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ORIGINAL ARTICLE
Relationship of cord blood IgE with maternal, fetal, and environmental factors in the Chinese population
Mengxue Chen†, Yutong Gu†, Quanhua Liu, Ruoxu Ji, Jianhua Zhang*, Li Hua*
Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Abstract
Introduction and objectives: Previous studies reported that history of pregnancy and delivery and family environment might influence cord blood IgE (CB-IgE) levels and development of allergies; however, the association between them is not well-established. This study aimed at investigating the IgE level in the newborn’s umbilical cord blood and its relationship with maternal, fetal, and environmental factors.
Materials and methods: A total of 989 mothers and their infants were analyzed in this study. Mothers were given a questionnaire that had a series of questions to evaluate demographic information, maternal allergic status, and environmental exposures during pregnancy. Neonatal cord blood samples were taken at the same time for IgE assay.
Results: By univariate analysis, we found statistically significant correlations between CB-IgE levels and gender (P = 0.000) and delivery mode (P = 0.017). By multivariate analysis, gender was found to have a significant association with CB-IgE levels (P = 0.001). No significant difference was found between CB-IgE levels and antenatal complications, the season of birth, birth weight, gestational age, and household income (P > 0.050).
Conclusions: In this study, newborn gender was found to be a strong predictor of elevated CB-IgE. The delivery mode was a probable predictor.
Key words: cord blood, IgE, gender, delivery mode, newborn
*Corresponding authors: Li Hua and Jianhua Zhang. Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. Email address: [email protected]; [email protected]
†Mengxue Chen and Yutong Gu contributed equally to the article.
Received 18 August 2020; Accepted 22 November 2020 Available online 1 May 2021
Copyright: Chen M, et al.
License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/
Introduction and objectives
Allergic diseases represent an important health problem worldwide and their prevalence and severity have been increasing in recent decades, leading to profound negative effects on patients’ quality of life and becoming a major public health burden in children.1–3 To prevent these common disorders and reduce the economic burden, the identification of prognostic markers pointing to increased risk of allergy development is of importance.4
Cord blood is an easily accessible biological material and has been used for searching prognostic markers for allergies, such as regulatory T cells, gene expression of cytokines, and IgE levels in cord blood. Since the 1970s, cord blood IgE (CB-IgE) has been investigated as a predictive marker for allergic diseases and gained much attention.4–6 Nowadays, although various studies demonstrated that elevated CB-IgE is affected by some different factors including maternal, paternal, placenta, and fetal characteristics, findings on each factor have been inconclusive and discordant.7–10 And results remain difficult to compare because of the influence of genetics and different ethnic groups on the CB-IgE.11,12 Regarding the scarcity of studies about CB-IgE in Chinese Han newborns, more studies are needed to be performed on different populations and situations.
This study aimed at investigating the CB-IgE level in Han newborns in Shanghai China, to specify the relationship between CB-IgE level and maternal, fetal, and environmental factors.
Materials and methods
Study population
In this study, 989 Chinese Han children were enrolled from the Shanghai Allergy Cohort, which was a prospective birth cohort with infants recruited between 2012 and 2013 at two large tertiary hospitals in Shanghai, Xinhua Hospital and the International Peace Maternity & Child Health Hospital. All participants provided written consent form before enrolling. The study was approved by the Ethics Committee of Xinhua Hospital and the International Peace Maternity & Child Health Hospital, and conducted according to the principles in the Declaration of Helsinki.
Epidemiologic information collection
A questionnaire was used to obtain information about newborns (including season of birth, birth weight, gestational age, gender, and delivery mode), mothers (including antenatal complications, maternal atopy, parity, previous pregnancy, maternal age, maternal prepregnancy BMI, and maternal education), and environmental factors [including household income, prenatal pet, and environmental tobacco smoke (ETS) exposures]. Antenatal complications included pregnancy hypertension, diabetes, infection, or intrauterine growth retardation. Maternal atopy was referred to those mothers who had asthma, allergic rhinitis, or atopic dermatitis along with detectable specific IgE. Prenatal pet exposure was defined as keeping cats or dogs at home during pregnancy. ETS included secondhand smoke or active smoking.
CB-IgE measurement
We used the ImmunoCAP Total IgE Low Range Assay to determine CB-IgE levels. Elevation of CB-IgE levels was cut-off at ≥0.5 kU/L.
