http://orcid.org/0000-0002-9387-2056
Figures
Abstract
Background
Night shift work surrounding pregnancy may contribute to the risk of developing atopic diseases in offspring due to alterations in the prenatal environment, from stress.
Objective
To examine the association of maternal night shift work surrounding pregnancy and offspring risk of developing atopic diseases from childhood to adolescence.
Methods
We examined the association between night shift work before and during pregnancy among 4,044 mothers in the Nurses’ Health Study II (NHSII) and atopic dermatitis, asthma and hay fever risk in 4,813 of their offspring enrolled in the Growing Up Today Study (GUTS). Mothers reported whether GUTS participants had ever been diagnosed with atopic dermatitis, asthma or hay fever in the GUTS Mothers’ questionnaire. Generalized estimating equation regression models were used to estimate multivariable adjusted odds ratios (OR) and 95% confidence intervals (CIs).
Results
There were no significant associations between pre-conception maternal night shift work and risk of atopic dermatitis, asthma or hay fever in their offspring. Among 545 mothers with information on night shift work during pregnancy, shift work also was not associated with atopic dermatitis, asthma or hay fever in the offspring. Stratified analyses by history of parental atopy and maternal chronotype showed some statistically significant findings, but they were inconsistent and no significant interaction was seen with increasing duration of night shift work.
Citation: Rada S, Strohmaier S, Drucker AM, Eliassen AH, Schernhammer ES (2020) Night shift work surrounding pregnancy and offspring risk of atopic disease. PLoS ONE 15(4): e0231784. https://doi.org/10.1371/journal.pone.0231784
Editor: Sara Ornaghi, Universita degli Studi di Milano-Bicocca Scuola di Medicina e Chirurgia, ITALY
Received: November 26, 2019; Accepted: March 31, 2020; Published: April 16, 2020
Copyright: © 2020 Rada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Data cannot be shared publicly because the authors do not own the data. Data are available from the Channing Division of Network Medicine Institutional Data Access Committee upon filing out a collaboration request form. The form and more detailed information can be found under https://www.nurseshealthstudy.org/researchers. The authors did not have special access privileges that others could not request.
Funding: This study was supported by Center for Disease Control and Prevention/The National Institute for Occupational Safety and Health grant 5R01OH009803 (PI: Schernhammer ES), as well as grant UM1 CA176726 from the National Institutes of Health.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Atopic diseases such as atopic dermatitis (AD), asthma and hay fever are among the most common chronic conditions in childhood and often coexist in the same individual [1,2]. Previous studies suggest there may be an “atopic march;” that these atopic manifestations progress sequentially beginning with AD and leading to asthma and/or hay fever [3,4]. AD is a common inflammatory skin disease that usually begins in childhood, with a prevalence of 20% in children worldwide [5]. AD can have detrimental effects on overall quality of life, whether the patient is a child or adult [6]. Among skin diseases, dermatitis is accountable for the largest global burden of disability-adjusted life years (DALYS) and morbidity (Years Lived with Disability) [7]. While AD is more prevalent in children under five years of age, current literature conveys that AD can persist into adolescence and adulthood [8–11]. It is important to understand this disease early on and how prenatal exposure to early life factors can potentially affect the onset and progression of this skin disease. Family history (e.g. shared genetics and environmental factors) has been mentioned as the most common driving factor for developing any atopic disease [1,12–16].
However, past research also suggested that changes in the prenatal environment, due to different maternal exposures [17–19], can influence the development of the fetus and potentially modulate the risk of diseases later in life [20].
Rotating night shift work is known to negatively impact circadian rhythms both in mothers working night shifts as well as in their unborn children [21,22]. It is considered an emerging risk factor for multiple chronic diseases and increased inflammation likely because of stress caused from circadian disruption [23–28].
In particular, stress due to night work appears to reduce oxidative DNA damage repair capacity due to melatonin suppression [29]. Previous studies have additionally reported epigenetic alterations in individuals who work night shifts [30,31], suggesting the potential for transgenerational impacts [32,33]. Further, the stress experienced from circadian rhythm changes during night shift work could potentially induce changes in the intrauterine environment [34,35], and is a potential risk factor for elevated immunoglobulin E (IgE) in cord blood, suggesting increased inflammation and transmission of IgE to the child, and T-helper 1 (Th1)/ T-helper 2 (Th2) imbalances in the in utero environment, all of which could enable the development of atopic diseases [36–38].
