Background: Around 30-40% of the world's population will experience allergy, the most common and earliest-onset noncommunicable disease. With a steady rise in the incidence of allergic disease over recent decades, up to 18% of children will suffer a respiratory, food or skin allergy before their 18th birthday. There is compelling evidence that the risk of developing allergy is influenced by early life events and particularly in utero exposures. Methods: A comprehensive literature review was undertaken which outlines prenatal risk factors and potential mechanisms underlying the development of allergy in childhood. Results: Exposures including maternal cigarette smoking, preterm birth and Caesarean delivery are implicated in predisposing infants to the later development of allergy. In contrast, restricted growth in utero, a healthy maternal diet and a larger family size are protective, but the mechanisms here are unclear and require further investigation. Conclusion: To ameliorate the allergy pandemic in young children, we must define prenatal mechanisms that alter the programming of the fetal immune system and also identify specific targets for antenatal interventions.

Keywords:
Diet, Allergy, Developmental programming, Epigenetics, Prenatal risk factors
1.
Pawanker R, Walter Canonica G, Holgate ST, Lockey RF (eds): Executive summary; in: WAO White Book on Allergy. World Allergy Organization, 2011.
2.
Jackson KD, Howie LD, Akinbami LJ: Trends in allergic conditions among children: United States, 1997-2011. NCHS Data Brief No. 121, May 2013. US Department of Health and Human Services. Centres for Disease Control and Prevention. National Centre for Health Statistics, 2013.
3.
Waterland RA, Michels KB: Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr 2007;27:363-388.
4.
Prescott S, Allen KJ: Food allergy: riding the second wave of the allergy epidemic. Pediatr Allergy Immunol 2011;22:155-160.
5.
Prescott S, Saffery R: The role of epigenetic dysregulation in the epidemic of allergic disease. Clin Epigenet 2011;2:223-232.
6.
Prescott SL: Early origins of allergic disease: a review of processes and influences during early immune development. Curr Opin Allergy Clin Immunol 2003;3:125-132.
7.
Prescott SL, Clifton V: Asthma and pregnancy: emerging evidence of epigenetic interactions in utero. Curr Opin Allergy Clin Immunol 2009;9:417-426.
8.
Landgraf MA, Landgraf RG, Jancar S, Fortes ZB: Influence of age on the development of immunological lung response in intrauterine undernourishment. Nutrition 2008;24:262-269.
9.
Landgraf MA, Landgraf RG, Silva RC, Semedo P, Camara NO, Fortes ZB: Intrauterine undernourishment alters Th1/Th2 cytokine balance and attenuates lung allergic inflammation in Wistar rats. Cell Physiol Biochem 2012;30:552-562.
10.
Mielck A, Reitmeir P, Wjst M: Severity of childhood asthma by socioeconomic status. Int J Epidemiol 1996;25:388-393.
11.
Heinrich J, Popescu MA, Wjst M, Goldstein IF, Wichmann HE: Atopy in children and parental social class. Am J Public Health 1998;88:1319-1324.
12.
Lewis SA, Britton JR: Consistent effects of high socioeconomic status and low birth order, and the modifying effect of maternal smoking on the risk of allergic disease during childhood. Respir Med 1998;92:1237-1244.
13.
Hodyl NA, Stark MJ, Scheil W, Grzeskowiak LE, Clifton VL: Perinatal outcomes following maternal asthma and cigarette smoking during pregnancy. Eur Respir J 2014;43:704-716.
14.
Ruijsbroek A, Wijga AH, Kerkhof M, Koppelman GH, Smit HA, Droomers M: The development of socio-economic health differences in childhood: results of the Dutch longitudinal PIAMA birth cohort. BMC Public Health 2011;11:225.
15.
Agache I, Akdis C, Jutel M, Virchow JC: Untangling asthma phenotypes and endotypes. Allergy 2012;67:835-846.
16.
Just J, Gouvis-Echraghi R, Rouve S, Wanin S, Moreau D, Annesi-Maesano I: Two novel, severe asthma phenotypes identified during childhood using a clustering approach. Eur Respir J 2012;40:55-60.
17.
Sheikh A, Strachan DP: The hygiene theory: fact or fiction? Curr Opin Otolaryngol Head Neck Surg 2004;12:232-236.
18.
Strachan DP: Hay fever, hygiene, and household size. BMJ 1989;299:1259-1260.
19.
Platts-Mills TA, Erwin E, Heymann P, Woodfolk J: Is the hygiene hypothesis still a viable explanation for the increased prevalence of asthma? Allergy 2005;60(suppl 79):25-31.
20.
Silvestri M, Franchi S, Pistorio A, Petecchia L, Rusconi F: Smoke exposure, wheezing, and asthma development: a systematic review and meta-analysis in unselected birth cohorts. Pediatr Pulmonol 2015;50:353-362.
21.
OECD Family Database: SF2.3: Mean age of mothers at first childbirth. 2009.
22.
