Preconception exposure to over-the-counter medications and antibiotics and the risk of childhood asthma in Lebanon: A cross-sectional study

Diana Malaeba, b, Souheil Hallit c, d*, Hala Sacred, Clara Rahmee, Bassem Malaebf, Rabih Hallitc, g, h, Pascale Salamehd, i, j

aSchool of Pharmacy, Lebanese International University, Beirut, Lebanon

bDepartment of Life and Science, Paris Est University, Paris, Lebanon

cFaculty of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh, Lebanon

dINSPECT-LB: Institut National de Sante Publique, Epidemiologie Clinique et Toxicologie-Liban, Beirut, Lebanon

eResearch Department, Psychiatric Hospital of the Cross, Jal Eddib, Lebanon

fAin W Zein Medical Village, Lebanon

gInfectious Disease Department, Bellevue Medical Center, Mansourieh, Lebanon

hInfectious Disease Department, Notre Dame des Secours University Hospital, Byblos, Lebanon

iFaculty of Pharmacy, Lebanese University, Hadat, Lebanon

jFaculty of Medicine, University of Nicosia, Nicosia, Lebanon


Objective: The aim of this study was to elucidate the relationship between the mother’s use of over-the-counter (OTC) medications during pregnancy and asthma in Lebanese children.

Methods: A cross-sectional study was conducted on Lebanese students in both public and private schools, between January and September 2017, involving 1000 children aged between 4 and 17 years.

Results: The intake of any medication as an independent variable throughout pregnancy reveals that being in a public school compared to a private one (Beta = 0.344) and breastfeeding (Beta = 0.51) were highly associated with lower odds of asthma, while having a positive family of allergic rhinitis (Beta = 2.129) and the intake of any medication during pregnancy (Beta = 7.052) were highly associated with higher odds of asthma.

A second logistic regression, taking as the dependent variable asthmatic versus healthy children and taking each OTC drug as an independent variable, showed that taking paracetamol once per week during pregnancy (Beta = 4.66) and proton pump inhibitors (PPIs) once per month (Beta = 3.498) compared to no intake were significantly correlated with higher probability of asthma.

Conclusion: Our findings showed that the intake of paracetamol, vitamin C, and PPIs during pregnancy is strongly correlated with asthma in the offspring. Since these factors are avoidable, it is necessary to raise awareness among healthcare professionals to reduce the prevalence of asthma in children.

Key words: asthma, breastfeeding, children, drugs, paracetamol, pregnancy, proton pump inhibitors

*Corresponding author: Souheil Hallit. Building 560, Street 8, 1st floor, Biakout, Lebanon. Email address: [email protected]

*Diana Malaeb and Souheil Hallit contributed equally to this manuscript

DOI: 10.15586/aei.v49i2.46

Received 8 July 2020; Accepted 12 September 2020; Available online 1 March 2021

Copyright: Diana Malaeb, et al.
License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0).


Asthma is the main reason why children miss school days and the third major cause of their hospitalization. It is the most common chronic inflammatory childhood disease in which many elements play a role in the hyperresponsiveness of the airways, leading to recurrent wheezing episodes, shortness of breath, tightness in the chest, and coughing, mostly at night or in the early morning.12 Many risk factors are involved in the increased propensity of asthma development in children, such as young age, male gender, low socioeconomic status, and private schools.3 It is well established that asthma is more prevalent in childhood, as wheezes are extremely common in the first year of life4 due to small airway narrowing, bronchoconstriction, and the presence of multiple recurrent viruses associated with cough and sputum production.5 Scientific evidence indicates that childhood asthma is more common in males since they have increased allergic inflammation and serum IgE levels, and smaller airway diameters, making boys more likely to develop asthma symptoms compared to girls.6 Another factor that may increase the risk of asthma development in children is the low socioeconomic status, which translates into the high exposure to stress, higher infection rates, increased risk of an atopic profile, and lower medical referral and regular follow-ups.7 Private schools also show a higher prevalence of asthma as children may be living in wealthy families, thus highly exposed to a variety of foods known to trigger asthma.8

Moreover, some of the known factors of childhood asthma include a family history of asthma in one or both parents, smoking, exposure to pesticides, and the use of medications during pregnancy.9 However, the etiology of childhood asthma remains unclear despite numerous studies within populations seeking to explain why some people develop asthma and other allergy-related diseases rather than others.10,11

The relationship between medication use during pregnancy and asthma in children has been widely studied and involves several drug classes. The increase in antibiotic use went hand in hand with an increase in asthma in children,12 triggering the investigation of the harmful effect of this class during the prenatal period13,14 and early childhood.1416 It is noteworthy that some antibiotics are dispensed as over-the-counter (OTC) drugs in Lebanon, although the law classifies them as prescription only drugs.1719 Paracetamol, an analgesic and antipyretic frequently used during pregnancy and in childhood, has been linked with the increased incidence of asthma.2022 Moreover, as a pleiotropic mediator that leads to pulmonary health, vitamin D seems to play a key role: children with asthma happen to be at increased risk of insufficient vitamin D. Epidemiological evidence suggests that low vitamin D levels in the serum of children with asthma are associated with additional symptoms, exacerbations, reduced function of the lung, and increased use of medications.23 Prenatal exposure to proton pump inhibitors (PPIs) and H2-blockers is a serious concern that may raise the risk of allergic disease in the offspring by increasing the risk of Th2-mediated conditions like asthma and allergies.24-26 Finally, non-steroidal anti-inflammatory drugs (NSAIDs) used during pregnancy are also involved in causing asthma in children, as the use of ibuprofen in the second and third trimesters and infant asthma at 18 months.27

To our best knowledge, no studies have assessed the effect of medication intake during pregnancy and asthma in children in Lebanon. Therefore, this study aims to elucidate the relationship between the mother’s use of medications during pregnancy and asthma in children.


