Raphael Fraser

Growth, body composition, and the onset of puberty: longitudinal observations in Afro-Caribbean children

CONTEXT Childhood growth and body composition may influence the onset of puberty. OBJECTIVE We examined the effects of birth size, growth rates throughout childhood, and body composition on the onset of puberty in Afro-Caribbean children. DESIGN AND SETTING This was a longitudinal birth cohort study (the Vulnerable Windows Cohort Study) in Jamaica. SUBJECTS AND MEASUREMENTS The anthropometry (weight, height, skinfold measurements, and waist circumference) of 259 children was measured at birth, at 6 wk, every 3 months to 2 yr, and then every 6 months. Tanner staging for puberty and orchidometry were performed every 6 months starting at approximately age 8 yr. Bioelectrical impedance was done at age 11 yr. RESULTS In the girls, thelarche, pubarche, and menarche occurred at median ages of 8.8, 9.9, and 12.0 yr, respectively. Pubarche in boys occurred at a median age of 11.3 yr when the median testicular volume was 2.8 ml. Faster weight gain during infancy (age 0-6 months) and childhood, but not birth size, was associated with more advanced puberty (P values <0.05). Fat mass at age 8 yr was associated with more advanced puberty (P values <0.001) in both sexes. At age 11 yr, lean mass, but not fat mass, was associated with more advanced puberty (P values <0.001). CONCLUSION These data support the hypothesis that faster growth throughout childhood, especially with fat mass accretion, is associated with more advanced puberty apart from menarche. With the onset of puberty, lean mass accretion significantly increases.

Newborn sickle cell disease screening: the Jamaican experience (1995–2006):

Objectives: The aim of this study was to evaluate the existing newborn sickle haemoglobinopathy screening programme in Jamaica. Methods: A retrospective analysis of infants screened during the period 8 November 1995 to 22 July 2006 was performed. Patient data for analyses was restricted to patients with homozygous (Hb SS) sickle cell disease. Published data from the Jamaican Sickle Cell Cohort Study was used to make comparisons with the study sample. Results: The study sample consisted of 435 patients with Hb SS disease. Acute chest syndrome was the most common clinical (non-death) event accounting for ∼50% of all events. Acute splenic sequestration, no longer a significant cause of mortality, was responsible for ∼32% of clinical events. Seven deaths (1.8%) occurred during the study period compared with 17.6% to the same age in the Jamaican Sickle Cell Cohort Study. There was a lower proportion of hospital admissions and episodes of serious illness in the study group compared with controls. Conclusions: Survival estimates for the study sample showed improvement compared with the Jamaican Sickle Cell Cohort Study. This study continues to demonstrate the benefits of, and as such shows support for, newborn screening and early interventions in sickle cell disease. In addition, it highlights some of the areas for continued focus and research development. Although the current system is providing an essential and beneficial service, the study emphasizes the need for newborn screening programmes to be comprehensive care systems to be fully effective.

Venous incompetence, poverty and lactate dehydrogenase in Jamaica are important predictors of leg ulceration in sickle cell anaemia

Clinical features and potential risk factors for chronic leg ulceration (duration >6 months) in homozygous sickle cell (SS) disease were examined in 225 subjects in the Jamaican Cohort Study. Potential risk factors included the number of HBA genes, steady state haematology, serum lactate dehydrogenase (LDH), venous incompetence, and socio‐economic status. Chronic ulcers occurred in 53 subjects with the highest risk of ulcer development at 18 years. The prevalence was 29·5% and cumulative incidence 16·7%. Gender or α‐thalassaemia trait did not affect the incidence of leg ulcer. Ulceration was associated with lower haemoglobin, red cell count, fetal haemoglobin, and socio‐economic status and higher reticulocyte count, platelet count, serum LDH and venous incompetence in univariate analyses. Venous incompetence [Hazard Ratio (HR) 3·0–4·0] and socio‐economic status (HR 0·8) were most consistently associated with leg ulceration on multivariate analysis. Regression models incorporating serum LDH suggested this to be a stronger predictor than haematological indices. The prevalence of ulcers at 30% is less than previous estimates in Jamaica, probably reflecting the lack of ascertainment bias in the Cohort Study, and also a real secular decline. In Jamaica, venous incompetence, low socio‐economic status, and high serum LDH were the strongest predictors of chronic ulceration.

