Nitrofurantoin monohydrate (Macrobid or Macrodantin) is an antibiotic frequently prescribed to treat and prevent urinary tract infections (UTIs). UTIs are common during pregnancy, making the safety profile of this medication a frequent concern. Nitrofurantoin is an effective tool for managing these infections, which, if left untreated, can lead to serious complications like pyelonephritis, preterm labor, and low birth weight. Its safety is highly dependent on the stage of gestation, with specific concerns arising at the beginning and end of the pregnancy term.
Safety Across Pregnancy Trimesters
The safety of nitrofurantoin is largely divided by the three trimesters of pregnancy. Historically, findings regarding its use during the first trimester, the critical period of organ development (organogenesis), have been mixed. Some studies suggested a slight association with certain congenital anomalies, such as clefts or specific heart defects. However, many large studies have found no increased risk of major malformations overall when the drug is used early in pregnancy.
The second trimester is the window when nitrofurantoin is most universally considered safe and is often a first-line treatment choice for UTIs. By this stage, the fetus’s major organs are fully formed, minimizing the risk of birth defects from drug exposure. Guidelines recommend its use for treating active infections and for prophylaxis against recurrent UTIs.
Use becomes restricted again during the third trimester, specifically as the pregnancy approaches term. Clinical guidelines strongly advise against using nitrofurantoin after 38 weeks of gestation, during labor, or when delivery is imminent. This restriction is due to a concern for a specific, transient blood disorder in the newborn, not a risk of birth defects.
Potential Risks and Side Effects
The primary concern dictating avoidance late in pregnancy is the risk of neonatal hemolytic anemia. This condition involves the premature breakdown of the newborn’s red blood cells, which can lead to jaundice and other complications. The risk stems from the fact that the newborn’s red blood cell enzyme systems, particularly glutathione, are often immature near term.
Nitrofurantoin is an oxidant drug; in a newborn with immature enzyme systems, this can cause oxidative stress and lead to hemolysis. The risk is significantly heightened if the baby has glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic disorder that reduces the red blood cell’s ability to handle oxidative stress. Avoiding the drug near delivery is a cautious measure because the baby’s G6PD status is often unknown before birth.
Maternal side effects are generally mild and include common gastrointestinal issues such as nausea, vomiting, or diarrhea. Very rare, serious side effects can include idiosyncratic reactions like pulmonary toxicity or liver damage. These reactions warrant immediate medical attention if symptoms like persistent cough, chest pain, or jaundice develop.
Clinical Guidelines for Use
Medical professionals use a time-sensitive approach when prescribing nitrofurantoin during pregnancy. It is frequently indicated as a first-line therapy for uncomplicated lower UTIs and asymptomatic bacteriuria, especially during the second trimester. The drug is highly effective because it concentrates well in the urine, targeting the infection site directly.
Standard treatment usually involves a dosage of 100 milligrams taken twice daily for a short course, typically 5 to 7 days. For women with recurrent UTIs, a lower daily dose of 100 milligrams can be prescribed for suppressive therapy throughout the remainder of the pregnancy. The American College of Obstetricians and Gynecologists (ACOG) considers its use appropriate in the second and third trimesters, and in the first trimester if no other suitable options are available.
A follow-up urine culture, known as a “test of cure,” is important to confirm the infection has been eradicated. This monitoring ensures the infection does not return or ascend to the kidneys, which poses a greater risk to the pregnancy. Although its historical classification was FDA Pregnancy Category B, current guidance remains highly protective regarding use near term.
Alternative Treatments for UTIs
When nitrofurantoin is not suitable—such as in the late third trimester, for patients with known G6PD deficiency, or if the bacteria is resistant—alternative antibiotics are available. Cephalosporins, such as cephalexin, are a common and effective first-line alternative used throughout all trimesters of pregnancy. This class of drugs has a well-established safety profile for both mother and fetus.
Fosfomycin is another alternative, often valued for its single-dose regimen, which can improve patient adherence. Other options include amoxicillin-clavulanate, selected based on the specific susceptibility profile of the bacteria. The selection of an alternative antibiotic is always guided by laboratory culture results to ensure the most effective medication is used.