Authors: Martina Panicola (Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy), Giulia Cereghetti (Family Medicine, Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland), Carlo Agostoni (Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy; Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy), Ilaria Alberti (Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy), Emilia Vassilopoulou (Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy; Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy), Silvia Bettocchi (Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy), Alice A. Bruni (Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy; Family Medicine, Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland), Mario G. Bianchetti (Family Medicine, Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland), Antonio Corsello (Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy), Gregorio P. Milani (Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy; Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy)
Categories: Original Article, adherence, family size, rickets, Sibship, vitamin D prophylaxis
Source: Acta Paediatrica (Oslo, Norway : 1992)
Doi: 10.1111/apa.70435
Authors: Martina Panicola, Giulia Cereghetti, Carlo Agostoni, Ilaria Alberti, Emilia Vassilopoulou, Silvia Bettocchi, Alice A. Bruni, Mario G. Bianchetti, Antonio Corsello, Gregorio P. Milani
This study investigated whether family composition and other household factors are associated with adherence to vitamin D supplementation during infancy.
A cross‐sectional survey was conducted between March 21 and April 30, 2023, among caregivers of infants aged 4 weeks to 12 months at the Ca′ Granda Hospital, Milan, Italy. The survey investigated demographic data, health status, daily vitamin D3 administration frequency, and family characteristics. Multiple logistic regression was used to identify factors associated with poor adherence.
A total of 241 caregivers completed the survey. Overall, 85% of infants received vitamin D supplements at least four times per week. Good adherence was more frequent in families with one child (91%) compared with those with two or more children (78%). In multivariable analysis, the presence of siblings was the only factor significantly associated with poor adherence (odds ratio 2.72, 95% confidence interval 1.25–5.92). No associations were found with caregiver education, infant age, chronic disease, intercurrent illness, or time spent outdoors.
In this cohort, adherence to vitamin D prophylaxis was significantly lower in families with more than one child. Awareness of this association could inform counselling strategies and the design of interventions to sustain adherence.
Most countries recommend prophylactic supplements of 400 IU (10 μg) of vitamin D per day throughout the first year of life [1, 2]. It is therefore considered a standard preventive measure in infancy, alongside routine newborn screening programs, vaccinations, and growth monitoring [3, 4].
However, adherence to supplementation is often inadequate. Poor adherence may be influenced by access barriers, administration challenges, formulation acceptability, and parental educational and cultural factors [5, 6, 7, 8].
Parents often approach their first child differently to subsequent children [9, 10]. With the first child, many are more cautious, detail‐oriented, and sometimes anxious, striving to follow all guidelines for the infant's health. With later children, parents' increased experience often makes them more relaxed, confident, and flexible, leading to less concern over previously essential details. Moreover, when caring for two or more children, parents generally have less time to devote to each individual child [9, 10]. Hence, we hypothesised that adherence to vitamin D prophylaxis would be higher in families with one child compared with those with two or more.
The aim of this study was to evaluate adherence to vitamin D prophylaxis and its modulators, focusing on potential differences between families with one and those with two or more children.
A survey was administered to caregivers of children aged between 4 weeks and 1 year, who attended the Department of Paediatrics at the Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico in Milan (Italy) for an acute condition or a scheduled check‐up between March 21 and April 30, 2023. Infants accompanied by a caregiver not responsible for the routine administration of drugs or unfamiliar with the Italian language were excluded. Immediately after enrolment, the caregiver accessed the survey by means of a Quick Response code.
For this purpose, we adapted a previously used survey [7] and pilot‐tested it.
The test involved initially five paediatricians to evaluate any unclear question or answer. To guarantee reproducibility, the finalised version was given twice to four physicians, with a two‐week gap between administrations, resulting in an intra‐rater agreement of more than 97%.
The final survey included questions about the child, the accompanying caregiver, and the child's family. Questions regarding the child covered age and sex, the number of siblings, and the existence of a chronic disease and its drug management. Additionally, information regarding the previous week was collected. This included the time spent outdoors (less than 30 min per day, 30–60 min per day, more than 60 min per day). The occurrence of intercurrent diseases, such as flu‐like symptoms or cough, was also recorded. In addition, daily vitamin D3 supplementation was assessed (never, 1–3 times per week, 4–6 times per week, every day). Caregivers were asked to specify their sex, age, and citizenship (Italian, European other than Italian, other), as well as the highest educational level (primary or secondary, tertiary). Completion of the questionnaire was estimated to take between 4 and 6 min. To submit the survey, it was mandatory to answer all questions.
Considering an α‐error of 5%, a power of 90%, and a 10% (50% vs 40%) difference in adherence between infants with and without siblings, the target enrolment was set at a minimum of 231 subjects [11].
Adherence to vitamin D supplementation was classified as good if infants received it at least 4 times per week (> 50%) and poor in those who received it less frequently. Categorical variables are shown as frequency. Dichotomous categorical data were compared using the Fisher's exact test [12], and ordered categorical data were compared using the Mann–Whitney U test [13]. Since the D'Agostino‐Pearson test indicated that the ages of infants and caregivers are not normally distributed [14], continuous data are presented as medians with interquartile ranges and were analysed using the Mann–Whitney U test [12]. To account for potential confounders, multiple logistic regressions were performed [15, 16]. Adherence to vitamin D prophylaxis was modelled as the dependent variable. Independent variables included presence of siblings, infant age, acute intercurrent illnesses, chronic diseases, time spent outdoors, and caregiver educational level. The reference categories were no siblings, no acute illness, no chronic disease, < 30 min/day spent outdoors, and primary or secondary education. R software 2.6–2 (R Foundation, Vienna, Austria) was used for analysis. A two‐tailed p‐value of 0.05 was considered statistically significant.
