Heart rate variability in response to the sleep-related movements in infants with and without colic

The activity of the autonomic nervous system depends on sleep stage. The imbalance of the autonomic nervous system together with over-reactivity to stimuli has been suggested to be an etiologic factor for infantile colic. This study was designed to estimate the reactivity of the autonomic nervous system to a sleep-time stimulus in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages and in colic and control infants. Overnight sleep polygraphic recordings were performed for 12 colic and 14 control infants at the age of 8 weeks. Movements were detected by a static-charge-sensitive bed. Extent of heart rate variability (HRV) was measured in response to spontaneous sleep-related movements. HRV analysis was performed over 2-min segments during NREM and REM sleep before and after 5-36-s long movement periods. Total (0.04-1.0 Hz), low (0.04-0.15 Hz) and high frequency (0.15-1.0 Hz) HRV increased after the movement periods in light NREM sleep (p < 0.001). These changes were not observed in REM sleep. No differences were found between the colic and the control groups in HRV. The observed difference in the response of the HRV between sleep stages is likely to reflect the different characteristics of heart rate control in NREM and REM sleep, but our results do not suggest that colic infants would have abnormal autonomic reactivity to stimuli while asleep.     

Longitudinal assessment of heart rate variability in very low birth weight infants during their NICU stay

BACKGROUND: Maturation of the autonomic nervous system has not been studied in high-risk very low birth weight (VLBW) infants in the first few weeks of life. AIM: To characterize developmental changes in autonomic nervous system activity of high-risk VLBW infants from 23 to 38 weeks post-menstrual age by measuring heart rate variability (HRV). STUDY DESIGN AND SUBJECTS: In this prospective cohort study 38 infants admitted to Children's Memorial Hermann Hospital NICU were longitudinally followed weekly or biweekly. Heart period data were recorded while infants were resting in active sleep. OUTCOME MEASURES: Growth of spectral power of HRV in low-frequency (0.05-0.25 Hz) and high-frequency (0.25-1.00 Hz) bands was modeled with linear mixed-effects models. The high-frequency power provides a measure of respiratory sinus arrhythmia (RSA). RESULTS: Low-frequency power increases with post-menstrual age, and intubated infants have lower HRV. The increase in low-frequency power is faster (0.50+/-0.12 dB/week) than the increase in RSA (0.17+/-0.09 dB/week). CONCLUSION: This longitudinal data exhibits developmental maturation of the RSA and of the low-frequency power of HRV in high-risk VLBW infants.     

Pacifier use modifies infant's cardiac autonomic controls during sleep

OBJECTIVE: The risk for sudden infant death (SIDS) was postulated to decrease with the use of a pacifier and by conditions increasing parasympathetic tonus during sleep. We evaluated the influence of a pacifier on cardiac autonomic controls in healthy infants. STUDY DESIGN: Thirty-four healthy infants were studied polygraphically during one night: 17 infants regularly used a pacifier during sleep and 17 never used a pacifier. Thumb users or occasional pacifier users were not included in the study. The infants were recorded at a median age of 10 weeks (range 6-18 weeks). Autonomic nervous system (ANS) was evaluated by spectral analysis of the heart rate (HR). The high frequency component of HR spectral analysis reflected parasympathetic tonus and the low frequency on high frequency ratio corresponded to the sympathovagal balance. RESULTS: Most infants (63.6%) lost their pacifier within 30 min of falling asleep. Sucking periods were associated with increases in cardiac sympathovagal balance. During non-sucking periods, in both REM and NREM sleep, infants using a pacifier were characterized by lower sympathetic activity and higher parasympathetic tonus compared with non-pacifier users. CONCLUSIONS: The use of pacifiers modifies cardiac autonomic controls during both sucking and non-sucking sleep periods. Non-nutritive sucking could regulate autonomic control in infants. These findings could be relevant to mechanisms implicated in the occurrence of sudden infant deaths during sleep.     

