Abdullah Al Mahmud

Reduction of cholera in Bangladeshi villages by simple filtration

Based on results of ecological studies demonstrating that Vibrio cholerae, the etiological agent of epidemic cholera, is commensal to zooplankton, notably copepods, a simple filtration procedure was developed whereby zooplankton, most phytoplankton, and particulates >20 μm were removed from water before use. Effective deployment of this filtration procedure, from September 1999 through July 2002 in 65 villages of rural Bangladesh, of which the total population for the entire study comprised ≈133,000 individuals, yielded a 48% reduction in cholera (P < 0.005) compared with the control.

Maternal–fetal–infant dynamics of the C3-epimer of 25-hydroxyvitamin D

BACKGROUND Poor vitamin D status (i.e. low serum 25-hydroxyvitamin D (25(OH)D)) has been associated with adverse clinical outcomes during pregnancy and childhood. However, the interpretation of serum 25(OH)D levels may be complicated by the presence of the C3-epimer of 25(OH)D. We aimed to quantify C3-epi-25(OH)D3 in pregnant women and fetuses, to explore the relationship of the C3-epimer between maternal and cord samples, and to establish whether infant C3-epimer abundance is explained by prenatal formation. METHODS In a sub-study of a randomized trial of prenatal vitamin D3, 25(OH)D3 and C3-epi-25(OH)D3 were quantified by LC-MS/MS in 71 sets of mother-fetus-infant serum samples, including maternal delivery specimens, cord blood, and infant specimens acquired at 3-28 weeks of age. RESULTS Without supplementation, median concentrations of C3-epi-25(OH)D₃ were higher in infants (6.80 nmol/L) than mothers (0.45 nmol/L) and cord blood (0 nmol/L). However, there was substantial variation such that C3-epi-25(OH)D₃ accounted for up to 11% (maternal), 14% (cord), and 25% (infant) of the total 25(OH)D₃. Supplemental vitamin D₃ significantly increased maternal-fetal C3-epi-25(OH)D₃, and was a preferential source of C3-epi-25(OH)D₃ compared to basal vitamin D, possibly due to C3-epi-cholecalciferol in the supplement. Multivariate regression did not suggest transplacental transfer of C3-epi-25(OH)D₃, but rather indicated its generation within the fetal-placental unit from maternally-derived 25(OH)D₃. Neither maternal nor fetal C3-epi-25(OH)D₃ is accounted for the relatively high concentrations of infant C3-epi-25(OH)D₃, suggesting rapid postnatal generation. CONCLUSIONS C3-epi-25(OH)D₃ is present in some pregnant women and fetuses, but does not appear to be efficiently transferred transplacentally. High C3-epimer concentrations in infancy are probably due to postnatal formation rather than fetal stores.

Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery

Background/Objectives:Many children have diets deficient in both iron and zinc, but there has been some evidence of negative interactions when they are supplemented together. The optimal delivery approach would maximize clinical benefits of both nutrients. We studied the effectiveness of different iron and zinc supplement delivery approaches to improve diarrhea and anemia in a rural Bangladesh population.Study Design:Randomized, double blind, placebo-controlled factorial community trial.Results:Iron supplementation alone increased diarrhea, but adding zinc, separately or together, attenuated these harmful effects. Combined zinc and iron was as effective as iron alone for iron outcomes. All supplements were vomited <1% of the time, but combined iron and zinc were vomited significantly more than any of the other supplements. Children receiving zinc and iron (together or separately) had fewer hospitalizations. Separating delivery of iron and zinc may have some additional benefit in stunted children.Conclusions:Separate and combined administration of iron and zinc are equally effective for reducing diarrhea, hospitalizations and improving iron outcomes. There may be some benefit in separate administration in stunted children.

Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka, Bangladesh

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.

