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. 2025 Nov 20;20(11):e0336062. doi: 10.1371/journal.pone.0336062

Birth month as a risk factor of allergic diseases: Analysis of database of about 50 thousand children

Alexander Pampura 1,2,#, Natalia Esakova 2,*,#, Daria Dolotova 2,#, Olga Serebryakova 3,‡, Nikita Chikunov 4,‡
Editor: Vasuki Rajaguru5
PMCID: PMC12633921  PMID: 41264568

Abstract

Background

The season of birth is a factor influencing the child during the neonatal adaptation period and potentially affecting the risk of allergies. The objective of this study was to ascertain the association between the month of birth and the subsequent development of allergic diseases in Moscow children, Russia.

Methods

in 2024 the de-identified data from medical records and parental questionnaires of 49,857 children under the age of 18 was retrieved from the Moscow Unified Medical Information and Analytical System. The database contained the information regarding the presence of atopic dermatitis, asthma, allergic rhinitis, age, sex and family history of allergies. The statistical processing involved the calculation of crude odds ratio (cOR), adjusted odds ratio (aOR) based on multivariate logistic regression.

Results

the odds of allergic rhinitis among children born between October and April was found to be significantly higher in comparison to July (reference), with the strongest association observed for December (aOR, 1,342; 95% CI, 1,203−1,497), January (aOR, 1,386; 95% CI, 1,243−1,546) and February (aOR, 1,371; 95% CI, 1,226−1,533). In these months, the odds were 34−38% higher than in July. The odds of atopic dermatitis among children born between August and February was significantly higher compared to April (reference), the greatest association observed for October (aOR, 1,169; 95% CI, 1,059−1,291), with the association being 16% higher than for April.

Conclusion

This is the first study in Russia to demonstrate that children born in October in Moscow face elevated odds of atopic dermatitis, while children born in December, January, and February are more susceptible to allergic rhinitis. The association detected was independent of sex, age, family allergic history and combination of allergic diseases, which merits further investigation.

Introduction

Atopic dermatitis (AD), allergic rhinitis (AR), and asthma are the most prevalent allergic diseases in children, frequently demonstrating an age-dependent sequence of sensitization and clinical manifestations, termed “the Atopic March”. AD commonly manifests in early childhood, preceding the development of AR and asthma. This observation indicates the pathogenetic relationship between these diseases, highlighting the importance of comprehensive investigations of potential risk factors for their development in the pediatric population [1–3].

A substantial body of research has revealed associations between male sex, family allergy history, characteristics of the causative allergen, genetic, environmental, infectious and other factors and the risk of AD, AR and asthma development [4–9]. A growing amount of research considers the role of the birth season as an important factor with a significant impact on the child during the neonatal adaptation period and potentially influencing the risk of developing allergic diseases. Thus, several studies have identified a heightened risk of developing AD, AR and asthma. However, the findings are not universally consistent, with some studies reporting no clear associations [10–19]. Notably, the season factor itself is heterogeneous, encompassing numerous uncontrolled and controlled factors. Such factors include air temperature and humidity, solar activity, the specificity and degree of allergen exposure (e.g., pollen, dust) in different seasons, the infectious burden, the seasonal variations in the nutrition of the nursing mothers, etc. For example, the winter months are characterized by minimal solar activity and, as a result, decreased vitamin D levels, as well as high exposure to house dust mites and epidermal allergens in homes, which can potentially increase odds of allergy among children born during this period. The possible roles of increased cord blood IgE levels in winter, increased immune activity in general in winter months, including gene expression of several interleukins are discussed [19]. Consequently, the impact of the season of birth on the risk of developing allergic diseases may exhibit notable variations across different regions, even within the same country, owing to the unique characteristics of each region.

A comprehensive understanding of the mechanisms and extent of the influence of the season of birth on the risk of allergic diseases is imperative for the optimization of preventive measures during pregnancy planning, as well as prior to and following childbirth. To date, few studies worldwide have examined this relationship, with no such studies having been conducted in Russia. The objective of this study was to ascertain the potential association between the month of birth and the odds of developing the most prevalent allergic diseases: AD, AR, and asthma, among children living in Moscow (central region of the Russian Federation).

Methods

The study was conducted in 2024 and included an analysis of the data from 49,857 children aged 0–18 years, retrieved from the Moscow Unified Medical Information and Analytical System (EMIAS). EMIAS is a modern information platform in Moscow, which contains electronic medical records available to the patient and the doctor. At each visit of a patient, the doctor (outpatient or inpatient) enters information into the EMIAS medical record, indicating the reason for the visit; in case of a disease, the diagnosis is specified; the same system displays appointments and results of laboratory and instrumental tests. All necessary information, including the diagnosis code according to ICD (International Classification of Diseases, 10th revision), is entered into the EMIAS by healthcare professionals. All patients (patient parents) provide digital informed consent upon first registration in the EMIAS. It is important to note that in Russia, the basic medical care for children and adults is provided through compulsory health insurance, i.e., free of charge. Children may visit a pediatrician due to illness (e.g., often in the case of an acute viral infection or in connection with some specific complaints or diseases), or patients may come without complaints or diseases, e.g., to obtain school or sectional certificates, to undergo a checkup or vaccination. Thus, the study population included both children with diseases and healthy children who visited a pediatrician. The exported dataset contained data exclusively from children whose parents had voluntarily completed a survey questionnaire (integrated within EMIAS) between February 2024 and November 2024 at a pediatrician’s office. The parental questionnaire aimed to ascertain the existence of a family allergy history. Thus, the main inclusion criteria for the formation of the database from EMIAS were: age under 18 years and a parentally fully completed questionnaire to identify family allergy history. We excluded all cases in which at least one of the study variables was missing, so there were no missing values in the dataset. All offload data underwent depersonalization and included medical records (both outpatient and inpatient) as well as parental questionnaire results.

The resulting dataset was searched for patients with established allergic diseases consistent with ICD-10 diagnosis codes as follows: L20.0, L20.8, L20.9 – AD; J30.1, J30.2, J30.3 –AR; and J45.0, J45.1, J45.8, J45.9 - asthma. To account for the influence of possible confounders on the association of these diseases with the month of birth, information on the age and sex of the child, as well as on the presence of family allergic history, was included in the dataset. The study was approved by the Local Ethics Committee at Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery (Protocol №1, dated January 19, 2024). All patients (patient parents) provide digital informed consent.

The data were assessed for normality of the distribution (Shapiro–Wilk test). The distribution of the patients’ age was described via medians and quartiles (Me [Q1; Q3]), given that the distribution of the data deviated from normal. Qualitative variables were described using absolute and relative frequencies. To examine the effects of birth month and season on the odds of developing allergic disease, crude and adjusted odds ratios (cOR and aOR, respectively) were calculated, for which both point estimates and 95% confidence interval (95% CI) were indicated. The influence of confounders on the aOR calculation was evaluated via multivariate logistic regression [20]. The Benjamini-Hochberg procedure was employed to address multiple comparisons, leading to an adjusted significance threshold level of 0.0281 [21]. The results are presented via bar and forest plots, and the analysis was conducted in the RStudio environment, leveraging the tidymodels and ggplot2 packages. In all the comparisons, either the period or the month of birth with the lowest incidence of the disease was used as a reference.