Butland BK, Strachan DP, Lewis S, Bynner J, Butler N, Britton J: Investigation into the increase in hay fever and eczema at age 16 observed between the 1958 and 1970 British birth cohorts. BMJ 1997;315:717-721.
23.
Strachan DP, Harkins LS, Golding J: Sibship size and self-reported inhalant allergy among adult women. ALSPAC Study Team. Clin Exp Allergy 1997;27:151-155.
24.
Ben-Shoshan M, Soller L, Harrington DW, Knoll M, La Vieille S, Fragapane J, Joseph L, St Pierre Y, Wilson K, Elliott SJ, Clarke AE: Eczema in early childhood, sociodemographic factors and lifestyle habits are associated with food allergy: a nested case-control study. Int Arch Allergy Immunol 2015;166:199-207.
25.
Kusunoki T, Mukaida K, Morimoto T, Sakuma M, Yasumi T, Nishikomori R, Heike T: Birth order effect on childhood food allergy. Pediatr Allergy Immunol 2012;23:250-254.
26.
Ohfuji S, Miyake Y, Arakawa M, Tanaka K, Sasaki S: Sibship size and prevalence of allergic disorders in Japan: the Ryukyus Child Health Study. Pediatr Allergy Immunol 2009;20:377-384.
27.
Strachan DP, Ait-Khaled N, Foliaki S, Mallol J, Odhiambo J, Pearce N, Williams HC; Group IPTS: Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood. Clin Exp Allergy 2015;45:126-136.
28.
Zekveld C, Bibakis I, Bibaki-Liakou V, Pedioti A, Dimitroulis I, Harris J, Newman Taylor AJ, Cullinan P: The effects of farming and birth order on asthma and allergies. Eur Respir J 2006;28:82-88.
29.
Karmaus W, Botezan C: Does a higher number of siblings protect against the development of allergy and asthma? A review. J Epidemiol Commun Health 2002;56:209-217.
30.
Cervantes D, Fischbach L, Goodman K, Phillips C, Chen S, Broussard C: Exposure to Helicobacter pylori-positive siblings and persistence of Helicobacter pylori infection in early childhood. J Pediatr Gastroenterol Nutr 2010; 50:481-485
31.
Athukorala C, Rumbold AR, Willson KJ, Crowther CA: The risk of adverse pregnancy outcomes in women who are overweight or obese. BMC Pregnancy Childbirth 2010;10:56.
32.
Callaway LK, Prins JB, Chang AM, McIntyre HD: The prevalence and impact of overweight and obesity in an Australian obstetric population. Med J Aust 2006;184:56-59.
33.
Forno E, Young OM, Kumar R, Simhan H, Celedon JC: Maternal obesity in pregnancy, gestational weight gain, and risk of childhood asthma. Pediatrics 2014;134:535-546.
34.
Aye IL, Lager S, Ramirez VI, Gaccioli F, Dudley DJ, Jansson T, Powell TL: Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways. Biol Reprod 2014;90:129.
35.
Tilburgs T, Scherjon SA, Claas FH: Major histocompatibility complex (MHC)-mediated immune regulation of decidual leukocytes at the fetal-maternal interface. J Reprod Immunol 2010;85:58-62.
36.
Guerin LR, Prins JR, Robertson SA: Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum Reprod Update 2009;15:517-535.
37.
Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, Moffett A, Colucci F, Hemberger M: Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci USA 2011;108:4012-4017.
38.
Saito S, Sakai M, Sasaki Y, Nakashima A, Shiozaki A: Inadequate tolerance induction may induce pre-eclampsia. J Reprod Immunol 2007;76:30-39.
39.
Mold JE, Michaelsson J, Burt TD, Muench MO, Beckerman KP, Busch MP, Lee TH, Nixon DF, McCune JM: Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 2008;322:1562-1565.
40.
Leveque L, Hodgson S, Peyton S, Koyama M, MacDonald KP, Khosrotehrani K: Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers. J Autoimmun 2014;50:51-58.
41.
Prescott SL, Tulic M, Kumah AO, Richman T, Crook M, Martino D, Dunstan JA, Novakovic B, Saffery R, Clifton VL: Reduced placental FOXP3 associated with subsequent infant allergic disease. J Allergy Clin Immunol 2011;128:886-887.e5.
42.
Blumer N, Herz U, Wegmann M, Renz H: Prenatal lipopolysaccharide exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma. Clin Exper Allergy 2005;35:397-402.
43.
Kunzmann S, Glogger K, Been JV, Kallapur SG, Nitsos I, Moss TJ, Speer CP, Newnham JP, Jobe AH, Kramer BW: Thymic changes after chorioamnionitis induced by intraamniotic lipopolysaccharide in fetal sheep. Am J Obstetr Gynecol 2010;202:476.e1-e9.
44.
Williams CL, Teeling JL, Perry VH, Fleming TP: Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring. BMC Biol 2011;9:49.
45.
