January 2025 Issue

CPE Monthly: Probiotics and the Microbiome During Pregnancy
By Alexandria Hardy, RDN, LDN
Today’s Dietitian
Vol. 27 No. 1 P. 34

Take this course and earn 2 CEUs on our Continuing Education Learning Library

There are over 100 trillion microorganisms present in the gut that can work in both therapeutic and complementary ways.1 Probiotics, or live microorganisms that can produce a favorable outcome to health, can impact different microbiomes by helping create a healthy and hospitable environment.2 Interest in probiotics is growing, with the global market expected to increase by 7.5% from 2021 to 2030.3 The majority of probiotic consumers are women in their childbearing years who may be interested in the expertise an RD can provide in helping them to navigate potential misinformation surrounding probiotics.2,4

Incorporating probiotics into the diet as a food source or as a supplement during pregnancy is associated with a reduced risk of infection, decrease in inflammation, and improved glucose metabolism.2 There is an increasing amount of research that supports consuming specific probiotic strains while pregnant for the improvement of perinatal and postpartum mental health, mastitis risk, and vaginal health, though there is currently no clinical gold standard regarding intake.5-7

The most common diseases that can occur during pregnancy typically fall into the endocrine or endothelial categories, putting pregnant women more at risk of developing gestational diabetes (GDM), CVD, and metabolic syndrome.1,8 The microbiome can impact all of these conditions and may even be indicative of future health for both mother and infant.1 Probiotics may play an important role in stabilizing the microbiome.

This continuing education course will provide an updated look at the impact of probiotic intake and supplementation during the pre- and postnatal period. The impact of the gut and female genital tract (FGT) microbiomes on pregnancy-related conditions including GDM, mastitis, and maternal mental health will be reviewed. The perception of probiotics by practitioners and patients will be assessed, and best practices regarding dietary source, supplements, quantities, and timing will be explored.

Pregnancy and Changing Microbiomes
Microbiomes change throughout the life cycle due to many variables, including diet, environment, hormone shifts, and metabolic and immunology status.9,10 A healthy gut microbiome in adults is typically dominated by the phyla Bacteroidetes, Firmicutes, Actinobacteria, and Verrucomicrobia.1,10 The first trimester gut bacteria profile resembles a nonpregnant female’s profile, with a proliferation of Firmicutes.9 Throughout pregnancy, the gut microbiota changes and Proteobacteria and Actinobacteria phyla often increase while Firmicutes decreases; this is seen primarily in the microbiota of the gut and vagina.1,11 These changes may be due to shifts in adipose tissue, blood glucose levels, insulin resistance, and proinflammatory cytokines that can occur during pregnancy. A pregnant woman’s gut microbiome may resemble that of an individual with metabolic syndrome by the third trimester.1,8 A destabilized or unbalanced microbiota can negatively impact the infant, whose own microbiota is strongly influenced by their delivery and feeding method.10

Fertility and Reproductive Outcomes
The Journal of Assisted Reproduction and Genetics published a review studying the microbiome of the FGT.12 Lactobacillus is the most prevalent strain of probiotic in the endometrium and vagina, and its proliferation is linked to improved reproductive outcomes and assisted reproductive techniques.12,13 Endometrial and vaginal microbiomes with high levels of Lactobacilli are associated with an increased chance of implantation resulting in pregnancy.13 A review published in the European Journal of Obstetrics and Gynecology and Reproductive Biology assessed the impact probiotics had on both male and female reproductive systems and fertility.13 Oral probiotic therapy improved sperm motility but there are mixed outcomes on their impact on female fertility.13 More research is needed to determine if probiotics can boost the concentration of Lactobacilli in the endometrial and vaginal microbiomes in women facing fertility challenges.13

How Probiotics Impact Quality of Life in Early Pregnancy
Supplementing with Lactobacillus probiotics is associated with improved quality of life in early pregnancy.14 A study of 32 women published in Nutrients found that taking two cycles of probiotics daily helped with hormonally driven changes in pregnancy, like nausea, bloating, fatigue, gastrointestinal distress, and constipation.14 More specifically, probiotic supplementation was associated with significantly milder symptoms of nausea, vomiting, and fatigue.14 The researchers theorized that changes in the gut microbiota that occur due to hormone fluctuations in pregnancy are able to be stabilized by probiotic intake, similar to how probiotics are able to ease nonpregnancy-related gastrointestinal distress like diarrhea or constipation.14

