ABSTRACT:

Objective:

To assess the impact of vitamin A supplementation on adult pregnant and puerperal women in Brazil regarding the content of vitamin A and secretory immunoglobulin A on colostrum and breast milk, in child's health conditions, and in mother-child binomial vitamin A status.

Methods:

A research was conducted in Medline, Scopus, Web of Science, and Lilacs electronic databases for the studies published between January 2000 and January 2014. The methodological quality of the studies was assessed according to Jadad scale. The study search was conducted in January 2014, independently by two authors.

Results:

Seven studies were found concerning the effects of vitamin A supplementation in the puerperal period on breast milk and infant morbidity. No study regarding pregnant women supplementation was found. The supplementation in the puerperal period raised the retinol content on breast milk, thus increasing the offer of vitamin A for the child and the concentration of secretory immunoglobulin A on colostrum. There was no description of effects on infant morbidity.

Conclusion:

It seems that the advantages of postpartum supplementation were not established in the Brazilian program, although the supplementation contributes to a better nutritional status of vitamin A for both the child and the puerperal woman and increases the offer of vitamin A for the newborn through the breast milk.

Keywords:
Vitamin A; Dietary supplements; Postpartum period; Pregnancy; Milk, human; Review.

INTRODUCTION

Vitamin A deficiency (VAD) is one of the main nutritional problems in the world, thus affecting around 19 million pregnant women and 190 million children at preschool age¹1. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em mulheres no pós-parto. Genebra: OMS; 2013. ²2. Brasil. Ministério da Saúde. Pesquisa Nacional de Demografia e Saúde da Criança e da Mulher - PNDS 2006. Brasília: Ministério da Saúde; 2009. ³1. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em mulheres no pós-parto. Genebra: OMS; 2013.. This shortage corresponds to an important amount of child morbidity and mortality indices⁴4. Black RE, Allen LH, Bhutta ZA, Caulfield LE, Onis M, Ezzati M, et al. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet 2008; 371(9608): 243-60., considering the great importance of vitamin A in the first stages of life, since the child's conception until postnatal development⁵5. Ramalho A, Dolinsky M. Carência de vitamina A no grupo materno-infantil. In: Accioly E, Saunders C, Lacerda EMA. Nutrição em Obstetrícia e Pediatria. 2ª ed. Rio de Janeiro: Cultura Médica/Guanabara Koogan; 2012. p. 57-76..

During the child's first six months of life, it is known that vitamin A hepatic reserves are very limited. Thus, monitoring and improvement of vitamin A nutritional status of puerperal women may help increasing the hepatic stocks and provide an appropriate amount of this vitamin to children, through breast milk consumption⁵5. Ramalho A, Dolinsky M. Carência de vitamina A no grupo materno-infantil. In: Accioly E, Saunders C, Lacerda EMA. Nutrição em Obstetrícia e Pediatria. 2ª ed. Rio de Janeiro: Cultura Médica/Guanabara Koogan; 2012. p. 57-76.. Hence, the child's diet, since birth and in the first years of life, causes repercussions throughout the subject's entire life. In addition, because breast milk is the most consumed food in the first phase of life, it is also considered the most important source of vitamin A to enlarge the newborn hepatic reserves⁶6. Saunders C, Ramalho RA, Leal MC. Estado nutricional de vitamina A no grupo materno-infantil. Rev Bras Saude Matern Infant 2001; 1(1): 21-9..

