Dentistry’s most significant failure may just be due to a lack of emphasis on women and children. Sadly, although the old saying” women and children first!’ was a reportedly common expression, that practice was not always the clinical norm. Fortunately, medical sleep specialists have published research concerning the occurrence of pregnancy-onset sleep apnea (1). The significance of pregnancy-onset sleep apnea is emphasized in the scientific literature, and the great potential for harm has also been reported (1-2).
Women with an Obstructive Sleep Apnea (OSA) diagnosis are more likely to have a cesarean delivery, gestational hypertension, preeclampsia, and preterm birth (3). The results of a large, national inpatient database study reported that pregnant women diagnosed with OSA during their hospital admission at delivery were “at significantly increased risk of having cardiomyopathy (aOR = 9.0 (95%CI, 7.47-10.87)), congestive heart failure (aOR = 8.94 (95%CI, 7.45-10.73)), and pulmonary embolism (aOR = 4.5 (95%CI, 2.3-8.9))”. This study also reported “a five-fold increase in in-hospital mortality during pregnancy or delivery in women with OSA” (4).
The tragedy is that pregnant mothers are rarely screened by their dental professional for sleep apnea, even though a simple report by the spouse would suffix to justify intervention (5). Well-designed population-based studies of maternal-fetal outcomes have been published (6). A simple oral appliance could often be the therapy that may be appropriate and may only be necessary for the gestational period. The use of home sleep apnea testing has been validated in pregnant women so that practitioners may feel comfortable using better home apnea testing, as with high-resolution pulse oximetry (7). Extensive clinical studies are warranted to investigate this hypothesis further.
Immune changes occur during pregnancy due to hormonal fluctuations (8). Gingival enlargement is oft-reported, and lymphoid tissue such as the adenoids and tonsils may also hypertrophy (9- 11). The airway patency may become restricted due to weight gain, and sleep positions may change, increasing both the severity and frequency of sleep apnea episodes (12). OSA is characterized by repeated upper airway constrictions during sleep, leading to apneas/hypopneas, causing arousals, oxygen desaturation, sympathetic activation, and endothelial dysfunction (15, 16); these pathophysiologic effects have been associated with the development of preeclampsia, perhaps due to abnormal placental physiology (15–17).
Furthermore, partial airway obstruction associated with spouse reports of snoring (17, 18, 19) and airflow limitation seen by polysomnography (19, 20) are common during pregnancy (18–21), along with apneas/hypopneas have been associated with adverse perinatal outcomes (2, 3, 20–23). Therefore, the required threshold to treat OSA during pregnancy should be below that for general treatment of obstructive sleep apnea (24, 25, and 26).
Changes in the oral microbiome during pregnancy and increased inflammatory biomarkers (27-28) are well documented. A case-control study reported that mean arterial blood pressures were significantly lower (p = 0.009) and serum nitric oxide levels were significantly higher (p < 0.001) in healthy pregnant women compared to healthy non-pregnant women (29). There was a non-significant progressive increase in serum nitric oxide levels during a healthy, normal pregnancy (30). An increase in periodontal disease may also be associated with reduced nitrate-reducing bacteria (30). Nitric oxide may have a role in the occurrence and development of periodontal disease by regulating the action of specific cytokines (31). Nitrate-reducing bacteria are associated with good periodontal health and perhaps with reduced respiratory effort (32-33).
Nitrate-reducing bacteria are now considered important commensals essential for host homeostasis and maintaining normosystolic blood pressure (34). Indeed, nitrate-reducing bacteria are crucial in reducing nitrates to nitrites, which are then further processed into nitric oxide after exposure to stomach acid (35). The absorbed nitric oxide is then concentrated by a factor of 10 in the host’s saliva and is considered instrumental in the host’s oral defense (35). For instance, nitrate-reducing commensals limit the growth of cariogenic bacteria (36). Levels of salivary nitrate and the presence of nitrate reductase, associated with other commensals, have been correlated with caries resistance, possibly due to the anti-microbial properties of nitric oxide (37).
Another important protective function of the nitrate-reducing bacteria is regulating host blood pressure (35). According to research studies, nitric oxide is a vasodilator that significantly moderates the host’s blood pressure (32). Studies with anti-microbial mouthwashes have demonstrated that losing nitrate reducers significantly increases the host blood pressure (36). Other benefits ascribed to the nitrate-reducing bacteria include protection against ischemia-reperfusion damage, restoration of NO homeostasis with associated cardioprotection, increased vascular regeneration after chronic ischemia, and reversing vascular dysfunction in the elderly (33).
Another role for the nitrate-reducing bacteria would be the added benefit of increasing the host’s capability for vasodilation, which is particularly important for the species and prevents erectile dysfunction (36-39). Airway epithelial cells also respond to increased Nitric Oxide levels with barrier protection and anti-pathogenic activity of the airway surface liquid (40-43). Therefore, maintaining the maternal oral microbiome during pregnancy is of paramount importance. Nitrate-reducing bacteria, such as Rothia aeria, inhibit oral pathogens and may also improve respiration while reducing inflammation from gluten-containing foods.
Microbiome researchers are interested in the multiple roles that many commensal bacteria perform for the host. For example, Rothia dentocariosa is both a gluten metabolizer and a nitrate reducer (44-45). Rothia dentocariosa is also maternally imprinted in both the placental and the fetal microbiome (46). One would suspect that evolution tends to favor efficient mechanisms such as this. However, chronic illnesses and debilitations appear to be increasing, requiring reflection into the evolutionary process and the perturbations that have recently occurred, creating this environment of now declining health (47).
