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Are there common triggers of preterm deliveries?
British Journal of Obstetrics and Gynaecology June 2001, Vol. 108, pp. 598±604
Are there common triggers of preterm deliveries? E. Petridou a,b,*, H. Salvanos c, A. Skalkidou a, N. Dessypris a, M. Moustaki a, D. Trichopoulos a,b Objective To assess the effect(s) of transient events which are perceived as stressful on the inseption of preterm delivery. Design A case±control study, with immature infants as cases and borderline term babies as controls. Setting A teaching maternity hospital in Athens. Population All infants born at less than 37 weeks of gestation, during a twelve-month period. Methods Information was collected about maternal socio-demographic and lifestyle characteristics, clinical variables and stressful events occurring within two weeks prior to delivery. Main outcome measures Factors affecting the risk of preterm delivery. Results Extreme prematurity (,33 weeks) is more common among younger (,25 years of age) and older (.29 years of age) women and is positively associated with parity, body mass index and smoking, whereas it is inversely associated with educational level, regular physical exercise and serious nausea/vomiting. After controlling for these factors, however, only coitus during the last weeks of pregnancy had a signi®cant triggering effect on prematurity (P 0.004, odds ratio 3.21, 95% CI 1.45 to 7.09 for very immature babies, and P 0.04, OR 2.20, 95% CI 1.03 to 4.70 for immature babies). On the contrary, several events perceived as stressful, such as illness of relatives or friends, husband's departure, loss of employment, were unrelated to the onset of premature labour. Conclusions Coitus during the last few weeks of pregnancy appears to increase the risk of preterm delivery, while a possible detrimental effect of physical exertion seems more limited. Stressful events should not receive undue attention as possible causes of preterm delivery.
INTRODUCTION Prematurity is associated with a large proportion of perinatal morbidity and mortality 1±6. Predictors of prematurity may be classi®ed in several ways, depending on the perspective 1,2,7±11. Among the factors considered in the literature, some affect the process of gestation, notably antenatal bleeding, chronic urinary tract infection, smoking and structural or functional uterine abnormalities. Others are generally of a transient nature and are thought of as triggers of preterm delivery 1,2,8,9, such as physical exertion, psychological stress and sexual intercourse. A study of the literature shows there is no agreement whether these factors, alone or in conjunction with more chronic factors that affect the process of gestation, are important triggers for preterm delivery, since there are studies which both support 12±20 and refute 21±29 the
a
Department of Hygiene and Epidemiology, Athens University Medical School, Greece b Department of Epidemiology, Harvard School of Public Health, Massacusetts, USA c Marika Iliadi Maternity Hospital, Athens, Greece * Correspondence: Dr E. Petridou, Department of Hygiene and Epidemiology, Athens University Medical School, 75 M. Asias st., 11527 Athens, Greece. q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S03 06-5456(00)0014 0-6
triggering role hypothesis. An important methodological complication is the likelihood of information (or reporting) bias: that is, women who have had a premature baby may be more likely to report adequately or over-report events that may be overlooked by women with a normal delivery. In order to assess the effect(s), of transient, perceived as stressful, events on the inception of delivery, we undertook a case±control study in Athens, Greece. We compared cases, de®ned as very premature (,33 gestational weeks) or premature (33-35 weeks) babies with borderline term (36-37 weeks) babies. METHODS During a 12-month period 5332 babies were delivered at Marika Iliadi maternity hospital from 1 January 1998 to 31 December 1998. Of these babies, 82 were twins (41 pairs) and 5250 were singletons. Of the singletons, 351 were born after a gestational period of less than 37 weeks. The mothers of 20 (6%) of these children were unable or unwilling to provide information, whereas for 86 of the remaining 331 immature babies, delivery was planned for various reasons. A total of 245 spontaneous and PROM (premature rupture of membranes) deliveries of singleton premature or borderline term babies, together with their mothers, were investigated in this study. Ninety-two very www.bjog-elsevier.com
COMMON TRIGGERS OF PRETERM DELIVERY 599
preterm babies (de®ned as ,33 gestational weeks, calculated on the basis of the recorded last normal menstrual period; 92 babies) and 95 preterm babies (33-35 weeks) were included as cases. Controls included 58 borderline or near term babies born after gestation duration of at least 36 but less than 37 completed gestational weeks. Sonographic con®rmation of the gestational age was available for about 50% of the newborn infants (117/ 245). We have chosen to restrict controls to those who were born only marginally at term in order to minimise information bias. The mean (standard deviation) birthweight was 1460 g (632.2 g) for very immature babies, 2355 grams (461.4 g) for immature babies and 2750 g (650.0 g) for borderline term infants. A single medically
quali®ed researcher (H.S.) interviewed all the mothers in any of these categories within 48h of delivery. The standard pre-coded questionnaire covered information about socio-demographic, clinical, gynaecological and maternity variables in general, as well as a series of questions referring to operationally de®ned transient events that took place at least once during the last two weeks of pregnancy. These events could be conceivably, although not necessarily plausibly, thought of as having the potential to trigger a preterm delivery. The analysis was performed initially through single cross classi®cations. Subsequently, the data concerning prolonged exposure to variables that have been reported to affect prematurity were modelled through multiple
Table 1. Distribution of 245 mothers of singleton babies by gestational age, life status of the newborn, and a series of socio-demographic, lifestyle and pregnancy-related variables. Values are given as n, n (%). Variable
,33 weeks n
Age (years) ,25 25-29 30 1 Body mass index (kgr/m 2) ,20 20.0-22.4 22.5-24.9 25.0-27.4 27.5 1 Education (years) #9 10-15 16 1 Tobacco consumption No Yes Alcohol consumption No Yes Coffee consumption No Yes Serious nausea & vomiting No Yes Regular physical activity No Yes Parity 1 child 2 31 Newborn life status Alive Dead History of preterm delivery Yes No All mothers