The World Health Organization (WHO) and the Pan American Health Organization (PAHO) have classified Brazil as an area with severe subclinical deficiency; thus, vitamin A supplementation has been implemented since 1983⁷7. Martins MC, Oliveira YP, Coitinho DC, Santos LMP. Panorama das ações de controle da deficiência de vitamina A no Brasil. Rev Nutr 2007; 20(1): 5-18.. In 2005, the Ministry of Health (MH) increased the supplementation program for puerperal women who live in high-risk locations³3. Brasil. Ministério da Saúde. Relatório de Gestão 2007-2010. Coordenação-Geral de Alimentação e Nutrição.; Brasília: Ministério da Saúde 2011. ⁷7. Martins MC, Oliveira YP, Coitinho DC, Santos LMP. Panorama das ações de controle da deficiência de vitamina A no Brasil. Rev Nutr 2007; 20(1): 5-18. ⁸8. Brasil. Ministério da Saúde. Portaria no. 729/GM de 13 de maio de 2005. Institui o Programa Nacional de Suplementação de Vitamina A e dá outras providências. 2005 .Disponível em: http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2005/GM/GM-729.htm (Acessado em 31 de agosto de 2013).
http://dtr2001.saude.gov.br/sas/PORTARIA... ⁹9. Ramalho RA, Padilha PC, Saunders C. Análise Crítica de estudos brasileiros sobre deficiência de vitamina A no grupo materno-infantil. Rev Paul Ped 2008; 26(4): 392-9. ¹⁰10. Brasil. Ministério da Saúde. Manual de condutas gerais do Programa Nacional de Suplementação de Vitamina A. Brasília: Ministério da Saúde 2013., through the administration of a single dose with 200,000 international units (IU) orally, in the immediate postpartum⁸8. Brasil. Ministério da Saúde. Portaria no. 729/GM de 13 de maio de 2005. Institui o Programa Nacional de Suplementação de Vitamina A e dá outras providências. 2005 .Disponível em: http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2005/GM/GM-729.htm (Acessado em 31 de agosto de 2013).
http://dtr2001.saude.gov.br/sas/PORTARIA... . Therefore, exclusive maternal breastfeeding during the six-month period, which works as a strategy to decrease the morbidity load in childhood¹¹11. World Health Organization. Long-term effects of breastfeeding: a systematic review. Geneva: WHO; 2013., consequently, becames an important strategy to improve the mother-child binomial vitamin A nutritional status¹²12. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. Suplementação materna com retinil palmitato no pós-parto imediato: consumo potencial por lactentes. Rev Saúde Pública 2009; 43(4): 572-9..

In 2011, the WHO¹1. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em mulheres no pós-parto. Genebra: OMS; 2013. revised vitamin A supplementation protocols for vulnerable groups. In conclusion, vitamin A in postpartum is effective for improving its status in mothers and children, but without evidence of morbimortality decrease. In the same year, the WHO started recommending vitamin A supplementation with daily or weekly doses for pregnant women, owing to the benefits achieved in this population group, which was affirmed again in 2013¹³13. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em gestantes.; Genebra: OMS 2013..

Given that the data of the Brazilian Child and Women Demography and Health Survey (Pesquisa Nacional de Demografia e Saúde -PNDS)²2. Brasil. Ministério da Saúde. Pesquisa Nacional de Demografia e Saúde da Criança e da Mulher - PNDS 2006. Brasília: Ministério da Saúde; 2009. show the alarming prevalence of retinol serum inadequacy, not only in areas considered at-risk by the MH⁸8. Brasil. Ministério da Saúde. Portaria no. 729/GM de 13 de maio de 2005. Institui o Programa Nacional de Suplementação de Vitamina A e dá outras providências. 2005 .Disponível em: http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2005/GM/GM-729.htm (Acessado em 31 de agosto de 2013).
http://dtr2001.saude.gov.br/sas/PORTARIA... but also in the entire Brazil - 17.4% of children younger than 5 years old and 12.3% of women in the reproductive age presented inappropriate vitamin A levels -, the objective of this article was to assess the impact of vitamin A supplementation during pregnancy or puerperium, in Brazilian adult women, on the outcomes: vitamin A content and immunoglobulins of colostrum and breast milk in child health conditions and mother-child binomial vitamin A status.

METHODS

This review was conducted following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA Statement)¹⁴14. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Ann Intern Med 2009; 151: 264-9.. Two authors independently carried out a survey in Medline, Scopus, Web of Science, and Lilacs electronic databases, during the month of January 2014, for studies published in Spanish, English, and Portuguese languages, during the period between January 2000 and January 2014. The keywords used for selection were in the databases of Descritores em Ciências da Saúde (DeCS) for Portuguese keywords and in the Medical Subject Headings (MeSH) for English ones. The search strategy used in Medline, Scopus, and Web of Science databases, and the English keywords applied were: "vitamin A" OR "dietary supplements" OR "postpartum period" OR "pregnancy" OR "milk, human" OR "colostrum" OR "prenatal care." The same search strategy was used in Lilacs database with the same terms; however, their corresponding words were in Portuguese. If possible, the filters were used comprising "humans, country, adults, language, year of publication, and type of study." This review does not have a registered protocol.