Results

Characteristics of the pediatric patients in Moscow

The final analysis included data from medical records of 49,857 patients aged 0–18 years (median age 7 [4;10] years), among whom 43.8% were female and 56.2% were male. The frequency of birth by month varied from 7.6% to 8.9%. The prevalence of AD was 29.4%, AR – 23.2%, asthma – 4.8%, family history of allergic disease was established in 50.9% of the children (Table 1).

Table 1. Characteristics of the pediatric patients in Moscow.

Characteristics of children

n = 49 857		 n (%) or Me [Q1; Q3]
Age (years) 7 [4;10]
Sex
Male n = 28,047 (56.2%)
Female n = 21,810 (43.8%)
Month of birth
January n = 4,206 (8.4%)
February n = 3,779 (7.6%)
March n = 4,128 (8.3%)
April n = 3,823 (7.7%)
May n = 3,948 (7.9%)
June n = 4,209 (8.4%)
July n = 4,452 (8.9%)
August n = 4,416 (8.9%)
September n = 4,243 (8,5%)
October n = 4,325 (8.7%)
November n = 4,104 (8.2%)
December n = 4,224 (8.5%)
Allergic diseases
Аtopic dermatitis n = 14,650 (29.4%)
Allergic rhinitis n = 11,566 (23.2%)
Asthma n = 2,415 (4.8%%)
Family history of allergy
Present n = 25,401 (50.9%)
Abscent n = 24,456 (49.1%)
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Association between the birth month/season and the odds of developing an allergic disease

For initial crude estimation of the association between the birth season and the odds of developing an allergic disease we categorized children’s birth seasons into those with high vs low prevalence of allergic disease compared with the yearly mean values. This resulted in periods of birth for children with high and low risk of disease. A high prevalence of AD was observed among patients born from September through February, of AR – from November through March, of asthma – from August through March (Fig 1).

Fig 1. Prevalence of allergic disease depending on the month of birth in children: categorization of high vs low seasons compared to yearly mean values.

Fig 1

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The proportions of patients born during high- and low- risk periods were further compared, and the comparisons revealed statistically significant differences (Table 2). In each comparison, the period with the lowest prevalence of the disease was used as a reference.

Table 2. Odds ratios for the risk of allergic disease in children during the period of birth associated with high risk, sex, age, family allergy history, presence of allergic disease AD, AR, asthma.

Parameter Allergic disease is present,

n (%) or

Me [Q1; Q3]		 Allergic disease is absent,

n (%) or

Me [Q1; Q3]		 cOR (95% CI) aOR (95% CI)
Atopic dermatitis

(n = 14650) 		Period of birth associated with high risk (September through February) 30.3% (n = 7545) 28.4% (n = 7105) 1.095 (1.053-1.138)

p<<0.001**		 1.075 (1.033-1.119)

p<<0.001**
Male sex 59% (n = 8646) 55.1% (n = 19401) 1.173 (1.128-1.220)

p<<0.001**		 1.042 (1.000-1.085)

p = 0.049*
Family allergy history 61.6% (n = 9027) 46.5% (n = 16387) 1.844 (1.773−1.918)

p<<0.001**		 1.568 (1.505-1.633)

p<<0.001**
AR 37.1% (n = 5442) 17.4% (n = 6124) 2.807 (2.688-2.931)

p<<0.001**		 2.335 (2.229 −2.446)

p<<0.001**
Asthma 7.8% (n = 1138) 3.6% (n = 1277) 2.236 (2.061-2.430)

p<<0.001**		 1.384 (1.269 −1.510)

p<<0.001**
Age, years 7 [5; 11] 7 [3; 10] 1.054 (1.049-1.059)

p<<0.001**		 1.023 (1,018-1.028)

p<<0.001**
Allergic rhinitis (n = 11566) Period of birth associated with high risk (November through March) 25.2% (n = 5156) 21.8% (n = 6410) 1.211(1.161-1.263)

p<<0.001**		 1.225 (1.170-1.282)

p<<0.001**
Male sex 66.4% (n = 7684) 53.2% (n = 20363) 1.743 (1.669-1.820)

p<<0.001**		 1.636 (1.561-1.714)

p<<0.001**
Family allergy history 68.5% (n = 7922) 4.7% (n = 17492) 2.585 (2.474-2.701)

p<<0.001**		 2.186 (2.085-2.291)

p<<0.001**
AD 47.1% (n = 5442) 24% (n = 9208) 2.807 (2.688-2.931)

p<<0.001**		 2.410 (2.301-2.525)

p<<0.001**
Asthma 12.9% (n = 1478) 2.4% (n = 928) 5.940 (5.457-6.466)

p<<0.001**		 3.428 (3.130-3.753)

p<<0.001**
Age, years 9 [6; 12] 6 [3; 10] 1.168 (1.162-1.175)

p<<0.001**		 1.156 (1.149-1.163)

p<<0.001**
Asthma

(n = 2415) 		Period of birth associated with high risk (August through March) 5,1% (n = 1688) 4.4% (n = 727) 1.149 (1.051-1.256)

p<<0.001**		 1.100 (1.003-1.207)

p = 0.043*
Male sex 72.5% (n = 1751) 55.4% (n = 26296) 2.121 (1.936-2.323)

p<<0.001**		 1.740 (1.584-1.912)

p<<0.001**
Family allergy history 72,54% (n = 1752) 49.9% (n = 23662) 2.656 (2.424−2.909)

p<<0.001** 		1.829 (1.663–2.012) p<<0.001**
AD 47.1% (n = 1138) 28.5% (n = 13512) 2.238 (2.061-2.430)

p<<0.001**		 1.491 (1.367-1.627)

p<<0.001**
AR 61.6% (n = 1478) 21.2% (n = 10079) 5.940 (5.457-6.466)

p<<0.001**		 3.530 (3.255-3.863)

p<<0.001**
Age, years 10 [7; 12] 7 [4; 10] 1.198 (1.184-1.211)

p<<0.001**		 1.161 (1.147-1.176)

p<<0.001**
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Reference – period with the lowest prevalence of the disease. Abbreviations: cOR- crude odds ratio; aOR- adjusted odds ratio; 95% CI – 95% confidence interval. Adjusted for periods of birth associated with high/low risk of disease, sex, age, family allergy history, the presence of allergic disease of interest -AD, AR, asthma – in combinations. Statistically significant differences are highlighted in bold. *p < 0.05; **p < 0.0281 (with Benjamini Hochberg adjustment).

The analysis of OR revealed the strongest association between the month/season of birth and the odds of developing AR. Furthermore, the odds of developing asthma among patients born between August and March was 10% higher (aOR, 1.100; 95% CI, 1.003–1.207) compared to those born in April through July (reference). In the case of AD, the association between birth month/season and the development of AD was less significant. Specifically, children born between September and February demonstrated a 1.075-fold increase in the likelihood of developing AD (aOR, 95% CI, 1.033–1.119) compared to those born between March and August (reference). The robustness of the observed seasonal effect on the odds of developing AD and AR was maintained when accounting for multiple comparisons (Table 2, Fig 2).

Fig 2. Periods of birth of children with high and low risk of allergic disease.

