Unexpected: Managing Oral Health in a Complicated Pregnancy

Good oral health and dental care are critical components of any healthy pregnancy. National Consensus Statements and numerous state health department guidelines offer recommendations for the safe delivery of dental care before and during pregnancy.¹ Recently, a series of articles in Compendium featured oral health and dental care during routine, healthy pregnancy and discussed collaborations with the perinatal team in the spirit of inter-professionalism and integrated healthcare.^2-5 Acknowledging that not all pregnancies are healthy and uneventful, this final article in the pregnancy and oral health series highlights aspects of complicated pregnancy to assist dental professionals in addressing the oral health needs of all pregnant women.

Some women experience health problems during pregnancy that can involve the well-being of the mother, her fetus, or both. These complications may make the pregnancy high-risk, wherein the mother and/or fetus are at greater risk for adverse outcomes during pregnancy or labor than in a typical, uneventful healthy pregnancy. Early and regular prenatal care can help decrease the risk of complications and improve pregnancy outcomes for both mother and fetus. Dental professionals have a duty to ask if a pregnant patient is receiving prenatal care, and if she is not, the dental professional should advise that prenatal care is essential and, if necessary, assist in referral or arranging care.

Adverse Pregnancy Outcomes

Annually, 1.1 million babies die from prematurity, and many that survive are disabled. Worldwide, 15 million babies are born preterm, which is the second most common cause of death in children younger than 5 years, after pneumonia.⁶ Preterm birth is a leading risk factor for deaths due to neonatal infections and contributes to long-term growth impairment and substantial long-term morbidity such as cognitive, visual, and learning impairments.⁷ All of these conditions are part of a broader spectrum, known as adverse pregnancy outcomes. Well-known adverse pregnancy outcomes include preterm delivery, pre-eclampsia, miscarriage/still birth, low birth weight (LBW) infants, pre-term LBW infants, and growth rrestriction.⁸ (See Table 1, Summary of Common Pregnancy Complications and Adverse Pregnancy Outcomes, which may be viewed online at compendiumce.com/go/2010.)

The financial burden of adverse pregnancy outcomes is considerable, and thus medical insurance plans are beginning to show an interest in promoting good oral health and access to dental care. The March of Dimes in 2008 reported on the costs of prematurity and complicated deliveries to US employers. Maternity and first-year costs combined for a premature baby were four times as high as those for a baby born without any complications ($64,713 and $15,047, respectively).⁹ Health plans typically pay more than 90% of these costs, and, not surprisingly, some plans now offer to reimburse pregnant women for out-of-pocket dental costs to encourage dental utilization and improved health outcomes for the mother and infant, with, of course, significant savings to the plan purchaser or employer.

Adverse pregnancy outcomes are generally associated with elevated local and systemic inflammatory mediators and/or intra-uterine infections. Adverse pregnancy outcomes primarily originate from ascending infections from the vagina or cervix or from hematogenous spread from known or unknown non-genital sources.¹⁰ Maternal periodontal disease represents one potential source of microorganisms that are known to routinely enter the circulation. Maternal periodontal disease directly and/or indirectly has mechanistic potential to influence the health of the fetal-maternal unit.¹¹

Preterm birth rates in the United States have not improved over the past 10 years, remaining around 10% of all live births.¹² Prematurity rates in Europe and other high-income countries are lower, around 5% to 9%.⁶ Preterm birth is a serious public health concern worldwide given its associated morbidity, mortality, and societal and economic costs. While the threshold for preterm delivery is anytime earlier than 37 weeks, very preterm babies are born as early as 32 weeks. Possible causes for preterm births are: spontaneous preterm labor, premature rupture of membranes, early induction of labor, or caesarean section due to fetal distress or maternal medical conditions. Pre-eclampsia is defined as maternal hypertension and proteinuria after the 20th gestational week. This is considered a major cause of maternal and perinatal morbidity and mortality. LBW infants that are born with less than 2500 grams weight or even very LBW with less than 1500 grams weight are also considered for close monitoring and advanced treatment.⁶

In addition to the physical issues that may face preterm and LBW infants throughout their lives, there are psychological impacts on parents as well. Parents of infants admitted to the neonatal intensive care unit (NICU) demonstrate clinically relevant levels of anxiety and if the NICU admission is associated with infant prematurity, the levels of anxiety in mothers and fathers increase.¹³ The sources of the high levels of stress on a family stemming from premature delivery may relate to concern about future ramifications of infant prematurity and/or pregnancy complications, financial considerations about the significant healthcare costs associated with a complicated pregnancy and delivery, and the differences between the expected outcomes and the present realities.¹⁴ Long term, parents of premature infants had a high prevalence (52%) of post-traumatic stress disorder and are more likely to have poor mental health, increased debt levels, higher levels of social isolation, and more interference with employment than parents of full-term infants.^15,16 Given the wide-reaching effects of preterm birth and pregnancy complications on parents and their offspring, dental professionals should be aware of these issues and work with families to optimize their oral health during what can be a difficult time.

