Respiratory viral infections among children with community-acquired pneumonia and pleural effusion.

Pleural effusion (PE), a complication of community-acquired pneumonia (CAP), is usually attributed to a bacterial infection. Nonetheless, viral infections have not been investigated routinely. We searched for bacterial and viral infections among 277 children hospitalized with CAP. Among these children 206 (74%) had radiographic confirmation, of whom 25 (12%) had PE. The aetiology was established in 18 (72%) PE cases: bacterial (n = 5; 28%), viral (n = 9; 50%), and viral-bacterial (n = 4; 22%) infections were found. Infection by rhinovirus (n = 3), enterovirus, Streptococcus pneumoniae (n = 2 each), Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, influenza A virus, and respiratory syncytial virus (RSV) (n = 1 each) were detected as probable sole infections. Parainfluenza virus 1/3 + influenza A virus and RSV + influenza A virus (n = 1 each) were identified as mixed viral-viral infections. Probable viral non-bacterial infection was identified in a third of the cases with CAP and PE. It is advisable to investigate viral as well as bacterial infections among children with CAP and PE.

Low-grade, systemic inflammation in adolescents: association with early-life factors, gender, and lifestyle.

Low-grade, systemic inflammation is related to increased risk of cardiovascular disease in adults. The proinflammatory state tracks from adolescence to adulthood. Identifying correlates of inflammation in adolescents could provide opportunities to prevent cardiovascular disease in adulthood. However, population-based data on correlates of inflammation in adolescence are limited. Therefore, the authors studied the associations of early-life factors, gender, and lifestyle with inflammation (measured by high-sensitivity C-reactive protein and leukocyte count) at age 16 years (2001-2002) in the prospective, population-based Northern Finland Birth Cohort 1986 Study (n = 5,240). In females, being born small for gestational age and current use of oral contraceptives were associated with the proinflammatory state. The association of birth size with inflammation was not observed in males. In logistic regression analyses, oral contraceptive use (odds ratio (OR) = 2.83), abdominal obesity (OR = 5.17), and smoking (OR = 2.72) were associated with elevation of both inflammation markers in females; abdominal obesity (OR = 5.72) and smoking (OR = 2.02) were associated in males. Thus, females appear more susceptible to the adverse effects of being born small for gestational age than males. Given the widespread use of oral contraceptives and the potential pathophysiologic consequences of the proinflammatory state, the association of oral contraceptive use with inflammation in adolescence may have public health implications.

Seasonal patterns of viral and bacterial infections among children hospitalized with community-acquired pneumonia in a tropical region.

Community-acquired pneumonia (CAP) is a common cause of morbidity among children. Evidence on seasonality, especially on the frequency of viral and bacterial causative agents is scarce; such information may be useful in an era of changing climate conditions worldwide. To analyze the frequency of distinct infections, meteorological indicators and seasons in children hospitalized for CAP in Salvador, Brazil, nasopharyngeal aspirate and blood were collected from 184 patients aged < 5 y over a 21-month period. Fourteen microbes were investigated and 144 (78%) cases had the aetiology established. Significant differences were found in air temperature between spring and summer (p = 0.02) or winter (p < 0.001), summer and fall (p = 0.007) or winter (p < 0.001), fall and winter (p = 0.002), and on precipitation between spring and fall (p = 0.01). Correlations were found between: overall viral infections and relative humidity (p = 0.006; r = 0.6) or precipitation (p = 0.03; r = 0.5), parainfluenza and precipitation (p = 0.02; r = -0.5), respiratory syncytial virus (RSV) and air temperature (p = 0.048; r = -0.4) or precipitation (p = 0.045; r = 0.4), adenovirus and precipitation (p = 0.02; r = 0.5), pneumococcus and air temperature (p = 0.04; r = -0.4), and Chlamydia trachomatis and relative humidity (p = 0.02; r = -0.5). The frequency of parainfluenza infection was highest during spring (32.1%; p = 0.005) and that of RSV infection was highest in the fall (36.4%; p < 0.001). Correlations at regular strength were found between several microbes and meteorological indicators. Parainfluenza and RSV presented marked seasonal patterns.

