Invited Presentations

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INV15

Gastroschisis

A. Cameron

The Queen Mothers Hospital, Glasgow, United Kingdom

Gastroschisis is a defect of the anterior abdominal wall with extrusion of fetal intestine into the amniotic cavity.

The incidence of gastroschisis is approximately 1 in 2500–300 live births but the incidence is increasing in many developed countries. It is now the most frequent congenital abnormality in the UK and it has a higher association with certain patient demographics. This includes teenage pregnancy, low socio economic status and some studies have found positive correlations with recreational drug use.

The defect in the abdominal wall is usually to the right of the umbilicus. The condition is amenable to prenatal diagnosis as free loops of bowel are seen floating in the amniotic cavity on ultrasound examination. Gastroschisis has an approximate 80–90% detection rate usually either by the finding of raised maternal serum alphafetoprotein estimation or at the routine fetal anomaly scan.

Gastroschisis is not commonly associated with abnormalities of other organ systems with the exception of small bowel atresia, which may complicate up to 30% cases.

Neonatal surgery of the abdominal defect is required in the immediate neonatal period. Some neonates have primary closure but many infants have a prolonged stay in hospital. The overall mortality is low and the long term survival is 90%. However some neonates have significant morbidity including surgical complications, need for total parenteral nutrition, sepsis and short gut syndrome.

In view of the good prognosis of gastroschisis, fetal medicine specialists have turned their attention to trying to identify those fetuses most at risk of adverse outcomes. A number of risk factors have been described – these include ultrasound evidence of a dilated stomach, dilatation of the small bowel, thickness of the bowel wall, fetal growth restriction or increased or decreased amounts of amniotic fluid. Unfortunately none of these ultrasound parameters have consistently been correlated with adverse outcome. Moreover, when a fetus with gastroschisis is delivered prematurely, the infant may suffer from complications of prematurity in addition to those of the anomaly itself.

The evidence base for ultrasound risk factors, timing, mode and place of delivery will be discussed and illustrated by case discussion.

INV16

Amnioinfusion: Is it Working?

A. Puertas-Prieto, M. Paz Carrillo, F. Montoya

“Virgen de las Nieves” University Hospital, Obstetric and Gynecological Department, Granada, Spain

Amnioinfusion is a technique that presents various indications, one therapeutic, in deliveries with repetitive decelerations of fetal heart rate. The other is prophylactic, either in deliveries where oligohydramnios are present to avoid the appearance of fetal heart rate decelerations due to compression of the umbilical cord, or with the intention of reducing the incidence of meconium aspiration syndrome in deliveries complicated by meconium-stained fluid.

Transcervical intrapartum amnioinfusion in deliveries where umbilical cord compression is suspected produces a reduction in variable decelerations of fetal heart rate (RR 0.54; 95% CI 0.43–0.68), the rate of cesarean deliveries due to non reassuring fetal state (NRFS) (RR 0.35; 95% CI 0.24–0.52) and neonatal hospital stay for more than three days (RR 0.40; 95% CI 0.26–0.62).

In deliveries with intrapartum oligohydramnios it produces a reduction in fetal heart rate abnormalities (RR 0.24; 95% CI 0.17–0.34), the incidence of acidosis at birth (RR 0.40; 95% CI 0.30–0.55) and cesarean rates due to NRFS (RR 0.23; 95% CI 0.15–0.35).

Conclusions about the value of amnioinfusion in complicated births with meconium-stained amniotic fluid are contradictory. According to a metaanalysis made by Hofmeyr in 2001for the Cochrane Controlled Trials Register, the use of amnioinfusion in these deliveries is associated with a reduction in the incidence of variable decelerations of fetal heart rate, overall cesarean rates and the incidence of meconium aspiration syndrome (RR 0.44; 95% CI 0.25–0.78).

A subsequent metaanalysis made by Xu and cols. in 2007 did not find improvements with the use of amnioinfusion for meconium-stained fluids in hospitals with standard perinatal surveillance, while in centres with limited peripartum surveillance it seems that there is a reduction of meconium aspiration syndrome (RR 0.25; 95% CI 0.13–0.47).

INV17

Intrauterine Infection, Prematurity and Neonatal Sepsis

C.P. Speer

University Children's Hospital, Würzburg, Germany

Intrauterine infections caused by various microbial pathogens and intrauterine inflammation are the leading cause of preterm birth. Amniotic fluid (AF) of women at term rarely contains bacteria whereas in more than 20% of patients who have preterm labour with intact membranes and deliver preterm, AF is colonized with bacteria. Following premature rupture of membranes (PROM), viable bacteria in AF can be detected in nearly one third of women delivering preterm. In addition, PROM and chorioamnionitis clearly affect the rate of infections as well as the overall morbidity of preterm infants. Upto 60% of very immature infants may have been exposed to chorioamnionitis, and a high proportion of them are born with inflamed lungs and signs of a fetal inflammatory response syndrome (FIRS). A number of investigators have convincingly shown that FIRS is associated with an increased risk of severe neonatal pulmonary und cerebral morbidity such as bronchopulmonary dysplasia, intracerebral hemorrhages and periventricular leukomalacia.

In Western countries early-onset sepsis is mainly caused by group B streptococci (GBS) and Escherichia coli whereas Klebsiella- and Pseudomonas species are the predominant microorganisms in developing countries. Approximately 1% of term newborns colonized with GBS will eventually develop severe early onset sepsis; the majority of infections present within 24 hours of life. In very immature preterm infants the risk for early-onset infections and case fatality rate are significantly higher when compared with term newborns.

INV18

Coagulation Disorders, Perinatal Stroke and Cerebral Palsy

E. Saliba

INSERM U930-CHRU, Université F. Rabelais Tours, Neonatology, Tours, France

With an estimated incidence of 1 in 2300 to 5000 births, stroke is more likely to occur in the perinatal period than at any time in childhood. Perinatal arterial stroke (PAS) is a disorder associated with significant long-term neurologic morbidity. Despite the lack of good epidemiologic studies, experts suggest that perinatal stroke is the most common cause of hemiparetic cerebral palsy while also contributing to some cases of bilateral motor impairment. Neurologic deficits or epilepsy occur in 50% to 75% of survivors of perinatal strokes, and sensorimotor deficits are most common. Estimates of the frequency of cerebral palsy after perinatal stroke are similar. Several risk factors have been identified, but their precise roles in causing stroke are not well understood. Epidemiological investigations of infants with perinatal stroke have observed an association with maternal and placental disorders, perinatal asphyxia, blood disorders, cardiac disorders, infection, trauma, and drugs. More than one risk factor is identified in many cases. Prothrombotic factors have been implicated in the pathogenesis of both arterial and venous cerebral infarction, and potentially could result in cerebral injury in either the fetal or perinatal periods. The association between blood disorders and perinatal stroke has been based on small series from referral centers. Blood disorders associated with stroke in neonates include polycythaemia, protein-C deficiency, prothrombin 20210A mutation, and the factor V Leiden (fVL) mutation. The fVL mutation, a dominant inherited coagulation abnormality, has been found in association with cerebral arterial and venous disorders in neonates and children. The fVL mutation is the most common inherited cause of thrombosis in white people. Alone, the fVL does not greatly increase risk, but its presence can interact with other genetic and environmental factors that increase risk. High concentrations of lipoprotein (a) are associated with perinatal stroke. Activated protein C resistance is the most cause of thrombosis. Whilst protein C has been implicated as an isolated prothrombotic factor for neonatal stroke there are currently no reports of protein S deficiency alone being implicated. Thrombophilias may also predispose to recurrent seizure disorders via the occurrence of perinatal stroke. Multiple factors are associated with high risk of thrombosis. Other factors related to coagulation, fibrinolysis, endothelial activation, and other potentially relevant processes await exploration. Normal pregnancy is recognized as a hypercoagulable state making assessment of prothrombotic factors difficult in the perinatal period. Measurement of the thrombotic factors in the affected infant is best deferred until at least three months of age when interpretation of functional levels is possible, although the role of routine testing in clinical practice remains to be determined.

INV19

Oxygen Administration for the Preterm Infant in the Delivery Room and Beyond

O. Saugstad

University of Oslo, Pediatric Research, Oslo, Norway

Oxygen supplementation has been part of standard therapy of newborn infants for almost 8 decades. Still we do not know the optimal way to administer this drug. The understanding of oxygen toxicity was a spin off effect when biological effects of radiation for the “Manhattan” project were investigated. In spite of the experiences from 50–60 years ago clinical trials testing out different aspects of oxygen therapy was not tried out. Not until recently trials have been conducted to study the optimal oxygen concentration during newborn resuscitation and the optimal oxygen saturation for very and extremely low birth weight infants and extremely low gestation age newborns (ELGANs). These studies have shown that hyperoxia around birth may trigger a series of ill effects and lead not only to retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) but also is associated with childhood cancer and developmental delays.

To date at least 10 studies report the effect of high versus low saturation in ELGANs strongly indicating that a SaO₂ > 93–95% is associated with higher rates of ROP and BPD. Ten studies including more than 2000 enrolled subjects have so far reported the effects of room air Vs 100% O₂ for term or near term babies in need of resuscitation. By using 100% O₂ neonatal mortality is significantly increased, and time to first breath is significantly delayed. Two resuscitation studies in ELGANs indicate that a FiO₂ of 30% is as efficient as 90–100% when initiating resuscitation of such small babies.

Both clinical and experimental studies clearly show that hyperoxia induces inflammation and cell death not only in the lungs and heart but also in the brain.

Conclusion: Today a routine use of pure oxygen for newborn resuscitation and SaO₂ > 95% for ELGANs the first weeks after birth should be avoided. A major challenge to contemporary neonatology is to change our routine oxygen therapy taking this new information into account.

INV20

Euroneostat: A European Information System on the Outcomes of Care for Very Low Birth Weight Infants

A. Valls-i-Soler, V. Carnielli, O. Claris, C. Corchia, M. Cuttini, J. de la Cruz, L. Halliday, M. Hallman, H. Hummler, J.I. Pijoán, C.R. Pallás, G. Sedin, M. Weindling

Hospital de Cruces, University of the Basque Country, Neonatal Epidemiology Unit, Department of Paediatrics, Bilbao, Spain

EuroNeoStat is a European project funded by SANCO involving over 50 NICUs from 23 European countries, affiliated to ESPR/ESN. It's an epidemiological watch study on the consequences of premature birth to gain insight into health care systems available for treatment of VLBW infants. Has created an information system to monitor short- and long-term outcomes of VLBWI, and collects relevant indicators to enable outcome comparisons and facilitates clinical research to improve quality of health care delivered to very immature (<32 wks) or very low birthweight infants (<1501 g). Results can be used for benchmarking, identify opportunities to improve the care process, evaluate health programmes and develop priorities for planning, promotion and evaluation of care, document clinical variability and push forward consensus in the health policies and strategies to be used for improving care of these high-risk premature infants.

