Michael Obladen

Changing practices of red blood cell transfusions in infants with birth weights less than 1000 g

OBJECTIVEnExtremely low birth weight (ELBW) infants frequently undergo transfusion because they are critically ill, often need artificial ventilation, and have the highest blood sampling loss in relation to their weight. During the last decade our transfusion guidelines were changed 3 times to become more restrictive. We hypothesized that these modifications substantially decreased the number of transfusions in our ELBW infants.nnnMETHODSnWe performed a single-center analysis of 256 infants with birth weights from 500 to 999 g who were admitted from 1989 to 1997 and included 3 study periods, each starting with newly modified transfusion guidelines in April 1989, September 1991, and January 1995. We evaluated prospectively recorded clinical data and retrospective chart analysis for transfusion-related information.nnnRESULTSnThe median number of transfusions per infant decreased from 7 in the first period to 2 in the third period, whereas donor exposure decreased from 5 to 1 and blood volume transfused decreased from 131 to 37 mL/kg birth weight (P <.01). The median venous hematocrit measured before transfusion decreased from 43% to 35% in infants who underwent ventilation and from 41% to 31% in spontaneously breathing infants. The median birth weight decreased from 870 to 740 g and the median gestational age from 27 to 25 completed weeks (P <.01). The overall survival rate was 75% and did not change. The incidences of retinopathy, intraventricular hemorrhage, and patent ductus arteriosus remained unchanged.nnnCONCLUSIONnOver this 9-year period with increasingly restrictive transfusion guidelines, the transfusion number decreased by 71% and the donor exposure by 80% in ELBW infants without adverse clinical effects.

Breast milk from mothers of very low birthweight infants: variability in fat and protein content.

While breast milk appears to be superior to formula for the development of very low birthweight (VLBW) infants, it is supplemented to meet the metabolic demands of the rapidly growing premature infant. To estimate the nutritional variability of breast milk from mothers of VLBW infants, protein (bicinchoninic acid method) and fat content (creamatocrit) were measured in breast‐milk spot samples from mothers of 20 VLBW infants, collected 4 times a day during the first 4 wk of lactation Protein content (median 1.9 g dl−1, range 1.1–3.5 g dl−1) and fat content (3.8/1.0–14.6 g dl−1) were highly variable and lacked a normal distribution over all samples and in individual womens milk. There was only a weak correlation between fat and protein (rs= 0.416, p < 0.001). Fat but not protein was lower in morning samples than in samples collected later in the day (p < 0.001). Protein but not fat content decreased during the weeks of lactation (rs=−0.446, p < 0.001). No impact of the babys gestational age was observed.

Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis

The aim of the study was to assess the effect of necrotizing enterocolitis (NEC) on neurodevelopmental outcome and growth. Neurodevelopmental outcome of 20 out of 22 suriviving very low birthweight infants (VLBW) diagnosed with NEC between 1992 and 1996 was compared with 40 control infants matched for gestational age and year of admission. Follow‐up studies were performed at 12 and 20 mo of corrected age. The German revision of the Griffiths scales was used for development assessment. Neurodevelopment was significantly delayed in infants with NEC at 12 mo (median general developmental quotient: 90.0 vs 97.8; p = 0.04) and 20 mo (86.4 vs 97.7; p = 0.004) of age. Somatic growth did not differ between infants with and without NEC. Fifty‐five percent of infants suffering from NEC but only 22.5% of the infants without NEC were severely retarded (developmental quotient < ‐2 SD of a control group of healthy newborns) at 20 mo of corrected age.

