, in particular, to compare exclusive breast feeding 4–5 months with exclusive breastfeeding 6 months or more. Thereby, provide evidence to inform breastfeeding policy.DesignA register-based cohort study.SettingA cohort was created by combining the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register, the Longitudinal integration database for health insurance and labour market studies, with the Uppsala Preventive Child Health Care database.Patients37 825 term and post-term singletons born to women who resided in Uppsala County (Sweden) between 1998 and 2010.Main outcome measuresNumber of hospitalisations for infectious diseases in early (ResultsThe risk of hospitalisations for infectious diseases decreased with duration of exclusive breastfeeding until 4 months of age. In early childhood, breast feeding was associated with a decreased risk of enteric and respiratory infections. In comparison with exclusive breast feeding 6 months or more, the strongest association was found between no breastfeeding and enteric infections (adjusted incidence rate ratios, aIRR 3.32 (95% CI 2.14 to 5.14)). In later childhood, breast feeding was associated with a lower risk of respiratory infections. In comparison with children exclusively breastfed 6 months or more, the highest risk was found in children who were not breastfed (aIRR 2.53 (95% CI 1.51 to 4.24)). The risk of hospitalisations for infectious diseases was comparable in children exclusively breastfed 4–5 months and children exclusively breastfed 6 months or more.ConclusionsOur results support breastfeeding guidelines that recommend exclusive breastfeeding for at least 4 months.

Background There is enough evidence to believe that young children’s social-emotional problems can have a long-term effect if extra support is not given early. Therefore, early identification of such problems and any differences between boys and girls are of importance. We utilized the 36-month interval of the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) among 3-year-olds aiming: 1) to report the normative values of social-emotional problems for Swedish boys and girls; 2) to identify ASQ:SE items that are most commonly endorsed by children with high level of social-emotional problems (high score on ASQ:SE); 3) to assess whether certain ASQ:SE items differ between boys and girls at the same level of social-emotional problems; and 4) to examine whether ASQ:SE performs well in identifying children with high level of social-emotional problems (high score on ASQ:SE). Method During 2014–2017, data were collected from 7179 three-year-old children (boys = 3719, girls = 3460) through Child Health Care in the Region Västerbotten in the northern part of Sweden. Unidimensionality was assessed by Confirmatory Factor Analysis and goodness-of-fit was reported. Item Response Theory was used to answer the aims of the study. Results Items regarding interest in sexual words, too little sleep, disinterest in things around, unhappiness and self-injury were more commonly endorsed by children with high levels of social-emotional problems, as reported by their parents. For the same level of social-emotional problem, girls were more likely to demonstrate difficulties in occupying themselves, clinging behaviour and repetitive behaviour. On the other hand, boys were more likely to score high in items regarding destruction of things on purpose, difficulty to name friends and to express feelings. We have also found that the ASQ:SE is suitable for identifying children with high level of social-emotional problems. Conclusion The salient point of our study was to increase knowledge about Swedish children’s social-emotional problems at 3-years of age based on the psychometric characteristics of the ASQ:SE using Item Response Theory model. The gender differences as well as those items that occurred at high levels of social-emotional problems should be of concern for everyday practice in Child Health Care.

Background Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. Methods Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. Results We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22–2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. Conclusions Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

Additional file 4: Table S1. List of serum metabolites that were analyzed and used in further analysis. 1Only sum of THM and mTHM were included in the analysis as ‘total folate’. 2The sums of the Asparagine and Aspartic acid and the f Glutamine and Glutamic acid levels were used in statistical analysis because of conversion between this forms in the stored samples. In the whole 45 biomarkers could be identified and included in the analysis.

Additional file 5: Table S2. Differences of biomarkers levels between mothers of children with infantile autism and Asperger’s syndrome.

