Physical Activity during Pregnancy and Newborn Body Composition: A Systematic Review

The current literature demonstrates that not only is exercise during pregnancy safe, but it has substantial maternal and infant benefits and appears to influence infant growth/size throughout pregnancy and at birth. However, many existing studies have investigated only the effects of prenatal exercise on birth weight. The purpose of this review was to determine the impact or association of maternal physical activity during pregnancy on neonatal body composition assessed between birth and two weeks of age. Electronic database searches were conducted on 29 July 2019 for randomized control trials and cohort studies, with an updated search completed on 8 January 2021. A total of 32 articles that met eligibility criteria were selected for review. Overall, prenatal exercise was not associated with infant body composition at birth. Yet, five of the studies identified suggest that infant body composition could be influenced by higher volumes of mid-to-late term prenatal physical activity. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (Registration No. CRD42020160138).


Introduction
Scientific evidence has demonstrated the safety and efficacy of exercise during the perinatal period [1][2][3][4][5]. Physical activity (PA) during pregnancy provides many maternal health benefits, including improved glucose control, lower gestational weight gain, lower systemic inflammation, reduced risk for preeclampsia, reduced risk for operative deliveries, and faster postpartum recovery time [1][2][3][4][5]. In addition to improvements in maternal health, physical activity during pregnancy has also been shown to benefit the neonate, including healthy growth and improved cognition and intelligence [6,7]. Specifically, exercise during pregnancy has been linked to lower and healthier infant birth weight (without increasing risk for low birth weight) [8,9].
Birth weight has been used historically to indicate a healthy intrauterine growth environment; however, birthweight is not a strong predictor of important future health outcomes [10], particularly at the individual level [11]. Despite the lack of evidence to support its connection to downstream outcomes, it is widely utilized clinically and is typically one of the first assessments of a newborn. One reason why birth weight may be a poor predictor of outcomes is it cannot adequately estimate fat mass relative to fat-free mass in infants. It also does not account for how much an infant "should have weighed" based on their length and genetic potential [11]. Assessing body composition at birth (i.e., fat mass versus fat-free mass) may provide additional details indicating healthy fetal/neonatal growth/size. Further, adiposity levels at birth are a better predictor of metabolic syndrome and other non-communicable diseases later in life than birthweight alone [12].
Taken together, understanding the relationship between physical activity during pregnancy and infant body composition is essential. Exercise during pregnancy appears to influence infant growth/size [9,13]; however, many existing studies have investigated only the effects of prenatal exercise on birth weight and not body composition. Over the past 10 years, research investigating the role of exercise during pregnancy on infant body composition has gained momentum. However, the existing evidence on the impact physical activity during pregnancy has on infant body composition is unclear and oftentimes conflicting. The conflicting results may be due to how physical activity was assessed, what timepoint during pregnancy exercise was studied, and the frequency, intensity, time, and type of exercise performed. The purpose of this systematic review is to determine the association of maternal physical activity during pregnancy and neonatal body composition assessed between birth and two weeks of age.

Methods
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review protocol was pre-registered with the International Prospective Registrar of Systematic Reviews (PROSPERO) registration number CRD42020160138. We followed the PRISMA reporting guidelines (see Appendix A).

Types of Study Designs
Eligible study designs included randomized controlled clinical trials (RCTs), prospective cohort studies, and retrospective cohort studies that assessed physical activity levels at any point during pregnancy and assessed infant body composition within two weeks of delivery. Studies were included regardless of intensity, duration, or mode of physical activity utilized. Only studies that were peer-reviewed with scientific credibility were included. The decision to include non-RCTs was based on several factors, including lack of existing RCTs assessing infant body composition as an outcome; poor adherence to interventions, making it difficult to truly evaluate the relationship between physical activity levels and infant outcomes; and the idea that other study designs may better allow assessment of physical activity as a continuous variable versus as a grouping variable (i.e., control group vs. exercise group).

