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DOI: 10.1111/1471-0528.

14672 Systematic review


www.bjog.org

Physical activity and the risk of preterm birth: a


systematic review and meta-analysis of
epidemiological studies
D Aune,a,b,c S Schlesinger,b T Henriksen,d OD Saugstad,e S Tonstadf
a
Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim,
Norway b Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK c Bjørknes
University College, Oslo, Norway d Section of Obstetrics, Division of Obstetrics and Gynaecology, Rikshospitalet, Oslo University Hospital,
Oslo, Norway e Department of Pediatric Research, Rikshospitalet, Oslo University Hospital, University of Oslo, Oslo, Norway f Department of
Preventive Cardiology, Oslo University Hospital, University of Oslo, Oslo, Norway
Correspondence: D Aune, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus,
Norfolk Place, Paddington, London W2 1PG, UK. Email d.aune@imperial.ac.uk

Accepted 9 March 2017. Published Online 30 May 2017.

Background Physical activity has been inconsistently associated I2 = 0%, n = 30) for early pregnancy physical activity. The
with risk of preterm birth, and the strength of the association and summary RR for a 3 hours per week increment in leisure-time
the shape of the dose–response relationship needs clarification. activity was 0.90 (95% CI: 0.85–0.95, I2 = 0%, n = 5). There was
evidence of a nonlinear association between physical activity and
Objectives To conduct a systematic review and dose–response
preterm birth, Pnonlinearity < 0.0001, with the lowest risk observed
meta-analysis to clarify the association between physical activity
at 2–4 hours per week of activity.
and risk of preterm birth.
Conclusion This meta-analysis suggests that higher leisure-time
Search strategy PubMed, Embase and Ovid databases were
activity is associated with reduced risk of preterm birth. Further
searched for relevant studies up to 9 February 2017.
randomized controlled trials with sufficient frequency and
Selection criteria Studies with a prospective cohort, case-cohort, duration of activity to reduce the risk and with larger sample sizes
nested case-control or randomized study design were included. are needed to conclusively demonstrate an association.
Data collection and analysis Data were extracted by one reviewer Keywords Meta-analysis, physical activity, preterm birth.
and checked for accuracy by a second reviewer. Summary
Tweetable abstract Physically active compared with inactive
relative risks (RRs) were estimated using a random effects
women have an 10–14% reduction in the risk of preterm birth.
model.
Linked article This article is commented on by BA Armson, p. 1827
Main results Forty-one studies (43 publications) including 20
in this issue. To view this mini commentary visit https://doi.org/10.
randomized trials and 21 cohort studies were included. The
1111/1471-0528.14723. This article has journal club questions by
summary RR for high versus low activity was 0.87 [95%
Brett Einerson, p. 1828 in this issue. To view these visit https://doi.
confidence interval (CI): 0.70–1.06, I2 = 17%, n = 5] for physical
org/10.1111/1471-0528.14795.
activity before pregnancy, and it was 0.86 (95% CI: 0.78–0.95,

Please cite this paper as: Aune D, Schlesinger S, Henriksen T, Saugstad OD, Tonstad S. Physical activity and the risk of preterm birth: a systematic review
and meta-analysis of epidemiological studies. BJOG 2017;124:1816–1826.

cognitive and developmental disabilities, and chronic diseases


Introduction
in adulthood. Apart from tobacco smoking, which is an estab-
In 2012 an estimated 15 million preterm births (defined as lished risk factor, maternal obesity has also been associated
birth before 37 completed weeks of gestation) occurred with increased risk of preterm birth, particularly very preterm
worldwide.1 Preterm births account for approximately 29% births in several studies,3,4 and this was confirmed in a recent
of the 3.6 million neonatal deaths worldwide,2 and is an meta-analysis that also found an increased risk of preterm
important risk factor for neonatal morbidity including births among overweight and obese pregnant women.5
breathing problems, infections and jaundice.2 Babies born Physical activity is an important determinant of over-
preterm have also been found to have a greater risk of weight and obesity,6 and reduces the risk of excess gestational