Current research would point to the “Hygiene hypothesis”: the use of anti-microbials, dietary shifts, and the resultant decrease in the human microbiome diversity (48-49). The old model of looking for increased pathogens is flawed. Indeed, the fault lies with the decrease in commensals that compete directly with the pathogens and modulate the host’s immune response (50). To improve the health of children, we must first improve the mother’s microbiome, as the maternal microbiome sets the stage for the child’s microbiome (51, 52). Even recent research into various cancers has demonstrated the role of the gut microbiome (influenced by the oral microbiome) and the maternal microbiome (53).
Pre-natal intervention has been studied with positive results reported by supplementing the mother with either probiotics or polyols (52, 54). Well-published studies using xylitol that involve nursing mothers and children have demonstrated a decrease in the maternal transmission of mutans streptococci (55). Certainly, intervention may be desired even earlier, preferably before pregnancy, as it is also reported that the mother’s antecedent use of antibiotics will affect the maternal microbiome (56-57). The placental microbiome is most closely related to the maternal oral microbiome (57). The presence of commensal bacteria in the placenta and developing fetus is considered to be essential to fetal immunological maturation (58). The oral health of the expecting mother should then be considered primarily important to the oral-systemic health of the fetus and, later, the child.
In addition, the placental microbiome appears to be developed quite early in the pregnancy by maternal imprinting (59). This maternal imprinting involved the transportation of viable commensals via circulating monocytes, correctly creating a fetal microbiome to program the developing child (60). Animal studies have demonstrated the transmission of maternal breast commensals into the amniotic fluid (61). But all this depends upon the mother actually having a healthy microbiome (62). The maternal microbiome can be influenced in numerous ways, including diet, exercise, and probiotic supplementation (63-67). In addition, polyols can help decrease the prevalence of pathogens before they are passed on to the child (52, 68-69). Pregnant women and those who are planning a pregnancy should have an office consultation, checking for sleep apnea, and the appropriate prebiotics and probiotics delivered to develop and maintain maternal-fetal health.
The effects of maternal sleep apnea on the developing child are now being discovered and finally recognized (70). Sleep apnea research utilizing animal models has demonstrated what clinicians have often been concerned about, that apneic and hypnic episodes may affect fetal brain development, resulting in many children with sensory issues and learning disabilities (71). Sleep apnea in the mother may also affect mandibular development, resulting in a child with a propensity for sleep apnea, as shown by animal models (72). This brings to light the fallacy of “long faces run in the family,” or the too often used weak explanation of “bad genes” or, even worse, “dad’s teeth in the mother’s jaw” statements the profession relied upon to explain a poorly understood phenomenon (72). The role of epigenetics should never be ruled out, as research constantly reminds us of its importance.
The vicious cycle of the airway, if the mother develops pregnancy sleep apnea, she will develop oral dysbiosis, which often results in periodontal disease and both nasal dysbiosis and gut dysbiosis (73- 77). The dysbiotic gateway microbiomes modulate the immune system, resulting in further dysbiosis and the disappearance of important commensals. In addition, the immune responses with increased mucous production as a defensive measure and increased lymphoid tissue increase airway difficulties. The cycle continues, with the lack of important commensals, such as nitrate-reducing bacteria, that increase both oral and systemic disease, sometimes resulting with a miscarriage, premature birth, stillbirth, or low birth weight infant (74). The child’s sleep pathology may be further expressed by the effects of immune dysfunctions (allergies, etc.) and changes in the craniofacial respiratory complex (59, 74, and 76). Appropriate treatment would be to supplement the mother with probiotics and prebiotics, in addition to providing treatment of the sleep apnea end articles. If a practitioner does not feel comfortable treating pregnancy sleep apnea, then a timely referral is highly recommended for the health of the mother and the child.
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Mark L. Cannon is a Professor of Otolaryngology, Division of Dentistry at Northwestern University, Feinberg School of Medicine, an Attending Physician at Ann and Robert Lurie Children’s Hospital and a member of the International Association of Pediatric Dentistry. In addition to being the founder of Associated Dental Specialists of Long Grove (1981); he is the Research Coordinator of the Pediatric Dental residency program at Ann and Robert Lurie Children’s Hospital, Chicago, Illinois.
Dr. Cannon has 40 years of experience in pediatric dentistry and has presented lectures both nationally and internationally. Dr. Cannon has presented guest lectures at the University of Athens, Greece, Sao Paulista State University, UNESP, Aracatuba, Brazil, University of Texas- Houston, University of Alabama-Birmingham, University of Michigan Ann Arbor, Yonsei University, Beijing Medical University, CES (Medellin, Colombia) and at the University of Illinois, Chicago, Department of Pediatric Dentistry.
He has had presentations to the following organizations; I.A.D.R./A.A.D.R., the American Academy of Pediatric Dentistry, the American Society of Dentistry for Children, Academy of Dental Materials, World Congress of Biological Materials, International Association of Pediatric Dentistry, Pediatric Dental Association of Asia, Australasian Academy of Pediatric Dentistry, World Congress of Preventive Dentistry, Mexican Association of Pediatric Dentistry and the European Association of Pediatric Dentistry.
He lectures on many oral health topics including evolutionary oral medicine, the gateway microbiomes, biologic and bioactive dental materials (patents owner), probiotics, and all aspects of everyday Pediatric oral health. Dr. Cannon has humbly accepted two invitations by the Karolinska Institutet, first to the Nobel Forum (2016) and secondly to the Nobel Assembly (2017). Most of all, Dr. Cannon is the proud father of five, all of whom are very accomplished. He is also a very proud grandfather!
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