General study design

This cross-sectional study, conducted between January and September 2017, enrolled Lebanese students from public and private schools. Schools were randomly selected based on the list of the Lebanese Ministry of Higher Education. A total of 34 schools were contacted from all the Lebanese regions: 17 public schools (5 in Beirut, 3 in South Lebanon, 1 in Nabatieh, 2 in Mount Lebanon, 5 in North Lebanon, and 1 in Beqaa) and 17 private schools (6 in Beirut, 6 in Mount Lebanon, 2 in North Lebanon, 1 in Nabatieh, and 2 in Beqaa). Eight schools (1 public and 7 private schools) declined to participate, and 26 out of 34 (76.47%) schools agreed to participate and thus the questionnaires were distributed to students between grades 1 and 9. All students aged 4–17 years were eligible, except those with chronic respiratory conditions or whose parents refused to participate.

A standardized questionnaire was distributed to participants to document asthma status and evaluate respiratory symptoms using validated International Study of Asthma and Allergies in Childhood (ISAAC) items. Students were asked to take it home, fill it out by their parents, and return it to school. The questionnaires were then collected back anonymously.

Sample size calculation

A sample of 886 patients was targeted to allow an adequate power for bivariate and multivariable analyses to be carried out according to the Epi-info sample size calculations, since paracetamol use during pregnancy was associated with an increased risk of wheezing in the offspring in a previous study21 (adjusted odds ratio = 2.10 and with a 95% confidence interval). A total of 1300 questionnaires were distributed to take into account refusals and loss of participants at follow-up, and gather all possible drug intake during pregnancy.

Data collection

The questionnaire used was self-administered, anonymous, in Arabic (the native language in Lebanon) and required around 25 min to complete. It assessed the sociodemographic characteristics, including age, gender, actual weight and height, the number of younger and older siblings, parents’ level of education, and medical history (asthma, eczema, and rhinitis) of parents and siblings, in addition to questions assessing behaviors during pregnancy, that is, smoking (cigarette and waterpipe), alcohol consumption, and OTC medication use. It also included questions related to environmental conditions during early childhood, such as home humidity assessed by the presence of humidity and molds seen on walls, heating system in the household, and childhood history of recurrent otitis, or cardiac issues. Previous studies can show more details about the questionnaire.2836

The questions that assessed OTC medications used during pregnancy encompassed the most studied medications that showed a correlation with an asthma diagnosis, that is, antibiotics,1114 paracetamol,15 vitamin D,2021 anti-reflux and acid-suppressive drugs,2426 ibuprofen,27 and vitamin C.37 The frequencies of intake were divided into the following: never or occasionally, once every month, one-three times every month, once every week, two to four times a week, and more than five times a week. In some drugs variables, the frequencies were collapsed into several levels where cells do not contain 0.

This last section was translated into Arabic from the standardized and validated respiratory disease questionnaire of the American Thoracic Society.38

The completed questionnaires were placed in sealed envelopes at the end of the collection process and sent for data entry.

The sample was divided into two groups: 1) a control group of healthy children with neither a physician-diagnosed respiratory illness nor respiratory symptoms (wheezing, coughing, and dyspnea), and 2) a group of children diagnosed asthma with symptoms (chronic wheezing, cough, and dyspnea), and an affirmative answer to the question “did your doctor ever tell you that your child has asthma?” Children were excluded from the analysis if they had respiratory symptoms without a physician’s diagnosis of asthma.

Statistical analysis

A study-independent person analyzed the collected data using Statistical Package for Social Sciences (SPSS) software, version 23.0. Since missing data constituted less than 10% of the total data, it was not replaced in the database. Continuous variables are presented as mean and standard deviation and categorical variables as frequencies. Parametric tests were used since the variables showed normal distribution. Correlations between medication use during pregnancy and asthma diagnosis were obtained by the Pearson chi-square test or the Fisher test when needed. Two multivariable logistic regressions took the presence vs. absence of asthma as the dependent variable and used independent variables showing a p < 0.2 in the bivariate analysis to protect against residual confounding. In the first regression, the intake of any medication was taken as an independent variable, while in the second regression, each OTC drug was taken as an independent variable. A value of p < 0.05 was considered statistically significant.


Sociodemographic and other characteristics of the children

Out of the 1300 distributed questionnaires, 1000 (76.92%) were collected back from the children or their parents in schools. No comparison could be done between those who participated and those who did not since no data were available about those who did not participate. Table 1 summarizes the sociodemographic and socioeconomic features of the children and their parents. Our results showed that the mean age of children was 10.34 ± 3.96 years (49.6% of boys and 50.4% of girls), with nearly the same distribution among governorates. Around 31% of these children had humidity at home, while 11.2% had a history of recurrent ear infections, and 1.2% had a history of heart problems.