Additional file 4: Table S1. List of serum metabolites that were analyzed and used in further analysis. 1Only sum of THM and mTHM were included in the analysis as ‘total folate’. 2The sums of the Asparagine and Aspartic acid and the f Glutamine and Glutamic acid levels were used in statistical analysis because of conversion between this forms in the stored samples. In the whole 45 biomarkers could be identified and included in the analysis.

Additional file 3: Figure S3. Biomarker levels in each study participant, with a hierarchical cluster analysis based on Euclidian distances with complete linkage. Each column represents a participant and each row a biomarker. Heat map colors represent standardized log-transformed biomarker levels in all participants (red) and below mean biamarker levels (blue).

Summary Background Internet‐based treatments have proven effective for various health issues. There is a need to scale up interventions targeting children with obesity, also in less densely populated areas where the prevalence in many countries is higher than in urban areas. The aim of this study was to design and implement an internet‐based program as an add‐on to standard treatment for childhood obesity. Methods Web‐Childhood Obesity Prevention (Web‐COP) was a prospective feasibility study with a pre‐ post‐ design. The intervention consisted of four group‐based education sessions at the clinic, physical activity on prescription, and a new 12‐week internet‐based program. Web‐COP was offered to children with obesity (International Obesity Task Force Body Mass Index (IOTF‐BMI) ≥ 30 kg/m2) and their parents in two counties in Northern Sweden from August 2018 to June 2019. The primary outcome was change in BMI standard deviation score (BMI‐SDS). Results The study included 55 children 5–13 years of age. The internet‐based component was well received, and retention rate was 51/55 (92.7%). Data was analysed for 51 children. Mean BMI‐SDS was 3.3 at start and decreased by 0.2, 0.3, and 0.4 at two, four, and six months from baseline. Using a continuous algorithm, 42/51 (81%), children lowered their BMI‐SDS and 33/51 (65%) lowered their BMI. Conclusion Adding group sessions and an internet‐based program to standard care was feasible and two thirds of included children with obesity reduced their BMI.

Anti-secretory factor is a protein that regulates secretory and inflammatory processes and preterm birth is associated with inflammation. Therefore, our hypothesis was that anti-secretory factor might play a role in immune reactivity and homeostasis during pregnancy.Following spontaneous onset of labor and preterm or term delivery, placenta biopsies were collected. The levels of anti-secretory factor and markers of inflammation (CD68, CD163) and vascularization (CD34, smooth muscle actin) were analyzed by immunohistochemistry.The 61 placental biopsies included 31 preterm (37 weeks of gestation) and 30 term (37-41 weeks) samples. The preterm placentas exhibited lower levels of anti-secretory factor (p = 0.008) and larger numbers of CD68-positive cells (p0.001) compared to term. Preterm placentas had blood vessel of smaller diameter (p = 0.036) indicative of immaturity. The level of interleukin-6 in cord blood was higher after very preterm than term birth, suggesting a fetal inflammatory response. The placenta level of anti-secretory factor was positively correlated to the length of gestation (p = 0.025) and negatively correlated to the levels of the inflammatory markers CD68 (p = 0.015) and CD163 (p = 0.028).Preterm delivery is associated with low levels of anti-secretory factor in placenta. Inflammation, a potential trigger of preterm birth, is more pronounced in the preterm placenta and inversely related to the placental level of anti-secretory factor, suggesting both a link and a potential target for intervention.

Measures to reduce the spread of COVID-19 have been associated with reduction in other respiratory infections. Results of a national Swedish cohort study of infant pertussis during April 2020–September 2021 were compared with those during January 2014–March 2020. The number of pertussis cases decreased significantly during the COVID-19 pandemic, from an average of 21 infant cases per quarter of a year before the pandemic to an average of 1 case per quarter during the pandemic. Swedish strategies to mitigate the spread of COVID-19 seem to have had an impact on pertussis incidence in infants.

