Trends of the Prevalence of Pre-gestational Diabetes in 2030 and 2050 in Belgrade Cohort.

The aim of this study was to analyze the trends in diabetes in pregnancy in Belgrade, Serbia for the period of the past decade and forecast the number of women with pre-gestational diabetes for the years 2030 and 2050. The study included the data on all pregnant women with diabetes from the registry of the deliveries in Belgrade, by the City Institute of Public Health of Belgrade, Serbia for the period between 2010 and 2020 and the published data on the deliveries on the territory of Belgrade. During the examined period the total number of live births in Belgrade was 196,987, and the prevalence of diabetes in pregnancy was 3.4%, with the total prevalence of pre-gestational diabetes of 0.7% and overall prevalence of GDM of 2.7%. The average age of women in our study was significantly lower in 2010 compared to 2020. The forecasted prevalence of pre-gestational diabetes among all pregnant women for 2030 is 2% and 4% for 2050 in our cohort. Our study showed that the prevalence of pre-gestational diabetes has increased both among all pregnant women and among women with diabetes in pregnancy in the past decade in Belgrade, Serbia and that it is expected to increase further in the next decades and to further double by 2050.

Combined hereditary thrombophilias are responsible for poor placental vascularization development and low molecular weight heparins (LMWH) prevent adverse pregnancy outcomes in these patients.

BACKGROUND: Even though thrombophilias are associated with negative pregnancy outcomes (PO), there is not a consensus of when thrombophilias should be screened for, or how they affect placental vascularization during pregnancy. Therefore, the main aim of this study was to discover inherited thrombophilias (IHT) in the first trimester in women with otherwise no indications for thrombophilia screening, based on their vascularization parameters. LMWH treatment in improvement of placental vascularization and PO was also assessed. Finally, the classification of thrombophilias based on observed obstetric risks was proposed. METHODS: Women were included in study based on their poor gestational sac and later utero-placental juncture vascularization signal and screening for inherited thrombophilias. LMWH were then initiated and Resistance index of Uterine artery (RIAU) was followed alongside PO (preterm birth, preeclampsia, placental abruption, intrauterine growth reduction). Study group consisted of women with combined inherited thrombophilias. Control group consisted of patients with inherited thrombophilias who have received LMWH therapy since pregnancy beginning. FINDINGS: Out of 219 women, 93 had IHT, and 43 had combined IHT. All pregnancies both in both groups ended up with live births. Vaginal birth was more present in the control group (p < .001), and all women in study group delivered by CS. Premature birth was present in 8.4% of patients in control group, and in 32.55% of the patients in the study (p < .001). PE wasn't noted, and only 1 case of PA in control group. In the control group, 6.5% patients had IUGR, and 32.55% in the study group (p < .05). Based on RIAU and PO, thrombophilia categories were established: S (severe), MO (moderate), MI (mild) and L (low). Higher risk thrombophilias had higher RIAU later in the pregnancy, earlier pregnancy termination and Intrauterine Growth Reduction (IUGR). CONCLUSIONS: Thrombophilias should be considered and screened when poor vascularization is noted early in the pregnancy with Doppler sonography. Intervention with LMWH prevents adverse PO in these patients.

Uptake of Human Papillomavirus Vaccine and Intention to Vaccinate among Healthy Pregnant Women in Serbia: A Cross-Sectional Study on Awareness, Knowledge, and Attitudes.

We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted at the University Clinic of Gynecology and Obstetrics, Belgrade, Serbia among pregnant women attending their regular gynecological check-ups at the 12th gestational week. Knowledge about HPV and HPV vaccine was assessed using a specifically designed 12-item and 5-item questionnaires. Out of total 265 included women, 79.3% had heard of HPV, and 37.5% knew that HPV vaccine exists. HPV vaccine knowledge score was associated with higher odds for a positive attitude towards vaccination of both female (OR = 4.10, 95% CI 1.50-11.29) and male (OR = 3.71, 95% CI 1.52-9.01) child. The number of children (OR = 1.32, 95% CI 1.04-1.67) and high vaccine knowledge score (OR = 1.64 95% CI 1.13-2.39) were independent predictors associated with willingness to vaccinate child against HPV. The gynecologist was the preferable point of reference for information seeking about the HPV vaccine. Despite relatively high HPV awareness and knowledge among pregnant women in Serbia, about one-third of them are HPV vaccine aware, and are willing to vaccinate their children against HPV.

The prognostic value of amplitude-integrated electroencephalography in neonates with hypoxic-ischemic encephalopathy.