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Physical activity and preterm birth: a meta-analysis

weight gain,7–10 and has been associated with reduced risk of reference lists of previous reviews of the subject and of the
other obesity-related pregnancy complications, including studies included in the analysis for any further studies. DA
gestational diabetes11 and preeclampsia.12 Several random- conducted the initial screening of all the records, and DA
ized trials,13–31 cohort studies32–54 and case-control stud- and SS conducted the screening of the potentially relevant
ies55–63 have investigated the association between physical records in duplicate. Any discrepancies between the review-
activity and preterm births, but the results have been incon- ers were resolved by discussion.
sistent, with some studies showing significant inverse associ-
ations,32–34,55,56,59 while other studies reported no significant Study selection, and assessment of study quality
associations.13–19,21,23,24,26–31,35,37–39,41–43,45,57,58,63–65 Several and risk of bias
of the studies showed non-significant inverse associa- To be included, the study had to have a prospective cohort,
tions,19,24,30,35,38,39,41,42 but may have been limited by low case-cohort, nested case-control (within a cohort) or ran-
statistical power. However, even among the studies that domized study design, and to investigate the association
reported inverse associations there was considerable variabil- between physical activity and risk of preterm birth and be
ity in the strength of the associations reported, with some published in English language. Abstracts, grey literature
studies reporting a 15–20% reduction in risk with high phys- and unpublished studies were not included. Estimates of
ical activity,35,36,38,42 while other studies reported up to a 40– the relative risk (RR; hazard ratio, risk ratio, odds ratio)
80% reduction in risk.19,32–34,41,46,55,56,59 It is possible that had to be available with the 95% confidence intervals
differences in the timing, amount, type and intensity of phys- (CIs), and for the dose–response analysis, a quantitative
ical activity or different degrees of adjustments for con- measure of activity level and the total number of cases and
founders or other study characteristics could explain some of person-years or participants had to be available in the pub-
this variation in the results. To clarify whether physical activ- lication or on request from the authors. For cohort studies
ity before or during pregnancy is associated with the risk of we included only studies that provided risk estimates that
preterm birth, we conducted a systematic review and meta- were adjusted for at least one confounder, while we included
analysis of epidemiological studies on the subject. We were all randomized trials as they are considered adjusted due to
particularly interested in clarifying the dose–response rela- the randomization process. We calculated the RRs and 95%
tionship between physical activity, including total, leisure- CIs for the randomized trials based on the distribution of
time and occupational physical activity, and preterm birth, cases and non-cases when risk estimates were not provided in
potential confounding, and other study characteristics that the paper using standard formula66 We included studies on
could explain the observed heterogeneity in the results. total and all subtypes of leisure-time physical activity, but for
occupational activity we only included studies of total occu-
pational activity and walking. Studies of physically demand-
Methods
ing work, such as prolonged standing, heavy lifting, physical
Search strategy exertion, occupational fatigue and demanding posture, were
We searched the PubMed and Embase databases up to 15 excluded as they have been summarized in a recent meta-ana-
December 2014 for cohort studies (including prospective lysis.67 A list of excluded studies and the reason for exclusion
cohorts, case-cohorts and nested case-control studies within is provided in Table S1.
cohort studies), and randomized trials of physical activity
(including total, leisure-time and occupational physical Data extraction
activity) and risk of preterm birth (defined as birth before The following data were extracted from each study in
37 completed weeks of gestation), and the searches were duplicate by DA and SS: the first author’s last name, publi-
later updated to 9 February 2017. We used the following cation year, country where the study was conducted, the
search terms: (‘physical activity’ OR ‘leisure activity’ OR study name, follow-up period, sample size, gender, age,
exercise OR sports OR walking OR biking OR running OR number of cases, exposure, physical activity level, RRs and
fitness OR ‘exercise test’ OR inactivity OR sedentary) AND 95% CIs for each physical activity level and variables
(‘preterm birth’ OR preterm OR ‘premature birth’ OR pre- adjusted for in the analysis.
maturity OR ‘preterm labor’ OR ‘premature labor’ OR
‘preterm delivery’ OR ‘premature delivery’ OR ‘premature Risk of bias and study quality assessment
labor’ OR ‘birth outcomes’ OR ‘birth outcome’ OR ‘preg- We used the Cochrane Collaboration’s tool to assess the
nancy outcomes’ OR ‘pregnancy outcome’) AND (‘case- risk of bias of the randomized trials.68 The risk of bias
control’ OR retrospective OR cohort OR cohorts OR assessment was based on random sequence generation, allo-
prospective OR longitudinal OR ‘follow-up’ OR ‘cross-sec- cation concealment, blinding of participants and personnel,
tional’ OR trial OR ‘relative risk’ OR ‘hazard ratio’ OR blinding of outcome assessment, incomplete outcome data,
‘odds ratio’ OR odds OR regression). We also searched the selective reporting and other biases. The quality of the