33-35 weeks %
n
36-37 weeks %
n
%
23 25 44
25.0 27.2 47.8
28 22 45
29.5 23.1 47.4
12 19 27
20.7 32.8 46.5
25 20 18 12 17
27.2 21.7 19.6 13.0 18.5
19 27 27 11 11
20.0 28.4 28.4 11.6 11.6
13 16 12 10 7
22.4 27.6 20.7 17.2 12.1
43 42 7
46.7 45.7 7.6
35 49 11
36.8 51.6 11.6
22 25 11
37.9 43.1 19.0
57 35
62.0 38.0
73 22
76.8 23.2
45 13
77.6 22.4
90 2
97.8 2.2
94 1
98.9 1.1
58 0
100.0 0.0
32 60
34.8 65.2
50 45
52.6 47.4
25 33
43.1 56.9
61 31
66.3 33.7
57 38
60.0 40.0
30 28
51.7 48.3
84 8
91.3 8.7
87 8
91.6 8.4
46 12
79.3 20.7
41 30 26
42.3 30.9 26.8
60 23 17
60.0 23.0 17.0
32 18 13
50.8 28.6 20.6
69 23
75.0 25.0
89 6
93.7 6.3
56 2
96.5 3.5
17 75 92
18.5 81.5 100.0
16 79 95
16.8 83.2 100.0
10 48 58
17.2 82.8 100.0
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
600 E. PETRIDOU ET AL.
logistic regression (core model) 30. In the core model, a quantal (binary) variable concerning the life status of the newborn at the end of the ®rst 24 hours after the delivery was also included. Life status as a predictor variable accommodates confounding that can be introduced if the mother provides information of variable accuracy (more or less accurate) depending on the life status of the newborn. However, there may still be the potential of some residual bias, because the interviewer was not blind to gestational age. History of a transient event was subsequently introduced to assess whether this event had any effect on a preterm delivery after adjusting for the core variables and life status of the newborn. Variables concerning transient events were alternatively introduced in the model. Separate models were run for very premature and premature deliveries, always using a single control series, which was formed by the borderline term deliveries. The study was approved by the Ethics Committee of the University of Athens Medical School. All women participated following their consent to contribute to an investigation concerning conditions and events surround-
ing their ªrelatively earlyº delivery, without explicit mention of triggering events. RESULTS Table 1 shows the frequency distribution of a total of 245 mothers of singleton babies by gestational age of the newborn, a series of socio-demographic and pregnancy variables as well as life status of the newborn. The lifestyle variables, including physical activity, refer to the average behaviour throughout the pregnancy, whereas serious nausea and vomiting occur during the ®rst months of the pregnancy. Body mass index is calculated on the basis of the recorded pre-pregnancy weight. No woman in this study had a sexually transmitted disease during pregnancy or had been hospitalised for an infectious disease during that period. The data in Table 1 are univariate, and thus likely to be confounded, but the distribution patterns are similar to those derived from the literature. Table 2 shows multiple logistic regression-derived
Table 2. Multiple logistic regression-derived, mutually adjusted odds ratios (ORs) and 95% con®dence intervals (95% CI) for a very premature (,33 weeks) or a premature (33-35 weeks) delivery versus borderline term singleton delivery (36-37 weeks) by a series of prolonged-exposure factors (core model). Variable
Age (years)
Body mass index (kgr/m 2)
Parity Education Tobacco consumption Coffee consumption Serious nausea & vomiting Regular physical activity Additionally introduced variable Newborn life status
Category or increment
Very premature (,33 weeks) ORs
95% CIs
Premature (33-35 weeks) P
,25 25-29 30 1
1.23 Baseline 1.17
0.45
3.37
0.68
0.51
2.70
0.71
,20 20.0-22.4 22.5-27.4 27.5 1
1.23 0.77 Baseline 1.88
0.48 0.31
3.12 1.91
0.66 0.57
0.62
5.72
One more child (ordinal)
1.27
0.78
6 more years (ordinal)
0.75
No Yes
ORs
95% CIs
P
1.94 Baseline 1.47
0.69
5.43
0.21
0.65
3.29
0.35
0.28 0.35
1.81 2.05
0.48 0.71
0.27
0.71 0.84 Baseline 0.72
0.23
2.27
0.58
2.07
0.34
0.78
0.47
1.30
0.34
0.42
1.32
0.32
0.99
0.56
1.74
0.97
Baseline 1.88
0.82
4.28
0.14
Baseline 1.48
0.60
3.68
0.40
No Yes
Baseline 1.18
0.56
2.50
0.66
Baseline 0.70
0.34
1.43
0.33
No Yes
Baseline 0.50
0.23
1.06
0.07
Baseline 0.82
0.40
1.69
0.60
No Yes
Baseline 0.45
0.16
1.26
0.13
Baseline 0.30
0.11
0.83
0.02
Alive Dead
Baseline 10
2.2
50.0
0.003
Baseline 1.39
0.24
7.69
0.71
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
COMMON TRIGGERS OF PRETERM DELIVERY 601
mutually adjusted odds ratios for a very premature or preterm delivery, rather than a borderline term delivery in relation to prolonged exposure variables. Most ®ndings are not statistically signi®cant, but they point to expected directions. Thus, extreme prematurity is more common among younger and older women as compared with women 25±29 years old; tends to increase with increased parity and increased BMI; and tends to decline with higher education. Tobacco smoking increases the likelihood of extreme prematurity, whereas regular physical activity and serious nausea and vomiting are inversely related to extreme prematurity risk. There is also a highly signi®cant association between extreme prematurity and the likelihood of perinatal death. Results concerning premature (33±35 weeks) delivery are, in general, closer to the null, compared with those concerning extremely preterm delivery. Table 2 provides the context of the study but does not address issues surrounding possible consequences of transient stressful events. In Table 3 the number and percentages of speci®ed transient exposures, by gestational age at delivery, during the last two weeks of the respective pregnancy are shown. The interpretation of these data requires comparison of the corresponding proportions across three categories of gestational age at delivery, as well as control for the prolonged exposure predictors of prematurity shown in Table 2. Confounding does not depend on statistical signi®cance and thus, non- signi®-
cantly associated factors in Table 2 still need to be accounted for 31. Table 4 shows multiple logistic regression-derived odds ratios for a very premature singleton delivery without adjustment (®rst two columns), after adjustment for stable risk factors of prematurity (second two columns) and after adjustment for stable risk factors of prematurity as well as for life status of the newborn (as a predictor for over reporting or more complete reporting; last two columns). Table 5 is of similar structure, but it concerns premature rather than very premature deliveries. Interpretation of the results require, in addition to biological plausibility, a degree of consistency between Tables 4 and 5 and a gradient of odds ratios from very premature to immature babies. For two of the variables in Table 3, (loss of job of self or husband and imprisonment or court appearance of a close family member) and for one variable in Table 5 (separation from spouse) no event was recorded in the respective case series. Thus, only Fisher's P value could be calculated. In all these instances, however, the respective P-value was far from signi®cant and in all three instances the event appeared to be inversely associated with preterm delivery, a biologically implausible relation. For only two of the variables were the results statistically signi®cant, consistent or descriptively impressive: (Tables 4 and 5). Thus, for none of the statistically unrelated variables can be inferred that they have a triggering
