Respiratory syncytial virus infections in Turkey: a 2-year epidemiological study Murat Yurdakök Hacettepe University, Ankara

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2 Respiratory syncytial virus infections in Turkey: a 2-year epidemiological study Murat Yurdakök Hacettepe University, Ankara Respiratory syncytial virus (RSV) infections may lead to severe respiratory diseases, particularly in infants and young children. Prophylactic anti-rsv monoclonal antibodies are recommended in high-risk infants. In order to determine the timing of prophylaxis, the seasonal variations of RSV had to be determined. In the present study, we reported the results of an epidemiological study conducted in 32 hospitals of Turkey between May 2008 and September 2010, on children <2 years of age hospitalized with the diagnosis of lower respiratory tract infection (LRTI). Children who had used palivizumab against RSV infection, and the cases in which respiratory samples could not be collected in 24 hours after hospitalization or in 24 hours after emergency room (ER) or outpatient clinic administration were excluded from the study. RSV Respi-strip test kits were used to detect RSV in nasalwashing samples, nasopharyngeal aspirates, and in nasal and nasopharyngeal swabs. The meteorological data, including average monthly temperature, relative humidity and rainfalls of all cities were obtained from the Turkish State Meteorological Service. During the study period, 3464 children (61.9% boys), with a mean age of 6.4 months, were evaluated. RSV positivity was 16.9% (585 patients) in all samples. The highest RSV positivity rate was among children aged 0-3 months among the age groups (27.4%). When Turkey was evaluated as a whole, RSV peaks were in January and March, in the first and second years of the study, respectively. RSV activity had a biennial pattern; an early season with a strong activity was followed by a late season with a weak RSV activity. RSV was positively correlated with relative humidity and rain falls, and was negatively correlated with temperature. The current study shows the seasonal variation of RSV infections in Turkey in two consecutive years.

3 The birth rate in Turkey Basak Tezel Ministry of Health, Turkey For almost forty years after the establishment of the republic in 1923, the government of Turkey encouraged population growth. Use of contraceptives and distribution of information about them were prohibited by law, and the state provided financial incentives to encourage large families. During the 1950s, however, members of the political elite gradually became concerned that the country s relatively high population growth rate of nearly 3 percent was hurting economic development. A 1965 family planning law provided for the establishment of the Family Planning Division within the Ministry of Health and Social Assistance to extend birth control information and services to as many couples as possible. A 1967 law decriminalized abortion and authorized use of this procedure for a broad range of medical causes. Access to abortion was liberalized further by legislation in 1983 stipulating that a pregnancy could be terminated lawfully upon request in a public hospital up to ten weeks after conception. Family planning services have expanded considerably since the mid-1960s. A primary focus has been on educating couples about the material and health benefits of both limiting and spacing births. The Ministry of Health adopted the 1978 International Congress on Primary Health Care recommendations that family planning be combined with maternal and child health services and undertaken in cooperation with state hospitals, maternity hospitals, health centers, and clinics in both urban and rural areas. In addition to its support of public education about family planning, the ministry has solicited the cooperation of volunteer associations and international organizations to promote its programs. But despite concerted government efforts to encourage smaller families, Turkey s birth rate between 1965 and 1994 declined at a relatively slow pace, falling only from thirty-three to twenty-eight births per 1,000 population. By 2008, the demographic indicators in Turkey are as follows; Total fertility rate (per woman) 2,13 (2008 DHS) Population increase rate ( ) 13,4 Crude birth rate ( ) 17,9 Births ( 000) 1,273 The strategies implemented in planning of fertility are considered in the scope of reproductive rights. Persons may have a child of any number and of at any time. On completion of their fertility or wishing to have pregnancy interval, they decide themselves which method they will use, they may use this method as long as they want and they can access this method free of charge.