Heart rate variability analysis in full-term infants: spectral indices for study of neonatal cardiorespiratory control

The heart rate and respirations of twenty healthy full-term infants between 30 and 60 h postnatal age were studied during quiet sleep with the objective of defining spectral indices which represent normal neonatal heart rate variability (HRV) characteristics. Total HRV power and the distribution of power across different frequency bands varied considerably among infants. Cluster analysis on the measured variables indicated that the population divided into two groups that represented significantly different patterns of HRV behavior. In one group (11 subjects), infants had lower breathing rates and HRV power in a band about the respiration frequency [respiratory sinus arrhythmia (RSA) band] was more than 20% of the total power (TP). Additionally, the ratio of low frequency band power to RSA band power was less than 4. The other group of neonates (nine subjects) had relatively higher breathing rates, RSA power less than 20% of total power, and low frequency to RSA power ratio greater than 4. Regression analysis of low frequency versus TP and RSA versus TP graphs gave strong support to the hypothesis that there were indeed two distinct patterns of HRV behavior. Separation of apparently normal neonates into two groups may be attributed partially to differences in respiratory rates and breathing patterns. However, it is possible that differences in the balance between sympathetic and parasympathetic nervous system control, perhaps related to autonomic maturation, also contribute to group separation. The indices developed from HRV spectral analysis in this investigation may be of value in the study of cardiorespiratory control in neonates.     

Ghrelin and motilin concentration in colicky infants

Aim: To evaluate serum ghrelin and motilin concentration in infants with infantile colic. Methods: A case-control study was conducted on fasting blood venous samples obtained from 18 infants with infantile colic and 20 healthy infants to measure ghrelin (RIA test) and motilin (RIA test). Results: Colicky infants showed higher ghrelin serum levels (2534.2±600.0 pg/ml; ln 7.8±0.2) than controls (2126.1±281.3 pg/ml; ln 7.6±0.1) (p = 0.011). Serum motilin concentration was significantly higher in colicky infants (94.6±23.2 pmol/l) than in controls (64.1±30.1 pmol/l) (p=0.001). Motilin concentrations were higher in formula-fed colicky infants (104.5±20.4 pmol/l) than in breastfed ones (82.2±21.3 pmol/l) (p = 0.038).

Conclusion: Our finding shows that ghrelin and motilin concentrations are higher in infants with colic than in controls, supporting an organicistic aetiopathogenesis of this disorder. Furthermore, the role of ghrelin on gastrointestinal motility may open new doors to better understand the aetiology of infantile colic.     

The development of autonomic cardiovascular control is altered by preterm birth

Objectives

Autonomic dysfunction, either sympathetic or parasympathetic, may explain the increased incidence of Sudden Infant Death Syndrome (SIDS) among preterm infants, as well as their subsequent heightened risk of hypertension in adulthood. As little is known about the development of autonomic function in preterm infants, we contrasted autonomic cardiovascular control across the first 6 months after term-corrected age (CA) in preterm and term infants.

Study design

Preterm (n = 25) and age matched term infants (n = 31) were studied at 2–4 weeks, 2–3 months and 5–6 months CA using daytime polysomnography. Blood pressure and heart rate were measured during quiet (QS) and active (AS) sleep. Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic + parasympathetic activity), high frequency (HF, respiratory-mediated changes + parasympathetic activity), and LF/HF ratio (sympatho-vagal balance).

Results

In preterm infants, HF HRV increased, LF/HF HRV decreased and LF BPV decreased with age (p < 0.05); these changes were most evident in AS. Compared to term infants, preterm infants in QS exhibited lower LF, HF and total HRV at 5–6 months; higher HF BPV at all ages; and lower LF BPV at 2–4 weeks (p < 0.05).

Conclusions

With maturation, in preterm infants, parasympathetic modulation of the heart increases while sympathetic modulation of blood pressure decreases. Compared to term infants, preterm infants exhibit lesser parasympathetic modulation of the heart along with greater respiratory-mediated changes and lower sympathetic modulation of blood pressure. Impaired autonomic control in preterm infants may increase their risk of cardiovascular dysfunction later in life.     

