Nausea, Lifestyle & Oral Health2007

• Nausea and vomiting• Lifestyle concerns with nutritional

implications:– alcohol– caffeine– smoking– drugs– Non-nutritive sweeteners– oral health– physical activity

Nausea & Vomiting: Cochrane Library, 2003 Quinlan et al, Am Fam Phys, 2003

Background

• 70-85% of women experience nausea with pregnancy

• ~ ½ experience vomiting• 35% of women with employment lose

time from work due to nausea – an average of 62 hours

• Almost 50% of women report that their work efficiency is reduced by n&v

Etiology

• Unknown• Nausea less common in those who

subsequently experience miscarriage• More common in twin pregnancies• Emerging findings: recent studies implicate

helicobacter pylori – H pylori infections more common in women with

n&v– Case reports that eradication of infection with

antibiotics ameliorates symptoms

Hyperemesis Gravidarum

• Severe nausea and vomiting• Affects one in 200 pregnancies• Most common reason for hospitalization in early

pregnancy• Clinical features: Persistent vomiting, dehydration,

ketonuria, electrolyte disturbances, weight loss• 159 per million pregnant women died in England

between 1931-1940 (before IV fluid replacement therapy was available)

• (Charlotte Bronte died of hyperemesis in her fourth month of pregnancy)

Cochrane Conclusions

• B6 “appears to be effective in reducing the severity of nausea.”

• Results of P6 acupressure trends are “equivocal.”

• “No trials of treatment for hyperemesis gravidarum show evidence of benefit.”

Effectiveness and safety of ginger in the treatment of pregnancy-induced

nausea and vomiting (Borelli. Obstet Gynecol. 2005) • Six double-blind RCTs with a total of 675

participants and a prospective observational cohort study (n = 187) met all inclusion criteria

• Four of the 6 RCTs (n = 246) showed superiority of ginger over placebo; the other 2 RCTs (n = 429) indicated that ginger was as effective as the reference drug (vitamin B6) in relieving the severity of nausea and vomiting episodes.

Borelli, cont.

• absence of significant side effects or adverse effects on pregnancy outcomes

• CONCLUSION: Ginger may be an effective treatment for nausea and vomiting in pregnancy. However, more observational studies, with a larger sample size, are needed to confirm the encouraging preliminary data on ginger safety.

Nausea and vomiting of pregnancy: an evidence-based review (Davis, J Perinat Neonatal Nurs. 2004)

• n&v rates less in women taking perinatal multivitamin

• Mild to moderate n&v reduced by P6 acupuncture site pressure wristband (new battery operated electrical nerve stimulator)

• First step is dietary & lifestyle changes

Davis, cont….

• If diet/lifestyle fail to bring relief drug therapy may be indicated.

• Most drugs will not be tested in pregnant women

• Pharmacologic treatments include:– B6 (pyradoxine)– B6 plus doxylamine (an antihistamine)=

Bendectin

American Gastroenterological Association Institute Medial Position Statement on the Use

of Gastrointestinal Medication in Pregnancy (2006)

• Metoclopramide, prochlorperazine, promethazine, trimethobenzamide and ondansetron* are considered low-risk drugs based on studies in pregnant women and can be used for nausea and vomiting and for hyperemesis gravidarum. Granisetron and dolasetron have not been studied in human pregnancies.”

*Reglan, Compazine , Phenergan , Tebamide, Zofran

Letter from Staroselsky et al., Gastroenterology, 2007: Re Bendectin

• AGA guideline missing doxylamine (with or without B6)

• Doxyamine-pyridozine (Bendectin) was approved by FDA for Tx of N&V in pregnancy, but “unfounded” lawsuits claiming risk of congenital malformations forced company to stop production in 1983.

Starokelsky letter, cont.

• Meta-analysis of studies found no differences in birth defects with Bendectin.

• Doxalamin-pyridoxine available in Canada and use associated with lower hospitalization for HG.

• >30 million infants have been exposed without increased malformations.

• “Failure to acknowledge the safety and effectiveness of this drug is against the principals of evidence-based medicine.”