Postpartum Mental Health
Maternal mental health disorders like depression and anxiety can afflict as many as 20% of women in the postpartum period, yet the intersection of mental health and probiotic intake is a relatively new area of study.15,16 A complex, mostly unknown relationship seems to exist between the microbiota and the gut-brain axis.5

A review in Frontiers in Psychiatry proposed utilizing probiotic supplementation in the perinatal period to decrease the likelihood of maternal mental health disorders.15 Both Lactobacillus and Bifidobacterium phyla were associated with a decrease in anxiety scores and depression-related symptoms.15 More research is needed to create standardized recommendations, including specific strains and types of probiotics that may be most helpful.15 Ideally, probiotic supplementation could help establish microbiome stability and increase the variety of microbiota present to boost mother-infant attachment and lessen the risk of neuropsychiatric disorders like anxiety and depression.5

Probiotic Perceptions
Consumers often receive their initial impressions regarding probiotics from commercial sources and come to their health care practitioners with an established perception.17 They may be willing to try probiotic supplements because they are readily available in many locations and price points, but often lack the knowledge necessary to picking an efficacious brand or strain.

Maternal Perception of Probiotics
A study published in Public Health Nutrition assessed maternal perception and usage of probiotics during pregnancy and infant consumption between 6 and 24 months of age.18 Five hundred nineteen Turkish women were surveyed using the Sociodemographic Information Form and the Probiotic Information and Attitudes Form.18 The mothers’ main source of information regarding probiotics prior to the survey was media.18 Only 20.2% of the mothers were able to define what a probiotic is and 33.1% could accurately identify probiotic-containing foods.18 Interestingly, nearly half of the women surveyed consumed probiotics during their pregnancy.18 The majority of mothers strongly agreed that probiotic products were beneficial and could boost immunity and aid in digestion.18 The mothers were more likely to obtain their probiotics through dietary sources vs a supplement; they were also more likely to give their infants dietary sources of probiotics including cheese and homemade yogurt.18 Women who possessed a robust baseline knowledge of probiotics were more likely to be older, be well educated, be employed, have family support, and be actively breastfeeding.18 The mothers in the study had an overall positive association with probiotics, but the researchers surmised that creating opportunities for educational engagement around probiotics throughout the pre- and postnatal periods may be helpful to improve identification of probiotics and their functionality.18

Probiotic Proficiency in the Multidisciplinary Team
Though many members of the multidisciplinary team (MDT) may be asked about probiotics, they may not feel confident making evidence-based recommendations based on their own current level of expertise. However, the MDT is positioned to influence consumers’ ideas about probiotics, both positively and negatively.19 It’s important that practitioners consistently seek out evidence-based research to educate themselves on the subject.19

A cross-sectional survey published in Clinical Nutrition European Society for Parenteral and Enteral Nutrition reviewed health practitioners’ familiarity and comfort in discussing probiotic usage with consumers.19 One thousand three hundred sixty RDs, general practitioners, and pediatricians responded to the survey, and 86.3% positively recognized the place of probiotics in medicine. 19 A little over one-half of the RDs surveyed (55.7%) knew the World Health Organization definition of a probiotic, and 91% of responders desired further education on the use of probiotics in a clinical setting.19 Another study published in Topics in Clinical Nutrition reported similar findings, with 88% of the health care providers surveyed relating a familiarity with the products.20 Despite this familiarity, 45% of health care providers did not recommend them and 75% did not read current research about probiotics.20

Providing continuing education activities and using screening questions to guide patient education may help both the MDT and pregnant women to feel more confident regarding probiotic usage. Considering the format in which this education is presented to pregnant women may also be important, as misinformation is common in mainstream sources, particularly social media.

