[TREATMENT WITH INO OF INFANTS WITH PPHN.]

PPHN is a life threatening disease that appears as a result of high pulmonary vascular resistance and persistent right to left shunt across foramen ovale and ductus arteriosus. The treatment of PPHN is complex and often ineffective. iNO is important part of the pathogenetic treatment of the disease. We present six infants with PPHN treated with iNO. The clinical effect of the drug was quick and the hemodynamics stabilized. All infants survived without side effects and with better neurodevelopment outcome.

[Treatment of PPHN with iNO in an Infant with Trombophilia and Thrombus in PDA. Clinical Case.]

PPHN is common in 1-2/1000 newborn infants. The morbidity and mortality accompanying the disease are extremely high. The treatment is frequently ineffective. The therapy with iNO is the fir l strategy based therapy of PPHN. We present the clinical case of an infant with congenital pneumonia and secondary PPHN treated with iNO. During the clinical observation of the infant congenital trombophilia was diagnosed, due to the presence of a thrombus in PDA. The outcome was favorable.

[BRONCHOPULMONARY DYSPLASIA IN VERY LOW BIRTH WEIGHT INFANTS--THE OLD NEW PROBLEM].

BACKGROUND: The advances in perinatal intensive care have increased the survival rate of extremely low birthweight (ELBW) and gestational age infants. Among them the risk of developing bronchopulmonary dysplasia (BPD) remains high. AIM: To evaluate the frequency of BPD by birthweight and gestational age, to identify the main postnatal risk factors and the associated comorbidities. METHODS: 683 VLBW infants (< 1500g) were admitted in NICU from 2008 to 2010. 597 survived more than 28 days and were included in this study. BPD was diagnosed if supplemental O2 for the first 28 days was necessary; the severity was assessed by the need of O2 and/or ventilator support at 36 gestational weeks (gw). RESULTS: 27.6% (n = 164) infants were with supplemental O2 at 28d of life (BPD-group), 10.9% (n = 65) were with moderate, 3.9% (n = 23) with severe BPD (FiO2 > 30% and/or ventilator support). Infants with BPD were with significantly higher CRIB (9.9 ± 3.1) compared with those without BPD (4.0 ± 3.0), p < 0.0001. The frequency decreased progressively from almost 100% at 23gw or birthweight < 600g to single cases after 31gw and bitthweight > 1200g. Logistic regression analysis showed that each gestational week decreased the odds of BPD by 60%; each CRIB point increased the odds by 62%. Each point increment in 1/5 min Apgar-scores reduced the risk by 40%/50% respectively The need for ventilator support increased from 1.4 ± 2.7 days (no-BPD group) to 52.8 ± 5.1 days (severe-BPD infants), p < 0.05. Postnatal complications significantly increasing the odds for BPD were found to be: PDA - 19.7, Pneumothorax - 12.1 times. There was a significant correlation between BPD, severe brain injury and ROP (p < 0.000 1). CONCLUSION: The frequency of BPD strongly correlates with gestational age and birthweight and CRIB. Additional risk factors are low A pgar scores, PDA and air leak syndrome. Associated comorbidities as severe brain injury and ROP further worsen the long term prognosis.

[BRONCHOPULMONARY DYSPLASIA--WHAT DO WE KNOW TODAY?].

The survival of great number of extremely premature newborn babies is associated with increased risk of damage of the newborn lung and development of chronic lung disease/Broncopulmonary dysplasia. The lower the gestational age and weight, the greater the frequency of BPD. The disease leads to impairment of the normal alveolization and vascularization of the premature lung. There are new theories for the pathogenesis of BPD and new staging of the disease. These changes lead to new therapeutic strategies.

[TREATMENT OF EXTREMELY PREMATURE NEWBORN INFANT WITH INO. CLINICAL CASE].

Prolonged inhaled nitric oxide (iNO) from birth in preterm neonates with BPD improves endogenous surfactant function as well as lung growth, angiogenesis, and alveologenesis. As a result there is a reduction in the frequency of the "new" form of BPD in neonates under 28 weeks of gestation and birth weight under 1000 gr. Delivery of inhaled nitric oxide is a new method of prevention of chronic lung disease. According to a large number of randomized trials iNO in premature neonates reduces pulmonary morbidity and leads to a reduction of the mortality in this population of patients. This new therapy does not have serious side effects. We represent a clinical case of extremely premature newborn infant with BPD treated with iNO.

[Neonatal hypoxic-ischemic brain injury: pathogenesis and neuropathology].