Procalcitonin is useful in identifying bacteraemia among children with pneumonia.

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was > or =2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT > or =2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country.

We report an investigation for 16 bacteria and viruses among 184 children hospitalized with pneumonia in Salvador, Brazil. Etiology was established in 144 (78%) cases. Viral, bacterial, and mixed infections were found in 110 (60%), 77 (42%), and 52 (28%) patients, respectively. Rhinovirus (21%) and Streptococcus pneumoniae (21%) were the most common pathogens. Our results demonstrate the importance of viral and pneumococcal infections among those patients.

Asthmatic persons are prone to the persistence of Chlamydia pneumoniae antibodies.

Acute Chlamydia pneumoniae infection may initiate asthma or worsen asthmatic symptoms. In crowded conditions, such as military service, young men are susceptible to respiratory infections, including C. pneumoniae. We recruited 127 asthmatic and 391 nonasthmatic military conscripts, followed up their respiratory tract infections and the kinetics of serum C. pneumoniae antibodies, and assessed the association between C. pneumoniae and asthma during 6 months of military service in 2 intake groups. During the 6-month period, in the July intake group, IgG antibody prevalence decreased from 60.3% to 43.8% in asthmatic and from 55.6% to 22.6% in nonasthmatic conscripts. In the January intake group, IgG antibody prevalence increased from 38.3% to 48.4% in asthmatic and from 37.2% to 43% in nonasthmatic recruits. IgG and IgA antibodies persisted more often in the asthmatic groups. In conclusion, the prevalence of IgG antibodies showed seasonal variation. Military recruits seem to be most vulnerable to C. pneumoniae infections during the period from January to June. The antibody titer changes were more rapid than previously thought.

Chlamydia pneumoniae antibody levels before coronary events in the Helsinki Heart Study as measured by different methods.

The lack of specific tests for the diagnosis of chronic Chlamydia pneumoniae infection has led to the use of enzyme immunoassay (EIA) instead of the gold standard, that is, microimmunofluorescence (MIF), in the measurement of C. pneumoniae antibodies. We assessed the predictive values of C. pneumoniae antibody levels and seroconversions measured by MIF and EIA for coronary events in the prospective Helsinki Heart Study. Sera from 239 cases with coronary events and 239 controls were available at the baseline and data from 210 cases and 211 controls before and after the event. The agreement between MIF and EIA antibody levels was best in high antibody titers. In conditional logistic regression analysis, only high IgA MIF titers (>/=40) at the baseline predicted future coronary events, and the participants with MIF seroconversion between consecutive sera had a higher (nonsignificant) risk for coronary events than the controls. The difference in the kinetics of EIA and MIF antibodies demonstrated that MIF should remain the gold standard.

Novel enzyme immunoassay utilizing lipopolysaccharide-binding protein as a capture molecule for the measurement of chlamydial lipopolysaccharide in serum.

Chlamydia pneumoniae causes respiratory tract infections. It has a tendency to cause persistent infections, which have been associated with several chronic diseases (e.g., atherosclerosis). At present, there is no reliable method for the diagnosis of chronic C. pneumoniae infection. We developed a novel enzyme immunoassay (EIA) for the quantification of chlamydial lipopolysaccharide (cLPS) in human serum. Serum cLPS was solubilized with detergent and then captured by LPS-binding protein (LBP). LBP-LPS complexes were bound to the solid phase with anti-cLPS monoclonal antibody, and the bound complexes were detected with anti-LBP antibodies. The new method was used to quantify serum cLPS in acute coronary syndrome (ACS) patients (n = 102) and their healthy controls. cLPS was detected in 77.5% of ACS patients and in 52% of controls (P < .001) with geometric mean concentrations of 1.87 and 0.61 microg/mL (P < .001), respectively. The novel cLPS EIA method will provide a potential diagnostic tool for C. pneumoniae infection.

Serum C-reactive protein and Chlamydia trachomatis antibodies in preterm delivery.