Statistical analysis
All data were entered into the statistical software package SPSS version 25.0 for Windows. We first determined the percentiles of CB-IgE and the prevalence of elevated CB-IgE in the newborns. Then, we used univariate analysis to examine the correlations of CB-IgE levels with different groups of related factors and performed a multivariable analysis to estimate the independent relationship between CB-IgE levels and the analyzed related factors after adjusting for potential confounders. P-Values ≤0.05 were considered statistically significant.
Ethical approval
The study was approved by the Ethics Committee of Xinhua Hospital and the International Peace Maternity & Child Health Hospital, and conducted according to the principles in the Declaration of Helsinki.
Results
CB-IgE levels of the study subjects
This study was performed on 989 mother–newborn pairs. The distribution of CB-IgE level in newborns is presented in Table 1. Data show the quartile values (Q1 = 0.11 kU/L, Q2 = 0.24 kU/L, Q3 = 0.54 kU/L), minimum (0.01 kU/L), and maximum (75.60 kU/L) of CB-IgE. Participants had a mean CB-IgE concentration of 0.94±3.96 kU/L. Overall, 27.10% of Shanghai newborns had CB-IgE levels ≥0.5 kU/L.
Table 1 CB-IgE levels of the study subjects (n = 989).
| CB-IgE | |
|---|---|
| Q1 (kU/L) | 0.11 |
| Q2 (kU/L) | 0.24 |
| Q3 (kU/L) | 0.54 |
| Min (kU/L) | 0.01 |
| Max (kU/L) | 75.60 |
| Mean ± SD (kU/L) | 0.94 ± 3.96 |
| The prevalence of elevated CB-IgE % (CB-IgE ≥ 0.5 (kU/L)) |
27.10 |
CB-IgE: cord blood IgE.
Correlations between CB-IgE levels and epidemiologic factors
Table 2 shows that newborn gender and delivery mode were found to have a significant correlation with CB-IgE levels (P < 0.05). Male gender and cesarean section were associated with higher CB-IgE levels.
Table 2 Correlations between CB-IgE levels and epidemiologic factors.
| CB-IgE | N | Median | Interquartile range | P-valuea |
|---|---|---|---|---|
| Newborn gender | ||||
| Female | 466 | 0.20 | 0.34 | 0.000* |
| Male | 499 | 0.28 | 0.54 | |
| Delivery mode | ||||
| Vaginal | 229 | 0.21 | 0.32 | 0.017* |
| Cesarean section | 737 | 0.24 | 0.47 | |
| Antenatal complicationsb | ||||
| No | 763 | 0.23 | 0.41 | 0.458 |
| Yes | 177 | 0.25 | 0.54 | |
| Maternal atopyc | ||||
| No | 824 | 0.23 | 0.41 | 0.098 |
| Yes | 129 | 0.29 | 0.56 | |
| Parity | ||||
| None | 868 | 0.24 | 0.43 | 0.754 |
| ≥1 | 98 | 0.21 | 0.42 | |
| Previous pregnancy | ||||
| None | 629 | 0.24 | 0.42 | 0.555 |
| ≥1 | 337 | 0.23 | 0.45 | |
| Prenatal pet exposure | ||||
| No | 857 | 0.23 | 0.43 | 0.830 |
| Yes | 105 | 0.27 | 0.45 | |
| Prenatal ETS exposure | ||||
| No | 577 | 0.24 | 0.43 | 0.789 |
| Yes | 387 | 0.23 | 0.45 | |
| Birth weight (g) | ||||
| <2500 | 24 | 0.24 | 0.88 | 0.966 |
| 2500–4000 | 857 | 0.23 | 0.42 | |
| ≥4000 | 85 | 0.22 | 0.42 | |
| Gestational age (weeks) | ||||
| <37 | 33 | 0.15 | 0.32 | 0.080 |
| 37–39 | 686 | 0.24 | 0.49 | |
| ≥40 | 247 | 0.22 | 0.36 | |
| Season of birth | ||||
| Summer (Jun–Aug) | 170 | 0.25 | 0.44 | 0.287 |
| Autumn (Sep–Nov) | 451 | 0.26 | 0.43 | |
| Winter (Dec–Feb) | 337 | 0.22 | 0.39 | |
| Maternal education | ||||
| Middle school or lower | 28 | 0.18 | 0.24 | 0.524 |
| High school | 112 | 0.22 | 0.38 | |
| College or higher | 825 | 0.24 | 0.44 | |
| Maternal age (years) | ||||
| <25 | 62 | 0.25 | 0.60 | 0.866 |
| 25–29 | 500 | 0.22 | 0.39 | |
| 30–34 | 325 | 0.25 | 0.50 | |
| ≥35 | 77 | 0.21 | 0.64 | |
| Maternal prepregnancy BMI (kg/m2) | ||||
| <18.5 | 150 | 0.23 | 0.51 | 0.390 |
| 18.5–24.9 | 694 | 0.23 | 0.41 | |
| 25–29.9 | 92 | 0.29 | 0.76 | |
| ≥30 | 26 | 0.30 | 0.49 | |
| Household income | ||||
| <100K | 273 | 0.25 | 0.45 | 0.524 |
| ≥100K | 540 | 0.22 | 0.41 | |
| Unknown | 176 | 0.24 | 0.42 | |
CB-IgE: cord blood IgE; ETS: environmental tobacco smoke.
