Size at birth, postnatal growth and risk of obesity

Epidemiological studies over the last 15 years have shown that size at birth, early postnatal catch-up growth and excess childhood weight gain are associated with an increased risk of adult cardiovascular disease and type 2 diabetes. At the same time, rising rates of obesity and overweight in children, even at pre-school ages, have shifted efforts towards the identification of very early factors that predict risk of subsequent obesity, which may allow early targeted interventions. Overall, higher birth weight is positively associated with subsequent greater body mass index in childhood and later life; however, the relationship is complex. Higher birth weight is associated with greater subsequent lean mass, rather than fat mass. In contrast, lower birth weight is associated with a subsequent higher ratio of fat mass to lean mass, and greater central fat and insulin resistance. This paradoxical effect of lower birth weight is at least partly explained by the observation that infants who have been growth restrained in utero tend to gain weight more rapidly, or 'catch up', during the early postnatal period, which leads to increased central fat deposition. There is still debate as to whether there are critical early periods for obesity: does excess weight gain during infancy, childhood or even very early neonatal life have a greater impact on long-term fat deposition and insulin resistance? Early identification of childhood obesity risk will be aided by identification of maternal and fetal genes that regulate fetal nutrition and growth, and postnatal genes that regulate appetite, energy expenditure and the partitioning of energy intake into fat or lean tissue growth.     

Meningitis in infancy in England and Wales: follow up at age 5 years

ObjectiveTo describe important sequelae occurring among a cohort of children aged 5 years who had had meningitis during the first year of life and who had been identified by a prospective national study of meningitis in infancy in England and Wales between 1985 and 1987.DesignFollow up questionnaires asking about the children''s health and development were sent to general practitioners and parents of the children and to parents of matched controls. The organism that caused the infection and age at infection were also recorded.SettingEngland and Wales.ParticipantsGeneral practitioners and parents of children who had had meningitis before the age of 1 year and of matched controls.ResultsAltogether, 1584 of 1717 (92.2%) children who had had meningitis and 1391 of 1485 (93.6%) controls were successfully followed up. Among children who survived to age 5 years 247 of 1584 (15.6%) had a disability; there was a 10-fold increase in the risk of severe or moderate disability at 5 years of age among children who had had meningitis (relative risk 10.3, 95% confidence interval 6.7 to 16.0, P<0.001). There was considerable variation in the rates of severe or moderate disability in children infected with different organisms.ConclusionThe long term consequences of having meningitis during the first year of life are significant: 32 of 1717 (1.8%) children died within five years. Not only did almost a fifth of children with meningitis have a permanent, severe or moderately severe disability, but subtle deficits were also more prevalent.

What is already known on this topic

Meningitis in infancy is associated with important long term consequencesThere is considerable variation in outcome depending on which organism caused the infection

What this study adds

This follow up study of 1717 children who had meningitis in infancy found that they had a 10-fold increase in risk of severe or moderate disabilities at age 5 years compared with children in the control groupThe outcome of having meningitis was associated with the age at infection, and children who had meningitis in the neonatal period were more likely to have health and development problems than those older than 1 monthSubtle deficits, such as middle ear disease and visual and behavioural problems, were more prevalent among children who had had meningitis in infancy     

Longitudinal association of maternal attempt to lose weight during the postpartum period and child obesity at age 3 years

The effect of maternal attempt to lose weight during the postpartum period on later child weight has not been explored. Among 1,044 mother-infant pairs in Project Viva, we estimated longitudinal associations of maternal attempt to lose weight during the postpartum period with child weight and adiposity at age 3 years and examined differences in associations by type of weight loss strategy used. Using covariate-adjusted linear and logistic regression models, we estimated associations before and after adjusting for maternal weight-related variables including prepregnancy BMI. At 6 months postpartum, 53% mothers were trying to lose weight. At age 3 years, mean (s.d.) child BMI z-score was 0.44 (1.01) and 8.9% of children were obese. Children whose mothers were trying to lose weight at 6 months postpartum had higher BMI z-scores (0.30 (95% confidence interval (CI) 0.18, 0.42)) and were more likely to be obese (3.0 (95% CI 1.6, 5.8)) at 3 years of age. Addition of maternal prepregnancy BMI to the models attenuated but did not eliminate the associations seen for BMI z-score (0.24 (95% CI 0.12, 0.36) and obesity (2.4 (95% CI 1.2, 4.7)). Attempting to lose weight by exercising alone was the only weight loss strategy that consistently predicted higher child BMI z-score (0.36 (95% CI 0.14, 0.58)) and odds of obesity (6.0 (95% CI 2.2, 16.5)) at age 3 years. In conclusion, we observed an association between maternal attempt to lose weight at 6 months postpartum, particularly through exercise alone, measured using a single item and child adiposity at age 3 years. This association should be thoroughly examined in future studies.     

