We previously reported that regular aerobic physical activity during pregnancy is associated with lower fetal heart rate (FHR) and higher HR variability (HRV) at rest (26,28). “Physical activity” is a term used to describe many types of aerobic and anaerobic activities (other than activities of daily living) an individual can participate in when he or she is not working at a job. These activities vary in intensity and duration and all involve some level of energy expenditure measured in kilocalories. The intensity of physical activity refers to the amount of work completed per unit time (e.g., kcal·min−1), whereas the duration of physical activity is expressed as the total amount of time spent in physical activity during a week or month. When examining relationships between physiological adaptations to physical activity and disease risk, it is important to consider both the intensity and duration of physical activity, such as the dose response (25).
Dose–response findings generally provide a stronger case for inferring causality between variables. Significant dose–response associations have been found between physical activity and cardiorespiratory fitness in adults, cardiovascular disease risk (20), and all-cause mortality (34). In adults, lower HR and increased HRV from exercise are associated with a decreased risk of CHD, stroke, and lower cardiovascular mortality rates (33,41,42).
Fetal HR and its variability are easily measured during pregnancy and provide evidence for fetal well-being and appropriate autonomic nervous system development. Because the autonomic nervous system is involved in the regulation of most physiological processes, HRV provides an advanced indicator of fetal health. In response to maternal cigarette smoking, FHR is bradycardic (FHR < 120 bpm) and is coupled with lower HRV, indicative of the negative effects of nicotine exposure and most likely hypoxia during development (17,29). Similarly, fetuses exposed to alcohol have lower HR, with little or no HRV (19) and associated with poor pregnancy outcomes. Furthermore, the persistence of HR and HRV within individuals is well established (6,13–15), as well as how these measures relate to developmental outcomes. For example, slower HR and increased HRV in the fetus are associated with significantly higher motor development indices and better language development at 2 yr (14). The measures of HR and HRV are used during pregnancy to determine overall health and appropriate nervous system development of the fetus, which can be extrapolated to relate to later development after birth.
Physical activity during pregnancy results in several positive maternal effects: shorter labor and delivery times, faster recovery after delivery, decreased pregnancy discomforts, and fewer pregnancy complications (8,27). In addition, this is found to have minimal risk to the fetus (8,27). Although the importance of physical activity during pregnancy for the mother is fairly clear, there is no empirical evidence demonstrating a physical activity dose response and fetal outcomes. The purpose of this retrospective analysis was to determine whether a dose response relationship exists between maternal physical activity and fetal cardiac autonomic nervous system function. We hypothesized that higher maternal intensity and duration of activity would result in lower fetal HR and increased HRV in a dose–response manner, with no effect on sympathovagal balance.
The women in this study (n = 66) were part of a longitudinal nonblinded study designed to determine the effects of self-reported exercise on fetal cardiac autonomic nervous system function. All protocols were approved by the Kansas City University of Medicine and Biosciences and the University of Kansas Medical Center institutional review boards and human subjects committees. Written informed consent was obtained from each participant. Women were tested between 10:00 a.m. and 5:00 p.m. All women were healthy without any pregnancy-related complications and 23–39 yr with singleton pregnancies. All women were nonsmokers with no history of alcohol or drug use. Because we found significantly lower HR and increased HRV in fetuses exposed to maternal exercise only at 36-wk gestational age in the previous study (26), we limited this retrospective analysis to that time point. Fifty-one women remained in the study at 36-wk gestational age. One subject did not complete the questionnaire properly and was excluded from the analysis leaving a sample size of 50. Prepregnancy body mass index (BMI) was calculated using the formula [weight (kg) / height (m) squared]. The prepregnancy height and weight were self-reported on the questionnaire.
Physical activity questionnaire.
At 36-wk gestational age, the Modifiable Physical Activity Questionnaire was used to assess all leisure time physical activities performed during the past 9 months of pregnancy, plus 3 months before pregnancy. For this study, data for the months pertaining to the third trimester (months 10 through 12) were extracted and used to calculate the physical activity variables subjected to the statistical analyses. Physical activities consisted of aerobic (e.g., walking, jogging), anaerobic (e.g., weight lifting, yoga), and lifestyle (e.g., gardening, cleaning house) activities. Occupational and daily-living (e.g., getting dressed) activities were not assessed. This questionnaire was selected because it is a reliable and valid instrument for assessing the duration and intensity of physical activity in various populations including pregnant women (10,23). Duration (minutes during the third trimester) was derived by multiplying the number of sessions by session length (min) for all physical activities performed during the third trimester. Intensity in kilocalories per minute was computed by multiplying the activity’s MET, metabolic equivalent for physical activity, value by the subject’s body weight (kg) and then dividing by 60 min (2). We measured maternal current body weight with a calibrated scale when women came to their 36-wk visit. Given that pregnancy involves weight gain, which affects energy expenditure, the intensity values were expressed relative to body weights of the subjects at 36-wk gestational age providing the weight-adjusted intensity (kcal·min−1·kg−1) variable.