aP-values for Mann–Whitney U-test or Kruskal–Wallis H-test.
bAntenatal complications included pregnancy hypertension, diabetes, infection, or intrauterine growth retardation.
cMaternal atopy was referred to those mothers who had asthma, allergic rhinitis, or atopic dermatitis along with detectable specific IgE.
*P≤0.05.
Correlations between CB-IgE elevation and epidemiologic factors
As shown in Table 3, after adjusting for multiple newborn and maternal factors, newborn gender remained associated with CB-IgE elevation. Male was at a higher risk of elevated CB-IgE (OR = 1.642, P = 0.001).
Table 3 Correlations between CB-IgE elevation and epidemiologic factors.
| Variable | Elevated CB-IgE, n (%) | Crude OR | 95% CI | P-valuea | aOR | 95% CI | P-valuea |
|---|---|---|---|---|---|---|---|
| Newborn gender | |||||||
| B Female | 105 (22.5) | 1.000 | 1.000 | ||||
| Male | 156 (31.3) | 1.564 | (1.172,2.086) | 0.002* | 1.642 | (1.212, 2.224) | 0.001* |
| Delivery mode | |||||||
| Vaginal | 50 (21.8) | 1.000 | 1.000 | ||||
| Cesarean section | 212 (28.8) | 1.446 | (1.017,2.055) | 0.040* | 1.342 | (0.914,1.969) | 0.133 |
| Antenatal complicationsb | |||||||
| No | 206 (27.0) | 1.000 | 1.000 | ||||
| Yes | 51 (28.8) | 1.094 | (0.762,1.572) | 0.626 | 1.064 | (0.718,1.576) | 0.757 |
| Maternal atopyc | |||||||
| No | 219 (26.6) | 1.000 | 1.000 | ||||
| Yes | 41 (31.8) | 1.287 | (0.861,1.923) | 0.218 | 1.217 | (0.793,1.868) | 0.369 |
| Parity | |||||||
| None | 235 (27.1) | 1.000 | 1.000 | ||||
| ≥1 | 27 (27.6) | 1.024 | (0.642,1.635) | 0.920 | 1.013 | (0.582,1.763) | 0.964 |
| Previous pregnancy | |||||||
| None | 169 (26.9) | 1.000 | 1.000 | ||||
| ≥1 | 93 (27.6) | 1.037 | (0.771,1.396) | 0.808 | 1.001 | (0.699,1.433) | 0.995 |
| Prenatal pet exposure | |||||||
| No | 234 (27.3) | 1.000 | 1.000 | ||||
| Yes | 28 (26.7) | 0.968 | (0.612,1.530) | 0.890 | 1.077 | (0.662,1.752) | 0.765 |
| Prenatal ETS exposure | |||||||
| No | 158 (27.4) | 1.000 | 1.000 | ||||
| Yes | 105 (27.1) | 0.987 | (0.739,1.319) | 0.932 | 0.976 | (0.711,1.341) | 0.882 |
| Birth weight (g) | |||||||
| <2500 | 8 (33.3) | 1.000 | 1.000 | ||||
| 2500–4000 | 231 (27.0) | 0.738 | (0.312,1.748) | 0.490 | 0.427 | (0.132,1.374) | 0.154 |
| ≥4000 | 23 (27.1) | 0.742 | (0.280,1.966) | 0.548 | 0.378 | (0.104,1.364) | 0.137 |
| Gestational age (weeks) | |||||||
| <37 | 7 (21.2) | 1.000 | 1.000 | ||||
| 37–39 | 196 (28.6) | 1.486 | (0.634,3.479) | 0.362 | 2.170 | (0.686,6.862) | 0.187 |
| ≥40 | 59 (23.9) | 1.166 | (0.481,2.823) | 0.734 | 1.891 | (0.571,6.261) | 0.297 |
| Season of birth | |||||||
| Summer (Jun–Aug) | 46 (27.1) | 1.000 | 1.000 | ||||
| Autumn (Sep–Nov) | 131 (29.0) | 1.104 | (0.744,1.638) | 0.625 | 1.079 | (0.697,1.673) | 0.732 |
| Winter (Dec–Feb) | 85 (25.2) | 0.909 | (0.598,1.381) | 0.656 | 0.882 | (0.556,1.399) | 0.593 |
| Maternal education | |||||||
