Eric C. Eichenwald

Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants.

Objectives. Premature infants experience brain injury, ie, germinal matrix–intraventricular hemorrhage (GMH-IVH) and periventricular leukomalacia (PVL), in considerable part because of disturbances in cerebral blood flow (CBF). Because such infants are susceptible to major fluctuations in mean arterial blood pressure (MAP), impaired cerebrovascular autoregulation would increase the likelihood for the changes in CBF that could result in GMH-IVH and PVL. The objectives of this study were to determine whether a state of impaired cerebrovascular autoregulation could be identified reliably and conveniently at the bedside, the frequency of any such impairment, and the relation of the impairment to the subsequent occurrence of severe GMH-IVH and PVL. Patients and Methods. To monitor the cerebral circulation continuously and noninvasively, we used near-infrared spectroscopy (NIRS) to determine quantitative changes in cerebral concentrations of oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (Hb) from the first hours of life. Our previous experimental study showed a strong correlation between a measure of cerebral intravascular oxygenation (HbD), ie, HbD = HbO2 − Hb, determined by NIRS, and volemic CBF, determined by radioactive microspheres. We studied 32 very low birth weight premature infants (gestational age: 23–31 weeks; birth weight: 605-1870 g) requiring mechanical ventilation, supplemental oxygen, and invasive blood pressure monitoring by NIRS from 1 to 3 days of age. MAP measured by arterial catheter pressure transducer and arterial oxygen saturation measured by pulse oximetry were recorded simultaneously. The relationship of MAP to HbD was quantitated by coherence analysis. Results. Concordant changes (coherence scores >.5) in HbD and MAP, consistent with impaired cerebrovascular autoregulation, were observed in 17 of the 32 infants (53%). Eight of the 17 infants (47%) developed severe GMH-IVH or PVL or both. Of the 15 infants with apparently intact autoregulation, ie, coherence scores <.5, only 2 (13%) developed severe ultrasonographic lesions. Thus, for the entire study population of 32 infants, 8 of the 10 with severe lesions exhibited coherence scores >.5. Conclusions. We conclude that NIRS can be used in a noninvasive manner at the bedside to identify premature infants with impaired cerebrovascular autoregulation, that this impairment is relatively common in such infants, and that the presence of this impairment is associated with a high likelihood of occurrence of severe GMH-IVH/PVL.

Early-Onset Group B Streptococcal Disease in the Era of Maternal Screening

Background. With the widespread implementation of intrapartum antibiotic prophylaxis (IAP), the rate of early-onset neonatal sepsis and meningitis caused by Streptococcus agalactiae (group B streptococcus [GBS]) has decreased dramatically, especially in term infants. However, cases of GBS disease continue to occur despite IAP and incur significant morbidity and mortality. Inaccurate screening results, improper implementation of IAP, or antibiotic failure all may contribute to persistent disease. Objective. To determine if clinical, procedural, or microbiologic factors influenced persistent early-onset GBS disease (EOGBS) cases in a single large maternity service after the institution of a screening-based protocol for IAP. Methods. Retrospective review of all cases of culture-proven EOGBS at the Brigham and Womens Hospital (Boston, MA) from 1997 to 2003. Serotyping and surface protein analyses were performed on available disease isolates. Results. A total of 67260 infants were live-born during this period. Twenty-five cases of EOGBS (0.37 of 1000 live births) were identified. The overall incidence of EOGBS progressively decreased with different approaches to IAP. Of the 25 cases identified after institution of a screening-based protocol, 17 (68%) occurred in term infants (1 death), and 8 (32%) occurred in preterm infants (3 deaths). Among the mothers of term infants, 14 of 17 (82%) had been screened GBS negative; 1 was GBS unknown. More than half of the mothers of term infants who had screened GBS negative (8 of 14) had intrapartum risk factors for neonatal infection but did not receive antibiotics before delivery. Ten of the 17 term infants were evaluated for infection because of clinical signs of illness, and the remainder were evaluated because of intrapartum sepsis risk factors. Of the mothers of preterm infants, by the time of delivery 3 of 8 had been documented as GBS positive, 2 of 8 had been documented GBS negative, and 3 of 8 remained unknown. Only 1 of 25 women received adequate IAP, but the isolate was resistant to the administered antibiotic (clindamycin). Antibiotic resistance was not a factor in any other case, and no dominant serovariant was identified among tested isolates. Procedural errors (lack of recognition of documented GBS colonization or failure to evaluate infants at risk for sepsis) were identified in 4 cases. Conclusions. The majority of the remaining cases of EOGBS occurred in infants whose mothers screened negative for GBS colonization. Even in the setting of a maternal GBS-screening program, efforts to evaluate and treat infants with intrapartum clinical risk factors for early-onset sepsis remain important. Until effective vaccines against GBS are available for clinical use, development and implementation of rapid and sensitive techniques for screening for GBS status and antibiotic susceptibility at presentation may help prevent additional cases of invasive GBS disease.