4 The birth rate in Italy Angelo Basilicata Presidente SIPO per la Provincia di Benevento The report covers the analysis of data at the Italian level of information both on health and epidemiology, and socio-demographic. We take into account the number of maternity facilities in Italy, the number of shares and the number of live births in 2008 to survey. In addition, the shares are divided into those that occurred in public institutions and those that occurred in nursing homes and elsewhere, also shows the percentage of births occurring in facilities with at least one thousand shares per year and the percentage of births occurring in facilities with less than five hundred shares per year. Are shown as a percentage of births to mothers who are not Italian citizens and the distribution of this phenomenon in the Italian regions and the allocation of geographic areas from which those mothers. Are given the average age, schooling and work of Italian mothers and foreign mothers. Are shown as percentages in the presence of the father of the child or family member or a trusted person next to her mother at the time of spontaneous birth. The use of the performance of cesarean delivery is indicated in the media and the regional differences in Italy, as well as the percentage of the propensity of caesarean section in nursing homes are accredited and in public hospitals, the percentage rate of cesarean delivery in women compared with Italian citizenship women with foreign citizenship. The tests performed during pregnancy, including amniocentesis, a visit earlier that you submit the Italian women and foreign women as well as their schooling. E indicates the number of shares that have been used to Assist Reproduction Techniques (ART), the techniques used for in vitro fertilization (IVF-ICSI) The percentage of babies born weighing less than one thousand five hundred grams, those born between fifteen hundred and twenty-five hundred grams and Apgar scores at birth index, stillbirths and births on the rate of mortality, those born with birth defects, and the percentage indication of the cause of births and deaths due to malformations.

5 Promotion of breastfeeding in Turkey Basak Tezel Ministry of Health, Turkey Several scientific studies have shown the benefits of breastfeeding especially for infants, mothers, families and communities. Breast milk includes many nutritional, developmental, psychological, social, economic, environmental and disease protection benefits. Even if a breastfeeding is a natural event such as birth, mothers should be supported in this respect. Initiating and maintaining a successful breastfeeding the mothers should be supported by all the health care system actively not only by their families and society during the prenatal term, at birth and after birth. Although it is known that breastfeeding is contributing to improve the health of infants and mothers, breastfeeding rates have decreased over the world. For this reason, to promote the breastfeeding movement has been started by many countries, international organizations and scientific studies. Studies accelerated in the 1990s and The Baby-Friendly Hospital Initiative (BFHI), launched in 1991, is an effort by UNICEF and the World Health Organization to ensure that all maternities,whether free standing or in a hospital, become centers of breastfeeding support in 130 countries. Within the program of Promotion of Breastfeeding and Baby Friendly Health Care Facilities carried out in cooperation with UNICEF since 1991, and the hospitals having training about breastfeeding and implementing correct breastfeeding applications are evaluated by an international standard form. The hospitals getting at 80 or over points from based on 100 points awarded as Baby-Friendly Hospital with the decision of the Breastfeeding Committee. Furthermore the primary health care facilities, cities, counties, villages, companies carrying out studies to promote the breastfeeding are awarded as a baby-friendly. So far, 817 hospitals, over 700 primary health care facilities and 78 provinces has taken the title of babyfriendly. Now, more than 90% of births in Turkey are in baby-friendly health facilities. As well as the support for to initiate breastfeeding in health facilities, "Mother Support" Groups are formed in order to ensure the continuation of breastfeeding. All these studies aim to ensuring a healthy beginning and a healthy continuation life for our infants.

6 Nutrient deficiencies in premature babies Gerardo Chirichiello M.D. Neonatal and ICU Director Clinica Malzoni Avellino (Italy) In the last past decades the improved survival of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants has underscored the problem of postnatal growth failure of these subjects. The transition from intrauterine to extrauterine environment should occur with minimal disruption in nutritional support. Notwithstanding the evident improvement in general management of these infants during the hospital stay, most of them acquire a significant extrauterine growth restriction (EUGR). Most of VLBW infants exhibit some catch-up growth, especially in the late childhood and adolescence, but they generally remain smaller than their term peers. However, the most worrying aspect is related to the detrimental effect of growth impairment, especially if involving head circumference, on neurodevelopment outcomes of these infants. The efforts of the neonatologists should be focus on improving, how much as possible, the early nutrient management of these infants, allowing them to reach an adequate growth rate (at least g/kg/d), then avoiding the need of a late unphysiological catch-up growth. Early aggressive parenteral and enteral nutrition strategies may lead to reducing cumulative deficits of energy and protein that occur during the first weeks of life. These strategies decrease the degree of postnatal weight loss, reduce the age that birthweight has regained and the age that full enteral nutrition is achieved. Recent guidelines for preterm parenteral nutrition (PN) recommend an earlier and higher intake of amino acids (AA) and energy to avoid postnatal catabolism and approximate normal fetal growth. In the past physicians refrain from administering protein or amino acids to preterm neonates from birth onward, fearing that these infants were too immature to metabolize high amino acid loads and that administration of amino acids from birth onward would result in metabolic derangements. However recent studies show that early amino acid administration is safe and well tolerated by the premature neonate. This article provides clinical practicum to guide the use of early parental nutrition and both minimal enteral nutrition and advancing enteral nutrition. Protein accretion rates by fetuses at 24 to 25 weeks, 27 to 28 weeks, and 30 to 32 weeks gestation have been estimated to be 4.0, 3.6, and 3.3 g/kg per day, respectively. Infusion of AA with glucose as early as the first postnatal day decreases protein catabolism and enhances net protein accretion. Thus, reducing the number of hours that infants receive suboptimal nutrition (without AAs) has been

