Abstract
Background
Maternal body mass index (BMI) before pregnancy and gestational weight gain (GWG) have been implicated in offspring health, yet their specific impact on the development of allergic diseases remains unclear. We aimed to evaluate associations between pre‐pregnancy BMI and GWG with asthma, rhinitis, eczema, food allergy, anaphylaxis, and allergic sensitization during childhood and adolescence.
Methods
We analyzed 7280 mother–child pairs from Generation XXI, a Portuguese population‐based birth cohort. Maternal BMI was categorized per World Health Organization criteria and grouped into underweight/normal weight vs. overweight/obesity. GWG was considered using Institute of Medicine (IOM) guidelines and GWG z‐scores. Allergic outcomes were assessed via parent‐reported physician diagnosis at 4, 7, 10, and 13 years, and allergic sensitization was determined at 10 years using ImmunoCAP. Associations were analyzed using logistic regression models adjusted for confounders.
Results
Children of mothers with excessive GWG had increased odds of asthma at ages 7 and 13 (aOR = 1.30; 95% CI 1.01–1.66 and aOR = 1.29; 95% CI 1.01–1.65, respectively), and rhinitis at 4 (OR = 1.48; 95% CI 1.10–1.98). Higher GWG z‐score group was associated with increased odds of asthma (aOR = 1.33; 95% CI 1.03–1.72), rhinitis (aOR = 1.54; 95% CI 1.13–2.09), and sensitization (aOR = 1.44; 95% CI 1.05–1.97). Lower GWG z‐score group was associated to higher eczema odds at 13, while higher reduced eczema odds at age 4. Maternal overweight/obesity was associated with lower odds of eczema at age 13 (aOR = 0.73; 95% CI 0.60–0.88). Apart from eczema, maternal BMI showed no significant associations with others allergic diseases.
Conclusion
Higher GWG is associated with increased odds of childhood asthma, rhinitis, and sensitization. In contrast, maternal overweight/obesity is linked to lower odds of eczema, suggesting condition‐specific effects of maternal weight on childhood allergy risk.
Keywords: allergic diseases, body mass index, early life exposures, gestational weight gain, perinatal health
Key message.
Excessive gestational weight gain is a modifiable risk factor associated with an increased risk of asthma, rhinitis, and allergic sensitization in children, underscoring the importance of maintaining a healthy maternal weight during pregnancy.
1. INTRODUCTION
Allergic diseases are among the most common chronic conditions in childhood and have become a global public health concern. These immune‐mediated disorders result from complex interactions between genetic predisposition and environmental exposures. The increasing prevalence of allergic diseases worldwide, documented in both the International Study of Asthma and Allergies in Childhood (ISAAC) and Global Asthma Network studies, highlights the need to understand early‐life determinants that could guide preventive strategies. 1 , 2
The prenatal period represents a critical window for immune system programming and growth development, including the lungs. During this time, environmental exposures, as maternal nutritional status, may influence the fetal epigenome and shape immune system and airways development, potentially altering asthma and other allergies risk in later life. Maternal body mass index (BMI) before pregnancy and gestational weight gain (GWG) have been identified as modifiable exposures that may influence offspring health outcomes. 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 Emerging evidence links higher maternal BMI with increased risk of asthma and wheezing in children, 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 20 , 21 , 22 while the role of GWG remains less consistent and less studied, especially in relation to allergic diseases beyond asthma. 11 , 14 , 20 , 22
Importantly, previous studies have shown methodological heterogeneity in defining GWG, often failing to account for pre‐pregnancy BMI or gestational age. The Institute of Medicine (IOM) guidelines offer a BMI‐specific framework for GWG recommendations, yet adherence to these guidelines remains suboptimal globally. 23 Additionally, no studies on this theme have utilized GWG reference charts considering maternal BMI and gestational age, which could provide a more individualized assessment of weight gain adequacy.
Considering this we aimed to investigate the associations between maternal pre‐pregnancy BMI and GWG—classified using both IOM criteria and GWG z‐scores—with the development of asthma, rhinitis, eczema, food allergy, anaphylaxis, and allergic sensitization in offspring from early childhood through adolescence.
2. METHODS
2.1. Study participants
This study is part of Generation XXI (G21), which is a prospective population‐based birth cohort. 24 , 25 Between April 2005–August 2006, mothers and newborns from all public obstetrical and neonatal care units in the metropolitan area of Porto, Portugal, were invited to participate. At the time of enrollment, these units accounted for 92% of all deliveries in the region.
A total of 8495 mothers (92%) and 8647 newborns accepted to participate. These participants were re‐evaluated at the age of 4 (n = 7459, 86%), 7 (n = 6889, 80%), 10 (n = 6397, 74%), and 13 years of age (n = 4640, 54%).
In this study, we excluded 296 twins, 299 mother–child pairs without information on weight or height before pregnancy and 916 without information on allergic diseases, leaving up 7280 participants for our analysis regarding the association between BMI pre‐pregnancy and allergic diseases. Further, 373 participants were excluded due to not having information on GWG, 4 due to a weight gain below −20 kg and 3 due to a GWG z‐score below −14, leaving 6901 mother–child pairs for our analysis regarding the association between GWG and allergic diseases. For all the models, the sample size varied according to the sample size of the different variables at different ages. More information on the Flowchart is presented in Figure S1. Regarding differences between included and excluded participants, included participants were more likely to have older and more educated mothers, and a lower prevalence of maternal smoking during pregnancy. Additionally, some allergic outcomes were more frequently reported among included participants. However, key variables were included in the adjusted models and according to Cohen's h and d and Cramér's V, effect size values were not substantial, <0.30. 26 , 27 A detailed comparison of included and excluded participants is presented in Table S1.
2.2. Ethical considerations
All phases complied with Ethical Principles for Medical Research Involving Human Subjects in the Declaration of Helsinki*. All evaluations were approved by the University of Porto Medical School/São João Hospital Centre Ethics Committee, except the 13‐year follow‐up that was approved by the ISPUP Ethics Committee. Procedures were explained to participants, and an informed consent was signed by one of the parents/legal guardians (at 13 years also signed by participants). The baseline evaluation was additionally approved by the Data Protection National Commission and the study follows the present EU General Data Protection Regulation under close supervision of the Data Protection Office of ISPUP. *World Medical Association Declaration of Helsinki, 2013. Available at: https://www.wma.net/what‐we‐do/medical‐ethics/declaration‐of‐helsinki/.
2.3. Maternal anthropometrics
Baseline information was gathered either through direct interviews or from medical records. Within 72 h after childbirth, trained interviewers conducted face‐to‐face interviews and evaluations using structured questionnaires and standardized procedures.
Pre‐pregnancy weight was used as the baseline measure to estimate pre‐pregnancy BMI and GWG. Pre‐pregnancy weight was based on a self‐report and defined as the usual body weight before pregnancy, weight at the beginning of pregnancy, or in the first pre‐natal medical visit if it occurred before the 13th gestational week. The mother reported the weight at the end of pregnancy at enrollment. Weight was retrieved from clinical records for mothers who did not provide this information. The interviewer measured height at recruitment to the nearest 0.1 cm without shoes. If measurement was not possible, height was taken from the national ID card.
