Objectives. Whether extremely low birth weight (ELBW) infants are at risk of cerebral hypoperfusion is uncertain because key issues concerning their cerebral blood flow (CBF) and mean arterial pressure (MAP) are unresolved: (1) whether CBF is pressure-passive or autoregulated; (2) the normal level of MAP; and (3) whether inotropic drugs used to increase MAP might inadvertently impair CBF. We addressed these issues in ELBW infants undergoing intensive care.
Methods. CBF (measured by near-infrared spectroscopy) and MAP were measured in 17 infants aged 1.5 to 40.5 hours.
Results. Five infants remained normotensive (MAP 37 ± 2 mm Hg, [mean ± SEM]); twelve became hypotensive (MAP 25 ± 1 mm Hg) and were treated with dopamine (10–30 μg · kg−1 per min). CBF of hypotensive infants (14 ± 1 mL · 100 g−1 per min) was lower than the CBF of normotensive infants (19 ± mL · 100 g−1 per min). After commencement of dopamine in hypotensive infants, MAP increased (29 ± 1 mm Hg) and CBF also increased (18 ± 1 mL · 100g−1 per min). CBF was correlated with MAP in hypotensive infants before (R = 0.62) and during (R = 0.67) dopamine, but not in normotensive infants. A breakpoint was identified in the CBF versus MAP autoregulation curve of untreated infants at MAP = 29 mm Hg; no breakpoint was evident in dopamine-treated infants.
Conclusions. In ELBW infants (1) cerebral autoregulation is functional in normotensive but not hypotensive infants; (2) a breakpoint exists at ∼30 mm Hg in the CBF-MAP autoregulation curve; and (3) dopamine improves both MAP and CBF.
Hypotensive Extremely Low Birth weight Infants Have Reduced Cerebral Blood Flow.
Editor: This investigation illustrates many misconceptions and unwarranted assumptions that the perinatal professions apply to the preterm child. The first paragraph mentions conflicting CBF data in “stable” preterm infants and in those with respiratory distress. Abnormalities are noted in MAP and CBF in “well” preterm infants and “sick” preterm infants; the authors aptly describe the evidence as “confounding.” If abnormalities of autoregulation are found in sick and comparatively well neonates, are abnormalities sometimes normal? What differentiates the “well” from the “sick” preterm infant; is it infection, metabolism, tumor, trauma, genetics or something else? The only process that will correct this confusion is definition of the physiological norm.
An animal pseudo-model for the ELBW infant exists. A kangaroo “Joey”, delivered in the immature post-embryonic state, weighing a few grams, clamps and snaps its own cord, claws its way from the vulva into a pouch-incubator, elongates a nipple into a feeding tube and produces the next healthy kangaroo generation – physiologically. The human mother has lost the marsupial pouch and nipple over evolutionary time, but has the 26 -week human preemie lost the genetic capability of normal pulmonary respiration and physiological umbilical cord closure?
In this group of 17 ELBW infants, immediate intubation and ventilation, presumably done after immediate cord clamping, prevented an answer for that question, however, a very similar group of 17 infants, [1] 27-32 weeks gestation, that had delayed cord clamping with gravity assisted placental transfusion (not quite physiological cord closure) had remarkably normal lung function compared to the cohort of 19 that were immediately clamped. The author, Kinmond, comments: “We did not time the onset of respiration relative to cord clamping, but many infants in the [delayed clamping] group were already crying.”
Indeed, initial pulmonary ventilation in the physiological neonate (no cord clamp used) may be much more a functional result of placental transfusion than contraction of the diaphragm and expansion of the rib cage. Jaykka [2] demonstrated that perfusion of the fetal lung resulted in “erection” and AERATION of alveoli. Gunther [3] demonstrated how powerful that perfusion and erection could be – 100+ mls of blood forced into the inferior vena cava, heart and lungs within 30 seconds by the contracting (physiological) maternal uterus. Gunther also showed that the neonate controls and terminates the placental transfusion reflexively, with blood volume increasing in a stepwise manner with successive uterine contractions until optimal transfusion has occurred; the umbilical vessels then close permanently. One would expect ELBW infants to be similarly endowed.
Respiratory distress syndrome (RDS) and hyaline membrane disease (HMD) are manifestations of hypovolemia and hypovolemic shock – shock lung. RDS occurs at any age and HMD can be induced in newborn rabbits and puppies by withdrawing blood volume, and in foals and primates by immediate cord clamping. [4, 5] The most frequent clinical manifestation of RDS is retraction respiration (RR) (gasping, intercostal recession), also termed “air hunger” in the exsanguinated adult.
