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ObjectiveHIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD.Design/methodsA nested 1 : 1 case-control study ( N  = 362) was conducted within a multicountry randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (

Neonatal seizures are common among patients with acute brain injury or critical illness and can be difficult to diagnose and treat. The most common etiology of neonatal seizures is hypoxic-ischemic encephalopathy, with other common causes including ischemic stroke and intracranial hemorrhage. Neonatal clinicians can use a standardized approach to patients with suspected or confirmed neonatal seizures that entails laboratory testing, neuromonitoring, and brain imaging. The primary goals of management of neonatal seizures are to identify the underlying cause, correct it if possible, and prevent further brain injury. This article reviews recent evidence-based guidelines for the treatment of neonatal seizures and discusses the long-term outcomes of patients with neonatal seizures.

BackgroundThere is a lack of research on the relationship between water fluoridation and pregnancy outcomes.ObjectivesWe assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California.MethodsWe linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7 ppm (the current level recommended by the US Department of Health and Human Services) and 0.5 ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z-scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers.ResultsFluoride levels ranged from 0 to 2.5 ppm, with a median of 0.51 ppm. There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7 ppm [-2.2g; 95% confidence interval (CI): -4.4, 0.0] and to 0.5 ppm (-5.8g; 95% CI: -10.0, -1.6). There were small negative associations with birth-weight-for-gestational-age z-scores for both hypothetical interventions (0.7 ppm: -0.004; 95% CI: -0.007, 0.000 and 0.5 ppm: -0.006; 95% CI: -0.013, 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7 ppm [risk difference (RD)=-0.001; 95% CI: -0.002, 0.000 and 0.5 ppm (-0.001; 95% CI: -0.003, 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention.ConclusionWe estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z-scores in California. https://doi.org/10.1289/EHP13732.

PurposeTo determine whether a diagnosis of a perinatal mood and anxiety disorder (PMAD) is associated with adverse perinatal outcomes.MethodsMental health symptom screening and diagnostic data from 82 women with single gestation in the Healthy Babies Before Birth study conducted from 2013 to 2018 were obtained by clinic interview. If a woman scored over 10 on the Patient Health Questionnaire (PHQ-9) or endorsed the suicidality item; or scored over 7 on the Overall Anxiety Severity and Impairment Scale (OASIS), a Structured Clinical Interview for DSM-IV (SCID) Axis I Disorders was administered. An adverse perinatal outcome was operationalized as a diagnosis of gestational diabetes mellitus, intrauterine growth restriction, preeclampsia, chorioamnionitis, hemorrhage, fetal death, preterm birth, or a low birthweight baby, and abstracted from the medical records.ResultsWomen were between 22.0 and 45.0 years old (Mean age = 33.1 ± 4.3). Mean BMI was 24.7 ± 5.6 (Range 16.8 to 47.1). Nineteen percent (16) of the 82 women had a SCID diagnosis of a PMAD. Thirty-seven percent (30) had a diagnosed adverse perinatal outcome. Multiple logistic regression was conducted with these predictors: SCID diagnosis of a PMAD, maternal age, BMI. All predictors were significant with respective odds ratios as follows: OR = 3.58, 95% CI 1.03-12.44, p = .045; OR = 2.30, 95% CI 1.21-4.38, p = .011; OR = 1.69, 95% CI 1.06-2.69, p = .027.ConclusionsA PMAD diagnosis was associated with 3.5 times higher odds of having an adverse perinatal outcome. For every 5 years a woman aged or every five units her BMI increased her odds of having an adverse perinatal outcome increased. Older age and increased BMI are well established adverse perinatal outcome risk factors. These results suggest that mental illness risk should also be consistently assessed in obstetric settings.

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to

BackgroundSynthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1-2 spot samples during pregnancy and limited diversity of populations.ObjectiveTo study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program.ResultsWhile many associations were modest and statistically imprecise, a 1-unit increase in log10 pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log10 pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: -67%, -2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: -53%, 8%).DiscussionIn a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life.

This perspective explores the transformative potential of data-driven insights to understand and address women's reproductive health conditions. Historically, clinical studies often excluded women, hindering comprehensive research into conditions such as adverse pregnancy outcomes and endometriosis. Recent advances in technology (e.g., next-generation sequencing techniques, electronic medical records (EMRs), computational power) provide unprecedented opportunities for research in women's reproductive health. Studies of molecular data, including large-scale meta-analyses, provide valuable insights into conditions like preterm birth and preeclampsia. Moreover, EMRs and other clinical data sources enable researchers to study populations of individuals, uncovering trends and associations in women's reproductive health conditions. Despite these advancements, challenges such as data completeness, accuracy, and representation persist. We emphasize the importance of holistic approaches, greater inclusion, and refining and expanding on how we leverage data and computational integrative approaches for discoveries so that we can benefit not only women's reproductive health but overall human health.