Table 1 Characteristics of the children who underwent study enrollment and their parents who completed the questionnaire.

Variable Children Mother Father
Age, years (m ± SD) 10.34 ± 3.96 - -
Weight in kg (m ± SD) 54.04 ± 11.67 - -
Height in m (m ± SD) 1.59 ± 0.12 - -
Gender: no (%) - -
Male 496 (49.6)
Female 504 (50.4)
Place of baby residence: no (%)
Beirut 143 (14.3) - -
Mount Lebanon 139 (13.9) - -
South 149 (14.9) - -
North 138 (13.8) - -
Bekaa 121 (12.1) - -
Nabatieh 150 (15.0) - -
Akkar 160 (16.0) - -
School type: no (%) - -
Private 80 (8.0) - -
Public 920 (92.0) - -
Child vaccinations: no (%)
No 153 (15.3) - -
Yes 847 (84.7) - -
Method of baby delivery: no (%)
Normal 530 (53.0) - -
C-section 470 (47.0) - -
Asthmatic diagnosis: no (%) 107 (10.7) - -
Child still suffering from asthma: no (%)
No 44 (4.4) - -
Yes 63 (6.3) - -
Smoke regularly: no (%) - 357 (35.7) 503 (50.3)
Level of education
Illiterate - 25 (2.5) 28 (2.8)
Primary school - 43 (4.3) 194 (19.4)
Complementary - 187 (18.7) 325 (32.5)
Secondary school - 482 (48.2) 345 (34.5)
University - 263 (26.3) 108 (10.8)
Cigarettes - 215 (21.5) 369 (36.9)
Waterpipe - 135 (13.5) 108 (10.8)
Others - 7 (0.7) 7 (0.7)
Family history of asthma
Sister 2 (0.2) - -
Brother 25 (2.5) 9 (9.0) 57 (5.7)
Others 26 (2.6) - -
Family history of eczema
Sister 8 (0.8) 11 (1.1) 7 (0.7)
Family history of allergic rhinitis
Sister 11 (1.1) 15 (1.5) 7 (0.7)
Brother 26 (2.6)
Others 23 (2.3)
Kindergarten child attendance 180 (18.0)
Table 1 Continued
Variable Children Mother Father
Number of siblings older than child
No 199 (19.9) - -
1–2 siblings 533 (53.3) - -
>3 siblings 268 (26.8) - -
Number of siblings younger than child
No 381 (38.1) - -
1-2 siblings 511 (51.1) - -
>3 siblings 108 (10.8) - -
Intake of medication during pregnancy 222 (22.2)
Humidity in the home 34 (31.8) - -
Fuel for heating - -
Gas 49 (45.8)
Oils 9 (8.4)
Firewood 25 (23.4)
Electricity 16 (15.0)
Central heating 8 (7.5)
Smoking during pregnancy 29 (27.1) - -
Alcohol intake during pregnancy 7 (6.5) - -
Children recurrent history of ear infections 60 (7.4) 21 (24.4) 12 (11.2)
Children history of heart problems 7 (0.9) 0 (0.0) 2 (1.9)

Bivariate analysis of factors associated with asthma diagnosis

A remarkably higher percentage of asthmatic children were born to mothers who took any OTC medication (all classes included) during pregnancy (60.7% vs. 17.6%; p < 0.0001) compared to children whose mothers did not take any medication during pregnancy. Compared to children whose mothers did not take any medication during pregnancy, a substantially higher percentage of children with asthma were born to mothers who took paracetamol 1–3 times per month (31.8% vs. 2.2%) and once weekly (4.6% vs. 1.9%), respectively, and ibuprofen 1–3 times per month (13.1% vs. 1.9%) during their pregnancy. The same applies for the intake of acetylsalicylic acid once per month or more (23.4% vs. 0%), amoxicillin/clavulanic acid once a month (18.7% vs. 0%), vitamin C 2–4 times per week (19.6% vs. 3.8%), PPIs once per month or more (24.3% vs. 2.8%).

Furthermore, a significantly higher proportion of asthmatic children were born to mothers who took any OTC medication (all classes included) during lactation (4.8% vs. 0%), went to private schools (17.8% vs. 6.8%), and were delivered by C-section (57.9% vs. 45.7%). Finally, a higher proportion of children with asthma had a positive family history of asthma, eczema, allergic rhinitis, and allergy (Table 2).

Table 2 Bivariate analysis of factors associated with asthma diagnosis.

