Chlorothiazide in Pregnancy and Breastfeeding

Risk Factor: CM*
Class: Diuretics

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
Questions and Answers

Fetal Risk Summary

Chlorothiazide is a member of the thiazide group of diuretics. The information in this monograph applies to all members of the group, including the pharmacologically and structurally related diuretics, chlorthalidone, indapamide, metolazone, and quinethazone.

Reproduction studies in mice (500 mg/kg/day), rats (60 mg/kg/day), and rabbits (50 mg/kg/day) revealed no external malformations or growth impairment, and no effect on fetal survival (1). However, these studies did not include a thorough examination for visceral anomalies and skeletal defects (1).

Data from published reports indicate that thiazide and related diuretics are infrequently administered during the 1st trimester. In the past, when these drugs were routinely given to prevent or treat toxemia, therapy was usually begun in the 2nd or 3rd trimester and adverse effects in the fetus were rare (2,3,4,5,6,7,8,9,10 and 11). No increases in the incidence of congenital defects were discovered, and thiazides were considered nonteratogenic (12,13,14 and 15).

In contrast, the Collaborative Perinatal Project monitored 50,282 mother-child pairs, 233 of whom were exposed in the 1st trimester to thiazide or related diuretics (16, pp. 371373). All of the mothers had cardiovascular disorders, which makes interpretation of the data difficult. However, an increased risk for malformations was found for chlorthalidone (20 patients) and miscellaneous thiazide diuretics (35 patients, excluding chlorothiazide and hydrochlorothiazide). For use anytime during pregnancy, 17,492 exposures were recorded and only polythiazide showed a slight increase in risk (16, p. 441). The statistical significance of these findings is unknown and independent confirmation is required.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, a number of newborns had been exposed to this class of diuretics during the 1st trimester: 20 (chlorothiazide), 48 (chlorthalidone), and 567 (hydrochlorothiazide) (Franz Rosa, personal communication, FDA, 1993). The number of major birth defects observed, the number expected, and the incidence for each drug were: 2/1/10.0%, 2/2/4.2%, and 24/22/4.2%, respectively. Specific data were available for six defect categories (observed/expected): cardiovascular defects 0/0, 1/0.5, and 7/6; oral clefts 0/0, 0/0, and 0/1; spina bifida, 0/0, 0/0, and 0/0.5; polydactyly, 0/0, 0/0, and 1/2y; limb reduction defects 0/0, 0/0, and 0/1; and hypospadias 1/0, 0/0, and 1/1, respectively. Although the number of exposures is small for two of the diuretics, these data do not support an association between the drug and congenital defects.

Many investigators consider diuretics contraindicated in pregnancy, except for patients with heart disease or chronic hypertension, because they do not prevent or alter the course of toxemia and they may decrease placental perfusion (8, 17,18,19,20 and 21). A 1984 study determined that the use of diuretics for hypertension in pregnancy prevented normal plasma volume expansion and did not change perinatal outcome (22). In 4,035 patients treated for edema in the last half of the 3rd trimester (hypertensive patients were excluded), higher rates were found for induction of labor, stimulation of labor, uterine inertia, meconium staining, and perinatal mortality (20). All except perinatal mortality were statistically significant compared with 13,103 controls. In another study, a decrease in endocrine function of the placenta as measured by placental clearance of estradiol was found in three patients treated with hydrochlorothiazide (23).

Chlorothiazide readily crosses the placenta at term, and fetal serum levels may equal those of the mother (24). In 10 women following 2 weeks of hydrochlorothiazide, 50 mg/day, the cord:maternal plasma ratio determined 213 hours after the last dose ranged from 0.10 to 0.80 (25). Chlorthalidone also crosses the placenta (26). Other diuretics probably cross to the fetus in similar amounts, although specific data are lacking.

Thiazides are considered mildly diabetogenic because they can induce hyperglycemia (18). Several investigators have noted this effect in pregnant patients treated with thiazides (27,28,29 and 30). Other studies have failed to show maternal hyperglycemia (31,32). Although apparently a low risk, newborns exposed to thiazide diuretics near term should be observed closely for symptoms of hypoglycemia resulting from maternal hyperglycemia (30).