Mahadevan reply, 2007

• “We limited our scope to agents used by physicians practicing in the United States who treat women during pregnancy.”

•Lack of understanding and support from others• Inability to take vitamins or eat healthy• Taking medications perceived as risky• Missing out on the “fun” of being pregnant• Loss of a “normal” pregnancy• Lost work days or quitting work• Putting life “on hold”• Longing to eat and drink normally• Money expended on care and support• Lack of energy, fatigue• Irritability and lack of enjoyment of life• Memory loss or inability to think clearly• Burden of care and time on others• Lack of socialization, isolation

Stress Associated with N&V

cont…

• Inability to prepare for birth and arrival of baby• Inability to care for family and home•Wanting pregnancy over or to end the misery• Others’ perception that hyperemesis is only in her mind• Reluctance of doctors to treat because of cost or liability• Weight loss or inadequate weight gain for gestational age of baby• Sense of inadequacy and failure at being unable to cope or function• Difficulty bonding with infant• Lack of energy and socialization with other children• Lack of excitement about infant’s arrival

Adverse effects of substance use determined by:

• Timing

• Dosage

• Duration

• Number of substances

• Environment (nutrition, health status)

• Individual susceptibility

Effects of substance abuse include:

• Increased health problems, including risk of AIDS

• Compromised nutritional status/weight gain

• Higher rates of OB complications

• Psychosocial/economic/legal problems

• Parenting difficulties

• Higher rates of child abuse/neglect

Alcohol: Background Per capita alcohol consumption has risen

through the second half of this century in the US

70% of individuals between the ages of 20 and 34 consume alcohol

Alcohol consumption peaks in the 20-40 year old group

MMWRDecember 24, 2004 / 53(50);1178-

1181

BRFSS, 2002

MMWRDecember 5, 2002

BRFSS

Alcohol: Background, cont. Women are at disadvantage because less

gastric first pass metabolism due to lower levels of alcohol dehydrogenate in intestinal mucosa

Fetus has no alcohol dehydrogenase activity Alcohol crosses placenta easily by passive

diffusion – fetal levels mimic maternal levels The amniotic fluid acts as a reservoir for

alcohol.

FAS Diagnostic Criteria- Fetal Alcohol Study Group of the Research Society on Alcoholism

• Prenatal and/or postnatal growth retardation (<10th % ca)

• Central nervous system involvement (neurologic abnormality, developmental delay or intellectual impairment)

• Characteristic facial dysmorphology with at least 2 of these 3 signs: Microcephally ( OFC < 3rd %ile) Micoopthalmia and/or short palpevral fissures Poorly developed philtrum, thin upper lip, and or

flattening of the maxillary area

FAS, cont.

Other organ systems often involved. Some with nutritional implications:

Cleft palate Eustachian tube dysfunction Array of cardiac, renal, and skeletal defects that

may require surgical repair

FAE – Fetal Alcohol Effects or PFAE

• Exhibit some components of FAE, but not all

• Most common sign is retarded growth both pre and postnatal

• Can have significant developmental and behavioral components

Fetal Alcohol Spectrum Disorders (FASD)

• Surgeon General’s Advisory (2005)– “FASD is the full spectrum of birth defects caused

by prenatal alcohol exposure.”– “The spectrum may include mild and subtle

changes, such as a slight learning disability and/or physical abnormality, through full-blown Fetal Alcohol Syndrome, which can include severe learning disabilities, growth deficiencies, abnormal facial features, and central nervous system disorders.”

FAS/FAE Incidence

FAS – 1.9 per 1000 births, 25 per 1000 among women who drink heavily

FAE – 3 to 5 per 1000 births, 90 per 1000 among women who drink heavily

FASD is leading cause of mental retardation in the western world

Pathophysiology

• Combination of – Toxic effects of ethanol and it’s derivatives– Nutritional factors– Genetic predisposition

Toxic effects• Both alcohol and derivative acetaldehyde directly

damage developing and mature nervous systems• Impair nucleic acid synthesis• Disrupts protein synthesis• Cell membrane narcosis• High maternal alcohol levels associated with

dehydration, fetal hypoxia and acidosis, placental pathology and dysfunction, and endocrine disturbances.

