Abstract
Background:
Pediatric inpatient mortality rates are as high as 11% in parts of sub-Saharan Africa. Unscheduled clinic visits also burden children in sub-Saharan Africa. Our objective was to identify factors associated with hospital admissions and unscheduled clinic visits among Tanzanian children <24 months of age.
Methods:
We conducted a secondary analysis of two trials conducted in Dar es Salaam, Tanzania. We performed univariate and Poisson multivariable regression analyses to identify factors associated with hospital admissions and unscheduled clinic visits.
Results:
Of 4,784 children <24 months of age, 293 (6.1%) were hospitalized at least once and 1,308 (27.3%) had ≥ 1 unscheduled clinic visit. Infants and children who were exposed to but HIV-negative had increased risk of hospital admission (aRR 3.67, 95% CI 2.45–5.50, P<0.001) compared to HIV-unexposed children. Those who were HIV-positive had even higher risk of hospital admission compared to those not exposed to HIV (aRR 10.87, 95% CI 7.01–16.89, P<0.001). Birthweight and breastfeeding status were not associated with increased risk of hospital admission. Children with Apgar scores < 7 (aRR 1.32, 95% CI 1.03–1.69, P=0.001), not exclusively breastfed up to 6 months of age (aRR 1.34, 95% CI 1.12–1.60, P=0.001), and who were HIV-exposed and -negative (aRR 2.35, 95% CI 2.08–2.66, P<0.001) or HIV-positive (aRR 3.02, 95% CI 2.52–3.61, P<0.001) had higher risk of unscheduled clinic visits.
Conclusions:
Exposure to HIV and being HIV-positive were associated with the greatest risk for hospital admission and unplanned clinic visits among infants and children in Tanzania. Targeting these vulnerable populations in interventional studies may reduce morbidity.
Keywords: hospital admissions, pediatric, infants, children, Tanzania, HIV
Introduction
Despite recent reductions in overall childhood mortality,1 pediatric inpatient mortality rates range from 3% to 11% in sub-Saharan Africa2 with 44–59% of these deaths occurring in the first 48 hours of admission.3–5 Early inpatient deaths are often due to factors present prior to admission as well as inadequate or untimely care provided upon presentation.3 Identifying children at risk of hospital admission is a step in preventing death and other adverse outcomes in sub-Saharan Africa.
Unscheduled clinic visits for illnesses also burden children and their families in sub-Saharan Africa. Prior prospective studies in Uganda and The Gambia have shown that children with recent hospital admissions for malaria and those with malnutrition frequently have unscheduled clinic visits for illness.6,7 However, studies evaluating other risk factors for unscheduled clinic visits for illness are lacking. Moreover, children exposed to and positive for human immunodeficiency virus (HIV) have high rates of death after unscheduled clinic visits for illness.8 Identification of factors present prior to unscheduled clinic visits for illness may help direct resources to children at risk of such clinic visits.
Thus, our objective was to identify maternal, socioeconomic, and child-level factors associated with hospital admissions and unscheduled clinic visits for illness in Tanzanian infants and children <24 months of age. We hypothesized that hospital admissions and unscheduled clinic visits for illness would be more common among children from lower socioeconomic status (SES) and among those with exposure to HIV, and those who were HIV-positive.
Materials and Methods
Study Design
We conducted a secondary analysis of prospectively collected data from two large micronutrient supplementation trials conducted in Dar es Salaam, Tanzania (NCT00197730 and NCT00421668).9,10 Ethical approval for these trials was granted by the Muhimbili University of Health and Allied Science Committee of Research and Publications, the Tanzanian National Institute of Medical Research, the Tanzanian Food and Drug Authority, and the Harvard T.H. Chan School of Public Health Human Subjects Committee. All caregivers provided written informed consent for enrollment in these trials.
Complete methodology of the two clinical trials from which these data were obtained has been described previously.9,10 In brief, the first trial randomized infants born to mothers who tested positive for HIV to either daily multivitamins (vitamins B complex, vitamin C, and vitamin E) or placebo beginning at six weeks of age for 24 months.9 The second trial randomized infants born to mothers who tested negative for HIV to receive zinc, zinc and multivitamins, multivitamins, or placebo at six weeks of age for 18 months.10 The first trial was conducted between August 2004 and November 2007. The second trial took place between August 2007 and December 2009. In both trials, enrolled participants were followed with planned, monthly clinic visits during which morbidity was assessed through standardized forms evaluating for prior unscheduled clinic visits, hospital admissions, and signs and symptoms present during the preceding month. Standardized techniques were used to measure the height and weight of infant and children participants.11 Study nurses also recorded hospital admissions and unplanned clinic visits in the preceding month during planned clinic visits. Infants and children who missed their scheduled clinic visits were visited in their homes by study nurses. All hospital admission and unplanned clinic visit data were included in the analysis until the time of death or loss to follow up.