Biomagnetic signals were recorded using an investigational 83-channel dedicated fetal biomagnetometer (CTF Systems, Inc., Port Coquitlam, BC), housed in a magnetically shielded room (26). The axial gradiometer sensors are spatially distributed to cover the gravid maternal abdomen. Pregnant subjects were comfortably seated, slightly reclined and in contact with the surface of the biomagnetometer interface without applying pressure to the abdomen. The data were acquired in a continuous 18-min recording using a 300-Hz sampling rate and a recording filter of 0–75 Hz. Data were digitally filtered between 1 and 40 Hz offline (bidirectional fourth-order Butterworth filter).
Processing magnetocardiogram signals.
All 18-min multivariate data recordings were presented to an Infomax independent component analysis algorithm implemented in the EEGLAB toolbox, free download from University of California San Diego, (12) to segregate maternal magnetocardiogram (MCG), fetal magnetocardiogram, and various fetal movements with distinct and previously characterized biomagnetic signatures (18,37,38). The fetal magnetocardiogram was identified and fiducial R peaks were automatically detected using a template-matching algorithm designed by our team to generate the interbeat-interval time series (18,26,37,38). All MCG traces were manually checked (L.E.M., K.M.G.) for incorrectly marked or missed beats. Then, once all the R peaks were marked, the traces were submitted for HRV analysis.
HR and HRV measures.
The metrics applied to the fetal interbeat-interval time series are as follows (Table 1):
- HR expressed in beats per minute.
- The root mean square of successive differences (RMSSD) between consecutive interbeat intervals is associated with parasympathetic innervation; hereafter, this will be called short-term HRV.
- The SD of interbeat-interval series (SDNN, as NN is the acronym for normal-to-normal intervals) is associated with parasympathetic and sympathetic innervation; hereafter, this will be called overall HRV.
The interbeat-interval time series was converted to frequency using a fast Fourier transform. From this, we derived power in the following frequency bands (Table 1): very low frequency (VLF—mainly sympathetic control) (0.02–0.08 Hz), low frequency (LF—sympathetic and parasympathetic control) (0.08–0.2 Hz), and high frequency (HF—mainly parasympathetic control) (0.4–1.7 Hz). We chose these frequency bands on the basis of the work of David et al. (11). Ratios of VLF/LF, VLF/HF, and LF/HF provided a measure of sympathovagal balance.
Fetal activity state was determined by visual inspection of the HR pattern generated from the interbeat-interval time series (32,35,44) by two independent investigators (L.E.M. and K.M.G.). If state determination differed between the investigators, a third opinion was obtained, and a consensus was reached. Each recording was classified as either an active (2F, 4F) or a quiet (1F, 3F) activity state.
The level of significance was set a priori at α < 0.05, and all statistical analyses were performed using SAS version 9.2, and Figure 1 was prepared by the Statistical Package for Social Sciences (SPSS, version 17.1; Chicago, IL, 2009).
Maternal and fetal measures were summarized as means ± SD if their distributions were approximately normal or by quartiles if they were skewed. The Spearman correlation procedure was used to assess relationships between maternal physical activity and HR and HRV. Multiple regression analyses were also performed for a fetal HRV measure demonstrating significant correlations with a maternal exercise measure. In these analyses, HR and HRV were regressed (in separate models) on each of the maternal physical activity measures with covariates (maternal age, maternal resting HR, maternal weight gain, prepregnancy BMI, and fetal activity state) entered in the model. Parsimonious models were obtained by a backward elimination procedure, and potential interaction terms were included. Absolute and relative intensity variables were highly correlated (r = 0.83, P < 0.0001, results not shown), and thus, factoring body weight into intensity estimates did not alter the strengths of its association with the fetal measures. Therefore, only the results for the absolute intensity variable are presented and discussed in the results.
