(2023) 23:78
Tsuchida et al. BMC Pediatrics
https://doi.org/10.1186/s12887-023-03878-6

BMC Pediatrics

RESEARCH

Open AccessSeason of birth and atopic dermatitis in early
infancy: results from the Japan Environment
and Children’s Study
Akiko Tsuchida1,2, Toshiko Itazawa3, Kenta Matsumura1,2, Hiroshi Yokomichi4, Zentaro Yamagata4,5,
Yuichi Adachi6, Hidekuni Inadera1,2* and on behalf of the Japan Environment and Children’s Study Group

Abstract
Background Atopic dermatitis (AD) is reported to be more prevalent in children who were born in autumn than inspring. Here, we investigated how early the association between season of birth and eczema or AD can be observedin the postnatal period. We also examined whether specific prevalence outcomes for infant eczema and AD differedaccording to sex and maternal history of allergic disease in a large Japanese cohort.
Methods Using data of 81,615 infants from the Japan Environment and Children’s Study, we examined the associations of birth month or season with four different outcomes—eczema at 1 month, 6 months, and 1 year of age andphysician-diagnosed AD up to 1 year of age—using multiple logistic regression analysis. We also analyzed the effectof maternal history of allergic disease on these outcomes stratified by infant sex.
Results The risk of eczema at 1 month was highest in infants born in July. In contrast, infants born in autumn had
higher risks of eczema at 6 months (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 2.10–2.30) and at
1 year (aOR, 1.08; 95% CI, 1.02–1.14) and of physician-diagnosed AD up to 1 year of age (aOR, 1.33; 95% CI, 1.20–1.47)
compared with infants born in spring. Eczema and AD were more prevalent in infants with a maternal history of allergic disease, particularly boys.
Conclusions Our findings suggest that the prevalence of AD is associated with the season of observation. Eczema isprevalent in infants born in autumn, and this phenomenon was observed in infants as young as 6 months old. The risk
associated with being born in autumn was particularly clear in boys with a maternal history of allergic disease.
Trial registration UMIN0​00030​786
Keywords Atopic dermatitis, Birth month, Birth season, Eczema*Correspondence:
Hidekuni Inadera
inadera@med.u-toyama.ac.jp
1
Department of Public Health, Faculty of Medicine, University of Toyama,
2630 Sugitani Toyama 930‑0194, Toyama, Japan
2
Toyama Regional Center for Japan Environment and Children’s Study,
University of Toyama, Toyama, Japan3
Department of Pediatrics, Saitama Medical University, Saitama, Japan
4
Department of Health Sciences, University of Yamanashi, Yamanashi,
Japan
5
Koshin Regional Center for Japan Environment and Children’s Study,
University of Yamanashi, Yamanashi, Japan

6

Department of Pediatrics, Faculty of Medicine, University of Toyama,
Toyama, Japan© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of thislicence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Tsuchida et al. BMC Pediatrics(2023) 23:78

BackgroundAtopic dermatitis (AD) is a common allergic inflammatory skin disorder in children. Its etiology is not fully
understood, but it is presumed to be multifactorial withinteractions among genetic and environmental factors[1]. In terms of the genetic factors involved, the risk ofdeveloping AD is known to be higher if one parent has anallergic history than if neither parent such allergic history[2, 3], and mothers with AD may more readily transmit
AD to their offspring compared with fathers [4, 5]. The
sex of the child is also recognized to affect the development of allergic diseases. For example, boys are reported
to be more susceptible to childhood asthma [6–8]. Nevertheless, the effects of sex on AD development, withand without maternal history of allergic disease, remain
unclear.
In terms of the environmental factors involved, theseverity of AD is known to change in relation to theseasons, and many people with AD in Japan experience
exacerbations in winter [9]. A link has also been foundbetween the prevalence of early childhood eczema andclimate factors [10], with associations found with outdoor temperature and humidity [11]. Low indoor or outdoor humidity exacerbated subclinical eczema, thereby
increasing the disease prevalence, through damage to thebarrier function of the skin [10, 11]. Moreover, because
rapid adaptations are required in the first few months oflife after transitioning from the in utero environment tothe very different ex utero environment, interest is growing in how prenatal as well as postnatal environmental
exposures might contribute to AD risk in early childhood.
Season of birth or month of birth can be used as a surrogate factor for potential environmental exposures during the prenatal and early postnatal periods. Factors thatexhibit seasonal variation include temperature, humidity, dryness, exposure to sunlight, and outdoor physicalactivity [12, 13]. Studies of the relationship between season of birth and allergy have suggested that early infancy
is of particular importance for the later development ofallergic diseases [14, 15]. Many studies have reported that
AD is more prevalent in children born in autumn than inspring in the northern hemisphere [14–22].
The International Study of Asthma and Allergies inChildhood (ISAAC) has developed a questionnaire forlarge-scale screening of AD and other allergic diseases in
the general population [23, 24], but no widely used questionnaires have been developed to determine prevalence
in infancy. Therefore, little information is available on theprevalence and development of skin lesions in the early
postnatal period. Most previous studies assessed AD
prevalence among children 6 years and older, and there
are scant data on the prevalence of eczema and development of AD in younger children, especially those under