Impact of Probiotics on the Mother’s Gut and Vaginal Microbiomes
Using probiotics during pregnancy may be a simple, affordable way to improve pregnancy-related outcomes.21,22 Issues like constipation, insulin resistance, and maternal mental health are all able to be influenced through the gut and vaginal microbiome by probiotics. Some of these benefits may best be conferred via probiotic supplementation while others
may be obtained through a probiotic-rich food source.

Constipation
A triple-blind, randomized study from the Iranian Red Crescent Medical Journal studied the impact of probiotic-enriched yogurt on constipated pregnant women.23 Sixty healthy pregnant women ate 300 g of yogurt three times daily for a weeklong period, with the treatment group receiving yogurt enriched with the probiotic strains Bifidobacterium and Lactobacillus 4.8 × 1010 colony-forming units (CFUs) as the control group consumed conventional yogurt.23 Each group consumed their yogurt an hour before eating other foods and was encouraged to avoid other nonstudy-sanctioned probiotics and laxatives.23

Baseline defecation for each group was similar at 2.1 per week for the treatment group and 2.3 per week for the control.23 Both groups had improved metrics throughout the study with no statistically significant differences; these included an improvement in both constipation symptoms and their number of defecations per week.23 Members of both groups reported minor gastrointestinal complaints throughout the study. The researchers concurred that practitioners should encourage pregnant women to add dairy products into their daily eating routines to aid in constipation-related complications.23

Gestational Diabetes
A case-control study in the Iranian Journal of Public Health studied the impact of probiotic yogurt intake on GDM in pregnant Chinese women.24 A control group of 126 pregnant women and 123 women with GDM were interviewed on their prepregnancy and pregnancy consumption of probiotic yogurt, defined in this study as yogurt that contained strains of Lactobacillus acidophilus and Bifidobacterium.24

The study’s findings showed that there was no connection between prepregnancy probiotic yogurt consumption and the development of GDM, but that there was a significant negative association between first and second trimester probiotic yogurt intake and the development of GDM.24 The study also revealed that pregnant women who were not diagnosed with GDM were more likely to consume probiotic yogurt.24 These findings illustrate that incorporating probiotic yogurt into the regular dietary pattern of pregnant women may help prevent the development of GDM and maintain a stable blood glucose response.24

Group B Streptococcus
The Taiwanese Journal of Obstetrics and Gynecology published a prospective, double blind randomized clinical trial assessing the impact of a probiotic supplement on the colonization rate of group B streptococcus (GBS) in 110 GBS-positive pregnant women.25 GBS colonization is found in 15% to 40% of pregnant women and can pass to the infant, possibly causing neonatal sepsis, meningitis, or pneumonia in the first week postbirth.25 GBS-positive women are typically treated with antibiotics four hours prior to giving birth, but up to 50% of GBS-positive women are unable to receive them due to laboring too quickly.25 This study aimed to discover if probiotics taken prior to delivery may be used as a supplemental treatment to the antibiotics.25

In this study, the women were evenly randomized between the placebo and probiotic groups; both groups consumed two capsules before bed beginning at 35 to 37 weeks’ gestation and continued taking them until giving birth.25 The probiotic strains used in this study were Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, chosen for their antimicrobial properties and because they are the primary bacteria present in the vaginal microbiome.25 Upon delivery (an average of three weeks after the study began), 42.9% of the GBS-positive women in the probiotic group had a negative GBS culture compared with 18% of the placebo group.25 These findings suggest that these specific Lactobacillus probiotic strains may aid in rebalancing vaginal microbiota, though a larger sample size is recommended.25 Additionally, future research may want to expand the window of probiotic consumption beyond three weeks for maximum benefits.25

