Perinatal exposure to traffic related air pollutants and the risk of infection in the first six months of life: a cohort study from a low-middle income country.

OBJECTIVE: There is limited study from low-and-middle income countries on the effect of perinatal exposure to air pollution and the risk of infection in infant. We assessed the association between perinatal exposure to traffic related air pollution and the risk of infection in infant during their first six months of life. METHODS: A prospective cohort study was performed in Jakarta, March 2016-September 2020 among 298 mother-infant pairs. PM2.5, soot, NOx, and NO2 concentrations were assessed using land use regression models (LUR) at individual level. Repeated interviewer-administered questionnaires were used to obtain data on infection at 1, 2, 4 and 6 months of age. The infections were categorized as upper respiratory tract (runny nose, cough, wheezing or shortness of breath), lower respiratory tract (pneumonia, bronchiolitis) or gastrointestinal tract infection. Logistic regression models adjusted for covariates were used to assess the association between perinatal exposure to air pollution and the risk of infection in the first six months of life. RESULTS: The average concentrations of PM2.5 and NO2 were much higher than the WHO recommended levels. Upper respiratory tract infections (URTI) were much more common in the first six months of life than diagnosed lower respiratory tract or gastro-intestinal infections (35.6%, 3.5% and 5.8% respectively). Perinatal exposure to PM2.5 and soot suggested increase cumulative risk of upper respiratory tract infection (URTI) in the first 6 months of life per IQR increase with adjusted OR of 1.50 (95% CI 0.91; 2.47) and 1.14 (95% CI 0.79; 1.64), respectively. Soot was significantly associated with the risk of URTI at 4-6 months age interval (aOR of 1.45, 95%CI 1.02; 2.09). All air pollutants were also positively associated with lower respiratory tract infection, but all CIs include unity because of relatively small samples. Adjusted odds ratios for gastrointestinal infections were close to unity. CONCLUSION: Our study adds to the evidence that perinatal exposure to fine particles is associated with respiratory tract infection in infants in a low-middle income country.

The effect of exposure to traffic related air pollutants in pregnancy on birth anthropometry: a cohort study in a heavily polluted low-middle income country.

BACKGROUND: Ambient air pollution has been recognized as one of the most important environmental health threats. Exposure in early life may affect pregnancy outcomes and the health of the offspring. The main objective of our study was to assess the association between prenatal exposure to traffic related air pollutants during pregnancy on birth weight and length. Second, to evaluate the association between prenatal exposure to traffic related air pollutants and the risk of low birth weight (LBW). METHODS: Three hundred forty mother-infant pairs were included in this prospective cohort study performed in Jakarta, March 2016-September 2020. Exposure to outdoor PM2.5, soot, NOx, and NO2 was assessed by land use regression (LUR) models at individual level. Multiple linear regression models were built to evaluate the association between air pollutants with birth weight (BW) and birth length (BL). Logistic regression was used to assess the risk of low birth weight (LBW) associated with all air pollutants. RESULTS: The average PM2.5 concentration was almost eight times higher than the current WHO guideline and the NO2 level was three times higher. Soot and NOx were significantly associated with reduced birth length. Birth length was reduced by - 3.83 mm (95% CI -6.91; - 0.75) for every IQR (0.74 × 10- 5 per m) increase of soot, and reduced by - 2.82 mm (95% CI -5.33;-0.30) for every IQR (4.68 µg/m3) increase of NOx. Outdoor air pollutants were not significantly associated with reduced birth weight nor the risk of LBW. CONCLUSION: Exposure to soot and NOx during pregnancy was associated with reduced birth length. Associations between exposure to all air pollutants with birth weight and the risk of LBW were less convincing.

The effect of non-organophosphate household pesticides exposure during pregnancy on infants birth sizes and growth rate: a cohort study.