Introduction: Vaccination with formulations containing pneumococcal protein antigens such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) may extend serotype-related protection of pneumococcal conjugate vaccines (PCVs) against Streptococcus pneumoniae. Methods: This phase II, multi-center, observer-blind trial conducted in Europe (NCT01204658) assessed 2 investigational vaccines containing 10 serotype-specific polysaccharide conjugates of PHiD-CV and either 10 or 30 mu g of dPly and PhtD each. Infants randomized 1:1:1:1 received 4 doses of PHiD-CV/dPly/PhtD-10, PHiD-CV/c1Ply/PhtD-30, PHiD-CV, or 13-valent PCV (PCV13), co-administered with DTPa-HBV-IPV/Flib, at ages 2, 3, 4 and 12-15 months. Occurrences of fever >40.0 degrees C following primary vaccination with PHiD-CV/dPly/PhtD vaccines compared to PHiD-CV (non-inferiority objective), dose superiority, safety and immunogenicity were assessed. Results: 575 children received primary vaccination, and 564 booster vaccination. The non-inferiority objective was met; no fever >40.0 degrees C causally related to vaccination was reported during primary vaccination. Incidence of adverse events appeared similar between the 3 PHiD-CV groups. Serious adverse events were reported in 13, 9, 21 (1 related to vaccination), and 17 children in the PHiD-CV/c1Ply/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, and PCV13 groups, respectively. PHiD-CV/dPly/PhtD-30 was superior to PHiD-CV/c1Ply/PhtD-10 in terms of post-dose 3 anti-Ply and Anti-PhtD antibody levels. Anti-Ply and anti-PhtD antibody levels were higher in both PHiD-CV/dPly/PhtD groups than in controls and increased from post-primary to post-booster timepoint. Post-primary and booster vaccination, for each PHiD-CV serotype, >= 98.5% of participants in PHiD-CV/dPly/PhtD groups had antibody concentrations >= 0.2 mu g/mL, except for 6B (>= 72.3%) and 23 F (>= 82.7%) post-primary vaccination. Similar results were observed in the PHiD-CV group. Immune responses to protein D and DTPa-HBV-IPV/Hib were within similar ranges for the 3 PHiD-CV groups. Conclusion: Both PHiD-CV/dPly/PhtD formulations co-administered with DTPa-HBV-IPV/Hib in infants were well-tolerated and immunogenic for dPly and PhtD antigens, while immune responses to serotype-specific, protein D and co-administered antigens did not appear altered in comparison to PHiD-CV group.

Background: Dark skin and low exposure to sunlight increase the risk of vitamin D insufficiency in children. Objective: The aim of the study was to evaluate the amount of vitamin D needed to ascert ...

Background Young children’s social-emotional problems can have a long-term effect if not treated early. In order to deepen our knowledge about children’s social and emotional functioning, we utilized the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) among 3-year-olds in Sweden aiming: 1) to identify ASQ:SE items that are most commonly endorsed by children with high level of social-emotional problems; and 2) to assess whether certain ASQ:SE items differs between boys and girls at the same level of social-emotional problems. Methods During 2014-2017 data was collected from 7179 three-year-old children through Child Health Care in a northern county of Sweden within the Salut Child Health Promotion Programme. Item Characteristic Curve (ICC) and Differential Item Functioning (DIF) were used to identify the characteristics of children with high social-emotional problems and to determine whether an item exhibit uniform between boys and girls at the same level of social-emotional problems. Results Items regarding interest in sexual words, too little sleep, disinterest in things around, unhappiness and self-injury were more commonly endorsed by children with high levels of social-emotional problems. Additionally, on the same level of social-emotional problem girls were more likely to score high in items regarding difficulties to occupy herself, clinging behaviour and repetitive behaviour while boys were more likely to score high in items regarding difficulty to name friends, difficulty to express feelings and destruction of things on purpose. Conclusions This study has increased our knowledge about Swedish young children’s social emotional functioning already at the age of three by detecting which items are most closely connected to high level of social-emotional problems and differences between boys and girls. However, whether the results detected in this analysis are reflecting their parents’ expectations more than child behaviour requires further investigations. Key messages Children with high level of social-emotional problems were rated high on items regarding interest in sexual words, too little sleep, disinterest in things around, unhappiness and self-injury. On equal levels of social-emotional problems, girls were more often reported with internalizing problematic behaviours and boys were more often reported with externalizing problematic behaviours.

