Pregnancy & Preterm-Low-Birth-Weight (PLBW) Infants

An estimated 10,000 babies are born each day in the United States. Of these babies, 800 are born at low birth weight and 150 at very low birth weight (87,88); more than 50% will die; and a significant number will have permanent deficits. Oral infections seem to increase the risk for or contribute to low-birth-weight (LBW) in newborns. LBW, defined as a birth weight of <2,500 g, is a major public health problem in both developed and developing countries.

The incidence of preterm delivery and LBW is about 10% of all live births in the United States, and has not decreased significantly over the last ten years. LBW in preterm infants remains a significant cause of perinatal morbidity and mortality. Compared to normal-birth-weight infants, low-birth-weight infants are more likely to die during the neonatal period, and LBW survivorsface neurodevelopment disturbances, respiratory problems, and congenital anomalies.

Researchers have found that pregnant women with periodontitis were 7.5 times more likely to have a preterm-LBW infant than were pregnant women without periodontitis, and concluded that 18.2% of preterm-LBW babies may result from periodontal disease. Studies in humans have demonstrated that women who have LBW as a consequence of either preterm labor or premature rupture of membranes tend to have more severe periodontal disease than mothers with normal-birth-weight infants. Other researchers reported that the risk of preterm birth was directly related to the severity of periodontitis. It has also been suggested that periodontal pathogens disseminate systemically within the mother and can gain access to the fetal environment.

Risk factors for preterm-LBW infants include older (>34 years) and younger (<17 years) maternal age, African-American ancestry, low socioeconomic status, inadequate prenatal care, drug, alcohol, and/or tobacco abuse, hypertension, genitourinary tract infection, diabetes, multiple pregnancies, and previous preterm LBW infants. Although increasing efforts have been made to diminish the effects of these risk factors through preventive interventions during prenatal care, they have not reduced the frequency of preterm-LBW infants.

Evidence of increased rates of amniotic fluid infection, chorioamnion infection and chorioamnionitis supports an association between preterm birth and LBW and infection during pregnancy. Even in the absence of any bacterial infection in the vagina (vaginosis) or cervical area, the chorioamnion is often inflamed, which suggests that distant sites of infection or sepsis may be targeting the placental membranes. Vaginosis is caused by gram-negative anaerobic bacteria is a significantrisk factor for prematurity, and is usually associated with thesmallest, most premature neonatal deliveries. The biological mechanisms can involve bacterially induced activation of cell-mediated immunity leading to cytokine production and the ensuing synthesis and release of prostaglandin (PG), which appears to trigger preterm labor. Elevated levels of cytokines (IL-1, IL-6,and TNF- ), which are all potent inducers of both PG synthesis and labor, have been found in the amniotic fluid of patients in preterm labor with amniotic fluid infection. Intra-amnionic levels of PGE and TNF-rise steadily throughout pregnancy until a critical threshold is reached to induce labor, cervical dilation, and delivery.

Periodontal disease, as a remote gram-negative infection, could potentially affect pregnancy outcome. The ratio of anaerobic gram-negative to aerobic bacterial species has been shown to increase in dental plaque in the second trimester of pregnancy.The gram-negative bacteria associated with progressive periodontal disease can produce a variety of bioactive molecules that can directly affect the host. One microbial component, lipopolysaccharides (LPS), can activate macrophages and other cells to synthesize and secrete a wide assortment of molecules, including the cytokines IL-1, TNF-, IL-6, and PGE and matrix metalloproteinases. If they escape into the general circulation and cross the placental barrier, they could increase the physiologic levels of PGE and TNF-in the amniotic fluid, thus inducing premature labor. Offenbacher and co-workers measured the levels of PGE and IL-1 in gingival crevicular fluid (GCF) in order to determine whether these intermediaries were related to current pregnancy outcome. The results also indicated that GCF PGE levels were significantly higher in mothers of preterm-LBW infants than in mothers of normal-birth-weight infants. A significant inverse preterm LBW and GCF PGE level association was also reported. These data suggest a dose-response relationship for increased GCF PGE as a marker of current periodontal disease activity and decreasing birth weight. They also measured the levels of four periodontal pathogens associated with mature plaque and progressing periodontitis,Tannerella forsythia P. gingivalisA. actinomycetemcomitans, andTreponemadenticola, and found them to be higher in mothers with preterm-LBW infants than in controls.

