Drug Levels

The half-life of caffeine in late pregnancy is much longer than in nonpregnant women; however, the maternal half-life returns to normal within the first week postpartum.[7] Smokers have more rapid clearance of caffeine and shorter half-lives than nonsmokers because smoking induces CYP1A2. Caffeine clearance is very low in preterm and newborn infants, but reaches adult values by 3 to 5 months of age.[4]

Maternal Levels. Caffeine appears in breastmilk with a peak usually occurring about 1 hour after a dose.[8-10] Most studies did not measure active metabolites in milk.

Five women who were 4 months to 1 year postpartum were given a dose of 150 mg of caffeine orally as caffeine sodium benzoate solution 2 hours after breakfast. Average caffeine levels at 30, 60 and 120 minutes after the dose were 1.6, 1.5, and 0.9 mg/L, respectively. One woman also received a 300 mg dose on a separate occasion and her milk caffeine levels were about double those after her 150 mg dose.[11]

Two nursing mothers who were 7 and 13 weeks postpartum ingested tablets containing a total of 128 mg of caffeine. Milk samples were taken over 12 and 48 hours in the 2 women, respectively. Peak milk levels of 1.3 and 1.6 mg/L occurred at 1.5 and 2 hours, respectively.[9]

A mother who drank 3 cups of coffee over a 1-hour period and then coffee at will throughout the day had milk caffeine concentrations ranging from 0.32 to 1.15 mg/L in 8 milk samples taken over a 10.5 hour period.[12]

Fifteen women ingested a caffeine-containing beverage of their choice (coffee or tea) containing caffeine in amounts ranging from 35 to 336 mg. Their breastfed infants ranged from 2 weeks to 9 months of age. Eleven of the women had caffeine detectable in their breastmilk with peak levels ranging from 2.1 to 7.2 mg/L. The 4 mothers with undetectable caffeine (<0.2 mg/L) had ingested less than 100 mg of caffeine. The mean half-life of caffeine in milk was 6.1 hours.[8]

Nine nursing mothers ingested 750 mg of caffeine (5 doses of 150 mg) in instant coffee daily for 5 days. Pooled 24-hour milk samples were collected on days 5 and 9 after no caffeine had been taken for 4 days. Caffeine concentration in the mothers’ milk averaged 4.3 mg/L, ranging from undetectable (<0.25 mg/L) to 28.6 mg/L. By day 9, caffeine was undetectable in all milk samples. The authors estimated that at this caffeine intake, infants would receive 0.6 to 0.8 mg/kg daily.[13]

Eleven nursing mothers randomly consumed 5 cups of decaffeinated coffee or 5 cups of decaffeinated coffee with a total of 500 mg of added caffeine daily for 5 days in a randomized, double- blinded study. Their infants averaged 47 days (range 22 to 71 days) of age. During a 24-hour collection period on day 5, milk of the women who consumed caffeine contained an average of 3.1 mg/L, which amounted to an average of 2.4 mg or 0.5 mg/kg daily intake for the infants.[3]

Six women who were 3.5 to 17 weeks postpartum were given a single oral tablet of caffeine containing 100 mg of caffeine. Ten breastmilk samples from each breast were collected over the next 24 hours. The average peak milk levels from both breasts was 2.5 mg/L at 1 hour after the dose. Caffeine concentrations in milk from both breasts fell with an average half-life of 7.2 hours.[10] Using milk AUC data from 5 of the women, an exclusively breastfed infant would receive about 10% of the weight-adjusted maternal dose.

Five nursing mothers who were 6 to 28 weeks postpartum received a single dose of 200 mg of caffeine as tablets. Blood and milk samples were taken over the next 24 hours for measurement of caffeine and 3 active caffeine metabolites, paraxanthine, theobromine, and theophylline. The peak caffeine levels in milk occurred at about 1 hour, but peak metabolite levels in milk occurred later at about 5 to 10 hours for paraxanthine and 10 to 15 hours for theobromine and theophylline. The authors estimated that an exclusively breastfed infant would receive a caffeine dose of 7% and a total xanthine dose of 18% of the maternal weight-adjusted dosage.[5]

After one mother consumed a cup of espresso containing 80 mg of caffeine, breastmilk caffeine concentration had a peak value of 2.05 ng/L two hours after the expresso. Caffeine was undetectable (< 0.01 ng/L) in breastmilk after 24 hours. The authors estimated that the woman’s 2-month-old infant ingested 167 mL/kg of milk and 0.1 mg/kg of caffeine daily which was 8.9% of the mother’s weight-adjusted dosage. The half-life of caffeine in breastmilk was 4 hours.[14]

Four mothers anonymously donated milk samples for analysis. Caffeine was found in their milk samples in concentrations of 33, 35, 988 and 1011 ng/gram of milk.[15]

A study of 100 women in Poland found a strong correlation between caffeine ingestion based on 3-day food frequency questionnaires and milk caffeine content. There was also a strong correlation between caffeine and its primary metabolite paraxanthine in milk. Theobromine, and to a lesser extent theophylline, were also found in milk. The highest amount of caffeine in milk was found in hindmilk after 4 weeks of lactation.[16]

Infant Levels. Nine breastfed infants aged 14 days to 19 weeks of age had saliva caffeine levels measured after maternal ingestion of 1 cup of coffee. All but 2 were completely breastfed. Among the 7 fully breastfed infants, saliva caffeine levels ranged from 0.21 to 0.75 mg/L between 1 and 6 hours after the maternal ingestion of caffeine.[17]

Fifteen nursing mothers ingested a beverage containing caffeine in amounts ranging from 35 to 336 mg. Caffeine was not detected (<0.2 mg/L) in the urine of any of their infants over the 5-hour collection period that began 2 hours after the maternal caffeine intake.[8]

A 7-day-old breastfed infant’s urine contained 1 mg/L of caffeine about 24 to 40 hours after his mother took a combination of butalbital 50 mg with acetaminophen 325 mg and caffeine 50 mg every 6 hours for 24 hours.[18]

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