Trends in Mortality and Morbidity in Infants Under 500 Grams Birthweight: Observations from Our Neonatal Intensive Care Unit (NICU).

BACKGROUND In our previous study, some changes were presented in obstetric care and we studied the morbidity and mortality trends of infants with <500 grams birth weight. Several neonatal protocol changes occurred during the study period. The aim of this study was to analyze the changes in mortality and morbidity of premature infants in light of changing neonatal protocols. MATERIAL AND METHODS We performed a retrospective study of premature infants with <500 grams birth weight, born at our department between 2006 and 2015. We divided the study period into two 5-year epochs and compared mortality and morbidity rates. We calculated the duration of mechanical ventilation and non-invasive respiratory support, and also investigated the potential impact of the differences in clinical practice. RESULTS The survival rate was 30.8% during first epoch, which was significantly lower than the 70.4% survival rate during second epoch. There was no difference in the rate of complications between the 2 epochs. The total number of ventilator and non-invasive ventilation days was significantly lower in the second epoch. CONCLUSIONS We found significant differences in survival rates but no change in the incidence of morbidities between the 2 epochs. Therefore, although the number of neonates surviving with morbidities has increased, so did the number of those with intact survival. The increased survival of infants born with <500 grams birth weight is not associated with increased rate of morbidities. Protocol changes may have contributed to these findings; however, in a retrospective study it is not possible to separate the impact of individual changes.

Morbidity and mortality trends in very-very low birth weight premature infants in light of recent changes in obstetric care.

OBJECTIVE: In this study, we describe trends in morbidity and mortality of preterm infants with less than 500mg birth weight in the changing landscape of obstetric and neonatal care. STUDY DESIGN: During a ten year study period between 2006 and 2016 we assessed outcome data for all neonates with less than 500mg birth weight born at our Neonatal Intensive Care Unit. We divided study subjects into two groups based on whether their birth date fell in the first half (2006-2010; n=39) versus the second half (2011-2015; n=27) of the study period comparing clinical outcomes in the two groups. We also assessed several clinical parameters for association with postnatal survival by comparing relative frequencies for each clinical parameter among surviving infants versus mortality cases. RESULTS: Survival rate for preterm neonates with less than 500mg birth weight born between 2006 and 2010 was 30.8%. This survival rate rose to 70.4% in the second half of the study period between 2011 and 2015 (p<0.05). Among surviving babies premature birth was found to be predominantly associated with maternal hypertension or intrauterine growth restriction while in those who died premature birth due to premature rupture of membranes and spontaneous preterm labor were significantly more common. All surviving infants with less than 500mg birth weight were born via cesarean section whereas among those who died cesarean section had been performed in only 80% and vaginal delivery in 20% representing a significant difference between the groups (p<0.05). The majority (90.3%) of surviving infants with less than 500mg birth weight had received surfactant therapy while the proportion of neonates receiving surfactant therapy among mortality cases was significantly lower (65.2%; p<0.05). DISCUSSION: Our findings suggest that among premature neonates with less than 500mg birth weight preterm delivery due to premature rupture of membranes and intrauterine infections represents the worse mortality risk. Steroid prophylaxis and measures to prevent and treat intrauterine infections with appropriate use of antibiotics can markedly improve survival in these cases. In premature neonates with less than 500mg birth weight survival is more favorable after cesarean section compared to vaginal delivery.

Expression of VEGF in neonatal urinary obstruction: does expression of VEGF predict hydronephrosis?

BACKGROUND: In animal studies, the inhibition of VEGF activity results in high mortality and impaired renal and glomerular development. Mechanical stimuli, like mechanical stretch in respiratory and circulatory systems, results in an elevated expression of VEGF. In animal models, the experimental urinary obstruction is associated with stretching of tubular cells and activations of the renin-angiotensin system. This results in the upregulation of vascular endothelial growth factor (VEGF) and TNF-alfa. MATERIAL/METHODS: Tissue samples from urinary tract obstruction were collected and immunohistochemistry was performed in 14 patients (average age: 7.1±4.1 years). The control histology group consisted of ureteropelvic junction tissue from 10 fetuses after midtrimester artificial abortion. The fetuses did not have any failure at ultrasound screening and pathological examination. The mean gestational age was 20.6 weeks of gestation (±2.2SD). Expression of VEGF was detected with immunohistochemistry method. RESULTS: Expression of VEGF was found in varying intensity in the submucosa and subserosa layers, but only in the test tissue (placental tissue). The tissue of the patients with urinary obstruction and the tissue of the fetal ureteropelvic junction without urinary obstruction were negative for expression of VEGF. The repeated examination showed negative cells and no color staining. CONCLUSIONS: The pressure due to congenital urogenital obstruction resulting in mechanical stress in cells did not increase the expression of VEGF in young children in our study. To find a correlation between urogenital tract obstruction and increased expression of VEGF, we need to perform more examinations because the connection may be of therapeutic significance.

