Corinna Binder-Heschl

The timing of umbilical cord clamping at birth: physiological considerations

While it is now recognized that umbilical cord clamping (UCC) at birth is not necessarily an innocuous act, there is still much confusion concerning the potential benefits and harms of this common procedure. It is most commonly assumed that delaying UCC will automatically result in a time-dependent net placental-to-infant blood transfusion, irrespective of the infant’s physiological state. Whether or not this occurs, will likely depend on the infant’s physiological state and not on the amount of time that has elapsed between birth and umbilical cord clamping (UCC). However, we believe that this is an overly simplistic view of what can occur during delayed UCC and ignores the benefits associated with maintaining the infant’s venous return and cardiac output during transition. Recent experimental evidence and observations in humans have provided compelling evidence to demonstrate that time is not a major factor influencing placental-to-infant blood transfusion after birth. Indeed, there are many factors that influence blood flow in the umbilical vessels after birth, which depending on the dominating factors could potentially result in infant-to-placental blood transfusion. The most dominant factors that influence umbilical artery and venous blood flows after birth are lung aeration, spontaneous inspirations, crying and uterine contractions. It is still not entirely clear whether gravity differentially alters umbilical artery and venous flows, although the available data suggests that its influence, if present, is minimal. While there is much support for delaying UCC at birth, much of the debate has focused on a time-based approach, which we believe is misguided. While a time-based approach is much easier and convenient for the caregiver, ignoring the infant’s physiology during delayed UCC can potentially be counter-productive for the infant.

Increase in pulmonary blood flow at birth: role of oxygen and lung aeration.

There is no well‐established, direct correlation between local aeration and perfusion in the lungs immediately following birth. In a new study of simultaneous X‐ray imaging and angiography in near‐term rabbits, we investigated the relative contributions of lung aeration and increased oxygenation in the increase in pulmonary perfusion at birth. We demonstrated that partial lung aeration induces a global increase in pulmonary blood flow that is independent of changes in inspired oxygen. These results show that mechanisms unrelated to oxygenation or the spatial relationships that match ventilation to perfusion initiate the large increase in pulmonary blood flow at birth.

Do Sustained Lung Inflations during Neonatal Resuscitation Affect Cerebral Blood Volume in Preterm Infants? A Randomized Controlled Pilot Study.

Background Sustained lung inflations (SLI) during neonatal resuscitation may promote alveolar recruitment in preterm infants. While most of the studies focus on respiratory outcome, the impact of SLI on the brain hasn’t been investigated yet. Objective Do SLI affect cerebral blood volume (CBV) in preterm infants? Methods Preterm infants of gestation 28 weeks 0 days to 33 weeks 6 days with requirement for respiratory support (RS) were included in this randomized controlled pilot trial. Within the first 15 minutes after birth near-infrared spectroscopy (NIRS) measurements using ‘NIRO-200-NX’ (Hamamatsu, Japan) were performed to evaluate changes in CBV and cerebral tissue oxygenation. Two groups were compared based on RS: In SLI group RS was given by applying 1–3 SLI (30 cmH2O for 15 s) continued by respiratory standard care. Control group received respiratory standard care only. Results 40 infants (20 in each group) with mean gestational age of 32 weeks one day (±2 days) and birth weight of 1707 (±470) g were included. In the control group ΔCBV was significantly decreasing, whereas in SLI group ΔCBV showed similar values during the whole period of 15 minutes. Comparing both groups within the first 15 minutes ΔCBV showed a tendency toward different overall courses (p = 0.051). Conclusion This is the first study demonstrating an impact of SLI on CBV. Further studies are warranted including reconfirmation of the present findings in infants with lower gestational age. Future investigations on SLI should not only focus on respiratory outcome but also on the consequences on the developing brain. Trial Registration German Clinical Trials Register DRKS00005161 https://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do

Borderline hypotension: how does it influence cerebral regional tissue oxygenation in preterm infants?

Abstract Aim: To monitor cerebral regional tissue oxygenation (crSO2) of preterm infants continuously and to analyze the influence of arterial hypotension on crSO2. Methods: In this prospective, observational study crSO2, peripheral oxygen saturation (SpO2), heart rate (HR) and mean arterial blood pressure (MABP) were monitored continuously for 24 h, starting within the first 6 h after birth. Furthermore, cerebral fractional tissue oxygen extraction (cFTOE) was calculated. Preterm neonates with and without arterial hypotension (MABP below the gestational age in weeks) were compared to each other. Results: Forty-six preterm infants could be analyzed, 17 with (33.4 ± 1.9 weeks, 2016.5 ± 548.5 g) and 29 without arterial hypotension (33.3 ± 1.3 weeks, 1924.7 ± 451.9 g). Altogether, we detected 30 episodes of hypotension, with a mean duration of 1.6 ± 1.2 h per infant and a mean decrease in MABP of 2.2 ± 0.9 mmHg. During hypotension mean crSO2 was 7 5 ± 11%, 2 h prior to that 76 ± 10% and 2 h after the hypotension 7 7 ± 10%, therefore no significant alterations could be observed. Moreover, there was no significant difference in mean 24-h crSO2, SpO2 and cFTOE between the two groups. Conclusion: Mild short-term hypotensive episodes in preterm infants did not affect crSO2. This suggests that cerebral autoregulation is maintained in case of borderline-hypotension and may protect infants from cerebral injury.