| Middle school or lower | 6 (21.4) | 1.000 | 1.000 | ||||
| High school | 27 (24.1) | 1.165 | (0.428,3.170) | 0.765 | 1.125 | (0.396,3.194) | 0.826 |
| College or higher | 230 (27.9) | 1.417 | (0.567,3.540) | 0.455 | 1.291 | (0.489,3.407) | 0.606 |
| Maternal age (years) | |||||||
| <25 | 17 (27.4) | 1.000 | 1.000 | ||||
| 25–29 | 128 (25.6) | 0.911 | (0.503,1.648) | 0.758 | 0.891 | (0.480,1.652) | 0.713 |
| 30–34 | 92 (28.3) | 1.045 | (0.569,1.920) | 0.887 | 0.997 | (0.526,1.891) | 0.993 |
| ≥35 | 24 (31.2) | 1.199 | (0.573,2.506) | 0.630 | 1.156 | (0.525,2.545) | 0.718 |
| Maternal prepregnancy BMI (kg/m2) | |||||||
| <18.5 | 42 (28.0) | 1.000 | 1.000 | ||||
| 18.5–24.9 | 182 (26.2) | 0.914 | (0.616,1.356) | 0.655 | 0.866 | (0.572,1.310) | 0.495 |
| 25–29.9 | 29 (31.5) | 1.184 | (0.672,2.085) | 0.559 | 1.134 | (0.622,2.065) | 0.682 |
| ≥30 | 9 (34.6) | 1.361 | (0.563,3.292) | 0.494 | 1.435 | (0.550,3.746) | 0.461 |
| Household income | |||||||
| <100K | 74 (27.1) | 1.000 | 1.000 | ||||
| ≥100K | 146 (27.0) | 0.997 | (0.718,1.383) | 0.983 | 0.922 | (0.635,1.337) | 0.667 |
| Unknown | 48 (27.3) | 1.008 | (0.659,1.544) | 0.969 | 1.051 | (0.659,1.675) | 0.835 |
aP-values for binary logistic regression.
*P≤0.05.
Discussion
In this study, we found that CB-IgE levels were not normally distributed and that most CB-IgE levels were below 0.5 kU/L, as stated in previous reports.9 A total of 268 (27.10%) infants had elevated CB-IgE (≥0.5 kU/L), which was similar to Ferguson et al.13 (19.30%) and Chieh-An Liu et al.’s (23.70%) reports.14 Most studies have shown that elevated CB-IgE levels have a role in the future development of allergic diseases.4,5,15–18 For example, elevated CB-IgE has been a useful measure of subsequent risk of food allergy/urticaria at 12 months19 and a cohort study showed that the risk of allergy development at the age of 4 (OR = 2.92) and 10 (OR = 1.73) was significantly correlated with increased IgE level in newborn umbilical cord blood.20 Hence, CB-IgE level is believed to be correlated with allergic diseases. Then we evaluated the effect of variable factors on CB-IgE levels.
Our study showed that newborn gender was positively correlated with CB-IgE levels. Consistent with our findings, Petrovičová et al.,21 De Amici et al.,8 Iraj Mohammadzadeh et al.,16 Scirica et al.,22 and Chien-Han Chen et al.23 also found that the CB-IgE level was higher in male newborns, possibly because of interaction between interleukin-13 (IL-13) and CB-IgE, which is modified by male sex.24 And CB-IgE levels might reflect early differences in immune system development and function between boys and girls that contribute to the known predominance of asthma and related symptoms among boys rather than girls before puberty.25 Based on the results of previous studies and our findings, it seems that gender is an important factor concerning the IgE level.