Neonatal thrombocytopenia has been reported following the use near term of chlorothiazide, hydrochlorothiazide, and methyclothiazide (15,27,33,34,35,36,37 and 38). Other studies have not found a relationship between thiazide diuretics and platelet counts (39,40). The positive reports involve only 11 patients; however, although the numbers are small, 2 of the affected infants died (27,34). The mechanism of the thrombocytopenia is unknown, but the transfer of antiplatelet antibody from the mother to the fetus has been demonstrated (38). Thiazide-induced hemolytic anemia in 2 newborns was described in 1964 following the use of chlorothiazide and bendroflumethiazide at term (33). Thiazide diuretics may induce severe electrolyte imbalances in the mother's serum, in amniotic fluid, and in the newborn (41,42 and 43). In one case, a stillborn fetus was attributed to electrolyte imbalance and/or maternal hypotension (41). Two hypotonic newborns were discovered to be hyponatremic, a condition believed to have resulted from maternal diuretic therapy (42). Fetal bradycardia, 6570 beats/minute, was shown to be secondary to chlorothiazide-induced maternal hypokalemia (43). In a 1963 study, no relationship was found between neonatal jaundice and chlorothiazide (44). Maternal and fetal deaths in two cases of acute hemorrhagic pancreatitis were attributed to the use of chlorothiazide in the 2nd and 3rd trimesters (45).

In summary, the published experience with 1st trimester use of thiazides and related diuretics does not indicate these agents are teratogenic. One large study (the Collaborative Perinatal Project) did find an increased risk of defects when diuretics were used during the 1st trimester in women with cardiovascular disorders, but causal relationships cannot be inferred from these data without independent confirmation.

Diuretics are not recommended for the treatment of pregnancy-induced hypertension because of the maternal hypovolemia characteristic of this disease. Other risks to the fetus or newborn include hypoglycemia, thrombocytopenia, hyponatremia, hypokalemia, and death from maternal complications. Moreover, thiazide diuretics may have a direct effect on smooth muscle and inhibit labor.

[*Risk Factor D if used in pregnancy-induced hypertension.]

Breast Feeding Summary

Chlorothiazide is excreted into breast milk in low concentrations (46). Following a single 500-mg oral dose, milk levels were less than 1 mg/mL at 1, 2, and 3 hours. The authors speculated that the risks of pharmacologic effects in nursing infants would be remote. However, it has been stated that thrombocytopenia can occur in the nursing infant if the mother is taking chlorothiazide (47). Documentation of this is needed (48). Chlorthalidone has a very low milk:plasma ratio of 0.05 (26).

In one mother taking 50 mg of hydrochlorothiazide (HCTZ) daily, peak milk levels of the drug occurred 510 hours after a dose and were about 25% of maternal blood concentrations (49). The mean milk concentration of HCTZ was about 80 ng/mL. An infant consuming 600 mL of milk/day would thus ingest about 50 mg of the drug, probably an insignificant amount (49). The diuretic could not be detected in the serum of the nursing 1-month-old infant, and measurements of serum electrolytes, blood glucose, and blood urea nitrogen were all normal.

Thiazide diuretics have been used to suppress lactation (50,51). However, the American Academy of Pediatrics considers bendroflumethiazide, chlorthalidone, chlorothiazide, and hydrochlorothiazide to be compatible with breast feeding (52).


