Roel Nijland

Maturation of the human fetal brain as observed by 1H MR spectroscopy.

Proton MRS was used to monitor cerebral metabolite tissue levels in 35 normal fetuses during development in the gestational age range of 30–41 weeks. First, MRI in three orthogonal orientations was performed. A volume of interest (VOI) (15–43 cc) of fetal brain tissue was then selected for 1H MRS. For localization, two pulse sequences (stimulated echo acquisition mode (STEAM) at TE = 20 ms, and point‐resolved spectroscopy (PRESS) at TE = 135 ms) were applied. The MR spectra of the brain showed signals for inositol (Ino), choline (Cho), creatine (Cr), and N‐acetyl (NA) compounds. From 30 to 41 weeks the absolute tissue level of NA, and the ratios of NA/Cr and NA/Cho increased, whereas the ratio of Cho/Cr decreased. These changes reflect maturation of the brain. Considering the diagnostic value of proton MRS in pediatric neurology, this new approach may also be useful for characterizing pathological conditions in the fetal brain. Magn Reson Med 48:611–616, 2002.

Arterial oxygen saturation in relation to metabolic acidosis in fetal lambs

OBJECTIVE We studied the relationship between preductal arterial oxygen saturation and metabolic acidosis in 18 chronically instrumented fetal lambs (gestational age 119 to 133 days) in two experimental designs. In the first group the onset of metabolic acidosis was determined. In the second group the progression of metabolic acidosis was studied as was the cardiovascular and hormonal changes resulting from hypoxemia. STUDY DESIGN In nine fetal lambs maternal fraction of inspired oxygen was lowered stepwise by increasing flows of nitrogen delivered into the trachea through a small indwelling catheter (group 1), and in nine fetal lambs maternal blood flow was reduced stepwise by means of a vascular occluder (group 2). RESULTS Baseline arterial oxygen saturation values ranged from 26% to 67% with normal pH and extracellular fluid base excess values in both groups 1 and 2. In both groups pH and extracellular fluid base excess started to decrease below 30% arterial oxygen saturation, with a progressive decrease below 20% arterial oxygen saturation to an end value for pH of 7.14. In some fetal lambs pH and extracellular fluid base excess decreased initially at 20% to 30% arterial oxygen saturation and then stabilized at the lower level. Fetal heart rate in group 1 increased during hypoxemia from 155 to 179 beats/min. In group 2 baseline fetal heart rate was 153 beats/min and fell with every step change in arterial oxygen saturation but subsequently increased to 172 beats/min by the end of the period of hypoxemia. Baseline values for epinephrine, norepinephrine, dopamine, cortisol, and mean arterial pressure were not related to baseline arterial oxygen saturation levels, and each of these variables was increased at the end of hypoxemia in group 2. CONCLUSION Preductal arterial oxygen saturation can reach values between 20% and 30% before anaerobic metabolism starts. During the progressive acidosis blood pressure was increased, which can be attributed to a strong rise in catecholamines.

Neonatal complications in newborns with an umbilical artery pH <7.00

OBJECTIVE Our purpose was to determine the significance of an umbilical artery pH < 7.00 in relation to neonatal morbidity and mortality. STUDY DESIGN Between 1986 and 1993 acid-base assessment of the umbilical artery was performed routinely in 10,699 deliveries. In a retrospective cohort study 84 nonanomalous neonates with an umbilical artery pH < 7.00 were individually matched with 84 neonates with an umbilical artery pH > 7.24. Matched variables included year of delivery, gender, parity, maternal age, delivery mode, fetal presentation, gestational age, and birth weight. Differences in morbidity between the two groups during the neonatal period (until 28 days after delivery) were investigated. RESULTS Neonates with an umbilical artery pH < 7.00 versus > 7.24 showed significant differences in the following: neonatal condition directly post partum; neurologic, respiratory, cardiovascular, and gastrointestinal complications; and neonatal intensive care unit admissions. No significance was found in renal dysfunction and mortality rate. The proportion of premature infants (< 37 weeks) was 17% in both groups. In the acidotic group a 1-minute Apgar score < or = 3 and a 5-minute Apgar score < 7 was predictive for neonatal complications. CONCLUSIONS Severe intrapartum asphyxia, quantified by an umbilical artery pH < 7.00, poses a threat to the neonates health.