Genetic risk score predicting risk of rheumatoid arthritis phenotypes and age of symptom onset

Background

Cumulative genetic profiles can help identify individuals at high-risk for developing RA. We examined the impact of 39 validated genetic risk alleles on the risk of RA phenotypes characterized by serologic and erosive status.

Methods/Principal Findings

We evaluated single nucleotide polymorphisms at 31 validated RA risk loci and 8 Human Leukocyte Antigen alleles among 542 Caucasian RA cases and 551 Caucasian controls from Nurses'' Health Study and Nurses'' Health Study II. We created a weighted genetic risk score (GRS) and evaluated it as 7 ordinal groups using logistic regression (adjusting for age and smoking) to assess the relationship between GRS group and odds of developing seronegative (RF− and CCP−), seropositive (RF+ or CCP+), erosive, and seropositive, erosive RA phenotypes. In separate case only analyses, we assessed the relationships between GRS and age of symptom onset.In 542 RA cases, 317 (58%) were seropositive, 163 (30%) had erosions and 105 (19%) were seropositive with erosions. Comparing the highest GRS risk group to the median group, we found an OR of 1.2 (95% CI = 0.8–2.1) for seronegative RA, 3.0 (95% CI = 1.9–4.7) for seropositive RA, 3.2 (95% CI = 1.8–5.6) for erosive RA, and 7.6 (95% CI = 3.6–16.3) for seropositive, erosive RA. No significant relationship was seen between GRS and age of onset.

Conclusions/Significance

Results suggest that seronegative and seropositive/erosive RA have different genetic architecture and support the importance of considering RA phenotypes in RA genetic studies.     

喀什市3～5岁维吾尔族、汉族儿童患龋情况及风险性评估

目的调查喀什市维吾尔族、汉族3~5岁儿童患龋情况及患龋风险因素的相关资料,建立儿童个体龋风险评估(caries risk assessment,CRA)模型,为当地儿童龋病风险性评估和制定综合防控计划提供样本及参考数据。方法采用分层、整群抽样的方式随机抽取喀什市3所幼儿园397名3~5岁健康儿童作为研究对象,进行口腔检查和龋风险评估。分别应用卡方检验、方差分析及Logistic回归分析方法对龋风险评估相关因素进行统计分析。结果 (1)喀什市3~5岁汉族与维吾尔族儿童分布在CAR低度组、中度组和高度组三组比较差异均有统计学意义(χ~2=8.055,P=0.018)。(2)汉族与维吾尔族儿童的龋在不同CAR分度组的差异均具有统计学意义(F1=47.46,P=0.000;F2=74.5,P=0.000)。(3)汉族和维吾尔族在龋风险评估各组之间的患龋率差异有统计学意义(χ~2_1=98.21,P=0.000;χ~2_2=154.89,P=0.000)。(4)多因素Logistic回归分析风险评估相关因素结果显示:年龄更大[OR=1.769,P=0.001]、母亲患有龋齿[OR=2.274,P=0.004]、经常用奶瓶和牛奶或果汁[OR=0.705,P=0.000]、经常吃零食[OR=4.825,P=0.000]是婴幼儿龋的危险因素;刷牙[OR=0.319,P=0.019]、辅助儿童刷牙[OR=0.305,P=0.002]是婴幼儿龋的保护因素。结论喀什市3~5岁儿童患龋情况严重,龋风险评估高的儿童占大多数,应加强口腔健康教育,开展多种防龋措施。     

Prenatal stress and balance of the child's cardiac autonomic nervous system at age 5-6 years

Objective

Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child.

Methods

Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12–20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80^th percentiles). Indicators of cardiac ANS in the offspring at age 5–6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions.

Results

2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p≥0.17). Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p≥0.07).

Conclusion

Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac ANS balance in the offspring, at least in rest, and at the age of five-six years.     

Persistence of specific bactericidal antibodies at 5 years of age after vaccination against serogroup B meningococcus in infancy and at 40 months

Background:

The multicomponent serogroup B meningococcal (4CMenB) vaccine induces antibodies against indicator strains of serogroup B meningococcus under various schedules. We investigated the persistence of antibodies in 5-year-old children 18–20 months after their last dose (at about 3.5 years of age).