ª 2017 Royal College of Obstetricians and Gynaecologists 1817


Aune et al.

cohort studies was assessed using the Newcastle-Ottawa smoking, alcohol, parity, hypertension, diabetes and body
scale,69 which ranks studies based on the selection (repre- mass index (BMI)], and meta-regression analyses were used
sentativeness of the exposed cohort, selection of the non- to test for heterogeneity between subgroups.
exposed cohort, ascertainment of exposure, demonstration Publication bias was assessed with Egger’s test,77 and the
that the outcome was not present at the start of the study), results were considered to indicate publication bias when
comparability (adjustment for confounding factors) and P < 0.10. We conducted sensitivity analyses excluding one
the outcome (outcome assessment, long enough follow-up, study at a time to ensure that the results were not simply
adequacy of follow-up of cohorts). due to one large study or a study with an extreme result.
The statistical analyses were conducted using Stata, version
Statistical methods 13.0 software (StataCorp, College Station, TX, USA).
We used random effects models70 to calculate summary RRs
and 95% CIs for the highest versus the lowest level of physi-
Results
cal activity, and for the dose–response analysis. The average
of the natural logarithm of the RRs was estimated, and the Out of a total of 2053 records identified by the search, 41
RR from each study was weighted by the inverse of its vari- studies (43 publications) were included in the meta-analysis
ance and was then unweighted by a variance component that of physical activity and preterm birth, including 20 ran-
corresponds to the amount of heterogeneity in the analysis. domized trials,13–21,23–31,64,65 and 21 cohort studies (23
A two-tailed P < 0.05 was considered statistically significant. publications; Figure 1; Tables S2 and S3).32–54 Thirteen
We used the method described by Greenland and Long- studies were from Europe, 15 studies were from North
necker71 for the linear dose–response analysis, and computed America, five from South America, four from Asia, and
study-specific slopes (linear trends) and 95% CIs from the four from Australia and New Zealand (Tables S2 and S3).
natural logs of the RRs and CIs across categories of physical The definition of preterm birth was consistent across stud-
activity. The method requires that the distribution of cases ies (<37 weeks; Tables S2 and S3).
and person-years or non-cases and the RRs with the variance
estimates for at least three quantitative exposure categories 2053 records identified in total:
are known. We estimated the distribution of cases or person- 715 records identified in the PubMed database
years in studies that did not report these, but reported the 889 records identified in the Embase database
447 records identified in the Ovid database
total number of cases/person-years.72 The median or mean 2 records identified from other searches
physical activity level in each category was assigned to the
corresponding RR for each study. For studies that reported
1870 excluded based on
the physical activity by ranges of activity, we estimated the information in title or abstract
midpoint for each category by calculating the average of the
lower and upper bound. When the highest or lowest category
183 given detailed assessment
was open-ended, we assumed the open-ended interval length
to be the same as the adjacent interval. We examined a 142 studies excluded
potential nonlinear dose–response relationship between 48 not relevant data,
physical activity and preterm birth by using restricted cubic outcome or exposure
15 abstracts
splines with 3 knots at 10%, 50% and 90% percentiles of the 14 case-control studies
distribution, which was combined using multivariate meta- 10 reviews
analysis.73,74 A P-value for nonlinearity was obtained by test- 9 protocols
ing that the coefficient of the second spline term was equal to 9 combined diet and
activity interventions
zero.75 7 no risk estimates
Heterogeneity between studies was assessed by the Q-test 7 not relevant activity
and I2.76 A P-value for the Q-test < 0.05 indicated statisti- 6 meta-analyses
cally significant heterogeneity. I2 is the amount of total vari- 4 duplicates
4 cross-sectional studies
ation that is explained by between-study variation. I2 values 3 yoga/stretching
of approximately 25%, 50% and 75% are considered to 3 unadjusted risk estimates
indicate low, moderate and high heterogeneity, respectively. 3 comment
Sources of heterogeneity were explored in subgroup analyses
41 studies included (43 publications)
stratified by study design, geographic location, study quality
20 randomized trials (20 publications)
(cohorts), risk of bias (randomized trials), number of cases
21 cohort studies (23 publications)
as an indicator of study size, and adjustment for confound-
ing factors [including age, education, income, drug use, Figure 1. Flow-chart of study selection.

