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To determine the prevalence of postpartum depression (PPD) and postpartum stress (PPS) and identify associated risk factors among mothers of preterm and low birth weight (LBW) infants. We conducted a secondary analysis of data collected from 255 mothers with preterm and LBW infants admitted to the neonatal intensive care unit (NICU) at Korle‐Bu Teaching Hospital, Accra, Ghana. A standardized interviewer‐administered questionnaire collected data on maternal, pregnancy, birth, and infant characteristics. The questionnaire also included the Patient Health Questionnaire‐9 (PHQ‐9) and the Perceived Stress Scale‐4 (PSS‐4) to assess PPD and PPS, respectively. Simple and multivariable linear regression analyses were performed to identify factors associated with PPD and PPS. The prevalence of moderate to moderately severe PPD was 3.9%, and that of PPS was 43.5%. The multivariable linear regression analysis showed that an increased number of prenatal care visits (β‐estimate = 0.26; 95% confidence interval [CI] 0.08–0.43; P < 0.01) was positively associated with higher scores on the PHQ‐9, whereas gestational age at birth (β = −0.21; 95% CI –0.40 to −0.03; P = 0.02) was inversely associated with PHQ‐9 scores. Moreover, a longer gestational period at the first prenatal care visit (β = 0.25; 95% CI 0.05–0.45; P = 0.01) and following the Islamic religion were associated with elevated scores on the PSS‐4 (β = 0.95; 95% CI 0.11−1.80; P = 0.011). Our findings underscore the presence of moderate PPD levels and high PPS levels among mothers. Active screening, diagnosis, and treatment for mothers at risk of mental health disorders during the peripartum period could enhance coping mechanisms for mothers navigating the challenging NICU environment and transitioning to the home environment. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To determine the pattern, degree and prevalence of optic disc optical coherence tomography (OCT) alterations in adults born preterm with very low birth weight (VLBW; birth weight < 1500 g).Optic disc OCT was assessed in 98 VLBW participants and 139 term‐born controls from birth cohorts in Finland and Norway at the mean age of 36 years. The participants had not been treated for retinopathy of prematurity and had no diagnosed brain abnormality. OCT assessment included parameters for optic disc size, neural rim and peripapillary retinal nerve fibre layer thickness (pRNFLT), and for the foveal developmental stage. Background data, visual acuity, refractive error and intraocular pressure were recorded.In the VLBW group, optic disc neural rim and pRNFLT were significantly decreased, most frequently in the nasal and inferior sectors. In 40% (95% CI: 33–47) of the VLBW eyes, nerve fibre thickness of at least one optic disc sector was below the fifth percentile of the control group, including 9% (95% CI: 6–14) subgroup falling below the first percentile, that is, clinically below normal limits. VLBW participants with nerve fibre thickness below the fifth percentile did not differ by perinatal data or foveal developmental stage from the other VLBW participants. All participants had normal visual acuity.A moderate decrease of the optic disc neural rim and pRNFLT is frequently seen in clinically healthy adults born preterm with VLBW. Awareness of the VLBW‐related optic disc nerve fibre shallowness especially in the inferior and nasal sectors is important while evaluating acquired optic disc pathology in adulthood. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions This research was conducted to evaluate the effects of Reiki and facilitated tucking position on pain, stress and physiologic parameters in preterm infants during orogastric tube (OGT) insertion.The study used a single‐blind, parallel‐group randomised controlled experimental design. It was carried out in the neonatal intensive care unit of a hospital in Niğde/Turkey between February 2022 and January 2023. A total of 45 preterm infants, who met the study criteria and whose sample size was determined according to power analysis, were randomly divided into three groups. As an intervention, the facilitated tucking position was applied to the first group, and Reiki was applied to the second group during OGT insertion. Routine application continued in the control group. The Infant Introductory Information Form, Physiological Parameter Follow‐up Chart, Infant Stress Scale (ISS) and Premature Infant Pain Profile Scale‐Revised (PIPP‐R) were used for data collection. Significance was accepted as P < 0.05 in the statistical analysis.It was determined that the infants were homogeneously distributed between the experimental and control groups (P > 0.05). Infants who received the facilitated tucking position and Reiki intervention had better physiological stability compared to the control group (P < 0.05). The group with the lowest average stress (1.53 ± 0.99) and pain scores (4.06 ± 1.22) during OGT insertion was the facilitated tucking group (P < 0.001). After the procedure, stress and pain scores in both the facilitated tucking group and the Reiki group were found to be significantly lower than those in the control group (P < 0.001).The results of the study showed that the facilitated tucking position during OGT insertion was especially effective in reducing the pain and stress of infants. Both the facilitated tucking position and Reiki were determined to be effective interventions in reducing the pain and stress of infants more quickly after the procedure. The results of study contribute to the recommendation that NICU nurses should include non‐pharmacological methods to decrease the pain of preterm infants during procedural pain. [ABSTRACT FROM AUTHOR]

Moderate‐late preterm‐born infants experience more frequent and severe respiratory tract infections and wheezing compared to term‐born infants. Decreasing the risk on respiratory tract infections and wheezing in this group is vital to improve quality of life and reduce medical consumption during infancy, but also to reduce the risk on asthma and COPD later in life. Until now, moderate‐late preterm infants are underrepresented in research and mechanisms underlying their morbidity are largely unknown, although they represent 80% of all preterm‐born infants. In order to protect these infants effectively, it is essential to understand the role of the immune system in early life respiratory health and to identify strategies to optimize immune development and respiratory health. This review elaborates on risk factors and preventative measures concerning respiratory tract infections and wheezing in preterm‐born infants, exploring their impact on the immune system and microbiome. Factors discussed are early life antibiotic use, birth mode, feeding type and living environment. Further, differences in adaptive and innate immune maturation between term and preterm infants are discussed, as well as differences in local immune reactions in the lungs. Finally, preventative strategies are being explored, including microbiota transplantation, immune modulation (through pre‐, pro‐, syn‐ and postbiotics, bacterial lysates, vaccinations, and monoclonal antibodies) and antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Pre‐procedural antisepsis is a critical component of hospital‐acquired infection prevention in the neonatal intensive care unit (NICU). However, broadly utilized topical antiseptic agents pose an elevated risk of disruption to neonatal skin integrity, and evidence‐based guidelines are lacking. This systematic review of the literature sought to assess and characterize the predisposing risk factors for and types of neonatal skin injury from topical antiseptic agents.A systematic search of Medline Ovid, Embase, Web of Science, CINAHL, and Cochrane Library was conducted, including academic literature providing data on neonatal skin injuries related to topical antisepsis in the NICU.A total of 19 articles (99 patients) met the inclusion criteria. Of the available data, most reported skin injuries were described in extremely preterm (98.1%) and very low birth weight (98.4%) infants. The majority of reported adverse cutaneous events were attributed to chlorhexidine preparations (74.8%), followed by octenidine (18.2%), povidone‐iodine (6.1%), and isopropyl alcohol (2.0%). Erythema (40.1%), skin breakdown (23.4%), and chemical burns (17.5%) were the skin reactions reported most frequently, followed by skin irritation (8.3%), and skin necrosis (2.8%).Our findings indicate that both extremely preterm and very low birth weight infants are particularly susceptible to skin toxicities from pre‐procedural antiseptic preparations. These data underscore the need for future research to support the development of guidelines which minimize iatrogenic cutaneous injuries in the neonatal population, specifically for the care of infants under 2 months of age, for whom current recommendations are lacking due to a paucity of data. [ABSTRACT FROM AUTHOR]

Background: Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing. Materials and Methods: A convenience sample of a multicenter birth cohort (SAREPREM) of moderate‐late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression. Results: Seventy‐six children were included in the study; 33 were classified as non‐wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non‐wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers. Conclusions: Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late‐preterm infants. [ABSTRACT FROM AUTHOR]