Fig 2

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Odds ratio and 95% CI for outcomes (development of allergic disease) depending on the period of birth, sex, and family history of allergy. Reference – period with the lowest prevalence of the disease. Abbreviations: cOR- crude odds ratio; aOR- adjusted odds ratio; 95% CI – 95% confidence interval. Adjusted for periods of birth associated with high/low risk of disease, sex, age, family allergy history, the presence of allergic disease of interest -AD, AR, asthma – in combinations.

In the study population, male pediatric patients represented the majority of cases, with proportions ranging from 59% to 72.5% among the specific diseases. The analysis revealed that children with asthma presented the highest prevalence of a family allergy history, reaching 72.5%. This prevalence was followed by the group of patients with AR and AD, where it amounted to 68.5% and 61.6%, respectively. The OR evaluation demonstrated that male patients and children with a family allergy history presented a significantly greater odds of developing the allergic disease under consideration than female patients and children without a family allergy history, respectively. The strongest associations between disease development and demographic factors were observed for patients with asthma (male sex: aOR, 1.740; 95% CI, 1.584–1.912; family allergy history: aOR, 1.829; 95% CI, 1.663–2.012) and AR (male sex: aOR, 1.636; 95% CI, 1.561–1.714; family allergy history: aOR, 2.186; 95% CI, 2.085–2.291). The weakest associations between the disease development and demographic factors were observed for patients with AD (male sex: aOR, 1.042; 95% CI, 1.000–1.085; family allergy history: aOR, 1.568; 95% CI, 1.505–1.633). In general, we observed that the association between the odds of developing AR, asthma and AD and the demographic parameters (family allergy history, sex of the patient) were stronger than those observed for the birth month/season. Despite this observation, the association between the birth month/season and the odds of developing AD, AR and asthma remained statistically significant following the OR analysis with consideration of confounders (Table 2, Fig 2).

To perform a more comprehensive evaluation, we conducted a study to ascertain the association between the specific birth month of the children and the subsequent development of allergic disease (Table 3, Fig 3). In all comparisons, the month of birth with the lowest disease prevalence determined in the initial crude estimate was used as the reference (Fig 1).

Table 3. Odds ratio for the risk of developing allergic disease in children born in different months of the year.

Birth Month Allergic disease is present,

n (%)		 Allergic disease is absent,

n (%)		 cOR (95% CI) aOR (95% CI)
Atopic dermatitis January 8.6% (n = 1263) 8.4% (n = 2943) 1,142 (1,037-1,259)

p = 0.007**		 1,113 (1,007-1,231)

p = 0.035*
February 8% (n = 1171) 7.4% (n = 2608) 1,195 (1,082−1,320)

p<<0.001**		 1,155 (1,042-1,279)

p = 0.006**
March 8.3% (n = 1212) 8.3% (n = 2916) 1,106 (1,003-1,220)

p = 0.043*		 1,088 (0,984−1,203)

p = 0.101
April 7.1% (n = 1044) 7.9% (n = 2779) Reference Reference
May 7.4% (n = 1085) 8.1% (n = 2863) 1,009 (0,913−1,115)

p = 0.860		 1,027 (0,927−1,138)

p = 0.610
June 8.2% (n = 1195) 8.6% (n = 3014) 1,055 (0,957−1,164)

p = 0.280		 1,067 (0,965−1,180)

p = 0.207
July 8.7% (n = 1271) 9.0% (n = 3181) 1,064 (0,966−1,171)

p = 0.210		 1,094 (0,990−1,208)

p = 0.077
August 8.9% (n = 1298) 8.9% (n = 3118) 1,108 (1,006-1,220)

p = 0.036*		 1,117 (1,012-1,234)

p = 0.028**
September 8.6% (n = 1260) 8.5% (n = 2983) 1,124 (1,020-1,239)

p = 0.018**		 1,140 (1,031-1,259)

p = 0.01**
October 9% (n = 1318) 8.5% (n = 3007) 1,167 (1,060−1,285)

p = 0.002**		 1,169 (1,059−1,291)

p = 0.002**
November 8.5% (n = 1243) 8.1% (n = 2861) 1,156 (1,049−1,275)

p = 0.003**		 1,155 (1,045-1,277)

p = 0.005**
December 8.8% (n = 1290) 8.3% (n = 2934) 1,170 (1,062−1,289)

p = 0.001**		 1,152 (1,043-1,273)

p = 0.005**
Allergic rhinitis January 9.5% (n = 1097) 8.1% (n = 3109) 1,358 (1,229−1,501)

p<<0.001**		 1,386 (1,243−1,546)

p<<0.001**
February 8.6% (n = 993) 7.3% (n = 2786) 1,372 (1,238−1,520)

p<<0.001**		 1,371 (1,226−1,533)

p<<0.001**
March 8.8% (n = 1023) 8.1% (n = 3105) 1,268 (1,146−1,404)

p<<0.001**		 1,276 (1,143−1,424)

p<<0.001**
April 7.5% (n = 865) 7.7% (n = 2958) 1,126 (1,014-1,250)

p = 0.027**		 1,149 (1,025-1,288)

p = 0.017**
May 7.2% (n = 832) 8.1% (n = 3116) 1,028 (0,925−1,142)

p = 0.609		 1,043 (0,931−1,170)

p = 0.466
June 7.8% (n = 907) 8.6% (n = 3302) 1,057 (0,954 −1,173)

p = 0.289		 1,055 (0,943−1,180)

p = 0.347
July 7.9% (n = 918) 9.2% (n = 3534) Reference Reference
August 8.3% (n = 959) 9.0% (n = 3457) 1,068 (0,964−1,183)

p = 0.206		 1,039 (0,931−1,161)

p = 0.494
September 8% (n = 929) 8.7% (n = 3314) 1,079 (0,974−1,196)

p = 0.146		 1,070 (0,957−1,196)

p = 0.237
October 8.6% (n = 1000) 8.7% (n = 3325) 1,158 (1,046-1,281)

p = 0.005**		 1,147 (1,027-1,280)

p = 0.015**
November 8.4% (n = 969) 8.2% (n = 3135) 1,190 (1,074−1,318)

p = 0.001**		 1,183 (1,059−1,323)

p = 0.003**
December 9.3% (n = 1074) 8.2% (n = 3150) 1,313 (1,187−1,451)

p<<0.001**		 1,342 (1,203−1,497)

p<<0.001**
Asthma January 9.4% (n = 228) 8.4% (n = 3978) 1,307 (1,072−1,594)

p = 0.008**		 1,218 (0,992−1,496)

p = 0.06
February 7.6% (n = 184) 7.6% (n = 3595) 1,167 (0,948−1,438)

p = 0.145		 1,032 (0,832−1,281)

p = 0.775
March 8.6% (n = 207) 8.3% (n = 3921) 1,204 (0,983−1,474)

p = 0.072		 1,115 (0,904−1,375)

p = 0.310
April 7.6% (n = 183) 7.7% (n = 3640) 1,147 (0,931−1,413)

p = 0.189		 1,117 (0,899−1,386)

p = 0.318
May 6.9% (n = 166) 8.0% (n = 3782) 1,001 (0,809−1,239)

p = 0.992		 0,988 (0,792−1,232)

