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Michael Obladen
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ABSTRACT: Wet nursing was widely practiced from antiquity. For the wealthy, it was a way to overcome the burdens of breastfeeding and increase the number of offspring. For the poor, it was an organized industry ensuring regular payment, and in some parishes the major source of income. The abuse of wet nursing, especially the taking in of several nurslings, prompted legislation which became the basis of public health laws in the second half of the 19th century. The qualifications demanded from a mercenary nurse codified by Soran in the 2nd century CE remained unchanged for 1,700 years. When artificial feeding lost its threat thanks to sewage disposal, improved plumbing, the introduction of rubber teats, cooling facilities and commercial formula, wet nursing declined towards the end of the 19th century.
Neonatology 07/2012; 102(3):222-8. · 2.66 Impact Factor
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ABSTRACT: Background: Vascular endothelial growth factor (VEGF) and its receptors regulate angiogenesis (formation of blood vessels). The soluble VEGF receptor 1 (sFlt-1) binds VEGF as a potent antagonist. Objective: The objective of this study was to compare VEGF and sFlt-1 levels in milk from mothers of preterm (n = 50) versus term (n = 49) infants in a longitudinal study. Methods: Milk samples were collected on days 3 and 28 of lactation. Vascular endothelial growth factor and sFlt-1 were quantified by sandwich-type enzyme-linked immunosorbent assay. Results: Vascular endothelial growth factor and sFlt-1 were found in high concentrations in early milk (lactation day 3) from mothers of preterm and term infants and were lower in mature milk (lactation day 28). On day 3, median VEGF concentration was lower in preterm than in term milk (37.1 vs 53.9 ng/mL, P < .01). Otherwise, VEGF (day 28) and sFlt-1 (days 3 and 28) did not differ in preterm versus term milk. Conclusions: It was shown for the first time that sFlt-1 is present in human milk. Early human milk contains high concentrations of VEGF and sFlt-1, which decrease over the course of lactation.
Journal of Human Lactation 06/2012; 28(4):522-8. · 1.15 Impact Factor
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ABSTRACT: Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in an in vitro model of hyperoxia-induced injury to immature oligodendrocytes. Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 microM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed. Suramin lead to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling. These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.
Neurotoxicity Research 04/2012; 13(3-4):197-207. · 3.51 Impact Factor
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Michael Obladen
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ABSTRACT: Before safe artificial nutrition, refrigeration, and microorganisms became known, thrush was a severe and frequently lethal disease in foundling hospitals. Overcrowded and understaffed, these institutions were the ideal breeding ground for this disease. Malnutrition, especially when breastfeeding was denied, contributed to the fatal course. Nosocomial infections and high mortality led to a prejudice against infant hospitals in the late 19th century. Candida albicans was discovered in 1840 when a cooperation at the Paris Foundling Hospital between the Hungarian emigrant David Gruby and the Swede Frederik Berg led to this organism being the first pathogen to be identified. After World War II, Candida infections increased with the use of antibiotics. The disease became less threatening after the development of nystatin, the result of an interdisciplinary cooperation in New York between the microbiologist Elizabeth Hazen and the biochemist Rachel Brown.
Neonatology 10/2011; 101(3):159-65. · 2.66 Impact Factor
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Michael Obladen
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ABSTRACT: The interest in the limit of viability originated from various sources, including legal requirements, the rejection of mechnical life support, competition for resources, concerns about handicaps, and proximity to the fetus with its limited rights. Gestational age was determined from menstrual history by Hippocratic writers, who established the tenacious idea that 7-, but not 8-month infants could survive. Naegele's rule, already published by Boerhaave in 1744, was correct when applied to the last day of menstruation. Birth weight and length were not measured until the end of the 18(th) century. This remarkable disinterest resulted from superstition, grossly inaccurate measurements by the authorities Mauriceau and Smellie, and the conversion chaos of the pre-metric era. A table is provided with historic mass and length units allowing to determine birth weight and body length in the older literature. The idea of viability is a remnant of vitalism, a medical doctrine popularized in 1780 by Brown. Many short-lived statements defined its limit, but until now what was meant by viability remained nebulous.