Lim RH, Kobzik L, Dahl M: Risk for asthma in offspring of asthmatic mothers versus fathers: a meta-analysis. PLoS One 2010;5:e10134.
46.
Berz JB, Carter AS, Wagmiller RL, Horwitz SM, Murdock KK, Briggs-Gowan M: Prevalence and correlates of early onset asthma and wheezing in a healthy birth cohort of 2- to 3-year olds. J Pediatr Psychol 2007;32:154-166.
47.
Davidson R, Roberts SE, Wotton CJ, Goldacre MJ: Influence of maternal and perinatal factors on subsequent hospitalisation for asthma in children: evidence from the Oxford Record Linkage Study. BMC Pulm Med 2010;10:14.
48.
Illi S, Weber J, Zutavern A, Genuneit J, Schierl R, Strunz-Lehner C, von Mutius E: Perinatal influences on the development of asthma and atopy in childhood. Ann Allergy Asthma Immunol 2014;112:132-139.e1.
49.
Martel MJ, Beauchesne MF, Malo JL, Rey E, Perreault S, Forget A, Blais L: Maternal asthma, its control and severity in pregnancy, and the incidence of atopic dermatitis and allergic rhinitis in the offspring. J Pediatr 2009;155:707-713.e1.
50.
Metsala J, Kilkkinen A, Kaila M, Tapanainen H, Klaukka T, Gissler M, Virtanen SM: Perinatal factors and the risk of asthma in childhood - a population-based register study in Finland. Am J Epidemiol 2008;168:170-178.
51.
Berin MC: Bugs versus bugs: probiotics, microbiome and allergy. Int Arch Allergy Immunol 2014;163:165-167.
52.
Nauta AJ, Ben Amor K, Knol J, Garssen J, van der Beek EM: Relevance of pre- and postnatal nutrition to development and interplay between the microbiota and metabolic and immune systems. Am J Clin Nutr 2013;98:586S-593S.
53.
von Mutius E, Radon K: Living on a farm: impact on asthma induction and clinical course. Immunol Allergy Clin North Am 2008;28:631-647.
54.
Navarro S, Cossalter G, Chiavaroli C, Kanda A, Fleury S, Lazzari A, Cazareth J, Sparwasser T, Dombrowicz D, Glaichenhaus N, Julia V: The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol 2011;4:53-65.
55.
Schaub B, Liu J, Hoppler S, Schleich I, Huehn J, Olek S, Wieczorek G, Illi S, von Mutius E: Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol 2009;123:774-782 e5.
56.
Perkin MR, Strachan DP: Which aspects of the farming lifestyle explain the inverse association with childhood allergy? J Allergy Clin Immunol 2006;117:1374-1381.
57.
Pfefferle PI, Buchele G, Blumer N, Roponen M, Ege MJ, Krauss-Etschmann S, Genuneit J, Hyvarinen A, Hirvonen MR, Lauener R, Pekkanen J, Riedler J, Dalphin JC, Brunekeef B, Braun-Fahrlander C, von Mutius E, Renz H, Group PS: Cord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE Study. J Allergy Clin Immunol 2010;125:108-115 e1-e3.
58.
Conrad ML, Ferstl R, Teich R, Brand S, Blumer N, Yildirim AO, Patrascan CC, Hanuszkiewicz A, Akira S, Wagner H, Holst O, von Mutius E, Pfefferle PI, Kirschning CJ, Garn H, Renz H: Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J Exp Med 2009;206:2869-2877.
59.
Lauener RP, Birchler T, Adamski J, Braun-Fahrlander C, Bufe A, Herz U, von Mutius E, Nowak D, Riedler J, Waser M, Sennhauser FH; ALEX Study Group: Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children. Lancet 2002;360:465-466.
60.
Kaplan JL, Shi HN, Walker WA: The role of microbes in developmental immunologic programming. Pediatr Res 2011;69:465-472.
61.
Mann ER, Landy JD, Bernardo D, Peake ST, Hart AL, Al-Hassi HO, Knight SC: Intestinal dendritic cells: their role in intestinal inflammation, manipulation by the gut microbiota and differences between mice and men. Immunol Lett 2013;150:30-40.
62.
Putignani L, Del Chierico F, Petrucca A, Vernocchi P, Dallapiccola B: The human gut microbiota: a dynamic interplay with the host from birth to senescence settled during childhood. Pediatr Res 2014;76:2-10.
63.
Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, Ho SM: Relation of DNA methylation of 5′-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 2009;4:e4488.
64.
Slaats GG, Reinius LE, Alm J, Kere J, Scheynius A, Joerink M: DNA methylation levels within the CD14 promoter region are lower in placentas of mothers living on a farm. Allergy 2012;67:895-903.
65.
Klose RJ, Bird AP: Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 2006;31:89-97.
66.
Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh RF, Wiencke JK, Kelsey KT: Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 2009;5:e1000602.
67.
