Impact of early growth on blood pressure from childhood to adulthood: birth-twenty cohort

A thesis Submitted to the Faculty of Health Sciences, University of Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa 2016Background Childhood hypertension is of great concern parallel to the obesity epidemic and early manifestation of antecedents of primary hypertension like arteriosclerosis. Patterns of early growth are associated with spiraling rates of raised blood pressure (BP) in paediatric populations. However, not much is known about early growth and its effect on BP from childhood to early adulthood. This study hypothesizes early life growth is associated with BP from childhood to adulthood. Methods Data for this study came from a sample of black children from the Birth to Twenty cohort study of children born in Soweto, Johannesburg in 1990. Firstly, persistence of elevated BP between ages 5 and 18 was estimated from sex, anthropometry and BP measurements. Secondly, the association between socio-economic status (SES) change between infancy and adolescence computed from physical household assets and BP at 18 years of age was evaluated using multivariable analyses. Finally, longitudinal BP trajectories were identified using group-based trajectory modeling and multinomial models were used to assess the association of BW, RWG and RHG, and BP trajectories adjusted for several covariates. Results The prevalence of hypertension ranged between 8.4 to 24.4% and risk of maintaining the elevated BP status was almost 2-fold between ages 5 and 18 years: RRR: 1.60(95%CI: 1.29- 2.00). An upward social mobility was associated with a 5mmHg reduction in SBP (β: -4.85, 95%CI: - 8.22 - -1.48). Three distinct early patterns of BP development called trajectory groups were identified for SBP and diastolic BP (DBP) for each sex; namely: “lower”, “middle” and “upper.” A kilogram increase in birth weight (BW) reduced the odds of being in the middle compared to lower SBP trajectory (OR: 0.75, 95%CI: 0.58-0.96), while RWG in infancy was associated with a 4-fold increased odds of being in the upper vs lower SBP trajectory for boys (OR: 4.11, 95%CI: 1.25-13.51). In girls, relative weight gain (RWG) (OR: 1.63, 95%CI: 1.08-2.46; 1.77(1.22-2.56)) and relative height gain (RHG) (OR: 1.90, 95%CI: 1.27-2.86; 2.12(1.39-3.23)) in infancy and mid-childhood was associated with almost 2-fold increase in odds of being in the upper vs lower trajectory. The middle SBP trajectory in girls was predicted by RWG (OR: 1.33, 95%CI: 1.00-1.76) and RHG (OR: 1.58, 95%CI: 1.15-2.17) in infancy. DBP trajectories were significantly but inconsistently associated with RWG and RHG for boys and RWG in mid-childhood and infancy in girls for the middle and upper trajectories. Conclusions Distinct BP trajectories are established in childhood and persist into early adulthood. Improving SES throughout childhood may have a protective effect on BP. Policy recommendations around early identification of children with elevated BP accompanied by interventions targeted at optimal growth and interrupting the atypical BP trajectories may reduce the burden of disease attributed to hypertension, especially in girls.MT201

Improving viral load testing using a quality improvement approach in Blantyre, Malawi

Background Viral load (VL) testing coverage remains low particularly in resource limited countries despite recommendation by World Health Organization, and Malawi is no exception. A quality improvement (QI) approach was used to improve VL testing coverage from 27% to a target of 80% at an urban health facility in Malawi. Methods A QI study employing a time-series quasi-experimental design with no comparison group was conducted at Chilomoni health centre in Blantyre from April 2020 to July 2020. A retrospective record review of all patient records (257) from 8 weeks before the study was conducted to determine baseline VL testing coverage. Root cause analysis of low VL testing coverage was done using fish-bone tool and factors prioritized using a Pareto-chart. Priority factors included inadequate capacity to update electronic medical records and competing tasks. Change ideas were identified and prioritized using an effort-impact matrix. Two change ideas; re-orienting ART providers on VL test order in EMR and dedicated ART provider to serve VL tested patients were implemented and tested in 5 Plan-Do-Study-Act (PDSA) cycles from the Model for Improvement (MFI), each lasting one week. The latter was tested, and adapted in 3 cycles, and eventually adopted for monitoring for another 5 weeks. VL testing coverage was tracked throughout the study using run charts and p-charts. Results VL testing coverage increased from 27% to 71% by the end of the study, with children aged 0 to 14 years having the lowest coverage throughout the study. Conclusion The MFI as a QI approach improved VL testing coverage through implementation of contextualized change ideas. A reliable data system, leadership buy-in and commitment are important for sustained improvement. Future research should focus on evaluating sustainability of improved VL testing coverage at the health facility and assessing barriers to VL testing among the paediatric population

