Jeffrey P. Phelan

Nucleated red blood cells: A marker for fetal asphyxia?

OBJECTIVE Our purpose was to determine whether a relationship exists between the presence of nucleated red blood cells, hypoxic ischemic encephalopathy, and long-term neonatal neurologic impairment. STUDY DESIGN Nucleated red blood cell data from 46 singleton term neurologically impaired neonates were compared with cord blood nucleated red blood cells of 83 term nonasphyxiated newborns. The neurologically impaired neonates group was also separated as follows: nonreactive, nonreactive fetal heart rate from admission to delivery; tachycardia, reactive fetal heart rate on admission followed by tachycardia with decelerations; rupture, uterine rupture. The first and highest nucleated red blood cells value and the time to nucleated red blood cells disappearance were assessed. RESULTS The neurologically impaired neonates group exhibited a significantly higher number of nucleated red blood cells per 100 white blood cells (34.5 +/- 68) than did the control group (3.4 +/- 3.0) (p < 0.00001). When the neurologically impaired neonates are separated as to the basis for the neurologic impairment, distinct nucleated red blood cell patterns were observed. Overall, the nonreactive group exhibited the highest mean nucleated red blood cell (51.4 +/- 87.5) count and the longest clearance times (236 +/- 166 hours). CONCLUSION In this limited population, nucleated red blood cell data appear to aid in identifying the presence of fetal asphyxia. When asphyxia was present, distinct nucleated red blood cells patterns were identified that were in keeping with the observed basis for the fetal injury. In general, the closer the birth was to the asphyxial event, the lower was the number of nucleated red blood cells. Thus our data suggest that cord blood nucleated red blood cells could assist in the timing of fetal neurologic injury.

Neonatal nucleated red blood cell and lymphocyte counts in fetal brain injury

Objective To determine whether neonatal lymphocyte or nucleated red blood cell (RBC) counts can be used to date fetal neurologic injury. Methods Singleton, term infants with hypoxic-ischemic encephalopathy, permanent neurologic impairment, and sufficient laboratory data were divided into two groups: infants with preadmission injury, manifested by a nonreactive fetal heart rate (FHR) pattern from admission until delivery; and infants with acute injury, manifested by a normal FHR pattern followed by a sudden prolonged FHR deceleration. Lymphocyte and nucleated RBC values were compared with published high normal counts for normal neonates: 8000 lymphocytes/mm3 and 2000 nucleated RBCs/mm3. Results The study population consisted of 101 neonates. In the first hours of life, lymphocyte counts were elevated among injured newborns, and then the counts rapidly normalized. Brain-injured neonates were 25 times more likely to have a lymphocyte count greater than 8000 than were normal neonates (54 [62%] of 87 versus 6 [7%] of 84; odds ratio 25.5; 95% confidence interval 8.8, 80.1; P < .001). The mean lymphocyte count tended to be higher in the pread-mission-injury group than in the acute-injury group. In comparison, nucleated RBC values were not correlated as strongly with neonatal hours of life; nucleated RBC counts tended to be higher and persist longer among neonates with preadmission injury than among those with acute injury. Conclusion Compared with normal levels, both lymphocyte and nucleated RBC counts were elevated among neonates with fetal asphyxial injury. Both counts appear to be more elevated and to remain elevated longer in newborns with preadmission injury than in infants with acute injury. However, the rapid normalization of lymphocyte counts in these injured neonates limits the clinical usefulness of these counts after the first several hours of life.

Uterine activity patterns in uterine rupture: a case-control study

Objective To determine whether uterine activity patterns are associated with intrapartum uterine rupture. Methods Because of the infrequency of uterine rupture, a case-control design was implemented. Cases were women who sustained uterine ruptures during a trial of labor, resulting in a neurologically impaired neonate. Controls were women who had a successful vaginal birth after cesarean (VBAC) or vaginal delivery with no history of uterine scar. The uterine activity patterns of cases were compared with those of each control group for number of contractions per hour, uterine tetany (contraction longer than 90 seconds), and uterine hyperstimulation (five or more contractions in a 10-minute period). Results The final study population consisted of 18 rupture patients, 35 VBAC patients, and 33 spontaneous vaginal delivery patients. Women in the rupture group had fewer contractions per hour (15.8 ± 7.3) than VBAC (19.7 ± 5.5) (P < .05) or spontaneous delivery group (19.4 ± 6.6) (P < .10). VBAC patients were five times as likely to have 16 or more contractions per hour than were rupture patients, 95% confidence interval [CI] 1.3, 21.3, P < .02). Patients who had spontaneous delivery were 3.5 times more likely to have 16 or more contractions per hour than were rupture patients (95% CI 0.9, 14.1, P = .08). The rupture group had equal or less uterine tetany than did the controls. Conclusion Uterine activity patterns and oxytocin use do not appear to be associated with the occurrence of intrapartum uterine rupture.

