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Background Both undiagnosed celiac disease and some chronic childhood diseases are associated with lower academic achievement. However, there is little knowledge of achievements in those diagnosed with celiac disease. Our aim was to investigate school achievements in upper secondary school among Swedish adolescents with celiac disease. Methods We performed a retrospective cohort study using register data. We analyzed choice of upper secondary school program, completion of upper secondary school including achievements of basic eligibility for college/university, and final grade in individuals with celiac disease diagnosed before 15 years of age, born 1991–97. We compared with the Swedish population of the same birth years. Analyses were adjusted for sex, year of birth, living region at 17 years of age, and parental education as well as income. Results The cohort included 734 074 individuals, whereof 3 257 (62% females) with celiac disease. There was no significant difference in choice of upper secondary school program. No significant difference was found in completion or achieving basic eligibility for college/university in adjusted analyses. The mean final grade in the celiac disease group was 13.34 (standard deviation 4.85) compared to 12.78 (standard deviation 5.01) in the reference population (p p = 0.012). Conclusions We found that diagnosed celiac disease does not negatively affect school achievements in upper secondary school. This finding suggests the diagnosis, treatment and follow-up programs of celiac disease could reverse potential deleterious academic processes.

BackgroundEvery year an estimated 7.9 million babies are born with birth defect. Of these babies, more than 3 million die and 3.2 million have disability. Improving nationwide information on prevalence of birth defect, risk factor and consequence is required for better resource allocation for prevention, management and rehabilitation. In this study, we assess the prevalence of birth defect, associated risk factors and consequences in Nepal.MethodThis is a prospective cohort study conducted in 12 hospitals of Nepal for 18 months. All the women who delivered in the hospitals during the study period was enrolled. Independent researchers collected data on the social and demographic information using semi-structured questionnaire at the time of discharge and clinical events and birth outcome information from the clinical case note. Data were analyzed on the prevalence and type of birth defect. Logistic regression was done to assess the risk factor and consequences for birth defect.ResultsAmong the total 87,242 livebirths, the prevalence of birth defects was found to be 5.8 per 1000 live births. The commonly occurring birth defects were anencephaly (3.95%), cleft lip (2.77%), cleft lip and palate (6.13%), clubfeet (3.95%), eye abnormalities (3.95%) and meningomyelocele (3.36%). The odds of birth defect was higher among mothers with age ConclusionMaternal age younger than 20 years and advantaged ethnicity were risk factors of birth defects. Babies with birth defect have high risk for birth asphyxia, neonatal infection and pre-discharge mortality at birth. Further evaluation on the care provided to babies who have birth defect is warranted.FundingSwedish Research Council (VR).

Background: Mental health in adolescence is an increasing global public health concern. Over half of all mental disorders debut by 14 years of age and remain largely untreated up to adulthood, underlining the significance of early detection. The study aimed to investigate whether parental distress rating at the child's age of 15 predicts a probable mental diagnosis in a three-year follow-up. Methods: All data was derived from the Finnish Family Competence (FFC) Study. The analysis focused on whether parental CBCL (Child Behavior Checklist) rating (n = 441) at the child's age of 15 years predicted the outcome of the child's standardised DAWBA (Development and Well-Being Assessment) interview at offspring's 18 years. Results: Multivariable analysis showed that a one-unit increase in the total CBCL scores increased the relative risk of a DAWBA-based diagnosis by 3% (RR [95% CI] 1.03 [1.02-1.04], p < 0.001). Conclusions: Parental CBCL rating in a community sample at the adolescent's age of 15 contributes to early identification of adolescents potentially at risk and thus benefitting from early interventions. CC BY 4.0© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Published online: 04 April 2022Correspondence: kristina.carlen@his.se

