The Intestinal and Cerebral Regional Hemodynamic Changes in Term and Preterm Infants During Early Postnatal Life - A Review
Keyword : Blood flow velocity; Middle cerebral artery; Newborn premature infants; Regional hemodynamics; Superior mesenteric artery
Major adaptive changes occurred in the cardiovascular system of the newborn infants after birth. Alteration of the pattern and course of circulation and of the distribution of blood flow to the various regions followed the onset of ventilation, elimination of the placental circulation, and closure of the fetal shunt pathways. It is, therefore, pertinent to investigate the regional circulation as it relates to the systemic hemodynamic changes during this transitional period. We chose to examine the changes of the intestinal circulation and that of a vital regional circulation, the brain.
To characterize the early neonatal intestinal and cerebral circulations, we studied the Doppler blood flow velocities (BFV) of the superior mesenteric (M), middle cerebral (C) arteries, and aortic orifice for calculation of cardiac output (CO) of infants who were:
The measurements were made sequentially in each infant during the first hours of life and on days 3-7 or days 3-14. The findings were related to the changes of the systemic hemodynamics, i.e., CO, heart rate (HR), and blood pressure (BP). The response to feeding was assessed by pre- and postprandial measurements.
An ultrasound duplex scanner with pulsed Doppler and color flow mapping was used for the BFV, cardiac output measurement and detection of patency of ductus arteriosus (PDA). Transducers used were 7.5 MHz for tissue imaging and 6.0 MHz for Doppler recordings. Details of methodology was as previously reported.1-2 Briefly, measurements were made in (a) superior mesenteric artery: the transducer was placed on mid-abdomen above the umbilicus in the sagittal plane and using color flow mapping the superior mesenteric artery was located as it originated from the abdominal aorta just below the celiac artery. Doppler sample volume was placed a few millimeters distal to the artery's origin and angle correction was used when necessary. When stable Doppler waveforms were obtained, the curve was traced and BFV, i.e. mean, maximum velocities were calculated using the programmed software. The end diastolic flow velocity was manually calculated from the hard copy; (b) middle cerebral artery, the transducer was placed perpendicular to the pterion part of the temporal bone above the ear and BFV measured with sample volume placed parallel to flow and waveforms traced as above; (c) cardiac output, the transducer was placed at the right upper parasternal area in long axis and sample volume at the level of aortic orifice for aortic flow velocity. The velocity waveform was considered optimal when the leaflet signals were on the recording and the characteristic sound of aortic Doppler signal was maximal. The aortic diameter was measured as the distance between the aortic leaflets at their attachments in systole when the leaflets were maximally separated (parasternal long axis view). By entering the diameter of the aortic orifice after the aortic velocity curve was traced, the instrument was programmed to calculate stroke volume and the cardiac output was obtained by multiplying volume by heart rate. Cardiac output was normalized for body weight and expressed in ml/min/kg. In the VLBW infants, to obviate the difficulty of the upper sternal approach for the left ventricular output in intubated infants, the right ventricular output was obtained using the parasternal short axis view where the diameter of the pulmonic valve orifice was measured when the leaflets were maximally separated and the main pulmonary artery flow velocity sampled at the orifice.
The statistical methods used were analysis of variance for repeated measures (ANOVA), various T-tests, and the Pearson Correlation test.
Results and Discussion
In full term infants, the preprandial mean MBFV or Vmean was relatively high at one hour of age, (Vmean was 33 cm/s) with low end diastolic flow velocity (EDFV, 0.05 cm/s). At two to six hours old, MBFV decreased significantly, especially the EDFV (50-98%). This was followed by increases to the one hour level at 24 hours old and day 3 with tripling of the EDFV. There were no further changes through day 5. All infants had a PDA with left to right shunt at 2 hours of age, 75% of the infants closed their PDA by 24 hours, and 100% had closed by day 3. At 2 hours, the low MBFV was accompanied by increased CO, low BP. With closure of the PDA, CO decreased and BP increased to the one hour level and was maintained thereafter. Catecholamine surge at birth may have contributed to the initially higher MBFV and the fall in BFV that followed at 2-6 hours probably reflected ductal steal and waning catechol effect. The subsequent increase in MBFV on day 3 can be explained by closure of the PDA and priming effects of food once feeding schedules were established. A significant (85-90%) postprandial increase in MBFV was demonstrated consistently.