Aim: Evaluate the additional burden of centralised neonatal care on families of extremely preterm infants cared for away from their planned hospital of birth. Methods: Retrospective cohort study using national data for infants 23+0 to 27+6 weeks of gestation admitted for neonatal care from 2011 to 2016. The number of transfers on the first day of life (potential maternal–infant separation), time away from the maternal booking hospital (BH) and distance from the maternal residence were quantified. Results: Of 14 719 included infants, 2803 (19%) underwent postnatal transfer on the first day of life. A total of 8622 (59%) infants were cared for away from their BH for a median of 39 days (interquartile range [IQR] 15–69), 30% spending >60 days away over a median of two episodes (range 1–12). Median return road travelling distances for parents to their local BH was 13 km (IQR 8–26), but this increased to 74 km (IQR 32–148) for those cared for in a non‐BH. Conclusion: Centralised neonatal care improves infant outcomes but introduces additional burdens on the families of extremely preterm infants cared for away from their BH. Additional support, including accommodation and financial aid, could help minimise the impact on these families, facilitate family integrated care and improve parental wellbeing. [ABSTRACT FROM AUTHOR]

Background: Processing speed is a foundational skill supporting intelligence and executive function, areas often delayed in preterm‐born children. The impact of early‐life nutrition on gray matter facilitating processing speed for this vulnerable population is unknown. Methods: Magnetic resonance imaging and the Wechsler Preschool and Primary Scale of Intelligence‐IV Processing Speed Index were acquired in forty 5‐year‐old children born preterm with very low birth weight. Macronutrient (grams per kilogram per day) and mother's milk (percentage of feeds) intakes were prospectively collected in the first postnatal month and associations between early‐life nutrition and the primary outcome of brain regions supporting processing speed were investigated. Results: Children had a mean (SD) gestational age of 27.8 (1.8) weeks and 45% were male. Macronutrient intakes were unrelated, but mother's milk was positively related, to greater volumes in brain regions, including total cortical gray matter, cingulate gyri, and occipital gyri. Conclusion: First postnatal month macronutrient intakes showed no association, but mother's milk was positively associated, with volumetric measures of total and regional cortical gray matter related to processing speed in preterm‐born children. This exploratory analysis suggests early‐life mother's milk supports processing speed by impacting structural underpinnings. Further research is needed on this potential strategy to improve preterm outcomes. [ABSTRACT FROM AUTHOR]

Sepsis is a leading cause of death in preterm neonates. The increased susceptibility to sepsis is due to prolonged hospitalization, the need for invasive procedures, and immaturity of innate and adaptive immunity. Chlorhexidine gluconate is a popular topical disinfectant that was not recommended for use in preterm neonates until 2012. Thus, there are few studies assessing the role of chlorhexidine gluconate in antisepsis for preterm neonates. A better understanding of the safety and efficacy of chlorhexidine gluconate as an antiseptic agent for preterm neonates is the first step in establishing best practice guidelines for this population. [ABSTRACT FROM AUTHOR]

Background: Preterm birth (before 37 completed weeks of gestation) is associated with an increased risk of adverse health and developmental outcomes relative to birth at term. Existing guidelines for data collection in cohort studies of individuals born preterm are either limited in scope, have not been developed using formal consensus methodology, or did not involve a range of stakeholders in their development. Recommendations meeting these criteria would facilitate data pooling and harmonisation across studies. Objectives: To develop a Core Dataset for use in longitudinal cohort studies of individuals born preterm. Methods: This work was carried out as part of the RECAP Preterm project. A systematic review of variables included in existing core outcome sets was combined with a scoping exercise conducted with experts on preterm birth. The results were used to generate a draft core dataset. A modified Delphi process was implemented using two stages with three rounds each. Three stakeholder groups participated: RECAP Preterm project partners; external experts in the field; people with lived experience of preterm birth. The Delphi used a 9‐point Likert scale. Higher values indicated greater importance for inclusion. Participants also suggested additional variables they considered important for inclusion which were voted on in later rounds. Results: An initial list of 140 data items was generated. Ninety‐six participants across 22 countries participated in the Delphi, of which 29% were individuals with lived experience of preterm birth. Consensus was reached on 160 data items covering Antenatal and Birth Information, Neonatal Care, Mortality, Administrative Information, Organisational Level Information, Socio‐economic and Demographic information, Physical Health, Education and Learning, Neurodevelopmental Outcomes, Social, Lifestyle and Leisure, Healthcare Utilisation and Quality of Life. Conclusions: This core dataset includes 160 data items covering antenatal care through outcomes in adulthood. Its use will guide data collection in new studies and facilitate pooling and harmonisation of existing data internationally. [ABSTRACT FROM AUTHOR]

The gut microbiota undergoes substantial development from birth, and its development in the initial years of life has a potentially lifelong effect on the health of the individual. However, various factors can disrupt the development of the gut microbiota, leading to a condition known as dysbiosis, particularly in preterm infants. Current studies involving adults have suggested that the gut microbiota not only influences the gut but also has multidimensional effects on remote organs; these pathways are often referred to as the gut–organ axis. Imbalance of the gut microbiota may lead to the development of multiple diseases. Recent studies have revealed that gut dysbiosis in preterm infants may cause several acute morbidities—such as necrotizing enterocolitis, late‐onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity—and it may also influence long‐term outcomes including neurodevelopment and somatic growth. This review mainly presents the existing evidence regarding the relationships between the gut microbiota and these morbidities in preterm infants and explores the role of the gut–organ axis in these morbidities. This paper thus offers insights into the future perspectives on microbiota interventions for promoting the health of preterm infants. [ABSTRACT FROM AUTHOR]

Objectives Design Setting Participants Main Outcome Measures Results Conclusions Trial Registration Accurate assessment of gestational age (GA) is important at both individual and population levels. The most accurate way to estimate GA in women who book late in pregnancy is unknown. The aim of this study was to externally validate the accuracy of equations for GA estimation in late pregnancy and to identify the best equation for estimating GA in women who do not receive an ultrasound scan until the second or third trimester.This was a prospective, observational cross‐sectional study.57 prenatal care centres, France.Women with a singleton pregnancy and a previous 11–14‐week dating scan that gave the observed GA were recruited over an 8‐week period. They underwent a standardised ultrasound examination at one time point during the pregnancy (15–43 weeks), measuring 12 foetal biometric parameters that have previously been identified as useful for GA estimation.A total of 189 equations that estimate GA based on foetal biometry were examined and compared with GA estimation based on foetal CRL. Comparisons between the observed GA and the estimated GA were made using R2, calibration slope and intercept. RMSE, mean difference and 95% range of error were also calculated.A total of 2741 pregnant women were examined. After exclusions, 2339 participants were included. In the 20 best performing equations, the intercept ranged from −0.22 to 0.30, the calibration slope from 0.96 to 1.03 and the RSME from 0.67 to 0.87. Overall, multiparameter models outperformed single‐parameter models. Both the 95% range of error and mean difference increased with gestation. Commonly used models based on measurement of the head circumference alone were not amongst the best performing models and were associated with higher 95% error and mean difference.We provide strong evidence that GA‐specific equations based on multiparameter models should be used to estimate GA in late pregnancy. However, as all methods of GA assessment in late pregnancy are associated with large prediction intervals, efforts to improve access to early antenatal ultrasound must remain a priority.The proposal for this study and the corresponding methodological review was registered on PROSPERO international register of systematic reviews (registration number: CRD4201913776). [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance This study was undertaken to examine the association between different patterns of antiseizure medication (ASM) use during pregnancy and adverse obstetric outcomes (preterm birth, low birth weight [LBW], and small for gestational age [SGA]).This retrospective cohort study used the Birth Certificate Application and National Health Insurance data in Taiwan (January 1, 2004 through December 31, 2018). We retrieved weekly ASM among pregnant women with epilepsy who were prepregnancy chronic users and used group‐based trajectory modeling to identify distinct patterns of use. Logistic regressions were adopted to examine the association between patterns of ASM use and risk of preterm birth, LBW, and SGA. In addition, we revealed postnatal ASM utilization pattern among these prepregnancy chronic users as an exploratory study.Of 2175 pregnant women with epilepsy, we identified four patterns of ASM use during pregnancy: frequent and continuous (64.87%), frequent but discontinuous (7.08%), intermittent (19.72%), and intermittent and discontinuous users (8.32%). Compared to frequent and continuous users, the adjusted odds ratios for preterm birth in frequent but discontinuous, intermittent, and intermittent and discontinuous users were .83 (95% confidence interval [CI] = .47–1.48), .71 (95% CI = .47–1.05), and .88 (95% CI = .52–1.49), respectively. Similar results were observed for LBW and SGA. In the exploratory study, we found that most of our study subjects maintained the same patterns before and after delivery.After considering duration and timing of exposure, our study did not find an association between four distinct patterns of ASM use and adverse obstetric outcomes among women with epilepsy. The findings suggested that optimal seizure control could be received for pregnant women with epilepsy after evaluating the risks and benefits. [ABSTRACT FROM AUTHOR]