Background Breastfeeding is associated with health benefits for both the mother and infant and is therefore important to support; moreover, parental leave is a beneficial factor for breastfeeding. The Swedish parental leave is generous, allowing each parent to take 90 days; additionally, a further 300 days can be taken by either parent. Generally, mothers take 70% of the parental leave days, mainly during the first year. However, breastfeeding duration has declined in the last decade, and it is not known how shared parental leave is associated with the duration of breastfeeding. Aim To investigate how parental leave is associated with the duration of exclusive and partial breastfeeding of the infant during the first 12 months after birth. An additional aim was to describe infants’ and parents’ characteristics and mode of birth in association with the duration of exclusive and partial breastfeeding. Methods This cross-sectional study was part of the Swedish Pregnancy Planning Study, conducted in Sweden in 2012–2015. The parents were recruited at 153 antenatal clinics in nine counties. In total, 813 couples completed a follow-up questionnaire 1 year after birth. Linear regression models were used to analyse the association between parental leave and the duration of breastfeeding. Results Infants were exclusively breastfed for, on average, 2.5 months (range 0–12 months) and partially breastfed, on average, 7 months (range 0–12 months). Most of the parental leave was taken by the mother (mean = 10.9 months) during the infant’s first 12 months, while the partner took 3 months, on average. The parental leave (used and planned) during the infant’s first 24 months were, on average, 21 months. In the multivariate linear regression analysis, mothers’ and partners’ high level of education (p p = 0.044, respectively), mothers’ higher age (p = 0.049), non-instrumental vaginal birth (p = 0.004) and longer parental leave for the first 24 months (p Conclusion The duration of partial breastfeeding was associated with higher parental educational level, higher age, non-instrumental vaginal birth and longer parental leave.

Background Pulmonary hypertension (PAH) among children and adults has been linked to premature birth, even after adjustments for known risk factors such as congenital heart disease and chronic lung disease. The aim of this population-based registry study was to assess the risk of PAH following exposure to premature birth and other factors in the decades when modern neonatal care was introduced and survival rates increased. Methods Data on pulmonary hypertension and perinatal factors were retrieved from population-based governmental and national quality registers. Cases were adults and children over five years of age with pulmonary hypertension born from 1973 to 2010 and individually matched to six controls by birth year and delivery hospital. Conditional multiple logistic regression was performed to assess the risk of pulmonary hypertension following premature birth and to adjust for known confounding factors for the total study population and for time of birth, grouped into five-year intervals. Results In total, 128 cases and 768 controls were included in the study group. Preterm birth was over three times more common among cases (21%) than among controls (6%). The overall adjusted risk of pulmonary hypertension was associated with premature birth, OR = 4.48 (95% CI; 2.10–9.53). Maternal hypertension, several neonatal risk factors and female gender were independently associated with PAH when potential confounders were taken into account. For each five-year period, the risk of PAH following premature birth increased several times for children born in the 2000s and later, OR = 17.08 (95% CI 5.60–52.14). Conclusions Preterm birth, along with other factors, significantly contributes to PAH. PAH following premature birth has increased over the last few decades. Our study indicates that new, yet unknown factors may play a role in the risk of preterm-born infants developing PAH later in life.