Association of socioeconomic status change between infancy and adolescence, and blood pressure, in South African young adults: Birth to Twenty Cohort

ObjectiveSocial epidemiology models suggest that socioeconomic status (SES) mobility across the life course affects blood pressure. The aim of this study was to investigate the association between SES change between infancy and adolescence, and blood pressure, in young adults, and the impact of early growth on this relationship.SettingData for this study were obtained from a ‘Birth to Twenty’ cohort in Soweto, Johannesburg, in South Africa.ParticipantsThe study included 838 Black participants aged 18 years who had household SES measures in infancy and at adolescence, anthropometry at 0, 2, 4 and 18 years of age and blood pressure at the age of 18 years.MethodsWe computed SES change using asset-based household SES in infancy and during adolescence as an exposure variable, and blood pressure and hypertension status as outcomes. Multivariate linear and logistic regressions were used to investigate the associations between SES change from infancy to adolescence, and age, height and sex-specific blood pressure and hypertension prevalence after adjusting for confounders.ResultsCompared to a persistent low SES, an upward SES change from low to high SES tertile between infancy and adolescence was significantly associated with lower systolic blood pressure (SBP) at the age of 18 years (β=−4.85; 95% CI −8.22 to −1.48; p<0.01; r2=0.1804) after adjusting for SES in infancy, small-for-gestational-age (SGA) and weight gain. Associations between SES change and SBP were partly explained by weight gain between birth and the age of 18 years. There was no association between SES mobility and diastolic blood pressure, mean arterial pressure or hypertension status.ConclusionsOur study confirms that upward SES change has a protective effect on SBP by the time participants reach young adulthood. Socioeconomic policies and interventions that address inequality may have the potential to reduce cardiovascular disease burden related to BP in later life

Transitioning to Dolutegravir in a Programmatic Setting: Virological Outcomes and Associated Factors Among Treatment-Naive Patients With HIV-1 in the Kilombero and Ulanga Antiretroviral Cohort in Rural Tanzania.

BACKGROUND Virological outcome data after programmatic transition from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to dolutegravir (DTG)-based antiretroviral therapy (ART) regimens in sub-Saharan Africa (SSA) outside of clinical trials are scarce. We compared viral suppression and associated factors in treatment-naïve people living with HIV (PLHIV) starting DTG- based versus NNRTI-based ART. METHODS We compared virological suppression at 12 months, after treatment initiation in the two cohorts of participants aged ≥15 years, initiating DTG- and NNRTI-based ART. Drug resistance was assessed among participants with viremia ≥50 copies/mL on DTG. RESULTS Viral suppression was achieved for 165/195 (85%) and 154/211 (73%) participants in the DTG- and NNRTI- cohorts, respectively (P = 0.003). DTG-based ART was associated with >2 times the odds of viral suppression versus NNRTI-based ART (adjusted odds ratio, 2.10 [95% confidence interval {CI}, 1.12-3.94]; adjusted risk ratio, 1.11 [95% CI, 1.00-1.24]). HIV-1 genotypic resistance testing (GRT) before ART initiation was done in 14 of 30 viremic participants on DTG, among whom nucleoside reverse transcriptase inhibitor (NRTI), NNRTI, and protease inhibitors resistance was detected in 0 (0%), 2 (14%) and 1 (7%), respectively. No resistance was found in the 2 of 30 participants with available GRT at the time of viremia ≥50 copies/mL. CONCLUSIONS Virological suppression at 1 year was higher in participants initiating DTG- versus NNRTI-based ART. In those with viremia ≥50 copies/mL on DTG-based ART, there was no pretreatment or acquired resistance to the DTG co-administered NRTIs, although the number of samples tested was small

The associations between adult body composition and abdominal adiposity outcomes, and relative weight gain and linear growth from birth to age 22 in the Birth to Twenty Plus cohort, South Africa.

BACKGROUND: The growing prevalence of overweight and obesity in low- or middle-income countries precipitates the need to examine early life predictors of adiposity. OBJECTIVES: To examine growth trajectories from birth, and associations with adult body composition in the Birth to Twenty Plus Cohort, Soweto, South Africa. METHODS: Complete data at year 22 was available for 1088 participants (536 males and 537 females). Conditional weight and height indices were generated indicative of relative rate of growth between years 0-2, 2-5, 5-8, 8-18, and 18-22. Whole body composition was measured at year 22 (range 21-25 years) using dual energy x-ray absorptiometry (DXA). Total fat free soft tissue mass (FFSTM), fat mass, and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were recorded. RESULTS: Birth weight was positively associated with FFSTM and fat mass at year 22 (β = 0.11, p<0.01 and β = 0.10, p<0.01 respectively). Relative weight gain from birth to year 22 was positively associated with FFSTM, fat mass, VAT, and SAT at year 22. Relative linear growth from birth to year 22 was positively associated with FFSTM at year 22. Relative linear growth from birth to year 2 was positively associated with VAT at year 22. Being born small for gestational age and being stunted at age 2 years were inversely associated with FFSTM at year 22. CONCLUSIONS: The importance of optimal birth weight and growth tempos during early life for later life body composition, and the detrimental effects of pre- and postnatal growth restriction are clear; yet contemporary weight-gain most strongly predicted adult body composition. Thus interventions should target body composition trajectories during childhood and prevent excessive weight gain in early adulthood