After database search, the following inclusion criteria were applied: original clinical trial articles carried out in Brazil; sample of adult healthy women; intervention with vitamin A supplementation, during pregnancy or puerperium, combined, or not, with vitamin E. Studies combining vitamins A and E supplementation were included because, in Brazil, vitamin A supplements distributed by the "Brazilian Program of Vitamin A Supplementation"¹⁰10. Brasil. Ministério da Saúde. Manual de condutas gerais do Programa Nacional de Suplementação de Vitamina A. Brasília: Ministério da Saúde 2013. for puerperal women present an association with a small amount of vitamin E. In investigations with puerperal women, such population may not have received vitamin A supplementation during pregnancy. Exclusion criteria of the article included studies using supplementation associated with other micronutrients, with the exception of vitamin E, and gestation of more than one fetus.

The initial process of data collection was done through reading the titles and abstracts of available studies, followed by the selection of full articles available for a thorough analysis. As a search complement, bibliographic reference lists of each article included in the review were consulted to identify any possible important study that was not previously found. Only studies with approval of the Research Ethics Committee were included. Data were then extracted with regard to the year of publication, author, city where the study was carried out, sample size, administration and dose moment of supplement, and main results.

The methodological quality and bias risk of studies included in the systematic review were analyzed using Jadad scale¹⁵15. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clin Trials 1996; 17: 1-12., which assesses the quality of clinical trials based on information about randomization, study blinding, and sample losses. This scale varies from 0 to 5 points, considering studies of high quality and low bias of those with scores higher than 3. All disagreements regarding the inclusion or not of some articles were discussed between the two authors, which tried to get into an agreement; in the event of no agreement, a third author would be consulted. This review did not need the approval of the Research Ethics Committee to be conducted.

RESULTS

The electronic search initially found 35,494 studies. When tracking such researches, 35,435 titles were excluded, remaining only 59 publications, owing to the following main reasons: intervention in other population groups; supplementation of other micronutrients combined or not with vitamin A; other interventions together with, or not, the supplementation (probiotics, physical activity, and among others); studies with animals; and studies carried out in other countries. After this phase, articles underwent an abstract analysis, where 31 articles were excluded. The remaining 28 studies were considered appropriate to a full evaluation of its content to choose the eligible ones. At the end of this phase, seven articles were included in the literature review. The details of study search are described in Figure 1.

No studies using a large dose of vitamin A supplementation were found during gestations, which were carried out in Brazil. Six studies with puerperal women were conducted in northeast cities, two in Recife (which studied the same sample) and four in Natal. A trial was carried out at southeast that is a region that does not belong to the MH distribution program of vitamin A in large doses¹⁰10. Brasil. Ministério da Saúde. Manual de condutas gerais do Programa Nacional de Suplementação de Vitamina A. Brasília: Ministério da Saúde 2013. ²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7.. Studies are in Portuguese (n = 3) and English (n = 4) languages.

Table 1 summarizes the characteristics of the included articles, with regard to the place of performance, the moment when the intervention was conducted, the doses of administered supplements, the number of participants in each study, the main results, and the evaluation of manuscript quality (two studies¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6. ²⁰20. Santos CS, Kruze I, Fernandes T, Andreto LM, Figueiroa JN, Diniz AS. The effect of a maternal double megadose of vitamin A supplement on serum levels of retinol in children aged under six months. J Nutr Metab 2013; 2013: 876308. reached a score above 3). Five articles described a randomization performance in the distribution of participants to intervention groups in their methods¹²12. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. Suplementação materna com retinil palmitato no pós-parto imediato: consumo potencial por lactentes. Rev Saúde Pública 2009; 43(4): 572-9. ¹⁶16. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. A randomized trial evaluating the effect of 2 regimens of maternal vitamin A supplementation on breast milk retinol levels. J Hum Lact 2010; 26: 148-57. ¹⁷17. Ribeiro KDS, Araújo KF, Dimenstein R. Efeito da suplementação com vitamina A sobre a concentração de retinol no colostro de mulheres atendidas em uma maternidade pública. Rev Assoc Med Bras 2009; 55(4): 452-7. ¹⁸18. Lima MSR, Ribeiro PPC, Medeiros JMS, Silva IF, Medeiros ACP, Dimenstein R. Influence of postpartum supplementation with vitamin A on the levels of immunoglobulin A in human colostrum. J Pediatr (Rio J) 2012; 88(2): 115-8. ¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6. ²⁰20. Santos CS, Kruze I, Fernandes T, Andreto LM, Figueiroa JN, Diniz AS. The effect of a maternal double megadose of vitamin A supplement on serum levels of retinol in children aged under six months. J Nutr Metab 2013; 2013: 876308.. The studies performed by Fernandes et al.¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6., Santos et al.²⁰20. Santos CS, Kruze I, Fernandes T, Andreto LM, Figueiroa JN, Diniz AS. The effect of a maternal double megadose of vitamin A supplement on serum levels of retinol in children aged under six months. J Nutr Metab 2013; 2013: 876308., and Martins et al.²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7. used the term "double-blind"; the studies of Bezerra et al.¹⁶16. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. A randomized trial evaluating the effect of 2 regimens of maternal vitamin A supplementation on breast milk retinol levels. J Hum Lact 2010; 26: 148-57., Fernandes et al.¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6., Santos et al.²⁰20. Santos CS, Kruze I, Fernandes T, Andreto LM, Figueiroa JN, Diniz AS. The effect of a maternal double megadose of vitamin A supplement on serum levels of retinol in children aged under six months. J Nutr Metab 2013; 2013: 876308., and Martins et al.²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7. presented information regarding losses and their causes. One of the articles mentions the occurrence of loss, but it does not show its causes¹²12. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. Suplementação materna com retinil palmitato no pós-parto imediato: consumo potencial por lactentes. Rev Saúde Pública 2009; 43(4): 572-9..