Little is known about prenatal occupational exposure as a risk factor for childhood and adolescent atopic diseases and there are no studies so far that specifically assessed the association of night shift work before and during pregnancy and the incidence of offspring atopic diseases. The aim of this study is to determine the association between maternal night shift work before pregnancy and during pregnancy and the risk of ever developing AD, asthma or hay fever in the offspring. We hypothesized that the risk of these atopic diseases in the offspring will be increased if mothers worked night shifts before pregnancy and that this risk would be even more elevated if mothers also worked night shifts during pregnancy. Because individual chronotype may interact with working times and thereby modulate disease risk [39], we tested how chronotype may modulate these associations.
Methods
Study population
The Nurses’ Health Study II (NHSII) is an ongoing prospective cohort study of female registered nurses that was established in 1989. A total of 116,429 nurses, aged 25 to 42 responded to a mailed questionnaire regarding their lifestyle, health behaviors and medical histories. Follow-up questionnaires are mailed biennially and used to update this information. Children, aged 9 to 15, who were born to women from the NHSII between 1987 and 1995, were invited to participate in the Growing Up Today Study (GUTS) in 2004. After obtaining maternal consent, invitation letters and questionnaires were mailed to 17,280 children which inquired about their health and lifestyle factors. Of these children, 10,918 completed and returned the questionnaires. Follow-up questionnaires, used to updated information on health and lifestyle, were mailed in 2006, 2008, 2011 and 2013. Mothers of GUTS participants also completed questionnaires related to their children in 2009.
Exposure assessment
Maternal history of rotating night shift work before conception.
Nurses were first asked to report the total number of years they worked rotating night shifts on the NHSII baseline questionnaire in 1989. Rotating night shift work was defined as working “at least three nights per month in addition to working days or evenings in the respective month”. This was updated in 1991 and 1993. The 2001 questionnaire retrospectively assessed night shift work duration for the time between 1993 and 1995. Since GUTS children were born up until 1995, baseline shift work history and updated shift work information was added together to derive a cumulative shift work exposure for shift work before conception from 1989 to 1995.
Maternal rotating night shift work during pregnancy.
In 2001, NHSII participants who had reported one pregnancy since 1993 and were working as a nurse were sent a supplementary questionnaire which inquired about specific occupational exposures, including rotating shift work during their most recent pregnancy since 1993.
Outcome assessment
The primary outcome was physician-diagnosed AD reported by the mother in the 2009 GUTS Mothers’ questionnaire, where mothers were asked if their child “ever had physician-diagnosed eczema (AD)”. As secondary outcomes we considered maternal reports of physician-diagnosed asthma and hay fever (also from 2009), since individuals with these atopic diseases are more likely to have a true AD diagnosis [2].
Additionally, we had information on child-reported AD outcomes from the GUTS questionnaires in 2006, 2008, 2013. These were combined with maternal reports of AD to obtain more consistent reports of AD diagnosis.
Covariate assessment
The 2009 GUTS Mothers’ questionnaire assessed if mothers ever breastfed their child. Data regarding maternal and paternal physician-diagnosed eczema, asthma and hay fever was also obtained from this questionnaire. Parental atopy was derived by combining NHSII participant’s report of her own physician-diagnosed eczema, asthma or hay fever, as well as their child’s biological father’s diagnosis. Maternal age at delivery was calculated by computing the difference between mother’s and child’s dates of birth. Using the validated food frequency questionnaire (FFQ) from the 1991 main NHSII questionnaire, we were able to examine maternal diet quality, from which alcohol intake and the Alternative Healthy Eating Index (AHEI) was derived [40]. Energy expenditure in metabolic equivalent (MET) hours per week was derived from the 1989 baseline questionnaire when participants were asked to report frequency of various physical activities. Smoking habits and weight and height measurements before pregnancy were collected biennially and the information that was closest to, but before the conception of the first child included in the study, was used for determining smoking status and to calculate body mass index (BMI).
We obtained US Census tract data from 1989, including median household income and percentage of the population having a college degree in the neighborhood the mother lived, which was used to depict the family’s socioeconomic status (SES) around the child’s birth and early childhood. Other variables used to capture SES include family household income in 2001, husband’s level of education in 1999, and geographic region where GUTS children were living at baseline in 2004.
