Blood flow assessed by color Doppler imaging in retinopathy of prematurity.

OBJECTIVE: To quantify central retinal arterial and venous blood flow using ultrasound color Doppler imaging. STUDY DESIGN: In this prospective observational study, eyes of eight preterm infants with retinopathy of prematurity stage 2 and of eight preterm infants without retinopathy (gestational age <30 weeks, birth weight <1500 g) were evaluated by color Doppler imaging. RESULT: Ocular blood flow velocities measured at 28±1 days of life did not differ significantly in the eyes of preterm infants who subsequently did and did not develop retinopathy. Development of retinopathy was associated with highly significant (P<0.0001 each) increases in central retinal vein maximum velocities (from 1.99±0.36 to 3.72±0.61 cm s(-1)), central retinal artery systolic flow velocities (from 6.44±1.52 to 9.87±1.99 cm s(-1)) and flow velocity integrals (from 1.27±0.30 to 2.17±0.50 cm) at 64±13 days of life. In infants without retinopathy, no significant changes were observed except for an increase in central retinal vein maximum velocities (from 1.96±0.22 to 2.62±0.44 cm s(-1), P=0.003). CONCLUSION: Retinopathy of prematurity appears to be accompanied by increased retinal blood flow.

Electrocortical Activity at 7 Days of Life is Affected in Extremely Premature Infants with Patent Ductus Arteriosus.

BACKGROUND: The aim of this study was to determine whether the aEEG at 7 days of life is influenced by the presence of a PDA in non-sedated extremely low gestational age preterm infants. PATIENTS: We prospectively recruited infants born at less than 28 weeks of gestation between 11/2007 and 12/2009. METHOD: aEEGs were recorded at seven days of life and assessed by using the Burdjalov score and the electronically assessed lower border (eLBA). Kruskal-Wallis-Test and linear regression analysis were performed to determine how GA and a PDA affect the aEEG score and the eLBA. Using linear regression analysis we tested which components of the score are affected by a PDA. RESULTS: We recruited 44 infants with a GA of 26.5/7 (23.4/7-27.6/7) weeks and a birth weight of 837 (461-1230) g. The total sum of score points increased from 4 (1-6) to 8 (5-9) points in infants born at 23/24 weeks and 27 weeks of gestation, respectively. In infants with relevant PDA the aEEG scored lower with 8 (3-10) points compared to those with PDA: 5 (1-8) points. Linear regression analysis showed a positive influence of GA and a negative influence of a PDA on the total score. GA had a positive influence on SWC and the visually assessed LBA. A PDA had a negative influence on continuity. The eLBA increased from 4.61 (3.18-5.53) µV to 5.27 (3.38-6.51) µV in infants of 23/24 vs. 27 gestational weeks, but was not significantly influenced by a PDA. CONCLUSION: A PDA has a negative influence on the total Burdjalov score and continuity at 7 days of age in infants born at less than 28 weeks of gestation. The electrocortical disturbances may be the consequence of a diminished cerebral perfusion in the presence of a PDA.

Pilot study of experiences and needs of 111 fathers of very low birth weight infants in a neonatal intensive care unit.

OBJECTIVE: To study the experiences and needs of the fathers of very low birth weight (VLBW, <1500 g) infants in a neonatal intensive care unit (NICU). STUDY DESIGN: An anonymous self-report questionnaire was administered to fathers of VLBW infants born between Jan 1, 2008 and December 31, 2009 at two tertiary NICUs. RESULT: A total of 111 of 273 fathers responded to the questionnaire. Responses to a variety of items, including self-perception, parenting attitudes, confidence, emotional pressure to satisfaction and self-efficacy as a parent were similar for the fathers of this survey and previous results for mothers of VLBW infants. Fathers judged direct bedside support by the NICU team as sufficient. However, 54.4% of fathers reported missing nonbedside interventions such as VLBW father-specific baby care courses, seminars or workshops, and platforms or chatrooms on the internet. CONCLUSION: Bedside support of fathers, accomplished by the NICU team, could be complemented by additional father-specific non-bedside support, such as peer-education measures or interactive mass media.

Urinary NT-proBNP and ductal closure in preterm infants.