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Physical activity and preterm birth: a meta-analysis

Leisure-time physical activity before pregnancy for high versus low vigorous intensity activity was 0.36 (95%
Five cohort studies 36,41,46,47,78
were included in the analysis CI: 0.04–3.09, I2 = 66.6%, Pheterogeneity = 0.08; Figure 4B).
of pre-pregnancy leisure-time physical activity and the risk
of preterm birth including 633 cases and 12 723 partici- Total physical activity during pregnancy
pants. The summary RR for high versus low pre-pregnancy Four cohort studies32,41,54,82 were included in the analysis
physical activity was 0.87 (95% CI: 0.70–1.06, I2 = 16.5%, of total physical activity (including leisure-time and occu-
Pheterogeneity = 0.31, n = 5; Figure 2A). Because of differ- pational physical activity) during pregnancy and preterm
ences in the way the data were reported, it was not possible birth, and included >466 cases and 7519 participants. The
to conduct dose–response analyses. summary RR for high versus low total physical activity was
0.95 (95% CI: 0.63–1.42, I2 = 56.8%, Pheterogeneity = 0.07;
Leisure-time physical activity during pregnancy Figure 4C).
Twenty randomized trials13–20,23–31,64,65,79 and 10 cohort
studies33,34,37–39,41,42,44,45,47 were included in the analysis of Occupational physical activity during pregnancy
leisure-time physical activity during pregnancy and the risk Two cohort studies41,48 were included in the analysis of
of preterm birth, and included >8621 cases among 171 595 occupational physical activity and preterm birth, and
participants. The summary RR for high versus low physical included 349 cases and 6581 participants. The summary RR
activity in early pregnancy was 0.86 (95% CI: 0.78–0.95, for high versus low occupational activity was RR = 0.67
I2 = 28%, Pheterogeneity = 0.12; Figure 3). The summary RR (95% CI: 0.33–1.34, I2 = 0%, Pheterogeneity = 0.82; Fig-
was significant for cohort studies (summary RR = 0.84, ure 4D).
95% CI: 0.73–0.96, I2 = 21.7%, Pheterogeneity = 0.24), but
not for randomized clinical trials (summary RR = 0.91, Walking during pregnancy
95% CI: 0.72–1.15, I2 = 0%, Pheterogeneity = 0.76); however, Five cohort studies34,39,44,49,51 and two randomized tri-
there was no between-subgroup heterogeneity, P = 0.61. als64,65 were included in the analysis of walking during
There was no evidence of publication bias with Egger’s test, pregnancy and preterm birth, and included 1065 cases and
P = 0.89 and Begg’s test, P = 0.63 (Figure S1). The sum- 26 903 participants. The summary RR for high versus
mary RR ranged from 0.84 (95% CI: 0.75–0.94) when the low walking was 1.09 (95% CI: 0.68–1.75, I2 = 72.3%,
study by Bird et al.47 was excluded to 0.87 (95% CI: Pheterogeneity < 0.0001; Figure 4E).
0.79–0.97) when the study by Mishra et al.80 was excluded
(Figure S2). Five studies38,41,42,45,81 were included in the Bicycling during pregnancy
dose–response analysis, and the summary RR was 0.90 Five randomized trials19,23,26,28,31 and one cohort study40
(95% CI: 0.85–0.95, I2 = 0%, Pheterogeneity = 0.67) per investigated the association between bicycling during preg-
3 hours per week increase in leisure-time activity nancy and the risk of preterm birth, and included 3706
(Figure 2B), and 0.84 (95% CI: 0.76–0.91, I2 = 0%, cases and 74 682 participants. The summary RR for high
Pheterogeneity = 0.67) for a 5 hours per week increase in lei- versus low bicycling was 0.84 (95% CI: 0.69–1.04, I2 = 0%,
sure-time activity during pregnancy. There was evidence of Pheterogeneity = 0.44; Figure 4F).
a nonlinear association between physical activity during
pregnancy and preterm birth, Pnonlinearity < 0.0001, with a Subgroup, sensitivity and meta-regression analyses
reduction in risk up to 2–4 hours per week of activity, but In subgroup and meta-regression analyses, we found no
no further reductions in risk with higher levels of activity significant heterogeneity between subgroups when studies
(Figure 2C; Table S4). were stratified by study type, geographic location, number
of cases, physical activity assessment, risk of bias (random-
Moderate physical activity during pregnancy ized controlled trials), study quality (cohorts) or adjust-
Two cohort studies39,44 were included in the analysis of ment for confounding factors, including age, education,
moderate physical activity during pregnancy and preterm income, drug use, smoking, alcohol, parity, hypertension,
birth, and included 349 cases and 6581 participants. The diabetes or BMI (Table S5). In general, there was low or
summary RR for high versus low moderate intensity physi- moderate heterogeneity in most of the subgroup analyses.
cal activity was 0.64 (95% CI: 0.22–1.83, I2 = 79.4%, The inverse association between physical activity and pre-
Pheterogeneity = 0.03; Figure 4A). term birth was significant only among the cohort studies
with a high study quality, although there was no between-
Vigorous physical activity during pregnancy subgroup heterogeneity (Table S5). The risk of bias assess-
Two cohort studies35,41 were included in the analysis of vigor- ment showed that eight studies had low, eight studies had
ous physical activity during pregnancy and preterm birth, and unclear and four studies had high risk of bias (Table S6).
included 301 cases and 3346 participants. The summary RR The mean (median) study quality score for the modified

