Parental experience in neonatal intensive care units strongly impacts family satisfaction and emotional well-being. This study explored associations between parental neonatal intensive care unit experience, sociodemographic and hospitalization factors, and anxiety-depressive symptoms. A cross-sectional study was conducted with 84 parents of neonatal intensive care unit-admitted infants. Measures included parental experience (EMPATHIC-N), satisfaction with professionals, and anxiety-depressive symptoms (PHQ-4), along with sociodemographic and hospitalization data. Analyses comprised descriptive statistics, group comparisons, correlations, and mediation modeling. Participants were mainly highly educated European mothers. Most infants stayed <1 week; parental participation occurred 1day-6 months post-discharge. Families reported high willingness to return (77.1%) and recommend the neonatal intensive care unit (79.5%). Satisfaction with nurses and physicians was high (8.3/10), though four EMPATHIC-N items scored below 75%. Anxiety-depressive symptoms were present in 24.4%, inversely correlating with satisfaction and some specific EMPATHIC-N items. Mediation analysis showed healthcare team satisfaction explained 70% of the effect of parental experience on anxiety-depressive symptoms. Satisfaction with the healthcare team plays a central role in the emotional distress of parents after their experience in the neonatal intensive care unit, so improving care initiatives that enhance it could reduce anxiety and depression in parents.
This study aims to evaluate the clinical efficacy of nirsevimab in preventing respiratory syncytial virus (RSV) infection in preterm infants, highlighting its potential to improve neonatal respiratory health. We conducted a retrospective cohort study involving preterm infants admitted to the Neonatology Department of Inner Mongolia Maternity and Child Health Care Hospital between November 2024 and January 2026. The immunization group included infants receiving nirsevimab, while the non-immunized group was matched via propensity score matching. Both groups received standard care. Clinical data, as well as diagnostic and therapeutic processes, were collected. The efficacy and safety of nirsevimab were evaluated, and the incidence and severity of RSV-associated respiratory infections in two groups were followed up (severe cases were defined as those requiring respiratory support or experiencing adverse outcomes). (1) Compared with the non-immunized group, the efficacy rate of preventing RSV-associated respiratory infections was significantly higher in the nirsevimab immunized group (98.73% vs. 84.81%), with a statistically significant difference (p < 0.05). (2) In the non-immunized group, twelve preterm infants (15.18%) developed RSV-associated respiratory infections, among whom 4 cases (5.06%) required non-invasive ventilator support, 2 cases (2.53%) experienced myocardial injury, 1 case (1.26%) had liver injury, 1 case (1.26%) experienced myocardial injury combined with liver injury, and 1 case (1.26%) exhibited wheezing symptoms. (3) All preterm infants infected with RSV in the non-immunized group required rehospitalization, with an average hospital stay of 15.5 days; in contrast, no rehospitalization was required in the immunized group. (4) No significant adverse reactions were observed in the immunized group following nirsevimab injection. During the RSV epidemic season, our findings indicate that prophylactic treatment with nirsevimab significantly reduces the incidence of RSV infection in preterm infants, decreases the rehospitalization due to RSV infection in preterm infants, and demonstrates a favorable safety profile.
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Fabry disease (FD) is an X-linked, monogenic lysosomal storage disorder, caused by mutations in the GLA gene. GLA encodes the lysosomal hydrolase alpha-galactosidase A and enzyme deficiency leads to accumulation of its substrate globotriaosylceramide (Gb3), culminating in multisystemic symptoms. Here, we generated a human induced pluripotent stem cell line from a female FD patient, carrying a c.644A > G missense mutation. The hiPSCs showed a normal karyotype, typical stem cell morphology, expression of pluripotency markers and were capable of trilineage differentiation. Therefore, MHHi040-A represents a valuable resource for future FD studies, investigating both disease mechanisms as well as novel therapeutic strategies.
