Physical activity confers myriad benefits to the uncomplicated pregnancy,1 benefits that can have long-term health impacts for the developing fetus.2,3 Our understanding that intrauterine environments can program susceptibility to future disease has developed over the last 2 decades.4 This work has highlighted that in-utero exposures can influence the risk of cardiovascular disease (CVD),5 the leading cause of global morbidity6 and mortality.7 We recently reported that maternal physical activity is favorably associated with lower levels of maternal pregnancy triglycerides and a higher concentration of high-density lipoprotein cholesterol (HDL-c),8 established precursors of CVD.9 It is unknown if maternal physical activity confers similar benefits, that is a more favorable blood lipid profile, to the developing fetus. This is important to investigate, as cord blood lipid profiles track over time to early childhood10 (when they can begin to initiate and progress preclinical signs of CVD11), and subsequently to adulthood12 when the clinical manifestations of CVD arise.13 This study investigated associations of maternal physical activity with neonatal cord blood lipid levels.
Methods
Born in Bradford (BiB) is a prospective birth cohort study of 12,453 women who were recruited at 26- to 28-weeks gestation and who delivered 13,818 live births between 2007 and 2010. Full study details are provided elsewhere.14 In a pseudorandomly selected subgroup of BiB participants, cord blood lipid samples were collected.15 For the purposes of this complete case investigation, the subgroup was restricted to singleton pregnancies and women who were free from preexisting hypertension and diabetes before pregnancy. The final sample comprised 1634 mother–neonate pairs. Characteristics of the included subgroup were similar to those of all other BiB participants (Supplementary Table 1 [available online]), who were broadly representative of the obstetric population in Bradford at the time of recruitment.14 The BiB study was approved by the Bradford Research Ethics Committee (ref 07/H1302/112), and all mothers provided written informed consent.
Maternal physical activity was assessed at recruitment using the General Practice Physical Activity Questionnaire, which has been validated against accelerometry16 and exhibits face validity in the BiB cohort.8 Mothers were assigned to 1 of 4 activity levels (inactive/somewhat active/moderately active/active) based on their self-reported occupational physical activity level, physical exercise, and walking in the last week. The active category is consistent with meeting the recommended minimum of 150 min/wk of moderate-intensity physical activity.17
Cord blood samples were obtained at delivery by the attending midwife. Samples were refrigerated at 4°C in EDTA tubes until collected by laboratory staff within 12 hours. Samples were then spun, frozen, and stored at −80°C.15 Following transfer to the Biochemistry Department of Glasgow Royal Infirmary, enzymatic reagents were used to determine serum concentrations of total cholesterol, triglycerides, HDL-c, low-density lipoprotein cholesterol (LDL-c), and very low-density lipoprotein cholesterol (Cobas C311 autoanalyzer; Roche Diagnostics, Basel, Switzerland). Cord blood adiponectin was measured using commercially available ELISA kits (Quantikine human adiponectin immunoassay; R&D Systems, Minneapolis, MN).
Women consented to the abstraction and use of data from their obstetric medical records and at recruitment completed an interviewer-administered questionnaire. The questionnaire collated information regarding ethnicity, social and economic circumstances, smoking, alcohol, caffeine intake, and sleep. Interviews were conducted in a variety of languages. Maternal weight at ∼12-weeks gestation was combined with height to derive early pregnancy body mass index (in kilograms per meter squared). Gestational age at birth was calculated as the number of weeks elapsed between conception (based on ultrasound examination at ∼12-weeks) and delivery. Full details of covariables are available elsewhere.8
For description, participant characteristics were summarized by maternal pregnancy physical activity level, and Pearson correlation coefficients were calculated between maternal blood lipid levels (measured at recruitment8) and cord blood lipid concentrations. For the main analysis, linear regression models were used to calculate differences in cord blood lipid concentrations among the 4 groups of maternal physical activity (reference group: inactive); p values from trend tests across physical activity categories are also presented. Models were initially adjusted for maternal age, ethnicity, early pregnancy body mass index, socioeconomic status, parity, season of physical activity assessment, and neonate sex. Adjustments for maternal smoking in pregnancy, delivery mode, birth weight, and gestational age were subsequently added as they changed β coefficients between exposures and outcomes by ≥10%.18 All cord blood lipid distributions were skewed and were natural log transformed prior to analyses; the data have been back-transformed by exponentiation. Results are presented as marginal means with 95% confidence intervals. Analyses were performed in Stata/SE software (version 15.0; Statacorp, College Station, TX).
