Palatability of vitamin d3 preparations modulates adherence to the supplementation in infancy.

Introduction

The consequences of vitamin D deficiency can be severe. It is therefore recommended that Swiss infants have a minimum intake of 10 µg of vitamin D3 per day during the first 12 mo of life (1). For this purpose they are prescribed an “alcoholic” preparation that contains vitamin D3 (1).

Infants given preparations containing vitamin D3 either dissolved in alcohol or in peanut oil very much prefer the “oily” form (2). As a consequence, beginning on the first of January 2005, we replaced the traditional "alcoholic" vitamin D3 formulations and replaced it with the peanut oil formulation.

There are conflicting data concerning whether palatability is important for adherence to the recommended regimen of care and persistence with it over time (3, 4). The adherence to the supplementation with vitamin D3 was therefore compared in Swiss infants prescribed either “alcoholic” or “oily” vitamin D3. A preliminary account of the results obtained in infants prescribed “alcoholic” vitamin D3 has been published elsewhere as a letter (5).

Subjects and Methods

One hundred forty Swiss infants ranging in age between 4 and 7 mo who presented at our emergency room with minor acute diseases entered the study. The infants were prescribed 10 µg vitamin D3 per day either as “alcoholic” vitamin D3 (Vi-De3: Wild AG, Basel, Switzerland; 113 µg/ml [= 2.5 µg/drop] vitamin D3 dissolved in 65% ethanol) or “oily” vitamin D3 (Oleovit D3: Fresenius Kabi AG, Bad Homburg, Germany; 450 µg/ml [= 10.0 µg/drop] vitamin D3 dissolved in peanut oil).

Informed consent from the families and approval of the protocol by our institutional review board were granted for this not commercially sponsored study. The inquiry was performed between October 2003 and March 2004 with 70 infants prescribed four drops daily of “alcoholic” vitamin D3 (5) and between October 2005 and March 2006 with 70 infants prescribed one drop daily of “oily” vitamin D3. The parents of the infants anonymously completed a written questionnaire containing 3 closed-ended questions dealing with the vitamin D3 supplementation. The questions focused on the adherence to the recommended vitamin D3 supplementation during the preceding month [possible answers: a) never, i.e. less than once a week, b) 1–3 times a week, c) 4 times a week or more], the recommendations given by health care providers [possible answers: a) adequate recommendation, b) inadequate recommendation], and the taste-elicited reaction of the child to the administration of vitamin D3 [possible answers: a) favorable, b) unfavorable].

The adherence to the supplementation with vitamin D3 was considered good in families using vitamin D3 four times a week or more and poor in families using vitamin D3 three times a week or less.

Parental educational level was used as an indicator of socioeconomic background and classified as low (pre-primary, primary and lower secondary education), middle (upper secondary education), and high (post-secondary education).

The Mann-Whitney-Wilcoxon test and the χ2-test with the Yates correction for continuity were used for analysis. A P value of <0.05 was regarded as statistically significant.

Results

Sex ratio, age, the socioeconomic status and the main nutritional source were similar in the “alcoholic” vitamin D3 group and the “oily” vitamin D3 group. More than 90% of the 140 questionnaires were answered by the mother, with or without the father of the child (Table 1).

Table 1.

Demographic characteristics of children enrolled and their families

The adherence to the recommended supplementation with vitamin D3 was poor in 36 of the 70 families prescribed the “alcoholic” vitamin D3 (four drops daily) formulation: 20 never used vitamin D3 and 16 used it one to three times a week (Table 2). The remaining 34 families used vitamin D3 four times a week or more. A better (P<0.001) adherence was noted in the “oily” vitamin D3 group (one drop daily), as indicated by the fact 54 families used vitamin D3 four times a week or more. Eleven families used “oily” vitamin D3 one to three times a week, while 5 families never used “oily” vitamin D3. A certain number in both the “alcoholic” vitamin D3 group (18 out of 70 families) and the “oily” vitamin D3 group (16 out of 70 families) stated that health care providers rarely failed to recommend or encourage the appropriate vitamin D3 supplementation. Parents of children prescribed “alcoholic” vitamin D3 more frequently (46 versus 9; P<0.001) reported an unpleasant taste-elicited reaction in their children as compared to children prescribed “oily” vitamin D3.