Estimation of the herd protection of Haemophilus influenzae type b conjugate vaccine against radiologically confirmed pneumonia in children under 2 years old in Dhaka, Bangladesh

BACKGROUND Herd protection of Haemophilus influenzae type b (Hib) conjugate vaccine has been associated with excessive decrease of invasive Hib diseases, i.e., pneumonia and meningitis, with increased national or regional Hib vaccine coverage. Only a few studies have examined herd protection at the individual level and even less evidence is available from Asia. We examined Hib vaccine herd protection against radiologically confirmed pneumonia among children less than 2 years old. METHODS We incorporated data from a matched case-control study and a vaccine coverage survey in Dhaka, Bangladesh. Pneumonia cases (n=343) were confirmed by radiology. For each case, two controls with conditions other than pneumonia or meningitis were selected from the same hospital. Hib vaccine coverage was calculated as percentages of children who received at least 2 doses of Hib vaccine from a survey in the neighborhood centered on each case and control. Conditional logistic regression was fit to examine the association between vaccine coverage and risk of radiologically confirmed pneumonia. RESULTS Neighborhood Hib vaccine coverage varied from 0% to 63.5% for cases and from 8.7% to 61.5% for controls, respectively. Cases were less likely to have neighborhood coverage higher than 20% (OR=0.49, 0.52, 0.55, and 0.69 for coverage 20-29%, 30-39%, 40-49%, and ≥50%, respectively) than coverage <20%, compared to controls, although the estimates for coverage 40-49% and ≥50% were not statistically significant. CONCLUSIONS The study indicates that Hib vaccine may provide herd protection, even when the coverage is as low as 20-39%, in a low-income country. Asian countries should consider herd protection in implementing effective vaccine policy with limited resources.

Maternal and neonatal colonization in Bangladesh: prevalences, etiologies and risk factors

Objective:To estimate the prevalence of maternal colonizers in South Asia and their potential to colonize the umbilicus, an important precondition causing neonatal sepsis.Study design:We conducted a cross-sectional study at a maternity center in Dhaka with 1219 pregnant women and a subset of 152 newborns from 15 January to 31 October 2011. During labor, study paramedics collected vaginal swabs for bacterial culture and rectal swabs for Group B Streptococcus (GBS) testing. Community health workers collected neonatal umbilical swabs. Log-binomial regression models were used to estimate risk ratios.Result:In all, 454 women (37.2%, 95% confidence interval (CI) 34.5 to 40.0%) were colonized. The most common organisms isolated were Staphylococcus aureus, Non-GBS and GBS. A total of 94 women (7.7%, 95% CI 6.2 to 9.2%) were colonized with GBS. The risk of GBS umbilical colonization was higher (RR=12.98, 95% CI 3.97 to 42.64) among newborns of mothers with GBS colonization.Conclusion:Newborns of mothers colonized with GBS are at higher risk of developing umbilical colonization.

Vitamin D and fetal–neonatal calcium homeostasis: findings from a randomized controlled trial of high-dose antenatal vitamin D supplementation

Background:There is current interest in the maternal–fetal effects of antenatal vitamin D supplementation, yet little data regarding vitamin D’s role in neonatal calcium homeostasis. We determined to assess the effect of high-dose antenatal vitamin D supplementation on fetal and neonatal calcium concentrations.Methods:In a double-blinded, placebo-controlled trial in Bangladesh, 160 pregnant women were randomized to oral vitamin D3 (35,000 IU/wk) or placebo from 26 to 29 wk of gestation.Results:Total serum calcium (Ca) was higher in cord blood of those supplemented vs. placebo (2.66 ± 0.1 vs. 2.61 ± 0.2 mmol/l; P = 0.04), but the difference in albumin-adjusted calcium was not statistically significant. Change in Ca concentration from birth to day 3 of life was attenuated by vitamin D (−0.10 ± 0.17) compared with placebo (−0.22 ± 0.18 mmol/l; P = 0.02). Maternal 25-hydroxyvitamin D (25(OH)D) (P = 0.04) and cord 25(OH)D (P < 0.01) were associated with day 3 infant Ca, suggesting that the effect of supplementation was mediated by change in maternal–infant vitamin D status. Six infants in each of the supplemented and placebo groups had transient hypercalcemia/hypercalcuria; in all the hypercalcemia/hypercalcuria was asymptomatic, spontaneously resolved, and unassociated with nephrocalcinosis at 1 mo of life.Conclusion:High-dose antenatal third-trimester vitamin D supplementation attenuated the early postnatal calcium nadir, without increasing the risk of postnatal hypercalcemia.Pediatric Research (2014); 76 3, 302–309. doi:10.1038/pr.2014.83

Early-onset neonatal sepsis in Dhaka, Bangladesh: risk associated with maternal bacterial colonisation and chorioamnionitis

To estimate the risk of early‐onset neonatal sepsis among newborns of mothers with chorioamnionitis and/or bacterial colonisation in Dhaka.

Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU) in pregnant and non-pregnant women

BackgroundImprovements in antenatal vitamin D status may have maternal-infant health benefits. To inform the design of prenatal vitamin D3 trials, we conducted a pharmacokinetic study of single-dose vitamin D3 supplementation in women of reproductive age.MethodsA single oral vitamin D3 dose (70,000 IU) was administered to 34 non-pregnant and 27 pregnant women (27 to 30 weeks gestation) enrolled in Dhaka, Bangladesh (23°N). The primary pharmacokinetic outcome measure was the change in serum 25-hydroxyvitamin D concentration over time, estimated using model-independent pharmacokinetic parameters.ResultsBaseline mean serum 25-hydroxyvitamin D concentration was 54 nmol/L (95% CI 47, 62) in non-pregnant participants and 39 nmol/L (95% CI 34, 45) in pregnant women. Mean peak rise in serum 25-hydroxyvitamin D concentration above baseline was similar in non-pregnant and pregnant women (28 nmol/L and 32 nmol/L, respectively). However, the rate of rise was slightly slower in pregnant women (i.e., lower 25-hydroxyvitamin D on day 2 and higher 25-hydroxyvitamin D on day 21 versus non-pregnant participants). Overall, average 25-hydroxyvitamin D concentration was 19 nmol/L above baseline during the first month. Supplementation did not induce hypercalcemia, and there were no supplement-related adverse events.ConclusionsThe response to a single 70,000 IU dose of vitamin D3 was similar in pregnant and non-pregnant women in Dhaka and consistent with previous studies in non-pregnant adults. These preliminary data support the further investigation of antenatal vitamin D3 regimens involving doses of ≤70,000 IU in regions where maternal-infant vitamin D deficiency is common.Trial registrationClinicalTrials.gov (NCT00938600)

Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial

BackgroundVitamin D regulates bone mineral metabolism and skeletal development. Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and/or birth outcomes; however, there is scant evidence from controlled trials, leading the World Health Organization to advise against routine vitamin D supplementation in pregnancy. Importantly, little is known about the effect of maternal vitamin D status on infant linear growth in communities in South Asia where stunting is highly prevalent and maternal-infant vitamin D status is commonly suboptimal.Methods/DesignThe Maternal Vitamin D for Infant Growth study is a randomized, placebo-controlled, dose-ranging trial of maternal vitamin D supplementation during pregnancy and lactation in Dhaka, Bangladesh. The primary aims are to estimate (1) the effect of maternal prenatal oral vitamin D3 supplementation (4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk, administered as weekly doses) versus placebo on infant length at 1 year of age and (2) the effect of maternal postpartum oral vitamin D3 supplementation (28,000 IU/wk) versus placebo on length at 1 year of age among infants born to women who received vitamin D 28,000 IU/wk during pregnancy. Generally healthy pregnant women (n = 1300) in the second trimester (17–24 weeks of gestation) are randomized to one of five parallel arms: placebo 4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk in the prenatal period and placebo in the postpartum period or 28,000 IU/wk in the prenatal period and 28,000 IU/wk in the postpartum period. Household- and clinic-based follow-up of mother-infant pairs is conducted weekly by trained personnel until 26 weeks postpartum and every 3 months thereafter. The primary trial outcome measure is length for age z-score at 1 year of age. Anthropometric measurements, clinical information, and biological specimens collected at scheduled intervals will enable the assessment of a range of maternal, perinatal, and infant outcomes.DiscussionThe role of vitamin D in maternal and infant health remains unresolved. This trial is expected to contribute unique insights into the effects of improving maternal-infant vitamin D status in a low-income setting where stunting and adverse perinatal outcomes represent significant public health burdens.Trial registrationClinicalTrials.gov identifier: NCT01924013. Registered on 13 August 2013