A systematic review to investigate whether birth weight affects the autonomic nervous system in adulthood

Vidigal, Giovanna de Paula; Gonzaga, Luana Almeida; Porto, Andrey Alves; Garner, David Matthew; Cardoso, Vinicius Ferreira; Valenti, Vitor Engrácia

doi:10.1590/1984-0462/2024/42/2023002

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Revista Paulista de Pediatria

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Review Article • Rev. paul. pediatr. 42 • 2024 • https://doi.org/10.1590/1984-0462/2024/42/2023002 copy

A systematic review to investigate whether birth weight affects the autonomic nervous system in adulthood

Uma revisão sistemática para investigar se o peso ao nascer afeta o sistema nervoso autônomo na vida adulta

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To evaluate the relationship between birth weight and the autonomic nervous system in adulthood through a systematic review.

Data source:

This is a systematic review of publications without limitation of year and language. We included studies involving the autonomic nervous system and birth weight in adults. Manuscripts were selected based on electronic searches of Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science Cochrane Library and Scopus databases, using “Autonomic Nervous System” OR “Heart Rate” OR “Heart Rate Variability” AND “Birth Weight” as a search strategy. This review is registered on the International Prospective Register of Systematic Reviews — PROSPERO (ID: CRD42020165622).

Data synthesis:

We found 894 articles; 215 were excluded for duplicity. Of the remaining 679 studies, 11 remained. Two were excluded because they did not specifically treat the autonomic nervous system or birth weight. There were nine publications, two cohort and seven cross-sectional studies. The main findings were that extreme, very low, low or high birth weight may have some impact on the autonomic nervous system in adult life.

Conclusions:

Birth weight outside the normality rate may have a negative influence on the autonomic nervous system, causing autonomic dysfunction and increasing the risk of cardiovascular diseases in adult life. Thus, the importance of the follow-up of health professionals from pregnancy to gestation and throughout life, with preventive care being emphasized.

Keywords:
Autonomic nervous system; Birth weight; Cardiovascular diseases; Cardiovascular system; Heart rate

Author	Follow up	Final sample	Main conclusions
Phillips & Barker¹⁸18 Phillips DI, Barker DJ. Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome? Diabet Med. 1997;14:673-7. https://doi.org/10.1002/(SICI)1096-9136(199708)14:8<673::AID-DIA458>3.0.CO;2-9 https://doi.org/10.1002/(SICI)1096-9136(...	No	449 subjects LBW and NBW 46-54 years and healthy	Raised blood pressure and insulin resistance may partly result from a primary increase in SNS activity that is initiated in utero and persists into adult life.
Weitz et al.²⁰20 Weitz G, Deckert P, Heindl S, Struck J, Perras B, Dodt C. Evidence for lower sympathetic nerve activity in young adults with low birth weight. J Hypertens. 2003;21:943-50. https://doi.org/10.1097/00004872-200305000-00019 https://doi.org/10.1097/00004872-2003050...	No	26 subjects LBW and NBW 20-30 years and healthy	Findings do not suggest that changes in sympathetic outflow to the muscle vascular bed are responsible for the increased prevalence of hypertension in this group of subjects.
Ward et al.¹⁶16 Ward AM, Moore VM, Steptoe A, Cockington RA, Robinson JS, Phillips DI. Size at birth and cardiovascular responses to psychological stressors: evidence for prenatal programming in women. J Hypertens. 2004;22:2295-301. https://doi.org/10.1097/00004872-200412000-00011 https://doi.org/10.1097/00004872-2004120...	No	179 subjects LBW, NBW, HBW ~30 years	Cardiovascular responses to psychological stressors may be programmed antenatally and suggest a potential mechanism linking reduced fetal growth with raised blood pressure and cardiovascular disease in adulthood.
Jones et al.¹⁵15 Jones A, Beda A, Ward AM, Osmond C, Phillips DI, Moore VM, et al. Size at birth and autonomic function during psychological stress. Hypertension. 2007;49:548-55. https://doi.org/10.1161/01.HYP.0000257196.13485.9b https://doi.org/10.1161/01.HYP.000025719...	No	179 subjects LBW and NBW ~26 years	The study suggests that women and girls who were small at birth have greater sympathoadrenal activity than their higher birth weight peers, whereas men and boys who were small at birth have an enhanced adrenocortical response to stress, although this needs confirmation.
Mathewson et al.¹⁴14 Mathewson KJ, Van Lieshout RJ, Saigal S, Boyle MH, Schmidt LA. Reduced respiratory sinus arrhythmia in adults born at extremely low birth weight: evidence of premature parasympathetic decline? Int J Psychophysiol. 2014;93:198-203. https://doi.org/10.1016/j.ijpsycho.2014.04.005 https://doi.org/10.1016/j.ijpsycho.2014....	Yes. 35 years	77 subjects ELBW and NBW 22-35 years	RSA may also be less stable over time in some ELBW survivors than is generally the case for NBW controls, suggesting a decrement in parasympathetic regulatory control that may warrant closer monitoring as ELBW survivors age.
Perkiömäki et al.¹⁷17 Perkiömäki N, Auvinen J, Tulppo MP, Hautala AJ, Perkiömäki J, Karhunen V, et al. Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life. PLoS One. 2016;11:e0161604. https://doi.org/10.1371/journal.pone.0161604 https://doi.org/10.1371/journal.pone.016...	No	4078 subjects LBW, NBW, HBW 46 years and healthy	The findings suggest that greater, not depressed, prenatal growth may contribute to poorer cardiovascular autonomic regulation and the related cardiac risk in later life in men.
Bao et al.¹⁹19 Bao S, Kanno E, Maruyama R. Blunted autonomic responses and low-grade inflammation in mongolian adults born at low birth weight. Tohoku J Exp Med. 2016;240:171-9. https://doi.org/10.1620/tjem.240.171 https://doi.org/10.1620/tjem.240.171...	No	21 subjects LBW, NBW, HBW 23-24 years and healthy	The study suggests that LBW relates to increased low-grade inflammation and blunted autonomic function in healthy young Mongolian adults, and these might be preliminary steps of hypertension development in LBW individuals.
O'Hare et al.¹³13 O'Hare C, Kuh D, Hardy R. Association of early-life factors with life-course trajectories of resting heart rate: more than 6 decades of follow-up. JAMA Pediatr. 2018;172:e175525. https://doi.org/10.1001/jamapediatrics.2017.5525 https://doi.org/10.1001/jamapediatrics.2...	Yes. 6 decades	4799 subjects LBW and NBW 6 up to 69 years	Higher birth weight and conditional BMI change were associated with lower RHR at age 6 and across the life course.
Haraldsdottir et al.²¹21 Haraldsdottir K, Watson AM, Beshish AG, Pegelow DF, Palta M, Tetri LH, et al. Heart rate recovery after maximal exercise is impaired in healthy young adults born preterm. Eur J Appl Physiol. 2019;119:857-66. https://doi.org/10.1007/s00421-019-04075-z https://doi.org/10.1007/s00421-019-04075...	No	28 subjects VLBW and NBW ~26-29 years	The study demonstrates that HRR is significantly slower in healthy young adults born preterm compared to age-matched, term-born controls.