Page 2 of 12

1 year of age. Up to 1 year of age, the diagnosis of AD
is not common because the typical skin lesions are notobvious at that age. Moreover, physicians may not see
children with eczema because over-the-counter medications are readily available to treat the symptoms. Yet,
early eczema is regarded as the beginning of the atopic
march [5, 25]. Indeed, atopic eczema is one of the earliest
clinical manifestations of allergic disease [26] and occurs
most commonly in the first months of life [27, 28]. It is
important, therefore, to clarify how the season or monthof birth affects the trajectory of the skin lesions in infants
up to 1 year of age.
In this study, using data from a large Japanese birthcohort, we sought to clarify the effects of season of birthand maternal history of allergic disease on the development of eczema in infants up to 1 year of age. We wanted
to determine how early in the postnatal period the association between the season of birth and eczema can beobserved. Moreover, we examined the influence of sex of
the infant and maternal history of allergic disease on thedevelopment of eczema and the diagnosis of AD in early
infancy.

Methods
Study design and participants

We analyzed data obtained in the Japan Environment andChildren’s Study (JECS), which is investigating the effects
of environmental factors on children’s health. JECS is
an ongoing nationwide government-funded prospective
birth cohort study that was started in January 2011 [29,30]. It is funded directly by the Ministry of the Environment, Japan, and involves collaboration among the JECS
Programme Office (National Institute for Environmental Studies), the Medical Research Center for the JECS(National Center for Child Health and Development),
and 15 regional centers [29, 30]. Pregnant women arecontacted through cooperating health care providers
and/or local government offices that issue the Maternaland Child Health Handbooks and those consenting toparticipate are registered. The population characteristicsof the JECS cohort are highly representative of the Japanese population according to vital statistics published by
the government [30].
Ethics statement

JECS participants were recruited during their pregnancy by research coordinators after receiving face-toface explanations of the overall aims of the study, andinformed consent was obtained from all participants.
JECS is conducted in accordance with the Declaration of Helsinki and applicable national regulations andguidelines. All procedures involving human subjects for
the JECS protocol were reviewed and approved by the

Tsuchida et al. BMC Pediatrics(2023) 23:78

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Ministry of the Environment’s Institutional Review Board
on Epidemiological Studies (100,910,001) and the ethics
committees of all participating institutions.

questionnaires or missing response to items on theinfant’s skin status or physician-diagnosed AD. Finally,
we analyzed the data for 81,615 infants (Fig. 1).

Study data

Exposure classification

This study used the jecs-qa-20210401 dataset (jecsta-20190930), which contains information on demographic factors, medical history, obstetric history,
physical and mental health, lifestyle, occupation, housing
situation, and socioeconomic status, obtained from participant responses to self-administered questionnaires ortranscribed from the medical records by physicians, midwives, nurses, and/or research coordinators. The dataset
contains the records of 103,057 pregnancies with information on mother–infant pairs. Of these, we excluded
5,647 multiple registrations (second or third registrationof the same mother), 948 multiple births (twins or more),and 3,521 miscarriages or stillbirths. Among the remaining 92,941 singleton live births from unique mothers,
an additional 11,352 were excluded due to unreturnedFirst, we considered the month of birth as an exposure
factor in our analysis. Then, we used season of birth foranalysis. In a previous study, we found the highest incidence of AD in 3-year-olds born in October–December
and the lowest incidence in those born in April–June[20]. Therefore, in this study, we classified seasons as
spring (April–June), summer (July–September), autumn(October–December), and winter (January–March).

Fig. 1 Participant flow diagram

Outcomes

Information on dermatitis was collected by distributing
questionnaires to the caregivers (mainly mothers) of theinfants at 1 month, 6 months, and 1 year after delivery.
Although various definitions of AD and eczema havebeen reported [31], the present study refers to “eczema”

Tsuchida et al. BMC Pediatrics(2023) 23:78

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Table 1 Demographic and obstetric characteristics of the infants

Table 1 (continued)

Characteristicn (%) or mean (SD)

Characteristic

January

6,400 (7.8%)

February

5,736 (7.0%)

Gestational weeks (w), (n = 81,459)

March

6,175 (7.6%)

April

6,308 (7.7%)

Breastfeeding only

34,548 (42.5%)May6,559 (8.0%)

Mixed feeding

45,740 (56.2%)

June

6,292 (7.7%)

Infant formula only

1,062 (1.3%)

July

7,171 (8.8%)

August8,190 (10.0%)

September

8,305 (10.2%)

October

7,691 (9.4%)

November

6,461 (7.9%)

December

6,327 (7.8%)

Month of birth, (n = 81,615)