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Aune et al.

A
Leisure-time physical activity before pregnancy and preterm birth,
high vs. low analysis
Relative Risk
Study (95% CI)

Bird, 2016 0.99 ( 0.79, 1.24)

Vamos, 2015 0.55 ( 0.33, 0.91)

Jukic, 2012 0.60 ( 0.10, 2.80)

Orr, 2006 0.95 ( 0.62, 1.46)

Haas, 2005 0.81 ( 0.52, 1.27)

Overall 0.87 ( 0.70, 1.06)

.2 .5 .75 1 1.5 2 3
Relative Risk

B
Leisure-time physical activity during pregnancy and preterm birth,
per 3 hours per weekt
Relative Risk
Study (95% CI)

Tinloy, 2014 1.11 ( 0.69, 1.77)

Jukic, 2012 0.97 ( 0.76, 1.24)

Owe, 2012 0.90 ( 0.84, 0.98)

Hegaard, 2008 0.71 ( 0.45, 1.13)

Juhl, 2008 0.88 ( 0.81, 0.96)

Overall 0.90 ( 0.85, 0.95)

.2 .5 .75 1 1.5 2 3
Relative Risk

C
Leisure- time physical activity during pregnancy and preterm birth,
nonlinear dose-response analysis

1.0

0.8
RR

0.6
0 1 2 3 4 5 6 7
Physical activity during pregnancy (hours/wk)
Best fitting cubic spline
95% confidence interval

Figure 2. Leisure-time physical activity before and during pregnancy and preterm birth.

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Physical activity and preterm birth: a meta-analysis

Relative Risk
Study (95% CI)
Randomized controlled trials
Wang, 2017 0.60 ( 0.14, 2.57)
Barakat, 2016 0.76 ( 0.46, 1.28)
Garnæs, 2016 0.98 ( 0.14, 6.80)
Seneviratne, 2016 2.30 ( 0.20, 29.60)
Taniguchi, 2016 0.19 ( 0.02, 2.10)
Halse, 2015 1.50 ( 0.33, 7.00)
Nobles, 2015 1.03 ( 0.47, 2.25)
Barakat, 2014 0.55 ( 0.21, 1.39)
Barakat, 2014 0.87 ( 0.24, 3.10)
Ghodsi, 2014 3.00 ( 0.45, 20.51)
Kong, 2014 0.35 ( 0.03, 4.03)
Renault, 2014 1.32 ( 0.49, 3.57)
Salvesen, 2014 1.05 ( 0.57, 1.92)
Kasawara, 2013 0.53 ( 0.26, 1.06)
Tomic, 2013 1.57 ( 0.72, 3.47)
Price, 2012 3.34 ( 0.28, 40.27)
Haakstad, 2011 2.04 ( 0.38, 10.89)
Cavalcante, 2009 0.84 ( 0.28, 2.53)
Barakat, 2008 0.65 ( 0.13, 3.16)
Santos, 2005 1.89 ( 0.26, 14.12)
Subtotal 0.91 ( 0.72, 1.15)

Cohort studies
Bird, 2016 0.98 ( 0.76, 1.24)
Sealy-Jefferson, 2014 0.77 ( 0.44, 1.36)
Tinloy, 2014 1.12 ( 0.67, 1.86)
Jukic, 2012 0.60 ( 0.30, 1.20)
Owe, 2012 0.86 ( 0.73, 1.07)
Hegaard, 2008 0.70 ( 0.38, 1.28)
Juhl, 2008 0.81 ( 0.64, 1.04)
Orr, 2006 0.93 ( 0.63, 1.38)
Hatch, 1998 0.11 ( 0.02, 0.81)
Misra, 1998 0.51 ( 0.27, 0.95)
Subtotal 0.84 ( 0.73, 0.96)

Overall 0.86 ( 0.78, 0.95)

.01 .1 .25 .5 .75 1 1.5 2 3 5


Relative Risk

Figure 3. Leisure-time physical activity during pregnancy and preterm birth.

