O efeito conjunto de gemelaridade e prematuridade no aleitamento materno exclusivo na alta hospitalar / The joint effect of twinning and prematurity on exclusive breastfeeding at hospital discharge / El efecto conjunto de la gemelaridad y la prematuridad en la lactancia materna exclusiva al momento del alta hospitalaria

Objetivo: estimar a prevalência de Aleitamento Materno Exclusivo (AME) entre gemelares pré-termos e investigar o efeito de nascer gemelar e pré-termo no AME na alta hospitalar. Método: coorte prospectiva de recém-nascidos em uma instituição localizada no Rio de Janeiro, no período de 13 de março de 2017 a 12 de outubro de 2018. Dados coletados em questionário e prontuário médico. Foi utilizado DAG para construção do modelo conceitual, análise exploratória dos dados e regressão logística múltipla. Resultados: a prevalência de AME na alta hospitalar de gemelares pré-termos foi de 47,8%. Pré-termos apresentaram maior chance de não estarem em AME na alta hospitalar. Não gemelares apresentaram maior chance de não estarem em AME na alta hospitalar. Conclusão: pouco mais da metade dos gemelares pré-termo não estavam em AME na alta hospitalar. Prematuros tiveram maior chance de não estarem em AME. Não gemelares pré-termo apresentaram maior chance de não estarem em AME.

Objective: to estimate the prevalence of Exclusive Breastfeeding (EBF) in preterm twins and to investigate the effect of twin and preterm birth on EBF at hospital discharge. Method: prospective cohort of newborns in an institution located in Rio de Janeiro, from March 13, 2017, to October 12, 2018. Data collected through a questionnaire and medical records. A DAG was used to build the conceptual model, exploratory data analysis and multiple logistic regression. Results: prevalence of EBF at hospital discharge of preterm twins of 47.8%. Preterm infants were more likely to not be on EBF at hospital discharge. Non-twins were more likely to not be on EBF at hospital discharge. Conclusion: just over half of preterm twins were not on EBF at hospital discharge. Preterm infants had a greater chance of not being on EBF. Preterm non-twins were more likely to not be on EBF.

Objetivo: estimar la prevalencia de Lactancia Materna Exclusiva (LME) entre gemelos prematuros y investigar el efecto de nacer gemelo y prematuro en la LME al momento del alta hospitalaria. Método: cohorte prospectiva de recién nacidos en una institución ubicada en Rio de Janeiro, entre 13//marzo/2017 y 12/octubre/2018. Los datos se recolectaron mediante cuestionario y expediente médico. Se utilizó DAG para la construcción del modelo conceptual, análisis exploratorio de los datos y regresión logística múltiple. Resultados: la prevalencia de LME en el alta hospitalaria de gemelos prematuros fue del 47,8%. Los prematuros tuvieron mayor probabilidad de no estar en LME en el alta hospitalaria. Los no gemelares tuvieron mayor probabilidad de no estar en LME en el alta hospitalaria. Conclusión: poco más de la mitad de los gemelos prematuros no estaban en LME en el alta hospitalaria. Los prematuros tuvieron mayor probabilidad de no estar en LME. Los no gemelos prematuros presentaron mayor probabilidad de no estar en LME.

Preterm Birth Research in Southeast Asia and its Association with Socioeconomic Determinants and Burden of Disease: A Bibliometric Analysis.

Objective: The aim of this study was to assess research productivity on preterm birth (PTB) in Southeast Asian (SEA) countries and its correlation with socioeconomic characteristics and burden of disease. Methods: A systematic review of preterm birth publications by SEA authors indexed in Scopus, PubMed, ClinicalTrials. gov, and Cochrane was done. Case reports, cohorts, control trials, reviews and cost analysis studies done by SEA researches involving pathophysiology, diagnosis, management, and complications of preterm birth was included in the study while published letters to editors were excluded. The correlation of bibliometric indices, namely Scopus citations, and PlumX metrics indices (citations, usage, captures, mentions, and social media), with socioeconomic status and burden of preterm birth in SEA countries were analyzed by computing for the correlation coefficient (r) and p-value at an alpha of 0.05. Results: Thailand had the highest number of publications and the highest count across all bibliometric indices among all countries in SEA. The percent gross domestic product (GDP) per capita allotted for research and development (R & D) had direct correlation with publications and captures while crude birth rates had indirect correlation with publications, citations, and captures. Neonatal mortality had indirect correlation with publications and captures. Conclusion: Support for research and development is essential to increase research productivity in SEA, which in turn may help in finding solutions to decrease the rate of preterm birth in the region.