BACKGROUND: To date, there is limited evidence on the effect of antenatal exposure to non-organophosphate household pesticides on infant health. Our hypothesis is that antenatal exposure to non-organophosphate household pesticides will be associated with birth sizes and infant growth rate. METHODS: In this prospective cohort study, 284 mother-infant pairs were studied. Mothers were recruited at the third trimester in two primary care centers and one private hospital in Jakarta, Indonesia. Mothers filled out questionnaires about exposure to non-organophosphate household pesticides at the 3rd trimester of pregnancy. Birth weight and length were measured at birth. Afterwards, the weight, height, and head circumference (HC) were measured at 7 days, 1, 2, 4, and 6 months of age. Linear mixed modeling and linear regression was performed to calculate growth rate of each infant. Multivariable linear regression adjusted for confounders was used to assess the association between household pesticides exposure and birth sizes and infant growth rate. RESULTS: Based on self-report questionnaires, 133 (46.8%) mothers were exposed to household pesticides during pregnancy. The mean HC at day 7 in the exposed group was - 7.1 mm (95%CI -13.1;-1.2) lower than in the non-exposed group. The difference was more prominent in the non-mosquito pesticide group (linear regression coefficient: - 22.1 mm, 95%CI -36.5;-7.6). No material associations were found between antenatal exposure to household pesticides with other growth measures, including weight gain, length gain, HC increment and weight-to-length gain rates. No modification of effects by breastfeeding was found. CONCLUSIONS: Our findings suggest that antenatal exposure to household non-organophosphate pesticides is associated with smaller head circumference at birth.

Pulmonary Vasodilator Therapy in Children with Single Ventricle Physiology: Effects on Saturation and Pulmonary Arterial Pressure.

In children with single ventricle physiology, increased pulmonary vascular resistance may impede surgical progression or result in failing single ventricle physiology. The use of pulmonary vasodilators has been suggested as a potential therapy. However, knowledge on indication, dosage, and effect is limited. A retrospective case notes review of all (n = 36) children with single ventricle physiology, treated with pulmonary vasodilators by the UK Pulmonary Hypertension Service for Children 2004-2017. Therapy was initiated in Stage 1 (n = 12), Glenn (n = 8), or TCPC (n = 16). Treatment indications were high mean pulmonary arterial pressure, cyanosis, reduced exercise tolerance, protein-losing enteropathy, ascites, or plastic bronchitis. Average dose of sildenafil was 2.0 mg/kg/day and bosentan was 3.3 mg/kg/day. 56% had combination therapy. Therapy was associated with a reduction of the mean pulmonary arterial pressure from 19 to 14 mmHg (n = 17, p < 0.01). Initial therapy with one or two vasodilators was associated with an increase in the mean saturation from 80 to 85%, (n = 16, p < 0.01). Adding a second vasodilator did not give significant additional effect. 5 of 12 patients progressed from Stage 1 to Glenn, Kawashima, or TCPC, and 2 of 8 from Glenn to TCPC during a mean follow-up time of 4.7 years (0-12.8). Bosentan was discontinued in 57% and sildenafil in 14% of treated patients and saturations remained stable. Pulmonary vasodilator therapy was well tolerated and associated with improvements in saturation and mean pulmonary arterial pressure in children with single ventricle physiology. It appears safe to discontinue when no clear benefit is observed.

Effects of paediatric HIV infection on childhood vasculature.