Normal Physiological Changes

This article will review some common complications of pregnancy that may influence the provision of non-emergent dental care in an outpatient setting. First, however, a brief review of the normal physiological changes that occur during pregnancy is warranted. After conception, both the fetally derived placenta penetrating into maternal uterine tissue and the growing fetus it surrounds derive all nutrients from maternal sources. The placenta, which is highly vascularized, allows the exchange of nutrients and waste between the mother and fetus. This exchange occurs via the umbilical cord that connects the fetus with the placenta. This nutrient-rich environment allows the fetus to develop within the amniotic fluid and amniotic sac. The amniotic sac consists of a bilayer of walls, the amnion and the chorion, which like the placenta are attached to the uterus through the decidua and the myometrium.

As the fetus grows in size, the increasing need for nutrients and the decreasing amount of space become critical parameters for overall survival of mother and fetus. Thus, as a pregnancy progresses, amniotic fluid levels of prostaglandin E2 and inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-beta, rise steadily until a critical threshold level is reached. This threshold level of inflammatory cytokines within the amniotic fluid then induces rupture of the amniotic sac membranes and initiates uterine contraction, cervical dilation, and delivery.¹⁷ This normal process can be interrupted by external stimuli that increase local or systemic inflammatory mediators and/or block such mediators. This, then, represents a triggering mechanism for the interaction of periodontal disease and preterm birth.¹¹

 

Maternal Factors

Existing Health Conditions

Certain health conditions affecting individuals prior to becoming pregnant may influence pregnancy risk and outcomes.^8,18-21

Hypertension: While controlled hypertension is usually managed with medications and lifestyle modification during pregnancy, uncontrolled hypertension may lead to kidney damage and pre-eclampsia and can put the fetus at risk for low birth weight (<2500 grams). Blood pressure monitoring should be performed at every healthcare visit for pregnant patients so that changes may be detected and patients can be referred to receive adequate care.^20,21 Additionally, women with hypertension may be prescribed low-dose aspirin to delay or prevent the onset of pre-eclampsia. Patients should not discontinue aspirin if they receive dental care.²²

Obesity: Individuals with obesity prior to pregnancy have an increased risk of gestational diabetes and sleep apnea during pregnancy as well as preterm birth. Obesity prior to pregnancy is also associated with an increased risk of congenital heart defects, and it is recommended that pregnancy weight gain be limited to 15 to 25 pounds for individuals who were overweight pre-pregnancy and 11 to 20 pounds for those with obesity.^20,21

Polycystic ovary syndrome (PCOS): Women with PCOS have higher rates of pregnancy loss prior to 20 weeks of gestation and an increased risk of gestational diabetes, pre-eclampsia, and delivery by cesarean section.^20,21

Diabetes: Women who have been diagnosed with diabetes prior to pregnancy have risks associated with their blood glucose levels and glycemic control. High blood glucose in the first trimester, when a woman may not yet know she is pregnant, can have significant consequences for the pregnant patient and her fetus.^20,21 Infants born to mothers with diabetes, in particular insulin-dependent women, may have two to six times greater likelihood of major birth defects, including damage to the heart and major blood vessels, brain and spine abnormalities, urinary tract and kidney malformation, digestive tract defects, miscarriage, and still birth. Maternal risks include hypo- and hyperglycemia and ketoacidosis, which can be life threatening. Pregnancy may also change macronutrient metabolism for diabetic patients, altering treatment and monitoring needs.^20,21

Kidney disease: Mild impairment of kidney function may be compatible with a healthy pregnancy. Decreased kidney function has been associated with preterm delivery, low birth weight, and pre-eclampsia. Nearly 20% of women who develop pre-eclampsia early in pregnancy are found to have undiagnosed kidney disease. Frequent monitoring and alterations in diet and medication may be required for pregnant patients with kidney disease.^20,21

