The introduction of allergenic foods to the infant diet in a UK cohort: the impact of family history of allergy

doi:10.21203/rs.3.rs-3621004/v1

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The introduction of allergenic foods to the infant diet in a UK cohort: the impact of family history of allergy

https://doi.org/10.21203/rs.3.rs-3621004/v1

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Background/Objective: To describe the introduction of highly allergenic foods in a UK population sample, and to determine whether the introduction of highly allergenic foods differed in infants with family history of allergy.

Subjects/Methods: A population birth cohort study recruited eligible pregnant women while they were attending an antenatal ultrasound clinic appointment at a UK city hospital. Parental-reported family history of allergy and infant diet was collected through structured interviews at recruitment and postal questionnaires. Parents reported on their infants’ diet at around 6 months (n = 216), around 12 months (n = 193) and around 24 months of age (n = 139).

Results: Most highly allergenic foods were introduced to infants at around 6-9 months. However, nut and egg were introduced much later, and 21% of children had not been exposed to egg and 35% of infants had not been exposed to nuts by 12 months. Infants with a family history of allergy were introduced to highly allergenic foods at a similar time to other infants but were more likely to have diets that avoided foods due to allergy than other infants (most commonly dairy, soya, egg and nuts).

Conclusions: As many parents delayed the introduction of egg and nuts beyond one year of age and infants with a family history of allergy were more likely to have diets that avoided foods due to allergy, these behaviours might affect the development of allergies in infants and could be a modifiable risk factor for allergy development.

Health sciences/Risk factors

Health sciences/Health care/Nutrition

Health sciences/Health care/Public health/Epidemiology

Health sciences/Health care/Disease prevention/Lifestyle modification

Allergic disease is highly prevalent in the UK and worldwide.¹ Observational studies which reported an association between allergy and early exposure to allergenic foods, initially led to recommendations to introduce allergenic foods later into children’s diets as a method of preventing food allergies. However more recent, well controlled RCTs have failed to support food avoidance as a method of allergy prevention and these studies, including Learning About Peanut (LEAP²) and Early Introduction of Food to Avoid Intolerance (EAT³) have instead shown that early introduction of allergenic foods is associated with lower incidence of food allergies. Simons et al. ⁴ demonstrated that in a population cohort study, children who were introduced to peanut after 1 year of age, were more likely to have a peanut allergy at 3 years of age than children who were introduced to peanut earlier.

In 2008, global allergy prevention guidelines were updated to remove the recommendation to delay the introduction of allergenic foods⁵. In 2017, the National Institute of Allergy and Infectious Disease (NIAID) recommend that high-risk children should be introduced to peanut-containing foods as early as 4-6 months of age⁶, and the Scientific Advisory Committee on Nutrition (SACN) report in the UK suggests that the introduction of peanut and egg should start along with other solids⁷.

There is limited evidence of the extent to which these updated recommendations have been accepted by the UK population. However, a recent study showed that they are not being followed in Saudi Arabia, where highly allergenic foods such as peanut and fish were typically not introduced until infants were older than one year⁸. Furthermore, there has been limited research investigating whether infants at higher risk of allergic disease (those with a first degree relative with allergy) are introduced to foods, including highly allergenic foods in a different manner. Van Odijk et al.⁹ reported that families with a history of allergic disease did not differ in the timing of foods, including allergenic foods, however Schoetzau et al.¹⁰ reported that mothers with a family risk of eczema delayed introducing solid foods compared to mothers without a family history or eczema, and Venter et al.¹¹ reported that mothers with a family history of allergy were more likely to breastfeed exclusively for longer, and to avoid the introduction of peanuts for longer than women without a family history of allergy. Grimshaw ^12,13 reported that up until one year, the diet of children with and without food allergies were similar but by 2 years of age the two groups had significantly different diets and the non-allergic children were more likely to be eating a diet richer in fruit, vegetables and home-prepared foods. Different diets or delayed introduction of allergenic foods in high risk infants might affect the development of allergies in infants and could be a modifiable risk factor for allergy development.

