European Journal of Clinical Nutrition (2006) 60, 610–613
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ORIGINAL ARTICLE
Coffee drinking and risk of preterm birth F Chiaffarino1, F Parazzini1,2, L Chatenoud1, E Ricci1, L Tozzi2, V Chiantera1, C Maffioletti2 and L Fedele3 1
Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy; 2I Clinica Ostetrico Ginecologica, Universita` di Milano, Milan, Italy and 3Clinica Ostetrico Ginecologica, Universita` di Milano, Ospedale S. Paolo, Milan, Italy
Objectives: We analysed the association between coffee drinking before and during the three trimesters of pregnancy and the risk of preterm birth of babies normal for gestational age (NGA) or small for gestational age (SGA). Methods: Case–control study conducted in University clinics of North Italy. Cases were 502 women who delivered at o37 weeks of gestation. The controls included 1966 women who gave birth at term (X37 weeks of gestation) to healthy infants on randomly selected days at the hospitals where cases had been identified. Results: There was inverse association for coffee consumption in the third trimester of pregnancy in SGA cases compared to NGA (heterogeneity test between OR: w12 ¼ 5.6811 Po0.05). In comparison with not drinkers, all the ORs of overall intake of caffeine were closed near the unity for both SGA and NGA preterm birth. Conclusion: Compared with no consumption, a low consumption of coffee during pregnancy may not have significant effects on preterm birth.
European Journal of Clinical Nutrition (2006) 60, 610–613. doi:10.1038/sj.ejcn.1602358; published online 4 January 2006 Keywords: coffee; preterm birth; risk factors; epidemiology; small for gestational age; normal for gestational age
Introduction Caffeine is known to cross the placenta and reach the fetus (Soyka, 1979) and the clearance of caffeine, in pregnant women is delayed (Aldridge et al., 1979). Studies on caffeine and preterm births have produced conflicting results (Fenster et al., 1991; Olsen et al. 1991; McDonald et al., 1992; Fortier et al., 1993; Pastore and Savitz, 1995; Peacock et al., 1995; Eskenazi et al., 1999). Most of these studies are limited because lack of the information about multiple sources of caffeine and many studies did not control for any confounders. Trimester detail is also important because third-trimester consumption is likely to
Correspondence: Dr F Chiaffarino, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea, 62 – 20157 Milano, Italy. E-mail:
[email protected] Guarantor: F Parazzini. Contributors: FP was the principal investigator of the study giving the study hypothesis and planning the study design, FC and LC analysed the data, FC and FP drafted the paper, ER and VC assisted in analyses and writing, LF contributed to the conception and design of the study, LT and CM was involved in the baseline surveys for the study, LC took part in planning the study and interpreting the data and commented on the manuscript. Received 27 October 2004; revised 12 October 2005; accepted 17 October 2005; published online 4 January 2006
be most important for analysing preterm delivery (Pastore and Savitz, 1995). Preterm birth can be associated with intrauterine growth retardation. This condition could differ from preterm birth of a child with normal weight (respect to his gestational age). This study analyses the effect of coffee consumption on the risk of preterm birth with the opportunity of distinguish babies small for gestational age (SGA) and babies normal for gestational age (NGA).
Methods We conducted a case–control study from 1989 to 1999. Cases were 502 women who delivered at 28 to o37 weeks gestation (mean age 31 years, range 16–44 years) identified at the University of Milan and of Verona. (Parazzini et al., 2003). Gestational age was confirmed by ultrasound examination before the 20th week of gestation. An infant was defined as SGA according to Parazzini et al. (1995). Cases and controls were interviewed in the same hospital during 3 days after delivery. The proportion of cases and controls interviewed in the first, second and third day after delivery was similar.