Variable Healthy Diagnosed asthma Pearson chi-square P-value
Intake of any medication during pregnancy 157 (17.6%) 65 (60.7%) 103.085 <0.001
Intake of drug in pregnancy trimester 7.686 0.053
First 16 (10.2%) 11 (16.9%)
Second 30 (19.1%) 17 (26.2%)
Third 11 (7.0%) 0 (0.0%)
All trimesters 100 (63.7%) 37 (56.9%)
Paracetamol intake during pregnancy 295.318 <0.001
Never or occasionally 702 (78.6%) 41 (38.3%)
Once per month 122 (13.7%) 9 (8.4%)
One to three times per month 20 (2.2%) 34 (31.8%)
Once per week 2 (1.9%) 41 (4.6%)
Two to Four times per week or more 8 (0.9%) 21 (19.6%)
Ibuprofen intake during pregnancy 41.422 <0.001
Never or occasionally 830 (92.9%) 91 (85.0%)
Once per month or more 41 (4.7%) 2 (2.2%)
One to three times per month 17 (1.9%) 14 (13.1%)
Once per week or more 5 (0.6%) 0 (0%)
Propranolol intake during pregnancy 2.946 0.099
Never or occasionally 869 (97.3%) 107 (100.0%)
Once per month or more 24 (2.7%) 0 (0.0%)
Acetylsalicylic acid intake during pregnancy 205.422 <0.001
Never or occasionally 891 (99.8%) 82 (76.6%)
Once per month or more 0 (0.0%) 25 (23.4%)
Amoxicillin/clavulanic Acid intake during pregnancy 258.355 <0.001
Never or occasionally 889 (99.6%) 75 (70.1%)
Once per month 0 (0.0%) 20 (18.7%)
One to three times per month 0 (0.0%) 9 (8.4%)
Once per week or more 4 (0.4%) 3 (2.8%)
Vitamin C intake during pregnancy 66.647 <0.001
Never or occasionally 766 (85.8) 74 (69.2)
Once per month 27 (3.0) 3 (2.8)
One to three times per month 0 (0.0) 2 (1.9)
Once per week 43 (4.8) 7 (6.5)
Two to four times per week 34 (3.8) 21 (19.6)
More than five times per week 23 (2.6) 0 (0.0)
Fish oil intake during pregnancy 1.825 0.177
Never or occasionally 878 (98.3%) 107 (100.0)
Once per month or more 15 (1.7%)
Probiotics intake during pregnancy 0 (0.0%) 2.196 0.138
Never or occasionally 875 (98.0) 107 (100.0%)
Once per month or more 18 (2.0%) 0 (0.0%)
Proton pump inhibitors intake during pregnancy 174.056 <0.001
Never or occasionally 868 (97.2%) 81 (75.7%)
Once per month or more 125 (2.8%) 26 (24.3%)
Vitamin D intake during pregnancy 29.687 0.996
Never or occasionally 809 (90.6%) 97 (90.7%)
Once per month or more 84 (9.4%) 10 (9.3%)
H2 blockers intake during pregnancy 1.578 0.657
Never or occasionally 880 (98.5%) 107 (100.0%)
Once per month or more 13 (1.5%) 0 (0.0%)
Intake of any OTC medication during lactation 0 (0.0%) 5 (4.8%) 43.149 <0.001
Gender 3.337 0.082
Male 434 (48.6) 62 (57.9)    
Female 459 (51.4) 45 (42.1)    
Place of baby residence – 1.717 0.788
Beirut 126 (14.1%) 17 (15.9%)    
Mount Lebanon 124 (13.9%) 15 (14.0%)    
North 264 (29.6%) 34 (31.8%)    
South 267 (29.9%) 32 (29.9%)    
Bekaa 112 (12.5%) 9 (8.4%)    
School type 15.498 <0.001
Private 61 (6.8%) 19 (17.8%)
Public 832 (93.2%) 88 (82.2%)
Method of baby delivery 5.761 0.018
Normal 485 (54.3%) 45 (42.1%)
C-section 408 (45.7%) 62 (57.9%)
Breastfeeding (yes) 717 (80.3%) 67 (62.6%) 17.626 <0.001
Father level of education 23.007 0.167
Illiterate 28 (3.1%) 0 (0.0%)
Primary 171 (19.1%) 23 (21.5%)
Complementary 295 (33.0%) 30 (28.0%)
Secondary/university 399 (44.7%) 54 (50.5%)
Mother level of education 22.667 <0.001
Illiterate 24 (2.7%) 1 (0.9%)
Primary school 40 (4.5%) 3 (2.8%)
Complementary 151 (16.9%) 36 (33.6%)
Secondary school 447 (50.1%) 35 (32.7%)
University 231 (25.9%) 32 (29.9%)
Positive family history
Asthma 51 (5.7%) 75 (70.1%) 359.656 <0.001
Eczema 4 (0.4%) 22 (20.6%) 170.114 <0.001
Allergy 213 (23.9%) 90 (84.1%) 164.292 <0.001
Allergic Rhinitis 69 (7.7%) 15 (14.0%) 133.868 <0.001

Multivariable analysis

A first logistic regression considered children with diagnosed asthma versus healthy children as the dependent variable and the intake of any medication during pregnancy as an independent variable. The results showed that attending a public school (compared to a private one) (Beta = 0.344) and breastfeeding (Beta = 0.51) were significantly correlated with lower odds of asthma, whereas having a positive family history of allergic rhinitis (Beta = 2.129) and the intake of any medication during pregnancy (Beta = 7.052) were significantly correlated with higher odds of asthma (Table 3, Model 1).

Table 3 Multivariable analysis.