Comparison of intravitreal bevacizumab monotherapy and combined laser photocoagulation and intravitreal bevacizumab therapy in the same session in the treatment of aggressive retinopathy of prematurity.

PURPOSE: To compare the results of intravitreal bevacizumab (IVB) monotherapy and combined intravitreal bevacizumab and laser photocoagulation (LPC) therapies applied in the same session to patients with aggressive retinopathy of prematurity (A-ROP) in our clinic. METHODS: The study included 67 eyes of 37 patients diagnosed with A-ROP and treated. Forty-nine eyes treated with anti-vascular endothelial growth factor agent injection monotherapy for A-ROP treatment were included in the first group. The second group consisted of 18 eyes that received injection therapy and LPC treatment. The clinical findings of the two groups were investigated, and their treatment results were compared. RESULTS: Recurrence was observed in 19 of the 49 (38%) eyes in the first group, but there was no recurrence in any of the cases in the second group. While only IVB was applied to eight cases with recurrence, the combination of LPC and IVB treatment was applied to 11 cases. A second recurrence was detected in two of the eight cases that had received IVB monotherapy as a treatment for recurrence and in three of the 11 cases that had received LPC and IVB. The treatment outcomes of the two groups did not statistically significantly differ (P = 0.181). CONCLUSION: We consider that the combined simultaneous LPC and IVB treatment we applied in A-ROP cases is an effective approach, particularly for cases where there are concerns about the patient's ability to attend follow-up appointments.

Early cognitive assessment in premature infants: the discriminatory value of eye-tracking vs. Bayley Scales.

Introduction: The testing of visuocognitive development in preterm infants shows strong interactions between perinatal characteristics and cognition, learning and overall neurodevelopment evolution. The assessment of anticipatory gaze data of object-location bindings via eye-tracking can predict the neurodevelopment of preterm infants at the age of 3 years; little is known, however, about the early cognitive function and its assessment methods during the first year of life. Methods: The current study presents data from a novel assessment tool, a Delayed Match Retrieval (DMR) paradigm via eye-tracking was used to measure visual working memory (VWM) and attention skills. The eye-tracking task that was designed to measure infants' ability to actively localize objects and to make online predictions of object-location bindings. 63 infants participated in the study, 39 preterm infants and 24 healthy full term infants - at a corrected age of 8-9 months for premature infants and similar chronological age for full term infants. Infants were also administered the Bayley Scales of Infant and Toddler Development. Results: The analysis of the Bayley scores showed no significant difference between the two groups while the eye-tracking data showed a significant group effect on all measurements. Moreover, preterm infants' VWM performance was significantly lower than full term's. Birth weight affected the gaze time on all Areas Of Interest (AOIs), overall VWM performance and the scores at the Cognitive Bayley subscale. Furthermore, preterm infants with fetal growth restriction (FGR) showed significant performance effects in the eye-tracking measurements but not on their Bayley scores verifying the high discriminatory value of the eye gaze data. Conclusion: Visual working memory and attention as measured via eye-tracking is a non-intrusive, painless, short duration procedure (approx. 4-min) was found to be a significant tool for identifying prematurity and FGR effects on the development of cognition during the first year of life. Bayley Scales alone may not pick up these deficits. Identifying tools for early neurodevelopmental assessments and cognitive function is important in order to enable earlier support and intervention in the vulnerable group of premature infants, given the associations between foundational executive functional skills and later cognitive and academic ability.

Bacterial species in cord blood and their significance in the context of clinical use.

