The effect of at-birth vitamin A supplementation on differential leucocyte counts and in vitro cytokine production: an immunological study nested within a randomised trial in Guinea-Bissau

Vitamin A supplementation (VAS) at birth was not associated with improved survival in a randomised, placebo-controlled trial in Guinea-Bissau. However, a negative sex-differential effect, which became evident after diphtheria–tetanus–pertussis (DTP) vaccination, was noted; among girls who had received DTP, VAS at birth was associated with two-fold higher mortality than placebo. The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the randomised trial. Guided by the mortality results, we further explored whether VAS had a differential effect according to sex and DTP status. At 6 weeks after randomisation and supplementation, we measured differential leucocyte counts and TNF-α, interferon-γ, IL-10, IL-13 and IL-5 production in a whole-blood culture assay. A total of 471 children were included. VAS compared with placebo at birth was associated with a higher proportion of monocytes (relative risk ratio 1·26, 95 % CI 1·07, 1·49, P= 0·04), while spontaneous TNF-α production was lower in the VAS group (geometric mean ratio 0·54, 95 % CI, 0·37, 0·78, P= 0·001). Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP, resulting in significant three-way interactions between VAS, sex and DTP vaccination status (P= 0·03 and P= 0·04, respectively) for spontaneous TNF-α and IL-10 production. The results substantiate the potential role of VAS as an immunomodulatory intervention, which has different effects depending on concomitant health interventions and the sex of the recipient.

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The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea-Bissau

BMC Pediatrics ◽

10.1186/1471-2431-11-77 ◽

2011 ◽

Vol 11 (1) ◽

Cited By ~ 8

Author(s):

Dorthe Yakymenko ◽

Christine S Benn ◽

Cesario Martins ◽

Birgitte R Diness ◽

Ane B Fisker ◽

...

Keyword(s):

Vitamin A ◽

Randomised Trial ◽

Female Mortality ◽

Vitamin A Supplementation ◽

Male And Female ◽

Guinea Bissau ◽

The Impact ◽

Different Doses

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The effects of maternal and infant vitamin A supplementation on vitamin A status: a randomised trial in Kenya

British Journal Of Nutrition ◽

10.1017/s0007114507705019 ◽

2007 ◽

Vol 98 (2) ◽

pp. 422-430 ◽

Cited By ~ 25

Author(s):

R. A. Ayah ◽

D. L. Mwaniki ◽

P. Magnussen ◽

A. E. Tedstone ◽

T. Marshall ◽

...

Keyword(s):

Vitamin A ◽

Controlled Trial ◽

Randomised Trial ◽

Maternal Serum ◽

High Dose ◽

Serum Retinol ◽

Double Blind ◽

Vitamin A Supplementation ◽

Factors Affecting ◽

Vitamin A Status

Postpartum vitamin A supplementation of mothers and infants is recommended, but the efficacy has been questioned. In this double-blind, placebo-controlled trial, Kenyan mother–infant pairs were randomised to maternal vitamin A (400 000 IU) or placebo < 24 h postpartum, and infant vitamin A (100 000 IU) or placebo at 14 weeks. Milk retinol was determined at weeks 4, 14 and 26, and maternal and infant serum retinol at weeks 14 and 26. Infant retinol stores were assessed at week 26, using a modified relative dose response (MRDR) test. Among 564 women, serum retinol at 36 weeks gestation was 0·81 (sd 0·21) μmol/l, and 33·3 % were < 0·7 μmol/l. Maternal serum retinol was not different between groups, but milk retinol was higher in the vitamin A group: (0·67 v. 0·60 μmol/l; 0·52 v. 0·44 μmol/l; 0·50 v. 0·44 μmol/l at 4, 14 and 26 weeks, respectively). When expressed per gram fat, milk retinol was higher in the vitamin A group only at 4 weeks. Infant serum retinol was not different between groups. However, although most infants had deficient vitamin A stores (MRDR>0·06 %) at 26 weeks, vitamin A to infants, but not mothers, resulted in a lower proportion of infants with deficient vitamin A stores (69 v. 78 %). High-dose postpartum vitamin A supplementation failed to increase serum retinol and infant stores, despite modest effects on milk retinol. Infant supplementation, however, increased stores. There is a need for a better understanding of factors affecting absorption and metabolism of vitamin A.