Fetal and neonatal exposures to perinatal oxidative stress (OS) are key mediators of bronchopulmonary dysplasia (BPD). To characterize these exposures, adductomics is an exposure science approach that captures electrophilic addition products (adducts) in blood protein. Adducts are bound to the nucleophilic cysteine loci of human serum albumin (HSA), which has a prolonged half-life. We conducted targeted and untargeted adductomics to test the hypothesis that adducts of OS vary with BPD. We studied 205 preterm infants (≤28 weeks) and 51 full-term infants from an ongoing birth cohort. Infant plasma was collected at birth (cord blood), 1-week, 1-month, and 36-weeks postmenstrual age. HSA was isolated from plasma, trypsin digested, and analyzed using high-performance liquid chromatography-mass spectrometry to quantify previously annotated (known) and unknown adducts. We identified 105 adducts in cord and postnatal blood. A total of 51 known adducts (small thiols, direct oxidation products, and reactive aldehydes) were increased with BPD. Postnatally, serial concentrations of several known OS adducts correlated directly with supplemental oxygen exposure. The application of large-scale adductomics elucidated OS-mediated pathways of BPD. This is the first study to investigate the "neonatal-perinatal exposome" and to identify oxidative stress-related exposure biomarkers that may inform antioxidant strategies to protect the health of future generations of infants.

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB;

IntroductionPaneth cells are critically important to intestinal health, including protecting intestinal stem cells, shaping the intestinal microbiome, and regulating host immunity. Understanding Paneth cell biology in the immature intestine is often modeled in rodents with little information in larger mammals such as sheep. Previous studies have only established the distribution pattern of Paneth cells in healthy adult sheep. Our study aimed to examine the ontogeny, quantification, and localization of Paneth cells in fetal and newborn lambs at different gestational ages and with perinatal transient asphyxia. We hypothesized that ovine Paneth cell distribution at birth resembles the pattern seen in humans (highest concentrations in the ileum) and that ovine Paneth cell density is gestation-dependent.MethodsIntestinal samples were obtained from 126-127 (preterm, with and without perinatal transient asphyxia) and 140-141 (term) days gestation sheep. Samples were quantified per crypt in at least 100 crypts per animal and confirmed as Paneth cells through in immunohistochemistry.ResultsPaneth cells had significantly higher density in the ileum compared to the jejunum and were absent in the colon.DiscussionExposure to perinatal transient asphyxia acutely decreased Paneth cell numbers. These novel data support the possibility of utilizing ovine models for understanding Paneth cell biology in the fetus and neonate.

BackgroundWidespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results.ObjectivesWe conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex.MethodsWe included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex.ResultsThree OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (β for detect vs. nondetect=0.04-0.07); other chemicals showed null associations.DiscussionIn the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

Background: As the Sustainable Development Goal 3.2.1 deadline (2030) approaches, rapidly reducing under-5 mortality (U5M) gains more prominence. However, initiatives or interventions that aided Bangladesh in achieving Millennium Development Goal 4 showed varied effectiveness in reducing certain cause-specific U5M. Therefore, this study aimed to examine the predictors of the key cause-specific mortalities. Methods: This cross-sectional study was conducted using the Bangladesh Demographic and Health Survey 2011 and 2017-18 data. Cause-specific U5M was examined using multilevel multinomial mixed-effects analyses, and overall/all-cause U5M was examined using multilevel mixed-effects analyses. The respective estimates were compared. Results: The cause-specific analysis revealed that pneumonia and prematurity-related U5M were significantly associated with antenatal care and postnatal care, respectively. However, analysis of overall/all-cause U5M did not reveal any significant association with health services. Twins or multiples had a greater risk of mortality from preterm-related conditions (adjusted Relative Risk Ratio (aRRR): 38.01, 95% CI: 19.08–75.7, p <.001), birth asphyxia (aRRR: 6.52, 95% CI: 2.51–16.91, p <.001), and possible serious infections (aRRR: 11.12, 95% CI: 4.52–27.36, p <.001) than singletons. Children born to mothers 18 years or younger also exhibited a greater risk of mortality from these three causes than children born to older mothers. This study also revealed an increase in the predicted risk of prematurity-related mortality in the 2017-18 survey among children born to mothers 18 years or younger, children born to mothers without any formal education, twins or multiples and children who did not receive postnatal care. Conclusions: This research provides valuable insights into accelerating U5M reduction; a higher risk of preterm-related death among twins underscores the importance of careful monitoring of mothers pregnant with twins or multiples through the continuum of care; elevated risk of death among children who did not receive postnatal care, or whose mothers did not receive antenatal care stresses the need to strengthen the coverage and quality of maternal and neonatal health care; furthermore, higher risks of preterm-related deaths among the children of mothers with low formal education or children born to mothers 18 years or younger highlight the importance of more comprehensive initiatives to promote maternal education and prevent adolescent pregnancy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preterm birth is the major cause of perinatal mortality both in developed and developing countries. The prevalence of preterm birth is increasing every year and it is nearly more than 15 million preterm births worldwide according to WHO, approximately one million may die and many more may suffer from neurodevelopmental impairment. Antenatal MgSO4 can prevent neonatal seizures and neonatal deaths in preterms. Aims and Objective of the study: To evaluate the use of antenatal Mgso4 for neuroprotection of preterm infants. MATERIAL AND METHODS- This study was conducted in Department of Obstetrics and Gynecology in Sree Mookambika Institute Of Medical Sciences. A total of 20 pregnant women between 28-32 weeks gestation presenting to the emergency department with abdominal pain associated with cervical dilatation (cervical dilatation > 4cm) at risk of imminent preterm delivery(delivery definitely planned within 24 hours) were given Mgso4 4gm iv for about 20-30 min followed by maintenance dose of 1gm/hr for a period of 24 hrs before delivery or upto delivery and all the preterm neonates born to the 20 women were followed up for 2 years for neonatal seizures, deaths and gross motor dysfunction. RESULTS: Antenatal MGSO4 has better role when given at 28-32 weeks of gestation as only 2 neonates (10% of total preterms) born at 32-34 weeks gestation developed neonatal seizures. CONCLUSION: When antenatal MgSO4 administered at an appropriate dose with proper monitoring, there is no evidence of harm to the fetus, neonate or mother and it helps in neuroprotection of the preterms. [ABSTRACT FROM AUTHOR]

