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To determine the frequency of obstetrical adverse events and clinical outcome in infants following antenatal hyperimmune globulin (HIG) treatment for primary cytomegalovirus (CMV) infection in pregnancy. Data from 50 women including three twin pregnancies were retrospectively evaluated. Primary infection was defined by seroconversion or the presence of CMV-specific IgM and low IgG avidity. All women received two or more infusions of HIG (200 U/kg). Congenital CMV (cCMV) infection was diagnosed by detection of CMV in amniotic fluid and/or neonatal urine. We compared gestational age (GA) at birth, head circumference (HC) and birth weight (BW) of infants in our study cohort with those of live-born infants delivered in our clinic between 2015 and 2016. Median gestational age at time of maternal CMV diagnosis was 13 weeks. One-hundred-forty-one maternal HIG doses were given. No HIG-related severe adverse reactions occurred. Preterm birth rate was 4.2% (2/47) in singleton pregnancies. None of the neonates had birth weight or head circumference

In a large cohort study of the German Neonatal Network (GNN) we aimed to evaluate whether less invasive surfactant administration (LISA) strategy is associated with complications of preterm birth. Within the observational period n = 7533 very-low-birth-weight infants (VLBWI) with gestational age 22 0/7 to 28 6/7 weeks were enrolled in GNN; n = 1214 VLBWI never received surfactant, n = 2624 VLBWI were treated according to LISA procedure, n = 3695 VLBWI had surfactant via endotracheal tube (ETT). LISA was associated with a reduced risk for adverse outcome measures including mortality [odds ratio (OR) 0.66 (95% CI: 0.51–0.84), p

Objective To assess whether breastmilk feeding is associated with a reduced risk of bronchopulmonary dysplasia (BPD). Secondary outcome measures analyzed were retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). Study design In an ongoing multicenter cohort study, the data of 1433 very low birth weight infants born before 32 weeks of gestation and discharged in 2013 were analyzed. We compared growth and neonatal complications of infants who received breastmilk exclusively (N = 223) with those who received formula feedings exclusively (N = 239). Logistic regression models were estimated for BPD, ROP, and NEC using nutrition as an independent variable. The Firth logistic regression model and Lasso were used for sensitivity analyses. Results Exclusively breastmilk-fed infants gained less weight compared with formula-fed infants. SDS for weight decreased between birth and discharge (median (Q1-Q3): formula −0.9 (−1.4 to [−0.5]) vs breastmilk −1.1 (−1.7 to [−0.6])). Exclusive formula feeding of very low birth weight infants was associated with increased risks of BPD (OR 2.6) as well as NEC (OR 12.6) and ROP (OR 1.80) after controlling for known risk factors. Conclusions Exclusive breastmilk feeding was associated with lower growth rates and a reduced risk of BPD as well as NEC and ROP.

Importance Treatment of respiratory distress syndrome in premature infants with continuous positive airway pressure (CPAP) preserves surfactant and keeps the lung open but is insufficient in severe surfactant deficiency. Traditional surfactant administration is related to short periods of positive pressure ventilation and implies the risk of lung injury. CPAP with surfactant but without any positive pressure ventilation may work synergistically. This randomized trial investigated a less invasive surfactant application protocol (LISA). Objective To test the hypothesis that LISA increases survival without bronchopulmonary dysplasia (BPD) at 36 weeks’ gestational age in extremely preterm infants. Design, Setting, and Participants The Nonintubated Surfactant Application trial was a multicenter, randomized, clinical, parallel-group study conducted between April 15, 2009, and March 25, 2012, in 13 level III neonatal intensive care units in Germany. The final follow-up date was June 21, 2012. Participants included 211 of 558 eligible (37.8%) spontaneously breathing preterm infants born between 23.0 and 26.8 weeks’ gestational age with signs of respiratory distress syndrome. In an intention-to-treat design, infants were randomly assigned to receive surfactant either via a thin endotracheal catheter during CPAP-assisted spontaneous breathing (intervention group) or after conventional endotracheal intubation during mechanical ventilation (control group). Analysis was conducted from September 6, 2012, to June 20, 2013. Intervention LISA via a thin catheter. Main Outcomes and Measures Survival without BPD at 36 weeks’ gestational age. Results Of 211 infants who were randomized, 104 were randomized to the control group and 107 to the LISA group. Of the infants who received LISA, 72 (67.3%) survived without BPD compared with 61 (58.7%) of those in the control group. The reduction in absolute risk was 8.6% (95% CI, −5.0% to 21.9%; P = .20). Intervention group infants were less frequently intubated (80 infants [74.8%] vs 103 [99.0%]; P P = .04) and severe intraventricular hemorrhage (11 infants [10.3%] vs 23 [22.1%]; P = .02), and the combined survival without severe adverse events was increased in the intervention group (54 infants [50.5%] vs 37 [35.6%]; P = .02; absolute risk reduction, 14.9; 95% CI, 1.4 to 28.2). Conclusions and Relevance LISA did not increase survival without BPD but was associated with increased survival without major complications. Because major complications are related to lifelong disabilities, LISA may be a promising therapy for extremely preterm infants. Trial Registration isrctn.org Identifier:ISRCTN64011614

