Plasticity in developmental programming has evolved to provide the best chances of survival and reproductive success to the organism under changing environments. The window of developmental ...plasticity extends from preconception to early childhood, and involves epigenetic responses to environmental changes, which exert their effects during life history phase-transitions. This review provides a comprehensive presentation of translational epigenetics as it pertains to child health, growth, and maturation. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs.
Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developmental origins of health and disease and life-history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies in response to local ecological and/or social conditions. The window of developmental plasticity extends from preconception to early childhood and involves epigenetic responses to environmental changes, which exert their effects during life-history phase transitions. These epigenetic responses influence development, cell- and tissue-specific gene expression, and sexual dimorphism, and, in exceptional cases, could be transmitted transgenerationally. Translational epigenetic research in child health is a reiterative process that ranges from research in the basic sciences, preclinical research, and pediatric clinical research. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs.
To evaluate gender differences in score on 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and Signals Of Functional Impairment (SOFI) and to relate these scores to ...radiographic joint destruction.
In all, 549 patients with early RA (62% women) from the BARFOT (for "Better Anti-Rheumatic FarmacOTherapy") study were included. At baseline, 1, 2 and 5 years DAS28, HAQ and SOFI scoring, and radiographs of hands and feet were performed. The radiographs were scored using the van der Heijde-Sharp score.
In women the DAS28 was significantly higher than in men due to higher scores for general health and tender joints. Likewise, HAQ and VAS pain were rated significantly higher in women. The SOFI score was worse in men during the first 2 years, depending on higher upper limb scores. Total Sharp score (TotSharp), erosion score and joint space narrowing score did not differ between the sexes at any time point. The DAS28 area under the curve (AUC) correlated significantly with TotSharp at 5 years in both genders (r = 0.316, r = 0.313) mainly owing to swollen joints and erythrocyte sedimentation rate (ESR). The SOFI AUC correlated significantly with TotSharp in women (r = 0.135 to 0.220) but not in men.
Despite a similar degree of radiographic joint destruction women had, compared with men, worse scores for DAS28 and HAQ, possibly due to higher pain perception and less muscular strength and perhaps because men overestimate their functional capacity.
Aim
To establish normal reference values for penile size in Nigerian newborn boys and to compare those values with standards from other populations.
Methods
A total number of 261 healthy newborn boys ...delivered at gestational ages of 28 weeks or more were enrolled in the study. Penile lengths and widths were measured within 72 h of birth.
Results
The mean (±SD) penile length in the 261 Nigerian males studied was 3.4 ± 0.48 cm, while the mean mid‐shaft diameter was 1.2 ± 0.14 cm. Compared with data from other populations, Nigerian newborn boys had similar penile sizes to those reported for US Caucasian boys (mean 3.4 cm), but significantly greater penile sizes than those reported for boys from China and Hong Kong (mean 3.0 and 3.1 cm, respectively; both p < 0.001). There was a slight, but significant, difference in size between Nigerian and Malaysian boys, with Malaysian boys having greater penile sizes (mean 3.5 cm; p < 0.05).
Conclusion
A Nigerian newborn with a penile length of <2.39 cm can be considered to have a micropenis.
Aim
This study aims to document secular differences in anthropometry (level and variability of weight, height, BMI) in two cohorts born around 1990 and 1974 and examined as young adults.
Methods
...Descriptive results are presented for the complete cohorts. The final analysis age‐matched the cohorts (mean, 18.8 years) and employed CDC z‐scores to compare means and distributions of weight, height and BMI.
Results
Z‐scores for weight, height and BMI were higher in later‐born (1990) boys, while in girls weight and height increased over this period without resulting in increased BMI. At the same time, in boys the BMI variances increased, confirming a simultaneous emergence of more overweight and more underweight. In girls, the BMI variance did not increase significantly. Sensitivity analyses, excluding subjects not born in Sweden, confirmed increasing BMI trends in boys.
Conclusion
This study documents that gender differences in the recent childhood obesity epidemic can also be observed in young Swedes as they enter adulthood. Comparing two cohorts of high school students born around 1974 or 1990, less favourable trends in weight status were seen in boys than in girls. Finally, secular increases in height, already observed earlier in the 20th century, continued in these more contemporary cohorts.