Introduction - Preterm labour refers to the initiation of labour prior to 37 weeks and after 28 weeks of gestation, characterised by consistent uterine contractions that result in gradual cervical modifications. Urinary tract infection (UTI) is one of the several causes of preterm labour. The aim of this study is to evaluate first trimester urinary tract infection and risk of preterm labour pain. Material and methods- The present cross-sectional hospital based study was conducted at department of obstetrics and gynecology among 100 women with preterm labour pain during the study period of one year. Midstream urine samples were collected from all and culture test was performed. Results were analyzed using SPSS version 25.0 Results- Maximum patients were in the age group of 25 to 29 years (50%). 92% of them live in rural area. 70% of patients had normal urine examination and 30% were suffering from UTI. 3% of women had pyleonephritis and 97% had no complications. Organisms isolated from urine culture and sensitivity were : E.coli (68%), cogaulase negative staph (11%), S.aureus (10%), Klebsiella (6%) and GBS (5%). Conclusion – Untreated urinary tract infection (UTI) can be linked to obstetric problems and lead to preterm birth. The predominant bacterial illness that occurs during pregnancy is urinary tract infections (UTIs). It is recommended that all women undergo screening for urinary tract infections (UTIs) during their initial antenatal appointment. Upon diagnosis, it is crucial to rapidly administer an appropriate antibiotic that is both effective and safe. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between sleep stages and neural microstructure – measured using diffusion tensor imaging – of the posterior limb of the internal capsule and corticospinal tract in preterm infants. A retrospective cohort of 50 preterm infants born between 24 + 4 and 29 + 3 weeks gestational age was included in the study. Sleep stages were continuously measured for 5–7 consecutive days between 29 + 0 and 31 + 6 weeks postmenstrual age using an in-house-developed, and recently published, automated sleep staging algorithm based on routinely measured heart rate and respiratory rate. Additionally, a diffusion tensor imaging scan was conducted at term equivalent age as part of standard care. Region of interest analysis of the posterior limb of the internal capsule was performed, and tractography was used to analyze the corticospinal tract. The association between sleep and white matter microstructure of the posterior limb of the internal capsule and corticospinal tract was examined using a multiple linear regression model, adjusted for potential confounders. The results of the analyses revealed an interaction effect between sleep stage and days of invasive ventilation on the fractional anisotropy of the left and right posterior limb of the internal capsule (β = 0.04, FDR-adjusted p = 0.001 and β = 0.04, FDR-adjusted p = 0.02, respectively). Furthermore, an interaction effect between sleep stage and days of invasive ventilation was observed for the radial diffusivity of the mean of the left and right PLIC (β = −4.1e-05, FDR-adjusted p = 0.04). Previous research has shown that, in very preterm infants, invasive ventilation has a negative effect on white matter tract maturation throughout the brain. A positive association between active sleep and white matter microstructure of the posterior limb of the internal capsule, may indicate a protective role of sleep in this vulnerable population. • Active sleep positively influences white matter microstructure in preterm infants. • Interaction between sleep stages and days of invasive ventilation affects brain development. • Active sleep shows a protective role in preterm infants with longer invasive ventilation days. • Increased AS is associated with higher fractional anisotropy in the PLIC. [ABSTRACT FROM AUTHOR]