AIMS: Human immunodeficiency virus (HIV) infection may alter childhood vascular properties and influence future cardiovascular risk. Whether vascular changes are associated with HIV infection per se or antiretroviral therapy (ART) is unknown. We investigated the effects of ART-naive or ART-exposed HIV infection in children on childhood vascular characteristics. METHODS AND RESULTS: We performed vascular ultrasound to measure carotid intima media thickness (cIMT), distensibility, and elastic modulus on 114 children with vertically acquired HIV infection (56 ART-naive, 58 ART treated) and 51 healthy children in Jakarta, Indonesia. Children also underwent clinical and blood examinations. We used general linear modelling to estimate associations between HIV infection/treatment status and vascular characteristics with adjustment for confounders or possible mediators. Vascular measurements were successful in 42 ART-naive HIV-infected [median age 4.0 years (min 0.4-max 11.5)]; 53 ART-treated HIV infected [5.7 years (0.6-12.2), median ART duration 2.4 years (0.1-9.9)]; and 48 healthy children, 6.5 years (2.4-14.0). The ART-naive HIV infected had thicker cIMT (difference 70.4 µm, 95% CI 32.1-108.7, P < 0.001), adjusted for age, sex, socioeconomic status, parental smoking, body mass index, systolic and diastolic blood pressure, LDL cholesterol, and HbA1c. Addition of high-sensitivity C-reactive protein (hs-CRP) level to the model did not affect the results (71.6 µm, 31.9-111.2, P = 0.001). The ART-exposed children had similar cIMT dimensions to healthy children. Distensibility was not significantly different between HIV infected, either ART-naive or -exposed, and healthy children, but adjusted analysis including only ART-exposed children with controlled HIV (CD4+ ≥200/mm3 or CD4+ ≥15%) showed that the ART-exposed had an increased elastic modulus (difference 37.9 kPa, 95% CI 6.5-69.3, P = 0.02), and following adjustment for hs-CRP (35.5 kPa, 95% CI 4.2-66.8, P = 0.03). CONCLUSION: ART-naive HIV infection in children is associated with increased cIMT. Children with ART-controlled HIV may have increased arterial stiffness, although further confirmation is required.

Transcatheter Closure of Patent Ductus Arteriosus in Adolescents and Adults: A Case Series.

During 11 years period from January 2005 to December 2015 there were 18 adolescent and adult patients  who underwent transcatheter closure of PDA using PDA Amplatzer Duct Occluder (ADO). There were 9 cases with age of 14 to 18 years and 9 cases with age of more than 18 years where the oldest case was 46 years old. Two cases were male and 16 cases were female. Prior to procedures, clinical assessment, ECG, chest x-ray and transthoracic echocardiography (TTE) were performed to confirm the diagnosis of PDA. The procedures of device implantation was performed under conscious sedation in adults and using general anesthesia in adolescents.The size of PDA ranged from 1.6 mm to 11.1 mm. Based on Kritchenko classification, the type of PDA were 15 type A1 and 3type A2. Flow ratio between pulmonary to systemic circulation was between 1.1 and 5.9. The procedure time ranged from 60-189 minutes and the fluoroscopic time 7.1-77.3 minutes. The PA pressure ranged from 22 to 63 mmHg. Immediate results after procedures as seen in angiography showed complete closure in 14 cases and smoky residual shunt or minimal residual shunts in 4 cases, which probably due to the temporary leaking through the devices. In 24 hours, complete closure was achieved in all cases (100%) and continued until 1months. At 6 month follow up, there was no residual shunts detected and also there was no significant complications, such as device embolization or recanalization. This case series suggest that transcatheter closure of PDA in adolescents and adults using Amplatzer duct occluder (ADO) is effective and has excellent resultswithout significant complication. However, long-term follow up is required to assess long term efficacy and safety.

Transcatheter closure of patent ductus arteriosus: 11 years of clinical experience in Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

Transcatheter closure of patent ductus arteriosus (PDA) has been suggested to be the standard treatment of PDA. Although, in general, the procedure shows a high successful rate, outcomes may vary among pediatric cardiology centers. To evaluate the effectiveness of transcatheter closure of PDA in Cipto Mangunkusumo Hospital, Jakarta, Indonesia, this was a retrospective study on patients who underwent transcatheter closure of PDA in Cipto Mangunkusumo Hospital during the period of 2002-2013. Hospital registry was reviewed and data about patients' characteristics, PDA severity, procedure, and outcomes were retrieved. There were 298 patients, of whom 90 were males, who underwent transcatheter closure of PDA during the study period. Median age was 3.4 years (1 months-18 years), and median body weight was 12 (3.6-59) kg. The diameter of PDA ranged from 1.1 to 15.4 mm with a median of 3.7 mm. Device could be deployed in all patients, in which most were the Amplatzer ductal occluder (69.8 %) and the remainders were coils. Median fluoroscopy time was 15.4 (1.5-87) min, and procedure time was 76 (30-200) min. Complete closure was achieved in most patients (97.3 %), whereas device migration occurred in a minority (0.3 %) of patients. No major complication occurred during or after the procedure. Transient anemia and bradycardia were found in 3.7 and 1.3 % patients, respectively. Most patients were discharged from the hospital at 1 day after the procedure. Transcatheter closure method is a safe and effective procedure to close PDA.