Intrapartum Fever and Unexplained Seizures in Term Infants

Objective. Early-onset neonatal seizures are a strong predictor of later morbidity and mortality in term infants. Although an association of noninfectious intrapartum fever with neonatal seizures in term infants has been reported, it was based on only a small number of neonates with seizures. We therefore conducted a case control study to investigate this association further. Methods. All term infants with neonatal seizures born at Brigham and Womens Hospital between 1989 and 1996 were identified. For this study, cases consisted of all term neonates with a confirmed diagnosis of seizure born after a trial of labor for whom no proximal cause of seizure could be identified. Infants with sepsis or meningitis were excluded. Four controls matched by parity and date of birth were identified for each case. The rate of intrapartum maternal temperature >100.4°F was compared for case infants and controls. Potential confounding was controlled in logistic regression analysis. Results. Cases comprised 38 term infants with unexplained seizures after a trial of labor. We identified 152 controls. Infants with seizures were more likely to be born to mothers who were febrile during labor (31.6% vs 9.2%). In almost all cases, the fever developed during labor (94.7% cases, 97.4% controls). At admission, mothers of infants with seizures were not significantly more likely to have factors associated with concern about infection such as a white blood cell count >15 000/mm3 (28.9% vs 19.1%) and premature rupture of the membranes (15.8% vs 17.8%). In a logistic regression analysis controlling for confounding factors, intrapartum fever was associated with a 3.4-fold increase in the risk of unexplained neonatal seizures (odds ratio = 3.4, 95% confidence interval = 1.03–10.9). Conclusion. Our data indicate that intrapartum fever, even when unlikely to be caused by infection, is associated with a fourfold increase in the risk of unexplained, early-onset seizures in term infants.

Unstudied infants: outcomes of moderately premature infants in the neonatal intensive care unit

Background: Newborns of 30–34 weeks gestation comprise 3.9% of all live births in the United States and 32% of all premature infants. They have been studied much less than very low birthweight infants. Objective: To measure in-hospital outcomes and readmission within three months of discharge of moderately premature infants. Design: Prospective cohort study including retrospective chart review and telephone interviews after discharge. Setting: Ten birth hospitals in California and Massachusetts. Patients: Surviving moderately premature infants born between October 2001 and February 2003. Main outcome measures: (a) Occurrence of assisted ventilation during the hospital stay after birth; (b) adverse in-hospital outcomes—for example, necrotising enterocolitis; (c) readmission within three months of discharge. Results: With the use of prospective cluster sampling, 850 eligible infants and their families were identified, randomly selected, and enrolled. A total of 677 families completed a telephone interview three months after hospital discharge. During the birth stay, these babies experienced substantial morbidity: 45.7% experienced assisted ventilation, and 3.2% still required supplemental oxygen at 36 weeks. Readmission within three months occurred in 11.2% of the cohort and was higher among male infants and those with chronic lung disease. Conclusions: Moderately premature infants experience significant morbidity, as evidenced by high rates of assisted ventilation, use of oxygen at 36 weeks, and readmission. Such morbidity deserves more research.