The perinatal period represents a clinical setting of potential risk for injury to developing brain secondary to many causes, with the chance for long-lasting, profound neurocognitive deficits. Neonatal hypoxic-ischemic brain injury leads to serious long-term morbidities. The leading pathogenetic mechanisms are hypoxia and/or ischemia, as a result of perinatal asphyxia. Understanding of the underlying pathophysiology will help the physicians in the general supportive management and neuroprotection of the neonatal brain.

[Application of inhaled nitric oxide in extreme preterm neonates with with BPD].

Prolonged inhaled nitric oxide (iNO) from birth in preterm neonates with BPD improves endogenous surfactant function as well as lung growth, angiogenesis, and alveologenesis. As a result there is a reduction in the frequency of the "new" form of BPD in neonates under 28 weeks of gestation and birth weight under 1000 gr. Delivery of inhaled nitric oxide is a new method of prevention of chronic lung disease. According to a large number of randomized trials iNO in premature neonates reduces pulmonary morbidity and leads to a reduction of the mortality in this population of patients. This new therapy does not have serious side effects.

[Pulmonary hypertension of the newborn--recent advances in the management and treatment].

Pulmonary hypertension of the newborn is a clinical syndrome with diverse etiology in which the transition from fetal circulation with high pulmonary vascular resistance to postnatal circulation with low pulmonary vascular resistance failed. The persistence of high pulmonary vascular pressure leads to right-left shunts and marked cyanosis. Despite of the advances in neonatology, the treatment of some forms of PPHN is often difficult and mortality rate remains high. In infants with PPHN appropriate interventions are critical to reverse hypoxemia, improve pulmonary and systemic perfusion and preserve end-organ function. Our understanding for management of PPHN has evaluated over decades. This review summarizes the current strategies for treatment of pulmonary hypertension of the newborn: general care, cardiovascular support, the advantages and limitations of different ventilatory strategies, oxygen therapy, extracorporal membrane oxygenation, and the evidence-based inhaled nitric oxide therapy. The balance between pulmonary vasoconstrictor and vasodilator mediators plays an important role for pulmonary vascular resistance. Recent studies are designed to develop evidence-based therapies for regulation of pulmonary vascular tone, safe medications for selective pulmonary vasodilatation effective for treatment of PPHN and other forms of pulmonary hypertension in the neonatal intensive care unit.

[Socio-demographic characteristics and vitamin D status in women born before 32 weeks'].

UNLABELLED: Deficiency of vitamin D (25-OHD) is a health problem among prematurely born women and their newborns independently of the geographical location of the country. OBJECTIVES: To study serum levels of vitamin D in patients born before 32 weeks and their newborns at birth. To analyse the socio-demographic factors, complications of pregnancy and their relationship with vitamin D status of women. PATIENTS AND METHODS: The study has been carried out in the University hospital "Maichin dom" Sofia for the period August 2013-January 2014. 35 women who gave birth before 32 gestational week and their 41 newborns with birth weight < 1500g have been investigated. The serum level of vitamin D (25-OH D) in mother-infant pairs at birth and 8 weeks of age in infants has been investigated. The ECLIA method has been used. Serum levels of vit D (25-OHD) have been estimated as sufficient:(> 30 ng/ml), insufficient (21-29ng/ml) and deficient (< 20 ng/ml). RESULTS: At delivery according to their vit D (25- OHD) serum levels 63% of the mothers are defficient /12.61 ± 4.8 ng/ml/, 28.5% are insufficient/26.66 ± 2.59/and only 8.5%/40.4 ± 8.48/sufficient with normal levels of vitamin D. For newborns data are respectively 32%/ 20.08 ± 3.69/-deficient, 49%/27.39 ± 2.70/- insufficient and 19 %- sufficient/41.6 + 10/ There is a positive correlation between mother's and children's serum levels of vitamin D (25- OHD). Statistical significant differences are observed in the levels of vitamin D and the presence of infection and preeclampsia in the mothers. During the period of the study there were no seasonal variations in vit D (25-OHD) serum levels of mother-baby pairs. All newborns received Vit D3 1334 IU/daily from 20th day of age. At eight weeks of age sufficient levels of vitamin D have 70% of the children, but 30% of the newborns remains with inadequate supplementation/27.09 ng/ml/. CONCLUSION: 91.5% of mothers are with insufficient serum levels of vitamin D (25OHD) at birth, and a deficit is present in 63% of all women. Only in 8.5% of the women had normal values. This implies more effective monitoring and vitamin D prophylaxis during pregnancy.

[Respirtory distress in newborns of mothers with factor V-Leiden thrombophilia].