Newcastle-Ottawa score was 6.7 (7.0) out of eight possible found that higher leisure-time physical activity during
points (Table S7). pregnancy was associated with a statistically significant 14%
Because few studies could be included in the dose–re- decrease in the RR of preterm birth, and for each 3 hours
sponse analysis of leisure-time physical activity during per week increase in leisure-time physical activity during
pregnancy and the risk of preterm birth, we conducted a pregnancy there was a 10% reduction in the RR of preterm
sensitivity analysis restricting the high versus low analysis birth. There was evidence of a nonlinear association
to the five studies included in the dose–response analysis to between physical activity during pregnancy and preterm
see if these studies differed greatly from the overall result birth, with the lowest risk (15–16% reduction in RR)
among cohort studies. The summary RR was 0.84 (95% CI: observed at a physical activity level of approximately 2–
0.73–0.96) for these five cohort studies, which was similar 4 hours per week; however, some caution is needed in the
to the summary estimate 0.86 (95% CI: 0.78–0.95) for all interpretation of the nonlinear analysis as the number of
the cohort studies. data points at higher physical activity levels was limited.
The inverse association was significant in cohort studies,
but not in the randomized controlled trials; however, there
Discussion
was no heterogeneity by study design, and the small study
Main findings sizes and low number of cases may have contributed to the
This is to our knowledge the first dose–response meta-ana- lack of a significant association among the randomized tri-
lysis of physical activity and risk of preterm birth, and we als. Other measures of physical activity including leisure-

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Aune et al.

A C E
Moderate physical activity during pregnancy and preterm birth, high vs. low analysis Total physical activity during pregnancy and preterm birth, high vs. low analysis Walking during pregnancy and preterm birth, high vs. low analysis

Relative Risk
Relative Risk Relative Risk Study (95% CI)

Study (95% CI) Randomized controlled trials


Study (95% CI) Taniguchi, 2016 0.19 ( 0.02, 2.10)
Kong, 2014 0.35 ( 0.03, 4.03)
Rego, 2016 1.35 ( 0.74, 2.49) Subtotal 0.25 ( 0.05, 1.37)

Sealy-Jefferson, 2014 1.01 ( 0.71, 1.44) Currie, 2014 1.06 ( 0.67, 1.69) Cohort studies
Sealy-Jefferson, 2014 0.64 ( 0.43, 0.94)
Hegaard, 2008 1.01 ( 0.51, 2.01)
Jukic, 2012 1.20 ( 0.50, 3.10)
Hegaard, 2008 0.34 ( 0.14, 0.85) Misra, 1998 2.18 ( 1.38, 3.20)
Henriksen, 1995 1.40 ( 0.70, 2.50)
Magann, 1996 0.62 ( 0.44, 0.87) Launer, 1990 1.33 ( 0.85, 2.08)
Overall 0.64 ( 0.22, 1.83) Subtotal 1.21 ( 0.75, 1.95)
Overall 0.95 ( 0.63, 1.42)
Overall 1.09 ( 0.68, 1.75)

.01 .1 .25 .5 .751 1.5 2 3 5 .01 .1 .25 .5 .751 1.5 2 3 5 .01 .1 .25 .5 .75 1 1.5 2 3 5
Relative Risk Relative Risk Relative Risk

B D F
Vigorous physical activity during pregnancy and preterm birth, high vs. low analysis Occupational physical activity during pregnancy and preterm birth, high vs. low analysis Bicycling during pregnancy and preterm birth, high vs. low analysis