Early cessation of breast milk feeding in very low birthweight infants

This investigation was carried out to comparatively assess the duration of breast milk feeding and to analyze risk factors for early cessation of breast milk feeding in term and very preterm infants. A cohort study was performed in 89 consecutive very low birthweight (VLBW) infants (<1500 g) who survived for at least for one week, and 177 term infants with birthweights >2500 g born in the same hospital matched for gender and multiplicity. Median duration of breast milk feeding, as determined from charts and questionnaires mailed to the mothers at 6 and 12 months corrected age, was 36 days in VLBW infants, compared to 112 days in control infants (P<0.0001). In both VLBW and control infants, smoking during pregnancy, low maternal and low paternal school education were each significantly associated with short duration of breast milk feeding. In VLBW infants, multiple pregnancy and gestational age <29 weeks were each associated with prolonged breast milk feeding, as were maternal age >35 years and spontaneous pregnancy (as opposed to pregnancy following infertility treatment) in term infants. Multivariate analysis revealed that VLBW, smoking and low parental school education were independent negative predictors of breast milk feeding. While these results emphasize the need for special support of VLBW infant mothers promoting lactation, the relationships between smoking, school education and breast milk feeding in both strata show that efforts to increase breast milk feeding require a public health perspective.

Erythropoietin improves synaptic transmission during and following ischemia in rat hippocampal slice cultures

Erythropoietin (EPO) prevents neuronal damage following ischemic, metabolic, and excitotoxic stress. In this study evoked extracellular field potentials (FP) were used to investigate the effect of EPO on synaptic transmission in hippocampal slice cultures. EPO treated cultured slices (40 units/ml for 48 h) showed significantly increased FP during and following oxygen and glucose deprivation compared with untreated control slices. The addition of the Jak2 inhibitor AG490 (50 microM for 48 h) blocked the EPO effect. These data suggest that EPO improves synaptic transmission during and following ischemia in hippocampal slice cultures.

Complement system in healthy term newborns: reference values in umbilical cord blood.

ABSTRACT Activation of the complement system occurs in several diseases. For reliable identification of complement activation in neonates, we establish reference ranges of several components in cord blood of healthy term newborns. For this study, cord blood samples were taken from 125 healthy term newborns. Concentrations of C1r, C2, C5, C7, Properdin, and factors D, H, and I were determined by single radial immunodiffusion. C3a and C5a were measured by specific EIA and complement function was measured by hemolytic assays. The results were expressed as 5th percentile, median, and 95th percentile. The following respective concentrations were found: C1r: 27, 47, 65 mg/l; C2: 12.0, 18.0, 24.0 mg/l; C5: 64, 92, 127 mg/l; C7: 32, 60, 89 mg/l; Properdin: 5.6, 9.7, 14.2 mg/l; factor D: 3.6, 5.2, 7.3 mg/l; factor H: 178, 234, 296 mg/l; and factor I: 15, 24, 32 mg/l. The functional activity of the whole complement system was 24%, 43%, 97% and for the alternative pathway 39%, 58%, 76%. The concentration of the activated split products C3a was 4, 65, 255 μg/l and of C5a, 0.11, 0.26, 1.19 μg/l. These reference values may be important for the detection of deficiencies of native complement proteins or perinatal processes leading to an activation of the complement system.

Multisystem Organ Failure and Capillary Leak Syndrome in Severe Necrotizing Enterocolitis of Very Low Birth Weight Infants

BACKGROUNDnClassification systems for necrotizing enterocolitis (NEC) in preterm infants have been developed to define severity grades relevant for treatment and prognosis. Multisystem organ failure (MSOF) and capillary leak syndrome (CLS) also have prognostic value in these patients. The aim of this retrospective study was to investigate the incidence and predictive value of MSOF and CLS according to the classification criteria.nnnMETHODSnThe records of 1,022 very low birth weight infants admitted from 1982 to 1996 were reviewed for diagnosis of NEC stage IIA or higher (classification of Walsh and Kliegman). Among those patients (n = 50) the incidence of MSOF and CLS was determined, separately for surgical or conservative treatment.nnnRESULTSnTwelve patients were assigned to stage II, 22 to stage IIIa, and 16 to stage IIIb; 31 infants underwent operation. Mortality rate was not influenced by the grade. In eight patients only gastrointestinal symptoms were found, whereas in 23 patients, up to three organ systems and in 19 patients, four or more organ systems were affected. Mortality depended on the number of involved organ systems. CLS occurred postoperatively in 10 of the 31 infants; eight of them died.nnnCONCLUSIONnThe prognostic values of MSOF and CLS are higher than that of classification criteria in NEC of VLBW infants.