Nutrition Related Effects of Alcohol

• Poor nutritional status of mother• Reduced placental transfer of zinc and folic

acid associated in animal models• Alcohol impairs absorption, utilization, and

metabolism of nutrients• Poor zinc status has been associated with

adverse effects of alcohol many studies

Surgeon General’s Advisory (2005)

• Science: – Alcohol consumed during pregnancy increases the risk

of alcohol related birth defects, including growth deficiencies, facial abnormalities, central nervous system impairment, behavioral disorders, and impaired intellectual development.

– No amount of alcohol consumption can be considered safe during pregnancy.

– Alcohol can damage a fetus at any stage of pregnancy. Damage can occur in the earliest weeks of pregnancy, even before a woman knows that she is pregnant.

– The cognitive deficits and behavioral problems resulting from prenatal alcohol exposure are lifelong.

– Alcohol-related birth defects are completely preventable

Surgeon General’s Advisory (2005)

Recommendations:1. A pregnant woman should not drink alcohol during

pregnancy. 2. A pregnant woman who has already consumed alcohol

during her pregnancy should stop in order to minimize further risk.

3. A woman who is considering becoming pregnant should abstain from alcohol.

4. Recognizing that nearly half of all births in the United States are unplanned, women of child-bearing age should consult their physician and take steps to reduce the possibility of prenatal alcohol exposure.

5. Health professionals should inquire routinely about alcohol consumption by women of childbearing age, inform them of the risks of alcohol consumption during pregnancy, and advise them not to drink alcoholic beverages during pregnancy.

Caffeine• History:

– Rat based studies with high levels of caffeine found adverse pregnancy outcomes

– Early 1980s US FDA issued advisory about adverse effects of caffeine in pregnancy

– Further research found little association, FDA concludes that no strong evidence, urges moderation

– 1996 IOM review for WIC advised removing excessive caffeine intake from WIC risk criteria

– 1998 - USDA removed as WIC risk criteria

The Effects of Caffeine on Pregnancy Outcome Variables (Hinds et al.

Nutrition Review, 1996)

• Consumption:– In US 70-95% of pregnant women

consume caffeine - average intake is 99-185 mg/day

– 5-30% of pregnant women consume >300 mg/day

– Heavy caffeine intake more likely in women who smoke and those with lower education levels

The Effects of Caffeine on Pregnancy Outcome Variables (Hinds et al.

Nutrition Review, 1996)

• Metabolism– methylxantines cross the placenta to the

fetus where an equilibrium is achieved between maternal and fetal plasma

– half-life of caffeine in pregnancy changes from 5.2 to 18.1 hours in T2 and T3 and returns to non-pg levels a few weeks pp

The Effects of Caffeine on Pregnancy Outcome Variables (Hinds et al.

Nutrition Review, 1996)

• Birthweight:– consistent negative association across

studies between birthweight and caffeine consumption > 300 mg/day.

– This affect appears to be due to IUGR not preterm birth

– Data for intakes between 151 and 300 mg are conflicting

– Few adverse effects at intakes < 150 mg

The Effects of Caffeine on Pregnancy Outcome Variables (Hinds et al.

Nutrition Review, 1996)

• Preterm Labor and Delivery– “Generally, there appears to be no

relationship between caffeine consumption during pregnancy and premature labor and delivery in humans.”

The Effects of Caffeine on Pregnancy Outcome Variables (Hinds et al.

Nutrition Review, 1996)

• Spontaneous Abortions– High caffeine intake prior to and during

pregnancy was associated in several studies. Many studies failed to control for smoking, alcohol intake or parity

– Study results are inconclusive and contradictory

– Further research needed to determine if a true causal relationship exists.

The Effects of Caffeine on Pregnancy Outcome Variables (Hinds et al.

Nutrition Review, 1996)

• Congenital Malformations– Finnish registry of congenital malformation

study found no increased incidence even when women consumed < 6 cups of coffee a day.