Season of birth, (n = 81,615)

FemaleMean (SD)n (%) or mean (SD)39,710 (48.7%)
38.9 (1.5)

Feeding method during 1 month after birth, (n = 81,350)

Presence of older siblings at 1 month after birth, (n = 81,615)
Yes

Pet ownership, (n = 80,830)
Yes

Registered regional center, (n = 81,615)

42,695 (52.3%)
18,290 (22.6%)

Hokkaido

6,505 (8.0%)

Miyagi

6,700 (8.2%)

Spring (Apr–Jun)

19,159 (23.5%)

Fukushima

11,145 (13.7%)

Summer (Jul–Sep)

23,666 (29.0%)

Chiba

4,720 (5.8%)

Autumn (Oct–Dec)

20,479 (25.1%)

Kanagawa

5,402 (6.6%)

Winter (Jan–Mar)

18,311 (22.4%)

Koshin5,806 (7.1%)

Toyama4,587 (5.6%)

Maternal age (years), (n = 81,611)< 25

7,105 (8.7%)

Aichi

4,492 (5.5%)

25–29

22,273 (27.3%)

Kyoto

3,247 (4.0%)

30–34

29,405 (36.0%)

Osaka

6,268 (7.7%)

35–39

18,963 (23.2%)

Hyogo

4,185 (5.1%)≥ 40

3,865 (4.7%)

Tottori

2,499 (3.1%)

Kochi

5,487 (6.7%)< 4 million

29,578 (39.1%)

Fukuoka

6,117 (7.5%)

4 – < 6 million

25,337 (33.5%)

South Kyushu/Okinawa

4,455 (5.5%)≥ 6 million

20,786 (27.5%)< 13

27,846 (34.5%)

13 – 15

34,581 (42.8%)≥ 16

18,351 (22.7%)

Yes

40,799 (50.2%)

Annual household income (JPY), (n = 75,701)

Abbreviations: JPY Japanese yen, SD Standard deviation

Highest maternal educational level, (n = 80,778)

Maternal history of allergic disease, (n = 81,203)

Maternal intake of vitamin D during pregnancy (μg), (n = 81,177)
Mean (SD)

4.3 (2.8)

Maternal active smoking during pregnancy, (n = 80,587)
Never-smokers

47,828 (59.4%)

Quit smoking before pregnancy

19,133 (23.7%)

Quit smoking during early pregnancy

10,563 (13.1)

Continued smoking

3,063 (3.8%)

Maternal passive smoking during pregnancy, (n = 80,979)
Almost never

51,302 (63.4%)

Less than 1 day per week

9,712 (12.0%)

2–3 days per week

6,500 (8.0%)

4–6 days per week

3,877 (4.8%)

Every day

9,588 (11.8%)

Infant sex, (n = 81,613)
Male

41,903 (51.4%)

as judged by the parents based on the symptoms theyobserved and to “AD” as diagnosed by a physician. We
analyzed four outcomes reported on: eczema at 1 monthof age, eczema at 6 months of age, eczema at 1 year ofage, and physician-diagnosed AD reported at 1 year ofage. Eczema at 1 month of age was defined as an affirmative response to the question, “Has your baby ever had
a rash on the face, head, or neck or around the ear during the past month after birth?” Eczema at 6 months andeczema at 1 year of age were both defined as an affirmative response to the question, “Has your child ever had
an itchy rash that was coming and going for at least
2 months?”, which was based on an item from the ISAAC
questionnaire targeting 6–7-year-olds, the Japanesetranslation of which has been validated [23, 24]. Physician-diagnosed AD reported at 1 year of age was defined
as an affirmative response to the question, “Has yourchild ever been diagnosed by a physician as having AD?”.

Tsuchida et al. BMC Pediatrics(2023) 23:78

Statistical analysis

To identify the association between season of birth andthe four outcomes, we performed logistic regression
analysis [32] and determined the 95% confidence intervals (CIs). Multiple testing correction was performed
using the Benjamini–Hochberg method [33], and thefalse discovery rate was set at less than 0.05. Then, in
multivariable logistic regression analysis, we adjusted
for the following potential modifiers: maternal age,annual household income, maternal education level,maternal history of allergic disease (AD, bronchialasthma, allergic rhinitis, pollinosis, allergic conjunctivitis, and food allergy), maternal intake of vitamin D
during pregnancy, maternal active smoking, maternal
passive smoking, infant sex, gestational weeks, feeding
method during the first month after birth, presence ofolder siblings, pet ownership, and registered regional
center. These covariates were selected based on a previous study [22]. Vitamin D intake was obtained froma food frequency questionnaire [34] and was adjusted
for energy intake using the residual method. Multicollinearity assessed using generalized variance-inflation
factors greater than 10 was not detected.
To examine whether the relationship between season of birth and prevalence of eczema or AD differed
by infant sex or maternal allergic history, parent-judged
eczema and physician-diagnosed AD were analyzed
separately after stratification of the cohort by sex andmaternal history of allergic disease. SAS version 9.4
software (SAS Institute Inc., Cary, NC, USA) was used
for all statistical analyses.