OBJECTIVE: To assess the association between Chlamydia trachomatis antibodies, antibodies to C trachomatis heat shock proteins 60 and 10, and C-reactive protein (CRP) levels in maternal serum measured by highly sensitive CRP assay during the first trimester and spontaneous preterm delivery before 37 weeks of gestation. METHODS: This was a nested case-control study of 104 spontaneous preterm singleton deliveries (cases) and 402 term singleton deliveries, as controls, of mothers belonging to the population-based Northern Finland 1966 Birth Cohort. Data on 2,309 first deliveries were available from the Finnish Medical Birth Register. Serum C trachomatis and C pneumoniae antibodies were measured by the microimmunofluorescence test and chlamydial heat shock proteins 60 and 10 antibodies by enzyme immunoassay using recombinant proteins as antigens, and highly sensitive CRP levels were quantified with highly sensitive immunoenzymometric assay. RESULTS: Highly sensitive CRP levels were higher and C trachomatis immunoglobulin G levels (pools and individual serotypes) were more often present (thought not nominally significantly in all cases) in the women with preterm compared with term deliveries. Elevated immunoglobulin G levels of C trachomatis antibodies or elevated highly sensitive CRP levels alone, however, did not increase the estimated risk for preterm delivery, but when they were present simultaneously, the estimated risk for preterm delivery was 4-fold (odds ratio 4.3, 95% confidence interval 2.0-9.3). Among the women delivered at or before 34 weeks of gestation, the estimated risk was even more evident (odds ratio 5.6, 95% confidence interval 2.1-14.5). The preterm delivery rate was 26.5% for those with C trachomatis antibodies and 18.8% for those without C trachomatis antibodies. CONCLUSION: The results of the present study suggest that chlamydial infection in the first trimester is associated with preterm delivery. LEVEL OF EVIDENCE: II-2.

Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study.

The metabolic cardiovascular disease (CVD) risk factors of women with self-reported oligomenorrhea and/or hirsutism, which are symptoms of polycystic ovary syndrome (PCOS), were investigated in a general population-based Northern Finland Birth Cohort 1966 Study to determine whether women with PCOS symptoms at 31 yr would be distinguishable from asymptomatic controls in terms of CVD risk factors. A total of 518 cases with oligomenorrhea and/or hirsutism and 1036 randomly selected controls were analyzed. C-Reactive protein (CRP; median, 0.70 vs. 0.60 mg/liter; P = 0.026), triglycerides (mean, 0.97 vs. 0.91 mmol/liter; P = 0.039), body mass index (BMI; mean, 25.1 vs. 24.2 kg/m(2); P < 0.001), and waist/hip ratio (mean, 0.82 vs. 0.81; P = 0.001) were significantly higher, and high-density lipoprotein cholesterol levels were lower (mean, 1.60 vs. 1.66 mmol/liter; P = 0.002) in the cases compared with the controls. Total cholesterol, low-density lipoprotein cholesterol, and blood pressure showed no statistically significant differences between the cases and the controls. In terms of metabolic CVD risk factors, women reporting hirsutism alone were indistinguishable from the control group, and those who reported both oligomenorrhea and hirsutism had the most severe changes in risk factor profiles. Because obesity is strongly related to PCOS symptoms, the analyses were stratified by BMI. After stratification into normal weight (BMI, <25 kg/m(2)), overweight (25 kg/m(2) or=30 kg/m(2)) groups, the waist/hip ratio was significantly higher among the overweight cases (mean, 0.84 vs. 0.83; P = 0.04). Among the obese women, high-density lipoprotein cholesterol was significantly lower (mean, 1.32 vs. 1.48 mmol/liter; P = 0.002) among the cases, and triglycerides tended to be higher (mean, 1.43 vs. 1.27 mmol/liter; P = 0.068) than in controls. In conclusion, these results indicate that self-reported symptoms of oligomenorrhea and/or hirsutism, particularly in the presence of both symptoms, may be helpful to identify women with metabolic cardiovascular risk factor accumulation associated with PCOS.

High seroprevalence of Simkania negevensis in Jordan.