Types of Participants
Women of all pre-pregnancy body mass indices (BMIs) were included. Studies including women with gestational diabetes and preeclampsia were excluded. These specific conditions have known and particular effects on infant body size/composition and would make it difficult to discern the impact of physical activity on infant outcomes. Studies including multiple gestation pregnancies were also excluded.

Types of Outcome Measurements
For the mode of exercise, studies including all modes of physical activity were included (aerobic training, resistance training, combination training). The physical activity assessment could be through self-reporting (e.g., the Pregnancy Physical Activity Questionnaire), compliance to an intervention, or objective assessments (i.e., accelerometer, pedometer, or doubly-labeled water). Exercise data could be collected during any timepoint of pregnancy (1st, 2nd, 3rd trimester, or throughout pregnancy). For the outcome of infant body composition, the study had to include an assessment or estimate of infant adiposity (and not just birth weight). These included ponderal index, BMI, abdominal circumference, or body fat percentage from bioelectrical impedance, dual X-ray absorptiometry (DXA), skinfold anthropometry, or air-displacement plethysmography. Any studies including an initial assessment of body composition on infants >2 weeks of age were excluded.

Search Strategy
Electronic searching of PubMed/MEDLINE, EMBASE (Elsevier), Web of Science Core Collection (Thomson Reuters), and CINAHL (EBSCO) databases took place on 29 July 2019. Phrases and controlled vocabulary headings for each component of the population and outcome framework (PICO) were combined using OR and then using AND (exercise/physical activity, pregnancy, neonate, and body composition). The search strategy was first created in PubMed (See Appendix B) and then translated for each database platform as appropriate. Manual searches of reference lists were conducted on all eligible articles following the screening. An updated search was completed on 8 January 2021.

Assessment of Bias
The risk of bias (RoB) was assessed on all studies selected for inclusion. Randomized control trials (RCTs) were evaluated using Version 2 of the Cochrane risk-of-bias tool (RoB 2) [14]. Each RCT was assessed using the study's "per-protocol" effect by independent reviewers (CD, BM, EA). Discrepancies in RoB scoring were resolved by discussion between reviewers and an additional study team member (JM). Five bias domains were assessed (i.e., selection, performance, detection, attrition, and reporting), and an overall bias score was calculated.
RoB in case-control and single-arm cohort studies was evaluated using a modified Newcastle-Ottawa Scale (NOS) [15] (See Appendix C). Again, discrepancies in RoB scoring were resolved by discussion between reviewers and an additional study team member (JM). Three bias domains were assessed (i.e., selection, comparability, exposure/outcome), and an overall bias score was calculated (See Appendix D).

Data Management
All articles retrieved from the electronic databases were imported to EndNote, and duplicates were removed. After deduplication, titles and abstracts were uploaded to Rayyan, a web and mobile app for systematic reviews, for screening [16]. In stage one of screening, reviewers independently screened titles and abstracts of articles yielded by the search to identify potentially eligible studies based on the inclusion criteria (CD, BM). In stage two, if eligibility was unclear from the review of title and abstract, the full text was obtained for further assessment, and discrepancies were resolved by discussion between reviewers and consensus (CD, BM, JM, RT). In stage three of the screening process, full versions of relevant articles were obtained and carefully assessed to ensure they fit the predetermined study criteria. The full-text screening was conducted by two independent reviewers (CD, BM). Discrepancies were resolved by consensus among the study team (CD, BM, JM, RT).
Overall, prenatal exercise was not associated with infant body composition at birth. Of the 32 articles included, only five suggested a difference in infant body composition could be influenced by prenatal physical activity [20,33,34,36,46]. Specifically, those five studies found that women with a greater total volume of mid-to-late term physical activity gave birth to infants with less fat mass than those who had little to no PA throughout pregnancy.

