Every year, an estimated 15 million babies worldwide are born preterm (before 37 completed weeks of gestation), and this number is rising, according to the World Health Organization (WHO). The WHO ranked USA 6th for greatest number of preterm births in 2010, and in 2017 March of Dimes graded our nation as a “C” on their premature birth report card. In 2018 the USA had 1 in 10 babies as preterm births.
Intrauterine infection and inflammation may account for up to 40% of preterm births, but in many instances, the cause might be subclinical and difficult to detect. Preterm birth known risk factors include multiple pregnancies, smoking and substance abuse, history of preterm birth (PTB), maternal emotional stress during pregnancy, and limited prenatal and antenatal care. Preventing preterm births starts with preconception care and healthy pregnancy practices.
Why it matters: Preterm birth complications are the leading cause of death among children under 5 years of age, responsible for ~1 million deaths per year worldwide, and can lead to lifelong developmental and physical disabilities. New information on preterm birth (PTB) and the female reproductive microbiome’s potential impact on PTB rates is worth a much closer look.
Maternal Reproductive Microbiome
When figuring out how we as humans interact with the “friendly” bacteria, viruses, fungi, and other organisms in our body, the microbiome is where it’s at. All humans have unique, though similar, microbiomes throughout the body, with the gut microbiome being the most well researched. Disruption and variations to these microbiomes have shown to influence health on many levels including preterm birth rates.
The maternal reproductive microbiome, includes the vaginal microbiome (VBM), cervicovaginal, endometrial, and uterine microbiome, although oral and gut microbiomes also impact reproductive and pregnancy health. Changes to reproductive microbiomes greatly influence conception and pregnancy outcomes. Female reproductive microbiomes change throughout a lifetime and even between trimesters in pregnancy, shifting to less diversity with a predominance of Lactobacillus species, the most common probiotic or “friendly” bacteria, in late pregnancy.
A healthy vaginal microbiome (VBM) includes predominantly Lactobacillus species (90-95%), Atopobium, Dialister, Gardnerella, Megasphaera, Prevotella, Peptoniphilus, and Leptotrichia. Endometrial microbiome of <90% Lactobacillus species and >10% other bacteria is associated with reduced implantation as well as reduced rates of pregnancy, ongoing pregnancy and live births.
VBM variations in Lactobacillus species among women of different races and ethnicity follow PTB trends of those groups too. Lactobacillus crispatus is significantly higher among white non-Hispanic women than non-Hispanic black and Hispanic women. Non-Hispanic black and Hispanic women have significantly higher rates of diversity group bacteria. It was concluded that high vaginal diversity is associated with an increased risk of PTB and bacterial vaginosis. This follows the PTB trend, where PTB in non-Hispanic black women is higher compared to that of non-Hispanic white women.
Dysbiosis and Preterm Birth
Dysbiosis is the disruption of normal microbiome organisms. Vaginal microbiome can become imbalanced through exogenous/environmental factors such as drug use, behavioral practices, sexual activities, diet, hygiene practices, and stress; and endogenous/host factors including genetic background, age, hormonal status, vaginal pH, ethnicity, and immune system status.
Conception and pregnancy are dependent on balanced microbiomes in the mother’s body. VBM dysbiosis has been associated with decreased pregnancy rates in IVF patients, especially when Gardnerella vaginalis and Atopobium vaginae are elevated. Notice both of these bacteria are listed as healthy VBM, but quantity of microbes matters. In 2019 Journal of Gynecology Obstetrics and Human Reproduction stated “recent meta-analysis concluded that women with an abnormal vaginal microbiota are roughly 1.4 times less likely to have a successful early pregnancy development after IVF treatment when compared to women with normal microbiota.”
Recurrent miscarriage patients with elevated peripheral NK cells have more Gardnerella vaginalis and gram-negative anaerobes, demonstrating VBM association with changes in immune parameters and miscarriage. Bacterial vaginosis is found in 15-23% of pregnant women, half of whom are asymptomatic, with abnormal VBM in early pregnancy associated with a 5-fold increase in late miscarriage and early PTB. Short cervix in the second trimeter is a risk factor for PTB and studies show a significant association with Lactobacillus iners being dominant at 16 weeks gestation with both a short cervix and PTB. When Lactobacillus crispatus is dominant, it is highly predictive of term birth. Addressing VBM changes and other reproductive pathogenic infections is vital for preconception care and prevention of PTB.
