Table 2.

Results of observational studies assessing acid suppressant medications and development of allergic diseases

Author (year), Location	Confounders Included in Adjusted Analysis	Exposure	Outcome	Result
Prenatal exposure
Dehlink (2009), Sweden [24]	Year of birth, maternal age, maternal parity, maternal smoking, maternal BMI	Any ASM Any ASM	Asthma Allergic Disease*	aOR 1.51 (1.35-1.69) aOR 1.43 (1.29-1.59)
Hak (2013), United Kingdom [25]	Sex, birth order, maternal age, number of general practice visits	H2RA or PPI PPI Only	Asthma Asthma	aOR 1.72 (1.00-2.07) aOR 2.76 (0.98-8.17)
Andersen (2012), Denmark [26]	Year of birth, sex, birth order, country of birth, maternal age, maternal smoking, maternal asthma, mode of delivery, maternal antibiotics during pregnancy, gestational age	H2RA Only PPI Only	Asthma Asthma	aIRR 1.47 (1.32-1.65) aIRR 1.41 (1.27-1.56)
Kallen (2013), Sweden [27]	Year of birth, maternal age, maternal parity, maternal smoking, maternal BMI	Any ASM	Asthma	aOR 1.32 (1.18-1.54)
Mulder (2013), Netherlands [28]	Maternal age	Any ASM	Asthma	aOR 1.52 (1.11-2.09)
Mulder (2014), Netherlands [29]	Sex, maternal age, maternal use of antibiotics during pregnancy, maternal history of allergic disease, childhood use of ASM	Any ASM Any ASM Any ASM Any ASM H2RA Only PPI Only	Asthma Atopic Dermatitis Allergic Rhinitis Allergic Disease† Allergic Disease† Allergic Disease†	aHR 1.57 (1.20-2.05) aHR 1.32 (1.06-1.64) aHR 2.40 (1.42-4.04) aHR 1.37 (1.14-1.66) aHR 1.52 (1.11-2.09) aHR 1.25 (0.98-1.59)
Cea Soriano (2016), United Kingdom [30]	Sex, maternal asthma, maternal comorbidities (GERD, allergic disease), maternal use of NSAIDs during pregnancy, maternal use of antacids, antibiotics, antihistamines during pregnancy, maternal primary care visits and referrals in the year prior to pregnancy Ŧ	H2RA Only PPI Only	Asthma Asthma	aHR 1.32 (1.05-1.64) aHR 1.03 (0.76-1.40)
Yitshak-Sade (2016), Israel [31]	Sex, year of birth, maternal age, maternal asthma, maternal allergies, maternal use of antibiotics or NSAIDs, maternal use of metoclopramide or insulin, history of infertility, lack of parental care, preterm delivery, low birth weight, delivered by C-section, child H2RA or PPI exposure	Any ASM	Asthma	aRR 1.09 (1.01-1.17)
Childhood Exposure
DeMuth (2013), United States [37]	Age, sex, history of atopic dermatitis	Any ASM	Food Allergy	aPR 1.70 (1.10-2.50)
Jensen (2018), United States [38]	Maternal education	Any ASM	Eosinophilic Esophagitis	aOR 6.05 (2.55-14.40)
Mitre (2018), United States [39]	Sex, preterm delivery, delivery by C-section, other medication exposure in childhood	H2RA PPI	Asthma Atopic dermatitis Food allergy Allergic rhinitis Allergic conjunctivitis Anaphylaxis Medication allergy Urticaria Contact dermatitis Other Allergy Asthma Atopic dermatitis Food allergy Allergic rhinitis Allergic conjunctivitis Anaphylaxis Medication allergy Urticaria Contact dermatitis Other Allergy	aHR 1.25 (1.21-1.29) aHR 1.12 (1.09-1.14) aHR 2.18 (2.04-2.33) aHR 1.50 (1.46-1.54) aHR 1.48 (1.35-1.62) aHR 1.51 (1.38-1.66) aHR 1.70 (1.60-1.80) aHR 1.30 (1.24-1.35) aHR 1.25 (1.22-1.28) aHR 1.63 (1.55-1.71) aHR 1.41 (1.31-1.52) aHR 1.12 (1.07-1.17) aHR 2.59 (2.25-3.00) aHR 1.44 (1.36-1.52) aHR 1.15 (1.04-1.27) aHR 1.45 (1.22-1.73) aHR 1.84 (1.56-2.17) aHR 1.27 (1.17-1.38) aHR 1.21 (1.15-1.28) aHR 1.62 (1.45-1.80)
Adult Exposure
Ramirez (2012), Spain [40]	Age, sex and hospitalization ward	PPI Only	Drug Hypersensitivity	aOR 4.35 (2.00-9.45)

Abbreviations: ASM: acid suppressant medications, aOR: adjusted odds ratio, aHR: adjusted hazard ratio, aRR: adjusted relative risk, aIRR: adjusted incidence rate ratio, aPR: adjusted prevalence ratio, BMI: body mass index, C-section: cesarean section, GERD: gastroesophageal reflux disease, H2RA: histamine-2 receptor antagonist, NSAIDs: non-steroidal anti-inflammatory drugs, PPI: proton pump inhibitor.

^*Includes asthma, atopic dermatitis, food allergy, allergic rhinitis, and unspecified allergic reaction/anaphylaxis.

^†Includes asthma, atopic dermatitis or allergic rhinitis.

^ŦMultiple models reported with additive adjustment for confounding.