In 2009, maternal chronotype was assessed by a single question from the Morningness-Eveningness Questionnaire [41]. This question has been validated for classifying individuals as “definitely a morning type”, “rather more a morning than an evening type”, “rather more an evening than a morning type”, “definitely an evening type” or none of these [42].
Analysis sample
The final sample for the analysis assessing pre-conception shift work and atopy outcomes included 4,044 mothers who had given birth to 4,813 children. Of the original cohort of 10,918 children, 4,720 were excluded because they were born before 1989 (the first exposure assessment of maternal rotating night shift work occurred in 1989). Further exclusions were twins and triplets (87 mothers, 195 children), non-full-term pregnancies (<37 weeks gestation) (1,001 mothers, 1,183 children), and mother-child pairs that had missing exposure information (6 mothers, 7 children), see S1 Fig for an overview.
The sample used to assess the association of shift work during pregnancy and atopy outcomes comprised of mothers who participated in the occupational supplemental questionnaire in 2001. A total of 621 mother-child pairs were identified. Of these pairs, non-full-term pregnancies (72 mother-child pairs) were excluded as well as pairs with missing exposure information (4 mother-child pairs). A total of 545 mother-child pairs were included in the final analysis of rotating shift work during pregnancy and atopic outcomes in offspring.
Statistical analysis
Since siblings were included in the analysis relating maternal history of rotating night shift work before conception and atopic outcomes, we used generalized estimating equation (GEE) regression models to account for familial clustering in the estimation of odds ratios (ORs) and 95% confidence intervals (CIs) for AD, asthma and hay fever across four categories of cumulative rotating night shift work before conception (none, < 3years, 3–5 years, ≥ 6 years). We also examined these atopic outcomes in offspring by comparing mothers who ever worked rotating night shifts versus mothers who never worked rotating night shifts.
Basic models were adjusted for offspring age at baseline and sex. In multivariable model 1 (MV model 1), we further adjusted for maternal age at pregnancy, BMI and smoking status before pregnancy, AHEI diet score, physical activity, husband’s education level, parity, geographic region of residence at GUTS baseline, and the Census tract education rate in that region in 1989. Parental atopy was added to the existing covariates used in MV model 1 into our fully adjusted model (MV model 2). To test for possible effect modification, we assessed the association between night shift work and offspring atopic outcomes by including multiplicative interaction terms (night shift work and parental atopy; maternal chronotype) in multivariable regression models.
To obtain odds ratios and 95% CIs comparing children whose mothers worked night shifts during pregnancy to those whose mothers did not, we used standard multivariable logistic regression models with similar adjustment sets as described above.
All analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC) and all statistical tests were two-sided and considered statistically significant at p <0.05.
This study was approved by the Human Subjects Committees at the Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health (Boston, Massachusetts).
Results
Maternal history of rotating night shift work before conception
The 4,044 mothers in our analysis were, on average, 33.4 (±3.6) years of age when they gave birth to the children in this study. The 4,813 children were, on average, 11.7 (± 1.2) years of age when they were enrolled in the GUTS study with 46.6% being girls and 53.4% being boys. A total of 2,620 mothers (64.8%) ever worked rotating night shifts. When comparing maternal characteristics, there were minor differences across categories of shift work duration (Table 1). Mothers who reported working a longer duration of shift work were slightly older at delivery and had a slightly higher BMI. They were also more likely to be past or current smokers before pregnancy and to adhere to the AHEI diet. Mothers reporting a longer duration of shift work also had higher rates of caesarean deliveries. Mothers who worked 3–5 years of night shift work had a higher frequency of AD and also reported a higher frequency of fathers (child’s biological father) having AD.
Since differences between the age- and sex-adjusted versus multivariable models were small, we focused on the results from our fully-adjusted models (MV models 2). There was no overall association between maternal night shift work before pregnancy and maternal-reported offspring AD (ORever nightshifts = 0.98; 95% CI = 0.80–1.19) (Table 2). Shift work was also not associated with either asthma (ORever nightshifts = 1.09; 95% CI = 0.92–1.31) or hay fever (ORever nightshifts = 1.07; 95% CI = 0.89–1.28). There was no significant trend with increasing years of rotating night shift work (all Ptrend > 0.05).
