Does Alcohol Increase the Risk of Preterm Delivery?
Ulrik Kesmodel,1 Sjúrður Fróði Olsen,2 and Niels Jørgen Secher1
We evaluated the association between alcohol intake during
pregnancy and preterm delivery. Women attending routine
antenatal care at Aarhus University Hospital, Denmark, from
1989 –1991 and 1992–1996 were eligible. We included 18,228
singleton pregnancies in the analyses. We obtained prospective
information on alcohol intake at 16 and 30 weeks of gestation,
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other lifestyle factors, maternal characteristics, and obstetrical
risk factors from self-administered questionnaires and hospital
files. For women with alcohol intake of 1–2, 3– 4, 5–9, and
ⱖ10 drinks/week the risk ratio (RR) of preterm delivery was
0.91 (95% CI ⫽ 0.76 –1.08), 0.86 (95% CI ⫽ 0.64 –1.15), 0.89
(95% CI ⫽ 0.52–1.52), and 2.93 (95% CI ⫽ 1.52–5.63),
Keywords: alcohol, pregnancy, preterm delivery, cohort study.
Preterm delivery is an important contributor to neonatal
morbidity1 and mortality,2 and the incidence of preterm
delivery remains stable. A number of factors have been
found to be consistently associated with preterm deliv-
ery, including smoking,3 maternal risk factors such as
ethnicity,4 – 6 age,4,6 marital status,4 and various chronic
diseases,4 – 6 as well as obstetrical risk factors such as
multiple pregnancies,4 previous preterm delivery,4 – 6
uterine abnormalities,4 and malformations.7 Still, these
factors explain only a minority of preterm deliveries, and
apart from smoking most of the factors are not immedi-
ately preventable.
It remains controversial whether there is a safe level of
drinking during pregnancy,8,9 and whether alcohol in-
take in early or late pregnancy is of most importance.10,11
Intake of about one drink/day or more has consistently
been shown to be associated with reduced birth weight
and intrauterine growth restriction,12–14 and heavy ma-
ternal alcohol consumption is consistently found to be
associated with malformations,15 mental retardation,16 as
From 1Perinatal Epidemiological Research Unit, Department of Obstetrics, and
Gynaecology, Aarhus University Hospital, 8000 Aarhus C, Denmark and 2Ma-
ternal Nutrition Group, Danish Epidemiology Science Centre, Statens Serum
Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
Address correspondence to: Ulrik Kesmodel, Perinatal Epidemiological Research
Unit, Department of Obstetrics and Gynaecology, Skejby Sygehus, Aarhus
University Hospital, 8200 Aarhus N, Denmark.
This research was supported by The Faculty of Health Sciences, Aarhus Uni-
versity, and The Danish Research Foundation.
Submitted July 27, 1999; final version accepted February 3, 2000.
Copyright © 2000 by Lippincott Williams & Wilkins, Inc.
512
respectively, compared with intake of ⬍1 drink/week at 16
weeks gestation, and 0.69 (95% CI ⫽ 0.56 – 0.86), 0.82 (95%
CI ⫽ 0.60 –1.13), 0.97 (95% CI ⫽ 0.58 –1.64), and 3.56 (95%
CI ⫽ 1.78 –7.13) at 30 weeks. Adjustment for smoking habits,
caffeine intake, age, height, pre-pregnant weight, marital sta-
tus, occupational status, education, parity, chronic diseases,
previous preterm delivery, mode of initiation of labor, and sex
of the child did not change the conclusions, nor did restriction
of the highest intake group to women drinking 10 –14 drinks/
week (RR ⫽ 3.41 (1.71– 6.81) at 16 weeks and RR ⫽ 3.47
(1.64 –7.35) at 30 weeks). (Epidemiology 2000;11:512–518)
well as behavioral and psychosocial problems in child-
hood and adolescence.17,18 With regard to preterm de-
livery, however, results remain inconsistent.11,19 –21 Ex-
cessive alcohol consumption during pregnancy is
potentially preventable and clarification of the relation
between alcohol and preterm delivery is therefore im-
portant.