Breastfeeding is a crucial public health approach that reduces infant morbidity and mortality by providing essential nutrients and antibodies, and breast milk is easily digested. Breastfeeding and donated milk serve as a preventative measure against necrotising enterocolitis. Additionally, they protect against viruses and nosocomial sepsis. When a birthing parent's own milk is unavailable, alternative enteral nutrition for preterm or low‐birth‐weight infants is either donor human milk (DHM) or artificial formula. This study aimed to understand mothers' acceptance of the donor human milk bank (DHMB) and DHM. A qualitative phenomenological study was conducted in Limpopo Province, South Africa. The study used purposive sampling to select 23 mothers in postnatal and neonatal wards. Data collection was via in‐depth interviews using a semistructured interview guide. Manual data analysis using an interpretative phenomenological analysis (IPA) framework was used to coding. Concepts were grouped to generate themes. Three themes and nine subthemes were generated: (1) DHMBs (2) cultural perspective of DHMB, and (3) health considerations of DHM. Participants were unaware of the DHMB. Hesitancy in accepting DHM due to fear of contracting HIV was observed. Cultural beliefs are an influencing factor for use, while donation was driven by altruistic reasons, preventing waste, helping others and having previously benefited from DHM. The study found that mothers are willing to donate human milk. Willingness to donate can be increased by raising awareness about DHMB and addressing culture and safety concerns at antenatal clinics. Key messages: The study emphasises the possible willingness to accept the concept of donating and utilising donor human milk for newborns who do not have access to their mother's own milk. However, safety concerns, bonding and cultural issues should be addressed.Promoting breastfeeding and milk donation in communities requires addressing cultural and health concerns by utilising the service of community health workers.Education about safe breast milk banking before neonatal intensive care unit admission is also an important factor. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the association between syphilis in pregnancy and low birth weight, small for gestational age, and preterm birth. Methods: This longitudinal study used Brazilian National Information System for livebirths (SINASC) linked to the gestational syphilis cases from Notifiable Diseases Information System (SINAN) from 2011 to 2017. Descriptive statistics and logistic regression were used to compare the birth outcomes of pregnant women with and without syphilis. The study protocol was approved by the Research Ethics Committee of the Institute of Collective Health of the Federal University of Bahia (CAAE: registration no. 18022319.4.0000.5030). Results: A total of 17 930 817 live births were included in the study. Of these, 155 214 (8.7/1000) were exposed to syphilis during pregnancy. Maternal syphilis increased the odds of low birth weight (aOR 1.88, 95% CI: 1.85–1.91), small for gestational age (aOR 1.53, 95% CI: 1.51–1.56), and preterm birth (aOR 1.35, 95% CI: 1.33–1.37). Higher odds were observed for pregnant women with VDRL titer ≥64 and untreated maternal syphilis when compared to mothers without syphilis. Analysis stratified by prenatal care showed higher odds for all adverse birth outcomes for mothers attending ≤6 prenatal appointments. Conclusion: Our findings showed a strong association between gestational syphilis and adverse birth outcomes with increased odds observed among women with higher VDRL titers, lack of treatment, and fewer prenatal appointments. These results highlight the need for adequate screening and treatment for gestational syphilis during pregnancy to mitigate the risk of adverse birth outcomes. Synopsis: Gestational syphilis, lack of treatment, high VDRL titer, inadequate prenatal care increased the risk for low birth weight, small for gestational age, and preterm birth. [ABSTRACT FROM AUTHOR]

Aim: Adolescents born very preterm (VPT; <32 weeks of gestation) face an elevated risk of executive, behavioral, and socioemotional difficulties. Evidence suggests beneficial effects of mindfulness‐based intervention (MBI) on these abilities. This study seeks to investigate the association between the effects of MBI on executive, behavioral, and socioemotional functioning and reliable changes in large‐scale brain networks dynamics during rest in VPT young adolescents who completed an 8‐week MBI program. Methods: Neurobehavioral assessments and resting‐state functional magnetic resonance imaging were performed before and after MBI in 32 VPT young adolescents. Neurobehavioral abilities in VPT participants were compared with full‐term controls. In the VPT group, dynamic functional connectivity was extracted by using the innovation‐driven coactivation patterns framework. The reliable change index was used to quantify change after MBI. A multivariate data‐driven approach was used to explore associations between MBI‐related changes on neurobehavioral measures and temporal brain dynamics. Results: Compared with term‐born controls, VPT adolescents showed reduced executive and socioemotional functioning before MBI. After MBI, a significant improvement was observed for all measures that were previously reduced in the VPT group. The increase in executive functioning, only, was associated with reliable changes in the duration of activation of large‐scale brain networks, including frontolimbic, amygdala‐hippocampus, dorsolateral prefrontal, and visual networks. Conclusion: The improvement in executive functioning after an MBI was associated with reliable changes in large‐scale brain network dynamics during rest. These changes encompassed frontolimbic, amygdala‐hippocampus, dorsolateral prefrontal, and visual networks that are related to different executive processes including self‐regulation, attentional control, and attentional awareness of relevant sensory stimuli. [ABSTRACT FROM AUTHOR]

Objectives: To identify and internally validate metabolites predictive of spontaneous preterm birth (sPTB) using multiple machine learning methods and sequential maternal serum samples, and to predict spontaneous early term birth (sETB) using these metabolites. Design: Case–cohort design within a prospective cohort study. Setting: Cambridge, UK. Population or sample: A total of 399 Pregnancy Outcome Prediction study participants, including 98 cases of sPTB. Methods: An untargeted metabolomic analysis of maternal serum samples at 12, 20, 28 and 36 weeks of gestation was performed. We applied six supervised machine learning methods and a weighted Cox model to measurements at 28 weeks of gestation and sPTB, followed by feature selection. We used logistic regression with elastic net penalty, followed by best subset selection, to reduce the number of predictive metabolites further. We applied coefficients from the chosen models to measurements from different gestational ages to predict sPTB and sETB. Main outcome measures: sPTB and sETB. Results: We identified 47 metabolites, mostly lipids, as important predictors of sPTB by two or more methods and 22 were identified by three or more methods. The best 4‐predictor model had an optimism‐corrected area under the receiver operating characteristics curve (AUC) of 0.703 at 28 weeks of gestation. The model also predicted sPTB in 12‐week samples (0.606, 95% CI 0.544–0.667) and 20‐week samples (0.657, 95% CI 0.597–0.717) and it predicted sETB in 36‐week samples (0.727, 95% CI 0.606–0.849). A lysolipid, 1‐palmitoleoyl‐GPE (16:1)*, was the strongest predictor of sPTB at 12 weeks of gestation (0.609, 95% CI 0.548–0.670), 20 weeks (0.630, 95% CI 0.569–0.690) and 28 weeks (0.660, 95% CI 0.599–0.722), and of sETB at 36 weeks (0.739, 95% CI 0.618–0.860). Conclusions: We identified and internally validated maternal serum metabolites predictive of sPTB. A lysolipid, 1‐palmitoleoyl‐GPE (16:1)*, is a novel predictor of sPTB and sETB. Further validation in external populations is required. [ABSTRACT FROM AUTHOR]

