Gayatri Athalye-Jape

Background and Objective: Our previously reported randomised trial (ProPara) showed that supplementation with a live probiotic (P) compared with heat-inactivated probiotic (HP) was safe and had comparable intestinal anti-inflammatory effect in very preterm (VP) infants < 32 weeks. Assessing the long-term neurodevelopment of preterm infants exposed to HP in early postnatal life is important. We aimed to compare long-term neurodevelopmental outcomes among ProPara trial participants. Methods: Data on long-term outcomes, including composite disability, cerebral palsy (CP), and autism spectrum disorder, were obtained from unit database. Neurodevelopment was assessed using age-appropriate standardised tools at corrected age one, two, and three years and chronological age five years, including the Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition (WPPSI-IV). Results: Of the surviving children enrolled in the trial, follow-up data were available for 61 participants. Fifty-nine children completed at least one formal neurodevelopmental assessment during childhood, and 30 underwent school-age assessment at approximately five years chronological age. Rates of composite disability, CP, sensory impairment and median WPPSI-IV full-scale IQ scores at five years (P: 102; HP: 99; p = 0.599) were comparable between groups. Severe autism occurred in three P group infants. Developmental scores across all domains were comparable between groups. Conclusions: Neurodevelopmental outcomes through early childhood and at five years were broadly comparable between VP infants receiving early-life HP supplementation and those receiving live probiotics. Given the small sample size and incomplete follow-up, larger adequately powered randomised controlled trials are needed to confirm long-term safety.

Objective: To assess whether early hypernatremia (HN) and/or hyperglycemia (HG) in the first postnatal week are associated with adverse neurodevelopmental outcomes in extremely preterm (EP; 145 mmol/L and HG as blood glucose > 10 mmol/L within days 0–7. Infants were classified into HN, HG, or combined HN + HG groups; EP infants without HN/HG served as controls. This study included 748 EP infants: 374 with HN and/or HG and 374 controls. The primary outcome was an adverse neurodevelopmental outcome at 2 years’ corrected age. Results: On adjusted analyses, HN, HG and HN + HG were not associated with moderate-to-severe developmental impairment. Moderate-to-severe HN group showed a lower odds of moderate-to-severe developmental impairment than controls (18.3% vs 21.5%; adjusted OR 0.39, 95% CI 0.15–0.99; p = 0.047). Conclusions: Early hypernatremia and/or hyperglycemia were not associated with adverse neurodevelopment at 2 years’ corrected age.

Background and Aim: Early prediction of necrotising enterocolitis (NEC) in preterm infants is important given its significant health, economic and social–emotional burden. We aimed to validate a clinical risk score (Check‐NEC Score [CNS]) for this purpose in preterm infants. Methods: A case–control study was conducted using data (January 2020–December 2023) from very preterm infants (VP: gestation < 32 weeks) with confirmed NEC≥Stage II. CNS was calculated for cases and controls (matched for key confounders) at baseline (T1), 7 days (T2), and 72 h (T3) before NEC diagnosis. Receiver operating characteristic (ROC) analysis was used to determine the sensitivity, specificity, and area under the curve (AUC). Results: Twenty‐two cases of NEC≥Stage II diagnosed at a median (IQR) age of 17 (11–24) days were matched with 22 controls. Median CNS was significantly higher in cases compared to controls at T2 (8 vs. 7, p = 0.025) and T3 (8 vs. 7, p = 0.005). T3 CNS had the highest AUC (0.64, 95% CI 0.48–0.81). A cut‐off score of ≥ 11 at T2 had the highest specificity (95%, 95% CI 75%–99%). At T3, a cut‐off score of either ≥ 8 or ≥ 9 was best. Conclusion: CNS demonstrated acceptable predictive ability at 72 h with high specificity 7 days before NEC diagnosis, depending on the cut‐off score chosen.

Background: Probiotic supplementation for very preterm infants is a common practice in many neonatal units. Assessing the effects of early postnatal exposure to probiotics on long-term neurodevelopment, growth, and atopy-related outcomes is important. Extremely preterm (EP: p = 0.68], growth, BMI, and BP were comparable between the SS and TS groups. The total difficulty score or BRIEF–P executive indices, disability rates (none: 66.7% versus 55.4%), and atopy-related outcomes were comparable between groups. Conclusions: Both TS and SS Bifidobacterium probiotic formulations were safe, with comparable neurodevelopmental, growth, and atopy-related outcomes at school age.