Approximately 90 % of infants born before 28 full weeks(extremely-preterm-infants) receive erythrocyte transfusions in early life. Umbilical cord blood(UCB) has been investigated as an alternative source for erythrocyte transfusions to preterm neonates. This retrospective study aimed to compile/evaluate spectrum of bacteria groups/species intermittently detected in processed UCB at National-Swedish-Cord blood bank, (NS-CBB) during the years 2008-2020. Consecutive data from the years 2008-2020 were investigated. UCB from healthy newborns born after 37 full weeks of gestation was collected following clamping of cord (1 min) through cannulation of umbilical vein(vaginal-and C-section-deliveries). In total, 5194 cord blood units (UCBUs) that met NS-CBB-guidelines for total nucleated-cell-content(TNC) were manufactured from 8875 collections. Of 5194 UCBUs,77,6 % were from vaginal-and 22,4 % from C-section deliveries.Samples(10 mL) were collected from surplus eryhtrocyte fraction post-processing(n = 5194), transferred into BACT/ALERT® aerobic/anaerobic culture flasks and monitored 10 days using BACT/ALERT®-3D-Microbial-Detection-Systems. Positive samples were subcultured and typed for bacterial groups and/or species. Out of 5194 processed sampled UCB units,186 (3,6 %) were discarded due to positive sterility tests, 92 % were detected in samples from vaginal-deliveries and 8 % from C-section-deliveries. In all,16 different groups of bacteria and 27 species were identified. Common bacterial/groups and species were anaerobe gram-negative rods(n = 28),coagulase-negative-staphylococci(n = 21),gram-positive rods(n = 21),anaerobe-gram-positive cocci(n = 20) and viridans-streptococci(n = 13). Extracted from these results,in positive samples(n = 13) from C-section deliveries, bacteria were found:viridans-streptococci(n = 7),Aerococcus-urinae(n = 1), Staphylococcus lugdunensis(n = 1),other coagulase-negative staphylococci(n = 1) or a mix of aerobic/anaerobic bacteria(n = 3). Our results are in alignment with previously published contamination rates in processed UCBUs. Still, results point towards importance of strict microbial monitoring when manufacturing UCBUs to achieve patient-safe- products for stem-cell transplantation/transfusion.

Tear fluid cytokine analysis: a non-invasive approach for assessing retinopathy of prematurity severity.

PURPOSE: To determine whether there is a significant association between inflammatory cytokines in the tear fluid and the severity of Retinopathy of Prematurity (ROP). STUDY DESIGN: Retrospective cohort study. METHODS: The cytokine levels in tear fluids were determined in 34 eyes with ROP and 18 eyes without ROP. There were 15 eyes with severe ROP requiring treatment and 19 eyes with mild ROP not requiring treatment. For severe ROP eyes, tear fluids were collected before treatment. RESULTS: Significantly higher levels of CCL2 and vascular endothelial growth factor (VEGF) were detected in eyes with severe ROP compared to eyes with mild ROP and no ROP. When assessed for cytokine levels that discriminate each disease group, CCL2 showed a significant odds ratio of 1.76 for severity change (/quintile, P = 0.032, after adjusting for birth weight). Correlation analysis showed that birth weight correlated with IL-1α levels, and decreased weight gain increased IFN-γ levels. We next determined tear fluid cytokines which discriminate severe ROP using receiver operating characteristics' analysis. We found that combination of higher CCL2 levels, higher VEGF levels, and lower IFN-γ levels in the tear fluid had a stronger predictive value for severe ROP (area under curve, 0.85). CONCLUSION: The levels of CCL2, VEGF, and IFN-γ in tear fluid may serve as useful biomarkers for assessing the severity of ROP.

Prostanoid signaling in retinal vascular diseases.

The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.

The influence of previous preterm birth with singleton pregnancy on the risk of recurrence in subsequent twin pregnancy: a meta-analysis.

BACKGROUND: Preterm birth is a significant obstetrical concern around the globe. With this study, we aimed to determine whether a prior singleton pregnancy preterm birth increases the likelihood of preterm birth in subsequent twin pregnancies. We designed his systematic review to provide valuable information for pregnant women and obstetricians during counselling and for individuals involved in the planning of preventive strategies. METHODS: We comprehensively searched the PubMed, Embase and Scopus databases to identify relevant studies published until October 2023 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We applied a random-effects meta-analysis to the data gathered from the selected studies. RESULTS: Among the 460 initially identified studies, only eight met the eligibility criteria. The analysis of incidence revealed an event rate of 9.5% (95% CI, 4.4-19.5%) for a history of preterm singleton birth in the cohort of women with subsequent twin pregnancies. Subgroup analyses focused on the risk of preterm twin births (<37 weeks, <34 weeks and <32 weeks) in women with prior preterm singleton births. Our results revealed a significantly elevated risk of subsequent preterm twin births associated with prior preterm singleton births at <37 weeks (OR, 2.94; 95% CI, 1.99-4.33; p < .001), <34 weeks (OR, 1.89; 95% CI, 1.67-2.14; p < .001) and <32 weeks (OR, 2.51; 95% CI, 1.58-3.99; p < .001), without heterogeneity in the included studies. CONCLUSIONS: Our systematic analysis indicates a consistent and statistically significant association between a history of preterm singleton births and preterm twin births at various gestational ages. These findings underscore the importance of the obstetric history during assessments to predict the risk of preterm births in twin pregnancies. Clinicians should monitor pregnancies with a history of preterm singleton births, as targeted interventions and improved prenatal care can mitigate the risk of preterm birth during twin pregnancies.