Bronchopulmonary dysplasia (BPD) in preterm infants is frequently accompanied by neurodevelopmental impairment, yet the central neuropharmacological actions of dexamethasone (DEX), a commonly used therapy for severe or evolving BPD, remain incompletely understood. In particular, whether DEX exerts timing-dependent neuroprotection in the developing brain and the mechanisms underlying such effects are unclear. We investigated the neuroprotective effects of DEX in a neonatal rat double-hit model combining prenatal maternal lipopolysaccharide exposure with postnatal hyperoxia. A tapered DEX regimen was initiated on postnatal day (P)1, P3, or P8 to evaluate the therapeutic window. Lung pathology, survival, hippocampal injury, microglial reactivity, behavioral outcomes, resting-state functional magnetic resonance imaging (rs-fMRI), targeted metabolomics, and microglia-neuron coculture experiments were used to characterize pharmacological efficacy and mechanism. Among the tested regimens, DEX initiated at P3 produced the most consistent protective effects, improving alveolar structure, survival, hippocampal pathology, and microglial reactivity. P3-initiated DEX also improved recognition memory, exploratory/anxiety-related behavior, spatial memory retention, and motor coordination, and was associated with partial restoration of hippocampal functional connectivity. At the molecular level, DEX partially restored hippocampal glutamate/GABA balance, reduced Synapsin I phosphorylation, and normalized VGLUT1/VGAT associated synaptic abnormalities. Mechanistically, microglia-derived IL-1β promoted neuronal ERK/Syn1 activation, whereas DEX interrupted this inflammatory signaling axis in a microglia-neuron coculture system. Targeted metabolomics and perturbation experiments further showed that DEX increased Acod1-dependent itaconate reprogramming under inflammatory priming, thereby suppressing microglial IL-1β and downstream neuronal P-Syn1/Syn1 signaling. These findings identify a developmentally sensitive therapeutic window for DEX neuroprotection in neonatal BPD-associated brain injury and suggest that microglial Acod1-itaconate-dependent regulation of IL-1β/ERK/Syn1 signaling contributes to its central protective effects. This study expands the pharmacological interpretation of DEX beyond pulmonary benefit and supports an immunometabolic framework for understanding corticosteroid actions in the developing brain.
Excessive exposure to sedentary behavior (SB) is associated with cognitive decline and impaired brain health; however, the neurobiological mechanisms underlying this relationship remain unclear. Functional near-infrared spectroscopy (fNIRS) enables real-time monitoring of cerebral hemodynamics in naturalistic settings and offers unique technical advantages for understanding the effects of SB on brain health. Notably, methodological standardization specific to SB research is lacking, limiting cross-study comparisons and evidence synthesis despite established general fNIRS best practices. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Scopus, Web of Science, and PsycINFO through February 2026 for studies using fNIRS to assess SB's effects on brain function. Two independent reviewers conducted study selection, data extraction, and bias risk assessment. We systematically extracted and analyzed instrumentation specifications, spatial positioning, data processing pipelines, statistical methods, and quality control measures to identify methodological variations and best practice patterns in current research. From 36,477 initial records, 43 studies encompassing 2751 participants were included. Study types comprised acute (25 studies) and chronic interventions (8 studies) manipulating or monitoring SB patterns as well as cross-sectional studies (10 studies) analyzing the association between SB patterns and fNIRS-related parameters. Substantial heterogeneity was evident for specific methodological aspects, such as the use of diverse fNIRS systems and sampling rates (e.g., spanning 1.81-50.00 Hz), whereas others such as source-detector separation (i.e., 3.0 cm) were relatively homogenous across studies. Critical methodological issues included inadequate reporting of spatial registration and data quality control procedures, inconsistent implementation of multiple comparison corrections, and neglected monitoring of relevant environmental factors and physiological confounds. This review provides the first SB-specific standardized methodological framework for fNIRS applications, building on established fNIRS best practices and extending them to address unique challenges of SB research, encompassing 6 core domains: hardware configuration, extended monitoring protocols, data processing, statistical analysis, quality assessment, and SB-specific reporting. Recommendations are systematically classified by evidence level, distinguishing minimum reporting standards applicable across all laboratories from best practices and aspirational approaches for well-resourced settings. Minimum recommendations include reporting optode geometry and placement with sufficient detail for replication and, where feasible, using short-separation regression (or a clearly justified alternative) to mitigate systemic physiological confounds. These recommendations aim to enhance methodological rigor, promote cross-study comparability, and support the long-term goal of identifying SB-related neurobiological biomarkers.