In this study, the univariate analysis indicated that cesarean section was associated with higher CB-IgE levels, which is consistent with current results.7,21,26,27 The reason may be that cesarean section could induce neonatal stress and changes in intestinal flora.22
The present study has some limitations. Firstly, we did not collect blood samples from the mothers and could not measure maternal IgE levels; however, a strong positive association between maternal IgE level and CB-IgE level has been well proven.11,16 Secondly, we did not measure IgA levels in the cord blood as a marker of maternal blood contamination, but previous studies using cord blood IgA levels as an indicator of maternal contamination have reported a very low rate of contamination.28,29 Thirdly, subjects in this study should be followed up to reveal the link between CB-IgE elevation in boys and future allergy development. And the underlying mechanisms need to be explored in our future studies.
In conclusion, in this study, newborn gender was found to be a strong predictor of elevated CB-IgE. The delivery mode was a probable predictor.
Funding information
This research is funded by the Youth Program of National Nature Science Foundation of China (No. 81900018) and Project for Innovation Teams in Local High Level Universities in Shanghai.
Conflicts of interest
The authors declare no conflicts of interest.
REFERENCES
1. Akinbami LJ, Simon AE, Schoendorf KC. Trends in allergy prevalence among children aged 0–17 years by asthma status, United States, 2001-2013. J Asthma. 2016;53:356–362. 10.3109/02770903.2015.1126848
2. Liška J, Siala K, Čuláková B, Holeček V, Sobotová Š, Sýkora J et al. 10-Year experience with umbilical cord blood IgE and microbiome therapy. Ital J Pediatr. 2019;45:35. 10.1186/s13052-019-0620-3
3. Huang C, Liu W, Hu Y, Zou Z, Zhao Z, Shen L, et al. Updated prevalences of asthma, allergy, and airway symptoms, and a systematic review of trends over time for childhood asthma in shanghai, China. PLoS One. 2015;10:e0121577. 10.1371/journal.pone.0121577
4. Nissen SP, Kjaer HF, Høst A, Nielsen J, Halken S. Can family history and cord blood IgE predict sensitization and allergic diseases up to adulthood? Pediatr Allergy Immunol. 2015;26:42–48. 10.1111/pai.12264
5. Shah PS, Wegienka G, Havstad S, Johnson CC, Ownby DR, Zoratti EM.The relationship between cord blood immunoglobulin E levels and allergy-related outcomes in young adults. Ann Allergy Asthma Immunol. 2011;106:245–251. 10.1016/j.anai.2010.12.006
6. Chawes. Low-grade disease activity in early life precedes childhood asthma and allergy. Dan Med J. 2016;63:B5272.
7. Mohammad Nabavi, Raheb Ghorbani, Amir Massod Asadi, Mohammad Faranoush. Factors associated with cord blood IgE levels. Asian Pac J Allergy Immunol. 2013;31:157–162. 10.12932/AP0234.31.2.2013
8. De Amici M, Perotti F, Marseglia GL, Ierullo AM, Bollani L, Decembrino L, et al. Cord and blood levels of newborn IgE: correlation, role and influence of maternal IgE. Immunobiology. 2017;222:450–453. 10.1016/j.imbio.2016.08.004
9. Latifi-Pupovci H, Lokaj-Berisha V, Lumezi B. Relationship of cord blood immunoglobulin E and maternal immunoglobulin E with birth order and maternal history of allergy in Albanian mother/neonate pairs. Open Access Maced J Med Sci. 2017;5:751–756. 10.3889/oamjms.2017.150
10. Meulenbroek LA, Knippels LM. Cord blood IgE: fetal or maternal? Clin Exp Allergy. 2015;45:1012–1014. 10.1111/cea.12530
11. Hernández E, Barraza-Villarreal A, Escamilla-Núñez MC, Hernández-Cadena L, Sly PD, Neufeld LM, et al. Prenatal determinants of cord blood total immunoglobulin E levels in Mexican newborns. Allergy Asthma Proc. 2013;34:e27–e34. 10.2500/aap.2013.34.3688
12. Fereidouni M, Nami FA, Serki E, Arefi M. Evaluation of cord blood immunoglobulin E and its association with maternal factors in a group of Iranian newborns. J Cell Biochem. 2019;120:13658–13663. 10.1002/jcb.28639
13. Ferguson A, Dimich-Ward H, Becker A, Watson W, DyBuncio A, Carlsten C, et al. Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort. Pediatr Allergy Immunol. 2009;20:710–713. 10.1111/j.1399-3038.2009.00869.x
14. Liu C-A, Wang C-L, Chuang H, Ou C-Y, Hsu T-Y, Yang KD.Prediction of elevated cord blood IgE levels by maternal IgE levels, and the neonate’s gender and gestational age. Chang Gung Med J. 2003;26:561–569.