Aim: The aim of this review was to evaluate the evidence for interventions for behavioural sleep problem in infants. Methods: Systematic review based on a search in MEDLINE, Web of Science and PsychINFO in December 2017 for articles published in English during 2007-2017 about preventive and treatment interventions for sleep problems in infants. The review included controlled trials and meta-analyses with at least 20 infants in study groups assessed according to the Grading of Recommendations Assessment, Development and Evaluation criteria. Results: Out of 476 original articles assessed for eligibility, 12 studies were included in the synthesis. Interventions with behavioural, educational and massage strategies were evaluated. No intervention was evaluated in more than one trial. Five interventions with behavioural methods for establishing consistent routines or controlled crying showed modest short-term effects, while the evidence for elements of education was inconsistent. Studies of massage were of poor quality. Knowledge gaps were identified regarding interventions in cross-cultural context, involving fathers, in children below six months of age, in high-risk populations and consequences of interventions that include extinction. Conclusion: Some support for short-term effects of behavioural treatment strategies was found, but more studies are needed to establish evidence.

Aim: The aim of this review was to evaluate the evidence for interventions for infantile colic. Methods: This was a systematic review based on a literature search in December 2017 for articles published during 2007-2017 about preventive and treatment interventions for infantile colic in infants. The review included original randomised controlled trials (RCTs) and meta-analyses with at least 20 infants in each study group that were assessed according to GRADE criteria. Results: The review found moderately strong evidence that administration of Lactobacillus reuteri DSM 17938 shortened the crying duration, with positive evidence from three out of four national contexts. There were four RCTs of acupuncture, all with no or minimal effect on crying duration. All studies reviewed with a follow-up until or beyond three months of age show a quite steep decline over time in crying duration in both treatment and control groups. Conclusion: Lactobacillus reuteri DSM 17938 is a promising treatment for infantile colic with moderately strong evidence in this review, but studies in more populations are needed. Acupuncture is not an effective treatment for infantile colic. Systematic support strategies to parents with infantile colic are important knowledge gaps.

Background: Observational studies have linked low vitamin D status to unfavorable cardiometabolic risk markers, but double-blinded vitamin D intervention studies in children are scarce. Objectives: The aim was to evaluate the effect of different doses of a vitamin D supplement on cardiometabolic risk markers in young healthy Swedish children with fair and dark skin. Methods: Cardiometabolic risk markers were analyzed as secondary outcomes of a double-blind, randomized, milk-based vitamin D intervention trial conducted during late fall and winter in 2 areas of Sweden (latitude 63°N and 55°N, respectively) in both fair- and dark-skinned 5- to 7-y-old children. During the 3-mo intervention, 206 children were randomly assigned to a daily milk-based vitamin D3 supplement of either 10 or 25 µg or placebo (2 µg; only at 55°N). Anthropometric measures, blood pressure, serum 25-hydroxyvitamin D [25(OH)D], total cholesterol, HDL cholesterol, apoA-I, apoB, and C-reactive protein (CRP) were analyzed and non–HDL cholesterol calculated at baseline and after the intervention. Results: At baseline, serum 25(OH)D was negatively associated with systolic and diastolic blood pressure (β = −0.194; 95% CI: −0.153, −0.013; and β = −0.187; 95% CI: −0.150, −0.011, respectively). At follow-up, there was no statistically significant difference in any of the cardiometabolic markers between groups. Conclusions: We could not confirm any effect of vitamin D supplementation on serum lipids, blood pressure, or CRP in healthy 5- to 7-y-old children. The study was registered at clinicaltrials.gov (NCT01741324).