Perrin D, Ballestar E, Fraga MF, Frappart L, Esteller M, Guerin JF, Dante R: Specific hypermethylation of LINE-1 elements during abnormal overgrowth and differentiation of human placenta. Oncogene 2007;26:2518-2524.
68.
Novakovic B, Saffery R: The ever growing complexity of placental epigenetics - role in adverse pregnancy outcomes and fetal programming. Placenta 2012;33:959-970.
69.
Bouchard L, Hivert MF, Guay SP, St-Pierre J, Perron P, Brisson D: Placental adiponectin gene DNA methylation levels are associated with mothers' blood glucose concentration. Diabetes 2012;61:1272-1280.
70.
Nielsen CH, Larsen A, Nielsen AL: DNA methylation alterations in response to prenatal exposure of maternal cigarette smoking: a persistent epigenetic impact on health from maternal lifestyle? Arch Toxicol 2016;90:231-245.
71.
McDaniell R, Lee BK, Song L, Liu Z, Boyle AP, Erdos MR, Scott LJ, Morken MA, Kucera KS, Battenhouse A, Keefe D, Collins FS, Willard HF, Lieb JD, Furey TS, Crawford GE, Iyer VR, Birney E: Heritable individual-specific and allele-specific chromatin signatures in humans. Science 2010;328:235-239.
72.
Savenije OE, Mahachie John JM, Granell R, Kerkhof M, Dijk FN, de Jongste JC, Smit HA, Brunekreef B, Postma DS, Van Steen K, Henderson J, Koppelman GH: Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood. J Allergy Clin Immunol 2014;134:170-177.
73.
Shimizu M, Matsuda A, Yanagisawa K, Hirota T, Akahoshi M, Inomata N, Ebe K, Tanaka K, Sugiura H, Nakashima K, Tamari M, Takahashi N, Obara K, Enomoto T, Okayama Y, Gao PS, Huang SK, Tominaga S, Ikezawa Z, Shirakawa T: Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis. Hum Mol Genet 2005;14:2919-2927.
74.
Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO, Consortium G: A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 2010;363:1211-1221.
75.
Ramasamy A, Kuokkanen M, Vedantam S, Gajdos ZK, Couto Alves A, et al: Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. PLoS One 2012;7:e44008.
76.
Chen P, Zhang K, Zhou B, Zhang Z, Song Y, Pu Y, Yang Y, Zhang Y, Zhou R, Wang T, Zhang L: The variations in the IL1RL1 gene and susceptibility to preeclampsia. Immunol Invest 2014;43:424-435.
77.
Murk W, Risnes KR, Bracken MB: Prenatal or early-life exposure to antibiotics and risk of childhood asthma: a systematic review. Pediatrics 2011;127:1125-1138.
78.
Lapin B, Piorkowski J, Ownby D, Freels S, Chavez N, Hernandez E, Wagner-Cassanova C, Pelzel D, Vergara C, Persky V: Relationship between prenatal antibiotic use and asthma in at-risk children. Ann Allergy Asthma Immunol 2015;114:203-207.
79.
Stensballe LG, Simonsen J, Jensen SM, Bonnelykke K, Bisgaard H: Use of antibiotics during pregnancy increases the risk of asthma in early childhood. J Pediatr 2013;162:832-838 e3.
80.
Rautava S, Luoto R, Salminen S, Isolauri E: Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol 2012;9:565-576.
81.
Cheelo M, Lodge CJ, Dharmage SC, Simpson JA, Matheson M, Heinrich J, Lowe AJ: Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis. Arch Dis Childhood 2015;100:81-89.
82.
Amarasekera M, Prescott SL, Palmer DJ: Nutrition in early life, immune-programming and allergies: the role of epigenetics. Asian Pac J Allergy Immunol 2013;31:175-182.
83.
Weng M, Walker WA: The role of gut microbiota in programming the immune phenotype. J Dev Orig Health Dis 2013;4:203-214.
84.
Lodge CJ, Allen KJ, Lowe AJ, Dharmage SC: Overview of evidence in prevention and aetiology of food allergy: a review of systematic reviews. Int J Environ Res Public Health 2013;10:5781-5806.
85.
Thompson RL, Miles LM, Lunn J, Devereux G, Dearman RJ, Strid J, Buttriss JL: Peanut sensitisation and allergy: influence of early life exposure to peanuts. Br J Nutr 2010;103:1278-1286.
86.
Chatzi L, Garcia R, Roumeliotaki T, Basterrechea M, Begiristain H, Iniguez C, Vioque J, Kogevinas M, Sunyer J: Mediterranean diet adherence during pregnancy and risk of wheeze and eczema in the first year of life: INMA (Spain) and RHEA (Greece) mother-child cohort studies. Br J Nutr 2013;110:2058-2068.
87.
Chatzi L, Torrent M, Romieu I, Garcia-Esteban R, Ferrer C, Vioque J, Kogevinas M, Sunyer J: Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood. Thorax 2008;63:507-513.