Where a mother's own milk is not available or is insufficient, donor human milk (DHM) processed by a human milk bank (HMB) is the recommended next best alternative. HMBs exist in over 65 countries. However, most countries have yet to establish national policies or programmes that support the provision of DHM. In July 2019, a group of international experts in fields relevant to human milk banking gathered at a meeting organised by the Institute of Biomedical Ethics, University of Zurich, and co‐sponsored by the World Health Organisation. Prompted by the growing interest globally in creating and sustaining HMBs and addressing current safety and ethical concerns and standards, the aims of the meeting were to define knowledge gaps, determine the need for and scope of global guidelines and provide recommendations on steps that need to be taken at the international level. Following wide‐ranging discussions that included the integration of milk banks into health care systems, strategy and policy, quality and safety, the use of DHM and associated ethical considerations, the overall conclusion of the meeting was that in the absence of global recommendations on the implementation, operation and regulation of HMBs, evidence‐based guidance is urgently needed. Key points: Human milk banks (HMBs) exist in over 65 countries. Most countries with HMBs have yet to establish national policies to support the provision of donor human milk.An international group of experts in fields relevant to human milk banking met in 2019 to define knowledge gaps, determine the need and scope of global guidelines and provide recommendations.Evidence‐based guidance is urgently needed. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To describe the supporting and enhancing neonatal intensive care unit (NICU) sensory experiences (SENSE) program, associated research and opportunities for further study.A review of current materials on SENSE program implementation, publications related to SENSE development, and research on program implementation and patient outcomes was conducted to describe the SENSE program and its associated research.The SENSE program combines structured, evidence‐based, multisensory interventions with parent engagement in order to optimise outcomes in the complex NICU environment. Through a stepwise and scientific process, the SENSE program was developed to include specific doses and targeted timing (based on the infant's postmenstrual age, PMA) of evidence‐based interventions such as massage, auditory exposure, rocking, holding and skin‐to‐skin care for parents to provide their infants each day of NICU hospitalisation. It is adapted in context of concurrent medical interventions, infant behavioural responses, as well as NICU culture. The program is feasible to implement, acceptable to staff, and related to infants receiving more developmentally appropriate sensory exposures. Adaptations related to NICU culture and parent involvement have been reported. Research has identified relationships of the SENSE program to improved parent confidence, neurobehaviour and feeding at term age as well as improved communication 1 year of age.The literature related to the SENSE program is promising, but more research on efficacy and implementation is needed. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best‐corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term.In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term‐born controls were examined with spectral‐domain optical coherence tomography and BCVA at age 31–43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula.The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 μm (28.2) and 272.4 μm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 μm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA.Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion Perinatal mental health (PMH) conditions are associated with adverse outcomes such as maternal suicide, preterm birth and longer‐term childhood sequelae. Midwifery continuity of care (one midwife or a small group of midwives) has demonstrated benefits for women and newborns, including a reduction in preterm birth and improvements in maternal anxiety/worry and depression.To determine if midwifery care provided through a Midwifery Group Caseload Practice model is associated with improved perinatal outcomes for women who have anxiety and depression and/or other perinatal mental health conditions. An EPDS ≥ 13, and/or answered the thought of harming myself has occurred to me and/or women who self‐reported a history compared to standard models of care (mixed midwife/obstetric fragmented care).A retrospective cohort study using data routinely collected via an electronic database between 1 January 2018 31st of January 2021. The population were women with current/history of PMH, who received Midwifery Caseload Group Practice (MCP), or standard care (SC). Data were analysed using descriptive statistics for maternal characteristics and logistic regression for birth outcomes. One‐to‐one matching of the MCP group with the SC group was based on propensity scores.7,359 births were included MCP 12% and SC 88%. Anxiety was the most common PMH with the same proportion affected in MCP and SC. Adjusted odds of preterm birth and adverse perinatal outcomes were lower in the MCP group than the SC group (aOR (95%CI): 0.77 (0.55, 1.08) and 0.81 (0.68, 0.97), respectively) and higher for vaginal birth and full breastfeeding (aOR (95% CI): 1.87 (1.60, 2.18) and 2.06 (1.61, 2.63), respectively). In the matched sample the estimate of a relationship between MCP and preterm birth (aOR (95% CI): 0.88 (0.56, 1.42), adverse perinatal outcomes (aOR (95% CI): 0.83 (0.67, 1.05)) and breastfeeding at discharge (aOR (95% CI): 1.82 (1.30, 2.51)), stronger for vaginal birth (aOR (95% CI): 2.22 (1.77, 2.71)).This study supports positive associations between MCP and breastfeeding and vaginal birth. MCP was also associated with lower risk of adverse perinatal outcomes, though in the matched sample with a smaller sample size, the confidence interval included 1. The direction of the association MCP and preterm birth was negative (protective). However, in the matched sample analysis, the confidence interval was wide, and the finding was also consistent with no benefit from MCP. Randomised controlled trials are required to answer questions around preterm birth and adverse perinatal outcomes and further research is being planned. [ABSTRACT FROM AUTHOR]

Aim: The effect of different neonatal unit access hour policies on parental visiting duration is unknown. Therefore, we analysed the effects of access hours policies and parental education on parental visiting duration. Method: This prospective longitudinal cohort study was carried out in a level III neonatal unit from October 2020 to May 2022. Three cohorts were compared. The baseline cohort included 51 preterm infants with restricted visiting hours (October 2020 to May 2021). Cohort 1 comprised 35 preterm infants after liberalisation of visiting hours (June 2021 to November 2021). Cohort 2 consisted of 26 preterm infants after an educational program was implemented (December 2021 to May 2022). The primary outcome was the mean daily parental visiting duration. Results: Mean maternal visiting duration was 172 (standard deviation, SD ± 49.2), 195 (SD ± 64.4.), and 258 (SD ± 71.1) minutes/day at baseline and in cohorts 1 and 2 (significant increase from baseline and cohort 1 to cohort 2, p < 0.001). Mean paternal visiting duration did not change significantly across the cohorts: 133 (SD ± 47.2), 135 (SD ± 83.5), and 165 (SD ± 71.3) minutes/day. Conclusion: Liberalisation of access hours did not increase parental visiting duration. Parental and staff education significantly increased maternal but not paternal visiting duration. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of caffeine loading/maintenance administration on near‐infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. Methods: We conducted a multicentre case–control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. Results: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. Conclusion: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long‐term effect of caffeine in preterm infants. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to investigate visual function and vision‐related general health in adults that were born preterm with very low birth weight (VLBW: birth weight < 1500 g) in their 30s–40s. Methods: We recruited 137 adults born preterm with VLBW and 158 term‐born controls aged 31–43 years from two birth cohorts: the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight in a Lifetime Perspective study (Norway). We used neonatal data and measured refraction, best‐corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, visual fields, intraocular pressure (IOP), self‐reported vision‐targeted health status with the National Eye Institute Visual Function Questionnaire‐25. Results: VLBW adults had a lower BCVA ETDRS score than controls: mean (SD) better eye 86.7 (13.4) versus 90.2 (4.4), p = 0.02; mean (SD) worse eye 82.3 (14.9) versus 87.6 (4.6), p = 0.003. VLBW adults also had lower contrast sensitivity thresholds in several spatial frequencies and scored lower than controls in eight out of the 12 subscales of self‐reported vision‐targeted health status. Refraction, visual fields and IOP were similar between groups. Two VLBW participants were blind. None had been treated for retinopathy of prematurity. Conclusion: We suggest that lower visual function and vision‐related health represent life‐long consequences of prematurity and VLBW in the studied 31‐ to 43‐year‐old cohort. The underlying mechanisms remain to be determined. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association of Spanish compared to English primary household language on preterm (PT) infants' language outcomes in the United States and to examine associations with socio‐economic factors. Methods: This was a retrospective cohort of PT infants born <32 weeks gestation from Spanish‐speaking (n = 95) and English‐speaking homes (n = 1030) born 2005–2019. Language (primary outcome) and cognitive and motor skills (secondary outcomes) were measured using the BSID‐III at 18–24 months corrected age. Group differences were evaluated using bivariate comparisons and logistic regression analyses. Results: Mothers reporting Spanish‐speaking homes had higher rates of public insurance and lower educational achievement. Group newborn characteristics were similar. Preterm infants from Spanish‐speaking homes had significantly lower BSID‐III language composite, cognitive composite, receptive and expressive scores compared to infants from English‐speaking homes. Logistic regression modelling identified independent negative effects of Spanish‐speaking household OR 3.26 (CI 1.89–5.62) and public insurance OR 2.31 (CI 1.71–3.12) with a protective benefit derived from breast milk OR 0.68 (CI 0.50–0.92) when adjusting for medical morbidities, socio‐economic factors and gestational age. Conclusion: Public health policies and interventions in the United States should target language and cognitive outcomes of PT infants from Spanish‐speaking homes. [ABSTRACT FROM AUTHOR]