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability. We studied 379 neonates (54% male) born less than 30 weeks GA who had DNA methylation measured at neonatal intensive care unit discharge along with 3-year follow-up data. Cumulative prenatal risk was calculated from 24 risk factors obtained from maternal report and medical record and epigenome-wide neonatal DNA methylation was assayed from buccal swabs. At 3-year follow-up, child cognitive ability was assessed using the Bayley Scales of Infant and Toddler Development (third edition). Cumulative prenatal risk and DNA methylation at two cytosine–phosphate–guanines (CpGs) were uniquely associated with child cognitive ability. Using high-dimensional mediation analysis, we also identified differential methylation of 309 CpGs that mediated the association between cumulative prenatal risk and child cognitive ability. Many of the associated CpGs were located in genes (TNS3, TRAPPC4, MAD1L1, APBB2, DIP2C, TRAPPC9, DRD2) that have previously been associated with prenatal exposures and/or neurodevelopmental phenotypes. Our findings suggest a role for both prenatal risk factors and DNA methylation in explaining outcomes for children born preterm and suggest we should further study DNA methylation as a potential mechanism underlying the association between prenatal risk and child neurodevelopment. Public Significance Statement: Understanding what factors predict long-term developmental outcomes in children born less than 30 weeks gestation could help inform prevention and intervention efforts for this high-risk group. This study shows that prenatal risk factors and neonatal DNA methylation could help identify preterm children at high risk for poor cognitive outcomes at age 3 years. DNA methylation may also help explain some of the long-term effects of prenatal risk on child outcomes. [ABSTRACT FROM AUTHOR]

• PhIGFBP-1 is a promising low-cost and rapid biomarker unaffected by recent intercourse or contamination with urine. • Existing literature on this topic often treats this prognostic research question as a diagnostic research question. • In this prognostic factor meta-analysis, PhIGFBP-1 positive was found to be associated with higher odds of PTB. • When stratified by population, phIGFBP-1 positive was associated with higher odds of PTB in women with no prior PTB but not in women with risk factors for PTB. • Future research should use the prognostic research framework to address questions on this topic to maximise the clinical implications. To assess the prognostic value of cervicovaginal phosphorylated insulin-like growth factor-binding protein 1 (phIGFBP-1) to predict preterm birth in asymptomatic women during the second trimester of pregnancy. This is a systematic review and meta-analysis of prognostic factor studies. We searched MEDLINE and Embase to identify cohort studies on the prognostic value of mid-trimester phIGFBP-1 on preterm birth in asymptomatic women. We included studies with singleton and twin gestations if they did not receive treatment to reduce the risk of preterm birth. Two reviewers independently screened the titles and abstracts, evaluated full-text articles, extracted the data and performed the risk of bias assessment using the QUIPS tool. The primary outcome was preterm birth < 37 weeks' gestation. We conducted random-effects meta-analyses, with subgroup analyses on populations with different preterm birth risks. We included 17 studies with a total of 7618 participants. PhIGFBP-1 positive was associated with higher odds of preterm birth (12 studies, 7466 participants, OR 3.87, 95 %CI 1.60–9.32, I2 87 %). When stratifying by population, phIGFBP-1 positive was associated with higher odds of preterm birth in women with no prior history of preterm birth (6 studies, OR 4.43, 95 %CI 2.50–7.84) but not in women with risk factors for preterm birth (6 studies, OR 1.59, 95 %CI 0.57–4.42). Risk of bias due to confounding was high in included studies. While the prognostic value of PhIGFBP-1 in the prediction of preterm birth is a prognostic research question, it has been often treated as a diagnostic research question in the literature. PhIGFBP-1 may be a potential biomarker to predict PTB during mid-trimester in asymptomatic women, especially for women with low risk of PTB. However, the clinical value of phIGFBP-1 remains limited due to bias in confounding. Future research should use the prognostic research framework to address such questions on biomarkers to maximise the clinical implications. [ABSTRACT FROM AUTHOR]

• A greater volume and duration of prenatal exercise are associated with longer gestational length, improved neonatal health at birth, and reduced infant hospital stay in preterm deliveries. • Aiming for the recommended level of prenatal exercise dose is critical to improve neonatal health outcomes, even in preterm pregnancies. Preterm delivery typically increases health risk for neonates and is associated with longer infant hospital stay and financial burden. Prenatal exercise dose (frequency, intensity, type, time, volume) have been shown to influence birth outcomes. Increased prenatal exercise dose could therefore provide a critical reduction in health risk and financial burden in preterm neonates. It was our aim to explore the effects of prenatal exercise dose from a supervised exercise intervention in pregnant women on the occurrence of preterm (<37 weeks gestation) births, and the impact on health outcomes in preterm neonates. This study is a retrospective, secondary analysis of pooled data from three blinded, prospective, randomized controlled trials. Prenatal exercise dose were assessed in supervised aerobic, resistance, and combination sessions throughout pregnancy. In addition to gestational age, birth weight, resting heart rate, neonatal morphometrics (body circumferences, ponderal index), and health status (Apgar-1 and −5) metrics were obtained for 21 women at birth. One-way analysis of variance tests were used to assess the differences between dose grouped as tertiles, while Pearson correlations determined the association between dose and birth outcomes. Women exercised for an average of 19.6 wks (range: 6 – 21 wks) during pregnancy. Exercise during pregnancy tended to result in later preterm deliveries (p = 0.08). Greater prenatal exercise volume and duration were associated with reduced infant hospital stay post-delivery (p = 0.02). Weekly exercise volume was associated with increased Apgar scores (p = 0.01). Increased prenatal exercise volume and duration is associated with improved birth outcomes in preterm neonates. [ABSTRACT FROM AUTHOR]

