Decreased renal function among children born to women with obstructed labour in Eastern Uganda: a cohort study.

BACKGROUND: Over two million children and adolescents suffer from chronic kidney disease globally. Early childhood insults such as birth asphyxia could be risk factors for chronic kidney disease in later life. Our study aimed to assess renal function among children aged two to four years, born to women with obstructed labour. METHODS: We followed up 144 children aged two to four years, born to women with obstructed labor at Mbale regional referral hospital in Eastern Uganda. We used serum creatinine to calculate estimated glomerular filtration rate (eGFR) using the Schwartz formula. We defined decreased renal function as eGFR less than 90 ml/min/1.73m2. RESULTS: The mean age of the children was 2.8 years, standard deviation (SD) of 0.4 years. Majority of the children were male (96/144: 66.7%). The mean umbilical lactate level at birth among the study participants was 8.9 mmol/L with a standard deviation (SD) of 5.0. eGFR of the children ranged from 55 to 163 ml/min/1.73m2, mean 85.8 ± SD 15.9. Nearly one third of the children (45/144) had normal eGFR (> 90 ml/Min/1.73m2), two thirds (97/144) had a mild decrease of eGFR (60-89 ml/Min/1.73m2), and only two children had a moderate decrease of eGFR (< 60 ml/Min/1.73m2). Overall incidence of reduced eGFR was 68.8% [(99/144): 95% CI (60.6 to 75.9)]. CONCLUSION: We observed a high incidence of reduced renal function among children born to women with obstructed labour. We recommend routine follow up of children born to women with obstructed labour and add our voices to those calling for improved intra-partum and peripartum care.

A Clinical and Physiological Prospective Observational Study on the Management of Pediatric Shock in the Post-Fluid Expansion as Supportive Therapy Trial Era.

OBJECTIVES: Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy. DESIGN: We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints. SETTING: Pediatric wards of Mbale Regional Referral Hospital, Uganda, and Kilifi County Hospital, Kenya, conducted between October 2013 and July 2015. Data were analysed from August 2016 to July 2019. PATIENTS: Children (≥ 60 d to ≤ 12 yr) with severe febrile illness and clinical signs of impaired perfusion. INTERVENTIONS: IV maintenance fluid (4 mL/kg/hr) unless children had World Health Organization (WHO) defined shock (≥ 3 signs) where they received two fluid boluses (20 mL/kg) and transfusion if shock persisted. Clinical, electrocardiographic, echocardiographic, and laboratory data were collected at presentation, during resuscitation and on day 28. Outcome measures were 48-hour mortality, normalization of hemodynamics, and cardiac biomarkers. MEASUREMENT AND MAIN RESULTS: Thirty children (70% males) were recruited, six had WHO shock, all of whom died (6/6) versus three of 24 deaths in the non-WHO shock. Median fluid volume received by survivors and nonsurvivors were similar (13 [interquartile range (IQR), 9-32] vs 30 mL/kg [28-61 mL/kg], z = 1.62, p = 0.23). By 24 hours, we observed increases in median (IQR) stroke volume index (39 mL/m 2 [32-42 mL/m 2 ] to 47 mL/m 2 [41-49 mL/m 2 ]) and a measure of systolic function: fractional shortening from 30 (27-33) to 34 (31-38) from baseline including children managed with no-bolus. Children with WHO shock had a higher mean level of cardiac troponin ( t = 3.58; 95% CI, 1.24-1.43; p = 0.02) and alpha-atrial natriuretic peptide ( t = 16.5; 95% CI, 2.80-67.5; p < 0.01) at admission compared with non-WHO shock. Elevated troponin (> 0.1 µg/mL) and hyperlactatemia (> 4 mmol/L) were putative makers predicting outcome. CONCLUSIONS: Maintenance-only fluid therapy normalized clinical and myocardial perturbations in shock without compromising cardiac or hemodynamic function whereas fluid-bolus management of WHO shock resulted in high fatality. Troponin and lactate biomarkers of cardiac dysfunction could be promising outcome predictors in pediatric septic shock in resource-limited settings.

The clinical spectrum of severe childhood malaria in Eastern Uganda.

BACKGROUND: Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year. METHODS: A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months-12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma. RESULTS: A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16-1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72-7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39-9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29-4.06; P = 0.004). No independent association was found between mortality and either coma or hyperparasitaemia. CONCLUSIONS: Severe childhood malaria remains common in Eastern Uganda where it continues to be associated with high mortality. An unusually high proportion of children with severe malaria had jaundice or gave a history of having recently passed dark red or black urine, an issue worthy of further investigation.

High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.