Goal: Healthcare professionals (HCPs) working long shifts are prone to physical, emotional, and psychological stress leading to harmful effects on their mental health, an issue compounded by the COVID-19 pandemic. Novel efforts such as virtual reality (VR)-based immersion have been explored to mitigate this problem in HCPs. However, the studies vary in their clinical settings, scales used for measuring outcomes related to mental health, sample size, and other relevant parameters. We conducted a systematic review (SR) to collate all available evidence on the feasibility and efficacy of VR-based interventions for reducing stress, burnout, fatigue, and anxiety in HCPs. Methods: We searched major databases for comprehensive literature on HCP mental well-being measures in September 2023 and February 2024. Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) quality assessment tool, and PRISMA guidelines were used for reporting this SR. Principal Findings: A total of 17 studies out of 1,422 citations were included in the final analysis. The number of study participants ranged from 14 to 219 (1,053 total). Seven studies were randomized controlled trials, and the rest were pre-post intervention studies. Meta-analysis was not feasible because the included studies were heterogeneous in their study settings, methodology, and assessed mental health domain. Based on the EPHPP tool, one study had a strong global rating, two had a moderate rating, and 14 had a weak rating. Practical Applications: VR-based interventions during break times appear to be feasible and useful in addressing HCP stress, burnout, fatigue, and anxiety. However, limited high-quality studies warrant caution in interpretation.

Introduction: Preterm birth is associated with a 3.3-fold increased likelihood of autism diagnosis, with lower gestational age conferring higher likelihood. In Australia, autism is typically diagnosed at around age four, potentially missing the optimal neuroplasticity window before age two. The Social Attention and Communication Surveillance—Revised (SACS-R) tool identifies early autism signs in children aged 11–30 months, enabling pre-emptive intervention. Aims: This quality improvement (QI) study assessed the acceptability, and feasibility of SACS-R for early detection of autism traits in 12-month-old infants born very preterm/VP (gestation < 32 weeks), from both caregiver and clinician perspectives. Methods: From September 2024 to February 2025, 47 VP infants attending the 12-month Neonatal Follow-up Clinic (NNFU) at King Edward Memorial Hospital (KEMH), Western Australia, were assessed using SACS-R. Caregivers completed acceptability and feasibility questionnaires; clinicians completed similar surveys. Forty-seven infants met inclusion criteria; 12 clinicians provided responses. Results: Of 47 infants, 4 (8.5%) were identified as having a high likelihood of autism and referred for early intervention. Among caregivers, 29 (61%) provided complete acceptability responses and 28 (59%) feasibility responses, both predominantly positive. Clinicians reported high satisfaction (83%) and ease of use (91%), with 74% supporting routine implementation. Concerns included parental understanding and overlap with other assessments. Conclusions: Our QI study indicates that the SACS-R is highly acceptable and feasible in neonatal follow-up for preterm infants. Larger-scale evaluation of diagnostic accuracy and practical refinements based on feedback are warranted to support routine integration in early surveillance programs.

Gut microbiota play a critical role in long-term health by supporting metabolism, immune function, inflammation regulation, and neurological development via the gut–brain axis. Beneficial bacteria enhance gut integrity through short-chain fatty acid production, pathogen inhibition, and mucosal barrier support. However, microplastics (MPs) and nanoplastics (NPs) can disrupt microbiome development, particularly in infants. MPs may delay microbial stabilization and promote antibiotic resistance through biofilm-associated gene transfer. In neonates, especially those exposed to intensive care, antibiotics, or formula feeding, MPs/NPs present an added challenge to microbiome establishment. Probiotics offer a potential intervention by restoring microbial balance, strengthening gut barriers, and mitigating inflammation. Certain strains can bind or degrade environmental toxins, including MPs, heavy metals, and endocrine disruptors. Clinical studies support the use of probiotic mixtures to restore eubiosis. Given the limited availability of safe plastic alternatives in neonatal care, enhancing the gut microbiome through probiotics may help counteract the adverse effects of MPs/NPs. However, due to safety concerns—such as the FDA’s warning against live probiotics in preterm infants—future research should explore innovative, safe bioremediation strategies to support gut health in this vulnerable population.

