The relation between fetal growth retardation and cardiovascular and metabolic diseases in later life has been demonstrated in many studies. However, debate exists around the potential independent role of postnatal growth acceleration. Furthermore, it is unknown whether a potential effect of growth acceleration on cardiovascular and metabolic function is confined to certain timeframes.

Objective Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child. Methods Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12–20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80th percentiles). Indicators of cardiac ANS in the offspring at age 5–6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions. Results 2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p≥0.17). Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p≥0.07). Conclusion Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac ANS balance in the offspring, at least in rest, and at the age of five-six years.

Adverse intrauterine conditions can program hypertension. Because one of the underlying mechanisms is thought to be cardiac autonomic balance, we investigated the association between prepregnancy body mass index (BMI) and blood pressure and indicators of the autonomic balance in the child at age 5 to 6 years. Also investigated was whether these associations were mediated by standardized birth weight and child BMI. Pregnant women (n=3074) participating in the Amsterdam Born Children and their Development study completed a questionnaire at gestational week 14. At age 5 to 6 years, offspring’s sympathetic drive (pre-ejection period), parasympathetic drive (respiratory sinus arrhythmia), and heart rate were measured by electrocardiography and impedance cardiography at rest. Blood pressure was assessed simultaneously. After adjusting for possible maternal/offspring confounders, prepregnancy BMI was positively linearly associated with diastolic blood pressure (β=0.11 mm Hg; 95% confidence interval, 0.05–0.17), systolic blood pressure (β=0.14 mm Hg; 95% confidence interval, 0.07–0.21), but not with heart rate, sympathetic or parasympathetic drive. After adding birth weight and child BMI to the model, the independent effect size of prepregnancy body mass index on systolic blood pressure (β=0.07 mm Hg; 95% confidence interval, 0.00–0.14) and diastolic blood pressure (β=0.07 mm Hg; 95% confidence interval, 0.01–0.13) decreased by ≈50%. Birth weight did not mediate these relationships, but was independently and negatively associated with blood pressure. Child BMI was positively associated with blood pressure and partly mediated the association between prepregnancy BMI and blood pressure. In conclusion, higher prepregnancy BMI is associated with higher blood pressure in the child (aged 5–6 years) but does not seem to be attributable to early alterations in resting cardiac autonomic balance. Child BMI, but not birth weight, mediated the association between prepregnancy BMI and blood pressure.

The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ’s response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device 1-5, the VU University Ambulatory Monitoring System (VU-AMS, Amsterdam, the Netherlands, www.vu-ams.nl).

Background In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5–6 years. Methods Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5–6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed. Results In analysis adjusted for child’s physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001). Conclusions This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5–6 years.

Objective Early life stress has been shown to influence the developing autonomic nervous system. Stressors in infancy may program the autonomic nervous system resting state set point, affecting cardiovascular function in later life. Excessive crying may be an indicator of increased stress arousal in infancy. We hypothesized that excessive infant crying is related to altered cardiac autonomic nervous system activity and increased blood pressure at age 5–6 years. Methods In the Amsterdam Born Children and their Development study, excessive crying, maternal burden of infant care and maternal aggressive behavior in the 13th week after birth (range 11–16 weeks) were reported using questionnaires. Blood pressure, heart rate, heart rate variability and indicators of cardiac autonomic nervous system activity (sympathetic drive by pre-ejection period, parasympathetic drive by respiratory sinus arrhythmia) were measured at age 5–6 years during rest. Inclusion criteria were singleton birth, term-born, and no reported congenital or cardiovascular problems (N = 2153 included). Results Excessive crying (2.8%) was not associated with resting heart rate, heart rate variability, pre-ejection period, respiratory sinus arrhythmia nor with blood pressure at age 5–6 years. Conclusions Excessive infant crying as an indicator of increased stress arousal does not seem to be related to resting activity of the autonomic nervous system or blood pressure at age 5–6. Potential associations may become visible under stressed conditions.