Background Children with acute peripheral facial nerve palsy cannot yet be recommended corticosteroid treatment based on evidence. Adults with idiopathic facial nerve palsy are treated with corticosteroids, according to guidelines resulting from a meta-analysis comprising two major randomized placebo-controlled trials. Corresponding trials in children are lacking. Furthermore, acute facial nerve palsy in childhood is frequently associated with Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi. The efficacy and safety of corticosteroid treatment of acute facial nerve palsy associated with Lyme neuroborreliosis, has not yet been determined in prospective trials in children, nor in adults. Method This randomized double-blind, placebo-controlled study will include a total of 500 Swedish children aged 1–17 years, presenting with acute facial nerve palsy of either idiopathic etiology or associated with Lyme neuroborreliosis. Inclusion is ongoing at 12 pediatric departments, all situated in Borrelia burgdorferi endemic areas. Participants are randomized into active treatment with prednisolone 1 mg/kg/day (maximum 50 mg/day) or placebo for oral intake once daily during 10 days without taper. Cases associated with Lyme neuroborreliosis are treated with antibiotics in addition to the study treatment. The House-Brackmann grading scale and the Sunnybrook facial grading system are used for physician-assessed evaluation of facial impairment at baseline, and at the 1- and 12-month follow-ups. Primary outcome is complete recovery, measured by House-Brackmann grading scale, at the 12-month follow-up. Child/parent-assessed questionnaires are used for evaluation of disease-specific quality of life and facial disability and its correlation to physician-assessed facial impairment will be evaluated. Furthermore, the study will evaluate factors of importance for predicting recovery, as well as the safety profile for short-term prednisolone treatment in children with acute facial nerve palsy. Discussion This article presents the rationale, design and content of a protocol for a study that will determine the efficacy of corticosteroid treatment in children with acute facial nerve palsy of idiopathic etiology, or associated with Lyme neuroborreliosis. Future results will attribute to evidence-based treatment guidelines applicable also in Borrelia burgdorferi endemic areas. Trial registration The study protocol was approved by the Swedish Medical Product Agency (EudraCT nr 2017–004187-35) and published at ClinicalTrials.gov (NCT03781700, initial release 12/14/2018).

Background Early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic therapy in neonates with a negative blood culture. In the study we evaluated if a quality improvement initiative could reduce unwarranted antibiotic use in a safe way in term neonates with culture-negative sepsis. Methods The quality improvement initiative included new treatment guidelines and were introduced on 11 June 2018. The guidelines included C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. All term neonates treated for EOS at Ryhov Hospital, Jönköping, Sweden were studied before (period 1: 2016–2017) and after the introduction of the new guidelines (period 2: 11 June 2018 to 30 Sept 2019). Laboratory and clinical data were analysed. Results There were 7618 term neonates in period 1 and 5005 term neonates in period 2. We identified 140 (1.8%) EOS in period 1 and 97 (1.9%) EOS in period 2. During period 1 and 2, there were 61 (61/140, 44%) and 59 (59/97, 61%) EOS neonates, respectively, who met the criteria for shorter antibiotic treatment. The number of positive blood cultures were seven (0.92/1000 live births) and five (1.0/1000 live births) in period 1 and 2. The median C-reactive protein were 52 mg/L (37–62) in period 1 and 42 mg/L (31–56) in period 2 in the group who met the criteria of the guidelines. The duration of antibiotic therapy (Median: seven vs. five days, p p Conclusion C-reactive protein- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term infants. Trial registration Trial registration number: ISRCTN29535824. Date of registration: 28 May 2020. Retrospectively registered.

Background To increase health and well-being in young children, it is important to acknowledge and promote the child’s sleep behaviour. However, there is a lack of brief, validated sleep screening instruments for children. The aims of the study were to (1) present a Swedish translation of the PISI, (2) examine the factor structure of the Swedish version of PISI, and test the reliability and validity of the PISI factor structure in a sample of healthy children in Sweden. Methods The English version of the PISI was translated into Swedish, translated back into English, and agreed upon before use. Parents of healthy 3- to 10-year-old children filled out the Swedish version of the PISI and the generic health-related quality of life instrument KIDSCREEN-27 two times. Exploratory and confirmatory factor analyses for baseline and test-retest, structural equation modelling, and correlations between the PISI and KIDSCREEN-27 were performed. Results In total, 160 parents filled out baseline questionnaires (test), whereof 100 parents (63%) filled out the follow-up questionnaires (retest). Confirmative factor analysis of the PISI found two correlated factors: sleep onset problems (SOP) and sleep maintenance problems (SMP). The PISI had substantial construct and test-retest reliability. The PISI factors were related to all KIDSCREEN-27 dimensions. Conclusions The Swedish version of the PISI is applicable for screening sleep problems and is a useful aid in dialogues with families about sleep. Funding Agencies|Futurum Academy of Health and Care, Jonkoping County Council [FUTURUM-766061, FUTURUM-802921, FUTURUM-805951]; Forsknings-och stipendieforvaltningen i Ostergotland - US stiftelse for medicinsk forskning Barndiabetesforskning and Halsofonden [LIO-857851]; Linkoping University