Clinical care was provided in accordance with Tanzanian national guidelines. Antiretroviral therapy (ART) became widely available near the beginning of the trial with the cohort of mothers who were HIV-positive. Mothers were eligible for ART if they had World Health Organization (WHO) stage IV disease, a CD4 cell count of ≤200 cells/mL, or if they had WHO stage III disease and a CD4 cell count of ≤350 cells/mL. Children were tested for HIV at six weeks of age using DNA PCR testing (Amplicor HIV-1 DNA assay version 1.5, Roche Molecular Systems, Inc.) and again at 18 months of age using HIV ELISA testing (Enzygnost anti-HIV-1/2 Plus, Dade Behring). At the time of the trial, prevention of mother-to-child transmission was limited to nevirapine prophylaxis. Children were eligible for ART if they had CD4% <20 or pediatric WHO stage III disease. Infants born to HIV-positive mothers received prophylactic trimethoprim-sulfamethoxazole until the infant was six months old and for the duration of time the child continued breastfeeding.
Variables
Our primary outcomes were hospital admissions and unscheduled clinic visits for illnesses during the study period. Independent variables included maternal characteristics, proxies for SES, and child-level characteristics. These three groups of variables were selected prior to analysis based on a review of the literature of predictors of poor health outcomes among children in sub-Saharan Africa.12,13 Maternal characteristics included age, prior pregnancies, mid-upper arm circumference (MUAC), marital status, and formal education. SES characteristics included maternal employment, household assets, and daily food expenditure. Child-level characteristics included sex, birth weight, gestational age, Apgar score, breastfeeding, HIV status, and micronutrient received during the two clinical trials.
Analyses
We used descriptive statistics to evaluate maternal, socioeconomic, and child-level factors among children by ever hospitalization and ever having unscheduled clinic visits for illnesses during the study period. We calculated the frequency and proportion of each diagnosis for hospital admissions and unscheduled clinic visits. Poisson regression models were performed to identify risk factors associated with hospital admissions and unscheduled clinic visits. Risk ratios (RR) and 95% confidence intervals (CI) were used to assess the association between hospitalization, unscheduled clinic visits and each potential factor. Variables with P value <0.20 were included in the final multivariable analysis. All statistics were computed using SAS (version 9.4, SAS Institute, Cary, North Carolina, United States of America).
Results
There were 4,784 infants and children <24 months of age enrolled in the two trials; 2,505 (52.3%) were males and 647 (14.2%) were born before 37 weeks’ gestation. There were 2,387 infants who were exposed to HIV and 2,400 were not exposed to HIV. Over the two trial periods, 307 infants and children died. The median follow-up period was 22.9 months (interquartile range [IQR] 17.4–23.9) in the first trial and 18.0 (IQR 17.5–20.7) in the second trial.
Of the 4,784 infants and children <24 months of age in the two trials, 293 (6.1%) were hospitalized at least once. Twenty-seven had two hospitalizations (0.6%) and nine had three hospitalizations (0.2%). Among the 338 hospital admissions during the trials, 19 (5.6%) admissions were preceded by an unplanned clinic visit in the month before their hospital admission and 14 (4.1%) were followed by an unplanned clinic visit during the month after the hospital admission.
Hospital Admissions
Maternal, socioeconomic, and child-level clinical factors for infants and children who had a hospital admission during the trials and for those who did not are presented in Table 1. Malaria (n=188, 30.8%), pneumonia (n=170, 27.9%), and diarrhea (n=123, 20.2%) were the most common reasons for hospital admission for all children, including those born to women who were HIV-negative or HIV-positive.
Table 1.