The bacterium Simkania negevensis is a germ associated with respiratory diseases. This study aims at estimating the prevalence of Simkania in the Jordanian population. Serum samples from 664 Jordanian males and females, aged 2 to 86 years were collected. IgG and IgM Simkania-specific antibodies were detected using an indirect immunofluorescence test. Seropositivity titers for IgG and IgM were defined as 1:8 and 1:10, respectively. The overall prevalence of IgG antibody in all examined Jordanian nationals was 58.4%. IgG seropositivity was low in children under the age of 10 years (34.2%), and increased rapidly with age and ranged between 49.4% and 72%. Simkania-specific IgM was detected in 24.8% of subjects. IgM prevalence in children under 10 years was lowest (10.5%) and increased in older ages and remained above 20%. Overall detection rates of both IgG and IgM were significantly higher in females than males (60.7% vs. 54.5% for IgG and 26.7% vs. 21.7% for IgM). These data indicate that Simkania infection is highly prevalent in Jordan. The high level of seropositivity is most likely maintained by re-infections or chronic infections. Our data may serve as a basis to elucidate the pathogenesis of Simkania in Jordan.

Low mannose-binding lectin levels and MBL2 gene polymorphisms associate with Chlamydia pneumoniae antibodies.

OBJECTIVE: Mannose-binding lectin (MBL) has been shown to inhibit infection of host cells by Chlamydia pneumoniae in vitro. We studied if MBL levels and MBL2 polymorphisms associate with the presence of C. pneumoniae antibodies in vivo. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) of the MBL2 gene (promoter alleles H/L, X/Y and P/Q; and exon 1 variant alleles B, C and D and wild-type allele A) were genotyped and serum MBL concentrations and C. pneumoniae IgG, IgA and IgM antibodies were analysed in 889 Finnish military recruits. RESULTS: An MBL level below the median concentration and the MBL2 P/P genotype were significant risk factors of IgG or IgA seroconversions or the presence of IgM antibodies during military service (adjusted odds ratio (OR) 1.5; 95% confidence interval (CI) 1.1-2.1 and OR 1.5; 95% CI 1.0-2.2, respectively). In addition, the promoter Y/Y (OR 1.6; 95% CI 1.1-2.3) and exon 1 variant allele genotypes (OR 1.4; 95% CI 1.0-2.0) were possibly associated with elevated antibodies. CONCLUSIONS: These results suggest, for the first time, that low serum MBL levels and MBL2 polymorphisms may associate with elevated C. pneumoniae antibodies and seroconversions and thus support the previous findings in vitro.

Divergent modulation of Chlamydia pneumoniae infection cycle in human monocytic and endothelial cells by iron, tryptophan availability and interferon gamma.

Chlamydia pneumoniae is an obligatory intracellular bacterium causing chronic inflammatory diseases in humans. We studied the role of the nutritive factors, iron and tryptophan, towards the course of infection and immune response pathways in C. pneumoniae infected endothelial cells and monocytes. Human endothelial (EA.hy923) and monocytic cells (THP-1) were infected with C. pneumoniae, supplemented with iron or 1-methyltryptophan (1-MT), an inhibitor of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO), and subsequently stimulated with IFN-gamma or left untreated. The number of infected cells, the morphology and quantity of C. pneumoniae inclusion bodies, IDO activity and innate immune effector pathways were analysed. While neither iron challenge, IDO inhibition or IFN-gamma treatment had a significant effect on C. pneumoniae morphology or numbers within THP-1 monocytic cells, iron supplementation to EA.hy926 cells resulted in promotion of C. pneumoniae proliferation and differentiation while IFN-gamma had an inhibitory effect. Furthermore, the number of infected endothelial cells was significantly decreased upon 1-MT treatment. C. pneumoniae infection induced a pro-inflammatory immune response as evidenced by increased IDO activity, neopterin formation or TNF-alpha production in THP-1 but not in endothelial cells. These pathways were superinduced upon IFN-gamma treatment and partly modulated by iron supplementation. Our results demonstrate that the infectious cycle of C. pneumoniae behaves differently between monocytic and endothelial cells. While the intracellular pathogen remains in a persistent form within monocytes, it can differentiate and proliferate within endothelial cells indicating that endothelial cells are a preferred environment for Chlamydia. Nutritive factors such as iron have subtle effects on C. pneumoniae biology in endothelial, but not monocytic cells. Our results contribute to a better understanding of C. pneumoniae infection and its role in chronic inflammatory diseases such as atherosclerosis.