Maternal pre‐pregnancy BMI was calculated and categorized according to World Health Organization (WHO) definition: underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obesity (≥30.00 kg/m2). 28 For the association between maternal BMI and allergic diseases, BMI was classified into two categories: underweight/normal weight and overweight/obesity. Further sensitivity analyses with the four pre‐pregnancy maternal BMI categories, excluding the underweight category, are presented in Data S1.
GWG was defined as the difference between the weight before delivery and pre‐pregnancy weight. Women were categorized as gaining below (insufficient GWG), as recommended (adequate GWG), or above (excessive GWG) the IOM recommendations according to maternal pre‐pregnancy BMI. 29 We also calculated GWG z‐scores based on pre‐pregnancy BMI group‐specific reference charts for gestational weight gain which also considers gestational age, derived using data from 218,216 pregnant women across 33 cohorts in Europe, North America, and Oceania. 30 GWG z‐scores were also further categorized according to tertiles (1st: ≤ −0.48; 2nd: > −0.48 and ≤0.43; 3rd: >0.43).
2.4. Allergic outcomes
Data on allergic outcomes were collected through questionnaires based on the ISAAC standardized questionnaire. Asthma (4, 7, 10, 13 years), rhinitis (4, 7, 13 years), food allergy (13 years), anaphylaxis (13 years), and eczema (4, 7, 13 years) were defined as a positive answer to “Has your child/the adolescent ever been diagnosed with asthma/rhinitis/eczema/food allergy/anaphylaxis by a physician?”
For allergic sensitization, among the 6397 children evaluated at 10‐year follow‐up, blood samples were collected from 4047 participants. From this group, a subset of 1125 children was selected using a computer‐generated randomization sequence to assess specific IgE levels through the ImmunoCAP Phadiatop Infant test (Thermo Fisher Scientific, Uppsala, Sweden). A child was considered to have allergic sensitization if the specific IgE level was 0.35 kU/L or higher for at least one of the tested aeroallergens or food allergens. 31
2.5. Covariates
Covariates were selected according to previous literature if they were related to pre‐pregnancy BMI or GWG and allergic diseases. 32 , 33 Using a direct acyclic graph, DAG, we confirmed that all covariates reach the graphical criteria for confounding, ensuring appropriate control and clarifying the assumed relationships among variables. This included: maternal age at birth (in years); sex of the children; maternal education at baseline assessed through the number of completed schooling years and categorized into ≤9, 10–12, or >12 years 34 ; parity (primiparous/multiparous); maternal smoking status during pregnancy (ever vs. no smoking); and mother history of allergic diseases which was considered if a positive answer to the question “Before becoming pregnant, has a doctor ever diagnosed you with an illness – asthma/allergy/rhinitis – that compels you or has forced you to continue treatment?” was provided. DAG Figures are presented in Figures S2 and S3.
2.6. Statistical analysis
Continuous variables are presented as mean values and standard deviation (±SD) as they were normally distributed. Categorical variables are described as counts and proportions. To determine differences between groups, the t‐student test for independent variables and the One Way ANOVA tests were used for continuous normally distributed variables, according to the number of groups in the categorical variable. The chi‐square test was used for categorical variables.
Logistic regression models in crude and adjusted models were used to study the association between pre‐pregnancy BMI and GWG with allergic diseases, and the magnitude of the association was measured by Odds Ratio (OR) and its respective 95% confidence intervals (CI). For our adjusted models we used the following covariates: sex of the children, maternal age, maternal education, parity, maternal history of allergic diseases and maternal smoking during pregnancy. We further adjusted for maternal pre‐pregnancy BMI when studying the association between GWG and GWG z‐scores with allergic diseases. Child BMI was considered a potential mediator in the pathway between maternal weight status and allergic outcomes. Therefore, it was not included in the regression models to estimate the total effect of maternal nutritional status. Based on prior literature suggesting that the effects of GWG on child health outcomes may differ according to maternal BMI 35 we also explored the association between GWG with allergic diseases considering two categories of maternal pre‐pregnancy BMI (underweight/normal weight and overweight/obesity), interaction analysis are presented in Supplementarial material, Table 2. We observed a consistent interaction between GWG and sex regarding asthma, accordingly, we performed stratified analysis for this outcome, present on Table S3. Additionally, we fitted Generalized Estimating Equations models for asthma, rhinitis, and eczema to estimate the average effect of maternal factors across ages, while accounting for the correlation between repeated measures within participants. Results are presented in the Tables S4–S8. Multiple regression imputation was performed for covariates with missing data. The maximum proportion of missing values was 4.2% and ten imputed datasets were created. All analyses were performed in the IBM SPSS Statistics version 27 and R software version 4.2.1.
3. RESULTS
The final analysis comprised 7280 mother–child pairs with data on maternal pre‐pregnancy BMI (Table 1) and 6901 with information on GWG (Table 2). Of these, 31% of mothers had overweight or obesity prior to pregnancy, and 62.3% failed to meet the IOM recommendations for GWG.
TABLE 1.
Maternal and child characteristics according to pre‐pregnancy BMI categories in the generation XXI cohort.
| Total (n = 7280) | Underweight/normal weight (n = 5020, 69%) | Overweight/obese (n = 2260, 31.0%) | p‐value | |
|---|---|---|---|---|
| Sex, n (%) | 0.295 | |||
| Female | 3567 (49.0) | 2439 (48.6) | 1128 (49.9) | |
| Male | 3713 (51.0) | 2581 (51.4) | 1132 (50.1) | |
| Mother age, years, mean ± SD | 29.20 ± 5.51 | 28.79 ± 5.54 | 30.10 ± 5.33 | <0.001 |
| Maternal education, n (%) | <0.001 | |||
| ≤9 years | 3416 (47.2) | 2118 (42.4) | 1298 (57.6) | |
| ≥10 e ≤12 | 1983 (27.4) | 1402 (28.1) | 581 (25.8) | |
| >12 | 1845 (25.5) | 1472 (29.5) | 372 (16.6) | |
| Parity, multiparous, n (%) | 3062 (42.7) | 1906 (38.5) | 1156 (52.0) | <0.001 |
| Maternal history of allergic disease, n (%) | 1217 (17.4) | 825 (17.0) | 392 (18.3) | 0.161 |
| Maternal smoking in pregnancy, n (%) | 1582 (22.1) | 1170 (23.7) | 412 (18.5) | <0.001 |
| GWG categories, n (%) a | <0.001 | |||
| Insufficient | 1732 (25.1) | 1413 (29.5) | 319 (15.1) | |
| Adequate | 2604 (37.7) | 1992 (41.5) | 612 (29.1) | |
| Excessive | 2565 (37.2) | 1390 (29.0) | 1175 (55.8) | |
| GWG z‐score, mean ± SD | −0.02 ± 1.18 | 0.03 ± 1.17 | −0.13 ± 1.17 | <0.001 |
| Asthma, n (%) | ||||
| 4 years | 286 (4.3) | 192 (4.2) | 94 (4.6) | 0.508 |
| 7 years | 402 (6.3) | 278 (6.3) | 124 (6.2) | 0.859 |
| 10 years | 492 (8.2) | 329 (7.9) | 163 (8.9) | 0.196 |
| 13 years | 415 (9.6) | 280 (9.3) | 135 (10.2) | 0.395 |
| Rhinitis, n (%) | ||||
| 4 years | 286 (4.4) | 205 (4.5) | 81 (4.0) | 0.296 |
| 7 years | 504 (7.9) | 361 (8.2) | 143 (7.1) | 0.145 |
| 13 years | 420 (9.7) | 304 (10.1) | 116 (8.7) | 0.142 |
| Eczema, n (%) | ||||
| 4 years | 675 (12.7) | 499 (13.7) | 176 (10.4) | <0.001 |
| 7 years | 835 (13.5) | 612 (14.4) | 223 (11.5) | 0.002 |
| 13 years | 673 (15.6) | 514 (17.2) | 159 (12.0) | <0.001 |
| Food Allergy, n (%) | ||||
| 13 years | 150 (4.4) | 108 (4.6) | 42 (4.0) | 0.372 |
| Anaphylaxis, n (%) | ||||
| 13 years | 124 (2.9) | 89 (3.0) | 35 (2.6) | 0.530 |
| Sensitization (from 1078 children), n (%) | ||||
| 10 years | 432 (40.1) | 304 (42.5) | 128 (35.4) | 0.025 |
Note: Statistically significant results are indicated in bold (p < .05).