Maternal, socioeconomic, and child-level characteristics of children who had an unplanned admission and those without an unplanned admission.
| Children Not Hospitalized (n=4,491) | Children Hospitalized (n=293) | |
|---|---|---|
| Maternal Characteristics | ||
| Maternal Age (years) | ||
| <24 | 1,144 (25.9) | 42 (14.8) |
| 25–29 | 1,855 (41.9) | 136 (47.9) |
| 30+ | 1,425 (32.2) | 106 (37.3) |
| Formal education, n (%) | ||
| None | 181 (4.1) | 13 (4.5) |
| 1–7 years | 3,215 (72.0) | 213 (74.0) |
| ≥ 8 | 1,065 (23.9) | 62 (21.5) |
| Marital Status, n (%) | ||
| Single | 493 (11.1) | 41 (14.3) |
| Married or cohabitating with partner | 3,957 (88.9) | 246 (85.7) |
| Prior Pregnancies, n (%) | ||
| None | 1,218 (27.3) | 64 (22.2) |
| 1–4 | 3,115 (69.9) | 215 (74.4) |
| ≥ 5 | 123 (2.8) | 10 (3.5) |
| Maternal MUAC (cm), n (%) | ||
| ≥23 | 3, 985 (90.2) | 245 (84.2) |
| <23 | 434 (9.8) | 46 (15.8) |
| Socioeconomic Characteristics | ||
| Maternal Employment, n (%) | ||
| Housewife without income | 2,785 (63.4) | 187 (67.0) |
| Housewife with income | 1,057 (24.1) | 35 (12.5) |
| Other | 550 (12.5) | 57 (20.4) |
| Household Asset (TV), n (%) | ||
| Yes | 1,716 (38.5) | 118(40.8) |
| No | 2,742 (61.5) | 171(59.2) |
| Household Asset (Refrigerator), n (%) | ||
| Yes | 1,985 (44.6) | 93 (32.2) |
| No | 2,468 (55.4) | 196 (67.8) |
| Daily Food Expenditure per Person, n (%) | ||
| ≥1,000 Tanzanian Shillings | 1,726 (40.6) | 46 (16.9) |
| <1,000 Tanzanian Shillings | 2,527 (59.4) | 227 (83.1) |
| Child Characteristics | ||
| Sex, n (%) | ||
| Female | 2,168 (48.3) | 113 (38.6) |
| Male | 2,323 (51.7) | 180 (61.4) |
| Birthweight, n (%) | ||
| Low birthweight (< 2500 grams) | 226 (5.2) | 17 (6.0) |
| Not low birthweight (≥2,500 grams) | 4,153 (94.8) | 265 (94.0) |
| Prematurity, n (%) | ||
| Premature birth (< 37 weeks) | 604 (14.2) | 42 (14.8) |
| Not premature birth (≥ 37 weeks) | 3,662 (85.8) | 241 (85.2) |
| Apgar score, n (%) | ||
| 8–10 | 3,966 (97.1) | 251 (96.2) |
| < 7 | 118 (2.9) | 10 (3.8) |
| Breastfeeding, n (%) | ||
| Exclusive breastfeeding to 6 months | 4,158 (93.4) | 264 (90.4) |
| Not exclusive breastfeeding to 6 months | 292 (6.6) | 28 (9.6) |
| HIV status, n (%) | ||
| Unexposed | 2,346 (52.5) | 51 (17.5) |
| Exposed but HIV-negative | 1,827 (40.9) | 178 (61.0) |
| Exposed and HIV-positive | 292 (6.5) | 63 (21.5) |
| Micronutrient Supplementation, n (%) | ||
| Placebo | 1,651 (36.8) | 146 (49.9) |
| Multivitamin | 1,674 (37.3) | 116 (39.6) |
| Zinc | 582 (13.0) | 14 (4.8) |
| Zinc and Multivitamin | 584 (13.0) | 17 (5.8) |
On multivariable regression, children whose mothers were housewives with income (adjusted RR [aRR] 0.49, 95% CI 0.30–0.82, P=0.01) had reduced risk of hospital admission when compared to infants and children whose mothers were housewives but did not have an income (Table 2). Lower maternal nutritional status (MUAC < 23 cm) was not associated with greater risk of hospital admission among infants and children when compared to mothers with MUAC ≥ 23 cm (aRR 1.08, 95% CI 0.79–1.48, P=0.59). Male infants and children had increased risk of hospital admission in comparison to females (aRR 1.34 95% CI 1.08–1.68, P=0.01). Children exposed to and HIV-negative (aRR 5.02, 95% CI 2.97–8.48, P<0.001) and those who were HIV-positive (aRR 15.03, 95% CI 8.64–26.17, P<0.001) had increased risk of hospital admission in comparison to infants and children not exposed to HIV. Low birthweight (<2,500 grams) (RR 1.30, 95% CI 0.83–2.05, P=0.25) and non-exclusive breastfeeding (aRR 1.31, 95% CI 0.89–1.91, P=0.16) were not associated with greater risk of hospital admission compared to infants and children with birthweight > 2,500 grams and exclusive breastfeeding up to 6 months, respectively. Infants and children who received any form of multivitamin did not have a lower risk of hospital admission compared to those who received placebo on multivariable analysis.