OBJECTIVE: To explore the association of urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations and closure of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN: Blinded prospective study involving 136 preterm infants (median (interquartile range) gestational age 28 (26 to 30) weeks; birth weight 1030 (780 to 1270) g). NT-proBNP was determined in urine collected on day of life (DOL) 2, 7, 14 and 28. RESULT: Urinary NT-proBNP/creatinine ratios declined continuously between DOL 2 (74 (17 to 248) µg g(-1)) and DOL 28 (4 (2 to 12) µg g(-1)) and were significantly elevated in ventilated infants on DOL 2, 7 and 14, and in ventilated infants with a hemodynamically significant PDA on DOL 2. Furthermore, urinary NT-proBNP/creatinine ratios on day 14 were higher in 14 ventilated infants who did not respond to pharmacological treatment and subsequently required surgical PDA closure (247 (214 to 547) µg g(-1)) than in ventilated infants (n=7) with successful pharmacological PDA closure (55 (21 to 114) µg g(-1); P<0.05). A cutoff >210 µg g(-1) on day 14 had a sensitivity of 75% and specificity of 100% for predicting non-responsiveness to pharmacological treatment. CONCLUSION: Measurement of urinary NT-proBNP is a new and simple non-invasive test for preterm infants, which may be helpful in guiding PDA treatment decisions.

Predictive and concurrent validity of standardized neurodevelopmental examinations by the Griffiths scales and Bayley scales of infant development II.

Standardized examinations of preterm infants are used to identify candidates for early intervention. We aimed to assess the predictive power and concurrent validity of the mental development index of the Bayley scales of infant development II (Bayley MDI) and the Griffiths scales developmental quotient (Griffiths DQ) in healthy term and preterm infants <1500 g birth weight without major perinatal complications.137 Infants (89 term, 48 preterm) were examined by both tests at a corrected age of 6, 12, and 22 months, and 114 went on to undergo Bayley assessments at 39 months.There were significant correlations between Bayley and Griffiths results at 6, 12, and 22 months (r=0.530, 0.714, and 0.833, respectively, p<0.001) but Bland Altman plots revealed major systematic bias at 6 months (Griffiths>Bayley, mean differences 14.3±9.8) and 22 months (Bayley>Griffiths, mean difference 5.2±13.9) and wide 95% limits of agreement at 6, 12 and 22 months (35.9%, 40.0%, and 52.4%, respectively). The agreement for a presumptive diagnosis of developmental impairment in the group of preterm infants between Bayley examinations obtained at 39 months corrected age (reference) and previous examinations was poor at 6, 12, and 22 months for both Bayley and Griffiths (Cohen's kappa for Griffiths: 0.225, 0.192, 0.369; for Bayley: 0.121, 0.316, 0.369, respectively).Caution should be exercised when interpreting results from standardized neurodevelopmental examinations obtained during the first 2 years of life in comparatively well preterm infants.

Predicting neurodevelopmental impairment in preterm infants by standardized neurological assessments at 6 and 12 months corrected age.

AIM: Neurodevelopmental impairment in very preterm infants can be reasonably diagnosed by 18-24 months corrected age, whereas the predictive value of earlier assessments is debated. We hypothesized that neurological findings at 6 and 12 months indicative of subsequent cerebral palsy predict 18-24 months' neurodevelopmental impairment. METHODS: Neurodevelopmental examinations (Griffiths scales) at 20 months of age in 561 preterm infants (birth weight <1 500 g) were compared with results of standardized neurological examinations (Early Motor Pattern Profile; EMPP) and Griffiths scales at 6 (n = 451) and 12 months (n = 496) corrected age. RESULTS: Griffiths developmental quotients at 20 months were weakly but significantly related to EMPP scores at 6 (R(s) = 0.328) and 12 months (R(s) = 0.493). Areas under receiver operator characteristic curves for the EMPP to predict neurodevelopmental impairment (Griffiths scores

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

UNLABELLED: 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. CONCLUSION: Preterm infants developing NEC are at risk for neurodevelopmental impairment and need close neurodevelopmental follow-up for the first years of life.

The CRIB (Clinical Risk Index for Babies) score and neurodevelopmental impairment at one year corrected age in very low birth weight infants.