To assess prescribing practices and perspectives regarding the use of corticosteroids in the management of neonatal hypotension. Cross-sectional questionnaire-based electronic survey of neonatologists (n = 206) practicing at tertiary neonatal intensive care units across 30 academic centres in Canada. The overall response rate was 33% (72/206), with a completion rate was 94%. Most (48/72, 64%) worked in a unit that covered both inborn and outborn infants, and 53% (37/70) worked in units with >100 very low birth weight infants admitted annually. Among the 72 respondents, 39% use a loading dose, of whom most (57%) use 2 mg/kg. Dosing ranges were variable, most using either 0.5 mg/kg or 1 mg/kg, q6h. Among the 56% (40/72) of neonatologists who reported measuring cortisol before initiation of hydrocortisone, cut-offs for initiation of hydrocortisone varied from <100 to <500 nmol/L, most of whom (48%) used <100 nmol/L. Of 71 respondents, 92% (65) indicated that a randomized control trial examining the use of corticosteroids in neonatal hypotension is needed, of whom 52% (37) indicated that the intervention group should receiving hydrocortisone after one vasopressor/inotrope. This survey provides insight into the prescribing practices of tertiary neonatologists with regards to the use of corticosteroids in neonatal hypotension. While corticosteroids are frequently prescribed, there is variability in the indication, dosing, and duration of corticosteroid use. The findings from this survey can be used to inform further research, including a clinical trial, regarding the practice in the management of neonatal hypotension. [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: To establish neonatal pain management practices as an essential developmental supportive measure at a tertiary care unit. Methods: This quality improvement initiative was conducted as per Point-of-Care-Quality-Improvement Model over 6 mo, followed by 2 y of sustenance phase at a Neonatal Intensive Care Unit (NICU) in northern India. Infants of birth weight ≤1800 g were included and assessed for pain. Pain Assessment and Management Practices via Education and Reinforcement (PAMPER) group was created by resident doctors and nursing staff. The Premature Infant Pain Profile score was used for the assessment of pain. Limiting factors were analyzed using a fishbone diagram and interventions were done in multiple Plan-Do-Study-Act cycles. Results: At the end of interventions, 100% of procedures were assessed for pain. The mean (standard deviation) documented pain score for the first seven days was reduced from 12.8 (0.3) in the baseline phase to 7 (2.5). These interventions helped to sustain the practice in >70% of infants in the next 2 y. Conclusions: Low-cost interventions improved the pain assessment and management policy of authors' NICU with the establishment of a standard protocol. Audits and reinforcement at regular intervals helped in its long-term sustenance. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionsto assess the changes in the macular structure in children with history of prematurity and to find the relationship between retinopathy of prematurity (ROP) treatment and macular ultrastructural changes found in optical coherence tomography angiography study.a search for identifying relevant studies published in English using PubMed, Google Scholar, Scopus, and Web of Science databases from the date of inception to 21 October 2022 was conducted. Studies were included if their subjects were >5 years and used Optovue device for imaging. Twelve studies were included for final analysis. After extracting data, foveal avascular zone (FAZ), vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the foveal and parafoveal area, central foveal thickness (CFT), and visual acuity (VA) were compared between the study groups.in individual who were born full term the FAZ was significantly larger. The SCP and DCP VD was significantly higher in children with history of ROP treatment. Superficial parafoveal VD was significantly lower in term children than both treated groups. The CFT was significantly higher in children with history of ROP (treated and untreated) than the terms. VA was lower in laser and IVI treated children than terms and it was related to the changes in CFT, foveal superficial and deep VD and FAZ area.Patients with a history of ROP treatment have a significantly greater CFT, higher VD of foveal SCP and DCP, and lower VA than the term-born children. Furthermore, the FAZ is negatively associated with VA and CFT. [ABSTRACT FROM AUTHOR]

Background: Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks' gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. Methods: Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. Results: Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration ("Prion Disease", "Alzheimer's Disease", "Arachidonic Acid metabolism"). Adverse changes were independent of respiratory function during ventilation. Conclusions: Our data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens. [ABSTRACT FROM AUTHOR]

The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (< 30 weeks gestation; VPT), as they experience a significant disruption in the normal developmental trajectories and are at heightened risk of experiencing developmental impairments and delays. Variations in the epigenetic landscape during this period may reflect this disruption and shed light on the interrelationships between aging, maturation, and the epigenome. We evaluated how gestational age (GA) and age since conception in neonates [post-menstrual age (PMA)], were related to DNA methylation in buccal cells collected at NICU discharge from VPT infants (n = 538). After adjusting for confounders and applying Bonferroni correction, we identified 2,366 individual CpGs associated with GA and 14,979 individual CpGs associated with PMA, as well as multiple differentially methylated regions. Pathway enrichment analysis identified pathways involved in axonogenesis and regulation of neuron projection development, among many other growth and developmental pathways (FDR q < 0.001). Our findings align with prior work, and also identify numerous novel associations, suggesting that genes important in growth and development, particularly neurodevelopment, are subject to substantial epigenetic changes during early development among children born VPT. [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]

