임신과 관련된 위장관 질환

내 과 정 성 훈

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

Category A 인체를 대상으로 한 연구에서 임신 초기 태아에 대해 위험을 증명할 수 없는 경우 ( 임신 말기에도 위험의 증거가 없는 경우 ) 로서 태아에 해를 주는 것과 거리가 먼 경우

Category B 동물실험에서 태아에 대한 위험이 나타나지 않았거나 , 인체를 대상으로 확실하게 증명되지 않은 경우 . 동물실험에서 유해한 영향을 나타냈으나 , 임신 초기의 여성에서 증명이 안된 경우 ( 임신 말기 위험의 증거는 없음 )

Category C 동물실험에서 태아에 대한 유해한 영향 ( 기형 , 태아사망 등 ) 을 나타냈으나 인체에 대한 실험결과가 없는 약물 , 또는 인체나 동물에 있어서의 연구가 아직 없는 약물 ( 태아에 대한 위험성보다 엄마 몸에 대한 유익성이 클 경우에만 사용 )

Category D 태아에 대한 위험이 증명되었으나 산모에 사용함으로써 얻는 이익이 태아에 대한 위험보다 큰 경우 ( 임부의 생명이 위급한 경우나 다른 약물로 효과가 없는 경우에만 부득이하게 사용 )

Category X 인체와 동물 모두에서 태아의 기형이 증명된 약물 ( 임산부 , 가임 여성에게 금기 )

Contents

Diagnostic tools GI motility disorders

Nausea and vomiting Hyperemesis gravidarum Constipation Diarrhea GERD

Peptic ulcer disease Inflammatory bowel disease

Diagnostic Testing in Preg-nancy Radiologic and related studies

• Cell death• Teratogenic effects• Carcinogenesis• Genetic effects

• Missed diagnosis• Unnecessary elective abortion

Fetal risk of anomalies, growth re-striction, or abortion is not increased with radiation exposure of less than 5 Rad(50mGy).

Estimated Conceptus Dose

US / MRI better alternatives

Radioactive iodine contraindicated during pregnancy

MRI should be avoided in the 1st trimester

X-Ray/CT US/MRI

Gastrointestinal Endoscopy

Risk of Endoscopy to the Fetus

Risk Precipitating factor

Hypoxia Oversedation

Hypoperfusion Maternal positioning, arrhythmia, epinephrine use, maternal status

Teratogenensis Medication, radiation exposure

Uterine trauma Endoscopic trauma, abdominal compression techniques

Premature labor Uterine trauma, uterine compression

Risk of Endoscopy to the Mother

Risk Precipitating factor

Aspiration Abdominal distension

Hypotension IVC compression, anemia

Delayed diagnosis and treatment

Reluctance to employ tests and proce-dures, concern regarding administra-tion of medications, difficulty examin-ing abdomen, atypical presentation

Bowel and uterine trauma Distorted anatomy resulting from gravid uterus

Indications for Upper Endoscopy in Pregnancy

Indication

Significant or unremitting gastointestinal bleeding

Dysphagia or odynophagia

Severe or refractory abdominal pain

Severe or refractory nausea and vomiting

Feeding tube placement

Contraindication to Endoscopic Procedures

Obstetric condition

Imminent delivery

Abruptio placenta

Eclampsia

Summary of Recommendations for the Performance of Endoscopy in Breast-feeding Patients

Recommendation Grade

Breast Feeding may be continued after maternal fentanyl administration

B

Breast Feeding should be withheld for 4 h after midazo-lam administration

B

Continued breast feeding after propofol administration is not recommended, although it is unknown for how long it should be withheld

C

Penicillins, cephalosporins, and erythromycin are compat-ible with breast feeding; avoid quinolones and sulfon-amides