To evaluate if dietary vitamin D intake is adequate for sufficient vitamin D status during early winter in children living in Sweden, irrespective of latitude or skin color.As part of a prospective, comparative, 2-center intervention study in northern (63°N) and southern (55°N) Sweden, dietary intake, serum 25-hydroxyvitamin D (S-25(OH) D), associated laboratory variables, and sociodemographic data were studied in 5 to 7-year-old children with fair and dark skin in November and December.Two hundred six children with fair/dark skin were included, 44/41 and 64/57 children in northern and southern Sweden, respectively. Dietary vitamin D intake was higher in northern than southern Sweden (P = 0.001), irrespective of skin color, partly due to higher consumption of fortified foods, but only met 50-70% of national recommendations (10 μg/day). S-25(OH) D was higher in northern than southern Sweden, in children with fair (67 vs 59 nmol/L; P 0.05) and dark skin (56 vs 42 nmol/L; P 0.001). S-25(OH) D was lower in dark- than fair-skinned children at both sites (P 0.01), and below 50 nmol/L in 40 and 75% of dark-skinned children in northern and southern Sweden, respectively.Insufficient vitamin D status was common during early winter in children living in Sweden, particularly in those with dark skin. Although, higher dietary vitamin D intake in northern than southern Sweden attenuated the effects of latitude, a northern country of living combined with darker skin and vitamin D intake below recommendations are important risk factors for vitamin D insufficiency.

Adolescents have the highest rates of meningococcal carriage and transmission. Interrupting the adolescent habitat in order to reduce carriage and transmission within adolescents and to other age groups could help to control meningococcal disease at a population level. Compared to immunization strategies restricted to young children, a strategy focused on adolescents may have more profound and long-lasting indirect impacts, and may be more cost effective. Despite challenges in reaching this age-group, experience with other vaccines show that high vaccine coverage of adolescents is attainable.

ObjectiveThe aim of this study was to examine this association between maternal weight during pregnancy and the incidence of hospitalisations for infectious diseases during early childhood.DesignA population-based cohort study.SettingA national cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register and the Longitudinal integration database for health insurance and labour market studies.Patients693 007 children born in Sweden between 1998 and 2006.Main outcome measuresNumber of hospitalisations for infectious diseases during the first 5 years of life, overall and for categories of infectious diseases (lower respiratory, enteric, upper respiratory, genitourinary, perinatal, skin and soft tissue, neurological and eye, digestive tract, bloodstream and other infections).ResultsOverweight (body mass index (BMI) 25.0–29.9) and obesity (BMI≥30) during pregnancy were associated with a higher overall incidence of hospitalisations for infectious diseases, adjusted incidence rate ratio (IRR) 1.05 (95% CI 1.03 to 1.06) and adjusted IRR 1.18 (95% CI 1.16 to 1.21). Overweight and obesity during pregnancy were strongly associated with perinatal infections, adjusted IRR 1.34 (95% CI 1.25 to 1.44) and adjusted IRR 1.72 (95% CI 1.57 to 1.88). In contrast, we found no association between maternal weight during pregnancy and infections of skin and soft tissue, the nervous system, the digestive tract or the bloodstream.ConclusionsWe observed an association between overweight and obesity during pregnancy, and hospitalisations for infectious diseases during early childhood.