Relative Risk
Relative Risk Relative Risk Study (95% CI)
Randomized controlled trials
Study (95% CI) Study (95% CI) Ghodzi, 2014 3.00 ( 0.45, 20.51)
Kasawara, 2013 0.53 ( 0.26, 1.06)
Wang, 2017 0.60 ( 0.14, 2.57)
Seneviratne, 2016 2.30 ( 0.20, 29.60)
Jukic, 2012 0.08 ( 0.01, 1.00) Jukic, 2012 0.60 ( 0.20, 2.00)
Halse, 2015 1.50 ( 0.33, 7.00)
Subtotal 0.83 ( 0.44, 1.58)

Evenson, 2002 0.80 ( 0.48, 1.35) Teitelman, 1990 0.71 ( 0.35, 2.04)
Cohort study
Juhl, 2010 0.86 ( 0.69, 1.08)
Subtotal 0.86 ( 0.69, 1.08)
Overall 0.36 ( 0.04, 3.09) Overall 0.67 ( 0.33, 1.34)

Overall 0.84 ( 0.69, 1.04)

.01 .1 .25 .5 .751 1.5 2 3 5 .01 .1 .25 .5 .751 1.5 2 3 5 .01 .1 .25 .5 .75 1 1.5 2 3 5

Relative Risk Relative Risk Relative Risk

Figure 4. Moderate, vigorous, total and occupational physical activity, and walking and bicycling during pregnancy and preterm birth.

time physical activity before pregnancy, and total, moderate of physical activity (up to 5–7 hours per week) in relation to
or vigorous physical activity, bicycling, walking and occu- preeclampsia,12 gestational diabetes11 and type 2 diabetes,83
pational physical activity during pregnancy showed non- and any recommendations regarding physical activity need
significant associations in the direction of reduced risk, to take into consideration overall health, not just the risk of
most likely also due to low statistical power. preterm birth.

Strengths Limitations
Our meta-analysis also has several strengths. Because we only Our meta-analysis may have some limitations that could
included cohort studies and randomized trials, the possibility have affected the results. Unmeasured or residual con-
that recall bias and selection bias explains the results is founding could have influenced the results. Higher physical
reduced. The study quality of the cohort studies was high, activity is associated with other healthy behaviours and risk
and approximately half of the randomized trials were at low factors, including lower prevalence of smoking and over-
risk of bias. Among the cohort studies the inverse association weight/obesity. However, many of the studies included in
was only significant among studies with a high study quality, this meta-analysis adjusted for known confounding factors
although there was no between-subgroup heterogeneity. We such as age, BMI, smoking, and the associations persisted
conducted dose–response analyses and found evidence of a in subgroup analyses with adjustment for these variables
dose–response relationship up to 2–4 hours per week, but and there was no evidence of between-subgroup hetero-
no further reductions in risk with higher levels of activity; geneity with meta-regression analyses. The possibility of
however, because of few data points at higher levels of physi- confounding by less established risk factors including diet
cal activity further studies are needed to clarify the dose–re- cannot be ruled out, but needs clarification in future stud-
sponse relationship at higher levels of activity. In contrast, ies. We found no evidence of publication bias with the sta-
we have previously reported further benefits of higher levels tistical tests or by inspection of the funnel plot.

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Physical activity and preterm birth: a meta-analysis