Early family meetings in the neonatal intensive care unit (NICU) represent a crucial communication opportunity between families and clinicians. We examined clinician-family patterns of communication, patient-centeredness, and family perception during early family meetings. We audio-recorded "first family meetings" (meetings in the first 10 days of admission to review anticipated NICU course) for infants born < 35 weeks' gestational age in a level III NICU. We evaluated clinician and family contribution to meetings and coded clinician-family communication using the Roter Interaction Analysis System (RIAS). Additionally, the RIAS was used to quantify "patient-centeredness" using a ratio comparing psychosocial and socioemotional content to biomedical content. After each meeting, we administered a survey including demographics and the validated 14-item Communication Assessment Tool to assess family perception on a 5-point Likert scale. We used descriptive statistics to analyze communication and experience. We analyzed 19 meetings, including 16 in English and 3 interpreted (2 Portuguese, 1 Spanish). During meetings, clinicians spoke more (clinicians: 71.9%, parents: 25.0%) and asked more questions (clinician: 61.9%, parents: 36.0%) compared to families. The most frequent content was medical information from clinicians (20.1% of meeting time). The median patient-centeredness score was 0.95, suggesting a balance between psychosocial and medical content. The lowest rated Communication Assessment Tool items were 'encouraged me to ask questions' and 'discussed next steps;' for these items, 87.5% of families reported excellent. In early NICU family meetings, the amount of conversation was dominated by clinicians compared to parents, although medical and socioemotional discussion were relatively balanced. Families were satisfied with these meetings, but more work is needed to facilitate bidirectional communication. A routine, early NICU family meeting may allow time to discuss family context and emotional support in addition to medical information. Families can be encouraged to speak and ask more questions during meetings.
Alterations in prenatal growth affect postnatal outcomes, but the factors involved in prenatal growth are not clearly defined. Cord blood levels of insulin-like growth factor (IGF)-I are associated with weight and length at birth; however, how pappalysins (pregnancy-associated plasma protein [PAPP]-A and PAPP-A2) and stanniocalcins (STC-1 and STC-2) regulate IGF-binding protein (IGFBP) cleavage and IGF bioavailability in relation to birth size and nutritional status in full-term neonates is unknown. We aimed to determine the relationship between serum levels of PAPP-A and STCs with other components of the IGF axis and ponderal index (PI) in full-term small-for-gestational-age (SGA), adequate-for-gestational-age (AGA), or large-for-gestational-age (LGA) neonates (according to gestational age or PI). Twenty-six SGA, 131 AGA, and 22 LGA neonates were studied, and circulating levels of IGF axis parameters were evaluated according to weight, length, weight-to-length ratio, and PI. Small-for-gestational-age newborns had lower total and free IGF-I, total IGFBP-3, acid-labile subunit, and PAPP-A2 levels and higher total IGFBP-1 and IGFBP-2, intact IGFBP-4, and STC-1 levels than AGA newborns. Neonates in the first tertile of PI had lower total and free IGF-I and IGFBP-5 and higher IGFBP-1 and -2 levels than those in the third tertile. Pregnancy-associated plasma protein-A2 levels correlated positively with weight and length and inversely with IGFBP-4 and STC-1 levels. Insulin-like growth factor-I and PAPP-A2 levels are associated with length. Variations in IGF-I parameters, such as STCs and PAPPAs, according to length/weight or PI suggest that they play an important role in intrauterine growth and/or nutritional status.