Few studies have had access to information on alcohol
at different points in time during pregnancy and on
specific subcategories of preterm delivery.22,23 We exam-
ined the association between maternal alcohol con-
sumption during pregnancy and preterm delivery in a
Danish cohort of pregnant women with singleton preg-
nancies, using information on alcohol intake prospec-
tively collected twice during pregnancy as well as pro-
spective information on other life style factors, maternal
risk factors and obstetrical risk factors.
Subjects and Methods
STUDY POPULATION AND SELECTION PROCEDURE
All Danish-speaking pregnant women attending routine
antenatal care at the Department of Obstetrics and
Gynaecology, Aarhus University Hospital, Denmark,
from August 1989 through August 1991, and from Sep-
tember 1992 through October 1996, were invited to
participate in the cohort study. Nearly all women in the
area comply with the antenatal care program. Women
attending antenatal care in the interim period were not
included, because information on a number of covariates
was not collected during this period. These women,
however, were comparable with those included in the
study with respect to alcohol intake, smoking habits,
age, height and pre-pregnant weight. At 16 weeks of
Epidemiology September 2000, Vol. 11 No. 5
gestation, women were asked to fill in two self-adminis-
tered questionnaires: one for the medical record provid-
ing information on concurrent maternal alcohol intake
(drinks/week) and smoking habits at 16 weeks of gesta-
tion, maternal age, height, pre-pregnant weight, parity,
chronic diseases, and previous preterm deliveries; and a
research questionnaire providing information on caf-
feine intake, marital status, occupational status, and
school education. At 30 weeks of gestation, another
research questionnaire was mailed to all participants
asking about concurrent maternal alcohol intake and
smoking habits.
Information on birth outcome, including mode of
initiation of labor, malformations, and sex of the baby,
was obtained from birth registration forms filled in by
the attending midwife immediately after delivery.
Data from all questionnaires for the medical record
have been entered into the database twice, while rele-
vant information from the research questionnaires was
validated by logical checks. All birth registration forms
were manually checked and compared with the medical
records by a research midwife before data entry.
Live, singleton pregnancies, in which the babies had
no malformation (N ⫽ 24,926) were eligible for this
study. We excluded pregnancies for which both ques-
tionnaires had not been returned (N ⫽ 4,198), pregnan-
cies with no information on delivery or birth outcome or
gestational age ⬎315 days, mostly pregnancies delivered
elsewhere (N ⫽ 1,504), and pregnancies for which the
particular question on alcohol intake had not been an-
swered (N ⫽ 996), leaving a total of 18,228 pregnancies
(73%) for analysis. The available data on distribution of
alcohol intake (N ⫽ 23,299) and smoking habits (N ⫽
24,278) at 16 weeks of gestation indicated that pregnan-
cies included in and those excluded from this study
differed little on these variables. For 15,686 of the
18,228 pregnancies the 30 weeks’ questionnaire was
returned (mean gestational age at time of completing
the questionnaire: 212 days). These pregnancies were
comparable with those for which the questionnaire at 16
weeks had been filled in with respect to the distribution
of all covariates presented in Table 1.
Response to questions on alcohol consumption was
precoded into ⬍1, 1–2, 3– 4, 5–9, 10 –14, 15–19, 20 –29,
30 –39, ⱖ40 drinks/week. Owing to small numbers in
the highest alcohol intake categories, we categorized
information on alcohol into five groups for analysis (⬍1
drink/week, 1–2 drinks/week, 3– 4 drinks/week, 5–9
drinks/week, ⱖ10 drinks/week). The definition of a
drink followed the definition of the Danish National
Board of Health, one drink containing 12 gm or 15 ml of
pure alcohol, the equivalent of one normal beer, one
glass of wine or 4 ml of spirits. We calculated caffeine
intake from the average daily consumption of coffee (1
cup ⫽ 104 mg), tea (1 cup ⫽ 46 mg), drinking chocolate
(1 cup ⫽ 13 mg), and cola (1 bottle or 250 ml ⫽ 45
mg).24 Chronic diseases included all self-reported
chronic diseases, mostly hypertension, epilepsy, asthma,
allergies, and chronic bowel diseases. We categorized
initiation of labor into three groups (spontaneous; pre-
ALCOHOL IN PREGNANCY 513
mature rupture of membranes (PROM), induced labor)
on the basis of information at the beginning of labor,
independently of the final mode of delivery. Other co-
variates were categorized as in Table 1. All analyses were
performed first for alcohol intake at 16 weeks and sub-
sequently at 30 weeks, using smoking information at 16
and 30 weeks, respectively, for the multivariate analyses
described below.
