Taking antibiotics while pregnant: Impact on mom’s gut and baby’s health

Summary

  • Common infections in pregnant women that require antibiotic treatment are bacterial vaginosis and urinary tract infection. Yeast infection is also common during pregnancy, but it’s treated with antifungals.
  • Not all antibiotics are safe during pregnancy. And those that are, can still disrupt your gut microbiome. Your provider will help you choose the appropriate treatment.
  • There are several studies that have looked for associations between prenatal antibiotics and increased risk of children developing asthma, eczema, weight gain, or autism spectrum disorder later in life. While some studies have found such associations, others have not.
.
.

Can you take antibiotics while pregnant? Yes. Using them when appropriate during pregnancy will protect you and your baby from serious complications that may arise, for example, from an untreated urinary tract infection (UTI).

Although life saving in some situations, antibiotics may cause major disruptions in your gut microbiome. Keep reading to learn about common infections during pregnancy, different types of antibiotics, and possible effects these may have on your gut microbiome and on your baby’s health.

Let’s start by talking about three common infections that may occur during pregnancy, what antibiotics are typically used to treat these, and whether they are safe for you and your baby.

Click here to read about intrapartum antibiotics and how these may affect a baby's health.

Urinary tract infection

A urinary tract infection (UTI) typically develops when bacteria from the gut enter the urethra and go into the bladder [1]. About 1-2% pregnant women develop UTI [2]. It’s important to treat it as soon as possible to prevent progression to kidney infection (pyelonephritis), a serious condition that can lead to blood infection and that usually requires hospitalization.

Antibiotics commonly used to treat UTIs include [3]:

Amoxicillin, ampicillin, and cephalosporins (e.g. Cefaclor, Cefalexin)

These are generally considered safe during pregnancy [4].

Nitrofurantoin (e.g. Macrodantin®, Macrobid®) and trimethoprim-sulfamethoxazole (e.g. Bactrim® or Septra®)

These antibiotics are not recommended during the first trimester and near delivery if an alternative  treatment is available [5]. Some studies have linked them to an increased risk of birth defects (such as cleft lip or palate, jaundice, heart problems) when used during the first trimester of pregnancy, and to a higher risk of kernicterus (a type of brain damage caused by excess bilirubin in the blood) when used in the late third trimester.

But, because untreated UTIs could lead to serious consequences for both mom and baby, it may be reasonable to use nitrofurantoin or trimethoprim-sulfamethoxazole if no other option is available (e.g. if you are allergic to other antibiotics or bacterial resistance to other antibiotics was detected in urine culture), as the benefits outweigh their risk of use.

Trimethoprim may lower the levels of folic acid in the body [6]. Folic acid is often prescribed during pregnancy or when trying to conceive to lower the risk of certain birth defects in the baby. Before your body can use it, folic acid must convert to active folate 5-methyltetrahydrofolate (5-MTHF). Trimethoprim interferes with this conversion, so if you’re taking folic acid and trimethoprim, talk to your provider about potentially adjusting your dosage of folic acid. Alternatively, you can consider a 5-MTHF supplement, which is already in a usable form. Folic acid is known to prevent severe neural tube defects [7], [8] and to reduce the risk of preterm birth by 8-14% [9]-[11]. While the direct impact of 5-MTHF on these outcomes hasn’t been measured, it’s expected to be similar.

Fluoroquinolones (e.g. Ciprofloxacin, Levofloxacin)

These antibiotics are generally never prescribed in pregnancy because of a known risk of birth defects. Besides, in 2018 the FDA issued a press release that updated the adverse effects related to fluoroquinolone use (mental health side effects, hypoglycemia and others) [12].

Bacterial vaginosis

Bacterial vaginosis (BV) is a disruption of the vaginal microbiome: a reduction in Lactobacillus and an overgrowth of bacteria such as Gardnerella vaginalis, Atopobium vaginae, and Prevotella species [13], [14]. Typical symptoms may include fishy odor, a milky or gray vaginal discharge, and vaginal burning.

In pregnant women, BV has been associated with an increased risk of premature rupture of the amniotic sac and preterm birth [15]–[19]. Therefore, it’s recommended that all pregnant women with symptomatic BV receive treatment.