[Changes in the outcome for infants, with birth weight under 500 grams, at our department (First Department of Obstetrics and Gynecology, Semmelweis University, Budapest)]. / Az 500 gramm alatti születési súlyú koraszülöttek túlélésének változása klinikánkon.

INTRODUCTION: The mortality and morbidity of extremely low birth weight infants (birth weight below 1000 grams) are different from low birth weight and term infants. The Centers for Disease Control statistics from the year 2009 shows that the mortality of preterm infants with a birth weight less than 500 grams is 83.4% in the United States. In many cases, serious complications can be expected in survivals. AIM: The aim of this retrospective study was to find prognostic factors which may improve the survival of the group of extremely low birth weight infants (<500 grams). METHOD: Data of extremely low birth weight infants with less than 500 grams born at the 1st Department of Obstetrics and Gynecology, Semmelweis University between January 1, 2006 and June 1, 2012 were analysed, and mortality and morbidity of infants between January 1, 2006 and December 31, 2008 (period I) were compared those found between January 1, 2009 and June 1, 2012 (period II). Statistical analysis was performed with probe-t, -F and -Chi-square. RESULTS: Survival rate of extremely low birth weight infants less than 500 grams in period 1 and II was 26.31% and 55.17%, respectively (p = 0.048), whereas the prevalence of complications were not significantly different between the period examined. The mean gestational age of survived infants (25.57 weeks) was higher than the gestational age of infants who did not survive (24.18 weeks) and the difference was statistically significant (p = 0.0045). CONCLUSIONS: Education of the team of the Neonatal Intensive Care Unit, professional routine and technical conditions may improve the survival chance of preterm infants. The use of treatment protocols, conditions of the Neonatal Intensive Care Unit and steroid prophylaxis may improve the survival rate of extremely low birth weight infants.

Perioperative analgesia of infants during the therapy for retinopathy of prematurity.

BACKGROUND: In this retrospective investigation, we compared the main anesthesiologic aspects in the preoperative, perioperative, and postoperative care of 2 different surgical methods (cryotherapy, laser coagulation) for retinopathy of prematurity. MATERIAL/METHODS: A retrospective analysis of analgesia for retinopathy of prematurity was performed for a 14-year period. Infants treated from January 1994 to December 2007 were involved in the study. Before 1997, we performed transconjunctival cryotherapy with ketamine analgesia for 28 newborn infants, while in the last 10 years, laser photocoagulation was done with nalbuphine-diazepam analgesia in 85 cases. RESULTS: Significant differences were verified in gestational age of birth in the group of retinopathy of prematurity patients treated with cryotherapy compared with those treated with laser coagulation 27.9+/-2.7 weeks vs 26.4+/-2.4 weeks (P<.05). The difference in the need for postoperative ventilation (43% vs 19%; P<.05) as well as the number of cases with hypoxemia (54% vs 21%; P<.05) was significant, compared with the group of infants treated with cryotherapy with those treated with laser coagulation. CONCLUSIONS: This study demonstrates that intravenous analgesia (with ketamine or nalbuphine-diazepam) can be used in the surgical treatment of retinopathy of prematurity.

[Assessment of serum interleukin-6 with a rapid test. The diagnosis of neonatal sepsis can be established or ruled out]. / Szérum-interleukin-6-meghatározás gyorsteszt segítségével. Az újszülöttkori szepszis korai diagnózisa, kizárása.

INTRODUCTION: The mortality rate from sepsis is high and the risk of sepsis increases in prematurity in proportion to the decrease in birth weight. MATERIAL AND METHOD: The authors report the assessment of serum interleukin-6 levels in 12 term, at-risk newborn infants after birth and 60 VLBW neonates after detection of non-specific signs of infection or sepsis, treated in NICU at the Semmelweis University, 1st Department of Obstetrics and Gynecology in 2005-2006. The serum IL-6 level with a rapid test (Milenia Quickline IL-6 and PicoScan system) was investigated. The simultaneous assessment of C-reactive protein levels was analysed as well. RESULTS: The assessment of serum interleukin-6 and CRP levels for the early diagnosis of sepsis can be established or ruled out. The sensitivity of serum IL-6 level assessment was 100%. There were no false negative cases. The positive predictive value was 93%. There was a significant difference between the sepsis and infection group of VLBW infants in the serum Il-6 levels ( p = 0.048), and between the infection and non-infection groups in the interleukin-6 levels ( p < 0.005). CONCLUSIONS: In comparing the diagnostic value of IL-6 measurement in VLBW infants with signs of infection to the diagnostic methods currently in use, results showed that a combination of early assessment of IL-6 and CRP seems to increase diagnostic accuracy in attempting to differentiate between septic and nonseptic patients. Such increased accuracy will decrease neonatal morbidity as well as the financial cost of treatment.

TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells.

