Surfactant without intubation in preterm infants with respiratory distress: first multi-center data.

BACKGROUND: Recently in a report of a single center a method has been described to apply surfactant via a thin endotracheal catheter to very low birth weight infants spontaneously breathing with nasal continuous positive airway pressure. We now analyzed available multicenter data. PATIENTS AND METHODS: In a multicenter study investigating genetic risk factors, clinical and outcome data and data of antenatal and postnatal treatment of infants with a birth weight below 1,500 g were prospectively recorded. The measures of infants treated with the new method of surfactant application were compared to those of infants who received standard care. The analysis was restricted to infants with a gestational age below 31 weeks (n=1,541). RESULTS: 319 infants were treated with the new method and 1,222 with standard care. The need for mechanical ventilation during the first 72 h (29% vs. 53%, p<0.001), the rate of bronchopulmonary dysplasia defined as oxygen at 36 weeks of postmenstrual age (10.9 % vs. 17.5%, p=0.004) and the rate of death or bronchopulmonary dysplasia were significantly lower in the treatment group than in the standard care group. Surfactant, theophyllin, caffeine and doxapram were significantly more often and analgetics, catecholamines and dexamethasone were significantly less frequently used in the treatment group. CONCLUSIONS: A new method of surfactant application was associated with a lower prevalence of mechanical ventilation and better pulmonary outcome. A prospective controlled trial is required to determine whether this approach is superior to standard care.

Transmission of cytomegalovirus to preterm infants through breast milk.

OBJECTIVE: To evaluate the rate of virus excretion through breast milk and the incidence and significance of postnatal cytomegalovirus (CMV) transmission from mothers to premature infants. DESIGN: Prospective study of mother-child pairs after preterm delivery before 32 weeks or birth weight < 1500 g. Exclusion of donor breast milk and of CMV-seropositive blood. Material used was maternal CMV serostatus, ear swab of the infants at birth, sequential screening of breast milk and children's urine. Methods used were CMV-DNA PCR and viral cultures on fibroblasts. RESULTS: During a 12-month period 56 mother-infant pairs with 67 preterm infants were studied. Twenty-seven women (48%) were CMV-seronegative at birth; breast milk samples and the infants' urine remained CMV-negative. Twenty-nine women were CMV IgG-seropositive; 23 of 27 seropositive breast-feeding mothers excreted CMV through milk (85%); 25 of 27 (93%) had CMV DNA-positive results. CMV infection occurred in 17 of 67 infants (25%). CMV transmission was exclusively found in infants of seropositive mothers who excreted CMV and breast-fed their infants; 17 of 29 exposed infants became infected (59%). In 12 patients (gestational age, 29.9 +/- 1.8 weeks) CMV was detected at a postnatal age beyond 8 weeks; 5 of these infants had mild signs of a viral infection. However, 5 extremely low birth weight infants (gestational age, 24.4 +/- 0.5 weeks) were infected at an age of 4 to 7 weeks; 4 of these infants had marked symptoms of an acute CMV infection. CONCLUSION: In mothers of preterm infants a high incidence of CMV excretion into breast milk was detected. There is evidence that the most immature infants are at the greatest risk to acquire an early and symptomatic CMV infection.

Detection of cytomegaloviral DNA in human milk cells and cell free milk whey by nested PCR.