Abbreviations: GWG, gestational weight gain; SD, standard deviation.
According to the Institute of Medicine recommendations. Chi‐square (χ 2) tests were used to compare differences between categorical variables; independent samples t‐tests were used to compare continuous variables between groups. Statistically significant results are indicated in bold (p < .05).
TABLE 2.
Maternal and child characteristics according to gestational weight gain categories based on IOM guidelines in the generation XXI cohort.
| Total of participants (n = 6901) | Insufficient GWG (1732, 25.1%) | Adequate GWG (2604, 37.7%) | Excessive GWG (2565, 37.2%) | p‐value | |
|---|---|---|---|---|---|
| Sex, n (%) | 0.200 | ||||
| Female | 3377 (48.9) | 872 (50.3) | 1283 (49.3) | 1222 (47.6) | |
| Male | 3524 (51.1) | 860 (49.7) | 1321 (50.7) | 1343 (52.4) | |
| Mother age, years, mean ± SD | 29.20 ± 5.47 | 29.56 ± 5.76 | 29.33 ± 5.41 | 28.84 ± 5.31 | <0.001 |
| Maternal education, n (%) | <0.001 | ||||
| ≤9 years | 3202 (46.5) | 859 (49.7) | 1141 (44.0) | 1202 (47.0) | |
| ≥10 e ≤12 | 1890 (27.5) | 405 (23.4) | 726 (28.0) | 759 (29.6) | |
| >12 | 1791 (26.0) | 466 (26.9) | 726 (28.0) | 599 (23.4) | |
| Parity, multiparous, n (%) | 3062 (42.7) | 805 (47.0) | 1110 (43.2) | 977 (38.7) | <0.001 |
| Maternal history of allergic disease, n (%) | 1195 (17.4) | 306 (17.7) | 437 (16.9) | 452 (17.8) | 0.656 |
| Maternal smoking in pregnancy, n (%) | 1507 (22.1) | 335 (19.6) | 514 (19.9) | 658 (26.2) | <0.001 |
| Mother BMI, n (%) a | <0.001 | ||||
| Underweight | 264 (3.8) | 108 (6.2) | 112 (4.3) | 44 (1.7) | |
| Normal weight | 4531 (65.7) | 1305 (75.3) | 1880 (72.2) | 1346 (52.5) | |
| Overweight | 1495 (21.7) | 178 (10.3) | 458 (17.6) | 859 (33.5) | |
| Obesity | 611 (8.9) | 141 (8.1) | 154 (5.9) | 316 (12.3) | |
| Mother BMI, kg/m2, mean ± SD | 23.89 ± 4.23 | 23.31 ± 4.46 | 23.28 ± 3.85 | 24.89 ± 4.26 | <0.001 |
| Z‐score, mean ± SD | −0.20 ± 1.18 | −1.39 ± 0.80 | −0.15 ± 0.48 | 1.03 ± 0.82 | 0.001 |
| Asthma, n (%) | |||||
| 4 years | 273 (4.4) | 69 (4.4) | 88 (3.7) | 116 (5.0) | 0.088 |
| 7 years | 388 (6.4) | 101 (6.6) | 127 (5.5) | 160 (7.0) | 0.085 |
| 10 years | 467 (8.2) | 99 (7.1) | 172 (7.9) | 196 (9.3) | 0.047 |
| 13 years | 394 (9.6) | 95 (9.5) | 134 (8.4) | 165 (10.9) | 0.066 |
| Rhinitis, n (%) | |||||
| 4 years | 276 (4.4) | 66 (4.2) | 88 (3.7) | 122 (5.3) | 0.032 |
| 7 years | 484 (7.9) | 113 (7.4) | 183 (7.9) | 188 (8.3) | 0.644 |
| 13 years | 400 (9.7) | 101 (10.1) | 156 (9.8) | 143 (9.4) | 0.695 |
| Eczema, n (%) | |||||
| 4 years | 648 (12.8) | 162 (12.8) | 261 (13.7) | 225 (12.0) | 0.324 |
| 7 years | 805 (13.7) | 193 (13.3) | 328 (14.7) | 284 (12.8) | 0.169 |
| 13 years | 644 (15.7) | 177 (17.8) | 245 (15.4) | 222 (14.7) | 0.103 |
| Food allergy, n (%) | |||||
| 13 years | 146 (4.6) | 34 (4.6) | 60 (4.9) | 52 (4.2) | 0.684 |
| Anaphylaxis, n (%) | |||||
| 13 years | 121 (2.9) | 26 (2.6) | 54 (3.4) | 41 (2.7) | 0.389 |
| Sensitization (from 1019 children), n (%) | |||||
| 10 years | 405 (39.7) | 89 (40.1) | 144 (39.2) | 172 (40.0) | 0.969 |
Note: Chi‐square (χ2) tests were used for categorical variables; one‐way ANOVA was used for comparisons involving continuous variables across groups with three or more categories. Statistically significant results are indicated in bold (p < .05).
Abbreviations: BMI, body mass index; SD, standard deviations.
According to WHO criteria.
Children born to mothers with overweight or obesity exhibited lower odds of developing eczema at 13 years of age compared to those born to mothers with underweight or normal weight, with an adjusted odds ratio (aOR) of 0.73 (95% CI: 0.60–0.88) (Table 3). No significant associations were observed between maternal BMI and the other allergic diseases at any of the assessed time points. All analyses for anaphylaxis and food allergy are present in Tables S8–S10.
TABLE 3.
