Prevention of maternal-fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration.

OBJECTIVE: To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to prevent maternal-fetal transmission of cytomegalovirus (CMV) in women with primary first-trimester CMV infection. METHODS: This was a prospective observational study of women with confirmed primary CMV infection in the first trimester who had the first HIG administration at or before 14 weeks' gestation. All women had biweekly HIG treatment until 20 weeks' gestation at a dose of 200 IU/kg of maternal body weight. Each subject underwent amniocentesis at least 6 weeks after first presentation at about 20 weeks. Primary outcome was maternal-fetal transmission at the time of amniocentesis, and secondary outcome was the frequency of congenital CMV infection at birth. The results were compared with a historic cohort of women with first-trimester CMV infection who did not undergo HIG treatment and who had amniocentesis at about 20 weeks. RESULTS: Subjects were 40 pregnant women with a primary CMV infection, with a median gestational age at first presentation of 9.6 (range, 5.1-14.3) weeks. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks. Within this interval, HIG was administered between two and six times in each patient. While CMV immunoglobulin-G (IgG) monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV-IgG avidity indices remained stable over the whole treatment period. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5% (95% CI, 0-13.2%)). At delivery, two additional subjects were found to have had late-gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% (95% CI, 1.6-20.4%) in our 40 cases. All infected neonates were asymptomatic at birth. The matched historical control group consisted of 108 pregnancies. Thirty-eight transmissions (35.2% (95% CI, 26.2-45.0%)) occurred in the control group, which was significantly higher (P < 0.0001) than the transmission rate in the HIG treatment group. CONCLUSION: After a primary maternal CMV infection in the first trimester, biweekly HIG administration at a dose of 200 IU/kg prevents maternal-fetal transmission up to 20 weeks' gestation. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

[Combination of Excessive Weight Gain and Interleukin-8: A Possible Predictor of Necrotising Enterocolitis in Neonates?]. / Kann ein Gewichtssprung in Kombination mit einem Anstieg des Interleukin-8 eine nekrotisierende Enterokolitis bei Neonaten vorhersagen?

BACKGROUND: Weight gain before the clinical diagnosis of necrotising enterocolitis (NEC) is described as a predictive factor. HYPOTHESIS: Weight gain of more than 5% one day prior to clinical suspicion plus increase of plasma Iinterleukin-8 (IL-8) are predictive for NEC. METHODS: 48 infants with diagnosis of NEC stage II and III were enrolled in a case-control study. Oral and parenteral nutrition, diuresis and kinetics of weight and of IL-8 were documented. RESULTS: 31 infants with NEC-II and 17 infants with NEC-III were enrolled. Weight gain>5% occurred in 35.3% of NEC-III, in 0% of NEC-II and in 4.2% of the control group. IL-8 increased significantly [NEC-III (6 561.4 pg/mL) vs. NEC-II: (326.7 pg/mL) vs. control group (38.9 pg/mL); p<0.05]. Sensitivity of IL-8 in NEC-II was 87.10% (70.15-96.25) and in NEC-III 100.00% (80.33-100.00). Sensitivity of weight gain was 0.00% (0.00-11.32) in NEC-II and 35.29% (14.30-61.65) in NEC-III. CONCLUSION: Weight gain>5% was found in only 35.3% of the cases with NEC-III. Combination of weight gain and IL-8 did not improve the diagnosis of NEC.

Diagnostic value of immature myeloid information in early-onset bacterial infection in term and preterm neonates.