Human cytomegalovirus (HCMV) DNA can be detected in different compartments of human milk. A protocol for the preparation of milk whey free of fat and cells for the detection of human cytomegalovirus (HCMV) by nested PCR is presented. This is based upon the experience of the separation of more than 200 milk specimens of healthy seropositive breast feeding mothers. HCMV DNA could be detected in freshly centrifuged and filtrated milk whey specimens without contamination by cellular DNA. In limiting dilution experiments using HCMV plasmid DNA, the effect of different DNA extraction procedures from native milk and milk whey on the detection limit of cytomegaloviral DNA was demonstrated. About 200 viral genome equivalents/ml in milk whey or native milk were detectable by classical organic phenol/chloroform extraction or a spin column method, respectively. The detection of viral DNA in milk cells depended on a minimum number of milk cells (10(5)-2 x 10(5)) available for DNA extraction. In contrast to the findings of cytomegaloviral DNA in native sera or plasma of immunosuppressed patients we failed to amplify low level viral DNA from native breast milk by nested PCR due to an inhibition of Taq polymerase by lipid components. Finally, the course of cell associated and cell free DNAlactia was monitored. Analyzing sequential milk specimens, in some cases the presence of HCMV DNA in colostrum could be demonstrated. DNAlactia of milk cells and whey was partially discordant. Onset (week 1-4 after delivery) and duration (2 weeks up to more than 3 months) of DNAlactia showed distinct individual patterns. The methods described, allow further analysis of the mechanisms involved in the postnatal HCMV transmission by breast feeding seropositive mothers.

Polymorphisms in the Renin-Angiotensin system and outcome of very-low-birthweight infants.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE-ins/del) and the angiotensin II type 1 receptor 1166A/C polymorphism (ATR1166A/C) were reported to be associated with several unfavorable outcome parameters in preterm infants like bronchopulmonary dysplasia, persistent ductus arteriosus and impaired insulin sensitivity. OBJECTIVE: To confirm the above-mentioned associations in a large cohort of very-low-birthweight (VLBW) infants. METHOD: Clinical data of VLBW infants were prospectively recorded. The ACE-ins/del polymorphism and the ATR1166A/C polymorphism were determined by polymerase chain reaction in 1,209 and 1,168 infants, respectively. RESULTS: There was no significant association between ACE-ins/del or ATR1166A/C genotype and outcome parameters (death, intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, ventilation, supplemental oxygen at discharge, postnatal treatment with insulin, surgery for intestinal perforation/necrotizing enterocolitis/retinopathy of prematurity/persistent ductus arteriosus. CONCLUSION: Both known functional polymorphisms of the renin-angiotensin system do not seem to be associated with the outcome of VLBW infants.

[Mortality and morbidity of very premature infants in Baden-Württemberg depending on hospital size. Is the current degree of regionalization adequate?]. / Mortalität und Morbidität sehr unreifer Frühgeborener in Baden-Württemberg in Abhängigkeit von der Klinikgrösse. Ist der derzeitige Grad der Regionalisierung ausreichend?

BACKGROUND: Regionalization of perinatal and neonatal care improves outcome. The aim of this study was to compare outcome in preterm infants with a gestational age (GA) < 32 weeks in relation to patient volume. METHODS: Outcome data from the state-wide neonatal quality assurance system from 2003 - 2004 from all infants treated in one of the five largest perinatal centers in Baden-Wuerttemberg were subtracted from the total dataset. Data derived from these five centers was compared with data from all other remaining NICU's in the state. RESULTS: Mortality was 33.3 % vs. 15.0 % (other NICU's vs. five perinatal centers; p < 0.001) for infants < 26 weeks GA, 11.4 % vs. 8.9 % (n. s.) for infants 26 - 27 weeks GA, and 2.5 % vs. 3.5 % (n. s.) for infants 28 - 31 weeks GA. When analyzed as one group of infants < 28 weeks GA, mortality was 20.1 vs. 12.1 % (p = 0.003). The rate of intraventricular hemorrhage degrees III-IV was 30.2 % vs. 18.6 % (p = 0.015) for infants < 26 weeks GA, 14.5 % vs. 10.2 % (n. s.) for infants 26 - 27 weeks GA, and 2.9 % vs. 2.5 % (n. s.) for infants 28 - 31 weeks GA. The rate of periventricular leukomalacia was 11.3 % vs. 6.7 % (p = 0.18) for infants < 26 weeks GA, 6.1 % vs. 2.8 % (n. s.) for infants 26 - 27 weeks GA, and 2.8 % vs. 2.3 %; (n. s.) for infants 28 - 31 weeks GA. CONCLUSION: This study supports the hypothesis, that regionalization of neonatal care for very immature infants to few perinatal centers with a large case load may improve survival of these infants, and may reduce morbidity, associated with long-term sequelae.