Model 1: Logistic regression 1 taking controls versus diagnosed asthma as the dependent variable and the intake of any medication during pregnancy as an independent variable
Factor P-value OR 95% confidence interval
Lower limit Upper limit
School type (public vs. private*) 0.001 0.344 0.185 0.640
Breastfeeding (yes vs. no*) 0.004 0.510 0.322 0.808
Family history of allergic rhinitis (yes vs. no*) 0.020 2.129 1.129 4.017
Intake of any OTC medication during pregnancy (yes vs. no*) <0.001 7.052 4.556 10.918
Variables entered in the model: intake of any medication during pregnancy, gender, school type, method of baby delivery, breastfeeding, mother’s and father’s level of education, and positive family history.
Model 2: Logistic regression 2 taking controls versus diagnosed asthma as the dependent variable and taking each OTC medication as an independent variable
Factor P-value OR 95% confidence interval
Lower limit Upper limit
School type (public vs. private*) 0.002 0.332 0.166 0.664
Paracetamol intake during pregnancy once per week compared to no intake* <0.001 4.660 1.922 11.301
Proton pump inhibitors intake during pregnancy once per month or more compared to no intake* 0.01 3.498 1.356 9.023
Variables entered in the model: paracetamol, ibuprofen, propranolol, acetylsalicylic acid, amoxicillin/clavulanic acid, vitamin C, fish oil, and proton pump inhibitors, gender, school type, method of baby delivery, breastfeeding, mother’s and father’s level of education, and positive family history.

OR, odds ratio.

*Reference group; Numbers in bold indicate significant p-values.

A second logistic regression, taking asthmatic versus healthy children as the dependent variable and the intake of each OTC drug as an independent variable, showed that attending a public school compared to a private one (Beta = 0.332) was significantly associated with lower odds of asthma, whereas taking paracetamol once per week during pregnancy (Beta = 4.66) and PPIs once per month (Beta = 3.498) compared to no medication intake were significantly associated with higher odds of asthma (Table 3, Model 2).


This cross-sectional pilot study is the first to assess a potential correlation between maternal medication intake during pregnancy and childhood diagnosed asthma among Lebanese schoolchildren. It showed that the intake of some specific medications (paracetamol and PPIs) and a positive family history of allergic rhinitis were significantly linked to higher odds of childhood asthma, contrary to a recent Lebanese study34 that did not find any correlation. However, the literature is full of evidence regarding the relationship between mother’s intake of medications during pregnancy and childhood asthma.39,40

Effect of paracetamol on asthma

The use of paracetamol 2–4 times per week during pregnancy was associated with higher childhood asthma, in agreement with previous studies.20,21,4143 Many possible mechanisms can explain the causal link between paracetamol and asthma, the most common being the oxidant/antioxidant imbalance, as described by Koniman et al.41

Effect of proton pump inhibitors on asthma

Our findings revealed that the use of PPIs more than five times per week was associated with a high probability of asthma in the offspring. There is a controversy concerning this association; some studies did not find any link between the two variables,37,44 while others confirmed it.25,45

Effect of vitamin D on asthma

The intake of vitamin D during pregnancy was not involved in childhood asthma. A cohort study46 showed that maternal intake of vitamin D in the first three months and up to 32 weeks gestation increased the risk of childhood wheezing at the age of 5. However, other research found that vitamin D supplementation from 27 weeks gestation did not decrease wheezing or asthma in 3-year-old children.47 The results of these two trials suggest that vitamin D supplementation during the first and second trimesters (before 27 weeks of gestation) may be more appropriate.

Effect of antibiotics on asthma

Our findings showed no correlation between antibiotic consumption during pregnancy and childhood asthma. There is limited and inconsistent evidence regarding the role of some antibiotics in the development of asthma.39,4850 No specific antibiotics used by the mother during pregnancy were linked to asthma in the offspring.39 The mechanism by which antibiotics could influence the development of asthma in children is that they cross the placenta and enter the fetal bloodstream, causing neonatal microflora alterations, including the proliferation of resistant bacteria and immune developmental changes.5155 The postponed colonization of the gut microbiota of the child impairs the maturation of the immune system of the child and therefore affects asthma development.

Limitations and strengths

This study presents some potential limitations. Its cross-sectional design, and thus a low level of evidence, cannot infer causality. Because this study is retrospective, the possibility of recall bias may exist, leading to the overestimation of effects. Moreover, many variables, but not all factors that might have a risk on the development of asthma, were considered. The nonparticipation bias is also possible since we had a 23% refusal rate. Although the sample was recruited from all Lebanese governorates, the results are not generalizable to the whole population. The medical history of mothers was not reviewed in coordination with the asthma exacerbation in children. Residual confounding bias might also be possible since some variables (health insurance coverage, birth weight, prematurity, and early childhood bronchiolitis) were not taken into account in this study. Consequently, prospective studies taking into account these limitations are needed, mainly to get unbiased information on drug use, either by interviewing pregnant women or by checking medical records or registers of prescribed medications. The strengths of this study include the numerous subjects recruited from all geographic areas of Lebanon, in addition to the diagnosis of asthma that was defined according to international criteria.