BACKGROUND: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF). METHODS: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls. RESULTS: Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum histidine rich protein 2 (192/246 [78.0%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria. CONCLUSIONS: We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.

Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.

BACKGROUND: Severe anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa, with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarely identified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood (20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and poor outcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated with the optimal survival outcomes. METHODS: We evaluated the safety and efficacy of a higher volume of whole blood (30 ml/kg; Tx30: n = 78) against the standard volume (20 ml/kg; Tx20: n = 82) in Ugandan children (median age 36 months (interquartile range (IQR) 13 to 53)) for 24-hour anemia correction (hemoglobin >6 g/dl: primary outcome) and 28-day survival. RESULTS: Median admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed the randomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SA compared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01). From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001). Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were six deaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but none secondary to volume overload. CONCLUSION: A higher initial transfusion volume prescribed at hospital admission was safe and resulted in an accelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinical trial to establish the effect on short and longer-term survival is warranted. TRIAL REGISTRATION: ClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011.

Elevated blood pressure among children born to women with obstructed labour in Eastern Uganda: a cohort study.

BACKGROUND: Globally, high systolic blood pressure accounts for 10.8 million deaths annually. The deaths are disproportionately higher among black people. The reasons for this disparity are poorly understood, but could include a high burden of perinatal insults such as birth asphyxia. Therefore, we aimed to assess the incidence of elevated blood pressure and to explore associated factors among children born to women with obstructed labour. METHODS: We followed up children born to women with obstructed labour aged 25 to 44 months at Mbale regional referral hospital that had participated in the sodium bicarbonate trial ( Trial registration number PACTR201805003364421) between October 2021 and April 2022. Our primary outcome was elevated blood pressure defined as blood pressure (either systolic or diastolic or both) ≥ the 90th percentile for age, height, and sex in the reference population based on the clinical practice guideline for screening and management of high blood pressure in children and adolescents. We used logistic regression to estimate odds ratios between selected exposures and elevated blood pressure. RESULTS: The incidence of elevated blood pressure was (39/140, 27.9%: 95% (CI: 20.6-36.1)). Participants aged three years and above had twice the odds of elevated blood pressure as those aged less than three years (Adjusted odds ratio (AOR) 2.46: 95% CI (1.01-5.97). Female participants had 2.81 times the odds of elevated blood pressure as their male counterparts (AOR 2.81 95% CI (1.16-6.82). Participants with reduced estimated glomerular filtration rate had 2.85 times the odds of having elevated blood pressure as those with normal estimated glomerular filtration rate (AOR 2.85 95% CI (1.00-8.13). We found no association between arterial cord lactate, stunting, wealth index, exclusive breastfeeding, food diversity and elevated blood pressure. CONCLUSION: Our findings show a high incidence of elevated blood pressure among children. We encourage routine checking for elevated blood pressure in the pediatric population particularly those with known risk factors.

A cluster randomised trial to evaluate the effectiveness of household alcohol-based hand rub for the prevention of sepsis, diarrhoea, and pneumonia in Ugandan infants (the BabyGel trial): a study protocol.

BACKGROUND: Infections are one of the leading causes of death in the neonatal period. This trial aims to evaluate if the provision of alcohol-based hand rub (ABHR) to pregnant women for postnatal household use prevents severe infections (including sepsis, diarrhoea, pneumonia, or death) among infants during the first three postnatal months. METHODS: Through a cluster-randomised trial in eastern Uganda, 72 clusters are randomised in a 2-arm design with rural villages as units of randomisation. We estimate to include a total of 5932 pregnant women at 34 weeks of gestation. All women and infants in the study are receiving standard antenatal and postnatal care. Women in the intervention group additionally receive six litres of ABHR and training on its use. Research midwives conduct follow-up visits at participants' homes on days 1, 7, 28, 42, and 90 after birth and telephone calls on days 14, 48, and 60 to assess the mother and infant for study outcomes. Primary analyses will be by intention to treat. DISCUSSION: This study will provide evidence on the effectiveness of a locally available and low-cost intervention in preventing neonatal sepsis and early infant infections. If ABHR is found effective, it could be implemented by adding it to birthing kits. TRIAL REGISTRATION: Pan African Clinical Trial Registry, PACTR202004705649428. Registered 1 April 2020, https://pactr.samrc.ac.za/ .

High Burden of Neurodevelopmental Delay among Children Born to Women with Obstructed Labour in Eastern Uganda: A Cohort Study.