[CMV infections of the neonate: prevalence, diagnosis, therapy]. / CMV-Infektionen bei Neugeborenen: Prävalenz, Diagnostik und Therapie.

Infections with cytomegalovirus (CMV) are still a challenge for obstetricians as well as pediatricians. CMV is the most common congenital virus infection. In the case of a primary infection, the fetus of a seronegative pregnant woman is exposed to the risk of permanent organ damage. The intrauterine transmission rate in CMV-seropositive women is low but postnatal reactivation and transmission by breast milk occur more frequently, especially in premature babies. In this review we discuss the consequences of intrauterine and postpartum transmission from a neonatological point of view. With regard to the severity of the symptoms and possible long-term consequences, the time of infection with CMV is of great importance. Prevalence, diagnostic tools, and possible options for treatment or prevention differ for each mode of CMV infection.

[Ovarian hyperstimulation syndrome in preterm infants]. / Ovarielles Hyperstimulationssyndrom bei frühgeborenen Mädchen.

Ovarian cysts are a relatively frequent finding in fetuses and neonates. In preterm infants, a simultaneous occurrence of estradiol-producing ovarian cysts and edematous swelling of the vulva, the thighs and the lower abdominal wall was described by Sedin and co-workers in 1985 for the first time. This ovarian hyperstimulation syndrome occurred at a postconceptional age that slightly preceded the expected time of delivery. We report on four extremely low birth weight infants who were observed in the neonatal ward with ovarian cysts and stimulation of the external and internal genitalia, beginning at a postconceptional age of 35 to 39 weeks. The serum concentration of estradiol was within or above the range of the preovulatory peak of adults in all patients. Other causes of edema in preterm infants were excluded. The findings receded during 5 - 9 weeks. It is supposed, that in some cases the physiologically high concentration of gonadotropins in preterm infants stimulates the ovaries to produce ovarian cysts as well as to secrete high amounts of estradiol. This induces a transient stimulation of the external and internal genitalia as in idiopathic or transient precocious puberty.

[Hydrocephalus in one twin after massive reverse flow in the umbilical artery in the 2nd trimester]. / Hydrozephalus eines Zwillings nach massivem Rückstrom in der Nabelarterie im 2. Trimenon.

The case of a twin pregnancy with severe diastolic reverse flow in the umbilical artery of one of the twins at 23 weeks' gestation is reported. After delivery at 29 weeks' gestation, a congenital internal hydrocephalus was diagnosed in this twin. The most probable aetiology is an intrauterine periventricular haemorrhage. The severe diastolic reverse flow in the umbilical artery seems to represent a highly pathological flow pattern of prefinal degree, possibly leading to cerebral defects. The pathophysiology of the Doppler findings and the pathogenesis of the internal hydrocephalus are discussed.

[Chronic metabolic alkalosis in a newborn infant caused by congenital chloride diarrhea]. / Chronische, metabolische Alkalose bei einem Neugeborenen durch eine kongenitale Chloriddiarrhö.

The case of a female preterm infant (gestational age 36 weeks) is described, who presented with abdominal distension, diarrhoea, dehydration and metabolic alkalosis at the fifth day of life. After different diagnostic tests had been performed, congenital chloride diarrhoea was suspected and chloride supplementation was started. However, this diagnosis could not be confirmed, until the measurement of electrolytes in faeces had been improved. Then, we found the typically elevated fecal chloride concentration (130-153 mmol/l) which exceeded the sum of the fecal concentration of sodium (64-90 mmol/l) and potassium (28-35 mmol/l). The chloride supplementation was increased to 6 mmol/kg/d NaCl and 2 mmol/kg/d KCl. The most recent examination at the age of 1 year revealed the girl to be in good clinical condition, with normal growth and psychomotor-development and with no evidence of renal impairment.