Preterm birth, a global concern, prompted a study examining whether a prior preterm singleton birth raises the risk of preterm birth in subsequent twin pregnancies. Conducting a systematic review of 460 studies, only eight met the eligibility criteria. The meta-analysis revealed a 9.5% incidence of preterm singleton births in subsequent twin pregnancies. Further analysis demonstrated a significantly elevated risk of preterm twin births at <32 weeks for those with a history of preterm singleton births. The study concludes that a consistent and statistically significant association exists between prior preterm singleton births and increased preterm twin birth risk at various gestational ages. This underscores the importance of considering obstetric history in assessing preterm birth risk in twin pregnancies. Clinicians are advised to closely monitor pregnancies with a history of preterm singleton births for interventions targeted and improved prenatal care.

Extracorporeal Membrane Oxygenation Before 34 Wks' Gestation: A Single-Center Experience.

INTRODUCTION: Traditionally, gestational age <34 wk and weight <2 kg are considered relative contraindications to extracorporeal membrane oxygenation (ECMO). There is a paucity of information that explains the outcomes in this unique population of premature neonates. The purpose of this study is to examine outcomes of patients who undergo ECMO at <34 wk at a single institution. METHODS: A single-center retrospective review was performed for neonates managed with ECMO in the neonatal intensive care unit from January 2012 to April 2022. Characteristics and outcome data were collected. The primary outcome studied was survival at discharge. Secondary outcomes were intraventricular hemorrhage, ischemic brain injury, and thrombosis. Data were analyzed with descriptive statistics. RESULTS: Following exclusion, 107 patients were included with eight having initiating ECMO at <34 wk. Three (38%) patients, who received ECMO at <34 wk, incurred intraventricular hemorrhages compared to 14 (14%) in the ≥34-wk cohort. Two (25%), who underwent ECMO at <34 wk, exhibited signs of brain ischemia on imaging compared to 9 (9%) in those ≥34 wk, and 3 (38%) patients <34 wk experienced thrombosis compared to 31 (31%) in the ≥34-wk cohort. Five (63%) of those in the <34-wk cohort survived to discharge, similar to 61 (61%) in the ≥34 wk cohort. CONCLUSIONS: Our data suggest that EGA <34 wk may not be a contraindication for ECMO, with appropriate counseling of potential risks.

Relationship Between Prone Skills and Motor-Based Problem-Solving Abilities in Full-Term and Preterm Infants During the First 6 Months of Life.

Motor experiences shape cognitive development in infancy, with the prone position being one such crucial motor experience in the first 6 months of life. Although the motor benefits of the prone position are well-documented, its influence on early cognitive abilities remains insufficiently explored. This study quantified the relationship between prone motor skills and motor-based problem-solving abilities in 48 full-term and preterm infants aged 3-6 months. Prone skills were assessed using the Alberta Infant Motor Scale's prone domain. The Assessment of Problem-Solving in Play was utilized to measure motor-based problem-solving by observing how motor actions were used to solve toys. Advanced prone motor skills were correlated with an increase in sophisticated exploration skills and a concurrent decline in lower order exploration skills in all infants, with correlations being stronger in preterm infants. Notably, a 1-point increase in prone skills was associated with a 1.3-point increase in total motor-based problem-solving abilities in all infants. Our findings provide preliminary evidence for the contribution of prone play to cognitive development in infants, prompting considerations for assessment and intervention strategies. Further research is needed to ascertain if the delayed acquisition of prone motor skills is indicative of poor early problem-solving abilities in preterm infants.