88.
de Batlle J, Garcia-Aymerich J, Barraza-Villarreal A, Anto JM, Romieu I: Mediterranean diet is associated with reduced asthma and rhinitis in Mexican children. Allergy 2008;63:1310-1316.
89.
Erkkola M, Nwaru BI, Kaila M, Kronberg-Kippila C, Ilonen J, Simell O, Veijola R, Knip M, Virtanen SM: Risk of asthma and allergic outcomes in the offspring in relation to maternal food consumption during pregnancy: a Finnish birth cohort study. Pediatr Allergy Immunol 2012;23:186-194.
90.
Nwaru BI, Erkkola M, Lumia M, Kronberg-Kippila C, Ahonen S, Kaila M, Ilonen J, Simell O, Knip M, Veijola R, Virtanen SM: Maternal intake of fatty acids during pregnancy and allergies in the offspring. Br J Nutr 2012;108:720-732.
91.
Sausenthaler S, Koletzko S, Schaaf B, Lehmann I, Borte M, Herbarth O, von Berg A, Wichmann HE, Heinrich J, Group LS: Maternal diet during pregnancy in relation to eczema and allergic sensitization in the offspring at 2 years of age. Am J Clin Nutr 2007;85:530-537.
92.
Kremmyda LS, Vlachava M, Noakes PS, Diaper ND, Miles EA, Calder PC: Atopy risk in infants and children in relation to early exposure to fish, oily fish, or long-chain omega-3 fatty acids: a systematic review. Clin Rev Allergy Immunol 2011;41:36-66.
93.
Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL: Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol 2003;112:1178-1184.
94.
Leermakers ET, Sonnenschein-van der Voort AM, Heppe DH, de Jongste JC, Moll HA, Franco OH, Hofman A, Jaddoe VW, Duijts L: Maternal fish consumption during pregnancy and risks of wheezing and eczema in childhood: the Generation R Study. Eur J Clin Nutr 2013;67:353-359.
95.
Olsen SF, Osterdal ML, Salvig JD, Mortensen LM, Rytter D, Secher NJ, Henriksen TB: Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 years of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr 2008;88:167-175.
96.
Lee HS, Barraza-Villarreal A, Hernandez-Vargas H, Sly PD, Biessy C, Ramakrishnan U, Romieu I, Herceg Z: Modulation of DNA methylation states and infant immune system by dietary supplementation with omega-3 PUFA during pregnancy in an intervention study. Am J Clin Nutr 2013;98:480-487.
97.
Greenough A, Shaheen SO, Shennan A, Seed PT, Poston L: Respiratory outcomes in early childhood following antenatal vitamin C and E supplementation. Thorax 2010;65:998-1003.
98.
Martindale S, McNeill G, Devereux G, Campbell D, Russell G, Seaton A: Antioxidant intake in pregnancy in relation to wheeze and eczema in the first two years of life. Am J Respir Crit Care Med 2005;171:121-128.
99.
West CE, Dunstan J, McCarthy S, Metcalfe J, D'Vaz N, Meldrum S, Oddy WH, Tulic MK, Prescott SL: Associations between maternal antioxidant intakes in pregnancy and infant allergic outcomes. Nutrients 2012;4:1747-1758.
100.
Maslova E, Hansen S, Strom M, Halldorsson TI, Olsen SF: Maternal intake of vitamins A, E and K in pregnancy and child allergic disease: a longitudinal study from the Danish National Birth Cohort. Br J Nutr 2014;111:1096-1108.
101.
Maslova E, Hansen S, Jensen CB, Thorne-Lyman AL, Strom M, Olsen SF: Vitamin D intake in mid-pregnancy and child allergic disease - a prospective study in 44,825 Danish mother-child pairs. BMC Pregnancy Childbirth 2013;13:199.
102.
Miyake Y, Sasaki S, Tanaka K, Hirota Y: Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants. Eur Respir J 2010;35:1228-1234.
103.
Netting MJ, Middleton PF, Makrides M: Does maternal diet during pregnancy and lactation affect outcomes in offspring? A systematic review of food-based approaches. Nutrition 2014;30:1225-1241.
104.
Goldring ST, Griffiths CJ, Martineau AR, Robinson S, Yu C, Poulton S, Kirkby JC, Stocks J, Hooper R, Shaheen SO, Warner JO, Boyle RJ: Prenatal vitamin D supplementation and child respiratory health: a randomised controlled trial. PLoS One 2013;8:e66627.
105.
Comberiati P, Tsabouri S, Piacentini GL, Moser S, Minniti F, Peroni DG: Is vitamin D deficiency correlated with childhood wheezing and asthma? Front Biosci 2014;6:31-39.
106.
Medical Research Council Vitamin Study Research Group: Prevention of neural tube defects: results of the MRC Vitamin Study. Lancet 1991;338:131-137.
107.
Dunstan JA, West C, McCarthy S, Metcalfe J, Meldrum S, Oddy WH, Tulic MK, D'Vaz N, Prescott SL: The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Allergy 2012;67:50-57.