We calculated gestational age at delivery from early
ultrasonographically determined biparietal diameter in
13,184 (72.3%) pregnancies. All ultrasound scans were
performed before 20 completed weeks of gestation. For
5,018 pregnancies without a valid ultrasound scan, we
calculated gestational age from the last menstrual period.
For the remaining 26 pregnancies with no ultrasound
scan and no valid date for the last menstrual period, we
used the gestational age as reported on the birth regis-
tration form by the attending midwife. We defined pre-
term delivery as gestational age ⬍37 completed weeks
(⬍259 days) of gestation.
STATISTICAL METHODS
We used risk ratios (RR) to express the unadjusted
associations and odds ratios (OR) for the adjusted asso-
ciations between alcohol intake and preterm delivery.
We used the lowest alcohol intake group (⬍1 drink/
week) as a reference category. In the multivariate logis-
tic regression analyses, we included all the covariates in
Table 1 that changed the unadjusted point estimate of
the highest alcohol intake category by more than 10%,25
and, in a separate model, all the covariates in Table 1
based on a priori information that they might potentially
confound the results.25 The two models turned out to be
identical. All covariates were entered as categorical,
creating indicator variables equal to the number of vari-
ables minus one.
Results
Mean gestational age at birth was 281.4 days, and the
overall rate of preterm delivery was 4.2% (758/18,228).
Compared with women drinking ⬍1 drink/week, gesta-
tional age decreased by an average of 3– 4 days for
women drinking ⱖ10 drinks/week, while gestational age
was increased for women drinking 1–2 drinks/week (Ta-
ble 2 and 3). Bivariate analyses showed that women
drinking ⱖ10 drinks/week had a nearly 3 times increased
risk of preterm delivery compared with women drinking
⬍1 drink/week, whereas women drinking 1–9 drinks/
week appeared to have a slightly decreased risk of pre-
term delivery; they also showed that preterm delivery
was associated with a number of other factors (Table 1).
Stratification by smoking habits, caffeine intake, and
chronic diseases did not change the conclusions (data
not shown). The increased risk of preterm delivery re-
mained high for women drinking ⱖ10 drinks/week
whether initiation of labor was spontaneous, induced, or
due to PROM (Table 4).
Multivariate logistic regression analysis allowing for
potential confounding by smoking at 16 weeks of gesta-
514 Kesmodel et al Epidemiology September 2000, Vol. 11 No. 5

TABLE 1. Distribution and Unadjusted Risk Ratio of Preterm Delivery within Categories of Lifestyle Factors, Maternal