It also includes an initiative EuroNeoSafe, to promote a culture of patient safety in European units by creating a system of voluntary reporting of adverse events to minimising errors and other mistakes which might have a significant impact on morbidity and mortality.

In summary, in order to tackle successfully initiatives aiming at improving outcomes in the process of perinatal care of the most immature and vulnerable neonates, collaborative networking, an attitude of constructive criticism and thorough comparative analysis of the outcomes and incidents in the health-care process are indispensable. Further information for units interested in participating in these projects may be obtained by contacting our website or contacting the following national representatives: HU Bucher, Zurich, J Gadzinowski, Poznan; R Örs, Konya, R Plavka, Prague; B Urlesberger, Graz; LViacheslau, S Petersburg; D Virella, Coimbra; M Xanthou Athens.

INV21

Proinflammatory Cytokines and Chemokines in Neonatal Infection and Brain Damage

Marietta Xanthou

Professor of Pediatrics, Director of Neonatal Immunology Laboratory, ‘‘Agia Sofia'' Children's Hospital, Athens, Greece

Perinatal infections and asphyxia represent major causes of neonatal morbidity and mortality. During perinatal asphyxia, the inflammatory response to tissue injury and the production of cytokines occur after the excitotoxic cascade, at the reperfusion state, as hypoxia upregulates expression of proinflammatory cytokines and chemokines. These mediators when produced either in the brain during perinatal asphyxia or reaching the brain during perinatal infections mediate inflammatory responses which may result in brain damage. We have demonstrated increased serum levels of IL-6, IL-1β and sICAM-1 during asphyxia and infection. Elevated chemokine IL-8 levels were found in neonates with asphyxia, while during infection, IL-8 and IP-10 levels were increased. We also observed a dichotomy of reactivity of activated neonatal lymphocytes according to the insult: during infection they expressed increased IL-8 mRNA, while during asphyxia MCP-1 mRNA was increased. In animal studies and in clinical, epidemiologic and neuropathologic studies, an association between perinatal asphyxia and/or infection, inflammatory mediators and brain damage has been proposed. In premature infants, the increased vulnerability of neonatal brain should be also taken into consideration. The understanding of the pathophysiology of brain damage caused by these inflammatory mediators in neonates will lead to better therapeutic and preventive approaches.

INV22

Neuronal Damage Accompanies Perinatal White Matter Damage

E. Saliba

INSERM U930-CHRU, Université F. Rabelais Tours, Neonatology, Tours, France

Periventricular white matter injury (PWMI) is the major form of brain injury and the leading cause of chronic neurological disability in survivors of premature birth. PWMI does not occur in isolation. Neuronal damage in gray matter sites critical to cognition, memory, and learning is now acknowledged to be part of white matter lesions and to play an important role in cognitive defects in long-term survivors of prematurity. Recently the term “encephalopathy of prematurity” has been used for the constellation of neuronal abnormalities observed in premature infants, especially those with cerebral white matter injury. These gray matter abnormalities, identified initially by volumetric MRI studies, include defective growth of the cerebral cortex and deep nuclear structures in particular the thalamus and basal ganglia. These findings show that neuronal loss and impaired neuronal guidance accompany neonatal white matter damage and support the view that some of the dysfunctions seen in preterm infants reflect reduced connectivity between areas of the brain needed for integrating information. Multiple neuron populations in the telencephalon may be vulnerable to perinatal brain injury. GABA is the predominant telencephalon neurotransmitter during late gestation. Expression of the GABA pathway is maximal at 25 weeks of gestation in humans, a common time for premature birth injury. GABAergic neurons play a crucial role in cortical development. During the third trimester, GABAergic neurons migrate through the developing white matter and subplate. Similar to developing white matter, the subplate is susceptible to damage from perinatal brain injury. In mice, disruption of GABAergic signaling during development produces phenotypes with cognitive delay and behavioral problems similar to those described in children who have suffered perinatal brain injury. A significant loss of telencephalon GABAergic neuron expression was found in neonatal brains with PWMI. Patients with cerebral palsy often show signs of extrapyramidal motor dysfunction, suggesting physiologic disturbance of the basal ganglia. There is reason to believe that dopamine is important in developmental programs of the basal ganglia, brain nuclei implicated in motor and cognitive processing. Dopamine exerts effects through dopamine receptors, which are predominantly of the D1 and D2 (D1R and D2R) subtypes in the basal ganglia. Developmental studies on D1R and D2R in the rat striatum suggest that D1R and D2R may play roles in the neuronal development of the striatum. Furthermore, animal experiments show alterations of D1R and D2R in the striatum after an experimental perinatal hypoxic-ischemic insult. Improved knowledge about neuronal loss in white-matter damage has the potential to expand our understanding of interventions that might prevent or minimize brain damage in the most vulnerable neonates.

INV23

Neurosonography in Neonatal Period–What does 3D Add?

M. Stanojevic

Medical School University of Zagreb, Sveti Duh Hospital, Department of Obstetrics and Gynecology, Zagreb, Croatia

Background: Two-dimensional (2D) ultrasonography revolutionized neonatal brain assessment in the 1970s. Development of the computer technology enabled introduction of 3D ultrasonography to the clinical practice. We investigated if 3D ultrasonography made any substantial improvement in neuroimaging of the newborns.

Materials, methods and results: The first group of 30 newborns with median gestational age of 36 weeks (range 26 to 40) and median postnatal age of 4 days (range 2 to 60), underwent 3D imaging after the 2D real-time ultrasonography. The second group consists of 62 premature infants, below 2000g at birth, underwent 2D neurosonography. If 2D was unreliable, 3D was planned for the next examination. Aloka 230 device with 5 MHz sector probe was used for 2D, and Voluson 530 D Kretz Color System with vaginal 5–8 MHz 3D probe was used for 3D neuroimaging. The time needed for 3D compared to 2D data acquisition was shorter (5 vs. 14 minutes, Kruskal-Wallis rank sum test: H = 25,9; P = 0.003). All 62 prematures underwent 2D brain ultrasonography. Out of 18 newborns, in whom 3D brain ultrasonography was indicated, it was performed in only 10 due to the unavailability of the equipment or skilled examiner.

Conclusions: 3D provides more reliable information than 2D performed in the same patient. The time needed for data acquisition was shorter, while the time for data interpretation was longer for 3D, but it can be performed off-line. Unavailability of 3D equipment and skilled examiners prevent its extensive use in nonatology.

INV24

Fetal Programming

J.W. Dudenhausen

Charite, Kliniken für Geburtsmedizin, Berlin, Germany

Epidemiological and experimental data are intensively discussed which indicate that exposures during prenatal and prenatal life have lifelong consequences for the risk of developing obesity and consecutive metabolic and cardiovascular diseases. In this context, observations in offspring of mothers with diabetes during pregnancy as well as studies in children with low birth weight were most influencial. This lecture illustrates the current knowledge on perinatal programming on obesity and discusses possible etiopathologenetic mechanisms, focussing on epidemiological and animal studies on the consequences of exposure to maternal diabetes and perinatal over- or undernutrition. Against this background, the resultant far-reaching potential for primary prevention of obesity as well as the paradigmatic character of these hypotheses and observations for the general understanding of health and disease are high-lighed.

INV25

Is Maternal Origin a Risk Factor for Maternal GBS Colonization and Neonatal GBS Sepsis?

M.S. Schimmel

Shaare Zedek Medical Center, NICU, Jerusalem, Israel

Background: During the last two decades our maternal GBS carrier and neonatal sepsis rates has varied, 3.5%–11% and 0.2–0.9/1000 LB respectively. As a result, routine prenatal cultures were not recommended and intrapartum prophylaxis was mainly based on maternal risk factors.

Objective: An updated screening was performed in order to determine whether our preventive early neonatal sepsis policy is still applicable.

Design/Methods: In Jan. June 2002 we performed prospective randomized sampling of women admitted for delivery. Vaginal rectal cultures were obtained before 1^st pelvic examination. GBS was isolated using a selective broth medium and identified by latex agglutination and antigen B assay. Neonatal sepsis rate was defined as positive blood or CSF cultures for the period Jan-Dec 2002. Chi² and multivariate analysis were performed.

Results: Of the 637 sampled women 94 were GBS positive (14.7%). Fifty (7.8%) of the mothers were from N. America origin and there colonization rate was 26% (13:50) as opposed to mothers of other origins which was 13.8% (81:587) p = 0.02. In multivariate analysis, including variables of maternal age, parity, blood type, duration of rupture of membranes, infant gender and birth weight, N. America Origin was found to be the single risk for GBS carrier (p = 0.0273). Neonatal sepsis (8:9995) rate was 0.8/1000 LB for the entire population. The percentage of the N. America Origin mothers in the sampled population was 7.8% (50/637) their component in the GBS infected group was 37.5% (3:8) p = 0.016. No difference was noted in GBS serotype between origin groups.

Conclusions: Our survey identified N. America origin women as an increased risk factor for GBS colonization in the Israeli society. The high N American origin neonatal GBS sepsis rate was correlated with the increased colonization rate in the N American mothers. Given this higher carrier rate in N. America origin women we now recommend routine prenatal screening for GBS in women of N. American origin.

INV26

Nosocomial Sepsis, Risk Factors and Outcomes in Neonates 24 to <33 Weeks Gestation. Results of a Multicenter International Study Group

X. Carbonell-Estrany

Neonatology Service, Hospital Clínic, Institut Clínic de Ginecologia i Obstericia i Neonatologia, Barcelona, Spain

Background: Nosocomial sepsis remains a major risk for premature infants worldwide.

Objective: To prepare for future trials, a prospective cohort study was conducted to determine the incidence and description of nosocomial sepsis, the nosocomial Staphylococcal sepsis risk factors and their outcomes.

Design/Methods: Infants 24 to < 33 wks gestation expected to survive for ≥ 7 days were enrolled at 70 multinational centers and followed for 12 wks. Sample size was based on Staphylococcal (CONS + S. aureus) sepsis estimates. Sepsis was defined as ≥ 2 clinical signs and symptoms with: associated bacteremia in 2 cultures (A); or 1 culture (B); or 1 of 2 cultures (C). Only < 5% of subjects were excluded from the according to protocol cohort, thus analyses was performed on the total cohort.