Fetus-in-fetu (FIF) is an uncommon congenital anomaly arising from aberrant monozygotic twinning, in which a malformed parasitic twin becomes incorporated within the body of the host. Despite its rarity, FIF remains clinically relevant because it is frequently misdiagnosed as a teratoma, particularly when detected outside the neonatal period or at atypical anatomical sites. This review present a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-informed narrative synthesis of the human literature on FIF, integrating embryological concepts, diagnostic imaging features, genetic observations, and surgical management. A systematic search of major electronic databases identified 45 publications meeting predefined eligibility criteria. From these, 25 core studies were selected for in-depth narrative analysis based on diagnostic confirmation, methodological clarity, and avoidance of overlapping case reports. To contextualize the literature, a previously unreported human case of FIF associated with omphalocele and complex congenital cardiac anomalies was also described, illustrating current prenatal diagnostic pathways and multidisciplinary postnatal care. Across reported cases, FIF is most often diagnosed in infancy and is typically benign following complete surgical excision. Distinguishing FIF from mature teratoma relies on recognition of organized axial structures, symmetry, and shared monozygotic genetic identity. Although malignant transformation is rare, incomplete resection and immature tissue components warrant long-term surveillance. Improved prenatal imaging has enhanced early recognition of FIF, yet its developmental mechanisms remain incompletely understood. Future progress will likely depend on coordinated clinical reporting and translational research addressing early embryonic asymmetry, diagnostic refinement, and evidence-based follow-up strategies.
Umbilical artery thrombosis (UAT) is a rare but important cause of fetal compromise. Once considered a postnatal diagnosis, improved Doppler ultrasonography now permits antenatal identification. A unified synthesis of diagnostic features, mechanisms, and outcomes is needed to support clinical decision-making. The objective of the study is to summarize prenatal diagnostic characteristics, underlying pathophysiology, and perinatal outcomes of UAT, complemented by an illustrative clinical case. A PRISMA-guided search of PubMed, Scopus, Embase, and Web of Science through September 2025 identified reports describing prenatal or perinatal UAT confirmed by Doppler ultrasonography or histopathology. Fifty-five studies met the inclusion criteria. Extracted data included gestational age at diagnosis, Doppler findings, associated factors, mechanistic context, and outcomes. Study quality was appraised using NOS, JBI, AMSTAR-2, and ROBIS. Diagnosis occurred between 10 and 39 weeks, most often in the late second or third trimester. The hallmark prenatal finding was unilateral absent end-diastolic velocity with preserved flow in the contralateral artery. Additional indicators included color asymmetry, flow-trajectory disturbance, and wave-reflection changes. Mechanistic patterns reflected Virchow's triad, encompassing stasis, hypercoagulability, endothelial injury, and structural or placental contributors. Perinatal outcomes were generally favorable when unilateral thrombosis was detected and monitored, whereas unrecognized or bilateral occlusion was associated with fetal growth restriction or intrauterine demise. An illustrative case confirmed the value of advanced Doppler trajectory mapping in enabling early diagnosis and timely delivery. Targeted Doppler interrogation allows reliable prenatal detection of UAT. Incorporating mechanistic Doppler markers and standardized reporting may enhance diagnostic accuracy and support informed delivery planning.