The aim of the study was to evaluate vitamin D status and effects of vitamin D intervention on bone mineral density (BMD) and content (BMC) in children with fair and dark skin in Sweden during winter.In a 2-center prospective double-blinded randomized intervention study 5- to 7-year-old children (n = 206) with fair and dark skin in Sweden (55°N-63°N) received daily vitamin D supplements of 25 μg, 10 μg, or placebo (2 μg) during 3 winter months. We measured BMD and BMC for total body (TB), total body less head (TBLH), femoral neck (FN), and spine at baseline and 4 months later. Intake of vitamin D and calcium, serum 25-hydroxy vitamin D (S-25[OH]D), and related parameters were analyzed.Despite lower S-25(OH)D in dark than fair-skinned children, BMD of TB (P = 0.012) and TBLH (P = 0.002) and BMC of TBLH (P = 0.04) were higher at baseline and follow-up in those with dark skin. Delta (Δ) BMD and BMC of TB and TBLH did not differ between intervention and placebo groups, but FN-BMC increased more among dark-skinned children in the 25 μg (P = 0.038) and 10 μg (P = 0.027) groups compared to placebo. We found no associations between Δ S-25(OH)D, P-parathyroid hormone, P-alkaline phosphatase, and Δ BMD and BMC, respectively.BMD and BMC remained higher in dark- than fair-skinned children despite lower vitamin D status. Even though no difference in general was found in BMD or BMC after vitamin D intervention, the increase in FN-BMC in dark-skinned children may suggest an influence on bone in those with initially insufficient vitamin D status.

The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella.This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12-22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vázquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499.Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9·8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95·4% (95% CI 94·0-96·4) for MMRV and 67·2% (62·3-71·5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99·1% (97·9-99·6) for MMRV and 89·5% (86·1-92·1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths.The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination.GlaxoSmithKline Biologicals.

Inflammation and infection postpartum threaten the mother and her infant. Human milk provides a defense for the infant, but inflammatory complications like mastitis may lead to the cessation of breastfeeding. Antisecretory factor (AF) has a role in the regulation of secretory processes and inflammation. The objective of the study was to describe AF-levels in plasma and breast milk, and in relation to breast complications. Breastfeeding mothers (n = 95) were consecutively recruited at a Well Baby Clinic in Ume&aring, Sweden. At inclusion four weeks postpartum, samples of venous blood (10 mL) and breast milk (10 mL) were collected. Active AF was analyzed with ELISA using a monoclonal antibody mAb43, and was detected in all samples of plasma and breast milk with a positive correlation (Spearman coefficient = 0.40, p &lt, 0.001, Pearson correlation = 0.34, p &lt, 0.01). High AF-levels in plasma correlated with high AF-levels in breast milk. The results suggest a co-regulation between active AF in plasma and breastmilk, and/or a local regulation of AF in the breast. Further studies are needed to determine the pathways for the activation of AF-levels in breast milk and plasma.

We evaluated whether body mass index (BMI) and rapid growth in early life were associated with an increased risk of becoming overweight at 16 and 18 years of age.The study population comprised all children born in Sweden on the 15th of each month in 1981. Individuals born on the 5th, 10th and 20th of every month were added for counties with low population densities. Information on weight and height was collected from birth up to 18 years of age for 98.6% of the 3537 children identified.Weight at 12 months of age was associated with being overweight at both 16 and 18 years of age. Rapid weight gain from birth to 12 months was associated with higher odds for being overweight later in life, and the weight gain between 18 months and four years of age was the strongest risk factor for being overweight in late adolescence in both sexes. There was no association between a birthweight of2500 g or4500 g and being overweight at 16 or 18 years of age.Fast growth during early childhood was associated with an increased risk of being overweight later in life, emphasising the importance of early prevention.

Background: During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1) pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1) pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1) pdm09 vaccine. Methods: Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1) pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1) pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. Results: At day 0, >93.9% of all children had HI titers >= 1:40 for the A(H1N1) pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1) pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. Conclusion: AS03-adjuvanted A(H1N1) pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1) pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03adjuvanted A(H1N1) pdm09 vaccine.

Background: Mental health is an urgent public health challenge, and for some individuals the problem starts already in pre-school age. Increased knowledge is needed to guide evidence-based health-p ...