  1. Product information. Diuril. Merck, 2000.
  2. Finnerty FA Jr, Buchholz JH, Tuckman J. Evaluation of chlorothiazide (Diuril) in the toxemias of pregnancy. Analysis of 144 patients. JAMA 1958;166:1414.
  3. Zuspan FP, Bell JD, Barnes AC. Balance-ward and double-blind diuretic studies during pregnancy. Obstet Gynecol 1960;16:5439.
  4. Sears RT. Oral diuretics in pregnancy toxaemia. Br Med J 1960;2:148.
  5. Assoli NS. Renal effects of hydrochlorothiazide in normal and toxemic pregnancy. Clin Pharmacol Ther 1960;1:4852.
  6. Tatum H, Waterman EA. The prophylactic and therapeutic use of the thiazides in pregnancy. GP 1961;24:1015.
  7. Flowers CE, Grizzle JE, Easterling WE, Bonner OB. Chlorothiazide as a prophylaxis against toxemia of pregnancy. Am J Obstet Gynecol 1962;84:91929.
  8. Weseley AC, Douglas GW. Continuous use of chlorothiazide for prevention of toxemia in pregnancy. Obstet Gynecol 1962;19:3558.
  9. Finnerty FA Jr. How to treat toxemia of pregnancy. GP 1963;27:11621.
  10. Fallis NE, Plauche WC, Mosey LM, Langford HG. Thiazide versus placebo in prophylaxis of toxemia of pregnancy in primagravid patients. Am J Obstet Gynecol 1964;88:5024.
  11. Landesman R, Aguero O, Wilson K, LaRussa R, Campbell W, Penaloza O. The prophylactic use of chlorthalidone, a sulfonamide diuretic, in pregnancy. J Obstet Gynaecol Br Commonw 1965;72:100410.
  12. Cuadros A, Tatum H. The prophylactic and therapeutic use of bendroflumethiazide in pregnancy. Am J Obstet Gynecol 1964;89:8917.
  13. Finnerty FA Jr, Bepko FJ Jr. Lowering the perinatal mortality and the prematurity rate. The value of prophylactic thiazides in juveniles. JAMA 1966;195:42932.
  14. Kraus GW, Marchese JR, Yen SSC. Prophylactic use of hydrochlorothiazide in pregnancy. JAMA 1966;198:11504.
  15. Gray MJ. Use and abuse of thiazides in pregnancy. Clin Obstet Gynecol 1968;11:56878.
  16. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
  17. Watt JD, Philipp EE. Oral diuretics in pregnancy toxemia. Br Med J 1960;1:1807.
  18. Pitkin RM, Kaminetzky HA, Newton M, Pritchard JA. Maternal nutrition: a selective review of clinical topics. Obstet Gynecol 1972;40:77385.
  19. Lindheimer MD, Katz AI. Sodium and diuretics in pregnancy. N Engl J Med 1973;288:8914.
  20. Christianson R, Page EW. Diuretic drugs and pregnancy. Obstet Gynecol 1976;48:64752.
  21. Lammintausta R, Erkkola R, Eronen M. Effect of chlorothiazide treatment of renin-aldosterone system during pregnancy. Acta Obstet Gynecol Scand 1978;57:38992.
  22. Sibai BM, Grossman RA, Grossman HG. Effects of diuretics on plasma volume in pregnancies with long-term hypertension. Am J Obstet Gynecol 1984;150:8315.
  23. Shoemaker ES, Grant NF, Madden JD, MacDonald PC. The effect of thiazide diuretics on placental function. Tex Med 1973;69:10915.
  24. Garnet J. Placental transfer of chlorothiazide. Obstet Gynecol 1963;21:1235.
  25. Beermann B, Fahraeus L, Groschinsky-Grind M, Lindstrom B. Placental transfer of hydrochlorothiazide. Gynecol Obstet Invest 1980;11:458.
  26. Mulley BA, Parr GD, Pau WK, Rye RM, Mould JJ, Siddle NC. Placental transfer of chlorthalidone and its elimination in maternal milk. Eur J Clin Pharmacol 1978;13:12931.
  27. Menzies DN. Controlled trial of chlorothiazide in treatment of early pre-eclampsia. Br Med J 1964;1:73942.
  28. Ladner CN, Pearson JW, Herrick CN, Harrison HE. The effect of chlorothiazide on blood glucose in the third trimester of pregnancy. Obstet Gynecol 1964;23:55560.
  29. Goldman JA, Neri A, Ovadia J, Eckerling B, DeVries A. Effect of chlorothiazide on intravenous glucose tolerance in pregnancy. Am J Obstet Gynecol 1969;105:55660.