The aim of this retrospective study in assisted reproductive technology was to provide new evidence that: (1) visibility of the meiotic spindle (MS) in human oocytes with an extruded first polar body predicts not only nuclear maturation but also embryo ploidy; and (2) the interval between ovulation triggering and ICSI-mediated fertilization affects the chromosomal status of embryos. MS visibility was assessed using polarized light microscopy, and the trigger-to-fertilization interval was adjusted accordingly to increase the likelihood of complete oocyte nuclear maturation. Extending the trigger-fertilization interval based on MS status significantly increased the proportion of mature oocytes (displaying both MS and polar body) from 79% to 92% (p < 0.05), indicating ongoing spindle assembly. Of 1,879 oocytes examined under polarized light, 462 (24.5%) developed into embryos undergoing PGT-A. Embryos derived from immature oocytes (without visible MS or with a spindle bridge to the polar body) had a euploidy rate of 14%, compared with 42% in embryos from mature (visible MS) oocytes (p < 0.05). Differences in embryo euploidy were also associated with the interval between ovulation trigger and ICSI fertilization. Cycles with a trigger-ICSI interval 40-44 hours had a significantly higher likelihood of euploidy (47%) compared with cycles in which the trigger-ICSI interval was 36-39 hours (33%) (p < 0.05). Namely in women of advanced maternal age, who exhibit an increased risk of embryonic aneuploidy, spindle-guided assessment of oocyte maturation and quality may improve the prediction of subsequent embryo ploidy.
The microbiota-gut-brain axis (MGBA) has emerged as a critical regulator of neurodevelopment, with microbial metabolites serving as key signaling molecules that bridge the intestinal ecosystem and the central nervous system. This review gathers current evidence that connects disruptions in microbial metabolites to the pathogenesis of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Our comprehensive overview discusses major neuroactive metabolite classes-short-chain fatty acids (SCFAs), tryptophan derivatives, bile acids, and phenolic compounds-and their established roles functions in affecting neuroinflammation, epigenetic programming, synaptic function, and blood-brain barrier integrity. Converging evidence from human multi-omics studies and preclinical models frequently reported patterns of metabolic dysregulation in NDDs, including reduced SCFA production, altered kynurenine pathway metabolites, and accumulation of neurotoxic compounds such as para-cresol (p-cresol). However, substantial heterogeneity exists across studies, and causal evidence in humans remains predominantly associative. We further examine the critical early-life window during which the metabolite-producing microbiome is shaped by maternal factors, nutrition, and environmental exposures, with lasting consequences for neurodevelopmental trajectories. Finally, we discuss new intervention strategies such as probiotics, dietary substrates, fecal microbiota transplantation, and metabolite-based therapies, and propose a plan to transition from associative findings to causal, personalized approaches using microbial metabolites as biomarkers and therapeutic targets in child neurodevelopment.
Video capsule endoscopy (VCE) is a well-established diagnostic tool for examining the small bowel. Limited data exist on its use in infants. To our knowledge, we present the first detailed case of a successful PillCam®SB3-VCE performed in an 8-month-old infant weighing 7.5 kg with suspected small bowel bleeding following allogeneic hematopoietic stem cell transplantation. The capsule was endoscopically placed into the duodenum without prior bowel cleansing or patency capsule testing. VCE identified bleeding in the terminal ileum and cecum. This case demonstrates that VCE can be safely performed even in very young, low-weight infants when clinically necessary. However, due to anatomical and physiological challenges, VCE should be carefully considered in infants and applied cautiously on a case-by-case basis.
brain injury in extremely preterm infants has been mainly linked to right ventricular (RV) dysfunction during postnatal transition, whereas the contribution of left ventricular rotational mechanics (LVRM) remains undefined. We aimed to characterize early postnatal evolution of LVRM and compare it between infants with and without adverse short-term outcome. prospective observational cohort study. Targeted echocardiography was conducted within the first 24 h, at 24-72 h and on day 7. LV circumferential strain, radial displacement, basal/apical rotation, twist and torsion were evaluated using speckle-tracking. Adverse outcome was defined as the composite of death and/or adverse short-term neurological outcome, including significant interventricular hemorrhage, or white matter injury. among 63 infants, 29 (46%) presented the adverse outcome. During the first week, circumferential strain increased at all levels, radial displacement rose after 24 h and basal rotation shifted from mildly positive to negative. Apical rotation remained stable. LV twist and torsion increased within 72 h and then plateaued. No differences in LVRM parameters were noted between outcome groups. LVRM undergoes rapid maturation during early transition in extremely preterm infants. However, it is not associated with adverse outcome, consistent with a predominant role of RV function during this period. Left ventricular rotational mechanics (LVRM) demonstrate rapid maturation during the first postnatal week in extremely preterm infants, but do not differ between those with and without adverse short-term neurological outcome. This prospective longitudinal study shows that, despite dynamic changes in deformation and twist mechanics, LVRM is not associated with early brain injury or cerebral perfusion indices in ELGANs. The findings suggest limited early prognostic value of LVRM and reinforce the predominant role of right ventricular function in transitional hemodynamics and cardio-cerebral interactions in extremely preterm infants.