Author	Collected data	Protocol	Conclusion (Outcome)	Score
Phillips & Barker¹⁸18 Phillips DI, Barker DJ. Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome? Diabet Med. 1997;14:673-7. https://doi.org/10.1002/(SICI)1096-9136(199708)14:8<673::AID-DIA458>3.0.CO;2-9 https://doi.org/10.1002/(SICI)1096-9136(...	Birth data; Anthropometric measurements; Blood collection and oral glucose tolerance test.	BP and HR measurements after 5 minutes of rest; interview about family history and quality of life; BP and HR measurements.	In addition to increased HR, increased BP and insulin resistance during adulthood with LBW may occur due to increased intrauterine SNS activity; risk of CVD.	Good
Weitz et al.²⁰20 Weitz G, Deckert P, Heindl S, Struck J, Perras B, Dodt C. Evidence for lower sympathetic nerve activity in young adults with low birth weight. J Hypertens. 2003;21:943-50. https://doi.org/10.1097/00004872-200305000-00019 https://doi.org/10.1097/00004872-2003050...	Physical activity evaluation, laboratory screening, blood collection, anthropometric measurements, and 24-hour ambulatory BP measurement; electromyography of the superficial peroneal nerve; BP measurements, HR monitoring and respiratory.	Rest for 10 minutes with oscillometric BP measurement; performing maximum length inspiratory apnea; 10-minute recovery.	Low sympathetic activity in muscle vascular bed at basal conditions may be considered a primary biological marker in LBW; changes in sympathetic flow in muscular vascular bed are not responsible for the increase.	Good
Ward et al.¹⁶16 Ward AM, Moore VM, Steptoe A, Cockington RA, Robinson JS, Phillips DI. Size at birth and cardiovascular responses to psychological stressors: evidence for prenatal programming in women. J Hypertens. 2004;22:2295-301. https://doi.org/10.1097/00004872-200412000-00011 https://doi.org/10.1097/00004872-2004120...	Birth information; anthropometric measurements; health status and habits, and socioeconomic status; continuous monitoring of HR and BP.	Initial rest; three psychological tests, interspersed with a six-minute rest: I) color-word conflict task, II) mirror-tracing task, III) speech task.	Association between cardiovascular reactivity, psychological stressors and sizes at birth, leading to the hypothesis that these responses may be programmed in the prenatal period; increased BP and risk of CVD in adulthood.	Good
Jones et al.¹⁵15 Jones A, Beda A, Ward AM, Osmond C, Phillips DI, Moore VM, et al. Size at birth and autonomic function during psychological stress. Hypertension. 2007;49:548-55. https://doi.org/10.1161/01.HYP.0000257196.13485.9b https://doi.org/10.1161/01.HYP.000025719...	Birth information; information on state and current health habits and socioeconomic status; continuous BP and HR measurements; collection of saliva.	Initial rest of 20 minutes; three psychological tests, interspersed with a six-minute rest: I) stroop word-color conflict task, II) mirror-tracing task, III) speech task.	Impaired fetal growth, autonomic cardiovascular control and baroreflex function are related, and may be sex-dependent; possibility of SAH and later diseases.	Poor