Results
A total of 81,615 infants were analyzed in this study.
Distribution by month of birth ranged from 7.0% to10.2% (Table 1). Most infants were born in the summer, followed by the autumn, spring, and winter (29.0%,
25.1%, 23.5%, and 22.5%, respectively; Table 1). The
overall prevalence of parent-judged eczema was 61.0%
at 1 month, 33.0% at 6 months, and 18.7% at 1 year andthat for physician-diagnosed AD was 4.3% up to 1 yearof age.
Logistic regression analysis to examine the association between month of birth and each outcome
revealed that, compared with infants born in May as
a reference, infants born in July had the highest risk ofPage 5 of 12

eczema at 1 month (adjusted odds ratio [aOR], 1.25;
95% CI, 1.16–1.35; Fig. 2a), whereas infants born in
November had the highest risk at eczema at 6 months(aOR, 2.51; 95% CI, 2.32–2.73; Fig. 2b) and those bornin October had the highest risk at 1 year (aOR, 1.17;
95% CI, 1.07–1.27; Fig. 2c). Infants born in Octoberalso had the highest risk of physician-diagnosed AD(aOR, 1.40; 95% CI, 1.18–1.66; Fig. 2d).
When the infants were classified by season of birth,with those born in spring as a reference, infants bornin summer had the highest risk of eczema at 1 month(aOR, 1.19; 95% CI, 1.14–1.24; Table 2a), whereas thoseborn in autumn had the highest risks of eczema at
6 months (aOR, 2.19; 95% CI, 2.10–2.30; Table 2b) andat 1 year (aOR, 1.08; 95% CI, 1.02–1.14; Table 2c) and ofphysician-diagnosed AD up to 1 year of age (aOR, 1.33;
95% CI, 1.20–1.47; Table 2d).
Figure 3 shows the relationship between season ofbirth and prevalence of eczema at 1 month, 6 months,
and 1 year of age. At 6 months old, for infants bornin spring, information was collected in autumn. For
infants born in autumn, information was collected inspring. Although eczema at 6 months and at 1 year ofage are opposite with regards to the season of observation, the highest frequency was identified for infants
born in autumn at both ages. Between 1 and 6 monthsof age as well as between 6 months and 1 year of age,transitions in parent-judged eczema according to season of birth were categorized as no symptoms at either
time point (symptom-free), symptoms improving fromthe first to second time point (improvement), symptoms occurring between the first and second time
points (onset), and symptoms of the same severity atboth time points (persistent). The results showed that
infants with persistent eczema at either time point
examined were more likely to be born in autumn (Supplementary Table 1).
Finally, we stratified the results by sex and maternal history of allergic disease. Prevalence of the four outcomesin both sexes with a maternal history of allergic disease
was higher than in those without such history: eczema
at 1 month of age, 63.5% vs 58.5%; eczema at 6 monthsof age, 36.2% vs 29.7%; eczema at 1 year of age, 22.0% vs
15.5%; and physician-diagnosed AD, 5.6% vs 3.0%. Whenthe groups with and without maternal history allergic
disease were stratified by sex, prevalence was higher inboys than in girls for all four outcomes (Table 3).

(See figure on next page.)
Fig. 2 Odds ratios (95% CI) for outcomes in early infancy by birth month (N = 81,615). Adjusted for maternal age, annual household income,maternal educational level, maternal history of allergic disease, maternal intake of vitamin D during pregnancy, maternal active smoking during
pregnancy, maternal passive smoking during pregnancy, infant sex, gestational weeks, feeding method, presence of older siblings, pet ownership,and registered regional center. Bold letters indicate statistically significant differences calculated using the Benjamini–Hochberg method.
Abbreviations: AD, atopic dermatitis; aOR, adjusted odds ratio; cOR, crude odds ratio;95% CI, 95% confidence interval

Tsuchida et al. BMC Pediatrics(2023) 23:78

Fig. 2 (See legend on previous page.)

Page 6 of 12

Tsuchida et al. BMC Pediatrics(2023) 23:78

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Table 2 Odds ratios (95% CIs) for outcomes in early infancy by birth season (N = 81,615)
Season of birth

Case

Subtotal

PrevalencecOR (95% CI)

aOR (95% CI)

Spring (Apr–Jun)

12,017

19,15962.7%

Reference

Reference

Summer (Jul–Sep)

15,726

23,666

66.4%

1.18 (1.13–1.23)

1.19 (1.14–1.24)

Autumn (Oct–Dec)

12,02820,47958.7%

0.85 (0.81–0.88)

0.83 (0.80–0.87)

Winter (Jan–Mar)

10,04818,31154.9%

0.72 (0.69–0.75)