The RR symptom is a reflex response to insufficient filling of the right heart – low central venous pressure – and gasping creates intense pulses of negative intra-thoracic pressure that pull venous blood into the right heart. In the retracting preemie with low MAP, RR may also pull arterial blood from peripheral arteries into the thoracic aorta, resulting in almost tidal flow in the carotid arteries, pulses of negative blood pressure, and very deficient CBF. This intermittent loss of CBF may account for “conflicting CBF data” previously mentioned. Doppler flow in any peripheral artery will demonstrate the phenomenon during RR.
On MRI, IVH is visualized as a hemorrhagic infarct of the germinal matrix. Being the most metabolically active area of the preemie’s brain, the germinal matrix is the first area to infarct from deficient perfusion. Suarez [6] noted almost 100% correlation of RDS with IVH, and although IVH occurred in both of Kinmond’s groups, [1] ventricular dilatation (visible loss of brain tissue) occurred only in the immediately clamped group. Recently, the Cochrane review has reported decreased incidence of IVH in preemies with delayed cord clamping.
In this present group of ELBW infants, immediate intubation and continuous positive pressure ventilation prevented pathogenic retraction respiration, and apparently prevented IVH over a 48-hour period. If these infants had been left attached to their placentas and subjected to the physiological “Jaykka” effect of placental transfusion, would they have escaped intubation by crying spontaneously like Kinmond’s group? In the late clamped term infant, initial systolic BP is 80 mms Hg, in the immediately clamped infant, 60 mm Hg. [7] With placental transfusion, would the MAP of the ELBW control group have been 37 mms Hg? Would there have been any ELBW infants in the pre and post dopamine groups? These ELBW infants were not dopamine deficient; they were blood volume deficient. The correct treatment of hypovolemic hypotension is blood transfusion.
Late clamping (say after five minutes) is not the same as no clamping. Gunther recorded cord pulsation lasting nearly 20 minutes after birth, and in such cases, clamping at five minutes may have the “early- clamp” effect of hypovolemia.
On the other hand, the clamp might coincide with a transfusing uterine contraction. The result would be a child very “distended” with blood, blood that otherwise (no cord clamp used) would have drained back into the placenta during uterine diastole. Physiological cord closure results in an optimal blood volume. When used before physiological cord closure, the cord clamp is injurious; when used afterwards, it is harmless, and superfluous.
Unfortunately, no study has ever been done on delivering term or preterm babies physiologically without a cord clamp, but every other mammal on the planet, including primates and marsupials, does so very successfully. The reader is referred to an extensive review [8] on this subject entitled, 'When Should We Clamp the Umbilical Cord?' In conclusion to the review, there is no defined answer provided. (The correct answer is, “almost never.”) A study on neonates, term, preterm and ELBW that are sent to the nursery with cord and placenta intact, is long overdue. It would answer the above question, and stop the current epidemic of cord clamp injuries.
George Malcolm Morley, MB ChB FACOG
obgmmorley@aol.com
References:
Kinmond S et al. Umbilical Cord Clamping and Preterm Infants: a Randomized Trial. BMJ 1993; 306: 172-175
Jaykka S. Capillary Erection and Lung Expansion. Acta Paediatr. 1965 [nppl] 109.
Gunther M. The transfer of blood between the baby and the placenta in the minutes after birth. Lancet 1957;I:1277-1280.
Mahaffey Leo W. Rossdale, PD. CONVULSIVE SYNDROME IN NEWBORN FOALS RESEMBLING PULMONARY SYNDROME IN THE NEWBORN INFANT; The Lancet 1959 1223- 1225.
Windle W. Brain Damage by Asphyxia at Birth. Scientific American. 1969 Oct;221(4):76-84.
Suarez RD et al. Indomethacin Tocolysis and Intraventricular Hemorrhage. OBSTETRICS & GYNECOLOGY Vol. 97 No. 6 June 2001 921-925.
Peltonen T. Placental Transfusion, Advantage - Disadvantage. Eur J Pediatr. 1981;137:141-146
Philip A.G.S. Saigal S. When Should We Clamp the Umbilical Cord? Neonatal Reviews Vol.5 No.4 2004 e142 © 2004 American Academy of Pediatrics