Horst Buxmann

Incidence and clinical outcome of cytomegalovirus transmission via breast milk in preterm infants ≤31 weeks

Aim: To evaluate incidence, timing and clinical relevance of acquired human cytomegalovirus (HCMV) infection in preterm infants.

Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial

BACKGROUND Tolerating higher partial pressure of carbon dioxide (pCO2) in mechanically ventilated, extremely low birthweight infants might reduce ventilator-induced lung injury and bronchopulmonary dysplasia. We aimed to test the hypothesis that higher target ranges for pCO2 decrease the rate of bronchopulmonary dysplasia or death. METHODS In this randomised multicentre trial, we recruited infants from 16 tertiary care perinatal centres in Germany with birthweight between 400 g and 1000 g and gestational age 23-28 weeks plus 6 days, who needed endotracheal intubation and mechanical ventilation within 24 h of birth. Infants were randomly assigned to either a high target or control group. The high target group aimed at pCO2 values of 55-65 mm Hg on postnatal days 1-3, 60-70 mm Hg on days 4-6, and 65-75 mm Hg on days 7-14, and the control target at pCO2 40-50 mmHg on days 1-3, 45-55 mm Hg on days 4-6, and 50-60 mm Hg on days 7-14. The primary outcome was death or moderate to severe bronchopulmonary dysplasia, defined as need for mechanical pressure support or supplemental oxygen at 36 weeks postmenstrual age. Cranial ultrasonograms were assessed centrally by a masked paediatric radiologist. This trial is registered with the ISRCTN registry, number ISRCTN56143743. RESULTS Between March 1, 2008, and July 31, 2012, we recruited 362 patients of whom three dropped out, leaving 179 patients in the high target and 180 in the control group. The trial was stopped after an interim analysis (n=359). The rate of bronchopulmonary dysplasia or death in the high target group (65/179 [36%]) did not differ significantly from the control group (54/180 [30%]; p=0·18). Mortality was 25 (14%) in the high target group and 19 (11%; p=0·32) in the control group, grade 3-4 intraventricular haemorrhage was 26 (15%) and 21 (12%; p=0·30), and the rate of severe retinopathy recorded was 20 (11%) and 26 (14%; p=0·36). INTERPRETATION Targeting a higher pCO2 did not decrease the rate of bronchopulmonary dysplasia or death in ventilated preterm infants. The rates of mortality, intraventricular haemorrhage, and retinopathy did not differ between groups. These results suggest that higher pCO2 targets than in the slightly hypercapnic control group do not confer increased benefits such as lung protection. FUNDING Deutsche Forschungsgemeinschaft.

Recombinant activated Factor VII as a hemostatic agent in very low birth weight preterms with gastrointestinal hemorrhage and disseminated intravascular coagulation.

Objective Acute hemorrhage in preterm infants leads immediately to a life-threatening event because of the small circulating blood volume. The beneficial use of recombinant activated Factor VII (rFVIIa; NovoSeven, NovoNordisk, Gentofte, Denmark) as hemostatic treatment in neonates with hemorrhagic shock has been described. Necrotizing enterocolitis is a challenge in neonatology as the disease represents one of the leading causes of mortality in preterm infants. We report on the use of rFVIIa in very low birth weight (<1500 g), preterms with intestinal hemorrhage, and disseminated intravascular coagulation (DIC). Design Retrospective analysis of 5 cases. Patients Five preterm infants ≤28 weeks gestational age with DIC and hemorrhagic shock due to severe diffuse gastrointestinal bleeding. Intervention Intravenous bolus administration of 100 to 180-μg/kg rFVIIa (total of 9 doses) as rescue procedure after other interventions (substitution of platelets, fresh frozen plasma, red packed cells, surgery) failed to achieve hemostasis. Results Two patients with severe acidosis, hypothermia, and thrombopenia died in hemorrhagic shock, treatment with rFVIIa was unsuccessful. In 3 patients, rFVIIa was effective and gastrointestinal bleeding could be stopped. No acute adverse event, increasing bowel necrosis, increasing platelet consumption, or thromboembolic complications were observed. Conclusions In this small group of preterms with DIC, intestinal hemorrhage, and persistent hemorrhagic shock, rFVIIa was effective as a rescue therapy but failed in patients with severe acidosis, hypothermia, and thrombopenia.