Associations between maternal pre‐pregnancy BMI categories and offspring allergic diseases from childhood to adolescence.
| n | Asthma aOR (95% CI) | n | Rhinitis aOR (95% CI) | n | Eczema aOR (95% CI) | n | Allergic sensitization aOR (95% CI) | |
|---|---|---|---|---|---|---|---|---|
| 4 years | 6606 | 6571 | 5322 | ‐ | ‐ | |||
| Maternal underweight/normal weight | 4552 | Reference | 4526 | Reference | 3632 | Reference | ‐ | ‐ |
| Maternal overweight/obesity | 2054 | 1.09 (0.84–1.41) | 2045 | 1.01 (0.77–1.32) | 1690 | 0.84 (0.70–1.02) | ‐ | ‐ |
| 7 years | 6430 | 6413 | 6206 | ‐ | ‐ | |||
| Maternal underweight/normal weight | 4421 | Reference | 4408 | Reference | 4263 | Reference | ‐ | ‐ |
| Maternal overweight/obesity | 2009 | 0.95 (0.76–1.19) | 2005 | 0.90 (0.73–1.11) | 1943 | 0.91 (0.77–1.08) | ‐ | ‐ |
| 10 years | 5985 | ‐ | ‐ | ‐ | ‐ | 1078 | ||
| Maternal underweight/normal weight | 4156 | Reference | ‐ | ‐ | ‐ | ‐ | 716 | Reference |
| Maternal overweight/obesity | 1829 | 1.13 (0.92–1.38) | ‐ | ‐ | ‐ | ‐ | 362 | 0.77 (0.59–1.02) |
| 13 years | 4329 | 4327 | 4313 | ‐ | ‐ | |||
| Maternal underweight/normal weight | 3000 | Reference | 2996 | Reference | 2988 | Reference | ‐ | ‐ |
| Maternal overweight/obesity | 1329 | 1.07 (0.86–1.34) | 1331 | 0.91 (0.72–1.15) | 1325 | 0.73 (0.60–0.88) | ‐ | ‐ |
Note: Logistic Regression Model adjusted for sex of the children, maternal education, maternal age, smoking during pregnancy, maternal history of allergic diseases, and parity. Statistically significant results are indicated in bold (p < .05).
Excessive GWG, based on IOM criteria, was associated with increased odds of asthma at both 7 (aOR = 1.30; 95% CI: 1.01–1.66) and 13 years (aOR = 1.29; 95% CI: 1.01–1.65), as well as with rhinitis at 4 years (aOR = 1.48; 95% CI: 1.10–1.98). When GWG was analyzed using z‐scores that accounted for gestational age and maternal BMI, children whose mothers were in the highest tertile had greater odds of asthma at 7 years (aOR = 1.33; 95% CI: 1.03–1.72), rhinitis at 4 years (aOR = 1.54; 95% CI: 1.13–2.09), and allergic sensitization at 10 years (aOR = 1.44; 95% CI: 1.05–1.97) (Table 4).
TABLE 4.
Associations between gestational weight gain (IOM categories and Z‐scores) and offspring allergic diseases at ages 4, 7, 10, and 13 years.
| n | Asthma aOR (95% CI) | n | Rhinitis aOR (95% CI) | n | Eczema aOR (95% CI) | n | Allergic sensitization aOR (95% CI) | |
|---|---|---|---|---|---|---|---|---|
| 4 years | 6268 | 6234 | 5049 | ‐ | ‐ | |||
| IOM, Insufficient a | 1560 | 1.21 (0.87–1.68) | 1553 | 1.17 (0.84–1.63) | 1267 | 0.95 (0.77–1.18) | ‐ | ‐ |
| IOM, Adequate a | 2386 | Reference | 2369 | Reference | 1911 | Reference | ‐ | ‐ |
| IOM, Excessive a | 2322 | 1.33 (0.99–1.79) | 2312 | 1.48 (1.10–1.98) | 1871 | 0.89 (0.73–1.09) | ‐ | ‐ |
| GWG z‐score, continuous | 6263 | 1.06 (0.95–1.17) | 6229 | 1.09 (0.98–1.22) | 5047 | 0.96 (0.89–1.03) | ‐ | ‐ |
| GWG z‐score, 1st tertile | 2139 | 0.80 (0.59–1.10) | 2133 | 1.30 (0.95–1.78) | 1741 | 0.88 (0.72–1.07) | ‐ | ‐ |
| GWG z‐score, 2nd tertile | 2065 | Reference | 2049 | Reference | 1668 | Reference | ‐ | ‐ |
| GWG, z‐score, 3rd tertile | 2059 | 1.09 (0.82–1.47) | 2047 | 1.54 (1.13–2.09) | 1638 | 0.81 (0.66–0.998) | ‐ | ‐ |
| 7 years | 6107 | 6094 | 5893 | ‐ | ‐ | |||
| IOM, Insufficient a | 1523 | 1.21 (0.92–1.59) | 1517 | 0.92 (0.72–1.18) | 1454 | 0.90 (0.74–1.10) | ‐ | ‐ |
| IOM, Adequate a | 2313 | Reference | 2309 | Reference | 2228 | Reference | ‐ | ‐ |
| IOM, Excessive a | 2271 | 1.30 (1.01–1.66) | 2268 | 1.08 (0.87–1.35) | 2211 | 0.86 (0.72–1.03) | ‐ | ‐ |
| GWG z‐score, continuous | 6102 | 1.06 (0.97–1.16) | 6089 | 1.05 (0.96–1.14) | 5888 | 0.97 (0.90–1.03) | ‐ | ‐ |
| GWG z‐score, 1st tertile | 2086 | 1.03 (0.79–1.34) | 2081 | 1.09 (0.86–1.38) | 1994 | 0.99 (0.83–1.20) | ‐ | ‐ |
| GWG z‐score, 2nd tertile | 2011 | Reference | 2003 | Reference | 1936 | Reference | ‐ | ‐ |
| GWG, z‐score, 3rd tertile | 2005 | 1.33 (1.03–1.72) | 2005 | 1.25 (0.99–1.57) | 1958 | 0.90 (0.75–1.09) | ‐ | ‐ |
| 10 years | 5695 | ‐ | ‐ | ‐ | ‐ | 1019 | ||
| IOM, Insufficient a | 1401 | 0.89 (0.69–1.15) | ‐ | ‐ | ‐ | ‐ | 222 | 1.00 (0.71–1.42) |
| IOM, Adequate a | 2187 | Reference | ‐ | ‐ | ‐ | ‐ | 367 | Reference |
| IOM, Excessive a | 2107 | 1.15 (0.92–1.43) | ‐ | ‐ | ‐ | ‐ | 285 | 1.10 (0.81–1.49) |
| GWG z‐score, continuous | 5693 | 1.08 (0.99–1.17) | ‐ | ‐ | ‐ | ‐ | 1019 | 1.07 (0.95–1.20) |
| GWG z‐score, 1st tertile | 1949 | 0.87 (0.68–1.11) | ‐ | ‐ | ‐ | ‐ | 318 | 1.11 (0.80–1.54) |
| GWG z‐score, 2nd tertile | 1862 | Reference | ‐ | ‐ | ‐ | ‐ | 326 | Reference |
| GWG, z‐score, 3rd tertile | 1882 | 1.16 (0.92–1.46) | ‐ | ‐ | ‐ | ‐ | 375 | 1.44 (1.05–1.97) |
| 13 years | 4111 | 4108 | 4097 | ‐ | ‐ | |||
| IOM, Insufficient a | 1002 | 1.13 (0.86–1.49) | 999 | 1.02 (0.78–1.33) | 996 | 1.18 (0.95–1.47) | ‐ | ‐ |
| IOM, Adequate a | 1592 | Reference | 1589 | Reference | 1586 | Reference | ‐ | ‐ |
| IOM, Excessive a | 1517 | 1.29 (1.01–1.65) | 1520 | 0.97 (0.76–1.25) | 1515 | 1.01 (0.82–1.24) | ‐ | ‐ |
| GWG z‐score, continuous | 4111 | 1.03 (0.94–1.13) | 4108 | 0.95 (0.87–1.05) | 4097 | 0.96 (0.88–1.03) | ‐ | ‐ |
| GWG z‐score, 1st tertile | 1405 | 1.12 (0.86–1.45) | 1402 | 1.14 (0.88–1.47) | 1398 | 1.26 (1.02–1.56) | ‐ | ‐ |
| GWG z‐score, 2nd tertile | 1364 | Reference | 1363 | Reference | 1362 | Reference | ‐ | ‐ |
| GWG, z‐score, 3rd tertile | 1342 | 1.22 (0.94–1.59) | 1343 | 1.19 (0.92–1.54) | 1337 | 1.13 (0.91–1.40) | ‐ | ‐ |
Note: Logistic Regression Models adjusted for sex of the children, maternal education, maternal pre‐pregnancy BMI, maternal age, smoking during pregnancy, maternal history of allergic diseases, parity. Tertiles of GWG z‐score: 1st: ≤ −0.48; 2nd: > −0.48 and ≤0.43; 3rd: >0.43. Statistically significant results are indicated in bold (p < .05).