Results: 1009 infants were enrolled in the United States (382), Canada (121), and Europe (506) over 11 months. At enrollment: mean gestational age was 28.5 wks with 49%≤ 28 wks, mean age was 3.6 days, 53% were male, 68% were Caucasian, 35% were multiple gestation, mean SNAPPE II score was 23, 39% had premature rupture of membranes, 24% had rupture of membranes >12 hrs, 11% had chorioamnionitis, 57 % had premature labor, 27% had fetal distress, 67% were delivered by C-Section (73% emergent), 59% of women received antibiotics during pregnancy and 53% during labor/delivery, and 81% received steroids during pregnancy. 1111 sepsis work-ups were performed and 55% of neonates had at least one (range 0 to 10). 97% of work-ups had at least 2 signs/symptoms with: the most frequent being bradycardia, apnea, and respiratory distress; an increase in peripheral white blood cell count the most common laboratory parameter indicative of sepsis; 58% having chest x-rays (20% with bilateral infltrates). 57% had ≥ 2 peripheral blood cultures during work-ups. 26% of all infants had sepsis (A + B + C). Sepsis was due to: 85% Staphylococci (91% CONS); 17% gram negatives; 11% other gram positives; 4% fungi. Culture negative sepsis was suspected in 7.7% and focal infection in 7.2%. 37% of infants ≤ 28 wks had sepsis vs. 12% of infants >28 wks. Death was due to sepsis in 5.7 % of patients with sepsis, and 2.2% with Staphylococcal sepsis. Population, incidence, and organisms varied by region. 20.6% of infants had Staphylococcal sepsis (A + B + C) (91% CONS). Risk factors for Staphylococcal sepsis were birth weight or gestational age which were inversely associated, and prolonged rupture of membranes which was directly associated using univariate analysis. From a log-linear Poisson model, birth weight, gestational age, and respiratory support use were inversely associated with Staphylococcal sepsis. After adjustment for birth weight and gestation, risk of specific health outcomes associated with Staphylococcal sepsis included: increased bronchopulmonary dysplasia and surgery for retinopathy of prematurity; decreased intraventricular hemorrhage and surgery for patent ductus arteriosus; no impact on death, or necrotizing enterocolitis. After adjustment for birth weight and gestation, the risk of use of specific health care resources associated with Staphylococcal sepsis included increased: blood transfusions (number and volume), duration of respiratory support (but not endotracheal intubation), duration of vancomycin, duration of antibiotics, duration of pressors, duration of NICU stay, and duration of hospital stay, but not intravascular catheter use.

Conclusions: Nosocomial sepsis in premature infants is common with 85% due to Staphylococci. Nosocomial Staphylococcal sepsis is inversely associated with birth weight or gestational age. It is associated with increased adverse outcomes and heath care resource utilization. Using preset definitions, this study provides essential data to design future strategies.

INV27

Neonatal Nosocomial Staphylococcal Infection: Is there a Role for Antibody in Prevention?

L.E. Weisman

Baylor College of Medicine, Perinatal Center Texas Children's Hospital, Houston, United States

Coagulase negative staphylococci (CONS) and S. aureus are responsible for >75% of nosocomial infections in very low birth weight (VLBW) infants. These infections increase hospital stay, antibiotic use, and cost of care. Several antibodies for the prevention of neonatal staphylococcal infection have been evaluated including 1) Altastaph® (North American Biologics Inc.), 2) Veronate® (Inhibitex Inc.), and 3) Pagibaximab® (Biosynexus Inc.). We review these products. Altastaph® is a S. aureus serotype 5 and 8 vaccine induced hyperimmune polyclonal antibody. Its development has stopped due to efficacy failure in a Phase 2 study. Veronate® is a polyclonal antibody plasmapheresied from donors with high titers of MSCRAMM (microbial surface components recognizing adhesion matrix molecules) activity against CONS. Its development has stopped due to efficacy failure in a Phase 3 study. Pagibaximab® is a humanized mouse chimeric monoclonal antibody directed against lipoteichoic acid (LTA), a major cell wall component, which has completed a Phase 2 study suggesting efficacy. This antibody appears effective in-vitro against >90% CONS and S. aureus strains, and in animal models. A Phase I open label dose-ranging study of Pagibaximab® in healthy adults to evaluate safety and pharmacokinetics, a Phase I/II double-blind, placebo controlled, dose escalation, safety and pharmacokinetics study in the target population of VLBW neonates, and a Phase II randomized, double-blind, placebo-controlled, safety, pharmacokinetics, pharmacodynamics, and clinical activity study in VLBW neonates suggest safety and efficacy. Sustained antibody levels ≥ 500 μg/mL appear to be protective in-vitro, in animals, and may be protective of staphylococcal infection in high-risk neonates.

INV28

Therapeutic Drug Monitoring of Aminoglycosides in the Neonate: Useful or Useless

J. van den Anker

Children's National Medical Center, Pediatrics, Washington, United States

Aminoglycosides are used for the treatment of neonates with suspected or documented Gram-negative bacterial infection which is potentially life-threatening in neonates. Aminoglycosides are administered together with a penicillin such as ampicillin or amoxicillin. An evaluation of the use of antibioitics revealed that 60% of neonates receive at least one antibiotic during the first week of life of which aminoglycosides comprised 43%.

The high morbidity and mortality of bacterial infection in neonates require that the antibiotic therapy should be started as soon as the infection is suspected. The remarkable inter-individual variability in the pharmacokinetics of aminoglycosides requires that their optimal dose should be defined.

The aminoglycosides have a low therapeutic index and thus knowledge about their pharmacokinetics is essential. The pharmacokinetics of aminoglycosides in neonates are different as compared to adults and it is therefore necessary to study the pharmacokinetics of these drugs in neonates.

Over the past decades, it has become common to apply pharmacokinetic principles to design drug regimens. The therapy with aminoglycosides requires knowing their peak and trough concentrations, at least that is what many neonatologists and pediatricians still believe!

If there is indeed a place for therapeutic drug monitoring in the neonate during the first week of life will be discussed.

INV29

In Vitro Fertilization Conceived Very Low Birth Weight Infants are not at Higher Risk for Mortality and Morbidity–A Population Based Study

M.S. Schimmel

Shaare Zedek Medical Center, NICU, Jerusalem, Israel

Objective: To determine whether excess mortality, neonatal morbidity and congenital malformations occurred in in-vitro-fertilization (IVF) conceived compared to naturally conceived singleton, twin and triplet very low birth weight (VLBW) infants.

Design: population based observational study from 1995 through 2002.

Setting: Israel National VLBW infant database.

Patients: 8181 VLBW infants conceived naturally or by IVF were stratified into groups of singletons and complete sets of twins and triplets.

Interventions: none.

Main Outcome Measures: Neonatal mortality and morbidity.

Results: In the unadjusted analyses, mortality and neonatal morbidity rates were in general similar between the IVF and the naturally conceived infants stratified by plurality groups. When adjusted for multiple confounding variables, there was no excess neonatal mortality or morbidity among IVF conceived infants. The risk for congenital malformations adjusted for ethnicity, maternal age and parity was also not increased in the IVF conceived groups.

Conclusion: In our population, VLBW infants conceived by IVF were not at increased risk for congenital malformations, postnatal morbidity or mortality compared to naturally conceived infants.

INV30

New Concepts on Prevention and Treatment of Bronchopulmonary Dysplasia (BPD)

C.P. Speer

University Children's Hospital, Würzburg, Germany

Many strategies to prevent or ameliorate BPD have been evaluated so far. Evidence for a short term preventive effect exists for therepetitive intramuscular administration of high doses of vitamin A. Oxygen supplementation remains an important therapeutic strategy for patients with established BPD. Targeting the infants at lower oxygen saturation seems to reduce long term pulmonary morbidity without increasing the risk of adverse neurosensory outcome. In addition, prophylactic or very early surfactant administration in very immature infants may have a beneficial effect on the incidence of BPD. Currently there is no sufficient evidence for a routine use of inhaled nitric oxide (iNO) for the prevention of BPD. A temporary use of diuretics can improve lung function and oxygenation in these infants. Nonetheless existing data do not justify a sustained diuretic therapy.

As the pathogenesis of BPD is multifactorial, it is unlikely that one single agent will be identified as a ‘miracle drug’ in the prevention or treatment of the disease. The ‘miracle drug’ of the 1990s, dexamethasone, has almost completely lost its role in the management of extremely premature infants. Superoxide dismutase (SOD) and alpha1-Proteinase inhibitor have not proved to reduce the risk of moderate or severe BPD yet. The early administration of caffeine for prophylaxis and treatment of apnea of prematurity has been shown to reduce the risk of BPD and to improve the rate of survival without neurodevelopmental disability at follow-up.

INV31

Ureaplasma Associated Bronchopulmonary Dysplasia: Can it be Prevented?

L.E. Weisman

Baylor College of Medicine, Perinatal Center Texas Children's Hospital, Houston, United States

Ureaplasma infection significantly increases lung disease in high-risk neonates. We determined the impact of antibiotic prophylaxis on ureaplasma and oxygen induced lung disease in newborn mice. An ureaplasma clinical strain was used for all experiments. MIC was determined using CLSI guidelines. Antibiotic pharmacokinetics was measured in suckling mice. In both animal model development and prophylaxis experiments, pups were infected with an intramuscular ureaplasma daily for the 1^st 3 days of life, and followed 14 days for growth and survival. Surviving pups had blood culture, lung weights, lung pathology, lung morphometry, lung immunohistochemistry, bronchoalveolar lavage, and lung culture evaluated. In prophylaxis experiments, intraperitoneal erythromycin, azithromycin, or normal saline were given for the 1^st 3 days of life. The MIC was 62.5 ug/ml for erythromycin and 0.25 ug/ml for azithromycin. We observed in model development that the 0.8 FiO₂ + ureaplasma group survival and growth were significantly decreased, lung wet/dry weights and wet lung/body weight ratios were significantly increased and BAL and Lung PCR were positive 29% and 15%, respectively. In prophylaxis experiments, we observed significantly improved survival and growth with azithromycin versus normal saline controls, while erythromycin was not significantly different than the controls. In a neonatal mouse model of ureaplasma and oxygen induced lung disease, appropriate antibiotic prophylaxis improves survival and morbidity.

INV32

Daily Iatrogenic Teratology: Drugs, Alcohol, Smoking…

J.G. Nijhuis

Maastricht Univ. Med.Center, Head Dept Ob/Gyn, Maastricht, Netherlands

For the majority of potentially harmful drugs, no clear dose-related relative risk curves have been established. Therefore, there is no safe level, i.e. “no effect”, for any of these substances. For that reason, most countries advise to not smoke or use alcohol or drugs preconceptionally, during pregnancy and breastfeeding. In this presentation, attention is focused on the use of alcohol; a similar way of looking at risks is easily possible for other drugs, smoking, etc.