This paper describes the introduction of highly allergenic foods in a population sample at approximately 6, 12 and 24 months of age. It also examines these factors in high risk infants with family history of allergy.

The study aimed to investigate:

The time and type of foods introduced into infants’ diets in a population cohort
The association between family history of allergy and time and type of foods introduced to infants’ diet

Recruitment and eligibility

Participants were part of a longitudinal population-based cohort study, the XXXXXX Birth Cohort Project in XXXXXX, UK. Pregnant women were screened to check their eligibility for the registry whilst attending an antenatal ultrasound clinic appointment at XXXXXXX’s main hospital between 21st May 2015 and the 24th July 2017.

Individuals were eligible for the study if they met the following criteria: Pregnant women aged 16 or over, with a home address within the city’s eight postcodes, who had sufficient mental capacity to consent; booked to deliver their baby at the main hospital birthing centre, the midwifery led maternity centre or at home; planning to live in in the city for a year after the birth.

To reduce selection bias, eligible women were approached and screened, rather than using a volunteer approach. Interpreter services were available for non-English speakers, however no women required this service.

Full ethical approval for the Birth Cohort registry was given by XXXXXXX Research Ethics Committee (REC ref: XX/XX/XXXX) and all mothers gave informed consent. The Birth Cohort Registry was designed to gather data on a wide range of factors impacting on the health and development of babies, although this article is specifically focusing on the areas of the questionnaire related to allergy and diet.

Participants

A total of 390 participants consented to take part in the registry, with one participant joining twice with two different pregnancies, see Fig. 1 for data collection and participation flowchart. This article covers all waves of data collection to date; antenatally (Wave 0), at birth (Wave 1) when the baby was around 6 months (Wave 2), around 12 months (Wave 3), and around 24 months (Wave 4). Only live births were included in the registry for subsequent follow ups.

Wave 0 data was collected by an interview conducted by a research midwife with the mother in a private area of the antenatal clinic. Wave 1 data were collected by a research midwife from the mother’s medical information. Wave 2, 3 and 4 data were collected using self-completed questionnaires. Paper versions of the questionnaires were sent with self-addressed stamped envelopes and reminder questionnaires were sent after one month to parents who had not responded.

[Insert Fig. 1 here]

Measures

Socio-demographic and environmental characteristics

Parental socio-demographic data was collected from the mother antenatally, through the Wave 0 questionnaire, including maternal age, marital status, maternal & paternal education level, maternal & paternal employment status, ethnicity and parity of pregnancy. Wave 1 collected data at birth including the infant’s sex and date of birth.

Family History of Allergy

In Wave 0 mother self-report of family history of allergy was collected (maternal, paternal and sibling history of asthma, hay fever, itchy rash, wheeze, runny nose and food allergies).

Infant dietary intake

A parent reported food frequency questionnaire was completed in Waves 2, 3 and 4. This was an amended version of the Southampton Women’s Survey FFQ at 6 months which has been shown to be a valid measure of energy and nutrient intake in infants¹⁴. At Wave 2 the questionnaire consisted of a list of 28 foods and 10 drinks, at Waves 3 and 4, the questionnaire consisted of a list of 77 foods and 10 drinks, reflecting the greater range of foods likely to be consumed by an older child. For each food, the frequency of consumption over the previous month of each food and drink was recorded using a multiple response grid. Variety in the infant’s diet was calculated as the number of different food items consumed over the previous month.

In Waves 2 and 3 parents were also asked to report the age at which their infant was introduced to solid food and was first introduced to highly allergenic foods (including wheat, egg, milk, fish, nuts and sesame). For these responses, a single variable was created which considered replies to this question at either wave. If the parent had indicated a different answer in the two Waves e.g. reported that their infant was introduced to solid food from 20 weeks when asked at Wave 2 but reported 22 weeks when asked at Wave 3, the answer from Wave 2 was used as it was considered less affected by recall bias.