Table 2.
Multivariable regression analysis of demographic and clinical factors associated with hospitalization.
| Univariable | Multivariable | |||
|---|---|---|---|---|
| Risk Ratio (95% CI) | P value | Adjusted Risk Ratio (95% CI) | P value | |
| Maternal Characteristics | ||||
| Maternal Age (years) | ||||
| <24 | Referent | Referent | ||
| 25–29 | 1.84 (1.33–2.53) | <0.001 | 1.32 (0.94–1.87) | 0.11 |
| 30+ | 1.96 (1.41–2.72) | <0.001 | 1.29 (0.88–1.89) | 0.17 |
| Formal education (years) | ||||
| ≥ 8 | 0.86 (0.52–1.40) | 0.54 | ||
| 1–7 | 0.72 (0.43–1.23) | 0.23 | ||
| None | Referent | |||
| Marital Status | ||||
| Single | Referent | Referent | ||
| Married or cohabitating with partner | 0.80 (0.58–1.10) | 0.17 | 0.92 (0.66–1.29) | 0.66 |
| Prior Pregnancies | ||||
| None | Referent | Referent | ||
| 1–4 | 1.28 (0.99–1.67) | 0.06 | 1.04 (0.77–1.40) | 0.76 |
| ≥ 5 | 1.30 (0.67–2.53) | 0.43 | 1.09 (0.54–2.21) | 0.79 |
| Maternal MUAC (cm) | ||||
| ≥ 23 | Referent | Referent | ||
| < 23 | 1.61 (1.19–2.16) | 0.002 | 1.08 (0.79–1.48) | 0.59 |
| Socioeconomic Characteristics | ||||
| Maternal Employment | ||||
| Housewife without income | Referent | Referent | ||
| Housewife with income | 0.51 (0.60–0.72) | <0.001 | 0.49 (0.30–0.82) | 0.01 |
| Other | 1.54 (1.17–2.02) | 0.002 | 1.13 (0.87–1.46) | 0.33 |
| Household asset (TV) | ||||
| Yes | 1.05 (0.84–1.31) | 0.67 | ||
| No | Referent | |||
| Household asset (Refrigerator) | ||||
| Yes | 0.59 (0.46–0.74) | <0.001 | 1.00 (0.78–1.27) | 0.99 |
| No | Referent | Referent | ||
| Daily food expenditure per person | ||||
| ≥1,000 Tanzanian Shillings | Referent | Referent | ||
| <1,000 Tanzanian Shillings | 3.44 (2.54–4.65) | <0.001 | 1.04 (0.70–1.55) | 0.82 |
| Child Characteristics | ||||
| Sex | ||||
| Female | Referent | Referent | ||
| Male | 1.39 (1.12–1.73) | 0.003 | 1.34 (1.08–1.68) | 0.01 |
| Birthweight | ||||
| Low birthweight (< 2500 grams) | 1.30 (0.83–2.05) | 0.25 | ||
| Not low birthweight (≥2,500 grams) | Referent | |||
| Prematurity | ||||
| Premature birth (< 37 weeks) | 1.21 (0.90–1.62) | 0.21 | ||
| Not premature birth (≥ 37 weeks) | Referent | |||
| Apgar score | ||||
| 8–10 | Referent | Referent | ||
| < 7 | 1.65 (0.97–2.83) | 0.07 | 1.53 (0.89–2.65) | 0.12 |
| Breastfeeding, n (%) | ||||
| Exclusive breastfeeding to 6 months | Referent | Referent | ||
| Not exclusive breastfeeding to 6 months | 0.75 (0.52–1.08) | 0.12 | 1.31(0.89–1.91) | 0.16 |
| HIV status | ||||
| Unexposed | Referent | Referent | ||
| Exposed but HIV-negative | 4.32 (3.21–5.83) | <0.001 | 5.02 (2.97–8.48) | <0.001 |
| Exposed and HIV-positive | 13.00 (9.23–18.31) | <0.001 | 15.03 (8.64–26.17) | <0.001 |
| Micronutrient Supplementation | ||||
| Placebo | - | Referent | ||
| Multivitamin | - | 0.82 (0.65–1.03) | 0.09 | |
| Zinc | - | 1.29 (0.66–2.52) | 0.45 | |
| Zinc and Multivitamin | - | 1.63 (0.87–3.06) | 0.12 | |
Unscheduled Clinic Visits
Maternal, socioeconomic, and child-level characteristics of the 1,308 (27.3%) children who had unscheduled clinic visits for illness and the 3,476 (72.7%) who did not are summarized in Table 3. The most common diagnoses among the 1,640 reported diagnoses from unscheduled clinic visits were malaria (n=688, 42.0%), fever (n=206, 12.6%), cough or difficulty breathing (n=172, 10.5%), diarrhea (n=155, 9.5%), and upper respiratory tract infections (n=147, 9.0%).
