• For women who are pregnant:
• Trimethoprim can be used during pregnancy (although it should not be used first-line when other alternatives are available — for example, amoxicillin, if the bacterial sensitivity is known).
• For information on treating asymptomatic and symptomatic urinary tract infection in pregnancy, see Screening for and managing asymptomatic bacteriuria in pregnancy and Managing suspected acute cystitis during pregnancy.
• If trimethoprim is recommended for use during the first trimester:
• Ensure the woman is taking a folic acid supplement.
• For most women, prescribe folic acid 400 microgram daily.
• Consider a higher dose (5 mg daily) if the woman is at high risk of neural tube defects (for further information, see the section on Advice on folic acid in the CKS topic on Pre-conception - advice and management).
• For women who are breastfeeding
• Trimethoprim can be used in women who are breastfeeding.

These recommendations are based on information from the UK Teratology Information Service (UKTIS), (formerly the National Teratology Information Service [NTIS]), a reference text, and the manufacturers of trimethoprim [Actavis, 2007; Schaefer et al, 2007; NTIS, 2008].

Safety in pregnancy

• There is no strong evidence to suggest that trimethoprim is teratogenic and it has been used for many years in pregnant women [Schaefer et al, 2007].
• Concerns have been expressed about the use of trimethoprim during pregnancy because it is a folic acid antagonist, and low levels of folic acid have been associated with serious birth defects.
• The evidence on the risks of trimethoprim during pregnancy has been critically assessed by the UK Teratology Information Service (UKTIS), formerly the National Teratology Information Service (NTIS) [NTIS, 2008]. A similar systematic review was conducted by the Centers for Disease Control (CDC) in the USA, to assess the safety of trimethoprim-sulfamethoxazole used for prophylaxis in HIV-infected pregnant women [Forna et al, 2006]. The NTIS and CDC concluded that the benefits outweighed the risks, which were small. Additionally the NTIS concluded that:
• Trimethoprim should not be used in pregnant women who are folate deficient, or who are taking a folate antagonist (unless they are taking a folate supplement).
• In women with normal folate status, who are well nourished, use of trimethoprim for a short period is unlikely to induce folate deficiency.
• Trimethoprim is not licensed for use during pregnancy. This is reflected in the British National Formulary which recommends that it should avoided in the first trimester due to its anti-folate effect [BNF 57, 2009].

Folic acid supplement

• When trimethoprim is prescribed during the first trimester, the recommendation to co-prescribe a folic acid supplement is precautionary [Schaefer et al, 2007; NTIS, 2008].
• The standard folic acid dosage for pregnant women is usually recommended [Schaefer et al, 2007].
• In the UK, most pregnant women should be covered; folic acid supplementation (400 micrograms per day) is routinely recommended for women who wish to conceive and should be taken up to week 12 of pregnancy to prevent neural tube defects in the fetus. For some women at high risk of neural tube defects, a higher dose (5 mg per day) is recommended. For further information, see the section on Advice on folic acid in the CKS topic on Pre-conception - advice and management.

Breastfeeding

• Trimethoprim may be used during breastfeeding [Schaefer et al, 2007].
• Although it is excreted in breast milk, the manufacturer of trimethoprim states that short-term trimethoprim treatment is not contraindicated in women who are breastfeeding [Actavis, 2007].