Autoimmune diseases: Pregnancy can cause alterations to the mother's immune system to allow for gestation of the fetus in an immune-protected placental environment, which can cause flare-ups of autoimmune disease symptoms. Additionally, certain drugs, specifically folic acid antagonists and methotrexate, used to treat autoimmune diseases may be teratogenic and cannot be used during pregnancy.^20,21,23

Age

Young age: Pregnant individuals under 20 years old are more likely to develop hypertension and anemia and have a higher rate of preterm birth than women between 20 and 35 years. Younger pregnant individuals also have higher rates of sexually transmitted infections, which may affect fetal formation or preterm birth.^20,21

First-time pregnancy over 35 years: While most women over 35 years old have a healthy pregnancy, women with advanced maternal age are at a higher risk for gestational hypertension, gestational diabetes, miscarriage/stillbirth, ectopic pregnancy, fetal genetic disorders, prolonged and complicated labor, excessive bleeding during delivery, and cesarean section delivery.^20,21

Lifestyle Factors

Alcohol use: Drinking alcohol during pregnancy can increase the risk of fetal alcohol spectrum disorders (FASDs), sudden infant death syndrome (SIDS), and miscarriage/stillbirth. FASDs range from mild to severe and include intellectual and development disabilities, behavioral issues, and characteristic facial features (smooth philtrum, thin vermillion, and narrow palpebral fissures).^24,25 Despite being clearly established as a teratogen since the 19th century, alcohol is used by approximately 15% to 20% of pregnant women worldwide.²⁶ Currently, no data exists to demonstrate a threshold level of safe alcohol consumption during pregnancy.

Tobacco use: Tobacco use, including cigarette smoking and vaping, during pregnancy increases the rates of preterm birth, SIDS, miscarriage/stillbirth, decreased placental blood flow, and childhood health problems, including alterations of the infant's immune system and respiratory problems.²⁷

Drug use: Recreational drug use during pregnancy has significant deleterious effects on the fetus, including doubling the risk of stillbirth. Drug use during pregnancy can also result in newborns who are dependent upon these substances at birth. A national survey conducted in 2012 indicated that 5.9% of pregnant women use illicit drugs, resulting in more than 380,000 offspring exposed to illicit substances in utero.²⁸ The most commonly used illicit substance during pregnancy is marijuana, followed by opioids and cocaine.^29,30 Cannabis, opioid, and cocaine use have all been associated with low birth weight, premature birth, and fetal mortality.^31-33 Furthermore, neonates exposed to opioids are at risk for neonatal abstinence syndrome, which induces withdrawal symptoms after parturition.³⁴

Conditions of Pregnancy

During pregnancy certain conditions may increase the likelihood of serious complications and adverse pregnancy outcomes.^19-21

Plural Gestations

Pregnancy with twins or more fetuses increases the risk of preterm birth, low birth weight, and cesarean section, and the babies are more likely to spend time in the neonatal intensive care unit after birth. Due to increased weight gain (it is suggested that women carrying twins gain 35 to 45 pounds and those carrying triplets generally gain 50 to 60 pounds), patient positioning in the dental chair may be difficult and patients may experience more discomfort earlier in pregnancy than individuals with a singleton gestation.

Gestational Diabetes

Gestational diabetes develops during pregnancy and is usually screened for as a routine part of prenatal care. Development of gestational diabetes during pregnancy increases a woman's risk for developing type 2 diabetes mellitus later in life and also increases risk for gestational hypertension and preterm labor. Individuals who are diagnosed with gestational diabetes may require medication, diet counseling, and monitoring of their blood glucose levels throughout pregnancy and in the postnatal period.

Pre-eclampsia and Eclampsia

Pre-eclampsia is a sudden increase in a pregnant woman's blood pressure after 20 weeks' gestation. This hypertensive state can damage maternal organs, including kidneys, liver, and brain. In severe disease, hemolysis, thrombocytopenia, liver dysfunction, kidney dysfunction, peripheral edema, pulmonary edema, and visual disturbances may be seen. If left untreated, pre-eclampsia may result in seizures and is then labeled eclampsia. Risk factors for development of pre-eclampsia include primiparous individuals (first pregnancy); a history of pre-eclampsia in a previous pregnancy; pre-pregnancy health conditions such as hypertension, diabetes mellitus, kidney disease, or systemic lupus erythematosus; age ≥35 years; plural gestations; and obesity.³⁵

