Role of aminophylline in prevention of acute kidney injury in term neonates with severe perinatal asphyxia: a randomized open-label controlled trial.

Acute kidney injury (AKI) is one of the frequently observed complications in neonates with severe perinatal asphyxia. The efficacy of aminophylline in preventing or alleviating renal dysfunction in these neonates remains controversial. The current study aimed to explore whether treatment with aminophylline as adjunctive therapy is superior to standard care alone in preventing AKI in severely asphyxiated term neonates and to delineate the changes in other renal parameters. In this open-label randomized clinical trial, term neonates with severe asphyxia (n = 41) received a 5 mg/kg intravenous dose of aminophylline within the first hour after birth, in addition to standard care for birth asphyxia. The control group (n = 40) received standard care alone. Their daily urine output, weight, serum creatinine, renal functional status, and complications during the first 5 days of life were monitored and compared. The statistical package for social sciences version 25 was used for analysis. Approximately 24.39% of neonates in the aminophylline group developed AKI, compared to 35.0% in the control group (P = .088). Although urine output was generally higher in aminophylline-treated newborns than in the control group, this increase was not statistically significant (P > .05), with the most notable differences observed on the second and third postnatal days. Also, the changes in plasma creatinine levels between the two groups during this time were not statistically significant. Administering a single dose of aminophylline (5 mg/kg) within the first hour of life to severely asphyxiated term neonates might temporarily enhance urine output, but does not reduce the overall incidence of AKI.

The efficacy of aminophylline in preventing or alleviating renal dysfunction in severely asphyxiated term neonates remains inconclusive. In this open-label randomized clinical trial, severely asphyxiated term neonates in the intervention group were administered 5 mg/kg of intravenous aminophylline within the first hour of life, in addition to standard care for birth asphyxia. The control group received only the standard care. Although the difference was not statistically significant, newborns treated with aminophylline generally had higher urine output than those in the control group. There was no significant difference in the incidence of acute kidney injury or changes in plasma creatinine levels between the two groups. Complications and mortality rates were similar (P > .05) in both cohorts; however, neonates treated with aminophylline exhibited a slightly higher incidence of central nervous system side effects, including more frequent seizures, cerebral edema, and intracranial hemorrhages. Based on our study findings, we suggest that aminophylline therapy in this context should be limited to research settings and not used prophylactically.

Analysis of DNMT1 gene variants in progression of neural tube defects-an in silico to in vitro approach.

Neural tube defects (NTDs) are significant congenital deformities of the central nervous system among which spina bifida is the most common form that occurs due to defect in the neurulation process of embryogenesis. NTDs are among the most common type of birth defects occurring at a range of 0.5-10 in every 1000 live births worldwide and are thought to have multifactorial etiology, including multigenetic and epigenetic notions. Epigenetic regulations control differential gene expression in normal and disease phenotypes. DNA methylation is a significant epigenetic process, guided by DNMT1, one of the most important maintenance methylating agents. However, the relationship between DNMT1 and NTDs had always been inconclusive and poorly understood. In the present study, by utilizing in silico methodologies we tried to figure out potent single nucleotide variants (SNVs) that could play roles in generating functional differences in DNMT1 expression and we also tried to check (by in vitro method) if there is any connection between DNMT1 expression and spina bifida condition. A number of coding and non-coding (both intragenic and intergenic) SNVs of DNMT1 were found (using the in silico methods) that have potentials to alter its expression. From the in vitro experimentations, differential DNMT1 RNA expressions were found between spina bifida affected newborns and their respective mothers when compared with controls. It is the first report of NTD from Eastern India precisely showing inverse correlation between DNMT1 expression and occurrence of NTD. The findings of the present study could be further considered for early prognosis and future experimental designs.

Outcome of Neonates Born to COVID-Positive Women at 6 Months of Age.

OBJECTIVES: To compare clinical and neurodevelopmental outcome at the age of 6 months for neonates born to SARS-CoV-2-positive mothers. METHODS: Neonates of SARS-CoV-2 positive mothers, admitted in our hospital were assessed for growth, neurodevelopment by Amiel-Tison method, and Developmental Profile (DP3) at discharge as part of another study (July 2020). This data were retrieved and babies followed-up at the age of 6 months. Composite adverse outcome was death within 6 months post discharge or DP3 score <70 and hearing/visual deficit. RESULTS: Out of 131 enrolled at discharge, 127 (97%) were followed up. SARs-CoV-2 positive neonates (Group I; 19, 15%) had more symptoms (P=0.012), sepsis (P=0.014), pneumonia (P=0.029), longer hospital stay (P<0.001) following birth compared to group II (SARs-CoV-2 negative neonates;108, 85%). No baby in group I met definition of composite adverse outcome, while in group II it was 0.9% (1 child with DP3 <70 with hearing deficit) (P=1.0) without any difference in hospital readmission, growth, DP3 scores, or tone abnormalities. CONCLUSIONS: There is no difference in growth, neurodevelopment, and hospital readmission in early infancy among infected and non-infected babies born to SARS-CoV-2 positive mothers.

Molecular Insight into the Effect of a Single-Nucleotide Polymorphic Variation on the Structure and Dynamics of Methionine Synthase Reductase and Its Association with Neural Tube Defects.