Higher Rates of Hemolysis Are Not Associated with Albuminuria in Jamaicans with Sickle Cell Disease

Background Albuminuria is a marker of glomerular damage in Sickle Cell Disease (SCD). In this study, we sought to determine the possible predictors of albuminuria in the two more prevalent genotypes of SCD among the Jamaica Sickle Cell Cohort Study participants. Methods An age-matched cohort of 122 patients with HbSS or HbSC genotypes had measurements of their morning urine albumin concentration, blood pressure, body mass index, haematology and certain biochemistry parameters done. Associations of albuminuria with possible predictors including hematological parameters, reticulocyte counts, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels were examined using multiple regression models. Results A total of 122 participants were recruited (mean age 28.6 years ±2.5 years; 85 HbSS, 37 HbSC). 25.9% with HbSS and 10.8% with HbSC disease had microalbuminuria (urine albumin/creatinine ratio  =  30–300 mg/g of creatinine) whereas 16.5% of HbSS and 2.7% of HbSC disease had macroalbuminuria (urine albumin/creatinine ratio>300 mg/g of creatinine). Mean arterial pressure, hemoglobin levels, serum creatinine, reticulocyte counts and white blood cell counts were statistically significant predictors of albuminuria in HbSS, whereas white blood cell counts and serum creatinine predicted albuminuria in HbSC disease. Both markers of chronic hemolysis, i.e. AST and LDH levels, showed no associations with albuminuria in either genotype. Conclusions Renal disease, as evidenced by excretion of increased amounts of albumin in urine due to a glomerulopathy, is a common end-organ complication in SCD. It is shown to be more severe in those with HbSS disease than in HbSC disease. Rising blood pressure, lower hemoglobin levels and higher white blood cell counts are hints to the clinician of impending renal disease, whereas higher rates of hemolysis do not appear to play a role in this complication of SCD.

Developmental origins of cardiovascular risk in Jamaican children: The Vulnerable Windows Cohort Study

Both intra-uterine and early childhood development contribute to the risk of developing CVD in adult life. We therefore evaluated the maternal, placental, fetal, birth, infant and childhood determinants of cardiovascular risk in a cohort of Afro-Jamaican children. The Vulnerable Windows Cohort is a longitudinal survey of 569 mothers and their offspring recruited from the first trimester. The offsprings anthropometry was measured at birth, at 6 weeks, every 3 months to 1 year and then every 6 months. At mean age 11.5 years, fasting blood was sampled for glucose, insulin and lipids. Analyses were confined to 296 women and their offspring who had complete data. Waist circumference (WC) was related to maternal weight and BMI, placental weight and to the size of the offspring in utero, at birth and the rate of growth in childhood (P < 0.05). Total cholesterol, TAG and glucose concentrations were unrelated to maternal, placental, fetal, neonatal and childhood measurements. Fasting insulin and homeostasis model assessment of insulin resistance were related to maternal weight and BMI (P < 0.05), but not after adjusting for WC. HDL-cholesterol was inversely related to placental and birth weight, and inversely related to weight and BMI throughout childhood (P < 0.001), but not after adjusting for WC. Systolic blood pressure was directly related to maternal weight, childs height, weight and BMI (P < 0.05), but not after adjustment for WC. Systolic blood pressure and fasting glucose concentration were inversely related to birth weight in boys but directly associated in girls. We concluded that maternal anthropometry during pregnancy, fetal size, and childhood growth rate contribute to cardiovascular risk factors in childhood.

Hb S-β-Thalassemia: Molecular, Hematological and Clinical Comparisons

Clinical and hematological features are presented for 261 patients with identified β-thalassemia (β-thal) mutations. Mutations causing Hb S [β6(A3)Glu→Val]-β0-thal were IVS-II-849 (A>G) in 44%, frameshift codon (FSC) 6 (–A) in 14%, Hb Monroe [β30(B12)Arg→Thr] in 14%, and IVS-II-1 (G>A) in 10%. Mutations causing Hb S-β+-thal with 14-25% Hb A (type III) were –29 (A>G) mutation in 60%, –88 (C>T) in 22% and the polyadenylation signal site (polyA) (T>C) mutation in 14%, and in Hb S-β+-thal with 1-7% Hb A (type I), all had the IVS-I-5 (G>C) mutation. Hematologically, only minor differences occurred between the four Hb S-β0-thal mutations, but among the three mutations causing Hb S-β+-thal type III, levels of Hb A2, Hb F, hemoglobin (Hb), MCV and MCH were highest in the –88 and lowest in the polyA mutations. Clinically, Hb S-β0-thal and Hb S-β+-thal type I were generally severe, and Hb S-β+-thal type III disease with the –88 mutation was milder than that caused by the polyA mutation.