108.
Granell R, Heron J, Lewis S, Davey Smith G, Sterne JA, Henderson J: The association between mother and child MTHFR C677T polymorphisms, dietary folate intake and childhood atopy in a population-based, longitudinal birth cohort. Clin Exp Allergy 2008;38:320-328.
109.
Whitrow MJ, Moore VM, Rumbold AR, Davies MJ: Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol 2009;170:1486-1493.
110.
Yang L, Jiang L, Bi M, Jia X, Wang Y, He C, Yao Y, Wang J, Wang Z: High dose of maternal folic acid supplementation is associated to infant asthma. Food Chem Toxicol 2015;75:88-93.
111.
Zetstra-van der Woude PA, De Walle HE, Hoek A, Bos HJ, Boezen HM, Koppelman GH, de Jong-van den Berg LT, Scholtens S: Maternal high-dose folic acid during pregnancy and asthma medication in the offspring. Pharmacoepidemiol Drug Safety 2014;23:1059-1065.
112.
Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ: Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr 2013;98:1272-1281.
113.
Magdelijns FJ, Mommers M, Penders J, Smits L, Thijs C: Folic acid use in pregnancy and the development of atopy, asthma, and lung function in childhood. Pediatrics 2011;128:e135-e144.
114.
Azad MB, Coneys JG, Kozyrskyj AL, Field CJ, Ramsey CD, Becker AB, Friesen C, Abou-Setta AM, Zarychanski R: Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis. BMJ 2013;347:f6471.
115.
Bertelsen RJ, Brantsaeter AL, Magnus MC, Haugen M, Myhre R, Jacobsson B, Longnecker MP, Meltzer HM, London SJ: Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases. J Allergy Clin Immunol 2014;133:165-171.e1-e8.
116.
Liu X, Olsen J, Agerbo E, Yuan W, Cnattingius S, Gissler M, Li J: Birth weight, gestational age, fetal growth and childhood asthma hospitalization. Allergy Asthma Clin Immunol 2014;10:13.
117.
Lundholm C, Örtqvist AK, Lichtenstein P, Cnattingius S, Almqvist C: Impaired fetal growth decreases the risk of childhood atopic eczema: a Swedish twin study. Clin Exp Allergy 2010;40:1044-1053.
118.
Mebrahtu TF, Feltbower RG, Greenwood DC, Parslow RC: Birth weight and childhood wheezing disorders: a systematic review and meta-analysis. J Epidemiol Commun Health 2015;69:500-508.
119.
Mitchell EA, Clayton T, García-Marcos L, Pearce N, Foliaki S, Wong G: Birthweight and the risk of atopic diseases: the ISAAC phase III study. Pediatr Allergy Immunol 2014;25:264-270.
120.
Mu M, Ye S, Bai MJ, Liu GL, Tong Y, Wang SF, Sheng J: Birth weight and subsequent risk of asthma: a systematic review and meta-analysis. Heart Lung Circ 2014;23:511-519.
121.
Örtqvist AK, Lundholm C, Carlström E, Lichtenstein P, Cnattingius S, Almqvist C: Familial factors do not confound the association between birth weight and childhood asthma. Pediatrics 2009;124:e737-e743.
122.
Pike KC, Crozier SR, Lucas JS, Inskip HM, Robinson S; Southampton Women's Survey Study Group, Roberts G, Godfrey KM: Patterns of fetal and infant growth are related to atopy and wheezing disorders at age 3 years. Thorax 2010;65:1099-1106.
123.
Steffensen FH, Sorensen HT, Gillman MW, Rothman KJ, Sabroe S, Fischer P, Olsen J: Low birth weight and preterm delivery as risk factors for asthma and atopic dermatitis in young adult males. Epidemiology 2000;11:185-188.
124.
Tedner SG, Ortqvist AK, Almqvist C: Fetal growth and risk of childhood asthma and allergic disease. Clin Exp Allergy 2012;42:1430-1447.
125.
Turner S, Prabhu N, Danielan P, McNeill G, Craig L, Allan K, Cutts R, Helms P, Seaton A, Devereux G: First- and second-trimester fetal size and asthma outcomes at age 10 years. Am J Respir Crit Care Med 2011;184:407-413.
126.
Wjst M, Popescu M, Trepka MJ, Heinrich J, Wichmann HE: Pulmonary function in children with initial low birth weight. Pediatr Allergy Immunol 1998;9:80-90.
127.
Bocca-Tjeertes IF, Reijneveld SA, Kerstjens JM, de Winter AF, Bos AF: Growth in small-for-gestational-age preterm-born children from 0 to 4 years: the role of both prematurity and SGA status. Neonatology 2013;103:293-299.
128.
Siltanen M, Kajosaari M, Pohjavuori M, Savilahti E: Prematurity at birth reduces the long-term risk of atopy. J Allergy Clin Immunol 2001;107:229-234.
129.