One needs to consider the risks of using alcohol for the mothers' health, the risks for the course of the pregnancy, and effects on the fetus. As for any adult, the use of alcohol increases the immediate risk (accidents and injuries) and increases the risk of alcohol-related diseases. Obviously, many pregnancies are more or less unplanned, and many women stop drinking after the realization that they are pregnant, i.e. 14 days after conception.

The use of alcohol leads to an increased risk of abortion and preterm delivery. A five-fold increase of spontaneous abortion has been reported when using 5 or more drinks in the first trimester. The risk of premature birth has been established in women who use more than 4 drinks per week.

Fetal effects include growth retardation and facial dysmorphology, and certainly the fetal alcohol syndrome (FAS): characteristic facial abnormalities, impaired growth and abnormal function and/or structure of the fetal central nervous system. Obviously, this syndrome has lifelong problems, including learning and behavioral problems. Behavioral and learning problems have also been described in children who do not have FAS. And finally, the use of alcohol is not always known or reported and part of developing disturbances in children may be due to unknown use of alcohol in pregnancy.

Not much is known of the effect of low doses of alcohol on pregnancy and the fetus, this is certainly subject of debate in many countries. As long as safe levels have not been established, it seems wise to give a “no-use” advise. On the other hand, one should be aware that too aggressive counseling may lead to unnecessary anxiety in pregnant women who report to have used alcohol occasionally during their pregnancy.

INV33

Investigating the Interface between Development and Pharmacogenetics

J. van den Anker

Children's National Medical Center, Pediatrics, Washington, United States

Pediatric dosing regimens should be based on an understanding of the pharmacokinetic-pharmacodynamic relationship of drugs in neonates in stead of an empiric dosing regimen based on body weight alone.

Therefore, to define effective and safe dosing regimens for neonates of different gestational and postnatal ages, detailed information is needed on the pharmacokinetics (the drug-concentration versus time profile) and the pharmacodynamics (the drug-concentration versus effect relationship and the time-dependent transduction mechanism that governs the time course of the response). Both the pharmacokinetics and pharmacodynamics may change over the continuum of a neonate's life. In practice, this age-related variability must be considered in the context of all other sources of intra- and inter-individual variability resulting from genetic-, environmental- and disease related factors and drug interactions.

For example, the role of pharmacogenetic factors on treatment effect should be evaluated and included with all other clinical covariates. Age-related differences in pharmacokinetics may be caused by differences in absorption, distribution, metabolism and/or excretion. Differences in pharmacodynamics can be the result of age-related changes in receptor expression causing differences in target tissue sensitivity, and age-related changes in the function of in vivo transduction and homeostatic feedback mechanisms governing the intensity of the response.

This presentation will show the importance of investigating the interface between developmental changes in pharmacokinetics/pharmacodynamics and pharmacogenetics.

INV34

Adverse Pregnancy outcome, the Uteroplacental Interface, and Preventive Strategies

Y. Erata

Dokuz Eylul University, Medicine Faculty, Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, Izmir, Turkey

The development and maintenance of adequate placental circulation is essential to successful pregnancy outcome. In some circumstances, abnormal placental vasculature and disturbances of hemostasis result in inadequate maternal-fetal circulation. This placental vasculopathy is associated with gestational complications, such as preeclampsia, placental abruption, fetal growth restriction, and intrauterine fetal death. These vascular complications are known to contribute significantly to maternal and fetal morbidity and mortality.

Dekker and colleagues were the first to report an association between the presence of a thrombophilia and early-onset preeclampsia. Some obstetric vascular complications have also been associated with hereditary thrombophilias. Data from recent meta-analyses are consistent with an association between hereditary thrombophilias and the development of severe preeclampsia and early and late fetal losses.

Endothelial cell dysfunction, coagulation activation, deposition of fibrin/fibrin degradation products, and ultimately uteroplacental thrombosis lead to the clinical sequence of adverse pregnancy outcomes (APO). This prothrombotic cascade is fostered by the presence of one or more of the characteristic thrombophilic conditions, but is also seen with abnormal placentation secondary to failure of endovascular trophoblast invasion, which leads to placental ischemia. The placenta is known to play a key role in the pathogenesis of APO. The placental pathology of adverse outcomes like intrauterine growth restriction is similar in patients with and without underlying thrombophilia. These placental changes have been clearly identified and are known to occur in two stages. In the first stage there is failure of trophoblast invasion, and in the second stage there is systemic endothelial dysfunction.

A rational approach to these pre-thrombogenic conditions is to administer thromboprophylaxis during pregnancy. Women with prior APO in antecedent pregnancy are at high risk of an adverse maternal or fetal outcome in the subsequent pregnancy. Until recently, anti-platelet drugs, mostly low-dose aspirin (ASA), were acknowledged to reduce to some extent the incidence of recurrent preeclampsia in subsequent pregnancies. Administration of low moleculer weight heparin (LMWH) was found to be superior to low-dose ASA in women with one fetal loss and inherited thrombophilia in a prospective randomized trial. Furthermore it has been suggested that treatment with heparin and ASA is beneficial in improving the maternal-fetal outcomes in women with antiphospholipid antibody syndrome. But still there are no adequate, completed randomized trials for prophylactic measures; the roles of aspirin, calcium, and low molecular weight heparin need to be evaluated.

INV35

The Role of Inflammation in Preeclampsia

M. Sezik

Suleyman Demirel University, Faculty of Medicine, Department of Obstetrics and Gynecology, Isparta, Turkey

An inflammatory response is nonspecific and is part of the innate immunological system. Inflammatory leukocytes, endothelium, and platelets are the central elements. Normal pregnancy is a state of mildly increased inflammatory response, probably reflected by “physiological changes” such as leukocytosis, hypercoagulation, insulin resistance, hyperlipidemia, etc.

Preeclampsia is characterized by an abnormally increased systemic inflammation. Placental macrophage alterations, involving natural killer and dendritic cells have been defined in preeclampsia, leading to trophoblast apoptosis that might cause impaired spiral artery invasion. Placental hypoxia ensues, triggering production of more inflammatory cytokines and reactive oxygen species. Consequently, local inflammation in the placenta propagates into systemic maternal inflammation.

Insulin resistance, hyperlipidemia, obesity, chronic hypertension, and atherosclerosis are known to be associated with chronic inflammation. Women with these features have increased risk for developing preeclampsia and vice versa. Low-grade, chronic systemic inflammation encountered during preeclampsia persists decades postpartum. Therefore, the inflammation seems to be either maternal or placental in origin. In reality, both are probably acting together in a mixed fashion. It is hypothesized that when an inflammatory threshold is reached, the preeclampsia syndrome develops. Depending on this “threshold hypothesis”, maternal infections would be expected to be associated with preeclampsia by magnifying the inflammatory response. A recent meta-analysis confirmed a two-fold higher risk of preeclampsia with any kind of maternal infection. Particularly important are urinary tract microbial colonization and periodontal infections.

Another point of interest is whether inflammation is related to disease severity in preeclampsia. Leukocytosis was reported to be proportional with HELLP syndrome severity. Recently, we showed that leukocytosis was an independent predictor of in-hospital eclampsia in women who were not receiving prophylactic magnesium sulfate. In our database, leukocytosis was no more a risk factor when women that received magnesium sulfate were included in the analysis (unpublished data). Therefore, we speculate that magnesium sulfate might have neuroprotective and/or anti-inflammatory activity directed at the central nervous system.

Data on anti-inflammatory interventions to prevent or treat preeclampsia is scarce. Some interventions (treatment of HELLP syndrome with corticosteroids) have been discouraging. The dilemma arises from several causes: First, what we call as “anti-inflammatory drugs” might not have any effect on maternal inflammatory pathways and/or are not able to inhibit inflammation-induced changes. Second, anti-inflammatory interventions late in the course of the disease process could be ineffective. Finally, inflammation is perhaps the end-point of upstream molecular defect(s) causing the syndrome. Recently, deficiency of catechol-O-methyltransferase (COMT) in mice was shown to induce a preeclampsia-like picture. COMT catalyses conversion of 17-beta-estradiol to a non-toxic metabolite: 2-methoxyoestradiol (2-ME). Interestingly, administration of 2-ME to pregnant mice seems to suppress certain inflammatory markers and ameliorate preeclampsia-like features. 2-ME has vascular protective, anti-inflammatory and immunomodulatory effects.

In conclusion, preeclampsia is a syndrome with exaggeration of physiological systemic inflammation of pregnancy. Placenta is the initial stimulus for activation of inflammation. However, the presence of pre-pregnancy chronic inflammation is also a determining factor. Limiting the inflammatory response by treating maternal infections or novel anti-inflammatory interventions might reduce the incidence or severity of preeclampsia.

INV36

The Offspring of Maternal Diabetes. Perinatal Events and Future Outcome

M.R.G. Carrapato, S. Tavares, C. Prior, T. Caldeira

Hospital de São Sebastião, Department of Peadiatrics and Neonatology, Santa Maria da Feira, Portugal

Introduction: The 1989 St Vincent's Declaration stated, as a 5-year goal, “… that the outcome of the diabetic pregnancy should approach that of non-diabetic pregnancies” and indeed, over the last 25 years significant reductions in spontaneous abortions, stillbirths, congenital malformations and perinatal mortality have been achieved at least in centres with a special interest in diabetic pregnancy and in selected populations. However, reports have shown that even in western countries, spontaneous abortions may be as high as 17%, the stillbirth rate to be 5-times greater, congenital malformations to range from 4 to 10 times the usual rate, perinatal mortality to be 5-fold, neonatal mortality 15 times greater, and that infant mortality might be trebled as the result of diabetic pregnancies. These poor results have also been reported for type 2 diabetics and range from congenital malformations 11 times greater, a 2-fold risk of stillbirth, perinatal mortality 2.5 times higher, risk of neonatal deaths 3.5 times greater and a 6-fold risk of death in the first year of life. Gestational diabetes mellitus (GDM) usually develops in the second half of pregnancy. With advancing pregnancy considerable demands are placed upon insulin to meet increasing maternal metabolism. If the threshold is surpassed maternal hyperglycaemia may supervene. Although some studies also point to a higher incidence of congenital malformations in association with GDM, most cases are probably pre-GDM diagnosed in pregnancy especially type 2, with pre-pregnancy BMI and advanced maternal age playing a very conspicuous role. Congenital malformations aside, the whole spectrum of peri(neo)natal problems overlap those of pre-GDM and contribute to the high maternal-fetal and neonatal morbidities. It would therefore appear that nearly 15 years on from the St. Vincent's Declaration the goal of a similar outcome for diabetic and non-diabetic pregnancies has yet to be attained.