0.72 (0.69–0.75)a) Eczema at 1 monthof ageb) Eczema at 6 months of age
Spring (Apr–Jun)

4,668

19,15924.4%

Reference

Reference

Summer (Jul–Sep)

8,218

23,66634.7%

1.65 (1.58–1.72)

1.66 (1.59–1.74)

Autumn (Oct–Dec)

8,425

20,47941.1%

2.17 (2.08–2.27)

2.19 (2.10–2.30)

Winter (Jan–Mar)

5,599

18,31130.6%

1.37 (1.31–1.43)

1.38 (1.32–1.45)c) Eczema at 1 year of age
Spring (Apr–Jun)

3,514

19,15918.3%

Reference

Reference

Summer (Jul–Sep)

4,390

23,66618.5%

1.01 (0.97–1.07)

1.02 (0.96–1.07)

Autumn (Oct–Dec)

3,976

20,47919.4%

1.07 (1.02–1.13)

1.08 (1.02–1.14)

Winter (Jan–Mar)

3,415

18,31118.6%

1.02 (0.97–1.08)

1.04 (0.98–1.09)d) Physician diagnosed AD before 1 year of age
Spring (Apr–Jun)

731

19,159

3.8%

Reference

Reference

Summer (Jul–Sep)

1,036

23,666

4.4%

1.15 (1.05–1.27)

1.18 (1.06–1.30)

Autumn (Oct–Dec)

1,027

20,4795.0%

1.33 (1.21–1.47)

1.33 (1.20–1.47)

Winter (Jan–Mar)

696

18,3113.8%

1.00 (0.90–1.11)

1.00 (0.90–1.12)

Adjusted for maternal age, annual household income, maternal educational level, maternal history of allergic disease, maternal intake of vitamin D during pregnancy,maternal active smoking during pregnancy, maternal passive smoking during pregnancy, infant sex, gestational weeks, feeding method, food allergy symptoms at
1 month of age, presence of older siblings, pet ownership, and registered regional center. Bold letters indicate statistically significant differences calculated using theBenjamini–Hochberg method
Abbreviations: AD Atopic dermatitis, aOR Adjusted odds ratio, cOR Crude odds ratio, 95% CI 95% Confidence interval

To determine the association between season of birthand physician-diagnosed AD up to 1 year of age, subgroup analysis stratified by infant sex and maternal history of allergic disease revealed that, in girls, the aOR
was not significant among those without maternal history of allergic disease, but for girls with such maternal
history, those born in autumn showed a significant aOR
compared with those born in spring (Table 4). Intriguingly, for boys with maternal history of allergic disease,those born in summer or autumn had a higher risk of AD(summer: aOR, 1.36; 95% CI, 1.15–1.60; autumn: aOR,
1.37; 95% CI, 1.16–1.62).

Discussion
In this large prospective birth cohort, environmental factors indicated by month of birth were found to influence
the prevalence of eczema and AD diagnosis in infants
younger than 1 year of age. In particular, the prevalenceof eczema was found to be higher among those born inthe autumn. Moreover, the importance of male sex andmaternal history of allergic disease on the developmentof atopic eczema was evident. Because eczema is one of
the earliest clinical manifestations of allergic disease andnegatively affects quality of life [26, 28], our results may
be significant from a preventive standpoint. Improved
knowledge about the impact of season of birth on thedevelopment of eczema could inform future preventive measures to prevent skin barrier disruption, suchas appropriate skin care from early infancy, and thereby
reduce the risk of allergic diseases developing, especially in male infants with a maternal history of allergic
disease.
It is well established that events during our early lives
affect later life course trajectories [35, 36]. Previous studies have suggested that the initiation of antigen-specificresponses can occur in utero, mediated by immunoglobulin E. [37]. It is difficult to examine in utero factors
directly, however. Our results here do suggest the important involvement of early postnatal life in the development of eczema. Dry skin and the resulting skin barrier
disruption are believed to be one of the non-allergic etiological factors of AD [38] because they lead to immunological dysregulation, which in turn may lead to allergens
being sensitized epicutaneously, thereby inducing allergic inflammation of the skin. Our results suggest thatthe higher prevalence of eczema observed under certain

Tsuchida et al. BMC Pediatrics(2023) 23:78

Page 8 of 12

Fig. 3 Prevalence of eczema by season of birth. This figure shows the season of information collection for eczema in infants of the same age inmonths. At 6 months of age, for infants born in spring, information was collected in the autumn (October–December), while for infants born inautumn, information was collected in the spring (April–June). Thus, the seasons of information collection at 6 months and 1 year of age were
oppositeclimate conditions could be due to environmental triggering of subclinical disease in predisposed infants.
In Japan, children born in spring (the reference season in this study) spend their first few months in warm,
humid weather, which results in moist skin, whereas
those born in autumn spend their first few months incold, dry weather, which can result in dry skin. They arealso mainly at home in conditions that dry the skin. Winter in Japan, with its low indoor humidity and cold outside temperatures, is associated with a double negative

influence on the skin barrier. Thus, changes in skin condition in the first few months of life could play an important role in triggering allergic skin inflammation andultimately affect the prevalence of AD. Previous studies showed that the sex of the child was associated withthe development of allergic diseases in childhood [6–8].
Moreover, mothers with AD may transmit it to their children [4, 5]. In the present study, the prevalence of physician-diagnosed AD was higher in boys with a maternalallergic history irrespective of season of birth (Table 3).