Hypoxic-ischemic (HI) brain injury due to perinatal asphyxia causes long-term neurological morbidity in newborns. HI affects brain areas including the cortex, hippocampus, and basal ganglia. More recently the mammillary bodies (MBs), critical for memory, were also shown to be affected in patients, despite treatment with therapeutic hypothermia (TH). Here we characterized the kinetics and extent of MB damage in an established neonatal HI mouse model and evaluated the therapeutic potential of TH or a novel regenerative intervention: intranasal mesenchymal stem cell (MSC) therapy. HI was induced in 9-day-old mouse pups; structural and cellular MB damage was assessed at days 1 to 3 and day 28 post HI by immunohistochemistry. For TH, mice were placed at 32 °C for 3 hours directly post HI, and MB damage was assessed at day 10. For MSC therapy, mice received intranasally 0.5×106 MSCs at day 10 post HI and MB damage was assessed at day 28 post HI. At days 1 to 3 post HI, mice showed cell death, microglia activation, and early gliosis in the ipsilateral MB. Glial scarring was still present at day 28 post HI with concomitant ipsilateral MB atrophy. Additionally, HI induced mammillothalamic tract atrophy and reduced the expression of calbindin+ but not parvalbumin+ cells. While TH and intranasal MSCs both reduced the HI-induced cortical/hippocampal lesions, neither treatment reduced MB damage. Our novel findings demonstrate early onset and long-lasting MB damage in a neonatal HI mouse model, mirroring newborn patients. TH and MSCs therapy failed to protect the MBs, highlighting the importance for future research into treatment strategies to protect or repair this vulnerable structure.
To compare bedside ultrasonography (US) and abdominal radiography (AXR) within the same cohort for their ability to discriminate the need for surgical intervention in neonatal necrotising enterocolitis (NEC), and to evaluate the value of combining the two modalities. A total of 509 neonates admitted to our neonatal intensive care unit from January 2015 to December 2023 were included; all had a clinical diagnosis of NEC and underwent abdominal radiography (a supine cot-side view in all infants, with an additional erect view obtained in the radiology department only when the infant was stable enough to be transported) and bedside US within 24 h. They were divided into a surgical group (n = 88) and a conservative group (n = 421) by clinical outcome. Eight signs from each of AXR and US were recorded as binary variables. After univariate screening by the χ 2 or Fisher's exact test, an AXR model, a US model, and a combined model were fitted by multivariable logistic regression. Model discrimination was assessed by the area under the receiver operating characteristic curve (AUC); AUCs were compared by the DeLong test, and their 95% confidence intervals (CIs) were estimated from 1,000 bootstrap resamples. The added value of the combined model was measured by the net reclassification index (NRI) and the integrated discrimination improvement (IDI). Calibration was assessed by the Hosmer-Lemeshow (HL) test, the Brier score, and calibration curves. Firth's penalised logistic regression was used as a sensitivity analysis for signs with low cell counts. For neonates diagnosed with NEC during the same period but without US, the US signs were imputed by multiple imputation with chained equations (m = 20) and the models refitted, to assess the potential selection bias of the complete-case analysis. The surgical group had a lower gestational age [33.0(30.0, 36.0) week] and birth weight [1,730(1,235, 2,205) g] than the conservative group (35.0[32.0, 36.0] week; 2,200[1,727.5, 2,732.5] g; both P < 0.001). On multivariable analysis, five signs were independent predictors of surgical intervention: AXR portal venous gas [odds ratio (OR) = 32.76, 95% CI 7.11-150.94], AXR pneumoperitoneum (OR = 11.91, 95% CI 1.81-78.58), US