Transcatheter closure of post-operative residual ventricular septal defect using a patent ductus arteriosus closure device in an adult: a case report.

Transcatheter closure of perimembranous and muscular ventricular septal defect (VSD) has been performed widely and it has more advantages compare to surgery. However, transcatheter closure of residual VSD post operation of complex congenital heart disease is still challenging because of the complexity of anatomy and concern about device stability, so the operator should meticulously choose the most appropriate technique and device. We would like to report a case of transcatheter closure of residual VSD post Rastelli operation in a patient with double outlet right ventricle (DORV), sub-aortic VSD, severe infundibulum pulmonary stenosis (PS) and single coronary artery. The patient had undergone operations for four times, but he still had intractable heart failure that did not response to medications. On the first attempt. we closed the VSD using a VSD occluder, unfortunately the device embolized into the descending aorta, but fortunately we was able to snare it out. Then we decided to close the VSD using a patent ductus arteriosus (PDA occluder). On transesophageal echocardiography (TEE) and angiography evaluation, the device position was stable. Post transcatheter VSD closure, the patient clinical condition improved significantly and he could finally be discharged after a long post-surgery hospitalization. Based on this experience we concluded that the transcatheter closure of residual VSD in complex CHD using PDA occluder could be an effective alternative treatment.

Transcatheter closure of atrial septal defects in adolescents and adults: technique and difficulties.

AIM: to evaluate the results of transcatheter closure of atrial septal defect (ASD) in adolescents and adult. METHODS: a case series of patients undergoing transcatheter closure of ASD in RS Cipto Mangunkusumo, Jakarta during 2002 -2013. Transesophageal echocardiography, hemodynamic study, and angiography were performed before the procedure. Oxygen test was done if PA pressure was more than 2/3 of aortic pressure, followed by an occlusion test if no response observed to determine whether the device could be released. RESULTS: we enrolled 54 patients, of whom 26% were adolescents and 3% were males. Median body weight was 49 (26-75) kg and ASD size was 21 (9.4-39.6) mm. The procedure was done under general anesthesia in 26% of patients. Oxygen test was applied in 11% patients and occlusion test in 2% of patient. Transcatheter closure of ASD was successful in all patients using common technique (31%), right pulmonary vein-assisted (65%), left pulmonary assisted (2%), and cutting long sheath (2%). There was neither residual ASD nor complications observed. Mean fluoroscopy and procedure time were 29 (SD 18) and 109 (SD 36) minutes, respectively. Median hospital stay was 1 (1-3) day. CONCLUSION: transcatheter closure of ASD in adolescents and adults is safe and effective.

Survival of Left-to-Right Shunt Repair in Children with Pulmonary Arterial Hypertension at a Tertiary Hospital in a Low-to-Middle-Income Country.