Methods:

We assessed 5-year-old children who received the 4CMenB vaccine or a recombinant protein vaccine in a previous randomized trial. We also recruited 50 vaccine-naive 5-year-olds and administered 2 doses of 4CMenB to each child. We measured serum bactericidal antibody titres against 4 indicator strains of serogroup B meningococcus matched to each individual vaccine component and against 4 mismatched strains.

Results:

Of those who received the 4CMenB vaccine at 2, 4, 6, 12 and 40 months (n = 16), the percentage with protective antibody titres (≥ 1:4) at 60 months ranged from 44% to 88% against matched strains and from 13% to 81% against mismatched strains. Loss of protective titres was also observed for those who received the 4CMenB vaccine at 12, 40 and 42 months (n = 5) (80%–100% against matched strains, 60%–100% against mismatched strains) or at 40 and 42 months (n = 29) (31%–100% against matched strains, 41%–81% against mismatched strains). Administering the 4CMenB vaccine to 5-year-old children yielded protective titres against matched strains in 92%–100% and against mismatched strains in 59%–100%. The majority of these children reported injection-site pain (40/50 [80%] after dose 1, 39/46 [85%] after dose 2) and erythema (47/50 [94%] and 40/46 [87%], respectively); rates of fever were low (5/50 [10%] and 2/46 [4%], respectively).

Interpretation:

Waning of immunity by 5 years of age occurred after receipt of the 4CMenB vaccine in infancy, even with an additional booster at 40 months. The 4CMenB vaccine is immunogenic and was fairly well tolerated by 5-year-old children, although injection-site pain was noteworthy. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01027351","term_id":"NCT01027351"}}NCT01027351The multicomponent serogroup B meningococcal (4CMenB) vaccine is licensed in the European Union, Australia and Canada to prevent serogroup B meningococcal disease. It was developed using “reverse vaccinology,” in which candidate antigens were identified by interrogating the whole meningococcal genome.¹ The 4CMenB vaccine consists of 3 surface proteins (factor H binding protein [fHbp], Neisseria adhesin A [NadA] and Neisseria heparin-binding antigen [NHBA]), along with a fourth component, the outer membrane vesicle, which acts as both antigen and adjuvant.¹Group B meningococcal disease is a potentially devastating condition, with an average case fatality rate of 5.2% (data for England and Wales²), and over a third of survivors are left with measurable functional deficits.³ The incidence of laboratory-confirmed cases is about 1 per 100 000 population in England⁴ and 0.33 per 100 000 population in Canada.⁵ The recommendation of the United Kingdom Joint Committee on Vaccination and Immunisation that the 4CMenB vaccine be introduced into the routine UK immunization schedule should, if implemented, lead to a reduction in this morbidity and mortality.⁶ Data on the persistence of antibody responses following infant or toddler immunization, and after subsequent boosting, remain limited yet will be important for guiding implementation of this recommendation.We present here the results of a follow-on study investigating the persistence of antibodies 18–20 months after the last dose in 5-year-old children previously immunized under a variety of schedules with 4CMenB vaccine or another investigational vaccine (recombinant protein serogroup B meningococcal [rMenB] vaccine), which lacks the outer membrane vesicle component of the 4CMenB vaccine. Since the original infant study,⁷ 4CMenB vaccine has emerged as the preferred vaccine, because addition of the outer membrane vesicle component improves the breadth of strain coverage;⁸ however, the extension study continued follow-up for all of the original children, and all results are therefore presented here.     

Age at arrival and risk of obesity among US immigrants

Although immigrants are a rapidly growing subgroup, little is known about overweight/obesity among the foreign-born in the United States, especially regarding the effect of age at arrival. This study determined whether overweight/obesity prevalence is associated with age at arrival of immigrants to the United States. We analyzed data on 6,421 adult immigrants from the New Immigrant Survey (NIS), a study that is nationally representative of adult immigrants with newly acquired legal permanent residence (LPR). Multiple regression analyses tested the effects of duration of residence and age at arrival on overweight/obesity, defined by BMI of > or = 25 kg/m(2), and self-reported dietary change score. We found the relationship between duration of residence and overweight/obesity prevalence varied by age at arrival (P < 0.001). Immigrants < or = 20-years old at arrival who had resided in the United States > or = 15 years were 11 times (95% confidence interval: 5.33, 22.56) more likely to be overweight/obese than immigrants < 20-years old at arrival who had resided in the United States < or = 1 year. By comparison, there was no difference in overweight/obesity prevalence by duration among immigrants who arrived at >50 years of age. Higher self-reported dietary change is also associated with overweight/obesity. In conclusion, immigrants younger than 20 at arrival in the United States may be at higher risk of overweight/obesity with increasing duration of residence than those who arrive at later ages. Obesity prevention among young US immigrants should be a priority.     

