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Date of issue: January 2023, Version: 3

Methylthioninium chloride (methylene blue) is a heterocyclic aromatic compound used as an indicator in analytical chemistry, a histological stain, a germicide, a diagnostic dye to identify and visualise anatomical structures, and as an antidote in the treatment of methaemoglobinaemia. Prior to 1990 methylthioninium chloride was also used in diagnostic amniocentesis in twin pregnancies.

There are extremely limited data regarding first trimester exposure or maternal systemic administration of methylthioninium chloride during pregnancy. Four pregnancies with inadvertent methylthioninium chloride exposure in the first trimester and an additional nine with exposure in the first four months of pregnancy, all of which resulted in healthy live births, have been described in uncontrolled case reports/series. Two case reports of maternal systemic exposure at 30 and 34 weeks of gestation did not document any adverse maternal or fetal effects. One population-based cohort study was located which reported a non-significant increased risk of congenital malformation following exposure at any time in pregnancy. The available data are thus currently considered too limited to exclude the possibility of adverse fetal effects following maternal systemic exposure.

Intra-amniotic methylthioninium chloride exposure in the second trimester has been associated with increased risks of intestinal atresia, fetal death and stillbirth. Neonatal complications including haemolytic anaemia, hyperbilirubinaemia, methaemoglobinaemia, and respiratory distress have been reported following intra-amniotic exposure close to delivery.

As with all chemicals, unnecessary exposure to methylthioninium chloride should be avoided. However, where occupational exposure is unavoidable, precautions should be taken to ensure that exposure is well within the recommended exposure limits and not associated with toxic symptoms.

The management of methaemoglobinaemia during pregnancy should be the same as for a non-pregnant patient. If methylthioninium chloride is indicated in the treatment of a pregnant patient with methaemoglobinaemia, the risks to the fetus of leaving the mother untreated are likely to be substantially greater than the risk from maternal treatment. However, there are limited data to confirm this hypothesis.

Given the extremely limited published cases of first trimester and/or systemic methylthioninium chloride exposure, it is not possible to provide a fetal risk assessment following such an exposure. The mechanism by which second trimester intra-amniotic exposure induces intestinal atresia is as yet uncertain, and similar effects following other routes of exposure cannot be excluded. Enhanced fetal monitoring following methylthioninium chloride exposure at any stage of pregnancy may therefore be justifiable. Discussion with UKTIS is recommended in all cases.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

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