Journal of Perinatal Medicine 07/2011; 39(5):563-9. · 1.70 Impact Factor
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Michael Obladen
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ABSTRACT: Survivors of immaturity of outstanding intelligence include Fortunio Licetus, born in 1577, and Isaac Newton, born in 1643. Reliable descriptions began appearing around 1820, and over a dozen infants were born weighing under 1000 g and before World War II, who developed normally. From 1876 to 2006, the birth weight at which half of the infants survived dropped from 2200 to 600 g. Statistics depended on how abortion, stillbirth and live birth were defined, which differed greatly from country to country. WHO definitions in 1993 required the registration of all infants weighing 500 g (22 complete weeks) or above. This definition was not universally adopted, resulting in considerable underreporting. Many medical societies issued ethical recommendations concerning the obligatory or optional treatment of immature infants. The "window", at which treatment is optional has been set at 22-23 weeks (Japan, Germany), 23-24 weeks (UK, USA, Canada), or 24-26 weeks (France, Netherlands, Switzerland). Instead of assessing an infant's individual prognosis, and ignoring its gender, co-morbidities, and particular cause of premature delivery, these rules frequently relied on gestational age alone to initiate or withhold life support.
Journal of Perinatal Medicine 07/2011; 39(5):571-7. · 1.70 Impact Factor
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Michael Obladen
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ABSTRACT: Disturbed neurulation fascinated scientists of all times. In Egypt, anencephalic infants were venerated as animal-headed gods. Roman law required them to be killed. The medieval world held the mother responsible, either because of assumed imagination or "miswatching," or because of suspected intercourse with animals or devils. Modern embryology and teratology began with the use of the microscope by Malpighi in 1672. Details of neural tube closure were described by Koelliker in 1861 and by His in 1874. From 1822, genetic disease and familial recurrence due to insufficient nutrition were discerned and lower social class identified as a risk factor. It took a century to define the malnutrition as insufficient folate intake. The mandatory supplementation of folate in staple foods successfully reduced the incidence of neural tube defects in the United States, Australia, Canada, and Chile, but it was not adopted by most European countries.
Journal of child neurology 07/2011; 26(11):1452-61. · 1.59 Impact Factor
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ABSTRACT: Leptin is involved in the regulation of food intake and energy expenditure and is therefore important for growth and brain development. Analytical methods used for leptin measurement in human milk differ widely in the literature and yield varying results.
To compare different preparation methods for the analysis of leptin in human milk and to investigate the leptin levels in colostrum and mature human milk from mothers of preterm or term infants.
Mothers delivering a preterm (n=37) or a term infant (n=40) were recruited for a prospective study and were ask to collect breast milk on the 3rd and 28th day of lactation. Leptin, protein and fat concentrations were analysed. Clinical data of mother and child were recorded prospectively.
Skim milk was most appropriate for leptin analysis. Human milk leptin concentrations did not differ between preterm and term human milk. In term milk, leptin concentration on day 28 was lower than on day 3 (p<0.05). Milk leptin levels on the 3rd and 28th day were positively correlated with mothers' body mass index, but not with fat content in milk.
Skim milk was the most stabile preparation for leptin analysis. Preterm and term human milk contain leptin in equal concentrations. Human milk leptin depends on mothers' body mass index.