Blood pressure tracking in urban black South African children: birth to twenty cohort

Abstract Background Hypertension is an emerging public health problem in South Africa. Recent evidence from longitudinal studies has shown that hypertension in adulthood can be traced back to childhood. There is scarcity of longitudinal data on paediatric blood pressure (BP) particularly in African populations. The objective of this study is to assess the prevalence of hypertension and evaluate BP tracking between childhood and late adolescence among South African black Children. Methods This study utilized data from the Birth to Twenty cohort, which is comprised of children born in Soweto, Johannesburg in 1990 (N = 3273, 78.5 % black). Data on BP and anthropometry were collected at six follow-up periods between ages 5 and 18 years. Blood pressure status was classified using the Fourth report on National High Blood pressure program in children and adolescents. Pearson correlation coefficients and relative risk ratios (RR) were used to describe tracking of BP between childhood and late adolescence. Results The overall point prevalence ranged from 9.2 to 16.4 % for prehypertension and 8.4 to 24.4 % for hypertension. Tracking coefficients ranged from 0.20 to 0.57 for SBP and 0.17- 0.51 for DBP in both sexes over the 14 years of measurement. The proportion of children who maintained an elevated BP status between childhood, adolescence and age 18 years ranged from 36.1 % at age 5 years to 56.3 % at age 13 years. Risk of having elevated BP at 18 years ranged from; RR: 1.60 (95 % CI: 1.29–2.00) at 5 years to RR: 2.71 (95 % CI: 2.32–3.17) at 14 years of age. Conclusions This study reports high prevalence of elevated BP which tracks from early childhood into late adolescence. These findings emphasize the importance of early identification of children at risk of developing elevated BP and related risk factors plus timely intervention to prevent hypertension in adulthood

The associations between adult body composition and abdominal adiposity outcomes, and relative weight gain and linear growth from birth to age 22 in the Birth to Twenty Plus cohort, South Africa.

BACKGROUND: The growing prevalence of overweight and obesity in low- or middle-income countries precipitates the need to examine early life predictors of adiposity. OBJECTIVES: To examine growth trajectories from birth, and associations with adult body composition in the Birth to Twenty Plus Cohort, Soweto, South Africa. METHODS: Complete data at year 22 was available for 1088 participants (536 males and 537 females). Conditional weight and height indices were generated indicative of relative rate of growth between years 0-2, 2-5, 5-8, 8-18, and 18-22. Whole body composition was measured at year 22 (range 21-25 years) using dual energy x-ray absorptiometry (DXA). Total fat free soft tissue mass (FFSTM), fat mass, and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were recorded. RESULTS: Birth weight was positively associated with FFSTM and fat mass at year 22 (β = 0.11, p<0.01 and β = 0.10, p<0.01 respectively). Relative weight gain from birth to year 22 was positively associated with FFSTM, fat mass, VAT, and SAT at year 22. Relative linear growth from birth to year 22 was positively associated with FFSTM at year 22. Relative linear growth from birth to year 2 was positively associated with VAT at year 22. Being born small for gestational age and being stunted at age 2 years were inversely associated with FFSTM at year 22. CONCLUSIONS: The importance of optimal birth weight and growth tempos during early life for later life body composition, and the detrimental effects of pre- and postnatal growth restriction are clear; yet contemporary weight-gain most strongly predicted adult body composition. Thus interventions should target body composition trajectories during childhood and prevent excessive weight gain in early adulthood

Genetic risk score for adult body mass index associations with childhood and adolescent weight gain in an African population