Table 3.
Maternal, socioeconomic, and child-level characteristics of children who had an unscheduled clinic visit for illnesses and those without an unscheduled clinic visit for illnesses.
| Children Without Unscheduled Clinic Visit (n=3,476) | Children With ≥ 1 Unscheduled Clinic Visit (n=1,308) | |
|---|---|---|
| Maternal Characteristics | ||
| Maternal Age (years) | ||
| <24 | 957 (27.9) | 228 (17.8) |
| 25–29 | 1,400 (40.9) | 591 (46.1) |
| 30+ | 1,068 (31.2) | 463 (36.1) |
| Formal education, n (%) | ||
| None | 136 (3.9) | 58 (4.5) |
| 1–7 years | 2,486 (72.0) | 943 (72.7) |
| ≥ 8 | 830 (24.1) | 296 (22.8) |
| Marital Status, n (%) | ||
| Single | 380 (11.0) | 154 (11.9) |
| Married or cohabitating with partner | 3,062 (89.0) | 1140 (88.1) |
| Prior Pregnancies, n (%) | ||
| None | 980 (28.4) | 301 (23.2) |
| 1–4 | 2,373 (68.8) | 957 (74.0) |
| ≥ 5 | 97 (2.8) | 36 (2.8) |
| Maternal MUAC (cm), n (%) | ||
| ≥23 | 3,090 (90.3) | 1,139 (88.5) |
| <23 | 332 (9.7) | 148 (11.5) |
| Socioeconomic Characteristics | ||
| Maternal Employment, n (%) | ||
| Housewife without income | 2,163 (63.5) | 808 (63.9) |
| Housewife with income | 842 (24.7) | 250 (19.8) |
| Other | 401 (11.8) | 206 (16.3) |
| Household Asset (TV), n (%) | ||
| Yes | 1,307 (37.9) | 527 (40.7) |
| No | 2,143 (62.1) | 769 (59.3) |
| Household Asset (Refrigerator), n (%) | ||
| Yes | 1,585 (46.1) | 492 (38.0) |
| No | 1,860 (53.9) | 804 (62.0) |
| Daily Food Expenditure per Person, n (%) | ||
| ≥1,000 Tanzanian Shillings | 1,448 (44.1) | 323 (26.1) |
| <1,000 Tanzanian Shillings | 1,838 (55.9) | 916 (73.9) |
| Child Characteristics | ||
| Sex, n (%) | ||
| Female | 1,685 (48.5) | 595 (45.5) |
| Male | 1,790 (51.5) | 713 (54.5) |
| Birthweight, n (%) | ||
| Low birthweight (< 2500 grams) | 187 (5.5) | 56 (4.4) |
| Not low birthweight (≥2,500 grams) | 3,191 (94.5) | 1,226 (95.6) |
| Prematurity, n (%) | ||
| Premature birth (< 37 weeks) | 499 (15.1) | 147 (11.7) |
| Not premature birth (≥ 37 weeks) | 2,796 (84.9) | 1,107 (88.3) |
| Apgar score | ||
| 8–10 | 3,070 (97.4) | 1,146 (96.1) |
| < 7 | 82 (2.6) | 46 (3.9) |
| Breastfeeding, n (%) | ||
| Exclusive breastfeeding to 6 months | 212 (6.2) | 108 (8.3) |
| Not exclusive breastfeeding to 6 months | 3,228 (93.8) | 1,193 (91.7) |
| HIV status, n (%) | ||
| Unexposed | 1,978 (57.2) | 418 (32.2) |
| Exposed but HIV-negative | 1,253 (36.3) | 752 (57.9) |
| Exposed and HIV-positive | 225 (6.5) | 130 (10.0) |
| Micronutrient Supplementation, n (%) | ||
| Placebo | 1,263 (36.4) | 534 (40.8) |
| Multivitamin | 1,249 (35.9) | 541 (41.4) |
| Zinc | 476 (13.7) | 119 (9.1) |
| Zinc and Multivitamin | 487 (14.0) | 114 (8.7) |