Results remained unchanged when using children’s self-reported outcomes rather than maternal-reported outcomes (S1 Table). The proportion of mothers reporting atopic disease when their offspring did not were variable for the different outcomes (AD = 0.52; asthma = 0.22; hay fever = 0.67). We used consistent maternal-reported and child’s self-reported outcomes to present a more stringent outcome and though results slightly differed, they remained non-significant (AD ORever nightshifts = 1.19; 95% CI = 0.90–1.57; asthma ORever nightshifts = 1.06; 95% CI = 0.87–1.29; hay fever ORever nightshifts = 1.24; 95% CI = 0.93–1.64) (Table 3). S2 Table shows the associations between shift work and maternal reports of their offspring being diagnosed with all three atopic diseases (ORever nightshifts = 0.95; 95% CI = 0.60–1.49). S3 Table shows outcomes if mothers reported their child being diagnosed with either AD, asthma or hay fever. Although any report of night shift work was not associated with atopy risk (ORever nightshifts = 1.13; 95% CI = 0.97–1.31), we observed a suggestive trend of increased risk of atopy in offspring associated with longer duration of maternal night shift work (OR≥6yrs night work = 1.27; 95% CI = 0.99–1.63; Ptrend = 0.07).
We conducted stratified analyses by history of parental atopy (S4 Table) and maternal chronotype (S5 Table). While we observed some statistically significant findings, overall trends were inconsistent and no significant interaction was seen with increasing duration of night shift work (parental atopy Pinteraction = 0.06; maternal chronotype Pinteraction = 0.12).
Maternal rotating night shift work during pregnancy
Out of the 545 mother-child pairs included in this analysis, 20% of mothers ever worked night shifts during pregnancy. The association between maternal night shift work during pregnancy and risk of maternal-reported offspring AD was not significant (MV model 2, ORever nighshifts = 0.60; 95% CI = 0.30–1.20), neither did we observe any associations with risk of asthma (MV model 2, ORever nightshifts = 0.61; 95% CI = 0.28–1.29) or hay fever (MV model 2 ORever nightshifts = 0.80; 95% CI = 0.39–1.65) (see S6 Table).
Discussion
Overall, our study involving mothers from the NHSII cohort and their offspring in GUTS found no apparent association between maternal history of night shift work before pregnancy or during pregnancy and AD or other atopic diseases in their offspring. While a few associations were statistically significant in our stratified models, they were inconsistent and did not present any clear patterns of association.
Night shift work, a major source of chronic circadian disruption, has previously been linked to increased risk of chronic diseases [24,43–45] and has also been suggested as a biological, psychosocial and physiological health stressor [46,47] due to the substantial changes in circadian rhythm that night workers encounter. Circadian rhythm plays a role in the pathogenesis of allergic reactions and is important for regulating specific immune functions [48,49]. This suggests that the stress induced by changes in the circadian clock might have an impact on developing AD or other related diseases.
An animal study by Takita et al. investigated whether biological clock dysfunction affected the pathogenesis of contact hypersensitivity (CHS) in CLOCK mutant mice which elicits a similar response to human allergic contact dermatitis. They discovered that circadian dysfunction in CLOCK mutant mice impacted their allergic response exhibited by increased ear swelling after 24 hours, increased serum IgE concentration and increased number of mast cells when compared to wild-type mice [50]. This provides support for the hypothesis that disruptions in the circadian clock give way to the onset of allergic diseases.
Lin et al. found that—in humans—psychosocial stress in the mother is a potential risk factor for elevated cord blood IgE and hence in the newborn [36]. Immunoglobulin E is reportedly strongly associated with atopic multi-morbidities such as eczema, asthma and rhinitis, throughout childhood and adolescence within the individual [51], suggesting that not only lifestyle factors and behaviors during childhood influence the development of allergies, but that in utero exposures might also be important.
Maternal stress caused from different factors such as postnatal psychological problems [35], prenatal depression/anxiety [52,53] and employment/job strain [54,55] is shown to increase the risk of eczema and asthma in their offspring. A review by Chan et al. also examined studies addressing similar maternal stress factors and found postpartum and prenatal depression, anxiety and adverse life events to be associated with an increased risk of developing AD in their offspring '[56], but to our knowledge, there is no other study that has examined the relationship specifically between maternal night shift work exposure before and during pregnancy and AD.