Neural tube defects (NTDs) are among the common and severe congenital malformations in neonates. According to a WHO report, nearly three lakh babies are affected per year worldwide by NTDs. Most studies revealed that folate deficiency is the key element to promote NTD with other oligogenic and multifactorial elements. This folate is metabolized by the FOCM (folate one-carbon metabolism) pathway. The most important step in the FOCM pathway is the conversion of methionine to homocysteine, which is guided by the enzyme MTRR. Several single-nucleotide polymorphisms (SNPs) in the MTRR gene are strongly associated with the progression of NTD. A nonsynonymous allelic variant (rs1532268) of the protein leads to a missense mutation at the 202nd position from serine to leucine (S202L) and is associated with a higher disease prevalence in different populations. In our study, this SNP indicates a 2-fold increase in the risk of disease progression (p-value of 0.03; OR 2.76; 95% CI 1.08-7.11). Here, extensive molecular dynamics simulations and interaction network analysis reveal that the change of 202nd serine to leucine alters the structures of the FAD and NAD binding domains, which restricts the ligand binding. The S202L variation alters the functional dynamics that might impede the electron transport chain along the NADP(H)→ FAD→ FMN pathway and hamper phosphorylation by kinases like GSK-3 and CaM-II during the posttranscriptional modification of the protein. The present study provides functional insights into the effect of the genetic variations of the MTRR gene on the NTD disease pathogenesis.

Structural insight into the effect of polymorphic variation on the functional dynamics of methionine synthase reductase: Implications in neural tube defects.

Neural tube defects (NTDs), one of the most common birth defects, are strongly associated with the variations of several single nucleotide polymorphisms (SNPs) in the MTRR gene. The gene codes a key enzyme that is involved in the rejuvenation of methionine synthase activity. An allelic variant of the protein leads to missense mutation at 49th position from isoleucine to methionine (I49M) is associated with higher disease prevalence in different populations. Here, extensive molecular dynamics simulations and interaction network analysis reveal that the 49th isoleucine is a crucial residue that allosterically regulates the dynamics between the flavin mononucleotide (FMN) and NADP(H) binding domains. I49M variation alters the functional dynamics in a way that might impede the electron transport chain along the NADP(H) â†’ flavin adenine dinucleotide â†’ FMN pathway. The present study provides functional insights into the effect of the genetic variations of the MTRR gene on the NTDs disease pathogenesis.

Association of FOLH1, DHFR, and MTHFR gene polymorphisms with susceptibility of Neural Tube Defects: A case control study from Eastern India.

BACKGROUND: Worldwide, Neural tube defects (NTDs) are considered as major clinical problems imposing a huge socio-economic burden for both affected individuals and their families. In India, the prevalence of Neural tube defects is significantly high. This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India. METHODS: We enrolled 62 consecutive mothers with NTDs foetuses as cases and their corresponding age matched 73 mothers with healthy babies as controls (genetic power has been calculated). Four single nucleotide polymorphisms (FOLH1: rs202676, DHFR: rs70991108, MTHFR: rs1801133 and rs1801131) have been amplified by polymerase chain reaction (PCR) and sequenced. Statistical analysis has been undertaken to find out association with NTDs. RESULTS: Genotype and allele frequency analysis of these SNPs revealed that, rs1801133 (p.Ala222Val) was significantly associated with NTDs risk (p value = 0.028; odds ratio-2.31; 95% CI 1.08-4.93), whereas rs202676 (p.Tyr60His) showed protective role (p value = 0.0066; odds ratio-0.11; 95% CI 0.01-0.86). Serum homocysteine (Hcy) concentration was respectively higher in subjects carrying 222Ala/Val and 222Val/Val alleles (p value = 0.009; p value ≤ 0.0001). CONCLUSION: In conclusion, it can be stated that, rs1801133 was associated with neural tube defects risk in patients from the eastern part of India and it might be counted as a molecular marker for evaluating the susceptibility of NTDs.

Effect of kangaroo mother care on vital physiological parameters of the low birth weight newborn.

OBJECTIVES: Low birth weight (LBW; <2500 g), which is often associated with preterm birth, is a common problem in India. Both are recognized risk factors for neonatal mortality. Kangaroo mother care (KMC) is a non-conventional, low-cost method for newborn care based upon intimate skin-to-skin contact between mother and baby. Our objective was to assess physiological state of LBW babies before and after KMC in a teaching hospital setting. MATERIALS AND METHODS: Study cohort comprised in-born LBW babies and their mothers - 300 mother-baby pairs were selected through purposive sampling. Initially, KMC was started for 1 hour duration (at a stretch) on first day and then increased by 1 hour each day for next 2 days. Axillary temperature, respiration rate (RR/ min), heart rate (HR/ min), and oxygen saturation (SpO2) were assessed for 3 consecutive days, immediately before and after KMC. RESULTS: Data from 265 mother-baby pairs were analyzed. Improvements occurred in all 4 recorded physiological parameters during the KMC sessions. Mean temperature rose by about 0.4°C, RR by 3 per minute, HR by 5 bpm, and SpO2 by 5% following KMC sessions. Although modest, these changes were statistically significant on all 3 days. Individual abnormalities (e.g. hypothermia, bradycardia, tachycardia, low SpO2) were often corrected during the KMC sessions. CONCLUSIONS: Babies receiving KMC showed modest but statistically significant improvement in vital physiological parameters on all 3 days. Thus, without using special equipment, the KMC strategy can offer improved care to LBW babies. These findings support wider implementation of this strategy.

An anomalous left superior venacava draining into left atrium in association with fetal valproate syndrome.

Prenatal exposure of mother to valproic acid causes teratogenic effects on fetus. The authors report an 18 h-old girl with typical facial and limbs features of fetal valproate syndrome (FVS) along with abnormal draining of left superior vena cava into left atrium.