Over 250 million infants in low and middle-income countries do not fulfill their neurodevelopment potential. In this study, we assessed the incidence and risk factors for neurodevelopmental delay (NDD) among children born following obstructed labor in Eastern Uganda. Between October 2021 and April 2022, we conducted a cohort study of 155 children (aged 25 to 44 months), born at term and assessed their neurodevelopment using the Malawi Developmental Assessment Tool. We assessed the gross motor, fine motor, language and social domains of neurodevelopment. The incidence of neurodevelopmental delay by 25 to 44 months was 67.7% (105/155) (95% CI: 59.8-75.0). Children belonging to the poorest wealth quintile had 83% higher risk of NDD compared to children belonging to the richest quintile (ARR (Adjusted Risk Ratio): 1.83; 95% CI (Confidence Interval): [1.13, 2.94]). Children fed the recommended meal diversity had 25% lower risk of neurodevelopmental delay compared to children who did not (ARR: 0.75; 95% CI: [0.60, 0.94]). Children who were exclusively breastfed for the first 6 months had 27% lower risk of neurodevelopmental delay compared to children who were not (ARR: 0.73; 95% CI: [0.56, 0.96]). We recommend that infants born following obstructed labor undergo neurodevelopmental delay screening.

Decreased renal function among children born to women with obstructed labour in Eastern Uganda: a cohort study.

Background: Over two million children and adolescents suffer from chronic kidney disease globally. Early childhood insults such as birth asphyxia could be risk factors for development of chronic kidney disease in infancy. Our study aimed to assess renal function among children aged two to four years, born to women with obstructed labour. Methods: We followed up 144 children aged two to four years, born to women with obstructed labor at Mbale regional referral hospital in Eastern Uganda. We used estimated glomerular filtration rate (eGFR) by the Schwartz formula to calculate eGFR (0.413*height)/ serum creatinine as a measure of renal function. eGFR less than 90 ml/min/1.73m2 was classified as decreased renal function. Results: The mean age of the children was 2.8 years, standard deviation (SD) of 0.4 years. Majority of the children were male (96/144: 66.7%). The mean umbilical lactate level at birth among the study participants was 8.9 mmol/L with a standard deviation (SD) of 5.0. eGFR values ranged from 55 to 163ml/min/1.72m2, mean 85.8 ± SD 15.9. One third (31.3%) 45/144 had normal eGFR (> 90 ml/Min/1.72m2), two thirds (67.4%) 97/144 had a mild decrease of eGFR (60-89 ml/Min/1.72m2), and only 2/144 (1.4%) had a moderate decrease of eGFR. Overall incidence of reduced eGFR was 68.8% (99/144). Conclusion: We observed a high incidence of impaired renal function among children born to women with obstructed labour. We recommend routine follow up of children born to women with obstructed labour and add our voices to those calling for improved intra-partum and peripartum care.

Vitamin D deficiency in low-birth-weight infants in Uganda; a cross sectional study.

BACKGROUND: Vitamin D deficiency affects 7-86% of infants globally and results in recurrent infections, impaired growth and nutritional rickets. Low-birth-weight infants in Uganda are at risk of vitamin D deficiency due to limited sunlight exposure and dependence on breastmilk. We aimed to determine the prevalence and factors associated with vitamin D deficiency among low-birth-weight infants aged 6 weeks to 6 months at Mulago national referral hospital in Uganda. METHODS: We conducted a cross-sectional study at Mulago Hospital between September 2016 and March 2017. We enrolled infants born with low birth weight between six weeks and six months whose mothers were available and willing to provide informed consent. Upon obtaining informed consent, we administered a structured questionnaire and performed a physical examination on the participants. Blood was drawn for calcium, phosphorus and vitamin D estimation. We measured serum 25 hydroxy vitamin D (25(OH)D) using the electrochemiluminescence method. Vitamin D deficiency and insufficiency were defined as (25(OH)D) < 20ng/ml and from 20ng/ml to <30 ng/ml respectively. To determine factors associated with vitamin D deficiency, we fit multivariable logistic regression models with exposure factors determined a priori. Data were analysed using Stata version 14. RESULTS: We enrolled 297 participants, 49.2% (167/297) of whom were males. The median infant age was nine weeks (interquartile range 7-13). All infants had less than one hour of sunlight exposure and over 90.6% (269/297) had received multivitamin supplements containing vitamin D. The prevalence of vitamin D deficiency was 12.1% (36/297): 95% CI (8.9%-16.4%). The prevalence of vitamin D insufficiency was 19.9% (59/297): 95% CI (15.7%-24.8%). Boys had higher odds of vitamin D deficiency compared to girls [adjusted odds ratio 2.8: 95% CI 1.3-6.1]. CONCLUSION: Vitamin D deficiency was 12.1% among low-birth-weight infants in Uganda although almost all of them had received multivitamin supplements containing vitamin D. We recommend that more studies are done in low-birth-weight infants to assess the risk factors for vitamin D in these population in Uganda.