BACKGROUND: For quick detection of neonatal early-onset bacterial infection (EOBI) pro-inflammatory cytokines like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in combiantion with C-reactive Protein (CRP) have been used. Automated determination of immature myeloid information (IMI) seems to be an additional useful tool in the diagnosis of NBI. OBJECTIVE: To compare the diagnostic value of IMI, I/T-Ratio, plasma IL-6 and IL-8 levels and CRP in term and preterm neonates at time of clinical suspicion of EOBI. PATIENTS AND METHODS: 31 preterm and 123 term neonates with clinical and serological signs of EOBI were analysed. 91 preterm and 159 term neonates with risk factors but without proven EOBI served as non-infected controls. RESULTS: Neonates with EOBI showed significantly elevated IMI levels at time of first clinical suspicion of EOBI (Preterm: 1 028/µL (38-8 759) vs. 289/µL (6-3 126); Term: 1 268/µL (48-14 035) vs. 856/µL (19-5 735); p<0.05 respectively). I/T-Ratio, IL-6, IL-8 and CRP values were significantly higher in preterm and term neonates with EOBI (p<0.05). Sensitivity of IMI at a cut-off level of 650/µL was 84.2% [95%-CI: 74.0-91.6%] in preterm and 65.4% [95%-CI: 56.8-73.3%] in term infants. Specificity was 66.7% [95%-CI: 47.1-82.7%] and 53.9% [95%-CI: 43.8-63.7%], respectively. Combination of different infection parameters improved sensitivity up to 93.5% and specificity up to 98.9%. CONCLUSION: The diagnostic value of IMI in diagnosing EOBI in preterm and term neonates is not comparable to IL-6, IL-8 and CRP. Combination of IMI-Channel with IL-6, IL-8 or CRP improves their sensitivity, specificity and predictive value.

Are recommended phototherapy thresholds safe enough for extremely low birth weight (ELBW) infants? A report on 2 ELBW infants with kernicterus despite only moderate hyperbilirubinemia.

Two extremely low birth weight (ELBW) infants developed characteristic signs of kernicterus at 4 and 8 months corrected age despite only moderate neonatal hyperbilirubinemia (peak serum bilirubin <10 g/dl) and phototherapy being applied according to current guidelines. Both girls were from twin pregnancies and had fetal complications (donor in a twin-twin transfusion syndrome and acardius-acranius malformation in the second twin, respectively), connatal anemia (initial hematocrit 30%), and mild acidosis after birth. They had been neurologically normal at discharge except for abnormal otoacustic emissions (OAE). At the time kernicterus was diagnosed, both infants were nearly deaf, showed severe psychomotor retardation with dystonic features and had marked bilateral hyperintensities in the globus pallidum on MRI. Based on these and similar cases from the literature, we question whether current phototherapy guidelines are appropriate for high-risk ELBW infants. Lower thresholds may be preferable, at least if additional risk factors, such as anemia, are present.

Cognitive and psychosocial development of children with Pierre Robin sequence.

AIM: It is unclear whether cognitive impairment in Pierre Robin sequence (PRS) results from a primary disturbance affecting both the brain and the mandible or from recurrent upper airway obstruction (UAO). If the latter were true, cognitive impairment should be preventable by early treatment of UAO. We wanted to determine the cognitive and psychosocial outcome of children with PRS treated with a new device aimed at relieving UAO in infancy (pre-epiglottic baton plate). METHODS: Thirty-four children with PRS and 34 healthy controls aged 4-11 years completed the Kaufman-Assessment Battery for Children (K-ABC) and a self-concept inventory. Parents rated their children's emotional and behavioural problems. Multi- and univariate analyses of covariance were performed, controlling for gender, age, parental education, family income and parental depression. RESULTS: The cognitive development of the PR children was within the reference range. Compared to healthy children, however, the children with PRS performed significantly poorer. There were no significant differences concerning self-concept, emotional or behavioural problems. CONCLUSION: These children with non-syndromic PRS who had received treatment of UAO in infancy performed worse in the K-ABC. However, this did not reflect a major cognitive impairment.

Pathological prenatal Doppler sonography findings and their association with neonatal cranial ultrasound abnormalities in a high risk collective.

The aim of this study was to evaluate whether prenatal Doppler ultrasound plays a role in the risk assessment of neonatal abnormal cranial ultrasound findings (NACU). Doppler examinations of blood flow velocities in the umbilical artery (n = 132), the fetal middle cerebral artery (n = 96) and the ductus venosus (n = 46) were conducted in 132 consecutive high-risk cases. The cases were divided into three groups: normal (I), pathological (II) and highly pathological Doppler (III) results, according to the resistance index calculated and were assessed for any association between the Doppler groups and the short-term outcome of the neonate, especially NACU. A significant association was found between Doppler groups and gestational age at delivery, birth weight, length and head circumference, growth restriction, cesarean section rate, Apgar score and pH values. NACU was diagnosed significantly more often in the pathological (12.1%) and highly pathological (38.5%) Doppler groups than in the group with normal Doppler (1.7%; p < 0.001). Multivariate analysis showed that the Doppler groups (odds ratio 1.67, 95% confidence interval [CI] 1.14-2.84, p < 0.001) and gestational age at delivery (odds ratio 1.37, 95% CI 1.08-2.74; p < 0.001) were independent variables that could be used to predict NACU. The present study showed that a pathological prenatal Doppler result is highly predictive for NACU in addition to gestational age and can therefore be used for risk assessment.