CONTENT OF SERUM RETINOL, MATURE COLOSTRUM/MILK, AND VITAMIN A OFFER TO INFANTS

Bezerra et al.¹²12. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. Suplementação materna com retinil palmitato no pós-parto imediato: consumo potencial por lactentes. Rev Saúde Pública 2009; 43(4): 572-9. assessed the effect of maternal supplementation with a single dose of retinol palmitate in order to provide the infant vitamin A. In the study, 85 women were randomly distributed into two groups: one received a single dose of 200,000 IU, and the other received 0 IU. On the basis of retinol content obtained in breast milk and through simulations, vitamin A consumption among children was calculated 24 hours and 30 days after delivery.

Women receiving supplement presented a significant increase of retinol content on colostrum at 24 hours and of mature milk 30 days after supplementation, compared with controls (p < 0.05). Daily retinol supply to newborns through the colostrum, 24 hours after delivery, was of 1.63 µmol for controls and 2.9 µmol for the experimental group, considering an appropriate intake of 1.40 µmol/day and consumed milk volume of 500 mL/day. Thirty days after delivery, these values were of 0.64 µmol/day (control group - C) and 0.89 µmol/day (supplementation group - S), which corresponds to a 39% increase of retinol content in the supplemented group, compared with the control group. The value was 64% of the rate recommended for children aged 0-6 months (authors did not present statistical test values in this analysis). The study showed that the maternal supplementation with 200,000 IU of retinol palmitate in the immediate postpartum and the promotion of breastfeeding practices are efficient to improve vitamin A nutritional status for the mother-child binomial¹²12. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. Suplementação materna com retinil palmitato no pós-parto imediato: consumo potencial por lactentes. Rev Saúde Pública 2009; 43(4): 572-9..

In another study, Bezerra et al.¹⁶16. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. A randomized trial evaluating the effect of 2 regimens of maternal vitamin A supplementation on breast milk retinol levels. J Hum Lact 2010; 26: 148-57. evaluated the effect of two large different doses of retinol palmitate on retinol contents in the breast milk of healthy women. The sample comprised 199 puerperal women until 16 hours after delivery. Women were randomly divided into 3 groups and received supplements in the postpartum period, with a single dose of retinol palmitate of 200,000 IU (S1), a new dose of 200,000 IU, in a 24-hour interval (S2), or no supplementation (C). The mean retinol contents in the colostrum were of 94.8 ± 40 µg/dL (3.31 ± 1.40 µmol/L), 92.2 ± 52 µg/dL (3.22 ± 1.81 µmol/L), and 91.9 ± 53.5 µg/dL (3.21 ± 1.87 µmol/L), for groups C, S1, and S2, respectively (p = 0.96). Four weeks after delivery, the variance analysis of retinol values per milk volume presented a significant difference in the three means (p = 0.013), which were of 36.6 ± 17.4 µg/dL (1.28 ± 0.61 µmol/L) (C), 51.0 ± 28.6 µg/dL(1.78 ± 1.00 µmol/L) (S1), and 55.2 ± 31.5 µg/dL (1.93 ± 1.10 µmol/L) (S2). However, this difference was found only between group C and supplemented groups (p < 0.05). The lowest maternal deficiency percentage was seen in group S2 (20.7%), compared with groups S1 (34.5%) and C (46.7%); group S2 was considered moderately deficient, while groups S1 and C, very deficient. In this study, the analyzed variables - vitamin A consumption adaptation, food origin (animal or vegetal), maternal age, number of deliveries, anthropometric nutritional status, gestational hemoglobin, kind of delivery, and newborn gender-were not associated with retinol content in the milk¹⁶16. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. A randomized trial evaluating the effect of 2 regimens of maternal vitamin A supplementation on breast milk retinol levels. J Hum Lact 2010; 26: 148-57..