Intrapartum Fetal Asphyxial Brain Injury with Absent Multiorgan System Dysfunction

Current understanding of the physiologic mechanisms of intrapartum fetal asphyxial brain injury has suggested a strong association with multiorgan system injury. Thus the purpose here is to describe 14 cases of severe fetal brain injury with absent multiorgan system dysfunction (MSD). The study population was drawn from a national registry for brain injured infants. MSD was defined by clinical criteria demonstrated to reflect asphyxial injury to the pulmonary, renal, cardiac, hematologic, hepatic, and gastrointestinal systems. Involvement of one other organ in addition to the brain was defined as multiorgan system dysfunction. All infants were diagnosed with hypoxic-ischemic encephalopathy (HIE) in the neonatal period and went on to have permanent central nervous system (CNS) injury and MSD criteria were not met. Of the 292 term, singleton infants with HIE and permanent neurologic injury, 57 (20%) satisfied the entry criteria; of these, 14 (36%) had no MSD. The underlying basis for the fetal brain injury were: uterine rupture, 6 (43%), prolonged FHR deceleration, 5 (36%), fetal exsanguination, 1 (7%), cord prolapse, 1 (7%), and maternal cardiopulmonary arrest, 1 (7%). The mean duration of the prolonged FHR deceleration was 32.1 +/- 9.1 (range 19-51) minutes. All infants were later diagnosed with cerebral palsy. Intrapartum fetal asphyxial brain injury may not necessarily proceed through a physiologic mechanism in which the fetal circulation is centralized and endorgans damaged. These acute injuries, associated with a prolonged FHR deceleration, may be linked to severely decreased cardiac output and hypotension that cause vulnerable portions of the brain to be injured before other organs.

Acute fetal asphyxia and permanent brain injury: a retrospective analysis of current indicators

OBJECTIVE To determine whether a term neonate who has had sufficient intrapartum asphyxia to produce persistent brain injury will manifest the following four criteria: profound acidemia (arterial pH <7.00), an APGAR score < or =3 for 5 min or longer, seizures within 24 h of birth, and multiorgan system dysfunction. METHODS Singleton, liveborn, neurologically impaired neonates > or =37 weeks gestation who lived at least 6 days and had sufficient documentation of current intrapartum asphyxia criteria were retrospectively analyzed. Of these infants, solely neonates with acute fetal asphyxia due to a sudden prolonged FHR deceleration that lasted until delivery from a catastrophic event, e.g., uterine rupture, cord prolapse, were included. Organ system dysfunction was defined by separate criteria for each organ system. Dysfunction in one or more was defined as multiorgan system dysfunction. RESULTS Of the 292 eligible infants in the registry, 47 satisfied the entry criteria. In these 47 neonates, 10 (21%) satisfied all 4 criteria for intrapartum asphyxia. CONCLUSIONS Our retrospective study suggests that currently used indicators to define permanent fetal brain injury are not valid.

Does the Onset of Neonatal Seizures Correlate with the Timing of Fetal Neurologic Injury

The onset of seizures after birth has been considered evidence of an intrapartum asphyx-ial event. The present study was undertaken to determine whether the timing of neonatal seizures after birth correlated with the timing of a fetal asphyxial event. Thus, singleton term infants diagnosed with hypoxic ischemic encephalopathy and permanent brain injury had a mean birth to seizure onset interval of 9.8 ± 17.7 (range 1-90) hours. When these infants were categorized according to their fetal heart rate (FHR) patterns, the acute group (normal FHR followed by a sudden prolonged FHR deceleration that continued until delivery) tended to have earlier seizures than infants did within the tachycardia group (normal FHR followed by tachycardia, repetitive decelerations, and diminished variability) and the preadmission group (persistent nonreactive FHR pattern intrapartum). These seizure intervals were as follows: acute, 6.6 ± 18.0 (range 1-90) hours; tachycardia, 11.1 +17.1 (range 1-61) hours; and preadmission, 11.8 +17.9 (range 1-79) hours (p<0.05). But the range varied widely and no group was categorically distinct. In conclusion, the onset of neonatal seizures after birth does not, in and of itself, appear to be a reliable indicator of the timing of fetal neurologic injury.