What is the outcome? Neonatal complications of the IDM in spite of the high morbidities involved, are now quite well managed with intensive neonatal care. Whether these babies are more prone to developing neurological, behavioural and learning disabilities and, if so, whether they are due to an unfavourable intra-uterine metabolic environment or to other perinatal and early life events operating on different fetal determinants remains an open question. The long-term outcome, on the other hand, poses several questions. Some studies point to a higher incidence of childhood obesity in the offspring of these mothers whilst others fail to find such correlations. Conflicting results might be the result of the different methodologies involved, including different definitions and very often small numbers, without adequate control populations. A major issue is whether some adult diseases of metabolic and vascular disorders may have had a fetal origin- In recent years there has been accumulating evidence, both from animal studies and epidemiological data, to suggest that fetal bcell hyperplasia and hyperinsulinism may induce irreversible changes leading to obesity, glucose intolerance and even overt non insulin-dependent diabetes and, perhaps, a protective effect against type 1 diabetes later in life – a model very much in line with the ‘Barker Hypothesis' of the fetal origins of adult disease. If that is the case, how early in childhood do the metabolic changes start? We have shown that the offspring of diabetic mothers start to show sings os increased wheigt gain as early at 2 years of age; at 4 years of age a tendency to slight increments in systolic ans diastolic BP, although not significant – will these differences became significant at an older age? In addition, our results also showed that in woman with GDM there is also a postive family history of Type 2 diabetes especially on the maternal side and having been small for gestacional age at birth is another added risk for the development of GDM. What might be the relative weight of genetics versus intra-uterine events remains to be confirmed but it is quite interesting that at least in experimental models the prevention of hyperglycaemia in pregnancy significantly reduces the prevalence of diabetes in the next generations.

What can be done? Based on the assumption that poor maternal homeostasis is at the core of the problem and that tight metabolic control might change the outcome of a diabetic pregnancy to normal, why then are such poor results being reported even in developed countries? Admittedly, most of these bad performances are for pre-DM. But, even allowing for different data collection, lack of uniform criteria in definitions and case identification, the fact remains that overall results are far from satisfactory. It can be argued that they are due to poor medical and social care – and they most probably are. It can also be argued that poor metabolic control has not been achieved or that ‘good’ is not necessarily ‘optimal’. Alternatively, it can be put forward that there might be an abnormal genetic background contribution (evidence is pretty scanty) or that there might be other metabolic fuels besides glucose operating at different developmental stages of pregnancy thus accounting for the aetiopathogenesis of the whole syndrome. It is quite possible that some, or all, of these metabolic fuels may, per se or in synergie, play a significant role in the whole metabolic disturbance and it is quite conceivable that besides the classical approach to strict glucose control, other dietary manipulations with supplementation or replacement of deficient substracts might hold a promise for the near future. For the moment, however, priority should focus on intensive prenatal care for diabetic women and the identification of women for the development of GDM and, once diagnosed, placing them on a strict glycaemic control throughout pregnancy. The cost efficiency of screening oll women for GDM is often discussed and likewise, whether many of these women are over-treated unnecessarily. Argument, however, should concentrate not just on the immediate effects of GDM but on the long-term consequences for both the mother and her offspring.

INV37

The Role of Antepartum Transabdominal Amnioinfusion in the Management of Oligohydramnios in Pregnancy

B. Ahmed, F. Tariq Butt

Obstetrics and Gynaecology, Doha – Qatar, Doha, Qatar

Objective: The purpose of this study was to evaluate the role of transabdominal amnioinfusion in the management of oligohydramnios with the view to improving pregnancy outcome.

Methods: The study consisted of a retrospective analysis of 17 pregnant women presenting with oligohydramnios who were treated with amnioinfusion during pregnancy in a period from 2003–2006.

Results: The mean gestational age at first treatment was 24 weeks. The mean pre-procedure deepest pool of amniotic fluid was 1.8cm and post-procedure was 3.8cm. The mean number of infusions was 1.05. The mean first infusion to delivery interval was 31 days. Perinatal mortality was 88% and neonatal mortality was 35%, with only one baby surviving the neonatal period. There were 3 cases of chorioamnionitis, with one of these cases presenting with premature rupture of the membranes (PROM) at the time of amnioinfusion.

Conclusion: Transabdominal amnioinfusion is a useful procedure to reduce complications that result from oligohydramios. Although the results show a high perinatal mortality, it must be borne in mind that most of these pregnancies had multiple fetal abnormalities with an already predicted poor outcome. Importantly, as this procedure increases the latency period, it may be useful in preterm pregnancies where prolonging the duration of the pregnancy may result in better perinatal outcome by improving important factors that influence survival including increased birthweight.

INV38

Renal Blood Flow, Prediction and Prophylaxis of Renal Failure in Newborns

E. Baybarina

Research Centre for Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation

Objectives: To improve outcomes in critically ill newborns and to prevent acute renal failure due to renal ischemia.

Methods: Color Doppler ultrasonography was used to determine quantitative characteristics of renal blood flow in 134 critically ill term and preterm newborns on day 1,3,5 and 7 of life. The peak systolic and end-diastolic blood flow velocities as well as time-averaged maximal velocity were determined and the resistance index was calculated.

Criteria of acute renal failure: Plasma creatinine levels above 130μmol/l; duration of oligoanuria for more then 24 hours.

Criteria of nonoliguric renal failure: Plasma creatinine levels above 130μmol/l; absence of oligoanuria.

Criteria of renal hypoperfusion in the first day of life: Time-averaged maximal velocity of blood flow in the renal artery less than 9 cm/sec; resistance index exceeding 0.85; abnormal wave curves (absent or reversed diastolic flow).

Results: In case of renal hypoperfusion during the first hours of life, acute renal failure and nonoliguric renal failure developed in 9% and 26% of the newborns, respectively. Early correction of renal blood flow (by increasing a flow rate of IV fluids and using pentastarch or cardiotonics, if indicated) has resulted in a 2.5-fold decrease in the rate of acute renal failure.

Conclusion: Ultrasonic Dopplerography of renal blood flow can be regarded as a highly efficient method for early detection of renal ischemia.

INV39

Decision Making Regarding Withholding or Withdrawing Neonatal Intensive Care

J. Jenkins

Queen's University Belfast, Child Health, Antrim, United Kingdom

Decisions regarding withholding or withdrawing life-prolonging treatment for critically ill neonates are profoundly challenging for both clinicians and parents. Advancing technology can mean that, as well as the clinical complexities, these decisions raise difficult questions about the boundaries of ethically and legally sound good practice. It is also important that healthcare professionals and families have some common understanding and agreement about the appropriate basis for making these difficult decisions.

A series of studies across Europe have sought to inform the ethical and legal debates in this area, by providing better information about the actual experiences, understanding and attitudes of clinicians and parents. They highlight significant differences in views, between countries and between healthcare professionals and parents within each country, about the appropriate role of parents in making decisions about withholding and withdrawing treatments. There are also important differences, within and between countries, in how ethical and legal principles are applied in practice. These studies suggest that more should be done to provide guidance and support to healthcare professionals and information to parents, to reduce the scope for misunderstanding and conflict, and to ensure that the interests of the child have been properly considered.

This presentation will outline national guidance for healthcare professionals in the UK which has helped improve understanding between healthcare teams and families, and raised public awareness about the complexities of the issues and standards of good practice.

INV40

Sudden Infant Death Syndrome

A. Greenough

King's College London, Division of Asthma, Allergy and Lung Biology, London, United Kingdom

Sudden infant death syndrome (SIDS) is the unexpected death of an infant which remains unexplained after a thorough investigation, including a post-mortem. Possible mechanisms of SIDS include failure to arouse, infection and/or autonomic dysfunction. Prematurely born infants are at increased risk of SIDS, particularly if they are slept prone: the risk for prone versus supine sleeping for SIDS for term born infants is 13.9, but 48.4 in infants born prematurely. Yet surveys have demonstrated that neonatal practitioners do not emphasize that prone sleeping should be avoided following neonatal unit discharge. As a consequence, we have investigated the effect of sleeping position on respiratory function and control of prematurely born infants immediately prior to neonatal unit discharge at 36 weeks postmenstrual age (PMA). In the prone position, lung volume and oxygenation were superior, but the infants slept longer with greater sleep efficiency and had more central apnoeas and less arousals and awakenings. In asymptomatic infants, gastro-oesophageal reflux, although higher in the supine compared to the prone position, was much lower than the treatment level and was not significantly associated with apnoeas. Respiratory control was superior in the supine position as demonstrated by a faster ventilatory response to tube breathing and a greater response to a carbon dioxide challenge. Those results emphasize neonatal practitioners should recommend supine sleeping for prematurely born infants following neonatal unit discharge; this may, however, increase the supplementary oxygen requirements of BPD infants and parents need to be appropriately counselled.

INV41

Prematurity Prevention–An Update

E. Saling

Erich Saling-Institute of Perinatale Medicine, Berlin, Germany

Objective: Prevention of prematurity by the Prematurity-Prevention-Program including “Self-Care”-measures and discussion of recent research in this area.

Introduction: Ascending genital infections are the most important avoidable causes of early prematurity. Ascending genital infection and/or bacterial vaginosis start frequently with a disturbance of the vaginal protective lactobacillus system – which we consider as a “precursor”.

Our program is based on an anamnestic assessment of prematurity risk, the early detection of warning signs (including screening for pre-infection respectively infection signs by regular measurement of the vaginal pH) and, if necessary, the appropriate therapeutic measures. It includes – additionally to regular prenatal care – “Self-Care”-activities by the women themselves and special measures, for example the Early Total Cervix Occlusion (ETCO) for women with recurrent premature births.

Results:

“Self-Care”-measures: In all studies the rate of premature births could be considerably reduced. In Thuringia (more than 16,000 births in the study year) the rate of infants born <32 + 0 gw was reduced significantly from 1,58 % to 0.99% respectively in infants <1000g from 0.61% to 0.38%. After the campaign in Thuringia had been finished, the prematurity rates monitored in 2002 were again as high as before.

After an ETCO the rate of surviving children was about 80% in our own population (as opposed to 17 % in the pregnancies before the ETCO in the same group). Similarly good results have been obtained by other clinicians. With a general use of ETCO in multiple pregnancies Schulze (2008) was able to achieve a prematurity rate of only 17% as against a rate of 29% in cases without ETCO.