Mastitis
Mastitis and difficulty with breastfeeding due to pain may be linked to instability in the mammary microbiota.26 A study published in Clinical Infectious Diseases assessed the effectiveness of preventing lactational infectious mastitis with a probiotic, specifically Lactobacillus salivarius PS2, in pregnant women with a history of mastitis.27 Prior studies indicated that the use of a probiotic to treat established cases of mastitis was an effective substitute for antibiotics.27 A cohort of 108 pregnant women was randomized into a probiotic or placebo group. The placebo group received powdered milk while the probiotic group received 50 mg of freeze-dried probiotic Lactobacillus salivarius PS2.27 Supplementation began at 30 weeks and continued until the women delivered.27 Nearly one-half of the women (44) developed mastitis, but the probiotic group had a significantly smaller number of cases (14 vs 30 in the placebo group).27 Women in the probiotic group also experienced a significantly lower bacterial count in their milk than women in the placebo group.27 More research needs to be done on this specific population to see if the beneficial effects of ingesting a probiotic supplement in the later stages of pregnancy could be extrapolated to all pregnant women.27

Postpartum Depression and Anxiety
EBioMedicine, a biomedical open-access journal, investigated the relationship between postpartum anxiety and depression and probiotic supplementation.22 This randomized, double-blind, placebo-controlled study evaluated maternal mental health in over 400 women.22 The 212 women in the treatment group received a dosage of Lactobacillus rhamnosus HN001, 6×109 CFU daily.22 The placebo group was composed of 211 women who were given a placebo made of corn-derived maltodextrin; neither group was taking other probiotic supplements.22 Both groups took the supplements from study enrollment (when women were between 14 and 16 weeks’ gestation) until six months postpartum if breastfeeding.22

The Edinburgh Postnatal Depression Scale and State Trait Anxiety Intervention (six item version) were used to gauge risk of depression and anxiety at baseline and six and 12 months postbirth.22 The treatment group saw a statistically significant lower prevalence and symptoms of both anxiety and depression compared with the placebo group, both during pregnancy and in the postpartum period.22 The researchers emphasized that these findings should not be extrapolated onto different strains of probiotics without further testing but may be a promising intervention for mental health during the pre- and postpartum periods.22 The results were echoed in a review published in Healthcare, which found the same strain of Lactobacillus rhamnosus HN001 lessened postpartum depressive symptoms if supplementation was continued after birth.5

Impact of Probiotics on Infant Gut Microbiome
Probiotics are influential in the formation of the infant’s gut microbiome. Whether the probiotics are consumed by the mother or the infant and regardless of dietary source or supplement type, they have the ability to positively influence health outcomes like sepsis as well as the microbiota diversity.7,28

A study published in Frontiers in Microbiology evaluated the effects of probiotic supplementation on 31 mothers from 32 weeks gestational age through six months postpartum; infants were also assessed in the six-month postpartum period.29 The women were separated into a control group of 16 and a placebo group of 15 with the goal of analyzing the potential changes in both the infant and mother’s gut microbiota with a focus on diversity and microbial interaction.29 The gut microbiomes of both groups were studied using 16S rRNA gene sequencing and a molecular ecological network analysis.29

On average, the pregnant women in the treatment group consumed their probiotic supplement for 52 days and there were no significant clinical differences in either group at the conclusion of the study.29 Microbial diversity was unaffected, but the study indicated that probiotic supplementation may positively affect both the network and flourishing of the gut microbiome, leading to enhanced stability.29

This idea was echoed in Ecological Indicators in an article that explored the connections between stable networks in the gut microbiome and overall gut health.29,30 Though the heterogeneity of the gut microbiome changed over the study period for the infants, these changes were attributed to the growth and aging of the infant and not the supplements.29 More research is recommended to asses if probiotic supplementation affects the growth patterns of infants and to further explore the connection between probiotics and microbial networks.29

At birth, an infant’s gut microbiome is primarily composed of Enterococci, Staphylococci, and Enterobacteria.10 The infant microbiota is strongly influenced by the mother’s placental microbiota and is transferred through meconium.11 This balance shifts to include Lactobacillus, Clostridium, Bifidobacterium, and Bacteroides after the first few days and closely resembles an adult’s at around a year old.10 The proportion of Lactobacillus and Bifidobacterium is significantly higher when an infant is administered a probiotic; this is true for both pre- and full-term infants.28 The main factors affect microbiota composition include delivery method and potential complications, use of antibiotics, and type of feeding the infant receives (breast vs bottle).7,10

Several benefits are believed to be conferred upon an infant if the mother consumes a probiotic supplement during breastfeeding.5 These include the establishment of a robust immune system and a diverse, stable gut microbiome; a decrease in the risk of developing colic or regurgitating breast milk or formula; and a potential decrease in the development of atopic eczema.5 These benefits may also be conferred if probiotic supplement is given directly to the infant, but more research needs to be conducted to ensure best practices in development and manufacturing and to confirm label claims before standardizing probiotic supplementation recommendations in infants.