Background To increase the knowledge about physical activity (PA) patterns and correlates among children under the age of 4, there is a need for study’s using objective measurements. The aim of this study was therefore to investigate if objectively measured PA among 3-year-old children differed between day of week and time of day and whether it correlated to child weight status and sex as well as parental weight status and education. Methods Totally 61 children (51% girls) aged 3, participating in Early Stockholm Obesity Prevention Project were included. PA was measured with a tri-axial accelerometer (ActiGraph GT3X+) worn on the non-dominant wrist for one week. The main outcome was average PA expressed as counts per minute from the vector magnitude. PA and demographics/family-related factors were collected at baseline and at age 3. To analyze the results simple linear regression, ANOVA and paired t-tests were performed. Results The mean number of valid days was 6.7 per child. The children were more active on weekdays than weekends (p p = 0.0001). Children to parents with low education were more active (p = 0.01) than those with highly educated parents. No differences in PA by child weight status, sex nor parental weight status were found. Conclusions PA in 3-year-old children was lower during weekends than weekdays and varied over the day. Boys and girls had similar PA patterns, these patterns were independent of child or parental weight status. Children to parents with low education were more active than their counterparts. The fact that PA differed between weekdays and weekends indicates that PA might be affectable in 3-year-old children.

Background: There is a high risk that young children who show early signs of mental health problems develop symptoms in the same or overlapping areas some years later. The Strengths and Difficulties Questionnaire (SDQ) is widely used to screen externalizing and internalizing problems early in life. In Sweden 80-90% of all children aged 1-5 years go to preschool and preschool is thus an appropriate context for finding early signs of mental health problems among children. Methods: This study is part of a longitudinal project too investigate the frequency of emotional and behavioural problems for children between 1 and 5 years of age in Sweden. The SDQ including the impairment supplement questions were rated by preschool teachers too establish Swedish norms for SDQ in preschool children. Results: The sample involved 815 children with a mean age of 42 months (SD = 16, range 13-71 months). 195 children were followed longitudinally for three years. There were significant differences between boys and girls on all subscales except for the Emotional subscale. The prevalence of behavioural problems was similar to other that in European countries, except for Prosocial behaviour, which was rated lower, and Conduct problems, rated higher. Swedish children were estimated to have more problems in the preschool setting, scored by preschool teachers. The development of behaviour over time differed for the different subscales of SDQ. Conclusions: The teacher version of the SDQ, for 2-4 year-olds, can be used as a screening instrument to identify early signs of emotional distress/behavioural problems in young children. Preschool teachers seem to be able to identify children with problematic behaviour with the use of SDQ at an early age. The development of behaviour over time differs for the different subscales of SDQ. The Swedish norms for SDQ are to a large extent, similar to findings from other European countries. Funding Agencies|National Board of Health and Welfare (Socialstyrelsen); Sunnerdahls Handikappfond and the Futurum; Academy for Health and Care; Region Jonkoping County; Medical Research Council of Southeast Sweden [FORSS- 653271]