ICDs at higher age and clinical risk factors

Background

The implantable cardioverter defibrillator (ICD) is effective in preventing sudden cardiac death. However, in elderly patients (aged 75 years or older) the role of ICDs is still not well-defined and controversial.

Methods

We retrospectively analysed all clinical and survival data of all ICD patients who were ≥75 years at the date of implantation in the Erasmus MC, Rotterdam, the Netherlands and the University Hospital, Basel, Switzerland. Kaplan-Meier survival analysis was performed, and mortality predictors were identified. Mortality of the cohort was compared with a random sample of patients aged 60–70 years originating from the same database and to an age- and sex-matched cohort of Dutch persons.

Results

The study cohort consisted of 179 patients aged 75 years or older who were implanted between February 1999 and July 2008. The median follow-up time was 2.0 (IQR 2.8) years. Survival rates after 1, 2 and 3 years were 87, 82, 75 %, respectively. Survival was similar for primary and secondary prevention. Mortality in this study population could be predicted by combining four clinical risk factors: QRS duration >120 ms, NYHA class > II, renal failure and atrial fibrillation (AF). Survival was worse compared with the group of ICD patients aged 60–70 years and to the age- and sex-matched group of elderly persons. However, survival was not significantly worse when comparing elderly ICD patients without additional risk factors to the general population.

Conclusions

Elderly patients still have an acceptable survival probability independent of prevention indication, certainly if there are no additional clinical risk factors. The presence or absence of additional clinical risk factors should be taken into account when making the decision for implantation, since they strongly correlate with survival.     

Sea growth, smolt age and age at sexual maturation in Atlantic salmon

Relationships between growth at sea, smolt size and age at sexual maturation of Atlantic salmon Salmo salar were tested. The fish were offspring of brood stocks sampled in eight Norwegian rivers at latitudes between 59° and 70° N, hatchery reared and released at smolting at the mouth of the River Imsa (59° N). Smolt size influenced the subsequent growth rate of Atlantic salmon. The larger the fish were at release, the slower the yearly length increment at sea. Mean sea age at sexual maturity, measured as proportion of the returning adults attaining sexual maturity at sea age 2 years, was significantly correlated with mean growth rate during the first year at sea and mean smolt size ( r ²= 0·74, P < 0·001). Fish attaining maturity at a relatively high sea age were more fast growing during their first year at sea than those maturing at a younger age. The results indicate that high sea age at sexual maturation is a population-specific characteristic and associated with high early growth rate at sea.     

Early colonization with a group of Lactobacilli decreases the risk for allergy at five years of age despite allergic heredity

Background

Microbial deprivation early in life can potentially influence immune mediated disease development such as allergy. The aims of this study were to investigate the influence of parental allergy on the infant gut colonization and associations between infant gut microbiota and allergic disease at five years of age.

Methods and Findings

Fecal samples were collected from 58 infants, with allergic or non-allergic parents respectively, at one and two weeks as well as at one, two and twelve months of life. DNA was extracted from the fecal samples and Real time PCR, using species-specific primers, was used for detection of Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, Clostridium (C.) difficile, a group of Lactobacilli (Lactobacillus (L.) casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus. Infants with non-allergic parents were more frequently colonized by Lactobacilli compared to infants with allergic parents (p = 0.014). However, non-allergic five-year olds acquired Lactobacilli more frequently during their first weeks of life, than their allergic counterparts, irrespectively of parental allergy (p = 0.009, p = 0.028). Further the non-allergic children were colonized with Lactobacilli on more occasions during the first two months of life (p = 0.038). Also, significantly more non-allergic children were colonized with B. bifidum at one week of age than the children allergic at five years (p = 0.048).

Conclusion

In this study we show that heredity for allergy has an impact on the gut microbiota in infants but also that early Lactobacilli (L. casei, L. paracasei, L. rhamnosus) colonization seems to decrease the risk for allergy at five years of age despite allergic heredity.     