High seroprevalence of Simkania negevensis in Jordan

The bacterium Simkania negevensis is a germ associated with respiratory diseases. This study aims at estimating the prevalence of Simkania in the Jordanian population. Serum samples from 664 Jordanian males and females, aged 2 to 86 years were collected. IgG and IgM Simkania-specific antibodies were detected using an indirect immunofluorescence test. Seropositivity titers for IgG and IgM were defined as 1:8 and 1:10, respectively. The overall prevalence of IgG antibody in all examined Jordanian nationals was 58.4%. IgG seropositivity was low in children under the age of 10 years (34.2%), and increased rapidly with age and ranged between 49.4% and 72%. Simkania-specific IgM was detected in 24.8% of subjects. IgM prevalence in children under 10 years was lowest (10.5%) and increased in older ages and remained above 20%. Overall detection rates of both IgG and IgM were significantly higher in females than males (60.7% vs. 54.5% for IgG and 26.7% vs. 21.7% for IgM). These data indicate that Simkania infection is highly prevalent in Jordan. The high level of seropositivity is most likely maintained by re-infections or chronic infections. Our data may serve as a basis to elucidate the pathogenesis of Simkania in Jordan.

Simkania negevensis may be a true cause of community acquired pneumonia in children.

Simkania negevensis, a recently found Chlamydia-like organism, has been associated with bronchiolitis and pneumonia in children. S. negevensis findings have been common also in healthy, non-symptomatic subjects. Antibodies to S. negevensis were measured by microimmunofluorescence in 174 frozen paired sera obtained from children with community acquired pneumonia in a population-based study. There was evidence of S. negevensis infection in 18 (10%) cases. All diagnoses were based on the presence of specific IgM antibodies. The numbers of S. negevensis cases increased from 2 (4%) at <24 months to 7 (15%) at > or = 10 y of age. 12 (67%) were mixed infections with viruses or other bacteria. 16 children (9%) had measurable IgG antibodies to S. negevensis, but significant rises were not found in any cases. Thus, S. negevensis may be a real, though rare, cause of CAP in children, occurring often in mixed infections with viruses and other bacteria.

Simkania negevensis in community-acquired pneumonia in Italian children.

Simkania negevensis, a recently found Chlamydia-like organism, has been associated with respiratory infections in children and adults with pneumonia, but S. negevensis findings have been common also without any infection. The aims of the present paper were to evaluate S. negevensis in the aetiology of paediatric community-acquired pneumonia (CAP), its seroprevalence in north Italian children, and whether there is cross-reactivity between S. negevensis and Chlamydia pneumoniae serology. Antibodies to S. negevensis were measured by microimmunofluorescence (MIF) in 101 frozen paired sera obtained from children with CAP. Serological evidence (> or =4-fold increase or decrease in IgM or IgG) of acute S. negevensis infection was achieved in 5 (5%) cases. Two were mixed infections with Mycoplasma pneumoniae and 1 with respiratory syncytial virus. In total, 20-30% of the children had measurable antibodies to S. negevensis, with no association with age. No cross-reactivity was observed between antibodies to S. negevensis and C. pneumoniae. S. negevensis appears to be a real, though rare, cause of CAP in children.

Association of Chlamydia pneumoniae infection with HLA-B*35 in patients with coronary artery disease.