Complete fetal measures and physical activity data were obtained from 51 maternal–fetal pairs at 36-wk gestational age. Maternal and fetal descriptive statistics are presented in Table 2. All fetal HR recordings at 36-wk gestational age were within normal HR range (120–180 bpm), except one fetus whose HR was 115 bpm. This one fetus was in the calmest activity state during this recording, had HRs within the normal range at other recordings before and after this bradycardic measure, and was born a healthy baby. According to prepregnancy weight and BMI, 28% were overweight (BMI = 25–29.9), and 8% were obese (BMI ≥ 30). All women experienced weight gain during pregnancy. The majority (74%) of fetuses were in the active state during the MCG recording. The median value for maternal physical activity duration was 1800 min during the third trimester. The median intensity was 5.9 kcal·min−1, which is near the boundary (6.0 kcal·min−1) separating moderate- and vigorous-intensity levels of physical activity (2).
The intensity of maternal physical activity was inversely correlated with fetal HR (P < 0.005) and positively correlated with overall HRV (P < 0.05) and VLF (P < 0.05). Significant and positive correlations were found between the duration of physical activity and all fetal HRV measures (Table 3). There was no significant correlation between maternal physical activity measures and fetal cardiac sympathovagal balance (VLF/LF, VLF/HF, or LF/HF). There was no correlation between maternal sedentary time with fetal HR and HRV (results not shown) (Table 3).
Multiple Regression Results
Provided in Table 4 are the results of the analyses where each fetal measure was regressed on the maternal physical activity measures (duration or intensity) in separate models that also included the covariates and interaction terms (physical activity duration × fetal activity state or intensity × fetal activity state) as seen in Table 5.
Physical activity duration was not significantly associated with fetal HR even after adjusting the covariates of maternal resting HR and fetal activity state (both P < 0.05, Table 5). Fetuses in the active state and higher maternal resting HR were associated with higher fetal HR. The interaction term in the physical activity intensity model was significant (P < 0.001, Table 5), prompting a follow-up regression analysis on each activity state separately. As Figure 1 indicates, maternal physical activity intensity and fetal HR were significantly associated only when the fetus was in the active state (fetal HR decreased 3.5 bpm for every kilocalorie-per-minute increase in intensity, P < 0.001) but not in the quiet state (P = 0.15).
Time domain HRV measures.
After adjusting maternal age and fetal activity state, the overall HRV (SDNN) increased [exp(9.0 × 10−5 × 60)] = 1.005 times (or 0.5%) for every hour increment in exercise duration or increased [exp(0.04)] = 1.04 times (or 4%) for every unit increment in exercise intensity after adjusting fetal activity status.
Fetal short-term HRV (RMSSD) increased [exp(7.9 × 10−5 × 60)] = 1.005 times (or 0.5%) for every hour increment in duration (P = 0.005) or [exp(0.026)] = 1.026 times (or 2.6%) for every unit increase in intensity of exercise, although this effect was marginally significant (P = 0.06). None of the covariates or interactions was significantly associated with short-term HRV measures.
Frequency domain HRV measures.
Fetal VLF, LF, and HF increased significantly with physical activity duration (Table 4). For every hour increase in exercise duration, fetal VLF, LF, and HF increased 0.8%, 1.0%, and 0.9%, respectively. For every unit increase in exercise intensity, these measures increased 7.4%, 6.5%, and 4.3%, respectively (Table 4).
These study results provide evidence for a dose–response relationship between maternal physical activity levels and fetal cardiac autonomic nervous system control. Women who engaged in higher intensity physical activity had fetuses with lower HR and greater overall HRV. Furthermore, the greater the duration of physical activity women performed throughout the third trimester, the greater the increase in fetal HRV. These findings corroborate research literature showing that associations between physical activity and physiological responses vary as a function of physical activity duration and intensity (25). Moreover, they support current American Congress of Obstetrics and Gynecology (ACOG) recommendations encouraging pregnant women to engage in physical activity for 30 min three times a week or more if they were previously active (1). Although we observed enhanced fetal cardiac autonomic control when mothers participated in lighter intensity physical activity below the level recommended by ACOG, the minimum threshold of activity necessary for maternal benefits may be higher than that for the fetus. Although these findings warrant confirmation from other studies, their implications are intriguing considering the potential positive effects on physical activity compliance and adherence during pregnancy, especially for women who are sedentary.