Introduction: Many survivors of preterm birth (<37 weeks gestation) have lifelong respiratory deficits, the drivers of which remain unknown. Influencers of pathophysiological outcomes are often detectable at the gene level and pinpointing these differences can help guide targeted research and interventions. This study provides the first transcriptomic analysis of primary nasal airway epithelial cells in survivors of preterm birth at approximately 1 year of age. Methods: Nasal airway epithelial brushings were collected, and primary cell cultures established from term (>37 weeks gestation) and very preterm participants (≤32 weeks gestation). Ex vivo RNA was collected from brushings with sufficient cell numbers and in vitro RNA was extracted from cultured cells, with bulk RNA sequencing performed on both the sample types. Differential gene expression was assessed using the limma-trend pipeline and pathway enrichment identified using Reactome andGOanalysis. To corroborate gene expression data, cytokine concentrations were measured in cell culture supernatant. Results: Transcriptomic analysis to compare term and preterm cells revealed 2,321 genes differentially expressed in ex vivo samples and 865 genes differentially expressed in cultured basal cell samples. Over one third of differentially expressed genes were related to host immunity, with interferon signalling pathways dominating the pathway enrichment analysis and IRF1 identified as a hub gene. Corroboration of disrupted interferon release showed that concentrations of IFN-α2 were below measurable limits in term samples but elevated in preterm samples [19.4 (76.7) pg/ml/μg protein, p = 0.03]. IFN-γ production was significantly higher in preterm samples [3.3 (1.5) vs. 9.4 (17.7) pg/ml/μg protein; p = 0.01] as was IFN-β [7.8 (2.5) vs. 13.6 (19.5) pg/ml/μg protein, p = 0.01]. Conclusion: Host immunity may be compromised in the preterm nasal airway epithelium in early life. Altered immune responses may lead to cycles of repeated infections, causing persistent inflammation and tissue damage which can have significant impacts on long-term respiratory function. [ABSTRACT FROM AUTHOR]

Introduction: Foot length is quite simple as a proxy parameter, can be measured easily by a well calibrated ruler or tape and does not require much expertise which can help for early identification of preterm and low birth weight babies at the rural setup and early reference of high risk babies to higher centers to help in decreasing neonatal mortality and morbidity. This study has done to find a correlation between foot length, birth weight and gestational age assessed by various methods in both preterm and term babies and the utility of newborn foot length as screening tool to identify preterm babies. Material and Methods 400 newborn babies within 48 hours of birth whose mothers with documented LMP and dating USG done at 1st trimester were included in this study. Foot length was measured using sliding calipers which is having an accuracy of a millimeter. Results The preterm neonates had a mean foot length of 6.75, 6.46 and 7.28 cms, respectively. The mean foot length for term neonates was 7.65, 7.25 and 8.12 cms, respectively. It was observed that the foot length correlated significantly (p<0.05) with gestational age in all maturity groups. There was a significant positive correlation observed between gestational age as determined by all methods like USG, LMP and New Ballard Score and average foot length. [ABSTRACT FROM AUTHOR]

Introduction: Surfactant therapy has revolutionized the management of respiratory distress syndrome (RDS) in preterm neonates, significantly improving outcomes for this vulnerable population. When assessing the need for surfactant in preterm infants, especially those whose mothers received antenatal steroids, it is crucial to understand the interplay between these two interventions. Antenatal corticosteroids are known to enhance fetal lung maturation and reduce the incidence and severity of RDS. However, despite this benefit, some preterm infants still develop RDS, potentially necessitating surfactant administration. This article explores the factors influencing surfactant requirements in preterm neonates whose mothers have undergone antenatal steroid therapy, aiming to clarify the role of surfactant in this context and optimise neonatal care strategies. Aim and objective: To access the need of surfactant in preterm babies whose mother received antenatal steroids. Material and methods: The present observational study was conducted in Paediatric outpatient department of Acharya Shri Chander College of Medical Sciences and Hospitals and included a total of 121 babies who were delivered in the hospital over a period of three months, w.e.f. 1st April, 2024 to 31st June, 2024. The data was collected with the help of a structured clinical pro-forma. The collected data was recorded in Microsoft Excel sheet and statistical analysis was done with the help of SPSS version 21.0. Result: In our study, a total of 121 babies were delivered to 109 women in the study period with 97 singleton, 12 twins and no triplet or quadruple deliveries. All records were available and retrieved within the study period where only 43 babies were delivered prematurely between 26 weeks to 34 weeks and the majority of the babies 27 were born at 32-34 weeks of gestation (62.8%), followed by 14 babies were delivered at 28-32 weeks (32.6%), followed by 2 were delivered between 26-28 weeks (4.6%). Out of 43 babies, 24 babies (55.8%) were exposed to full course of dexamethasone antenatally and 7 babies (16.3%) received single dose of antenatal corticosteroids and remaining 12 babies (27.9%) were delivered prematurely didn’t receive antenatal corticosteroids. There was no baby who received a repeat course of antenatal corticosteroids. And it was found that out of 24 babies who received full course of antenatal corticosteroids developed respiratory distress and 18 required surfactant administration and rest 6 babies were managed only on CPAP mode of ventilation. Conclusion: The present study concludes reinforced the rationale behind the common practice of giving antenatal corticosteroids in preterm birth and also demonstrated the decrease in respiratory distress syndrome and use of surfactant for lung compliance. [ABSTRACT FROM AUTHOR]