Commonly used antibiotics to treat BV are:

Metronidazole (Flagyl®, Metrogel-Vaginal®, others)

Metronidazole may be taken orally as a pill, and it’s also available as a topical gel that is inserted into the vagina. Orally taken metronidazole reaches the placenta. Some studies with pregnant women taking metronidazole during the first trimester have shown increased risk of cleft lip in babies exposed to this antibiotic in-utero. Other studies haven’t shown increased risk for congenital anomalies. 

Just to be safe, it’s recommended to avoid oral metronidazole during the first trimester of pregnancy [20]. Unfortunately, there are no adequate and well-controlled studies on the use of metronidazole vaginal gel in pregnant women. Blood levels after a vaginal application of metronidazole are less than 2% of those after a 500 mg oral dose [21], so a vaginal gel would be preferable than oral metronidazole during pregnancy. Check with your provider before using this antibiotic.

Clindamycin (Cleocin®, Clindesse®, others)

This antibiotic is available as a cream that you insert into your vagina. Same as for metronidazole, there aren’t well-controlled studies on its use in pregnant women. One study linked the use of clindamycin with birth defects but it wasn’t clear whether this was for the vaginal application or in which trimester it was used [4]. If possible, it’s better to avoid its use during the first trimester.

Tinidazole (Tindamax®) 

Tinidazole is taken orally. It hasn’t been thoroughly studied during pregnancy so it’s not recommended during the first trimester.

Vaginal yeast infection

Vaginal yeast infection is caused by an overgrowth of Candida, a type of yeast (fungus) that may normally live in the vagina. Typical symptoms include a thick, white vaginal discharge with a cottage cheese-like consistency, vaginal and/or vulvar itching and irritation.

Having a yeast infection while pregnant may increase the risk of passing Candida to your baby during birth [22], [23]. These may produce oral candidiasis or diaper rash during the first year of life [24].

The standard treatment of a vaginal yeast infection is antifungals. These are the most common:

  • Miconazole (Monistat®, Vagistat®), available as a cream
  • Fluconazole, available as pills
  • Clotrimazole, available as a cream and vaginal suppositories
  • Nystatin, available as a cream and vaginal suppositories

Oral antifungals like fluconazole should be preferably avoided during pregnancy because it may increase the risk of malformations in the baby [25]. However, a single dose of fluconazole, which is the standard treatment for vaginal yeast infection, is not likely to significantly increase risk. Have a discussion with your provider about what treatment will work best for you.

Vaginal creams or suppositories are okay to use during pregnancy.

Effects of antibiotics on mom’s gut microbiome

An antibiotic doesn’t distinguish between good and bad bacteria. How much it impacts your gut microbiome will depend on things like the type of antibiotic, dose, and length of treatment.

For example, a couple of studies have shown that amoxicillin decreases the numbers of beneficial Bifidobacterium and increases the numbers of unfriendly Enterobacteriaceae [26], [27]. Ciprofloxacin generates a big disruption by reducing the levels of beneficial bacteria like Bifidobacterium and Faecalibacterium, and increasing the levels of Bacteroides, Blautia, Eubacterium, and Roseburia [28]. Other antibiotics like nitrofurantoin, used to treat UTI, seem to have a milder effect on the gut microbiome [28], [29].

The good news is that one of the studies found that for most people, these changes were temporary and returned to normal after a few weeks [26].

Taking antibiotics while pregnant may make your baby more prone to some conditions later in life

Finding associations between antibiotic exposure during pregnancy and conditions that affect the baby’s health in the future is not an easy task for researchers. Imagine that you took antibiotics during pregnancy, and then at age seven your child developed asthma. So much has happened in that child’s life, it’s hard to disentangle the effects of antibiotics during pregnancy from everything else.

Other things may have made your child more likely to develop asthma. Maybe you had a respiratory infection with a fever and that's why you were prescribed antibiotics. Or perhaps you used to smoke. These variables (an inherited sensitivity to respiratory diseases or smoking) can be larger factors in your child developing asthma.