Tsuchida et al. BMC Pediatrics(2023) 23:78

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Table 3 Prevalence of outcomes stratified by maternal history of allergic disease and infant sex
Without maternal history of allergic disease

With maternal history of allergic disease

Boys

Girls

Boys

Girls

n = 20,715

n = 19,689

n = 20,981

n = 19,816

n

%

n

%

n

%

n

%

Eczema at 1 month of age

12,66761.1%

10,98655.8%

13,89066.2%

12,01760.6%

Eczema at 6 months of age

6,964

33.6%

5,050

25.6%

8,438

40.2%

6,318

31.9%

Eczema at 1 year of age

3,663

17.7%

2,593

13.2%

5,113

24.4%

3,852

19.4%

Physician-diagnosed AD before
1 year of age

762

3.7%

436

2.2%

1,419

6.8%

857

4.3%

Abbreviation: AD Atopic dermatitis

Table 4 Odds ratios for physician-diagnosed AD by birth season stratified by maternal allergic history and sex
Season of birth

Case

Subtotal

Boys without maternal history of allergic disease (n = 20,715)

PrevalencecOR (95% CI)

aOR (95% CI)

Spring (Apr–Jun)

169

4,925

3.4%

Reference

Reference

Summer (Jul–Sep)

205

6,105

3.4%

0.98 (0.80–1.20)

0.98 (0.79–1.22)

Autumn (Oct–Dec)

231

5,102

4.5%

1.34 (1.09–1.63)

1.25 (1.01–1.55)

Winter (Jan–Mar)

157

4,583

3.4%

1.00 (0.80–1.25)

0.95 (0.75–1.19)

Girls without maternal history of allergic disease (n = 19,689)
Spring (Apr–Jun)

101

4,632

2.2%

Reference

Reference

Summer (Jul–Sep)

120

5,702

2.1%

0.96 (0.74–1.26)

0.96 (0.72–1.26)

Autumn (Oct–Dec)

145

4,970

2.9%

1.35 (1.04–1.74)

1.29 (0.99–1.69)

Winter (Jan–Mar)

70

4,385

1.6%

0.73 (0.54–0.99)

0.72 (0.52–0.98)

Boys with maternal history of allergic disease (n = 20,981)
Spring (Apr–Jun)

279

4,933

5.7%

Reference

Reference

Summer (Jul–Sep)

444

6,055

7.3%

1.32 (1.13–1.54)

1.36 (1.15–1.60)

Autumn (Oct–Dec)

399

5,271

7.6%

1.37 (1.17–1.60)

1.37 (1.16–1.62)

Winter (Jan–Mar)

297

4,722

6.3%

1.12 (0.95–1.33)

1.16 (0.97–1.38)

Girls with maternal history of allergic disease (n = 19,816)
Spring (Apr–Jun)

180

4,573

3.9%

Reference

Reference

Summer (Jul–Sep)

262

5,683

4.6%

1.18 (0.97–1.43)

1.20 (0.98–1.48)

Autumn (Oct–Dec)

251

5,033

5.0%

1.28 (1.05–1.56)

1.34 (1.09–1.64)

Winter (Jan–Mar)

164

4,527

3.6%

0.92 (0.74–1.14)

0.97 (0.78–1.22)

Adjusted for maternal age, annual household income, maternal educational level, maternal intake of vitamin D during pregnancy, maternal active smoking during
pregnancy, maternal passive smoking during pregnancy, gestational weeks, feeding method, presence of older siblings, pet ownership, and registered regional
center. Bold letters indicate statistically significant differences calculated using the Benjamini–Hochberg method
Abbreviations: cOR Crude odds ratio, aOR Adjusted odds ratio, 95% CI 95% Confidence interval

Infants born in the autumn in Japan tend to spend early
infancy in a season with little sunshine. A previous study
found higher levels of 25-hydroxy vitamin D and immunosuppressive cytokine IL-10 in the blood of infants born inspring than in those born in winter [39]. In line with this,low exposure to ultraviolet light and subsequently lower
levels of vitamin D and/or IL-10 may explain the association between season of birth and development of AD.
Vitamin D suppresses allergic sensitization by promoting­Fop3+ regulatory T cells [40]. Indeed, reduced vitamin

D and low fish intake by mothers during pregnancy havebeen correlated with increased incidence of AD in theirchildren [41, 42]. Several trials have shown that vitamin
D supplementation improves the clinical symptoms ofAD [43–45]. In our analysis, we adjusted the data for theamount of dietary vitamin D intake during pregnancy.
Therefore, we speculate that the influence of month ofbirth on the development of eczema in early infancy may
be dependent on the vitamin D produced through exposure to sunshine in the children.

