**6. GERD treatment in special populations: Pregnancy**

Pregnancy is considered a likely risk factor in GERD, with approximately 80% of pregnant women, in their third-trimester experiencing what is known as gestational reflux [51, 52]. This increased prevalence of gestational reflux is likely due to decreased LES pressure [51]. Heartburn and nausea may be expected in a healthy pregnancy, but there are concerns over specific agents used in treatment [51]. Treatment for gestational reflux calls for "step-up" therapy, starting with lifestyle modifications or alternative medicines such as acupuncture [51]. If that fails to provide enough relief, the following options would be antacids, sucralfate, or metoclopramide [51]. A step up from these regimens, if deemed ineffective, would be H2RAs, and a step up from that would be PPIs [51]. The American College of Gastroenterology (ACG) GERD guidelines do not have an extensive algorithm for gestational reflux [4]. The guidelines mention that sucralfate does not have a role in non-pregnant GERD patients, and PPIs are safe in pregnant patients if clinically indicated [4].

The FDA classified drugs for pregnancy in categories that help define a drug's potential risk of fetal harm [51]. Category A of the FDA's classification means that there are well-controlled studies in humans, and the drug shows no fetal risk [51]. None of the pharmacological options of therapy for gestational reflux are considered Category A [51]. Category B means that animal studies show no risks, but human studies do now show adequate evidence expressing safety [51]. All H2RA's, sucralfate, metoclopramide, and most PPIs except for omeprazole are Category B [51]. Category C shows that animal studies show risk, but human studies lack the evidence to support safety [51]. Omeprazole and cisapride are considered Category C drugs [51]. As for all of the antacids that are aluminum, calcium, or magnesium-containing, those fall under Category N by the FDA [51]. Category N is defined as no classification [51].

Following the step-up treatment guideline, lifestyle modifications such as eating smaller meals, not eating at night, elevating the head of the bed, and avoiding postural changes and dietary triggers are considered the first line [51]. Next on the step-up is antacids, sucralfate, or metoclopramide which are mostly considered safe with a few exceptions [51]. One exception is magnesium trisilicate which is not recommended long term [51]. Long-term use of magnesium trisilicate has been associated with nephrolithiasis, hypotonia, cardiovascular impairment, and respiratory disease in the fetus [51]. It is also recommended that pregnant women avoid sodium bicarbonate as it can cause fluid overload and metabolic alkalosis [51]. Sucralfate is Category B and is generally regarded as acceptable for use [51]. Metoclopramide is a promotility agent that is part of the step-up therapy for pregnant women. Another promotility agent is cisapride which has shown evidence of being embryotoxic and fetotoxic in animals, and the FDA has removed this drug for causing fatal cardiac arrhythmias [51]. H2RAs are generally safe for pregnancy, except for nizatidine [51]. Nizatidine has been known to cause spontaneous abortion, congenital malformations, low birth weight, and fewer live births have been reported in animal studies [51]. Ranitidine was the only H2RA whose efficacy during pregnancy has been established, but it has recently been removed from the market for having a carcinogenic metabolite NDMA [51]. Next on the step-up therapy is PPIs which are generally safe for use in pregnancy except for omeprazole [51]. Omeprazole is embryotoxic and fetotoxic in animals, and case reports in humans show similar concerns [51].