Early human development 06/2011; 87(6):415-9. · 2.12 Impact Factor
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Michael Obladen
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ABSTRACT: Deformations have been attributed to supernatural causes since antiquity. Cerebral palsy was associated with God's wrath, witchcraft, the evil eye, or maternal imagination. Greek scholars recommended prevention by tight swaddling, a custom that persisted into modern times. In the Middle Ages, the midwife's negligence was held responsible as was difficult teething. Morgagni described in 1769 that the neonatal brain can liquefy, and Bednar described leukomalacia in 1850 as a distinct disorder of the newborn. In 1861, Little associated cerebral palsies with difficult or protracted labor and neonatal asphyxia, but he was challenged by Freud, who in 1897 declared that most cases are prenatal in origin. In 1868, Virchow demonstrated inflammatory changes, a view recently confirmed by Leviton and Nelson. Although a causal relationship of cerebral palsy to the birth never has been established, the habit to put the blame for cerebral palsy on someone remained a frequent attitude.
Journal of child neurology 02/2011; 26(2):248-56. · 1.59 Impact Factor
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Michael Obladen
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ABSTRACT: Ductus arteriosus and foramen ovale were described by Galen without understanding their functions. His beliefs in soul localization and spiritization within the left ventricle established religious pneumatology which became a theological need in the Middle Ages. Pulmonary transit was recognized by Servetus and Colombo after the Reformation around 1550. This prompted Harvey's full understanding of the fetal circulation. Botallo did not describe the ductus arteriosus, but in 1564 redescribed the foramen ovale, making his way into the nomina anatomica by mistake. Most authors of the 19th and 20th century believed ductal patency to be passive, and postnatal closure to be an active process, explained by mechanical theories. After the discovery of prostaglandins by Bergstrom and Vane, Coceani proved that ductal patency is maintained by the relaxant action of prostaglandins.
Neonatology 01/2011; 99(2):83-9. · 2.66 Impact Factor
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Michael Obladen
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ABSTRACT: By 1769, it was known to Morgagni that the ductus arteriosus may persist until adulthood. In 1835, Jörg linked delayed postnatal closure with disturbed respiration, a discovery that was afterwards forgotten for a century. When blood gas analysis became available, the association between persisting patency and diminished oxygenation resurfaced. When it became known that prostaglandins played a role in maintaining ductal patency, the development of pharmacologic intervention with cyclooxygenase inhibitors immediately followed. This rapid progress was due to the interaction between basic science, pediatric cardiology, and neonatology disciplines at the Cardiovascular Research Institute in San Francisco, coordinated by Julius Comroe, as well as President Kennedy's foundation of the National Institute of Child Health and Development. This series of events exemplifies how clinical research became an integrated managed multidisciplinary endeavor in the 20th century.
Neonatology 01/2011; 99(3):163-9. · 2.66 Impact Factor
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Michael Obladen
Neonatology 12/2010; 99(4):312. · 2.66 Impact Factor
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ABSTRACT: Patent ductus arteriosus (PDA) is a frequent problem in preterm infants, and its incidence is inversely correlated with gestational age. The efficacy of medical treatment decreases with decreasing gestational age (GA), and failure rates as well as ductus ligation rates of 40% have been reported in <28 week GA newborns. The aim of this study was to determine whether echocardiographic parameters can predict response to ibuprofen treatment of PDA.
In a longitudinal study, 29 infants born <28 week GA were screened for a significant PDA (left atrial to aortic root ratio>1.4, anterior cerebral artery resistance index>0.8, and oxygen requirement>35%) at 24-72 h of life and, if a PDA was found, treated with 10-5-5mg/kg ibuprofen intravenously every 24h. Ductal parameters were monitored by serial echocardiography. Infant neurodevelopmental outcomes were assessed at 24 month corrected age.
All 15 infants with significant PDA responded to the ibuprofen loading dose indicated by reduced PDA diameters or increased PDA maximum flow velocities (PDA V(max)), and 7 patients showed an ongoing response resulting in a closed PDA after the 1st cycle (47%). Of the 8 non-responders, 7 received a 2nd cycle with 2 further responders (29%). All non-responders to the 2nd course had a PDA V(max)<or=180 cm/s and increasing ductal diameters after the 3rd ibuprofen dose of the 1st course.
Maximum flow velocity and diameter of the PDA at the end of the 1st cycle discriminate between responders and non-responders to further ibuprofen treatment.