Alexander G: Studies on the placenta of the sheep (Ovis aries L.). Effect of surgical reduction in the number of caruncles. J Reprod Fertil 1964;7:307-322.
130.
Robinson JS, Kingston EJ, Jones CT, Thorburn GD: Studies on experimental growth retardation in sheep. The effect of removal of endometrial caruncles on fetal size and metabolism. J Dev Physiol 1979;1:379-398.
131.
Wooldridge AL, Bischof RJ, Meeusen EN, Liu H, Heinemann GK, Hunter DS, Giles LC, Kind KL, Owens JA, Clifton VL, Gatford KL: Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep. Am J Physiol Regul Integr Comp Physiol 2014;306:R441-R446.
132.
Martino D, Prescott S: Epigenetics and prenatal influences on asthma and allergic airways disease. Chest 2011;139:640-647.
133.
Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li Z, Tomfohr J, Bailey N, Potts EN, Whitehead G, Brass DM, Schwartz DA: In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest 2008;118:3462-3469.
134.
Williams EA, Gebhardt BM, Morton B, Newberne PM: Effects of early marginal methionine-choline deprivation on the development of the immune system in the rat. Am J Clin Nutr 1979;32:1214-1223.
135.
Cromi A, Ghezzi F, Raffaelli R, Bergamini V, Siesto G, Bolis P: Ultrasonographic measurement of thymus size in IUGR fetuses: a marker of the fetal immunoendocrine response to malnutrition. Ultrasound Obstet Gynecol 2009;33:421-426.
136.
Hartge R, Jenkins D, Kohler H: Low thymic weight in small-for-dates babies. Eur J Obstet Gynecol Reprod Biol 1978;8:153-155.
137.
McDade TW, Beck MA, Kuzawa CW, Adair LS: Prenatal undernutrition and postnatal growth are associated with adolescent thymic function. J Nutr 2001;131:1225-1231.
138.
Ferguson AC: Prolonged impairment of cellular immunity in children with intrauterine growth retardation. J Pediatr 1978;93:52-56.
139.
Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PF: The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ 2010;88:31-38.
140.
Been JV, Lugtenberg MJ, Smets E, van Schayck CP, Kramer BW, Mommers M, Sheikh A: Preterm birth and childhood wheezing disorders: a systematic review and meta-analysis. PLoS Med 2014;11:e1001596.
141.
Bernsen RM, de Jongste JC, Koes BW, Aardoom HA, van der Wouden JC: Perinatal characteristics and obstetric complications as risk factors for asthma, allergy and eczema at the age of 6 years. Clin Exp Allergy 2005;35:1135-1140.
142.
Jaakkola JJ, Ahmed P, Ieromnimon A, Goepfert P, Laiou E, Quansah R, Jaakkola MS: Preterm delivery and asthma: a systematic review and meta-analysis. J Allergy Clin Immunol 2006;118:823-830.
143.
Sonnenschein-van der Voort AM, Arends LR, de Jongste JC, Annesi-Maesano I, Arshad SH, et al: Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children. J Allergy Clin Immunol 2014;133:1317-1329.
144.
Baraldi E, Filippone M: Chronic lung disease after premature birth. N Engl J Med 2007;357:1946-1955.
145.
Lahra MM, Beeby PJ, Jeffery HE: Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 2009;123:1314-1319.
146.
Katz O, Sheiner E: Asthma and pregnancy: a review of two decades. Expert Rev Respir Med 2008;2:97-107.
147.
Grabenhenrich LB, Gough H, Reich A, Eckers N, Zepp F, Nitsche O, Forster J, Schuster A, Schramm D, Bauer CP, Hoffmann U, Beschorner J, Wagner P, Bergmann R, Bergmann K, Matricardi PM, Wahn U, Lau S, Keil T: Early-life determinants of asthma from birth to age 20 years: a German birth cohort study. J Allergy Clin Immunol 2014;133:979-988.
148.
Powell H, Murphy VE, Taylor DR, Hensley MJ, McCaffery K, Giles W, Clifton VL, Gibson PG: Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial. Lancet 2011;378:983-990.
149.
Almqvist C, Cnattingius S, Lichtenstein P, Lundholm C: The impact of birth mode of delivery on childhood asthma and allergic diseases - a sibling study. Clin Exp Allergy 2012;42:1369-1376.
150.
Bager P, Wohlfahrt J, Westergaard T: Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy 2008;38:634-642.
151.
Nathan AM, de Bruyne J, Khalid F, Arumugam K: Caesarean section and asthma in Malaysian children: a case-control study. Asian Pac J Allergy Immunology 2012;30:204-208.
152.
Roduit C, Scholtens S, de Jongste JC, Wijga AH, Gerritsen J, Postma DS, Brunekreef B, Hoekstra MO, Aalberse R, Smit HA: Asthma at 8 years of age in children born by caesarean section. Thorax 2009;64:107-113.
153.