The use of medications during pregnancy seems to be a risk factor of asthma among schoolchildren in Lebanon. Our findings showed that the intake of paracetamol, vitamin C, and PPIs during pregnancy is strongly correlated with asthma in the offspring. Because these factors are avoidable, it is necessary to raise awareness among healthcare professionals to reduce the prevalence of asthma in children. Further prospective studies overriding the recall bias are warranted to confirm the accuracy of the results of this study.


The authors would like to thank all the patients who agreed to take part in this study.

Competing interests

The authors declare that they have no competing interest.



Ethical consideration

The study protocol was approved by the Faculty of Pharmacy’s Institutional Review Board at Lebanese International University, based on the fact that it was an observational study that respected the autonomy and confidentiality of the participants and caused minimal harm to them. All parents who agreed to participate in the study provided a written informed consent.

Authors’ contribution

The surveys were conceived and designed by DM, SH and PS. The data collection and entry were carried out by DM. DM, SH, and PS were involved in interpreting data and analyzing statistics. The manuscript was written by SH and DM. For intellectual content, all authors have critically revised the manuscript. The final manuscript was read and approved by all authors.

Availability of data and materials

There is no public access to all data generated or analyzed during this study to preserve the privacy of the identities of the individuals. The data set that supports the conclusions is available from the corresponding author upon request.

Consent to publish

Not applicable.


1. GINA guidelines. Global strategy for asthma management and prevention 2020. Available from: [Accessed February 8, 2020].

2. Cdc. National surveillance of asthma: United states, 2001 2010. Available from: http://www.Cdc.Gov/nchs/data/series/sr_03/sr03_035.Pdf. [accessed].

3. Trivedi M, Denton E. 2019. Asthma in children and adults-what are the differences and what can they tell us about asthma? Front Pediatr. 7:256. 10.3389/fped.2019.00256

4. Hallit S, Leynaert B, Delmas MC, Rocchi S, De Blic J, Marguet C, et al. 2018. Wheezing phenotypes and risk factors in early life: The ELFE cohort. PLoS One. 13(4):e0196711. 10.1371/journal.pone.0196711

5. Fuchs O, Bahmer T, Rabe KF, von Mutius E. 2017. Asthma transition from childhood into adulthood. Lancet Respir Med. 5(3):224–234. 10.1016/S2213-2600(16)30187-4

6. Genuneit J. 2014. Sex-specific development of asthma differs between farm and nonfarm children: A cohort study. Am J Respir Crit Care Med. 190(5):588–590. 10.1164/rccm.201403-0428LE

7. Kozyrskyj AL, Kendall GE, Jacoby P, Sly PD, Zubrick SR. 2010. Association between socioeconomic status and the development of asthma: Analyses of income trajectories. Am J Public Health. 100(3):540–546. 10.2105/AJPH.2008.150771

8. Kiboneka A, Levin M, Mosalakatane T, Makone I, Wobudeya E, Makubate B, Hopp R, Mazhani L, Kung SJ. 2016. Prevalence of asthma among school children in Gaborone, Botswana. Afr Health Sci. 16(3):809–816. 10.4314/ahs.v16i3.22

9. Mannino dm, homa dm, pertowski ca, et al. Surveillance for asthma-united states, 1960-1995. Mor mortal wkly rep cdc surveill summ 1998;47:1–27. Available from: http://www.Cdc.Gov/mmwr/preview/mmwrhtml/00052262.Htm. [accessed].

10. Waked M, Salameh P. 2006. Asthma, allergic rhinitis and eczema in 13-14-year-old schoolchildren across Lebanon. J Med Liban. 54(4):181–190.

11. Weiland SK, Bjorksten B, Brunekreef B, Cookson WO, von Mutius E, Strachan DP, International Study of A, Allergies in Childhood Phase IISG. 2004. Phase ii of the international study of asthma and allergies in childhood (ISAAC II): Rationale and methods. Eur Respir J. 24(3):406–412. 10.1183/09031936.04.00090303

12. Adriaenssens N, Coenen S, Versporten A, Muller A, Minalu G, Faes C, et al. 2011. European surveillance of antimicrobial consumption (ESAC): Outpatient quinolone use in Europe (1997-2009). J Antimicrob Chemother. 66 Suppl 6:vi47–56. 10.1093/jac/dkr457

13. Stensballe LG, Simonsen J, Jensen SM, Bonnelykke K, Bisgaard H. 2013. Use of antibiotics during pregnancy increases the risk of asthma in early childhood. J Pediatr. 162(4):832–838, e833.10.1016/j.jpeds.2012.09.049

14. Metsala J, Lundqvist A, Virta LJ, Kaila M, Gissler M, Virtanen SM. 2015. Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood. Clin Exp Allergy. 45(1):137–145. 10.1111/cea.12356

15. Goksor E, Alm B, Pettersson R, Mollborg P, Erdes L, Aberg N, et al. 2013. Early fish introduction and neonatal antibiotics affect the risk of asthma into school age. Pediatr Allergy Immunol. 24(4):339–344. 10.1111/pai.12078

16. Ong MS, Umetsu DT, Mandl KD. 2014. Consequences of antibiotics and infections in infancy: Bugs, drugs, and wheezing. Ann Allergy Asthma Immunol. 112(5):441–445, e441. 10.1016/j.anai.2014.01.022

17. Farah R, Lahoud N, Salameh P, Saleh N. 2015. Antibiotic dispensation by Lebanese pharmacists: A comparison of higher and lower socio-economic levels. J Infect Public Health. 8(1):37–46. 10.1016/j.jiph.2014.07.003

18. Salameh P, Sacre H, Hallit S, Hajj A. [(accessed Jan 13, 2020)]; antibiotic resistance in lebanon. Available from: http://resistancecontrol.Info/2017/antibiotic-resistance-in-lebanon/. [accessed].