OBJECTIVE: To assess the ability of the Clinical Risk Index for Babies (CRIB) to predict long-term neurodevelopmental impairment in very low birth weight (VLBW) infants. DESIGN: Single-center cohort study. SETTING: Tertiary neonatal care hospital and follow-up clinic. PATIENTS: Four hundred fifty-five VLBW infants consecutively admitted from 1992 to 1997 inclusive. MEASUREMENTS AND RESULTS: Calculations of CRIB scores from birth weight, gestational age, the presence of congenital malformations, worst base excess, maximum and minimum appropriate fraction of inspired oxygen (FIO2) during the first 12 h of life was possible in 430 infants. Three hundred eighty-six infants survived until discharge (89%) and 352 (91%) were examined at 1 year corrected age using the Griffiths scales of mental development. Major neurodevelopmental impairment (general quotient < 2 standard deviations below average) was observed in 76 infants (22%). CRIB scores and the individual CRIB components differed significantly between infants with and those without neurodevelopmental impairment. By logistic regression analysis, CRIB scores and minimum FIO2 were independent predictors of death, while CRIB and maximum FIO2 were independently associated with neurodevelopmental impairment. For combined poor outcome (death or impairment), CRIB, minimum and maximum FIO2 were independent predictors. In predicting major neurodevelopmental impairment, the area under the receiver operating characteristic curve for CRIB (0.703 +/- 0.035) did not differ significantly from that of birth weight (0.697 +/- 0.035) or any other CRIB component. CONCLUSION: While high CRIB scores are associated with major neurodevelopmental impairment, the CRIB score is of limited value for stratification in randomized trials or for adjustments in comparing performance between hospitals with neurodevelopmental impairment as the main outcome measure.

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

OBJECTIVE: Extremely 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: Over 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.

Parental and professional agreement in developmental assessment of very-low-birthweight and term infants.

The aim of this prospective follow-up study was to evaluate the accuracy of a parent-completed questionnaire compared with professionally detected developmental delay. Parents of 108 very-low-birthweight (VLBW) infants and parents of 279 term control infants completed the German version of the Revised Prescreening Developmental Questionnaire (R-PDQ) at the corrected age of 12 months. Simultaneously, infants underwent developmental examination using the Griffiths Developmental Scale. Sixty-nine VLBW infants were classified as not delayed, 16 as delayed by both methods (conegativity 76% and copositivity 94%), as compared to 240 and six term control infants (conegativity 88%, copositivity 94%). The questionnaire suggested delay in 22 VLBW infants and 32 control infants, which was not substantiated by professional examination (P=0.006). In contrast, examination-diagnosed delay was missed by the questionnaire in one infant in each group. The R-PDQ is a reliable monitoring instrument for both VLBW and term infants at the age of 12 months. Parents of VLBW infants tend to underestimate their infants' development.

Neurodevelopmental outcome after prenatal exposure to opiates.

UNLABELLED: To study the developmental effects of prenatal exposure to opiates, a prospective follow up study of 34 drug-exposed (opiates and nicotine) and 42 reference infants (nicotine exposure only) was conducted from January 1992 to September 1995. At the time of delivery, 12 of 34 mothers used opiates without medical control. Twenty-two mothers participated in a methadone maintenance programme. At 1 year, the average Griffiths Developmental Quotient (DQ) was lower in the drug-exposed group (mean: 100.5 vs. references 107.9; P < 0.001). This difference was mainly due to lower subscales "locomotor" (mean 100.8 vs. 111.4; P < 0.05) and "intellectual performance" (mean 100.8 vs. 108.5; P < 0.05) in the drug-exposed group. Severe developmental retardation mean DQ (-2 SD) was diagnosed in 2 drug-exposed infants. Mild developmental retardation (mean DQ: 1 SD- > 2 SD) was found in 7 drug-exposed and in 3 reference infants (P < 0.05). Neurological abnormalities were found more frequently in the drug-exposed group (11 vs. 3 infants; P < 0.01). Among the opiate-exposed infants, the subscales "hearing and speech" and "intellectual performance" were lower in the uncontrolled drug-using than in the methadone group. The 17 fostered infants showed no difference in developmental outcome compared with the 10 infants living with their biological parents (mean DQ: 100.0 versus 101.3). CONCLUSIONS: At 1 year infants prenatally exposed to opiates are at risk for mild psychomotor developmental impairment.