AIM: The main aim of the trial is to determine the frequency of respiratory distress syndrome / RDS/ and disorders of coagulation in infants of mothers with thrombophilia. MATERIALS AND METHODS: In 51 newborns of mothers with thrombophilia were evaluated the presence of respiratory distress and maternal-fetal infection /MFI/. The children were divided in two groups: Group I--16 newborns of mothers with thrombophilia and Group II--15 healthy children. We analyzed Hb, Ht, Er, Thr, prothrombin index /INR/, activated partial thromboplastin time /aPTT/ in both groups. RESULTS: The analysis of Hb, Ht, Er, Thr showed no evidence of anemia or coagulopathy with platelet consumption. In 64.7% of children was observed respiratory distress syndrome during the first days, 21.5% had severe respiratory distress /RD/, that required intubation and assisted ventilation. Only in 10/19.6%/ children with RDS there were data proving MFI/high CRP and positive microbiological samples/. There was no significant difference in the INR value in Group I/1.5 +/- 0.3/ and group II/1.6 +/- 0.1/. The children of mothers with thrombophilia had significantly more shortened aPTT/35, 1s +/- 4.2/ compared with the control group: aPTT/43.9 +/- 4,4/. CONCLUSION: The high incidence of RDS and shortened aPTT indicate that maternal thrombophilia is a risk factor for thrombosis in newborns. MFI that are accompanied with activated PAI also lead to thrombosis, especially in children in Neonatal Intensive Care Units. These results point out that there should be prevention of other risk factors for thrombosis such as dehydration and placement of central venous catheters.

[Blood transfusions suppress erythropoiesis in anemia of prematurity].

UNLABELLED: AIM AND TASKS: The major gene regulating erythropoietin /EPO/ synthesis is hypoxia induced factor/HIF/. Proceeding from the assumption that the transfusions /HT/ remove hypoxia due to anemia and inactivate HIF, the aim of the study was to show the decreased activity of erythropoiesis after HT MATERIALS AND METHODS: PATIENTS: 40 premature infants <34 g.a. and birth weight < 1400 g with anemia of prematurity. We analyzed: Hb /g/I/, Ht%, Thrx 10(9)/I, Ret%, 24-48 hours and 7-10 days after HT The dynamics of changes of blood lactate /mmol/l/level after HT was used as an indirect index of relative hypoxia/activated HIF/. The changes of Hb /g/l/ and Ht% determined the need of haemotransfusions. RESULTS: After HT along with the increase of Hb from 89, 7+/-10,0 to 119+/-13,3, there was significant decrease in Ret % from 2,4+/-1,1 to 1,4+/-0,5 7-10 day after HT There was also a reduction of Thr from 391,5+/-131,5 to 250, 7+/-57,2 and blood lactate in mmol/l from 2,5+/-1,1 to 1,5+/-0,7. The study showed that 7-10 days after HT the values of Hb and Ht decreased to baseline levels, that required new transfusion. CONCLUSION: Transfusion of packed red blood cells in patients with anemia of prematurity suppresses erythropoiesis, which is demonstrated by the significant reduction in reticulocyte count. The decreased level of blood lactate after HT shows elimination of the relative hypoxia that is required for hypoxia- induced expression of HIF and erythropoietin synthesis.

["In vitro" babies--dreams, that turned real, but a lot of questions and unknown items].

UNLABELLED: In vitro babies bring happiness to a lot of families. Their development, health and social problems are being studied in details. OBJECTIVES: To establish the well being of babies, born at the University Maternity Hospital "Maichin dom" following assisted reproduction (AR), probable risk factors immediately after birth and afterwards. Aims of the study are to look for a correlation between AR and the incidence and importance of medical problems, arising during the neonatal period: multiple pregnancy; prematurity; intrauterine growth retardation; neonatal mortality; inborn malformations and chromosomal diseases; CNS impairment; duration of hospitalization. STUDY DESIGN: This is a retrospective study including all 440 babies born thanks to AR (according to the available medical records) during the period 2008-2010 at the University Maternity Hospital "Maichin dom". A correlation between the main items observed and the number of babies in each pregnancy was investigated for the period 01.01.2010-31.12.2010. RESULTS: During the period 2008-2010 there are 99 babies from single pregnancy, 15 (15%) admitted to the NICU; 384 twin pregnancies (186 of them after AR)--733 babies and 15 foetus mortus. 114 IVF couplets (31%) or 221 babies (7 foetus mortus) are admitted to physiological neonatal ward, while 72 (63%) couplets or 137 babies (7 foetus mortus) are admitted to the NICU. There are 48 triplet pregnancies or 141 babies (3 f. mortus), 40 being IVF (83%) or 117 babies, all 40 AR triplets are admitted to the NICU. 269 babies (61% of all AR babies) need intensive treatment--mostly (94%) babies from multiple pregnancies. Mean birth weight was established to be 2060 g; with babies, requiring intensive treatment is 1408 g. Gestational age at birth is from 25 to 39 g.w.; with NICU patients mean gestational age is 32 g.w. Mean maternal age is relatively high--34 years with a wide range (24-50 years). A high incidence of operative deliveries is established--mostly with couplets and triplets. CONCLUSIONS: Rules of good clinical practice should be introduced with AR, aiming at reducing the number of multiple pregnancies. This should be priority for all national programs for assisted reproduction.