In contrast, CBFV was relatively unchanged during the first day of life though middle cerebral EDFV was low at 2 hours old. The mean CBFV, or Vmean corresponding to the low EDFV was normal, suggesting that PDA had less effect on the cerebral vascular bed than the mesenteric. The CBFV increased on day 3 and day 5, probably reflecting the increasing metabolic demand with age. Feeding did not affect the CBFV, CO, HR, or BP
In 33-35 week AGA preterm infants, a similar increase in intestinal and cerebral blood flow was suggested by the higher MBFV and CBFV on day 3 than on day 1. In those that were examined in the first hours of life both MBFV and CBFV were low due to the PDA. Upon closure of the PDA, the MBFV and CBFV increased by the end of first day and on day 3, and the CO decreased while BP increased. There were no further changes in BFVs through day 7 from day 3. Feeding had no effect on CBFV. In contrast to the term infants, these preterm infants showed the following:
The VLBW infants (BW 775 - 1245 gm.) were studied under different conditions than the infants in studies 1 and 2 as required by best practice treatment of their clinical conditions. The studies were made when they were clinically stable. The results were interpreted with this understanding. All these infants received prophylactic indomethacin for prevention of intraventricular hemorrhage. They did not have symptomatic PDA. The Doppler MBFV, CBFV, and CO were measured before indomethacin doses at 6, 30, and 54 hours of age and before and after nasogastric feeding on days 7 and 14. Preprandial mean and end diastolic MBFV did not change over the first 54 hours of life, but coincident with the initiation of feedings increased by 54% at 7 to 14 days. Postprandial mean MBFV increased 35% on day 7 and 17 % on day 14; unaccompanied by changes in CO, HR, and BP. In contrast, mean and end diastolic CBFV increased by 71 and 374% respectively from 6 to 54 hours of life with no further changes from 3 to 14 days. Cardiac output increased over the first 14 days of life. In summary, in these VLBW infants, cerebral and mesenteric regional BFV and CO increased significantly over the first 2 weeks of life, unrelated statistically to changes in PDA, BP, SaO2, pH, or PaCO2. Region specific patterns of hemodynamic maturation were observed, with CBFV increasing in the early hours of life and preprandial MBFV increasing only after enteral nutrition has been established. Within the limitation of the study conditions in these VLBW infants, after 6 hours of age, MBFV and CBFV appeared to be comparable to those of study 2 infants. Like the study 2 infants, the CBFV was somewhat lower than term infants. Indomethacin did not appear to prevent the maturational changes in CBFV and MBFV over time as seen in the older gestational age infants. However, transient reductions in these regional blood flows occurred with each indomethacin dosage, more pronounced in the CBFV than in MBFV.4 In the absence of a comparable study of VLBW infants not given prophylactic indomethacin, we are unable to rule out the possibility that these regional hemodynamic changes over time might have been modified for these infants.
In term infants, the early postnatal shunts through the PDA significantly affect the intestinal circulatory adjustment. Ductal steal caused a decreased superior mesenteric blood flow during the first 2-6 hours of life, thus a potential vulnerable period of this vascular bed for circulatory insufficiency may exist which can lead to the development of pathologic intestinal conditions; e.g. some feeding problems and necrotizing enterocolitis, especially when other risk factors coexisted, e.g. birth asphyxia, phototherapy.5
In the 33 to 35 weeks AGA preterm infants, both the intestinal and cerebral circulations are affected by ductal steal suggesting a potential vulnerability to circulatory insufficiency in both vascular beds during the early hours of postnatal life, i.e. the risk of development of necrotizing enterocolitis, cerebral ischemia exists, especially in the presence of other risk factors as mentioned above. Systemic hemodynamic compensatory mechanisms are evident with the intestinal circulatory response to feeding which suggest more effort required for a physiologic demand in these preterm than in term infants. Thus this increase in demand on the systemic circulation may also be potential vulnerability for the preterm infants.
In VLBW infants when indomethacin was given from 6 hours of age to prevent intraventricular hemorrhage (IVH), symptomatic PDA did not appear to be a problem from that age. Ductal steal from the mesenteric and cerebral regional circulations as seen in the bigger premature infants was not observed, though measurements were not made before 6 hours of age. The indomethacin might have reduced or obviated symptomatic PDA. However, the functional maturity of the two vascular beds in these VLBW infants could not be compared to the infants in study 1 and 2 because of the different study conditions. The vasoconstrictive response to indomethacin was transient and did not prevent the time course changes in both regional flows during the first two weeks of life.4 The protective effects of indomethacin for IVH did not appear to be associated with increased incidence of NEC or ileal perforations in the study infants4,6 though further study is indicated to confirm this. These VLBW infants were able to increase their MBFV postprandially under the study condition. The feeding response was however, of lower magnitude than in the term and larger preterm infants.4 Further study in this area is needed.
In conclusion, the regional hemodynamic changes in the cerebral and intestinal circulations of neonates showed not only region specificity, but also developmental age dependency.
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2. Martinussen M, Brubakk AM, Vik T, Yao AC. Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestation age preterm infants. Pediatr Res 1996;39:275-80.
3. Yanowitz TD, Yao AC, Werner JC, Pettigrew KD, Oh W, Stonestreet BS. Hemodynamic maturation in very low birth weight infants. Pediatr Res 1996;39:254A/1511.
4. Yanowitz TD, Yao AC, Werner JC, Pettigrew KD, Oh W, Stonestreet BS. Effects of prophylactic low dose indomethacin on hemodynamics in very low birth weight infants. J Pediatr 1997; In Press.
5. Yao AC, Martinussen M, Johansen, OJ, Brubakk AM. Phototherapy - associated changes in mesenteric blood flow response to feeding in term neonates. J Pediatr 1994;124:309-12.
6. Ment LR, Oh W, Erenkrantz RA, Philip AGS, Vohr B, Allan W. Low-dose indomethacin and prevention of intraventricular hemorrhage:A multicenter randomized trial. J Pediatr 1994;93:543-50.
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