Table 3. Distribution of 245 mothers of singleton babies by gestational age and speci®ed transient exposures during the last two weeks of index pregnancy. Variable
Serious personal injury Serious illness, immediate family Serious injury, immediate family Serious illness or injury, close friend or relative Serious disruption by a guest visit Serious family quarrel Quarrel with spouse Quarrel with spouse's family Husband's departure Expulsion from house Loss of employment of self or husband Serious ®nancial problem Court appearance or imprisonment Personal illness Other unpleasant event New medication Insomnia Sunbathing Exposure to cold weather conditions Intense house cleaning Great physical exertion Travel Sexual intercourse All mothers
,33 weeks
33-35 weeks
36-37 weeks
n
%
n
%
n
%
4 3 5 2 15 25 5 4 10 3 0 15 0 34 34 24 15 2 2 32 45 11 51 92
4.4 3.3 5.4 2.2 16.3 27.2 5.4 4.4 10.9 3.3 0.0 16.3 0.0 37.0 37.0 26.1 16.3 2.2 2.2 34.8 48.9 12.0 55.4 100.0
1 3 1 4 15 15 0 4 2 5 1 6 2 34 18 19 21 3 1 22 56 6 43 95
1.1 3.2 1.1 4.2 15.8 15.8 0.0 4.2 2.1 5.3 1.1 6.3 2.1 35.8 19.0 20.0 22.1 3.2 1.1 23.2 59.0 6.4 45.3 100.0
2 1 1 4 12 8 1 3 3 1 1 5 1 18 18 15 14 2 2 18 28 4 16 58
3.5 1.7 1.7 6.9 20.7 13.8 1.7 5.2 5.2 1.7 1.7 8.6 1.7 31.0 31.0 25.9 24.1 3.5 3.5 31.0 48.3 6.9 27.6 100.0
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
602 E. PETRIDOU ET AL. Table 4. Multiple logistic regression-derived, adjusted for the core model variables odds ratios (ORs) and 95% con®dence intervals (95% CIs) for a very premature delivery by speci®ed transient exposures during the last two weeks of the pregnancy. Variable
Serious personal injury Serious illness, immediate family Serious injury, immediate family Serious illness or injury, close friend or relative Serious disruption by a guest visit Serious family quarrel Quarrel with spouse Quarrel with spouse's family Husband's departure Expulsion from house Loss of employment of self or husband Serious ®nancial problem Court appearance or imprisonment Personal illness Other unpleasant event New medication Insomnia Sunbathing Exposure to cold weather conditions Intense house cleaning Great physical exertion Travel Sexual intercourse
Crude
Core model without life status
Core model with life status
OR
P
OR
P
OR
1.27 1.92 3.28 0.30
0.78 0.58 0.28 0.17
1.27 1.27 3.48 0.40
0.80 0.84 0.30 0.37
0.94 0.87 2.61 0.50
0.13 0.06 0.22 0.07
6.92 12.58 31.45 3.74
0.95 0.92 0.45 0.50
0.75 2.33 3.28 0.83 0.45 1.92 -
0.50 0.06 0.28 0.82 0.24 0.58 0.38
0.65 2.76 2.67 0.66 0.54 3.05
0.36 0.04 0.40 0.63 0.41 0.39
0.70 2.23 2.88 0.83 0.72 4.10
0.27 0.83 0.28 0.15 0.14 0.32
1.80 6.03 29.95 4.66 3.61 52.43
0.46 0.11 0.38 0.84 0.68 0.28
2.1 -
0.18 0.39
1.68
0.38
1.88
0.57
6.19
0.30
1.30 1.30 1.01 0.61 0.62 0.62
0.46 0.46 0.97 0.24 0.64 0.64
1.54 1.69 1.02 0.55 1.34 0.45
0.27 0.19 0.96 0.20 0.80 0.51
1.80 1.51 1.18 0.68 1.28 0.31
0.80 0.66 0.50 0.27 0.10 0.02
4.04 3.46 2.78 1.71 15.65 4.25
0.16 0.33 0.70 0.41 0.84 0.38
1.19 1.03 1.83 3.27
0.64 0.94 0.32 0.001
1.23 1.12 1.58 3.25
0.61 0.77 0.49 0.002
1.04 0.89 1.52 3.21
0.45 0.39 0.41 1.45
2.42 1.99 5.69 7.09
0.92 0.77 0.53 0.004
role on the onset of delivery. For one of the remaining two variables, great physical exertion in the last two weeks of pregnancy, there is weak evidence that it may affect premature, but not very preterm delivery. Thus, the pattern is overall unconvincing, although it can not conclusively be refuted. The other exception concerns ªsexual intercourse during the last two weeks of pregnancyº and the relevant results appear to be more credible. One or more acts of intercourse during the last two weeks of pregnancy appear to double the likelihood of a preterm delivery and triple the risk of a very preterm delivery. The association is not affected by control for either prolonged exposure variables or life status of the newborn and is robust with respect to statistical signi®cance. For very premature deliveries, rupture of the membranes may be an important intermediate factor (odds ratios: with membrane rupture 3.68; without membrane rupture 2.87). There is no such evidence, however, for premature deliveries (odds ratios: with membrane rupture 2.04; without membrane rupture 2.31). We have also evaluated the plausible hypothesis that an accumulation of several transient events may be able to trigger a preterm delivery, although each one of these events was innocuous. There was no such evidence in these data: an additive score of all stressful transient events in a particular woman, with exception of sexual
95% CI
P
intercourse, was unrelated to either premature or very preterm delivery. DISCUSSION The results of this study indicate that coitus and perhaps physical exertion during the later stages of gestation may increase the risk of a preterm delivery, although to a rather modest degree. On the contrary, we found no evidence that psychological stress can precipitate preterm delivery. The study design, did not allow evaluation of possible interactions between prolonged exposure characteristics (i.e. maternal age or regular smoking during pregnancy on the one hand, and triggering factors of physical of psychological nature on the other). Among the drawbacks of the present study is that the rarity of some transient events, in combination with the moderate size of the study, tends to reduce statistical power. Nevertheless, these are inherent problems that cannot easily be dealt with and in any case our study had comparable power to that of other similar investigations in the literature 15,26,32,33. Recently, there have been several studies utilizing the case±crossover design to assess transient effects 34±36. However, this elegant method is not applicable in situations where the underq RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
COMMON TRIGGERS OF PRETERM DELIVERY 603 Table 5. Multiple logistic regression-derived, adjusted for the core model variables odds ratios (ORs) and 95% con®dence intervals (95% CIs) for a premature delivery by speci®ed transient exposures during the last two weeks of the pregnancy. Variable
Serious personal injury Serious illness, immediate family Serious injury, immediate family Serious illness or injury, close friend or relative Serious disruption by a guest visit Serious family quarrel Quarrel with spouse Quarrel with spouse's family Husband's departure Expulsion from house Loss of employment of self or husband Serious ®nancial problem Court appearance or imprisonment Personal illness Other unpleasant event New medication Insomnia Sunbathing Exposure to cold weather conditions Intense house cleaning Great physical exertion Travel Sexual intercourse