Acute and chronic fetal hypoxia in monochorionic and dichorionic twins

Objective To assess the risk for acute and chronic fetal hypoxia in twin pregnancies. Methods We investigated 50 sets of twins (24–38 weeks gestation, 660–3200 g birth weight) admitted consecutively to our neonatal intensive care unit. Seventy-six infants were appropriate for gestational age (AGA; tenth to 90th percentile), 20 were small for gestational age (SGA; below the tenth percentile), and four were large for gestational age (above the 90th percentile). Twenty-six singleton AGA term newborns served as controls. Umbilical arterial pH was used as a marker for acute and umbilical venous erythropoietin concentration for chronic fetal hypoxia. The results are given as median followed by quartiles. Results We identified 40 sets of diamniotic-dichorionic twins and ten sets of diamniotic-monochorionic twins with transplacental vascular shunts. In the second-born twin, umbilical arterial pH was lower (7.29, 7.23–7.33) than in the firstborn (7.31, 7.25–7.34) (P = .03), and the incidence of a low pH (less than 7.20) was higher (19 versus 11%). Two secondborn twins and none of the firstborn twins had an umbilical arterial pH less than 7.05. In SGA twins, the erythropoietin concentration was elevated (34.8, 22.8–325 mU/mL) compared with that in AGA twins (16.2, 8.2–26.6 mU/mL) (P < .01). In AGA twins, erythropoietin concentration did not differ from that in AGA singleton newborns (19.6, 14.7–31.6 mU/mL). In 12 of 17 twin sets with weight discordancy greater than 15% and in all five twin sets with weight difference greater than 25%, erythropoietin concentration was higher in the smaller twin. The proportion of infants and of complete sets with elevated erythropoietin levels was higher (P < .01) in monochorionic than in dichorionic pregnancies. Conclusions The second-born twin is at increased risk for acute birth asphyxia. Fetal growth restriction in twin pregnancies is associated with chronic fetal hypoxia. Monochorionic twins are at higher risk for chronic fetal hypoxia than are dichorionic twins.

Severe Spinal Muscular Atrophy Variant Associated With Congenital Bone Fractures

Infantile autosomal recessive spinal muscular atrophy (type I) represents a lethal disorder leading to progressive symmetric muscular atrophy of limb and trunk muscles. Ninety-six percent cases of spinal muscular atrophy type I are caused by deletions or mutations in the survival motoneuron gene (SMN1) on chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with additional clinical features (respiratory distress, cerebellar hypoplasia) have been designated in the literature as infantile spinal muscular atrophy plus forms. In addition, the combination of severe spinal muscular atrophy and neurogenic arthrogryposis has been described. We present clinical, molecular, and autopsy findings of a newborn boy presenting with generalized muscular atrophy in combination with congenital bone fractures and extremely thin ribs but without contractures. (J Child Neurol 2002;17:718-721).

3-D ULTRASOUND QUANTIFICATION OF NEONATAL CEREBRAL VENTRICLES IN DIFFERENT HEAD POSITIONS

We determined the influence of head position on lateral ventricular cerebral volume in low-birth-weight infants by three-dimensional (3-D) ultrasound (US). Thirty-nine neonates were examined prospectively in a controlled and blinded study. We used a freehand 3-D US system to acquire data sets after head positioning for 3 h on left and right side in random order. The borders of the lateral ventricles were marked in stored cross-sections. Volumes were calculated as mean of duplicate measurements. Median volume of lateral cerebral ventricles was 1.03 (quartiles 0.78-1.36) mL. Median left ventricular volume was slightly larger than right one (p = 0.13). Down-side lateral ventricles showed smaller volumes than up-side positioned ventricles (p < 0.01). Freehand 3-D US allows quantification of small volumes as neonatal lateral cerebral ventricles. Head position influences the lateral cerebral ventricle volume in low-birth-weight infants.