Strengths of our study include longitudinal follow-up of detailed information of mothers and offspring as well as being able to consider multiple potential confounding variables. Our study has a few limitations that should be mentioned. Regarding night shift work during pregnancy, the timing of the supplemental pregnancy questionnaire reduced the time window (1993–1995) to obtain during-pregnancy exposure information. Consequently, we had limited power when assessing the relationship between during-pregnancy shift work exposure and atopic outcomes. Furthermore, our study relied solely on self-reported outcomes for atopic diseases, which could contribute to outcome misclassifications. Diagnoses for AD in GUTS have not been validated, however, self and caregiver-reported childhood AD has previously shown to be valid [57]. Unfortunately, we lack information regarding the age of diagnosis of AD, asthma, or hay fever. Since GUTS participants were aged 11 to 17 when they were first asked if they had ever been diagnosed with AD, this constitutes another possibility for outcome misclassification; however, in secondary analyses restricting to consistent self-report of the outcome by both the mother and the child, results remained largely unchanged. In previous studies, the most important factors associated with correctly remembering and reporting AD included long duration of AD in childhood, concomitant atopic disease, and eczema after the age of 15 [58,59]. Considering such a scenario in our study, we might have missed any associations between rotating night shift work of the mothers before and during pregnancy with less severe AD in their offspring, which appears unlikely if there is no association with presumably more severe/longer duration AD to begin with. Further, we only had limited information on paternal factors. Nevertheless, we could adjust for husband’s education as a proxy for socioeconomic status in all our multivariable models, which we considered the most important confounding variable possibly affecting both maternal shift work exposure and offspring weight outcomes. Lastly, since mothers in our analyses were slightly older than the nation’s average, these findings may not be generalizable to younger mothers.
In conclusion, we found no consistent associations between maternal night shift work and risk for atopic conditions in offspring. Future studies with more detailed exposure information and specific age at disease diagnosis would be helpful to examine this relationship in more detail.
Supporting information
S1 Fig. Flow chart showing how we derived the analysis sample from the full GUTS 2 cohort.
https://doi.org/10.1371/journal.pone.0231784.s001
(DOCX)
S1 Table. Child’s self-reported atopic dermatitis, asthma and hay fever: Adjusted odds ratios (OR) and 95% confidence intervals (CI) for offspring atopic dermatitis during childhood and adolescence according to maternal rotating night shiftwork history before pregnancy, restricted to singleton, full-term births.
https://doi.org/10.1371/journal.pone.0231784.s002
(DOCX)
S2 Table. All allergies outcome: Adjusted odds ratios (OR) and 95% confidence intervals (CI) for offspring atopic dermatitis during childhood and adolescence according to maternal rotating night shiftwork history before pregnancy, restricted to singleton, full-term births.
https://doi.org/10.1371/journal.pone.0231784.s003
(DOCX)
S3 Table. Any allergy outcome: Adjusted odds ratios (OR) and 95% confidence intervals (CI) for offspring atopic dermatitis during childhood and adolescence according to maternal rotating night shiftwork history before pregnancy, restricted to singleton, full-term births.
https://doi.org/10.1371/journal.pone.0231784.s004
(DOCX)
S4 Table. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for offspring atopic dermatitis, asthma and hay fever during childhood and adolescence according to maternal rotating night shiftwork history before pregnancy, restricted to singleton, full-term births, stratified by parental atopyx.
https://doi.org/10.1371/journal.pone.0231784.s005
(DOCX)
S5 Table. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for offspring atopic dermatitis, asthma and hay fever during childhood and adolescence according to maternal rotating night shiftwork history before pregnancy, restricted to singleton, full-term births, stratified by maternal chronotype (Definite morning type vs. Intermediate type vs. Definite evening type).
https://doi.org/10.1371/journal.pone.0231784.s006
(DOCX)
S6 Table. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for offspring atopic dermatitis, asthma and hay fever during childhood and adolescence by night shift exposure during pregnancy, restricted to singleton, full-term births.
https://doi.org/10.1371/journal.pone.0231784.s007
(DOCX)
Acknowledgments
We thank the thousands of participants in the Growing Up Today Study, as well as their mothers participating in the Nurses’ Health Study II.
References
- 1. Thomsen SF. Epidemiology and natural history of atopic diseases. Eur Clin Respir J. 2015 [cited 2020 Feb 10];2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26557262
- 2. Pinart M, Benet M, Annesi-Maesano I, von Berg A, Berdel D, Carlsen KCL, et al. Comorbidity of eczema, rhinitis, and asthma in IgE-sensitised and non-IgE-sensitised children in MeDALL: a population-based cohort study. Lancet Respir Med. 2014;2(2):131–40. pmid:24503268
- 3. Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol. 2003;112(6):S118–27.