Studies must take these variables and more into account when looking for associations. These variables are known as confounders. Sometimes studies will even look at healthy siblings to verify associations. If the mom took antibiotics during another pregnancy and that baby didn’t develop asthma, then it might not be the antibiotics, right?

This is why it’s so hard to find correlations and causation. And very often, results between different studies don’t agree.

Now that we’ve thought about how associations work, let’s take a look at the associations (or lack of these) researchers have found for prenatal antibiotic exposure:

  • Weight gain. There may be a slight association between prenatal antibiotics and increased risk of being overweight, but results vary among studies. Three medium-size studies found that prenatal exposure to antibiotics was associated with an increased risk of being overweight or obese [30]–[32]. But a big study of 43,365 children didn’t find strong associations. Well, it did find increased odds of being overweight at age 7, but this association was gone at age 11 [33]. 
  • Eczema. Once again, there may be an association between prenatal antibiotics and eczema, but results are not definitive. One small study found that antibiotics increased the risk of suffering this allergic condition [34]. Another big study found the same, and added that this association was higher for C-section babies [35]. Yet another study looked at prenatal low-dose antibiotic exposure (that is, antibiotics moms unintentionally ate through food) and found significant association with the baby developing eczema [36]. However, one large study that initially found an association, made a strict analysis by looking at healthy siblings and found that the association between antibiotics and eczema was lost [37]. 
  • Asthma. Most studies have found a positive association between prenatal antibiotics exposure and increased risk of developing asthma [38]–[48]. However, three studies found no such association. The first two concluded that the association was probably due to an inherited predisposition to respiratory infections [49], [50], and the third one found a significant association when antibiotics were taken before, during, or after pregnancy [51]. So if the association remained irrespective of the timing of the antibiotics, we can’t blame antibiotics during pregnancy.
  • Autism Spectrum Disorder (ASD). Once again, current evidence suggests there could be an association between prenatal antibiotics and higher risk of developing ASD, but more research is needed because not all studies agree. Two very big studies (with populations that may overlap) found a significant association between prenatal antibiotics and increased risk of ASD in children [52], [53]. But three small studies did not find any association [54]–[56].

So like we said, associations are complicated, and the jury is still out on the impact of antibiotics during pregnancy on these conditions. That’s why it's important to be mindful of the use of antibiotics during pregnancy and limit their use when possible.

Is there anything you can do to avoid taking antibiotics while pregnant?

Yes.

The first important thing is to only take antibiotics when absolutely necessary. Antibiotics only work against bacterial infections, not viral ones like the cold or the flu.

But providers sometimes prescribe antibiotics for viral infections. Why? One of the main reasons is that many patients feel better if they are prescribed something, and providers won’t take the time to explain [57], [58]. So don’t push your provider for a prescription if you don’t really need one.

To reduce your risk for BV, check our 10 tips for vaginal health. If you have a Community State Type 4 (CST 4), here are some things you can do for vaginal health with CST 4. Don’t know what type of vaginal community you have? Our Tiny Health vaginal test can help you with that.

There are also some alternative treatments that can help you reduce the risk of UTI and potentially address GBS colonization.

Provide extra support to your gut microbiome

Even if you follow all of our recommendations, sometimes it will be inevitable to take antibiotics. And taking them may be the best option for you and your baby. If that’s the case, taking a good brand of gut probiotics alongside the antibiotics may reduce the overall disruption to your gut microbiome.

You can also consider taking a Tiny Health microbiome test to see how antibiotics impacted your gut or vaginal microbiome. Our test can detect different Bifidobacterium species that are important to pass to the baby.

References

[1] “Urinary tract infection (UTI) - Symptoms and causes,” Mayo Clinic. Accessed: Jan. 20, 2022. [Online]. Available: https://www.mayoclinic.org/diseases-conditions/urinary-tract-infection/symptoms-causes/syc-20353447

[2] J. Schnarr and F. Smaill, “Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy,” Eur. J. Clin. Invest., vol. 38 Suppl 2, pp. 50–57, Oct. 2008, doi: 10.1111/j.1365-2362.2008.02009.x.