The study of Ribeiro et al.¹⁷17. Ribeiro KDS, Araújo KF, Dimenstein R. Efeito da suplementação com vitamina A sobre a concentração de retinol no colostro de mulheres atendidas em uma maternidade pública. Rev Assoc Med Bras 2009; 55(4): 452-7., with 91 puerperal women, analyzed the effect of supplementation with 200,000 IU of VA in retinol contents on colostrum, from the collection of blood sample and two milk samples, before and 24 hours after supplementation. In the beginning of supplementation (0 h), control and supplemented groups presented serum contents of 1.3 ± 0.4 and 1.4 ± 0.4 µmol/L (7% deficiency) and 3.5 ± 1.7 and 3.3 ± 1.8 µmol/L (p > 0.05) on colostrum, respectively. After 24 hours of supplementation, milk retinol in the supplemented group increased from 3.6 ± 1.9 to 6.8 ± 2.6 µmol/L (p < 0.0001). The study showed that women with inappropriate retinol content on colostrum at 0-h time (< 2.04 µmol/L) transferred more retinol to the colostrum than those with appropriate contents in 24 hours (increase of 326.1 and 86.5%, respectively).

Santos et al.²⁰20. Santos CS, Kruze I, Fernandes T, Andreto LM, Figueiroa JN, Diniz AS. The effect of a maternal double megadose of vitamin A supplement on serum levels of retinol in children aged under six months. J Nutr Metab 2013; 2013: 876308. analyzed the effect of maternal supplementation protocol with 400,000 (S = 81) and 200,000 IU (C = 92) on children's retinol contents after 2, 4, and 6 months of supplementation and the maternal dietetic consumption through a consumption frequency questionnaire. The intervention happened around 8-10 days after delivery, time when a new supplementation was conducted with 200,000 IU for group C, while group S received a placebo. As a result, food standards between the two groups were similar. No significant differences were found between the groups with regard to retinol contents in the second (p = 0.484), fourth, and sixth months of life (p = 0.421). Comparison of the supplementation effect before and after such procedures showed a significant increase for both groups in the infant's contents (p < 0.001).

Martins et al.²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7. carried out a randomized, double-blind, and placebo-controlled study in which 61 puerperal women participated, and 31 of them received the supplement with 200,000 IU (S), and 30 of them received a capsule including soy oil (C), who were followed up for a one-year period. The intervention happened between 20 and 30 days after delivery. Blood and breast milk samples were collected before supplementation and three months after delivery, and baby blood samples were also collected in the latter. The serum retinol mean between puerperal women was significantly increased in group S, compared with presupplementation contents, with 1.05 and 1.17 µmol/L rates, respectively (p = 0.026). There was also an increase when retinol contents were compared between groups S and C after supplementation, and the latter has a mean of 1.02 µmol/L (p = 0.032). A decrease of retinol contents in breast milk occurred in S, when compared with presupplementation contents, in which the mean values were 1.93 and 1.34 µmol/L (p < 0.0001), respectively, and between postsupplementation contents with a mean of 1.56 µmol/L (p = 0.0003). Another result was the significant difference in VAD prevalence in breast milk after the intervention of 16.1% in group S and 55.6% in group C (p = 0.002). Among children, VAD prevalence was 66%, and the mean of retinol content in the control group and the supplemented group (p = 0.458) was 0.64 ± 0.3 µmol/L and 0.69 ± 0.26 µmol/L, respectively²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7..

CONTENTS OF SECRETORY IMMUNOGLOBULIN A ON COLOSTRUM

Lima et al.¹⁸18. Lima MSR, Ribeiro PPC, Medeiros JMS, Silva IF, Medeiros ACP, Dimenstein R. Influence of postpartum supplementation with vitamin A on the levels of immunoglobulin A in human colostrum. J Pediatr (Rio J) 2012; 88(2): 115-8. assessed the supplementation effects on secretory immunoglobulin A (sIgA) contents of the colostrums of 96 mothers. Fifty-two participants in the supplementation group (S) received a large dose with 200,000 IU of retinol palmitate in the immediate postpartum. Colostrum samples were collected in the morning, and the supplement was administered right after in S participants. After 24 hours, a new collection was done. At 0-h time (before supplementation), the sIgA content mean was similar in both the groups, with 829.1 ± 337.6 mg/dL in the control and 827.3 ± 249.8 mg/dL in group S (p = 0.52). At 24 hours after supplementation, the mean contents of sIgA in group S were significantly higher than in group C, as follows: 501.2 ± 54.5 and 349.9 ± 177.2 mg/dL, respectively (p < 0.00001). During 24 hours after delivery, sIgA contents were lower than those found in the immediate postpartum (0 h), but the decrease was lower in group S (39.5%) than in group C (58.4%).