Coffee and preterm birth F Chiaffarino et al
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Table 1 Distribution of study subjects according to selected factorsa Preterm births
Controls
SGA No. (%)
NGA No. (%)
31 (16–42)
31 (18–44)
Gestational week at birth (week) Mean (range) 34 (28–36)
33 (23–36)
Age (years) Mean (range)
OR (95% CI) SGA
NGA
31 (14–45)
—
—
39 (37–42)
—
—
No. (%)
Education (years) p6 7–13 X14
10 (7.0) 105 (73.4) 28 (19.6)
17 (4.7) 274 (76.3) 68 (18.9)
53 (2.7) 1439 (73.2) 473 (24.1)
1.0 0.4 (0.2–1.0) 0.4 (0.2–1.1)
1.0 0.7 (0.4–1.2) 0.6 (0.3–1.0)
Parity 0 1 X2
103 (72.0) 31 (21.7) 9 (6.3)
220 (61.3) 100 (27.9) 39 (10.9)
1103 (56.1) 693 (35.3) 170 (8.7)
1.0 0.5 (0.3–0.8) 0.5 (0.2–1.0)
1.0 0.7 (0.6–1.0) 1.0 (0.6–1.5)
Smokingb No Yes
103 (72.0) 40 (28.0)
281 (78.3) 78 (21.7)
1677 (85.3) 289 (14.7)
1.0 2.6 (1.7–4.0)
1.0 1.6 (1.2–2.0)
Previous preterm birthsc No Yes
27 (67.5) 13 (32.5)
105 (75.5) 34 (24.5)
815 (94.4) 48 (5.6)
1.0 8.7 (3.9–19.7)
1.0 5.3 (3.2–8.8)
Hypertension in pregnancy No Yes
74 (51.8) 69 (48.2)
273 (74.0) 86 (24.0)
1863 (94.8) 103 (5.2)
1.0 17.4 (11.6–26.1)
1.0 5.8 (4.2–8.0)
Coffee drinking during third trimester (services/day) 0 71 (49.7) 1 44 (30.8) X2 28 (19.6)
157 (43.7) 95 (26.5) 107 (29.8)
750 (38.2) 626 (31.8) 590 (30.0)
1.0 0.7 (0.4–1.1) 0.5 (0.3–0.8)
1.0 0.7 (0.5–0.9) 0.8 (0.6–1.1)
Tead (services/day) 0 1 41
96 (67.1) 40 (28.0) 7 (4.9)
258 (71.9) 87 (24.2) 14 (3.9)
1417 (72.1) 477 (24.3) 72 (3.7)
1.0 1.4 (0.9–2.2) 1.7 (0.7–4.1)
1.0 1.1 (0.8–1.4) 1.1 (0.6–2.1)
Decaffeinated coffeed (services/day) 0 137 (95.8) X1 6 (4.2)
340 (94.7) 19 (5.3)
1876 (95.4) 90 (4.6)
1.0 1.1 (0.4–2.8)
1.0 1.1 (0.7–2.0)
Colad (services/day) 0 X1
129 (90.2) 14 (9.8)
335 (93.3) 24 (6.7)
1846 (93.9) 120 (6.1)
1.0 1.6 (0.8–3.0)
1.0 1.1 (0.7–1.8)
Overall intake of caffeined (services/day) 0 34 (23.8) 1 54 (37.8) X2 55 (38.5)
84 (23.4) 129 (35.9) 146 (40.7)
446 (22.7) 744 (37.8) 776 (39.5)
1.0 1.1 (0.7–1.8) 1.0 (0.6–1.7)
1.0 0.9 (0.6–1.2) 0.9 (0.7–1.3)
a In some cases the sum does not add up the total because of some missing values. SGA ¼ small for gestational age. NGA ¼ normal for gestational age. þ Reference category – OR ¼ Odds ratios adjusted for age, education, parity, smoking during the first trimester of pregnancy, gestational hypertension and history of preterm births. b During the first trimester of pregnancy. c Parous women only. d Average during pregnancy.
