The Characteristics of the Studies Included

SourceNo. AnalyzedStudy PeriodAge Range of Children, Follow-up in YearsaExposure AssessmentAsthma AssessmentDatabase
Cohort studies
 Dehlink et al11 (Sweden)585 7161995–2004>2 yThe trimester of exposure: first trimester (OR 1.38; 95% CI 1.22–1.57), later pregnancy (OR 1.34; 95% CI 1.11–1.63)Hospitalized or received prescription for medication for asthmaThe Swedish Hospital Discharge Register, The Swedish Prescribed Drug Register, and The Swedish Medical Birth Register
 Andersen et al12 (Denmark)197 0601996–2008The maximum follow-up time was 14 y with a median follow-up of 6.8 yTrimester of exposure: first trimester (HR 1.46; 95% CI 1.27–1.67), second and/or third trimester (HR 1.34; 95% CI 1.15–1.56), preconception and postpregnancy exposuresAsthma diagnosis or dispensations record for of antiasthmatic medicationDanish medical registries, The Aarhus University Prescription Database, and the Danish National Registry of Patients
 Mulder et al13
(Netherlands)33 5361995–2011The maximum follow-up time was 8 y with a median follow-up of 4.9 yTrimester of exposure: first and/or second trimester (HR 1.64; 95% CI 1.12–2.41); third trimester (HR 1.32; 95% CI 0.77–2.25)>2 inhaled steroid prescriptions within 12 moThe pregnancy IADB database
 Källén et al15 (Sweden)685 0151999–20072–6 yDuring the second or third trimester (OR 1.60, 95% CI 1.40–1.76)>5 prescription events for antiasthmatic drugsThe Swedish Medical Birth Register and The Swedish Prescribed Drug Register
 Yitshak-Sade et al14 (Israel)91 4281999–20083–13 yTrimester of exposure: first trimester (RR 1.08; 95% CI 0.97–1.21), second trimester (RR 1.11; 95% CI 0.93–1.32), third trimester: (RR 0.99; 95% CI 0.82–1.20)Hospitalization for asthma diagnosisClalit health services (health maintenance organization)
 Cea Soriano et al18 (United Kingdom)11 0101996–2010Maximum of 6 y follow-upTrimester of exposure (RR, 95% CI)b. Model A: first trimester (PPI: 1.16 [0.88–1.52], H2RA: 1.16 [0.84–1.61]); second trimester (PPI: 1.39 [0.89–2.18], H2RA: 1.77 [1.34–2.33]); third trimester (PPI: 1.04 [0.68–1.60], H2RA: 1.38 [1.14–1.68]). Model E: first trimester (PPI: 1.07 [0.76–1.51], H2RA: 1.15 [0.77–1.72]); second trimester (PPI: 1.11 [0.60–2.05], H2RA: 1.75 [1.25–2.47]); third trimester (PPI: 0.69 [0.36–1.30], H2RA: 1.20 [0.93–1.54])According to general practitioner, recorded clinical asthma eventsThe health improvement network databasec
Case-crossover studies
 Hak et al16 (United Kingdom)37481996–2010Mean age at diagnosis of asthma 3.6 yThe trimester of exposure. H2RA: first trimester (HR 1.15; 95% CI 0.77–1.72), second trimester (HR 1.75; 95% CI 1.25–2.47), third trimester (HR 1.20; 95% CI 0.93–1.54); PPI: first trimester (HR 1.07; 95% CI 0.76–1.51), second trimester (HR 1.11; 95% CI 0.60–2.05), third trimester (HR 0.69; 95% CI 0.36–1.30)Prescribed any asthma medications >3 times within 12 mo after the first diagnosis dateUnited Kingdom General Practitioners Research Database
 Mulder et al17 (Netherlands)12 5301995–2011≥5.5 yAfter adjustment for maternal age at birth, prenatal exposure to acid-suppressive drugs. Statistically significantly increased the odds of toddler having asthma by 52% (adjusted OR, 1.52; 95% CI 1.11–2.09)>2 prescriptions for asthma medications during follow-upThe pregnancy IADB database
  • IADB, InterAction Database; NA, not available.

  • a The minimum age of children and minimum medication dispensing when defining asthma.

  • b Model A: Cox proportional hazard model adjusted for the number of maternal primary care physician visits and referrals during the year before the last menstrual period date and year of delivery. Model E shows the Cox proportional hazard model adjusted for number of maternal primary care physician visits and referrals during the year before the last menstrual period date and year of delivery; maternal comorbidities (asthma, allergies, GERD, and peptic ulcer); maternal use of nonsteroidal anti-inflammatory drugs, antacids, antibiotics, and antihistamine medications during pregnancy; and sex of the infant.

  • c Automated computer search, manual confirmation, and secondary validation by questionnaire.