Antibiotic Use during Pregnancy: Too Much of a Good Thing?

Lixin Zhang, PhD ’99

Assistant Professor of Epidemiology and Biostatistics and of Microbiology and Molecular Genetics, Michigan State University

July 19, 2020

The discovery and use of antibiotics is one of the great achievements of public health in human medical history, on a level with clean water and vaccines in controlling infectious diseases.

Unfortunately, however, antibiotic use is not without its problems.

At therapeutic doses—whether for long-term or short-term use—antibiotics exert a strong selection pressure on the microbial community, often killing beneficial host microbiota and potentially leading to unhealthy microbial imbalances in the human gut.

Given the importance of human microbiota in health and disease, we must scrutinize not only the relationship between antibiotic use and health outcomes but must look especially closely at antibiotic exposure during pregnancy.

Exposure to antibiotics during pregnancy is extremely common. Around 70 percent of pregnant women using an antibiotic at least once during pregnancy, and antibiotics account for nearly 80 percent of all prescription medications used during pregnancy.¹

Antibiotics are prescribed to pregnant women for many good reasons: contexts of preterm labor, intrapartum fever during labor, prevention of neonatal Group B Streptococcus infection, and during cesarean sections. They might also be prescribed to pregnant women experiencing severe respiratory, urinary, sinus or infection symptoms or suffering from kidney infection, sexually transmitted infections, or bacterial vaginosis.

Antibiotic exposure during pregnancy affects not only the mother but also the developing fetus and subsequently the newborn. A healthy infant gut microbiome is critical to proper neonatal development. Exposure to microbes in utero and during birth lead to the development of initial microbiome, which plays a central role in the immune and metabolic programing of the newborn and thus affect the risk of developing diseases.²

Many factors influence the development of the newborn microbiome, including maternal diet and breastfeeding. Antibiotic exposure during these phases is critical both to the seeding and selection of a newborn’s microbial community. Consequent health issues related to such exposures have been explored but mainly on chronic conditions such as allergic diseases, asthma, childhood obesity, and autism spectrum disorders.

As an infectious disease epidemiologist, I am most interested in the infection disease related outcomes. My own work examines whether antibiotic exposure during pregnancy and birth creates a reservoir of resistance genes and organisms in the newborn gut that can increase the risk of neonatal infections

As a participating investigator in the Child Health Advances from Research with Mothers (CHARM) study—an alliance of scientists and providers from five Michigan institutions whose goal is to improve the health of mothers and children in the state—I am able to access stool samples from mothers and newborns of the Michigan pregnancy cohort. We recently examined the perinatal risk factors for fecal antibiotic resistance gene patterns in pregnant women and their infants.³ In analyzing antibiotic resistomes—all antibiotic-resistant genes present in a subject’s gut microbiome—it seems that infants have more and more diverse antibiotic resistance genes compared to pregnant women. Infant samples often contain antibiotic resistance genes different from those found in their own mother’s resistome, suggesting that environment also plays an important role in the acquisition of resistant genes at early age.

I also examine how antibiotic use impacts neonatal sepsis, a blood infection in newborns that can pose major health risks. While antibiotic use during labor has greatly reduced early-onset neonatal infections, evidence suggests such practices may lead to additional and more severe infections later on (late-onset neonatal sepsis).⁴ Newborn sepsis incidence is relatively low in the general population in developed countries, so it is difficult to obtain the sample size needed for a prospective cohort study in Michigan. We are currently studying this question with populations in Indonesia. We have found that despite high antibiotic use, incidence of these blood infections in newborn’s remains very high.

Multidrug-resistant bacteria is certainly part of the problem here. In the era of wide antibiotic use, the changing epidemiology of neonatal sepsis may be due to the disruption of the newborn gut microbiota from antibiotic exposure.

An infant’s developing microbiome depends on a variety of interactions between gut bacteria and the host, and the introduction of antibiotics at any stage and at any level has the potential to interrupt these health-building processes in ways that can affect a child’s health immediately after birth and potentially for the rest of their life.

References

1. Mitchell, Gilboa, Werler, Kelley, et al. “Medication Use during Pregnancy, with Particular Focus on Prescription Drugs: 1976-2008.” American Journal of Obstetrics and Gynecology 205/1 (July 2011); Bookstaver, Bland, Griffin, Stover, et al. “A Review of Antibiotic Use in Pregnancy.” Pharmacotherapy 35/11 (Nov 2015):1052-62.
2. Rautava. “Early Microbial Contact, the Breast Milk Microbiome, and Child Health.” J Dev Orig Health Dis 7/1 (Feb 2016):5-14.
3. Sosa-Moreno, Zhang, et al. “Perinatal Risk Factors for Fecal Antibiotic Resistance Gene Patterns in Pregnant Women and Their Infants.” PLOS ONE 15/6 (June 2020):e0234751. While this simple survey of mothers did not indicate an association between antibiotic use at any time during pregnancy and a reduced resistome, a pilot study using more detailed medical records on antibiotic use suggests a potential association.
4. Schrag and Verani. “Intrapartum Antibiotic Prophylaxis for the Prevention of Perinatal Group B Streptococcal Disease: Experience in the United States and Implications for a Potential Group B Streptococcal.” Vaccine 31 Supp 4 (Aug 2013):D20-26.

About the Author

Lixin Zhang, PhD ’99, is assistant professor of Epidemiology and Biostatistics, with a joint appointment in Microbiology and Molecular Genetics, at Michigan State University. Zhang earned his PhD in Epidemiological Sciences from the University of Michigan School of Public Health, where he worked as a faculty member in the Center for Molecular and Clinical Epidemiology of Infectious Diseases, Assistant Research Scientist, and Research Assistant Professor. Zhang’s research interests are in infectious disease epidemiology, pathogen genomics, and bioinformatics. Specifically, he is interested in understanding the emergence, transmission, and maintenance of pathogens and antimicrobial resistance in both hospital and community settings by incorporating molecular data into population-level analyses.

This article is based on a presentation Zhang had planned to present at a symposium celebrating the retirement of Dr. Carl Marrs, professor emeritus of Epidemiology. Marrs served for more than two decades as associate professor of Epidemiology at the University of Michigan School of Public Health and, with Drs. Betsy Foxman and Janet Gilsdorf, a core faculty member in the Center for Molecular and Clinical Epidemiology of Infectious Diseases (MAC-EPID). Zhang‘s research continues the MAC-EPID tradition by integrating laboratory and population approaches in his studies.

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