p = 0.916
June 7.9% (n = 191) 8.5% (n = 4018) 1,0849 (0,882−1,332)

p = 0.442		 1,052 (0,850−1,303)

p = 0.641
July 7.7% (n = 187) 9.0% (n = 4265) Reference Reference
August 9.3% (n = 224) 8.8% (n = 4192) 1,219 (0,999−1,487)

p = 0.051		 1,202 (0,978−1,477)

p = 0.08
September 8.7% (n = 211) 8.5% (n = 4032) 1,194 (0,976−1,460)

p = 0.085		 1,178 (0,956−1,452)

p = 0.125
October 8.9% (n = 214) 8.7% (n = 4111) 1,187 (0,971−1,451)

p = 0.094		 1,123 (0,912−1,384)

p = 0.274
November 8.4% (n = 204) 8.2% (n = 3900) 1,193 (0,974−1,462)

p = 0.089		 1,128 (0,914−1,392)

p = 0.263
December 8.9% (n = 216) 8.4% (n = 4008) 1,229 (1,006-1,502)

p = 0.044*		 1,134 (0,921−1,397)

p = 0.235
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Reference – month of birth with the lowest disease prevalence determined in the initial crude estimate. Abbreviations: cOR- crude odds ratio; aOR- adjusted odds ratio; 95% CI – 95% confidence interval. Adjusted for month, sex, age, family allergy history, the presence of allergic disease of interest -AD, AR, asthma – in combinations. Statistically significant differences are highlighted in bold. *p < 0.05; **p < 0.0281 (with Benjamini Hochberg adjustment).

Fig 3. Odds ratio and 95% CI for outcomes (development of allergic disease) by birth month.

Fig 3

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Reference – month of birth with the lowest disease prevalence determined in the initial crude estimate. Abbreviations: cOR- crude odds ratio; aOR- adjusted odds ratio; 95% CI – 95% confidence interval. Adjusted for month, sex, age, family allergy history, the presence of allergic disease of interest – AD, AR, asthma – in combinations.

Analysis of the OR revealed an association between the specific month of birth and the odds developing AR and AD. In all the comparisons, the month of birth with the least incidence of the disease was used as a reference. In particular, the individuals born between October and April presented a substantially greater odds of developing AR compared with those born in July (reference), with the strongest associations observed in December (aOR, 1.342; 95% CI, 1.203–1.497), January (aOR, 1.386; 95% CI, 1.243–1.546), and February (aOR, 1.371; 95% CI, 1.226–1.533). The odds of AR development in these months were 34–38% greater than that in July, and the significance of the association was confirmed via OR analysis when the adjustment for multiple comparisons was taken into account (Table 3, Fig 3).

The extent to which a specific month influenced the likelihood of developing AD was somewhat lower. For example, the odds of AD development among individuals born between August and February was significantly higher compared to those born in April (reference), with the strongest association observed in October (aOR, 1,169; 95% CI, 1,059−1,291), where it was 16% higher compared to April. The association observed for October remained significant following the adjustment for multiple comparisons (Table 3, Fig 3).

In the case of asthma, the association between the month of birth and the odds of asthma development was observed in January (cOR, 1.307; 95% CI, 1.072–1.594) and December (cOR, 1.229; 95% CI, 1.006–1.502) compared with July (reference). However, when the effects of all other variables were accounted for, all differences between months ceased to be statistically significant.

Discussion

This is the first study in Russia to demonstrate that children born in October in Moscow face an elevated odd of atopic dermatitis, while children born in December, January, and February are more susceptible to allergic rhinitis. Our data showed that the association detected was independent of sex, age, family allergic history and combination of allergic diseases.

The reported estimates of AD, AR and asthma prevalence in the pediatric population vary significantly, due to demographic characteristics of different samples, regional variations, different methodologies of data collection etc. In Europe and the USA, the prevalence of AD in children is up to 20% [22]. In about 80% of patients with AD, the onset of the disease occurs early in their lives [23]; importantly, 10–30% of children with AD also have asthma and AR [24,25]. According to the epidemiological International Study of Asthma and Allergies in Childhood, ISAAC, AR symptoms are experienced, on average, by 8.5% of children aged 6–7 years and 14.6% of schoolchildren aged 13–14 years, asthma symptoms – in 11.8% children aged 6–7 years and 13.8% schoolchildren aged 13–14 years. [26–28]. Our study revealed that, compared with global trends, children residing in Moscow, Russia, presented high prevalences of AD (29.4%) and AR (23.2%), with a somewhat lower asthma prevalence of 4.84%. The differences we obtained may be associated with different methodologies for collecting clinical and anamnestic data, and different climatic, geographical, and socio-economic characteristics of the regions.

The family allergy history has been demonstrated to significantly increase the risk of developing allergic disease, whereas the effect of sex is ambiguous and depends on the child’s age. For example, meta-analyses have shown that in infants and preschool children AD, asthma and AR are more prevalent among boys than among girls, whereas during puberty, these diseases become more prevalent among female patients [29–31]. In our study, the median age of the patients was 7 years, with male patients and children with a family allergy history being at greater odds of developing all three allergic diseases, which is consistent with the general trend. The association between demographic factors and disease development was the strongest for patients with asthma and the weakest for those with AD.

The associations between the birth season as a factor significantly influencing the child during the neonatal adaptation period, and the risk of developing allergic diseases, have been investigated in several studies [10−19]. To date, this is the first study of this nature in Russia. In this study of children residing in Moscow we revealed an association between the period and month of birth and the odds of developing AR and AD. For asthma, we did not find a similar significant association, which may be due to the later manifestation of asthma compared with AD and AR, and the consequent lower and/or more distant influence of the seasonal birth factor. The odds of AD development were significantly greater in children born between August and February, whereas the highest odds of AR development were observed for children born between October and April. The strongest association between the specific month of birth and the odds of AR development was established among children born in February, January and December. In the case of AD, the strongest association between the specific month of birth and the odds of AD development was established for children born in October. Notably, the season/month of birth was an independent criterion influencing the odds of diseases development, as the degree of association did not depend on demographic parameters, including sex, age, family allergic history, and overlapping allergic disease of interest. It can be hypothesized that these results can be explained by the Moscow climate characteristics. Moscow is a part of the central region of the Russian Federation, where the climate is intermediate between mild European and strongly continental Asian climates, with distinct seasonal patterns: long rainy autumns, moderately humid and cold winters, warm summers. The coldest months of the year are December, January and February, which have the highest associations with the odds of developing the allergic diseases in question. Among the factors determining the autumn-winter seasonality and having potential significance in the context of the odds of allergic disease, one can additionally highlight the low degree of solar activity typical for the Moscow region, high exposure to household allergens of house dust, high infectious load, etc. In addition, a seasonal increase in exposure to pet allergens in residential areas of Moscow may have a certain impact. This sensitization to cat and dog allergens appears to be extremely widespread among Russians [32]. The possible roles of decreased vitamin D levels in serum, increased cord blood IgE levels in winter, increased immune activity in general in winter months, including gene expression of several interleukins (IL-4, IL-5), etc., are actively discussed [19,33]. Cesarean section is an important known and common perinatal factor that most studies suggest may increase the odds of allergic diseases [34,35]. It could be assumed that the higher frequency of cesarean section in the fall and winter months could to some extent determine the association of the season of birth and the odds of AD and AR that we observed. However, in Russia, cesarean sections are performed only when strict indications exist and there are no data on the frequency of cesarean sections in different periods of the year. In an Iranian study, Nasiri R. et al. reported that seasonal (monthly) variations of the weather (humidity and temperature) have a significant impression on preeclampsia prevalence, which is one of the important indications for cesarean section [36]. Based on time of conception the lowest prevalence of preeclampsia was found in winter and early spring, which corresponds to the lowest frequency of cesarean section in the fall and winter period. Thus, the effect of cesarean section on the association of season of birth and risk of allergic disease is ambiguous but extremely interesting and requires further study.

