Discomforts • Nausea and vomiting • Heartburn • Lifestyle concerns with nutritional implications: • alcohol • caffeine • smoking • Illicit drugs • Non-nutritive sweeteners • physical activity • oral health
Nausea & Vomiting:Cochrane Library, 2003 (new review protocol established in 2009)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: 2003 • 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.”
Stress Associated with N&V • 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 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
Interventions for Heartburn in PregnancyCochrane, 2008 • Up to 80% of women in third trimester • Not well understood – pregnancy hormones influence • Lower esophageal sphincter • Gastric clearance • 3 studies, 286 women • “little information to draw conclusions about the overall effectiveness of interventions to relieve heartburn in pregnancy.”
Staged approach: Lifestyle modification: Smaller meals, no late night eating, elevate head of bed, avoiding foods/mediations causing heartburn Discuss risk/benefits of drug TX (RCTs not done) The management of heartburn in pregnancy (Richter, 2005. Alimentary Pharmacology & Therapeutics)
The management of heartburn in pregnancy (Richter, 2005. Alimentary Pharmacology & Therapeutics)
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
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: • A pregnant woman should not drink alcohol during pregnancy. • A pregnant woman who has already consumed alcohol during her pregnancy should stop in order to minimize further risk. • A woman who is considering becoming pregnant should abstain from alcohol. • 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. • 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
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.”
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)
Coffee and Health: A Review of Recent Human Research (Higdon and Frei; Crit Rev Food Sci and Nutrition, 2006)
Conception • Many studies find > 300 mg/d associated with delay in time to conception (some do not find this effect) • Author’s conclusions: “it may be prudent for women who are having difficulty conceiving to limit caffeine consumption to less than 300 mg/d in addition to eliminating tobacco use and decreasing alcohol consumption.”
Spontaneous Abortion • Conflicting studies • Women who decrease Caffeine due to N&V, more likely to have viable pregnancies. • “Most studies that observed significant associations between self-reported coffee or caffeine consumption and the risk of spontaneous abortion did so at intake levels of at least 300 mg/d of caffeine.”
Fetal Growth • “Several studies found that maternal caffeine intakes ranging from 200-400 mg/d were associated with decreases in mean birth weight of about 100 g.” • “A meta-analysis that combined the results of eight epidemiological studies found that maternal caffeine consumption greater than 150 mg/d increased the risk of low birth weight by approximately 50%.”
Preterm Delivery • “Most epidemiological studies have not found coffee or caffeine consumption to be associated with the risk of preterm delivery.”
Birth Defects • “At present, there is no convincing evidence from epidemiological studies that maternal caffeine consumption ranging from 300-1000 mg/d increases the risk of congenital malformations in humans.”