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Editor—Ford et al 1 examined the association between maternal caffeine intake during pregnancy and the risk of sudden infant death and found a higher risk for babies whose mothers consumed more than 400 mg/day of caffeine during the first and/or the third trimester of pregnancy (with increased risk especially for the third trimester group).
We are concerned because preterm babies, especially those of low and very low birthweight, are routinely treated with caffeine or theophylline to prevent apnoea and brachycardia at a gestational time which is equivalent to the “third trimester of pregnancy.” The question as to whether we can compare the dose given to the neonates with the 400 mg/day taken by pregnant women, the amount found to increase the risk of SIDS.
When we look at the common dose of caffeine citrate (between 3 mg/kg/day and 5 mg/kg/day, after a rather high loading dose) it seems to be somewhat lower than the amounts postulated in Ford’s study (assuming that the pregnant woman weighs about 75 kg on average, 400 mg/day would be equivalent to 5.33 mg/kg/day in preterm infants, for example). However, even considering the higher distribution volumes, the pharmacokinetic studies with premature neonates2 3show a markedly lower clearance than the values reported for adults.
We have not been able to find any data for fetal serum concentrations of caffeine, but fetal values would be expected to decrease faster in utero than after delivery, owing to maternal excretion.
The possible explanation suggested for an increased risk of SIDS is the effect of caffeine on the brainstem, which may cause increased vulnerability of the respiratory centre.3 If this theory is right, we cannot find any basic difference in the situation of fetal and neonatal “treatment.”
So, the question remains: is the higher incidence of SIDS in premature babies the result of neonatal caffeine treatment?
Dr Ford et al respond: Caffeine treatment for apnoea in prematurity is current standard neonatal practice.1-4 Very premature infants have about a fivefold increased risk of SIDS compared with their full term counterparts.1-5 1-6 Bock et altherefore speculate whether this higher incidence of SIDS in premature infants might be related to caffeine treatment. To our knowledge, there is no satisfactory answer to this question. However, as in all treatments, a balance needs to be struck between the benefit of the treatment and any downstream adverse effects. Their question is important and needs careful study.