Cerebral Hemodynamic Changes During Intensive Care of Preterm Infants

OBJECTIVES. The objectives of this study were to examine the circulatory changes experienced by the immature systemic and cerebral circulations during routine events in the critical care of preterm infants and to identify clinical factors that are associated with greater hemodynamic-oxygenation changes during these events. METHODS. We studied 82 infants who weighed <1500 g at birth and required intensive care management and continuous blood pressure monitoring from an umbilical arterial catheter. Continuous recording of cerebral and systemic hemodynamic and oxygenation changes was performed. We studied 6 distinct types of caregiving events during 10-minute epochs: (1) quiet baseline periods; (2) minor manipulation; (3) diaper changes; (4) endotracheal tube suctioning; (5) endotracheal tube repositioning; and (6) complex events. Each event was matched with a preceding baseline. We examined the effect of specific clinical factors and cranial ultrasound abnormalities on the systemic and cerebral hemodynamic oxygenation changes that were associated with the various event types. RESULTS. There were highly significant differences in hemodynamics and oxygenation between events overall and baseline epochs. The magnitude of these circulatory changes was greatest during endotracheal tube repositioning and complex caregiving events. Lower gestational age, higher illness severity, chorioamnionitis, low Apgar scores, and need for pressor-inotropes all were associated with circulatory changes of significantly lower magnitude. Cerebral hemodynamic changes were associated with early parenchymal ultrasound abnormalities. CONCLUSIONS. Routine caregiving procedures in critically ill preterm infants are associated with major circulatory fluctuations that are clinically underappreciated and underdetected by current bedside monitoring. Our data underscore the importance of continuous cerebral hemodynamic monitoring in critically ill preterm infants.

Interneonatal intensive care unit variation in growth rates and feeding practices in healthy moderately premature infants

BACKGROUND:Variation in care and outcomes of very low birth weight infants (VLBW) in neonatal intensive care units (NICU) has been widely reported in the past decade. Less is known about care provided to healthy premature infants born between 30 and 35 weeks gestational age (GA). We have previously reported inter-NICU variation in discharge (D/C) timing and achievement of maturational milestones in this population.OBJECTIVE:To compare inter-NICU growth outcomes and feeding practices in healthy, moderately premature infants.METHODS:Records of 450 infants, 30 to 35 weeks gestation, without medical or surgical complications, and consecutively discharged from 15 Massachusetts NICUs (nine Level II and six Level III) were reviewed. Final analyses included 382 infants with hospital length of stay >6 days (d).RESULTS:GA at birth and birth weight (BW) were 33.2 weeks (SD 1.2) and 2024 g (389). Mean Z-score decreased 0.67z (0.37) from birth to D/C. Weight loss from birth to 7 d averaged 4.0%. Mean growth velocity from 7 d to D/C was 13.3 g/k/d (5.2) with net growth velocity of 5.5 g/k/d (5.6). Mean net growth velocity ranged from 0.1 to 8.4 g/k/d (p<0.001) among study NICUs. Time of initiation, rate of advancement and caloric density of feedings also varied significantly between NICUs.CONCLUSION:Mean NICU growth velocity of healthy, moderately premature infants did not achieve in utero growth standards. There was significant inter-NICU variation in growth outcomes and feeding practices. Further study is needed to identify practices associated with better growth in this healthy moderately premature infant population.

Current Definitions of Hypotension Do Not Predict Abnormal Cranial Ultrasound Findings in Preterm Infants