Newborn's neural representation of instrumental and vocal music as revealed by fMRI: A dynamic effective brain connectivity study.

Music is ubiquitous, both in its instrumental and vocal forms. While speech perception at birth has been at the core of an extensive corpus of research, the origins of the ability to discriminate instrumental or vocal melodies is still not well investigated. In previous studies comparing vocal and musical perception, the vocal stimuli were mainly related to speaking, including language, and not to the non-language singing voice. In the present study, to better compare a melodic instrumental line with the voice, we used singing as a comparison stimulus, to reduce the dissimilarities between the two stimuli as much as possible, separating language perception from vocal musical perception. In the present study, 45 newborns were scanned, 10 full-term born infants and 35 preterm infants at term-equivalent age (mean gestational age at test = 40.17 weeks, SD = 0.44) using functional magnetic resonance imaging while listening to five melodies played by a musical instrument (flute) or sung by a female voice. To examine the dynamic task-based effective connectivity, we employed a psychophysiological interaction of co-activation patterns (PPI-CAPs) analysis, using the auditory cortices as seed region, to investigate moment-to-moment changes in task-driven modulation of cortical activity during an fMRI task. Our findings reveal condition-specific, dynamically occurring patterns of co-activation (PPI-CAPs). During the vocal condition, the auditory cortex co-activates with the sensorimotor and salience networks, while during the instrumental condition, it co-activates with the visual cortex and the superior frontal cortex. Our results show that the vocal stimulus elicits sensorimotor aspects of the auditory perception and is processed as a more salient stimulus while the instrumental condition activated higher-order cognitive and visuo-spatial networks. Common neural signatures for both auditory stimuli were found in the precuneus and posterior cingulate gyrus. Finally, this study adds knowledge on the dynamic brain connectivity underlying the newborns capability of early and specialized auditory processing, highlighting the relevance of dynamic approaches to study brain function in newborn populations.

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.

Evolution of the Umbilical Cord Blood Proteome Across Gestational Development.

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 24 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. Proteins that function in structural development and growth (e.g., extracellular matrix organization, lipid particle remodeling, and blood vessel development) are more abundant earlier in gestation. In later gestations, proteins with increased abundance are in immune response and inflammatory pathways, including complements and calcium-binding proteins. Furthermore, these data contribute to the knowledge of the physiologic state of neonates across gestational age, which is crucial to understand as we strive to best support postnatal development in preterm infants, determine mechanisms of pathology causing adverse health outcomes, and develop cord blood biomarkers to help tailor our diagnosis and therapeutics for critical neonatal conditions.

Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity.

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Variability in COVID-19 Symptom Presentation During Pregnancy and its Impact on Maternal and Infant Outcomes Across the Pandemic.

BACKGROUND: With the dominance of different SARS-CoV-2 variants, the severity of COVID-19 has evolved. We aimed to investigate the difference in symptom prevalence and the association between symptoms and adverse pregnancy outcomes during the dominance of Wild-type/Alpha, Delta, and Omicron. METHODS: COVID-19 related symptom prevalence, maternal and specific neonatal outcomes of 5431 pregnant women registered in this prospective study were compared considering the dominant virus variant. Logistic regression models analyzed the association between specific symptoms and intensive care unit (ICU) admission or preterm birth. RESULTS: Infection with the Delta variant led to an increase in the symptom burden compared to the Wild-type/Alpha variant and the highest risk for respiratory tract symptoms, feeling of sickness, headache, and dizziness/drowsiness. An infection with the Omicron variant was associated with the lowest risk of dyspnea and changes in smell/taste but the highest risk for nasal obstruction, expectoration, headaches, myalgia, and fatigue compared to the Wild-type/Alpha and Delta variant dominant periods. With the progression of the Wild-type/Alpha to the Delta variant neonatal outcomes worsened. Dyspnea and fever were strong predictors for maternal ICU admission and preterm birth independent of vaccination status or trimester of infection onset. CONCLUSION: The symptom burden increased during the Delta period and was associated with worse pregnancy outcomes than in the Wild-type/Alpha area. During the Omicron dominance there still was a high prevalence of less severe symptoms. Dyspnea and fever can predict a severe maternal illness.

Outpatient versus inpatient management of preterm prelabor rupture of membranes: A systematic review and meta-analysis.

