Antenatal Neuroprotective Magnesium Sulfate in Very Preterm Infants and Its Association With Feeding Intolerance.

INTRODUCTION/OBJECTIVE: Magnesium sulfate (MgSO 4 ) treatment is widely used for fetal neuroprotection despite the controversy concerning the side effects. There is limited data regarding the impact of various cumulative maternal doses and neonatal serum magnesium (Mg) levels on short-term neonatal morbidity and mortality. We opted to carry out a study to determine the impact of neonatal serum Mg levels on neonatal outcomes. METHOD: We conducted this prospective observational study between 2017 and 2021. Antenatal MgSO 4 was used for neuroprotective purpose only during the study period. Inborn preterm infants delivered between 23 and 31 6/7 weeks of gestation were enrolled consecutively. Babies who underwent advanced resuscitation in the delivery room, inotropic treatment due to hemodynamic instability in the first 7 days of life, >12 hours since the discontinuation of maternal MgSO 4 treatment, severe anemia, and major congenital/chromosomal anomalies were excluded from the study. The subgroup of babies with serum Mg level at the 6th hour of life underwent an analysis. A neonatal Mg concentration of 2.5 mg/dL was used to classify MgSO 4 -exposed patients into 2 groups (<2.5 mg/dL and ≥2.5 mg/dL). Another analysis was performed between babies whose mothers were exposed to MgSO 4 and those not exposed. Finally, the groups' neonatal outcomes were compared. RESULTS: Of the 584 babies, 310 received antenatal MgSO 4 . The birth weights were significantly lower in the MgSO 4 exposed group (1113 ± 361 g vs 1202 ± 388 g, P = 0.005). Antenatal corticosteroid usage and intrauterine growth restriction were also noted to be higher. The MgSO 4 group was more likely to have bronchopulmonary dysplasia, prolonged invasive ventilation, necrotizing enterocolitis, delayed enteral nutrition, and feeding intolerance ( P < 0.05). MgSO 4 treatment was shown as an independent risk factor for feeding intolerance when corrected for confounders (odds ratio 2.13, 95% confidence interval: 1.4-3.1, P = 0.001). Furthermore, serum Mg level significantly correlated with feeding intolerance ( r = 0.21, P = 0.002). CONCLUSION: This study highlighted the effect of MgSO 4 treatment and the potential superiority of serum Mg level as a predictor of immediate neonatal outcomes, particularly delayed enteral nutrition and feeding intolerance. Further studies are warranted to ascertain the optimal serum Mg concentration of preterm infants in early life to provide maximum benefit with minimal side effects.

Diagnostic role of optic nerve sheath diameter and brain blood flow in neonates with hypoxic-ischemic encephalopathy.

PURPOSE: The primary aim was to study the optic nerve sheath diameter (ONSD) measurements and cerebral blood flows in neonates with hypoxic-ischemic encephalopathy (HIE) who were at risk of cerebral edema and to compare the measurements with healthy neonates. METHODS: Neonates diagnosed as Stage II and III HIE patients were enrolled in the study group. ONSD measurements and blood flow Doppler studies in the first 24-48 h of life during hypothermia and following hypothermia treatment. Magnetic resonance imaging (MRI) and transfontanelle ultrasonography were performed within the first 4-7 days of life in all HIE patients. Saved US and MRI images were assessed by a blind pediatric radiologist later on. RESULTS: Data from a total of 63 infants (42 in the HIE group and 21 in the control group) were analyzed. Both the right and left ONSD measurements were comparable between HIE and control groups. However, both resistive index (RI) and pulsatility index (PI) of the middle cerebral artery were found to be significantly lower in HIE (0.69 ± 0.09 and 1.14 (0.98-1.30)) group when compared with controls (0.75 ± 0.04 and 1.41 (1.25-1.52)) (p < 0.01). Ultrasonographic ONSD measurements were significant and strongly correlated with MRI ONSD measurements for both sides (r = 0.91 and r = 0.93, p < 0.01). Doppler studies during normothermia were comparable with the control group and significantly increased following therapeutic hypothermia. CONCLUSION: Ultrasonographic ONSD measurements can be reliably performed in term neonates with high compatibility to MRI. No significant effect on ONSD measurements was found related to asphyxia and therapeutic hypothermia despite the significant alteration observed in Doppler studies.

A novel scoring system (YASHMA) predicting brain injury in asphyxiated newborns.

BACKGROUND: Hypoxic-ischemic encephalopathy is a complication of adverse intrapartum events and birth asphyxia resulting in brain injury and mortality in late preterm and term newborns. OBJECTIVES: In this study, we aimed to predict brain damage on magnetic resonance imaging (MRI) with a new scoring system. METHODS: Yieldly And Scorable Holistic Measuring of Asphyxia (YASHMA) is generated for detection of brain injury in asphyxiated newborns. Total scores were calculated according to scores of birth weight, gestation weeks, APGAR scores at first and fifth minutes, aEEG patterns and epileptic status of patients. The major outcome of the scoring system was to determine correlation between poor scores and neonatal brain injury detected on MRI. RESULTS: In hypothermia group with brain injury, low gestational weeks and lowest APGAR scores, abnormal aEEG findings were statistically different from others. YASHMA scores were statistically significant with high sensitivity, specificity, AUC and 95% confidence interval values. CONCLUSIONS: YASHMA scoring system is feasible and can be suggestive for detecting brain injury in low-income countries.