Low degree of regionalization and high transfusion rates in very low birthweight infants: a survey in Germany.

Although anemia is common in very low birthweight (VLBW) infants, widely accepted guidelines for red blood cell transfusions are lacking. Questionnaires regarding transfusion policy in VLBW infants in 1994 were sent to 391 German pediatric departments. 208 questionnaires were returned. 51 departments reported not to admit VLBW infants. Thus, results are based on 157 completed questionnaires. 54% of the respondents admitted less than 30 VLBW infants per year and 52% of the VLBW infants were admitted to departments with less than 50 VLBW infants per year. Overall transfusion rate ranged from 0 to 100% (median 65%). This range narrowed with the departments' size indicating stricter guidelines with less variation. Indication for transfusion varied considerably depending on the infants' postnatal age and need for ventilatory support. 34% of the respondents applied directed transfusions, most frequently from the infant's father. 70% used satellite packs. 51% stored the packs up to 7 days, 10% longer than 14 days. Red cells were irradiated in 35%, and washed in 23% of the departments. Median single transfusion volume was 12 ml/kg. We conclude that regionalization of VLBW infants in Germany is far from completeness and that hospital policies for transfusion show large variety especially in small departments.

Comparison of mortality risk: a score for very low birthweight infants.

AIM: To develop and evaluate a score which quantifies mortality risk in very low birthweight (VLBW) infants (birthweight below 1500 g) at admission to the neonatal intensive care unit. METHODS: Five hundred and seventy two VLBW infants admitted from 1978 to 1987 were randomly assigned to a cohort (n = 396) for score development and a cohort (n = 176) for score validation. Two hundred and ninety four VLBW infants admitted from 1988 to 1991 were used to compare risk adjusted mortality between the two eras. RESULTS: Using multiple regression analysis, birthweight, Apgar score at 5 minutes, base excess at admission, severity of respiratory distress syndrome, and artificial ventilation were predictive of death in the development cohort. According to regression coefficients, a score ranging from 3 to 40 was developed. At a cutoff of 21, it predicted death in the validation cohort with a sensitivity of 0.85, a specificity of 0.73, and a correct classification rate of 0.76. The area under the receiver operating characteristic curve was 0.86. There was no significant difference in risk severity and in risk adjusted mortality between the eras 1978-87 and 1988-91. CONCLUSION: The present score is robust, easily obtainable at admission, and permits early randomisation based on mortality risk.

Parents' estimation of psychomotor development in very low birthweight (VLBW) infants.

BACKGROUND: Within a longitudinal developmental surveillance project we tested the accuracy of the Revised Prescreening Developmental Questionnaire (R-PDQ) to detect developmental retardation in very low birthweight (VLBW) infants. METHODS: Seventy surviving VLBW-infants born between July 1992 and December 1993 were re-examined at 6 months corrected age. The parent-completed questionnaires (n = 67) were compared with developmental assessment using the Griffiths Developmental Scale. RESULTS: At 6 months corrected age, normal results of the Griffiths Developmental Scale (developmental quotient > or = 81) were found in 61/67 (91%) VLBW-infants and in 45/67 (67%) questionnaires (no or one 'delay'). The parents identified all six infants with psychomotor retardation on the Griffiths Developmental Scale (co-positivity 100%). However, only 45/61 infants with normal development were so identified with the R-PDQ (co-negativity 74%, positive predictive value 27%). CONCLUSIONS: The R-PDQ discovered all infants whose developmental quotient was two standard deviations below the mean on the Griffiths Developmental Scale. The relatively high proportion of false positive R-PDQ results corresponded to lower developmental quotients within the normal range. Therefore, the R-PDQ provides a useful screening instrument for VLBW-infants.

Differences in morbidity and mortality according to type of referral of very low birthweight infants.