Supplementation vs Dietary Sources of Probiotics
Probiotics can be consumed as a part of the diet or in supplement form. Both sources have advantages and disadvantages, including stability, accessibility, and cost. Members of the MDT, particularly dietitians, are well positioned to conduct dietary recalls and assess the best source of probiotics for interested consumers.

Dietary Sources
Yogurt is one of the most accessible and frequently consumed food sources of probiotics available during pregnancy, both for its price point, versatile usage, and safety profile.21,31 Other probiotic-rich foods can include fermented items like kefir, algae, miso, pickles, kimchi, natto, olives, raw unfiltered apple cider vinegar, and kombucha.31,32

It’s important for the MDT to communicate that not all fermented foods contain live cultures or microorganisms due to processing, formation, or stability issues.17,33,34 It can be difficult for consumers to accurately assess the quantity and quality of probiotics present in dietary sources as different strains and species vary in microorganism levels and intestinal transit time.33 The International Scientific Association for Probiotics and Prebiotics released a consensus statement that provides specific examples and helps delineate between probiotic foods and fermented foods; this would be worthwhile reading for the MDT.35

A review in Cureus explored the effects of probiotic yogurt on maternal health and pregnancy related outcomes.32 Thirteen articles were analyzed and the reviewers reached a consensus that consuming a probiotic-rich yogurt while pregnant may improve pregnancy outcomes.32 These can be broken into categories like metabolic outcomes (GDM, insulin resistance, calcium deficiency), inflammatory outcomes (elevated oxidative stress and C-reactive protein), and infectious outcomes, namely in diversifying the gut and vaginal microbiome and reducing the risk of using antibiotics for bacterial vaginosis.32 Though the specific mechanism is unknown for many of these actions, members of the MDT can safely encourage the consumption of culturally appropriate probiotic-rich foods to their pregnant patients.32

Supplements
Probiotic supplements are typically consumed as a capsule, liquid, or powder and are more likely than foods to contain a multitude of different cultures and strains.33,36 As dietary supplements, they are not regulated by the FDA and many products may list claims that are not supported by scientific research or study.33 Manufacturers are legally required to list only the total weight of the microorganisms on the label as opposed to also adding the CFU; the total weight of the supplement can include both dead and alive microorganisms and misrepresents the efficacy of the product.33

The CFU count represents the quantity of strains that should be alive and functional at the conclusion of the product’s shelf life and is a better indicator of viability.33 Using specific strains to target potential areas of concern may be helpful, as Lactobacillus is associated with an improvement in maternal mental health and stabilization of the mammary microbiota when breastfeeding while Limosilactobacillus may decrease colic symptoms.5,26 Members of the MDT should stay current with the latest research so they are able to accurately assess supplements for efficacy and to recommend the appropriate strain to alleviate symptoms or improve outcomes.

Probiotic Supplementation During Pregnancy: A Risk vs Benefit Analysis
The International Scientific Association for Probiotics and Prebiotics encourages practitioners to help patients evaluate a product’s label and claims before selecting a supplement.33,34 Probiotics are measured in CFUs, which specify the quantity of viable cells in a serving of the product, which are generally listed on the Supplement Facts panel on the back of the product. Choosing a probiotic supplement by the quantity of CFUs it contains at the time of manufacturing is not recommended, as this number can decrease over the supplement’s lifespan.33

The Academy of Nutrition and Dietetics published a position paper on supplementation that encourages the regular use of supplementation only when dietary needs are not being adequately met through the diet.37 Pregnancy is an example of one of these stages that may warrant supplementation, ideally under the guidance of a health care professional like an RD.37 Dietitians should assess current dietary and supplement intake and review safety and efficacy data with a patient before recommending probiotic supplement.37