The effect of pulsating arteries on reflectance pulse oximetry: measurements in adults and neonates.

Objective. The objective of our study was to describe the results from human experiments during normoxia that demonstrate the effect of pulsating arteries on the measured arterial oxygen saturation (Spo2) using a reflectance pulse oximeter sensor.Methods. In 6 healthy adults and 7 healthy neonates, a Nellcor reflection sensor (FS-10 oxisensor, Nellcor, Inc., Pleasanton, CA) was placed in three different positions: (1) on the forehead, (2) on the temporal area, with the photodiode placed over the superficial temporal artery, and (3) on the temporal area, with the light-emitting diodes (LEDs) placed over the superficial temporal artery.Results. Placement of the sensor in position 2 resulted in a significantly lower Spo2 reading, compared to sensor position 1: 5.8% (p<0.01) lower for adults and 7.5% (p<0.01) lower for neonates. Placement of the sensor in position 3 resulted in significantly larger plethysmographic signals, compared to sensor position 1; but, the Spo2 readings were alike.Conclusions. Pulsating arteries can affect the reliability of reflection pulse oximetry. Depending on the position of the sensor, a falsely low Spo2 value can be observed.

Accuracy of fetal pulse oximetry and pitfalls in measurements

Pulse oximetry is a technique for estimating arterial oxygen saturation continuously and non-invasively. Reflectance pulse oximetry might become useful for monitoring the fetus during labour but it is much more susceptible to all kinds of physiological variations than the well-established transmission pulse oximetry for neonatal or adult monitoring. This review focuses on the accuracy of reflectance pulse oximetry. Results of human, animal, in vitro and theoretical models indicate that factors such as; blood volume fraction differences, haematocrit, and blood flow differences are major sources for inaccurate pulse oximetry readings in the fetal arterial oxygen saturation range of 10-80%. These factors cannot be overcome by systems using two wavelengths sensors with the 660/890 or 940 nm combination. Reported precision values (S.D. of difference between pulse oximeter and blood sample saturation) range between 2.5 and 12.9% for various 660 nm sensors. Most sensors were tested only once with a limited number of animals. A new 735/890 nm sensor (Nellcor Puritan Bennett) demonstrates a promising accuracy (precision around 5%) in two studies. Various other sensors have also been developed, but are not or scarcely evaluated. Without thorough establishment of the reliability of this technique, clinical fetal oxygen saturation data are still of limited value.

1H-NMR spectroscopy of cerebrospinal fluid of fetal sheep during hypoxia-induced acidemia and recovery.

The purpose of the study was to investigate the sequence of processes occurring during and after hypoxia-induced acidemia. We used proton nuclear magnetic resonance spectroscopy, which provides an overview of metabolites in cerebrospinal fluid (CSF), reflecting neuronal metabolism and damage. The pathophysiological condition of acute fetal asphyxia was mimicked by reducing maternal uterine blood flow in 14 unanesthetized pregnant ewes. CSF metabolites were measured during hypoxia-induced acidemia, and during the following recovery period, including the periods at 24 and 48 h after the hypoxic insult. Maximum values of the following CSF metabolites were reached during severe hypoxia (pH ≤ 7.00): glucose, lactate, pyruvate, hypoxanthine, alanine, β-hydroxybutyrate, choline, creatine, myo-inositol, citrate, succinate, valine, and an unknown metabolite characterized by a resonance at 1.56 ppm in the proton nuclear magnetic resonance spectrum. Twenty-four hours after the hypoxic insult, myo-inositol was increased, and alanine was decreased 48 h after the hypoxic insult, both compared with control values. Choline levels in CSF had a linear relationship with arterial pH (r = 0.26, p < 0.005). During severe hypoxia, CSF levels of succinate and choline are increased. Increased CSF levels of succinate may indicate dysfunction of the mitochondrial respiratory chain, whereas elevated CSF choline levels may indicate disrupted cell membranes. The increase of the CSF myo-inositol level after 24 and 48 h may indicate osmolytic cell changes causing cell edema. Decreased alanine level may represent changes in the source of excitatory amino acid synthesis.

Hypoxia in fetal lambs: a study with (1)H-MNR spectroscopy of cerebrospinal fluid.