Fatal hepatic veno-occlusive disease in a newborn infant.

We describe a newborn infant with veno-occlusive disease (VOD) of the liver. Prior to discharge from the hospital, the newborn, who had been treated for suspected neonatal infection, suddenly developed sepsis-like symptoms. The size of the liver as well as serum activity of hepatic enzymes increased progressively. Initial Doppler-flow studies demonstrated an absent flow in the vena portae, a finding that was compatible with vena portae thrombosis or occlusion of other hepatic veins. A therapy with recombinant tissue plasminogen activator (rt-PA) was initiated; due to extensive bleedings from various sides, the fibrinolytic therapy had to be withdrawn 12 hours later, when Doppler-flow examination revealed a reverse flow in hepatofugal direction. Despite supportive therapy, the general condition of the patient deteriorated continuously, finally resulting in liver and renal failure. Our patient died 19 days after birth. The autopsy demonstrated obliterative lesions of the centrilobular and sublobular hepatic veins, the classical signs of VOD of the liver. Despite extensive diagnostics and examinations, the etiology of VOD could not been elucidated in this newborn.

Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding.

BACKGROUND: Breastfeeding practices strongly influence the epidemiology of human cytomegalovirus infection. By contrast with term neonates, few data are available on transmission of infection from mothers to preterm infants during breastfeeding. METHODS: 151 mothers and their 176 preterm infants (gestational age at birth <32 weeks or birthweight <1500 g) were prospectively screened for cytomegalovirus infection by serology, virus culture, and PCR. The roles of cell-free and cell-associated cytomegalovirus excretion during lactation were analysed longitudinally in relation to transmission, by maximum-likelihood estimates. FINDINGS: Of the 69 seronegative breastfeeding control mothers, none had detectable cytomegalovirus DNA in breastmilk and none of their 80 infants shed the virus in urine. The proportion of cytomegalovirus reactivation in seropositive breastfeeding mothers was 96% (73 of 76). The early appearance of viral DNA in milk whey (median 3.5 days post partum in transmitters; 8 days in non-transmitters; p=0.025) and infectious virus in milk whey (10 days and 16 days, respectively; p=0.005) were risk factors for transmission. The cumulative rate of transmission was 37% (27 of 73 mothers; 33 infants). The infection of the neonates had a mean incubation time of 42 days (95% CI 28-69). About 50% of the infected infants had no symptoms, but four had sepsis-like symptoms. INTERPRETATION: The proportion of cytomegalovirus reactivation during lactation almost equals maternal seroprevalence. Breastfeeding as a source of postnatal cytomegalovirus infection in preterm infants has been underestimated and may be associated with a symptomatic infection.

[Breast feeding of very preterm infants of HCMV-seropositive mothers]. / Muttermilchernährung der sehr unreifen Frühgeborenen von HCMV-seropositiven Müttern -- Stellungnahme.

Preterm infants can be infected with human cytomegalovirus (HCMV) transmitted via breast milk of their HCMV-seropositive mothers, 96 % of whom reactivate the virus during lactation. 38 % of exposed VLBW infants become infected, with 48 % of these developing at least one symptom. Whether priority should be given to the multiple advantages of breast milk feeding or to the avoidance of a possible HCMV infection by exclusive formula feeding still cannot be decided due to insufficient data on the long-term outcome of infected infants. Inactivation of HCMV in breast milk can be achieved safely only via heat treatment, but the clinical consequences resulting from the use of pasteurized breast milk are unknown. Given the above situation, the authors decided to continue breast-feeding of VLBW and ELBW infants in their units after obtaining informed parenteral consent, until data for an evidence-based decision become available.