- 4. Spergel JM. From atopic dermatitis to asthma: the atopic march. Ann Allergy, Asthma Immunol. 2010;105(2):99–106.
- 5. Asher MI, Montefort S, Björkstén B, Lai CK, Strachan DP, Weiland SK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet. 2006;368(9537):733–43. pmid:16935684
- 6. Drucker AM, Wang AR, Li W-Q, Sevetson E, Block JK, Qureshi AA. The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association. J Invest Dermatol. 2017;137(1):26–30. pmid:27616422
- 7. Karimkhani C, Dellavalle RP, Coffeng LE, Flohr C, Hay RJ, Langan SM, et al. Global Skin Disease Morbidity and Mortality. JAMA Dermatology. 2017;153(5):406. pmid:28249066
- 8.
Thomsen SF. Epidemiology and natural history of atopic diseases. http://dx.doi.org/10.3402/ecrj.v2.24642
- 9. Margolis JS, Abuabara K, Bilker W, Hoffstad O, Margolis DJ. Persistence of Mild to Moderate Atopic Dermatitis. JAMA Dermatology. 2014;150(6):593. pmid:24696036
- 10. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: A US population–based study. J Allergy Clin Immunol. 2013;132(5):1132–8. pmid:24094544
- 11. Ballardini N, Kull I, Lind T, Hallner E, Almqvist C, Östblom E, et al. Development and comorbidity of eczema, asthma and rhinitis to age 12—data from the BAMSE birth cohort. Allergy 2012;67(4):537–44. pmid:22335548
- 12.
Williams HC, editor. Genetic epidemiology of atopic dermatitis. In: Atopic Dermatitis: The Epidemiology, Causes and Prevention of Atopic Eczema. Cambridge University Press; 2000.
- 13. Williams HC. Epidemiology of atopic dermatitis. Clin Exp Dermatol. 2000;25(7):522–9. pmid:11122223
- 14. Wen H-J, Chen P-C, Chiang T-L, Lin S-J, Chuang Y-L, Guo Y-L. Predicting risk for early infantile atopic dermatitis by hereditary and environmental factors. Br J Dermatol. 2009;161(5):1166–72. pmid:19785611
- 15. Wadonda-Kabondo N, Sterne JAC, Golding J, Kennedy CTC, Archer CB, Dunnill MGS, et al. Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study. Arch Dis Child. 2004;89(10):917–21. pmid:15383434
- 16. Küster W, Petersen M, Christophers E, Goos M, Sterry W. A family study of atopic dermatitis. Clinical and genetic characteristics of 188 patients and 2,151 family members. Arch Dermatol Res. 1990;282(2):98–102. pmid:2353830
- 17. Vaughn AR, Tannhauser P, Sivamani RK, Shi VY. Mother Nature in Eczema: Maternal Factors Influencing Atopic Dermatitis. Pediatr Dermatol. 2017;34(3):240–6. pmid:28523877
- 18. Dumas O, Varraso R, Gillman MW, Field AE, Camargo CA. Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma. Allergy. 2016;71(9):1295–304. pmid:26969855
- 19. Drucker AM, Pope EI, Field AE, Qureshi AA, Dumas O, Camargo CA. Association Between Maternal Pre-Pregnancy Body Mass Index, Gestational Weight Gain, and Offspring Atopic Dermatitis: A Prospective Cohort Study. J Allergy Clin Immunol Pract. 2019;7(1):96–102.e2. pmid:30414948
- 20. Barker DJ. The Wellcome Foundation Lecture, 1994. The fetal origins of adult disease. Proc R Soc London Ser B Biol Sci. 1995;262(1363):37–43.
- 21. Nehme PA, Amaral F, Lowden A, Skene DJ, Cipolla-Neto J, Moreno CRC. Reduced melatonin synthesis in pregnant night workers: Metabolic implications for offspring. Med Hypotheses. 2019;132:109353. pmid:31421432
- 22. Nehme PA, Amaral FG, Middleton B, Lowden A, Marqueze E, França-Junior I, et al. Melatonin profiles during the third trimester of pregnancy and health status in the offspring among day and night workers: A case series. Neurobiol Sleep Circadian Rhythm. 2019;6:70–6.
