Maternal dietary indexes are not linked to early childhood wheezing or atopic eczema

Several recent studies have investigated the association between maternal diet during pregnancy and wheezing or asthma in children. However, whether a specific dietary pattern during pregnancy protects children from wheezing or atopic diseases remains unclear. This study investigated the association between The Alternative Healthy Eating Index for Pregnancy (AHEI‐P), the Dietary Inflammatory Index (DII), and the risk for wheezing and atopic eczema in children during the first year of life.

largely explained by epigenetic mechanisms, including histone acetylation and DNA methylation changes.It is suggested that prenatal nutrition impacts early life airway development, lung function, and the development of innate and adaptive immune systems through epigenetic modulations.4][15] Impaired lung function or altered immune responses by genetic predisposition or environmental exposure might also predispose to the effects of other environmental factors, like viral infections, in the development of asthma. 3,16ly a few studies have examined the association between maternal overall dietary pattern or maternal dietary inflammatory potential during pregnancy and wheezing or asthma in offspring.
To clarify the association between maternal diet during preg- Information on maternal age and BMI and paternal atopic diseases was collected during the first trimester, and information on maternal use of tobacco was collected throughout pregnancy.
Questionnaires on infant health have been collected starting at 1 year of age and will be collected annually after that up to the age of 7 years.Information on the children's sex, gestational age at birth, birth weight, and health issues during the neonatal period were obtained from the Hospital Register.Web-based food frequency questionnaires (FFQ) were obtained during the third trimester.We used FFQ modified from the FFQ validated in the Kuopio Breast Cancer Study. 22,23The FFQ comprises a list of 160 food items with nine response options from "never" to "six or more times per day." The output of calculated food consumption and nutrient intakes provided more than 60 nutrients and 100 food groups.In addition, the FFQ provides information about supplement use.We calculated the average daily food, nutrients, and energy intake by using the Finnish national food composition database. 24The participants who completed the FFQ during the third trimester of pregnancy and 12-month follow-up questionnaires on infant health were included in this study.Those participants who lacked data of maternal body mass index (BMI) (n = 69), and all the twins (n = 12) were excluded from the analysis.A total of 1330 mother-child pairs were included in this study.

| Dietary indexes
The Alternative Healthy Eating Index for Pregnancy (AHEI-P) and the Dietary Inflammatory Index (DII) were calculated using dietary data from the third trimester FFQ.
The AHEI-P is a modified version of the Alternate Healthy Eating Index (AHEI). 25,26The original AHEI is a valid measure of diet quality that focuses on food items associated with decreased chronic disease risk.To make AHEI more suitable for pregnant women, Rifas-Shiman et al. included folate, calcium, and iron components and excluded the alcohol component, and because some participants may avoid nuts due to allergic sensitization, the nuts and soy protein-component were excluded and tofu and soybeans were included in the vegetable component. 26The AHEI-P contains nine dietary components: vegetables, fruit, the ratio of white to red meat, fiber, trans fat, the ratio of polyunsaturated to saturated fatty acids, folate, calcium, and iron.Dietary recommendations for pregnant women determine the minimum and maximum points of each component, with a maximum score of 10 points for each component.The scores for the individual dietary components were summed to get the total AHEI-P score for each participant.The total AHEI-P score is on a 90-point scale, and a higher total AHEI-P score indicates better dietary quality.
The DII determines the inflammatory potential of a participant's overall diet.Accurate instructions for DII scoring are reported elsewhere. 27The DII contains 45 dietary parameters reported to affect blood interleukin (IL-1β, IL-4, IL-6, and IL-10), Tumor Necrosis Factor-alpha (TNFα), and C-reactive protein (CRP) levels.In this study, we calculated DII scores according to 31 parameters out of 45.We lacked data on the consumption of

Key Message
Using two different dietary indexes, we found that neither the Alternative Healthy Eating Index for Pregnancy (AHEI-P) nor the Dietary Inflammatory Index (DII) during pregnancy is associated with wheezing or atopic eczema in children during the first year of life.More research on maternal diet during pregnancy and its relation to wheezing and atopic eczema in offspring is needed.garlic, onion, some seasonings such as thyme and turmeric, and some nutrients such as eugenol and flavonols because they cannot be calculated reliably based on the FFQ used.A negative DII score indicates an anti-inflammatory diet, while a positive DII score indicates a pro-inflammatory diet.

| Outcomes
The question on children's wheezing was based on The International Study of Asthma and Allergies in Childhood (ISAAC)-phase one manual questionnaire, 28 which is designed to define asthma symptoms among children who do not have a doctor's diagnosis of asthma.
The wheezing outcome was defined as a "yes" answer to the following question: "Has your child ever had wheezing or whistling in the chest?".In addition, doctor-diagnosed bronchiolitis was included in the wheezing outcome to include all the children with any wheezing symptoms in the analysis.We defined the eczema outcome as an answer of "yes" to the following question: "Has your child ever had doctor-diagnosed atopic eczema?".