Objective: Small‐for‐gestational‐age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA‐PI) at 19–24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. Methods: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19–24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH‐21st fetal growth standards. The performance of UtA‐PI to predict the delivery of a SGA neonate was assessed using receiver‐operating‐characteristics (ROC)‐curve analysis. Results: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA‐PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA‐PI were 64.4% (95% CI, 61.5–67.3%) and 75.8% (95% CI, 69.3–82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA‐PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). Conclusions: This is the first Chinese study to evaluate the role of UtA‐PI at 19–24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA‐PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Human milk extracellular vesicles (HM EVs) are proposed to protect against disease development in infants. This protection could in part be facilitated by the bioactive EV cargo of proteins and RNA. Notably, mothers birth infants of different gestational ages with unique needs, wherein the EV cargo of HM may diverge. We collected HM from lactating mothers within two weeks of a term or preterm birth. Following purification of EVs, proteins and mRNA were extracted for proteomics and sequencing analyses, respectively. Over 2000 protein groups were identified, and over 8000 genes were quantified. The total number of proteins and mRNA did not differ significantly between the two conditions, while functional bioinformatics of differentially expressed cargo indicated enrichment in immunoregulatory cargo for preterm HM EVs. In term HM EVs, significantly upregulated cargo was enriched in metabolism‐related functions. Based on gene expression signatures from HM‐contained single cell sequencing data, we proposed that a larger portion of preterm HM EVs are secreted by immune cells, whereas term HM EVs contain more signatures of lactocyte epithelial cells. Proposed differences in EV cargo could indicate variation in mother's milk based on infants' gestational age and provide basis for further functional characterisation. [ABSTRACT FROM AUTHOR]

We assessed the potential effectiveness of human milk banking and lactation support on provision of human milk to neonates admitted in the newborn unit (NBU) at Pumwani Maternity Hospital, Kenya. This pre–post intervention study collected data from mothers/caregivers and their vulnerable neonates or term babies who lacked sufficient mother's milk for several reasons admitted in the NBU. The intervention included establishing a human milk bank and strengthening lactation support. Preintervention data were collected between 5 October 2018 and 11 November 2018, whereas postintervention data were collected between 4 September 2019 and 6 October 2019. Propensity score‐matched analysis was performed to assess the effect of the intervention on exclusive use of human milk, use of human milk as the first feed, feeding intolerance and duration of NBU stay. The surveys included 123 and 116 newborns at preintervention and postintervention, respectively, with 160 newborns (80 in each group) being included in propensity score matched analysis. The proportion of neonates who exclusively used human milk during NBU stay increased from 41.3% preintervention to 63.8% postintervention (adjusted odds ratio [OR]: 2.68; 95% confidence interval [CI]: 1.31, 5.53) and those whose first feed was human milk increased from 55.0% preintervention to 83.3% postintervention (adjusted OR: 5.09; 95% CI: 2.18, 11.88). The mean duration of NBU stay was 27% (95% CI: 5.8%, 44.0%) lower in the postintervention group than in the preintervention group. The intervention did not affect feeding intolerance. Integrating human milk banking and lactation support may improve exclusive use of human milk among vulnerable neonates in a resource limited setting. Key messages: Mother's milk is recommended for feeding preterm and low birthweight neonates.However, when the provision of mother's milk is not feasible, the use of donor human milk—from a human milk bank—is recommended.In this quasi‐experimental study, human milk banking and lactation support intervention increased the exclusive use of human milk during hospital stay and the use of human milk as the first feed among neonates admitted in the newborn unit at Pumwani Maternity Hospital, Kenya.The intervention also reduced the duration of stay in the newborn unit and there was no impact on feeding intolerance.Human milk banking and lactation support may improve the exclusive use of human milk among vulnerable neonates in a resource‐limited setting. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is associated with adverse mental health outcomes, including internalizing problems, social difficulties and inattention. Interventions are needed beyond infancy and toddlerhood to support children and their families. We examined the feasibility and acceptability of the I‐InTERACT Preterm pilot study, an online parenting intervention for preterm children ages 3–8. Method: Families participated in a weekly intervention comprised of seven sessions with online modules followed by videoconference coaching sessions with a therapist. Following completion of the study, caregivers completed a survey to assess their satisfaction and were asked to participate in a voluntary semi‐structured interview to provide feedback. We anticipated greater than a 50% participation rate (enrollment feasibility) and 75% completion rate (adherence feasibility). We also hypothesized that at least 80% of participants would be satisfied with the intervention (acceptability). Results: Nineteen of 32 families (59%) enrolled in the study, suggesting adequate enrollment feasibility. Feasibility of programme completion (adherence) was lower than anticipated (59%). Regarding satisfaction, all caregivers agreed that the programme's information was relevant to them and their family. Nearly all participants (92%) indicated that they had a better understanding of the effects of preterm birth on behaviour, that they enjoyed the programme, that it met their expectations and that they recommend the programme to others. In qualitative interviews, caregivers expressed satisfaction with the content, skills they learned, and receiving direct coaching. Caregivers suggested improvements to increase intervention feasibility and skill implementation, including offering biweekly sessions and more hands‐on coaching. Conclusion: Our largely satisfactory acceptability rates suggest the value of and need for a parenting intervention for children born preterm past the initial period of early development. Future directions include modifying the intervention in response to caregiver feedback to improve recruitment, engagement and adherence. [ABSTRACT FROM AUTHOR]

Premature birth may result in specific cardiovascular responses to hypoxia and hypercapnia, that might hamper high‐altitude acclimatization. This study investigated the consequences of premature birth on baroreflex sensitivity (BRS) under hypoxic, hypobaric and hypercapnic conditions. Seventeen preterm born males (gestational age, 29 ± 1 weeks), and 17 age‐matched term born adults (40 ± 0 weeks) underwent consecutive 6‐min stages breathing different oxygen and carbon dioxide concentrations at both sea‐level and high‐altitude (3375 m). Continuous blood pressure and ventilatory parameters were recorded in normobaric normoxia (NNx), normobaric normoxic hypercapnia (NNx + CO2), hypobaric hypoxia (HHx), hypobaric normoxia (HNx), hypobaric normoxia hypercapnia (HNx + CO2), and hypobaric hypoxia with end‐tidal CO2 clamped at NNx value (HHx + clamp). BRS was assessed using the sequence method. Across all conditions, BRS was lower in term born compared to preterm (13.0 ± 7.5 vs. 21.2 ± 8.8 ms⋅mmHg−1, main group effect: p < 0.01) participants. BRS was lower in HHx compared to NNx in term born (10.5 ± 4.9 vs. 16.0 ± 6.0 ms⋅mmHg−1, p = 0.05), but not in preterm (27.3 ± 15.7 vs. 17.6 ± 8.3 ms⋅mmHg−1, p = 0.43) participants, leading to a lower BRS in HHx in term born compared to preterm (p < 0.01). In conclusion, this study reports a blunted response of BRS during acute high‐altitude exposure without any influence of changes in inspired CO2 in healthy prematurely born adults. [ABSTRACT FROM AUTHOR]