- 23. Wang X-S, Armstrong MEG, Cairns BJ, Key TJ, Travis RC. Shift work and chronic disease: the epidemiological evidence. Occup Med (Lond). 2011;61(2):78–89.
- 24. Vetter C, Devore EE, Wegrzyn LR, Massa J, Speizer FE, Kawachi I, et al. Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women. JAMA. 2016;315(16):1726. pmid:27115377
- 25. Wegrzyn LR, Tamimi RM, Rosner BA, Brown SB, Stevens RG, Eliassen AH, et al. Rotating Night-Shift Work and the Risk of Breast Cancer in the Nurses’ Health Studies. Am J Epidemiol. 2017;186(5):532–40. pmid:28541391
- 26. Pan A, Schernhammer ES, Sun Q, Hu FB. Rotating Night Shift Work and Risk of Type 2 Diabetes: Two Prospective Cohort Studies in Women. Groop L, editor. PLoS Med. 2011;8(12):e1001141. pmid:22162955
- 27. Puttonen S, Viitasalo K, Härmä M. Effect of Shiftwork on Systemic Markers of Inflammation. Chronobiol Int. 2011;28(6):528–35. pmid:21797781
- 28. Morris CJ, Purvis TE, Mistretta J, Hu K, Scheer FAJL. Circadian Misalignment Increases C-Reactive Protein and Blood Pressure in Chronic Shift Workers. J Biol Rhythms. 2017;32(2):154–64. pmid:28347188
- 29. Bhatti P, Mirick DK, Randolph TW, Gong J, Buchanan DT, Zhang JJ, et al. Oxidative DNA damage during night shift work. Occup Environ Med. 2017;74(9):680–3. Available from: pmid:28652381
- 30. Zhu Y, Stevens RG, Hoffman AE, Tjonneland A, Vogel UB, Zheng T, et al. Epigenetic impact of long-term shiftwork: pilot evidence from circadian genes and whole-genome methylation analysis. Chronobiol Int. 2011;28(10):852–61. pmid:22080730
- 31. Gaine ME, Chatterjee S, Abel T. Sleep Deprivation and the Epigenome. Front Neural Circuits. 2018;12:14. pmid:29535611
- 32. Strohmaier S, Devore EE, Vetter C, Missmer S, Heather Eliassen A, Rosner B, et al. Night Shift Work Before and During Pregnancy and Offspring Weight Outcomes Through Adolescence. Obesity. 2018;26(9):1491–500. pmid:30226007
- 33. Strohmaier S, Devore EE, Vetter C, Eliassen AH, Rosner B, Okereke OI, et al. Night shift work before and during pregnancy in relation to depression and anxiety in adolescent and young adult offspring. Eur J Epidemiol. 2019;34(7):625–35. pmid:31081539
- 34. Matteo B, Palmer KT, Coggon D, Carugno M, Cromi A, Ferarrio MM. Shift work and pregnancy outcomes: a systematic review with meta-analysis of currently available epidemiological studies. 2BJOG an Int J Obstet Gynaecol. 2011;118(12):1429–37.
- 35. Wang IJ, Wen HJ, Chiang TL, Lin SJ, Guo YL. Maternal psychologic problems increased the risk of childhood atopic dermatitis. Pediatr Allergy Immunol. 2016;27(2):169–76. pmid:26647908
- 36. Lin Y-C, Wen H-J, Lee Y-L, Guo YL. Are maternal psychosocial factors associated with cord immunoglobulin E in addition to family atopic history and mother immunoglobulin E? Clin Exp Allergy. 2004;34(4):548–54. pmid:15080806
- 37. Tegethoff M, Greene N, Olsen J, Schaffner E, Meinlschmidt G. Stress during Pregnancy and Offspring Pediatric Disease: A National Cohort Study. Environ Health Perspect. 2011;119(11):1647–52. pmid:21775267
- 38. Warner JA. Primary sensitization in infants. Ann Allergy, Asthma Immunol. 1999;83(5):426–30.
