Perrault syndrome: The Way Forward After Genetic Counselling?

A female, term neonate, born via vaginal delivery to a G5P1D1A3 hypothyroid mother with a history of an elder sibling being homozygous for HSD17B4 mutation, diagnosed while working up his progressive neurological disorder and succumbing to the same. The family screening revealed that both parents were heterozygous carriers of the same mutation in the gene HSD17B4 After genetic counselling, amniocentesis revealed the fetus to be having homozygosity for the same mutation. In view of precious pregnancy, normal antenatal scans and investigations, the pregnancy was continued, and baby was born with a birth weight of 2.65 kg and had a smooth perinatal transition. Parents were counselled regarding the course of the illness, possible complications and the need for regular follow-up. Ultrasound of the abdomen, pelvis and head was normal in the neonatal period. She was vaccinated as per the national schedule and gaining weight normally.

An Approach to Re-evaluate the Reference Cutoff of the Parameters of Newborn Screening: An Observational Study.

Background Unless a cutoff level of the parameters of newborn screening (NBS) is defined, a screening test's results would end in high recall rates and apprehensive parents. The study aimed to establish a cutoff level of the healthy term newborns. Materials and methods The study was a retrospective observational data analysis on a cohort of 1158 term newborns who underwent NBS in our institute. The percentile distribution of the NBS parameters was computed and the 99th percentile value was considered the new cutoff. For lower values, such as neonatal glucose 6-phosphate dehydrogenase (nG6PD) and neonatal biotinidase (nBIOT), low percentile values were regarded as new cutoff value. Results Neonatal thyroid stimulating hormone (nTSH), nG6PD, neonatal immunoreactive trypsinogen (nIRT), and nBIOT showed a wide variation in the distribution. Most newborns had neonatal galactose (nGAL), nIRT, and nBIOT values above the median. The 99th percentile value of nTSH was 14.5 mIU/L, and that of neonatal 17-hydroxyprogesterone (n17-OHP) was 43.7 nmol/L. The 1.0th percentile value for nG6PD was decreased to 2.18 IU/gHb. The new cutoff values for nBIOT, nIRT, neonatal phenylketonuria (nPKU) and nGAL were 48.59 U, 95.3 µg/L, 2.3 mg/dL and 15.9 mg/dL. The mean and median nTSH values did not significantly differ (p=0.99) in the first five days of birth. On the contrary, the study population depicted considerably raised levels of n17-OHP on day 3, followed by a sharp decrease (p=0.029). Similarly, nIRT displayed significant differences in the first five days (p=0.017). Conclusion Using the 99th percentile values of the NBS parameters as the new cutoff levels might be beneficial in terms of the recall rates and cost burden.

Association of Methylenetetrahydrofolate Reductase Gene Polymorphism in Mothers With Adverse Clinical Outcomes in Neonates.

BACKGROUND: The presence of polymorphic methylenetetrahydrofolate reductase (MTHFR) in mothers poses a risk for numerous detrimental outcomes in neonates. The present study investigated the association of maternal MTHFR A1298C and C677T single nucleotide polymorphisms (SNPs) with the clinical outcomes in their neonates. MATERIALS AND METHODS: The cross-sectional study included 60 mothers and their neonates. Blood samples from mothers were analyzed for MTHFR A1298C and C677T SNP genotyping by real-time polymerase chain reaction. Clinical details of mothers and neonates were documented. Study groups were stratified based on wild, heterozygous, and mutant genotypes for the respective polymorphisms observed in mothers. Multinomial regression was applied for the association, followed by gene model formulation to estimate the impact of the genetic variants on the outcomes. RESULTS: The frequency percentages of mutant CC1298 and TT677 genotypes were 25% and 8.06%, respectively, and the mutant allele frequencies (MAF) were 42.5% and 22.5%. Percentages of adverse outcomes such as intrauterine growth restriction, sepsis, anomalies, and mortality were higher in neonates born to mothers with homozygous mutant genotypes. Maternal C677T MTHFR SNPs revealed a significant association with neonatal anomalies (p = 0.001). The multiplicative risk model depicted OR (95% CI) for CT vs. CC+TT as 3.0 (95% CI: 0.66-13.7), and for TT vs. CT+CC was 15 (95% CI: 2.01-112.12). The C677T SNP in mothers predicted a dominant model for neonatal death (OR (95% CI): 5.84 (0.57-60.03), p = 0.15), whereas the A1298C reported recessive model for 1298CC mothers (OR (95% CI): 11 (1.05-115.5), p = 0.02). Both the genotypes assumed a recessive model for adverse neonatal outcomes: OR (95%CI) for CC vs. AA+AC was 3.2 (0.79-12.9, p = 0.1), and for TT vs. CC+CT was 5.48 (0.57-175.7, p = 0.2). The risk for sepsis in neonates was nearly six times higher in those born from mothers with homozygous CC1298 and TT677 than in the wild and heterozygous variants. CONCLUSION: Mothers with C677T and A1298C SNPs are highly susceptible to adverse outcomes in their neonates. Hence, screening the SNPs during the antenatal period can purposefully serve as a better predictive marker, following which proper clinical management could be planned.

Intrinsically Resistant Bacteria as Looming Disaster: A Rare Case Report of Elizabethkingia meningoseptica Meningitis in a Neonate.