[3] P. J. Habak and J. Griggs, “Urinary Tract Infection In Pregnancy,” in StatPearls, Treasure Island (FL): StatPearls Publishing, 2022. Accessed: Jan. 20, 2022. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK537047/

[4] F. T. Muanda, O. Sheehy, and A. Bérard, “Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study,” Br. J. Clin. Pharmacol., vol. 83, no. 11, pp. 2557–2571, Nov. 2017, doi: 10.1111/bcp.13364.

[5] “ACOG Committee Opinion No. 494: Sulfonamides, nitrofurantoin, and risk of birth defects,” Obstet. Gynecol., vol. 117, no. 6, pp. 1484–1485, Jun. 2011, doi: 10.1097/AOG.0b013e3182238c57.

[6] K. Meidahl Petersen et al., “The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial,” Am. J. Ther., vol. 23, no. 2, pp. e382-387, Apr. 2016, doi: 10.1097/MJT.0000000000000372.

[7] M. Viswanathan, K. A. Treiman, J. Kish-Doto, J. C. Middleton, E. J. L. Coker-Schwimmer, and W. K. Nicholson, “Folic Acid Supplementation for the Prevention of Neural Tube Defects: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force,” JAMA, vol. 317, no. 2, pp. 190–203, Jan. 2017, doi: 10.1001/jama.2016.19193.

[8] Q. Zhou et al., “Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China,” BMC Pregnancy Childbirth, vol. 24, no. 1, p. 114, Feb. 2024, doi: 10.1186/s12884-024-06283-8.

[9] Z. Li, R. Ye, L. Zhang, H. Li, J. Liu, and A. Ren, “Periconceptional folic acid supplementation and the risk of preterm births in China: a large prospective cohort study,” Int. J. Epidemiol., vol. 43, no. 4, pp. 1132–1139, Aug. 2014, doi: 10.1093/ije/dyu020.

[10] J.-S. Zheng et al., “Pre-conceptional intake of folic acid supplements is inversely associated with risk of preterm birth and small-for-gestational-age birth: a prospective cohort study,” Br. J. Nutr., vol. 115, no. 3, pp. 509–516, Feb. 2016, doi: 10.1017/S0007114515004663.

[11] Y. He, A. Pan, F. B. Hu, and X. Ma, “Folic acid supplementation, birth defects, and adverse pregnancy outcomes in Chinese women: a population-based mega-cohort study,” The Lancet, vol. 388, p. S91, Oct. 2016, doi: 10.1016/S0140-6736(16)32018-9.

[12] O. of the Commissioner, “FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions,” FDA. Accessed: Jan. 20, 2022. [Online]. Available: https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics-risks-mental-health-and-low-blood-sugar-adverse

[13] C. A. Muzny et al., “Identification of Key Bacteria Involved in the Induction of Incident Bacterial Vaginosis: A Prospective Study,” J. Infect. Dis., vol. 218, no. 6, pp. 966–978, Aug. 2018, doi: 10.1093/infdis/jiy243.

[14] S. Srinivasan et al., “More than meets the eye: associations of vaginal bacteria with gram stain morphotypes using molecular phylogenetic analysis,” PloS One, vol. 8, no. 10, p. e78633, 2013, doi: 10.1371/journal.pone.0078633.

[15] R. G. Brown et al., “Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes,” Transl. Res. J. Lab. Clin. Med., vol. 207, pp. 30–43, May 2019, doi: 10.1016/j.trsl.2018.12.005.

[16] M. A. Elovitz et al., “Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery,” Nat. Commun., vol. 10, no. 1, p. 1305, Mar. 2019, doi: 10.1038/s41467-019-09285-9.

[17] J. M. Fettweis et al., “The vaginal microbiome and preterm birth,” Nat. Med., vol. 25, no. 6, pp. 1012–1021, Jun. 2019, doi: 10.1038/s41591-019-0450-2.

[18] A. C. Freitas, A. Bocking, J. E. Hill, D. M. Money, and VOGUE Research Group, “Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth,” Microbiome, vol. 6, no. 1, p. 117, Jun. 2018, doi: 10.1186/s40168-018-0502-8.