| Statistical analyses
The research data were analyzed using IBM SPSS Statistics Version 27.Diet scores were examined both as categorical and continuous variables.For categorical analysis, both diet scores were divided into tertiles.The risk for wheezing and atopic eczema was examined in every tertile group, comparing their odds ratios to the highest (i.e., the healthiest, T3) AHEI-P group and the lowest (i.e., the most anti-inflammatory, T1) DII group, using logistic regression analysis.
Logistic regression was also used when examining the association between dietary patterns and outcomes as continuous variables.
To determine covariates associated with the outcomes, the chisquare test and Fisher's exact tests were used to analyze categorical variables, while one-way ANOVA was used in the analysis of continuous variables.Variables that displayed statistical or borderline significance, as well as variables that have previously been suggested to be important confounders, were included in the multivariate analysis.The variables included in the multivariate model were parental history of atopic disease (maternal or paternal asthma or atopic eczema or hay fever), duration of breastfeeding, child's sex, maternal smoking during pregnancy, BMI in the first trimester, gestational age at birth, and mode of delivery.

| RE SULTS
Table 1 shows the basic characteristics of the 1330 mother-child pairs.The mean age of mothers in the first trimester was 30.5 years (SD ± 4.7), and the mean BMI was 24.8 (SD ± 5.0) kg/m 2 .During pregnancy, the mean AHEI-P score among all mothers was 58.1 (SD 10.1) and the mean DII score among all mothers was −0.095 (SD 2.3).Among all pairs, 57% reported parental atopic disease.Among all children, 14% had wheezing, and 16% had doctor-diagnosed atopic eczema in the first year of life.
No difference was detected in AHEI-P scores between wheezers In unadjusted and adjusted analysis, no significant associations were detected between AHEI-P or DII scores and wheezing or atopic eczema (Table 3).Neither AHEI-P nor DII scores were associated with wheezing or atopic eczema when scores were grouped as tertiles and evaluated in unadjusted and adjusted analysis (Table 4).b Alternate Healthy Eating Index modified for Pregnancy.
c Reported maternal or paternal asthma or atopic eczema or hay fever.
d Birth weight standardized for gestational age and sex.
e ≥1 month of partial or exclusive breastfeeding.
f Reported doctor-diagnosed atopic eczema.
g Reported wheezing in the last 12 months (including doctor-diagnosed bronchiolitis).
In summary, there was no significant association between AHEI-P or DII and wheezing or atopic eczema in children during the first year of life when analyzed by continuous variables and by tertiles (Tables 3 and 4).

| DISCUSS ION
In the present study, we investigated the association between maternal diet during pregnancy and wheezing or atopic eczema during the first year of life.We used DII to measure dietary inflammatory potential during pregnancy and AHEI-P to measure diet quality during pregnancy.No association was found between AHEI-P or DII and self-reported wheezing or doctor-diagnosed atopic eczema in children during the first year of life among 1330 mother-child pairs in a KuBiCo study in Finland.
In this study, a total of 57% of participants reported some parental atopic disease pointing out a potential participation bias.It is always possible that parents with atopic diseases are more likely to participate in the birth cohort studies.According to a National FinTerveys study, 10% of Finnish men and 14% of women reported doctor-diagnosed asthma, and 27% and 33%, consequently reported hay fever. 29In another Finnish population study (Health 2000 Survey), the prevalence of atopic eczema in adulthood was reported to be 15.1%. 30Since most of our study children had both parents, our high number of parental atopic diseases is well in line with these studies, although they are not exactly comparable.
In our cohort, both wheezing and atopic eczema were more common in boys than in girls.Male sex is a well-known risk factor for wheezing in infants, 31,32 and it has also been shown in several studies that atopic eczema might be more common in males in early childhood. 33,34According to our findings, there was a protective