Discussion: The “self-care”-program for pregnant women proved to be a very efficient method for the prevention of prematurity and should be recommended to every pregnant woman. In cases where this is not possible, at least the doctors and midwives should measure the vaginal-pH regularly, but then the success rate is lower. Other high standard measures such as measurement of cervical length and fetal Fibronectine may be additional measures according to the situation. More research in this area is necessary. The early total cervix occlusion is an effective preventive measure for women with recurrent late abortions or premature births and it seems to be also a good measure to prevent premature births in multiple pregnancies.

Keywords:prematurity prevention, vaginal pH measurement, vaginal infection, Self-Care, Early Total Cervix Occlusion, protective lactobacillus system

Further information on: www.saling-institute.org

INV42

Developmental Origins of Hypertension: Low Birth Weight Associated with Cardio-Vascular Disease at Adulthood

U. Simeoni, F. Boubred, I. Ligi, C. Buffat, V. Andres

Université de la Méditerranée, Division of Neonatology, Marseille, France

The concept that a critical window exists during early pregnancy and the early postnatal period, during which environmental factors can program life long lasting alterations of physiology and susceptibility to disease remains one of the more astonishing issues raised by biology in the last decades. Studies on blood pressure and early growth show that in both children and adults there is an inverse relationship between birth weight and arterial blood pressure: blood pressure is increased by reduced birth weight, the size of this effect ranging between 1 to 3 mmHg/kg of birth weight. Such findings have been replicated with various animal models of intrauterine growth restriction, in guinea pig, sheep and particularly rat. Knowledge on the mechanisms of such early programming of cardio-vascular function and risk of disease at adulthood are partially known, and are likely to be multiple. While evidence of the early programming of cardiovascular function and disease is provided by studies including subjects whose low birth weight is likely to be caused principally by IUGR, recent studies raised the issue of the long term consequences of low or very low birth weight due to preterm birth. Premature birth has been shown to be associated with elevated arterial blood pressure in adulthood independent on birth weight.

Organ specific mechanisms involve principally the kidney and the vasculature. The developing kidney has been shown to be one key organ involved in the programming of hypertension in adulthood, due in particular to the definitive reduction of the total number of nephrons, which is a characteristic of low birth weight and intra-uterine growth restriction, although available data suggest that nephrogenesis is altered in premature infants as well. Vascular mechanisms involve both the media and the endothelium. Elastin content in the arterial media at birth has been shown to be decreased in low birth weight infants. As elastin half-life is several decades long, this may explain decreased arterial elasticity at adulthood and pave the way to hypertension. Endothelial dysfunction has been characterized in terms of early altered endothelium-dependent vasodilating capacity in low birth weight infants, in particular when postnatal growth is accelerated.

Molecular mechanisms involved in the memory of events that occur prenatally or during the early stages of growth are still poorly understood. Transriptome analysis reveals that the expression of a huge number of genes, involved in various biologic systems such as apoptosis, is up- or down regulated. Moreover, epigenetic alterations of gene expression, due to CpG DNA methylation/demythlation or alteration of structure of histones are likely to be involved.

Improved knowledge on the mechanisms of the early programming of hypertension may open new research areas for prevention, and nutritional or pharmacological intervention.

INV43

Is 3D Ultrasound Useful in the Diagnostic of Neonatal Brain Disorders?

M. Stanojevic

Medical School University of Zagreb, Sveti Duh Hospital, Department of Obstetrics and Gynecology, Zagreb, Croatia

Introduction: In the 1990's, a new technique of 3D and 4D ultrasound (US) was developed, enabling depiction of neonatal brain in the third dimension in real-time.

Aim: To present the development of the indications for 3D brain US in neonatal period, with the review of the literature and to present the author's experience with the method.

Material and methods: According to available literature, brain 3D is used in selected groups of newborns in order to improve diagnostics.

Results: Brain 3D is more convenient than 2D, due to shorter time of data acquisition. 3D brain US plays very important role as diagnostic tool to determine the prognosis of the brain disorders (intracranial hemorrhage, hypoxic ischemic brain injury, congenital anomalies of the brain) in newborns, which can possibly influence the quality of life of newborns and their families. 3D US is valuable imaging modality for depiction of neonatal brain, although still not used so often as conventional 2D.

Conclusion: 3D US of neonatal brain has been considered as significant improvement compared to the 2D due to: shorter time of data acquisition, possibility of comprehensive and thorough analysis of data set, volume rendering and measurement.

INV44

New Fetal Neurobehavioral Scoring Test in High Risk Pregnancies

A. Kurjak

Medical School University of Zagreb, Sveti Duh Hospital, Department of Obstetrics and Gynecology, Zagreb, Croatia

Direct assessment of functional development of the fetal central nervous system is not possible, but the assessment of fetal behavior may provide the possibility to distinct between normal and abnormal brain development. Since the ultrasonographic technique allowed the investigation of spontaneous fetal motor activity in utero first studies of spontaneous prenatal movements and fetal behavior were performed and published. 2D ultrasound was considered somewhat subjective method because information needs observer interpretation. The latest development of three-dimensional (3D) and four dimensional (4D) sonography that overcame some of the limitations of 2D methods enable precise study of fetal and even embryonic activity and behavior. Our findings on the behavior in the high-risk pregnancies for cerebral palsy assessed by the ultrasonographic techniques will be presented.

INV45

Sonographic Imaging of the Posterior Fossa–Is the Enlarged Cisterna Magna always Pathologic? 2&3DUS EVALUATION

Y. Zalel

Sheba Medical Center, Tel – Hashomer, Israel

Agenesis of the cerebellar vermis is an uncommon defect, and it is usually detected while evaluating the posterior fossa. It could be as part of the DWM or as an isolated finding. It could also present as complete agenesis or partial, i.e. inferior vermian agenesis. It may be impossible to correctly diagnose antenatally a defect in the cerebellar vermis in all cases. A very high proportion of disagreement was found between prenatal ultrasonic diagnosis of Dandy-Walker malformation or variant and autopsy findings, emphasizing the need in accurate sonographic demonstration of the cerebellar vermis.

The purpose of our presentation is to evaluate the posterior fossa of the fetal brain.

It is emphasized, that the diagnosis of vermian agenesis (especially partial agenesis) cannot be made prior to 18 weeks of gestation!!

Detailed US of the posterior fossa should include not only the measurements of the vermis, but also the structure of the vermis (primary fissure, fastigium), but also the relationship to the cisterna magna, the 4^th ventricle, the tentorium as well as to the pons.

Enlargement of the posterior fossa – Is it always pathological??

It depends on the gestational age. Also, the possibility of rotation of the vermis should be included in the differential diagnosis. The demonstration of the normal vermis on mid-sagittal plane in cases with “enlarged cisterna magna” on standard plane raises the possibility of rotation of the vermis.

When comparing ultrasound to MRI of the fetal posterior fossa, it is sometimes easier to perform a perfect midline sagittal slice with US than with MRI before 25 weeks. Early MRI adds little new information compared with well-conducted US.

The contribution of 3D-US to the sonographic demonstration of the posterior fossa is emphasized.

INV46

Postnatal Steroid Treatment of Preterm Infants: Current Aspects

P. Groneck

Klinik für Kinder und Jugendliche, Leverkusen, Germany

Due to the unfavourable effects on cerebral development, the use of postnatal steroids has significantly been reduced in preterm infants during the last 8 years. However, as steroids also decrease mortality, up to 8–19% of neonates with birthweight below 1500 g are currently still being treated. The main indications are hypotension refractory to catecholamines and bronchopulmonary dysplasia (BPD). The unfavourabe effects on brain development are predominantly related to the use of dexamethasone. Although prenatal treatment with betamethasone is associated with better outcome results compared to prenatal dexamethasone, betamethasone has not been studied postnatally. Hydrocortisone has been used to treat hypotension and BPD, and does not lead to an increased risk of developmental disabilities. This may be due to its mineralocorticoid effects, by which the expression of antiapoptotic genes are increased within the brain. In contrast, dexamethasone leads to an increased expression of proapoptotic genes. Whether the clinical effects of hydrocortisone on lung function compare to those of dexamethasone, has not been studied. A clinical study should compare the short and long term effects of dexamethasone, betamethasone and hydrocortisone in severely sick patients, in whom postnatal steroid treatment is considered. Due to its better risk profile, hydrocortisone currently seems to be the preferrable drug.

INV47

Impact of Antenatal and Postnatal Interventions on Respiratory Outcomes

A. Greenough

King's College London, Division of Asthma, Allergy and Lung Biology, London, United Kingdom

Pulmonary hypoplasia, incomplete development of the lung, is the commonest single abnormality found at post-mortem, being present in 15 to 20% of early neonatal deaths. It can be a primary condition but more often is secondary to a variety of antenatal events. In utero treatment, particularly of congenital diaphragmatic hernia, is becoming increasingly available, but not without risks. As a consequence, accurate antenatal diagnosis of pulmonary hypoplasia is essential. The results of 3D ultrasound, particularly using virtual organ computer aided analyser, are predictive of death or survival and we have recently demonstrated significantly correlate with respiratory outcomes. BPD, a common adverse outcome of very premature delivery, has a multifactorial aetiology, but is more common if there is antenatal infection/inflammation in combination with a postnatal insult. Antenatal steroids may prime the lung for ventilation induced injury [1]: in a sheep model, intra-amniotic endotoxin and betamethasone had similar effects on the fetal lung [2] and antenatal glucocorticoids may impair the preterm lung's ability to down regulate endotoxin induced inflammation [3]. Those results highlight the importance of diagnosing and treating antenatal infection before routinely administering glucocorticoids. Meta-analyses of randomised trials of ventilation modes have demonstrated only high frequency oscillatory ventilation (HFOV) significantly (albeit modestly) reduces BPD. Non-randomised data also suggest HFOV may also be associated with less reduction in lung function at one year of age.

INV48

CPAP Era in Russia: Results and Perspectives

E. Baybarina

Research Centre for Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation

Objectives: To evaluate the effectiveness of new strategy of respiratory therapy in preterm infants with respiratory distress syndrome.

Methods: Comparison of the results of new strategy of respiratory therapy (early nasal constant positive airway pressure (CPAP), INSURE method, if artificial ventilation indicated – early extubation) vs. traditional strategy – to start respiratory therapy in preterm infants with artificial ventilation. New strategy of respiratory therapy was introduced in our institution in 2005. We compared two populations of preterm babies with GA less than 33 weeks – 90 born in 2003–2005 (group 1) and 110 in 2006-2008 (group 2). Strategy of early therapeutic use of surfactant was applied to both groups.