Fetal Conditions

Many genetic and/or congenital fetal conditions can be identified in utero and may indicate that a pregnancy is designated high risk. These may include genetic abnormalities, fetal malformations, Rhesus blood group incompatibility, growth restriction, placental positioning, and/or placental insufficiency/abruption.^19-21

Oral Health Needs and Oral Care in the Dental Office

Dental professionals should be aware of common pregnancy complications and symptoms that may affect the overall health of or delivery of dental care to pregnant women. Common pregnancy complications include: dyspnea (seen in 60% to 70% of pregnant patients, usually later in pregnancy), nausea and vomiting (experienced by approximately 66% of pregnant women, usually in the first and early second trimester), and gastroesophageal reflux/heartburn (reported by 30% to 70% of pregnant women and related to progesterone-induced delayed gastric emptying and pyloric sphincter laxity).³⁶

In addition to these relatively mild pregnancy complications, a significant number of pregnant women experience more severe problems, including: gestational diabetes, which affects up to 45% of pregnant women, who may require pre-procedural blood glucose monitoring³⁷; decubitus hypertension or "vena cava syndrome" (seen in approximately 8%), which can cause sudden blood pressure drops and syncope when a pregnant patient is in a horizontal position³⁷; and pre-eclampsia, which occurs in an estimated 3% to 10% of pregnancies and can be fatal for both mother and fetus.³⁸

A dental practice should be able to provide patient counseling regarding mitigation of the potential oral side effects of these symptoms. The office also should be flexible to adjust the time of day and duration of pregnant patients' dental appointments as well as be sensitive to patients wanting to alter their position within the dental chair.

Performing a thorough review of medical history to identify risk factors and an assessment of blood pressure at each dental appointment will allow the dental health professional to serve as an additional screening site for the aforementioned more serious pregnancy complications. Patients with significant risk factors, such as diabetes, chronic hypertension, renal disease, plural gestation, obesity, and advanced maternal age, who also present with a repeated elevated blood pressure above 140/90 mmHg should be referred for further prenatal evaluation as quickly as feasible. Monitoring of these individuals and daily use of 81 mg aspirin has been demonstrated to reduce the risk of development of life-threatening pre-eclampsia during pregnancy.³⁹

The alterations in hormone levels that occur in pregnancy have widespread effects, including in the oral cavity. Patients with pregnancy complications can be expected to experience similar oral changes and symptoms, including pregnancy gingivitis, pregnancy epulis, gingival hyperplasia, pyogenic granuloma, acid erosion/tooth wear, salivary alterations, and increased caries risk.² In patients for whom significant active dental intervention may prove problematic, preventive dental care and identification and reduction of risk factors such as food cravings, excessive added sugars, or inflammation may allow for a reduction in the need for more significant interventions throughout the perinatal period.³⁶ Coordination with the perinatal team to identify the ideal dental treatment scenario and appropriate prescription of medication will allow for bidirectional communication regarding the oral and overall health of the pregnant patient.⁴

A summary of medications that may be used during pregnancy is presented in Table 2.^40-42 (Table 2, Common Drugs Used in a Dental Setting and Their Indications for Use During Pregnancy, may be viewed online at compendiumce.com/go/2010.) In general, acetaminophen should be considered the first-line analgesic for use in pregnancy, and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided. Furthermore, while many antibiotics (eg, amoxicillin, metronidazole, erythromycin, penicillin V, cephalosporins, and clindamycin) are generally considered to be safe during pregnancy, clinicians should undertake judicious prescribing patterns and weigh the risks to benefits in each clinical scenario.^40-42

Pregnancy is a unique period with various physiologic changes that support the formation and maturation of the fetus. It is the current recommendation of the American College of Obstetricians and Gynecologists that all pregnant patients should receive emergent and routine dental care throughout pregnancy.²² A failure in treating developing oral problems could have both maternal and fetal health effects. Furthermore, dentists are in a position to co-manage patients with perinatal healthcare providers and serve as an additional screening opportunity for some of the most serious pregnancy complications. Thus, it is critical that dental professionals gain a basic understanding of the underlying physiological changes of pregnancy, including potential adverse symptoms and complications, and how these may affect oral health and the delivery of dental care. This understanding will aid in the development of a comprehensive, interdisciplinary treatment plan and the delivery of the necessary medical, nutritional, and oral healthcare, and provide tools for relevant and appropriate counseling.

