Chlorothiazide readily crosses the human placenta, with umbilical cord blood levels approximately equivalent to maternal plasma.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, of whom 233 were exposed to thiazide or related diuretics during the first trimester. An increased risk of malformations was found for thiazide diuretics, although the fact that the population studied had underlying cardiovascular disease makes implication of drug use alone difficult. Use of thiazides after the first trimester does not seem to carry this risk. Thiazide diuretics may, however pose metabolic risks to the mother and fetus (hyponatremia, hypokalemia, thrombocytopenia, hyperglycemia), and may have a direct effect on smooth muscle, resulting in inhibition of labor.

The Michigan Medicaid surveillance study showed no association between some thiazide diuretics and congenital defects (written communication, Franz Rosa, MD, Food and Drug Administration, 1994). This report is a summary of information from two studies, one in which 390 of 104,000 pregnant women from 1980 to 1983, and one in which 567 of 229,000 pregnant women from 1985 to 1992 received a related drug, hydrochlorothiazide (HCTZ). In the first study 28 total defects and 6 cardiovascular defects were observed (25 and 4 were expected, respectively). In the second study, 24 total defects and 7 cardiovascular defects were observed (22 and 6 were expected, respectively). Cleft palate was not observed in either study. These data do not support an association between HCTZ and congenital defects. These data are considered pertinent to other thiazide diuretics, although the number of exposures to chlorothiazide is too small to make definitive conclusions relative to this drug, per se.

Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

Chlorothiazide has been assigned to pregnancy category C by the FDA. Animal data have failed to reveal evidence of teratogenicity, but the data are considered limited since visceral or skeletal abnormalities were not sought. There are no controlled data from human pregnancy. Some retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. The routine use of chlorothiazide during pregnancy in patients without heart disease is considered contraindicated by some experts.

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Chlorothiazide is secreted into human milk in low concentrations. While a rare case of thrombocytopenia has been reported in one nursing infant whose mother was taking chlorothiazide, adverse effects in the nursing infant are unlikely. Chlorothiazide is considered compatible with breast-feeding by the American Academy of Pediatrics; however, the manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

In one case, a single chlorothiazide 500 mg dose resulted in milk drug concentrations of less than 1 mcg per mL at 1, 2, and 3 hours. This usually represents an insignificant amount of chlorothiazide to the infant such that adverse effects in the nursing infant are unlikely.

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