Tsuchida et al. BMC Pediatrics(2023) 23:78

It is well recognized that the prevalence of AD is higher
in infants born in autumn than in those born in spring [14,15, 17–20]. A recent systematic review and meta-analysis
also indicated that AD was significantly associated with
autumn and winter births compared with spring births in
the northern hemisphere [46]. However, our results showthat eczema or rash was more prevalent at 1 month of age
in infants born in the summer compared with those bornin other seasons. Thus, the eczema seen at this age may bemuch more influenced by the season of observation. In
Japan, hot and humid conditions in summer are associatedwith the prevalence of eczema in 1 month olds [47–49]. In
our study, the prevalence was particularly high in 1 montholds (61.0%) compared with older infants, probably
because eczema at this age shows a high degree of clinical heterogeneity, similar to other forms of eczema suchas seborrheic dermatitis, intertrigo, and diaper dermatitis. In addition, about 60% of infants who had symptoms
of eczema at 6 months no longer showed such symptoms
at 1 year of age, which is a similar findings to that of previous Japanese studies where atopic dermatitis observedin infants younger than 6 months old remitted with age[50]. Although there are differences in prevalence between
6 months and 1 year of age, both time points show a higher
prevalence among children born in autumn.
This study has several strengths. First, the prospective
design of JECS, with the regular return of questionnaires,
minimizes recall bias concerning the child’s AD. Also,JECS has a well-powered sample size, which enabledadjustment for various confounders in logistic regression analysis. The dataset covers about 45% of live births
within the study areas, and the characteristics of the participants are similar to those of other women according
to the Japanese vital statistics data, so the cohort is considered representative of the Japanese population [30].
We also studied the effect of possible confounders.
Nonetheless, this study has some limitations. Presence of eczema was determined from responses on aself-reported parental questionnaire. The rather broad
question used might result in overestimates of eczema
prevalence through the inclusion of other entities such asallergic contact dermatitis, and differences in the wording of survey questions at 1 month and at 6 months and1 year of age might have an effect as well. We identified
AD based on caregiver-reported physician diagnosis at
1 year of age, and the prevalence might differ if the outcome assessment were to be conducted using data collected from the medical records. Also, the reported
diagnosis was not necessarily made by an allergy specialist.
Furthermore, genetic polymorphisms known to be associated with the development of AD, such as filaggrin [51],
could not be considered in this study.

Page 10 of 12

A combination of multiple indicators, such as use oftherapeutic agents and eczema characteristics, is considered to be the most confirmatory for the diagnosis of AD[31]. Because diagnosing AD in infants under 1 year of
age is difficult, it is necessary to clarify those infants who
are more susceptible to seasonal exposure, taking into
account genetic polymorphisms and other factors. It isalso necessary to clarify whether our results observed inJapan are generalizable to children in other parts of theworld.

Conclusions
Our results indicate that eczema and diagnosis of AD
are more prevalent at age 6 months and 1 year in infants
born in autumn than in those born in spring. However, at
1 month of age, eczema is more prevalent in infants bornin summer. Thus, eczema in 1-month-olds may be influenced by the season of observation. The climate in early
infancy seems to affect skin condition and ultimately
influence the development of AD. Our results suggestthat caregivers of male infants with a maternal history ofallergic disease, and particularly those born in autumn,
should pay careful attention to the infant’s skin.
Abbreviations
AD	Atopic dermatitisaOR	Adjusted odds ratiocOR	Crude odds ratio
CI	Confidence interval
JECS	Japan Environment and Children’s Study

Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s12887-​023-​03878-6.
Additional file 1: Supplemental Table 1. Number (%) of childrenborn
in each season stratified by transition in eczema status between time
pointsin infancy.
Acknowledgements
We thank the children and their families who participated in this study.
We also thank everyone involved in data collection and all members of
the JECS Group as of 2022: Michihiro Kamijima (Principal Investigator,
Nagoya City University, Nagoya, Japan), Shin Yamazaki (National Institute forEnvironmental Studies, Tsukuba, Japan), Yukihiro Ohya (National Center forChild Health and Development, Tokyo, Japan), Reiko Kishi (Hokkaido University, Sapporo, Japan), Nobuo Yaegashi (Tohoku University, Sendai, Japan),
Koichi Hashimoto (Fukushima Medical University, Fukushima, Japan),
Chisato Mori (Chiba University, Chiba, Japan), Shuichi Ito (Yokohama City
University, Yokohama, Japan), Zentaro Yamagata (University of Yamanashi,Chuo, Japan), Hidekuni Inadera (University of Toyama, Toyama, Japan),Takeo Nakayama (Kyoto University, Kyoto, Japan), Tomotaka Sobue (Osaka
University, Suita, Japan), Masayuki Shima (Hyogo Medical University, Nishinomiya, Japan), Hiroshige Nakamura (Tottori University, Yonago, Japan),Narufumi Suganuma (Kochi University, Nankoku, Japan), Koichi Kusuhara(University of Occupational and Environmental Health, Kitakyushu, Japan),and Takahiko Katoh (Kumamoto University, Kumamoto, Japan).