Examining the production and storage conditions of probiotic-rich foods like yogurt to ensure maximum probiotic value is imbued to the consumer is key to delivering on probiotic claims. Viability can also be increased by discerning which type of probiotic strain is most helpful for the issue that is being addressed while also assessing the hardiness or resistance of the strain.21,23 A review in PLOS One found that studies that included probiotic supplementation at or above a 107 CFU dose produced the most favorable effects, particularly on metabolic health.21 The most commonly used strains are Lactobacillus and Bifidobacterium, but establishing a gold standard for strain type, quality, initiation of consumption, and length of consumption is also needed to better understand how probiotic foods and supplements may be used as complementary or therapeutic alternatives in pregnancy-related outcomes.21,36,38

Areas of Future Research and Study Limitations
Pregnancy encompasses a finite period of time, so the follow-up period in many studies is relatively short compared with an average randomized controlled trial. It may be challenging to enroll participants in food-based trials (particularly in the first trimester) as pregnant women may suffer from nausea and vomiting that prohibits their inclusion.

There are also stringent enrollment requirements for this population. Potential participants may also be hesitant to consume a probiotic supplement during pregnancy as they are often marketed as dietary supplements, which do not require FDA approval or regulation. Conversely, some women may be drawn to more natural therapies and may be eager to add in a complementary supplement. Expanding the sample size in studies and including a more diverse subset of pregnant women are important considerations when moving forward with research concerning the gut and FGT microbiomes and pregnancy.22

Continuing to fund large-scale clinical trials to determine the efficacy and potential benefits of consuming probiotic foods and supplements during pregnancy and the postpartum period is an important step forward, as is establishing the MDT as an educated resource for patient queries.

Putting It Into Practice
The area of maternal and infant microbiome research is seen as potentially significant in terms of improving postpartum and perinatal health outcomes.39 Consuming probiotics during pregnancy is generally regarded as safe with minimal adverse effects.1 Utilizing probiotics to improve pregnancy-related outcomes has been positively associated with maternal health.2 These outcomes include GDM, constipation, postpartum depression, GBS, and mastitis.2,5,23-25

Probiotic consumption can help to heal the gut and FGT microbiomes by increasing the variety of microbiota that colonize the gut and vaginal tract.38 A systematic review and meta-analysis published in Nutrients analyzed the safety of pre- and probiotics during pregnancy and lactation.2 There were no serious adverse events reported; minor adverse effects were primarily found in the mother and consisted of changes in vaginal discharge and loose stools.2

Presenting expectant mothers with evidence-based research regarding the inclusion of probiotic rich food/supplements may help them make informed decisions to improve infant and maternal physical and health outcomes. Members of the MDT, particularly RDs, should keep abreast of current research regarding probiotics and pay particular attention to studies that reference their potential role in pregnancy and postpartum health. RDs should also be prepared to answer questions from clients in person or on social media regarding common probiotic supplements and dietary sources of probiotics. By focusing on debunking myths and providing bite-sized science-based steps that are simple to apply and engage with, they can help set up expectant mothers for success.

— Alexandria Hardy, RDN, LDN, is owner of Pennsylvania Nutrition Services.

Learning Objectives
After completing this continuing education course, nutrition professionals should be better able to:
1. Assess how probiotics impact the gut and female genital tract microbiomes and how they can affect pregnancy-related outcomes.
2. Analyze the perception of probiotic usage during pregnancy from both a professional and consumer perspective.
3. Discuss the potential benefits of probiotics on the infant gut microbiome.