Intrauterine growth retardation, or being small for gestational age (SGA), has a life-long impact on a fetus's potential for development and survival. The incidence and relative risk of short stature ...in children born SGA were studied using a Swedish healthy full-term (37-43 wk of gestation) singleton birth cohort (n = 3650) from Göteborg, followed from birth to final height at about 18 y of age. Most infants, defined as SGA on the basis of a birth length less than -2 standard deviation scores (SDS) below the mean (SGAL infants), showed catch-up growth during the first 6 mo after birth, and by 1 y only 13.4% of the SGAL infants were below -2 SDS in height. This percentage decreased further during childhood to reach a value of 7.9% at 18 y of age. Although most SGAL infants have catch-up growth in early life, those who do not constitute 21% of short, prepubertal children. At 18 y of age, 22% of the total short population were short at birth (< -2 SDS), whereas when birth weight was used to define SGA, only 14% of the 18-y-old short population were light at birth. SGAL infants were found to have a 7-fold higher risk for short final stature (relative risk, 7.1; 95% confidence interval, 3.7-13.6) in comparison with the non-SGAL group. In a multiple linear regression analysis, both birth length and mid-parental height were found to be significantly related to the magnitude of catch-up growth from birth to 18 y of age. Neither the length of gestation nor birth weight showed such a relationship. It is concluded that the vast majority (> 86%) of "healthy" full-term singleton SGAL infants will achieve catch-up in height during the first 6-12 mo of life, and that this is almost independent of whether birth weight or birth length is used to define SGA. Of the remaining, non-catch-up SGA infants, about 50% remain short in final height, and thus constitute a high risk group for persistent short stature.
To evaluate if remission induced by low-dose prednisolone during the first 2 years of rheumatoid arthritis (RA) in the BARFOT glucocorticoid (GC) study had a sustained effect on radiological damage ...for a total of 4 years.
A total of 150 of 211 eligible patients with RA who had been randomised to the 7.5 mg prednisolone group (P) or no prednisolone group (NoP) in addition to the initial disease-modifying antirheumatic drugs were included. Radiographs of hands and feet were scored using the Sharp-van der Heijde scoring method. A patient was considered to be in remission if the 28-joint count disease activity score was <2.6.
Mean (SD) age was 53 (14) and 57 (12) years for the patients in the P and NoP groups, respectively. 64% were female, 64% rheumatoid factor positive, and disease duration at baseline was 6 months. At 2 years the proportion of patients in remission in the P and NoP groups was 55 vs 30%, p = 0.003. Longitudinal analysis showed that over the entire course of the disease, patients on prednisolone had a higher probability of being in remission. Patients in remission at 2 years, compared with those not in remission, had significantly lower total Sharp score, erosion score and joint space narrowing score at 2 and 4 years. The changes in bone mineral density during the 4 years did not differ between those in remission and those with active disease, and were similar in the two treatment groups.
Prednisolone 7.5 mg daily in addition to disease-modifying anti-rheumatic drugs increases the rate of remission in patients with early RA, which has a beneficial and sustained effect on radiological damage.
This study aimed to update growth reference values for height, weight and head circumference in order to reflect the changes in body size in the Swedish population during the past two decades. The ...data came from a large longitudinal growth study on 3650 full-term healthy Swedish children who were born between 1973 and 1975. All of these 1801 girls and 1849 boys had longitudinal data for height and weight from birth to final height. Comparison with previous Swedish growth reference values based on children born between 1955 and 1958 revealed that there have been secular changes in body size. For instance, at 18 y of age, the updated height and weight reference values are 180.4 cm for males and 167.7 cm for females, i.e. 1.9 cm taller and 5.7 kg heavier for males and 2.3 cm taller and 3.4 kg heavier for females compared with the previous reference values.
These new growth reference values provide current national standards for growth monitoring and evaluation since the year 2000.
Aim
To relate height, weight and body mass index (BMI) of prepubertal children in Sagamu, Nigeria, to parental socio‐economic class (SEC).
Methods
Cross‐sectional study of 1606 children aged ...5–11 years from eight public and eight private primary schools. Height, weight and BMI from 1557 prepubertal children were standardized using two references: US‐CDC birth cohorts 1929–1974 and Swedish birth cohort 1974.