Motilin, vasoactive intestinal peptide and gastrin in infantile colic

Intestinal hyperperistalsis is one part of the clinical picture in infantile colic. Three gut hormones involved in the regulation of gut motility; motilin, vasoactive intestinal peptide (VIP) and gastrin, were measured with the RIA method in: 40 infants with infantile colic, (age 2-22 weeks), 42 healthy age-matched infants, 11 children (age 3-36 months) with gastrointestinal disorders, and 20 children (age 3-36 months) with non-gastrointestinal disorder. Basal s-motilin levels were raised in infants with infantile colic (p less than 0.01) and in children with other gastrointestinal disorders (p less than 0.001). Formula-fed infants had higher basal s-motilin levels than the breast-fed infants (p less than 0.05). P-VIP and s-gastrin levels were raised in children with other gastro-intestinal disorders (p less than 0.05), but not in infantile colic. Formula-fed colicky infants had higher s-gastrin levels than the breast-fed colicky infants (p less than 0.05). We suggest that the increased s-motilin level in infantile colic might account in part for the clinical picture of this disorder.     

Colicky infants according to maternal reports in telephone interviews and diaries: a large Scandinavian study

In this population-based study the colic incidence was 9.4%, according to telephone interviews with the parents made when the infants were 5 weeks of age (n = 1628), and parental concern about infant crying was common. However, 7-day diaries of colicky and control infants (n = 116 + 119) revealed low distress amounts in colicky infants in general. In the subgroup of Wessel-colicky infants (n = 37), distress episodes were frequent and long lasting, and there was a high proportion of colicky crying versus fussing and normal crying. Even if there may be a reduction in the infantile colic incidence and support for the hypothesis that infantile colic is at least partially "in the eye of the beholder," that is, the concerned parent, a subgroup of infants may be more "genuinely colicky." Women who had stated in late-pregnancy interviews that there is a risk of spoiling an infant with too much physical contact were more likely to have infants with colic, and their infants were more distressed, even when given the same amount of physical contact. This finding warrants further elucidation.     

Patent ductus arteriosus in preterm infants is associated with cardiac autonomic alteration and predominant parasympathetic stimulation

Background

Hemodynamic disorders in patent ductus arteriosus (PDA) may alter the stimulation of the autonomic nervous system.

Aim

The objective of this study was to analyze the orthosympathetic–parasympathetic balance in preterm infants with PDA.

Study design and subjects

Patients were included from consecutive admissions to Amiens University Hospital from 2009 to 2011. We defined a PDA group and a Control group (echographic criteria). For each patient, three 4-minutes segments of ECG were recorded during quiet sleep and the RR chronologic series were extracted, and spectral (Fourier Transform) and time-domain analyses were performed. For each parameter of heart rate variability (HRV), average of three measures was determined and analysed.

Results

Forty-four patients were included for analysis. The total HRV power, LF/HF ratio and SDNN were lower in the PDA group (n = 22, gestational age 28.2 w ± 1.9) than in the Control group (n = 22, gestational age 28.8 w ± 2). The decrease in LF power destabilized the autonomic balance in favour of parasympathetic stimulation. After adjustment for postconceptional age, PDA was still associated with parameters of autonomic neural stimulation.

Conclusion

These results suggest association of PDA with predominance of parasympathetic stimulation in preterm infants. The mechanisms of homeostasis in patients with PDA are very complex and involve both circulatory adaptations and control by autonomic pathway. If confirmed, our results could be interesting for future researches aiming to verify the interest of new targeted therapies for the management of PDA.     

Motilin, Vasoactive Intestinal Peptide and Gastrin in Infantile Colic

ABSTRACT. Intestinal hyperperistalsis is one part of the clinical picture in infantile colic. Three gut hormones involved in the regulation of gut motility; motilin, vasoactive intestinal peptide (VIP) and gastrin, were measured with the RIA method in: 40 infants with infantile colic, (age 2–22 weeks), 42 healthy age-matched infants, 11 children (age 3–36 months) with gastrointestinal disorders, and 20 children (age 3–36 months) with non-gastrointestinal disorder. Basal s-motilin levels were raised in infants with infantile colic ( p <0.01) and in children with other gastrointestinal disorders ( p <0.001). Formula-fed infants had higher basal s-motilin levels than the breast-fed infants ( p <0.05). P-VIP and s-gastrin levels were raised in children with other gastrointestinal disorders ( p <0.05), but not in infantile colic. Formula-fed colicky infants had higher s-gastrin levels than the breast-fed colicky infants ( p <0.05). We suggest that the increased s-motilin level in infantile colic might account in part for the clinical picture of this disorder.     