Greater efficiency of human growth hormone therapy in children below five years of age with growth hormone deficiency. A 5-year follow-up study

The effect of human growth hormone (hGH) therapy was studied in 39 prepubertal children with growth hormone deficiency (24 with isolated growth hormone deficiency; 15 with multiple pituitary hormone deficiencies) who had been treated for 2-5 years. They were divided into two groups according to age at the initiation of therapy: group A (n = 21), 0.7-4.8 years (mean chronological age, 2.9 +/- 1.4 years, and bone age, 1.2 +/- 0.9 years); group B (n = 18), 5.2-9.9 years (mean chronological age, 7.4 +/- 1.3 years, and bone age, 4.0 +/- 1.5 years). hGH was given at an initial dose of 2-4 IU 3 times/week, raised to 4-6 IU 3 times/week when growth velocity slowed. In the first year, the mean height SDS gain was 1.7 for group A and 0.8 for group B, and in the second year, 1.1 and 0.1, respectively. Subsequently this remained consistent. Bone age advancement was significantly slower in the younger group (3.8 vs. 5.8 years during 5 years) although this group had a greater catch-up response to therapy. It is concluded that hGH therapy is significantly more effective in achieving normalization of height when treatment is initiated at an early age.     

Morphofunctional characteristics of microcirculation in the skin of girls 5-17 years of age

In 261 girls year-to-year morphofunctional transformations of spatial composition of the skin microcirculatory bed have been studied at rest and after a dynamic local load. By means of biomicroscopy main regularities in development of the skin capillary network have been revealed in the nail torus in the postnatal ontogenesis. Formation of the microvessels reactivity during various age periods and maturation of mechanisms of the compensatory-adaptive reactions are connected with formation of the definitive composition of the microcirculatory bed, that in girls corresponds to 11-12 years. Qualitative transformations in the skin capillary network bring certain quantitative changes in the structural microcirculatory parameters--increasing diameter of microvessels and increasing density of functioning capillaries.     

Association between different growth curve definitions of overweight and obesity and cardiometabolic risk in children

Background:

Overweight and obesity in young people are assessed by comparing body mass index (BMI) with a reference population. However, two widely used reference standards, the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) growth curves, have different definitions of overweight and obesity, thus affecting estimates of prevalence. We compared the associations between overweight and obesity as defined by each of these curves and the presence of cardiometabolic risk factors.

Methods:

We obtained data from a population-representative study involving 2466 boys and girls aged 9, 13 and 16 years in Quebec, Canada. We calculated BMI percentiles using the CDC and WHO growth curves and compared their abilities to detect unfavourable levels of fasting lipids, glucose and insulin, and systolic and diastolic blood pressure using receiver operating characteristic curves, sensitivity, specificity and kappa coefficients.

Results:

The z scores for BMI using the WHO growth curves were higher than those using the CDC growth curves (0.35–0.43 v. 0.12–0.28, p < 0.001 for all comparisons). The WHO and CDC growth curves generated virtually identical receiver operating characteristic curves for individual or combined cardiometabolic risk factors. The definitions of overweight and obesity had low sensitivities but adequate specificities for cardiometabolic risk. Obesity as defined by the WHO or CDC growth curves discriminated cardiometabolic risk similarly, but overweight as defined by the WHO curves had marginally higher sensitivities (by 0.6%–8.6%) and lower specificities (by 2.6%–4.2%) than the CDC curves.

Interpretation:

The WHO growth curves show no significant discriminatory advantage over the CDC growth curves in detecting cardiometabolic abnormalities in children aged 9–16 years.Pediatric obesity is associated with dyslipidemia, insulin resistance and elevated blood pressure.^1–6 Thus, accurately identifying children with obesity is crucial for clinical management and public health surveillance.Lipid screening is recommended for young people who are overweight,^7,8 but studies show that estimates of the prevalence of overweight and obesity are 1%–7% lower using the growth curves of the Centers for Disease Control and Prevention (CDC) versus those of the World Health Organization (WHO).^9–11 Although the CDC and WHO definitions of overweight and obesity both use approximations of overweight and obese values of body mass index (BMI) when children reach 19 years of age, the CDC growth curves use data from more recent samples of young people.^12,13 Given the recent rise in the prevalence of obesity among young people, using a heavier reference population may lead to fewer children being identified as overweight and obese, and an identical BMI value may not trigger a clinical investigation.⁷ The Canadian Paediatric Society, in collaboration with the College of Family Physicians of Canada, Dietitians of Canada and Community Health Nurses of Canada, recently recommended that physicians switch from the CDC to the WHO growth curves for monitoring growth for Canadian children aged 5–19 years.¹⁴ This is a major change for health providers caring for the estimated 8 million children in Canada.¹⁵Understanding how using the different growth curves affects the identification of adverse cardiometabolic risk profiles is essential for the appropriate management of overweight and obesity among young people. Thus, our objectives were to assess whether the association between BMI percentiles and cardiometabolic risk differs between the definitions of overweight and obesity based on the WHO and CDC growth curves, and to compare the sensitivity and specificity of these definitions in detecting cardiometabolic risk.