Abbreviations: GWG, gestational weight gain; IOM, institute of medicine.
According to the Institute of Medicine Guidelines for Gestational Weight Gain.
In contrast, higher GWG was associated with reduced odds of eczema at age 4 (aOR = 0.81; 95% CI: 0.66–0.998), while lower GWG was linked to increased odds of eczema at 13 years (aOR = 1.26; 95% CI: 1.02–1.56). No significant associations were found between GWG and either food allergy or anaphylaxis (Tables S11–S13).
Stratified analyses by maternal BMI revealed that among mothers with underweight or normal weight, being in the highest tertile of GWG z‐score was associated with increased odds of asthma and rhinitis during early childhood, as well as reduced odds of eczema at age 4 and increased odds at age 13 if GWG was in the lowest tertile. Among mothers with overweight or obesity, higher and lower GWG was associated with increased odds of allergic sensitization at 10 years of age (Table 5). Further sensitivity analyses with maternal BMI categories (normal weight excluding underweight category vs. overweight/obesity) are presented in (Table S14). Results were overall consistent when excluding underweight mothers, with similar effect sizes observed.
TABLE 5.
Associations between gestational weight gain Z‐score tertiles and offspring allergic diseases stratified by maternal pre‐pregnancy BMI.
| GWG z‐score | n | Asthma aOR (95% CI) | n | Rhinitis aOR (95% CI) | n | Eczema aOR (95% CI) | n | Allergic Sensitization aOR (95% CI) | |
|---|---|---|---|---|---|---|---|---|---|
| 4 years | |||||||||
| Maternal underweight/normalweight | 1st tertile | 1434 | 0.93 (0.63–1.38) | 1429 | 1.63 (1.10–2.42) | 1157 | 0.88 (0.69–1.11) | ‐ | ‐ |
| 2nd tertile | 1385 | Reference | 1369 | Reference | 1106 | Reference | ‐ | ‐ | |
| 3rd tertile | 1533 | 1.35 (0.95–1.93) | 1527 | 2.07 (1.42–3.01) | 1201 | 0.78 (0.61–0.99) | ‐ | ‐ | |
| Maternal overweight/obesity | 1st tertile | 705 | 0.63 (0.37–1.05) | 704 | 0.86 (0.50–1.48) | 584 | 0.87 (0.59–1.29) | ‐ | ‐ |
| 2nd tertile | 680 | Reference | 680 | Reference | 562 | Reference | ‐ | ‐ | |
| 3rd tertile | 526 | 0.70 (0.40–1.21) | 520 | 0.76 (0.42–1.36) | 437 | 0.93 (0.62–1.39) | ‐ | ‐ | |
| 7 years | ‐ | ‐ | |||||||
| Maternal underweight/normalweight | 1st tertile | 1401 | 1.16 (0.84–1.60) | 1398 | 1.14 (0.86–1.51) | 1335 | 0.93 (0.75–1.15) | ‐ | ‐ |
| 2nd tertile | 1345 | Reference | 1338 | Reference | 1291 | Reference | ‐ | ‐ | |
| 3rd tertile | 1484 | 1.39 (1.02–1.89) | 1483 | 1.36 (1.03–1.79) | 1453 | 0.88 (0.71–1.09) | ‐ | ‐ | |
| Maternal overweight/obesity | 1st tertile | 685 | 0.79 (0.49–1.22) | 683 | 1.02 (0.67–1.56) | 659 | 1.17 (0.83–1.65) | ‐ | ‐ |
| 2nd tertile | 666 | Reference | 665 | Reference | 645 | Reference | ‐ | ‐ | |
| 3rd tertile | 521 | 1.25 (0.80–1.97) | 522 | 1.02 (0.65–1.60) | 505 | 0.97 (0.67–1.41) | ‐ | ‐ | |
| 10 years | |||||||||
| Maternal underweight/normalweight | 1st tertile | 1315 | 0.82 (0.60–1.11) | ‐ | ‐ | ‐ | ‐ | 204 | 0.87 (0.58–1.31) |
| 2nd tertile | 1259 | Reference | ‐ | ‐ | ‐ | ‐ | 205 | Reference | |
| 3rd tertile | 1406 | 1.26 (0.95–1.66) | ‐ | ‐ | ‐ | ‐ | 270 | 1.33 (0.91–1.94) | |
| Maternal overweight/obesity | 1st tertile | 634 | 0.96 (0.64–1.44) | ‐ | ‐ | ‐ | ‐ | 114 | 1.78 (1.01–3.12) |
| 2nd tertile | 603 | Reference | ‐ | ‐ | ‐ | ‐ | 121 | Reference | |
| 3rd tertile | 476 | 0.93 (0.60–1.43) | ‐ | ‐ | ‐ | ‐ | 105 | 1.86 (1.02–3.40) | |
| 13 years | |||||||||
| Maternal underweight/normalweight | 1st tertile | 949 | 1.10 (0.79–1.52) | 946 | 1.16 (0.85–1.59) | 945 | 1.30 (1.02–1.65) | ‐ | ‐ |
| 2nd tertile | 914 | Reference | 913 | Reference | 911 | Reference | ‐ | ‐ | |
| 3rd tertile | 1002 | 1.28 (0.94–1.75) | 1002 | 1.27 (0.94–1.72) | 998 | 1.09 (0.86–1.40) | ‐ | ‐ | |
| Maternal overweight/obesity | 1st tertile | 456 | 1.17 (0.75–1.83) | 456 | 1.07 (0.67–1.72) | 453 | 1.18 (0.78–1.80) | ‐ | ‐ |
| 2nd tertile | 450 | Reference | 450 | Reference | 451 | Reference | ‐ | ‐ | |
| 3rd tertile | 340 | 1.11 (0.68–1.79) | 341 | 0.99 (0.59–1.65) | 339 | 1.29 (0.84–2.01) | ‐ | ‐ | |
Note: Logistic Regression Model adjusted for sex of the children, maternal education, maternal age, smoking during pregnancy, maternal history of allergic diseases, parity. Tertiles of GWG z‐score: 1st: ≤ −0.48; 2nd: > −0.48 and ≤0.43; 3rd: >0.43. Statistically significant results are indicated in bold (p < .05).
