Prolonged mechanical ventilation and intracranial hemorrhage: impact on developmental progress through 18 months in infants weighing 1,200 grams or less at birth.

In this prospective, longitudinal study, the relative impact of intracranial hemorrhage and prolonged mechanical ventilation on developmental progress during the first 18 months of life of infants weighing 1,200 g or less at birth was examined. A total of 159 surviving infants were divided into two groups: infants with and those without intracranial hemorrhage. These groups were then subdivided into groups of infants receiving prolonged mechanical ventilation (greater than 21 days) and those mechanically ventilated for 21 days or less, thus creating four subgroups. Group 1 (intracranial hemorrhage and prolonged mechanical ventilation) and group 3 (intracranial hemorrhage and no prolonged mechanical ventilation) showed no statistically significant differences for severity of intracranial hemorrhage, persistence of ventriculomegaly, or presence of periventricular leukomalacia. A repeated-measures analysis of variance demonstrated a main effect for prolonged mechanical ventilation on outcome as measured by the Bayley Mental Development Index and Bayley Psychomotor Development Index at 4, 8, 12, and 18 months of age (corrected for prematurity). Forward stepwise regression revealed prolonged mechanical ventilation to the best predictor of Bayley indexes at all ages except 4 months of age, for which the Psychomotor Development Index was best predicted by length of hospitalization. No main effect for intracranial hemorrhage was demonstrated, but the motor performance of infants with intracranial hemorrhage declined significantly with age. By contrast prolonged mechanical ventilation was associated with uniformly poor performance at every age and serves as a powerful marker for poor developmental progress during the first 18 months of life in infants weighing 1,200 g or less at birth.

The effect of bronchopulmonary dysplasia on growth at school age.

OBJECTIVE: To determine the effect of bronchopulmonary dysplasia (BPD) on growth at school age. DESIGN: A prospective cohort study. METHODS: The sample included 406 children selected from a reconstructed cohort of infants of very low birth weight previously enrolled in a multisite, randomized, controlled clinical trial. The children were contacted at 8 to 10 years of age. Height, weight, and head circumference (HC) were measured. Possible confounders including sociodemographic data, and neonatal factors were also recorded. RESULTS: The children in the BPD group were significantly smaller in weight (z score, -0.50 +/- 1.19 SD vs -0.06 +/- 1.30 SD) and HC (z score, -1.41 +/- 1.32 SD vs -0.63 +/- 1.62 SD) than those without BPD. However, after controlling for cofounders (using analysis of covariance), no significant differences were demonstrated between the two groups. Power analyses showed that a difference of at least 0.43 z score units could have been detected. The previously documented associations between BPD and suspected confounders were reconfirmed. CONCLUSIONS: Significant differences were noted between children with and without BPD for weight and HC but not height. When possible confounders were taken into account, the differences were no longer appreciated. Thus, the previously reported poor growth in children with BPD may have been related to other factors and not necessarily to BPD.

Plasma estriol in the evaluation of third-trimester gestational age.

This study attempts to confirm previous reports of a clinically useful serum unconjugated estriol surge at 36 weeks' gestation. Although an apparently physiologic estriol surge occurred at 36 +/- 2.1 weeks in 25 of 32 patients, clinical reality makes weekly plasma sampling difficult. In individual cases, use of the "surge point" predicted gestational age within a 4-week range with only 66% accuracy, and potentially serious errors in dating occurred. Other biochemical (lecithin:sphingomyelin, phosphatidylglycerol) and sonographic methods are superior in resolving problems with dating gestational age in the third trimester.

Serial plasma and urinary aluminum levels and tissue loading in preterm twins.

Serial plasma, urinary, and postmortem tissue aluminum levels were determined in 32-week, appropriate-for-gestational-age twins from 45 to 151 days postnatal age. Estimated total aluminum absorptions were 56.7 mg, and 28 mg, twin A and twin B, respectively. At autopsy, Twin A had a hypoplastic right kidney while Twin B had normal kidneys. Mean plasma aluminum levels (twin A, 34.2 micrograms/liter and twin B, 32.3 micrograms/liter) and urinary aluminum levels expressed as aluminum creatinine ratios (twin A, 11.3 and twin B, 8.5) were similar. These levels were elevated compared to normal plasma aluminum levels of 5.1 +/- 3.6 (1 SD) and urinary aluminum creatinine ratios of 0.64 +/- 0.75 (1 SD). Twin A had higher tissue aluminum levels than twin B in all tissues except for brain. Bone and liver aluminum contents for both twins were increased as compared to infants receiving short-term or no parenteral nutrition. We conclude; (1) tissue aluminum loading occurs in infants receiving aluminum-containing solutions, (2) plasma and urinary aluminum levels are poor predictors of tissue aluminum content, (3) enteral solutions may add significant aluminum exposure.