European Journal of Clinical Nutrition
Coffee and preterm birth F Chiaffarino et al
612 The controls who met the inclusion criteria were 1966 women (mean age 31 years, range 14–45 years) who gave birth at term (X37 weeks of gestation) to healthy infants at the hospitals where cases had been identified. The interviewers surveyed the obstetric wards on randomly selected days. Controls were comparable to cases with reference to age (5 year age categories). Overall participation was over 95%. Questions included information on coffee and other methylxanthine-containing beverages (tea, cola and decaffeinated coffee), the average number of cups per day and the duration of the habit in years before pregnancy. The intake of caffeine was estimated summing up number of cup or glasses/day of coffee, tea and cola. Birth weight, gestational age, women age, previous preterm births and hypertension in pregnancy were checked with clinical records; all the other information was obtained from personal interviews. We used unconditional multiple logistic regression, with maximum likelihood fitting (Breslow and Day, 1980) including terms for age, education, parity, smoking during the first trimester of pregnancy, gestational hypertension and history of preterm births. No marked differences emerged in the estimated multivariate OR in comparison with the age adjusted ones, thus only multivariate estimates are presented in the tables. When appropriate, differences between the OR for SGA and NGA cases was assessed by a likelihood ratio test (distributed as a w2) for heterogeneity obtained by comparing the fit of two different polychotomous logistic regression models, one of them constrained to give the same estimate for the two groups of cases (Dubin and Pasternack, 1986).
Results Cases smoked more frequently than controls: the corresponding OR were 2.6 and 1.6 for SGA birth and NGA birth, respectively. Likewise, previous preterm births were more frequently among cases than controls: the corresponding OR were 8.7 and 5.3 for SGA birth and NGA birth, respectively (Table 1). Hypertension in pregnancy was present in 48.2% of preterm births of SGA babies and in 24% of NGA babies. There was inverse association for coffee consumption in the third trimester of pregnancy in SGA cases compared to NGA (heterogeneity test between OR: w21 ¼ 5.6811; Po0.05). Cola and decaffeinated coffee consumption during pregnancy had no effects, while tea consumption tended to increase the risk of preterm birth of SGA babies, although not significantly. In comparison with not drinkers, all the ORs of overall intake of caffeine were closed near the unity for both SGA and NGA preterm birth.
Discussion In this study, no clear association emerged between coffee and risk of preterm birth, except for a more marked inverse European Journal of Clinical Nutrition
association for coffee consumption in the third trimester of pregnancy in SGA cases compared to NGA. This latter effect could be due to a small increase in consumption in the control group (probably related to a decrease in nausea), whereas the coffee consumption in the SGA group decreases, probably because women in the third trimester of pregnancy, with nonphysiological fetal growth, pay greater attention to their health and therefore tend not to drink too much coffee. In our study population coffee consumption was low. We considered pregnant women, who could drink less than no pregnant women. Approximately 50% women drink coffee with median intake of one cup of coffee/day; these data appear according to a Danish study (Wisborg et al., 2003) where 57% of women drank coffee, but the coffee intake is higher: 22% of women drank more than four cups of coffee a day. We observed a higher proportion of SGA than expected one. This is due to the fact we conducted the study in second level centers. Previous studies found a small positive association between caffeine consumption and preterm delivery (Williams et al., 1992; Bracken et al., 2003), but they did not controlled for confounders. Most previous studies, which took some confounding factors into account, found no association (Fenster et al., 1991; McDonald et al., 1992; Fortier et al., 1993; Pastore and Savitz, 1995; Peacock et al., 1995). We found a modest positive association between tea consumption and risk of SGA preterm birth, but this was not significant. A Danish study showed a weak association between preterm deliveries and tea consumption, where the adjusted OR for eight or more cups/day of tea was 1.6, but this was of borderline statistical significance (95% CI 1.0–2.7). (Olsen et al., 1991). In conclusion, a low consumption of coffee during pregnancy may not have significant effects on preterm birth, compared with no consumption.
Acknowledgements We thank Cristina Bosetti MD, for helping statistical analysis and Mrs Ivana Garimoldi for her editorial assistance. Partly supported by the Commission of the European Communities (contract no. QLK1-CT-2000-00069).
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