Table 2.

Adherence to the supplementation with vitamin D3, recommendations given by health care providers, and taste-elicited reaction (= “palatability”) of the vitamin D3 formulations

The taste-elicited reaction to vitamin D3 was more often reported as unfavorable (P<0.001) in families with poor (32 out of 52 families) than in those with good adherence (23 out of 88 families) to the supplementation.

Six families of the “alcoholic” vitamin D3 group with poor adherence to the supplementation spontaneously reported in the footnote of the questionnaire, their concern in relation to the content of ethanol in the vitamin D3 preparation. On the other hand within the “oily” vitamin D3 group, 5 families with at least one older child spontaneously reported in the footnote of the questionnaire the preference of their child for the “oily” vitamin D3 as compared to that of the “alcoholic” vitamin D3 that had been prescribed in the past for their older infants.

The parental educational level and the milk nutrient source of the children did not affect the results of the inquiry.

Discussion

Poor adherence to the recommended regimen of care is a recognized problem in the pediatric populations (3, 4, 6). In the present inquiry the reported non-adherence to the supplementation with vitamin D3 was less for infants prescribed the “oily” preparation than for those prescribed the "alcoholic" preparation. This result was significantly related to the reaction of the children to the prescribed vitamin D3 preparation and perhaps even to irrational fears of side-effects related to the toxic potential of ethanol content of some vitamin D3 preparations.

Understanding the prescribed medication regimen and acceptance of the need for adherence are central issues to enhance adherence to the recommended regimen of care (3, 4, 6). The results of the present inquiry indicate that health care providers very often recommended and appropriately encouraged the supplementation with vitamin D3.

There are conflicting data concerning whether children distinguish between different commercial preparations and, thus, whether palatability is important for adherence to the recommended regimen of care. For example in some studies children clearly disliked some suspensions, but adherence was not measured. On the other side some retrospective observations and the present study indicate that the unpleasant taste or rough texture have a negative influence on adherence (3, 4, 6). The problem with palatability studies might be the lack of a “gold standard” for taste. Furthermore the usefulness of parental reports or facial hedonic scales in young children has been questioned. In our experience, however, simplified facial hedonic scales may be used to assess palatability among newborns and infants (2).

In addition to the unpleasant taste-elicited reaction of the child the poor adherence to the supplementation with the “alcoholic” formulation is also related to the fact that 10 µg of vitamin D3 are contained in four drops of the “alcoholic” and in one drop of the “oily” formulation.

“Alcoholic” vitamin D3 formulations contain a negligible amount of ethanol (2). Nonetheless, the present data support the assumption that irrational concerns related to the toxic potential of ethanol contribute to poor adherence to the recommended medication. Data from the literature demonstrate an inverse relationship between adverse effects or fears of adverse effects and adherence to the recommended regimen, although this finding is not universal (3, 4, 6).

Approximately 50% and 75% of our parents reported that they were adherent with the prescribed supplementation with "alcoholic" vitamin D3 and “oily” vitamin D3, respectively. It is important to stress, however, that parent's reporting of adherence is sometimes overrated, as indicated by the fact that in children with sickle cell disease the adherence with prophylactic penicillin administration reported by the parents was much higher than the effective adherence measured using pharmacy records [7].

In conclusion the causes of poor adherence are poorly understood and sometimes puzzling but the present data suggest that in infants prescribed vitamin D3 to prevent nutritional rickets poor adherence is not related to the parental educational level or to the failure of health care providers to recommend or to appropriately encourage the supplementation. In our experience fears of adverse effects and especially the taste-elicited reaction of the child to the administered vitamin D3 influence adherence to the recommended medication.