Results show that increases in residential greenspace correspond with higher birthweight  among Black, but not white , infants. Additional analyses suggest that prior evidence of perinatal benefits associated with residential greenspace among white mothers may arise from residential selection; no such bias is observed for Black mothers. Taken together, these findings support urban greening initiatives in historically under-resourced neighborhoods. Efforts to evenly distribute residential greenspace may reduce persistent racial disparities in birth outcomes, an important step towards promoting health equity across the life course.Growing research investigates the perinatal health benefits of greenspace in a mother’s prenatal environment. However, evidence of associations between residential greenspace and birth outcomes remains mixed, limiting the relevance this work holds for urban policy and greening interventions. Past research relies predominantly on cross-sectional designs that are vulnerable to residential selection bias, and rarely tests effect modification by maternal race/ethnicity, which may contribute to heterogeneous findings. This study uses a rigorous, longitudinal sibling comparison design and maternal fixed effect analyses to test whether increases in maternal exposure to residential greenspace between pregnancies precede improved birth outcomes among non-Hispanic (NH) white ( In the US, the incidence of adverse birth outcomes including preterm birth (PTB) and low birthweight (LBW) exceed those of all other high-income countries. PTB and LBW—defined as delivery at less than 37 weeks of gestational age and birthweight of less than 2500 g—increase infant mortality risk, impair childhood development, reduce earnings and educational attainment into adulthood, and impose substantial hospital-based obstetric costs ,2,3. GivResearch on PTB, LBW, and other perinatal health outcomes  indicates complex etiologies that involve interactions between individual biological and behavioral factors and environmental conditions ,2,5. GroHowever, evidence on associations between residential greenspace and birth outcomes appears mixed. Inconsistent findings limit the relevance this work holds for policies and interventions that aim to improve urban greenspace and, ultimately, promote perinatal health in under-resourced neighborhoods. Researchers have proposed plausible explanations for equivocal results, including that: (1) maternal characteristics associated with both place of residence and perinatal health may explain positive associations between greenspace and birth outcomes ,14 and , which further controlled for unobserved maternal characteristics, no longer rejected the null. Taken together, these findings suggest that differential selection into greener neighborhoods among mothers with lower risks of adverse birth outcomes may explain past findings on greenspace and perinatal health .Alternate explanations for inconsistent findings include that individual factors may modify associations between residential greenspace and birth outcomes. Race/ethnicity, income, and education (among other characteristics) may influence a mother’s ability to access and use green spaces in the residential environment to improve health. The racial, ethnic, and socioeconomic composition of a study sample may thus influence the direction or magnitude of associations between greenspace and perinatal health, producing heterogeneous results . SupportSome work suggests that maternal race/ethnicity may also modify associations between neighborhood greenspace and perinatal health. Although empirical evidence remains mixed, research documents plausible pathways through which greenspace may differentially improve birth outcomes among racially minoritized mothers ,40,41,42At least one prior study found that race/ethnicity modifies the association between residential greenspace and birth outcomes. Using cross-sectional data in the UK, Dadvand et al.  showed tThis study examines racial/ethnic differences in longitudinal associations between residential greenspace and birth outcomes, including infant birthweight and SGA, among siblings born in California between 2005 and 2015. I use several analytic strategies with increasing levels of rigor to investigate potential residential selection bias ,14 and sI hypothesized that, in cross-sectional analyses adjusted for observed maternal and neighborhood characteristics, residential greenspace would correspond with higher birthweight and lower odds of SGA among all racial/ethnic subgroups. However, I predicted that sibling comparison  analyses, which further control for unobserved time-invariant characteristics of mothers , would show protective effects of greenspace on births only among NH Black mothers. Moreover, I expected the results of maternal fixed effects analyses to hold for mothers who did not move between births, such that within-neighborhood increases in residential greenspace would precede higher birthweight and lower odds of SGA among NH Black mothers.I retrieved data on all live births in California (CA) between January 2005 and December 2015 from the California Department of Public Health (CDPH) Birth Cohort Files (BCFs). The CA BCF contains data recorded from the US Standard Certificate of Birth, including maternal and infant health and demographic characteristics, for more than 99.99% of births in California. The CA BCF also includes information on mothers’ residential addresses at the time of birth, which I geocoded and linked to census tract-level measures of greenspace and disadvantage (described below). CDPH records the race  and ethnicity  of the mother, which I used to classify into the following categories, consistent with the literature: non-Hispanic (NH) white, Black, Hispanic, Asian, and ‘other’ . The State of California and the University of California, Irvine, approved the study .n = 185,930). I also excluded birth records missing data on the mother’s date of birth (n = 2183), last name , and first name (n = 2934) as I required this information to match siblings delivered by the same mother. To develop the sibling linkage algorithm , an open-source probabilistic record linkage program developed by the Division of Cancer Prevention within the Centers for Disease Control and Prevention (CDC). The CA BCFs for the years 2005 to 2015 include records for 5,814,502 live births. I excluded records of non-singleton birth events, given that multiple births interfere with the sibling linkage process . Urban areas, according to the Census Bureau, encompass densely settled neighborhoods comprising at least 50,000 residents. Based on this definition, many neighborhoods typically identified as suburbs are also categorized as urban . This distinction is substantively relevant, as relations between