Circadian rhythm of heart rate and heart rate variability.

BACKGROUND: Measurements of heart rate variability (HRV) are increasingly used as markers of cardiac autonomic activity. AIM: To examine circadian variation in heart rate and HRV in children. SUBJECTS: A total of 57 healthy infants and children, aged 2 months to 15 years, underwent ambulatory 24 hour Holter recording. Monitoring was also performed on five teenagers with diabetes mellitus and subclinical vagal neuropathy in order to identify the origin of the circadian variation in HRV. METHODS: The following variables were determined hourly: mean RR interval, four time domain (SDNN, SDNNi, rMSSD, and pNN50) and four frequency domain indices (very low, low and high frequency indices, low to high frequency ratio). A chronobiological analysis was made by cosinor method for each variable. RESULTS: A significant circadian variation in heart rate and HRV was present from late infancy or early childhood, characterised by a rise during sleep, except for the low to high frequency ratio that increased during daytime. The appearance of these circadian rhythms was associated with sleep maturation. Time of peak variability did not depend on age. Circadian variation was normal in patients with diabetes mellitus. CONCLUSION: We have identified a circadian rhythm of heart rate and HRV in infants and children. Our data confirm a progressive maturation of the autonomic nervous system and support the hypothesis that the organisation of sleep, associated with sympathetic withdrawal, is responsible for these rhythms.     

Cow's milk whey protein elicits symptoms of infantile colic in colicky formula-fed infants: a double-blind crossover study

There are several causes of infantile colic. The aim of this study was to evaluate, under controlled conditions, whether bovine whey proteins can elicit symptoms of infantile colic in colicky formula-fed infants. The mean age for entering the study was 6.4 weeks and the mean age for colic debut was 3.7 weeks. In 24 of 27 infants with severe colic, the symptoms disappeared when they were given a cow's milk-free diet (Nutramigen). These 24 infants were entered into a double-blind crossover study. The infants (receiving cow's milk-free diet) were given the contents of identical capsules with each meal during day 6. The same procedure was repeated on day 10. The capsules contained either whey protein powder (with Nutramigen added) or human albumin powder (with Nutramigen added). Eighteen infants receiving the whey protein-containing capsules reacted with colic, two infants receiving placebo reacted with colic (P less than .001), and four infants did not react at all. Crying hours per day for the 24 infants were 5.6 hours for formula-fed infants and 0.7 hour for cow's milk-free diet-fed infants (P less than .001). Crying hours per day were 3.2 hours for the infants receiving whey protein capsules and 1.0 hour for those receiving placebo (P less than .001). In conclusion, bovine whey protein can elicit symptoms of infantile colic in colicky formula-fed infants.     

Circadian rhythm of heart rate and heart rate variability

BACKGROUND—Measurements of heart rate variability (HRV) are increasingly used as markers of cardiac autonomic activity.AIM—To examine circadian variation in heart rate and HRV in children.SUBJECTS—A total of 57 healthy infants and children, aged 2 months to 15 years, underwent ambulatory 24 hour Holter recording. Monitoring was also performed on five teenagers with diabetes mellitus and subclinical vagal neuropathy in order to identify the origin of the circadian variation in HRV.METHODS—The following variables were determined hourly: mean RR interval, four time domain (SDNN, SDNNi, rMSSD, and pNN50) and four frequency domain indices (very low, low and high frequency indices, low to high frequency ratio). A chronobiological analysis was made by cosinor method for each variable.RESULTS—A significant circadian variation in heart rate and HRV was present from late infancy or early childhood, characterised by a rise during sleep, except for the low to high frequency ratio that increased during daytime. The appearance of these circadian rhythms was associated with sleep maturation. Time of peak variability did not depend on age. Circadian variation was normal in patients with diabetes mellitus.CONCLUSION—We have identified a circadian rhythm of heart rate and HRV in infants and children. Our data confirm a progressive maturation of the autonomic nervous system and support the hypothesis that the organisation of sleep, associated with sympathetic withdrawal, is responsible for these rhythms.     