C

Grade B, observational studies; Grade C, expert opinion

Drugs used during En-doscopy

Medication FDA Category

Meperidine B

Fentanyl C

Diazepam D

Midazolam D

Propofol B

Scopolamine(Anticholinergic) C

Lidocaine B

Naloxone B

Flumazenil C

Medications for Endoscopy: Recommendations

Use smallest effective dosages

Involve patients in decisions about potentially fetotoxic drugs

When alternative drugs available, use safest one

Avoid category D drugs

Do not use category X drugs

Avoid optional drugs

Contact pharmacologist or review literature about drug teratogenicity

Consider involvement of anesthesiologist for sedatives

General Endoscopy: Recommendations

Gasatrointestinal Motility Disoders

Nausea and vomiting

Hyperemesis gravidarum

Constipation

Diarrhea

GERD

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

Hyperemesis gravidarum

Severe, debilitating condition characterized by vomit-ing 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

Treatment Supportive therapy Ingestion of multiple small-portion meals

high in carbohydrate and low in fats Antiemetics; backbone Vitamin B6; good alternative psychotherapy

NVP

Nonphamaco-logic

Phamacologic

Dietary change - small, frequent meal - Avoid fatty, spicy, odorous foodsLifestyle modifica-tion - frequent naps - shorten work day

Complemen-tary & alter-native

Drugs

Ginger p.o.Acupres-sure

Pyridoxine –doxylamine

Add antihistamine (Diphenhydramine or meclizine

Add dopamine antag-onist (metoclo-pramide)

IV fluid with vitamin B12On-dansetron

Methylpred-nisolone

MildModerate to severeHG

persistent

Persistent with dehy-dration

persistentpersistent

Persistent without dehy-dration

+

+

Gastroesophageal Reflux Disease

“ 위 내용물의 비정상적인 식도로의 역류로 인한 증상 혹은 점막손상”

30~50% of pregnant women (up to 80%)

Symptoms worse during 3rd trimester and abate soon after delivery

 Montreal Classification of GERD

Am J Gastroenterol 2006

Pathogenesis

This high incidence may relate to a hypo-tonic LES and GI dysmotility, attributed to gestational hormones(progesterone) gastric compression by the gravid uterus

Treatment

H2 antagonists gener-ally 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 ab-sorbed medications should be tried first.

Peptic Ulcer Dis-ease

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. pylori 에 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 pos-

sibly 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 con-tent 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 famotidine are preferable because nizatidine is possibly toxic to the fetus, and cimetidine has antiandro-genic effects.

Treatment II

PPI were initially reserved for refractory, severe, or compli-cated GERD and PUD during pregnancy.

Lansoprazole, rabeprazole, and pantoprazole (FDA B) ap-pear to be safer than omeprazole (FDA C), and are there-fore recommended during pregnancy.

Metoclopramide is probably not teratogenic, but frequently causes maternal side effects.

Helicobacter pylori eradication should be deferred until af-ter parturition and lactation because of concern about the fetal safety of administered antibiotics such as clar-ithromycin 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 avoid-

ance 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 in-

crease 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 concep-tion and to aggressively treat flares medically in order to prevent complications

Effect of pregnancy on IBD

ZS Heetun et al., Aliment Pharmacol Ther 2007;26:513

• Pregnancy does not appear to increase the severity of, or mor-bidity due to, preexisting IBD

• Disease activity prior to conception seems to be the most im-portant factor determining the cause of the illness during ges-tation.

IBD and Breast-Feeding

Oral 5-ASA products or corticosteroids is gener-ally safe (poorly secreted in milk)

Topical mesalamine is probably safe during

breast-feeding

No data about AZT/6-MP, ciprofloxacin, metron-

idazole

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 nonpreg-nant individuals, namely high-dose glucocorticoids, intra-venous 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-ges-tational-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 differ-ential diagnosis includes obstetric, gynecologic, and gas-trointestinal 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 de-creases in frequency (or becomes inactive) during preg-nancy.

Abdominal ultrasound is the most useful imaging modality to evaluate gastrointestinal conditions during pregnancy.   

Summary II

EGD and flexible sigmoidoscopy can be performed when strongly indicated during pregnancy, for example, for sig-nificant 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 indi-cated 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 in-clude misoprostol, which is an abortifacient (category X), methotrexate (category X), 6-mercaptopurine (category D), azathioprine (category D), most chemotherapeutic agents, and certain antibiotics.

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