On multivariable analysis, infants and children whose mothers were older than age 25 years had increased risk of unscheduled clinic visits (aRR 1.33, 95% CI 1.15–1.55, P<0.001 for age 25–39 years and aRR 1.37, 95% CI 1.17–1.61, P<0.001 for age 30+ years, both compared to age mothers <25 years) (Table 4). Compared with children with birthweight ≥ 2500 grams, children with low birthweight had reduced risk of unscheduled clinic visits (aRR 0.76, 95% CI 0.60–0.97, P=0.02). Infants and children who had Apgar scores < 7 (aRR 1.32, 95% CI 1.03–1.69, P=0.02), who were not exclusively breastfed up to 6 months of age (aRR 1.34, 95% CI 1.12–1.61, P=0.001), and who were either exposed to but HIV-negative (aRR 2.60, 95% CI 2.23–3.03, P<0.001) or HIV-positive (aRR 3.35, 95% CI 2.74–4.11, P<0.001) had higher risk of unscheduled clinic visits compared to infants and children with Apgar scores ≥ 7 at birth, who were exclusively breastfed up to 6 months, and who were HIV unexposed, respectively. Infants and children who received any form of multivitamin did not have a lower risk of unscheduled clinic visits compared to those who received placebo on multivariable analysis.
Table 4.
Multivariable regression analysis of demographic and clinical factors associated with unscheduled clinic visits for illnesses.
| Univariate | Multivariate | |||
|---|---|---|---|---|
| Risk Ratio (95% CI) | P value | Adjusted Risk Ratio (95% CI) | P value | |
| Maternal Characteristics | ||||
| Maternal Age (years) | ||||
| <24 | Referent | Referent | ||
| 25–29 | 1.36 (1.14–1.62) | <0.001 | 1.33 (1.15–1.55) | <0.001 |
| 30+ | 1.36 (1.14–1.63) | <0.001 | 1.37 (1.17–1.61) | <0.001 |
| Formal education (years) | ||||
| ≥ 8 | 1.25 (0.97–1.62) | 0.08 | 1.09 (0.85–1.40) | 0.47 |
| 1–7 | 1.19 (0.94–1.51) | 0.15 | 1.12 (0.89–1.41) | 0.31 |
| None | Referent | Referent | ||
| Marital Status | ||||
| Single | 1.07 (0.90–1.27) | 0.45 | ||
| Married or cohabitating with partner | Referent | |||
| Prior Pregnancies | ||||
| 0 | Referent | Referent | ||
| 1–4 | 1.14 (0.99–1.31) | 0.06 | 1.07 (0.94–1.21) | 0.29 |
| ≥ 5 | 0.99 (0.69–1.43) | 0.96 | 0.87 (0.62–1.21) | 0.41 |
| Maternal MUAC (cm) | ||||
| ≥ 23 | Referent | |||
| < 23 | 0.90 (0.77–1.06) | 0.22 | ||
| Socioeconomic Characteristics | ||||
| Maternal Employment | ||||
| Housewife without income | Referent | Referent | ||
| Housewife with income | 0.96 (0.81–1.14) | 0.63 | 0.83 (0.70–0.99) | 0.04 |
| Other | 1.17 (1.02–1.34) | 0.03 | 1.10 (0.98–1.23) | 0.08 |
| Household asset (TV) | ||||
| Yes | 1.15 (1.03–1.28) | 0.01 | 1.04 (0.93–1.16) | 0.45 |
| No | Referent | Referent | ||
| Household asset (Refrigerator) | ||||
| Yes | 1.15 (1.02–1.30) | 0.03 | 1.01 (0.92–1.14) | 0.78 |
| No | Referent | Referent | ||
| Daily Food Expenditure per Person | ||||
| ≥1,000 Tanzanian Shillings | Referent | |||
| <1,000 Tanzanian Shillings | 1.08 (084–1.39) | 0.55 | ||
| Child Characteristics | ||||
| Sex | ||||
| Female | Referent | Referent | ||
| Male | 1.15 (1.03–1.29) | 0.01 | 1.08 (0.99–1.19) | 0.07 |
| Birthweight | ||||
| Low birthweight (< 2500 grams) | 0.79 (0.61–1.02) | 0.07 | 0.76 (0.60–0.97) | 0.02 |
| Not low birthweight (≥2,500 grams) | Referent | Referent | ||
| Prematurity, n (%) | ||||
| Premature birth (< 37 weeks) | 0.90 (0.77–1.06) | 0.22 | ||
| Not premature birth (≥ 37 weeks) | Referent | |||
| Apgar Score | ||||
| 8–10 | Referent | Referent | ||