Results: In group 2 among babies with GA less than 26 weeks 100% required ventilation, with GA 26 weeks – 75%, 27 weeks – 55%, 28 weeks – 50%, 29 weeks 35%. Duration of artificial ventilation and respiratory support in group 1 was 9 and 10 days and in group 2–5.4 and 4.5 days respectively. Incidence of intraventricular hemorrhage grade II-III in group 1 was 27%, in group 2–10%. With implementation of new strategy incidence of ventilator associated pneumonia as well as total costs for treatment decreased. Similar results were achieved in different clinics in Russia.

Conclusion: Early CPAP strategy is effective and is now quickly spreading among perinatal centers in Russia. Perinatal audit needed to improve implementation of early CPAP.

INV49

4 D Fetal Echocardiography in the Study of Structural Cardiac Diseases

G. Rizzo¹, A. Capponi², M. Vendola¹, M.E. Pietrolucci¹, D. Arduini¹

¹Università Roma Tor Vergata, Dept Ob/Gyn, Roma, Italy, ²Ospedale G.B: Grassi, Dept Ob/Gyn, Roma, Italy

Congenital heart defects (CHD) are the most frequent malformation in the human fetus and are the leading cause of mortality due to malformations in the first year of life (2). Despite its clinical importance screening performed by ultrasonographic examination during the second trimester of pregnancy has shown widely divergent results with reported a low detection rates mainly due to the difficulties in obtaining an adequate examination of the fetal heart. Studies on the efficacy of screening for the detection of the congenital heart diseases have differed widely withsensitivities ranging between 10% and 81% – Moreover with the current technology and with a proper training of the examiners the demonstration of the four chamber view allows the detection of 40–50% congenital heart diseases in a low risk group of pregnancies. Additional visualization of the outflow tracts increases the rate to 65–70%.

Four-dimensional (4D) ultrasound of the fetal heart has been recently suggested as a tool to improve the detection rate of CHD by decreasing the dependency on operator skills required in two-dimensional ultrasound scans but few data are available on its impact in clinical practice. Objective of this review is to asses the role of 4D echocardiography with spatio-temporal image correlation (STIC) during routine second trimester examination and in fetuses with CHD. In particular will be described the technique of obtaining 4D volume of the fetal heart, how to navigate in the volume to obtain diagnostic planes and how to use semiautomatic and automatic software of analysis.

The standard fetal cardiac anatomy survey can be performed in the second trimester fetus by 4D STIC in both normal and abnormal hearts. This approach may reduce the operator dependency in diagnosis CHD.

INV50

Guidelines for IUGR: Definition, Diagnosis and Management

G.P. Mandruzzato

Istituto per l'Infanzia, Burlo Garofolo, Department of Obstetrics and Gynecology, Trieste, Italy

Intrauterine growth restriction (IUGR) is a major problem in perinatal medicine. In prospective studies by using serial ultrasonic biometry it has been shown that is observable in 8% of a general population. Moreover 52% of stillbirths are associated with IUGR and 10% of perinatal mortality cases in Europe are consequence of unrecognized severe IUGR. Evidence exists that the management and the clinical outcome can be improved by using fetal monitoring capacities that are available today. Of course in order to make it possible a timely recognition of the growth restriction is crucial. As for any other condition the recognition depends on a clear definition. The best available definition has been offered by ACOG. “IUGR is a fetus that fails to reach his potential growth.” Therefore what is matter of interest is the function (growth) and not the result (weight). It must be remembered that SGA and IUGR are not synonymous as many SGA are not IUGR and many IUGR are not SGA. The practical consequence is that for IUGR recognition at least 2 fetal biometry scans are necessary looking for any deviation from the expected individual curve of growth. As IUGR can be the consequence of maternal, placental and fetal conditions after IUGR recognition it is necessary to assess the aetiology. In fact the management and outcome are strongly dependent on it. In the majority of the cases IUGR is consequence of placental vasculopathy inducing chronic fetal hypoxaemia (CFH). In this condition the careful monitoring of CFH represent the basis of a rationale management especially in choosing the time of the delivery.

INV51

Early Hemodynamic Changes in Fetuses Developing Growth Retardation

G. Rizzo¹, A. Capponi², M.E. Pietrolucci¹, O. Cavicchioni¹, C. Boccia¹, D. Arduini¹

¹Università Roma Tor Vergata, Dept Ob/Gyn, Roma, Italy, ²Ospedale G.B: Grassi, Dept Ob/Gyn, Roma, Italy

Changes in the distribution of cardiac output(CCO) to the placenta (placenta/CCO fraction) have been reported in growth retarded (IUGR) fetuses but the temporal sequence of these modifications inrelation with other hemodynamic changes of fetal arterial and venous circulations is still unknown. Aim of this study was to evaluate during the second trimester the values of CCO tothe placenta in a group of fetuses at high risk to develop IUGR.

We therefore studied pregnancies characterized by bilateral notches in uterine artery at 20 to 24 weeks. At this gestational age we measured fetal biometry, Doppler velocity waveforms from umbilical artery, middle cerebral artery, ductus venosus, intra-abdominal portion of the umbilical vein and outflow tracts of right and left ventricles. The diameter of aorta and pulmonary valves and umbilical vein were also measured and CCO (i.e. left cardiac output + right cardiac output) and placental blood flow calculated. The placenta/CCO fraction was calculated as the % of placental blood flow on CCO.

Pregnancy were divided according their outcome in normal outcome and fetal weight (group A), birthweight <10° centile with normal Doppler in umbilical artery during all gestation (group B) pregnancies with birthweight <10° centile and abnormal umbilical Doppler later in gestation (group C). There were no significant differences among groups at 20 to 23 weeks in fetal biometric parameters and Pulsatility Index (PI) values from UA, MCA and DV and CCO, while significantly reduced value of placental/CCO fraction were evidenced in group C but not in group B.

In fetuses developing IUGR the placental/CCO fraction is reduced and changes occur earlier than the modifications in fetal size and PI values from arterial and venous vessels. This may be the expression of a more extensive recirculation of umbilical blood within the fetal body in the attempt to improve the extraction of oxygen and nutrients in the early stage of placental insufficiency.

INV52

Immunological aspect of Spontaneous Abortion

Z. Fatusic

University Clinical Center Tuzla, OB/Gyn Clinic, Tuzla, Bosnia and Herzegovina

Spontaneous and habitual abortion are one of mostpainful expeiriences for couples expecting a child. It is a extraction orexpulsion from its mother of a fetus weighing 500 g or less or pregnancy termination before 24 completed weeks of gestation. The incidence ofspontaneous abortion is 15%–25% of all recognised pregnancies. 1%–2% of all womenabort habitually. Out of many recognised causes of spontaneous and habitual abortion, 10%–50% still are unexplained.

The most number of unexplained abortions have immunological reason. By pre-embrional recognisation of maternal immune system starts subsequent immunoprotective mechanism. There the key role has PIBF (Progesterone induced blocking factor) whose production depends of sufficient circulating progesteron concentration. PIBF supports Th-2cytokines, inhibits nuclear killer cells (NK cells), induces an increased production of asymmetric, non-cytotoxic blocking antibodies. The production of pro-inflammatory, cytotoxic cytokines interferon- ? (IFN-?), tumor necrosis factor -?, (TNF-?), interleukin-2(IL-2) is reduced.

There is the controversy about treatment of spontaneous and habitual abortion: from “do nothing” to routine pharmacological “support of every the pregnancy”.

Keywords:spontaneous abortion, habitual abortion, immunology

INV53

Short Lifespan of Corpus Luteum during Early Pregnancy

A. Tekay¹, A. Ruokonen², I. Järvelä¹

¹Oulu University, Dept of Obstetrics and Gynecology, Oulu, Finland, ²Oulu University, Dept. of Clinical Chemistry, Oulu, Finland

Background: Most important task of the corpus luteum (CL) is to produce sufficient progesterone until the luteoplacental shift occurs. The primary aim of this research was to evaluate changes in the CL vasculature during early pregnancy.

Methods: Twenty naturally conceived pregnancies were examined weekly from week 5 to week 11 using 3-dimensional (3-D) power Doppler ultrasonography. In addition, the human chorionic gonadotrophin (hCG), P and 17-OH progesterone (17-OHP) levels were measured.

Results: The vascular supply in the ovary containing the CL was greatest at week 5, and thereafter, declined continuously until week 11. The decrease in the vasculature correlated with the decrease in 17-OHP. Mean hCG levels reached a maximum at week 8. P levels reached the nadir at week 7 and increased after that.

Conclusions: Vasculature in the CL appears to be created already by the fifth week of pregnancy and it does not enlarge despite of rising hCG levels.

INV54

The Dietary Intakes and Eating Patterns of Low-Income Pregnant and Postpartum Women

F. Ford

University of Sheffield, Sheffield, United Kingdom

Objectives: To examine if a new food-support benefit ‘Healthy Start’ (HS) improves the dietary intake of low-income pregnant and postpartum women in Sheffield.

Design: A before-and-after study comparing nutritional behaviour of pregnant and postpartum women who were beneficiaries of, or eligible for the Welfare Food Scheme (WFS) (Phase 1) or HS (Phase 2).

Setting: Large obstetric unit, UK.

Participants: Phase 1, 186 pregnant women (90 WFS and 96 HS) and Phase 2, 154 postpartum women (86 WFS and 64 HS). Inclusion criteria: Caucasian, English-speaking, living in Sheffield, free of nutrition-related pre-existing medical conditions, recipient of, or eligible for, food-support benefit.

Main outcome measures: Dietary intakes using a validated, interviewer-administered, semi-quantified food frequency questionnaire (FFQ), vitamin supplementation.

Results: Pregnant HS women had significantly higher energy (P = 0.0001) and nutrient intakes i.e. iron (P = 0.0001), calcium (P = 0.0001), folate (P = 0.0001) and vitamin (P = 0.001) compared to the WFS women. Postpartum HS women had significantly higher energy (P = 0.001) and nutrient intakes i.e. iron (P = 0.003), calcium (P = 0.0001), folate (P = 0.0023) and vitamin C (P = 0.001) than WFS women. Observed differences in nutrient intakes remained significant after controlling for the potential confounding effect of a number of known factors i.e. education and age. Uptake of periconceptional vitamin and mineral supplements was low in both groups. None of the HS were receiving the HS vitamins.

Conclusions: Pregnant and postpartum HS women increased their food consumption and more of them met the recommended dietary intakes for calcium, folate, iron and vitamin C when compared with WFS women, although this may have resulted in excessive energy intakes. HS could be more effective if the nutrition capacity of health professionals was improved.