Although the result from the 20 randomized clinical trials increased risk of preterm birth in several studies.85–89 Physical
was not statistically significant, most of the trials were very activity improves insulin sensitivity,90–92 and may decrease
small (14 of the trials had <10 cases, five trials had between the inflammatory response that is suggested as a risk factor
17 and 39 cases, and the largest trial had 66 cases), and had for preterm birth.93 Higher levels of tumour necrosis factor-
therefore too low statistical power to detect an association. a (TNF-a) have been related to the onset of labour and
Some of them may have had a physical activity level that may preterm birth,94,95 and physically active women have lower
have been too low to reduce risk, and there may also be levels of TNF-a than inactive women.96,97
issues with low compliance and contamination of the control
groups, which could have biased the estimates toward the
Conclusion
null. The percentage of withdrawals was similar in the inter-
vention and control groups in most of the clinical trials, thus In conclusion, these results suggest that higher physical
attrition bias is less likely to have affected the results. activity is associated with reduced risk of preterm birth.
Another limitation was that few of the studies reported Any additional studies should try to further clarify the
results in such a way that they could be included in dose– dose–response relationship, joint effects between physical
response analyses (for example in three-four or more cate- activity before and during pregnancy and risk of preterm
gories by hours or MET-hours per month or week), and births, and associations between specific subtypes and
therefore the dose–response analyses may not have been intensities of physical activity and risk of preterm birth, as
representative for all the studies. This problem has also well as clinical subtypes and severity of preterm births. Fur-
been observed in our previous meta-analyses of physical ther well-designed large randomized controlled trials with a
activity and preeclampsia,12 gestational diabetes11 and type sufficient level of activity to reduce the risk are also needed
2 diabetes,83 and point to a need for more standardized to conclusively demonstrate an association. However, con-
reporting of physical activity data in epidemiological stud- sidering benefits of physical activity for the prevention of
ies. Based on the nonlinear dose–response analysis, the data obesity and other pregnancy outcomes, our results support
suggest that 2–4 hours per week of physical activity will be previous recommendations for pregnant women to be
needed to reduce the risk of preterm birth by 15–16%, active on most if not all days of the week.
although for other pregnancy complications further benefits
are observed for higher levels of activity.11,12 Acknowledgement
Because most of the morbidity and mortality associated The authors thank Dr Darren C. Greenwood (Biostatistics
with preterm births occurs in infants born very premature, Unit, Centre for Epidemiology and Biostatistics, University
a further limitation of the present study is that most of the of Leeds, Leeds, UK) for providing the Stata code for the
studies included in this meta-analysis reported results for nonlinear dose–response analyses.
preterm birth overall, and did not present results according
to clinical subtype or severity. One study reported similar Disclosure of interest
inverse associations for very premature births (<33 weeks) None declared. Completed disclosure of interests form
as for premature births (33–35 weeks),62 while another available to view online as supporting Information.
study that found no association found no differences by
subtypes of severity.84 Any further studies could try to clar- Contribution to authorship
ify if the association differs by clinical subtypes or severity. DA designed the project, conducted the literature search
and analyses, and wrote the first draft of the paper. SS con-
Interpretation tributed to the study screening and data extraction. DA,
Several potential mechanisms may explain the inverse associ- SS, TH, ODS, ST interpreted the data, revised the subse-
ation we observed between physical activity and preterm quent drafts for important intellectual content and
birth. Physical activity is essential for weight control, and approved the final version of the paper to be published.
reduces the risk of adiposity and excess gestational weight
gain,7–9 which has been associated with increased risk of pre- Details of ethics approval
term birth.5 Although the association was slightly stronger Ethical approval was not needed as the study uses already
among studies that did not adjust for BMI and reduced adi- published data.
posity partly may explain the association, there was still a sig-
nificant 21% reduction in the RR among studies that adjusted Funding
for BMI, suggesting a clinically relevant reduction in risk inde- This project has been funded by Liaison Committee
pendent of BMI. Physical activity also reduces the risk of type between the Central Norway Regional Health Authority
2 diabetes,83 gestational diabetes11 and preeclampsia,12 obe- (RHA) and the Norwegian University of Science and Tech-
sity-related conditions that have been associated with nology (NTNU) and the Imperial College National Institute

ª 2017 Royal College of Obstetricians and Gynaecologists 1823


Aune et al.

of Health Research (NIHR) Biomedical Research Centre 9 Lof M, Hilakivi-Clarke L, Sandin S, Weiderpass E. Effects of pre-
(BRC). pregnancy physical activity and maternal BMI on gestational weight
gain and birth weight. Acta Obstet Gynecol Scand 2008;87:524–30.
10 Streuling I, Beyerlein A, Rosenfeld E, Hofmann H, Schulz T, von KR.
Supporting Information Physical activity and gestational weight gain: a meta-analysis of
intervention trials. BJOG 2011;118:278–84.
Additional Supporting Information may be found in the 11 Aune D, Sen A, Henriksen T, Saugstad OD, Tonstad S. Physical
online version of this article: activity and the risk of gestational diabetes mellitus: a systematic
review and dose-response meta-analysis of epidemiological studies.
Figure S1. Funnel plot of leisure-time physical activity Eur J Epidemiol 2016;10:967–97.
during pregnancy and preterm birth. 12 Aune D, Saugstad OD, Henriksen T, Tonstad S. Physical activity and
Figure S2. Influence analysis of leisure-time physical the risk of preeclampsia: a systematic review and meta-analysis.
activity during pregnancy and preterm birth. Epidemiology 2014;25:331–43.
Table S1. List of excluded studies and exclusion reason. 13 Santos IA, Stein R, Fuchs SC, Duncan BB, Ribeiro JP, Kroeff LR, et al.
Aerobic exercise and submaximal functional capacity in overweight
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