Early human development 08/2010; 86(8):503-8. · 2.12 Impact Factor
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Michael Obladen
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ABSTRACT: A human being born without heart and head, i.e., the acardius/acranius malformation, has been described since antiquity. Superstition and fear made it a mystical disorder, a sign of God's wrath. The inquisition ruled that acranic infants should not be baptized and located the soul in the brain. Acardia was not associated with twin gestation until the reports of Mery in 1720 and Winslow in 1740. In 1850, Meckel identified the pathogenetic mechanism as reversed perfusion due to large arterio-arterial and veno-venous anastomoses; he believed the heart would fail to develop or arrest during development, and the acardiac fetus would be maintained by arterial perfusion from the pump twin. In 1859, Claudius articulated that after normal initial development, the heart degenerates when reversed flow in the aorta leads to thrombosis. Today, it is assumed that both mechanisms may exist. With the advent of prenatal ultrasound diagnosis and radiofrequency ablation of the acardiac twin's circulation, it became possible to save the pump twin.
Journal of Perinatal Medicine 05/2010; 38(3):247-53. · 1.70 Impact Factor
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ABSTRACT: Oxygen radicals are believed to contribute to typical diseases of prematurity, such as bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP) and necrotising enterocolitis (NEC). Our aim was to investigate whether these disorders are associated with disturbances in antioxidant enzyme activities and with low trace elements, which are co-factors of antioxidant enzymes. 209 infants with birthweight less than 1000g were enrolled into a European multicentre randomised erythropoietin (rhEPO) trial; 155 developed one or more of the above mentioned diseases. We analysed Zn, Cu, Fe, Se in plasma and red blood cells (RBCs), superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in RBCs on the 3rd and 68th day of life. Zn, Fe, Se in plasma, and Se in RBCs decreased (p<0.01), and Zn in RBC (p<0.001), CuZn-SOD (p<0.01) and CAT increased (p<0.05), whereas GSH-Px remained unchanged. No differences were observed between the rhEPO and control groups. Antioxidant enzyme activities did not correlate with gestational age. In infants with BPD, IVH, ROP, or NEC, CuZn-SOD and CAT (p<0.05) were higher at day 68 than in infants without these diseases. CuZn-SOD and GSH-Px at 3 days and CuZn-SOD at 68 days correlated positively (p<0.05) with the duration of oxygen treatment. In conclusion, in ELBW infants, trace element concentrations decreased over the first 10 weeks of life. Lower trace element concentrations, did not affect the activities of CuZn-SOD, GSH-Px, and CAT. Typical diseases of prematurity were not associated with decreased antioxidant enzyme activities.
Journal of Trace Elements in Medicine and Biology 04/2010; 24(2):111-8. · 1.68 Impact Factor
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Michael Obladen
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ABSTRACT: Twin-twin transfusion is the major cause of mortality and morbidity in monochorionic twins. Its pathogenesis has been gradually elucidated over the last three centuries. Among obstetricians, there was a long-lasting controversy on the existence of placental anastomoses and whether or not to tie the placental end of the firstborn infant's cord. However, a twin pregnancy practically never could be excluded. Stalpart van der Wiel described a twin-twin vessel connection in 1687. Studies on interfetal anastomoses using injection of placental vessels were published by Smellie in 1752, Osiander in 1781, and Brachet in 1821. Different types of anastomoses, and their associated fetal disorders were classified by Schatz in a series of papers at the end of the 19(th) century. With the advent of ultrasound and laser techniques, prenatal diagnosis and treatment became available in the last decade of the 20(th) century.
Journal of Perinatal Medicine 02/2010; 38(2):121-8. · 1.70 Impact Factor
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Michael Obladen
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ABSTRACT: Tongue-tie, or ankyloglossia, is poorly defined and involves a short, thick, fibrosed, or fixed lingual frenulum. Operative interventions were proposed already in Greek medicine. In the Middle Ages, competition arose between midwives, who used their nails to detach the frenulum, and surgeons, who were allowed to use instruments. During the last century, the justification for frenotomy shifted from improved language to enhanced feeding. Despite the high frequency of the intervention, little research has been performed on its benefit, which remains a controversial topic among different groups of health professionals.