OBJECTIVE. Hypotension is a commonly treated complication of prematurity, although definitions and management guidelines vary widely. Our goal was to examine the relationship between current definitions of hypotension and early abnormal cranial ultrasound findings. METHODS. We prospectively measured mean arterial pressure in 84 infants who were ≤30 weeks’ gestational age and had umbilical arterial catheters in the first 3 days of life. Sequential 5-minute epochs of continuous mean arterial pressure recordings were assigned a mean value and a coefficient of variation. We applied to our data 3 definitions of hypotension in current clinical use and derived a hypotensive index for each definition. We examined the association between these definitions of hypotension and abnormal cranial ultrasound findings between days 5 and 10. In addition, we evaluated the effect of illness severity (Score for Neonatal Acute Physiology II) on cranial ultrasound findings. RESULTS. Acquired lesions as shown on cranial ultrasound, present in 34 (40%) infants, were not predicted by any of the standard definitions of hypotension or by mean arterial pressure variability. With hypotension defined as mean arterial pressure < 10th percentile (<33 mmHg) for our overall cohort, mean value for mean arterial pressure and hypotensive index predicted abnormal ultrasound findings but only in infants who were ≥27 weeks’ gestational age and those with lower illness severity scores. CONCLUSIONS. Hypotension as diagnosed by currently applied thresholds for preterm infants is not associated with brain injury on early cranial ultrasounds. Blood pressure management directed at these population-based thresholds alone may not prevent brain injury in this vulnerable population.

CSF removal in infantile posthemorrhagic hydrocephalus results in significant improvement in cerebral hemodynamics

Rational intervention in infants with posthemorrhagic hydrocephalus (PHH) would be facilitated greatly by bedside measure of impaired cerebral perfusion, as there is substantial evidence that impaired perfusion and oxidative metabolism contribute to irreversible brain injury in hydrocephalus. Near-infrared spectroscopy (NIRS) measures changes in the cerebral concentration of oxygenated and deoxygenated hemoglobin and oxidized cytochrome oxidase at the bedside of infants continuously and noninvasively. The total hemoglobin and the hemoglobin difference signal are derived from the sum and difference, respectively, of oxygenated and deoxygenated hemoglobin. Changes in total hemoglobin reflect changes in cerebral blood volume; our previous work has shown that changes in hemoglobin difference signal reflect changes in cerebral blood flow. We hypothesized that cerebrospinal fluid (CSF) removal in infants with PHH would result in significant increases in cerebral perfusion, cerebral blood volume, and oxidative metabolism, as measured by NIRS. Continuous NIRS recordings were performed during CSF removal on 16 infants with PHH. There was a statistically significant increase in oxygenated hemoglobin (p = 0.001), total hemoglobin (p < 0.001), and hemoglobin difference signal (p = 0.006), but not oxidized cytochrome oxidase, accompanying CSF removal. There was no significant correlation between either the volume of CSF removed (in milliliters per kilogram body weight) or the opening pressure and the change in any of the measured or calculated NIRS signals. These findings demonstrate the pronounced effect of CSF removal on cerebral perfusion in infants with PHH. NIRS may be a useful technique to detect impending cerebral ischemia in such infants and thereby provide a means to guide the rational management of PHH.

PERINATALLY TRANSMITTED NEONATAL BACTERIAL INFECTIONS

Perinatally acquired bacterial infections remain a major contributor to morbidity and mortality in newborn infants, especially those delivered prematurely. Our understanding of the epidemiology, bacteriology, and pathogenesis of these infections has allowed development of better treatment and prevention strategies. Just as the bacteriology of perinatally acquired bacterial infections has changed over the past few decades, however, it is likely to continue to evolve. Whether widespread use of intrapartum antibiotics will alter the bacteriology and antibiotic resistance patterns seen in early-onset neonatal bacterial infections requires ongoing surveillance.

Cesarean delivery: emphasis on the neonate.

Introduction Cesarean delivery has been performed since ancient times with numerous references cited from Greek mythology and beyond. During the first half of the 16th century, cesarean delivery was performed only if the mother was dead or dying. Much has changed since then. Cesarean delivery for both maternal and fetal indications have improved outcomes and decreased the mortality and morbidity associated with childbirth. Specific fetal indications for cesarean delivery include malpresentation, cephalopelvic disproportion, failure of labor progression, specific maternal infections, nonreassuring fetal status, and multiple gestations. In most of these cases, the neonate benefits by this mode of delivery. The advantage to the neonate becomes less clear in cases of elective cesarean delivery at term. This article will review the fetal indications for cesarean delivery, with an emphasis on the potential benefits and detriments to the neonate.