15. Sadeghnejad A, Karmaus W, Davis S, Kurukulaaratchy RJ, Matthews S, Arshad SH. Raised cord serum immunoglobulin E increases the risk of allergic sensitisation at ages 4 and 10 and asthma at age 10. Thorax. 2004;59:936–942. 10.1136/thx.2004.024224
16. Mohammadzadeh I, Haghshenas M, Asefi S, Alizadeh-Navaei R. IgE level in newborn umbilical cord and its relationship with some maternal factors. Clin Mol Allergy. 2019;17:11. 10.1186/s12948-019-0115-1
17. Pesonen M, Kallio MJT, Siimes MA, Elg P, Björksten F, Ranki A. Cord serum immunoglobulin E as a risk factor for allergic symptoms and sensitization in children and young adults. Pediatr Allergy Immunol. 2009;20:12–18. 10.1111/j.1399-3038.2008.00736.x
18. Chen C-H, Lee YL, Wu M-H, Chen P-J, Wei T-S, Wu C-T, et al. Environmental tobacco smoke and male sex modify the influence of IL-13 genetic variants on cord blood IgE levels. Pediatr Allergy Immunol. 2012;23:456–463. 10.1111/j.1399-3038.2012.01278.x
19. Kaan A, Dimich-Ward H, Manfreda J, Becker A, Watson W, Ferguson A, et al. Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months. Ann Allergy Asthma Immunol. 2000;84(1):37–42. 10.1016/S1081-1206(10)62738-X
20. Sadeghnejad A, Karmaus W, Davis S, Kurukulaaratchy RJ, Matthews S, Arshad SH. Raised cord serum immunoglobulin E increases the risk of allergic sensitisation at ages 4 and 10 and asthma at age 10. Thorax. 2004;59(11):936–942. 10.1136/thx.2004.024224
21. Petrovičová O, Bánovčin P, Babušíková E, Jeseňák M. Factors modifying cord blood IgE levels—a pilot study. Epidemiol Mikrobiol Imunol. 2016;65:226–231.
22. Scirica CV, Gold DR, Ryan L, Abulkerim H, Celedón JC, Platts-Mills TAE, et al. Predictors of cord blood IgE levels in children at risk for asthma and atopy. J Allergy Clin Immunol. 2007;119:81–88. 10.1016/j.jaci.2006.09.002
23. Chen C-H, Lee YL, Wu M-H, Chen P-J, Wei T-S, Chen P-C, et al. Sex-moderated interactions between IL4/IL13 pathway genes and prenatal environment on cord blood IgE levels. Clin Exp Allergy. 2019;49:112811–38. 10.1111/cea.13419
24. Croner S, Kjellman N, Eriksson B, Roth A. IgE screening in 1701 newborn infants and the development of atopic disease during infancy. Arch Dis Child. 1982;57(5):364–368. 10.1136/adc.57.5.364
25. Caracta CF. Gender differences in pulmonary disease. Mt Sinai J Med. 2003;70(4):215–224.
26. Renz-Polster H, David MR, Buist AS, Vollmer WM, O’Connor EA, Frazier EA, et al. Caesarean section delivery and the risk of allergic disorders in childhood. Clin Exp Allergy. 2005;35:1466–1472. 10.1111/j.1365-2222.2005.02356.x
27. Negele K, Heinrich J, Borte M, von Berg A, Schaaf B, Lehmann I, et al. Mode of delivery and development of atopic disease during the first 2 years of life. Pediatr Allergy Immunol. 2004;15:48–54. 10.1046/j.0905-6157.2003.00101.x
28. Pfefferle PI, Sel S, Ege MJ, Büchele G, Blümer N, Krauss-Etschmann S, et al. Cord blood allergen-specific IgE is associated with reduced IFN-gamma production by cord blood cells: the Protection against Allergy-Study in Rural Environments (PASTURE) Study. J Allergy Clin Immunol. 2008;122:711–716. 10.1016/j.jaci.2008.06.035
29. Bergmann RL, Schulz J, Günther S, Dudenhausen JW, Bergmann KE, Bauer CP, et al. Determinants of cord-blood IgE concentrations in 6401 German neonates. Allergy. 1995;50:65–71. 10.1111/j.1398-9995.1995.tb02484.x