Crude
Core model without life status
Core model with life status
OR
P
OR
P
OR
0.30 1.86 0.61 0.59
0.33 0.60 0.73 0.47
0.27 1.20 0.91 0.82
0.32 0.88 0.95 0.80
0.27 1.15 0.91 0.83
0.02 0.11 0.04 0.18
3.71 12.34 23.27 3.84
0.33 0.91 0.96 0.81
0.72 1.17 0.81 2.53 3.17 0.61
0.44 0.74 0.38 0.78 0.32 0.30 0.73
0.66 1.40
0.38 0.52
0.66 1.41
0.26 0.50
1.65 3.92
0.38 0.51
1.17 2.33 3.76 0.84
0.85 0.39 0.26 0.90
1.19 2.28 3.65 0.84
0.23 0.33 0.36 0.04
6.25 15.89 36.67 15.75
0.84 0.40 0.27 0.90
0.72 1.23
0.59 0.87
0.79 0.93
0.73 0.95
0.80 0.94
0.22 0.08
2.96 11.80
0.74 0.96
1.24 0.52 0.72 0.89 0.91 0.30
0.55 0.09 0.40 0.77 0.92 0.33
1.49 0.50 0.75 0.93 2.39 0.44
0.32 0.08 0.49 0.86 0.43 0.56
1.51 0.50 0.74 0.92 2.41 0.45
0.69 0.23 0.32 0.41 0.28 0.03
3.34 1.10 1.70 2.08 20.68 6.65
0.31 0.09 0.47 0.84 0.42 0.56
0.67 1.54 0.91 2.17
0.28 0.20 0.89 0.03
0.75 2.21 1.13 2.21
0.49 0.04 0.87 0.04
0.75 2.22 1.16 2.20
0.33 1.05 0.27 1.03
1.72 4.68 4.98 4.70
0.50 0.04 0.85 0.04
lying probability density of a phenomenon, in this instance delivery, increases with gestational age. On the other hand, the study also has several advantages. An important advantage is the choice of a control group that allowed the effect of information bias to be minimised, because mothers of immature babies and mothers of marginally term babies are likely to share a psychology which is very different to a mother of a full term baby. Infants born at 35±36 weeks of gestation are not different from full term babies with respect to survival and residual disabilities 37. Therefore, infants of this gestational age can be considered as controls. Moreover, by controlling for life status of the newborn in the analysis, we have further reduced the likelihood of information bias, which may operate with particular force among mothers of stillborn babies. The majority of studies in the literature indicate that psychological factors may trigger a preterm delivery 12± 14,18 , although studies suggesting otherwise have also been reported 21,27. In our study no single factor of psychological stress was signi®cantly related to preterm delivery. Moreover, controlling for vital status of newborn had a tendency to bring the results closer to the null. There are several possible interpretations of this: it may be that most of the earlier studies did not adequately control q RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
95% CI
P
for information bias; that our study was not powerful enough to reveal a positive association of preterm delivery with one or more of the psychological stress-indicator variables; or that these variables were not properly re¯ecting psychological stress. We are inclined to accept the ®rst interpretation, but in any case, it seems that psychological variables used to assess the impact of essentially acute psychological stress do not have a strong triggering effect for a preterm delivery. Most previous studies 15,16,19, although by no means all 22,23,28, support the hypothesis that physical exertion can accelerate delivery. Our results provide some support for this hypothesis, although the evidence is limited to premature and does not appear to affect very premature deliveries. The converging evidence from the literature and the present study suggest that physical exertion may have an effect on preterm delivery but the association is of moderate strength. The literature concerning the effects of coitus on preterm delivery is contradictory: some studies indicate that there is such an effect 17,20, others that frequent sexual intercourse may increase the risk of a preterm delivery among women whose vagina is colonised by speci®c microorganisms 38, whereas others found no evidence for an effect of intercourse on the risk of
604 E. PETRIDOU ET AL.
prematurity 24±26,29. The mechanism through which coitus operates as a risk factor for preterm delivery should be further explored in order to identify pregnancies at increased risk. Our results cannot distinguish between the ®rst two hypotheses because we have no data concerning the effect of micro organism in vagina, but they tend to reject the third hypothesis that coitus at the later stage of pregnancy is innocuous. It is of interest that the detrimental effect concerns both very premature and immature babies, and it is robust to adjustment for possible confounders, including life status of the newborn. In conclusion, our study indicates that coitus during the last few weeks of pregnancy should be discouraged, as it appears to increase the risk of preterm delivery. The evidence concerning a possible detrimental effect of physical exertion is more limited, whereas we found no indication that psychological stress, as operationalised in our investigation, had any effect on preterm delivery.
15.
16. 17.
18. 19. 20. 21. 22. 23.
Acknowledgements The authors would like to thank Dr Sofatzis, Director of Neonatal Unit, Marika Iliadi Maternity Hospital, for his thoughtful comments and support in the preparation and execution of this project. This study was supported by departmental funds from the Department of Epidemiology, Harvard School of Public Health. References 1. Cunningham FG, MacDonald PC, Gant NF. Williams Obstetrics. Stamford, Connecticut: Appleton & Lange, 1997. 2. Berkowitz GS, Papiernik E. Epidemiology of preterm birth. Epidemiol Rev 1993;15:414±443. 3. Avery GB, Fletcher MA, MacDonald MG. Neonatology: Pathophysiology and Management of the Newborn. Philadelphia: Williams & Wilkins, 1999. 4. Weismiller DG. Preterm labor. Am Fam Physician 1999;59:593±602. 5. Erkkola R, Kero PO. Impact of prematurity on perinatal mortality and morbidity. Ann Med 1991;23:663±669. 6. LeFevre ML, Hueston WJ. Preterm birth. Prim Care 1993;20:639±653. 7. Goepfert AR, Goldenberg RL. Prediction of prematurity. Curr Opin Obstet Gynecol 1996;8:417±427. 8. Garbaciak Jr JA. Prematurity prevention: who is at risk? Clin Perinatol 1992;19:275±289. 9. Witter FR, Keith LG. Prematurity: Antecedents, Treatment, and Outcome. Boston: Little, Brown, & Co, 1993. 10. Yu VYH, Wood CE. Prematurity. New York: Churchill Livingstone, 1987. 11. Petridou E, Trichopoulos D, Tong D, et al. Modulators of length of gestation- a study in Greece. Eur J Public Health 1996;6:159±165. 12. Peacock JL, Bland JM, Anderson HR. Preterm delivery: effects of socio-economic factors, psychological stress, smoking, alcohol and caffeine. BMJ 1995;311:531±535. 13. Hedegaard M, Henriksen TB, Sabroe S, Secher NJ. Psychological distress in pregnancy and preterm delivery. BMJ 1993;307:234±239. 14. Hedegaard M, Henriksen TB, Secher NJ, Hatch MC, Sabroe S. Do
24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38.