Background: In low-to-middle-income countries, repair of the left-to-right shunts congenital heart disease (CHD) are often done with existing pulmonary arterial hypertension (PAH). Long-term outcomes data of this condition in either low-to-middle or high-income countries are limited. We conducted a study to evaluate the outcomes of children with PAH related to left-to-right shunt CHD who underwent surgical or transcatheter repair. Methods: All cases of PAH related to left-to-right shunt CHD repairs from 2015-2018 were retrospectively reviewed with additional new patients who underwent repair within our study period (2019-2020). Cases with complex congenital heart disease and incomplete hemodynamic echocardiography or catheterization measurements were excluded. Kaplan-Meier curves, log-rank test, Cox regression with Firth's correction and restricted mean survival time were used for survival analysis. Results: Of the 118 patients, 103 patients were enrolled and 15 patients were excluded due to complex congenital heart disease and missing hemodynamic measurements prior to repair. Overall, median age at intervention was 44 months, mPAP mean was 43.17 ± 16.05 mmHg and Pulmonary Vascular Resistance index (PVRi) mean was 2.84 ± 2.09 (WU.m2). Nine patients died after repair. The survival rate for patients with PAH-CHD at 1 day, 30 days and 1400 days (4 years) was 96.1%, 92.1%, and 91.0% respectively. Patients with persisting PAH after correction had -476.1 days (95% confidence interval [CI]: -714.4, -237,8) shorter survival over 4 years of follow up compared to patients with reversed PAH. PVRi was found to be the influencing covariate of the difference of restricted mean survival time between these groups. Conclusion: In low-to-middle income settings, with accurate PAH reversibility assessment prior to intervention, repair of left-to-right shunt CHD with existing PAH in children has a favourable outcome. Inferior survival is found in patients with persistence of PAH. PVRi at baseline predicts between-group survival difference.

Antenatal exposure to second hand smoke of non-smoking mothers and growth rate of their infants.

OBJECTIVES: There is limited evidence on the effect of exposure to second hand smoke (SHS) in non-smoking pregnant mothers and infant health. We assessed the effects of maternal antenatal exposure to SHS on infant growth rate, and secondarily, on birth weight, birth length and head circumference at birth. METHODS: In this prospective cohort, 305 mother-infant pairs were studied. Mothers filled out questionnaires about exposure to SHS in pregnancy at the 3rd trimester of pregnancy. Infant anthropometry was performed at birth, day 7, and months 1, 2, 4, and 6, postnatally. Linear mixed modeling and linear regression were used to calculate growth rates over the first 6 months. The association between SHS-exposure with growth rate and birth sizes was assessed using multivariate linear regression adjusted for confounders, with SHS as both number of cigarettes and as groups (no exposure, SHS < 23 cigarettes, SHS ≥ 23 cigarettes). RESULTS: Seventy-three mothers were not exposed and 232 were exposed. SHS exposure (per cigarette) was not related to gain in weight, length, head circumference, and weight for length. However, infants born to mothers exposed to ≥ 23 cigarettes/d had lower head circumference gain (-0.32 mm/m, 95% CI -0.60, -0.03) than those born to non-exposed mothers. SHS exposure (per cigarette) was not related to birth weight, length, and head circumference, but exposure to ≥ 23 cigarettes was related to lower head circumference at birth (-11.09 mm, -20.03, -2.16). CONCLUSIONS: Heavy antenatal exposure to SHS in non-smoking mothers results in reduced neonatal head circumference at birth and head circumference gain over the first 6 months of life. Our findings show no clear relations between exposure to SHS during pregnancy and other markers of neonatal growth and birth size.

Effects of HIV Infection on Pulmonary Artery Pressure in Children.