1H-NMR metabolic profiling of human neonatal urine.

OBJECT: The measurement of different urine components and their changes over time may provide comprehensive and early information about perinatal metabolic processes and physiological changes. We hypothesized that (1) H-NMR-spectroscopy generating a complex spectral profile without pre-selection of urinary metabolites could identify metabolites determining the neonatal physiological status and discriminating between different metabolic states. MATERIALS AND METHODS: We studied spot urine of three groups of neonates (healthy term-born, term-born with non-specific bacterial infections, and preterm neonates) for the first 6 days of life using (1) H-NMR-spectroscopy. In the group of healthy neonates metabolites changing were identified and their excretion patterns compared between groups. RESULTS: Six metabolites indicating physiological changes were identified: N-methylnicotinamide (NAD (+)-pathway), formate, hippurate, betaine (kidney development), taurine (neuronal development), and bile acids (hepatic clearance). While the dynamic changes over the first 6 days were the same for all metabolites in both groups of term-born neonates, the excretion of N-methylnicotinamide and taurine was significantly higher in preterm neonates compared to healthy term neonates and neonates with bacterial infections from the third day after birth (P < 0.05). CONCLUSION: Urine analysis using (1) H-NMR-spectroscopy could identify markers for perinatal metabolic changes. Further studies have to clarify if the proposed physiological interpretation will correlate with long-term physiological development.

[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.

The development of cerebral perfusion in healthy preterm and term neonates.

Quantitative measurement of cerebral blood flow (CBF) volume was performed by sonographic flowmetry of both internal carotid (ICA) and vertebral arteries (VA) in 113 healthy preterm and term infants of 32 - 42 weeks postmenstrual age (PA) in order to delineate the physiological characteristics of brain perfusion in a time period very sensitive to brain injury. Mean CBF volume increased with PA, beginning with 33 +/- 9 ml/min in neonates of 32 - 34 weeks and rising to 45 +/- 10, 58 +/- 13, 69 +/- 14, and 83 +/- 16 ml/min, respectively, in the PA groups of 35 - 36, 37 - 38, 39 - 40 and 41 - 42 weeks. There was no difference in CBF volume between the sexes. The bilateral sum of flow volumes in both ICA and VA rose markedly with PA. The relative contribution of bilateral VA flow volume to total CBF volume was 26 +/- 8 % and remained constant with PA. In addition, we calculated the approximate CBF (ml/100 g brain weight/min) using the brain weights of each child as estimated by means of an equation based on head circumference measurements. Estimated CBF correlated significantly with PA (r = 0.49; p

Treatment strategies for bronchopulmonary dysplasia with postnatal corticosteroids in Europe: the EURAIL survey.

AIM: To survey practices in 14 European countries and describe strategies for the prevention and treatment of bronchopulmonary dysplasia with postnatal steroids (PNS). METHODS: In 1999-2000 questionnaires covering the use of PNS were sent to every neonatal unit taking very preterm newborns in charge, in population-based areas covering at least 20000 births annually. One questionnaire was sent to surveyed unit. The participating areas were chosen by an expert from each country participating in the Europe Against Immature Lung (EURAIL) study group. RESULTS: Responses to 331 questionnaires were received; the mean response rate by countries was 84% (range 64-100%). Teaching hospitals accounted for 19% of the responding units. The number of extremely premature newborns (less than 28 wk of gestation) admitted yearly to these units was 0 in 16%, < 20 in 62%, 20-39 in 11% and > 39 in 11%. Overall, 67% of the centres used PNS: 48% initiated treatment in non-intubated infants and 53% at 7-14 d. Treatment duration was 4-15 d in 62% and > 15 d in 21%. PNS administration was limited to intubated infants less often in smaller units [odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6] and more often in non-teaching hospitals (OR 2.5, 95% CI 2.5-5.0). CONCLUSIONS: Although PNS have important side effects, they were still widely used in 1999 to treat or prevent chronic lung disease. Surprisingly, steroids are still prescribed in non-ventilated infants. PNS use should be based on guidelines derived from the evidence from randomized controlled trials. This evidence should be regularly updated and disseminated.