complex peritoneal effusion (OR = 16.94, 95% CI 3.65-78.76), US peritoneal effusion (OR = 7.53, 95% CI 4.04-14.03), and US portal venous gas (OR = 2.71, 95% CI 1.33-5.51). The AUCs of the AXR, US, and combined models were 0.696, 0.842, and 0.862. On the DeLong test, both the US and combined models were superior to the AXR model (both P < 0.001), whereas the difference between them was not significant (P = 0.067). The NRI and IDI of the combined model were 1.074 and 0.285 relative to the AXR model and 0.823 and 0.106 relative to the US model. All three models were well calibrated (HL test P > 0.05; Brier scores 0.116, 0.091, and 0.075). For neonates with a clinical diagnosis of NEC, bedside US was superior to AXR in the overall discrimination of the need for surgical intervention. AXR portal venous gas and pneumoperitoneum were complementary to the US findings of complex peritoneal effusion and peritoneal effusion; although adding AXR to US did not raise the AUC over US alone, it still added value in reclassifying borderline cases. US and AXR may serve as complementary modalities in the routine imaging work-up of NEC.
Acetaminophen (acetaminophen), alternatively referred to as paracetamol, is generally accepted as a safe pharmacologic choice to treat pain and fever during pregnancy. This review examines the prevalence and patterns of acetaminophen use during pregnancy and the historical context behind this widespread use. We discuss the emerging and controversial data linking acetaminophen use during pregnancy and adverse effects on the fetus and offspring. Furthermore, we draw on mechanistic evidence from preclinical studies and observational clinical studies that support the hypothesis that in addition to the fetus and newborn, there is a potential impact of acetaminophen on the placenta. We draw on mechanistic data from pre-clinical experiments and observational data from clinical studies to assess the association between APAP exposure and placental cellular injury, preeclampsia, and growth restriction. We conclude that additional research is needed to ensure the most informed pharmacologic management of pain and fever during pregnancy. Acetaminophen (acetaminophen), alternatively referred to as paracetamol, is generally accepted as a safe way to treat fever and pain during pregnancy. This review critically examines the commonality of acetaminophen exposures during pregnancy, the historical context that explains this widespread and growing use, and emerging and controversial data demonstrating fetal susceptibility to these exposures. We explore how that in addition to the fetus, the placenta may be susceptible to acetaminophen induced injury leading to adverse clinical outcomes. Finally, we highlight opportunities for future research.
Despite a significant decline in the incidence of neonatal sepsis, the clinical imperative to avoid missing life-threatening infection continues to drive widespread antibiotic overprescription. Antimicrobial stewardship is universally recognized and explicitly mandated within the UK 2024-2029 National Action Plan on Antimicrobial Resistance as a critical mechanism to combat resistance and prevent iatrogenic harms related to infant dysbiosis. However, a major misalignment exists within the current evidence base: most of the neonatal stewardship research is conducted in highly resourced, tertiary Neonatal Intensive Care Units (Level 3), even though most postnatal inpatient care occurs in Special Care Baby Units (Level 1) and Local Neonatal Units (Level 2). This Viewpoint explores the operational and structural barriers that limit the transferability of intensive-care stewardship models to lower-acuity settings, identifies key research gaps around baseline prescribing practices and multidisciplinary collaboration, and argues for the inclusion of Level 1 and 2 populations in future validation studies of emerging diagnostic tools for neonatal sepsis.