This study protocol was reviewed and approved by Comitato Etico Milano Area 2, Italy (approval number “25_2023bis”). Informed consent was obtained from parents or legal guardians to participate in the study.
A total of 342 potentially eligible caregivers were approached and 241 (70%) filled out the questionnaire. There were no missing data. The results of the questionnaire are presented in Table 1 and Figure 1. The 241 infants had a median age of slightly under 4 months and were predominantly accompanied by an Italian (87%) female (85%) caregiver. Overall, 85% of infants showed good adherence to vitamin D supplementation, comprising 99 infants supplemented 4–6 times per week and 107 supplemented daily. The remaining infants showed poor adherence, with 16 never receiving supplementation and 19 receiving it 1–3 times per week.

The adherence was good more frequently in families with one child than in families with multiple children (p = 0.0095). There was no significant difference in adherence with respect to infants' demographics, prevalence of chronic disease, history of intercurrent illness, time spent outdoors, and the caregiver educational level (Table 1).
Infant age, acute intercurrent illnesses, chronic diseases, time spent outdoors, and caregiver educational level were not significantly associated with poor vitamin D adherence in the multiple logistic regression (Table 2). A significant association was observed only for the presence of siblings (odds ratio 2.72, 95% confidence interval 1.25–5.92).
The results of this study indicate that in the Milan area, a region with no barriers to accessing vitamin D, adherence to vitamin D supplementation was excellent in infants up to 1 year of age. In fact, 85% of the children included in the inquiry study received vitamin D supplementation four or more times per week. The results also show that adherence was markedly higher in families with only one child (91%) than in those with two or more children (78%), thus supporting the research hypothesis.
Comparing the results of this survey to the results of other previous studies is difficult because of the variability in survey methodologies and the heterogeneity of paediatric populations. In this study, conducted in Northern Italy, adherence was higher than in Italian‐speaking Switzerland, where an almost identical survey was used in a paediatric population of similar age [5, 7]. Notably, adherence to vitamin D prophylaxis in infancy was higher in regions where Italian, French, or Spanish was spoken than in regions where German was spoken. Similar patterns were reported for parental willingness to vaccinate children and to treat childhood fever with antipyretic medications [17, 18, 19, 20]. Lastly, parental educational level did not modulate adherence to vitamin D prophylaxis.
In childhood, access to care, including preventive measures, is known to depend on factors such as parental education and citizenship [21, 22]. This study was the first to find the number of children within a family as a factor influencing adherence to a medication. The number of siblings can also affect the frequency of intercurrent infections within a family, as large families frequently experience circulation of infections due to increased pathogen exposure [23]. Some data have also suggested that having more siblings, particularly older ones, might reduce the risk of allergies. This is linked to a hypothesis proposing that early pathogen exposure helps the immune system lower the likelihood of allergic conditions [24].
The major strength of the study was the consideration of the number of children as a variable influencing adherence to vitamin D prophylaxis. The first limitation was related to the fact that adherence to prophylactic vitamin D was assessed based on information provided by adults accompanying the children, rather than being objectively verified, for example, by checking vitamin D purchases or measuring its circulating levels. Additionally, the data collected in Milan could not be readily extrapolated to other paediatric age groups or to other regions of Europe or the world. For this reason, we believe it is reasonable to replicate similar surveys elsewhere.
Ensuring consistent adherence to preventive measures, such as vitamin D supplementation, is essential to reduce the risk of deficiencies and related health issues in children. Given the challenges of maintaining high adherence, especially as family size increases, it is essential to explore and implement strategies that can effectively support families in following recommendations. Awareness of this issue among healthcare workers is essential. It is also just as crucial to encourage parents to adhere to vitamin D prophylaxis, as this simple measure plays a key role in preventing bone diseases. One possible solution is to create individualised plans based on the family situation [21], including administering the vitamin at wider intervals, such as weekly, rather than daily [1, 25].
Carlo Agostoni, Mario G. Bianchetti, Antonio Corsello and Gregorio P. Milani: designed the study; Martina Panicola, Giulia Cereghetti, Alice A. Bruni, Silvia Bettocchi, Antonio Corsello and Gregorio P. Milani prepared and pilot‐tested the survey; Martina Panicola, Ilaria Alberti, Silvia Bettocchi and Emilia Vassilopoulou and Antonio Corsello administered the survey to the study participants; Ilaria Alberti, Alice A. Bruni, Mario G. Bianchetti, Antonio Corsello and Gregorio P. Milani analyzed the data and prepared the figure; Martina Panicola, Giulia Cereghetti, Emilia Vassilopoulou, Mario G. Bianchetti and Gregorio P. Milani wrote the manuscript; Carlo Agostoni acquired funding, resources and supervised the study; all authors read, reviewed the proof and approved the final manuscript.
The study was partially funded by the Italian Ministry of Health (Ricerca Corrente).
The authors declare no conflicts of interest.