[Vitamin D levels in maternal--VLBW infants pairs].

UNLABELLED: Normal foetal growth depends on sufficient mother's vit D intake. Premature birth interrupts vit D and mineral mother-to-foetus transfer and leads to vit D deficiency and disturbs newborn mineral bone metabolism. OBJECTIVES: To determine vit. D plasma levels in mothers and their very low birth weight- (VLBW) newborns and the prevalence of vit D deficiency in this population, to investigate seasonal variation and analyse babies' vit D levels from birth to the 8 postnatal week. PATIENTS AND METHODS: The study has been carried out in the University hospital "Maichin dom" Sofia for the period 09.2011-01.2012 and there have been investigated 32 women and their 39 VLBW infants as a target group. 25-OHD level has been measured in maternal and newborn cord blood samples. The ECLIA method has been used. 25-OHD level has been tested second time at eight weeks of age in 34 infants. According to the maternal vit D levels the patients have been divided into 3 groups: Group. 1--vit D reference range level (> 30 ng/ml); Group. 2--vit D insufficiency (21-29 ng/ml), Group. 3--vit D deficiency (< 20 ng/ml). RESULTS: Low Vit. D levels have been estimated in 62.5% of mothers' group. Nevertheless, only 38.6% of all babies have been Vit. D deficient. In 61.4% of them vit D has been in normal range (32.4-35.7 ng/ml). A significant positive correlation between maternal and infants' vit D level at birth has been established (r = 0.516; p = 0.002). There have been found a significant seasonal dependence of vit D level at birth in the group too: vit D plasma levels have been estimated higher in September-October group compared to those in November-January group. Most of the blood samples in winter months showed lower vit. D levels than the autumn group. At 8 weeks of age 67.6% of the babies have been with vit D insufficiency. There has been a significant positive correlation between 25-OHD levels at birth and at weeks (r = 0.425; p = 0.012). CONCLUSION: Vit. D insufficiency has been found in 62.5% of the mothers at birth. Maternal vit. D deficiency is a significant risk factor for neonatal vit D deficiency. There is a clear seasonal dependency with a significantly lower 25-OHD level in the mothers and their VLBW babies in winter months.

[Treatment of anaemia of prematurity with SS-R-Hu-erythropoietin and significance of hypoxia-inducible factor].

UNLABELLED: The main cause of anaemia of prematurity is low erythropoietin levels. A few years ago hypoxia-inducible factor/HIF/gene transcriptor was established, regulating not only the synthesis of erythropoietin /EPO/, but also other growth factors as well as enzymes of anaerobic glycolysis, activated by hypoxia. OBJECTIVES: The aim of the study is to establish in clinical practice the role of hypoxia, respectively, activated HIF during treatment with erythropoietin by analyzing variations in hematological values; to examine blood lactate levels as an indicator of activated HIF and anaerobic glycolysis with Hb values 110-120 g/l; to analyze the number and impact of red blood cells transfusions on different categories of babies. STUDY DESIGN; The study includes 112 premature infants born before 34 weeks of gestation and below 1400 g. 90 babies, treated with EPO (700-1000 E/kg weekly dose in 2-3 applications, for 2-4 weeks), values of Hb g/l, Ht%, Ret%, Platelets 109/l were followed and compared. Treated babies were divided in two groups: group I--treatment (starting at Hb below 106 g/l, Ht less than 31%); group II--late prophylaxis (starting at Hb > or = 106 g/l, Ht > or = 31%). Blood lactate was examined in 22 non oxygen dependent premature babies without EPO treatment, with Hb 110-120 g/l, Ht 29-32%. RESULTS: We found that in group II during the first 7-10 days Hb decreases to 105.6 (+/- 9.4) g/l, rising up afterwards to 113.5 (+/-11.0) g/l at day 25-30. Ret reach maximal values at day 15-20 when Hb drops below 110 g/l and Ht below 31%. In group I at day 25-30 of treatment is observed a rise in Hb up to 117.3 (+/-11.3) and of Ht up to 32.7% (+/- 2.6) and no decrease of Hb and Ht values during the first 7-10 days, while Ret rise up to maximal values 6.5% (+/- 3.6) at day 7-10. With Hb levels of 116.4 (+/- 4.6) g/l we found an increase in blood lactate levels up to 2.6 (+/- 0.7) mmol/l as an indicator of relative hypoxia and activated HIF. Mean number of blood transfusions in group I is 3.01(+/- 1.7), versus 2.15 (+/- 1.7) in group II (statistically non-significant). In 29 infants in group II treatment was started at Hb 110-120 g/l and the mean number of red blood cell transfusion is 1.8 (1.5)--statistically significant difference with group I. In 32% from the treated infants we found platelets count rising above 500 x 109/l. CONCLUSIONS: The presence of hypoxia at low levels of Hb and Ht leads to more rapid activation of erythropoiesis. Nevertheless, these babies need more red blood cell transfusions due to clinical symptoms of hypoxia. Normoxia after red blood cell transfusion leads to decrease of reticulocytes count by 30% and platelets by 35% in spite of treatment. The presence of relative hypoxia with Hb 110-120 g/l u Ht 31-32% is optimal for starting treatment with EPO--levels, low enough for activation of HIF and high enough to avoid blood transfusions.