Examination
1. What should a consumer look for on the label to ensure they are receiving an efficacious probiotic supplement?
a. Total weight of all microorganisms
b. Total weight of living microorganisms
c. Colony-forming units at the end of the product’s lifespan
d. Colony-forming units at the time of production

2. A review in Cureus stated what type of probiotic food improved pregnancy outcomes?
a. Yogurt
b. Kimchi
c. Kefir
d. Kombucha

3. Which factor does not significantly impact a newborn’s gut microbiome?
a. Delivery method
b. Breastfeeding
c. Antibiotics
d. Skin to skin contact

4. What strain of probiotic is most prominent in the vaginal microbiome?
a. Bacteroides
b. Lactobacillus
c. Enterobacteria
d. Bifidobacterium

5. Roughly what percentage of Group B Streptococcus (GBS)-positive pregnant women had a negative GBS culture upon delivery when supplemented with probiotics?
a. 23%
b. 33%
c. 43%
d. 53%

6. What is the dominant phylum present in the maternal gut microbiome in the first trimester?
a. Bifidobacteria
b. Proteobacteria
c. Lactobacillus
d. Firmicutes

7. What is the minimum recommended colony-forming unit dosage for best outcomes per a review in PLOS One?
a. 107
b. 108
c. 109
d. 1010

8. On average, what percentage of pregnant women could correctly define a probiotic?
a. 10%
b. 20%
c. 30%
d. 40%

9. The Iranian Journal of Public Health found that consuming probiotic-rich yogurt during pregnancy was associated with a decreased risk in developing gestational diabetes mellitus due to which specific probiotic strains?
a. Lactobacillus rhamnosus and Bifidobacterium
b. Lactobacillus reuteri and Bifidobacterium
c. Lactobacillus acidophilus and Bifidobacterium
d. Lactobacillus salivarius and Bifidobacterium

10. Per a study published in EBioMedicine, what is the ideal time frame to begin probiotic supplementation to a woman with a goal of lessening maternal anxiety and depression?
a. Six to 13 weeks’ gestation
b. Fourteen to 27 weeks’ gestation
c. Twenty-eight to 40 weeks’ gestation
d. Immediately upon giving birth

References
1. Obuchowska A, Gorczyca A, Standylo A, et al. Effects of probiotic supplementation during pregnancy on the future maternal risk of metabolic syndrome. Int J Mol Sci. 2022;23(15):8253.

2. Sheyholislami H, Connor KL. Are probiotics and prebiotics safe for use during pregnancy and lactation? A systematic review and meta-analysis. Nutrients. 2021;13(7):2382.

3. Probiotics market size, share & trends analysis report By product (probiotic food & beverages, probiotic dietary supplements), by ingredient (bacteria, yeast), by end use, by distribution channel, and segment forecasts, 2021–2030. Grand View Research website. https://www.grandviewresearch.com/industry-analysis/probiotics-market. Published 2021. Accessed May 31, 2023.

4. Jarde A, Lewis-Mikhael AM, Moayyedi P, et al. Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2018;18(1):14.

5. Trifkovič KC, Mičetić-Turk D, Kmetec S, et al. Efficacy of direct or indirect use of probiotics for the improvement of maternal depression during pregnancy and in the postnatal period: a systematic review and meta-analysis. Healthcare. 2022;(10)6:970.

6. Tsakiridis I, Kasapidou E, Dagklis T, et al. Nutrition in pregnancy: a comparative review of major guidelines. Obstet Gynecol Sur. 2020;75(11):692-702.

7. Beck LC, Masi AC, Young GR, et al. Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants. Nature Microbiology. 2022;7:1525-1535.

8. Han MM, Sun JF, Su XH, et al. Probiotics improve glucose and lipid metabolism in pregnant women: a meta-analysis. Ann Transl Med. 2019;7:99.

9. Mesa MD, Loureiro B, Iglesia I, et al. The evolving microbiome from pregnancy to early infancy: a comprehensive review. Nutrients. 2020;12(1):133.

10. Zakaria ZZ, Al-Rumaihi S, Al-Absi RS, et al. Physiological changes and interactions between microbiome and the host during pregnancy. Front Cell Infect Microbiol. 2022;12:824925.

11. Hasan Mohajeri M, Brummer RJM, Rastall RA, et al. The role of the microbiome for human health: from basic science to clinical applications. Eur J Nutr. 2018;57:1-14.

12. Punzón-Jiménez P, Labarta E. The impact of the female genital tract microbiome in women health and reproduction: a review. J Assist Reprod Genet. 2021;38(10):2519-2541.