Bronchopulmonary dysplasia and postnatal growth in extremely premature black infants.

Bronchopulmonary dysplasia (BPD) may adversely affect the postnatal growth of the extremely premature infant; however, most studies have not controlled for birth weight. We studied 90 Black premature infants (mean birth weight 989 +/- 148 g). Weight was recorded biweekly until discharge and at 4, 8, and 12 months of age corrected for prematurity. Infants with BPD (N = 23) were contrasted with infants without BPD (N = 67). Data were modeled using the Count model: Stage I birth to term and Stage II term to 12 months. Birth weight was considered part of growth beginning in utero and multivariate analyses were used to control for BPD, gestational age, duration of hospitalization and socioeconomic status. After adjustment for birth weight, BPD did not explain the growth pattern. A lower gestational age was associated with a slower establishment of steady growth (P less than 0.01), while an increased duration of hospitalization was associated with a lower growth rate (P less than 0.05). Growth in stage II was not explained by study variables. 'Catch-up' growth was seen in both infants with and without BPD. We conclude that differences in growth among infants with BPD are mainly attributable to birth weight. We speculate that poorer growth may be seen in a sub-group of infants with severe BPD.

The value of the Infant/Child Monitoring Questionnaire for identification of developmental disability among neonatal intensive care unit graduates.

OBJECTIVE: We hypothesized that the Infant/Child Monitoring Questionnaire (ICMQ) could be used to identify at-risk infants eligible for developmental interventional services. STUDY DESIGN: Of this cross-sectional observational study, group A (n = 108) included a retrospective review of moderate risk infants scheduled for developmental assessment clinic (DAC) visits. Group B (n = 108) included moderate-risk infants whose parents completed the ICMQ. Group C (n = 67) included high-risk infants who were seen in the DAC and whose parents completed the ICMQ. RESULTS: For group A infants, 43.5% were seen in the DAC; 10.6% of these visits resulted in an intervention. For group B infants, 56.5% of parents completed the ICMQ; 66.7% of subsequent visits resulted in an intervention. For group C infants, comparison of ICMQ and DAC visits showed moderate agreement (kappa = 0.50). CONCLUSION: The ICMQ is a useful tool to identify moderate-risk infants requiring further intervention, but caution must be used when applied to high-risk infants.

Two year longitudinal followup of premature infants weighing less than or equal to 1,200 grams at birth: sequelae of intracranial hemorrhage.

Intracranial hemorrhage (ICH) is a major problem for the premature infant, occurring in more than one-third of surviving infants weighing less than or equal to 1,500 g at birth. The literature on perinatal ICH, as it relates to neurodevelopment outcome, is briefly reviewed, and preliminary results from our two-year followup of 75 less than or equal to 1,200-g infants are summarized. An analysis of pathophysiology, diagnosis, classification, and followup indicates that risk for ICH and its sequelae increases as gestational age and birth weight decrease. Hydrocephalus apparently no longer presents significant risk beyond that conveyed by the original hemorrhage. However, persistent posthemorrhagic ventriculomegaly and/or periventricular abnormalities serve as significant "markers" of risk for neuromotor delay through two years of age. In contrast, recovery of normal ventricular morphology by term gestational age apparently indexes a degree of recovery from ICH and predicts a more normal developmental outcome through the first two postnatal years.

Cranial sonography and neurological examination at term and motor performance through 19 months of age.

This study examined the role of cranial sonography and neurological examination in the prediction of developmental progress during the first 19 months of life in extremely preterm infants. Forty-seven infants with mean birth weight 993 +/- 197 g and gestational age 27.9 +/- 1.9 weeks were studied. Each infant was classified as normal, suspect, or abnormal using cranial sonography and a structured neurological examination. Developmental outcome was assessed using the Infant Neurological International Battery (INFANIB) at 4, 8, and 14 months and the Rockford Infant Developmental Evaluation Skills (RIDES) at 19 months. Sonographic classification was the best predictor of outcome through 14 months, F(2.72) = 12.4, p < .001. The neurological examination predicted performance only at 4 months. No infant classified as normal on both examinations was abnormal on follow-up. Infants with suspect or abnormal neurological examinations had normal outcomes if their sonographic findings were normal.

