Do Girls Have a Nutritional Disadvantage Compared with Boys? Statistical Models of Breastfeeding and Food Consumption Inequalities among Indian Siblings

Background

India is the only nation where girls have greater risks of under-5 mortality than boys. We test whether female disadvantage in breastfeeding and food allocation accounts for gender disparities in mortality.

Methods and Findings

Secondary, publicly available anonymized and de-identified data were used; no ethics committee review was required. Multivariate regression and Cox models were performed using Round 3 of India’s National Family and Health Survey (2005–2006; response rate = 93.5%). Models were disaggregated by birth order and sibling gender, and adjusted for maternal age, education, and fixed effects, urban residence, household deprivation, and other sociodemographics. Mothers’ reported practices of WHO/UNICEF recommendations for breastfeeding initiation, exclusivity, and total duration (ages 0–59 months), children’s consumption of 24 food items (6–59 months), and child survival (0–59 months) were examined for first- and secondborns (n = 20,395). Girls were breastfed on average for 0.45 months less than boys (95% CI: = 0.15 months to 0.75 months, p = 0.004). There were no gender differences in breastfeeding initiation (OR = 1.04, 95% CI: 0.97 to 1.12) or exclusivity (OR = 1.06, 95% CI: 0.99 to 1.14). Differences in breastfeeding cessation emerged between 12 and 36 months in secondborn females. Compared with boys, girls had lower consumption of fresh milk by 14% (95% CI: 79% to 94%, p = 0.001) and breast milk by 21% (95% CI: 70% to 90%, p<0.000). Each additional month of breastfeeding was associated with a 24% lower risk of mortality (OR = 0.76, 95% CI: 0.73 to 0.79, p<0.000). Girls’ shorter breastfeeding duration accounted for an 11% increased probability of dying before age 5, accounting for about 50% of their survival disadvantage compared with other low-income countries.

Conclusions

Indian girls are breastfed for shorter periods than boys and consume less milk. Future research should investigate the role of additional factors driving India’s female survival disadvantage.     

In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses

Background

RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants.

Methods and Principal Findings

209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The severity was assessed by recording SaO₂% at admission, a daily clinical score (scale 0–18), the duration of oxygen supplementation and the length of hospitalization. Viruses were identified in 94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only (3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV compared respectively with RSV and dual RSV/RV infection caused a significant less severe disease with a lower clinical score (5[3.2–6] vs. 6[4–8], p = 0.01 and 5.5[5–7], p = 0.04), a shorter time in oxygen supplementation (0[0–1] days vs. 2[0–3] days, p = 0.02 and 2[0–3] days, p = 0.03) and a shorter hospital stay (3[3–4.7] days vs.6 [5–8] days, p = 0.001 and 5[4–6] days, p = 0.04). Conversely, RSV infants had also longer duration of hospitalization in comparison with RSV/RV (p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of virus carried was independently associated with the duration of hospitalization.

Conclusion

This study underlined the role of RV in early respiratory diseases, as frequently carried by young infants with a first acute bronchiolitis. RSV caused the more severe disease and conversely RV the lesser severity. No additional effect of dual RSV/RV infection was observed on the severity.     

Differential Effects of Early Weaning for HIV-Free Survival of Children Born to HIV-Infected Mothers by Severity of Maternal Disease

Background

We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.

Methods

958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention) or to continued breastfeeding (control). Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART) became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.

Results

Of infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p = 0.98). Children of women with less severe disease during pregnancy (not eligible for ART) had worse outcomes if their mothers weaned as instructed (RH = 2.60 95% CI: 1.06–6.36) compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it) who weaned early had better outcomes (p-value interaction = 0.002). In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65–9.39) increase in HIV infection or death among infants of mothers with less severe disease.

Conclusion

Incomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding.

Trial Registration

Clinical trials.gov {"type":"clinical-trial","attrs":{"text":"NCT00310726","term_id":"NCT00310726"}}NCT00310726     

High Uptake of Exclusive Breastfeeding and Reduced Early Post-Natal HIV Transmission

Background

Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF.

Methods and Results

As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight.

Conclusions

Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children''s lives.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00310726","term_id":"NCT00310726"}}NCT00310726     

Survival of Infants Born to HIV-Positive Mothers,by Feeding Modality,in Rakai,Uganda

Background

Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. We compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda.