stressful life events affect duration of gestation and risk of preterm delivery? Epidemiology 1996;7:339±345. Luke B, Mamelle N, Keith L, et al. The association between occupational factors and preterm birth: a United States nurses' study. Research Committee of the Association of Women's Health, Obstetric, and Neonatal Nurses. Am J Obstet Gynecol 1995;173:849±862. Hickey CA, Cliver SP, Mulvihill FX, McNeal SF, Hoffman HJ, Goldenberg RL. Employment-related stress and preterm delivery: a contextual examination. Public Health Rep 1995;110:410±418. Brustman LE, Raptoulis M, Langer O, Anyaegbunam A, Merkatz IR. Changes in the pattern of uterine contractility in relationship to coitus during pregnancies at low and high risk for preterm labor. Obstet Gynecol 1989;73:166±168. Istvan J. Stress, anxiety and birth outcomes: a critical review of the evidence. Psychol Bull 1986;100:331±348. Misra DP, Strobino DM, Stashinko EE, Nagey DA, Nanda J. Effects of physical activity on preterm birth. Am J Epidemiol 1998;147:628±635. Naeye RL. Coitus and associated amniotic ¯uid infections. N Engl J Med 1979;301:1198±1200. King RS, Kiser WR. Psychological distress and preterm delivery. Unconvincing link. BMJ 1993;307:934. Simpson JL. Are physical activity and employment related to preterm birth and low birth weight? Am J Obstet Gynecol 1993;168:1231±1238. Armstrong BG, Nolin AD, McDonald AD. Work in pregnancy and birth weight for gestational age. Br J Ind Med 1989;46:196±199. Kurki T, Ylikorkala O. Coitus during pregnancy is not related to bacterial vaginosis or preterm birth. Am J Obstet Gynecol 1993;169:1130±1134. Ekwo EE, Gosselink CA, Woolson R, Moawad A, Long CR. Coitus late in pregnancy: risk of preterm rupture of amniotic sac membranes. Am J Obstet Gynecol 1993;168:22±31. Neilson JP, Mutambira M. Coitus, twin pregnancy, and preterm labor. Am J Obstet Gynecol 1989;160:416±418. Stein A, Campbell EA, Day A, McPherson K, Cooper PJ. Social adversity, low birth weight and preterm delivery. BMJ 1987;295:291±293. Klebanoff MA, Shiono PH, Rhoads GC. Outcomes of pregnancy in a national sample of resident physicians. N Engl J Med 1990;323:1040± 1045. Mills JL, Harlap S, Harley EE. Should coitus late in pregnancy be discouraged? Lancet 1981;2:914±917. Breslow NE, Day NE. Statistical methods in cancer research. Volume 1: The analysis of case-control studies. IARC Sci Publ 1980;32:5±338. McMahon B, Trichopoulos D. Epidemiology: Principles and Practice. Boston: Little, Brown & Co, 1996. Menard MK, Newman RB, Keenan A, Ebeling M. Prognostic signi®cance of prior preterm twin delivery on subsequent singleton pregnancy. Am J Obstet Gynecol 1996;174:1429±1432. Toth M, Witkin SS, Ledger W, Thaler H. The role of infection in the etiology of preterm birth. Obstet Gynecol 1988;71:723±726. Petridou E, Mittleman MA, Trohanis D, Dessypris N, Karpathios T, Trichopoulos D. Transient exposures and the risk of childhood injury: a case-crossover study in Greece. Epidemiology 1998;9:622±625. Redelmeier DA, Tibshirani RJ. Association between cellular-telephone calls and motor vehicle collisions. N Engl J Med 1997;336:453±458. Mittleman MA, Maclure M, Robins JM. Control sampling strategies for case-crossover studies: an assessment of relative ef®ciency. Am J Epidemiol 1995;142:91±98. Goldenberg RL, Nelson KG, Hale CD, et al. Survival of infants with low birth weight and early gestational age 1979-1981. Am J Obstet Gynecol 1984;149:508±511. Read JS, Klebanoff MA. Sexual intercourse during pregnancy and preterm delivery: effects of vaginal microorganisms. Am J Obstet Gynecol 1993;168:514±519.
Accepted 16 January 2001
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
Are there common triggers of preterm deliveries? E. Petridou a,b,*, H. Salvanos c, A. Skalkidou a, N. Dessypris a, M. Moustaki a, D. Trichopoulos a,b Objective To assess the effect(s) of transient events which are perceived as stressful on the inseption of preterm delivery. Design A case±control study, with immature infants as cases and borderline term babies as controls. Setting A teaching maternity hospital in Athens. Population All infants born at less than 37 weeks of gestation, during a twelve-month period. Methods Information was collected about maternal socio-demographic and lifestyle characteristics, clinical variables and stressful events occurring within two weeks prior to delivery. Main outcome measures Factors affecting the risk of preterm delivery. Results Extreme prematurity (,33 weeks) is more common among younger (,25 years of age) and older (.29 years of age) women and is positively associated with parity, body mass index and smoking, whereas it is inversely associated with educational level, regular physical exercise and serious nausea/vomiting. After controlling for these factors, however, only coitus during the last weeks of pregnancy had a signi®cant triggering effect on prematurity (P 0.004, odds ratio 3.21, 95% CI 1.45 to 7.09 for very immature babies, and P 0.04, OR 2.20, 95% CI 1.03 to 4.70 for immature babies). On the contrary, several events perceived as stressful, such as illness of relatives or friends, husband's departure, loss of employment, were unrelated to the onset of premature labour. Conclusions Coitus during the last few weeks of pregnancy appears to increase the risk of preterm delivery, while a possible detrimental effect of physical exertion seems more limited. Stressful events should not receive undue attention as possible causes of preterm delivery.
INTRODUCTION Prematurity is associated with a large proportion of perinatal morbidity and mortality 1±6. Predictors of prematurity may be classi®ed in several ways, depending on the perspective 1,2,7±11. Among the factors considered in the literature, some affect the process of gestation, notably antenatal bleeding, chronic urinary tract infection, smoking and structural or functional uterine abnormalities. Others are generally of a transient nature and are thought of as triggers of preterm delivery 1,2,8,9, such as physical exertion, psychological stress and sexual intercourse. A study of the literature shows there is no agreement whether these factors, alone or in conjunction with more chronic factors that affect the process of gestation, are important triggers for preterm delivery, since there are studies which both support 12±20 and refute 21±29 the
a
Department of Hygiene and Epidemiology, Athens University Medical School, Greece b Department of Epidemiology, Harvard School of Public Health, Massacusetts, USA c Marika Iliadi Maternity Hospital, Athens, Greece * Correspondence: Dr E. Petridou, Department of Hygiene and Epidemiology, Athens University Medical School, 75 M. Asias st., 11527 Athens, Greece. q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S03 06-5456(00)0014 0-6
triggering role hypothesis. An important methodological complication is the likelihood of information (or reporting) bias: that is, women who have had a premature baby may be more likely to report adequately or over-report events that may be overlooked by women with a normal delivery. In order to assess the effect(s), of transient, perceived as stressful, events on the inception of delivery, we undertook a case±control study in Athens, Greece. We compared cases, de®ned as very premature (,33 gestational weeks) or premature (33-35 weeks) babies with borderline term (36-37 weeks) babies. METHODS During a 12-month period 5332 babies were delivered at Marika Iliadi maternity hospital from 1 January 1998 to 31 December 1998. Of these babies, 82 were twins (41 pairs) and 5250 were singletons. Of the singletons, 351 were born after a gestational period of less than 37 weeks. The mothers of 20 (6%) of these children were unable or unwilling to provide information, whereas for 86 of the remaining 331 immature babies, delivery was planned for various reasons. A total of 245 spontaneous and PROM (premature rupture of membranes) deliveries of singleton premature or borderline term babies, together with their mothers, were investigated in this study. Ninety-two very www.bjog-elsevier.com
COMMON TRIGGERS OF PRETERM DELIVERY 599
preterm babies (de®ned as ,33 gestational weeks, calculated on the basis of the recorded last normal menstrual period; 92 babies) and 95 preterm babies (33-35 weeks) were included as cases. Controls included 58 borderline or near term babies born after gestation duration of at least 36 but less than 37 completed gestational weeks. Sonographic con®rmation of the gestational age was available for about 50% of the newborn infants (117/ 245). We have chosen to restrict controls to those who were born only marginally at term in order to minimise information bias. The mean (standard deviation) birthweight was 1460 g (632.2 g) for very immature babies, 2355 grams (461.4 g) for immature babies and 2750 g (650.0 g) for borderline term infants. A single medically
quali®ed researcher (H.S.) interviewed all the mothers in any of these categories within 48h of delivery. The standard pre-coded questionnaire covered information about socio-demographic, clinical, gynaecological and maternity variables in general, as well as a series of questions referring to operationally de®ned transient events that took place at least once during the last two weeks of pregnancy. These events could be conceivably, although not necessarily plausibly, thought of as having the potential to trigger a preterm delivery. The analysis was performed initially through single cross classi®cations. Subsequently, the data concerning prolonged exposure to variables that have been reported to affect prematurity were modelled through multiple
Table 1. Distribution of 245 mothers of singleton babies by gestational age, life status of the newborn, and a series of socio-demographic, lifestyle and pregnancy-related variables. Values are given as n, n (%). Variable
,33 weeks n
Age (years) ,25 25-29 30 1 Body mass index (kgr/m 2) ,20 20.0-22.4 22.5-24.9 25.0-27.4 27.5 1 Education (years) #9 10-15 16 1 Tobacco consumption No Yes Alcohol consumption No Yes Coffee consumption No Yes Serious nausea & vomiting No Yes Regular physical activity No Yes Parity 1 child 2 31 Newborn life status Alive Dead History of preterm delivery Yes No All mothers
33-35 weeks %
n
36-37 weeks %
n
%
23 25 44
25.0 27.2 47.8
28 22 45
29.5 23.1 47.4
12 19 27
20.7 32.8 46.5
25 20 18 12 17
27.2 21.7 19.6 13.0 18.5
19 27 27 11 11
20.0 28.4 28.4 11.6 11.6
13 16 12 10 7
22.4 27.6 20.7 17.2 12.1
43 42 7
46.7 45.7 7.6
35 49 11
36.8 51.6 11.6
22 25 11
37.9 43.1 19.0
57 35
62.0 38.0
73 22
76.8 23.2
45 13
77.6 22.4
90 2
97.8 2.2
94 1
98.9 1.1
58 0
100.0 0.0
32 60
34.8 65.2
50 45
52.6 47.4
25 33
43.1 56.9
61 31
66.3 33.7
57 38
60.0 40.0
30 28
51.7 48.3
84 8
91.3 8.7
87 8
91.6 8.4
46 12
79.3 20.7
41 30 26
42.3 30.9 26.8
60 23 17
60.0 23.0 17.0
32 18 13
50.8 28.6 20.6
69 23
75.0 25.0
89 6
93.7 6.3
56 2
96.5 3.5
17 75 92
18.5 81.5 100.0
16 79 95
16.8 83.2 100.0
10 48 58
17.2 82.8 100.0
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600 E. PETRIDOU ET AL.