Our data on AD are consistent with the results of the majority of similar studies carried out in different countries, even those with less pronounced seasonality and warm winters. Yokomichi H. et al. in a study involving 100,304 Japanese children aged up to 3 years and born between 2011 and 2014, reported that the highest incidence of AD occurs in children born between October and December, and the lowest occurs between April and June [10]. Considering the effects of UV (photoperiod length) and ambient humidity on the skin barrier, the authors specifically assessed these factors. The combination of a short photoperiod and low humidity was shown to be associated with the highest incidence of AD. The results of another study by Japanese colleagues, which evaluated the associations of the season of birth with AD at different ages of the child up to 1 year of age, suggest a high risk of AD at 6 months in children born in autumn. This risk was particularly notable in boys whose mothers had allergic diseases [11]. Kuo CL et al. reported that in Taiwan, children born between October and December have a high risk of AD, with the highest risk occurring in December [12]. A systematic review (9 articles with 726,378 children aged 0–12 years) in Northern Hemisphere countries far from the equator reported a high incidence of AD among children born in the autumn and winter months [13].

In turn, the associations of the season of birth with the odds of asthma and AR vary across studies, which may be different from AD, and this finding is not as clearly consistent with our results. Thus, according to Hänninen R et al. in Finland, birth in the autumn-spring period was significantly associated with AR, and birth in the autumn or winter was significantly associated with asthma [14]. A similar population-based study in this region revealed that those born between January and June were at increased odds of asthma [15].

In a study of schoolchildren in Taiwan, it was noted that children born in winter (August to October) had a greater prevalence of asthma compared to children born in the spring (February to April), and no similar associations were found for AR and AD [16]. In Japan, Saitoh Y et al. analyzed the associations of birth month with sensitization to aeroallergens and the occurrence of allergic diseases among 755 schoolchildren aged 12–13 years. Sensitization to house dust mites was less common in children born between January and March, and sensitization to Japanese cedar pollen was significantly more common in children born between December and January. A significantly greater prevalence of asthma was observed among children born between November and December, for AR – between August and October. This study did not find an association between AD and the season of birth [17]. According to Knudsen T. et al. in Denmark, asthma and sensitization to house dust mites were more common in persons born in autumn, whereas AR and sensitization to pollen were not associated with the season of birth [18]. Overall, our data and the data from various studies regarding the association of season of birth with the odds of developing AR and asthma demonstrate heterogeneity, but no study showed an increased odds of AR and asthma among those born in the summer months. This observation probably supports the positive effect of warm climatic conditions among those born in the summer months on reducing the odds of developing allergic diseases.

Therefore, the seasonality factor is not homogeneous and includes many uncontrolled and controlled aspects that require further investigation. Available data on the effect of the season of birth on the odds of allergy in different regions can vary considerably, demonstrating specific geographic patterns, even within the same country, in addition, the size of the patient sample, research methodology, and adjustments for various factors may be of significant importance for these differences. Understanding the mechanisms and degree of influence of the season of birth on the odds of allergic diseases can certainly be useful in designing and interpretating the results of preventive interventions, optimal personalized prevention during pregnancy planning, as well as before and after the birth of the child. Specifically, based on our data, a potential strategy for preventing allergic diseases in children in Moscow could be planning pregnancy with the birth of children in the spring-summer period between March and July to reduce the risk of AD and in the spring-autumn period between May and September to reduce the risk of AR, especially in cases of family allergy history. Regardless of the season of birth, important preventive measures include: breastfeeding, correcting and maintaining normal vitamin D levels in blood, moisturizing and maintaining the skin’s barrier function, reducing the infectious load, introducing complementary foods in a timely manner, creating a supportive social and psychological environment, etc. Furthermore, the influence of seasonality on the risk of developing allergy should be considered when planning further epidemiological studies, interpreting the data obtained, and developing prevention strategies based on them. Further epidemiologic studies are needed to accumulate evidence of the identified association of season and month of birth with allergic disease odds, and additional research is needed to find new potential factors that may determine and/or strengthen this association. Such factors include, for example, increasing exposure and sensitization to epidermal allergens (cats, dogs) in autumn and winter, viral infections in the first year of life, such as COVID-19, the presence of children older than 2 years of age in the family (i.e., preschool and school age), which contribute to the infant’s early exposure to respiratory viruses, the socioeconomic status of the family, which to some extent may offset already known factors (medication correction of vitamin D levels, travel to countries with warmer climates, monitoring of the child’s health, etc.), conception season, use of in vitro fertilization, premature birth, negative perinatal factors (prematurity, hypoxia, etc.). In addition, it is relevant to study not only the association of season and month of birth with the risk of allergic disease, but also the possible influence of season of birth on the severity and prognosis of the disease.

Limitations

The limitations of the present study include the fact that the following factors were not taken into account in the analysis: sensitization, age of disease manifestation and diagnosis, disease severity, additional seasonality factors such as ambient air humidity and degree of solar activity, vitamin D levels, specificity and degree of allergen exposure in different periods of the year, infectious load, month of conception and gestational age and others. These factors may have potential implications for the observed association between season of birth and allergic disease odds, for example, perhaps if vitamin D levels were taken into account in the data analysis, the highest odds of developing AD may have been observed in children born not in October, but in the cold winter months with minimal solar activity (December and February). The sample included only children whose parents had previously completed a survey regarding family allergy history. In addition, parental responses may be subjective and not always accurate (e.g. parental recall bias). The analysis did not take into account the socioeconomic status of the family, which may influence the objectivity of parents’ assessment of child health and other factors. The sample included only children living in Moscow and did not include children living in other regions of Russia.

Conclusions

This is the first study conducted in Russia to evaluate the association between the month of birth and the odds of developing allergic disease in children. In our work, we found that children born between August and February have greater odds of AD development among children living in Moscow, and that children born between October and April have greater odds of AR development. The strongest association between specific birth month and the odds of AD development was recorded among those born in October, the strongest association between specific birth months and the odds of AR was recorded among those born in the winter months (December, January and February). Our data showed that the association detected was independent of sex, age, family allergic history and combination of allergic diseases. Based on our data, an additional potential strategy for preventing allergic diseases among children living in Moscow could be planning pregnancy with the birth of children in the spring-summer period between March and July to reduce the risk of AD and in the spring-autumn period between May and September to reduce the risk of AR, especially in cases of family allergy history. Further studies are needed to gather evidence for the observed associations of season and month of birth with disease risk while considering additional factors and to better understand the mechanisms underlying this association. Furthermore, the possible association between season of birth and the risk of developing allergies should be taken into account when planning further epidemiological studies, interpreting the obtained data and developing preventive strategies based on them.