Neonatology 09/2009; 97(2):83-9. · 2.66 Impact Factor
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ABSTRACT: We report a case of severe polycythemia in the recipient twin of a pregnancy with twin-to-twin transfusion syndrome (TTTS). Stage I TTTS was suspected at initial presentation (24 weeks) due to discordant growth associated with a twin oligo-polyhydramnios sequence. Increasing peak systolic velocity (PSV) in the middle cerebral artery (MCA) of the donor twin indicated fetal anemia. In addition, we observed a decreasing MCA-PSV of the recipient twin, indicating polyglobulia. Close follow-up without intervention showed a stable course of TTTS without progression to higher stages.Following caesarean section at 31 2/7 weeks due to preterm premature rupture of membranes of the leading donor twin, the donor twin showed anemia (hematocrit 28%) whereas the recipient twin demonstrated severe polycythemia (hematocrit 88%). Inter-twin difference of reticulocyte counts was high (38% for the donor and 5% for the recipient twin). Transfusion and partial exchange transfusion (PET) were performed in the donor and in the recipient twin, respectively. Normal hematocrit levels were achieved without complication. Perinatal outcome of both twins was good. Conclusion: Even in a stable course of pregnancy with stage I TTTS, severe polycythemia of the recipient twin can occur and can require careful PET in a specialized center.
Fetal Diagnosis and Therapy 05/2009; 25(2):206-10. · 1.05 Impact Factor
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ABSTRACT: Speech development is frequently impaired in very low birth weight (VLBW) infants. Few and controversial data have been published on concepts regarding the influence of bilingual education.
The objectives of the current study were to assess the influence of parental bilingualism on speech development and neurodevelopmental outcome in low risk VLBW infants.
Monocentric prospective controlled cohort study with standardized follow-up.
We recruited 50 singleton VLBW infants each from monolingual and bilingual families as well as 90 term control infants. The infants were free of disease and congenital malformation.
Griffiths scales of infant development at the corrected ages of 6 and 12 months, Bayley Scales of Infant Development II (BSID II) with 22 months.
In general, both bilingual and monolingual VLBW infants achieved age-specific milestones at the corrected age of 6, 12 and 22 months. However, bilingual VLBW infants achieved significantly lower scores than their monolingual peers in all cognitive subscales. The influence of maternal education on the neurodevelopmental outcome of the preterm infants was not significant; the subscales' correlation with socioeconomic or biological parameters was poor. However, a clear differentiation between social status and bilingual environment importance for speech development was not possible.
In the setting of the present investigation, parental bilingualism is associated with slower neurodevelopment in VLBW infants during the first 2 years of life.
Early human development 05/2009; 85(7):449-54. · 2.12 Impact Factor
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Michael Obladen
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ABSTRACT: Necrotizing enterocolitis (NEC) is not a new disease but one that has been reported since special care units began to house preterm infants. It was observed in foundling hospitals in Paris [Billard, 1828] and Vienna [Bednar, 1850] and, as it occurred in clusters, was regarded as a nosocomial infection in the infant hospitals of Zurich [Willi, 1944] and Berlin [Ylppo, 1931]. Clinical and patho-anatomic characterization was achieved by Schmidt and Quaiser in 1952. The unproven hypothesis of mesenteric hypoperfusion as a major etiological factor arose from animal models and analogous perforating disorders in term infants. Despite similarities between NEC and clostridial infections, few studies employed anaerobic culture techniques. The pathogenesis remains unclear and its distinction from related disorders uncertain. It is unlikely that strategies to prevent NEC will be successful unless the disease is better understood.
Neonatology 05/2009; 96(4):203-10. · 2.66 Impact Factor