13. Corbett GA, Crosby DA, McAuliffe FM. Probiotic therapy in couples with infertility: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2021;256:95-100.

14. Liu AT, Chen S, Jena PK, Sheng L, Hu Y, Wan YJY. Probiotics improve gastrointestinal function and life quality in pregnancy. Nutrients. 2021;13(11):3931.

15. Desai V, Kozyrskyj AL, Lau S, et al. Effectiveness of probiotic, prebiotic, and synbiotic supplementation to improve perinatal mental health in mothers: a systematic review and meta-analysis. Front Psychiatry. 2021;12:622181.

16. Browne PD, Bolte A, Claassen E, de Weerth C. Probiotics in pregnancy: protocol of a double-blind randomized controlled pilot trial for pregnant women with depression and anxiety (PIP pilot trial). Trials. 2019;20:440.

17. Fijan S, Frauwallner A, Varga L, et al. Health professionals’ knowledge of probiotics: an international survey. Int J Environ Res Public Health. 2019;16(17):3128.

18. Guner UC, Kissal A. Mothers’ knowledge, attitudes and practices regarding probiotic use during pregnancy and for their infants in Turkey. Public Health Nutrition. 2021;24(13):4297-4304.

19. Wilson Z, Whitehead K. A cross sectional survey to assess healthcare professionals' attitudes to and understanding of probiotics. Clin Nutr ESPEN. 2019;34:104-109.

20. Oliver L, Rasmussen H, Gregoire M, Chen Y. Health care provider's knowledge, perceptions, and use of probiotics and prebiotics. Top Clin Nutr. 2014;29(2):139-149.

21. Zheng J, Feng Q, Zheng S, Xiao X. The effects of probiotics supplementation on metabolic health in pregnant women: an evidence based meta-analysis. PLOSOne. 2018;13(5):e0197771.

22. Slykerman RF, Hood F, Wickens K, et al. Effect of Lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: a randomised double-blind placebo-controlled trial. EBioMedicine. 2017;24:159-165.

23. Mirghafourvand M, Rad AH, Charandabi SMA, Fardiazar Z, Shokri K. The effect of probiotic yogurt on constipation in pregnant women: a randomized controlled clinical trial. Iran Red Crescent Med J. 2016;18(11):e39870.

24. Chen X, Jiang X, Huang X, He H, Zheng J. Association between probiotic yogurt intake and gestational diabetes mellitus: a case-control study. Iran J Public Health. 2019;48(7):1248-1256.

25. Ho M, Chang YY, Chang WC, et al. Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to reduce Group B Streptococcus colonization in pregnant women: a randomized controlled trial. The TJOG. 2016;55(4):515-518.

26. Maldonado-Lobón JA, Díaz-López MA, Carputo R, et al. Lactobacillus fermentum CECT 5716 reduces staphylococcus load in the breastmilk of lactating mothers suffering breast pain: a randomized controlled trial. Breastfeed Med. 2015;10(9):425-432.

27. Fernández L, Cárdenas N, Arroyo R, et al. Prevention of infectious mastitis by oral administration of Lactobacillus salivarius PS2 during late pregnancy. Clin Infect Dis. 2016,62(5):568-573.

28. Chang CM, Tsai MH, Liao WC, et al. Effects of probiotics on gut microbiomes of extremely preterm infants in the neonatal intensive care unit: a prospective cohort study. Nutrients. 2022;14(15):3239.

29. Huang T, Li Z, Tye KD, et al. Probiotic supplementation during pregnancy alters gut microbial networks of pregnant women and infants. Front Microbiol. 2022;13:1042846.

30. Liu S, Yu H, Yu Y, et al. Ecological stability of microbial communities in Lake Donghu regulated by keystone taxa. Ecological Indicators. 2022;136:108695.

31. Getting probiotics naturally during pregnancy. American Pregnancy Association website. https://americanpregnancy.org/healthy-pregnancy/medication/getting-probiotics-naturally-during-pregnancy/. Accessed April 5, 2023.

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