Results
Descriptive statistics for the cord blood lipid subgroup are presented in Table 1. More than half of women (60.4%) were inactive, one-fifth were somewhat active (18.2%), and fewer were classified as moderately active (12.0%) and active (9.4%), respectively. Inactive women were more frequently of Pakistani origin, multiparous, and were moderately or most deprived. Correlations between maternal and cord blood lipids were calculable for 1510 mother–neonate pairs and were consistently weak (total cholesterol, 0.08; HDL-c, 0.16; LDL-c, 0.06; triglycerides, 0.08).
Maternal and Neonatal Characteristics, Overall and Stratified by Pregnancy Physical Activity Level
| Overall (N = 1634) | Inactive (n = 987) | Somewhat active (n = 298) | Moderately active (n = 196) | Active (n = 153) | P difference | |
|---|---|---|---|---|---|---|
| Maternal age, y | 27.2 (5.5) | 27.1 (5.5) | 27.4 (5.7) | 27.3 (5.7) | 27.3 (5.3) | .84 |
| Ethnicity, n (%) | ||||||
| White British | 627 (38.4) | 280 (28.4) | 144 (48.3) | 109 (55.6) | 94 (61.4) | |
| Pakistani-origin | 779 (47.7) | 583 (59.1) | 101 (33.9) | 56 (28.6) | 39 (25.5) | |
| Other/mixed | 228 (13.9) | 124 (12.6) | 53 (17.8) | 31 (15.8) | 20 (13.1) | <.001 |
| Socioeconomic status, n (%) | ||||||
| Least deprived | 621 (38.0) | 274 (27.8) | 163 (54.7) | 101 (51.5) | 83 (54.3) | |
| Moderately deprived | 759 (46.5) | 522 (52.9) | 117 (39.3) | 66 (33.7) | 54 (35.3) | |
| Most deprived | 254 (15.5) | 191 (19.4) | 18 (6.1) | 29 (14.8) | 16 (10.5) | <.001 |
| Parity, n (%) | ||||||
| 0 | 603 (36.9) | 322 (32.6) | 134 (45.0) | 78 (39.8) | 69 (45.1) | |
| 1 | 489 (29.9) | 288 (29.2) | 93 (31.2) | 65 (33.2) | 43 (28.1) | |
| ≥2 | 542 (33.2) | 377 (38.2) | 71 (23.8) | 53 (27.0) | 41 (26.8) | <.001 |
| Early pregnancy body mass index, kg/m2 | 24.8 (7.0) | 24.7 (7.2) | 25.1 (6.6) | 25.0 (7.5) | 24.3 (6.1) | .59 |
| Smoked in pregnancy or 3 mo before, n (%) | ||||||
| No | 1353 (82.8) | 838 (84.9) | 244 (81.9) | 150 (76.5) | 121 (79.1) | |
| Yes | 281 (17.2) | 149 (15.1) | 54 (18.1) | 46 (23.5) | 32 (20.9) | .02* |
| Season of physical activity report, n (%) | ||||||
| Spring | 364 (22.3) | 226 (22.9) | 55 (18.5) | 41 (20.9) | 42 (27.5) | |
| Summer | 457 (23.0) | 256 (25.9) | 85 (28.5) | 74 (37.8) | 42 (27.5) | |
| Autumn | 412 (25.2) | 247 (25.0) | 79 (26.5) | 41 (20.9) | 45 (29.4) | |
| Winter | 401 (24.5) | 258 (26.1) | 79 (26.5) | 40 (20.4) | 24 (15.7) | .01 |
| Delivery mode, n (%) | ||||||
| Vaginal | 1258 (77.0) | 774 (78.4) | 228 (76.5) | 140 (71.4) | 116 (75.8) | |
| Caesarean | 376 (23.0) | 213 (21.6) | 70 (23.5) | 56 (28.6) | 37 (24.2) | .19 |
| Neonate sex, n (%) | ||||||
| Male | 824 (50.4) | 482 (48.8) | 153 (51.3) | 104 (53.1) | 85 (55.6) | |
| Female | 810 (49.6) | 505 (51.2) | 145 (48.7) | 92 (46.9) | 68 (44.4) | .35 |
| Gestational age, wk | 39.6 (2.4) | 39.5 (1.6) | 39.8 (1.4) | 39.5 (1.7) | 39.6 (1.6) | .12 |
| Birth weight, g | 3263 (523) | 3236 (514) | 3316 (516) | 3302 (588) | 3293 (498) | .06 |
Note: For continuous variables, values are mean (SD) except values for early pregnancy body mass index which are median (interquartile range) due to skewness. Differences between physical activity categories calculated by chi-square, analysis of variance, and Kruskal–Wallis tests as appropriate.
*Significant difference did not persist in a logistic regression analysis that included adjustment for ethnicity (P difference = .13).
