Gastrointestinal Agent (Antisecretory)
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Although the toxicity of aluminum has been well documented, there is no evidence that normal doses of aluminum-containing medications, such as sucralfate, present a risk to the fetuses of pregnant women with normal renal function. A study showing an association between in utero exposure to gastric acid-suppressing drugs and childhood allergy and asthma requires confirmation. Oral absorption of aluminum is poor, with only an average of 12% retained in one study of six normal subjects ingesting 1–3 g/day of aluminum (1). Moreover, no evidence has been found to suggest that aluminum is actively absorbed from the gastrointestinal tract (1). Because of these characteristics and the lack of reports of adverse fetal effects in humans or animals attributable to sucralfate, the risk to the fetus is probably nil. A 1985 review on the use of gastrointestinal drugs during pregnancy and lactation by the American College of Gastroenterology classified sucralfate as an agent whose potential benefits outweighed any potential risks (2).
FETAL RISK SUMMARY
Sucralfate is an aluminum salt of a sulfated disaccharide that inhibits pepsin activity and protects against ulceration. The drug is a highly polar anion when solubilized in strong acid solutions, which probably accounts for its poor gastrointestinal absorption. Its ulcer protectant and healing effects are exerted through local, rather than systemic, action (3). The small amounts that are absorbed, up to 2.2% of a dose in one study using healthy males (4), are excreted in the urine (3,4).
In mice, rats, and rabbits, sucralfate had no effect on fertility and was not teratogenic with doses up to 50 times those used in humans (3). Sucralfate is a source of bioavailable aluminum (1,5). Each 1-g tablet of sucralfate contains 207 mg of aluminum (1). The potential fetal toxicity of this drug relates to its aluminum content.
When administered parenterally to pregnant animals, aluminum accumulated in the fetus, causing an increased perinatal mortality and impaired learning and memory (6,7). Teratogenic effects, however, were not observed (7). Prolonged exposure to the metal has caused neurobehavioral and skeletal toxicity (8). A 1985 review of aluminum described these toxic effects on the brain and bone tissue as dialysis encephalopathy in patients with renal failure and a unique form of osteodystrophy in uremic patients (1). Aluminum received from IV fluids may also be related to osteopenia in premature infants (9). A 1991 report described the results of a study of 88 pregnancies in women exposed to high amounts of aluminum sulfate that had been accidentally added to the city’s water supply (10). Except for an increased rate of talipes (clubfoot) (four cases, one control; p = 0.01), there was no evidence that the exposure was harmful to the fetuses. Several theoretical explanations for the four cases of clubfoot were offered by the investigators, including the possibility that the observed incidence occurred by chance (10).
In patients with end-stage chronic renal failure, the use of sucralfate to bind phosphate resulted in serum aluminum levels comparable to those obtained from the antacid aluminum hydroxide (5). Administration of sucralfate to normal subjects did not increase plasma aluminum concentrations, but evidence of tissue aluminum loading was found in experiments with animals (1).
Analysis of 97 amniotic fluid samples, mostly from women undergoing amniocentesis for advanced maternal age, found a mean aluminum concentration of 93.4 mcg/L (range 37–149 mcg/L) (11). The authors of this study did not mention whether the women were consuming aluminum-containing medications, and the measured levels are apparently the normal baseline for the patient population studied.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 183 newborns had been exposed to sucralfate during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of five (2.7%) major birth defects were observed (eight expected). Specific data were available for six defect categories, including (observed/expected) 1/2 cardiovascular defects, 1/0 oral clefts, 0/0 spina bifida, 1/0.5 polydactyly, 0/0.5 limb reduction defects, and 1/0.5 hypospadias. These data do not support an association between the drug and congenital defects.
A population-based observational cohort study formed by linking data from three Swedish national healthcare registers over a 10-year period (1995–2004) was reported in 2009 (12). The main outcome measures were a diagnosis of allergic disease or a prescription for asthma or allergy medications. The drug types included in the study were gastric acid suppressors, including H2-receptor antagonists, prostaglandins, proton pump inhibitors, combinations for eradication of Helicobacter pylori, and drugs for peptic ulcer and gastroesophageal reflux disease, such as sucralfate. Of 585,716 children, 29,490 (5.0%) met the diagnosis and 5645 (1%) had been exposed to gastric acid suppression therapy in pregnancy. Of these children, 405 (0.07%) were treated for allergic disease. For developing allergy, the odds ratio (OR) was 1.43 and the 98% confidence interval (CI) was 1.29–1.59, irrespective of the drug, time of exposure during pregnancy, and maternal history of allergy. For developing childhood asthma, but not other allergic diseases, the OR was 1.51 and the 95% CI was 1.35–1.69, irrespective of the type of acid-suppressive drug and the time of exposure in pregnancy. The authors proposed three possible mechanisms for their findings: (a) exposure to increased amounts of allergens could cause sensitization to digestion labile antigens in the fetus; (b) maternal Th2 cytokine pattern could promote an allergy-prone phenotype in the fetus; and (c) maternal allergen-specific immunoglobulin E could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Several limitations of the study that might have affected their findings were identified, including a general increase in childhood asthma but not necessarily an increase in allergic asthma (12). The study requires confirmation.
BREASTFEEDING SUMMARY
Minimal, if any, excretion of sucralfate into milk should be expected because only small amounts of this drug are absorbed systemically.
References
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2.Lewis JH, Weingold AB. The use of gastrointestinal drugs during pregnancy and lactation. Am J Gastroenterol 1985;80:912–23.
3.Product information. Carafate. Hoechst Marion Roussel, 2000.
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12.Dehlink E, Yen E, Leichtner AM, Hait EJ, Fiebiger E. First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: a population-based register study. Clin Exp Allergy 2009;39:246–53.