Data Availability

The data cannot be openly accessible due to legal restrictions. The Moscow Department of Health legally owns the data of this study. Access to the database can be requested through the official email address from the Local Ethics Committee at Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery: doc@pedklin.ru.

Funding Statement

The study was sponsored by Moscow Center for Innovative Technologies in Healthcare and was funded by grant from the Moscow government [research project No. 2412-41/22].

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Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: This manuscript presents a novel and region-specific epidemiological study on the association between birth month and allergic diseases (AD, AR, and asthma) in children. The dataset size and analytical methods are commendable. This is the first study of its kind in Russia and adds valuable data to the international literature on seasonal and perinatal risk factors for allergy.

Major Comments:

The conclusion implies causality (e.g., "seasonality is an independent factor"). This wording should be revised to reflect an association rather than causation due to the observational nature of the study.

While asthma was included, its adjusted odds ratios were not statistically significant. This point should be addressed more clearly in the Discussion section.

Limitations such as parental recall bias, self-selection in the data collection process, and potential unmeasured confounding (e.g., vitamin D levels, exposure to specific allergens) should be more explicitly discussed.

Figures and tables should include more descriptive legends for better standalone comprehension.

Minor Comments:

Minor language edits are suggested, such as:

“requiring merits further investigation” → “which merits further investigation”

"In the Russian" → "In Russia"

Reviewer #2: Thank you for the opportunity to review this study on month of birth and allergic outcomes based in Moscow, Russia.

It is nice to see some Russian data on this topic and excellent that the authors have put it in the context of other findings particularly in the northern hemisphere with similar seasonality.

Some comments:

1. METHODS: The main issue with this study is that it potentially is affected by selection bias. The study population has been selected as children who went to a pediatric visit. Does this mean that the study population is only children who have some kind of illness or do all children in Russia go to pediatricians? I think more context needs to be supplied. In Western countries usually only children with very particular issues go to pediatricians, and often only if their parents can afford it. Therefore, there could be two layers of selection bias which effect the generalisability of these findings - only children with illnesses, and only wealthy people. Please put more context and description around these points. The fact that there are 50 000 children who go to pediatricians in only a 9 month period seems really large, so I think explanations about practices in Russia would help. Is there a way to include the general population in this study? if not, then it needs to be specified in the abstract, main findings, discussion that these findings are within a population of children with health issues and the issues with generalisability must be discussed in the Limitations section.

2. METHODS: Is there a way the authors can adjust for socioeconomic status which is an important confounder and potential source of selection bias in this study? if not, please discuss in limitations and its effect.

3. METHODS: Is it possible to adjust for month of conception or adverse perinatal outcomes such as gestational age? these could both be affecting the outcomes

4. METHODS: Related to point 1, please provide more information about what the EMIAS is and how data is collected.

5. METHODS: Was it the pediatricians who assigned the ICD-10 code from the visit?

6. METHODS: I think it would help if you provided inclusion and exclusion criteria to the study population. I am unsure if they only people included were those with allergy or whether the ICD 10 codes were used to define the outcomes of interest.

7. RESULTS: I am surprised that the children started at age 4 years, since AD, AR and asthma often show up in younger children. Please again provide context as to why this is.

8. RESULTS: The term 'odds' should be used instead of 'risk' eg in the abstract and in the results. Risk implies relative risk which is different to an odds ratio. Similarly use 'association' rather than 'correlation'.

9. RESULTS: Please refer to the formatting instructions of the journal for decimal places and inclusion of p values. Usual practice is to have 2 rather than 3 DP and to not include p values.

10. DISCUSSION: The first paragraph of the discussion should be a summary of the findings, please add this.

11. DISCUSSION: there needs to be more discussion about why there is heterogeneity between findings in this area, it is not enough to just say there is heterogeneity, some thoughts on why this is, and what your study adds are needed

12. DISCUSSION: an important undiscussed factor to explain the associations is perinatal factors associated with season which are also highly related to allergic outcomes. For instance, I am wondering if preterm births, low birth weight and caesarean sections are more likely to happen in winter which could explain the findings?

12. DISCUSSION: related, there needs to be more discussion about why the month of BIRTH is driving long term outcomes. that it could be affecting outcomes 6 months later as in some other studies makes sense, but month of birth on disease 4-18 years later seems a big claim. How do we know it is not the exposure in the first few months after birth or the month of conception or the exposures during pregnancy? I am trying to suggest to consider in the discussion what month of birth represents in a broader context. As the authors say, there are so many factors that could be influencing (confounding or mediating) these findings. Could the authors suggest given the breadth of literature on this topic which areas the research should branch into rather than more of the same?

**********

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Reviewer #1: No

Reviewer #2: No

**********

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PLoS One. 2025 Nov 20;20(11):e0336062. doi: 10.1371/journal.pone.0336062.r003

Author response to Decision Letter 1

4 Jun 2025

Reviewer #1

1. The conclusion implies causality (e.g., "seasonality is an independent factor"). This wording should be revised to reflect an association rather than causation due to the observational nature of the study.

The authors' response:

Dear reviewer! We have changed the wording (e.g., "seasonality is an independent factor") to reflect an association rather than causation.

2. While asthma was included, its adjusted odds ratios were not statistically significant. This point should be addressed more clearly in the Discussion section.

The authors' response:

Dear reviewer! The absence of a statistically significant association between asthma and month of birth is noted in the Discussion section.

3. Limitations such as parental recall bias, self-selection in the data collection process, and potential unmeasured confounding (e.g., vitamin D levels, exposure to specific allergens) should be more

explicitly discussed.

The authors' response:

Dear reviewer! We have included additional points in the limitation section.

4. Figures and tables should include more descriptive legends for better standalone comprehension.

The authors' response:

Dear reviewer! We have corrected the title of table 2.

5. Minor language edits are suggested, such as:

“requiring merits further investigation” → “which merits further investigation”

"In the Russian" → "In Russia"

The authors' response:

Dear reviewer! We have corrected minor language edits.

Reviewer #2

1. METHODS: The main issue with this study is that it potentially is affected by selection bias. The study population has been selected as children who went to a pediatric visit. Does this mean that the study population is only children who have some kind of illness or do all children in Russia go to pediatricians? I think more context needs to be supplied. In Western countries usually only children with very particular issues go to pediatricians, and often only if their parents can afford it. Therefore, there could be two layers of selection bias which effect the generalisability of these findings - only children with illnesses, and only wealthy people. Please put more context and description around these points. The fact that there are 50 000 children who go to pediatricians in only a 9 month period seems really large, so I think explanations about practices in Russia would help. Is there a way to include the general population in this study? if not, then it needs to be specified in the abstract, main findings, discussion that these findings are within a population of children with health issues and the issues with generalisability must be discussed in the Limitations section.

The authors' response:

Dear reviewer! In Russia, the basic medical care for children and adults is provided through compulsory health insurance, i.e. free of charge. Children may visit a pediatrician due to illness (e.g., often in the case of an acute viral infection or in connection with some specific complaints or diseases), or patients may come without complaints or diseases, e.g., to obtain school or sectional certificates, to undergo a checkup or vaccination. Therefore, the study population included both children with diseases and healthy children. In our study there are no such two levels of selection bias: children with diseases and only wealthy people. We have added additional information to the Methods section.