BACKGROUND: Pulmonary hypertension may complicate human immunodeficiency virus (HIV) infection and result in right ventricular (RV) failure and premature death. There are limited data of the effects of childhood HIV infection or antiretroviral therapy (ART) on pulmonary artery pressure (PAP). OBJECTIVES: To establish if there is an association between childhood HIV infection or its treatment and pulmonary artery pressure. METHODS: The study conducted a cross-sectional study of 102 HIV-infected (48 ART-naïve, 54 ART-exposed) and 51 HIV-uninfected children in Jakarta, Indonesia, to estimate PAP using echocardiography parameters: tricuspid regurgitation peak velocity (TRV), left ventricular systolic index and diastolic eccentricity index (EI), and RV systolic function, assessed by tricuspid annulus plane systolic excursion. The association between either ART-naive or ART-exposed HIV and PAP was explored using general linear modelling adjusted for potential confounders. RESULTS: ART-exposed HIV-infected children had higher TRV (adjusted difference: 0.36 m/s; 95% confidence interval [CI]: 0.12 to 0.60; p = 0.003) and diastolic EI (adjusted difference 0.06; 95% CI: 0.01 to 0.11; p = 0.02) than did uninfected children. The EI in ART-exposed children was significantly higher than normal. ART-naive HIV-infected children had a lower tricuspid annulus plane systolic excursion (adjusted difference: -2.2 mm; 95% CI: -3.73 to -0.71; p = 0.004), despite no difference in TRV (adjusted difference: 0.18 m/s; 95% CI: -0.06 to 0.43 m/s; p = 0.14). Seven (13%) ART-exposed and 4 (8.3%) ART-naïve HIV-infected children had pulmonary hypertension. Within-HIV group comparisons showed that accounting for lower respiratory tract infections attenuated the lower RV systolic function in ART-naïve children but not in ART-exposed children (difference: -1.1 mm; 95% CI:-2.8 to 0.7 mm; p = 0.22), but not the higher left ventricular eccentricity indexes in the ART-exposed children (systolic difference: 0.07; 95% CI: 0.02 to 0.12; p = 0.007; diastolic difference: 0.08; 95% CI: 0.02 to 0.14; p = 0.006). CONCLUSIONS: ART-exposed HIV infection is associated with higher estimated PAP. Reduced RV systolic function is seen in ART-naïve HIV infection. Lower respiratory tract infection partly explains lower systolic RV function in ART-naïve relative to ART-exposed HIV infection.

Increased Carotid Intima-Media Thickness in Children with a History of Dengue Hemorrhagic Fever.

We assessed carotid intima-media thickness (cIMT) and arterial stiffness in 28 children and adolescents with previous dengue hemorrhagic fever (DHF) (mean interval between DHF and cardiovascular assessment, 8.4 years), and 34 controls in a low-resource setting. Participants with previous DHF had an adjusted increased cIMT of 42.6 µm (95% confidence interval [CI]: 10.0-75.3, P = 0.01), and 61.7 µm (95% CI: 21.5-102.0, P < 0.01) in a subgroup analysis on dengue shock syndrome. There were no differences in arterial stiffness. In this first exploratory study, children and adolescents with a history of DHF had an increased cIMT, which may be modulated by dengue severity.

Pre-pregnancy parental BMI and offspring blood pressure in infancy.

AIMS: A growing body of evidence suggests that a higher maternal pre-pregnancy body mass index results in higher offspring's blood pressure, but there is inconsistency about the impact of father's body mass index. Furthermore, evidence is limited with regard to low and middle income countries. We aimed to determine the association between parental pre-pregnancy body mass index and offspring's blood pressure during the first year of life. METHODS: In 587 infants of the BReastfeeding Attitude and Volume Optimization (BRAVO) trial systolic and diastolic blood pressure were measured twice at the right leg in a supine position, using an automatic oscillometric device at day 7, month 1, 2, 4, 6, 9 and 12. Parental pre-pregnancy body mass index was based on self-reported weight and height. Linear mixed models were performed to investigate the associations between parental pre-pregnancy body mass index and offspring blood pressure patterns. RESULTS: Each unit increase in maternal body mass index was associated with 0.24 mmHg (95% confidence interval 0.05; 0.44) and 0.13 mmHg (0.01; 0.25) higher offspring's mean systolic and diastolic blood pressure, respectively, during the first year of life. A higher offspring blood pressure with increased maternal pre-pregnancy body mass index was seen at birth and remained higher during the first year of life. The association with systolic blood pressure remained similar after including birth size and offspring's weight and height over time. The association with diastolic blood pressure attenuated slightly to a non-significant result after including these variables. Paternal body mass index was not associated with offspring's blood pressure. CONCLUSION: Higher maternal pre-pregnancy body mass index, but not paternal pre-pregnancy body mass index, is associated with higher offspring blood pressure already from birth onwards.

Characterization of rhinovirus C from a 4-year-old boy with acute onset dilated cardiomyopathy in Jakarta, Indonesia.