4. DISCUSSION
In this population‐based birth cohort, we found that a higher GWG, when exceeding IOM guidelines or falling in the highest tertile of GWG z‐scores, was associated with increased odds of asthma, rhinitis, and allergic sensitization. In contrast, a higher GWG z‐score and maternal pre‐pregnancy overweight or obesity were associated with reduced odds of eczema, while a lower GWG z‐score increased the odds. These findings highlight the complex and condition‐specific role of maternal weight, both before and during pregnancy, as an early‐life determinant of childhood allergic diseases.
4.1. Maternal pre‐pregnancy BMI and allergic diseases
Our findings suggest that maternal overweight or obesity before pregnancy is associated with lower odds of eczema in offspring at 13 years. This observation aligns with previous research, including a meta‐analysis that reported reduced odds of atopic dermatitis in children born to mothers who were overweight or obese prior to pregnancy. 36 However, the authors of that meta‐analysis cautioned against interpreting these associations as protective, noting that the inverse relationship did not hold consistently across subgroup analyses considering more robust study designs, different age groups, excluding studies with fewer than 10,000 cases, non‐U.S. cohorts, and studies using medical records. 36 Nonetheless, another recent meta‐analysis also supports a subtle inverse association, reporting slightly reduced odds of “eczema ever” among children of overweight mothers and a similar but non‐significant trend for maternal obesity. 37
A study from 2022 explored the influence of maternal BMI measurement methods. 38 When stratified by whether pre‐pregnancy weight was measured or self‐reported, the study found that objectively measured maternal obesity was associated with a reduced risk of dermatitis (adjusted hazard ratio [aHR] = 0.93; 95% CI: 0.90–0.97), whereas self‐reported obesity showed a slightly increased risk (aHR = 1.05; 95% CI: 1.00–1.10). 38 These findings suggest that reliance on self‐reported weight may attenuate or obscure associations in some studies.
Maternal pre‐pregnancy BMI has been inversely associated with cord‐blood immunoglobulin E levels, a marker of the immune response of the fetus, and typically increased in eczema. 9 These findings point to a potential protective effect of higher maternal BMI against the development of eczema, although the underlying mechanisms remain unclear. It is also possible that factors associated with maternal overweight may play a mediating role. Our study contributes to this ongoing discussion by providing longitudinal evidence from childhood into adolescence, underscoring the need for future research to disentangle the biological or environmental pathways through which maternal adiposity may influence eczema risk.
In our study, we did not find any significant association between pre‐pregnancy BMI and other allergic diseases. In two meta‐analyses, maternal obesity before pregnancy was associated with higher odds of wheeze and asthma in the offspring, as was maternal overweight. 18 , 37 In our study, asthma was based on parental report of a physician diagnosis. In the metanalysis by Liu et al. associations between maternal BMI and childhood asthma were weaker when asthma was identified through parental report rather than medical diagnosis. In fact, for maternal overweight, the association lost statistical significance. This suggests that reliance on parental report may attenuate true associations due to potential misclassification of asthma. 18
A recent large study by Rosenquist et al., 39 analyzed nearly 100,000 mother–child pairs using electronic medical records. Asthma was defined based on International Classification of Diseases diagnostic codes and asthma medication dispensing, ensuring high specificity. The study reported small increases in asthma risk across maternal BMI categories, some of which did not reach statistical significance. 39 Likewise, a recent cohort study found no associations between early‐pregnancy BMI and physician‐diagnosed asthma (validated through medication reimbursement data). 32 Together, these studies suggest that results may differ depending on the definition and ascertainment of asthma, which may partly explain the null findings observed in our cohort. 40 , 41
Similarly to our study, in the meta‐analysis by Zhang et al. maternal overweight and maternal obesity before pregnancy were not associated with an increased risk of rhinitis in the offspring. 37 As for allergic sensitization, two prospective cohort studies, comparable to ours, found no associations between early‐pregnancy BMI and allergic sensitization measured by IgE levels. 8 , 41
4.2. Maternal GWG and allergic diseases
Our findings indicate that excessive GWG, as defined by the IOM, is associated with increased odds of asthma in offspring at both 7 and 13 years of age, as well as increased odds of rhinitis at 4 years. When GWG was examined using z‐scores– accounting for maternal BMI and gestational age– children whose mothers were in the highest tertile of GWG z‐score had significantly greater odds of having asthma at 7 years, of rhinitis at 4 years, and of allergic sensitization at 10 years of age.
These results align with previous studies reporting a positive association between higher GWG and allergic diseases, particularly asthma. 3 , 7 , 11 , 18 , 20 A meta‐analysis suggested that each 1 kg increase in GWG was associated with a 1.5% increase in childhood asthma or wheezing odds. 3 Although that meta‐analysis included heterogeneous GWG definitions and did not use IOM categories, pooled results from high GWG groups consistently indicated elevated odds. 3 A more recent meta‐analysis further supported these findings, showing increased odds of asthma with GWG above 20 kg. 18 However, in two meta‐analyses, when examining studies using IOM‐defined categories, excessive GWG was not significantly associated with asthma, 18 , 37 possibly reflecting the limited number of studies using this definition.
Individual cohort and cross‐sectional studies further support this findings. The Danish National Birth Cohort reported that GWG ≥25 kg was associated with nearly double the odds of severe asthma. 11 Although no link with hay fever was found in that cohort, the Shanghai Children Allergy Study, a large cross‐sectional study of over 15,000 mother–child pairs, found that excessive GWG, as defined by the IOM, increased the risk of both asthma and allergic rhinitis. 20
Considering allergic sensitization, our results indicate a significant positive association with GWG z‐score, which aligns with findings from the Shanghai study where mothers with GWG above IOM recommendations had increased prevalence ratios for sensitization. 20 In contrast, a Finnish birth cohort found no association between GWG and sensitization. 32 However, that study used weekly weight gain categories that did not account for pre‐pregnancy BMI and gestational age, which may have obscured differences.