Problems and challenges in the diagnosis of vertical infection with human cytomegalovirus (CMV): Lessons from two accidental cases

Human cytomegalovirus (CMV) is considered as the most common cause of congenital infection in humans and the overall burden for the public health system is rather high. About 1/10 of vertically infected newborns present or develop severe signs of cytomegalic inclusion disease (CID), with the classical triad of chorioretinitis, microcephaly and cerebral calcifications. However the most symptomatic cases are detected postnatal and methods of diagnostic virology raised the questions for the gold standard in laboratory screening. The current problems in diagnosis and therapy are outlined in two different cases: An acute primary CMV infection with no clinical signs of illness in both mother and child and a secondary CMV-infection resulting in necrotizing CMV encephalitis in the fetus. Beside virus detection in whole blood samples and other fluids, newly adopted laboratory assays like the destination of CMV-IgG avidity were necessary. Furthermore a serologic screening for pregnant women should be implicated routinely. Passive IgG treatment of the mother was helpful but the ultimate goal in prevention of congenital CMV infection is to develop a vaccine, which would be administered to seronegative women.

Three-Dimensional Body Scanning: A New Method to Estimate Body Surface Area in Neonates

Background: Body surface area (BSA) is usually estimated by calculation with mathematical formulae. Three-dimensional body scanning (3D scan) offers a suitable alternative. Objectives: We determined the BSA in healthy term and near-term neonates by 3D scanning. This system should be useful in the setting of intensive care medicine. Methods: The measuring system consisted of a projector, two cameras, mirrors and a computer, and used the fringe projection technique with visible light. The infants were examined in a supine position; the hidden parts of the bodies were corrected for using a mathematical factor developed with a baby doll model. Results of the 3D scans were compared with those from five mathematical formulae for each subject. Results: A total of 209 infants were studied by 3D scanning, of whom 53 had acceptable images and were selected for further analysis. The mean BSA was 2,139 cm2 (SD 223.72). The minimal BSA was 1,587 cm2, the maximal 2,670 cm2, with a good correlation to body weight and length. One mathematical formula (Du Bois and Du Bois) showed a distinct underestimation of BSA compared to 3D scanning, the others an overestimation. Mean percentage similarity was from 96.8 to 100.9%. Conclusions: 3D scanning is an accurate and practical method to estimate BSA in newborns. Individual and repeated measurements from day to day are possible. Further studies are warranted in preterm and sick neonates.

Influenza Vaccination Rates Among Parents and Health Care Personnel in a German Neonatology Department

The influenza vaccination is recommended for all German pregnant women and health care personnel (HCP). We are the first to publish vaccination rates of mothers of hospitalized newborns and HCP in neonatal units. Between September 2016 and March 2017, data were collected in our level-III neonatology department in this descriptive multidisciplinary study, using an anonymous questionnaire. As a result, 513 persons were asked to participate, including 330 parents and 183 HCP. We received an 80.3% (412/513) response rate, 87.3% (288/330), and 67.8% (124/183) from parents and HCP, respectively. Ten percent (16/160) of mothers and 4.7% (6/127) of fathers had been vaccinated in 2016–2017 and 54.4% (87/160) mothers and 52.2% (66/127) fathers ever in their lifetime. In 2016–2017, 51.2% (21/41) of physicians had been vaccinated, 25.5% (14/55) of nurses, and 50.0% (14/28) of other staff members. When comparing those who had more than five influenza vaccinations in their life time, physicians were at 43.9% (18/41) versus nurses at 10.9% (6/55) (p < 0.01), and other HCP at 7.4% (2/27) (p < 0.01). The influenza vaccine uptake rate of 10% in mothers of hospitalized neonates is disappointingly low, resulting in 90% of hospitalized neonates being potentially vulnerable to influenza infection at a time where the risk for influenza-related complication can be severe.

Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study

Background Tolerating higher partial pressures of carbon dioxide (PCO2) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial. Methods Infants (n=359) between 400 and 1000 g birth weight and 23 0/7–28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO2 or to a control group with mildly elevated PCO2 targets. Neurodevelopmental follow-up examinations were available for 85% of enrolled infants using the Bayley Scales of Infant Development II, the Gross Motor Function Classification System (GMFCS) and the Child Development Inventory (CDI). Results There were no differences in body weight, length and head circumference between the two PCO2 target groups. Median Mental Developmental Index (MDI) values were 82 (60–96, high target) and 84 (58–96, p=0.79). Psychomotor Developmental Index (PDI) values were 84 (57–100) and 84 (65–96, p=0.73), respectively. Moreover, there was no difference in the number of infants with MDI or PDI <70 or <85 and the number of infants with a combined outcome of death or MDI<70 and death or PDI<70. No differences were found between results for GMFCS and CDI. The risk factors for MDI<70 or PDI<70 were intracranial haemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, necrotising enterocolitis and hydrocortisone treatment. Conclusions A higher PCO2 target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO2 targets to optimise short-term outcomes is a safe option. Trial registration number ISRCTN56143743.

Prenatal Ultrasound Screening for Fetal Anomalies and Outcomes in High-Risk Pregnancies due to Maternal HIV Infection: A Retrospective Study

Objective. To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection. Study Design. The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated. Results. One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20–22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported. Conclusion. The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken.

Purpura Fulminans after Therapeutic Hypothermia in an Asphyxiated Neonate with Streptococcemia

OBJECTIVE Therapeutic hypothermia is an established therapeutic regimen in severely asphyxiated term neonates. The amount of cerebral injury is reduced resulting in an improved neurologic outcome. Therapeutic hypothermia-induced side effects mostly affect the circulatory system, kidney, and liver. However, asphyxia and hypothermia in itself reduce the hemostatic capacity of each individual organism. STUDY DESIGN A case of a neonate with severe asphyxia and purpura fulminans after hypothermia is described. RESULTS AND CONCLUSION Although purpura fulminans cannot be attributed to hypothermia solely, the influence of hypothermia on hemostasis may have promoted severe coagulopathy with a fatal outcome. Further studies are necessary to reveal therapeutic hypothermia as a trigger for severe coagulopathies in asphyxiated neonates, especially in those with sepsis and overt coagulopathy prior to therapeutic hypothermia.

Percentiles of Lymphocyte Subsets in Preterm Infants According to Gestational Age Compared to Children and Adolescents.

Preterm newborns show an increased susceptibility to infections, conceivably related to their immature immune system. To gain further knowledge about the immune development in early preterm infants, we aimed to establish references for lymphocyte subsets and compare the maturation process during hospitalization to healthy term‐born children and adolescents. For this purpose, peripheral blood samples (n = 153) were collected from 40 preterm infants, gestational age (GA) 26–30 week between 2nd and 6th day of life, and were monitored in intervals of every 2 or rather 4 weeks until the end of hospitalization. Furthermore, we analysed single sample controls of 10 term neonates. We compared these data with results of a study in healthy children and adolescent (n = 176). Flow cytometry of immune cell subsets was performed as single‐platform analysis using 10‐colour flow cytometry. Based on preterms age, our percentile model allows readout of absolute cell count for lymphocytes, B cells, T cells, NK cells, T8 and T4 cells. The median (minimum) value of T‐, B‐ and NK cells after birth was 2800 (600), 790 (120) and 140 (20) cells/μl, respectively. Major differences were found in absolute cell numbers of B cells, and in the frequency of regulatory T cells, most pronounced in the earliest preterm infants (GA 26). Compared to healthy children and adolescents, preterm infants reached lymphocyte counts in between the 5th and 50th percentile when discharging the hospital. This prospective observational study provides reference percentiles for lymphocytes subsets of preterm infants. These data are conducive to interpret immunological capability of preterm infants with possible immune disorders appropriate.