Cognitive performance at school age of very low birth weight infants with bronchopulmonary dysplasia.

The hypothesis was that bronchopulmonary dysplasia (BPD) adversely affects cognitive performance at school age. This prospective cohort study examined three groups of children at 8 to 10 years of age. Group 1 (n = 311) consisted of very low birth weight (VLBW) infants without BPD and Group 2 (n = 95) consisted of VLBW infants with BPD. Group 3 (n = 188) consisted of term infants without BPD. Regression analysis determined the effect of BPD on eight performance measures while controlling for possible confounding variables. Children in Group 3 had the best performance and children in Group 2 had the poorest performance on all measures. These differences were significant (p = .0001) for the Full Scale IQ, Performance IQ, and reading and math grades and ages. Children in Groups 3 and 1 performed better than children in Group 2 for the Verbal IQ (p = .0001) and the Developmental Test of Visual-Motor Integration (p = .0012), but for these two measures there was no significant difference between children in Groups 3 and 1. Thus, poorer performance was found in VLBW infants with a history of BPD.

Use of high-frequency jet ventilation in the management of congenital tracheoesophageal fistula associated with respiratory distress syndrome.

Two preterm infants (28 weeks, 960 g; 32 weeks, 1,870 g) with very large tracheoesophageal fistulas suffered from respiratory distress syndrome and failed to respond to conventional mechanical ventilation despite placement of a decompressive gastrostomy. Pulmonary air leaks developed in both, resulting in transdiaphragmatic pneumoperitoneum, and significant gas flow occurred through the gastrostomy tube despite placement under water-seal. High-frequency jet ventilation was instituted in each case and resulted in improved pulmonary gas exchange at lower mean airway pressure (12.0 to 6.7 cm H2O; 11.0 to 8.0 cm H2O) and in prompt resolution of air leaks. Both patients remained refractory to reinstitution of conventional ventilation until division of the fistula in the first patient and complete resolution of the respiratory distress syndrome in the second.

Association of increased cardiothoracic ratio and intrauterine growth retardation.

Clinical observation suggested an association between an increased cardiothoracic ratio (CT) and growth retardation (IUGR) in the premature neonate. To investigate this hypothesis, a case-control study was performed. Study subjects included 23 cases (IUGR) and 55 control (appropriate for gestational age [AGA]) premature infants with birthweights 2000 gm or less; Apgar scores greater than 5 at 5 minutes; no congenital heart disease; no polycythemia; no toxoplasmosis, rubella, cytomegalovirus, or herpes infection. In random order, the first chest radiograph of each infant (less than 24 hours) was reviewed by a single radiologist, unaware of the infant's growth status. The CT ratio was computed after measuring the widest internal width of the bony thorax and the cardiac diameter. Mean birthweight (+/- 1 SD) of the IUGR infants was 1161 +/- 289 g and of AGA infants was 1401 +/- 401 g (p less than 0.002); the mean gestational ages (+/- 1 SD) were 33.2 +/- 2.8 and 30.8 +/- 2.5 weeks (p less than 0.001). Mean CT for IUGR infants was 0.57 +/- 0.07 (+/- 1 SD) versus AGA infants, 0.51 +/- 0.04 (+/- 1 SD), p less than 0.001. When the infants were stratified by growth status and CT ratio, 11 of 23 IUGR and 1 of 55 AGA infants had an increased CT ratio p less than 0.0001. When birthweight and gestational age were covaried, growth status remained the best predictor of CT, p = 0.005. There is a strong association of increased CT and growth retardation in premature infants with birthweights 2000 gm or less.

Lidocaine toxicity after maternal pudendal anesthesia in a term infant with fetal distress.

There have been many reports of lidocaine toxicity especially after maternal paracervical block anesthesia. We recently treated a term infant with evidence of fetal distress who presented with symptoms of lidocaine toxicity after maternal pudendal anesthesia. The infant developed apnea and bradycardia soon after birth which responded to mechanical ventilation and epinephrine. A prolonged Q-T interval was noted on day 1 which normalized by day 3. Cord blood was assayed and revealed an elevated lidocaine level. Lidocaine toxicity has been associated with fetal distress secondary to fetal ion trapping in the presence of acidosis. Although good response to supportive therapy occurred in our patient, other methods of therapy such as exchange transfusion and treatment of seizures may be required in some cases. Awareness of this now uncommon syndrome will lead to prompt diagnosis, appropriate work-up, and management.