Effect of Therapeutic Hypothermia Treatment on Acute Phase Reactants.

OBJECTIVE: In our study, we aimed to examine the effect of therapeutic hypothermia treatment on C-reactive protein (CRP) and interleukin-6 (IL-6) in infants with hypoxic ischemic encephalopathy (HIE). METHODS: The data of the patients with the diagnosis of HIE we followed up in our unit between 2017 and 2018 were analyzed retrospectively. Patients who died during follow-up and patients with proven septicemia at the time of examination were excluded from the study. The routine CRP and IL-6 values ​​of the patients included in the study were compared before and after hypothermia treatment. RESULTS: Therapeutic hypothermia treatment applied for 72 hours was found to cause a statistically significant increase in CRP after treatment when compared with the values ​​measured before treatment (0.6 (0.2-1.9) before and median (P25-75), and after treatment 7.5 (4-18) and median (P25-75) mg/L, p=0.00). While IL-6 was found to be high in the early period due to the effect of hypoxia, it was found to be low after hypothermia treatment (80.5 (40-200) median (P25-75) - 32 (18-50) median (P25-75) pg/ml, p=0.131). While the white blood cell count was high before hypothermia treatment due to hypoxia, it was found to be low after treatment (24600 (19600-30100) median (P25-75) -11300 (8800-14200) median (P25-75)/µL, p=0.001). CONCLUSION: White blood cells and IL-6 can be found to be high due to hypoxia without infection, and CRP can be found to be high after therapeutic hypothermia treatment without infection. The effect of hypoxia and hypothermia should be considered when evaluating acute phase reactants.

Could red cell distribution width be used for predicting cardiac injury in neonates with COVID-19?

BACKGROUND: Coronavirus disease 2019 (COVID-19) can affect people of all age groups and it can occasionally cause life-threatening clinical illnesses in immunologically immature populations, especially in newborns. High red cell distribution width (RDW) values were used as an early prognostic biomarker of some neonatal diseases. We aimed to determine the prognostic value of RDW in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infected neonates. METHODS: Newborns with positive SARS-CoV-2 polymerase chain reaction (PCR) test from a nasopharyngeal swab sample, who had refractory fever (>38°C and lasting more than 24 h during hospitalization), were screened for multisystem inflammatory syndrome in newborns (MIS-N), systemic inflammatory indexes calculated and cardiologic evaluations. Due to troponin levels (high: >45 ng/L and low: ≤45 ng/L) patients were grouped. RESULTS: Out of the 68 SARS-CoV-2 PCR-positive newborns, 26 patients had refractory fever. Comparison of laboratory findings between the high and low-troponin groups showed that RDW and neutrophil/lymphocyte ratio values were significantly higher in patients with high troponin levels (p = 0.022 and p = 0.030, respectively). The cut-off values with optimal sensitivity and specificity were determined as 1.00 for neutrophil/lymphocyte ratio (p = 0.205) and 16.6 for RDW (p = 0.014). None of the patients died. CONCLUSIONS: Neonatal COVID-19 generally has a benign prognosis, but can progress to severe disease and cases of MIS-N are rare. RDW could be prognostic in the diagnosis and management of neonates with SARS-CoV-2 infection with high troponin levels.

Long-term neurodevelopmental outcomes in very low birth weight infants with and without patent ductus arteriosus: A retrospective case control observational study.

BACKGROUND: Patent ductus arteriosus (PDA) has been associated with early morbidities and long-term developmental problems in very preterm infants. AIMS: The aim of this study is to investigate the effect of patent ductus arteriosus and medical treatment on long-term developmental outcomes in very low birth weight infants. STUDY DESIGN: This is a retrospective case control observational study. SUBJECT: The study included preterm infants who were born before 30 weeks' gestation and birth weight less than 1,500 g and underwent neurodevelopmental testing at a corrected age of 24 months during follow-up in our centre. The results of neurodevelopmental assessment using the Bayley Scales of Infant Development II at 24 months of corrected age and other morbidities were recorded. RESULTS: Of 820 infants screened, the 2-year data of 647 infants (78%) were analysed. The mean gestational age was 27.4 weeks (±1.7 weeks), mean birth weight was 980 g (±250 g) and 283 (44%) of the infants received pharmaceutical treatment for hemodynamically significant PDA. The prevalence of neurodevelopmental impairment was higher in infants with PDA compared to those without PDA (odds ratio [OR], 1.6; 95% CI, 1.13-2.29; chi-square, Fisher's exact test P = .009). However, when birth weight and gestational age were corrected for as covariates and other risk factors were added to the analysis, PDA alone was not an independent risk factor for neurodevelopmental problems (OR, 1.12; 95% CI, 0.824-1.549; P = .450). There was no difference between the groups who received ibuprofen or paracetamol for PDA. CONCLUSION: Although we have not found an association between hemodynamically significant PDA and poor neurodevelopment, this potentially needs to be investigated.

