The Influence of the Timing of Cord Clamping on Postnatal Cerebral Oxygenation in Preterm Neonates: A Randomized, Controlled Trial
Department of Neonatology, University Hospital Zurich, Zurich, Switzerland
OBJECTIVE. Our goal was to investigate the effect of placentofetal transfusion on cerebral oxygenation in preterm infants by near-infrared spectroscopy.
SUBJECTS. A total of 39 preterm infants with a median gestational age of 30.4 weeks were randomly assigned to an experiment group (n = 15) and a control group (n = 24).
INTERVENTIONS. The delivery of the infants in the experiment group was immediately followed by maternal administration of syntocinon, the infant was placed 15 cm below the placenta, and cord clamping was delayed by 60 to 90 seconds. The infants in the control group were delivered conventionally. At the ages of 4 and 24 hours, cerebral hemoglobin concentrations, cerebral blood volume, and regional tissue oxygenation were measured by near-infrared spectroscopy.
RESULTS. Cerebral blood volume was not different between the 2 groups at the age of 4 hours (6.1 vs 5.8 mL/100 g of tissue) nor at the age of 24 hours (6.2 vs 6.2 mL/100 g of tissue). Mean regional tissue oxygenation of the experiment group was higher at the ages of 4 hours (69.9% vs 65.5%) and of 24 hours (71.3% vs 68.1%).
CONCLUSION. Delayed clamping of the umbilical cord improves cerebral oxygenation in preterm infants in the first 24 hours.
Is Nephrocalcinosis in Preterm Neonates Harmful for Long-term Blood Pressure and Renal Function?
OBJECTIVE. The aim of our study was to examine long-term effects of nephrocalcinosis in prematurely born children.
PATIENTS AND METHODS. Preterm neonates (gestational age <32 weeks) with (n = 42) and without (n = 32) nephrocalcinosis were prospectively studied at a mean age of 7.5 (±1.0) years.
RESULTS. Blood pressure did not differ in ex-preterm infants with and without nephrocalcinosis but was significantly higher than expected for healthy children. In comparison to healthy children, more ex-preterm infants with neonatal nephrocalcinosis had (mild) chronic renal insufficiency (glomerular filtration rate: <85 mL/min per 1.73 m2; 6 of 40); this is in contrast to ex-preterm infants without neonatal nephrocalcinosis (2 of 32). Tubular phosphate reabsorption and plasma bicarbonate were significantly lower in children with nephrocalcinosis compared with children without nephrocalcinosis. In addition, more ex-preterm infants with and without nephrocalcinosis than expected had low values for plasma bicarbonate and early-morning urine osmolality compared with healthy children. Kidney length of ex-preterm infants with and without nephrocalcinosis was significantly smaller than expected in healthy children of the same height. Nephrocalcinosis persisted long-term in 4 of 42 children but was not related to blood pressure, kidney length, or renal function.
CONCLUSIONS. Nephrocalcinosis in preterm neonates can have long-term sequelae for glomerular and tubular function. Furthermore, prematurity per se is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. Long-term follow-up of blood pressure and renal glomerular and tubular function of preterm neonates, especially with neonatal nephrocalcinosis, seems warranted.
Auditory Neural Maturation After Exposure to Multiple Courses of Antenatal Betamethasone in Premature Infants as Evaluated by Auditory Brainstem Response
Department of Pediatrics, Division of Neonatology, Golisano Children's Hospital at Strong, University of Rochester, Rochester, New York
OBJECTIVE. Our goal was to determine if multiple courses of antenatal betamethasone affect auditory neural maturation in 28 to 32 weeks' gestational age infants.