Methodology/Principal Findings

One hundred eighty two infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counseling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy (ART) if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving ART. Infant HIV infection was detected by PCR (Roche Amplicor 1.5) during the follow-up visits. Kaplan Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR) of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast-feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%–29%) among the formula-fed compared to 3% (95% CI = 1%–9%) among the breast-fed infants (unadjusted hazard ratio (HR)  = 6.1(95% CI = 1.7–21.4, P-value<0.01). There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted RH = 2.8[95%CI = 0.67–11.7, P-value = 0.16]

Conclusions/Significance

Formula-feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. Our findings suggest that formula-feeding should be discouraged in similar African settings.     

Nevirapine Resistance and Breast-Milk HIV Transmission: Effects of Single and Extended-Dose Nevirapine Prophylaxis in Subtype C HIV-Infected Infants

Background

Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the “six-week extended-dose nevirapine” (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.

Methods/Findings

Standard population sequencing and cloning for viral subpopulations present at ≥5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant''s blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.

Conclusions/Significance

Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00061321","term_id":"NCT00061321"}}NCT00061321     

Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda

Introduction

Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.

Methods

Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).

Results

78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7–6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7–9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0–2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8–5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).

Conclusions

HHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda.     

Task Shifting Routine Inpatient Pediatric HIV Testing Improves Program Outcomes in Urban Malawi: A Retrospective Observational Study

Background

This study evaluated two models of routine HIV testing of hospitalized children in a high HIV-prevalence resource-constrained African setting. Both models incorporated “task shifting,” or the allocation of tasks to the least-costly, capable health worker.

Methods and Findings

Two models were piloted for three months each within the pediatric department of a referral hospital in Lilongwe, Malawi between January 1 and June 30, 2008. Model 1 utilized lay counselors for HIV testing instead of nurses and clinicians. Model 2 further shifted program flow and advocacy responsibilities from counselors to volunteer parents of HIV-infected children, called “patient escorts.” A retrospective review of data from 6318 hospitalized children offered HIV testing between January-December 2008 was conducted. The pilot quarters of Model 1 and Model 2 were compared, with Model 2 selected to continue after the pilot period. There was a 2-fold increase in patients offered HIV testing with Model 2 compared with Model 1 (43.1% vs 19.9%, p<0.001). Furthermore, patients in Model 2 were younger (17.3 vs 26.7 months, p<0.001) and tested sooner after admission (1.77 vs 2.44 days, p<0.001). There were no differences in test acceptance or enrollment rates into HIV care, and the program trends continued 6 months after the pilot period. Overall, 10244 HIV antibody tests (4779 maternal; 5465 child) and 453 DNA-PCR tests were completed, with 97.8% accepting testing. 19.6% of all mothers (n = 1112) and 8.5% of all children (n = 525) were HIV-infected. Furthermore, 6.5% of children were HIV-exposed (n = 405). Cumulatively, 72.9% (n = 678) of eligible children were evaluated in the hospital by a HIV-trained clinician, and 68.3% (n = 387) successfully enrolled into outpatient HIV care.

Conclusions/Significance

The strategy presented here, task shifting from lay counselors alone to lay counselors and patient escorts, greatly improved program outcomes while only marginally increasing operational costs. The wider implementation of this strategy could accelerate pediatric HIV care access in high-prevalence settings.     

Micronutrient Fortification to Improve Growth and Health of Maternally HIV-Unexposed and Exposed Zambian Infants: A Randomised Controlled Trial

Background

The period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age.

Methods and Findings

We conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z<−2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors.

Conclusions

In the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants.

Trial registration

Controlled-Trials.com ISRCTN37460449     

Exclusive Breastfeeding,Diarrhoeal Morbidity and All-Cause Mortality in Infants of HIV-Infected and HIV Uninfected Mothers: An Intervention Cohort Study in KwaZulu Natal,South Africa

Introduction

Antiretroviral drug interventions significantly reduce the risk of HIV transmission to infants through breastfeeding. We report diarrhoea prevalence and all-cause mortality at 12 months of age according to infant feeding practices, among infants born to HIV-infected and uninfected mothers in South Africa.

Methods

A non-randomised intervention cohort study that followed both HIV-infected and HIV-uninfected mothers and their infants until 18 months of age. Mothers were supported in their infant feeding choice. Detailed morbidity and vital status data were collected over the first year. At the time, only single dose nevirapine was available to prevent mother-to-child transmission of HIV.