Risk Factors, and Obstetrical Risk Factors (N ⴝ 18,228)* (For alcohol intake and smoking at 30 weeks N ⴝ 15,686*)

Preterm
N N % RR 95% CI†
Alcohol at 16 weeks (drinks/week)
⬍1† 12,479 533 4.3 1.00
1–2 4,084 158 3.9 0.91 0.76–1.08
3–4 1,257 46 3.7 0.86 0.64–1.15
5–9 344 13 3.8 0.89 0.52–1.52
ⱖ10 64 8 12.5 2.93 1.52–5.63
Alcohol at 30 weeks (drinks/week)
⬍1† 10,183 400 3.9 1.00
1–2 3,790 103 2.7 0.69 0.56–0.86
3–4 1,297 42 3.2 0.82 0.60–1.13
5–9 366 14 3.8 0.97 0.58–1.64
ⱖ10 50 7 14.0 3.56 1.78–7.13
Smoking at 16 weeks (cigarettes/day)
0† 13,013 464 3.6 1.00
1–9 2,223 108 4.9 1.36 1.11–1.67
ⱖ10 2,568 173 6.7 1.89 1.60–2.24
Smoking at 30 weeks (cigarettes/day)
0† 11,624 364 3.1 1.00
1–9 1,746 59 3.4 1.08 0.82–1.41
ⱖ10 2,265 141 6.2 1.99 1.65–2.40
Caffeine (mg/day)
⬍400† 12,666 480 3.8 1.00
ⱖ400 5,562 299 5.0 1.32 1.14–1.52
Maternal age (years)
⬍20 208 14 6.7 1.68 1.00–2.82
20–24 2,562 124 4.8 1.21 0.99–1.48
25–29† 7,523 301 4.1 1.00
30–34 5,685 207 3.6 0.91 0.77–1.08
ⱖ35 2,250 112 5.0 1.24 1.01–1.54
Maternal height (cm)
⬍160 1,234 67 5.4 1.32 1.01–1.72
160–164 3,752 182 4.9 1.18 0.97–1.43
165–169† 5,470 225 4.2 1.00
170–174 5,050 203 4.0 0.98 0.81–1.18
ⱖ175 2,427 67 2.8 0.67 0.51–0.88
Maternal prepregnant weight (kg)
⬍50 879 49 5.6 1.33 0.99–1.79
50–59† 6,785 284 4.2 1.00
60–69 6,713 261 3.9 0.93 0.79–1.10
70–79 2,336 96 4.1 0.98 0.78–1.23
ⱖ80 1,197 50 4.2 1.00 0.74–1.34
Marital status
Married/cohabiting† 17,290 699 4.0 1.00
Single 816 55 6.7 1.67 1.28–2.17
Occupational status
Employed† 11,728 468 4.0 1.00
Not employed 2,771 123 4.4 1.11 0.92–1.35
Rehabilitation/social security 1,020 67 6.6 1.65 1.29–2.11
Student 1,891 67 3.5 0.89 0.69–1.14
School education (years)
⬍10 1,840 95 5.1 1.47 1.18–1.84
10 5,427 272 5.0 1.43 1.23–1.67
⬎10† 10,409 365 3.6 1.00
Parity
0† 9,526 430 4.5 1.00
1 6,261 225 3.6 0.80 0.68–0.93
ⱖ2 2,441 103 4.2 0.94 0.76–1.15
Chronic diseases
No† 17,521 715 4.1 1.00
Yes 707 43 6.1 1.49 1.11–2.01
Previous preterm delivery
No† 17,532 659 3.8 1.00
Yes 696 99 14.2 3.78 3.11–4.61
Initiation of labor
Spontaneous† 12,091 261 2.2 1.00
Premature rupture of membranes 3,664 260 7.1 3.29 2.78–3.89
Induced 2,451 236 9.6 4.46 3.76–5.29
Sex of child
Boy† 9,353 404 4.3 1.00
Girl 8,874 354 4.0 0.92 0.80–1.06
* For some covariates N does not sum to the total N owing to missing information for some individuals.
95% CI: 95% confidence interval for the risk ratio.
† Referent category.
Epidemiology September 2000, Vol. 11 No. 5 ALCOHOL IN PREGNANCY 515

TABLE 2. Mean Gestational Age and Adjusted Odds Ratios (OR) for Pre- was little changed in multivariate
term Delivery by Alcohol Intake Level at 16 Weeks of Gestation analyses (OR ⫽ 3.46, 95% CI ⫽ 1.45–
8.25).