[19] H. Leitich, B. Bodner-Adler, M. Brunbauer, A. Kaider, C. Egarter, and P. Husslein, “Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis,” Am. J. Obstet. Gynecol., vol. 189, no. 1, pp. 139–147, Jul. 2003, doi: 10.1067/mob.2003.339.

[20] C. B. Weir and J. K. Le, “Metronidazole,” in StatPearls, Treasure Island (FL): StatPearls Publishing, 2022. Accessed: Jan. 20, 2022. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK539728/

[21] “Metronidazole,” in Drugs and Lactation Database (LactMed), Bethesda (MD): National Library of Medicine (US), 2006. Accessed: Jan. 20, 2022. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK501315/

[22] G. Y. Ali, E. H. S. S. Algohary, K. A. Rashed, M. Almoghanum, and A. A. Khalifa, “Prevalence of Candida colonization in preterm newborns and VLBW in neonatal intensive care unit: role of maternal colonization as a risk factor in transmission of disease,” J. Matern.-Fetal Neonatal Med. Off. J. Eur. Assoc. Perinat. Med. Fed. Asia Ocean. Perinat. Soc. Int. Soc. Perinat. Obstet., vol. 25, no. 6, pp. 789–795, Jun. 2012, doi: 10.3109/14767058.2011.622005.

[23] R. M. Al-Rusan, A. M. G. Darwazeh, and I. M. Lataifeh, “The relationship of Candida colonization of the oral and vaginal mucosae of mothers and oral mucosae of their newborns at birth,” Oral Surg. Oral Med. Oral Pathol. Oral Radiol., vol. 123, no. 4, pp. 459–463, Apr. 2017, doi: 10.1016/j.oooo.2017.01.003.

[24] S. Ersoy-Evans, H. Akıncı, S. Doğan, and N. Atakan, “Diaper Dermatitis: A Review of 63 Children,” Pediatr. Dermatol., vol. 33, no. 3, pp. 332–336, May 2016, doi: 10.1111/pde.12860.

[25] Y. Zhu et al., “Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study,” BMJ, vol. 369, p. m1494, May 2020, doi: 10.1136/bmj.m1494.

[26] S. E. Ladirat et al., “Exploring the effects of galacto-oligosaccharides on the gut microbiota of healthy adults receiving amoxicillin treatment,” Br. J. Nutr., vol. 112, no. 4, pp. 536–546, Aug. 2014, doi: 10.1017/S0007114514001135.

[27] K. Pallav et al., “Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers: a randomized clinical trial,” Gut Microbes, vol. 5, no. 4, pp. 458–467, Jul. 2014, doi: 10.4161/gmic.29558.

[28] A. J. Stewardson et al., “Collateral damage from oral ciprofloxacin versus nitrofurantoin in outpatients with urinary tract infections: a culture-free analysis of gut microbiota,” Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis., vol. 21, no. 4, p. 344.e1–11, Apr. 2015, doi: 10.1016/j.cmi.2014.11.016.

[29] E. Mavromanolakis, S. Maraki, G. Samonis, Y. Tselentis, and A. Cranidis, “Effect of norfloxacin, trimethoprim-sulfamethoxazole and nitrofurantoin on fecal flora of women with recurrent urinary tract infections,” J. Chemother. Florence Italy, vol. 9, no. 3, pp. 203–207, Jun. 1997, doi: 10.1179/joc.1997.9.3.203.

[30] N. T. Mueller et al., “Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity,” Int. J. Obes. 2005, vol. 39, no. 4, pp. 665–670, Apr. 2015, doi: 10.1038/ijo.2014.180.

[31] A. Mor et al., “Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study,” Int. J. Obes. 2005, vol. 39, no. 10, pp. 1450–1455, Oct. 2015, doi: 10.1038/ijo.2015.129.

[32] A. E. Cassidy-Bushrow et al., “Prenatal antimicrobial use and early-childhood body mass index,” Int. J. Obes. 2005, vol. 42, no. 1, pp. 1–7, Jan. 2018, doi: 10.1038/ijo.2017.205.