INV55

Management of Post-Partum Hemorrhage

J.W. Dudenhausen

Charite, Kliniken für Geburtsmedizin, Berlin, Germany

PPH is one of the top five causes of maternal mortality in the industrial world and in the developing countries. It is an obstetrical emergency that can follow vaginal or caesarean delivery. It is important to coordinate activities among the specialists involved in the treatment of the woman. Etiology and risk factors are atony, trauma, coagulation defects. The lecture will illustrate nonoperative and operative interventions (uterotonic drugs, fluid resuscitation and transfusion, inspection of cervix and vagina for lacerations, tamponade, aterial embolization, uterine vessel ligation by laparotomy or laparoscopy, uterus compression sutures, internal iliac artery ligation, hysterectomy).

INV56

Fetal Pulse Oximetry and Stan 21. Intrapartum Fetal Pulse Oximetry Behaviour during Fetal Heart Rate Decelerations

A. Puertas-Prieto, M. Paz Carrillo, F. Montoya

“Virgen de las Nieves” University Hospital, Obstetric and Gynecological Department, Granada, Spain

Fetal Pulse oximetry (FSpO₂) consists of measuring oxygen saturation of fetal arterial hemoglobin, and aims to improve upon previous methods by providing direct, continuous measurement of fetal oxygenation status. It seeks to document the behavior of FSpO₂ during different types of deceleration.

When de evolution of FSpO₂ is assessed throughout the evolution of fetal heart rate decelerations, its seems that FSpO₂ during the course of labor in all groups of decelerations decreases significantly in parallel with the maximum decrease in decelerations and during recovery of heart rate. Once heart rate has recovered, fetal oxygen levels return to values similar to those recorded before the onset of deceleration. However, the lack of similarity in the depth of the nadir between early, late and variable decelerations, on one hand, and prolonged decelerations on the other hand is evidence that FSpO₂ behaves differently in the latter type of deceleration.

This distinct behaviour of prolonged decelerations may lie in the fact that the mechanism that triggers deceleration acts during a period long enough to cause a decrease in fetal oxygenation.

Fetal oxygenation in all types of deceleration, including prolonged decelerations, returns to basal levels once the episode has concluded. This may mean that in the decelerations we analyzed, situations that cause changes in FHR tracings are not related with persistent changes in FSpO₂ levels.

Each deceleration may be treated as a separate entity, but also considering each deceleration as part of a history of repeated changes in heart rate. In other words, we looked for evidence of a relationship between FSpO₂ levels and a number of cardiotocographic patterns. In this sense the value of FSpO₂, before the decelerations began showed that basal values were highest for early decelerations, followed by prolonged and variable decelerations, and were lowest for late decelerations. This result is evidence that different patterns of FHR are reflected as different degrees of fetal oxygenation, and that late decelerations, per se, do not indicate more significant periodic oxygen deprivation to the fetus than do variable decelerations. Rather, late decelerations are simply a sign of an overall lower basal fetal oxygenation status. Thus, in fetuses with cardiotocographic evidence of integrity of their metabolic reserve, basal levels of FSpO₂ are clearly above the lower limit of normality (30%).

INV57

The Markers of Infection/Inflammation in Management of Preterm Labour

Z. Hájek¹, A. Germanová², M. Koucky¹, J. Kobilkova³, A. Parizek¹, T. Zima², M. Kalousova²

¹University Hospital, 1st School of Medicine, Charles University, Obstetrics and Gynaecology, Prague, Czech Republic, ²University Hospital, 1st School of Medicine, Charles University, Institute of Clinical Biochemistry and Laboratory Diagnostics, Prague, Czech Republic, ³Institute for Care of Mother and Child, Prague, Czech Republic

Objective: The optimal combination of markers predicting infection/inflammation and clinical evaluation of symptoms are the crucial steps in management of threatened preterm labour, especially in cases of PPROM. In management is very important to use antibiotics, corticosteroids and postpone the preterm birth as long as possible or recognise the right time for termination of pregnency in case of severe intraamniotic inflammation.

Methods: The basic infection markers, bacterial culture including the detection of sexual transmitted diseases, ultrasound measurement of the uterine cervix, were combined with markers (IL-6, sRAGE) We added also cytological cervicovaginal smear using Bethesda classification 2001.

Results: Studying relationship to routine inflammation markers, there is a negative correlation between sRAGE and leukocyte count (r = −0.325, p < 0.05).

Women with threatening preterm birth had significantly higher concentration of serum sRAGE in comparison with healthy pregnant women (818.85 ± 328.52 pg/ml vs. 668.80 ± 295.73 pg/ml, p < 0.05). Patients with PPROM had significantly lower levels of sRAGE compared with other patients with threatening premature labour (600.09 ± 324.41 pg/ml, p < 0.05). Patients with PPROM had significantly increased IL-6 concentration (5.59 ± 9.24 pg/ml, p < 0.05) compared to patients with contractions (2.38 ± 3.33 pg/ml) or vaginal dilatation (2.16 ± 3.51 pg/ml). Bethesda cytological smear has a high sensitivity but a very low specificity.

Conclusion: sRAGE could represent a promising marker for premature labour in combination with the level of leucocytes resp. neutrophils and IL6. The combinations of markers with clinical evaluation of the symptoms and US measurement of the uterine cervix contribute for the right management of preterm labour.

INV58

The Contribution of 3D-US to the Prenatal Diagnosis of Chromosomal Abnormalities

Y. Zalel

Shebaari Medical Center, Tel – Hashomer, Israel

The 3D US images provided additional information in 53 anomalies (51%), were equivalent to 2D US images in 46 anomalies (45%), and were disadvantageous in four anomalies (4%). The 3D US was most helpful in evaluating fetuses with facial anomalies, hand and foot abnormalities and axial spine and neural tube defects.

NT – Three-versus two-dimensional ultrasound for nuchal translucency thickness measurements: comparison of feasibility and levels of agreement. There was a statistically significant underestimation of the NT by 2D transabdominal as compared with 3D transvaginal ultrasound of 0.1 mm and by 3D transvaginal as compared with 2D transvaginal ultrasound of even 0.1 mm. 3D transvaginal ultrasound of the nuchal fold has increased feasibility to 2D transvaginal ultrasound within a short examination time and with minimal, but significant, measurement differences.

Nasal bone – Three-dimensional ultrasound with maximal mode rendering: a novel technique for the diagnosis of bilateral or unilateral absence or hypoplasia of nasal bones in second-trimester screening for Down syndrome. Unilateral absence or hypoplasia of nasal bones is an important and new observation in fetuses with Down syndrome. This differentiation is best demonstrated on 3D ultrasound with maximal mode rendering.

Palate – S. Campbell. Ultrasound antenatal diagnosis of cleft palate by a new technique: the 3D reverse face view. B. R. Benacerraf. Cleft of the secondary palate without cleft lip diagnosed with three-dimensional ultrasound and magnetic resonance imaging in a fetus with Fryns' syndrome. G. Pilu. A novel technique for visualization of the normal and cleft fetal secondary palate: angled insonation and three-dimensional ultrasound. J. M. Faure. Sonographic assessment of normal fetal palate using three-dimensional imaging: a new technique.

Mandible – Chromosomal abnormalities were detected in 66% (37/56) of the fetuses with micrognathia. A much better demonstration of the malformation using 3D irrespective of fetal posture!

Limb deformities – Fetal midphalanx of the fifth digit, Polydactyly, Clinodactyly, Syndactyly, Club Foot. In 28 of 41 suspected cases the diagnosis of abnormalities was determined after examination by 3D sonography.

Sutures – Most (82–100%) cranial sutures and fontanels could be visualized with 3D ultrasound. However, the sagittal suture and posterior fontanel were visualized in only 47% and 42%, respectively.

Ribs – agenesis of the 12th rib in a fetus with trisomy 21 and more.

Ambiguous Genitalia – 3DUS can aid in the DD between hypospadias and micropenis. Provides a better demonstration to the parents.

Vascular abnormalities & Chromosomal aberrations – Fetal Aberrant right subclavian artery and DS. The prevalence of ARSA is 1.41% in the normal population, as opposed to 37.5% among DS fetuses in this small study group (Odds Ratio 42.04!).

INV59

Consequences of Introducing a National Policy of First Trimester Combined Screening for Down's Syndrome

A. Tabor

Copenhagen University Hospital, Dept. of Fetal Medicine, Copenhagen, Denmark

Objective: To evaluate the changes in prenatal diagnostic practice after the introduction of first trimester combined screening for Down's syndrome.

Background: New guidelines from the National Board of Health recommend screening for all women, irrespective of age, and only chorionic villus sampling (CVS) or amniocentesis (AC) to women having a combined risk of having a fetus with Down's syndrome? 1:300.

Methods: The guidelines were introduced in the 15 Danish counties in 2004–2006. From the Danish Central Cytogenetic Registry, we retrieved data on number of CVS and AC, as well as on number of pre- and postnatally diagnosed cases of Down's syndrome. Data on screening performance were collected from all obstetrical departments.

Results: The number of pregnancies in which an invasive procedure was performed decreased from 6,555 in 2002 to 3,102 in 2006, or by 53%. The invasive testing rate thus decreased from 10.3% to 4.8 % during this period. The proportion of CVS increased from 51% to 69% during the same five years. The number of newborns with Down's syndrome decreased from around 60 per year prior to 2005 to 30 per year in the following years. The screen-positive rate in the different departments ranged from 2 to 6%.

Conclusion: At a national level it was possible to halve the proportion of women having a CVS or AC following the introduction of a national first trimester screening policy, and at the same time reduce the number of newborns with Down's syndrome by around 50%.

INV60

CVS and Amniocentesis–What are the Real Risks?

A. Tabor

Copenhagen University Hospital, Dept. of Fetal Medicine, Copenhagen, Denmark

Objective: To assess the miscarriage rate attributable to amniocentesis (AC) and chorionic villus sampling (CVS).

Background: The risk of abortion following CVS and AC was investigated in randomised clinical trials in the 1980's and early 1990's. Amniocentesis was evaluated versus no procedure and found to increase the abortion rate by 1.0%. The risk following CVS was found to be comparable to that of AC.

Since then the image resolution of the ultrasound machines has increased and some studies have shown that the miscarriage rate associated with an invasive procedure was less than 0.5%.

Material: The latest meta-analysis from 2007 and a national register based cohort study including all women who had an AC (n = 32 852) or CVS (n = 31 355) in Denmark between 1996 and 2006.

Results: The abortion rate following AC and CVS was between 0.5 and 1.0% in the meta-analysis as well as in this prospective study.

Conclusion: The miscarriage rate attributable to an invasive prenatal genetic procedure is between 0.5 and 1.0%, and there seems to be no difference between CVS and AC.