INTRODUCTION: To compare neonatal, obstetrical, and maternal outcomes associated with outpatient versus inpatient management of pregnancies with preterm prelabor rupture of membranes (PPROM). MATERIAL AND METHODS: A search of MEDLINE, EMBASE, the Cochrane Database and Central Register from January 1, 1990 to July 31, 2023 identified randomized controlled trials (RCTs) and cohort studies comparing outpatient with inpatient management for pregnant persons diagnosed with PPROM before 37 weeks' gestation. No language restriction was applied. We applied a random effects model for meta-analysis. Trustworthiness was assessed using recently published guidance and Risk of bias using the RoB 2.0 tool for RCTs and ROBINS-I tool for cohort studies. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the certainty of evidence (COE). Outcomes of interest included perinatal mortality, neonatal morbidities, latency and gestational age at delivery, and maternal morbidities. RCTs and cohort studies were analyzed separately. This study was registered in the International Prospective Register of Systematic Reviewsr: CRD42022295275. RESULTS: From 2825 records, two RCTs and 10 cohort studies involving 1876 patients were included in the review and meta-analysis. Outpatient management protocols varied but generally included brief initial hospitalization, strict eligibility criteria, and surveillance with laboratory and ultrasound investigations. Outpatient management showed lower rates of neonatal respiratory distress syndrome (cohort: RR 0.63 [0.52-0.77, very low COE]), longer latency to delivery (RCT: MD 7.43 days [1.14-13.72 days, moderate COE], cohort: MD 8.78 days [2.29-15.26 days, low COE]), higher gestational age at birth (cohort: MD 7.70 days [2.02-13.38 days, low COE]), lower rates of Apgar scores <7 at 5 min of life (cohort: RR 0.66 [0.50-0.89, very low COE]), and lower rates of histological chorioamnionitis (cohort: RR 0.74 [0.62-0.89, low COE]) without increased risks of adverse neonatal, obstetrical, or maternal outcomes. CONCLUSIONS: Meta-analysis of data from RCTs and cohort studies with very low-to-moderate certainty of evidence indicates that further high-quality research is needed to evaluate the safety and potential benefits of outpatient management for selected PPROM cases, given the moderate-to-high risk of bias in the included studies.

Comparison of Intravitreal Ranibizumab and Laser Photocoagulation in the Treatment of Type I Retinopathy of Prematurity in Malaysia: A One-Year Follow-Up Study.

PURPOSE: This study aimed to evaluate the treatment efficacy, anatomical outcomes, and refractive outcomes of laser photocoagulation (LPC) and intravitreal ranibizumab (IVR) in the treatment of type I retinopathy of prematurity (ROP) at one-year follow-up. METHODS: This is a retrospective study on the treatment of type I ROP and aggressive ROP (A-ROP) using LPC or IVR in three Malaysian hospitals providing pediatric ophthalmology services from January 2019 to December 2021. Information on gestational age, birth weight, ROP zone and stage, and underlying comorbidities was collected. Parameters for evaluating treatment efficacy include the time taken to achieve complete regression, the regression rate, and the reactivation rate. The anatomical and refractive outcomes were evaluated at one year of adjusted age. RESULTS: This study included 92 eyes from 46 infants. Of these, 42 eyes received LPC as the initial treatment, while 50 eyes underwent IVR. A higher percentage of infants with cardiovascular disease were treated with IVR (66.7%) compared to LPC (40%) (p<0.05). However, there were no significant differences in gestational age, birth weight, respiratory distress syndrome, sepsis, or intraventricular hemorrhage between the two treatment groups (p>0.05). Infants treated with LPC had a higher regression rate than those treated with IVR, but they were also significantly more myopic and had worse best-corrected visual acuity (BCVA). Conversely, infants treated with IVR experienced a significantly higher reactivation rate compared to those treated with LPC. Logistic regression analysis showed no significant associations between gestational age, birth weight, plus disease, zone 1 ROP, and the choice of initial treatment with the reactivation of ROP. CONCLUSIONS: Both LPC and IVR effectively treat type I ROP in infants, with IVR yielding superior anatomical and refractive outcomes and LPC offering a lower reactivation rate. Understanding individual patient characteristics is crucial for treatment selection.

Perinatal influences on academic achievement and the developing brain: a scoping systematic review.