Table 2 shows neonatal cord blood lipid and adiponectin levels stratified by maternal pregnancy physical activity. There was no strong evidence for effect modification by ethnic group (P ≥ .11), so the results are presented for the whole sample combined and adjusted for ethnicity. There was a significant trend across categories to indicate that higher physical activity was associated with higher cord blood total cholesterol; levels were significantly higher in neonates of women who were moderately active in pregnancy compared with neonates of women who were inactive. Analysis of individual components revealed that there was only a positive association of maternal physical activity with cord blood HDL-c; values were significantly higher in neonates of women who were somewhat active and moderately active, respectively, compared with neonates of women who were inactive. For neonates of active women, the confidence interval was consistent with higher cord blood HDL-c in comparison with neonates of inactive women, but the difference was not statistically significant, likely due to type II error caused by fewer observations. There was no evidence for associations of pregnancy physical activity with neonatal cord blood trigylycerides, LDL-c, very low-density lipoprotein cholesterol, or adiponectin concentrations.
Associations of Maternal Pregnancy Physical Activity With Neonatal Cord Blood Lipid Concentrations
| Number of participants (no. in each activity category) | Inactive | Somewhat active | Moderately active | Active | P trend | |
|---|---|---|---|---|---|---|
| Total cholesterol, mmol/L | 1634(987/298/196/153) | 1.63 (1.60–1.65) Ref. | 1.66 (1.62–1.71) .19 | 1.69 (1.64–1.75) .04 | 1.68 (1.62–1.75) .13 | .03 |
| Triglycerides, mmol/L | 1634(987/298/196/153) | 0.49 (0.48–0.50) Ref. | 0.48 (0.46–0.50) .21 | 0.50 (0.47–0.52) .76 | 0.49 (0.46–0.52) .99 | .26 |
| High-density lipoprotein cholesterol, mmol/L | 1634(987/298/196/153) | 0.61 (0.60–0.62) Ref. | 0.64 (0.62–0.67) .02 | 0.64 (0.61–0.67) .04 | 0.64 (0.61–0.67) .10 | .02 |
| Low-density lipoprotein cholesterol, mmol/L | 1634(987/298/196/153) | 0.74 (0.72–0.76) Ref. | 0.75 (0.72–0.79) .43 | 0.77 (0.73–0.81) .16 | 0.76 (0.72–0.80) .41 | .17 |
| Very low-density lipoprotein cholesterol, mmol/L | 1634(987/298/196/153) | 0.22 (0.22–0.23) Ref. | 0.22 (0.21–0.23) .24 | 0.23 (0.21–0.24) .73 | 0.22 (0.21–0.24) .96 | .92 |
| Adiponectin, µg/mL | 1634(987/298/196/153) | 29.6 (28.8–30.4) Ref. | 30.2 (28.7–31.7) .50 | 28.7 (27.0–30.5) .37 | 28.7 (26.8–30.8) .46 | .35 |
Note: Data are estimated marginal means (95% confidence interval) adjusted for maternal age, ethnicity, early pregnancy body mass index, socioeconomic status, parity, season of physical activity assessment, maternal smoking in pregnancy, neonate sex, delivery mode, gestational age, and birth weight. Beside estimates are P values. Bold font denotes significantly different values compared with the referent inactive group (P < .05) or across physical activity categories (P trend < .05). Adjusting for other maternal lifestyle factors (alcohol consumption, caffeine intake, sleep problems, and use of dietary supplements), measurement factors related to maternal physical activity (gestational age at the time of reporting, if women were feeling well and were able to enjoy their normal daily activities, whether or not maternal physical activity was reported during Ramadan), pregnancy complications (diagnosis of gestational diabetes and gestational hypertension), and neonate abdominal circumference did not appreciably influence associations and were not retained in models.
Discussion