BACKGROUND/AIM: Diagnosis of perinatal hypoxic-ischemic encephalopathy (HIE) and early prediction neurological outcome is important and difficult. The aim of this study was to determine the prognostic value of amplitude-integrated electroencephalography (aEEG) for abnormal neurodevelopment outcome in a neonate with HIE. METHODS: A total of 90 neonates > 32 gestational age (GA) with HIE were enrolled prospectively. All neonates with HIE were categorized into three grades according to the Sarnat and Sarnat clinical scoring system (mild HIE, moderate HIE and severe HIE). aEEG traces were recorded with a cerebral function monitor (CFM) during the first 72 h of life. The neurodevelopment outcome was assessed at 12 months of age of corrected gestational age. RESULTS: The pattern of aEEG correlated with the severity of HIE (p < 0.0001) and subsequent neurodevelopment outcome (p < 0.001). We found that aEEG background patterns exhibited superior prediction of abnormal outcomes at 12 months of age (sensitivity of 91.7% and specificity of 94.3%, positive predictive value of 78.6% and negative predictive value of 98.1%) when compared to aEEG seizure (sensitivity of 94% and specificity of 48%, positive predictive value of 57% and a negative predictive value of 92%). Electroclinical dissociation seizure was detected in 28% of the neonates with HIE. CONCLUSIONS: Our results confirm that aEEG is simple and accurate bedside diagnostic method for assessing extension of hypoxic-ischemic brain damage and early identification of neonates with perinatal HIE who are at high risk of neurodevelopmental impairment.

The role of oxidative stress in perinatal hypoxic-ischemic brain injury.

INTRODUCTION: The pathogenesis of perinatal hypoxic-ischemic brain damage is highly complex. OBJECTIVE: The aim of this study was to assess the role of oxidative stress in hypoxic-ischemic brain injury and subsequent abnormal neurological outcome in infants with perinatal hypoxic-ischemic encephalopathy (HIE). We estimated perinatal oxidative brain damage measuring activity of glutathione peroxidase (GPX) in cerebrospinal fluid (CSF) as an indirect biomarker of free radical production during cerebral hypoxia-ischemia in correlation with the level of intracellular enzyme neuron specific enolase (NSE) in CSF as a biomarker of extend of brain injury. METHODS: Ninety neonates (>32 GA) with perinatal HIE were enrolled prospectively. HIE was categorized into three stages according Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated EEG. CSF for GPX analysis and NSE analysis was taken in the first 72 hours of life. Neurodevelopment outcome was assessed at 12 months of corrected gestational age. RESULTS: GPX activity in CSF was in good relation with clinical stage of HIE (p < 0.0001) and GA (p < 0.0001) and significantly corresponded with subsequent neurodevelopment outcome (p < 0.001). GPX activity in CSF showed a strong correlation with NSE levels in CSF (p < 0.001) as the biomarker of extent of brain injury. CONCLUSION: Our results suggest that oxidative stress might be important contributing factor in perinatal hypoxic-ischemic brain damage, particularly in preterm neonates.

[Predictive value of color Doppler neuro-sonography for the development of neurological sequels in newborn infants with hypoxic ischemic encephalopathy].

BACKGROUND/AIM: The use of color Doppler neurosonography (cD-US) allows simultaneous examination of parenchymal and vascular cerebral structures. Evaluation of cerebral blood flow velocities (CBFV) and vascular resistance are important in assessment of cerebral circulation in neonates with hypoxic ischemic encephalopathy (HIE). The aim of this study was to evaluate the predictive value of cD-US for abnormal neurodevelopmental outcome in the neonates with HIE. METHODS: A total of 90 neonates (> 32 weeks gestational age) with HIE were enrolled prospectively. All the neonates with HIE were categorized into three grades according to the Sarnat and Sarnat clinical staging system: mild HIE, moderate HIE, and severe HIE. cD-US was performed simultaneously during the first 24 h of life. Neurodevelopment outcome was assessed at 12 months of age in all the neonates. RESULTS: The values of CBFV and the values of index resistance (RI) correlated with the severity of HIE (p < 0.0001) and subsequent neurodevelopmental outcome (p < 0.001). We detected a significant difference in values of CBFV and in values of RI between preterm and full-term neonates (p < 0.01). The cut-off value of RI for poor neurodevelopmental outcomes was 0.81. CONCLUSIONS: cD-US could be very useful and safe diagnostic tool for assessing severity of HIE and subsequent adverse neurodevelopmental outcome.

New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury.