Risk of Bias Assessment
The overall risk of bias for randomized controlled trials was low to-moderate. Approximately 54% of the studies (7 of 13) were rated as having "some concerns" for the overall potential risk of bias [21,22,24,25,[27][28][29] (Figure 2). This rating was primarily due to the seven studies being rated as having "some concerns" in the performance risk of bias domain, which was assessed by rating deviations from the intended intervention. There was a low risk of selection bias for all studies, as all studies reported a random allocation sequence. Only one study did not provide enough information regarding the allocation sequence being concealed until after participants were enrolled/assigned to the intervention [23]. A summary of the RCT RoB scoring is listed in Figure 2.
For case-control and cohort studies, the risk of bias was generally low to moderate. We did not detect strong evidence of publication bias in these studies (See Appendix D). For case-control and cohort studies, the risk of bias was generally low to mod We did not detect strong evidence of publication bias in these studies (See Appendi

Discussion
Overall, this systematic review suggests maternal PA during pregnancy has min implications on neonatal adiposity, except for extremely high volumes of PA. How due to the variability in numerous elements of the study design (e.g., PA assess method, neonatal adiposity assessment method, and timing of data collections), mained a challenge to synthesize findings. These data suggest that maternal physic tivity does not appear to have a negative or detrimental impact on the body compos of the neonate, which is an important conclusion given fear of harm to the unborn ch a factor that prevents many women from getting or staying active during pregnancy In this review, we report that five studies noted a relationship between maternal PA

Discussion
Overall, this systematic review suggests maternal PA during pregnancy has minimal implications on neonatal adiposity, except for extremely high volumes of PA. However, due to the variability in numerous elements of the study design (e.g., PA assessment method, neonatal adiposity assessment method, and timing of data collections), it remained a challenge to synthesize findings. These data suggest that maternal physical activity does not appear to have a negative or detrimental impact on the body composition of the neonate, which is an important conclusion given fear of harm to the unborn child is a factor that prevents many women from getting or staying active during pregnancy [48]. In this review, we report that five studies noted a relationship between maternal PA and infant body composition [20,33,34,36,46]; however, none of them reported utilizing rigorous methods for assessing both maternal PA and neonatal body composition.

Summary of Studies That Showed Increased Maternal PA Is Associated with Decreased Neonatal Adiposity
Only one of thirteen randomized clinical trials had findings indicating that maternal PA has an impact on neonatal anthropometrics [20]. Specifically, findings from this study indicate that previously active women that decrease their physical activity levels by 67% (below the recommended 150 min/week) starting at mid-pregnancy through delivery, had heavier babies at birth (3.9 kg) with a higher amount of body fat (12.1%) compared to women who maintained relatively moderate to high levels of physical activity (at least 150 min/week) from mid-pregnancy to delivery (3.4 kg, 7.9%). Given that RCTs are the highest level of evidence, and 12 of 13 did not detect significant differences in neonatal adiposity between active and inactive women (with a variety of activities and intervention protocols), these collective findings suggest physical activity has a minimal impact on offspring adiposity.
Out of the 16 single-arm cohort studies that were identified, three studies found that maternal physical activity levels were associated with smaller amounts of neonatal adiposity [33,34,36]. In the most recent study from Collings et al., 2020, the authors found that among British white women there was a negative dose-response relationship. Women with moderate to high levels of maternal physical activity during mid-pregnancy (150 min or more per week of moderate intensity exercise) were associated with smaller infant skinfold measurements. However, this relationship was not apparent in the portion of the cohort that identified as ethnic minorities.
The second cohort study by Dahly et al., 2018, determined that the prevalence of babies born with very high fat mass was lowest among women that engaged in frequent moderate-intensity exercise early in pregnancy [34]. While neonatal body composition was assessed with air displacement plethysmography, maternal physical activity was subjectively self-reported with a one-question survey at 15 weeks gestation. This is problematic, as oftentimes physical activity levels change throughout pregnancy [49]. In addition, the maternal PA data were collected with a non-validated single question with only three possible responses (none, some (1-3 times per week) or often (4+ times per week)), which may lead to a lack of sensitivity for detecting important relationships.
The third cohort study, by Harrod et al., 2014, found that increasing levels of maternal physical activity, particularly during late pregnancy, are negatively correlated to neonatal adiposity [36]. In this cohort, women with high levels of late-pregnancy activity had an increased likelihood of SGA compared to women with low levels of physical activity. The authors suggest that the effect could be attributed to a decrease in neonatal fat mass, because there were no differences in neonatal fat-free mass stratified by total energy expenditure quartiles.
Out of three case-control cohort studies included, one study found a relationship between maternal physical activity and neonatal body composition [46]. Clapp and Capeless, 1990, compared infant outcomes between conditioned recreational runners and aerobic dancers (who maintained activity at or above 50% of preconception levels) and matched inactive controls. Infants born to active women had lower birth weight, ponderal index, two-site skinfold thickness, and calculated percent body fat, leading to the conclusion that continuation of regular aerobic exercise results in a reduction in neonatal fat mass. Specifically, the authors reported that differences in neonatal fat mass explained over 70% of the difference in birth weight [46].