7 emphasized recently ad an important goal of neonatal intensive care. The purpose of early AA supplementation is to provide preterm infants with substrate that promotes protein deposition that closely approximates fetal energy production and growth. When nonprotein energy intake is 80 to 85 kcal/kg per day and AA intake is 2.7 to 3.5 g/kg per day, nitrogen retention and growth might actually approach the intrauterine rate. Recent studies have challenged the older practice at 0.5 to 1 g/kg per day of AA and gradually advancing the AA infusion rate. In a retrospective study, Valentine and associates suggested that providing 3 g/kg per day of AA within 24 hours of birth to VLBW infants was safe and associated with better weight gain and shorter duration of PN administration. ELBW infants may require up to 4g/kg per day of intravenous AA to maintain stores and promote growth. More research is needed to establish optimal AA requirements in critically ill infants and in those who have sepsis and renal and hepatic dysfunction. Blood urea nitrogen (BUN) represents the complex interaction of hydration status, renal function, energy quality and quantity, and degree of illness. Rising BUN values are, therefore, not just a reflection of the ELBW infant s intolerance to AA infusion. In fact, studies of fetal AA oxidation suggest that higher BUN reflects appropriate AA utilization for both energy and lean mass production.

8 References: Embleton N. E., Pang N., Cooke R. J.: Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics 2001 Feb; 107 (2): Clark R. H., Wagner C.L., R.J. Merritt, Bloom B.T., Neu J., Young T. E., Clark D. A.: Nutrition in the neonatal intensive care unit: How do we reduce the incidence of extrauterine growth restriction? J Perinatol 2003; 23: Clark R. H., Thomas P., Peabody J.: Extrauterine growth restriction remains a serious problem in prematurely born neonates. Pediatrics 2003; 111; Valentine CJ, Fernandez S, Rogers LK, et al. : Early amino acid administration improves preterm infant weight. J Perinatol. 2009; 29: Thureen PJ, Hay WW Jr.: Early aggressive nutrition in preterm infants. Semin Neonatol. 2001;6:

9 Metabolic Screening in Turkey: Current Practice and Future Perspectives Fatih EZGÜ, MD Ass. Prof. of Pediatrics Gazi University Faculty of Medicine Department of Pediatric Nutrition and Metabolism, Ankara, Turkey Inborn errors of metabolism comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product. The majority of inborn errors of metabolism are genetically transmitted in an autosomal recessive manner. The incidence of inborn errors of metabolism is generally higher in populations where consanguineous marriages are frequent. The concept of newborn screening for metabolic disorders has gained significant attention especially during 1960s. Dr. Robert Guthrie, an American microbiologist, was the first scientist to use dried blood spot testing, namely Guthrie Test, for the newborn screening of phenylketonuria. Since then, parallel to the significant progress in the area of biochemical and genetic testing techniques, the tools for newborn screening were significantly improved. The frequency of consanguineous marriages in Turkey is around 25 %. As a result of this fact, the incidence of inborn errors of metabolism is high, the most common one probably being phenylketonuria. The first newborn screening project in Turkey was initiated for phenylketonuria at Hacettepe University Faculty of Medicine, Ankara, in In 1993 this initiative was made available to whole Turkey. During 2006, National Newborn Screening Program was initiated by the Ministry of Health under the supervision and guidance of the Mother and Child Health and Family Planning Office as well as Refik Saydam National Health Maintenance Office. Currently this program includes newborn screening for three disorders: Phenylketonuria, biotinidase deficiency and congenital hypothyroidism. Within the frame of the program, national advisory committees have been organized which created diagnostic and treatment guidelines for the newborn cases who are screened positive during the initial assessments. During 2010, a total of newborns have been screened with a coverage rate of % 95,7. The screening results in 2010 revealed 182 newborns with phenylketonuria and 199 newborns with biotinidase deficiency. Currently, significant effort has been put forward by the universities and also by the Ministry of Health both to improve the quality of the screening system but also to implement new techniques such as tandem mass spectrometry and molecular diagnostics.