– No association is supported by current research

The Effects of Caffeine on Pregnancy Outcome Variables (Hinds et al.

Nutrition Review, 1996

• Clinical applications– Caffeine intake should be limited to

between 150 mg and 300 mg per day– Women in the last trimester and those who

smoke are most susceptible to adverse effects.

Maternal exposure to caffeine and risk of congenital anomalies (Brown,

Epidemiology, 2006)

• Review of 7 (of 25 published) studies that met inclusion criteria

• Conclusion: “There is no evidence to support a teratogenic effect of caffeine in humans. Current epidemiologic evidence is not adequate to assess the possibility of a small change in risk of congenital anomalies resulting from maternal caffeine consumption.”

Maternal Caffeine Consumption and Spontaneous Abortion: Review of

Epidemiologic Evidence (Epidemiology, 2004)

• Most studies find positive association between maternal caffeine intake and sp ab, but causality has not been established

• All studies have limitations: – selection and recall bias– poor exposure measurements– issues related to timing of exposure and fetal

demise• (Lively discussion in other venues: Are women who have

strong coffee aversion due to nausea early in pregnancy more likely to sustain pregnancy? Ann Epi, 2006)

Caffeine Metabolism, Genetics and Perinatal Outcomes (Ann Epidemiol 2005)

• Wide individual variation in caffeine metabolism– Due to variation in CYP1A2 enzyme

activity• “Measuring maternal, fetal and neonatal

caffeine metabolites may allow for a more precise measure of fetal caffeine exposure.”

Coffee and Health: A Review of Recent Human Research (Higdon and Frei; crit

rev food sci and nutrition, 2006

• “Currently available evidence suggests that it may be prudent for pregnancy women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion of impaired fetal growth.”

Smoking

• 25-30% of US women smoke during pregnancy; down from 40% in 1967

• Cochran review found that 30 trials of intensive intervention programs in pregnant women lead to smoking cessation in 6.6-9.2% of women.

Adverse Outcomes of Maternal Smoking

• Cigarette smoking is the single most important factor affecting birthweight in developed countries (DiFranza, Pediatrics, 2004)

– Twice the risk of LBW– Lower birthweight (~200g)

• Perinatal: Moderately increased risk of preterm delivery, perinatal mortality, spontaneous abortion

• Long term: modest reduction in long term growth and intellectual development of fetus.

Nutritional Risks Associated with Smoking

• No breakfast (38% of smokers vs. 18% of non-smokers)

• Lower dietary intakes of fruits and vegetables, protein, zinc, riboflavin, thiamin, iron

Nutritional Risks Associated with Smoking, cont.

• Smoking appears to:– decrease the availability of dietary energy– increase requirement for iron– reduce availability of B12, amino acids,

vitamin C, folate, and zinc

• Lower serum vitamin C, B6, E, folate, beta carotene

Norkus et al. FASEB, 1989 and Ann NY Acad Sci 1987

Smokers Non-Smokers

Cord vit. C (mg/dl) 0.61 1.68

Placental vit. C(mg/dl)

10.1 20.9

Cord vit. E (mg/dl) 0.2 0.3

Maternal plasmacarotene (g dl

19 44

Cord carotene(g dl

7 20

Vitamin C and PROM

• PROM occurs in 8-10 % of all pregnancies

• Vitamin C is required for collagen synthesis

• Maternal plasma and placental vitamin C is lower in women with PROM

Nutritional Risks Associated with Smoking, cont.

• Increased carboxyhemoglobin in smokers blood leads to increased cutoff point for anemia.

• Women who smoke may have lower prepregnancy weights and may have lower pregnancy weight gains.

Annotation: Cigarette Smoking, Nutrition, and Birthweight (Rasmussen & Adams, AJPH, 1997)

• “Smoking and maternal weight gain are independent, additive predictors of birthweight.”

• “It does not appear that encouraging smokers to gain more weight than nonsmokers with a similar BMI will eliminate the negative effects of smoking on birthweight.”