Maternal and newborn health priority setting partnership in rural Uganda in association with the James Lind Alliance: a study protocol.

BACKGROUND: Maternal and newborn deaths and ill health are relatively common in low income countries, but can adequately be addressed through locally, collaboratively designed, and responsive research. This has the potential to enable the affected women, their families and health workers themselves to explore 'why maternal and newborn adverse outcomes continue to occur. The objectives of the study include; To work with seldom heard groups of mothers, their families, and health workers to identify unanswered research questions for maternal and newborn health in villages and health facilities in rural UgandaTo establish locally responsive research questions for maternal and newborn health that could be prioritised together with the public in UgandaTo support the case for locally responsive research in maternal and newborn health by the ministry of health, academic researchers and funding bodies in Uganda. METHODS: The present study will follow the James Lind Alliance (JLA) Priority Setting Partnership (PSP) methodology. The project was initiated by an academic research group and will be managed by a research team at the Sanyu Africa Research Institute on a day to day basis. A steering group with a separate lay mothers' group and partners' group (individuals or organisations with interest in maternal and newborn health) will be recruited. The PSP will be initiated by launch meetings, then a face-to-face initial survey for the collection of raw unanswered questions; followed by data collation. A face-to-face interim prioritisation survey will then be performed to choose questions before the three separate final prioritisation workshops.The PSP will involve many participants from an illiterate, non-internet population in rural eastern Uganda, but all with an interest in strategies to avert maternal and newborn deaths or morbidities in rural eastern Uganda. This includes local rural women, their families, health and social workers, and relevant local groups or organisations.We will generate a top 10 list of maternal and newborn health research priorities from a group with no prior experience in setting a research agenda in rural eastern Uganda. DISCUSSION: The current protocol elaborates the JLA methods for application with a new topic and in a new setting translating the JLA principles not just into the local language, but into a rural, vulnerable, illiterate, and non-internet population in Uganda. The face-to-face human interaction is powerful in eliciting what exactly matters to individuals in this particular context as opposed to online surveys.This will be the first time that mothers and lay public with current or previous experience of maternal or neonatal adverse outcomes will have the opportunity to identify and prioritise research questions that matter to them in Uganda. We will be able to compare how the public would prioritise maternal health research questions over newborn health in this setting.

Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda.

Background: Severe anaemia in children requiring hospital admission is a major public health problem in malaria-endemic Africa. Affordable methods for the assessment of haemoglobin have not been validated against gold standard measures for identifying those with severe anaemia requiring a blood transfusion, despite this resource being in short supply. Methods: We conducted a prospective descriptive study of hospitalized children aged 2 months - 12 years at Mbale and Soroti Regional Referral Hospitals, assessed to have pallor at triage by a nurse and two clinicians. Haemoglobin levels were measured using the HemoCue ® Hb 301 system (gold standard); the Haemoglobin Colour Scale; Colorimetric and Sahli's methods. We report clinical assessments of the degree of pallor, clinicians' intention to transfuse, inter-observer agreement, limits of agreement using the Bland-Altman method, and the sensitivity and specificity of each method in comparison to HemoCue ® Results: We recruited 322 children, clinically-assessed by the admitting nurse (n=314) as having severe (166; 51.6%), moderate (97; 30.1%) or mild (51; 15.8%) pallor. Agreement between the clinicians and the nurse were good: Clinician A Kappa=0.68 (0.60-0.76) and Clinician B Kappa=0.62 (0.53-0.71) respectively ( P<0.0001 for both). The nurse, clinicians A and B indicated that of 94/116 (81.0%), 83/121 (68.6%) and 93/120 (77.5%) respectively required transfusion. HemoCue ® readings indicated anaemia as mild (Hb10.0-11.9g/dl) in 8/292 (2.7%), moderate (Hb5.0-9.9g/dl) in 132/292 (45.2%) and severe (Hb<5.0g/dl) in 152/292 (52.1%). Comparing to HemoCue® the Sahli's method performed best in estimation of severe anaemia, with sensitivity 84.0% and specificity 87.9% and a Kappa score of  0.70 (0.64-0.80). Conclusions: Clinical assessment of severe pallor results has a low specificity for the diagnosis of severe anaemia. To target blood transfusion Hb measurement by either Hemocue® or Sahli's method for the cost of USD 4 or and USD 0.25 per test, respectively would be more cost-effective.