2. METHODS: Is there a way the authors can adjust for socioeconomic status which is an important confounder and potential source of selection bias in this study? if not, please discuss in limitations and its effect.

The authors' response:

Dear reviewer! Visiting a pediatrician in Russia is free of charge, so socioeconomic status is not an important factor and potential source of selection bias in this study. The EMIAS system does not take into account the socioeconomic status of the family. We have included this aspect in the limitation section.

3. METHODS: Is it possible to adjust for month of conception or adverse perinatal outcomes such as gestational age? these could both be affecting the outcomes.

The authors' response:

Dear reviewer! Unfortunately, we cannot make an adjustment for the month of conception and gestational age, since this information is not in the EMIAS system. We have included this aspect in the limitation section.

4. METHODS: Related to point 1, please provide more information about what the EMIAS is and how data is collected.

The authors' response:

Dear reviewer! We have added information about EMIAS to the Methods section.

5. METHODS: Was it the pediatricians who assigned the ICD-10 code from the visit?

The authors' response:

Dear reviewer! If a child visits a pediatrician with a disease, the pediatrician makes a diagnosis with diagnosis code according to ICD-10.

6. METHODS: I think it would help if you provided inclusion and exclusion criteria to the study population. I am unsure if they only people included were those with allergy or whether the ICD 10 codes were used to define the outcomes of interest.

The authors' response:

Dear reviewer! The main inclusion criteria for the formation of the database from EMIAS were: age under 18 years and a parentally completed questionnaire to identify family allergy history. We have specified these criteria in the methods section.

7. RESULTS: I am surprised that the children started at age 4 years, since AD, AR and asthma often show up in younger children. Please again provide context as to why this is.

The authors' response:

Dear reviewer! The median age of the children whose parents completed the questionnaire is given in the article. This age is not related to the onset of allergic disease, i.e. the data download only recorded the fact that the child had the disease in the medical record, which could have been at any year of life.

8. RESULTS: The term 'odds' should be used instead of 'risk' eg in the abstract and in the results. Risk implies relative risk which is different to an odds ratio. Similarly use 'association' rather than 'correlation'.

The authors' response:

Dear reviewer! We have changed the term 'risk' to 'odds', and the term 'correlation' to 'association'.

9. RESULTS: Please refer to the formatting instructions of the journal for decimal places and inclusion of p values. Usual practice is to have 2 rather than 3 DP and to not include p values.

The authors' response:

Dear reviewer! We checked the Submission Guidelines (https://journals.plos.org/plosone/s/submission-guidelines ) and found the following phrase in the Statistical Reporting section:

“P-values. Report exact p-values for all values greater than or equal to 0.001. P-values less than 0.001 may be expressed as p < 0.001, or as exponentials in studies of genetic associations.”

The practice of reporting p-values with three decimal places while presenting results in medicine has been highlighted in many statistical guidebooks and articles (https://pmc.ncbi.nlm.nih.gov/articles/PMC7642026/ , https://pmc.ncbi.nlm.nih.gov/articles/PMC8024217/ , https://pmc.ncbi.nlm.nih.gov/articles/PMC8005799/)

Additionally, the third decimal place can be very important, especially in case of adjustment for multiplicity, as can be seen from our tables (for example, p-values of 0.028 or 0.027 from Table 3, that are very close to the adjusted threshold). We would like to present our results to readers in the most transparent way.

10. DISCUSSION: The first paragraph of the discussion should be a summary of the findings, please add this.

The authors' response:

Dear reviewer! We have added the first paragraph to the discussion section.

11. DISCUSSION: there needs to be more discussion about why there is heterogeneity between findings in this area, it is not enough to just say there is heterogeneity, some thoughts on why this is, and what your study adds are needed

The authors' response:

Dear reviewer! Overall, our data and the data from various studies regarding the association of season of birth with the odds of developing AR and asthma demonstrate heterogeneity, but no study showed an increased odds of AR and asthma among those born in the summer months. This observation probably supports the positive effect of warm climatic conditions among those born in the summer months on reducing the odds of developing allergic diseases.

Available data on the effect of the season of birth on the odds of allergy in different regions can vary considerably, demonstrating specific geographic patterns, even within the same country, in addition, the size of the patient sample, research methodology, and adjustments for various factors may be of significant importance for these differences.

We have added this information to the discussion section.

12. DISCUSSION: an important undiscussed factor to explain the associations is perinatal factors associated with season which are also highly related to allergic outcomes. For instance, I am wondering if preterm births, low birth weight and caesarean sections are more likely to happen in winter which could explain the findings?

The authors' response:

Dear reviewer! Cesarean section is an important known and common perinatal factor that most studies suggest may increase the odds of allergic diseases. It could be assumed that the higher frequency of cesarean section in the fall and winter months could to some extent determine the association of the season of birth and the odds of AD and AR that we observed. However, in Russia, cesarean sections are performed only when strict indications exist and there are no data on the frequency of cesarean sections in different periods of the year. In an Iranian study, Nasiri R. et al. reported that seasonal (monthly) variations of the weather (humidity and temperature) have a significant impression on preeclampsia prevalence, which is one of the important indications for cesarean section. Based on time of conception the lowest prevalence of preeclampsia was found in winter and early spring, which corresponds to the lowest frequency of cesarean section in the fall and winter period. Thus, the effect of cesarean section on the association of season of birth and risk of allergic disease is ambiguous but extremely interesting and requires further study.

We have added this information to the discussion section.

13. DISCUSSION: related, there needs to be more discussion about why the month of BIRTH is driving long term outcomes. that it could be affecting outcomes 6 months later as in some other studies makes sense, but month of birth on disease 4-18 years later seems a big claim. How do we know it is not the exposure in the first few months after birth or the month of conception or the exposures during pregnancy? I am trying to suggest to consider in the discussion what month of birth represents in a broader context. As the authors say, there are so many factors that could be influencing (confounding or mediating) these findings. Could the authors suggest given the breadth of literature on this topic which areas the research should branch into rather than more of the same?

The authors' response:

Dear reviewer! Further epidemiologic studies are needed to accumulate evidence of the identified association of season and month of birth with allergic disease odds, and additional research is needed to find new potential factors that may determine and/or strengthen this association. Such factors include, for example, increasing exposure and sensitization to epidermal allergens (cats, dogs) in autumn and winter, viral infections in the first year of life, such as COVID-19, the presence of children older than 2 years of age in the family (i.e., preschool and school age), which contribute to the infant's early exposure to respiratory viruses, the socioeconomic status of the family, which to some extent may offset already known factors (medication correction of vitamin D levels, travel to countries with warmer climates, monitoring of the child's health, etc.), conception season, use of in vitro fertilization, premature birth, negative perinatal factors (prematurity, hypoxia, etc.). In addition, it is relevant to study not only the association of season and month of birth with the risk of allergic disease, but also the possible influence of season of birth on the severity and prognosis of the disease.

We have added this information to the discussion section.