[Early parenteral nutrition with very low and extremely low birth weight infants--practical approach].

UNLABELLED: Newborn infants with birth weight 1500 g and less (VLBW/ELBW) have higher nutritional needs, but enteral feeding is often insufficient or impossible. Parenteral nutrition (PN) as an important component of intensive care with them minimizes the risk of nutritional deficiency. OBJECTIVE: To evaluate the safety and efficacy of early PN administration in VLBW/ELBW infants. STUDY DESIGN: The prospective study includes 23 newborn babies with birthweight below 1500 g who were admitted to the NICU from 01.03. to 20.04. 2009. With all babies a PN was started from the first day of life with dextrose and amino acid solutions, adding lipid solutions in gradually increasing quantity on the second day. During the first 20 days of life for each baby were calculated on a daily basis the exact quantities of energy and the essential nutritional substances as well as the balance among them. All babies were followed up for weight gain, presence or absence of complications, related with parenteral nutrition as well as for: blood sugar, acid-base status, total serum protein, electrolytes, urea, triglycerides, billirubin, alkaline phosphatase, ASAT ALAT RESULTS: We found that due to the small infusion volumes during the first days, the minimal daily needed nutrition levels are reached at day 4-5. Nutritional intake at day 7-10 in most children is enough for growth. A positive mean weight gain for the whole group 6.6 g/kg/d (SD 6.2) is observed. Negative weight gain during the first 20 days is observed only with two critically ill babies with substantial reduction of infusion volume. In 9 babies a transient increase in urea levels was observed during the first week, 5 babies had an increase in triglycerides as a symptom of bad lipid tolerance. In 7 babies on prolonged total PN an increase in alkaline phosphatase is observed. Conclusions. Early and sufficient PN in newborn babies below 1500 g guarantees the daily intake of energy and essential nutritive substances for adequate growth and is a basic component of intensive therapy. It should be corresponding to the nutritional needs as well as to the clinical condition; matching the severity of complications and carried under strict laboratory control.

[Neonatal infections. Diagnostic markers of infection].

Infections are highly prevalent in the neonatal period. Unfortunately the symptoms of infection are non-specific and are seen in other neonatal diseases as: respiratory distress syndrome, metabolic diseases, intracranial hemorrhages. Diagnosis is based on the clinics, microbiologic tests and laboratory markers of infection. Considering the high mortality and serious morbidity associated with neonatal sepsis, a diagnostic marker with a very high sensitivity and negative predictive value approaching 100% is desirable. Unfortunately there is no laboratory marker that has all of the characteristics of ideal infection marker. Procalcitonin, interleukins 6 and 8, CD 11b are early, sensitive markers of infection. C- reactive protein is a late specific marker of infection. CD 64 is the most sensitive marker of late, nosocomial infection. Serial measurement of infection markers will certainly improve the diagnostic sensitivity of these tests, because in most circumstances it is not certain at which stage of the infection the specimen should be taken for analysis. In addition, the use of multiple markers, in particular, combining an early sensitive marker with a late specific test will further enhance the diagnostic accuracy of these mediators in identifying infected cases.