This study found that maternal pregnancy physical activity was favorably associated with a higher concentration of neonatal cord blood HDL-c. The association was modest in scale, but may be underestimated due to errors in self-reported physical activity. It is also important to consider that any positive influence on cord blood HDL-c may be meaningful because cord blood lipid levels track over time10,12 and an adverse lipid profile in childhood can initiate preclinical signs of CVD.11 Furthermore, even in the absence of any other blood lipid abnormality, low HDL-c has been shown to elevate CVD risk in adulthood.19
We are aware of only 2 other studies that have investigated this topic. In a Canadian study of 442 mother–neonate pairs, there was no evidence for an association between self-reported physical activity with a latent parameter that represented cord blood HDL-c, apolipoprotein A1, and LDL-c.20 Similarly, no associations with traditional blood lipids were found in 51 women from Austria who underwent an assessment of physical activity by accelerometry at 10- to 14-weeks gestation. However, in that study, unadjusted analyses did show that cord blood exhibited a more favorable composition of HDL-c (lower oxidized HDL-c and higher apolipoprotein A1) in neonates of women who met the recommended level of physical activity compared with those who did not.21 The current study is the first to provide evidence of an independent association between pregnancy physical activity with higher cord blood HDL-c. Importantly, compared with neonates of women who were inactive, cord blood HDL-c levels were higher even in neonates of women who were merely somewhat active in pregnancy. Hence, even small volumes of physical activity well below the recommended minimum (150 min/wk of moderate-intensity physical activity) were beneficial. This supports current UK guidelines that “every activity counts” and that inactive pregnant women should gradually accumulate physical activity throughout the week.17
Safety concerns are often cited by pregnant women as a barrier to physical activity.22 This may partly explain why fewer than 10% of our study participants were active. Reassuringly, the results of this study, coupled with previous observations made in the same cohort,8 add to growing evidence that pregnancy physical activity is not only safe but is beneficial for the short- and long-term health prospects of both mother and child. Women should be encouraged to be physically active while pregnant and reassured that evidence suggests that it is safe. A recent systematic review concluded that multicomponent interventions can successfully increase pregnancy physical activity levels, with the most promising strategies including group exercise classes, information provision about recommended levels of physical activity and suitable exercises, and guidance about how to overcome perceived barriers including the management of various pregnancy-related symptoms.23 This information should also be disseminated to health care professionals who are well placed to advocate physical activity but who may lack the confidence, knowledge, and resources to deliver appropriate and safe advice.24 The results of this study further highlight that Pakistani-origin women and women from deprived backgrounds are the most inactive in pregnancy, and thus, they may be considered priority recipients of efforts to increase physical activity. Targeting these women (who are also more susceptible to pregnancy complications25) could help to reduce health inequalities by reducing the risk of adverse pregnancy outcomes and their long-term sequelae in high-risk groups.