Maternal and social risk, prenatal and obstetric care, resuscitation and neonatal care in very-low-birthweight infants (VLBW) may vary with the type of referral. In 453 VLBW's (< 1500 g) admitted to our neonatal intensive care unit 1987-1992, we classified transport type as: A: No transport (n = 240), B: Maternal transport (n = 88), C: Infant transport (n = 125). Stepwise multiple discriminant function was determined for the identified factors. The risk of mortality was investigated by logistic regression analysis. In group A, mean maternal age was higher and mothers' social status lower than in groups B and C. In group B, infants were considerably smaller and less mature, but when adjusted for gestational age, suffered less frequently from RDS, obviously due to more frequent induction of lung maturation. In group C, less than half of the infants were resuscitated by a neonatologist. Infants of this group were frequently hypothermic at admission and required prolonged artificial ventilation more frequently. Total VLBW survival averaged 77%, increasing from 69 to 88% within the study period. Total rate of severe intraventricular hemorrhage was 4.8% in surviving infants. VLBW infants with different forms of referral differ in their inherent risk. After maternal transport they have less morbidity despite a higher grade of immaturity. Regionalization of perinatal care for these infants remains the greatest potential for further reduction in infant mortality.

Diminished cord blood lymphocyte L-selectin expression in neonatal bacterial infection.

L-Selectin, a leukocyte surface glycoprotein involved in white blood cell extravasation, is rapidly down-regulated after leukocyte activation. We prospectively determined lymphocyte L-selectin expression in freshly obtained cord blood samples of 98 neonates (gestational age 25-42 weeks). In eight infants with bacterial infection, the mean percentage of L-selectin(high) lymphocytes was 32.5% (SD 20.1%), compared to 60.1% (SD 18.7%) in the control group (P < 0.01). A percentage of L-selectin(high) lymphocytes of less than 42% had a sensitivity of 75% and a specificity of 82% in identifying infected newborns. Cord blood lymphocyte L-selectin expression was independent of gestational age, birth weight, umbilical artery pH, hematocrit, white blood cell count, absolute neutrophil count, C-reactive protein level, or maternal fever before delivery while there was a weak correlation with the newborn's immature/total ratio and platelet count. To our knowledge, this is the first report demonstrating downregulation of human lymphocyte L-selectin expression following activation of the immune system in vivo.

[Reducing the incidence and morbidity of very low birth weight premature infants after maternal transport to a perinatal center]. / Senkung von Häufigkeit und Morbidität sehr untergewichtiger Frühgeborener nach mütterlichem Transport in ein perinatales Zentrum.

An improvement in the mortality and morbidity of very low-birth-weight infants could be confirmed by the regionalisation of high-risk pregnancies. The immaturity of premature newborn limits the therapeutic success. Our aim is therefore on the one hand, to make an early diagnosis of patients at risk of threatened premature delivery, and secondly, to provide intensive therapy for women already showing symptoms of premature delivery, to achieve the best possible prognosis. A reduction in the number of very low birth-weight infants and their mortality and morbidity rate appears to be possible if the pregnant women can be placed in a perinatal centre in good time; if the pregnancy can be prolonged and fetal lung maturation can be induced by betamethasone; if the delivery can be managed carefully, avoiding hypoxaemia, shock situations, and trauma; in certain cases this would mean performing a caesarean section by isthmo-cervical longitudinal incision; if primary neonatal care is performed by an experienced neonatologist. With the standard of neonatology as it is today, a considerable increase in the survival rates of very low birth-weight infants can hardly be expected. Nevertheless, to cut down their numbers is the biggest potential for the future reduction of the infant mortality rate.

Accelerated lung maturation following maternal steroid treatment in infants born before 30 weeks gestation.

A meta-analysis was performed of 9 controlled trials of maternal beta-/dexamethasone treatment in which the incidence of RDS in infants born before 30 weeks gestation was reported. A significant decrease could be shown in 250 immature infants. The number of cases was to small for analysis of lower gestational ages or for the demonstration of a reduction in mortality. In a separate study of 135 infants born before 30 weeks gestation tracheal aspirate phospholipid analysis was performed using thin layer chromatography. 64 of them had been exposed prenatally to steroids. Significantly more of these infants had a mature L/S ratio > or = 2.7 (p < 0.02) and prenatal glucocorticoid treatment was associated with a markedly increased survival rate (odds ratio 2.4, p < 0.02). We conclude from the meta-analysis of the literature and from the findings of our study, that accelerated lung maturation follows prenatal steroid treatment with a reduction in RDS-incidence even in very immature fetuses. Consequently it would be appropriate to administer glucocorticoids combined with tocolysis since this has been shown to be beneficial for those women threatening to deliver prematurely at less than 30 weeks gestation.