Streptococcus pneumoniae commonly causes respiratory tract infections including acute otitis media and pneumonia. In this study, we evaluated the impact of general infant pneumococcal vaccination, introduced in Sweden in 2009, on respiratory tract infections.We studied the incidence of respiratory tract infections and antibiotic consumption in Västerbotten County, Sweden, during 2005-2014 using the County Council's diagnosis register.Comparing the prevaccination period of 2005-2008 to 2014, the incidences of all-cause acute otitis media decreased significantly in children aged 0-4 and five years to 17 years, by 41.5% and 20.9%, respectively. In addition, we also noted significant reductions in sinusitis and other upper respiratory tract infections, and some reductions in adults. Antibiotic consumption for upper respiratory tract infections decreased by 37.1%, with the largest decrease occurring in children aged 0-4 years. For pneumonia, the incidence significantly decreased by 28.6% for children aged 0-4 years, with no significant changes in older children or adults.Pneumococcal vaccination was followed by reduced incidence of upper respiratory tract infections and antibiotic consumption in vaccinated children, with some indications of possible herd immunity. For pneumonia, a major reduction was noted limited to the youngest children.

We studied the response to high doses of egg yolk containing antisecretory factor (B221® , Salovum®) in young children with acute diarrhoea, presenting to the Children's Hospital, Lahore, Pakistan.In a randomised, placebo-controlled trial, 36 children aged 7 to 60 months with acute diarrhoea of unknown aetiology, with mild-to-moderate dehydration, were randomised to the Salovum® or placebo groups. Initially, 16 grams of Salovum® or ordinary egg yolk (placebo) mixed in oral rehydration salts was given, followed by 8 g every 5 h until recovery. The number and consistency of stools were recorded.The two groups were comparable in age, gender, duration of diarrhoea, hydration and nutritional status, although the proportion with watery stools was higher in the Salovum® group (p = 0.04). Reduction in the frequency of stools was seen at 7 versus 18 h (p0.0001) and normalising of stool consistency was 10 versus 18 h, p0.03) in the Salovum® and placebo groups. The overall effect was 35 versus 70 h in the two groups (p = 0.001). No side effects were reported.High doses of AF in the form of Salovum® effectively and safely reduce childhood diarrhoea of a likely broad aetiology.

The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

Background: As 13-valent pneumococcal conjugate vaccine (PCV13) is introduced, children who began vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) may complete their vaccination with PCV13. This open-label phase 3 study evaluated immunogenicity and safety of PCV13 in Swedish infants and toddlers previously given 1 or 2 doses of PCV7 during infancy. Methods: Healthy infants previously given PCV7 at ages 3 months (group 1; n = 118) or 3 and 5 months (group 2; n = 116) received PCV13 at ages 5 (group 1) and 12 months (both groups). IgG responses were assessed 1 month after each PCV13 dose and before the 12-month dose. Local reactions and systemic events were collected for 7 days postvaccination. Other adverse events were also collected. Results: Post-5-month dose, IgG geometric mean concentrations (GMCs) in group 1 were 1.56-4.70 mu g/ml for most PCV7 serotypes except 6B (0.40 mu g/ml) and 23F (0.57 mu g/ml) and 0.72-1.88 mu g/ml for most of the 6 additional serotypes, except 6A (0.28 mu g/ml). Post-12-month dose, IgG GMCs for the PCV7 serotypes were 2.93-9.63 mu g/ml (group 1) and 3.33-9.30 mu g/ml (group 2); and for the 6 additional serotypes, 1.85-14.65 mu g/ml (group 1) and 1.34-13.16 mu g/ml (group 2). GMCs increased by >4-fold in both groups from pre- to post-12-month dose. Proportions of subjects in group 1 with pneumococcal serotype-specific IgG concentrations >= 0.35 mu g/ml (WHO-designated postprimary reference antibody level) post-5-month dose were 92.2-99.1% for most PCV7 serotypes except 6B (53.0%) and 23F (62.6%) and 80.9-100.0% for most of the 6 additional serotypes except 6A (36.8%). Local reactions and fever were mostly mild or moderate. Conclusions: PCV13 was immunogenic and safe in infants and toddlers previously partially immunized with PCV7. Even a single dose in an infant or toddler induces an immune response to the 6 additional serotypes. (C) 2013 Published by Elsevier Ltd.