INTRODUCTION: Myocarditis, inflammation of the heart muscle, can be caused by infections, autoimmune disease or exposure to toxins. The major cause of myocarditis in the paediatric population is viral infection, including coxsackievirus B3, adenovirus, herpesvirus, parvovirus, influenza A and B, and hepatitis. Here, we report the detection of rhinovirus C in a boy with a clinical presentation of myocarditis, suggesting a possible causative role of this virus in this case. CASE PRESENTATION: A previously well 4.5-year-old boy presented with increasing breathlessness for a week prior to admission. He also had upper respiratory tract infection a few days before the event. An echocardiogram revealed severe left ventricle (LV) systolic dysfunction with dilation of the LV. RNA was extracted from serum and two nasal swabs, and tested with conventional PCR at the family level for viruses including enterovirus, dengue, chikungunya, influenza, herpesvirus, paramyxovirus and coronavirus. Further characterization of the enterovirus group was carried out using PCR with primers targeting the VP4/VP2 gene, followed by sequencing. Molecular tests showed the presence of rhinovirus C genetic material in both serum and swab samples. Phylogenetic analysis of the VP4/VP2 region showed 96-97 % similarity with the closest strain isolated in Ulaanbaatar (Mongolia) and Japan in 2012. CONCLUSION: We report the possible association of rhinovirus C and myocarditis in a child presenting with acute onset of dilated cardiomyopathy.

Association between human immunodeficiency virus infection and arterial stiffness in children.

Background Human immunodeficiency virus infection (HIV) is associated with increased cardiovascular risk and adverse cardiovascular outcome in adults. Early recognition of changes in vascular properties might prove essential in cardiovascular prevention in HIV-infected patients. We investigated the relations between HIV infection and arterial stiffness in children. Methods This cross-sectional study included 51 HIV-infected and 52 healthy children (age 3.2-14.5 years, 49 males). All infected children had acquired HIV by vertical transmission and were receiving antiretroviral therapy at time of assessment. Arterial stiffness was measured by pulse wave velocity and aortic augmentation index, using the Arteriograph system (Tensiomed Kft, Budapest, Hungary). We applied multivariable general linear modeling to evaluate the relationship between HIV infection and arterial stiffness with further adjustment for confounders and possible intermediary variables. Findings represent mean group differences with 95% confidence intervals and p values. Results Aortic augmentation index was higher by 9.0% (5.6-12.5, p < 0.001) in HIV-infected than in healthy children. Adjustment for blood pressure, protease inhibitor use, biomarkers for level of inflammation, lipid- and glucose-metabolism, as possible intermediary variables, did not appreciably alter the results. There were no significant differences in pulse wave velocity between HIV-infected and healthy children (mean difference 0.28 m/s, -0.14-0.69, p = 0.19). Conclusion HIV-infected children have an increased aortic augmentation index, compared to healthy children. Early cardiovascular assessment may be important in targeted prevention for HIV-infected children.

Pro-Inflammatory Markers in Relation to Cardiovascular Disease in HIV Infection. A Systematic Review.

BACKGROUND: In the past years many inflammatory markers have been studied in association with clinically manifest cardiovascular disease (CVD) and carotid intima-media thickness (CIMT) in HIV-infected patients, to obtain insights in the increased cardiovascular risk observed in HIV infection. This systematic review provides an oversight of the current knowledge. METHODS: A search was performed in PubMed, Embase and Cochrane in July 2014, identifying all articles from 1996 onwards addressing the relation between inflammatory markers and CVD or CIMT in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis was focused on the immune markers that were most frequently assessed. The review protocol was registered in the PROSPERO database at 11 July 2014 (registration number CRD42014010516). This review was performed according to the PRISMA guideline. FINDINGS: Forty articles were selected; eight addressing cardiovascular disease (CVD) and thirty-two addressing CIMT. C-reactive protein (CRP), interleukin-6 (IL-6) and d-dimer were assessed most frequently in relation to the occurrence of CVD; in four out of eight studies. All three markers were positively related to CVD in three out of four studies. Studies addressing CIMT were too heterogeneous with respect to patient populations, inflammatory markers, CIMT measurement protocols and statistical methods to allow for a formal meta-analysis to obtain summary statistics. CRP, IL-6 and soluble vascular cell adhesion molecule (sVCAM-1) were the most studied markers in relation to CIMT. None of the inflammatory markers showed an association with CIMT. INTERPRETATION: This review showed a relation between some inflammatory markers and CVD, however, no consistent relation is observed for CIMT. Statistical approaches that yields effect estimates and standardized CIMT protocols should be chosen. Further research should focus on prospective studies and a selected set of inflammatory markers.