PATIENTS AND METHODS. A retrospective cohort study
was performed to compare auditory neural maturation between
premature infants exposed to 1 course of betamethasone and infants
exposed to
2 courses of
betamethasone. Inclusion criteria included all 28 to 32 weeks'
gestational age infants delivered between July 1996 and December
1998 who had auditory brainstem response testing performed (80-dB
click stimuli at a repetition rate of 39.9/second) within 24 hours
of postnatal life as part of bilirubin-auditory studies. Infants
with toxoplasmosis, rubella, cytomegalovirus, herpes infections,
chromosomal disorders, unstable conditions, exposure to antenatal
dexamethasone, and exposure to <1 complete course of betamethasone
were excluded. Auditory waveforms were categorized into response
types on response replicability and peak identification as types 1
through 4 (type 1 indicating most mature). Absolute and interpeak
wave latencies were measured when applicable. Categorical and
continuous variables were analyzed by using the
2
test and Student's t test, respectively.
RESULTS. Of 174 infants studied, 123 received antenatal steroids. Of these, 50 received 1 course and 29 received 2 courses of betamethasone. There were no significant differences in perinatal demographics between the 2 groups. After controlling for confounding variables, there was no significant difference in mean absolute wave latencies, mean interpeak latencies, or distribution of response type between the 2 groups. There also was no significant difference in any auditory brainstem response parameters between infants exposed to 1 course of betamethasone (n = 50) and infants exposed to >2 courses of betamethasone (n = 17).
CONCLUSION. Compared with a single recommended course of antenatal steroids, multiple courses of antenatal betamethasone are not associated with a deleterious effect on auditory neural maturation in 28 to 32 weeks' gestational age infants.
Measles-Mumps-Rubella and Varicella Vaccine Responses in Extremely Preterm Infants
Departments of Pediatrics, University of Rochester, Rochester,
New York
OBJECTIVE. Extremely preterm infants mount lower antibody responses than term infants to several vaccines. The objective of this study was to measure the immunogenicity of measles-mumps-rubella and varicella vaccines in preterm and term children.
METHODS. Immune status before immunization and immune
response after immunization with measles-mumps-rubella and
varicella vaccines at 15 months of age were compared in 32 infants,
16 of whom were preterm (<29 weeks' gestation) and 16 of whom
were term (
37
weeks' gestation) at birth. Blood was drawn before vaccination and
3 to 6 weeks thereafter. Measles antibody was measured by plaque
reduction neutralization assay. Mumps and rubella immunoglobulin G
were measured in available sera by enzyme-linked fluorescent
immunoassay. Varicella immunoglobulin G was measured in available
sera by glycoprotein enzyme-linked immunosorbent assay. Values that
were above or below the assay limits were assigned values double or
half those limits, respectively. The primary outcome was the
geometric mean antibody titer.
RESULTS. Preterm children had lower mumps and rubella geometric mean titers than did term children before vaccine, and nearly all children were seronegative for each of the 4 vaccine antigens before immunization. Measles, mumps, rubella, and varicella geometric mean titers were similar between groups after vaccine. All children were seropositive for measles after vaccine, whereas 13 of 14 preterm and 11 of 13 term children were seropositive for mumps, 13 of 14 preterm and 13 of 13 term children were seropositive for rubella, and 11 of 16 preterm and 9 of 15 term children were seropositive for varicella.
CONCLUSIONS. Preterm children mounted antibody responses that were similar to those of term children after measles-mumps-rubella and varicella vaccines at 15 months of age.
Admission Temperature of Low Birth Weight Infants: Predictors and Associated Morbidities
Department of Pediatrics, Brown Medical
School, Brown University, Providence, Rhode Island
BACKGROUND. There is a paucity of information on the maintenance of body temperature at birth for low birth weight infants.
OBJECTIVES. We examined the distribution of temperatures in low birth weight infants on admission to the NICUs in the Neonatal Research Network centers and determined whether admission temperature was associated with antepartum and birth variables and selected morbidities and mortality.
METHODS. Infants without major congenital anomalies born during 2002 and 2003 with birth weights of 401 to 1499 g who were admitted directly from the delivery room to the NICU were included. Bivariate associations between antepartum/birth variables and admission temperature and selected morbidities/mortality and admission temperature were examined, followed by multivariable linear or logistic regressions to detect independent associations.