[33] T. Jess et al., “Antibiotic use during pregnancy and childhood overweight: A population-based nationwide cohort study,” Sci. Rep., vol. 9, no. 1, p. 11528, Aug. 2019, doi: 10.1038/s41598-019-48065-9.

[34] S. Dom et al., “Pre- and post-natal exposure to antibiotics and the development of eczema, recurrent wheezing and atopic sensitization in children up to the age of 4 years,” Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol., vol. 40, no. 9, pp. 1378–1387, Sep. 2010, doi: 10.1111/j.1365-2222.2010.03538.x.

[35] S. Timm, V. Schlünssen, J. Olsen, and C. H. Ramlau-Hansen, “Prenatal antibiotics and atopic dermatitis among 18-month-old children in the Danish National Birth Cohort,” Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol., vol. 47, no. 7, pp. 929–936, Jul. 2017, doi: 10.1111/cea.12916.

[36] M. Geng et al., “Prenatal low-dose antibiotic exposure and children allergic diseases at 4 years of age: A prospective birth cohort study,” Ecotoxicol. Environ. Saf., vol. 225, p. 112736, Dec. 2021, doi: 10.1016/j.ecoenv.2021.112736.

[37] M. Mubanga, C. Lundholm, B. M. D’Onofrio, M. Stratmann, A. Hedman, and C. Almqvist, “Association of Early Life Exposure to Antibiotics With Risk of Atopic Dermatitis in Sweden,” JAMA Netw. Open, vol. 4, no. 4, p. e215245, Apr. 2021, doi: 10.1001/jamanetworkopen.2021.5245.

[38] S. Yoshida, K. Ide, M. Takeuchi, and K. Kawakami, “Prenatal and early-life antibiotic use and risk of childhood asthma: A retrospective cohort study,” Pediatr. Allergy Immunol. Off. Publ. Eur. Soc. Pediatr. Allergy Immunol., vol. 29, no. 5, pp. 490–495, Aug. 2018, doi: 10.1111/pai.12902.

[39] M. Kashanian, S. S. Mohtashami, M. H. Bemanian, S. A. J. Moosavi, and M. Moradi Lakeh, “Evaluation of the associations between childhood asthma and prenatal and perinatal factors,” Int. J. Gynaecol. Obstet. Off. Organ Int. Fed. Gynaecol. Obstet., vol. 137, no. 3, pp. 290–294, Jun. 2017, doi: 10.1002/ijgo.12141.

[40] B. Mulder et al., “Antibiotic use during pregnancy and asthma in preschool children: the influence of confounding,” Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol., vol. 46, no. 9, pp. 1214–1226, Sep. 2016, doi: 10.1111/cea.12756.

[41] P. Wu et al., “Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma,” PloS One, vol. 11, no. 3, p. e0151705, 2016, doi: 10.1371/journal.pone.0151705.

[42] S. Chu, H. Yu, Y. Chen, Q. Chen, B. Wang, and J. Zhang, “Periconceptional and Gestational Exposure to Antibiotics and Childhood Asthma,” PloS One, vol. 10, no. 10, p. e0140443, 2015, doi: 10.1371/journal.pone.0140443.

[43] B. Lapin et al., “Relationship between prenatal antibiotic use and asthma in at-risk children,” Ann. Allergy Asthma Immunol. Off. Publ. Am. Coll. Allergy Asthma Immunol., vol. 114, no. 3, pp. 203–207, Mar. 2015, doi: 10.1016/j.anai.2014.11.014.

[44] J. Metsälä, A. Lundqvist, L. J. Virta, M. Kaila, M. Gissler, and S. M. Virtanen, “Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood,” Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol., vol. 45, no. 1, pp. 137–145, Jan. 2015, doi: 10.1111/cea.12356.

[45] L. G. Stensballe, J. Simonsen, S. M. Jensen, K. Bønnelykke, and H. Bisgaard, “Use of antibiotics during pregnancy increases the risk of asthma in early childhood,” J. Pediatr., vol. 162, no. 4, pp. 832-838.e3, Apr. 2013, doi: 10.1016/j.jpeds.2012.09.049.