Results

Among 2,589 infants, detailed feeding data and vital status were available for 1,082 HIV-exposed infants and 1,155 HIV non-exposed infants. Among exclusively breastfed (EBF) infants there were 9.4 diarrhoeal days per 1,000 child days (95%CI. 9.12-9.82) while among infants who were never breastfed there were 15.6 diarrhoeal days per 1,000 child days (95%CI. 14.62-16.59). Exclusive breastfeeding was associated with fewer acute, persistent and total diarrhoeal events than mixed or no breastfeeding in both HIV-exposed infants and also infants of HIV uninfected mothers. In an adjusted cox regression analysis, the risk of death among all infants by 12 months of age was significantly greater in those who were never breastfed (aHR 3.5, p<0.001) or mixed fed (aHR 2.65, p<0.001) compared with those who were EBF. In separate multivariable analyses, infants who were EBF for shorter durations had an increased risk of death compared to those EBF for 5-6 months [aHR 2.18 (95% CI, 1.56-3.01); p<0.001].

Discussion

In the context of antiretroviral drugs being scaled-up to eliminate new HIV infections among children, there is strong justification for financial and human resource investment to promote and support exclusive breastfeeding to improve HIV-free survival of HIV-exposed and non-exposed infants. Trial Registration: ClinicalTrials.gov NCT01948557; http://clinicaltrials.gov/     

Family Characteristics as Risk Factors for Childhood Acute Lymphoblastic Leukemia: A Population-Based Case-Control Study

Background

To date, few risk factors for childhood acute lymphoblastic leukemia (ALL) have been confirmed and the scientific literature is full of controversial “evidence.” We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL).

Methodology/Principal Findings

In this population-based nationwide matched case-control study, patients 0–14 years of age with ALL diagnosed 1991–2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05–1.31; p = 0.004), remaining stable (trend OR 1.14, 95% CI 0.99–1.31; p = 0.060) after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01–1.28, p = 0.032) and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0–14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0–4 years (OR per sibling 0.85, 95% CI 0.68–1.06; p = 0.141) and a positive trend for ALL diagnosed at age 5–9 (OR 1.34, 95% CI 1.05–1.72; p = 0.019), with some evidence for an effect modification (p-value for interaction  = 0.040).

Conclusions

As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.     

Fecal Calprotectin Excretion in Preterm Infants during the Neonatal Period

Background

Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults.

Objective

To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut.

Methodology

F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge.

Principal Findings

Although median f-calprotectin excretion was 138 µg/g, a wide range of inter- and intra-individual variation in f-calprotectin values (from day 3 to day 78) was observed (86% and 67%, respectively). In multivariate regression analysis, f-calprotectin correlated negatively with ante and per natal antibiotic treatment (p = 0.001), and correlated positively with the volume of enteral feeding (mL/kg/d) (p = 0.009), the need to interrupt enteral feeding (p = 0.001), and prominent gastrointestinal colonization by Clostridium sp (p = 0.019) and Staphylococcus sp (p = 0.047).

Conclusion

During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment.     

Breastfeeding Is Not a Risk Factor for Mother-to-Child Transmission of Hepatitis B Virus

Background

Many clinicians do not encourage breastfeeding in hepatitis B virus (HBV) carriers, since HBV DNA can be detected in breast milk and breast lesions may increase exposure of infants to HBV. The aim of this study was to determine whether breastfeeding may add risk for perinatal HBV transmission.

Methodology/Principal Findings

Totally 546 children (1–7-year-old) of 544 HBV-infected mothers were investigated, with 397 breastfed and 149 formula-fed; 137 were born to HBeAg-positive mothers. All children had been vaccinated against hepatitis B but only 53.3% received hepatitis B immune globulin (HBIG). The overall prevalence of HBsAg+, HBsAg−/anti-HBc+, and anti-HBs (≥10 mIU/ml) in children was 2.4%, 3.1%, and 71.6% respectively. The HBsAg prevalence in breast- and formula-fed children was 1.5% and 4.7% respectively (P = 0.063); the difference was likely due to the higher mothers'' HBeAg-positive rate in formula-fed group (formula-fed 49.0% vs. breastfed 15.9%, P<0.001). Further logistic regression analyses showed that breastfeeding was not associated with the HBV infection in the children, adjusting for the effect of maternal HBeAg status and other factors different between the two groups.

Conclusions/Significance

Under the recommended prophylaxis, breastfeeding is not a risk factor for mother-to-child transmission of HBV. Therefore, clinicians should encourage HBV-infected mothers to breastfeed their infants.     