Mean Gestational
Age Using information on alcohol in-
Alcohol Intake take at 30 weeks of gestation, rather
(drinks/wk) N Days SD OR 95% CI
than at 16 weeks, resulted in similar
⬍1† 12,479 281.3 12.8 1.00 unadjusted effect estimates (Table 1),
1–2 4,084 281.8 12.9 0.90 0.74–1.10 and women drinking 1–2 drinks/week
3–4 1,257 281.5 12.4 0.72 0.51–1.01
5–9 344 281.6 11.3 0.74 0.41–1.36 had a substantially decreased risk of
ⱖ10 64 277.1 17.9 2.76 1.24–6.13 preterm delivery. The increased risk of
† Referent category. preterm delivery remained high for
women drinking ⱖ10 drinks/week
whether initiation of labor was spon-
tion, caffeine intake, maternal age, height, pre-pregnant taneous, or due to PROM (Table 6). Stratified analyses
weight, marital status, occupational status, school edu- and multivariate regression analyses using information
cation, parity, chronic diseases, previous preterm deliv- on smoking at 30 weeks of gestation as described above
eries, mode of initiation of labor, and sex of the child, did not change these conclusions (Table 3). Truncation
yielded comparable results (Table 2). When controlling of the highest alcohol intake group at 14 drinks/week did
for alcohol intake at 30 weeks of gestation in the regres- not change this conclusion for women drinking 10 –14
sion model, the odds ratio decreased for the highest drinks/week (N ⫽ 44, 6 preterm): OR ⫽ 3.47 (95%
intake group from 2.76 (95% CI ⫽ 1.24 – 6.13) (Table 2) CI ⫽ 1.64 –7.35). When controlling for alcohol intake
to 1.41 (95% CI ⫽ 0.39 –5.18), and when stratifying at 16 weeks of gestation in the regression model the risk
alcohol intake at 16 weeks by intake at 30 weeks, the of preterm delivery remained high for the high intake
association completely disappeared (Table 5). Similar group: OR ⫽ 3.00 (95% CI ⫽ 1.02– 8.80), and when
regression analyses (excluding mode of initiation of la- stratifying alcohol intake at 30 weeks by intake at 16
weeks the association remained high (Table 5). Restrict-
bor) for each type of preterm delivery did not substan-
ing analyses to the women’s first pregnancy in the cohort
tially change the unadjusted estimates.
resulted in estimates of association of a similar magnitude.
To eliminate confounding of the estimates by effects
of excessive use of alcohol, we reanalysed data truncat-
ing the highest alcohol intake group at 14 drinks/week. Discussion
This categorization resulted in a risk ratio for the group We found that women reporting an alcohol intake of
of women drinking 10 –14 drinks/week (N ⫽ 48, 7 ⱖ10 drinks/week had a 3 times higher risk of preterm
preterm) of 3.38 (95% CI ⫽ 1.70 – 6.73). This estimate delivery compared with women drink-
ing ⬍1 drink/week even after adjust-
TABLE 3. Mean Gestational Age and Adjusted Odds Ratios (OR) for Pre- ment for a number of covariates.
term Delivery by Alcohol Intake Level at 30 Weeks of Gestation Women reporting intake of 1–2
drinks/week had a decreased risk of
Mean Gestational preterm delivery compared with
Age
Alcohol Intake women drinking ⬍1 drink/week even
(drinks/wk) N Days SD OR 95% CI after adjustment for a number of co-
⬍1† 10,183 281.7 11.7 1.00 variates, particularly when using infor-
1–2 3,790 282.4 11.2 0.70 0.55–0.88 mation at 30 weeks of gestation. Fol-
3–4 1,297 282.3 11.1 0.76 0.55–1.08 lowing this pattern mean gestational
5–9 366 281.8 12.5 0.86 0.49–1.51
ⱖ10 50 278.3 14.7 3.10 1.30–7.36 age was decreased for women drinking
† Referent category.

TABLE 4. Unadjusted Risk Ratio (RR) for Subtypes of Preterm Delivery by Alcohol Intake Level at 16 Weeks of Gestation

Premature Rupture of
Spontaneous Preterm Delivery Membranes Induced Preterm Delivery
Preterm Preterm Preterm
Alcohol Intake
(drinks/wk) N n RR 95% CI n RR 95% CI n RR 95% CI
⬍1† 12,612 183 186 164
1–2 4,076 55 0.91 0.67–1.22 47 0.79 0.58–1.08 55 1.07 0.80–1.44
3–4 1,257 15 0.80 0.48–1.35 19 1.00 0.63–1.57 12 0.78 0.45–1.38
5–9 344 5 1.01 0.42–2.43 6 1.11 0.51–2.43 2 0.40 0.11–1.69
ⱖ10 63 3 3.22 1.07–9.67 2 3.39 1.01–11.33 3 2.36 0.88–6.53
† Referent category.