Cardiac Effects of Antiretroviral-Naïve versus Antiretroviral-Exposed HIV Infection in Children.

BACKGROUND: Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown. METHODS: This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values. RESULTS: Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children. CONCLUSIONS: ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter and higher mass, but less functional impairment.

Effects of paediatric HIV infection on electrical conduction of the heart.

OBJECTIVE: To investigate the effects of HIV infection in children on heart electrical conduction, particularly to delineate the effects of HIV infection from treatment. METHODS: On a 12-lead ECG, available for 37 antiretroviral therapy (ART) naïve, 42 ART-exposed vertically-acquired HIV-infected and 50 healthy children in Jakarta, Indonesia, we measured cardiac conduction parameters: PR, QRS, and QTc (corrected using Bazett's formula) intervals. The associations between HIV infection/treatment status and ECG intervals were evaluated using general linear modelling with further adjustment for potential confounders or intermediary variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children. RESULTS: Although not exceeding the clinical threshold for long QT (QTc >460 ms for girls and >440 ms for boys) compared to healthy children, mean QTc intervals were longer in ART-naïve (difference 18.2 ms, 95% CI 7.0 to 29.3) and, to greater extent, in ART-exposed HIV-infected children (difference 28.9 ms, 19.3 to 38.5). Following adjustment for RR interval, age and height, prolongation of PR interval was seen only in ART-naïve HIV-infected children (difference 12.9 ms, 2.4 to 23.3). Cardiac mass/function, high-sensitive C reactive protein, cholesterol and glycated haemoglobin levels, systolic and diastolic blood pressures, or postnatal parental smoking exposure did not affect these associations. No difference in the QRS interval was observed between groups. CONCLUSIONS: Prolongation of the QTc interval occurs in ART-naïve HIV-infected children and, to a greater extent, in the ART-exposed children, whereas a longer PR interval appears to be seen only among ART-naïve HIV-infected children.

BReastfeeding Attitude and Volume Optimization (BRAVO) trial: study protocol for a randomized controlled trial.

BACKGROUND: A growing body of evidence shows the short-term benefits of breastfeeding, which include protection against infections, allergies, and lung diseases. However, evidence on the long-term benefits of breastfeeding is scarce and often conflicting. The BReastfeeding Attitude and Volume Optimization (BRAVO) trial is designed to study the effect of breastfeeding on early signs of later chronic diseases, particularly cardiovascular, respiratory, and metabolic risks later in life. In addition, the effectiveness of breastfeeding empowerment in promoting breastfeeding will also be evaluated. METHODS/DESIGN: This study is an ongoing randomized trial in Jakarta, Indonesia, that began in July 2012. Pregnant women are being screened for their breastfeeding plan in the third trimester, and those with low intention to breastfeed are randomly allocated to either receiving an add-on breastfeeding-optimization program or usual care. Primary outcomes include breastfeeding rate, lung function, and blood pressure during the first year of life and vascular/cardiac characteristics, which will be measured at the age of 4 to 5 years. Child growth and infection/illness episodes are measured, whereas cognitive testing is planned for the children at 5 years of age. DISCUSSION: To date, 784 women (80 %) have been randomized of the 1,000 planned, with satisfactory completeness of the 1-year follow up (90.1 %). Included mothers are of lower socioeconomic status and more often have blue-collar jobs, similar to what was observed in the pilot study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01566812 . Registered on 27 March 2012.