In fetal lambs, severe hypoxia (SH) will lead to brain damage. Mild hypoxia (MH) is thought to be relatively safe for the fetal brain because compensating mechanisms are activated. We questioned whether MH, leading to mild acidosis, induces changes in cerebral metabolism. Metabolites in cerebrospinal fluid (CSF) samples, as analyzed by proton magnetic resonance spectroscopy, were studied in two groups of seven anesthetized near-term fetal lambs. In group I, SH leading to acidosis with an arterial pH <7.1 was achieved. In group II, MH with an intended pH of 7.23–7.27 was reached [start of MH (SMH)], and maintained during 2 h [end of MH (EMH)]. During SH, choline levels in CSF, a possible indicator of cell membrane damage, were increased. Both during SH and at EMH, CSF levels of lactic acid, alanine, phenylalanine, tyrosine, lysine, branched chain amino acids, and hypoxanthine were increased compared with control values and with SMH, respectively. At EMH, the hypoxanthine CSF-to-blood ratio was increased as compared with SMH. These results indicate that prolonged MH leads to energy degradation in the fetal lamb brain and may not be as safe as assumed.

The ductus arteriosus, pre- and post-ductal oxygen saturation measurements in fetal lambs

In the fetus, the arterial oxygen saturation (SaO2) in the ascending aorta is higher than in the descending aorta. We questioned whether this difference over the ductus arteriosus (delta SaO2) would change during hypoxaemia. Therefore, six chronically instrumented fetal lambs (119-126 days of gestation) were studied, by changing the inspired oxygen (FIO2) via a tracheal tube to the ewe. The SaO2 was measured intermittently every 15 min with blood samples obtained from the ascending and descending aorta, and continuously with 2 pulse oximeters at both sides of the ductus arteriosus. delta SaO2 was at a level of 3.4-5.3% and had a tendency to decrease at preductal SaO2 levels of 10-20% and at pH levels below 7.25. The precision of the pulse oximeters, expressed as standard deviation of the differences between sample SaO2 and pulse oximeter SaO2, was around 5.0% for the individual calibration curves. This precision was not enough to show details of the course of delta SaO2 between the blood samples. Our results show that there is no change in delta SaO2 across the ductus arteriosus.

Reflectance pulse oximetry in fetal lambs: Subcutaneous vessels and vasoconstriction affect its reliability

Objective. Reflectance pulse oximetry (RPOX) has been introduced for intrapartum fetal surveillance. The purpose of this study was to describe two possible effects on the reliability of RPOX, namely the effect of the presence of a subcutaneous vein and the effect of vasoconstriction by adrenaline, both at fetal SaO2 levels.Methods. In four anesthetized fetal lambs, a prototype 660/890 nm reflectance sensor (Nellcor Inc.) was placed on the fetal head, with the photodiode of the sensor precisely over a superficial subcutaneous vein. Measurements were made before and after coagulation of the vein. In five anesthetized fetal lambs, one or two reflectance sensors were placed on the fetal head and/or neck and adrenaline was administered in doses of 0.02 to 0.04 mg via a brachial artery. Pulse oximeter saturation readings (SPO2) were compared with continuous arterial oxygen saturation (SaO2) values obtained using a fiberoptic catheter (Opticath, Abbott) in the carotid artery.Results. When the sensor was placed over the vein, the pulse oximeter read 18% to 24% too low at a SaO2 level of 20% to 50%. After coagulation of the vein, SpO2 readings were in agreement with fiberoptic SaO2 values. Administration of adrenaline resulted in a large overestimation of the SaO2 in 6 of the 7 measurements.Conclusions. Subcutaneous veins and vasoconstriction can affect the reliability of reflectance pulse oximetry. As comparable situations may occur during labor, SpO2 readings should be interpreted with caution when this kind or comparable types of RPOX sensors are used at low SaO2 levels.

Notes on the apparent discordance of pulse oximetry and multi-wavelength haemoglobin photometry

Multi‐wavelength photometers, blood gas analysers and pulse oximeters are widely used to measure various oxygen‐related quantities. The definitions of these quantities are not always correct. This paper gives insight in the various definitions for oxygen quantities. Furthermore, the possible influences of dyshaemoglobins and fetal haemoglobin on the accuracy of pulse oximetry are discussed.