Clinicians treating a pregnant woman Differentiate symptoms that are normal during pregnancy vs. serious disorders Disorder and Pregnancy Safe evaluation tools Risk of disease against risk of treatment Safely treat without causing adverse effects on mother or fetus
United States FDA Pharmaceutical Pregnancy Categories
Contents Diagnostic tools GI motility disorders Nausea and vomiting Hyperemesisgravidarum Constipation Diarrhea GERD Peptic ulcer disease Inflammatory bowel disease
Diagnostic Testing in Pregnancy Radiologic and related studies
Nausea and vomiting Frequent (70~90%) particularly in 1st trimester Mild to moderate; physiologically statistically normal m/c complaints during the 1st 5 months of pregnancy Symptoms begin by 4~6 weeks, peak in 8~12 weeks and resolve by 3~4 months “morning sickness” Excellent prognosis
Risk factors Younger, obese, women from western cultures Fewer than 12 years of former education Women who experience nausea and vomiting while taking oral contraceptives Corpus luteum in the right ovary Heaviness of placenta Nonsmoker History of nausea in previous pregnancy History of nausea and vomiting in pt’s mother
Hyperemesisgravidarum Severe, debilitating condition characterized by vomiting severe enough to result in weight loss(>5% of body weight), dehydration, hypokalemia, or acidosis Up to 2% Exclusion diagnosis Gastroenteritis Cholecystitis Pyelonephritis Primary hyperparathyroidism Liver dysfunction
Pathogenesis Estrogen and hCG increase during 1st trimester Increased progesterone and reduced motilin levels Gastric dysrhythmia in EGG H. pylori infection
H2 antagonists generally safe, including 1st trimester Ironically, majority of studies of PPI safety involve omeprazole
Constipation I Prevalence 11~38% Symptoms tend to be worse in the 1st and 3rd trimester Progesterone affects small intestine and colon motility and may inhibit motilin release Motilin(stimulatory GI hormone) decrease Enlarging uterus physically affect the small bowel motility
Constipation II Initial treatment Patient education Reassurance Increased physical activity Increased fluid intake Dietary supplementary of fiber (bran or wheat fiber)
Diarrhea When a pregnant woman presents with new-onset diarrhea, a standard evaluation is indicated. If the diarrhea appears to be mild and nonspecific but sufficiently bothersome to warrant treatment, non-systemically absorbed medications should be tried first.
Peptic Ulcer Disease True incidence of PUD during pregnancy is unknown, but very low Only 6 cases in 23000 deliveries (Lancet 1969) Beneficial effect on PUD 혈장의 히스타민 분해효소 증가로 위점막의 히스타민 농도 감소하고 위산 분비 감소 에스트로겐 증가로 위산 분비 억제 프로제스테론 증가로 위점막의 점액 분비 증가 면역학적 내성으로 H. pylori에 대한 면역학적 공격이나 점막손상 감소 EGF 증가로 위십이지장 점막 성장 촉진 임신중 술, 담배, NSAIDS, 스트레스등의 궤양 원인을 피하고 충분한 영양과 휴식 취함
Treatment I Antacids are generally safe for the fetus, magnesium should be avoided near delivery (retard labor and possibly cause neurologic depression in the newborn) sodium bicarbonate should be avoided throughout pregnancy(fluid overload or metabolic alkalosis) Antacids must be administered frequently because of low potency, and frequent administration can cause diarrhea or constipation and electrolyte or mineral abnormalities. Sucralfate has minimal systemic absorption, but its aluminum content is of concern to the fetus in mothers with renal insufficiency. H2 receptor antagonists are useful in treating GERD and PUD when symptoms are more severe or occur later in pregnancy. Ranitidine and famotidineare preferable because nizatidine is possibly toxic to the fetus, and cimetidine has antiandrogenic effects.
Treatment II PPI were initially reserved for refractory, severe, or complicated GERD and PUD during pregnancy. Lansoprazole, rabeprazole, and pantoprazole(FDA B) appear to be safer than omeprazole (FDA C), and are therefore recommended during pregnancy. Metoclopramide is probably not teratogenic, but frequently causes maternal side effects. Helicobacter pylori eradication should be deferred until after parturition and lactation because of concern about the fetal safety of administered antibiotics such as clarithromycin and metronidazole.
Inflammatory Bowel Disease The majority of cases of IBD first present in women younger than age 30 years, the years of peak fertility. IBD may be more common in women than in men; some authors report approximately 30% greater risk Effects on fertility; controversy Pregnancy rates may be spuriously low because of sexual avoidance and voluntary childlessness. Female fertility itself, however, does not appear to be impaired by uncomplicated IBD. UC patients treated with total colectomy and IPAA;three-fold increase in the risk of infertility (pelvic adhesions and fallopian tube scarring) Male fertility is impaired by sulfasalazine treatment, which causes decreased sperm counts that usually return to normal within 6 months of discontinuing the drug.
Effect of IBD on pregnancy Inactive IBD; minimal effects on the course and outcome of pregnancy Risk appear to be related to the disease activity rather than to the medication Active, nonfulminant UC combined abortion/stillbirth rate 18~40%, Fulminant UC necessitating surgery ~60% Severe CD necessitating surgery maternal fetal mortality rates ~60% There is every reason to strive for remission before conception and to aggressively treat flares medically in order to prevent complications
Pregnancy does not appear to increase the severity of, or morbidity due to, preexisting IBD
Disease activity prior to conception seems to be the most important factor determining the cause of the illness during gestation.
ZS Heetun et al., Aliment PharmacolTher 2007;26:513
IBD and Breast-Feeding Oral 5-ASA products or corticosteroids is generally safe (poorly secreted in milk) Topical mesalamine is probably safe during breast-feeding No data about AZT/6-MP, ciprofloxacin, metronidazole MTX and cyclosporine; contraindicated
Treatment Most experts agree that during gestation affected patients should continue optimized prepregnancy therapy to avoid possible flares resulting from medication withdrawal. Treatment of fulminant colitis is the same as in nonpregnantindividuals, namely high-dose glucocorticoids, intravenous antibiotics, cyclosporine, and salvage biological therapies. IBD patients are at risk for poor pregnancy outcomes, even if they have mild or inactive disease. Major complications include premature birth, low-birth-weight and small-for-gestational-age infants, and increased cesarean section rates. The risk of fetal malformations in this setting is unclear.
Summary I The differential diagnosis of gastrointestinal symptoms and signs is particularly extensive during pregnancy. The differential diagnosis includes obstetric, gynecologic, and gastrointestinal disorders related to pregnancy Pregnancy can affect the clinical presentation, frequency, or severity of gastrointestinal diseases. For example, GERD markedly increases in frequency, whereas PUD markedly decreases in frequency (or becomes inactive) during pregnancy. Abdominal ultrasound is the most useful imaging modality to evaluate gastrointestinal conditions during pregnancy.
Summary II EGD and flexible sigmoidoscopycan be performed when strongly indicated during pregnancy, for example, for significant acute upper and lower gastrointestinal bleeding, respectively. Most gastrointestinal drugs appear to be relatively safe to the fetus and can be used with caution when strongly indicated during pregnancy, especially during the second and third trimesters after organogenesis has occurred (FDA category B and C). Gastrointestinal drugs to be avoided during pregnancy include misoprostol, which is an abortifacient (category X), methotrexate (category X), 6-mercaptopurine (category D), azathioprine (category D), most chemotherapeutic agents, and certain antibiotics.