Measurement of volume of cerebral blood flow in healthy preterm and term neonates with ultrasound.

Changes in cerebral blood flow are important in the pathogenesis of ischaemic brain damage, but standard methods cannot measure volume of cerebral blood flow quantitatively in neonates. We used colour duplex sonography of the extracranial cerebral arteries to measure volume of global cerebral blood flow in 67 healthy preterm and term neonates. Volume of cerebral blood flow increased between the postmenstrual ages of 34 weeks (median 33 mL/min [range 23-43]) and 42 weeks (85 mL/min [57-104]). However, intersession and interobserver variability was quite large. This non-invasive method will allow quantitative bedside monitoring of global brain perfusion in preterm and term neonates with pathological disorders, and could also be used to monitor effects of neuroprotective measures.

[Newborn with phocomelia and thrombocytopenia. Case report]. / Neugeborenes mit Phokomelie und Thrombozytopenie - Ein Fallbericht.

Associated malformations and symptoms may be decisive in the differential diagnosis of neonatal phocomelia. We report on a neonate with phocomelia, petechiae and thrombocytopenia. This constellation is typical for the phocomelia-thrombocytopenia-syndrome, a variant of the thrombocytopenia-absent radius-(TAR) syndrome. During the neonatal period platelet transfusions were necessary. Relevant bleeding and development delays were not evident until the age of seven months. Cardinal symptoms of the TAR syndrome are bilaterally absent radius and neonatal thrombocytopenia. The patient presented with phocomelia of the upper extremities which occurs in only 5 - 10 % of the patients with TAR syndrome. Further abnormalities include additional bone and joint disorders and haematopoietic problems, such as thrombocytopenia. Bleeding episodes mainly occur in the first year of life, hence platelet transfusions may be necessary during this period. A new experimental approach is the Interleukin-6-mediated stimulation of thrombopoiesis. Usually platelet counts reach normal values in adults. The main problem remains a satisfactory management of various limb defects.

Three-dimensional computer morphometry of the maxilla and face in infants with Pierre Robin sequence--a comparative study.

OBJECTIVE: To analyze the morphology of the maxillary crest in infants with Pierre Robin sequence using an anthropometric coordinate system and to compare the data with those of healthy infants. SETTING: The study was performed at a craniofacial center servicing a large geographic area. PARTICIPANTS: The study involved eight infants aged 1-28 days (average, 7 days) with an established diagnosis of Pierre Robin sequence and six healthy infants aged 1-43 days (average, 22 days). MAIN OUTCOME MEASURES: Physical models of the maxilla and face obtained by alginate replication were analyzed by computer morphometry yielding the three-dimensional topology of the maxillary crest. RESULTS: The maxillary crest of children with Pierre Robin sequence shows an increased inclination relative to the transverse plane (30 +/- 3.9 degrees) as compared with that of healthy infants (20 +/- 2.9 degrees). The maxillary crest of the patients is shortened in the sagittal direction by comparison with healthy controls. CONCLUSIONS: The increased inclination of the maxilla in infants with Pierre Robin sequence may aggravate the retroposition of the mandible and may thus be a pathogenetic factor contributing to the severe respiratory problems.

Circulatory changes following intrauterine closure of the ductus arteriosus in the human fetus and newborn.

Prenatal detection of intrauterine closure of the ductus arteriosus unrelated to maternal administration of non-steroidal anti-inflammatory drugs or glucocorticoids made it possible to study the circulation in this condition in the human fetus and newborn by pre- and postnatal echocardiography and neonatal cardiac catheterization. At 38 weeks, the fetus presented intrauterine ductal closure associated with right ventricular dilatation and marked hypertrophy of the right ventricle and the interventricular septum, as well as severely diminished right ventricular fractional shortening and diminished pulmonary blood flow. Blood flow redistribution was characterized by reduced blood flow through the right heart and increased right-to-left shunting across the dilated foramen ovale. Pathological Doppler waveforms of the inferior vena cava and the ductus venosus were found, although the cardiotocogram was normal. Following unsuccessful induction of labour a Caesarean section was performed. Postnatal echocardiography confirmed the prenatal findings. Cardiac catheterization, performed because of persistent dependence on additional oxygen administration, revealed increased pulmonary vascular resistance, reduced pulmonary blood flow, and prolonged right-to-left shunt across the foramen ovale. Reduced peripheral pulmonary artery diameters were shown angiographically. Follow-up examinations revealed regression of right ventricular hypertrophy and recovery of right ventricular and pulmonary function. The findings confirm results from haemodynamic studies in animal experiments.