In Waves 2, 3 and 4, parents were asked whether they were avoiding any food in their child’s diet due to allergy and if yes, they were asked to specify which foods

Data Analysis

Only questionnaires with complete responses were included in each analysis, those with missing data were excluded from analysis. SPSS (IBM, version 26) was used to analyse the data. Categorical variables were expressed as frequency and percentage and the χ² test was used to test these relationships. Repeated measures ANOVA was used to test the change in continuous variables (e.g. variety of foods eaten) over time. Binary logistic regressions were used to determine the effects of family history of allergy on the likelihood that infants’ introduction to each allergenic food was delayed (9 months or later, compared to before 9 months)

Demographic characteristics of parents and infants

[Insert Table 1]

Table 1

Parental and infant demographic characteristics of sample
Parental demographics
	Total Population	Wave 2 Population	Wave 3 Population	Wave 4 Population
N	390	216	193	139
Maternal Age Mean (SD) [Range]	31 years (4.85) [18–43]	33 years* (4.38) [19–44]	34 years* (4.25) [22–44]	35 years* (3.87) [24–45]
Higher level of Maternal Education**	223 (57%)	151 (70%)*	138 (72%)*	102 (73%)*
Higher level of Paternal Education**	164 (42%)	113 (52%)	99 (51%)	83 (60%)
Maternal Ethnicity
White British	318 (82%)	174 (81%)	161 (83%)	114 (82%)
White other	44 (11%)	31 (14%)	26 (13%)	19 (14%)
Mixed/multiple ethnic groups	6 (2%)	2 (1%)	1 (1%)	1 (1%)
Asian/Asian British	13 (3%)	6 (3%)	4 (2%)	3 (2%)
Black/African/Caribbean/Black British	6 (1.5%)	2 (1%)	1 (1%)	1 (1%)
Other ethnic group	2 (1%)	-	-	-
Not specified	1 (1%)	1 (1%)	-	1 (1%)
Infant Demographics
N		220	199	145
Sex: Male N (%)		191 (49%)	113 (51%)	97 (49%)
Age (SD) [range] months		6 (0.91) [5–10]	13 (1.1) [11–17]	25 (0.99) [23–30]
Birth Order: First born (no siblings)	165 (42%)	108 (50%)	98 (51%)	67 (48%)
Variety of food eaten in previous month		12.1 (5.94)*	46.6 (9.32)*	48.2 (8.77)*
Consulted GP about any allergic symptoms		53 (24%)	79 (40%)	42 (29%)
Avoiding any foods due to allergy		32 (15%)	32 (16%)	15 (10%)
Family History of Allergy	(Any close family history)
Asthma	149 (38%)	69 (32%)	59 (31%)	38 (27%)
Hay fever	208 (53%)	114 (53%)	102 (53%)	71 (51%)
Itchy Rash	117 (30%)	65 (30%)	60 (31%)	40 (29%)
Wheeze	140 (36%)	25 (12%)	63 (33%)	34 (24%)
Runny Nose	183 (47%)	106 (49%)	97 (50%)	66 (47%)
Food Allergy	110 (28%)	60 (28%)	56 (29%)	41 (29%)
Note. p < .05, *Higher level of education refers to having obtained a higher education qualification (normally beyond age 18) which includes bachelor degrees, as well as degree apprenticeships, and foundation degrees.

Demographic characteristics of participants who responded to each wave of data collection are shown in Table 1, as well as the prevalence of allergy among close family members (biological mother, father or siblings) of the infant. Participants were predominately white British (> 80%) which is representative of XXXXXX city (79%). However, respondents to Waves 2–4 were typically highly educated (> 70% Higher Education), which is higher than average for XXXXXXX’s population (35% Higher Education).

Respondents to the questionnaire were older, and more likely to have attended higher education compared to non-respondents. However, there was no difference in the percentage of mothers of white British ethnicity for respondents compared to non-respondents

In all waves of data collection, hay fever was the most commonly reported allergy and more than 50% of infants had at least one close family member with hay fever. Around 28% of infants had a close family member with a food allergy, and 38% of infants had a close family member with asthma.