Background: The diagnosis of Lyme neuroborreliosis (LNB) in Europe is based on clinical symptoms and laboratory data, such as pleocytosis and anti-Borrelia antibodies in serum and CSF according to guidelines. However, the decision to start antibiotic treatment on admission cannot be based on Borrelia serology since results are not available at the time of lumbar puncture. Therefore, an early prediction test would be useful in clinical practice. The aim of the study was to develop and evaluate a clinical prediction test for children with LNB in a relevant European setting. Method: Clinical and laboratory data were collected retrospectively from a cohort of children being evaluated for LNB in Southeast Sweden. A clinical neuroborreliosis prediction test, the NeBoP score, was designed to differentiate between a high and a low risk of having LNB. The NeBoP score was then prospectively validated in a cohort of children being evaluated for LNB in Central and Southeast Sweden (n = 190) and controls with other specific diagnoses (n = 49). Results: The sensitivity of the NeBoP score was 90 % (CI 95 %; 82-99 %) and the specificity was 90 % (CI 95 %; 85-96 %). Thus, the diagnostic accuracy (i.e. how the test correctly discriminates patients from controls) was 90 % and the area under the curve in a ROC analysis was 0.95. The positive predictive value (PPV) was 0.83 (CI 95 %; 0.75-0.93) and the negative predictive value (NPV) was 0.95 (CI 95 %; 0.90-0.99). Conclusion: The overall diagnostic performance of the NeBoP score is high (90 %) and the test is suggested to be useful for decision-making about early antibiotic treatment in children being evaluated for LNB in European Lyme endemic areas. Funding Agencies|Center of Clinical Research Dalarna (CKF); Swedish Society of Medicine; Research Council in the Uppsala-Orebro region (RFR); Samaritan Foundation; Lions Foundation

Background The early environment is important for child development and wellbeing. Gene-by-environment studies investigating the impact of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphisms by life events on mental health and behaviour problems have been inconclusive. Methodological differences regarding sample sizes, study population, definitions of adversities and measures of mental health problems obstacle their comparability. Furthermore, very few studies included children. The aim of this study was to examine the associations between a broad range of risk factors covering pregnancy and birth, genetic polymorphism, experience of multiple life events and psychosocial environment, and child behaviour at age 3, using a comparably large, representative, population-based sample. Methods A total of 1,106 children, and their mothers, were followed from pregnancy to age 3. Information on pregnancy and birth-related factors was retrieved from the Medical Birth Register. Questionnaires on depressive symptoms, child behaviour and child experiences of life events were filled in by the mothers. Child saliva samples were used for genotyping the 5-HTTLPR and BDNF Val66Met polymorphisms. Multiple logistic regression was used to investigate the association between psychological scales and genetic polymorphisms. Results Symptoms of postpartum depression increased the risk of both internalizing and externalizing problems. Experience of multiple life events was also a predictor of behavioural problems across the scales. No gene-by-environment or gene-by-gene-by-environment interactions were found. Children of immigrants had an increased risk of internalizing problems and parental unemployment was significantly associated with both internalizing and externalizing type of problems. Conclusion This study shows the importance of the psychosocial environment for psychosocial health in preschool children, and adds to the literature of null-findings of gene-by-environment effects of 5-HTTLPR and BDNF in children. Electronic supplementary material The online version of this article (doi:10.1186/s12887-016-0614-x) contains supplementary material, which is available to authorized users.

Background: This study analyses whether a mother's exposure to different forms of Intimate Partner Violence (IPV) during pregnancy was associated with the index child linear growth, and whether these associations were modified by the gender of the child. Methods: A pregnancy cohort of 478 women in Leon, Nicaragua, resulted in 461 live births. From this group, 81% (375/461) children were available for anthropometric follow-up at 40 to 46 months. Analysis of covariance (ANCOVA) was used to assess the association between IPV and height-for-age Z-scores, adjusting for confounding factors. Results: Sixty-three percent (236/375) of the mothers had been exposed to some form of IPV during pregnancy (emotional, physical, sexual or controlling behavior). After adjustment for confounding factors, maternal exposure to any IPV during pregnancy was associated with 0.24 lower mean height-for-age Z-scores (p = 0.02). A separate analysis of each IPV type showed that emotional, physical or sexual IPV during pregnancy were not significantly associated with lower mean height-for-age Z-scores, whereas ever exposure to controlling behavior by the father of the child was related to 0.29 lower mean height-for-age Z-scores (p < 0.01) When stratified by gender, these associations remained significant only for young girls. Conclusions: This study has contributed to the growing amount of evidence pointing to the pervasive effect of different forms of IPV on child health. Our study highlights the relevance of maternal autonomy for linear child growth, especially for young girls in the Nicaraguan context. Originally included in thesis in manuscript form with title: "Intimate partner violence, maternal social resources, and early child growth: a community-based cohort study in Nicaragua".