Tsuchida et al. BMC Pediatrics(2023) 23:78

CONSORTIUM Name
Michihiro ­Kamijima7, Shin ­Yamazaki8, Yukihiro ­Ohya9, Reiko ­Kishi10, Nobuo­Yaegashi11, Koichi ­Hashimoto12, Chisato M­ ori13, Shuichi I­to14, Zentaro­Yamagata5, Hidekuni ­Inadera2, Takeo ­Nakayama15, Tomotaka ­Sobue16, Masayuki ­Shima17, Hiroshige ­Nakamura18, Narufumi S­ uganuma19, Koichi K­ usuhara20,
and Takahiko Katoh.21
7
Aichi Regional Center for Japan Environment and Children’s Study, Nagoya
City University, Nagoya, Japan.
8Japan Environment and Children’s Study Programme Office, National Institutefor Environmental Studies, Tsukuba, Japan.
9
Medical Support Center for the Japan Environment and Children’s Study,
National Center for Child Health and Development, Tokyo, Japan.
10
Hokkaido Regional Center for Japan Environment and Children’s Study, Hokkaido University, Sapporo, Japan.
11
Miyagi Regional Center for Japan Environment and Children’s Study, Tohoku
University, Sendai, Japan.
12
Fukushima Regional Center for Japan Environment and Children’s Study,
Fukushima Medical University, Fukushima, Japan.
13
Chiba Regional Center for Japan Environment and Children’s Study, Chiba
University, Chiba, Japan.
14
Kanagawa Regional Center for Japan Environment and Children’s Study,
Yokohama City University, Yokohama, Japan.
5
Koshin Regional Center for Japan Environment and Children’s Study, University of Yamanashi, Yamanashi, Japan
2
Toyama Regional Center for Japan Environment and Children’s Study, University of Toyama, Toyama, Japan
15
Kyoto Regional Center for Japan Environment and Children’s Study, Kyoto
University, Kyoto, Japan.
16
Osaka Regional Center for Japan Environment and Children’s Study, Osaka
University, Suita, Japan.
17
Hyogo Regional Center for Japan Environment and Children’s Study, Hyogo
Medical University, Nishinomiya, Japan.
18
Tottori Regional Center for Japan Environment and Children’s Study, Tottori
University, Yonago, Japan.
19
Kochi Regional Center for Japan Environment and Children’s Study, Kochi
University, Nankoku, Japan.
20
Fukuoka Regional Center for Japan Environment and Children’s Study, University of Occupational and Environmental Health, Kitakyushu, Japan.
21
South Kyushu/Okinawa Regional Center for Japan Environment and Children’s Study, Kumamoto University, Kumamoto, Japan.
Authors’ contributions
A.T. and H.I. drafted the paper and analyzed the data. A.T., T. I, K. M, Y.A, and H.I.
conceived and designed the study. A.T., T. I, K. M, H.Y., Z.Y., Y.A, H.I., and the JECS
group critically reviewed the draft and checked the analyses. The JECS Group
collected the data and obtained funding. All authors approved the submissionof the manuscript in its current form.
Funding
The JECS is funded by the Ministry of the Environment, Japan. The findings
and conclusions of this article are solely the responsibility of the authors anddo not represent the official views of the Japanese government.
Availability of data and materials
Data are unsuitable for public deposition due to ethical restrictions and thelegal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No. 57 of 30 May 2003, amendment 9 September 2015)
to publicly deposit data containing personal information. Ethical Guidelines
for Medical and Health Research Involving Human Subjects enforced by theJapan Ministry of Education, Culture, Sports, Science, and Technology and theMinistry of Health, Labour and Welfare also restrict the open sharing of epidemiological data. All inquiries about access to data should be sent to: jecs-en@nies.go.jp. The person responsible for handling enquiries sent to this e-mailaddress is Dr. Shoji F. Nakayama, JECS Programme Office, National Institute forEnvironmental Studies.

Page 11 of 12

Declarations
Ethics approval and consent to participate
The JECS comprehensive protocol was reviewed and approved by the Japan
Ministry of the Environment’s Institutional Review Board on Epidemiological Studies (100910001) and the ethics committees of all participating institutions. This
specific study was approved by the Ethics Committee of the University of Toyama(R2019184). The JECS is conducted in accordance with the Helsinki Declarationand other national regulations, and written informed consent was obtained fromparents/guardians of any participants who were below 16 years of age.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 8 September 2022 Accepted: 31 January 2023

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