Objective: To determine the etiology, risk factors and antibiotic resistance in neonatal sepsis. Study Design: Cross-sectional study. Setting: Department of Pediatric Medicine, National Institute of Child Health, Karachi, Pakistan. Period: October 2023 to March 2024. Methods: A total of 174 neonates of both genders, with suspected neonatal sepsis were analyzed. Neonatal and maternal characteristics were noted. Blood sample was collected in aseptic environment and sent to institutional laboratory for blood culture and drug susceptibility testing. Results: In a total of 174 neonates, 101 (58.0%) were boys. The mean age, and weight were 9.61±7.86 years, and 2.25±0.85 kg, respectively. Neonatal sepsis on the basis of positive blood culture was reported in 38 (21.8%) neonates. Preterm birth had significant association with neonatal sepsis (44.7% vs. 26.5%, p=0.019). History of maternal UTI during pregnancy had significant linkage with neonatal sepsis (36.8% vs. 11.0%, p<0.001). History of maternal fever during pregnancy had statistically significant association with neonatal sepsis (34.2% vs/ 19.1%, p=0.049). E. Coli, and Klebsiella were the most commonly found bacterial isolates, noted in 8 (21.1%), and 4 (10.5%) neonates, respectively. Most commonly used antimicrobial drugs were found to have high resistance rates against most frequent bacterial isolates. Conclusion: E. Coli, and Klebsiella were the most commonly found bacterial isolates in neonatal sepsis. Preterm birth, maternal history of UTI, and maternal history of fever were found to be significant factors linked to neonatal sepsis. Most commonly used antimicrobial drugs were found to have high resistance patterns which should raise alarms. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether there is an association between the gestational age at the onset of preeclampsia in recurrent cases and the gestational age at the onset of preeclampsia in previous pregnancies. Methods: This retrospective nested case–control study was designed to investigate whether gestational age at diagnosis and at delivery in recurrent cases of preeclampsia correlates with gestational age at diagnosis and delivery in the previous cases of preeclampsia in the same individuals. The database of a Ukrainian research network was used to find patients with the diagnosis of preeclampsia between 2019 and 2021. The database was further queried to identify those with a history of preeclampsia in a previous pregnancy. The comparison was made using the Pearson correlation coefficient. Results: One hundred and three patients who were diagnosed with preeclampsia were identified. Of those, 15 had recurrent preeclampsia, 2 of whom had preeclampsia in 2 previous pregnancies. There was no statistically significant correlation: based on gestational age at delivery R = − 0.28 (P = 0.30; 95% confidence interval (− 0.69 to 0.28) and based on gestational age at the time of diagnosis R = − 0.14 (P = 0.62; − 0.60 to 0.41). Conclusion: Our data do not find an association between the gestational age of recurrent preeclampsia and preeclampsia diagnosed in a previous pregnancy. This supports the idea that there is single pathogenesis for preeclampsia regardless of the gestational age. It suggests that there are variations in the course of preeclampsia that may be determined by the capacity of the compensatory mechanisms. [ABSTRACT FROM AUTHOR]

• Prenatal docosahexaenoic acid (DHA) supplementation at doses 450-800 mg/day led to significantly higher infant birth weights. • The study indicates a trend towards a reduced risk of preterm births with DHA supplementation. • The finding suggests DHA may support full-term pregnancies, reducing the likelihood of premature delivery. • Quality assessment of the included studies revealed a low risk of bias. This study aimed to investigate the effects of prenatal docosahexaenoic acid (DHA) supplementation on pregnancy outcomes through a systematic review and meta-analysis. We hypothesized that prenatal DHA intake through supplements will improve pregnancy outcomes. Detailed literature search was performed using online databases such as PubMed, EMBASE, and Google Scholar till November 2022, to identify the randomized controlled trials (RCT) with maternal intake of DHA supplementation during the latter half of pregnancy compared to the placebo/control. Based on the inclusion and exclusion criteria, nine RCTs involving 5710 subjects were included. This meta-analysis showed that DHA supplementation (450-800 mg/day) was associated with a significantly higher birth weight of infants (Inverse variance [IV]: 101.71 [57.36-146.06] at 95% CI, P =.00001, I2 = 0%), and fewer low birth weights (LBWs) (Mantel–Haenszel [M–H]: 0.53 [0.33-0.86] at 95% CI, P =.01, I2 = 72%), with lesser but statistically insignificant pre-term births (PTB) (M–H: -0.02 [-0.04 to 0.00] at 95% CI, P =.07, I2 = 0%) compared to the placebo. However, the DHA supplementation has no effect on gestational length (IV: -2.26 [-9.64 to 5.12] at 95% CI, P =.55, I2 = 100%) compared to the placebo. In conclusion, the outcomes of this meta-analysis showed that prenatal DHA supplementation (450-800 mg/day) may reduce the risk of preterm births and increase infant birth weight. "A meta-analysis of studies investigating DHA and pregnancy revealed that DHA supplementation at dose 450-800 mg/day has significantly reduced the risk of preterm births and increased infant birth weight." (Abbreviation: DHA—Docosahexaenoic acid) [Display omitted] [ABSTRACT FROM AUTHOR]