Hancox RJ, Landhuis CE, Sears MR: Forceps birth delivery, allergic sensitisation and asthma: a population-based cohort study. Clin Exp Allergy 2013;43:332-336.
154.
Menezes AM, Hallal PC, Matijasevich AM, Barros AJ, Horta BL, Araujo CL, Gigante DP, Santos IS, Minten G, Domingues MR, Dumith SC, Barros FC: Caesarean sections and risk of wheezing in childhood and adolescence: data from two birth cohort studies in Brazil. Clin Exp Allergy 2011;41:218-223.
155.
Pyrhonen K, Nayha S, Hiltunen L, Laara E: Caesarean section and allergic manifestations: insufficient evidence of association found in population-based study of children aged 1 to 4 years. Acta Paediatr 2013;102:982-989.
156.
Cho CE, Norman M: Cesarean section and development of the immune system in the offspring. Am J Obstet Gynecol 2013;208:249-254.
157.
Hallstrom M, Eerola E, Vuento R, Janas M, Tammela O: Effects of mode of delivery and necrotising enterocolitis on the intestinal microflora in preterm infants. Eur J Clin Microbiol Infect Dis 2004;23:463-470.
158.
Bjorksten B: Effects of intestinal microflora and the environment on the development of asthma and allergy. Springer Semin Immunopathol 2004;25:257-270.
159.
Hodyl NA, Grzeskowiak LE, Stark MJ, Scheil W, Clifton VL: The impact of Aboriginal status, cigarette smoking and smoking cessation on perinatal outcomes in South Australia. Med J Aust 2014;201:274-278.
160.
Wang IJ, Chen SL, Lu TP, Chuang EY, Chen PC: Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis. Clin Exp Allergy 2013;43:535-543.
161.
Higgins M, Mc Auliffe F: A review of maternal and fetal growth factors in diabetic pregnancy. Curr Diabetes Rev 2010;6:116-125.
162.
Mendola P, Mannisto TI, Leishear K, Reddy UM, Chen Z, Laughon SK: Neonatal health of infants born to mothers with asthma. J Allergy Clin Immunol 2014;133:85-90.e1-e4.
163.
Schaubel D, Johansen H, Dutta M, Desmeules M, Becker A, Mao Y: Neonatal characteristics as risk factors for preschool asthma. J Asthma 1996;33:255-264.
164.
Liu C-A, Wang C-L, Chuang H, Ou C-Y, Hsu T-Y, Yang KD: Prenatal prediction of infant atopy by maternal but not paternal total IgE levels. J Allergy Clin Immunol 2003;112:899-904.
165.
Allan K, Devereux G: Diet and asthma: nutrition implications from prevention to treatment. J Am Diet Assoc 2011;111:258-268.
166.
Grieger JA, Wood LG, Clifton VL: Improving asthma during pregnancy with dietary antioxidants: the current evidence. Nutrients 2013;5:3212-3234.
167.
Miyake Y, Tanaka K, Okubo H, Sasaki S, Arakawa M: Maternal consumption of dairy products, calcium, and vitamin D during pregnancy and infantile allergic disorders. Ann Allergy Asthma Immunol 2014;113:82-87.
168.
Litonjua AA: Childhood asthma may be a consequence of vitamin D deficiency. Curr Opin Allergy Clin Immunol 2009;9:202-207.
169.
Mullins RJ, Camargo CA Jr: Shining a light on vitamin D and its impact on the developing immune system. Clin Exp Allergy 2011;41:766-768.
170.
von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C: Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol 2010;11:344-349.
171.
Karlberg JP, Albertsson-Wikland K, Kwan EY, Lam BC, Low LC: The timing of early postnatal catch-up growth in normal, full-term infants born short for gestational age. Horm Res 1997;48(suppl 1):17-24.
172.
Sonnenschein-van der Voort AM, Howe LD, Granell R, Duijts L, Sterne JA, Tilling K, Henderson AJ: Influence of childhood growth on asthma and lung function in adolescence. J Allergy Clin Immunol 2015;135:1435-1443.
173.
Contreras YM, Yu X, Hale MA, Callaway CW, Bareyan D, McKnight RA, Joss-Moore LA, Enioutina EY, Lane RH: Intrauterine growth restriction alters T-lymphocyte cell number and dual specificity phosphatase 1 levels in the thymus of newborn and juvenile rats. Pediatr Res 2011;70:123-129.
174.
Badr G, Mohany M: Maternal perinatal undernutrition attenuates T-cell function in adult male rat offspring. Cell Physiol Biochem 2011;27:381-390.
175.
Ke X, Lei Q, James SJ, Kelleher SL, Melnyk S, Jernigan S, Yu X, Wang L, Callaway CW, Gill G, Chan GM, Albertine KH, McKnight RA, Lane RH: Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genom 2006;25:16-28.
176.
MacLennan NK, James SJ, Melnyk S, Piroozi A, Jernigan S, Hsu JL, Janke SM, Pham TD, Lane RH: Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats. Physiol Genom 2004;18:43-50.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.