INFANT MORBIDITY

Maternal supplementation effect with high doses of 400,000 and 200,000 IU of retinol palmitate in the event of health problems in such children was assessed by Fernandes et al.¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6. in a randomized, triple-blind study that followed up these children since birth until 6 months of life, with the same intervention that was used in the study by Santos et al.²⁰20. Santos CS, Kruze I, Fernandes T, Andreto LM, Figueiroa JN, Diniz AS. The effect of a maternal double megadose of vitamin A supplement on serum levels of retinol in children aged under six months. J Nutr Metab 2013; 2013: 876308.. A total of 276 women took the supplementation, among whom 134 received 400,000 IU (G1) and 142 received 200,000 IU (G2). At the end of the study, 115 children from G1 and 109 from G2 were followed up during the first six months of life. Study results showed no significant differences between the groups with regard to intercurrences - diarrhea (relative risk [RR]: 0.96 [95%CI: 0.72-1.28]), fever (RR: 0.92 [95%CI: 0.75-1.14]), otitis (RR: 0.94 [95%CI: 0.48-1.85]), and acute respiratory failure (RR: 1.03 [95%CI: 0.88-1.21]). The need for venous rehydration (RR: 2.08 [95%CI 0.64-2.07]) and use of antibiotics (RR: 0.80 [95%CI 0.43-1.47]) were not different between groups either. The adjusted analysis for breastfeeding stated that duration time for this practice did not add benefits in the decrease of children problems. There were no reports regarding toxicity, and no children presented signals of xerophthalmia¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6..

DISCUSSION

Only seven studies carried out in Brazil regarding supplementation were found with large vitamin A doses and their possible consequences for the mother-child binomial. The limited number of investigations and the methodological differences between them difficult the generalization of results.

Including only studies conducted in Brazil was chosen because of the current discussion about vitamin A supplementation effectiveness in pregnant and puerperal women, as pointed out by the WHO¹1. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em mulheres no pós-parto. Genebra: OMS; 2013. ¹³13. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em gestantes.; Genebra: OMS 2013.. Searching for evidence on the impact of this supplementation in population with a known risk of VAD, such as Brazil, is important for the restructuration and/or elaboration of new public policies to end this deficiency. This discussion adds results of studies that indicate VAD as not being exclusive of areas considered endemic by the MH and that other parts of the country may be benefited with strategies for controlling and eradicating the issue²2. Brasil. Ministério da Saúde. Pesquisa Nacional de Demografia e Saúde da Criança e da Mulher - PNDS 2006. Brasília: Ministério da Saúde; 2009. ³3. Brasil. Ministério da Saúde. Relatório de Gestão 2007-2010. Coordenação-Geral de Alimentação e Nutrição.; Brasília: Ministério da Saúde 2011..

Positive aspects of the studies added in this review are mainly the improvement of vitamin A nutritional status of the child and mother. Thus, the concepts are benefited with the increase of retinol and immunoglobulin contents in mother's milk.

Women with low serum contents before supplementation revealed more advantages with the intervention than those with appropriate contents, given the higher increase in vitamin A contents of the latter. This represents an advantage, mainly for infants, because the colostrum has a key role in VA inventory. Its relevance is also on the fact that immunoglobulins present a role to protect against infections that may assail the newborn, thus emphasizing the vitamin A role on the immunological system. The higher consumption of antibodies by newborns may bring more protection against infectocontagious diseases and, consequently, decrease of morbidity in infants²²22. van de Perre P. Transfer of antibody via mother's milk. Vaccine 2003; 21: 3374-6.. However, such statement could not be confirmed in this review, because the study that evaluated the supplementation of sIgA contents did not aim at determining the consumption of this immunoglobulin and its impact on child's health¹⁸18. Lima MSR, Ribeiro PPC, Medeiros JMS, Silva IF, Medeiros ACP, Dimenstein R. Influence of postpartum supplementation with vitamin A on the levels of immunoglobulin A in human colostrum. J Pediatr (Rio J) 2012; 88(2): 115-8..