| < 7 | 1.36 (1.05–1.75) | 0.02 | 1.32 (1.03–1.69) | 0.02 |
| Breastfeeding | ||||
| Exclusive breastfeeding to 6 months | Referent | Referent | ||
| Not exclusive breastfeeding to 6 months | 1.34 (1.12–1.60) | 0.001 | 1.34 (1.12–1.61) | 0.001 |
| HIV Status | ||||
| Unexposed | Referent | Referent | ||
| Exposed but HIV-negative | 2.46 (2.22–2.73) | <0.001 | 2.60 (2.23–3.03) | <0.001 |
| Exposed and HIV-positive | 2.16 (2.67–3.74) | <0.001 | 3.35 (2.74–4.11) | <0.001 |
| Micronutrient Supplementation | ||||
| Placebo | - | Referent | ||
| Multivitamin | - | 1.03 (0.93–1.14) | 0.51 | |
| Zinc | - | 1.21 (0.98–1.50) | 0.07 | |
| Zinc and Multivitamin | - | 1.19 (0.95–1.47) | 0.11 | |
Discussion
Our results from two large, micronutrient trials indicate that identification of independent factors predicting hospital admission among infants and children <24 months of age in surveillance programs may be difficult. However, male sex, HIV infection, and HIV exposure without infection were associated with greater risk of hospital admission and children whose mothers had incomes were at lower risk of hospital admission on multivariable analysis. In contrast, several clinical factors were independently predictive of unscheduled clinic visits for illness including higher maternal age, low Apgar score, low birthweight, and HIV exposure or infection. The most common reasons for hospital admission and unscheduled clinic visits were malaria, pneumonia, and diarrhea, aligning with the most common causes of morbidity and mortality in sub-Saharan Africa.14,15
Due to the large burden of inpatient mortality among children in sub-Saharan Africa, prediction models to determine poor outcomes for children at the time of hospitalization have been developed.16,17 Moreover, the implementation of formal triage systems at hospitals in sub-Saharan Africa can reduce inpatient morbidity and mortality.18,19 However, a public health approach, taking into account upstream determinants of health prior to presentation to a hospital or clinic, could potentially be used in surveillance programs or in programs with community health workers conducting routine home visits to identify children at risk of hospital admission and unscheduled clinic visits for illnesses.
There is a wealth of literature describing poorer health outcomes among HIV-positive infants and children compared to HIV-negative infants and children20–23 and there is a growing body of evidence describing poor outcomes among children exposed to but HIV-negative.24–28 Similar to the findings of a small cohort study in South Africa comparing HIV-exposed and -negative infants to those who were unexposed,29 our results demonstrated a higher risk of hospital admission and unscheduled clinic visits for illnesses among infants and children who are both HIV-positive and exposed but HIV-negative, thus underscoring the importance of targeting infants and children exposed to but HIV-negative as well as those who are HIV-positive in treatment and care programs to potentially prevent adverse outcomes in similar settings.