BACKGROUND: Pathogenesis of perinatal hypoxic-ischemic brain injury (HIE) is complex. In this study, we examined the role of neuroinflammation, oxidative stress and growth factors in perinatal hypoxic-ischemic brain damage. METHODS: Ninety neonates (>32 weeks' gestation) with perinatal HIE were enrolled prospectively. Perinatal HIE was categorized into three stages according to the Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated electroencephalography. Cerebrospinal fluid (CSF) for interleukin-6 (IL-6) and glutathione peroxidase analysis was taken in the first 48 h of life and subsequent CSF for neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF) analysis 72 h after birth. Neurodevelopmental outcome was assessed at 12 months of corrected gestational age using the Denver Developmental Screening Test. RESULTS: Concentrations of NSE in CSF correlated with severity of HIE (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Concentrations of IL-6 in CSF were markedly increased in neonates with severe HIE (P < 0.0001) and those with subsequent neurological sequels, but were normal in the majority of neonates with mild and moderate HIE. Glutathione peroxidase activity in CSF was significant with the stage of HIE (P < 0.0001) and gestational age (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Advanced stage of HIE was associated with increased concentrations of VEGF in CSF (P < 0.0001). Neurological outcomes at 12 months of age correlated best with CSF level of NSE (P < 0.001) and IL-6 (P < 0.001). CONCLUSION: Our results suggest that neuroinflammation plays a principal role in perinatal hypoxic-ischemic brain damage and we postulate that oxidative stress and upregulation of VEGF might be important contributing factors in the pathogenesis of hypoxic-ischemic brain injury, particularly in preterm neonates.

[Normal values of cerebral blood flow velocities in neonates].

INTRODUCTION: There was used color Doppler ultrasonography (cD-USI), allowing simultaneous examination of parenchymal and vascular cerebral structures. The evaluation of blood flow velocities in cerebral arteries is important in the assessment of cerebral circulation in hypoxic-ischaemic and haemorrhagic brain damage in neonates. OBJECTIVE: The aim of this study was to estimate normal values of cerebral blood flow velocities (CBFV) and Doppler indices--pulsatility index (PI) and resistance index (RI)--in the anterior cerebral artery (ACA) during the first days of life in infants. METHODS: CBFV, PI and RI were obtained during the first week of life with cD-US in 70 infants divided in four groups of gestational age (GA): < or =28 gestational weeks (GW); 29-32 GW; 33-36 GW; and > or =37 GW. Infants with congenital malformations, severe perinatal asphyxia, cerebral haemorrhagic lesion, DAP or severe hypotension were excluded. RESULTS: The mean GA of infants was 34.5 +/- 5.5 GW (range 26-40 GW) and the mean birth weight (BW) was 2540 +/- 950 g (range 750-4000 g). In the 1st group of 10 infants, < or =28 GW, the mean BW was 950 +/- 110 g and values of RI were 0.59 +/- 0.10 and PI 1.06 +/- 0.080. In the 2nd group of 20 infants, 29-32 GW, the mean BW was 1350 +/- 290 g and values of RI were 0.60 +/- 0.10 and PI 1.10 +/- 0.15. In the 3rd group of 20 infants, 33-36 GW, the mean BW was 1950 +/- 750 g and values of RI were 0.63 +/- 0.08 and PI 1.15 +/- 0.30. In the 4th group of 20 infants, > or =37 GW, the mean BW was 3540 +/- 950 g and values of RI were 0.65 +/- 0.05 and PI 1.18 +/- 0.35. CONCLUSION: Values of CBFV progressively increase with GA and BW due to progressive increase of cardiac output, blood pressure and closing of ductus arteriosus. Values of RI and PI gradually increase with GA and BW as a result of progressive maturation and opening of vascular cerebral bed with a reduction of the cerebrovascular resistance.

[The serum level of C-reactive protein in neonatal sepsis].

INTRODUCTION: C-reactive protein (CRP) is the most common diagnostic marker of infection. OBJECTIVE: Objectives of this study were to determine the serum CRP level in neonates with sepsis and establish the influence of gestational age (GA) on the CRP level in the first few weeks after birth. METHOD: Diagnosis of neonatal sepsis was established by the presence of clinical signs of sepsis, isolation of the causative agent of sepsis and abnormal haematological parameters. All neonates were divided into two groups: early onset sepsis (EOS) and late onset sepsis (LOS). According to GA all neonates were divided into three groups: < 32 GA, 32-36 GA and > or = 37 GA. Serum CRP was measured 0-72 h after the onset of signs and symptoms of infection. RESULTS: This study included all neonates with sepsis at our Institute during 2003. EOS was diagnosed in 130 neonates (mean age was 33 weeks; range 27-41 weeks) and 33 infants (mean age 29 weeks; range 27-38 weeks). We defined a relevant CRP response as a concentration of > 10 mg/l for term and near term neonates and > 5 mg/l for preterm neonates. The maximum concentrations of CRP were reached 48 hr after the first symptoms of neonatal sepsis. CONCLUSION: CRP levels are proportional with increasing GA and body weight in EOS. The effects of gestational age do not influence CRP levels in LOS. Maturation changes in the immune system are the most likely explanation for this and partly the organisms responsible for an infection may be different at different gestational ages and also in EOS and LOS. There is no correlation with serum CRP levels and with the severity of the disease and bad prognosis in EOS.