Objective Preterm infants are at risk of acquiring human cytomegalovirus (CMV) infection through breast milk transmission, possibly leading to serious symptoms, as suggested by previous studies. Over a period of 8.5 years, we compared infants infected postnatally with CMV with noninfected controls to determine whether CMV infection transmitted through breast milk poses serious acute risks. Study design CMV monitoring included maternal serologic testing and biweekly viral culture and polymerase chain reaction in breast milk and infant urine. Clinical and laboratory test findings were assessed retrospectively in infected infants and controls matched for gestational age during the initial hospital stay. Results Forty CMV-infected infants met the study criteria. They had lower minimal platelet and neutrophil counts and a higher frequency of C-reactive protein (CRP) elevations to 10 to 20 mg/L than their matched controls ( P ≤ .001). But no association of CMV infection with bronchopulmonary dysplasia, necrotizing enterocolitis, growth, or CRP elevations to > 20 mg/L was found. Cholestasis appeared in 3 infants in the CMV-infected group, but disappeared within 10 weeks. Conclusions Neonatal symptoms related to postnatal CMV infection were transient and had no affect on neonatal outcome in these infants, in contrast with uncontrolled reports. Whether withholding or pasteurizing breast milk is warranted, however, depends on long-term outcome.

Background: After elimination of CMV transmission by blood products we have still observed preterm infants with postnatally acquired CMV infections. 16 preterm infants with CMV infection by breast milk were identified. Methods: CMV-DNA PCR and viral cultures. Criteria of transmission: CMV in breast milk; viruria in preterm infants; exclusions of congenital infection, of donor's breast milk and of CMV seropositive blood transfusions. Results: 8 infants (50 %) had marked symptoms of an acute CMV infection: sepsis-like symptoms with apnoea and bradycardia (4), cholestasis/hepatitis (4/2), thrombocytopenia (6), neutropenia (5). Infection in the latter group occurred at an median postnatal age of 46 vs. 62 days in asymptomatic infected infants (p < 0.01). Conclusion: There is a high incidence of symptomatic CMV infections in preterm infants due to breast milk transmission. An early postnatal CMV infection seems to be associated with a symptomatic clinical course.

BACKGROUNDThe FTO gene, located on chromosome 16q12.2, and the MAF gene, located on chromosome 16q22-23, were identified as genes harboring common variants with an impact on obesity predisposition. We studied the association of common variants with birth weight, gain of body weight, body mass index (BMI), Ponderal index and relevant neonatal outcomes in a large German cohort of infants with a birth weight below 1500 grams.METHODSThe single nucleotide polymorphisms rs9939609 (FTO gene) and rs1424233 (MAF gene) were genotyped using allelic discrimination assays in a prospective multicenter cohort study conducted in 15 neonatal intensive care units in Germany from September 2003 until January 2008. DNA samples were extracted from buccal swabs according to standard protocols.RESULTS1946 infants were successfully genotyped at FTO and 2149 infants at MAF. Allele frequencies were not significantly different from other European cohorts. The polymorphisms were in Hardy-Weinberg equilibrium. The polymorphisms did not show associations with birth weight, BMI and Ponderal Index at discharge, and weight gain, neither testing for a dominant, additive nor for a recessive model.DISCUSSIONSince an association of the polymorphisms with weight gain has been demonstrated in multiple populations, the lack of association in a population of preterm infants with regular tube feeding after birth and highly controlled feeding volumes provides evidence for the hypothesis that these polymorphisms affect food intake behavior and hunger rather than metabolism and energy consumption.

Introduction: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. Methods: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. Results: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. Discussion: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care. © 2012 Härtel et al. OA gold

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.

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.Prospective study of mother-child pairs after preterm delivery before 32 weeks or birth weight1500 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.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.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.

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.

To the Editor: During labor at term, a 23-year-old woman took a 30-minute tub bath for relaxation in the morning, in water with a temperature of 37°C. She gave birth to a 3170-g boy later that day. Mother and child left the clinic three days later. At day 11, the infant had poor suckling, lethargy, and seizures. Meningitis with bacteremia was diagnosed by the isolation of Pseudomonas aeruginosa from cerebrospinal fluid, blood, and a conjunctival swab. In spite of immediate antipseudomonal chemotherapy (ampicillin, cefotaxime, and gentamicin), acute hydrocephalus developed. Ventriculostomy with external drainage and a ventriculoperitoneal shunt were required. Over . . .

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.151 mothers and their 176 preterm infants (gestational age at birth32 weeks or birthweight1500 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.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.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.

Objective: Incidence and significance of postnatal CMV transmission by breast milk in premature infants.