Interestingly, we also observed that higher GWG z‐score was associated with lower odds of eczema at 4 years, while lower GWG z‐score was linked to higher odds of eczema at 13 years. Prior literature on this topic has been inconsistent. One meta‐analysis found that GWG above 15–25 kg was associated with a higher risk of atopic dermatitis, as was excessive GWG by IOM criteria. 36 However, a more recent meta‐analysis based on IOM categories did not replicate these findings. 37 Moreover, the Shanghai study found lower odds of eczema in children whose mothers gained less than the IOM recommendation, 20 while the U.S.‐based Growing Up Today Study reported no significant associations. 14 These discrepancies likely reflect differences in how GWG was defined. Studies using crude weight thresholds (e.g., <10 kg or >25 kg) may not adequately account for gestational age or maternal BMI. The use of GWG z‐scores, which integrate both, may provide a more individualized measure of weight gain adequacy and may capture associations that IOM cutoffs miss. When we stratified our analysis by maternal BMI category, the increased eczema risk associated with lower GWG was only observed among mothers with underweight or normal BMI. This suggests that low GWG may be more detrimental in pregnancies with limited maternal reserves, which may predispose to suboptimal fetal nutrition or altered immune system development.
Taken together, our results add to a growing body of evidence suggesting that, overall, an inadequate GWG, low or high, may influence the risk of allergic diseases in offspring. Several mechanisms may underlie these associations. Excessive GWG has been linked to a pro‐inflammatory state in pregnancy, characterized by elevated cytokines such as TNF‐α and C‐reactive protein (CRP). 40 , 41 , 42 One study found that children of mothers in the highest GWG tertile had elevated TNF‐α in early life, which in turn was associated with a higher risk of asthma. 40 Other research has shown that excessive GWG is associated with increased maternal CRP levels, which have been linked to wheezing and respiratory infections in offspring. 43 , 44 A different hypothesis is that the onset of allergic diseases could be connected to excessive GWG through the exposure of the fetus to poor dietary patterns during pregnancy, which are often connected to more energy‐dense foods and consequently may cause excessive GWG. 43 In fact, a healthier diet during pregnancy has been shown to decrease the odds of asthma in offspring. 44 Excessive GWG also appears to negatively influence infants' gut microbiota, decreasing the alpha diversity and abundance of neonatal gut microbiota. 45 In turn, a low alpha diversity has been associated with an increased risk of allergic diseases. 46
Interestingly, maternal obesity has been associated with lower cord blood IgE levels, whereas eczema is typically linked to elevated IgE. 9 This may suggest that maternal obesity or high GWG may modify fetal immune development in a way that reduces IgE‐mediated pathways during perinatal life, possibly lowering the risk of eczema. However, other allergic conditions may still be promoted through IgE‐independent mechanisms, driven by systemic inflammation and immune dysregulation in later life.
Overall, our findings support the hypothesis that excessive GWG may promote allergic disease development through inflammatory, metabolic, and microbial pathways (Figure 1). On the other hand, insufficient weight gain may also be deleterious to the offspring, causing suboptimal development. These effects may be amplified or modified by maternal BMI, highlighting the importance of personalized GWG guidance based on pre‐pregnancy nutritional status. Further research is needed to clarify causality and mechanisms, but from a public health perspective, our results reinforce the value of promoting healthy weight gain during pregnancy as a potential strategy for reducing allergy risk in the next generation.
FIGURE 1.
Pathways through which maternal nutritional status indicators may influence allergic diseases.
4.3. Strenghts and limitations
The limitations of this study should be acknowledged. First, pre‐pregnancy weight was primarily self‐reported, which may introduce recall bias and misclassification. However, previous research indicates strong agreement between self‐reported and measured weights, particularly when recall occurs within 1 year postpartum, as in our study. 47 Moreover, only total GWG was considered with no trimester‐specific measurements available. Even if gestational age was accounted for when using the GWG z‐scores, the trajectory of GWG may be a relevant factor in this association. 22 Additonally, we could not account for other potential nutritional factors during pregnancy that may have contributed to greater GWG and, in turn, allergic diseases. 43 It is also important to recognize that the mechanisms underlying each allergic disease may differ. While maternal adiposity may influence immune and growth‐related pathways, genetic factors, such as filaggrin mutations, play a major role in skin barrier dysfunction and susceptibility to eczema. Information on filaggrin mutations or other genetic variants was not available in our cohort. Moreover, diagnoses of allergic diseases were based on parental reports of physician diagnoses, which may be prone to misclassification. In addition, we did not distinguish between asthma phenotypes nor account for asthma severity; nonetheless, this approach is commonly used in epidemiological studies and likely results in non‐differential bias, which tends to attenuate associations. 48 Additionally, paternal history of allergic disease and smoking exposure in infancy were not included due to limited data availability and low prevalence, respectively. Finally, as with all observational studies, residual confounding cannot be entirely ruled out, although we used a DAG to guide careful covariate selection.
Notwithstanding these limitations, our study has several strengths. We leveraged data from a large, prospective, population‐based birth cohort with repeated follow‐up assessments extending into adolescence, enabling us to explore allergic outcomes at multiple developmental stages, with an extended follow up time. We also examined six distinct allergic outcomes (asthma, rhinitis, eczema, food allergy, anaphylaxis, and allergic sensitization), allowing us to assess the consistency of associations across different immune‐mediated conditions. Moreover, although allergic outcomes are biologically related, correlations between conditions in our data were tested and they were consistently weak (coefficients ranging from 0.065 to 0.221), supporting their analysis as distinct outcomes. Furthermore, we tested potential interactions of GWG with maternal BMI and GWG and maternal BMI with child's sex, providing additional insight into the complexity of these associations. The use of standardized validated questionnaires and objective measures of allergic sensitization adds robustness to outcome assessment. We employed both IOM‐based GWG categories and GWG z‐scores considering gestational age and pre‐pregnancy BMI, allowing for a more individualized and biologically relevant analysis of weight gain adequacy. Moreover, our stratified analyses by maternal BMI categories provided additional insights into how pre‐pregnancy nutritional status may modify the relationship between GWG and allergic disease. Finally, despite losses to follow‐up, effect size analyses comparing included and excluded participants' characteristics indicated only minor differences. Together, these methodological strengths enhance the relevance of our findings and contribute to the growing body of evidence supporting the importance of maternal health before and during pregnancy in shaping long‐term allergic outcomes in children.
5. CONCLUSION
Our findings suggest that maternal weight before and during pregnancy influences the development of allergic diseases in children, with differing effects for eczema, asthma, rhinitis, and allergic sensitization.
AUTHOR CONTRIBUTIONS
Mónica Rodrigues: Conceptualization; methodology; data curation; investigation; formal analysis; visualization; writing – original draft; writing – review and editing. Susana Santos: Conceptualization; methodology; investigation; formal analysis; writing – original draft; writing – review and editing; supervision. Pedro Moreira: Conceptualization; supervision; writing – original draft; writing – review and editing. Francisca Castro Mendes: Writing – review and editing. André Moreira: Conceptualization; supervision; writing – original draft; writing – review and editing.