logistic regression (core model) 30. In the core model, a quantal (binary) variable concerning the life status of the newborn at the end of the ®rst 24 hours after the delivery was also included. Life status as a predictor variable accommodates confounding that can be introduced if the mother provides information of variable accuracy (more or less accurate) depending on the life status of the newborn. However, there may still be the potential of some residual bias, because the interviewer was not blind to gestational age. History of a transient event was subsequently introduced to assess whether this event had any effect on a preterm delivery after adjusting for the core variables and life status of the newborn. Variables concerning transient events were alternatively introduced in the model. Separate models were run for very premature and premature deliveries, always using a single control series, which was formed by the borderline term deliveries. The study was approved by the Ethics Committee of the University of Athens Medical School. All women participated following their consent to contribute to an investigation concerning conditions and events surround-
ing their ªrelatively earlyº delivery, without explicit mention of triggering events. RESULTS Table 1 shows the frequency distribution of a total of 245 mothers of singleton babies by gestational age of the newborn, a series of socio-demographic and pregnancy variables as well as life status of the newborn. The lifestyle variables, including physical activity, refer to the average behaviour throughout the pregnancy, whereas serious nausea and vomiting occur during the ®rst months of the pregnancy. Body mass index is calculated on the basis of the recorded pre-pregnancy weight. No woman in this study had a sexually transmitted disease during pregnancy or had been hospitalised for an infectious disease during that period. The data in Table 1 are univariate, and thus likely to be confounded, but the distribution patterns are similar to those derived from the literature. Table 2 shows multiple logistic regression-derived
Table 2. Multiple logistic regression-derived, mutually adjusted odds ratios (ORs) and 95% con®dence intervals (95% CI) for a very premature (,33 weeks) or a premature (33-35 weeks) delivery versus borderline term singleton delivery (36-37 weeks) by a series of prolonged-exposure factors (core model). Variable
Age (years)
Body mass index (kgr/m 2)
Parity Education Tobacco consumption Coffee consumption Serious nausea & vomiting Regular physical activity Additionally introduced variable Newborn life status
Category or increment
Very premature (,33 weeks) ORs
95% CIs
Premature (33-35 weeks) P
,25 25-29 30 1
1.23 Baseline 1.17
0.45
3.37
0.68
0.51
2.70
0.71
,20 20.0-22.4 22.5-27.4 27.5 1
1.23 0.77 Baseline 1.88
0.48 0.31
3.12 1.91
0.66 0.57
0.62
5.72
One more child (ordinal)
1.27
0.78
6 more years (ordinal)
0.75
No Yes
ORs
95% CIs
P
1.94 Baseline 1.47
0.69
5.43
0.21
0.65
3.29
0.35
0.28 0.35
1.81 2.05
0.48 0.71
0.27
0.71 0.84 Baseline 0.72
0.23
2.27
0.58
2.07
0.34
0.78
0.47
1.30
0.34
0.42
1.32
0.32
0.99
0.56
1.74
0.97
Baseline 1.88
0.82
4.28
0.14
Baseline 1.48
0.60
3.68
0.40
No Yes
Baseline 1.18
0.56
2.50
0.66
Baseline 0.70
0.34
1.43
0.33
No Yes
Baseline 0.50
0.23
1.06
0.07
Baseline 0.82
0.40
1.69
0.60
No Yes
Baseline 0.45
0.16
1.26
0.13
Baseline 0.30
0.11
0.83
0.02
Alive Dead
Baseline 10
2.2
50.0
0.003
Baseline 1.39
0.24
7.69
0.71
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COMMON TRIGGERS OF PRETERM DELIVERY 601
mutually adjusted odds ratios for a very premature or preterm delivery, rather than a borderline term delivery in relation to prolonged exposure variables. Most ®ndings are not statistically signi®cant, but they point to expected directions. Thus, extreme prematurity is more common among younger and older women as compared with women 25±29 years old; tends to increase with increased parity and increased BMI; and tends to decline with higher education. Tobacco smoking increases the likelihood of extreme prematurity, whereas regular physical activity and serious nausea and vomiting are inversely related to extreme prematurity risk. There is also a highly signi®cant association between extreme prematurity and the likelihood of perinatal death. Results concerning premature (33±35 weeks) delivery are, in general, closer to the null, compared with those concerning extremely preterm delivery. Table 2 provides the context of the study but does not address issues surrounding possible consequences of transient stressful events. In Table 3 the number and percentages of speci®ed transient exposures, by gestational age at delivery, during the last two weeks of the respective pregnancy are shown. The interpretation of these data requires comparison of the corresponding proportions across three categories of gestational age at delivery, as well as control for the prolonged exposure predictors of prematurity shown in Table 2. Confounding does not depend on statistical signi®cance and thus, non- signi®-
cantly associated factors in Table 2 still need to be accounted for 31. Table 4 shows multiple logistic regression-derived odds ratios for a very premature singleton delivery without adjustment (®rst two columns), after adjustment for stable risk factors of prematurity (second two columns) and after adjustment for stable risk factors of prematurity as well as for life status of the newborn (as a predictor for over reporting or more complete reporting; last two columns). Table 5 is of similar structure, but it concerns premature rather than very premature deliveries. Interpretation of the results require, in addition to biological plausibility, a degree of consistency between Tables 4 and 5 and a gradient of odds ratios from very premature to immature babies. For two of the variables in Table 3, (loss of job of self or husband and imprisonment or court appearance of a close family member) and for one variable in Table 5 (separation from spouse) no event was recorded in the respective case series. Thus, only Fisher's P value could be calculated. In all these instances, however, the respective P-value was far from signi®cant and in all three instances the event appeared to be inversely associated with preterm delivery, a biologically implausible relation. For only two of the variables were the results statistically signi®cant, consistent or descriptively impressive: (Tables 4 and 5). Thus, for none of the statistically unrelated variables can be inferred that they have a triggering
Table 3. Distribution of 245 mothers of singleton babies by gestational age and speci®ed transient exposures during the last two weeks of index pregnancy. Variable