Results
Children in private schools were taller and heavier than those in public schools (p < 0.0001). Most children (73.2%) belonged to lower SEC, 17.6% to middle and 9.2% to upper. HeightSDS, weightSDS and BMISDS increased with increasing parental SEC. Upper SEC children were taller and heavier with higher BMIs than those from lower SEC (p < 0.0001). HeightSDS, weightSDS and BMISDS were below ‘0’ in all SEC and gender groups (all p < 0.002). Younger children were taller and heavier than the older (p < 0.0001).
Conclusion
Fathers/mothers with higher education/occupation had taller and heavier children with higher BMI than other groups. Children in private schools were taller and heavier than children in public schools. Disparities in parental SEC still constrain optimal child growth in Nigeria: whereas height and weight of children of upper SEC were close to the US‐CDC29–74 reference mean, they were still below Swedish74 reference mean representing more optimal growth.
The aim of this prospective, longitudinal, controlled study is to describe the long-term safety and efficacy of growth hormone (GH) administration on craniofacial morphology in boys with short ...stature. Forty-six boys, who started GH treatment at the Department of Paediatrics Göteborg Paediatric Growth Research Centre, were consecutively included in the study. Twenty-five boys were classified as growth hormone-deficient (GHD) and 21 as idiopathic short stature (ISS). The patients were injected with 33 (n = 31) or 67 (n = 15) μg GH/kg body weight/day. The mean age at the start of treatment was 11.8 years standard deviation (SD) 1.7. To assess craniofacial growth, standard lateral cephalometric radiographs were obtained at the start of GH treatment, annually during 4 years, and at the end of GH treatment or when growth was less than 1 cm/year. The mean follow-up period was 6.4 years (SD 1.4). Growth changes were compared with boys from a semi-longitudinal reference group of 130 healthy subjects, 7–21 years of age. t-tests for independent and paired samples and multiple regression analysis were applied. Age- and gender-specific standard deviation scores for the cephalometric variables were calculated. Repeated measures analysis of variance was used to identify significant covariates over time, such as low/high GH dose and GHD/ISS and orthodontic treatment. During the study period, eight (out of 40) boys were treated with fixed orthodontic appliances, three with functional appliances (activators), and three with other appliances (plates and lingual arches). During GH treatment period, an overall enhancement in growth of the facial skeleton was observed in boys with short stature. The changes induced by GH yielded a more prognathic growth pattern, a more anterior position of the jaws in relation to the cranial base, and increased anterior rotation of the mandible. The mandibular corpus length and anterior face height of the GH-treated boys were greater at the end of the study compared with the boys in the reference group. No differences in growth response were noted either between the GHD and ISS boys or between those treated with either 33 (low dose) or 67 (high dose) μg GH/kg body weight/day. The only change that remained significantly correlated with orthodontic treatment was the alteration in mandibular ramus height, showing a larger change in the boys who had not undergone orthodontic therapy. The findings of this study demonstrate that GH treatment has a favourable influence on the craniofacial growth pattern of boys with short stature without acromegalic features.
Objective: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of ...the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting radiographic outcome.
Methods: In a cohort (n = 1589) of consecutive, newly diagnosed patients with RA, 112 cases with RN at inclusion (7%) were identified. Each case was compared to two age- and sex-matched controls without nodules from the same cohort. Radiographs of the hands and feet were performed at inclusion, after 1, 2, and 5 years and scored according to the modified Sharp van der Heijde Score (SHS; range 0-448).
Results: Fifty-two cases with RN and 139 controls without RN had available radiographs at baseline and after 5 years. Cases were more often rheumatoid factor (RF) positive and anti-cyclic citrullinated peptide (anti-CCP) positive, and had higher disease activity and radiographic damage scores at baseline (7.9 vs. 2.5). After 5 years, there was more extensive radiographic damage among the cases (mean SHS progression 21.7 vs. 13.5). In bivariate analysis, positive RF, positive anti-CCP, SHS, and RN were strong baseline predictors for radiographic progression up to 5 years. In multivariate analysis, positive anti-CCP and SHS at baseline were independently associated with radiographic progression.
Conclusion: The presence of RN at baseline is a marker of extra-articular involvement and severe disease, and a predictor of subsequent joint damage.
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