10 Metabolic screening in Italy Norberto Nosari U.O di Terapia Intensiva Neonatale Presidio Ospedaliero di Nocera Inferiore In all neonatal Italian structures has long been compulsorily performed on newborns, newborn screening, which identifies four genetically inherited diseases: hypothyroidism, cystic fibrosis, phenylketonuria, and in some cases, galactosemia. The analysis is performed on a drop of blood drawn from the heel of every newborn child between the 48th and 72nd hours of life, steeped in a special paper (tissue paper) that spot, is dried and sent to the Regional Screening Center reference. An early diagnosis of these diseases is very important because it allows you to start early therapy or dietary requirements, which are usually able to allow an adequate growth and development and a good overall state of health. Screening for Cystic Fibrosis as well as drops of blood is collected, usually within the first 24 hours of life, a small sample of meconium. Rarely, if the blood collected with the first sampling was insufficient or equivocal, it may be necessary to repeat a blood test at a distance, always from the heel. Parents of infants in whom the screening test results are normal will not receive any communication. Only infants in whom the screening test results are abnormal, or inappropriate questions will be recalled for further study. With the same card and without any further withdrawals could be diagnosed, in addition to these four diseases, other diseases using the new genetic screening technique that broadened tandem mass spectrometry. The tandem mass spectrometry, which provides a conventional configuration of a system of sampling and HPLC coupled to a triple quadruple mass spectrometer, is able to identify the critical metabolites, markers of many metabolic diseases, using a small amount of blood collected and dried on special cards. In a single sample can identify up to 50 metabolites very quickly getting valuable information for the diagnosis of different types of diseases: amminoacidopatie, acidurias organic betaossidazione fatty acids, lysosomal diseases etc.il result of a screening test is not, however yet a definitive diagnosis: if the result is positive, indicating the suspicion of the disease and in this case, the screening center to report the patient care center which will provide further analysis to biochemical and molecular confirmation of the disease or not. The importance of having a test suitable for early screening is linked to the fact that babies from birth usually show no symptoms, but that appear when the cells start to be too clogged by substances that are not defective enzymes were able to demolish. This allows a reduction in early morbidity, hospitalizations and

11 premature death (cot death), as well as a reduction of the birth of other affected family members because it is offered to families the possibility of genetic screening. These hereditary metabolic diseases are called "Rare Diseases", but are not so rare: it is approximately 600 hereditary diseases involving the biochemistry of metabolism and affect an estimated one child in every 500 newborns, but only one in four is recognized in time. Diseases that have a variable severity, which can lead to death or irreparably affect the quality of life, but which, nevertheless, in most cases can be effectively countered if identified early symptoms. Expanded screening in Italy is applied by law only in the Region of Tuscany. Since May of 2007 started the first and currently only a pilot project for expanded metabolic screening in southern Italy between the UO TIN of the hospital of Nocera Inferiore and CEINGE of Naples, with subsequent involvement of other hospitals in the same region. This project has allowed us to detect only among infants related to neonatal intensive care hospital of Nocera well Inferioe 4 cases (2 MCADD, betaketotiolasi 1 deficiency, 1 maternal vitamin B12 deficiency). While other regions are gearing up for expanded metabolic screening can be activated to all infants in their territory (in Emilia Romagna, Veneto and Liguria and a pilot project in part of Lazio) one hopes that this method can rapidly be offered all newborns Italian.

