best use of medicine in pregnancy

Pregnancy is an incredibly exciting time for many soon-to-be parents. However, there are a few difficult decisions that need to be made during this time, especially when it comes to taking medications. Macrobid, also known as nitrofurantoin, is an antibiotic that is sometimes prescribed for pregnant women, particularly for urinary tract infections (UTIs). In this blog post, I will discuss my personal experience with taking Macrobid during pregnancy. I will explain what this medication is, the potential risks and benefits of taking it while pregnant, and the potential side effects. I will also offer advice to other pregnant women considering taking this medication.

Literature Review:

U.S.-based case control study using questionnaires.

Case and control mothers were interviewed by telephone in English or Spanish using a computer‐based questionnaire 6 weeks to 24 months after the delivery.

Mothers asked whether they had a UTI at any point from 1 month prior to conception until the end of the third month of pregnancy, and which antibiotic they were prescribed.

• Mothers were read specific antibiotic names to help them remember which ones they had been prescribed. Mothers had to remember the timing and duration at that point but not the dosage.

No verification by study authors of timeline or accuracy of patient recall.

Mothers who did not know whether they were exposed, or were unsure regarding timing of exposure, were excluded from analysis.

Participation rate was moderate, with 70.5% of case mothers and 67.2% of control mothers.

Total of 150 case exposures to nitrofurantoin.

66 birth defect associations analyzed.

• Anophthalmia or microphthalmos (OR 3) are the two birth defects for which nitrofurantoin is linked to an increased risk. 7; 95% CI, 1. 1-12. 2), hypoplastic left heart syndrome (OR 4. 2; 95% CI, 1. 9-9. 1), atrial septal defects (OR 1. 9; 95% CI, 1. 1-3. 4), and cleft lip with cleft palate (OR 2. 1; 95% CI, 1. 2-3. 9).
• Penicillins (intercalary limb deficiency) and cephalosporins (atrial septal defects) have also been linked to an increased risk of birth defects; however, tetracycline use has not been linked to an increased rate of birth defects. Tetracyclines were designated as category D-positive evidence of fetal risk in humans.

Take Home Point: This study was flawed by irreconcilable recall bias, included a relatively small number of total nitrofurantoin case exposures. It lacks face validity, given that tetracyclines (a known teratogen) seemed to be associated with less adverse events than penicillins or cephalosporins.

U.S.-based case control study using questionnaires.

Case and control mothers were interviewed by telephone in English or Spanish using a computer‐based questionnaire 6 weeks to 24 months after the delivery.

Mothers asked whether they had a UTI at any point from 3 months prior to conception until delivery, and which antibiotic they were prescribed.

No verification by study authors of timeline or accuracy of patient recall.

Low participation rate, with 67% of case mothers and 64% of control mothers.

Total of 60 case exposures to nitrofurantoin.

22 birth defect associations analyzed.

• No discernible increase in risk, with the exception of 1: a higher risk of oral clefts (OR 1). 97; 95% CI, 1. 10-3. 53), which occurred in 37 patients.

No increased risk was noted among 21 other categories, including the oral cleft subsets of cleft palate and cleft lip—only when these subsets were combined did the result meet statistical significance.

The authors noted that individual birth defects are rare, and absolute risks should drive treatment decisions.

Take Home Point: This was an extremely small study, similarly flawed by recall bias.

Study #1 and Study #2 are both case-control studies, which are generally a useful study design for rare occurrences or when there is a long latency period between exposure and disease manifestation (e. g. However, they are by their very nature subject to biases in observation and selection, as well as being vulnerable to difficult-to-control confounders (other exposures or contributors that may account for the observed birth defects). Patients in these studies, for instance, were unable to recall the specifics of other over-the-counter medications they had taken, which could have been a significant confounder in the case of popular OTC drugs like NSAIDs that have been linked to birth defects. Additionally, despite the fact that patients and controls are frequently matched, it is impossible to tell whether birth defects are linked to the exposure (antibiotic) or the underlying condition (urinary tract infection). Last but not least, case-control studies cannot establish incidence rates or causal links between exposure and outcome (only associations).

Norwegian population-based cohort study.

180,120 total pregnancies were analyzed, including 5,794 nitrofurantoin exposures (1,334 during the first trimester).

• The Norwegian Prescription Database was used to extract data on antibiotic exposure. Any antibiotic that was prescribed was taken by the patient, and this was considered exposure to the antibiotic.