  30. Senior B, Slone D, Shapiro S, Mitchell AA, Heinonen OP. Benzothiadiazides and neonatal hypoglycaemia. Lancet 1976;2:377.
  31. Lakin N, Zeytinoglu J, Younger M, White P. Effect of chlorothiazide on insulin requirements of pregnant diabetic women. JAMA 1960;173:3534.
  32. Esbenshade JH Jr, Smith RT. Thiazides and pregnancy: a study of carbohydrate tolerance. Am J Obstet Gynecol 1965;92:2701.
  33. Harley JD, Robin H, Robertson SEJ. Thiazide-induced neonatal haemolysis? Br Med J 1964;1:6967.
  34. Rodriguez SU, Leikin SL, Hiller MC. Neonatal thrombocytopenia associated with ante-partum administration of thiazide drugs. N Engl J Med 1964;270:8814.
  35. Leikin SL. Thiazide and neonatal thrombocytopenia. N Engl J Med 1964;271:161.
  36. Prescott LF. Neonatal thrombocytopenia and thiazide drugs. Br Med J 1964;1:1438.
  37. Jones JE, Reed JF Jr. Renal vein thrombosis and thrombocytopenia in the newborn infant. J Pediatr 1965;67:6812.
  38. Karpatkin S, Strick N, Karpatkin MB, Siskind GW. Cumulative experience in the detection of antiplatelet antibody in 234 patients with idiopathic thrombocytopenic purpura, systemic lupus erythematosus and other clinical disorders. Am J Med 1972;52:77685.
  39. Finnerty FA Jr, Assoli NS. Thiazide and neonatal thrombocytopenia. N Engl J Med 1964;271:1601.
  40. Jerkner K, Kutti J, Victoria L. Platelet counts in mothers and their newborn infants with respect to antepartum administration of oral diuretics. Acta Med Scand 1973;194:4735.
  41. Pritchard JA, Walley PJ. Severe hypokalemia due to prolonged administration of chlorothiazide during pregnancy. Am J Obstet Gynecol 1961;81:12414.
  42. Alstatt LB. Transplacental hyponatremia in the newborn infant. J Pediatr 1965;66:9858.
  43. Anderson GG, Hanson TM. Chronic fetal bradycardia: possible association with hypokalemia. Obstet Gynecol 1974;44:8968.
  44. Crosland D, Flowers C. Chlorothiazide and its relationship to neonatal jaundice. Obstet Gynecol 1963;22:5004.
  45. Minkowitz S, Soloway HB, Hall JE, Yermakov V. Fatal hemorrhagic pancreatitis following chlorothiazide administration in pregnancy. Obstet Gynecol 1964;24:33742.
  46. Werthmann MW Jr, Krees SV. Excretion of chlorothiazide in human breast milk. J Pediatr 1972;81:7813.
  47. Anonymous. Drugs in breast milk. Med Lett Drugs Ther 1976;16:257.
  48. Dailey JW. Anticoagulant and cardiovascular drugs. In Wilson JT, ed. Drugs in Breast Milk. Australia (Balgowlah):ADIS Press, 1981:614.
  49. Miller ME, Cohn RD, Burghart PH. Hydrochlorothiazide disposition in a mother and her breast-fed infant. J Pediatr 1982;101:78991.
  50. Healy M. Suppressing lactation with oral diuretics. Lancet 1961;1:13534.
  51. Catz CS, Giacoia GP. Drugs and breast milk. Pediatr Clin North Am 1972;19:15166.
  52. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.

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Questions and Answers

what does chlorothiazide do to your phosphorus and calcium levels?,

Chlorothiazide is a "thiazide" diuretic. They can lower all your electrolytes except calcium. For some reason, you can get a high calcium.

Could prescription medicine negate the affects of the Plan-B pill?, The prescription medicine that I'm taking is labetalol, chlorothiazide, and lisinopril for my high-blood pressure. I want to make sure that these medicines could make the Plan-B pill not work if I took it.

I tried looking up information but I was unable to find anything. Anyone know anything?

There are no interactions that I know of between Plan B (levonorgestrel) and the medications you are taking.