19. Badro DA, Sacre H, Hallit S, Amhaz A, Salameh P. 2020. Good pharmacy practice assessment among community pharmacies in lebanon. Pharm Pract (Granada). 18(1):1745. 10.18549/PharmPract.2020.1.1745

20. Shaheen SO, Newson RB, Henderson AJ, Headley JE, Stratton FD, Jones RW, et al. 2005. Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin e in childhood. Clin Exp Allergy. 35(1):18–25. 10.1111/j.1365-2222.2005.02151.x

21. Shaheen SO, Newson RB, Sherriff A, Henderson AJ, Heron JE, Burney PG, et al. 2002. Paracetamol use in pregnancy and wheezing in early childhood. Thorax. 57(11):958–963. 10.1136/thorax.57.11.958

22. Lourido-Cebreiro T, Salgado FJ, Valdes L, Gonzalez-Barcala FJ. 2017. The association between paracetamol and asthma is still under debate. J Asthma. 54(1):32–38. 10.1080/02770903.2016.1194431

23. Gupta A, Bush A, Hawrylowicz C, Saglani S. 2012. Vitamin d and asthma in children. Paediatr Respir Rev. 13(4):236–243; quiz 243. 10.1016/j.prrv.2011.07.003

24. Dehlink E, Yen E, Leichtner AM, Hait EJ, Fiebiger E. 2009. First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: A population-based register study. Clin Exp Allergy. 39(2):246–253. 10.1111/j.1365-2222.2008.03125.x

25. Mulder B, Schuiling-Veninga CC, Bos HJ, De Vries TW, Jick SS, Hak E. 2014. Prenatal exposure to acid-suppressive drugs and the risk of allergic diseases in the offspring: A cohort study. Clin Exp Allergy. 44(2):261–269. 10.1111/cea.12227

26. Yitshak-Sade M, Gorodischer R, Aviram M, Novack L. 2016. Prenatal exposure to h2 blockers and to proton pump inhibitors and asthma development in offspring. J Clin Pharmacol. 56(1):116–123. 10.1002/jcph.574

27. Nezvalova-Henriksen K, Spigset O, Nordeng H. 2013. Effects of ibuprofen, diclofenac, naproxen, and piroxicam on the course of pregnancy and pregnancy outcome: A prospective cohort study. BJOG. 120(8):948–959. 10.1016/j.reprotox.2013.02.024; 10.1111/1471-0528.12192

28. Hallit S, Assi TB, Hallit R, Salameh P. 2017. Allergic diseases, smoking, and environmental exposure among university students in lebanon. J Asthma. 2018 Jan;55(1):35–42. 10.1080/02770903.2017.1306075

29. Hallit S, Raherison C, Abou Abdallah R, Hallit R, Salameh P. 2017. Correlation of types of food and asthma diagnosis in childhood: A case-control study. J Asthma. 0. 10.1080/02770903.2017.1379535

30. Hallit S, Raherison C, Malaeb D, Hallit R, Kheir N, Salameh P. 2018. The AAA risk factors scale: A new model to screen for the risk of asthma, allergic rhinitis and atopic dermatitis in children. Med Princ Pract. 10.1159/000490704

31. Hallit S, Raherison C, Malaeb D, Hallit R, Waked M, Kheir N, et al. 2018. Development of an asthma risk factors scale (ARFS) for risk assessment asthma screening in children. Pediatr Neonatol. 10.1016/j.pedneo.2018.05.009

32. Hallit S, Raherison C, Waked M, Hallit R, Layoun N, Salameh P. et al. 2018. Validation of the mini pediatric asthma quality of life questionnaire and identification of risk factors affecting quality of life among Lebanese children. J Asthma. 1–11. 10.1080/02770903.2018.1441417

33. Hallit S, Raherison C, Waked M, Salameh P. 2017. Validation of asthma control questionnaire and risk factors affecting uncontrolled asthma among the Lebanese children’s population. Respir Med. 122:51–57. 10.1016/j.rmed.2016.11.018

34. Hallit S, Salameh P. 2017. Exposure to toxics during pregnancy and childhood and asthma in children: A pilot study. J Epidemiol Glob Health. 7(3):147–154. 10.1016/j.jegh.2017.04.004

35. Hallit S, Raherison C, Waked M, Salameh P. 2017. Association between caregiver exposure to toxics during pregnancy and childhood-onset asthma: A case-control study. Iran J Allergy Asthma Immunol. 16(6):488–500.

