Cardiorespiratory physiology in the safe passage study: protocol, methods and normative values in unexposed infants

Abstract

Aim: The Safe Passage Study, conducted by the Prenatal Alcohol in SIDS and Stillbirth Network, is investigating contributions of prenatal alcohol exposure to foetal and infant demise. This current report presents physiological data from full-term infants with no prenatal exposure to alcohol or maternal smoking.

Methods: Data are from 666 infants from the Northern Plains (North and South Dakota) and South Africa. A standardised protocol assessed cardiorespiratory function during baseline and head-up tilts shortly after birth and at one month of age.

Results: Analyses revealed significant increases in heart rate and decreases in BP from the newborn to one-month time period as well as diminished heart rate responses to head-up tilt in one-month-old infants.

Conclusion: The Safe Passage Study was successful in characterising physiology in a large number of infants at sites known to have elevated risks for SIDS. Results demonstrate that even with low prenatal adverse exposures, there are significant changes in cardiorespiratory function as infants enter the window of increased risk for SIDS.

Keywords: SIDS; Autonomic development; Blood pressure; Heart rate; Respiration.

Figure 1

Schematic of cardiorespiratory assessments. Small blocks above the segments of the protocol (e.g. Baseline-1, Tilt-1) are epochs used for the current analyses. Epoch sizes (small blocks) varied in durations. Baseline 1 epochs, epochs during which blood pressure was measured, and all but the first epoch comprising the post tilt period are 60 seconds in duration. The epoch preceding the first head up tilt was 90 seconds. The epochs immediately after head-up or tilts back to flat were 15 seconds in duration. All other epochs were 30 seconds in duration.

Figure 2

Means±SE for Active Sleep (AS) and Quiet Sleep (QS) heart rate (HR) (A), breathing rate (B), systolic BP (C), and diastolic BP (D) during the 10 minute baseline prior to head–up tilts for newborns and at 1 month. Values were computed after removal of statistical outliers. Results from mixed models regression indicated the following significant effects: A) in both QS and AS HR is higher at 1 month (p<0.001), in newborns and at 1 month HR is higher in AS than in QS (p<0.001); B) there is no significant effect of age for breathing rate in QS, in AS breathing rate is higher at 1 month than in newborns (p<0.03), at both ages breathing rate is higher in AS than in QS (p<0.001); C) in QS systolic BP is lower at 1 month (p<0.03); D) diastolic BP is lower at 1 month in both sleep states (p<0.001).

Figure 3

Means±SE for Active Sleep (AS) and Quiet Sleep (QS) standard deviation of r-wave to r-wave intervals (SD-RRi) (A), standard deviation of breath to breath intervals (SD-BBi) (B), root mean square of successive differences in RRi, a time domain measure beat to beat variability in heart rate (rMSSD of RRi (log₁₀)) (C), and a spectral measure of high frequency variability in RRi (HF-RRi variability (log₁₀)) (D) during the 10 minute baseline prior to head–up tilts for newborns and at 1 month. Values were computed after removal of statistical outliers. Results from mixed models regression indicated the following significant effects: A) in both QS and AS SD-RRi is lower at 1 month (p<0.001), in newborns and at 1month SD-RRi is higher in AS than in QS (p<0.001); B) for breathing rate variability there was a significant decrease with age in QS and AS (p<0.002, p<0.001), and SD-BBi was significantly higher in AS than QS at both ages (p<0.001); C) the time domain measure of beat-to-beat HRV (rMSSD) was significantly lower at 1 month for both sleep states (p<0.001), and there were no significant effects of sleep state at either age; D) the spectral measure of high frequency variability in HR (HF-RRi) was significantly lower at 1 month in both QS (p<0.002) and AS (p<0.001), andthere were no significant effects of sleep state on HF-RRi at either age.

Figure 4

Means±SE changes from baseline following 45° head-up tilts for Active Sleep (AS) and Quiet Sleep (QS) heart rate (HR) (A), breathing rate (B), systolic BP (C), and diastolic BP (D) for newborns and at 1 month. Values were computed after removal of statistical outliers. *** indicates changes following tilts were significant at the p<0.001 level, ns indicates the change was not significant. Results from mixed models regression indicated the following additional significant effects: A) changes in HR with tilt were greater in newborns than at 1 month for QS (p<0.001) and AS (p<0.02); B) there were no significant effects of age on changes in breathing rate, the decrease in breathing rate with head-up tilting in newborns was greater in AS than in QS (p<0.03), at 1 month there was no significant effect of sleep state; C) there were no significant effects of age for changes in systolic BP in either sleep state; D) changes in diastolic BP in AS were greater at 1 month than in newborns (p<0.04).

Figure 5

Means±SE changes from baseline following 45° head-up tilts during AS and QS in the root mean square of successive differences in RRi (rMSSD) A), and maximum – minimum heart rate B) for newborns and at 1 month. Values were computed after removal of statistical outliers. *, **, and *** indicates changes were significant at p<0.05, p<0.01, and p<0.001 levels respectively, ns indicates the change was not significant. Results from mixed models regression indicated the following significant effects: A) there was a significant difference in the change in rMSSD between newborn and 1 month of age (p<0.001), in newborns the decrease in rMSSD was greater in QS than in AS (p<0.002), at 1 month, there was a significant difference in the change in rMSSD between AS and QS (p<0.003); B) maximum – minimum HR following tilt showed no significant effect of age during QS, but in AS this HR response was greater at 1 month than in newborns (p<0.002), this measure of HR response to head-up tilting did not differ by state in the newborn period but was greater in AS at 1 month of age (p<0.002).