Elizabethkingia meningoseptica is a recognized cause of neonatal meningitis with high mortality rate of approximately 57%, but clinical data detailing these infections remain limited from India. Though this bacteria has a Gram-negative character, it is usually multidrug resistant to antibiotics usually prescribed for Gram-negative bacterial infections and susceptible to antibiotics for Gram-positive bacteria, thus poses a serious challenge to the treating clinicians. Such cases of neonatal meningitis is most commonly associated with prematurity with birth weight < 2,500 g, but here we report an uncommon case of neonatal meningitis due to this rare pathogen in a full-term neonate with weight as per gestational age. The isolate was multidrug resistant and discrepancy was seen between disc diffusion and automated antibiotic susceptibility testing for few antibiotics. The case was successfully managed by treatment with combination of piperacillin-tazobactam, vancomycin, chloramphenicol, and rifampicin for a total duration of 28 days, due to prompt identification of the causative organism and initiation of appropriate antimicrobial therapy early. E. meningoseptica can cause severe infection, with risk of high mortality and neurological sequelae in neonates. Intensive care and multidisciplinary interventions are crucial for case management.

Retrospective analysis to identify the association of various determinants on birth weight.

OBJECTIVES: LBW is the strong determinant of neonatal morbidity and mortality with a global prevalence of nearly 15%. India's prevalence, though not yet established, ranges from 16-30% and influenced by maternal nutritional status, antenatal care and associated maternal morbidity. Hence, the study was aimed to determine the influencing parameters for occurrence of LBW. STUDY DESIGN: A retrospective observational study conducted for all live newborns delivered in a tertiary care centre during the study period of twenty four months. METHODS: Data from institutional medical record section was recorded on predesigned questionnaire from a total of 1216 newborns. RESULTS: The percentage of LBW was found to be 27.55% (335/1216) with a proportion of LBW to NBW babies was approximately 1:3. The occurrence of LBW was significantly higher in babies of anemic mothers (59.39%, P < 0.0001), young mothers (30.39%, P < 0.01), mothers with parity ≥ 3 (35.71%, P < 0.05), those with <3 ANC check-up (56.88%, P < 0.0001) and those with premature delivery (71.57%, P < 0.0001). Maternal anemia (OR 4.7, 95%CI 3.4-6.7, P < 0.001); ANC with <3 visits (OR 2.2, 95%CI 1.4-3.4, P < 0.01) and prematurity (OR 7.6, 95%CI 5.1-11.2, P < 0.0001) were considered as independent risk factor for LBW. Significant association of neonatal complications was found with LBW babies (OR 1.6, 95%CI 1.1-2.5, P < 0.05). CONCLUSIONS: Inadequate antenatal care, maternal anemia and other maternal illness causing premature delivery are considered critical determinants for LBW and thus associated with high neonatal mortality and morbidity. Continued focus for improving the overall maternal health status would lead to lowering burden of LBW.

Prophylactic propranolol for prevention of ROP and visual outcome at 1†year (PreROP trial).

OBJECTIVE: To evaluate the role of prophylactic propranolol in the prevention of retinopathy of prematurity (ROP) in infants ≤32 weeks of gestational age and their visual outcome at 1 year of corrected gestational age. DESIGN: Randomised double blind placebo controlled trial, parallel group nrolment with allocation ratio of 1:1. SETTINGS: Two level III neonatal intensive care units. PARTICIPANTS: 109 preterm neonates of ≤32 weeks of gestation with postnatal age ≤8 days old. INTERVENTION: Study group: Infants with gestational age between 26 and 32 weeks were started on propranolol prophylaxis (0.5 mg/kg/dose every 12 hours) on seventh completed day of life, till a corrected gestational age of 37 weeks or complete vascularisation of retina whichever was later. Control group infants received a placebo. OUTCOME MEASURES: Primary: ROP of all grades; Secondary: evaluation of complications due to propranolol, ROP needing treatment with laser and/or antivascular endothelial growth factor (anti-VEGF) and visual outcome at 12 months corrected age. RESULTS: Prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in the incidence of ROP (56.8% vs 68.6%; p=0.39), need for laser therapy (21.56% vs 31.37%; p=0.37), treatment with anti-VEGF (3.92% vs 15.68%; p=0.09) or visual outcomes at 1 year in the study and control groups, respectively, though these reductions were not statistically significant. Decreasing trends favouring propranolol in all other ROP-related outcomes were also noted in the study group. CONCLUSIONS: Prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in all outcomes of ROP though statistically not significant. TRIAL REGISTRATION NUMBER: CTRI/2013/11/004131.

Enteral paracetamol or Intravenous Indomethacin for Closure of Patent Ductus Arteriosus in Preterm Neonates: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of enteral paracetamol and intravenous indomethacin for closure of patent ductus arteriosus (PDA) in preterm neonates. DESIGN: Randomized controlled trial. SETTING: Level III neonatal intensive care unit. PARTICIPANTS: 77 preterm neonates with birth weight ?1500 g and PDA size ?1.5 mm, with left to right ductal flow with left atrium to aortic root ratio >1.5:1; diagnosed by 2D-Echo within first 48 hours of life. INTERVENTION: Paracetamol drops through the infant feeding tube (15 mg/kg/dose 6 hourly for 7 days) or intravenous indomethacin (0.2 mg/kg/dose once daily for 3 days). OUTCOME MEASURES: Primary: PDA closure rate assessed by echocardiography. Secondary: need for surgical closure of PDA, renal impairment, gastrointestinal bleed, necrotising enterocolitis, hepatotoxicity, pulmonary hemorrhage, sepsis, hypothermia, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia and mortality. RESULTS: PDA closure rate was 100% (36/36) in enteral paracetamol group as compared to 94.6% (35/37) in intravenous indomethacin group (P=0.13). The secondary outcomes were also similar between the two groups. There was no occurrence of hepatotoxicity. CONCLUSIONS: Enteral paracetamol is safe but not superior to intravenous indomethacin in the treatment of PDA in preterm neonates.