Serious personal injury Serious illness, immediate family Serious injury, immediate family Serious illness or injury, close friend or relative Serious disruption by a guest visit Serious family quarrel Quarrel with spouse Quarrel with spouse's family Husband's departure Expulsion from house Loss of employment of self or husband Serious ®nancial problem Court appearance or imprisonment Personal illness Other unpleasant event New medication Insomnia Sunbathing Exposure to cold weather conditions Intense house cleaning Great physical exertion Travel Sexual intercourse All mothers
,33 weeks
33-35 weeks
36-37 weeks
n
%
n
%
n
%
4 3 5 2 15 25 5 4 10 3 0 15 0 34 34 24 15 2 2 32 45 11 51 92
4.4 3.3 5.4 2.2 16.3 27.2 5.4 4.4 10.9 3.3 0.0 16.3 0.0 37.0 37.0 26.1 16.3 2.2 2.2 34.8 48.9 12.0 55.4 100.0
1 3 1 4 15 15 0 4 2 5 1 6 2 34 18 19 21 3 1 22 56 6 43 95
1.1 3.2 1.1 4.2 15.8 15.8 0.0 4.2 2.1 5.3 1.1 6.3 2.1 35.8 19.0 20.0 22.1 3.2 1.1 23.2 59.0 6.4 45.3 100.0
2 1 1 4 12 8 1 3 3 1 1 5 1 18 18 15 14 2 2 18 28 4 16 58
3.5 1.7 1.7 6.9 20.7 13.8 1.7 5.2 5.2 1.7 1.7 8.6 1.7 31.0 31.0 25.9 24.1 3.5 3.5 31.0 48.3 6.9 27.6 100.0
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602 E. PETRIDOU ET AL. Table 4. Multiple logistic regression-derived, adjusted for the core model variables odds ratios (ORs) and 95% con®dence intervals (95% CIs) for a very premature delivery by speci®ed transient exposures during the last two weeks of the pregnancy. Variable
Serious personal injury Serious illness, immediate family Serious injury, immediate family Serious illness or injury, close friend or relative Serious disruption by a guest visit Serious family quarrel Quarrel with spouse Quarrel with spouse's family Husband's departure Expulsion from house Loss of employment of self or husband Serious ®nancial problem Court appearance or imprisonment Personal illness Other unpleasant event New medication Insomnia Sunbathing Exposure to cold weather conditions Intense house cleaning Great physical exertion Travel Sexual intercourse
Crude
Core model without life status
Core model with life status
OR
P
OR
P
OR
1.27 1.92 3.28 0.30
0.78 0.58 0.28 0.17
1.27 1.27 3.48 0.40
0.80 0.84 0.30 0.37
0.94 0.87 2.61 0.50
0.13 0.06 0.22 0.07
6.92 12.58 31.45 3.74
0.95 0.92 0.45 0.50
0.75 2.33 3.28 0.83 0.45 1.92 -
0.50 0.06 0.28 0.82 0.24 0.58 0.38
0.65 2.76 2.67 0.66 0.54 3.05
0.36 0.04 0.40 0.63 0.41 0.39
0.70 2.23 2.88 0.83 0.72 4.10
0.27 0.83 0.28 0.15 0.14 0.32
1.80 6.03 29.95 4.66 3.61 52.43
0.46 0.11 0.38 0.84 0.68 0.28
2.1 -
0.18 0.39
1.68
0.38
1.88
0.57
6.19
0.30
1.30 1.30 1.01 0.61 0.62 0.62
0.46 0.46 0.97 0.24 0.64 0.64
1.54 1.69 1.02 0.55 1.34 0.45
0.27 0.19 0.96 0.20 0.80 0.51
1.80 1.51 1.18 0.68 1.28 0.31
0.80 0.66 0.50 0.27 0.10 0.02
4.04 3.46 2.78 1.71 15.65 4.25
0.16 0.33 0.70 0.41 0.84 0.38
1.19 1.03 1.83 3.27
0.64 0.94 0.32 0.001
1.23 1.12 1.58 3.25
0.61 0.77 0.49 0.002
1.04 0.89 1.52 3.21
0.45 0.39 0.41 1.45
2.42 1.99 5.69 7.09
0.92 0.77 0.53 0.004
role on the onset of delivery. For one of the remaining two variables, great physical exertion in the last two weeks of pregnancy, there is weak evidence that it may affect premature, but not very preterm delivery. Thus, the pattern is overall unconvincing, although it can not conclusively be refuted. The other exception concerns ªsexual intercourse during the last two weeks of pregnancyº and the relevant results appear to be more credible. One or more acts of intercourse during the last two weeks of pregnancy appear to double the likelihood of a preterm delivery and triple the risk of a very preterm delivery. The association is not affected by control for either prolonged exposure variables or life status of the newborn and is robust with respect to statistical signi®cance. For very premature deliveries, rupture of the membranes may be an important intermediate factor (odds ratios: with membrane rupture 3.68; without membrane rupture 2.87). There is no such evidence, however, for premature deliveries (odds ratios: with membrane rupture 2.04; without membrane rupture 2.31). We have also evaluated the plausible hypothesis that an accumulation of several transient events may be able to trigger a preterm delivery, although each one of these events was innocuous. There was no such evidence in these data: an additive score of all stressful transient events in a particular woman, with exception of sexual
95% CI
P
intercourse, was unrelated to either premature or very preterm delivery. DISCUSSION The results of this study indicate that coitus and perhaps physical exertion during the later stages of gestation may increase the risk of a preterm delivery, although to a rather modest degree. On the contrary, we found no evidence that psychological stress can precipitate preterm delivery. The study design, did not allow evaluation of possible interactions between prolonged exposure characteristics (i.e. maternal age or regular smoking during pregnancy on the one hand, and triggering factors of physical of psychological nature on the other). Among the drawbacks of the present study is that the rarity of some transient events, in combination with the moderate size of the study, tends to reduce statistical power. Nevertheless, these are inherent problems that cannot easily be dealt with and in any case our study had comparable power to that of other similar investigations in the literature 15,26,32,33. Recently, there have been several studies utilizing the case±crossover design to assess transient effects 34±36. However, this elegant method is not applicable in situations where the underq RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
COMMON TRIGGERS OF PRETERM DELIVERY 603 Table 5. Multiple logistic regression-derived, adjusted for the core model variables odds ratios (ORs) and 95% con®dence intervals (95% CIs) for a premature delivery by speci®ed transient exposures during the last two weeks of the pregnancy. Variable
Serious personal injury Serious illness, immediate family Serious injury, immediate family Serious illness or injury, close friend or relative Serious disruption by a guest visit Serious family quarrel Quarrel with spouse Quarrel with spouse's family Husband's departure Expulsion from house Loss of employment of self or husband Serious ®nancial problem Court appearance or imprisonment Personal illness Other unpleasant event New medication Insomnia Sunbathing Exposure to cold weather conditions Intense house cleaning Great physical exertion Travel Sexual intercourse
Crude
Core model without life status
Core model with life status
OR
P
OR
P
OR
0.30 1.86 0.61 0.59