The quality of cranial ultrasound has improved over time, with advancing technology leading to higher resolution, faster image processing, digital display, and back-up. However, some brain lesions may remain difficult to characterize: since higher frequencies result in greater spatial resolution, the use of additional transducers may overcome some of these limitations. The very high-frequency transducers (18-5 MHz) are currently employed for small parts and lung ultrasound. Here we report the first case series comparing the very high-frequency probes (18-5 MHz) with standard micro-convex probes (8-5 MHz) for cranial ultrasound in preterm infants. In this case series, we compared cranial ultrasound images obtained with a micro-convex transducer (8-5 MHz) and those obtained with a very high-frequency (18-5 MHz) linear array transducer in 13 preterm infants ≤ 32 weeks gestation (9 with cerebral abnormalities and 4 with normal findings). Ultrasound examinations using the very high-frequency linear transducer and the standard medium-frequency micro-convex transducer were performed simultaneously. We also compared ultrasound findings with brain MRI images obtained at term corrected age. Ultrasound images obtained with the very high-frequency (18-5 MHz) transducer showed high quality and accuracy. Notably, despite their higher frequency and expected limited penetration capacity, brain size is small enough in preterm infants, so that brain structures are close to the transducer, allowing for complete evaluation. Conclusion: We propose the routine use of very high-frequency linear probes as a complementary scanning modality for cranial ultrasound in preterm infants ≤ 32 weeks gestation. What is Known: • Brain lesions in preterm infants may remain insufficiently defined through conventional cranial ultrasound scan. • Higher frequency probes offer better spatial resolution but have a narrower filed of exploration and limited penetration capacity. What is New: • Very high-frequency probes were compared with standard medium-frequency probes for cranial ultrasound in infants ≤ 32 weeks' gestation. • Thanks to the smaller skull size of preterm infants, the new very high-frequency transducers allowed a complete and accurate evaluation. [ABSTRACT FROM AUTHOR]

While neonatal necrotising enterocolitis (NEC) is associated with high mortality rates in newborns, survivors can face long-term sequelae. However, the relationship between NEC and neurodevelopmental impairment (NDI) in preterm infants remains unclear. To explore the relationship between neonatal NEC and neurodevelopmental outcomes in preterm infants, we searched PubMed, EMBASE, and the Cochrane Library from their inception to February 2024 for relevant studies. Studies included were cohort or case–control studies reporting neurodevelopmental outcomes of NEC in preterm infants. Two independent investigators extracted data regarding brain damage and neurodevelopmental outcomes in these infants at a corrected age exceeding 12 months. Odds ratios (ORs) were pooled using a random effects model. We included 15 cohort studies and 18 case–control studies, encompassing 60,346 infants. Meta-analysis of unadjusted and adjusted ORs demonstrated a significant association between NEC and increased odds of NDI (OR 2.15, 95% CI 1.9–2.44; aOR 1.89, 95% CI 1.46–2.46). Regarding brain injury, pooled crude ORs indicated an association of NEC with severe intraventricular haemorrhage (IVH) (OR 1.42, 95% CI 1.06–1.92) and periventricular leucomalacia (PVL) (OR 2.55, 95% CI 1.76–3.69). When compared with conservatively treated NEC, surgical NEC potentially carries a higher risk of NDI (OR 1.78, 95% CI 1.09–2.93) and severe IVH (OR 1.57, 95% CI 1.20–2.06). However, the risk of PVL did not show a significant difference (OR 1.60, 95% CI 0.47–5.40). Conclusions: Our meta-analysis provides evidence suggesting an association between NEC and NDI. Additionally, the severity of intestinal lesions appears to correlate with a higher risk of NDI. Further high-quality studies with comprehensive adjustments for potential confounding factors are required to definitively establish whether the association with NDI is causal. What is Known: • NEC is a serious intestinal disease in the neonatal period with a high mortality rate, and surviving children may have digestive system sequelae. • Compared with non-NEC preterm infants, the reported incidences of brain injury and neurodevelopmental disorders in NEC preterm infants are not the same. What is New: • The risk of neonatal brain injury and neurodevelopmental disorders in preterm infants with NEC is higher than that in non-NEC infants, and the risk of NDI in surgical NEC infants is higher than that in the conservative treatment group. • NEC may increase the risk of motor, cognitive, language development delays, and attention deficits in children. [ABSTRACT FROM AUTHOR]