TA B L E 3
Maternal dietary patterns by continuous variables, in relation to the wheezing and atopic eczema in children.
association between longer duration of breastfeeding and wheezing which is in line with previous studies. 31,32In our cohort, atopic eczema in children was associated strongly with parental atopic eczema.This association has been demonstrated previously in numerous studies. 11,12Parental atopic eczema may be an even more important risk factor for atopic eczema in children than parental asthma or allergic rhinitis/hay fever. 11Even though the association between maternal diet during pregnancy and the health of the offspring has been investigated in several studies, there is no clear consensus on what kind of diet would be the most beneficial. 35Only a few studies have examined the association between overall dietary patterns during pregnancy or maternal dietary inflammatory potential and wheezing or asthma or atopy in children.
Lange et al. 20 found no association between scores of AHEI-P and recurrent wheeze in their study of 1376 mother-child pairs from Project Viva.Chen et al. 18 found that higher DII score and lower Healthy Eating Index-2015 score were associated with increased asthma risk in offspring, but their study population differed from ours in terms of sample size, diet assessment method, and timing of prenatal diet assessment.In contrast to our negative mean DII score, their mean DII score was positive.Hanson et al. 13 found that a higher maternal DII score was associated with early transient wheeze trajectory among offspring but not with persistent wheeze or asthma in their study of 1424 mother-child pairs in Project Viva.Earlier studies have suggested that a prenatal Mediterranean diet or a diet rich in seafood may reduce the risk of wheezing and allergic diseases among offspring. 19,36These diets are high in fish which contains n-3 PUFA and vitamin D, both of which are associated with a lower risk of atopic eczema. 15,37e FFQ is a practical method for assessing dietary intake in large study group, although it has limitations.One limitation is that participants must recall their food consumption over the previous 3 months, which can be challenging and may result in inaccurate reporting.However, collecting dietary information during the third trimester of pregnancy reduces the participant's risk of reporting food intake that occurred before the participant was aware of the pregnancy.
AHEI-P is a modified version of validated AHEI to measure prenatal diet quality.A higher AHEI-P score has been associated with a lower blood glucose level and a lower risk for pre-eclampsia. 26An anti-inflammatory diet has been suggested as a preventive factor for cardiovascular diseases. 38Furthermore, Wood et al. 39 found that asthmatics had a more pro-inflammatory diet than healthy controls.
To minimize the risk of coincidence in results, we used tertiles instead of quartiles when analyzing dietary parameters by categorical variables.Although AHEI-P is based on the American Dietary Recommendations, they differ only slightly from Finnish recommendations for pregnant women. 40 used questions based on the ISAAC questionnaire to define wheezing in children.Although the questionnaire questions are considered reliable, there might be differences in the interpretation of the meaning of wheezing despite the exact description of wheezing attached to the question. 41We wanted to investigate wheezing in children regardless of etiology.Because the ISAAC question of wheezing does not exclude wheezing during respiratory tract infection we included doctor-diagnosed bronchiolitis in the wheezing outcome to ensure that all the children with any wheezing symptoms were included.Finnish definition of bronchiolitis is "the first wheezing episode in children during the first year of life." 42Bronchiolitis is often caused by a viral infection, but the Finnish definition does not define the etiology of wheezing.In addition, different etiologies of wheezing cannot be discriminated against by ISAAC questionnaire.
Furthermore, bronchiolitis in infancy is a risk factor for later asthma in children. 43Including children with bronchiolitis in the analysis did not change the results but we wanted to ensure that all the children who had wheezed during the first year of life were included in this study.
The ISAAC questionnaire was originally designed for children aged 5-6 and 13-14.However, using the same questions for younger children allows for long-term follow-up and comparison of results with other studies.

TA B L E 4
Maternal dietary patterns by tertiles, in relation to the wheezing and atopic eczema in children.

2 | ME THODS 2 . 1 |
nancy and atopic outcomes in offspring, we studied the association between maternal diet quality or maternal dietary inflammatory potential in the third trimester of pregnancy and their relation to the development of wheezing or atopic eczema in children during the first year of life in 1330 mother-child pairs who attended the Kuopio Birth Cohort (KuBiCo) study by completing web-based questionnaires.Study design and subjects This study was conducted as a part of the KuBiCo study.Data for the KuBiCo study has been collected since 2012, and 8110 mothers have been recruited during their prenatal clinic visits.All mothers lived in the District of Eastern Finland and were expected to give birth at Kuopio University Hospital.All the mothers have given their informed consent to participate in this cohort.The Research Ethics Committee of The Wellbeing Services County of Central Finland has reviewed and approved the KuBiCo protocol (dated 8 December 2011, Dnro 18U/2011).

TA B L E 1 Maternal
Abbreviation: DII, dietary inflammatory index.a Maternal BMI in the first trimester.
Comparison of covariates in relation to the wheezing and atopic eczema in children among 1330 child-mother pairs.
TA B L E 2 Note: Values are mean (SD) or N (%).aMaternalBMI in the first trimester.bReportedmaternal or paternal asthma or atopic eczema or hay fever.cBirthweight standardized for gestational age and sex.d ≥1 month of partial or exclusive breastfeeding.aUnadjustedanalysis.bMultivariablemodel adjusted for parental history of atopic disease (reported maternal or paternal asthma or atopic eczema or hay fever), duration of breastfeeding, child's sex, maternal smoking during pregnancy, maternal BMI in the first trimester, gestational weeks, and delivery mode.cAlternate Healthy Eating Index modified for Pregnancy.dDietary Inflammatory Index.
Multivariable model adjusted for parental history of atopic disease, duration of breastfeeding, child's sex, maternal smoking during pregnancy, maternal BMI in the first trimester, gestational weeks, and delivery mode.c Alternate Healthy Eating Index modified for Pregnancy.
a Unadjusted analysis.b