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double‐blind, placebo‐controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6‐OH‐ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6‐OH‐ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6‐OH‐ME were not detectable in the placebo group at any study time‐point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6‐OH‐ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6‐OH‐ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Staphylococcal scalded skin syndrome (SSSS) is a rare condition in premature infants. We report a case of SSSS in a preterm neonate who displayed all clinical manifestations at birth, leading to a fatal outcome from Candida parapsilosis fungemia. The clinical presentation was challenging to differential diagnosis. SSSS diagnosis was confirmed by skin biopsy. This case emphasizes the significance of early recognition and diagnosis of SSSS promptly for clinicians. Congenital SSSS in premature infants can be fatal, but with early recognition and appropriate supportive and antimicrobial therapy, outcomes can be improved and lives can be saved. [ABSTRACT FROM AUTHOR]

Objective Design Setting Sample Methods Main outcome measures Results Conclusions To examine the contribution of preterm birth and size‐for‐gestational age in stillbirths using six ‘newborn types’.Population‐based multi‐country analyses.Births collected through routine data systems in 13 countries.125 419 255 total births from 22+0 to 44+6 weeks’ gestation identified from 2000 to 2020.We included 635 107 stillbirths from 22+0 weeks’ gestation from 13 countries. We classified all births, including stillbirths, into six ‘newborn types’ based on gestational age information (preterm, PT, <37+0 weeks versus term, T, ≥37+0 weeks) and size‐for‐gestational age defined as small (SGA, <10th centile), appropriate (AGA, 10th–90th centiles) or large (LGA, >90th centile) for gestational age, according to the international newborn size for gestational age and sex INTERGROWTH‐21st standards.Distribution of stillbirths, stillbirth rates and rate ratios according to six newborn types.635 107 (0.5%) of the 125 419 255 total births resulted in stillbirth after 22+0 weeks. Most stillbirths (74.3%) were preterm. Around 21.2% were SGA types (PT + SGA [16.2%], PT + AGA [48.3%], T + SGA [5.0%]) and 14.1% were LGA types (PT + LGA [9.9%], T + LGA [4.2%]). The median rate ratio (RR) for stillbirth was highest in PT + SGA babies (RR 81.1, interquartile range [IQR], 68.8–118.8) followed by PT + AGA (RR 25.0, IQR, 20.0–34.3), PT + LGA (RR 25.9, IQR, 13.8–28.7) and T + SGA (RR 5.6, IQR, 5.1–6.0) compared with T + AGA. Stillbirth rate ratios were similar for T + LGA versus T + AGA (RR 0.7, IQR, 0.7–1.1). At the population level, 25% of stillbirths were attributable to small‐for‐gestational‐age.In these high‐quality data from high/middle income countries, almost three‐quarters of stillbirths were born preterm and a fifth small‐for‐gestational age, with the highest stillbirth rates associated with the coexistence of preterm and SGA. Further analyses are needed to better understand patterns of gestation‐specific risk in these populations, as well as patterns in lower‐income contexts, especially those with higher rates of intrapartum stillbirth and SGA. [ABSTRACT FROM AUTHOR]

Although historically pre‐eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body of literature has demonstrated that the placenta and its development is the root cause of many cases of these conditions. This has led to the term 'the great obstetrical syndromes' being coined to reflect this common origin. Although these conditions mostly manifest in the second half of pregnancy, a failure to complete deep placentation (the transition from histiotrophic placentation to haemochorial placenta at 10–18 weeks of gestation via a second wave of extravillous trophoblast invasion), is understood to be key to the pathogenesis of the great obstetrical syndromes. While the reasons that the placenta fails to achieve deep placentation remain active areas of investigation, maternal inflammation and thrombosis have been clearly implicated. From a clinical standpoint these mechanisms provide a biological explanation of how low‐dose aspirin, which affects the COX‐1 receptor (thrombosis) and the COX‐2 receptor (inflammation), prevents not just pre‐eclampsia but all the components of the great obstetrical syndromes if initiated early in pregnancy. The optimal dose of low‐dose aspirin that is maximally effective in pregnancy remains a question open for further research. Additionally, other candidate medications have been identified that may also prevent pre‐eclampsia, and further study of them may offer therapeutic options beyond low‐dose aspirin. Interestingly, three of the eight identified compounds (hydroxychloroquine, metformin and pravastatin) are known to decrease inflammation. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of low‐dose aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy. Design: Non‐prespecified secondary analysis of a randomised masked trial of LDA. Setting: The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR) clusters, a prospective, population‐based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Pakistan, India (two sites‐Belagavi and Nagpur) and Guatemala. Population: Nulliparous singleton pregnancies between 6+0 weeks and 13+6 weeks in six low‐middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial. Methods: We compared the incidence of HDP at delivery at three gestational age periods (<28, <34 and <37 weeks) between women who were randomised to aspirin or placebo. Women were included if they were randomised and had an outcome at or beyond 20 weeks (Modified Intent to Treat). Main Outcome Measures: Our primary outcome was pregnancies with HDP associated with preterm delivery (HDP@delivery) before <28, <34 and <37 weeks. Secondary outcomes included small for gestational age (SGA) <10th percentile, <5th percentile, and perinatal mortality. Results: Among the 11 976 pregnancies, LDA did not significantly lower HDP@delivery <28 weeks (relative risk [RR] 0.18, 95% confidence interval [CI] 0.02–1.52); however, it did lower HDP@delivery <34 weeks (RR 0.37, 95% CI 0.17–0.81) and HDP@delivery <37 weeks (RR 0.66, 95% CI 0.49–0.90). The overall rate of HDP did not differ between the two groups (RR 1.08, 95% CI 0.94–1.25). Among those pregnancies who had HDP, SGA <10th percentile was reduced (RR 0.81, 95% CI 0.67–0.99), though SGA <5th percentile was not (RR 0.84, 95% CI 0.64–1.09). Similarly, perinatal mortality among pregnancies with HDP occurred less frequently (RR 0.55, 95% CI 0.33–0.92) in those receiving LDA. Pregnancies randomised to LDA delivered later with HDP compared with those receiving placebo (median gestational age 38.5 weeks vs. 37.9 weeks; p = 0.022). Conclusions: In this secondary analysis of a study of low‐risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks but not in the overall rate of HDP. These results suggest that LDA works in part by delaying HDP. [ABSTRACT FROM AUTHOR]

Preterm‐born neonates are prone to impaired neurodevelopment that may be associated with disrupted whole‐brain structural connectivity. The present study aimed to investigate the longitudinal developmental pattern of the structural network from preterm birth to term‐equivalent age (TEA), and identify how prematurity influences the network topological organization and properties of local brain regions. Multi‐shell diffusion‐weighted MRI of 28 preterm‐born scanned a short time after birth (PB‐AB) and at TEA (PB‐TEA), and 28 matched term‐born (TB) neonates in the Developing Human Connectome Project (dHCP) were used to construct structural networks through constrained spherical deconvolution tractography. Structural network development from preterm birth to TEA showed reduced shortest path length, clustering coefficient, and modularity, and more "connector" hubs linking disparate communities. Furthermore, compared with TB newborns, premature birth significantly altered the nodal properties (i.e., clustering coefficient, within‐module degree, and participation coefficient) in the limbic/paralimbic, default‐mode, and subcortical systems but not global topology at TEA, and we were able to distinguish the PB from TB neonates at TEA based on the nodal properties with 96.43% accuracy. Our findings demonstrated a topological reorganization of the structural network occurs during the perinatal period that may prioritize the optimization of global network organization to form a more efficient architecture; and local topology was more vulnerable to premature birth‐related factors than global organization of the structural network, which may underlie the impaired cognition and behavior in PB infants. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to describe the distribution of gestational age at birth (GAB) to inform the estimation of GAB when clinical or obstetric estimates are not available for perinatal pharmacoepidemiology studies. Methods: We estimated GAB (median, mode, mean, and standard deviation) and percentage born at each gestational week in groups based on plurality and other variables for live births in CDC's U.S. birth data. Results: In 2020, 3 617 213 newborns had birth certificates with nonmissing GAB. Among singletons (3 501 693), median and mode GAB were both 39 weeks. Births with lower median GAB were from women with eclampsia (37 weeks) or receiving intensive care (37 weeks); newborns receiving intensive care (37 weeks); newborns with birth weight <2500 g (35 weeks), <1500 g (28 weeks), or <1000 g (25 weeks); and newborns not discharged alive (23 weeks). Among twins (112 633), median GAB was 36 weeks (mode, 37 weeks). Additional noteworthy groups were women with 0–6 prenatal visits (median, 34 weeks) or 7–8 prenatal visits (median, 35 weeks) or aged 15–19 years (median, 35 weeks). Conclusions: Some maternal and infant groups had distinct GAB distributions in the United States. This information can be useful in estimating GAB when individual‐level clinical estimates are not available, such as in database studies of medication use during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population. Methods: An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN‐associated liver disease (PNALD) at study entry were excluded. Results: The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided. Conclusion: Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022‐2023 Board of Directors. [ABSTRACT FROM AUTHOR]

