TABLE 1

The Limitations of Each of the Included Articles

SourceLimitations
Dehlink et al11The study did not show a change in the OR for developing allergy in allergic mothers on acid-suppressive treatment.
The no. cases for subanalysis might have been too small to reach statistical significance.
The study lacked information on the subsequent social and medical histories of the children.
The study did not address GERD and may be confounding the association.
Andersen et al12The study cannot remove the potential effect of exposure through breastfeeding because such data are not recorded in the routine registries in Denmark.
The study did not address GERD and may be confounding the association.
Mulder et al13The database contains information on the dispensing of drugs, including information about the dose and dispensing date. However, whether these drugs were actually taken by the mothers is unknown and may have led to a misclassification of exposure status.
The prescription database lacked the clinical indications for which the drugs are prescribed.
The authors had no information about potential risk factors, such as maternal smoking in pregnancy, birth order and/or parity, or perinatal factors, such as gestational age and/or birth wt. They cannot rule out unknown and unmeasured confounding.
The study did not address GERD and may be confounding the association.
Källén et al15Some nonasthmatic children may have been included, although antiasthmatic drugs had been prescribed.
The use of antibiotics and cough medicines gave increased risk estimates, which declined when indicators of maternal asthma were considered.
It may involve incomplete identification of concomitant drug use or maternal asthma.
The study did not address GERD and may be confounding the association.
Yitshak-Sade et al14The main possible bias in the study was confounding by indication, which was supported by a statistically significant association between maternal consumption of the medications 2 y after delivery and childhood asthma.
Residual confounding factors associated with asthma could exist in their databases.
There was a possibility of misclassification of the outcome at study.
Cea Soriano et al18The possible misclassification of maternal exposure to acid-suppressing drugs;
Residual confounding by unmeasured and unknown risk factors could be biasing the estimates upward.
Hak et al16Although ORs were materially elevated for PPIs and H2RAs, the OR was smaller overall, which suggests a class effect, but the study had inadequate statistical power to formally test this.
It is possible that the study missed some children who had undiagnosed asthma because some children did not seek medical attention or had mild asthma not treated chronically, as was required by the study definition including drug treatment.
The study did not address GERD and may be confounding the association.
Mulder et al17It is unknown whether the prescribed drugs were actually taken, which risks the misclassification of exposure.
Because the actual conception date was not known, misclassification of exposure might have resulted in an overestimation of actual use.
No information about the use of over-the-counter drugs is present in the database, which might have led to an underestimation of actual use.
There was a lack of diagnostic information.
The study did not address GERD and may be confounding the association.