FUNDING INFORMATION
G21 was funded by Programa Operacional de Saúde – Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health). This work was supported by FCT Fundação para a Ciência e Tecnologia, I.P. through the projects with references UIDB/04750/2020 and LA/P/0064/2020 and DOI identifiers https://doi.org/10.54499/UIDB/04750/2020 and https://doi.org/10.54499/LA/P/0064/2020. This work was supported by the Portuguese Foundation for Science and Technology–FCT–project reference 2023.02362.BD: 10.54499/2023.02362.BD and DOI identifier: https://doi.org/10.54499/2023.02362.BD. SS was supported by the European Union's Horizon Europe Research and Innovation Programme under the Marie Sklodowska‐Curie Postdoctoral Fellowship Grant Agreement No. 101109136 (URBANE). Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Research Executive Agency (REA). Neither the European Union nor the granting authority can be held responsible for them.
CONFLICT OF INTEREST STATEMENT
No conflicts of interest to report.
Supporting information
Figure S1: Flowchart of participant inclusion and exclusion from the generation XXI cohort for analysis of maternal BMI, gestational weight gain, and offspring allergic outcomes.
Figure S2: DAG (by daggity.net) on the association between maternal BMI pre‐pregnancy and allergic diseases. Birthweight, child BMI, breastfeeding and mode of delivery were considered mediators and, therefore, were not included in the adjusted models as confounders.
Figure S3: DAG (by daggity.net) on the association between GWG with allergic diseases. Birth weight, child BMI, breastfeeding and mode of delivery were considered mediators and, therefore, were not included in the adjusted models as confounders.
Table S1: Maternal and child characteristics according to included and excluded participants in the Generation XXI cohort.
Table S2: Interaction between maternal BMI and GWG IOM on allergic diseases.
Table S3: Logistic regression (crude and adjusted models) by sex regarding the association between GWG IOM categories and children's allergic diseases.
Table S4: Association between maternal BMI before pregnancy and allergic outcomes (adjusted GEE models). Complete cases analysis.
Table S4: Association between gestational weight gain (IOM categories) and allergic outcomes in children (adjusted GEE models). Complete cases analysis.
Table S6: Association between tertiles of gestational weight gain z‐score and allergic outcomes (adjusted GEE models). Complete cases analysis.
Table S7: Association between gestational weight gain z‐score (continuous) and allergic outcomes (adjusted GEE models). Complete cases analysis.
Table S8: Logistic Regression (crude and adjusted models) on the association between categories of maternal BMI before pregnancy (underweight + normal weight vs. overweight + obesity) with children's allergic diseases.
Table S9: Logistic Regression (crude and adjusted models) on the association between four categories of maternal BMI before pregnancy (underweight, normal weight, overweight and obesity) with children's allergic diseases. This analysis does not have imputed data.
Table S10: Logistic Regression (crude and adjusted models) on the association between categories of maternal BMI before pregnancy (normal weight, overweight + obesity–excluding underweight categories) with children's allergic diseases. This analysis does not have imputed data.
Table 11: Logistic Regression (crude and adjusted models) on the association between GWG IOM categories with children's allergic diseases.
Table 12: Logistic regression (crude and adjusted models) regarding the association between GWG z‐score as a continuous variable with children's allergic diseases.
Table 13: Logistic regression (crude and adjusted models) regarding the association between GWG z‐score tertiles with children's allergic diseases.
Table 14: Association between GWG z‐score tertiles with children's allergic diseases by maternal BMI categories (normal weight vs. overweight + obesity–excluding underweight). This analysis does not have imputed data.
ACKNOWLEDGMENTS
We gratefully acknowledge the families enrolled in Generation XXI for their kindness, the participating hospitals and their staff for their help and support, and all previous and current research and field team members for their enthusiasm and perseverance. Open access publication funding provided by FCT (b‐on).
Rodrigues M, Santos S, Mendes FC, Moreira P, Moreira A. Excessive gestational weight gain and risk of asthma, rhinitis and allergic sensitization: Results from a Portuguese birth cohort. Pediatr Allergy Immunol. 2026;37:e70357. doi: 10.1111/pai.70357
Editor: Jon Genuneit
DATA AVAILABILITY STATEMENT
The data from Generation XXI are not publicly available due to privacy or ethical restrictions. The data can be made available for research proposals to the Generation XXI Executive Committee (generationxxi@ispup.up.pt) upon request. Further information about Generation XXI can be obtained via the Generation XXI website www.geracao21.com or by emailing generationxxi@ispup.up.pt.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1: Flowchart of participant inclusion and exclusion from the generation XXI cohort for analysis of maternal BMI, gestational weight gain, and offspring allergic outcomes.
Figure S2: DAG (by daggity.net) on the association between maternal BMI pre‐pregnancy and allergic diseases. Birthweight, child BMI, breastfeeding and mode of delivery were considered mediators and, therefore, were not included in the adjusted models as confounders.
Figure S3: DAG (by daggity.net) on the association between GWG with allergic diseases. Birth weight, child BMI, breastfeeding and mode of delivery were considered mediators and, therefore, were not included in the adjusted models as confounders.
Table S1: Maternal and child characteristics according to included and excluded participants in the Generation XXI cohort.
Table S2: Interaction between maternal BMI and GWG IOM on allergic diseases.
Table S3: Logistic regression (crude and adjusted models) by sex regarding the association between GWG IOM categories and children's allergic diseases.
Table S4: Association between maternal BMI before pregnancy and allergic outcomes (adjusted GEE models). Complete cases analysis.
Table S4: Association between gestational weight gain (IOM categories) and allergic outcomes in children (adjusted GEE models). Complete cases analysis.
Table S6: Association between tertiles of gestational weight gain z‐score and allergic outcomes (adjusted GEE models). Complete cases analysis.
Table S7: Association between gestational weight gain z‐score (continuous) and allergic outcomes (adjusted GEE models). Complete cases analysis.
Table S8: Logistic Regression (crude and adjusted models) on the association between categories of maternal BMI before pregnancy (underweight + normal weight vs. overweight + obesity) with children's allergic diseases.
Table S9: Logistic Regression (crude and adjusted models) on the association between four categories of maternal BMI before pregnancy (underweight, normal weight, overweight and obesity) with children's allergic diseases. This analysis does not have imputed data.
Table S10: Logistic Regression (crude and adjusted models) on the association between categories of maternal BMI before pregnancy (normal weight, overweight + obesity–excluding underweight categories) with children's allergic diseases. This analysis does not have imputed data.
Table 11: Logistic Regression (crude and adjusted models) on the association between GWG IOM categories with children's allergic diseases.
Table 12: Logistic regression (crude and adjusted models) regarding the association between GWG z‐score as a continuous variable with children's allergic diseases.
Table 13: Logistic regression (crude and adjusted models) regarding the association between GWG z‐score tertiles with children's allergic diseases.
Table 14: Association between GWG z‐score tertiles with children's allergic diseases by maternal BMI categories (normal weight vs. overweight + obesity–excluding underweight). This analysis does not have imputed data.
Data Availability Statement
The data from Generation XXI are not publicly available due to privacy or ethical restrictions. The data can be made available for research proposals to the Generation XXI Executive Committee (generationxxi@ispup.up.pt) upon request. Further information about Generation XXI can be obtained via the Generation XXI website www.geracao21.com or by emailing generationxxi@ispup.up.pt.