12 Childhood Vasculitides Sevcan A. Bakkaloglu, MD Gazi University, Department of Pediatrics, Ankara, TÜRKİYE Vasculitides are disorders defined by the presence of inflammation in a blood vessel wall. The inflammation may occur as a primary process or secondary to an underlying disease. Clinical symptoms vary widely depending upon the types and location of the vessels involved and the extent of inflammation. The primary vasculitides may be classified according to their clinical manifestations, the size and type of the involved blood vessels, and the pathologic changes found within the vessel walls or presumed the underlying disease pathogenesis. The most recent classification criteria proposed by EULAR/PRINTO/PRES, after a statistical validation study, is primarily based upon the size of the involved vessel. Henoch Schönlein purpura (HSP) is the most common small vessel vasculitis in childhood followed by Kawasaki disease and polyarteritis nodosa, which are medium sized vasculitides. Other rarer vasculitides in children include Takayasu arteritis and ANCA (anti neutrophil cytoplasmic antibody) associated vasculitides, mainly Wegener s granulomatosis. HSP is the most common systemic small vessel vasculitis in childhood with estimated annual incidence of per 100,000 in children less than 17 years of age. It typically presents with palpable purpura on the lower extremities and buttocks, subcutaneous edema, artritis, abdominal pain and variable degree of renal involvement ranging from microscopic hematuria to nephrotic-nephritic syndrome. Kawasaki disease most frequently affects infants and young children under 5 years of age. This disease primarily invades the medium-sized muscular arteries, including coronary arteries. Diagnosis of KD is based on characteristic clinical signs and symptoms, which are classified as principal clinical findings and other clinical and laboratory findings. Childhood polyarteritis nodosa (also called macroscopic polyarteritis or classic polyarteritis nodosa) is a systemic necrotizing vasculitis affecting small and/or medium-sized arteries predominantly in skin, abdominal viscera, kidneys, CNS, and muscles. It typically presents with systemic symptoms (eg, fever, malaise, and weight loss) and signs of multisystem involvement. Wegener s granulomatosis is a systemic vasculitis with granulomatous inflammation of small and medium-sized arteries, typically affecting the upper and lower respiratory tract, and the kidneys. Takayasu arteritis is a chronic, inflammatory, large-vessel vasculitis of unknown cause that primarily affects the aorta and its major branches. Ongoing granulomatous inflammation leads to stenosis, thrombus, and aneurysm formation causing altered blood flow to major organs. Treatment of childhood vasculitides ranges from conservative treatment to intense immunosuppression and surgical interventions according to the extent and the severity

13 of the disease. Prognosis is excellent in HSP cases without renal involvement as is in Kawasaki disease with early treatment with IVIG. ANCA associated vasculitides have a variable prognosis related to the involvement of life theratening organs, which is improving with new treatment regimens including plasma exchange and rituximab. Takayasu arteritis has also improved prognosis due to the successful interventional radiological and surgical procedures.

14 Gastroesophageal reflux disease in children: which is the best treatment today? Carlo Tolone Clinica Pediatrica Seconda Università di Napoli Gastroesophageal reflux disease (GERD) has been recognized increasingly in infants, children and adolescents. The incidence is dependent on age and varies from 5% to 35% of the population. Symptoms of GERD differ depending on the age of the child and on the extent of the exposure of the esophageal epithelium to refluxed gastric contents. The most common symptom of GER in infants during the first year of life is regurgitation/vomiting. Other possible symptoms of GERD during infancy include irritability, feeding refusal, arching and crying during feeding, burping/sobbing and failure to thrive. In infants, GERD has also been associated whit chronic respiratory disorders, including reactive airway disease, recurrent stridor, chronic cough and recurrent pneumonia. Symptoms in infants could be related to immaturity and physiologic reflux, which does not need pharmacologic therapy, but improves with time as the infant matures and relies more on solid food. The primary classes of agents used to treat GERD are acid suppressants such as histamine H2receptor antagonists and proton pump inhibitors (PPIs) as well as antiacids and prokinetic agents. The most common adverse events associated with PPI use in adults include nausea, vomiting, diarrhea, skin rush and headache, although these have been reported in <5% of subjects. In children and adolescents no adverse drug reactions associated with PPI therapy have been reported that have not been previously observed in adults. A prospective study performed in pediatric patients showing that the use of gastric acid inhibitors was associated with an increased risk of acute gastroenteritis and community acquired pneumonia in GERD-affected children has been reported. Unlike clinical studies have shown pantoprazol, and PPIs in general, to be safe and well tolerated when used in the treatment of pediatric patients with GERD. Besides results from studies of various available PPIs in infants aged < 1 year, including preterm infants and neonates, are currently being reported and some efficacy studies have also been reported. Studies have shown too the efficacy and safety of omeprazole for continous use for up to 2 years duration in children. PPIs should not be discontinued abruptly, because rebound of acid secretion occurs, which may per se cause symptoms and give the possibly false impression that the patient has an