Poor Adherence to National and International Breastfeeding Duration Targets in an Australian Longitudinal Cohort

Objectives

To report on the proportion and characteristics of Australian infants who are fed, and mothers who feed, in accordance with the national and international breastfeeding duration targets of six, 12 and 24 months. Furthermore, to examine the longitudinal breastfeeding duration patterns for women with more than one child.

Methods

Breastfeeding duration data for 9773 children have been self-reported by a national sample of 5091 mothers aged 30–36 years in 2009, participating in the Australian Longitudinal Study on Women’s Health.

Results

Only 60% of infants received the minimum recommended 6 months of breast milk, irrespective of breastfeeding exclusivity. Less than 30% of infants received any breast milk at 12 months, and less than 3% were breastfed to the international target of 24 months. Young, less educated, unmarried or low-income women were at an increased risk of premature breastfeeding cessation. For women with three or more children, nearly 75% of women who breastfed their first child for at least six months reached this breastfeeding duration target for their next two children.

Conclusion

While national breastfeeding rates are typically evaluated in relation to the infant, a novel component of our study is that we have assessed maternal adherence to breastfeeding duration targets and the longitudinal feeding practices of women with more than one child. Separate evaluations of maternal and infant breastfeeding rates are important as they differ in their implications for public health policy and practice.     

The Diagnostic and Prognostic Accuracy of Five Markers of Serious Bacterial Infection in Malawian Children with Signs of Severe Infection

Background

Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children.

Methodology and Principal Findings

Children presenting with a signs of meningitis (n = 282) or pneumonia (n = 95), were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74%) had SBI and 83 (22%) died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01). In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively). In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and CD163 was higher in non-survivors (p = 0.05). The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs) were 0.81 (95% CI 0.73–0.89) and 0.86 (95% CI 0.79–0.92) respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50–0.71).

Conclusions

Admission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting.     

Respiratory Symptoms and Airway Obstruction in HIV-Infected Subjects in the HAART Era

Background

Prevalence and risk factors for respiratory symptoms and airway obstruction in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART) are unknown. We evaluated respiratory symptoms and measured airway obstruction to identify the impact of HAART and other risk factors on respiratory symptoms and pulmonary function.

Methodology/Principal Findings

Two hundred thirty-four HIV-infected adults without acute respiratory symptoms were recruited from an HIV clinic. All subjects were interviewed and performed spirometry. Multivariate linear and logistic regressions were performed to determine predictors of respiratory symptoms, forced expiratory volume in one second (FEV₁) percent predicted, and FEV₁/forced vital capacity (FEV₁/FVC). Thirty-one percent of subjects reported at least one respiratory symptom. Smoking status (current or former versus never) (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.41–5.22, p = 0.003), higher log plasma HIV viral levels (OR = 1.12, 95%CI = 1.02–1.24, p = 0.02), and lower FEV₁/FVC (OR = 1.06 for every 0.01 decrease in FEV₁/FVC, 95%CI = 1.02–1.14, p = 0.001) were independent predictors of respiratory symptoms. Age (p = 0.04), pack-year smoking history (p<0.001), previous bacterial pneumonia (p = 0.007), and HAART use (p = 0.04) were independent predictors of decreased FEV₁/FVC.

Conclusions/Significance

Respiratory symptoms remain common in HIV-infected subjects, especially in those with a smoking history. Subjects who were older, had a greater pack-year history of smoking, or previous bacterial pneumonia had lower FEV₁/FVC ratios. Interestingly, use of HAART was independently associated with a decreased FEV₁/FVC, possibly secondary to an immune response to subclinical infections, increased autoimmunity, or other factors associated with HAART use.     

Sensitivity of Five Rapid HIV Tests on Oral Fluid or Finger-Stick Whole Blood: A Real-Time Comparison in a Healthcare Setting

Background

Health authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known.