• Women who quit smoking in pregnancy are at increased risk of excessive weight gain.

• Women who smoke are at increased risk of poor dietary intake.

• Therefore….

Annotation: Cigarette Smoking, Nutrition, and Birthweight (Rasmussen & Adams, AJPH, 1997)

“…individualized nutrition counseling is recommended in addition to smoking cessation.”

Illicit Drugs: Nutritional Implications

• Estimates of 10% of US newborns exposed to one or more illicit drugs in utero

• Illicit drug use strongly associated with inadequate weight gain, anemia, poor dietary habits

• Knight et al. (FASEB, 1992) found lower serum ferritin, folate, vitamin C and B12

levels in women when cord blood reflected illicit drugs

Illicit Drugs: Nutritional Implications

• Cocaine:– associated with fewer meals, increased

alcohol and caffeine and fat intake– 32% also classified as eating disordered

• Methadone– diarrhea, constipation, nausea, anorexia,

and dry mouth• Heroin

– altered glucose tolerance - delayed glucose response

Position of the American Dietetic Association: Use of nutritive and nonnutritive sweeteners

(Affirmed 2000, in effect until 2009)

• Toxicity testing during reproduction is required for FDA approval.

• “The safety of acesulfame-K, aspartame, sucralose, and neotame in pregnancy has been determined with rat studies.”

• Saccharin can cross the placenta and may remain in fetal tissues because of slow fetal clearance - It has been suggested that women consider careful use of saccharin during pregnancy.

Position of the American Dietetic Association: Use of nutritive and nonnutritive sweeteners

• Aspartame: issue relates to fetal exposure to aspartic acid, phe, or methanol. – Animal models show no changed fetal exposure to aspartic

acid with aspartame– Maternal bolus of aspartame at the 99th %ile of intake

results in peak plasma phe level in both normal (1.85 mg/dl) and PKU heterozygote subjects (2.67 mg/dl) below levels associated with neurological problems (18 mg/dl)

– Plasma response of methanol and formate are not significant after aspartame load

• “Use of aspartame within FDA guidelines appears safe for pregnant women.”

Exercise

• Benefits:– improved or maintained fitness– reduces anxiety and depression– eases pregnancy discomforts such as

constipation, backache, fatigue and varicose veins

Exercise

• Contraindications– previous experience of preterm labor– ob complications including vaginal

bleeding, incompetent cervix, ruptured membranes, compromised fetal growth

– Hx of medical problems (hypertension, heart disease, etc.) requires health care provider approval

Exercise

• Changes with pregnancy– tolerance for strenuous exercise decreases

as pregnancy progresses• work of breathing increases as enlarging uterus

crowds the diaphragm• oxygen needs increase

– if lying flat on back after the 4th month, risk of compression of vena cava with dizziness and interference with blood flow to the uterus

Exercise

Changes with pregnancy, cont.– may have increased efficiency of heat

dissipation– altered sense of balance with shift in center

of gravity– high hormonal levels associated with lax

connective tissue and increased joint susceptibility

Cochrane: Aerobic Exercise for Women During Pregnancy (2006)• 11 trials involving 472 women• “The trials were not of high methodologic quality.”• Results:

– Regular aerobic exercise during pregnancy appears to improve (or maintain) maternal physical fitness

– Non significant, but concerning increased risk of preterm birth in exercise groups. From 7 trials: Pooled RR 1.82 (95% CI 0.35-9.57).

– Data insufficient to infer important risk or benefits for mother or infant

Continuous, Strenuous, Vigorous Activity Throughout Pregnancy

(Gunderson, Clin Obstet gynecology, 2003)

• Can reduce birth weight & length of gestation

• Additional carbohydrate recommended before activity

• Increased need for B vitamins• Careful screening for nutritional &

herbal supplements• Athletes at higher risk for Fe depletion.

Exercise during pregnancy and the postpartum period. ACOG Committee on Obstetric Practice.

