Table 3.

Prenatal exposure to a farming environment, pets and common allergens and changes in the immune system of neonates (authors ordered by exposure, year and then alphabetically).

Author, Year [Ref]	Location Study Design N	Outcomes Assessed		Factor Assessed	Statistically Significant Main Findings
		Immune Cells Frequency	Cytokine Patterns/Ig
Farming environment
Ege et al. 2008 [109]	5 European countries (rural areas) Cohort N = 922		Specific IgE levels (food and common inhalants)	Maternal farm exposures	↓ grass pollen-specific IgE ↓ seasonal allergens -specific IgE ↑ cow’s milk-specific IgE ↑ food allergens -specific IgE
				Consumption of boiled farm milk	↑ cow’s milk-specific IgE ↑ food allergens-specific IgE
				Maternal exposure to animal sheds, contact to cattle, removing dung, cleaning the henhouse, handling silage and hay during pregnancy	↓ seasonal allergens-specific IgE
Schaub et al. 2009 [103]	Germany Cohort N = 82	Treg cells (counts)	Cytokine responses	Farming mothers	↑ Treg number and function ↓ Der p 1 plus PG-induced IL-5 ↑ Der p 1-induced IL-6 ↑ Der p 1 plus PG-induced IL-6
			Cytokine responses	Stables	↑ PG-induced CD4+CD25+ T cells ↓ Der p 1 plus PG-induced IL-5
			Cytokine responses	Number of animal species ≥2	↑ IL-10 ↑ Der p 1-induced IFN-γ ↑ PG-induced IFN-γ ↓ Der p 1 plus PG-induced IL-5
Keski-Nisula et al. 2010 [79]	Finland Cohort N = 423	Leukocytes (counts)	Cytokine responses	Father as farmer	↓ Leukocytes ↓ induced IFN-γ, IL-5 and IL-10
Pfefferle et al. 2010 [110]	5 European countries (rural areas) Cohort N = 625		Cytokine response	Maternal farm exposures	↑ induced IFN-γ
				House spent in barn	↑ induced TNF-α
				Contact with farm animal species Consumption of unskimmed farm milk Consumption of butter made of farm milk	↑ induced TNF-α and IFN-γ
				Consumption of yogurt made of farm milk	↓ induced IL-5 and IL-10
				Consumption of cheese made of farm milk	↑ induced IL-5
Lundell et al. 2015 [104]	Sweden Cohort N = 65		Cytokine production	Farming mothers	↑ B-cell activating factor (BAFF)
Indoor allergens
Heinrich et al. 2002 [107]	Germany Cohort N = 1332		IgE	Endotoxin	U-shaped association with IgE ↓ IgE (medium exposure to endotoxin)
				Dust mite (Der p 1)	↑ IgE (medium exposure to mite allergen)
Roponen et al. 2005 [112]	Finland Cross-sectional N = 29		Cytokine response	Endotoxin (in settled dust)	↑ induced-IL-6
Hagendorens et al. 2004 [115]	Belgium Cohort N = 22	Lymphocytes (%)	T cell cytokine production	Dust mite (Der p 1) during second trimester	↓ IFN-γ producing induced Th lymphocytes
Peters et al. 2009 [108]	USA Cohort N = 301		IgE	Dust mite (Der f 1 + Der p 1)	↑ Dust mite-specific IgE
				Cockroach (Bla g 1 + Bla g 2)	↓ cockroach-specific IgE (indirectly)
Lappalainen et al. 2012 [114]	Finland Cohort N = 228		Cytokine response	Staphylococcal enterotoxin B	↓ LPS-induced IFN-γ
				Mycobacterium spp.	↓ LPS-induced IL-8
				Combined chemical markers	↑induced TNF-α
Pets
Heinrich et al. 2002 [107]	Germany Cohort N = 1332		IgE	Cat-allergen exposure	↑ IgE
Roponen et al. 2005 [112]	Finland Cross-sectional N = 29		Cytokine response	Cat/Dog	↑ induced IL-6
Aichbhaumik et al. 2008 [105]	USA Cohort N = 1049		IgE	Cats Dogs	↓ IgE
Sybilski et al. 2009 [106]	Poland Retrospective study N = 173		IgE	Cats	↑ grass and grain pollen-specific IgE ↑ food-specific IgE
				Dogs	↓ grass and grain pollen-specific IgE
Lappalainen et al. 2010 [111]	Finland Cohort N = 228		Cytokine response	Dogs	↓ induced TNF-α
Uzuner et al. 2013 [113]	Turkey Cross-sectional N = 62		Cytokine production	Pets	NS

Der: Dermatophagoides pteronyssinus; IFN: interferon; Ig: Immunoglobulin; IL: interleukin; LPS: lipopolysaccharide; NS: no significant results PG: peptidoglycan; Treg: T regulatory cells; TNF: tumor necrosis factor.