Accuracy of PA Assessment (i.e., Type of Assessment, Timing, and Intensity)
Although a cohort design allows for free-living PA to be reported and/or recorded in addition to sports and exercise leisure-time PA, a randomized control trial that implements an intervention may be able to pinpoint specific PA modifying factors (i.e., duration, frequency, type, and intensity) and determine a direct causal relationship between exercise and infant body composition. It is plausible that specific modes, intensities, and/or volumes can have differential effects on infant body composition. Once again, this poses significant challenges to drawing broad conclusions about the relationship between general physical activity and infant adiposity.
While the Pregnancy Physical Activity Questionnaire (PPAQ) is commonly used across the literature, it has been found to overestimate leisure-time PA across all activity categories [50]. The PPAQ also only provides subjective/self-reported exercise information that is subject to recall bias. The accelerometer is the gold standard for objectively measuring free-living PA [51] and is the most reliable and accurate method for assessing MVPA during pregnancy [52]. Because only eight studies utilized objective accelerometry, conclusions regarding the role of PA on infant outcomes must be drawn carefully. In addition to the measurement of PA, the studies included in the review contained a variety of exercise modes (e.g., running, walking, dancing, swimming, cycling, weightlifting), once again posing a challenge in drawing definitive conclusions across studies, as different modes and intensities may have different implications for fetal growth.
Another factor that warrants consideration is the timepoint in pregnancy at which maternal physical activity assessments are taken. Some studies focus on early pregnancy, others on late pregnancy, and some assess throughout (See Tables 7-9). Upon careful examination, it is clear that the gestation period in which exercise occurs can impact the interpretation of the relationship between maternal activity levels and neonatal adiposity. Several studies reported late pregnancy activity levels [36,46], while others measured activity early on [34]. Once again, these differences in study design make it challenging to synthesize results, as maternal-fetal physiology changes drastically throughout pregnancy. Therefore, it is feasible that physical activity can impact fetal growth differently depending on the timepoint of pregnancy. For example, pregnant women become more insulin resistant as pregnancy progresses [53]; thus, fuel and substrate utilization change dramatically throughout a pregnancy [54]. The timing of pregnancy in which exercise occurs most likely confounds the relationship between exercise and infant adiposity.