Introduction and methods: In this PRISMA-compliant systematic review, we identify and synthesize the findings of research in which neuroimaging and assessments of achievement have been used to examine the relationships among aspects of developmental programming, neurodevelopment, and achievement in reading and mathematics. Results: Forty-seven studies met inclusion criteria. The majority examined the impact of prematurity (n = 32) and prenatal alcohol exposure (n = 13). Several prematurity studies reported a positive correlation between white-matter integrity of callosal fibers and executive functioning and/or achievement, and white matter properties were consistently associated with cognitive and academic performance in preterm and full-term children. Volumetric studies reported positive associations between academic and cognitive abilities and white and gray matter volume in regions such as the insula, putamen, and prefrontal lobes. Functional MRI studies demonstrated increased right-hemispheric language processing among preterm children. Altered activation of the frontoparietal network related to numerical abilities was also reported. Prenatal alcohol exposure studies reported alterations in white matter microstructure linked to deficits in cognitive functioning and academic achievement, including mathematics, reading, and vocabulary skills. Volumetric studies reported reductions in cerebral, cerebellar, and subcortical gray matter volumes associated with decreased scores on measures of executive functioning, attention, working memory, and academic performance. Functional MRI studies demonstrated broad, diffuse activation, reduced activation in canonical regions, and increased activation in non-canonical regions during numeric tasks. Discussion: A preponderance of studies linked prematurity and prenatal alcohol exposure to altered neurodevelopmental processes and suboptimal academic achievement. Limitations and recommendations for future research are discussed. Systematic review registration: Identifier: DOI 10.17605/OSF.IO/ZAN67.

Lissencephaly and Advanced-Stage Congenital Cytomegalovirus Infection in a Neonate.

This case report investigates the management of a 24-week-old neonate with congenital cytomegalovirus (CMV) infection and its sequelae, including severe intrauterine growth restriction, thrombocytopenia, and brain anomalies, ultimately progressing to lissencephaly. The diagnostic challenges included delayed clinical suspicion of congenital CMV, which was not identified until after delivery through CMV DNA polymerase chain reaction, and differentiating its symptoms from other potential causes of the neonate's condition. Aggressive interventions included antibiotics, antiviral therapy with ganciclovir, and supportive measures such as intubation, CPR, respiratory support, blood transfusions, and management of coagulopathy. Despite these efforts, the patient deteriorated due to progressive hypoperfusion, hypoxemic cardiorespiratory failure, and disseminated intravascular coagulopathy. Due to the poor prognosis and extent of multiorgan damage, support was withdrawn per parental consent. This case highlights the complications encountered when managing an advanced-stage neonatal CMV infection and emphasizes the importance of a multidisciplinary and holistic approach to guide diagnosis and treatment.

Mortality and neurodevelopmental outcomes at 2 years' corrected age of very preterm infants with necrotising enterocolitis or spontaneous intestinal perforation: The EPIPAGE-2 cohort study.

PURPOSE: The primary objective was to evaluate the impact of necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) on mortality and neurodevelopmental outcomes at 2 years' corrected age (CA) in infants born before 32 weeks' gestation (WG). METHODS: We studied neurodevelopment at 2 years' CA of infants with NEC or SIP who were born before 32 WG from the EPIPAGE-2 cohort study. The primary outcome was death or the presence of moderate-to-severe motor or sensory disability defined by moderate-to-severe cerebral palsy or hearing or visual disability. The secondary outcome was developmental delay defined by a score < 2 SDs below the mean for any of the five domains of the Ages and Stages Questionnaire. RESULTS: At 2 years' CA, 46% of infants with SIP, 34% of infants with NEC, and 14% of control infants died or had a moderate-to-severe sensorimotor disability (p < 0.01). This difference was mainly due to an increase in in-hospital mortality in the infants with SIP or NEC. Developmental delay at 2 years' CA was more frequent for infants with SIP than controls (70.8% vs 44.0%, p = 0.02) but was similar for infants with NEC and controls (49.3% vs 44.0%, p = 0.5). On multivariate analysis, the likelihood of developmental delay was associated with SIP (adjusted odds ratio = 3.0, 95% CI 1.0-9.1) but not NEC as compared with controls. CONCLUSION: NEC and SIP significantly increased the risk of death or sensorimotor disability at 2 years' CA. SIP was also associated with risk of developmental delay at 2 years' CA.