0.33 0.60 0.73 0.47
0.27 1.20 0.91 0.82
0.32 0.88 0.95 0.80
0.27 1.15 0.91 0.83
0.02 0.11 0.04 0.18
3.71 12.34 23.27 3.84
0.33 0.91 0.96 0.81
0.72 1.17 0.81 2.53 3.17 0.61
0.44 0.74 0.38 0.78 0.32 0.30 0.73
0.66 1.40
0.38 0.52
0.66 1.41
0.26 0.50
1.65 3.92
0.38 0.51
1.17 2.33 3.76 0.84
0.85 0.39 0.26 0.90
1.19 2.28 3.65 0.84
0.23 0.33 0.36 0.04
6.25 15.89 36.67 15.75
0.84 0.40 0.27 0.90
0.72 1.23
0.59 0.87
0.79 0.93
0.73 0.95
0.80 0.94
0.22 0.08
2.96 11.80
0.74 0.96
1.24 0.52 0.72 0.89 0.91 0.30
0.55 0.09 0.40 0.77 0.92 0.33
1.49 0.50 0.75 0.93 2.39 0.44
0.32 0.08 0.49 0.86 0.43 0.56
1.51 0.50 0.74 0.92 2.41 0.45
0.69 0.23 0.32 0.41 0.28 0.03
3.34 1.10 1.70 2.08 20.68 6.65
0.31 0.09 0.47 0.84 0.42 0.56
0.67 1.54 0.91 2.17
0.28 0.20 0.89 0.03
0.75 2.21 1.13 2.21
0.49 0.04 0.87 0.04
0.75 2.22 1.16 2.20
0.33 1.05 0.27 1.03
1.72 4.68 4.98 4.70
0.50 0.04 0.85 0.04
lying probability density of a phenomenon, in this instance delivery, increases with gestational age. On the other hand, the study also has several advantages. An important advantage is the choice of a control group that allowed the effect of information bias to be minimised, because mothers of immature babies and mothers of marginally term babies are likely to share a psychology which is very different to a mother of a full term baby. Infants born at 35±36 weeks of gestation are not different from full term babies with respect to survival and residual disabilities 37. Therefore, infants of this gestational age can be considered as controls. Moreover, by controlling for life status of the newborn in the analysis, we have further reduced the likelihood of information bias, which may operate with particular force among mothers of stillborn babies. The majority of studies in the literature indicate that psychological factors may trigger a preterm delivery 12± 14,18 , although studies suggesting otherwise have also been reported 21,27. In our study no single factor of psychological stress was signi®cantly related to preterm delivery. Moreover, controlling for vital status of newborn had a tendency to bring the results closer to the null. There are several possible interpretations of this: it may be that most of the earlier studies did not adequately control q RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604
95% CI
P
for information bias; that our study was not powerful enough to reveal a positive association of preterm delivery with one or more of the psychological stress-indicator variables; or that these variables were not properly re¯ecting psychological stress. We are inclined to accept the ®rst interpretation, but in any case, it seems that psychological variables used to assess the impact of essentially acute psychological stress do not have a strong triggering effect for a preterm delivery. Most previous studies 15,16,19, although by no means all 22,23,28, support the hypothesis that physical exertion can accelerate delivery. Our results provide some support for this hypothesis, although the evidence is limited to premature and does not appear to affect very premature deliveries. The converging evidence from the literature and the present study suggest that physical exertion may have an effect on preterm delivery but the association is of moderate strength. The literature concerning the effects of coitus on preterm delivery is contradictory: some studies indicate that there is such an effect 17,20, others that frequent sexual intercourse may increase the risk of a preterm delivery among women whose vagina is colonised by speci®c microorganisms 38, whereas others found no evidence for an effect of intercourse on the risk of
604 E. PETRIDOU ET AL.
prematurity 24±26,29. The mechanism through which coitus operates as a risk factor for preterm delivery should be further explored in order to identify pregnancies at increased risk. Our results cannot distinguish between the ®rst two hypotheses because we have no data concerning the effect of micro organism in vagina, but they tend to reject the third hypothesis that coitus at the later stage of pregnancy is innocuous. It is of interest that the detrimental effect concerns both very premature and immature babies, and it is robust to adjustment for possible confounders, including life status of the newborn. In conclusion, our study indicates that coitus during the last few weeks of pregnancy should be discouraged, as it appears to increase the risk of preterm delivery. The evidence concerning a possible detrimental effect of physical exertion is more limited, whereas we found no indication that psychological stress, as operationalised in our investigation, had any effect on preterm delivery.
15.
16. 17.
18. 19. 20. 21. 22. 23.
Acknowledgements The authors would like to thank Dr Sofatzis, Director of Neonatal Unit, Marika Iliadi Maternity Hospital, for his thoughtful comments and support in the preparation and execution of this project. This study was supported by departmental funds from the Department of Epidemiology, Harvard School of Public Health. References 1. Cunningham FG, MacDonald PC, Gant NF. Williams Obstetrics. Stamford, Connecticut: Appleton & Lange, 1997. 2. Berkowitz GS, Papiernik E. Epidemiology of preterm birth. Epidemiol Rev 1993;15:414±443. 3. Avery GB, Fletcher MA, MacDonald MG. Neonatology: Pathophysiology and Management of the Newborn. Philadelphia: Williams & Wilkins, 1999. 4. Weismiller DG. Preterm labor. Am Fam Physician 1999;59:593±602. 5. Erkkola R, Kero PO. Impact of prematurity on perinatal mortality and morbidity. Ann Med 1991;23:663±669. 6. LeFevre ML, Hueston WJ. Preterm birth. Prim Care 1993;20:639±653. 7. Goepfert AR, Goldenberg RL. Prediction of prematurity. Curr Opin Obstet Gynecol 1996;8:417±427. 8. Garbaciak Jr JA. Prematurity prevention: who is at risk? Clin Perinatol 1992;19:275±289. 9. Witter FR, Keith LG. Prematurity: Antecedents, Treatment, and Outcome. Boston: Little, Brown, & Co, 1993. 10. Yu VYH, Wood CE. Prematurity. New York: Churchill Livingstone, 1987. 11. Petridou E, Trichopoulos D, Tong D, et al. Modulators of length of gestation- a study in Greece. Eur J Public Health 1996;6:159±165. 12. Peacock JL, Bland JM, Anderson HR. Preterm delivery: effects of socio-economic factors, psychological stress, smoking, alcohol and caffeine. BMJ 1995;311:531±535. 13. Hedegaard M, Henriksen TB, Sabroe S, Secher NJ. Psychological distress in pregnancy and preterm delivery. BMJ 1993;307:234±239. 14. Hedegaard M, Henriksen TB, Secher NJ, Hatch MC, Sabroe S. Do
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Accepted 16 January 2001
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 598±604