Low SES is a well-described factor contributing to poor outcomes among children in sub-Saharan Africa.12,30–32 Children from lower SES in sub-Saharan Africa have less access to quality health care and may have worse health outcomes than those from higher SES.13,33 To our knowledge, the contribution of low SES to hospital admissions in Tanzania has not been described previously. In our study, infants and children whose mothers reported having an income, as a marker of improved SES, had lower risk of hospital admission. Since SES is a complex and multifactorial metric, our finding may indicate improved access to nutrition, improved hygiene, and other factors for infants and children with mothers who are employed. Future studies assessing the impact of interventions to improve socioeconomic status among infants and children in Tanzania are merited. Such interventions may reduce hospital admissions and unplanned clinic visits.
In our study, higher maternal age and factors present at birth were associated with greater risk of unscheduled clinic visits for illness in the first two years of life. The association between higher maternal age and increased unscheduled clinic visits aligns with prior work in Tanzania that demonstrated increased hospitalization rates among infants of mothers who were older.34 We conjecture that this may be due to ability to seek care for their infants and children, though further study is necessary to elucidate the explanation of this finding. Similar to prior studies in high-income countries,35–37 our findings suggested that low Apgar scores at birth may be implicated in morbidity due to respiratory illnesses through infancy and early childhood. Infants with low birthweight had reduced risk of unscheduled clinic visits for illnesses in our study, though the 95% CI neared 1. This finding was surprising as prior work in Tanzania has demonstrated that low birth weight is associated adverse outcomes requiring clinical care including anemia, wasting, and stunting later in infancy.38,39 Low birth weight has also been associated with mortality in prospective studies in Tanzania.40
Our secondary analysis has several limitations. First, this study was conducted prior to the implementation of universal ART for infants and children who are HIV-positive in Tanzania.41,42 As such, rates of hospital admission and clinic visits in our study may have been higher than rates in the setting of universal antiretroviral therapy coverage. However, our findings may reflect contemporary hospital admission and unplanned clinic visit rates in areas with low ART coverage as approximately half the world’s children with HIV were not receiving ART in 2018.43 Second, we did not have access to information about the initiation of ART among infants and children born to mothers who were HIV-positive. Third, data for this study came from two clinical trials with micronutrient supplementation, potentially limiting the generalizability to other populations. Fourth, since our results come from two cohorts with scheduled clinic visits and self-reported clinic visits and symptoms, there may have been under- or over-reporting of illnesses. Also, the regularly scheduled clinic visits in these trials may have reduced the likelihood of care seeking for acute illnesses as caregivers may have anticipated being seen by a physician during the scheduled clinic visits. This would have led to an underestimate of the frequency of unscheduled clinic visits for illness. Moreover, we were not able to control for secular trends including increased availability of oral rehydration solution for the management of diarrhea, epidemiologic changes in stunting, more widespread vaccination coverage, and changes in age-appropriate breastfeeding practices, which have been shown to reduce mortality in Tanzania.44 Lastly, though our secondary analysis consisted of large numbers of patients and allowed for analysis controlling for multiple maternal, socioeconomic, and patient-level factors associated with hospital admission and unscheduled clinic visits, it is possible that there were unmeasured confounding factors leading to the measured phenomena. Future studies assessing the role of other factors that may contribute to hospital admissions and unplanned clinic visits such as access to both transportation and healthcare facilities, healthcare facility capacity, and timing of the receipt of healthcare services, are merited.
Conclusions
Exposure to HIV and being HIV-positive conferred the greatest risk for hospital admission and unplanned clinic visits among infants and children <24 months of age in Tanzania. Our findings highlight the need to not only target HIV-positive infants and children, but also those exposed to but HIV-negative in treatment and care programs. Close, scheduled follow-up of infants with low Apgar scores and from lower SES backgrounds may reduce morbidity. Targeting these vulnerable populations in future interventional studies may reduce morbidity in other urban, east African settings.
Acknowledgements:
We thank the families, infants, and children for their participation in these studies. We also thank the clinical and laboratory staff who contributed to this study.
Source of Funding: This work was supported by the National Institutes of Health (NICHD R01 HD048969-01, NICHD R01 HD043688-01, K24DK104676 and 2P30 DK040561).
Footnotes
Disclosures: The authors have no conflicts of interest to disclose.
Trial Registration: The two trials included in this secondary analysis were registered in clinicaltrials.gov (NCT00197730 and NCT00421668). NCT00197730 was registered on September 20, 2005. NCT00421668 was registered on January 12, 2007.
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