15% of parents reported that they were avoiding giving their infants certain foods due to allergy at Wave 2, 16% at Wave 3 and 10% at Wave 4 (see Table 1). The most commonly reported foods that were being avoided due to allergy at Wave 2 were: dairy (n = 14, yogurt n = 1), soya (n = 6), egg (n = 5), nuts (n = 5) and fruits (banana, n = 2; strawberries, n = 1; orange, n = 1). At Wave 3 commonly avoided foods were dairy (n = 14, milk and cheese, n = 2), egg (n = 8), nuts (n = 8), soya (n = 6) and fruits (banana n = 1; blueberries, n = 1; watermelon, n = 1; cucumber, n = 1; and strawberries, n = 1). And at Wave 4 the most commonly avoided foods were dairy (n = 6), nuts (n = 4), egg (n = 3), soya (n = 3) and fruits (banana, n = 2; raspberries, n = 1; tomato, n = 2; kiwi, n = 1; blueberries, n = 1; apricot, n = 1).

Time and Type of Foods Introduced into Infants’ Diets

The mean age for introduction of solid foods was 22.7 weeks (SD = 3.40, range 6–36 weeks). Most highly allergenic foods were introduced to infants at around 6–9 months. Wheat was introduced earlier than the other allergenic foods: 31% of infants were introduced to wheat before they reached 6 months, and nearly all infants had been introduced to wheat by the time they were 9 months (97%). Nuts were introduced latest with only 38% of infants being introduced to nuts by the time they were 9 months old, and 35% of infants never having exposure to nuts by Wave 3 (around 12 months). Egg and sesame were also introduced to infants later, and 21% of infants had not been exposed to eggs and 16% had not been exposed to sesame by Wave 3 (around 12 months) see Table 2.

Table 2

Number of children who were introduced to highly allergenic foods at each age (in months)
	Age (months) N (%)
	< 3	3 to < 6	6 to < 9	9 to < 12	12+	Never
Wheat	2 (1%)	70 (30%)	154 (66%)	4 (2%)	-	2 (1%)
Egg	-	9 (5%)	120 (60%)	22 (11%)	7 (4%)	41 (21%)
Milk	1 (< 1%)	34 (16%)	158 (73%)	12 (6%)	4 (2%)	7 (3%)
Fish	-	9 (4%)	134 (63%)	52(25%)	5 (2%)	12 (6%)
Nuts	1 (< 1%)	3 (2%)	69 (35%)	41 (21%)	12 (7%)	69 (35%)
Sesame	1 (< 1%)	5 (3%)	91 (46%)	52 (26%)	18 (9%)	32 (16%)

[Insert Table 2]

Repeated measure ANOVA showed that the variety of foods eaten by infants increased as they aged (see Table 1). Both the increase in variety of foods eaten from Wave 2 to Wave 3, and the increase in Wave 3 to Wave 4, were statistically significant.

The association between family history of allergy and time and type of foods introduced to infants’ diet

There was no difference in the age of introduction of solid food between the infants with any family history of any allergy and infants without a family history of these allergies (t(135) = 1.47, p = .144, ns).

As shown in Table 3, none of the binary logistic regression models which assessed the effects of family history of allergy on the likelihood that infants’ introduction to each allergenic food was delayed, were statistically significant. Family history of allergy did not make a significant contribution to delayed introduction (9 months or later compared to before 9 month) of any of these allergenic foods.