Summary

While the overwhelming number of pregnancies in the United States are relatively uncomplicated, some women do experience health problems during pregnancy that may alter oral health and the provision of oral healthcare in a dental office. These complications range in severity from mild to serious and can involve the mother's health, the fetus's health, or both. The dental team should be aware of the possible pregnancy complications and their potential effects on oral health. Open communication with perinatal healthcare providers, including referral for early and regular prenatal care, can help decrease the risk of pregnancy complications, better manage potential oral health needs, and improve pregnancy outcomes for both mother and fetus.

About the Authors

Maria L. Geisinger, DDS, MS
Professor, Director, Advanced Education Program in Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, Alabama

David C. Alexander, BDS, MSc, DDPH
Adjunct Professor, Epidemiology and Health Promotion, New York University College of Dentistry, New York, New York; Principal, Appolonia Global Health Sciences LLC, Green Brook, New Jersey

Irina F. Dragan, DDS, DMD, MS
Assistant Professor, Director, Faculty Education and Instructional Development, Department of Periodontology, Tufts University School of Dental Medicine, Boston, Massachussetts

Queries to the author regarding this course may be submitted to authorqueries@aegiscomm.com.

References

1. Oral Health Care During Pregnancy Expert Workgroup. 2012. Oral Health Care During Pregnancy: A National Consensus Statement.Washington, DC: National Maternal and Child Oral Health Resource Center.

2. Dragan IF, Veglia V, Geisinger ML, Alexander DC. Dental care as a safe and essential part of a healthy pregnancy. Compend Contin Educ Dent. 2018;39(2):86-91.

3. Geisinger ML, Dragan IF, Alexander DC. Healthy pregnancy: a patient-centered approach to counseling and behavioral change. Compend Contin Educ Dent.2018;39(5):286-290.

4. Alexander DC, Geisinger ML, Shenoy S, Dragan IF. Collaborating with the perinatal team for optimal oral health before, during, and after a healthy pregnancy. Compend Contin Educ Dent. 2018;39(10):678-684.

5. Geisinger ML, Alexander DC, Dragan IF, Mitchell SC. Dental team's role in maternal and child oral health during and after pregnancy. Compend Contin Educ Dent.2019;40(2):90-96.

6. World Health Organization. Preterm birth. WHO website. 2018. https://www.who.int/news-room/fact-sheets/detail/preterm-birth. Accessed March 16, 2020.

7. Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388
(10063):3027-3035.

8. US Dept of Health and Human Services. What are the risk factors for preterm labor and birth? National Institutes of Health website. https://www.nichd.nih.gov/health/topics/preterm/conditioninfo/who_risk. Accessed March 13, 2020.

9. Thomson Reuters. The Cost of Prematurity and Complicated Deliveries to U.S. Employers. Report prepared for the March of Dimes. October 29, 2008. http://www.marchofdimes.com/peristats/pdfdocs/cts/ThomsonAnalysis2008_SummaryDocument_final121208.pdf. Accessed March 13, 2020.

10. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet.2008; 371(9606):75-84.

11. Madianos PN, Bobetsis YA, Offenbacher S. Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms. J Clin Periodontol. 2013;40(suppl 14):S170-S180.

12. 2019 March of Dimes Report Card. March of Dimes website. https:/www.marchofdimes.org/mission/reportcard.aspx. Accessed March 16,2020.

13. Carter JD, Mulder RT, Bartram AF, Darlow BA. Infants in a neonatal intensive care unit: parental response. Arch Dis Child Fetal Neonatal Ed.2005;90(2):F109-F113.

14. Fighting premature birth: the prematurity campaign. The emotional toll. March of Dimes website. https://www.marchofdimes.org/mission/the-emotional-toll.aspx. Accessed March 13, 2020.

15. Misund AR, Nerdrum P, Diseth TH. Mental health in women experiencing preterm birth. BMC Pregnancy Childbirth. 2014;14:263-270.

16. Lakshamanan A, Agni M, Lieu T, et al. The impact of preterm birth <37 weeks on parents and families: a cross-sectional study in the 2 years after discharge from the neonatal intensive care unit. Health Qual Life Outcomes. 2017;15(1):38-50.

17. Haram K, Mortensen JH, Wollen AL. Preterm delivery: an overview. Acta Obstet Gynecol Scand. 2003;82(8):687-704.

18. Martin JA, Hamilton BE, Osterman MJK, et al. Births: Final Data for 2016. National Vital Statistics Reports. 2018;67(1):1-55. Centers for Disease Control and Prevention website. https://www.cdc.gov/nchs/data/nvsr/nvsr67/nvsr67_01.pdf. Accessed March 13, 2020.