Role of derived neutrophil-to-lymphocyte ratio, uric acid-to-creatinine ratio and Delta neutrophil index for predicting neonatal outcomes in pregnancies with preeclampsia.

We aimed to compare the maternal and neonatal systemic inflammatory markers, platelet indices and new indices in biochemical parameters in women with preeclampsia and healthy controls. The secondary aim was to investigate whether there was a relationship between maternal hematological markers and neonatal outcomes. A retrospective case control study was conducted in a tertiary hospital. Maternal demographic and birth characteristics, complete blood count indices, derived neutrophil to lymphocyte ratio (dNLR), Delta neutrophil index (DNI), uric acid-to-creatinine (Cre) ratio and uric acid-to-alanine transaminase ratio, neonatal hematological parameters were compared between the preeclamptic group and control group. The study consisted of 170 cases (84 preeclampsia and 86 control). Neutrophil-to-lymphocyte ratio (NLR), dNLR, blood urea nitrogen (BUN), creatinine (Cre), uric acid, LDH, aspartate transaminase (AST) and alanine aminotransferase (ALT), uric acid-to-Cre ratio and uric acid-to-ALT ratio were higher and statistically significant in the preeclamptic group than in control ones (p: 0.000 - BUN, Cre, uric acid, LDH, p: 0.001 - AST, p: 0.004 - ALT, p: 0.000 - uric acid-to-Cre ratio, p: 0.009 - uric acid-to-ALT ratio, respectively). NLR and platelet-to-lymphocyte (PLR) ratio were significantly higher in newborns of preeclamptic mothers (p: 0.039; p: 0.004, respectively). A low-moderate correlation between maternal uric acid-to-Cre ratio and neonatal PLR was detected (r: 0.193; p: 0.013). Moreover, moderate negative correlations between maternal PLR (r:-0.231, p: 0.002), uric acid (r: 0.332, p:0.000) and adverse neonatal outcomes were found. Uric acid and PLR, which can be easily calculated clinically may predict adverse neonatal outcomes.IMPACT STATEMENTWhat is already known about this topic? Preeclampsia is known as a significant cause of maternal morbidity and mortality. Haematological indices have been evaluated for the prognosis of many kinds of disease.What do the results of this study add? This study has focussed on new combined haematological-biochemical indices and its relationship with neonatal outcomes. Both higher NLR, derived NLR, DNI and lower PLR were recorded as useful markers for preeclampsia.What are the implications of these findings for clinical practice and/or further research? Some indices that were calculated by assessing basic and simple blood parameters may help clinicians to predict clinical outcomes of preeclampsia.

Fetal pulmonary artery Doppler parameters in pregnancies complicated with intrahepatic cholestasis of pregnancy: a prospective case-control study

Objective: The primary aim of this study was to determine whether pulmonary artery acceleration time (AT) to ejection time (ET) ratio (PATET) was altered in fetuses of mothers with intrahepatic cholestasis of pregnancy (IHCP). The secondary aim was to investigate the association between fetal pulmonary artery Doppler parameters with neonatal outcomes in pregnancies complicated by IHCP. Material and Methods: This prospective case control study was conducted in a tertiary perinatal-neonatal center. A total of 18 fetuses whose mothers' pregnancies were complicated by IHCP were included as the study group and a total of 37 fetuses of mothers with healthy pregnancies were selected as controls. Fetal pulmonary artery Doppler parameters (AT; ET; AT/ET ratio) were assessed and neonatal outcomes were evaluated. Results: Mean pulmonary artery AT, ET and PATET were significantly different between the groups (p=0.001, p=0.024 and p=0.003, respectively). The mean PATET value in the IHCP group was 0.217±0.029 while in the control group it was 0.180±0.020. While PATET values were correlated with gestational age at birth, respiratory distress and need for neonatal intensive care admission were not correlated with PATET. Conclusion: Higher values of PATET may be a useful biomarker of fetal lung damage, secondary to IHCP.

Late Administration of Surfactant May Increase the Risk of Patent Ductus Arteriosus.

Introduction: Early rescue surfactant is the most effective way of administering surfactant but many infants still receive surfactant later. Our aim was to explore the association between timing of surfactant administration and the development of patent ductus arteriosus and other neonatal morbidities. Materials and method: This retrospective study analyzed 819 preterm infants under 30 weeks of gestational age and under 1,500 g. Results: Five hundred and ninety three infants received surfactant during the study period, of these 365 received it within 2 h of life (early group) and 228 received it after two h (late group). Patent ductus arteriosus was detected in 175 (48%) of the early group and 168 (74%) of the late group, p = 0.001. Multinominal logistic regression analysis demonstrated that receiving surfactant after 2 h of life has a OR 3.5 (2.2-5.64 95 % CI) and a p-value of 0.001 for developing patent ductus arteriosus. Conclusion: In this study population we observed that late surfactant administration is associated with increased risk of patent ductus arteriosus.