5-Hydroxy-3-indole acetic acid levels in infantile colic: Is serotoninergic tonus responsible for this problem?

Abstract Levels of 5-hydroxy-3-indole acetic acid (5-OHIAA), a metabolite of serotonin, were studied in infants with infantile colic in order to investigate the aetiology of infantile colic pathogenesis. The study included 16 patients with infantile colic and 10 control subjects. Random urinary 5-OH IAA levels of colicky infants were found to be higher than those in the control group. This finding suggested that high serotonin levels may be responsible for infantile colic.     

Heart rate variability in infants with apparent life-threatening events

Heart rate variability (HRV) is often used as an index of sympatho-vagal balance. A decreased HRV has been observed in patients with central hypoventilation and in infants who have later succumbed to sudden infant death syndrome (SIDS). The aim of the present study was to investigate whether HRV is altered in infants with apparent life-threatening events (ALTE), a group with an increased risk of SIDS. Fifty infants with ALTE were compared with 50 age- and sex-matched controls. ECG was recorded overnight in all infants. Two sequences of RR intervals free of artefacts were selected from each sleep state and spectral analysis of RR variability was performed. The mean and SD of RR and the low (LFPow) and high (HFPow) frequency power were analysed. In active sleep (AS) the LF/HF ratio was lower in ALTE infants, but no differences were seen in either the LFPow or the HFPow. In quiet sleep (QS), however, ALTE infants had higher SD-RR (p = 0.006), greater HFPow (p = 0.02) and VLFPow (very low frequency power, p = 0.02) than the control infants. The same results were seen when the two sleep states were combined for analysis, ALTE infants had higher SD-RR (p = 0.004), HFPow (p = 0.006) and VLFPow (p = 0.04). Conclusion: The different HRV pattern in ALTE infants compared to healthy controls suggests an altered autonomic control.     

Macromolecular absorption in infants with infantile colic

Intestinal absorption of macromolecules, using human alpha-lactalbumin (alpha-LA) as a marker, was studied in breast-fed and formula-fed infants with infantile colic. Serum samples taken at 30 and 60 min after an intake of human milk were analyzed for alpha-LA by a competitive radioimmunoassay technique. Breast-fed infants with infantile colic had significantly higher s-alpha-LA levels compared with age-matched breast-fed control infants 0-1 month of age: median value 926 micrograms alpha-LA/l serum/l human milk/kg bodyweight (n = 11) versus 150 (n = 34); 1-2 months of age: 173 (n = 22) versus 31 (n = 16); 2-3 months of age: 132 (n = 8) versus 11 (n = 16). Similarly, formula-fed colicky infants had significantly higher s-alpha-LA levels than age-matched formula-fed control infants 1-2 months of age: median value 126 (n = 12) versus less than 10 (n = 14); 2-3 months of age: 156 (n = 11) versus less than 10 (n = 10). The increased absorption of the macromolecule human alpha-lactalbumin in infantile colic suggests that the gut mucosa is affected in infants with infantile colic.     

Infants with colic have a normal sleep structure at 2 and 7 months of age

OBJECTIVE: To compare nighttime sleep structure between infants with colic and a control group. STUDY DESIGN: Sleep and cry times of 15 infants with colic and 16 infants in a control group were recorded with the use of a daily diary at the ages of 5 weeks and 6 months. The diary was kept at home for a 1-week period. Overnight polygraphic sleep recordings in a sleep laboratory were performed when the infants were 2 months of age and were repeated for 11 infants with colic and 14 infants in a control group at 7 months of age. RESULTS: Daily sleep time was shorter in infants with colic compared with the control group at 5 weeks of age (P =.001). Polygraphic data showed a similar sleep structure between the study groups at 2 and 7 months of age. Infants with colic had somewhat more obstructive apneas during rapid eye movement sleep at the age of 2 months (P =.04), and they had fewer awakenings at the age of 7 months than the control group (P =.003). CONCLUSION: Infants with colic had normal sleep polygraphic finding at 2 and 7 months of age including sleep structure, movements, and breathing. Despite the shorter reported daily sleep times, the polygraphic data did not suggest infantile colic to be associated with a sleep disorder.     