Maternal Reproductive Microbiome Treatment for Preterm Birth Prevention
SUPPORTIVE STRATEGIES - PRECONCEPTION
Both partners need a full assessment of current and past infections, immune function status, stress levels, exercise regimen, contraception choices, optimal weight balance and dietary practices, oral hygiene, past antibiotic use and avoidance, and proper promotion of Lactobacillus species to fully understand the potential occurrence for PTB.
PRE AND PRO BIOTIC SUPPLEMENTATION BENEFITS
Maternal:
~Reduction of preterm birth, gestational diabetes, gestational weight gain, and preeclampsia
~Prevention of group B streptococcus colonization
~Reduction postpartum depression
~Alleviation of GI related complaints and antibiotic associated side effects
~Heavy metal and pesticide detoxification
~Reduction in vaginal and urinary tract infections
Neonatal:
~Reduction in colic
~Elimination of necrotizing enterocolitis (NEC), atopy, neurological disorders
~Support for allergies
~Reduction in antibiotic resistance
~Development of healthy immune system with proper maternal priming
PROBIOTICS
Cochrane meta analysis showed 81% reduction in genital infections with oral probiotics alone. Probiotics have been proven to compete with and inhibit pathogen growth, thereby balancing the inflammatory cascade commonly observed in PTB. Lactobacillus crispatus and Bifidobacterium species are applied as a vaginal paste to improve VBM. Probiotic gargles can help with oral dysbiosis and allow for healthy microbiome repopulation.
DIETARY
Dietary support is essential for VBM health, studies show after one month on a standard American diet, a 71% increase in endotoxin activity. Endotoxins are an integral component of the outer membrane of gram-negative bacteria, E. coli, chlamydia and gonorrhea are all gram-negative bacteria. A sedentary lifestyle results in higher levels of endotoxins too, so get the body moving and eat a whole foods diet.
Prebiotics, food for the friendly probiotics, and fiber are necessary in growing a healthy microbiome. Inulin, fructo-oligosaccharides, lactulose, galacto-oligosaccharides, psyllium, and resistant starch can all help VBM. Apple cider vinegar and pink salt are beneficial in electrolyte status and regulating pH, lower vaginal pH improves Lactobacillus growth, and diminishes Gardnenella and harmful bacteria overgrowth. Fermented foods are helpful in reasonable amounts, don’t overdo them. Avoidance of sugar, yeast, alcohol, and caffeine will improve the overall status of the microbiome.
ESSENTIAL OIL
Tea tree, sandalwood, or thyme oils are used in cervicovaginal washes for their antimicrobial actions. Prior to pregnancy thyme essential oil with salt can be used as a gargle for oral health. See a trained professional for preparation and application instructions of essential oils.
SUPPLEMENTS
CoQ10 can be used a swish and swallow during pregnancy for mouth and gum health. Vitamin C boosts immune function for better maintenance of a healthy microbiome.
Oral berberine modulates the gut microbiome through enriching short chain fatty acid producing-bacteria and reducing microbial diversity.
Progesterone helps with embryo implantation and maintaining pregnancy in the first trimester, and it is now known to regulate Bifidobacterium. Therefore if progesterone is deficient, PTB may increase due to the low levels of Bifidobacterium.
When seeking treatment, know not all women’s health or reproductive healthcare professionals consider the microbiome when evaluating a couple for preconception care, infertility, or recurrent miscarriages. Seek the guidance of a health professional with the knowledge to best support you.
Conclusion
With millions of preterm births each year, and all the complications and costs that accompany PTB, a thorough health history of both partners, balancing all microbiomes, and eradication of pathogenic infections should be a top priority before trying to become pregnant. Correcting imbalances before conception can greatly improve the pregnancy experience and overall health of the fetus, allowing higher likelihood of full term birth.