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The Effect of Neonatal Vitamin A Supplementation on the Risk of Atopy; Long-term Follow-up on a Randomized Controlled Trial in Guinea-Bissau

European Journal of Nutrition & Food Safety ◽

10.9734/ejnfs/2015/20959 ◽

2015 ◽

Vol 5 (5) ◽

pp. 551-552

Author(s):

Sofie Aage ◽

Nick Kiraly ◽

Kassarai Costa ◽

Stine Byberg ◽

Morten Bjerregaard-Andersen ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Vitamin A ◽

Controlled Trial ◽

Vitamin A Supplementation ◽

Randomized Controlled ◽

Guinea Bissau ◽

Long Term Follow Up

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Randomised trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, west Africa

The Lancet ◽

10.1016/s0140-6736(96)12019-5 ◽

1997 ◽

Vol 350 (9071) ◽

pp. 101-105 ◽

Cited By ~ 89

Author(s):

Christine Stabell Benn ◽

Peter Aaby ◽

Carlitos Balé ◽

Jørn Olsen ◽

Kim Fleischer Michaelsen ◽

...

Keyword(s):

Vitamin A ◽

Antibody Response ◽

West Africa ◽

Randomised Trial ◽

Measles Vaccine ◽

Vitamin A Supplementation ◽

Guinea Bissau

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The effect of high-dose vitamin A supplementation at birth on measles incidence during the first 12 months of life in boys and girls: an unplanned study within a randomised trial

British Journal Of Nutrition ◽

10.1017/s0007114510005532 ◽

2011 ◽

Vol 105 (12) ◽

pp. 1819-1822 ◽

Cited By ~ 6

Author(s):

Birgitte R. Diness ◽

Cesário L. Martins ◽

Carlitos Balé ◽

May-Lill Garly ◽

Henrik Ravn ◽

...

Keyword(s):

Vitamin A ◽

Incidence Rate Ratio ◽

Controlled Trial ◽

Randomised Trial ◽

High Dose ◽

Vitamin A Supplementation ◽

Normal Birth ◽

Infection Surveillance ◽

Measles Incidence ◽

High Dose Vitamin

Vitamin A treatment reduces mortality during acute measles infection, and vitamin A supplementation (VAS) to children above 6 months of age may reduce the incidence of measles infection. The effect of VAS at birth on measles incidence is unknown. In a randomised placebo-controlled trial in Guinea-Bissau, normal-birth-weight newborns were randomised to 50 000 IU (15 mg) VAS or placebo. During the trial, a measles epidemic occurred. We linked data from the trial with data from the measles infection surveillance and studied the effect of VAS on the measles incidence before 12 months of age in both sexes. A total of 165 measles cases were identified among the 4183 children followed from 28 d of age. Up to 6 months of age, the incidence rate ratio of measles for VAS compared with placebo was 0·54 (95 % CI 0·25, 1·15) among boys and 1·57 (95 % CI 0·80, 3·08) among girls (test of interaction, P = 0·04). The corresponding figures at 12 months were 0·67 (95 % CI 0·43, 1·05) and 1·17 (95 % CI 0·76, 1·79) (test of interaction, P = 0·08). VAS compared with placebo tended to be associated with less measles hospitalisation or death during the first 6 months of life in boys (P = 0·06), but not in girls. VAS at birth may affect the susceptibility to measles infection during the first 6 months of life in a sex-differential manner.

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The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production

British Journal Of Nutrition ◽

10.1017/s0007114515004869 ◽

2015 ◽

Vol 115 (4) ◽

pp. 619-628 ◽

Cited By ~ 5

Author(s):

Kristoffer Jarlov Jensen ◽

Ane Bærent Fisker ◽

Andreas Andersen ◽

Erliyani Sartono ◽

Maria Yazdanbakhsh ◽

...

Keyword(s):

Vitamin A ◽

Cytokine Production ◽

Controlled Trial ◽

Geometric Mean ◽

Measles Vaccine ◽

Vitamin A Supplementation ◽

Cell Counts ◽

Cytokine Responses ◽

Helper Cell Type

AbstractAs WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP≥5 mg/l (28 v. 12 %; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95 % CI 1·44, 10·90) but not in males (GMR 0·44; 95 % CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.

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