- 39. Luyster FS, Strollo PJ, Zee PC, Walsh JK, Boards of Directors of the American Academy of Sleep Medicine and the Sleep Research Society. Sleep: A Health Imperative. Sleep. 2012;35(6):727–34. pmid:22654183
- 40. McCullough ML, Feskanich D, Stampfer MJ, Giovannucci EL, Rimm EB, Hu FB, et al. Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. Am J Clin Nutr. 2002;76(6):1261–71. pmid:12450892
- 41. Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol. 1976 4(2):97–110. pmid:1027738
- 42. Megdal SP, Schernhammer ES. Correlates for poor sleepers in a Los Angeles high school. Sleep Med. 2007;9(1):60–3. pmid:17869576
- 43. Vetter C, Devore EE, Ramin CA, Speizer FE, Willett WC, Schernhammer ES. Mismatch of Sleep and Work Timing and Risk of Type 2 Diabetes. Diabetes Care. 2015;38(9):1707–13. pmid:26109502
- 44. Papantoniou K, Castaño-Vinyals G, Espinosa A, Aragonés N, Pérez-Gómez B, Burgos J, et al. Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study. Int J Cancer. 2015;137(5):1147–57. pmid:25530021
- 45. Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, et al. Rotating Night Shifts and Risk of Breast Cancer in Women Participating in the Nurses’ Health Study. JNCI J Natl Cancer Inst. 2001;93(20):1563–8. pmid:11604480
- 46. Straif K, Baan R, Grosse Y, Secretan B, Ghissassi F El, Bouvard V, et al. Carcinogenicity of shift-work, painting, and fire-fighting. Lancet Oncol. 2007;8(12):1065–6. pmid:19271347
- 47. Puttonen S, Härmä M, Hublin C. Shift work and cardiovascular disease—pathways from circadian stress to morbidity. Scandinavian Journal of Work, Environment & Health. Vol. 36, 96–108.
- 48. Scheiermann C, Kunisaki Y, Frenette PS. Circadian control of the immune system. Nat Rev Immunol. 2013;13(3):190–8. pmid:23391992
- 49. Paganelli R, Petrarca C, Di Gioacchino M. Biological clocks: their relevance to immune-allergic diseases. Clin Mol Allergy. 2018;16(1):1.
- 50. Takita E, Yokota S, Tahara Y, Hirao A, Aoki N, Nakamura Y, et al. Biological clock dysfunction exacerbates contact hypersensitivity in mice. Br J Dermatol. 2013;168(1):39–46. pmid:22834538
- 51. Ballardini N, Bergström A, Wahlgren C-F, van Hage M, Hallner E, Kull I, et al. IgE antibodies in relation to prevalence and multimorbidity of eczema, asthma, and rhinitis from birth to adolescence. Allergy. 2016;71(3):342–9. pmid:26505741
- 52. Chang HY, Suh DI, Yang S-I, Kang M-J, Lee S-Y, Lee E, et al. Prenatal maternal distress affects atopic dermatitis in offspring mediated by oxidative stress. J Allergy Clin Immunol. 2016;138(2):468–475.e5. pmid:27016803
- 53. Cookson H, Granell R, Joinson C, Ben-Shlomo Y, Henderson AJ. Mothers’ anxiety during pregnancy is associated with asthma in their children. J Allergy Clin Immunol. 2009;123(4):847–53.e11. pmid:19348924
- 54. Wang IJ, Wen HJ, Chiang TL, Lin SJ, Chen PC, Guo YL. Maternal employment and atopic dermatitis in children: a prospective cohort study. Br J Dermatol. 2013;168(4):794–801. pmid:23528059
- 55. Larsen AD. The effect of maternal exposure to psychosocial job strain on pregnancy outcomes and child development. Dan Med J. 2015;62(2).
- 56. Chan C, Law B, Liu Y-H, Ambrocio A, Au N, Jiang M, et al. The Association between Maternal Stress and Childhood Eczema: A Systematic Review. Int J Environ Res Public Health. 2018;15(3):395.
- 57. Silverberg JI, Patel N, Immaneni S, Rusniak B, Silverberg NB, Debashis R, et al. Assessment of atopic dermatitis using self-report and caregiver report: a multicentre validation study. Br J Dermatol. 2015;173(6):1400–4. pmid:26186170
- 58. Moberg C, Meding B, Stenberg B, Svensson A, Lindberg M. Remembering childhood atopic dermatitis as an adult: factors that influence recollection. Br J Dermatol. 2006;155(3):557–60. pmid:16911281
- 59. Mortz C, Andersen K, Bindslev-Jensen C. Recall Bias in Childhood Atopic Diseases Among Adults in The Odense Adolescence Cohort Study. Acta Derm Venereol. 2015;95(8):968–72. pmid:25916800