January 2002

“The current Centers for Disease Control and Prevention and American College of Sports Medicine recommendation for exercise, aimed at improving the health and well-being of nonpregnant individuals, suggests that an accumulation of 30 minutes or more of moderate exercise a day should occur on most, if not all, days of the week. In the absence of either medical or obstetric complications, pregnant women also can adopt this recommendation.”

Exercise during pregnancy and the postpartum period. ACOG Committee on Obstetric Practice.

January 2002

• Exercise may be beneficial in primary prevention of GDM

• Avoid– supine position (may result in obstruction

of venous return)– motionless standing– exertion above 6,000 feet altitude

Avoid

• Sports with high potential for trauma: ice hockey, soccer, basketball

• Increased risk of falling: gymnastics, downhill skiing, vigorous racket sports, horseback riding

• Scuba diving (increased risk of decompression sickness)

Postpartum

• Physiological changes persist 4 to 6 weeks postpartum

• Return to vigorous exercise should be gradual

• Return to physical activity may be protective against postpartum depression if exercise is stress relieving- not inducing

Oral Health: Major Concepts (Academy of General Dentistry)

• Increased risk for gingivitis (red,swollen, tender gums that are more likely to bleed) associated with increased estrogen and progesterone

• Frequent consumption of high cho foods may be used to combat nausea

• Cariogenic bacteria may be passed from mother to infant

• Periodontal disease is associated with preterm birth

Pregnancy Gingivitis

• 30-75% of women experience gingival changes such as edema, hyperplasia, redness, and bleeding

• Hormonal changes cause greater reaction to dental plaque

• Women who are plaque and inflammation-free at beginning of pregnancy have only 0.03 chance of gingivitis

Periodontitis• Definition: an infection caused by specific

bacterial plaque that involves loss of bone, fiber, and gum tissue attachment for the tooth.

• Smoking associated with increased prevalence and severity of periodontitis

• Periodontal infections caused by gram-negative pathogens are associated with increase in preterm delivery and/or PROM - one mediating factor is prostaglandin production triggered by bacterial products.

• Women with diabetes are at higher risk

Periodontitis (cont.)

• Pathogens and bacterial products may translocate and inhibit normal clearance of enteric organisms from genitourinary tract.

• Overgrowth of gram negative bacteria and infection can be associated with preterm birth.

Periodontal Health and Birth Outcomes (report on a policy and practice forum held Dec. 2006)

• “There is evidence of an association between periodontal disease and increased risk of preterm birth and low birthweight, especially in economically disadvantaged populations, but potential biases (especially in terms of inconsistent definitions) and the limited number of RCTs prevent clear conclusions.”

• “Currently, there is insufficient evidence to support the provision of treatment during pregnancy for the purpose of reducing adverse birth outcomes.”

Can preterm birth be prevented by periodontal treatment?

• NIDCR funded two large RCT – women assigned to treatment or no treatment – Oral Therapy to Reduce Obstetric Risk

(OPT) – results published in 2006– Maternal Oral Therapy to Reduce Obstetric

Risk (MOTOR) – results due in 2008

OPT: Treatment of Periodontal Disease and the Risk of Preterm Birth

(Michalowicz et al. NEJM, Nov. 2006)

• 823 women with periodontal disease, enrolled between 13-17 weeks gestation, randomized to:– Scaling and root planing before 21 weeks; monthly

polishings– Scaling and root planing after delivery

• Major Outcomes: – no difference in rates of preterm birth or low

birthweight– no adverse outcomes associated with treatment

American Academy of Periodontology Statement Regarding Periodontal

Management of the Pregnant Patient (2004)

• Achieve a high level of oral hygiene prior to becoming pregnant and throughout pregnancy

• Periodonal treatment (eg; scaling and root planing) is usually scheduled in second trimester

• Emergencies such as acute infection and abcess may require immediate treatment regardless of stage of pregnancy)

• Consultation with prenatal care provider

Oral Health: Recommendations

• Frequent dental cleanings (3 to 6 months)• Daily oral care routines including brushing

and flossing at least twice daily and after eating

• Use of toothpastes and rinses with fluoride• Consider cariogensis in food choices and

patterns.• Offer smoking cessation programs