Quality of life of patients with epilepsy living in Kingston, Jamaica

Quality of life in epilepsy has not been documented in the English-speaking Caribbean. The aim of this study was to explore the quality of life of persons with epilepsy (PWE) living in Jamaica and determine the impact of socioeconomic factors by examining two socially distinct groups in semiprivate (Epilepsy Centre of Jamaica) and public (Kingston Public Hospital) outpatient clinics. One hundred nine consecutive patients were interviewed. Quality of life was assessed using the Quality of Life in Epilepsy-31 inventory (QOLIE-31). Both groups were matched for gender, epilepsy syndrome, epilepsy duration, and number of antiepileptic drugs. Predictors of quality of life included number of antiepileptic drugs (P=0.039), epilepsy duration (P<0.05), and functional status (P<0.001). Neither seizure frequency nor socioeconomic status predicted QOLIE-31 scores. Mean QOLIE-31 total score (61.57 vs 49.2, P<0.001) and QOLIE-31 subscale scores (with the exception of the Seizure Worry score [53.8 vs 48.2, P=0.08]) were significantly higher than the corresponding t scores. The QOLIE-31 can reliably be used in Jamaica. Our findings suggest Jamaicans living with epilepsy perceive themselves as having a better than expected quality of life.

Seizures in the Jamaica cohort study of sickle cell disease

Although there is some evidence that epilepsy is more common in Sickle Cell Disease (SCD), we sought to establish the incidence rates, risk factors for and specific types of seizures in a SCD cohort followed from birth, and how seizure occurrence affects morbidity and mortality. We examined all records of persons in the Jamaica cohort Study of Sickle Cell Disease (JSSCD) clinically identified as having experienced a seizure during their lifetime. At first presentation, seizures were classified as Febrile Convulsion, Acute Symptomatic Seizure or Single Unprovoked Seizure. The seizure classification was revised to include Epilepsy if seizures recurred. Thirty‐eight persons in the JSSCD (N = 543) were identified with seizures. The 5‐year cumulative incidence of febrile convulsions was 2·2%. The incidence rate of epilepsy (all genotypes) was 100/100 000 person‐years, 139/100 000 for the SS genotype. Despite limited availability of diagnostic investigations, clinical seizures were associated with increased all‐cause mortality. Male gender (Odds Ratio [OR]: 4·0[95% confidence interval [CI]; 1·03–20·0]) and dactylitis in childhood (OR: 17·4 [95% CI; 4·82–62·85]) were associated with increased risk of developing epilepsy. Epilepsy in persons with SCD is 2–3 times more common than in non‐sickle populations and is associated with increased all‐cause mortality in all sickle cell genotypes.

Predictors of physical activity energy expenditure in Afro-Caribbean children

Background/Objectives:We hypothesized that maternal size during pregnancy and birth size are determinants of childhood physical activity energy expenditure (PAEE). Also, childhood PAEE is inversely related to adiposity and levels of cardiovascular risk factors.Subjects/Methods:The Vulnerable Windows Cohort Study is a longitudinal observational study of 569 Afro-Jamaican mothers recruited from the first trimester and their offspring. Anthropometry, bioelectrical impedance, PAEE (using the Actical monitor) and cardiovascular risk factors (blood pressure, fasting glucose, insulin and lipids) were measured in 124 boys and 160 girls at a mean age of 13.2 years.Results:Boys had more fat-free mass (FFM) and expended more energy than girls (12.3±3.3 vs 9.6±2.8 kcal/kg/day; P<0.001). Maternal weight was associated with childs PAEE (r=0.29; P<0.001). PAEE was not significantly associated with birth weight. Maternal weight, after adjusting for childs age and sex, was positively associated with the childs FFM, fat mass and %fat (P-values ⩽0.01). Age- and sex-adjusted PAEE was positively associated with FFM, fat mass and % fat (P-values <0.001), but not after adjusting for current weight. Age- and sex-adjusted PAEE was positively associated with triglycerides, insulin and systolic blood pressure (P-values <0.05), but not after adjusting for weight and height. PAEE was associated with fasting glucose after controlling for age, sex, weight and height (r=−0.12; P=0.02).Conclusions:Maternal size, but not birth weight, is a determinant of childhood PAEE. PAEE is not strongly associated with childhood body composition, but is inversely related to fasting glucose concentration.

The effect of earlier puberty on cardiometabolic risk factors in Afro-Caribbean children

Abstract An earlier onset of puberty is associated with increased cardiometabolic risk. We investigated whether this relation was independent of faster childhood growth or current size in an Afro-Caribbean birth cohort (n=259). Anthropometry was measured at birth and then 6-monthly. Tanner staging started at age 8 years. Cardiometabolic risk factors were measured at mean age 11.5 years. In boys, pubarchal stage and testicular size were associated with lower high-density lipoprotein cholesterol, higher systolic blood pressure, and higher homeostasis model assessment of insulin resistance score, but not after adjusting for current body mass index (BMI) or rate of growth (up to age 8 years). In girls, earlier menarche and greater breast development were associated with higher fasting glucose even after adjusting for current BMI or prior growth. Pubarchal stage was associated with systolic blood pressure, even after adjusting for current BMI and prior growth. We concluded that earlier puberty is independently associated with cardiometabolic risk in girls but not in boys.