Accuracy of Infant Anthropometric Assessments (i.e., Type of Assessment and Timing)
Another aspect of study design that may play a role in interpreting the relationship between maternal PA and infant anthropometrics is the accuracy of the infant assessment. The majority of included studies utilized skinfolds and/or ponderal indices, both of which are considered poor and imprecise measures of assessing infant body composition [55]. They are often used due to low cost and feasibility; however, it is clear that more accurate assessments of infant body composition (e.g., air displacement plethysmography) are needed in order to design high-quality studies. In addition to the type of anthropometric assessment tool being used, studies often vary in the timepoint at which they assess infant anthropometrics. Varying the timepoint of assessment can be problematic when comparing across studies, as infant size changes rapidly during early development [56]. For example, once the infant starts receiving either breastmilk or formula, that difference in dietary composition alone can impact infant growth patterns [57]. In order to minimize the impact of the infant's external environment and nutrient consumption (which can make it nearly impossible to draw any sort of conclusion about the direct impact of physical activity during pregnancy on infant adiposity), studies should attempt to take newborn assessments within the first 48 h of life. However, when observing the findings in Tables 7-9, many studies assessed infant adiposity around 2 weeks of age.

Is There an Optimal Amount of Physical Activity to Ensure Healthy Neonatal Adiposity?
Evidence suggests that only extreme levels of physical inactivity/activity seem to influence neonatal adiposity. Specifically, higher levels of maternal physical activity and vigorous maternal physical activity, particularly when performed throughout late pregnancy, are consistently associated with decreased neonatal fat mass. There may be a "threshold" point where moderate exercise is beneficial but heavy exercise is detrimental, at least with respect to birth weight [58]. It is unclear what the threshold is at this point. This does have some clinical utility in terms of being able to appropriately counsel the increasing number of women that wish to maintain high levels of physical activity during pregnancy. An increasing number of elite female athletes are choosing to enter motherhood during their competitive years. In fact, a recent consensus statement suggests that since the fertile age of many athletes overlaps with timing for peak performance, adequate information about the implications of exercise during pregnancy is needed so women can make informed decisions [59]. This systematic review adds to the body of literature that suggests pregnant women can feel reassured that they can continue exercise, but depending on the activity, may have to make small adjustments in intensity and volume in order to maintain appropriate fetal growth [59].
It is also possible that a minimal level of physical activity exists to prevent overgrowth. In fact, moderate maternal physical activity promotes appropriate fetal growth. For example, work from Barakat et al. suggests that light intensity resistance exercise training performed during the second and third trimester might attenuate the adverse consequences of maternal body weight before pregnancy on neonatal anthropometrics [17]. Specifically, Barakat et al. found that maternal body weight was positively and significantly associated with birthweight in the control group, but there was no association in the exercise training group. Others have reported that maternal pre-pregnancy BMI and gestational weight gain are positively and independently associated with neonatal adiposity [60]. It is possible that the impact of maternal physical activity on neonatal adiposity may differ according to maternal pre-pregnancy weight status and/or gestational weight gain status.

Conclusions
Despite the inherent limitations discussed above, which limit the ability to draw conclusions across studies, some important findings were noted. Collectively, the studies suggest that continuing a regular physical activity regimen during pregnancy does not compromise fetoplacental growth. This is critically important, as many women do not engage in appropriate levels of PA due to fear of harm to the unborn child [48]. Pregnant women should be counselled to continue or begin physical activity regimens, as it appears that physical activity (at reasonable intensities and volumes) has minimal effects on infant body composition.
Given the ongoing obesity epidemic, there is a need to identify children at risk of developing obesity as early in life as possible [48]. It is a challenge to identify neonates at risk as there are no published norms for "appropriate" or "ideal" levels of neonatal body fat percentage and/or fat mass (as exist for adults). Because of this, it is difficult to determine "ideal" amounts of PA as it relates to the impact of PA on infant body composition. However, given there were no clear trends of maternal PA on infant body fat percentage among the studies included in this review, it seems reasonable to conclude that PA during pregnancy, at most any level, is beneficial to the mother without unfavorably compromising fetal growth. With PA during pregnancy having substantial maternal and neonatal benefits [1], results from this review add to the consensus that health care providers should continue to encourage PA among patients while dispelling myths that PA could be harmful to the growth of the baby.  Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
pp. 5-6 Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.
pp. 5-6 Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g., for all measures, time points, analyses), and if not, the methods used to decide which results to collect.
pp. 5-6 10b List and define all other variables for which data were sought (e.g., participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.