Attachment

Submitted filename: Response to Reviewers.docx

pone.0336062.s001.docx (27.8KB, docx)

Decision Letter 1

Vasuki Rajaguru

1 Sep 2025

Dear Dr. Esakova,

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Academic Editor

PLOS ONE

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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: (No Response)

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: (No Response)

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: (No Response)

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: (No Response)

Reviewer #3: Yes

**********

Reviewer #1: (No Response)

Reviewer #3: Dear authors,

This study makes an important contribution to understanding seasonal birth effects on allergic diseases in Russian children. The large sample size, appropriate statistical methods, and novel geographic context are significant strengths. The findings generally align with global patterns showing increased allergy risk in autumn/winter births, likely mediated by vitamin D deficiency and other seasonal factors. Many methodological and statistical issues have been addressed in previous reviews. I have attached a file with some recommendations for improvement:

1. Abstract: Minor spelling corrections

I. "Crude odd ratio" should be "crude odds ratio" (line 31)

II. Consider stating the study period (2024) in methods

III. The phrase "elevated odd" (line 41) should be "elevated odds"

2. Introduction:

I. Lines 58-65: The sentence beginning with "Notably, the season factor itself is heterogeneous..." is overly complex and should be broken into shorter, clearer statements for better readability.

II. The connection between seasonal factors and specific mechanisms (vitamin D pathways, allergen exposure) could be included with more current evidence.

3. Methods: The manuscript does not address how missing data were managed. Authors should either: Describe the specific approach used for handling missing values (e.g., complete case analysis, multiple imputation) OR explicitly state if there were no missing values in the dataset

4. Results: The relatively low asthma prevalence (4.8%) compared to global ISAAC estimates (11.8-13.8%) requires more discussion.

5. Discussion: Recommended additional discussion of potential prevention strategies based on findings

6. Limitations: Missing discussion about generalizability beyond Moscow

7. Conclusion: Recommended to include clinical implications discussion for prevention strategies

Thank you

**********

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Reviewer #1: No

Reviewer #3: Yes:  Durga Datta Chapagain

**********

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Attachment

Submitted filename: renamed_4ea54.docx

pone.0336062.s002.docx (16.6KB, docx)
PLoS One. 2025 Nov 20;20(11):e0336062. doi: 10.1371/journal.pone.0336062.r005

Author response to Decision Letter 2

16 Oct 2025

Response to Reviewer:

1. Abstract: Minor spelling corrections

I. "Crude odd ratio" should be "crude odds ratio" (line 31)

The authors' response:

Dear reviewer! We have corrected minor spelling edits. (line 31)

II. Consider stating the study period (2024) in methods

The authors' response:

Dear reviewer! The study period (2024) is included in methods. (line 27, line 79)

III. The phrase "elevated odd" (line 41) should be "elevated odds"

The authors' response:

Dear reviewer! We have corrected minor spelling edits. (line 41)

2. Introduction:

I. Lines 58-65: The sentence beginning with "Notably, the season factor itself is heterogeneous..." is overly complex and should be broken into shorter, clearer statements for better readability.

The authors' response:

Dear reviewer! The sentence was broken into shorter. (lines 59-62)

II. The connection between seasonal factors and specific mechanisms (vitamin D pathways, allergen exposure) could be included with more current evidence.

The authors' response:

Dear reviewer! We have added additional information to the Introduction section. (lines 62-67)

3. Methods: The manuscript does not address how missing data were managed. Authors should either: Describe the specific approach used for handling missing values (e.g., complete case analysis, multiple imputation) OR explicitly state if there were no missing values in the dataset

The authors' response:

Dear reviewer! We excluded all cases in which at least one of the study variables was missing, so there were no missing values in the dataset. We have added additional information to the Methods section. (lines 99-100)

4. Results: The relatively low asthma prevalence (4.8%) compared to global ISAAC estimates (11.8-13.8%) requires more discussion.

The authors' response:

Dear reviewer! Our study revealed that, compared with global trends, children residing in Moscow, Russia, presented high prevalences of AD (29.4%) and AR (23.2%), with a somewhat lower asthma prevalence of 4.84%. The differences we obtained may be associated with different methodologies for collecting clinical and anamnestic data, and different climatic, geographical, and socio-economic characteristics of the regions. We have added additional information to the Discussion section. (lines 241-243)

5. Discussion: Recommended additional discussion of potential prevention strategies based on findings

The authors' response:

Dear reviewer! Specifically, based on our data, a potential strategy for preventing allergic diseases in children in Moscow could be planning pregnancy with the birth of children in the spring-summer period between March and July to reduce the risk of AD and in the spring-autumn period between May and September to reduce the risk of AR, especially in cases of family allergy history. Regardless of the season of birth, important preventive measures include: breastfeeding, correcting and maintaining normal vitamin D levels in blood, moisturizing and maintaining the skin's barrier function, reducing the infectious load, introducing complementary foods in a timely manner, creating a supportive social and psychological environment, etc. Furthermore, the influence of seasonality on the risk of developing allergy should be considered when planning further epidemiological studies, interpreting the data obtained, and developing prevention strategies based on them. We have added additional information to the Discussion section. (lines 340-350)

6. Limitations: Missing discussion about generalizability beyond Moscow

The authors' response:

Dear reviewer! The sample included only children living in Moscow and did not include children living in other regions of Russia. We have added information about this limitation. (lines 376-378)

7. Conclusion: Recommended to include clinical implications discussion for prevention strategies

The authors' response:

Dear reviewer! Based on our data, an additional potential strategy for preventing allergic diseases among children living in Moscow could be planning pregnancy with the birth of children in the spring-summer period between March and July to reduce the risk of AD and in the spring-autumn period between May and September to reduce the risk of AR, especially in cases of family allergy history. Further studies are needed to gather evidence for the observed associations of season and month of birth with disease risk while considering additional factors and to better understand the mechanisms underlying this association. Furthermore, the possible association between season of birth and the risk of developing allergies should be taken into account when planning further epidemiological studies, interpreting the obtained data and developing preventive strategies based on them. We have added additional information to the Conclusion section. (lines 388-397)

Attachment

Submitted filename: Response_to_Reviewers_auresp_2.docx

pone.0336062.s003.docx (24.8KB, docx)

Decision Letter 2

Vasuki Rajaguru

20 Oct 2025

Birth month as a risk factor of allergic diseases: analysis of database of about 50 thousand children

PONE-D-25-05996R2

Dear Dr. Natalia Esakova,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Vasuki Rajaguru, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All the required revisions are amended.

Acceptance letter

Vasuki Rajaguru

PONE-D-25-05996R2

PLOS ONE

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Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Response to Reviewers.docx

    pone.0336062.s001.docx (27.8KB, docx)
    Attachment

    Submitted filename: renamed_4ea54.docx

    pone.0336062.s002.docx (16.6KB, docx)
    Attachment

    Submitted filename: Response_to_Reviewers_auresp_2.docx

    pone.0336062.s003.docx (24.8KB, docx)

    Data Availability Statement

    The data cannot be openly accessible due to legal restrictions. The Moscow Department of Health legally owns the data of this study. Access to the database can be requested through the official email address from the Local Ethics Committee at Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery: doc@pedklin.ru.

    Articles from PLOS One are provided here courtesy of PLOS

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