Author	Collected data	Protocol	Conclusion (Outcome)	Score
Mathewson et al.¹⁴14 Mathewson KJ, Van Lieshout RJ, Saigal S, Boyle MH, Schmidt LA. Reduced respiratory sinus arrhythmia in adults born at extremely low birth weight: evidence of premature parasympathetic decline? Int J Psychophysiol. 2014;93:198-203. https://doi.org/10.1016/j.ijpsycho.2014.04.005 https://doi.org/10.1016/j.ijpsycho.2014....	EEG and ECG and ASR records at 22–26 years and 30–35 years.	ECG: Continuous recording for 2 minutes at rest in the sitting position; 30-35 years: continuous registration for 6 minutes; ASR registration for 5 minutes.	Altered parasympathetic regulation in adults with ELBW, which can early identify the risk of CVD.	Good
Perkiömäki et al.¹⁷17 Perkiömäki N, Auvinen J, Tulppo MP, Hautala AJ, Perkiömäki J, Karhunen V, et al. Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life. PLoS One. 2016;11:e0161604. https://doi.org/10.1371/journal.pone.0161604 https://doi.org/10.1371/journal.pone.016...	Health and lifestyle status questionnaires; examination of blood collection, the oral glucose tolerance test, BP, HR, RF, BRS.	3 minutes in sitting position; 3 minutes standing, with spontaneous breathing.	Higher prenatal growth may contribute to cardiovascular risk in middle-aged men; in women, of course.	Good
Bao et al.¹⁹19 Bao S, Kanno E, Maruyama R. Blunted autonomic responses and low-grade inflammation in mongolian adults born at low birth weight. Tohoku J Exp Med. 2016;240:171-9. https://doi.org/10.1620/tjem.240.171 https://doi.org/10.1620/tjem.240.171...	Questionnaire on BW, anthropometric data, quality of life, family history, blood collection; BP and HR measurements in lying, sitting and immediately after sitting positions.	15 minutes in supine position; Postural change; 15 minutes in sitting position	Increased low-grade inflammation and reduced autonomic function in LBW in adult Mongolians; May be determinant for development of SAH.	Good
O'Hare et al.¹³13 O'Hare C, Kuh D, Hardy R. Association of early-life factors with life-course trajectories of resting heart rate: more than 6 decades of follow-up. JAMA Pediatr. 2018;172:e175525. https://doi.org/10.1001/jamapediatrics.2017.5525 https://doi.org/10.1001/jamapediatrics.2...	Social, anthropometric and developmental records at birth and throughout life; resting HR and anthropometric measurements throughout life (for six decades). Maximal power, exhaustion time, maximum aerobic capacity, VO₂max test.	HR measurement at rest in sitting position.	Critically high resting CF and increased middle age are not associated with CVD risk; Early life is essential in determining the course of resting HR until adulthood.	Fair
Haraldsdottir et al.²¹21 Haraldsdottir K, Watson AM, Beshish AG, Pegelow DF, Palta M, Tetri LH, et al. Heart rate recovery after maximal exercise is impaired in healthy young adults born preterm. Eur J Appl Physiol. 2019;119:857-66. https://doi.org/10.1007/s00421-019-04075-z https://doi.org/10.1007/s00421-019-04075...	Weight and height; Global Physical Activity Questionnaire; breath-to-breath; HR and ventilatory and metabolic parameters; maximal power, exhaustion time, maximum aerobic capacity, VO₂max test, ventilatory threshold; HR recovery.	Two progressive exercise tests on vertical cycle ergometer: I) breathing normal air and II) breathing hypoxic air. Normal protocol until they are no longer able to maintain 55 rpm for more than 5s; rest of 45 minutes; inhalation of hypoxic gas; hypoxic protocol until maximum exhaustion.	Significantly slower HR recovery in healthy preterm young adults; lower aerobic fitness in these individuals; increased cardiovascular risk and mortality.	Good

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[1] Corresponding author. E-mail: vitor.valenti@unesp.br