Many studies detect elevated numbers of mast cells in tumors, but it is still controversial whether they are beneficial or detrimental for tumor cells. Furthermore, many tumors, such as melanomas, produce large quantities of transforming growth factor (TGF)-beta and during tumorigenesis the apoptotic and growth-inhibitory effects of TGF-betas are lost. Based on these data we investigated the gene expression changes in TGF-betaI-treated human mast cells with DNA microarray and detected 45 differentially regulated genes, among them T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). As the major sources of TIM-3 ligand galectin-9 are not tumor cells, but rather mast cells, this raises the possibility of an autocrine mechanism resulting in local immunosuppression through the elevated TIM-3 expression by TGF-betaI. Interestingly, not only melanoma tissue sections contained TIM-3-positive mast cells, but we detected this protein also in melanoma cells. Furthermore, TIM-3 was expressed in both WM35 and HT168-M1 melanoma cell lines at a higher level than in isolated epidermal melanocytes, which can contribute to the lower adhering capacity of tumor cells. In conclusion, the immunoregulatory molecule TIM-3 in TGF-beta-stimulated mast cells and melanoma cells may support the survival of this tumor type.

[The outcome of triplet pregnancies at the First Department of Obstetrics and Gynecology, Semmelweis University, in the last 15 years]. / Hármas ikerterhességek kimenetele a Semmelweis Egyetem I. Szülészeti és Nôgyógyászati Klinikáján az elmúlt 15 év alatt.

INTRODUCTION AND METHODS: The authors analysed the data of 307 live-birth newborns and premature infants who were born from 104 triplet pregnancies between 1 January 1990 and 31 December 2005 at the Semmelweis University First Department of Obstetrics and Gynecology. AIMS AND RESULTS: In 86% of the triplet pregnancies conception took place with the help of assisted reproduction technology, the number of which has rapidly increased in the last 15 years. 60% of the triplet pregnancies ended before the 34th week of gestation and the birth weight of more than one third of the infants was less than 1,500 grams. Among the infants treated in the Neonatal Intensive Care Unit the most common diagnosis was connatal pneumonia, which was followed by hyaline membrane disease due to the low birth weight. In the past 15 years, the mortality of triplets was at 6.5%. The birth weight of those who died before reaching the age of six months was, with two exception cases, below 1500 grams. CONCLUSION: According to our data the chance of survival of triplets was poorer in category of birth weight under 1000 grams than those of premature infants born of single pregnancies with the same weight. In vitro fertilisation in the case of triplets increases the occurrence of premature deliveries and the number of infants with very low weight. Long-term monitoring data reveals that in such cases, neurological lesions and the occurrence of a chronic disease, which greatly influences the future quality of life for the child as well as for its family, is more frequent between the very low birth weight infants.

[The combined effect of prenatal steroid prophylaxis, neonatal surfactant therapy and reduction of risk of complications from respiratory life support on survival rate of very low birthweight infants]. / Az antenatalis szteroid profilaxis bevezetésének, a neonatalis surfactant terápia alkalmazásának és a respirációs szövodmények csökkentésének együttes hatása az igen kis súlyú újszülöttek túlélésére.

INTRODUCTION: Retrospective analysis on some factors possibly influencing survival rate of very low birthweight infants on respiratory life support has been carried out. AIM: The aim was to find out about roles played by prenatal steroid prophylaxis, neonatal surfactant therapy and methods of reduction of complication risk emanating from respiratory life support in the outcome of treatment. METHOD: The frequency rate of pneumothorax, pneumomediastinum and bronchopulmonary dysplasia was comparatively examined for all very low birthweight (less than 1500 g) neonates treated by respiratory life support in the I. Department of Obstetrics and Gynecology, Semmelweis University in 1999 (n = 178) and in 1989 (n = 78). Corresponding data were compared using t-tests. RESULTS: In 100% of the 1999 patients in the focus of the current investigation (178 newborn infants) have received prenatal steroid prophylaxis and 55% of them (98 neonates) have received neonatal surfactant therapy. Respiratory life support resulted in pneumothorax in 7.8% of them (14 patients) and bronchopulmonary dysplasia in 12.3% of them (22 neonates). Frequency rate of complications for the neonates under investigation attributable to respiratory support or initial illness decreased from 38.6% in 1989 to 19.6% in 1999, a difference proven significant by t-test (p < 0.05). Survival rate increased from 34.6% in 1989 to 63.5% in 1999, which is again a significant difference indicated by t-test (p < 0.05). The differences are especially consequential considering that the average gestation age of the infants in the 1999 group was lower than that of the infants in the 1989 group. CONCLUSION: Decrease in complication rate emanating from respiratory support and increase in survival rate over the 10 year period between 1989 and 1999 can be attributed to the combined effect of improvement in respiratory support therapy applied (aiming to minimise its adverse effects like barotrauma and volutrauma more effectively by refined technological means) and of the introduction of administering prenatal steroid prophylaxis and (if judged necessary) neonatal surfactant therapy. A considerable limitation of this study is the lack of separation of independent variables (the separate effects due to the separate treatments applied), but it is reasonable to believe that improvement was due to a combined effect of all changes in treatments indicated above. It is deemed probable that results can be further improved by finding ways to decrease barotrauma and volutrauma even more effectively than now.