Patients exposed to nitrofurantoin were “sicker”– more likely to smoke during pregnancy and to not take folic acid before and during pregnancy in comparison with unexposed women in the control group.

There was no association with major malformations (OR 0.79; 95% CI 0.55–1.13) or with a cardiovascular malformation (OR 0.95; 95% CI 0.55–1.64) among women who had been dispensed nitrofurantoin during the first trimester compared with unexposed women in the control group.

There was no association between exposure to nitrofurantoin use in the first trimester and the risk for any of the 11 predefined specific malformations.

• None of the 1,334 babies exposed to nitrofurantoin during the first trimester developed an oral cleft.

Take Home Point: In this large population-level study, not only was nitrofurantoin not associated with an increased risk of congenital malformations, not a single exposed patient developed an oral cleft.

Israeli population-based cohort study.

105,492 total pregnancies were analyzed, including 1,319 nitrofurantoin exposures during the first trimester.

• Information on birth defects and nitrofurantoin exposure obtained from four linked databases including HMO records (covering 70% of the district%E2%80%99s population) and the regional hospital (performing 98% of the region%E2%80%99s deliveries)

There was no association between exposure to nitrofurantoin use in the first trimester and the risk for any congenital malformations.

• None of the 1,319 nitrofurantoin-exposed patients developed an oral cleft.

Take Home Point: In yet another large population-level study, nitrofurantoin was again not associated with an increased risk of congenital malformations, and not a single exposed patient developed an oral cleft.

Study #3 and Study #4 are both cohort studies, which are always limited by information available in the records used for review, which may be incomplete or inaccurate. For instance, both studies used self-reports of smoking status as control data (a notoriously under-reported confounder). Cohort studies are susceptible to significant confounding, as well. There is no assurance that the antibiotic prescribed or filled was taken at all or for the full duration recommended in either study.

Observational studies comprise all four of the studies examining the connection between nitrofurantoin and birth defects. These trials are prone to recall bias and uncontrollable confounders, and it is frequently challenging to determine the true incidence of rare diseases. However, there is no strong evidence linking the use of nitrofurantoin in the first trimester to a significant risk of fetal abnormalities.

Why It Matters: Urinary tract infections complicate up to 10% of pregnancies, and untreated and undertreated infections have been associated with low birth weights, preterm labor, and neonatal sepsis (Delzell 2010). While cephalexin (recommended first line in first trimester UTIs by ACOG) is typically effective in the majority of urinary tract infections, growing resistance of some isolates to cephalosporins, as well as gram-positive organisms on which cephalexin has no activity—such as E. faecalis, which represented up to 12% of cultures in one recent investigation (Huttner 2018)—is concerning. Certainly, in patients with recent antibiotic use or in whom testing indicates lack of urinary nitrites (suggestive of an increased likelihood of E. faecalis infection (Larson 1997) (Weisz 2010)), it seems likely that the risk of undertreated infection outweighs the possibility of congenital malformation.

It is advised to review the ACOG committee’s recommendation to withhold nitrofurantoin unless no other treatment options are available. For patients with urinary tract infections in the first trimester of pregnancy, emergency physicians should have a low threshold for prescribing nitrofurantoin, especially if there is a suspicion of cephalosporin-resistant organisms, which includes those who have recently used antibiotics, previously resistant organisms, or nitrite-negative urinalyses. This best practice and the ACOG’s position can be reconciled through shared decision-making and clinical concern documentation.

What are the benefits of taking nitrofurantoin in pregnancy?

Treatment with nitrofurantoin can reduce the unpleasant UTI symptoms as well as some pregnancy complications, such as preterm birth, that are linked to untreated UTI.

Are there any risks of taking nitrofurantoin in pregnancy?

It is unknown whether using nitrofurantoin while pregnant will affect the baby. Nitrofurantoin is frequently recommended as the first-choice antibiotic treatment if a UTI is discovered during pregnancy.

Around the time of delivery, nitrofurantoin is typically avoided as it may result in the baby’s red blood cell levels being lower than normal.

FAQ

What happens if you take nitrofurantoin while pregnant?

What birth defects can nitrofurantoin cause?

Can antibiotics for UTI harm baby during pregnancy?

Can nitrofurantoin cause miscarriage in early pregnancy?

Macrobid (Nitrofurantoin) Use during Pregnancy