15 under-lying condition that requires continous treatment. Therefore, when PPI discontinuation is attempted, the drug should be tapered-the longer the cause of PPI has been, the longer the period of taper. Nevertheless acid-suppressive medications are actually over prescribed in children, especially in infants, and a growing body of evidence indicates that acid suppression whith an H2RA or PPI may result in a higher rate of complications in children. To manage the risk-benefit balance, acid suppressive drugs should be used whith caution. Moreover treatment strategies and options depend upon the severity of the GERD and may include lifestyle changes, thickening of feeds and placing the infant in a supine position. Initial pharmacological intervention is usually with antiacid therapy which neutralises gastric acid and reduces the symptoms of indigestion and oesophagitis. The major advantage of antacids is their rapid onset of action in providing relief. Alginate containing antacids form a raft that floats on the surface of the stomach contents which should reduce reflux and apport some protection to the oesophageal mucosa. Alginate preparations containing aluminium should be avoided in chronic use wherever possible, especially in neonates and infants with renal impairment, because of accumulation leading to an increased plasma-aluminium concentration. No evidence exists to suggest efficacy of prokinetic drugs, such as Metoclopramide, Domperidone, Cisapride, Bethanecol, Erythromicin, in reducing GERD in children. Surgical interventions such as Nissens fundoplication have usually been reserved for those patients who are resistent to drug therapy or who require long-term medical management. In conclusion for infant GERD: a) Many infants with a clinical diagnosis of GERD may have physiologic reflux which does not require pharmacologic therapy. b) Alginate are safe and can improve symptoms of GER. c) There is no evidence to support the use of prokinetics drugs. d) Ranitidine and PPI ( omeprazole and lansoprazole ) are effective medications ( PPI better than H2 antagonist). e) More evidence is needed for the PPI use in the treatment of GERD in infants with highpowered randomized controlled pediatric studies with medium to long term outcome date.

16 Pediatric Necrotizing Enterocolitis Maria Vendemmia Neonatal Intensive Care Unit, San Sebastiano Hospital, Caserta, Italy Necrotizing enterocolitis (NEC) is the most common GI emergency occurring in neonates. NEC represents a significant clinical problem and affects close to 10% of infants who weigh less than 1500 g, with mortality rates of 50% or more depending on severity. Although it is more common in premature infants, it can also be observed in term and near-term babies. Despite intensive study over the past 30 years, its etiology remains elusive. Initial symptoms may be subtle and can include one or more of the following: feeding intolerance, delayed gastric emptying, abdominal distention, ileus, decreased bowel sounds, abdominal wall erythema, hematochezia. Systemic signs are nonspecific and can include any combination of the following: apnea, lethargy, decreased peripheral perfusion, shock, cardiovascular collapse, bleeding diathesis. Although the pathogenesis of necrotizing enterocolitis remains uncertain, a large body of evidence suggests a multifactorial etiology, including the presence of abnormal bacterial flora, intestinal ischemia, reperfusion injury with activation of proinflammatory cellular cascades, and intestinal mucosal immaturityor dysfunction. The mortality rate ranges from 10% to more than 50% in infants who weigh less than 1500 g, depending on the severity of disease, compared with a mortality rate of 0-20% in babies who weigh more than 2500 g. Extremely premature infants (1000 g) are particularly vulnerable, with reported mortality rates of %. NEC is more prevalent in premature infants, with incidence inversely related to birth weight and gestational age. Although specific numbers range from 4% to more than 50%, infants who weigh less than 1000 g at birth have the highest attack rates. This rate dramatically drops to 3.8 per 1000 live births for infants who weigh g at birth. Similarly, rates profoundly decrease for infants born after weeks postconceptional age. Average age at onset in premature infants seems to be related to postconceptional age, with babies born earlier developing necrotizing enterocolitis at a later chronologic age. The average age of onset has been reported to be 20.2 days for babies born at less than 30 weeks estimated gestational age (EGA), 13.8 days for babies born at weeks EGA, and 5.4 days for babies born after 34 weeks gestation. Infants with patent ductus arteriosus are at higher risk for developing the disease, particularly if pharmacologic closure is attempted. Term infants develop necrotizing entericolitis much earlier, with the average age of onset within the first week of life or, sometimes, within the first 1-2 days of life. The physical findings in patients who develop necrotizing enterocolitis can be primarily GI, primarily systemic, indolent, fulminant, or any combination of these. A high index of clinical suspicion