Exposure to pain‐related stress from frequent invasive procedures in the neonatal intensive care unit (NICU) has been associated with altered physiological stress regulation, neurodevelopment, and behavior in children born very preterm (≤32 weeks gestation). Previously, in a cohort born 2003–2006 (Cohort 1), we found that, at 18 months corrected age (CA), children born extremely low gestational age (ELGA; 24–28 weeks) and very low gestational age (VLGA; 29–32 weeks), had higher pre‐test cortisol levels and a different pattern of cortisol output across a developmental assessment involving cognitive challenge compared to children born full‐term (FT; 39–41 weeks). Also, greater neonatal pain‐related stress exposure among the preterm children was related to higher pre‐test cortisol levels. Given the adverse long‐term effects of neonatal pain in preterm infants and the ensuing rise in clinical concerns to appropriately manage pain in the NICU in recent years, we aimed to examine whether our findings from Cohort 1 would still be evident in an independent cohort (Cohort 2) born 2006–2011 and recruited from the same tertiary NICU in Vancouver, Canada. We also compared the cortisol patterns, clinical and socio‐demographic factors, and their interrelationships between the two cohorts. In Cohort 2, our findings using multi‐level modeling support and extend our earlier findings in Cohort 1, demonstrating that children born ELGA display higher pre‐test cortisol levels than FT. As well, greater cortisol output across assessment was related to more anxiety/depressive behaviors in children born VLGA. Importantly, children born ELGA were exposed to less neonatal pain/stress, mechanical ventilation, and morphine in Cohort 2 than Cohort 1. In both cohorts, however, cortisol levels and patterns were related to neonatal pain/stress and clinical factors (days on mechanical ventilation, overall morphine exposure). Despite less exposure to pain/stress and adverse clinical factors in Cohort 2 compared to Cohort 1, cortisol levels and patterns across cognitive challenge in preterm children at 18‐month CA were consistent across the two independent cohorts. These findings highlight that, despite improvements to neonatal care, children born extremely preterm continue to display altered HPA axis activity, which is associated with their poorer neurodevelopmental and behavioral outcomes. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Ectopia cordis is a rare condition with expected low survival rate based on past studies. We encountered a case of a preterm and low birth weight infant with ectopia cordis. When the infant cried, the prolapse of the heart, liver, and intestinal tract worsened. A pressure‐applying protector was used to protect the organs and reduce the prolapse. Upon application, the infant's tachypnea and desaturation worsened. Fluoroscopic examination suggested that the pressure from the prolapsed regions was impeding pulmonary expansion and negatively affecting circulation. It is essential to carefully design a protector that accommodates the infant's growth. [ABSTRACT FROM AUTHOR]

Summary: The study objective was to explore associations of fetal and infant weight patterns and preterm birth with sleep and 24‐h activity rhythm parameters at school‐age. In our prospective population‐based study, 1327 children were followed from birth to age 10–15 years. Fetal weight was estimated using ultrasound in the second and third trimester of pregnancy. Birth weight and gestational age were available from midwife registries. Infant weight was measured at 6, 12 and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change of >0.67 standard deviation between the corresponding age intervals. At school‐age, sleep duration, sleep efficiency, wake after sleep onset, social jetlag, inter‐daily stability, and intra‐daily variability were assessed using tri‐axial wrist actigraphy for 9 consecutive nights. We observed that low birth weight (<2500 g) was associated with 0.24 standard deviation (95% confidence interval [CI] 0.04; 0.43) longer sleep duration compared to normal weight. Compared to normal growth, growth deceleration in fetal life and infancy was associated with 0.40 standard deviation (95% CI 0.07; 0.73) longer sleep duration, 0.44 standard deviation (95% CI 0.14; 0.73) higher sleep efficiency, and −0.41 standard deviation (95% CI −0.76; ‐0.07) shorter wake after sleep onset. A pattern of normal fetal growth followed by infant growth acceleration was associated with −0.40 standard deviation (95% CI −0.61; −0.19) lower inter‐daily stability. Preterm birth was not associated with any sleep or 24‐h rhythm parameters. Our findings showed that children with fetal and infant growth restriction had longer and more efficient sleep at school‐age, which may be indicative of an increased need for sleep for maturational processes and development after a difficult start in life. [ABSTRACT FROM AUTHOR]

Introduction: Multiple gestations are a risk factor for most pregnancy complications. The current study aimed to study whether offspring born after twin pregnancies are at increased risk for long‐term health complications. Material and methods: A retrospective cohort study was conducted in a large medical center, including all offspring born between the years 1991–2021, which were followed‐up until 18 years of age. Hospital‐based diagnoses of the offspring were categorized into main groups of morbidities: cardiac, respiratory, infectious, neurological, malignancy, and metabolic. Incidence of hospitalization with diagnoses from each main group was compared between twins and singletons, as well as time to first hospitalization. Cox proportional hazard models were used to study the association between twins vs singletons and hospitalizations by grouped morbidities, while adjusting for maternal age, ethnicity and gender, besides maternal recurrence in the cohort. Results: A total of 369 478 offspring were included in the analysis; of these 11 986 (3.2%) were twins and 357 492 (96.8%) were singletons. Twins were more likely to be delivered preterm (odds ratio = 17.65, 95% CI: 16.74–18.60), by cesarean delivery and following infertility treatments. Incidence of hospitalizations with all morbidity groups was slightly, some significantly, higher among twins, including cardiac: 1.9% vs 1.5%, respiratory; 8.4% vs 7.1%, neurological: 7.7% vs 7.4%, infectious: 26.0% vs 24.1%, and malignancies: 0.7% vs 0.4%. The risk remained higher in the multivariable analyses (adjusted hazard ratios ranging between 1.09–1.75). When stratifying by gestational age at delivery, the risk for most morbidities was lower among twins vs singletons born in similar gestational ages. Conclusions: Twins as compared to singletons are at increased risk for most morbidities due to their risk of being born earlier. [ABSTRACT FROM AUTHOR]

Aim: Necrotising enterocolitis (NEC) is the dominating surgical emergency in preterm neonates. The aims were to investigate indications, surgical management and mortality for surgically treated neonates with NEC. Methods: Data were retrieved from the Swedish Neonatal Quality Register for Swedish neonates with surgically treated NEC from 1 January 2017 to 31 December 2021. Diagnosis was validated by surgical records and histopathology. Neonates with isolated spontaneous intestinal perforation were excluded. Results: In total, 109 neonates were included. Median gestational age was 25 weeks (22–38), and median birth weight was 771 g (269–3920). Preoperative pneumoperitoneum was found in 32%, portal venous gas in 25% and clinical deterioration on conservative treatment in 26% of the neonates. Among the 97 neonates presenting with small bowel necrosis, single‐focal NEC occurred in 38 (39%), multifocal NEC in 35 (36%) and panintestinal NEC in 24 (25%). A primary anastomosis was performed in 10/87 (11%) of the neonates with bowel resection at primary surgery. Clip‐and‐drop technique was applied in 24/87 (28%).Mortality rate was 37%. Conclusion: Mortality was well comparable with earlier reports considering exclusion of spontaneous intestinal perforation (SIP) and the low gestational age of the study population. Resection of necrotic bowel with stoma formation was the dominating surgical method. [ABSTRACT FROM AUTHOR]