Laryngeal closure impedes non-invasive ventilation at birth

Background Non-invasive ventilation is sometimes unable to provide the respiratory needs of very premature infants in the delivery room. While airway obstruction is thought to be the main problem, the site of obstruction is unknown. We investigated whether closure of the larynx and epiglottis is a major site of airway obstruction. Methods We used phase contrast X-ray imaging to visualise laryngeal function in spontaneously breathing premature rabbits immediately after birth and at approximately 1 hour after birth. Non-invasive respiratory support was applied via a facemask and images were analysed to determine the percentage of the time the glottis and the epiglottis were open. Hypothesis Immediately after birth, the larynx is predominantly closed, only opening briefly during a breath, making non-invasive intermittent positive pressure ventilation (iPPV) ineffective, whereas after lung aeration, the larynx is predominantly open allowing non-invasive iPPV to ventilate the lung. Results The larynx and epiglottis were predominantly closed (open 25.5%±1.1% and 17.1%±1.6% of the time, respectively) in pups with unaerated lungs and unstable breathing patterns immediately after birth. In contrast, the larynx and the epiglottis were mostly open (90.5%±1.9% and 72.3%±2.3% of the time, respectively) in pups with aerated lungs and stable breathing patterns irrespective of time after birth. Conclusion Laryngeal closure impedes non-invasive iPPV at birth and may reduce the effectiveness of non-invasive respiratory support in premature infants immediately after birth.

Vagal denervation inhibits the increase in pulmonary blood flow during partial lung aeration at birth

Lung aeration at birth significantly increases pulmonary blood flow, which is unrelated to increased oxygenation or other spatial relationships that match ventilation to perfusion. Using simultaneous X‐ray imaging and angiography in near‐term rabbits, we investigated the relative contributions of the vagus nerve and oxygenation to the increase in pulmonary blood flow at birth. Vagal denervation inhibited the global increase in pulmonary blood flow induced by partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect. The results of the present study indicate that a vagal reflex may mediate a rapid global increase in pulmonary blood flow in response to partial lung aeration.

Lung ultrasound accurately detects pneumothorax in a preterm newborn lamb model

Pneumothorax is a common emergency affecting extremely preterm. In adult studies, lung ultrasound has performed better than chest x‐ray in the diagnosis of pneumothorax. The purpose of this study was to determine the efficacy of lung ultrasound (LUS) examination to detect pneumothorax using a preterm animal model.

Cerebral Blood Volume During Neonatal Transition in Term and Preterm Infants With and Without Respiratory Support

Background: Recently, we demonstrated that in healthy newborn infants cerebral blood volume (CBV) was decreasing continuously after birth. We hypothesized that this was due to the increase in oxygen delivery to the brain during neonatal transition. Thus delayed cerebral oxygen delivery in infants in need for respiratory support (RS) during postnatal stabilization might influence changes in CBV. Objective: Aim of the study was to evaluate transitional changes in CBV immediately after birth in term and preterm infants with and without need of RS. Methods: We performed a post-hoc analysis of data collected as primary and secondary outcome parameters in prospective observational studies and randomized controlled trials at the Medical University of Graz (Austria). NIRS measurements by using “NIRO 200-NX” (Hamamatsu, Japan) were carried out over the first 15 min after birth in term and preterm infants delivered by cesarean section with and without requirement for RS. Results: In 204 neonates, we observed a significant decrease in CBV within the first 15 min after birth (p < 0.001) with a trend toward smaller ΔCBV in neonates receiving RS (p = 0.097) compared to neonates without RS. Differences of ΔCBV between groups reached statistically significance (p < 0.05) at minutes 2, 6, and 7, and showed a trend (p < 0.1) at minutes 3, 4, and 5. After adjusting for gestational age, these differences became smaller and failed to reach significance. Conclusions: We observed a significant decrease of CBV in term and preterm infants with and without RS. Interestingly, ΔCBV was smaller in the first 7 min in neonates with RS reaching statistically significance (p < 0.05) at minutes 2, 6, and 7. This study cannot differentiate, whether RS itself or the condition leading to requirement for RS is responsible for the observed CBV behavior.

Cerebral tissue oxygen saturation is associated with N‐terminal probrain natriuretic peptide in preterm infants on their first day of life

This prospective observational study investigated if N‐terminal probrain natriuretic peptide (NT‐proBNP), a cardiac biomarker, correlated with cerebral tissue oxygen saturation (crSO2) in preterm infants on their first day of life.

Haemodynamic effects of prenatal caffeine on the cardiovascular transition in ventilated preterm lambs

Background Caffeine is routinely given to preterm infants hours after birth to treat apnea of prematurity. In view of it’s success, earlier administration in the delivery room is being considered, but little is known about how caffeine may effect the cardiovascular changes during the fetal to neonatal transition. Our aim was to determine the effect of prenatal caffeine administration on haemodynamic parameters in ventilated preterm lambs immediately after birth. Methods Catheters (carotid artery and jugular vein) and ultrasonic flow probes (pulmonary artery and carotid artery) were implanted in preterm lambs (~126 ±2 days of gestation; term is 147 days), immediately before delivery by caesarean section. Before the cord was clamped, lambs were intubated and a caffeine (10mg/kg caffeine-base; n = 9) or saline (n = 5) infusion was given intravenously to the ewe and lamb over a 15-minute period. Two minutes after clamping the cord, ventilation commenced with a sustained inflation (35 cm H2O for 30 seconds) followed by ventilation for 30 minutes (target tidal volume of 6-8ml/kg). Results Blood gas parameters and rectal body temperature were not different between the two groups. Changes in pulmonary blood flow (PBF) and carotid blood flow (CBF) did not differ significantly between groups. PBF increased significantly after ventilation onset in both groups (caffeine p = 0.022, saline p <0.001) and remained elevated thereafter. CBF did not increase but decreased after SI in the caffeine group. Blood pressure, heart rate, and peripheral oxygen saturation did not differ between groups at any stage of the study. Conclusion Prenatal caffeine infusion had no significant effect on acute haemodynamic parameters in ventilated preterm lambs during the cardiorespiratory transition.