17 is essential to minimize potentially significant morbidity or mortality. GI signs can include any or all of the following: increased abdominal girth, visible intestinal loops, obvious abdominal distention and decreased bowel, sounds, change in stool pattern, hematochezia, palpable abdominal mass, erythema of the abdominal wall. Systemic signs can include any of the following: respiratory failure, decreased peripheral perfusion, circulatory collapse. If abdominal signs are present, surgical consultation may be advisable. Disease progression ranges from indolent to fulminant, and early and expeditious involvement of surgical colleagues can be helpful, especially if appropriate surgical care requires transfer to another facility. Initial presentation of necrotizing enterocolitis (NEC) usually includes subtle signs of feeding intolerance, such as gastric residuals, abdominal distention, and/or grossly bloody stools. Abdominal imaging studies are crucial at this stage. In fact, radiographic studies should be obtained if any concern about necrotizing enterocolitis is present. The mainstay of diagnostic imaging is abdominal radiography. An anteroposterior (AP) abdominal radiograph and a left lateral decubitus radiograph (left-side down) are essential for initially evaluating any baby with abdominal signs. Perform abdominal radiography serially at 6-hour or greater intervals, depending on presentation acuity and clinical course. Characteristic findings on an AP abdominal radiograph include an abnormal gas pattern, dilated loops, and thickened bowel walls. Serial radiographs help assess disease progression. A fixed and dilated loop that persists over several examinations is especially worrisome. Radiographs can sometimes reveal scarce or absent intestinal gas, which is more worrisome than diffuse distention that changes over time. Pneumatosis intestinalis is a radiologic sign pathognomonic of necrotizing enterocolitis. It appears as a characteristic train-track lucency configuration within the bowel wall. Intramural air bubbles represent gas produced by bacteria within the wall of the bowel. Abdominal free air is ominous and usually requires emergency surgical intervention. For this reason, left-side down (left lateral) decubitus radiography is essential and allows the detection of intraperitoneal air, which rises above the liver shadow (right-side up) and can be visualized easier than on other views. Portal gas appears as linear branching areas of decreased density over the liver shadow and represents air present in the portal venous system. Its presence is considered a poor prognostic sign. Ascites is a late finding that usually develops when peritonitis is present or after bowel perforation, it is better appreciated on ultrasonography. Abdominal ultrasonography can be helpful when suspected necrotizing enterocolitis in neonates is evaluated. Diagnosis of necrotizing enterocolitis (NEC) is based on clinical suspicion supported by findings on radiologic and laboratory studies. Treatment of necrotizing enterocolitis depends on the degree of bowel involvement and severity of its

18 presentation. Objective staging criteria developed by Bell have been widely adopted or modified to help tailor therapy according to disease severity. Free air visible on abdominal radiograph is an indication for surgery. Surgical treatment includes resecting the affected portion of the bowel, with reanastomosis performed later. Strictures may occur, with or without a history of surgical intervention, which may require surgical treatment. When necrotizing enterocolitis is suspected, enteral feedings are withheld and parenteral nutrition is initiated. Centrally delivered formulations with appropriate nutritional components are infused for optimal IV nutrition. Enteral feedings are traditionally restarted days after findings on abdominal radiographs normalize in the case of nonsurgical necrotizing enterocolitis. Pharmacologic therapy for necrotizing enterocolitis (NEC) includes agents to treat the developing disease and those to provide supportive and symptomatic relief. Probiotics are emerging as a possible preventive therapy. Approximately 75% of all patients survive, with those requiring surgical intervention during the acute phase of the disease demonstrating much lower survival rates. Of those patients who survive, 50% develop a longterm complication. The 2 most common complications are intestinal stricture and short-gut syndrome.