(1) Background: The incidence of gestational diabetes mellitus (GDM) is rising globally. The current evidence indicates that GDM, especially in conjunction with maternal overweight, can alter the composition of infants’ gut microbiota, potentially increasing the risk of inflammatory diseases, metabolic disorders, and neurodevelopmental issues later in life. Probiotic supplantation early in life might establish eubiosis and mitigate future complications. To best of our knowledge, no study has evaluated the effects of probiotics on gut dysbiosis in the infants of mothers with GDM. (2) Methods: This study will be a single-centre, double-blind, randomized, placebo-controlled trial enrolling sixty neonates born after 35 weeks of gestation to mothers with GDM. The participants will be randomly assigned to receive either a triple-strain probiotic or a placebo for four months. The primary objective is to assess the effectiveness of probiotic supplementation in correcting gut dysbiosis in the infants of mothers with GDM at four months of age. Faecal microbiome composition shall be estimated using 16SrRNA and shotgun sequencing. The secondary outcomes will include the quantification of faecal short-chain fatty acids at birth and at four months, as well as growth and developmental assessments at four, twelve, and twenty-four months. (3) Trial registration: This trial protocol is registered (ACTRN12624000930583p) in the Australian Clinical Trials registry (ANZCTR).

Background: Heat-inactivated probiotics (HPs) may provide an effective alternative to live probiotics (P) by avoiding their risks (eg, probiotic sepsis) while retaining the benefits. We assessed the safety and efficacy of a HP in very preterm (VP: gestation Bifidobacterium breve M-16V, Bifidobacterium longum subsp. infantis M-63, Bifidobacterium longum subsp. longum BB536, total 3×10 ⁹ CFU/day) assuring blinding. Primary outcome was faecal calprotectin (FCP) levels were compared after 3 weeks of supplementation. Secondary outcomes included faecal microbiota and short chain fatty acid (SCFA) levels. Results: 86 VP infants were randomised to HP or P group (n=43 each). Total FCP and SCFA were comparable between HP and P groups within 7 days (T1) and between day 21 and 28 (T2) after supplementation. At T2, median (range) FCP was 75 (8–563) in the HP group and 80 (21–277) in the P group (p=0.71). Propionate was significantly raised in both groups, while butyrate was significantly raised in the HP group (all p0.05). Beta diversity showed similar community structures in both groups (all p>0.05). Changes in faecal Actinobacteria, Bacteroidetes and Bifidobacteriacae levels were comparable in both groups at T1 and T2. There was no probiotic sepsis. Conclusions: HP was safe and showed no significant difference in FCP as compared with a live probiotic. Adequately powered trials are needed to assess the effects of HP on clinically significant outcomes in preterm infants. Trial registration number: ACTRN12618000489291.

Probiotics are known to decrease incidences of necrotising enterocolitis, feeding intolerance, late-onset sepsis, and mortality in preterm infants. Administering an adequate dose is important for optimizing the benefits and safety of probiotics. We conducted a systematic review to assess the effect of probiotic dose escalation on clinical outcomes and gut microbiota in preterm neonates. We searched PubMed, EMBASE, EMCARE, Medline, Cochrane Library, Google Scholar, and MedNar databases in July 2023. Three studies were included. In one of the randomized studies (n = 149, gestation 27 to 33 weeks), no significant differences in faecal Lactobacillus and Bifidobacterium counts and clinical outcomes were seen between the high- and low-dose groups. There was a trend towards increased Lactobacillus and Bifidobacterium counts in the high-dose group. In the other randomized study (n = 120, birth weight 500 to 2000 gm), smaller infants (500 to 1000 gm) required higher doses to display Lactobacillus in their faeces. The cohort study (n = 12, gestation < 33 weeks) showed a trend towards an increase in faecal abundance of bifidobacteria and bacterial diversity in the B. infantis group with increasing dose/time. Limited evidence suggests a higher dose might improve gut colonization in preterm infants. Further studies are urgently needed to address this gap in the knowledge considering the increasing use of probiotics for preterm infants.