In line with observations made at birth,26 we found that maternal blood lipids were weakly correlated with neonatal cord blood lipids. This is reassuring, as it highlights that cord blood lipids represent neonate cardiovascular status (likely as a consequence of fetal and placental influences on cord blood biochemistry) as opposed to merely reflecting maternal lipids. It is a limitation of this study, nevertheless, that information for several covariables was self-reported and that the analyses were not adjusted for maternal dietary factors. Future studies should investigate longer term influences of maternal pregnancy physical activity on offspring cardiovascular health.
Conclusion
Maternal physical activity is beneficially associated with neonatal cord blood HDL-c levels. This novel finding highlights the potential for promoting physical activity in pregnancy to aid the early prevention of CVD.
Acknowledgments
Born in Bradford (BiB) is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, health professionals, and researchers who have made BiB happen. The BiB study receives core infrastructure funding from the
References
- 1.↑
Dipietro L, Evenson KR, Bloodgood B, et al; 2018 Physical Activity Guidelines Advisory Committee. Benefits of physical activity during pregnancy and postpartum. Med Sci Sports Exerc. 2019;51(6):1292–1302. doi:10.1249/MSS.0000000000001941
- 2.↑
Damm P, Houshmand-Oeregaard A, Kelstrup L, Lauenborg J, Mathiesen ER, Clausen TD. Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia. 2016;59(7):1396–1399. PubMed ID: 27174368 doi:10.1007/s00125-016-3985-5
- 3.↑
Catalano PM, Shankar K. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ. 2017;356:j1. PubMed ID: 28179267 doi:10.1136/bmj.j1
- 4.↑
Barker DJP. The origins of the developmental origins theory. J Intern Med. 2007;261(5):412–417. PubMed ID: 17444880 doi:10.1111/j.1365-2796.2007.01809.x
- 5.↑
Yeung EH, Robledo C, Boghossian N, Zhang C, Mendola P. Developmental origins of cardiovascular disease. Curr Epidemiol Rep. 2014;1(1):9–16. PubMed ID: 25364653 doi:10.1007/s40471-014-0006-4
- 6.↑
World Health Organization. Global Health Estimates 2016: Disease Burden by Cause, Age, Sex, by Country and by Region, 2000–2016. Geneva, Switzerland: World Health Organization; 2018.
- 7.↑
World Health Organization. Global Health Estimates 2016: Deaths by Cause, Age, Sex, by Country and by Region, 2000–2016. Geneva, Switzerland: World Health Organization; 2018.
- 8.↑
Collings PJ, Farrar D, Gibson J, West J, Barber SE, Wright J. Associations of pregnancy physical activity with maternal cardiometabolic health, neonatal delivery outcomes and body composition in a biethnic cohort of 7305 mother–child pairs: the Born in Bradford study [published online ahead of print September 26, 2019]. Sports Med. doi:10.1007/s40279-019-01193-8
- 9.↑
Yusuf PS, Hawken S, ⓞunpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937–952. PubMed ID: 15364185 doi:10.1016/S0140-6736(04)17018-9
- 10.↑
Bastida S, Sánchez-Muniz FJ, Cuena R, Perea S, Aragonés A. High density lipoprotein-cholesterol changes in children with high cholesterol levels at birth. Eur J Pediatr. 2002;161(2):94–98. PubMed ID: 11954759 doi:10.1007/s00431-001-0863-y
- 11.↑
Pires A, Sena C, Seiça R. Dyslipidemia and cardiovascular changes in children. Curr Opin Cardiol. 2016;31(1):95–100. PubMed ID: 26599060 doi:10.1097/HCO.0000000000000249
- 12.↑