Background: The International Network for Evaluating Outcomes in Neonates (iNeo) is a collaboration of population-based national neonatal networks including Australia and New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the UK. The aim of iNeo is to provide a platform for comparative evaluation of outcomes of very preterm and very low birth weight neonates at the national, site, and individual level to generate evidence for improvement of outcomes in these infants. Methods/design: Individual-level data from each iNeo network will be used for comparative analysis of neonatal outcomes between networks. Variations in outcomes will be identified and disseminated to generate hypotheses regarding factors impacting outcome variation. Detailed information on physical and environmental factors, human and resource factors, and processes of care will be collected from network sites, and tested for association with neonatal outcomes. Subsequently, changes in identified practices that may influence the variations in outcomes will be implemented and evaluated using quality improvement methods. Discussion: The evidence obtained using the iNeo platform will enable clinical teams from member networks to identify, implement, and evaluate practice and service provision changes aimed at improving the care and outcomes of very low birth weight and very preterm infants within their respective countries. The knowledge generated will be available worldwide with a likely global impact.

Background: Pregnancies resulting through oocyte donation have been associated with increased risk for adverse outcomes for the mother, such as gestational hypertensive disorders. However, little is known about possible neonatal complications of such pregnancies. The purpose of this study was to evaluate the neonatal health outcomes among singleton pregnancies in a population of relatively young and healthy oocyte recipients in Sweden, taking into account the medical indication leading to treatment. Methods: This cohort study involved 76 women conceiving with donated oocytes, 149 age-matched nulliparous women conceiving spontaneously and 63 women conceiving after non-donor IVF. Participants were recruited during 2005-2008 and followed up until delivery. Data on neonatal outcomes were retrieved from the National Birth Medical Register and the medical records of oocyte recipients from seven Swedish University Hospitals with IVF clinics. Logistic regression analyses were performed to examine the association of mode of conception and neonatal outcomes, adjusted for maternal age and BMI, gestational age and delivery by cesarean section. Results: Infants conceived through oocyte donation had higher odds for premature delivery [OR 2.36, 95 % CI (1.02-5.45)], for being small for gestational age [OR 4.23, 95 % CI (1.03-17.42)] and having Apgar score below 7 at 5 min [OR 10.57, 95 % CI (1.21-92.20)] compared to spontaneously conceived infants. Similar trends were observed when comparing infants conceived through oocyte donation to those conceived by traditional IVF. Furthermore, donor oocyte infants had a lower mean birthweight and length compared to autologous oocyte neonates (p = 0.013); however no differences were noted among infants born at term. Neonatal outcomes were more favorable among women with diminished ovarian reserve compared to those with other indications for oocyte donation. Conclusions: Infants conceived after oocyte donation in Sweden have higher odds of being born prematurely and having lower mean birthweight in comparison to non-donor infants. It seems that these unfavorable neonatal outcomes are present despite the age, weight and health restrictions applied to recipients before oocyte donation treatment in Sweden. Funding Agencies|Merck Serono; Family Planning Fond in Uppsala; Swedish Research Council for Health, Working Life and Welfare

Background Celiac disease is defined as a ‘chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Sweden has experienced an “epidemic” of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic. Methods A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child’s general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents. Results Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P Conclusion This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease. In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants for whom breastfeeding had been discontinued prior to gluten introduction. Regarding contribution to the Swedish celiac disease epidemic, which partly was attributed to concurrent changes in infant feeding, early infections probably made a minor contribution via the synergistic effect with gluten amount.