The immune system may interplay between Chlamydia pneumoniae infection and coronary artery disease (CAD). Major histocompatibility complex genes regulate innate and adaptive immunity. Patients with CAD (n = 100) and controls (n = 74) were enrolled. Human leukocyte antigens (HLA-A, HLA-B, and HLA-DRB1), four lymphotoxin alpha single-nucleotide polymorphisms, and complement C4A and C4B allotypes were typed, and their haplotypes were inferred. The presence of serum C. pneumoniae immunoglobulin A (IgA) (titer, > or =40) or IgG (titer, > or =128) antibodies or immune complex (IC)-bound IgG antibodies (titer, > or =2) was considered to be a serological marker suggesting chronic C. pneumoniae infection. C. pneumoniae IgA antibodies were found more frequently in patients than in controls (P = 0.04). Among the patients, multiple logistic regression analysis showed the HLA-B*35 allele to be the strongest-risk gene for C. pneumoniae infection (odds ratio, 7.88; 95% confidence interval, 2.44 to 25.43; P = 0.0006). Markers of C. pneumoniae infection were found more frequently in patients with the HLA-A*03-B*35 haplotype than in those without the haplotype (P = 0.007 for IgA; P = 0.008 for IgG; P = 0.002 for IC). Smokers with HLA-B*35 or HLA-A*03-B*35 had markers of C. pneumoniae infection that appeared more often than in smokers without these genes (P = 0.003 and P = 0.001, respectively). No associations were found in controls. In conclusion, HLA-B*35 may be the link between chronic C. pneumoniae infection and CAD.

Maternal serum Chlamydia pneumoniae antibodies and CRP levels in women with preeclampsia and gestational hypertension.

OBJECTIVE: To determine whether Chlamydia pneumoniae antibodies and highly sensitive C-reactive protein (hsCRP) levels in maternal sera are associated with preeclampsia or gestational hypertension. METHODS: C. pneumoniae antibodies and hsCRP levels were measured in maternal serum during first trimester (mean, 10.4 weeks of gestation) using the microimmunofluorescence (MIF) test and a highly sensitive immunoenzymometric assay, respectively. RESULTS: No differences in the IgG antibody levels against C. pneumoniae or hsCRP levels were seen between the women with preeclampsia or gestational hypertension and those in the reference group. However, the women with preeclampsia and preterm delivery had serum IgG antibodies to C. pneumoniae (IgG titre > or =32) significantly more often in their first trimester sera compared with women having preeclampsia and full-term deliveries (p = 0.03). In addition, the proportion of subjects with C. pneumoniae IgG antibodies (IgG titre > or =32) and/or elevated CRP levels (> or =3.8 mg/L, upper quartile) was double among the women with preeclampsia and elective preterm delivery compared with the women with preeclampsia who delivered at term (p = 0.01). CONCLUSION: Our results suggest that chronic C. pneumoniae infection and systemic low-grade inflammation may be associated with preeclampsia requiring elective delivery before 37 weeks gestation.

Size at birth, weight gain over the life course, and low-grade inflammation in young adulthood: northern Finland 1966 Birth Cohort study.

AIMS: Low-grade inflammation might mediate associations between size at birth, early life growth, excessive weight gain, and subsequent risk of cardiovascular disease in adult life. Our aim was to investigate relationships between fetal growth, weight over the life course, and low-grade inflammation measured by serum high sensitivity C-reactive protein (CRP) levels at 31 years. METHODS AND RESULTS: General population-based northern Finland 1966 Birth Cohort study of 5840 participants attending a clinical examination at 31 years, including measurement of CRP. Weight and height were assessed at birth, 12 months, and 14 and 31 years of age. CRP levels at 31 years were 16% [95% confidence interval (CI) 8, 23] higher per 1 kg lower birth weight, 21% (95% CI 2, 37) higher per 10 cm lower birth length, and 24% (95% CI 10, 36) higher per 1 kg/m3 lower ponderal index, after adjustment for potential confounders. Participants with highest tertile body mass index (BMI) at 31 years and lowest tertile birth weight had the highest average CRP levels. Per unit increase in BMI from 14 to 31 years was associated with 16% (95% CI 14, 17) higher CRP levels; the association was larger for those in the top BMI tertile at age 14 years. CONCLUSION: Systemic low-grade inflammation may lie on the causal pathway that relates impaired fetal growth and weight gain from childhood to adulthood to adverse adult cardiovascular health. Lifestyle changes from early life might be an important step in reducing cardiovascular risk in adults.