Juhola J, Magnussen CG, Viikari JSA, et al. Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the cardiovascular risk in young Finns study. J Pediatr. 2011;159(4):584–590. PubMed ID: 21514597 doi:10.1016/j.jpeds.2011.03.021
- 13.↑
Orozco-Beltran D, Gil-Guillen VF, Redon J, et al. Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study. PLoS One. 2017;12(10):e0186196. doi:10.1371/journal.pone.0186196
- 14.↑
Wright J, Small N, Raynor P, et al. Cohort profile: the born in bradford multi-ethnic family cohort study. Int J Epidemiol. 2013;42(4):978–991. PubMed ID: 23064411 doi:10.1093/ije/dys112
- 15.↑
Lawlor DA, West J, Fairley L, et al. Pregnancy glycaemia and cord-blood levels of insulin and leptin in Pakistani and white British mother-offspring pairs: findings from a prospective pregnancy cohort. Diabetologia. 2014;57(12):2492–2500. PubMed ID: 25273345 doi:10.1007/s00125-014-3386-6
- 16.↑
National Health Service. The General Practice Physical Activity Questionnaire (GPPAQ)—A screening tool to assess adult physical activity levels, within primary care. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/192453/GPPAQ_-_guidance.pdf. Published 2009.Accessed December 12, 2017.
- 17.↑
Department of Health and Social Care. UK Chief Medical Officers’ physical activity guidelines. 2019. https://www.gov.uk/government/publications/physical-activity-guidelines-uk-chief-medical-officers-report
- 18.↑
Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol. 1993;138(11):923–936. PubMed ID: 8256780 doi:10.1093/oxfordjournals.aje.a116813
- 19.↑
Huxley RR, Barzi F, Lam TH, et al. Isolated low levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease: an individual participant data meta-analysis of 23 studies in the asia-pacific region. Circulation. 2011;124(19):2056–2064. PubMed ID: 21986289 doi:10.1161/CIRCULATIONAHA.111.028373
- 20.↑
Morrison KM, Anand SS, Yusuf S, et al. Maternal and pregnancy related predictors of cardiometabolic traits in newborns. PLoS One. 2013;8(2):e55815. PubMed ID: 23418462 doi:10.1371/journal.pone.0055815
- 21.↑
Tatrai K. The effect of physical activity in pregnancy on the lipid profiles of mother and newborn, including HDL proteome. Geburtshilfe Frauenheilkd. 2014;74(S 01). doi:10.1055/s-0034-1388227
- 22.↑
Coll CVN, Domingues MR, Gonçalves H, Bertoldi AD. Perceived barriers to leisure-time physical activity during pregnancy: a literature review of quantitative and qualitative evidence. J Sci Med Sport. 2017;20(1):17–25. PubMed ID: 27372276 doi:10.1016/j.jsams.2016.06.007
- 23.↑
Chan CWH, Au Yeung E, Law BMH. Effectiveness of physical activity interventions on pregnancy-related outcomes among pregnant women: a systematic review. Int J Environ Res Public Health. 2019;16(10):1840. doi:10.3390/ijerph16101840
- 24.↑
Smith R, Reid H, Matthews A, Calderwood C, Knight M, Foster C. Infographic: physical activity for pregnant women. Br J Sports Med. 2018;52(5):532–533. doi:10.1136/bjsports-2017-098037
- 25.↑
Jenum AK, Mrøkrid K, Sletner L, et al. Impact of ethnicity on gestational diabetes identified with the WHO and the modified International Association of Diabetes and Pregnancy Study Groups criteria: a population-based cohort study. Eur J Endocrinol. 2012;166(2):317–324. PubMed ID: 22108914 doi:10.1530/EJE-11-0866
- 26.↑
Ghiasi A, Ziaei S, Faghihzadeh S. The relationship between levels of lipids and lipoprotein B-100 in maternal serum and umbilical cord serum and assessing their effects on newborn infants anthropometric indices. J Midwifery Reprod Health. 2014;2(4):227–232. doi:10.22038/JMRH.2014.3239