Pregnancy-Associated Gingivitis

Pregnancy is associated with an increase in prevalence, severity, and extent of gingivitis. The prevalence of gingivitis in pregnant women can vary between 30 – 100% and may be higher in women with previous pregnancies. During pregnancy, gingivitis increases in severity as early as the second month of pregnancy, increases further as the pregnancy advances, reaches a maximum around months 7 and 8, decreases in month 9, and returns to prepregnancy values in the postpartum period. These changes are independent of plaque accumulation, suggested that the host factors are involved in its pathogenesis. The clinical signs of pregnancy gingivitis are similar to the signs of plaque-induced gingivitis. For example, there is a significant increase in inflammatory indices such as gingival bleeding, pocket depth, and gingivial crevicular fluid. The percentage of bleeding sites may almost double in pregnant women compared to nonpregnant women. The percentage of pregnant women with pockets deeper than 4 mm may be twice that of nonpregnant women. In a significant percentage of women, there may also be significant enlargement of the gingiva, particularly affecting areas of previous gingival inflammation.

Female Hormone Changes

Pregnancy can influence gingival health. Changes in hormone levels during pregnancy promote an inflammation termed pregnancy gingivitis. Furthermore, oral bacterial anaerobes have been found to change during the normal hormonal cycle. This type of gingivitis may occur without changes in plaque levels.

  • Oral Contraceptives

Oral contraceptives may also produce changes in gingival health, and some birth control pill users have a high gingival inflammation level but a low plaque level. Birth control pills may cause changes such as alteration of the microvasculature, gingival permeability, and increased synthesis of estrogen PGs.

  • Estrogen Deficiency

Estrogen deficiency is also a risk factor for periodontal disease, and plays a role in the increased risk of osteopenia and osteoporosis seen in female patients. The influence of estrogen deficiency on osteopenia and osteoporosis and periodontitis is still unclear, however it has been suggested that estadiol supplementation was associated with a reduction in gingival inflammation and periodontal attachment loss in osteopenic/osteoporotic females in early menopause. Krall and others reported that estrogen users had more teeth remaining than non-users, and also decreased levels of several gingivitis and periodontitis severity indicators, when compared to estrogen-deficient females.


Significant and observable gingival inflammatory changes have been documented in association with the menstrual cycle. Long ago, “gingivitis intermenstrualis” was a term given to observations that consist of bright red bleeding lesions of the gingival (gums) between the teeth prior to menstruation. The symptoms of bleeding and swollen gingival tissues, and an increase in gingival fluids are most apparent in the presence of preexisting gingivitis, and minor increases in tooth mobility have also been reported.

It has been reported that gingival fluids increase at least 20% during ovulation in more than 75% of females studied. The level of gingival fluid appears to peak just before ovulation, coinciding with the highest levels of estradiol and progesterone in the circulation. Women with healthy gingival tissue experience very few significant oral changes as a result of menstruation. It has also been noted that during their menstrual cycles, women without clinical gingivitis showed no increase in gingival fluid, whereas those with gingivitis showed increases in gingival fluid.

  • Additional Oral Complications

It has been reported that, in addition to gingival inflammation, intraoral recurrent aphthous lesions, herpes labialis lesions, and infections with Candida albicans in some women which seem to be associated with increased progesterone levels during the reproductive cycle. These oral mucosal lesions would make chewing and swallowing painful, and these individuals would benefit from nutritional supplements and dietary modifications.  


Unlike the rhythmic patterns of the reproductive cycle, the onset of menopause is accompanied by irregular hormonal fluctuations (that is, estradiol ceases to be the major circulating estrogen and estrone) and lack of cyclic influences, which leads to a significantly different gingival appearance. Essentially, the sex steroid-induced gingival inflammatory changes witnessed during the reproductive years no longer occur to any degree.

The effect of reduced estrogen levels on epithelial keratinization, along with decreased salivary gland flow independent of medications, may have other significant effects on the periodontium.

Friedlander described an atrophic gingivitis in some post-menopausal women in which the gingival tissues develop an abnormal paleness. In other women, a menopausal gingival stomatitis may develop, characterized by shiny, dry, spontaneous bleeding, and pale to erythomatous colored gingival tissue. More commonly reported gingival lesions seen in women during this phase of life tend to be desquamative in nature. However, the role that steroid sex hormones play in the development and progression of these lesions remains obscure.

  • Additional Oral Complications

Most of these lesions occur in females of middle age, and exogenous estrogens have been used to treat these lesions. Oral discomfort is also commonly reported by post-menopausal females, with 20-90% of women reporting a burning sensation, xerostomia, or bad taste, while only 6% of pre-menopausal women report the same. As with desquamative lesions, estrogens have been successfully used to gain pain relief under these circumstances, eventhough direct correlation with these symptoms has yet to be established.

Endocrinology and Biochemistry

In addition to gingival changes, reduced estrogen levels certainly may impact overall collagen metabolism, including bone maintenance, and result in a tendency toward development of osteoporosis. A study also indicated an association between bone mineral density loss, periodontitis, and tooth loss in Japanese women after menopause.