Characteristics of heart period variability in intubated very low birth weight infants with respiratory disease

BACKGROUND: Heart period variability provides a measure of balance between the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS). Since the PNS develops during the final weeks of gestation, premature infants have an overriding SNS. Spectral power analysis of heart period variability reveals two main frequency regions, the low frequency region (LF) representing primarily SNS activity and the high frequency region (HF) representing PNS activity. OBJECTIVES: To identify the characteristics of heart period power in the LF and HF regions in very low birth weight (VLBW) infants in the neonatal intensive care unit across gestational age groups and between sleep and awake states. METHODS: Data were collected from 16 intubated and mechanically ventilated VLBW infants with respiratory disease. Using spectral analysis techniques, heart period power in the two main frequency regions was extracted. RESULTS: HF power did not improve with gestational age as expected. LF power did increase with age, albeit nonsignificantly. LF and HF power were not significantly different between awake and sleep states. CONCLUSIONS: The results of this preliminary study suggest that PNS tone does not improve with gestational age in VLBW infants with respiratory disease. The intensive care environment may stimulate a sympathetic response in these infants and disrupt normal PNS development.     

Macromolecular Absorption in Infants with Infantile Colic

ABSTRACT. Intestinal absorption of macromolecules, using human α-lactalbumin (α-LA) as a marker, was studied in breast-fed and formula-fed infants with infantile colic. Serum samples taken at 30 and 60 min after an intake of human milk were analyzed for α-LA by a competitive radioimmunoassay technique. Breast-fed infants with infantile colic had significantly higher s-α-LA levels compared with age-matched breast-fed control infants 0-1 month of age: median value 926 μg α-LA/I serum/I human milk/kg bodyweight (n= 11) versus 150 (n= 34); 1–2 months of age: 173 (n= 22) versus 31 (n= 16); 2–3 months of age: 132 (n= 8) versus 11 (n= 16). Similarly, formula-fed colicky infants had significantly higher s-α-LA levels than agematched formula-fed control infants 1-2 months of age: median value 126 (n= 12) versus < 10 (n= 14); 2–3 months of age: 156 (n= 11) versus < 10 (n= 10). The increased absorption of the macromolecule human α-lactalbumin in infantile colic suggests that the gut mucosa is affected in infants with infantile colic.     

Influence of maternal smoking on autonomic nervous system in healthy infants

To determine the influence of maternal smoking on autonomic nervous system in healthy infants, 36 infants were recorded polygraphically for one night. Their mothers were defined, according to their smoking frequency during pregnancy, as "nonsmokers" (no cigarettes smoked during pregnancy) or "smokers" (10 or more cigarettes per day). The infants had a median postnatal age of 10.5 wk (range 6 to 16 wk); 18 were born to nonsmokers, and 18 to smokers. During the whole night, spectral analyses of heart rate (HR) were evaluated as a function of sleep stages. Two major peaks were recognizable: a low-frequency component (LF) related to sympathetic and parasympathetic activities and a high-frequency component (HF) reflecting parasympathetic tonus. The ratio of LF/HF powers was calculated as an index of sympathovagal interaction. In REM sleep, "smokers" infants were characterized by significantly lower HF powers and normalized HF powers, and higher LF/HF ratios than "nonsmokers." The finding did not reach statistical significance in NREM sleep. In conclusion, maternal smoking induced changes in autonomic control and maturation in infants. These effects of cigarette smoke exposure can be added to those already reported and offer additional evidence for counseling mothers to stop smoking.