Table 3

Percentage of infants introduced late (9 months or later) to highly allergenic foods by family history of allergy
	Late introduction of:
	Wheat	Egg	Milk	Fish	Nuts	Sesame
Asthma No Asthma	1% 4%	22% 27%	7% 11%	27% 34%	60% 62%	45% 53%
Hayfever No Hayfever	3% 2%	28% 22%	12% 7%	30% 34%	58% 65%	51% 49%
Rash No Rash	4% 3%	31% 23%	14% 8%	27% 34%	60% 62%	44% 53%
Wheeze No Wheeze	1% 3%	22% 27%	5% 12%	25% 35%	58% 63%	47% 52%
Itch No Itch	3% 3%	28% 22%	8% 11%	29% 35%	59% 63%	53% 47%
Food Allergy No Food Allergy	5% 2%	24% 26%	8% 10%	37% 30%	69% 58%	47% 51%
¹Model χ² p	4.058 P = .669	4.430 P = .619	10.949 P = .090	4.866 P = .561	4.414 p = .658	4.466 P = .614
Note. The model (binary logistic regression) assessed the impact of family history of all allergies on late introduction of each type of allergenic food.

However, as shown in Table 4, at Wave 2, infants with a family history of every type of allergy were more likely to have diets avoiding certain foods due to allergy compared to infants without a family history of that allergy. At Wave 3, infants with a family history of asthma, hay fever, itchy rash or food allergy were more likely to have diets avoiding foods due to allergy and at Wave 4, infants with a family history of asthma or hay fever were more likely to have diets avoiding foods due to allergy, than infants without a family history of these allergies.

Table 4

The percentage of infants with diets that avoid food due to allergy in infants with compared to without a family history of allergy.
	Percentage of infants with diets that avoid foods due to allergy		χ² (p value)
	Family History of Asthma	No family history of Asthma
Wave 2 Wave 3 Wave 4	27% 24% 23%	10% 13% 6%	7.68 (p = .006) 11.05(p = .001) 9.88 (p = .002)
	Family History of Hay Fever	No Family History of Hay Fever
Wave 2 Wave 3 Wave 4	24% 25% 20%	8% 7% 1%	8.60 (p = .003) 11.05 (p = .001) 13.18 (p < .001)
	Family History of Itchy Rash	No Family History of Itchy Rash
Wave 2 Wave 3 Wave 4	25% 25% 13%	12% 7% 10%	4.72 (p = .030) 11.05 (p = .001) .277 (p = .599) ns
	Family History of Wheeze	No Family History of Wheeze
Wave 2 Wave 3 Wave 4	27% 23% 18%	11% 14% 8%	9.17 (p = .002) 2.62 (p = .106) ns 2.55 (p = .116) ns
	Family History of Runny Nose	No Family History of Runny Nose
Wave 2 Wave 3 Wave 4	23% 22% 12%	10% 12% 9%	6.75 (p = .009) 3.15 (p = .076) ns .412 (p = .521) ns
	Family History of Food Allergy	No Family History of Food Allergy
Wave 2 Wave 3 Wave 4	30% 32% 10%	11% 11% 10%	11.18 (p = .001) 12.04 (p = .001) .211(p = .646) ns

[Insert Table 4]

Repeated measures ANOVA showed that there was no significant difference in the variety of foods eaten by the infants who had a family history of allergy compared to infants without a family history of allergy (F(1) = .115, p = .735 ns) and there was also not a significant Group X time interaction (F(2) = .428, p = .652, ns).

This study aimed to investigate the time and type of foods introduced into infants’ diets in this population cohort and whether this differed in infants with a family history of allergy compared to infants without a family history of allergy.

Although there is no specific guidance for the optimal age of timing of introduction of highly allergenic foods, current guidelines for primary prevention of food allergy does not advise late introduction of allergenic foods ^15–17. And rather that highly allergenic foods are introduced alongside other solids. Research generally reports that early introduction of allergenic foods, particularly nuts and egg, is associated with lower risk of allergic disease¹⁸ and it has been suggested that high-risk children should be introduced to peanut-containing foods as early as 4–6 months of age ⁶⁷.

In this sample, most highly allergenic foods were introduced to infants at around 6–9 months. However, some allergenic foods were introduced much later, for example a fifth (21%) of children had not been exposed to egg and over a third of infants (35%) had not been exposed to nuts by 12 months. This suggests that a significant proportion of parents are delaying the introduction of allergenic foods to their infants. Similarly, between 10–16% of infants had diets that avoided foods due to allergy at each wave of data collection.