In pregnant women, an increased intensity of physical activity leads to increased catecholamine levels. The augmented maternal catecholamines from physical activity cross the placental barrier (30,31,43,46). Studies have shown increased HR during or immediately after maternal exercise, suggesting the fetal heart responds to exercise-induced internal alterations (i.e., physiological, biochemical) in the mother without signs of distress (3,4,9,21). Repeated exposure to these changes in utero, especially in the third trimester when cardiac autonomic innervation in the fetus is forming, may influence fetal development (45). From this interaction, there are two potential mechanisms. One potential mechanism that may explain how maternal exercise lowers fetal HR is by modulating changes in cardiac myocyte plasma membrane (i.e., adrenergic receptors, muscarinic receptors, fatty acid phospholipids). For example, exposure to epinephrine influences the polyunsaturated fatty acid composition of phospholipids (5) and β-adrenergic receptors, which interact with muscarinic receptors on fetal cardiomyocytes (24,39). Alternatively, exercise hormones also influence brain cholinergic neurons, the hypothalamic–pituitary–adrenocortical pathway, and cortisol levels (16). Because the placenta is an important endocrine organ that functions throughout pregnancy, it is possible that the effects of maternal exercise hormone levels exert a direct effect on the placenta and its endocrine function. Either or both of these mechanisms may have a role in how maternal exercise influences fetal cardiac autonomic regulation.
Interestingly, maternal factors (i.e., maternal age, maternal resting HR, maternal weight gain, prepregnancy BMI) did not influence the associations between physical activity and fetal parameters. Fetal cardiac autonomic control was enhanced in mothers who participated in physical activity regardless of the amount of weight they gained, their weight status before pregnancy, resting HR, or age. Conversely, fetal activity state was an important factor to consider for correct interpretation of the fetal–maternal relationships.
The results of this study are relevant for public health. Lower fetal HR and increased HRV were associated with greater maternal physical activity during pregnancy. These cardiac adaptations to physical exercise in adults are associated with decreased cardiovascular disease (33,41,42). A follow-up study of 17- to 20-yr subjects who were exposed to maternal exercise in utero found no evidence of obesity or cardiovascular disease compared with youth not exposed to maternal exercise during pregnancy (36). Given the current data regarding the benefits of physical activity during pregnancy, it is essential to develop focused health initiatives targeting the gestational period.
The results of this study should be interpreted with regards to its limitations. First, physical activity was ascertained using the Modifiable Physical Activity Questionnaire, which is a reliable and valid instrument for assessing physical activity in pregnant women (10,22,23). Nevertheless, this questionnaire is a self-report instrument that may be vulnerable to recall bias that could lead to inflated estimations of physical activity levels (40). Spearman correlation analysis found a negative a relationship (ρ = −0.31) between maternal intermittent physical activity (duration, P = 0.013) during 9 months and maternal resting HR at 36-wk gestational age; maternal activity is not related to other measures, such as age, weight, and weight gain. This finding supports the accuracy of maternal activity level reported in the questionnaire. The use of electronic monitors is warranted because it could provide additional insights. Second, without increased numbers of women, especially those who exercise at vigorous intensities and/or longer durations, we are not able to comment on the higher intensity and duration effects on the fetal cardiac development. We do not know at this time if the linear relationship flattens or drops at higher maternal intensities or durations. Third, because women who were actively exercising during pregnancy did so before conception, there may be other explanations for these findings. We are currently beginning a project to determine whether similar effects will occur in previously sedentary women. Lastly, although this was not a randomized controlled trial, the secondary analysis adjusting for maternal factors and fetal activity state strengthens confidence in the current findings.
There is strong support that maternal physical activity dose during pregnancy is associated with a fetal heart training response based on fetal HR and HRV measurements. Maternal age, resting HR, weight gain, and prepregnancy BMI are not major factors associated with fetal heart responses to maternal exercise. Fetal cardiac response to chronic maternal physical activity supports ACOG recommendations for regular aerobic exercise of moderate to vigorous intensity daily throughout pregnancy. Further research should explore other areas of how maternal exercise may benefit long-term health of the offspring. In light of the growing obesity pandemic, research can be done to determine whether maternal exercise has a long-term effect on body composition and risks of obesity or diabetes mellitus in offspring.
This study was supported by Kansas City University of Medicine and Biosciences intramural grants and HBIC pilot funds. HBIC is supported by a generous gift from Forrest and Sally Hoglund. This study was not supported by the National Institutes of Health, Wellcome Trust, Howard Hughes Medical Institute, or other external funds.
There are no professional relationships with companies or manufacturers to disclose for all authors. The poster of this article was presented at the American Physiological Society–FASEB Conference in Anaheim, CA, on April 26, 2010.
The authors thank the women who gave their time to participate in this study. They also thank Lori Blanck, R. EEG/EP T., and JoAnn Liermann, R.N., Ph.D., at the University of Kansas Medical Center’s Hoglund Brain Imaging Center (HBIC), for assistance in data collection and processing. The authors thank Mihai Popescu, Ph.D., and E. Anda Popescu, Ph.D., at the University of Kansas Medical Center’s HBIC for their contribution and expertise in designing the MATLAB routines for HR and HRV analyses.
The results of the present study do not constitute endorsement by the American College of Sports Medicine.
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