516 Kesmodel et al Epidemiology September 2000, Vol. 11 No. 5

TABLE 5. Unadjusted Risk Ratios (RR) for Preterm Delivery by Alcohol
Intake Level (Drinks/Week) at 16 Weeks of Gestation Stratified by Intake at 30
Weeks of Gestation and Vice Versa
Alcohol Intake Alcohol Intake
16 weeks 30 weeks N RR
ⱖ10 ⱖ10 19 4.03
ⱖ10 ⬍10 27 0.95
⬍10 ⱖ10 31 3.29
Referent category: ⬍1 drink/week at 16 and 30 weeks of gestation.
ⱖ10 drinks/week and increased for women drinking 1–2
drinks/week.
The rate of preterm delivery that we found was lower
than in many other studies but comparable with the
usual rate of preterm delivery in Denmark.26,27 Previous
studies have described an increased risk of preterm de-
livery and shorter gestation among alcoholics.28,29 The
results of Berkowitz et al showed that ⱖ14 drinks/week
may increase the risk of preterm delivery 3 times, and
the result appeared as a threshold level at 14 drinks/week
with no effect below this level.19 Little et al reported no
effect of alcohol during pregnancy, but found increasing
risk of preterm delivery with increasing consumption
before pregnancy.12 One study reported increased risk of
preterm delivery at substantially lower intake levels in
late pregnancy, but was unable to detect any effect
whatsoever of drinking in early pregnancy.11 Also a few
studies have reported that intake of 6 –10 drinks/week
may shorten gestation.10,30,31 Others, however, have been
unable to find any association between alcohol intake
and gestational age or preterm delivery.5,20,21,32–35
We found no major difference in the effect of alcohol
between women experiencing PROM, spontaneous or
induced preterm delivery, although the pathophysiolog-
ical mechanisms underlying these separate entities of
preterm delivery are probably different. To our knowl-
edge only two other studies have investigated potential
differences between these presumably separate causal
pathways of preterm delivery.22,23 Both studies found an
increased risk of induced preterm delivery. Adams et al
also found a slightly increased risk of spontaneous pre-
term labor/PROM (one group), whereas Harlow et al
found a slightly increased risk of preterm PROM, but a
decreased risk if any on spontaneous preterm delivery.
We believe that our data on mode of initiation of labor
have high validity, because they were
recorded and subsequently double
checked by independent midwives.
Nevertheless, the numbers in the
95% CI highest intake category were small.
The relation in our data between
1.42–11.43
0.14–6.48 alcohol intake during pregnancy and
1.31–8.26 preterm delivery appeared to be
J-shaped, particularly when using in-
formation on alcohol intake from late
pregnancy, indicating that women
with an intake of 1–2 drinks/week may have a slightly
decreased risk of preterm delivery compared with women
drinking ⬍1 drink/week. Other studies have described a
similar tendency,20,23,36 but this is the first study to report
a J-shaped association together with a threshold effect.
There may be different explanations for the J-shaped
curve: First, it may be due to the healthy drinker effect,
eg, that healthy women will generally tend to drink more
than women with chronic diseases; we adjusted for
chronic diseases, but disease status was self reported, and
some misclassification is likely to have taken place (eg,
epileptics not currently in medical treatment may have
underreported disease status, and women reporting aller-
gies may in fact not have been true allergic persons).
Second, intake of small amounts of alcohol may be
associated with a generally more healthful lifestyle.
Third, if women with a high alcohol intake not only
underreport but also completely deny their alcohol con-
sumption, the result might be seen as an apparent in-
crease in risk among women drinking ⬍1 drink/week.
Finally, the J-shape may have a biologic—as yet un-
known— explanation.