Impact of venous catheters on packed red blood cells.

This study was designed to test the hypothesis that there would be increased hemolysis, as indicated by an increase in plasma free hemoglobin and potassium, when packed cells were infused through small gauge percutaneous catheters (24 and 28 g, PC) compared with short catheters (24 g; SC). We were unable to study the 28 g PC because after 1 hour, at a flow rate of 10 ml/hr, only 2.4 ml packed cells were infused. There was a significant increase in plasma free hemoglobin when pre- and postinfusion values were compared (SC, p = 0.005; PC, p = 0.009), but a statistically significant increase in potassium only for the SC (p = 0.008). There were no significant differences between the catheters for either potassium or free hemoglobin. For either catheter the quantity of free hemoglobin transfused could potentially cause a significant rise in serum bilirubin and hemoglobinuria.

Real-time ultrasonographic surveillance in the detection of CNS involvement in systemic Candida infection.

Systemic candidiasis is becoming more common in the neonatal unit as the survival of extremely premature infants increases. Central nervous system (CNS) involvement occurs in 64% of infants with systemic infection. Real-time ultrasonography is useful in the diagnosis of CNS involvement and its sequelae as well as in monitoring the efficacy of therapeutic interventions. A patient with extensive CNS involvement is presented. Ultrasonographic findings are described and correlated with neuropathological examination of the brain.

Lateral positioning of the stable ventilated very-low-birth-weight infant. Effect on transcutaneous oxygen and carbon dioxide.

Eighteen stable very-low-birth-weight (VLBW) mechanically ventilated infants with chronic lung disease were studied to examine the effects of right and left lateral positioning in contrast to supine positioning on transcutaneous (tc) oxygen (tcPO2) and carbon dioxide measurements (tcPCO2). The neonates were studied at a median postnatal age of 31 days (range, 17 to 57 days) and had median birth weights and gestational ages of 975 g (range, 570 to 1360 g) and 27.5 weeks (range, 24 to 30 weeks), respectively. Median fraction of inspiratory oxygen was 0.32 (range, 0.23 to 0.40). The sequence of study positions was randomly determined. Sleep state as well as tcPO2 and tcPCO2 were recorded every 30 s for five minutes. A significant difference in mean tcPO2 or tcPCO2 was not detected for any of the positions. Lateral positioning may facilitate the development of midline behavior in VLBW infants. Care givers are often reluctant to position infants in side lying, however, because of concerns that ventilation or oxygenation might be compromised. We conclude that placing the stable VLBW mechanically ventilated infant in a side-lying position has no deleterious effects on oxygenation and ventilation, as measured by tcPO2 and tcPCO2, and therefore should be encouraged.

Effect of prenatal lignocaine on auditory brain stem evoked response.

To test the hypothesis that there would be a positive correlation between the interpeak wave (I-V) interval as measured by auditory brain stem evoked response and the ratio of umbilical cord blood arterial to venous lignocaine concentrations in infants born after maternal epidural anaesthesia, 10 normal infants born at full term by elective caesarean section were studied. Umbilical cord arterial and venous plasma samples were assayed for lignocaine, and auditory brain stem evoked responses were elicited at 35 and 70 dB at less than 4 (test 1) and greater than or equal to 48 hours (test 2). Mean wave I-V intervals were prolonged in test 1 when compared with test 2. Linear regression showed the arterial:venous ratio accounted for 66% (left ear) and 43% (right ear) of the variance in test 1 intervals. No association was found in test 2. In newborn infants, changes in serial auditory brain stem evoked response tests occur after maternal lignocaine epidural anaesthesia and these changes correlate with blood lignocaine concentrations.

Neonatal purpura fulminans in association with factor V R506Q mutation.

We report a case of neonatal purpura fulminans associated with activated protein C resistance. Analysis of DNA demonstrated heterozygosity for the factor V R506Q mutation. The neonate, at 8 hours of age, had progressive purpuric skin lesions and later had evidence of microvascular, hemorrhagic thrombosis in the brain. The baby was treated with fresh frozen plasma infusions and had complete resolution of the skin lesions and no apparent long-term complications. We suggest that activated protein C resistance testing be included in the initial evaluation of neonatal purpura fulminans.