19. US Dept of Health and Human Services. What are some common complications of pregnancy? National Institutes of Health website. https://www.nichd.nih.gov/health/topics/pregnancy/conditioninfo/complications. Accessed March 13, 2020.

20. US Dept of Health and Human Services. Pregnancy complications. Office on Women's Health website. https://www.womenshealth.gov/pregnancy/youre-pregnant-now-what/pregnancy-complications. Accessed March 13, 2020.

21. Overview of pregnancy complications. BMJ Best Practice website. Updated September 18, 2018. https://bestpractice.bmj.com/topics/en-gb/494/pdf/494.pdf. Accessed March 13, 2020.

22. ACOG Committee Opinion No. 743: Low-dose aspirin use during pregnancy. Obstet Gynecol. 2018;132(1):e44-e52.

23. Ponticelli C, Moroni G. Fetal toxicity of immunosuppressive drugs in pregnancy. J Clin Med. 2018;7(12):E552.

24. Goldberg EM, Aliani M. Metabolomics and fetal alcohol spectrum disorder. Biochem Cell Biol.2018;96(2):198-203.

25. Sokol RJ, Delaney-Black V, Nordstrom B. Fetal alcohol spectrum disorder JAMA.2003;290(22):2996-2999.

26. Popova S, Lange S, Probst C, et al. Global prevalence of alcohol use and binge drinking during pregnancy, and fetal alcohol spectrum disorder. Biochem Cell Biol. 2018;96(2):237-240.

27. Centers for Disease Control and Prevention. Tips from Former Smokers: Smoking, Pregnancy, and Babies. CDC website. March 2020. https://www.cdc.gov/tobacco/campaign/tips/diseases/pregnancy.html. Accessed March 16, 2020.

28. US Dept of Health and Human Services. Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality. National Survey on Drug Use and Health, 2012. Ann Arbor, MI: Inter-university Consortium for Political and Social Research [distributor]. 2015-11-23. https://doi.org/10.3886/ICPSR34933.v3. Accessed March 16, 2020.

29. Desai RJ, Hernandez-Diaz S, Bateman BT, Huybrechts KF. Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstet Gynecol. 2014;123(5):997-1002.

30. Ebrahim SH, Gfroerer J. Pregnancy-related substance use in the United States during 1996-1998. Obstet Gynecol. 2003;101(2):374-379.

31. Jaques SC, Kingsbury A, Henshcke P, et al. Cannabis, the pregnant woman and her child: weeding out the myths. J Perinatol. 2014;34(6):417-424.

32. Addis A, Moretti ME, Ahmed Syed F, et al. Fetal effects of cocaine: an updated meta-analysis. Reprod Toxicol. 2001;15(4):341-369.

33. Minozzi S, Amato L, Bellisario C, et al. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst Rev. 2013;(12):CD006318.

34. Patrick SW, Schumacher RE, Benneyworth BD, et al. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. JAMA.2012;307(18):1934-1940.

35. Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013;209(6):544.e1-544.e12.

36. Hamalatha VT, Manigandam T, Sarumathi T, et al Dental considerations in pregnancy-a critical review on the oral care. J Clin Diagn Res. 2013;7(5):948-953.

37. Silk H, Douglass AB, Douglass JM, Silk L. Oral health during pregnancy. Am Fam Physician. 2008;77(8):1139-1144.

38. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol.2009;33(3):130-137.

39. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for preeclampsia: US Preventive Services Task Force Recommendation Statement. JAMA.2017;317(16):1661-1667.

40. FDA/CDER SBIA Chronicles. Drugs in Pregnancy and Lactation: Improved Benefit-Risk Information. Silver Spring, MD: CDER Small Business and Industry Assistance (SBIA) Division of Drug Information, Office of Communications; January 22, 2015. https://www.fda.gov/files/drugs/published/%22Drugs-in-Pregnancy-and-Lactation--Improved-Benefit-Risk-Information%22-January-22--2015-Issue.pdf. Accessed March 16, 2020.

41. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 4th ed. Baltimore, MD: William and Wilkins; 1994.

42. Hass DA, Pynn BR, Sands TD. Drug use for the pregnant or lactating patient. Gen Dent. 2000;48(1):54-60.