COFFEE, CAFFEINE AND PREGNANCY
GENERAL
A 2002 review of the scientific literature concluded that
“It seems reasonable to conclude that no convincing evidence has been presented to show that caffeine consumption increases the risk of any reproductive adversity” (1).
This paper supports the opinion of the EU Scientific Committee on Foodstuffs who in 1999 stated that 'While intakes (of caffeine) up to 300mg/day appear to be safe, the possible question of effects on pregnancy and the offspring at regular intakes above 300 mg/day remains open. This suggests that moderation of caffeine intake, from whatever source, is advisable during pregnancy'.
DELAYED CONCEPTION
Eleven studies on effects of caffeine consumption on conception were reviewed recently (1) although not all published studies were included (6). The hypothesis that caffeine delays conception was originally suggested by a study of 104 women which showed that those who consumed an amount of caffeine equivalent to one cup of coffee were less likely to conceive than those who consumed smaller amounts (2). The design of this study has been questioned (1) and some of the design faults have been acknowledged by the authors (3). Criticisms include recruitment of women who did not have an equal probability of conceiving, elimination of 117 women who conceived in the first three months of the study, use of caffeine consumption estimated during the fourth month of trying to conceive as representative of consumption during the entire period and the possibility that caffeine intake might be a marker for anxiety, a known inhibitor of fertility.
Subsequent studies do not support the hypothesis that caffeine consumption delays conception. In a study of 2817 women, the average time to conception was no different in women who consumed more than 7 g caffeine per month and women who consumed 0.5 g per month and caffeine consumption was no higher in 1818 women with primary infertility than in 1765 controls (4). In a study of 11,888 pregnant Danish women there was no association between consumption of caffeine containing beverages and time to conception (5). A prospective study of 210 women found no significant association between delayed conception and consumption of coffee (6).
Studies reporting an association between caffeine consumption and delayed conception are frequently badly designed or wrongly interpreted. For example, the authors of a study of 1909 women reported odds ratios of 1.39 for consumption of 1-150 mg caffeine/day, 1.88 for consumption of 151-300 mg/day and 2.24 for consumption of over 300 mg/day after correction for last method of birth control, parity and cigarette smoking (7). In this study, delayed conception was defined as greater than 12 cycles. The last of these associations was statistically significant. However, it has been pointed out that correction for cigarette smoking, a known risk factor for delayed conception, actually increased risk of delayed conception when it should have decreased it (1). A second example is a study of 1430 women which indicated an increased risk of delayed conception associated with the consumption of more than 300 mg caffeine/day for one year in non-smokers but not in the entire study population (8). The dangers of concluding that a treatment effect exists in a subgroup of subjects when there is no evidence for the same effect in all subjects are well known (1). Cigarette smoking is an important risk factor for delayed conception. A study of 1341 pregnant women showed that conception was delayed by more than 12 cycles in all smokers irrespective of whether or not they drank coffee but not among non-smoking coffee drinkers (9).
A recent although not quite complete review of the scientific literature concluded that, “The claim that caffeine consumption by women delays conception has not been followed by convincing support” (1). Some studies finding an association between caffeine consumption and delayed conception found it only in a subgroup whereas others failed to correct for confounders. Cigarette smoking emerges from these studies as a far more likely explanation for delayed conception.
MISCARRIAGE/SPONTANEOUS ABORTION
Sixteen studies on association between caffeine consumption and spontaneous abortion were reviewed recently (1) but none of these studies addressed the issue raised by Stein and Susser (10). According to these authors, a healthy placenta produces a surge of one or more hormones, which in some women results in a reduced desire for aromatic and strongly flavoured beverages. Hence a high caffeine consumption in the first trimester of pregnancy would be a marker for a low rate of hormone production. A vulnerable implantation would be the result of a low rate of hormone production.
The first suggestion of an association between caffeine consumption and miscarriage came from a survey of 600 households (11). Out of 16 women who consumed more than 600 mg caffeine/day, only one had an uncomplicated delivery. Eight had a miscarriage, five stillbirths and two premature births. This study has been criticised on the grounds that the response rate was only 61%, data on caffeine-containing beverage consumption were collected a long time after the birth suggesting recall bias and there was no correction for confounders such as cigarette smoking, alcohol consumption or socio-economic status (12).
Several retrospective case control studies have examined the relationship between caffeine intake and spontaneous abortion. A case control study of 927 women is the only one to have classified spontaneous abortions as chromosomally normal or according to the type of chromosomal abnormality (13). Caffeine intake was estimated immediately before and after conception and during pregnancy. Caffeine intake around conception was associated with an increased risk of a monosomy X abortion, although there was no evidence for a dose response effect, but not with any other chromosomal abnormality or with chromosomally normal abortions. Caffeine consumption during pregnancy was reported to increase the risk of both chromosomally normal and chromosomally abnormal spontaneous abortions. A second case control study of 591 spontaneous abortions and 2558 controls measured serum paraxanthine (a metabolite of caffeine) levels (14). Spontaneous abortion was associated with very high levels of paraxanthine only. A third population-based case control study of 562 spontaneous abortions and 953 controls showed that women who consumed the most caffeine were at an increased risk of spontaneous abortion (15). However, the possibility that caffeine consumption is a marker for a vulnerable implantation was suggested by two of the authors of the first case control study (10) and could explain the results of all three. An alternative explanation would be confounding by other risk factors which is highly likely in case control studies.