Aim: We compared milk volumes, skin‐to‐skin contact and breastfeeding by the mothers of very preterm twins and singleton infants born at 28–32 weeks of gestation. Methods: This Norwegian longitudinal prospective comparative study was carried out in two neonatal intensive care units: one with single family rooms and one open bay unit. It comprised 49 singleton infants, 28 twins and their mothers. The mothers' milk volume and direct breastfeeding were recorded from birth until 4 months' of corrected age. They also answered the breastfeeding self‐efficacy scale and skin‐to‐skin contact was recorded. Results: The mothers of preterm twins produced doubled the volume of expressed milk at day 14, compared to the mothers of singletons (mean 816 ± 430 mL vs. 482 ± 372 mL, p < 0.05) and this difference was still sustained at 34 + 0 weeks/days (p < 0.02). Mothers of twins had their first breastfeeding attempt later than mothers of singletons (median of 133 h compared to 56 (p < 0.002). Preterm twins received less daily skin‐to‐skin contact (mean 157 ± 66 min each vs. 244 ± 109) (p < 0.001). There were no differences in receiving mother's own milk, exclusively direct breastfeeding or perceived breastfeeding self‐efficacy. Conclusion: Breastfeeding was initiated as successfully in preterm twins as singletons as the mothers' milk production doubled. [ABSTRACT FROM AUTHOR]

Objective: Our goal was to determine the efficacy of the American Society for Parenteral and Enteral Nutrition's recommended carnitine dosage of 5 mg/kg/day in maintaining normal serum free carnitine and total acylcarnitine levels in preterm neonates receiving parenteral nutrition (PN). Study Design: A retrospective cohort study was conducted on neonates born <30 weeks gestation and weighing <1250 g, comparing those who received carnitine supplementation to those without supplementation. Free carnitine and total acylcarnitine data were collected from routine newborn screens in the first days of life and on full enetral feeds. Univariate analysis was performed, and those factors that were significantly different between the two groups were adjusted for using mixed effects analysis. Results: There were 108 supplemented and 45 unsupplemented neonates in the study. At baseline, free carnitine (19.8 ± 3.3 vs 18.9 ± 3.7 µmol/L, P = 0.53) and total acylcarnitine (26.6 ± 5.1 vs 22.5 ± 7.1 µmol/L, P = 0.11) were similar between the two groups. At full enteral feeds, compared with unsupplemented group, supplemented infants had significantly higher free carnitine (27.1 ± 16.4 vs 17.1 ± 8.5 µmol/L, P < 0.001) and total acylcarnitine (30.3 ± 11.5 vs 20.2 ± 10.1 µmol/L, P < 0.001). None of the supplemented neonates developed biochemical carnitine deficiency as compared with 18% in the unsupplemented group (P < 0.001). No difference was observed in time to reach full lipid provision, and there were no differences in the change in the triglyceride levels from baseline to the time on full PN lipid provision (P = 0.39). Conclusion: Preterm neonates routinely supplemented with parenteral carnitine at 5 mg/kg/day demonstrated higher free carnitine and total acylcarnitine levels at full feeds, with none developing biochemical carnitine deficiency. [ABSTRACT FROM AUTHOR]

Key points Hypoxia‐ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low‐cost, easily applied biomarker of antenatal HI and evolving brain injury. Hypoxia‐ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low‐cost, easily applied biomarker of antenatal HI and evolving brain injury. [ABSTRACT FROM AUTHOR]

Key Clinical Message: POCUS could identify some of UVC complications at the bedside. It complements the clinical picture and helps narrowing the deferential diagnosis when there is a clinical deterioration. [ABSTRACT FROM AUTHOR]

Background: Secretory leukocyte protease inhibitor (SLPI) is an innate anti‐inflammatory and anti‐microbial peptide and produced in amnion of fetal membranes during pregnancy. However, studies on the association between SLPI levels in amniotic fluid and acute chorioamnionitis are limited. Afterbirth oral fluid (AOF) of the baby could be useful for representing the intra‐amniotic environment precisely just before delivery. This study aimed to determine the relationship between SLPI levels in AOF and acute histologic chorioamnionitis (HC). Methods: AOF of the baby was obtained during delivery from 24(0/7) to 36(6/7) weeks of gestational age (preterm group, n = 94) and from 37(0/7) to 41(6/7) weeks of gestational age (term group, n = 27) just after birth. SLPI expression levels among five classifications were compared to the intensity of acute HC as follows: no inflammation, acute subchorionitis, acute chorionitis, acute chorioamnionitis, and funisits. The SLPI and matrix metalloproteinase‐8 (MMP‐8) concentrations of AOF were determined using Enzyme Linked Immunosorbent Assay. Histologic examination of the placenta and membranes was performed after delivery. Results: SLPI concentrations in AOF inversely decreased according to the intensity of acute HC (161.62 ng/mL in funisitis, 134.83 ng/mL in acute chorioamnionitis, 749.35 ng/mL in acute chorionitis, 953.05 ng/mL in acute subchorionitis, and 1126.77 ng/mL in no inflammation [p =.021]). The MMP‐8 concentrations in AOF and maternal serum C‐reactive protein were the highest in funisitis. The SLPI/ MMP‐8 ratio was low in subgroup with acute chorioamnionitis and funisitis. Conclusion: Along with increased MMP‐8 levels, decreased SLPI levels in AOF of the baby could be an additional factor in predicting acute HC immediately after birth. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to examine prospective associations of sleep characteristics (duration, timing, quality) with dietary and anthropometric measures among toddlers born preterm (<35 weeks). Methods: Children participated in the Omega Tots trial at 10–17 months' corrected age (Ohio, USA; 26 April 2012 to 6 April 2017). Caregivers reported toddlers' sleep at baseline using the Brief Infant Sleep Questionnaire. After 180 days, caregivers reported toddlers' past month diet in a food frequency questionnaire, and anthropometry was measured using standardised protocols. The toddler diet quality index (TDQI: higher scores indicating better quality), and weight‐for‐length, triceps skinfold and subscapular skinfold z‐scores were calculated. Linear and logistic regression assessed adjusted associations with dietary and anthropometric outcomes at 180‐day follow‐up (n = 284), and linear mixed models assessed changes in anthropometry. Results: Daytime sleep was associated with lower TDQI (βadj per hour = −1.62 (95% CI: −2.71, −0.52)) whereas night‐time sleep was associated with higher TDQI (βadj = 1.01 (95% CI: 0.16, 1.85)). Night‐time awakenings and caregiver‐reported sleep problems were also associated with lower TDQI. Night awakening duration and sleep‐onset latency were associated with higher triceps skinfold z‐score. Conclusion: Daytime and night‐time caregiver‐reported sleep showed opposite associations with diet quality, suggesting that sleep timing may be important. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusions We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low‐ and middle‐income countries (LMICs).Descriptive multi‐country, secondary analysis of individual‐level study data of babies born since 2000.Sixteen subnational, population‐based studies from nine LMICs in sub‐Saharan Africa, Southern and Eastern Asia, and Latin America.Live birth neonates.We categorically defined five vulnerable newborn types based on size (large‐ or appropriate‐ or small‐for‐gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10‐type definition included low birthweight (LBW) and non‐LBW, and a four‐type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies.Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification.There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0–2.9), PT + LGA (median RR 7.3, IQR 2.3–10.4), PT + AGA (median RR 6.0, IQR 4.4–13.2) and PT + SGA (median RR 10.4, IQR 8.6–13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non‐LBW babies.Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health. [ABSTRACT FROM AUTHOR]