Abstract Background Ninety-seven independent single nucleotide polymorphisms (SNPs) are robustly associated with adult body mass index (BMI kg/m2) in Caucasian populations. The relevance of such variants in African populations at different stages of the life course (such as childhood) is unclear. We tested whether a genetic risk score composed of the aforementioned SNPs was associated with BMI from infancy to early adulthood. We further tested whether this genetic effect was mediated by conditional weight gain at different growth periods. We used data from the Birth to Twenty Plus Cohort (Bt20+), for 971 urban South African black children from birth to 18 years. DNA was collected at 13 years old and was genotyped using the Metabochip (Illumina) array. The weighted genetic risk score (wGRS) for BMI was constructed based on 71 of the 97 previously reported SNPs. Results The cross-sectional association between the wGRS and BMI strengthened with age from 5 to 18 years. The significant associations were observed from 11 to 18 years, and peak effect sizes were observed at 13 and 14 years of age. Results from the linear mixed effects models showed significant interactions between the wGRS and age on longitudinal BMI but no such interactions were observed in sex and the wGRS. A higher wGRS was associated with an increased relative risk of belonging to the early onset obese longitudinal BMI trajectory (relative risk = 1.88; 95%CI 1.28 to 2.76) compared to belonging to a normal longitudinal BMI trajectory. Adolescent conditional relative weight gain had a suggestive mediation effect of 56% on the association between wGRS and obesity risk at 18 years. Conclusions The results suggest that genetic susceptibility to higher adult BMI can be tracked from childhood in this African population. This supports the notion that prevention of adult obesity should begin early in life. The genetic risk score combined with other non-genetic risk factors, such as BMI trajectory membership in our case, has the potential to be used to screen for early identification of individuals at increased risk of obesity and other related NCD risk factors in order to reduce the adverse health risk outcomes later

Association of socioeconomic status change between infancy and adolescence and blood pressure in South African young adults: Birth to Twenty Cohort

OBJECTIVE. Social epidemiology models suggest that socioeconomic status (SES) mobility across the life course affects blood pressure. The aim of this study was to investigate the association between SES change between infancy and adolescence, and blood pressure, in young adults, and the impact of early growth on this relationship. SETTING. Data for this study were obtained from a ‘Birth to Twenty’ cohort in Soweto, Johannesburg, in South Africa. PARTICIPANTS. The study included 838 Black participants aged 18 years who had household SES measures in infancy and at adolescence, anthropometry at 0, 2, 4 and 18 years of age and blood pressure at the age of 18 years. METHODS. We computed SES change using asset-based household SES in infancy and during adolescence as an exposure variable, and blood pressure and hypertension status as outcomes. Multivariate linear and logistic regressions were used to investigate the associations between SES change from infancy to adolescence, and age, height and sex-specific blood pressure and hypertension prevalence after adjusting for confounders. RESULTS. Compared to a persistent low SES, an upward SES change from low to high SES tertile between infancy and adolescence was significantly associated with lower systolic blood pressure (SBP) at the age of 18 years (β=−4.85; 95% CI −8.22 to −1.48; p<0.01; r2=0.1804) after adjusting for SES in infancy, small-for-gestational-age (SGA) and weight gain. Associations between SES change and SBP were partly explained by weight gain between birth and the age of 18 years. There was no association between SES mobility and diastolic blood pressure, mean arterial pressure or hypertension status. CONCLUSIONS. Our study confirms that upward SES change has a protective effect on SBP by the time participants reach young adulthood. Socioeconomic policies and interventions that address inequality may have the potential to reduce cardiovascular disease burden related to BP in later life

Association Between Early Life Growth and Blood Pressure Trajectories in Black South African ChildrenNovelty and Significance

Early growth is associated with blood pressure measured on one occasion, but whether early life growth patterns are associated with longitudinal blood pressure trajectories is under-researched. Therefore, we sought to examine the association between early growth and blood pressure trajectories from childhood to adulthood. Blood pressure was measured on 7 occasions between ages 5 and 18 years in the Birth to Twenty cohort study, and conditional variables for growth in infancy and mid-childhood were computed from anthropometric measures (n=1937, 52% girls). We used a group-based trajectory modeling approach to identify distinct height-adjusted blood pressure trajectories and then tested their association with growth between birth and mid-childhood adjusting for several covariates. Three trajectory groups were identified for systolic and diastolic blood pressure: lower, middle, and upper in boys and girls, separately. In boys, predictors of the middle or upper systolic blood pressure trajectories versus the lower trajectory were in birth weight (odds ratio 0.75 [95% confidence interval 0.58-0.96] per SD) and relative weight gain in infancy (4.11 [1.25-13.51] per SD). In girls, greater relative weight gain and linear growth in both infancy and mid-childhood were consistently associated with an almost 2-fold higher likelihood of being in the upper versus lower systolic blood pressure trajectory. The associations for the diastolic blood pressure trajectories were inconsistent. These findings emphasize the importance of identifying children at risk of progression to high blood pressure. Accelerated growth in infancy and mid-childhood may be a key target for early life intervention in prevention of elevated blood pressure progression