19 Intrauterine Death in Multiple Gestation Salvatore Vendemmia 1, Maria Vendemmia 2 1 President of the Società Italiana di Pediatria Ospedaliera ( SIPO ) 2 Neonatal Intensive Care Unit, San Sebastiano Hospital, Caserta, Italy INTRODUCTION The incidence of multiple gestation has increased dramatically during the past two decades as a result of a shift in the maternal age distribution to older ages as well as increased use of fertility enhancement therapy. The frequency of single fetal demise in multiple gestation is reported as 0.5 to 6.8%, although early ultrasounds suggest a higher rate of early loss.(6) There may be complete reabsorption of a fetus, formation of a fetus papyraceus or development of a placental abnormality such as a cyst or amorphous material. The mummified and calcified fetus is even known as lithopedion. The timing of the fetal loss affects the outcome of the viable twin and the maternal complications. Causes of ante-partum death are cord accidents, vascular anastomoses with overwhelming blood volume shift, velamentous insertion of the umbilical cord (3). Most of cases, the cause of death is frequently unknown. In the present paper we briefly report our experience on 1 case of intrauterine death in multiple gestation, describing morbility of surviving co-twin. CASE REPORT Male infant, weighing 2500 g, was born at term by cesarean section without family history of disorder or chromosomal abnormalities. Neither X-ray exposition nor drug during pregnancy. No major anomalies were recognized at birth except for skin lesions, simmetrically involving the knees and the trunk. Skin lesions were caracterized by absence of cutis and subcutaneous with exposure of sinovia. Thorax X-rays demonstrated multiples fractures of the 6 th,7 th,8 th and 9 th ribs. Phisical, hematological and neurological evaluations provided normal results. Cutaneous punch biopsy at the second day of life showed flogosis of tissues and dermal fibrosis with absence of adenexal structures. Morphological evaluation of placenta revealed a monochorionic and diamniotic placenta, velamentous insertion of the umbilical cord and an intrauterine lithopedion of about 6 cm. Skin lesions, treated locally with antibiotic ointment, healed in 8 weeks, leaving only slight scarring. Follow up at three months showed normal growth of the baby; cutis of the knees was slight, smooth, anelastic and hypochromie, without contractures.

20 DISCUSSION Lithopedion is the name given to an extrauterine pregnancy that evolves to foetal death and calcification. Rarely it is a consequence of an undiagnosed abdominal pregnancy, where the dead foetus is retained in the maternal abdominal cavity and calcification ensues. Most cases of lithopaedion are detected incidentally while taking abdominal radiographs or intraoperatively. To date there are around 300 cases of lithopedions reported in the world medical literature.(11). In this case, a lithopedion was not detected into the abdominal cavity, but in the placenta of a twin pregnancy. The development of this pregnancy was normal until fetal death, after which dehydration of tissues and calcium infiltration occurred. A review of the literature indicates that congenital skin defects of body areas, as represented by this child, is a specific pattern of malformation distinct from isolated small congenital skin defects involving the vertex of the scalp.(2) Intrauterine lithopedion and a live co-twin with congenital skin defects and fractures are a very rare association. Aplasia cutis congenital is the clinical manifestation of an uncommon group of skin disorders. One postulated etiology is disseminated intravascular coagulation from release of thrombogenic maternal arising from placental injury or fetal demise. This leads to disruption of the ectodermal blood supply responsible for the skin defects. (4). It is supposed a disruptive vascular etiology, but it is relevant to exlcude both genetic and infective (syphillis, chickenpox, herpes) reasons. (15) Closure of skin defects with atrophic skin usually occurs in a few weeks, providing sometime contractures or desfiguring scars. More or less serious infective complications can occur. Finally, in a twin pregnancy, the death of one twin may have adverse effect on the surviving fetus. (7) Many types of anomalies have been reported and the nature of these anomalies probably depends on the stage of gestation at which the co-twin dies (8). Review of pooled data on 53 cases suggests that disruptions of the central nervous system are the most common complication (72%), followed by the gastrointestinal system (19%), kidneys (15%) and lungs (8%) (14). Cardiac malformations have also been reported, like cases of congenital skin defects (aplasia cutis congenital) involving the limbs and the trunk (5;10). Current view is that these different lesions may all be the result of transient hypotension. As one fetus dies and the vascular resistance falls, the living twin may exsanguinate into the dead monochorionic twin through vascular anastomosis, causing a damaging, if not lethal, hypoxic episode from the

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