In this sample, parents of the infants, both those with and without a family history of allergy did not appear to be following advice to introduce nuts and eggs alongside other solids, and nuts and eggs were introduced late, with a large proportion of infants not being exposed to either of these foods by one year of age. Delaying the introduction of nut and egg in the population and the avoidance of highly allergenic foods in high risk infants might affect the development of allergies in infants. However, these dietary decisions could be a modifiable risk factor for allergy development: in countries, such as Australia, where a national strategy has been implemented to communicate the recommendations to introduce allergenic foods earlier to infants, early introduction to allergenic foods has been well accepted by the population (see for example the Nip Allergies in the Bub strategy¹⁹ and the Early Nuts Study ²⁰). From the current study, it is not clear why parents are not following the current guidance to introduce allergenic foods alongside other foods during weaning, or why parents of infants with a family history of allergy choose to avoid certain foods due to allergy, future qualitative research would help to understand the factors underpinning these decisions. However, it may be that these behaviours are contributing to the high prevalence of allergic disease in the UK.

Furthermore, in the current study, although infants with a family history of allergy were introduced to allergenic foods at similar times to other infants, they were more likely to have diets that avoided particular foods than infants without a family history of allergy. The foods that were reported to be avoided by infants were most commonly dairy, soya, egg and nuts but also included a variety of fruits. This is likely to reflect that infants with a family history of allergy are introduced to allergenic foods at a similar time as other infants, but that their parents later decide to avoid these foods in their infants’ diets. Many of the foods being avoided in the infants’ diets are not highly allergenic foods, for example at each wave of data collection a number of parents reported avoiding fruits such as banana, which is uncommonly associated with allergy

One of the strengths of the current study was its longitudinal design, this ensured that the parents were less affected by recall bias in their reports of when they introduced foods to the infants as the parents were sent the questionnaires to completed when their infants were of an appropriate age. However, limitations of the study include reliance of parental-report measures, for example about the timing of introductions of highly allergenic foods required parents to understand the ingredients in pre-prepared infant foods. Furthermore, the participants involved in the study were more likely to be highly educated than the typical XXXXXX population. The response rate to the questionnaires ranged from 36–55%, and older, more highly educated mothers from the initial cohort were more likely to respond. These findings may not be replicable in younger, less well-educated populations.

In conclusion, in this sample, although most highly allergenic foods were introduced to infants along with other solid foods, many parents delayed the introduction of egg and nuts beyond one year of age. Furthermore, infants with a family history of allergy were more likely to have diets that avoided foods due to allergy. These behaviours may contribute to the development of allergic disease.

Financial Support

The study was funded by the University of XXXXXX

Ethical Approval:

This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving research study participants were approved by the South Central Berkshire B Research Ethics Committee (REC ref: 15/SC/0008). Written informed consent was obtained from all participants

Competing Interests:

None

Author Contribution

Statement: All authors were involved in the study design, SH, and GM were involved in data collection. SH wrote the first draft of the paper and conducted the analyses, all authors contributed to further drafts.

Acknowledgements:

The authors would like to thank the families who participated in this study and the Research Midwives at XXXXXX Hospital - Zoe Garner, Linda Lishman, Jess Madgwick, Gilly Stephens and Carole Hoyland. The authors also thank Professor Sasee Pallikadavath for all of his advice towards the Birth Cohort registry and the research-based learning students who assisted with the project

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There is NO conflict of interest to disclose.

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The introduction of allergenic foods to the infant diet in a UK cohort: the impact of family history of allergy

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Abstract

Figures

Introduction

Methods

Recruitment and eligibility

Participants

Measures

Socio-demographic and environmental characteristics

Family History of Allergy

Infant dietary intake

Data Analysis

Results

Demographic characteristics of parents and infants

Time and Type of Foods Introduced into Infants’ Diets

Discussion

Declarations

Financial Support

Author Contribution

Acknowledgements:

References

Additional Declarations

Status:

Version 1