Two prospective cohort studies did not find any significant associations between caffeine intake and risk of spontaneous abortion. The first of these recruited 431 pregnant women and identified all spontaneous abortions after day 21 of gestation and made 7 prospective assessments of caffeine intake (16). In women consuming more than 300 mg caffeine/day, risk of spontaneous abortion increased by 20% but this association was not significant. The second recruited 5144 pregnant women, 499 of which had a spontaneous abortion before week 20 of gestation (17). Odds ratios were 1.3 for consumption of 300 mg caffeine/day, 0.8 for consumption of 3 or more cups of caffeinated coffee/day, 1.5 for consumption of 3 or more cans of soda/day containing caffeine and 2.4 for consumption of 3 or more cups of decaffeinated coffee/day. Only the last of these associations was significant.
A recent review of the scientific literature concluded that “The association between caffeine consumption and spontaneous abortion may well reflect the Stein-Susser epiphenomenon (women with prominent nausea tend to reduce caffeine consumption and nausea appears to be a marker of good implantation, perhaps reflecting a favourable balance of hormones produced by a healthy placenta” (1).
The available evidence is clearly not consistent with the idea that caffeine consumption increases the risk of spontaneous abortion
LOW BIRTH WEIGHT AND PREMATURITY
Caffeine intake and low birth weight has been the subject of at least 29 published studies and caffeine intake and prematurity of at least 18 published studies (1).
In a comparison of 175 women who delivered before week 37 of gestation and 313 women who delivered after, there was no effect of drinking four or more cups of coffee per day during pregnancy on the risk of preterm delivery (18). A much larger study of 12,205 women published the same year found no significant association between coffee consumption and risk of low birth weight, short gestation or congenital malformations after correction for confounders (19).
One of the best designed and executed studies published in this area recruited 1513 women out of 1860 women who consecutively attended a London district hospital (20). Data were prospectively collected at three time points during gestation on coffee, tea and caffeine intake and on a wide variety of confounders. After adjustment for most of the confounders, coffee, tea or caffeine consumption were significantly associated with reduced birth weight. However, when the data were also corrected for smoking, these associations were no longer significant. In a prospective cohort study which recruited 431 pregnant women and identified all spontaneous abortions after day 21 of gestation and made 7 prospective assessments of caffeine intake, there was no association between caffeine intake and early foetal growth as assessed by crown-rump length on ultrasonic examination (16). In a second prospective study of 2291 mothers, an inverse association between caffeine intake and birth weight was observed after correction for confounders although there was no association with consumption of decaffeinated coffee (21). However, the authors noted that the small decrease in birth weight observed was unlikely to be clinically important unless six or more cups of coffee were consumed every day.
As observed in a recent review (1), “the larger the sample and the better the analyses, the more likely no association is seen between coffee/caffeine consumption and reduced birth weight”. The authors also pointed out that studies executed before smoking was socially undesirable tended to find no association between coffee/caffeine consumption and low birth weight. They suggested that “This raises the possibility that residual confounding really does plague this field since women have been admonished not to smoke if they are pregnant”.
FOETAL ANOMALIES
According to a recent review (1), there are at least 7 studies of caffeine intake and foetal anomalies. As observed in the review, poorly designed studies (22, 23, 24) tend to be the ones that show associations between caffeine/coffee consumption and foetal anomalies whereas the better studies (13, 19, 25, 26) show no such associations.
One of the better-designed and executed studies in this field is a hospital based
case-control study which looked at all children born in Finland between January 1980 and April 1982 with defects of the central nervous system (n = 112), orofacial clefts (n = 241), structural defects of the skeleton (n = 210) or cardiovascular malformations (n = 143) (26). After adjustment for confounders, there were no associations between coffee drinking during pregnancy and the risk of any of the anomalies studied. In addition no significant dose response relationship was observed.
The authors of a recent review (1) concluded that “No paper has been published on this topic during the last 12 years. Perhaps investigators of the antecedents of anomalies feel the matter is closed”.
BREAST FEEDING
The American Academy of Pediatrics Committee on Drugs has recently published a statement on the transfer of drugs and other chemicals into human milk (27). Caffeine was placed in Table 6 of this statement entitled “maternal medication usually compatible with breast feeding”. It was noted that when adverse effects of caffeine on the infant are reported they tend to include irritability and a poor sleeping pattern. However, such effects were not found in infants whose mothers had a moderate intake of caffeinated beverages corresponding to 2 to 3 cups of coffee per day. Six studies of caffeine secretion into human breast milk have been published (28, 29, 30, 31, 32, 33). Although caffeine has been found in breast milk the concentrations were not great enough to have pharmacological effects (30).
SUDDEN INFANT DEATH SYNDROME (SIDS)
It is highly unlikely that the consumption of caffeine-containing beverages is a risk factor for SIDS sometimes known as cot death. A case control study from New Zealand found that the consumption of 400 mg caffeine/day during the third trimester of pregnancy was associated with an increased risk of SIDS months after birth (34). However, no dose response relationship was found. As pointed out recently (1) this study is probably flawed due to residual confounding by smoking which was inadequately measured. This suggestion is supported by the results of a more recent study from Scandinavia on 244 SIDS cases and 869 controls which was unable to show associations between caffeine intake during or after pregnancy and the risk of SIDS after correction for confounders including smoking, maternal age, education and parity (35). However, case-control studies have inherently weak designs.
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