Some aspects might justify results on newborn's vitamin A nutritional status, such as: conceptuses are born with about less than 50% of the maternal hepatic reserves of retinol²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7.; vitamin A absorption might be influenced on gastrointestinal physiological immaturity in children younger than 6 months²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7.; and the cut point used for assessing the VAD in children younger than 6 months has been questioned²³23. World Health Organization. Guideline: Vitamin A supplementation in infants 1-5 months of age. Geneva: WHO 2011. .

Few studies, different purposes, and outlines may have influenced our results; therefore, caution is needed when transmitting such information for the entire Brazilian puerperal women. Maybe, these factors might influence on the comprehension about the real supplementation benefit of puerperal women in their children's health and vitamin A nutritional status, based on the results presented herein.

Although VA supplementation in the puerperium period can be considered a potentially efficient strategy to simultaneously improve VA nutritional status of women and infants, studies have pointed out that only one dose of 200,000 IU is not effective in the maintenance of vitamin A satisfactory contents²⁴24. Rice AL, Stoltzfus RJ, Francisco A, Chakraborty J, Kjolhede CL, Wahed MA. Maternal vitamin A or beta-carotene supplementation in lactating Bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency. J Nutr 1999; 129: 356-65. ²⁵25. Humphrey JH, Ichord RN. Safety of vitamin A supplementation of postpartum women and young children. Food Nutr Bull 2001; 22: 311-9.. Thus, the administration of a new large dose until 6 months after delivery is recommended²⁶26. World Health Organization. Report of an Informal Consultation on Vitamin A Supplementation, March 1-3, 2000, Yverdon-les-Bains, Switzerland. Geneva: WHO 2000.. Hence, the only three studies that approached the administration of a double dose of vitamin A in Brazilian investigations¹⁶16. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. A randomized trial evaluating the effect of 2 regimens of maternal vitamin A supplementation on breast milk retinol levels. J Hum Lact 2010; 26: 148-57. ¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6. demonstrated moderate benefits, when compared with the studies that assessed the single dose. In addition, a significant increase of retinol content in milk after four weeks postpartum¹⁶16. Bezerra DS, Araújo KF, Azevêdo GMM, Dimenstein R. A randomized trial evaluating the effect of 2 regimens of maternal vitamin A supplementation on breast milk retinol levels. J Hum Lact 2010; 26: 148-57., a decrease in child morbidity¹⁹19. Fernandes TF, Figueiroa JN, Arruda IKG, Diniz AS. Effect on infant illness of maternal supplementation with 400 000 IU vs 200 000 IU of vitamin A. Pediatrics 2012; 129(4): e960-6., and an increase of infant's retinol contents were not seen ²¹21. Martins TM, Ferraz IS, Daneluzzi JC, Martinelli Jr CE, Del Ciampo LA, Ricco RG, et al. Impact of maternal vitamin A supplementation on the mother-infant pair in Brazil. Eur J Clin Nutr 2010; 64(11): 1302-7.. Future investigations are needed to determine the pertinence of administering a second dose of vitamin A, to ensure appropriate contents of this nutrient for a longer period and, thus, to contribute for fighting VAD marginal ways in children under exclusive breastfeeding. Furthermore, investigations in this direction could establish the best moment for its administration.

The outcomes presented herein demonstrate an improvement in vitamin A nutritional status of puerperal women and in the content of this vitamin in breast milk. The increase of vitamin A content in breast milk was also described in a study carried out in areas with higher VAD prevalence, such as Africa; however, it was limited, and no great difference was seen in the vitamin content between supplemented and control groups²⁷27. Ayah RA, Mwaniki DL, Magnussen P, Tedstone AE, Marshall T, Alusala D, et al. The effects of maternal and infant vitamin A supplementation on vitamin A status: a randomised trial in Kenya. Br J Nutr 2007; 98(2): 422-30..

Lack of studies assessing the impact of the strategy under issue in Brazil, especially with regard to the decrease and prevention of maternal-infant morbimortality, shows that the real effects of vitamin A supplementation in postpartum needs more studying. In agreement with the findings presented herein about child's morbidity, a meta-analysis that assessed the impact of vitamin A supplementation in the puerperal period, including studies in Africa and Asia, did not describe any significant reduction on the main intercurrences for child's health (diarrhea and acute respiratory failure)²⁸28. Gogia S, Sachdev HS. Maternal postpartum vitamin A supplementation for the prevention of mortality and morbidity in infancy: a systematic review of randomized controlled trials. Int J Epidemiol 2010; 39: 1217-26.. This result is in agreement with the WHO outcomes, which led the organization to review the puerperium supplementation as a public health strategy¹1. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em mulheres no pós-parto. Genebra: OMS; 2013..