36. Diana Malaeb, Souheil Hallit, Hala Sacre, Rabih Hallit, Pascale Salameh, Factors associated with wheezing among Lebanese children: Results of a cross-sectional study, Allergologia et Immunopathologia, 2020, 10.1016/j.aller.2020.02.003.

37. Cea Soriano L, Hernandez-Diaz S, Johansson S, Nagy P, Garcia-Rodriguez LA. 2016. Exposure to acid-suppressing drugs during pregnancy and the risk of asthma in childhood: An observational cohort study. Aliment Pharmacol Ther. 43(3):427–437. 10.1111/apt.13486

38. Achieving healthy indoor air. Report of the ATS workshop: Santa Fe, New Mexico, November 16–19, 1995. 1997. Am J Respir Crit Care Med. 156(3 Pt 2):S31–64. 10.1164/ajrccm.156.3.rccm1563.suppl

39. McKeever TM, Lewis SA, Smith C, Hubbard R. 2002. The importance of prenatal exposures on the development of allergic disease: A birth cohort study using the west midlands general practice database. Am J Respir Crit Care Med. 166(6):827–832. 10.1164/rccm.200202-158OC

40. Rusconi F, Galassi C, Forastiere F, Bellasio M, De Sario M, Ciccone G, et al. 2007. Maternal complications and procedures in pregnancy and at birth and wheezing phenotypes in children. Am J Respir Crit Care Med. 175(1):16–21. 10.1164/rccm.200512-1978OC

41. Koniman R, Chan YH, Tan TN, Van Bever HP. 2007. A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma. Pediatr Allergy Immunol. 18(2):128–134. 10.1111/j.1399-3038.2006.00484.x

42. Kashanian M, Mohtashami SS, Bemanian MH, Moosavi SAJ, Moradi Lakeh M. 2017. Evaluation of the associations between childhood asthma and prenatal and perinatal factors. International Journal of Gynecology & Obstetrics. 137(3):290–294. 10.1002/ijgo.12141

43. Fan G, Wang B, Liu C, Li D. 2017. Prenatal paracetamol use and asthma in childhood: A systematic review and meta-analysis. Allergol Immunopathol (Madr). 45(6):528–533. 10.1016/j.aller.2016.10.014

44. Devine RE, Sheikh A, Nwaru BI. 2016. Acid-suppressive medications during pregnancy and risk of asthma and allergy in the offspring: Protocol for a systematic review. NPJ Prim Care Respir Med. 26:16001. 10.1038/npjpcrm.2016.1

45. Hak E, Mulder B, Schuiling-Veninga CC, de Vries TW, Jick SS. 2013. Use of acid-suppressive drugs in pregnancy and the risk of childhood asthma: Bidirectional crossover study using the general practice research database. Drug Saf. 36(11):1097–1104. 10.1007/s40264-013-0093-z

46. Allan KM, Prabhu N, Craig LC, McNeill G, Kirby B, McLay J et al. 2015. Maternal vitamin d and e intakes during pregnancy are associated with asthma in children. Eur Respir J. 45(4):1027–1036. 10.1183/09031936.00102214

47. Goldring ST, Griffiths CJ, Martineau AR, Robinson S, Yu C, Poulton S et al. 2013. Prenatal vitamin d supplementation and child respiratory health: A randomised controlled trial. PLoS One. 8(6):e66627. 10.1371/journal.pone.0066627

48. Marra F, Marra CA, Richardson K, Lynd LD, Kozyrskyj A, Patrick DM et al. 2009. Antibiotic use in children is associated with increased risk of asthma. Pediatrics. 123(3):1003–1010. 10.1542/peds.2008-1146

49. Kozyrskyj AL, Ernst P, Becker AB. 2007. Increased risk of childhood asthma from antibiotic use in early life. Chest. 131(6):1753–1759. 10.1378/chest.06-3008

50. Wickens K, Ingham T, Epton M, Pattemore P, Town I, Fishwick D, et al. 2008. The association of early life exposure to antibiotics and the development of asthma, eczema and atopy in a birth cohort: Confounding or causality? Clin Exp Allergy. 38(8):1318–1324. 10.1111/j.1365-2222.2008.03024.x

51. Jakobsson HE, Jernberg C, Andersson AF, Sjolund-Karlsson M, Jansson JK, Engstrand L. 2010. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One. 5(3):e9836. 10.1371/journal.pone.0009836

52. Bedford Russell A, Murch SH. 2006. Could peripartum antibiotics have delayed health consequences for the infant? BJOG: An International Journal of Obstetrics & Gynaecology. 113(7):758–765. 10.1111/j.1471-0528.2006.00952.x

53. Noverr MC, Huffnagle GB. 2005. The ‘microflora hypothesis’ of allergic diseases. Clin Exp Allergy. 35(12):1511–1520. 10.1111/j.1365-2222.2005.02379.x

54. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ et al. 2008. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of crohn disease patients. Proc Natl Acad Sci U S A. 105(43):16731–16736. 10.1073/pnas.0804812105

55. Marra F, Lynd L, Coombes M, Richardson K, Legal M, Fitzgerald JM et al. 2006. Does antibiotic exposure during infancy lead to development of asthma?: A systematic review and metaanalysis. Chest. 129(3):610–618. 10.1378/chest.129.3.610