It is well known that alcohol intake is usually under-
reported in questionnaires and interviews compared
with dairies,37,38 and a certain amount of underreporting
must be expected. Comparing our questionnaire data
with information on alcohol intake obtained from a
more elaborate, personal interview found a slight ten-
dency toward underreporting in the questionnaire.39 If
the reference group is large, however, underreporting
usually has little effect on the association between ex-
posure and outcome.40 Further, it is interesting to notice
that underreporting of alcohol intake may mask a true
threshold effect as a dose-response relation.40 Our find-
ing of a threshold effect thus cannot be attributed to

TABLE 6. Unadjusted Risk Ratio (RR) for Subtypes of Preterm Delivery by Alcohol Intake Level at 30 Weeks of Gestation

Premature Rupture of
Spontaneous Preterm Delivery Membranes Induced Preterm Delivery
Preterm Preterm Preterm
Alcohol Intake
(drinks/wk) N n RR 95% CI n RR 95% CI n RR 95% CI
⬍1† 10,170 137 134 128
1–2 3,784 30 0.57 0.39–0.85 41 0.83 0.59–1.16 32 0.77 0.53–1.12
3–4 1,297 12 0.70 0.39–1.25 19 1.07 0.68–1.71 11 0.67 0.37–1.21
5–9 366 4 0.82 0.31–2.20 6 1.15 0.52–2.52 4 0.93 0.36–2.40
ⱖ10 50 4 6.54 2.59–16.54 3 5.10 2.00–13.05 0
† Referent category.
Epidemiology September 2000, Vol. 11 No. 5
misclassification, although underreporting may have set
the threshold too low.
Gestational age was calculated from either early ul-
trasound scans or from last menstrual period. Restricting
analyses to women with valid ultrasound scans did not
change the conclusions (data not shown).
Even though this is one of the largest studies so far in
this area, the size and distribution of drinkers limits the
analysis. Thus, very few women reported an intake of
more than 14 drinks/week, making it impossible to assess
effects above this level. Examining the effect on very
preterm delivery (before 32 completed weeks of gesta-
tion) was also hampered by small numbers. The results,
however, were similar to those for preterm delivery, the
associations being even stronger for very preterm deliv-
ery (RR ⫽ 5.27 (95% ⫽ 1.32–21.01) for ⱖ10 drinks/
week at 16 weeks of gestation compared with ⬍1 drink/
week), which is well in line with an earlier report.22
The risk of preterm delivery was slightly higher when
using information on alcohol intake at 30 rather than 16
weeks of gestation. Although few women changed their
drinking habits substantially during the months between
filling in the questionnaires (data not shown), they
appeared enough to allow an informative analysis. Thus,
the regression models remained stable when including
alcohol intake at both points in time, and it seemed that
the apparent effect of alcohol intake at 16 weeks could
be explained by confounding effects of alcohol intake at
30 weeks of gestation. This conclusion was supported by
stratifying alcohol intake at 16 weeks by intake at 30
weeks and vice versa (Table 5). Only 86% of the women
filling in the questionnaire at 16 weeks filled in the
questionnaire at 30 weeks. These women, however, did
not differ much with regard to any of the covariates, and
restricting analyses at 16 weeks to women who had filled
in the questionnaire at 30 weeks did not change the
conclusions either.
Women drinking ⱖ10 drinks/week were older,
smoked more, were less well educated, and were more
often single than women with a lower alcohol intake
(data not shown). Women with a high alcohol intake
are also likely to differ with regard to a large number of
other socio-demographic factors not included in the
analyses leaving ample room for potential, unadjusted
(residual) confounding. Causal inferences should there-
fore be made with great caution.
The pathophysiology of how alcohol would induce
preterm delivery may be related to prostaglandins. Pros-
taglandins play an important role in relation to fetal
development and birth. Animal models have shown that
alcohol increases the production of prostaglandins, in-
cluding prostaglandins of the E series.41– 44 Prostaglandins
increase the cAMP activity thereby decreasing cell di-
vision,42,43 and an association between high levels of
cAMP and low birth weight has been described.44 In
humans, increased secretion of prostaglandins and
thromboxanes has been found in alcoholics and their
offspring.45
Our data suggest that the relation between alcohol
intake in pregnancy and preterm delivery may be J-
ALCOHOL IN PREGNANCY 517
shaped, with a threshold for adverse effect at 10 –14
drinks/week. This risk was independent of whether pre-
term labor was spontaneous, induced or due to PROM.
The risk seemed highest when using data on alcohol
intake in late pregnancy. The conclusion thus agrees
with the new recommendations from the Danish Na-
tional Board of Health, which suggest that there seems
to be a threshold effect for the adverse effect of alcohol
in pregnancy at one drink per day.
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