Section and Topic Item # Location Where Item Is Reported Checklist Item
Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

Effect measures 12
Specify for each outcome the effect measure(s) (e.g., risk ratio, mean difference) used in the synthesis or presentation of results.

Supplemental
Tables S1-S3 Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g., tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)). Describe any methods used to explore possible causes of heterogeneity among study results (e.g., subgroup analysis, meta-regression).

NA 13f
Describe any sensitivity analyses conducted to assess robustness of the synthesized results. NA

Reporting bias assessment 14
Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).

p. 3
Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. NA

Study selection 16a
Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.
Cite studies that might appear to meet the inclusion criteria but which were excluded, and explain why they were excluded. For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g., confidence/credible interval), ideally using structured tables or plots.

Supplemental
Tables S1-S3 Indicate where the review protocol can be accessed, or state that a protocol was not prepared. 24c Describe and explain any amendments to information provided at registration or in the protocol.

Support 25
Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review.

Competing interests 26
Declare any competing interests of review authors.
Availability of data, code, and other materials 27 Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.

Appendix B
This search strategy was developed with the assistance of an information specialist experienced with systematic reviews. The strategies combined medical subject headings (MeSH) and keywords for exercise/physical activity, pregnancy, neonate, and body composition.
PubMed Search Strategy:

Appendix C. Newcastle-Ottawa Quality Assessment Scale
Note: This scale has been adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort studies to perform a quality assessment of these studies for the systematic review.
Selection: Maximum of 7 stars.
(1) Representativeness of the exposed or high(er/est) PA cohort (a) truly representative of all subjects from which they were recruited (1 star) (b) somewhat representative (1 star) (c) selected group (e.g., nurses, volunteers) or a subset of larger cohort study (d) no description of the derivation of the cohort (2) Selection of the non-exposed (control or sedentary or low PA) cohort (a) drawn from the same community as the exposed cohort (1 star) (b) drawn from a different source (c) no description of the derivation of the non-exposed cohort (3) Ascertainment of exposure (maternal PA) (a) objective assessment (i.e., accelerometer), supervised exercise sessions, or validated measurement tool (PPAQ) (2 stars) (b) non-validated PA measurement tool (but the tool is available or described), self-report, or self-reported or written exercise session attendance/recall (1 star) (c) no description If applicable, answer choices "a" AND "b" AND "c" can be selected.
(1) Comparability of cohorts/groups based on the design or analysis. The subjects in different exposure or outcome groups are comparable, based on the study design or analysis. Confounding factors are controlled.
(a) study controls for maternal weight status (1 star) (b) study controls for neonatal sex and/or gestational age (1 star) (c) study controls for any additional factors (i.e., maternal age, gestational weight gain, parity, other factors related to maternal metabolic health, etc.) (1 star) (d) cohorts are not comparable based on the fact that the design or analysis failed to control for confounders Outcome (neonatal adiposity): Maximum of 4 stars.
(1) Assessment of outcome (neonatal adiposity) (a) gold standard assessment (e.g., ADP or DXA) and/or independent blind assessment (2 stars) (b) record linkage (1 star) (c) self-report (d) no description or other (2) Statistical test (a) the statistical test used to analyze the data is clearly described and appropriate, and the measurement of the associated is presented, including confidence interval and the probability level (p-value) (1 star) (b) the statistical test is not appropriate, not described, or incomplete (3) Adequacy of follow-up of cohorts (a) complete follow-up-all subjects accounted for (1 star) (b) subjects lost to follow-up unlikely to introduce bias-small number lost ≥80% follow-up, or description provided of those lost (1 star) (c) follow-up rate <80% and no description of those lost (d) no statement.