The WHO²⁹29. Organização Mundial da Saúde. Vitamina "A" na gestação e lactação: recomendações e relatório de uma consultoria. Recife: OMS; 2001. suggests vitamin A supplementation in pregnancy with doses considered safe for mother-child binomial. This recommendation was also done again in 2013¹³13. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em gestantes.; Genebra: OMS 2013., besides the observation that postpartum supplementation has not presented the expected results¹1. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em mulheres no pós-parto. Genebra: OMS; 2013. with regard to the decrease of maternal-infant mortality. The lack of studies about vitamin A supplementation in Brazilian pregnant women leaves a gap on the possible benefits of this intervention in such biological moment. Some points might suggest the lack of these studies. One of these would be that the MH never considered pregnant women as the target public of its VAD eradication programs. Another issue is that, for a long time, it was believed that administering vitamin A supplementary doses, besides the recommendations preconized during pregnancy, would not be safe and would increase the risks of teratogenic problems in the conceptuses. Supplementation in pregnancy is considered a benefit to increase maternal-child retinol serum contents; to form retinol hepatic reserves of the conceptus; to decrease the prevalence of gestational night blindness and iron deficiency; and to decrease maternal morbidity in places where VAD is a public health issue¹³13. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em gestantes.; Genebra: OMS 2013.. However, more studies are needed to confirm the protection against maternal mortality⁵5. Ramalho A, Dolinsky M. Carência de vitamina A no grupo materno-infantil. In: Accioly E, Saunders C, Lacerda EMA. Nutrição em Obstetrícia e Pediatria. 2ª ed. Rio de Janeiro: Cultura Médica/Guanabara Koogan; 2012. p. 57-76. ³⁰30. Pangaribuan R, Erhardt JG, Scherbaum V, Biesalski HK. Vitamin A capsule distribution to control vitamin A deficiency in Indonesia: effect of supplementation in pre-school children and compliance with the programme. Pub Health Nutr 2002; 6(2): 209-16. ³¹31. Oliveira JM, Rondó PHC. Evidências do impacto da suplementação de vitamina A no grupo materno-infantil. Cad Saúde Pública 2007; 23(11): 2565-75. ³²32. Dibley MJ, Jeacocke DA. Vitamin A in pregnancy: Impact on maternal and neonatal health. Food Nutr Bull 2001; 22(3): 267-84. ³³33. van den Broek N, Dou L, Othman M, Neilson JP, Gates S, Gülmezoglu AM. Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Data Syst Rev 2010; 10(11): 1-83..

It is worth mentioning other interventions to remove VAD, such as the increase of intake of food enriched with vitamin A and stimulus to consume foods that are vitamin sources, especially those of animal origin¹1. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em mulheres no pós-parto. Genebra: OMS; 2013. ¹³13. Organização Mundial da Saúde. Diretriz: Suplementação de vitamina A em gestantes.; Genebra: OMS 2013. ³⁴34. Ramalho A, Saunders C, Padilha PC. Tratar e prevenir a deficiência de vitamina A. In: Ramalho A. Fome Oculta: Diagnóstico, tratamento e prevenção. São Paulo, Atheneu; 2009. p. 247-63. ³⁵35. Santos EN, Velarde LGC, Ferreira VA. Associação entre deficiência de vitamina A e variáveis socioeconômicas, nutricionais e obstétricas de gestantes. Ciênc Saúde Colet 2010; 15(Supl. 1): 1021-30.. It is also worth highlighting the nutritional support during prenatal care, considering a study³⁶36. Chagas CB, Ramalho A, Padilha PC, Libera BD, Saunders C. Reduction of vitamin A deficiency and anemia in pregnancy after implementing proposed prenatal nutritional assistance. Nutr Hosp 2011; 26(4): 843-50. showing this practice (including intervention measures to prevent and treat VAD) as a protecting factor against the occurrence of gestational night blindness.

FINAL CONSIDERATIONS

Given the lack of results, evidences available regarding vitamin A supplementation effects on postpartum need more investigations in order to evaluate the real benefits of the intervention in Brazilian puerperal women who live, or do not live, in areas of higher VAD risk. This is necessary even if there is a contribution for the VA nutritional status improvement of puerperal woman and infant and in the offer, through breast milk, of the vitamin to the newborn.

References

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