[46] M.-J. Martel et al., “Determinants of the incidence of childhood asthma: a two-stage case-control study,” Am. J. Epidemiol., vol. 169, no. 2, pp. 195–205, Jan. 2009, doi: 10.1093/aje/kwn309.

[47] K. N. Turi et al., “Dose, Timing, and Spectrum of Prenatal Antibiotic Exposure and Risk of Childhood Asthma,” Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am., vol. 72, no. 3, pp. 455–462, Feb. 2021, doi: 10.1093/cid/ciaa085.

[48] C. S. Uldbjerg, J. E. Miller, D. Burgner, L. H. Pedersen, and B. H. Bech, “Antibiotic exposure during pregnancy and childhood asthma: a national birth cohort study investigating timing of exposure and mode of delivery,” Arch. Dis. Child., vol. 106, no. 9, pp. 888–894, Sep. 2021, doi: 10.1136/archdischild-2020-319659.

[49] J. Stokholm, A. Sevelsted, K. Bønnelykke, and H. Bisgaard, “Maternal propensity for infections and risk of childhood asthma: a registry-based cohort study,” Lancet Respir. Med., vol. 2, no. 8, pp. 631–637, Aug. 2014, doi: 10.1016/S2213-2600(14)70152-3.

[50] A. K. Örtqvist et al., “Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis,” BMJ, vol. 349, p. g6979, Nov. 2014, doi: 10.1136/bmj.g6979.

[51] K. Loewen, B. Monchka, S. M. Mahmud, G. ’t Jong, and M. B. Azad, “Prenatal antibiotic exposure and childhood asthma: a population-based study,” Eur. Respir. J., vol. 52, no. 1, p. 1702070, Jul. 2018, doi: 10.1183/13993003.02070-2017.

[52] H. Ó. Atladóttir, T. B. Henriksen, D. E. Schendel, and E. T. Parner, “Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study,” Pediatrics, vol. 130, no. 6, pp. e1447-1454, Dec. 2012, doi: 10.1542/peds.2012-1107.

[53] T. Wimberley et al., “Otitis media, antibiotics, and risk of autism spectrum disorder,” Autism Res. Off. J. Int. Soc. Autism Res., vol. 11, no. 10, pp. 1432–1440, Oct. 2018, doi: 10.1002/aur.2015.

[54] D. R. Guisso et al., “Association of Autism with Maternal Infections, Perinatal and Other Risk Factors: A Case-Control Study,” J. Autism Dev. Disord., vol. 48, no. 6, pp. 2010–2021, Jun. 2018, doi: 10.1007/s10803-017-3449-x.

[55] J. Isaksson, E. Pettersson, E. Kostrzewa, R. Diaz Heijtz, and S. Bölte, “Brief Report: Association Between Autism Spectrum Disorder, Gastrointestinal Problems and Perinatal Risk Factors Within Sibling Pairs,” J. Autism Dev. Disord., vol. 47, no. 8, pp. 2621–2627, Aug. 2017, doi: 10.1007/s10803-017-3169-2.

[56] B. George, M. S. R. Padmam, M. K. C. Nair, M. L. Leena, and P. S. S. Russell, “CDC Kerala 13: Antenatal, natal and postnatal factors among children (2-6 y) with autism--a case control study,” Indian J. Pediatr., vol. 81 Suppl 2, pp. S133-137, Dec. 2014, doi: 10.1007/s12098-014-1594-1.

[57] R. S. Md Rezal, M. A. Hassali, A. A. Alrasheedy, F. Saleem, F. A. Md Yusof, and B. Godman, “Physicians’ knowledge, perceptions and behaviour towards antibiotic prescribing: a systematic review of the literature,” Expert Rev. Anti Infect. Ther., vol. 13, no. 5, pp. 665–680, May 2015, doi: 10.1586/14787210.2015.1025057.

[58] J. Strumiło, S. Chlabicz, B. Pytel-Krolczuk, L. Marcinowicz, D. Rogowska-Szadkowska, and A. J. Milewska, “Combined assessment of clinical and patient factors on doctors’ decisions to prescribe antibiotics,” BMC Fam. Pract., vol. 17, p. 63, Jun. 2016, doi: 10.1186/s12875-016-0463-6.