RESULTS. There were 5277 study infants and the mean (±SD) birth weight and gestational age were 1036 ± 286 g and 28 ± 3 weeks, respectively. The distribution of admission temperatures was 14.3% at <35°C, 32.6% between 35 and 35.9°C, 42.3% between 36 and 36.9°C, and 10.8% at 37°C. The estimate of birth weight on admission temperature with and without intubation was +0.13°C and +0.04°C per 100-g increase in birth weight, respectively. The mean admission temperature for each center varied from 1.5°C below to 0.3°C above a reference center. On adjusted analyses, admission temperature was inversely related to mortality (28% increase per 1°C decrease) and late-onset sepsis (11% increase per 1°C decrease) but not to intraventricular hemorrhage, necrotizing enterocolitis, or duration of conventional ventilation.
CONCLUSIONS. Preventing decreases in temperature at birth among low birth weight infants remains a challenge. Associations with intubation and center of birth suggest that assessment of temperature control for infants intubated in the delivery room may be beneficial. Whether the admission temperature is part of the casual path or a marker of mortality needs additional study.
Mortality of Late-Preterm (Near-Term) Newborns in Utah
Departments of Pediatrics, Child Health Services Research, University of Utah School of Medicine, Salt Lake City, Utah
OBJECTIVES. The purpose of this work was to determine the relative risk for mortality and the causes and ages of death for late-preterm newborns (gestational age of 34–36 weeks) compared with those born at term.
METHODS. We reviewed data from birth and death certificates of infants born in Utah between 1999 and 2004. We calculated early neonatal (first week), neonatal (first 28 days), and infant (first year) mortality rates for each weekly estimated gestational age cohort from 34 to 42 weeks and, using 40 weeks as the reference, risk ratios for each cohort. Causes of death were grouped into 8 categories and compared for near term and term newborns. Crude mortality rates and risk ratios for death from all causes and for infants dying of all causes other than birth defects were measured.
RESULTS. Birth defects were the single-most common cause of death for both term and late-preterm newborns. Mortality rates for late-preterm newborns remained significantly higher after excluding those who died of birth defects from the comparisons.
CONCLUSIONS. Compared with those born at term, late-preterm (near-term) newborns have significantly higher mortality rates. Each weekly increase in estimated gestational age is associated with a decreasing risk of death. Birth defects are the leading cause of death among late-preterm newborns but do not entirely account for their higher risk of death.
Bacterial Imprinting of the Neonatal Immune System: Lessons From Maternal Cells?
Nestec, Nestlé Research Centre, Lausanne,
Switzerland
OBJECTIVE. We examined the presence of a natural bacterial inoculum in breast milk and its intracellular transport from the maternal intestine to the breast through the circulation.
METHODS. Breast milk and peripheral blood were collected aseptically from healthy donors at various times after delivery, and the presence of viable bacteria was determined through plating. Temporal temperature gradient gel electrophoresis was used to examine the bacterial ribosomal DNA content in milk cells, maternal peripheral blood mononuclear cells, and feces and in corresponding infant feces. Blood from nongravid nonlactating women served as control samples. Bacterial translocation to extraintestinal tissues was also evaluated in virgin, pregnant, and lactating mice.
RESULTS. Breast milk contained a low total concentration of microbes of <103 colony-forming units per mL. Temporal temperature gradient gel electrophoresis revealed that maternal blood and milk cells contained the genetic material of a greater biodiversity of enteric bacteria. Some bacterial signatures were common to infant feces and to samples of maternal origin. Bacterial translocation from the gut to mesenteric lymph nodes and mammary gland occurred during late pregnancy and lactation in mice.
CONCLUSIONS. Bacterial translocation is a unique physiologic event, which is increased during pregnancy and lactation in rodents. Human breast milk cells contain a limited number of viable bacteria but a range of bacterial DNA signatures, as also found in maternal peripheral blood mononuclear cells. Those peripheral blood mononuclear cells showed greater biodiversity than did peripheral blood mononuclear cells from control women. Taken together, our results suggest that intestinally derived bacterial components are transported to the lactating breast within mononuclear cells. We speculate that this programs the neonatal immune system to recognize specific bacterial molecular patterns and to respond appropriately to pathogens and commensal organisms.