Methods and Findings

200 adults with documented HIV-1 (n = 194) or HIV-2 infection (n = 6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2® was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2®, Determine HIV 1–2®, Determine® HIV-1/2 Ag/Ab Combo® and INSTI HIV-1/HIV-2®. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (p<0.0001). OraQuick was less sensitive on OF than on FSB (p = 0.008). Among the six patients with three or more negative tests, two had recent HIV infection and four patients on antiretroviral therapy had undetectable plasma viral load. When patients positive in all the tests were compared with patients who had at least one negative test, only a plasma HIV RNA level <200 cp/ml was significantly associated with a false-negative result (p = 0.009). When the 33 rapid tests negative on FSB were repeated on serum, all but six (5 negative with OraQuick, 1 with INSTI) were positive. The sensitivity of OraQuick, Determine and Determine Ag/Ab Combo was significantly better on serum than on FSB (97.5%, p = 0.04; 100%, p = 0.004; and 100%, p = 0.02, respectively).

Conclusion

When evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum.     

Does Simplicity Compromise Accuracy in ACS Risk Prediction? A Retrospective Analysis of the TIMI and GRACE Risk Scores

Background

The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems.

Methodology/Principal Findings

ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes.

Conclusions/Significance

The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.     

Gender,Migration and HIV in Rural KwaZulu-Natal,South Africa

Objectives

Research on migration and HIV has largely focused on male migration, often failing to measure HIV risks associated with migration for women. We aimed to establish whether associations between migration and HIV infection differ for women and men, and identify possible mechanisms by which women''s migration contributes to their high infection risk.

Design

Data on socio-demographic characteristics, patterns of migration, sexual behavior and HIV infection status were obtained for a population of 11,677 women aged 15–49 and men aged 15–54, resident members of households within a demographic surveillance area participating in HIV surveillance in 2003–04.

Methods

Logistic regression was conducted to examine whether sex and migration were independently associated with HIV infection in three additive effects models, using measures of recent migration, household presence and migration frequency. Multiplicative effects models were fitted to explore whether the risk of HIV associated with migration differed for males and females. Further modeling and simulations explored whether composition or behavioral differences accounted for observed associations.

Results

Relative to non-migrant males, non-migrant females had higher odds of being HIV-positive (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [1.49–1.99]), but odds were higher for female migrants (aOR = 2.55 [2.07–3.13]). Female migrants also had higher odds of infection relative to female non-migrants (aOR = 1.48 [1.23–1.77]). The association between number of sexual partners over the lifetime and HIV infection was modified by both sex and migrant status: For male non-migrants, each additional partner was associated with 3% higher odds of HIV infection (aOR = 1.03 [1.02–1.05]); for male migrants the association between number of partners and HIV infection was non-significant. Each additional partner increased odds of HIV infection by 22% for female non-migrants (aOR = 1.22 [1.12–1.32]) and 46% for female migrants (aOR = 1.46 [1.25–1.69]).

Conclusions

Higher risk sexual behavior in the context of migration increased women''s likelihood of HIV infection.     

Direct Evidence for the Presence of Human Milk Oligosaccharides in the Circulation of Breastfed Infants

Background

It has been hypothesized that human milk oligosaccharides (HMOs) confer systemic health benefits to breastfed infants; however, plausible mechanisms for some effects, such as systemic immunomodulation, require HMOs to access the bloodstream of the developing infant. While small concentrations of HMOs have been detected in the urine of breastfed infants there are no published studies of these oligosaccharides accessing the plasma compartment of breastfed infants. Here we determined the relative fractions of several ingested HMOs in infant urine and plasma. Plasma from formula-fed infants was used as a control.

Methods

Using gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry/tandem mass spectrometry (LC/MS/MS), and high performance liquid chromatography (HPLC), we analyzed the urine and plasma from 17 healthy formula-fed infants and 16 healthy breast-fed infants (and the milk from their mothers).

Results

Multiple HMOs were detected in the urine and plasma of breastfed infants, but not in formula-fed infants. Levels of 2′-fucosyllactose (2′FL), 3FL and lacto-N-neotetraose (LNnT) in both plasma (r = 0.98, p<0.001; r = 0.75, p = 0.002; r = 0.71, p = 0.004) and urine (r = 0.81, p<0.001; r = 0.56, p = 0.026; NS) correlated significantly with concentrations in the corresponding breast milk. The relative fractions of HMOs were low, 0.1% of milk levels for plasma and 4% of milk levels for urine. Within the breastfed cohort, there were significant differences between secretor and nonsecretor groups in levels of several fucosylated HMOs.

Conclusion

At least some ingested HMOs are absorbed intact into the circulation and excreted in the urine and their concentrations in these fluids correlate with levels of the corresponding mother''s milk. While relative fractions of absorbed HMOs were low, these levels have been shown to have biological effects in vitro, and could explain some of the postulated benefits of human milk.