Prenatal detection of double aneuploidy trisomy 10/monosomy X in a liveborn twin with exclusively monosomy X in blood.

Both double aneuploidy and trisomy 10 are rare chromosome findings. All five published cases of trisomy 10 in liveborns were found to be mosaic with an euploid cell line. In a liveborn female twin, double aneuploidy mosaicism 47,XX, + 10/45,X was detected prenatally by amniocentesis performed because of severe intrauterine growth retardation and malformations. Chromosome analysis from neonatal lymphocyte cultures revealed exclusively the 45,X cell line. Double aneuploidy mosaicism trisomy 10/monosomy X was confirmed from skin fibroblasts. The child died at the age of 7 weeks. This is the first reported case of double aneuploidy involving trisomy 10, and the first case of trisomy 10 without a normal cell line in a liveborn. Prenatal diagnosis of trisomy 10 in a liveborn has not been published so far. The case illustrates that in specific cases amniotic fluid cells may reflect the karyotype of the fetus better than blood.

Ductus arteriosus-dependent pulmonary circulation secondary to cardiac malformations in fetal life.

The objective of this study was to describe the characteristic prenatal findings of a ductus arteriosus-dependent pulmonary circulation secondary to cardiac malformations. B-mode, color and pulsed wave Doppler echocardiography were performed in seven fetuses with severe pulmonary stenosis or atresia. All findings were confirmed postnatally by echocardiography and cardiac catheterization or autopsy. Severe fetal pulmonary stenosis or atresia was characterized by decreased pulmonary valve diameters, frequently with reduced pulmonary artery diameters, increased flow velocities or absent flow across the stenotic pulmonary valve, increased ascending aorta diameters, slightly increased aortic velocities and normal umbilical and middle cerebral artery Doppler wave forms. In all cases, prenatal assessment of neonatal ductus dependence was possible by demonstrating reverse flow across the fetal ductus with peak systolic velocities ranging from 0.9-2.0 m/s and absent diastolic flow. Ductal diameters were slightly decreased, ranging from 2-4 mm. Prenatal detection of a ductus-dependent pulmonary circulation is a strong indication of the presence of severe pulmonary stenosis or atresia. Its diagnosis allows avoidance of maternal administration of drugs with constrictive effects upon the ductus, interdisciplinary planning of perinatal management, early postnatal confirmation of the diagnosis, and early postnatal intervention, in particular administration of prostaglandins to prevent life-threatening ductal closure.

Multiple (up to seven) different accessory small marker chromosomes: prenatal diagnosis and follow-up.

We report on the prenatal discovery of 3 up to 7 accessory small marker chromosomes per cell with postnatal confirmation in various tissues. By FISH it could be shown that every marker had a different origin.

[Perinatally-induced hypoxic-ischemic encephalopathy? Possibilities of retrospective evaluation from the neuropediatric viewpoint]. / Perinatal verursachte hypoxisch-ischämische Enzephalopathie? Möglichkeiten der retrospektiven Beurteilung aus neuropädiatrischer Sicht.

This paper analyzes the feasibility of determining retrospectively, from a neuropediatric standpoint, whether an existing neurological disorder can be traced back to a perinatal hypoxic-ischemic encephalopathy. In principal, we can assume that there is a correlation between this time and pathogenesis of the brain injury on the one hand and the neurological symptoms on the other if these conditions are fulfilled 1. In the first days of live term infants revealed cerebral symptoms (like abnormality of muscle tone and consciousness and seizures) which manifest themselves in a typical sequence and are combined with involvement of other organ systems. In pre-term infants the clinical signs are often not clearly definable. 2. The subsequent neurological disorder after the primary symptoms must be a spastic-less commonly in term infants a dyskinetic one. 3. Lesions typical for the child's gestational age are visible on magnetic resonance imaging.