greenspace and health (including birth outcomes) appear to differ by urbanicity, with more protective associations generally observed in urban areas. Elevated exposure to psychosocial and environmental stressors—risk factors that greenspace may mitigate—could explain the stronger effects of greenspace among urban populations [The CA BCF includes data on mothers’ addresses, zip codes, and city of residence. I geocoded maternal residential addresses at the time of each birth  to derive latitude and longitude point coordinates using ArcGIS software version 10.4 . I located addresses using a 2013 street directory and joined point coordinates with census tracts, a proxy for neighborhoods, based on 2010 US Census geography. I excluded sibling pairs if the maternal residential address provided in one or both sibling birth records did not reach a minimum location match score of 80%; with unknown, missing, or non-California census tracts; or if mothers lived in non-urban tracts  Normalized Difference Vegetation Index (NDVI) remote sensing product . The NDVI elected to include satellite images captured during the full calendar year to generate mean NDVI values, given that California (which is characterized by a Mediterranean-like climate) exhibits relatively little within-region variation in vegetation across different seasons. By contrast, as the third largest US state by area, California shows considerable between-region variation in vegetation . The cenNeighborhood Disadvantage. I merged individual-level data and measures of neighborhood greenspace with a census tract-level measure of neighborhood disadvantage. Consistent with past work, I calculated an index of neighborhood disadvantage using six variables retrieved from the 2010 U.S. Decennial Census: the proportion of households with income < USD 15,000, the proportion of households with income ≥ USD 50,000 (reverse coded), the proportion of families in poverty, the proportion of households receiving public assistance, the total unemployment rate, and the proportion of vacant housing units  . I standSociodemographic Characteristics. The CA BCFs for the years 2005 to 2015 include information on the demographic and socioeconomic characteristics of the mother. In addition to maternal race and ethnicity (described above), CDPH collects data on maternal age , previous live births , highest educational attainment , and insurance provider . This set of time-varying sociodemographic characteristics represent potential confounders as they may influence both a mother’s residential exposure to greenspace and her birth outcomes. As such, these measures were included as covariates in adjusted analyses .Birth Outcomes. Outcomes analyzed in the main text of this study include (1) birthweight in grams (g), a continuous variable, and (2) small-for-gestational age (SGA), a binary variable. I retrieved data on birthweight and gestational age at birth based on the last menstrual period from birth certificates. SGA gauges infant growth restriction while adjusting for the timing of parturition. To derive SGA, I used sex- and gestational-week-specific US national reference charts for birthweight to classify each infant birth into corresponding birthweight percentiles . I then n = 433,079); stayers remained in the same census tract across births , although they could have moved within the tract. The types of changes in greenspace that movers and stayers experience generally differs: movers experience between-neighborhood changes in greenspace (induced by moving to a new neighborhood) while stayers experience within-neighborhood changes in greenspace .Movers and Stayers. I defined movers as mothers whose census tract changed between their first and second birth  and separately for NH white, Black, Hispanic, and Asian mothers using two primary approaches. I initially performed cross-sectional analyses to examine relations between residential greenspace and birth outcomes . Next, I leveraged longitudinal data on a mother’s first and second births and used a ‘within-mother’  approach to estimate the effects of changes in greenspace on birth outcomes.In contrast to cross-sectional analyses, maternal fixed effects models include a mother-specific indicator variable to control for time-invariant characteristics of the mother . These aFor all models, I first estimated associations between neighborhood greenspace and birth outcomes in the full analytic sample of mothers  with at least two births in California between 2005 and 2015. I then stratified analyses by race/ethnicity to assess greenspace–birth outcome relations separately for NH white, Black, Hispanic, and Asian mothers. I used linear regression models to estimate associations between NDVI (modeled continuously) and birthweight (g) and logistic regression models to estimate associations between NDVI (modeled as quartiles) and the odds of SGA, PTB, and LBW. All statistical analyses were performed in SAS version 9.4 .Model 1 assessed the unadjusted association between residential greenspace and birth outcomes at time 2 . Model 2 controlled for individual- and neighborhood-level covariates that could affect both residential greenspace and birth outcomes, including maternal age, education, parity, insurance status, and neighborhood disadvantage, as well as the year of birth (to control for secular trends). Model 3 used a pooled cross-sectional approach to assess relations between residential greenspace and birth outcomes among siblings born at time 1  and time 2  in the within-mother sample. Given that these analyses include multiple births to the same mother, I clustered standard errors by mother and, building on Model 2, adjusted for year of birth and individual- and neighborhood-level covariates. However, unlike the longitudinal within-mother analyses described below, Model 3 does not control for unobserved time-invariant maternal characteristics.All within-mother analyses included a mother-specific indicator variable to control for time-invariant maternal characteristics and included birth data for both siblings. Model 4 examined the within-mother association between changes in residential greenspace and birth outcomes among siblings, adjusted for time-varying individual and neighborhood characteristics . Models 5 and 6 restricted within-mother analyses to mothers who remained in the same neighborhood (stayers) and mothers who moved to a different neighborhood (movers) between births, respectively.n = 922,263); the ‘stayers only’ sample (right column) shows the characteristics of mothers within the full sample who remained in the same neighborhood across births. Both the full within-mother sample and the restricted stayers only sample include mothers from racially and socioeconomically diverse backgrounds. Most mothers in the full sample    B and NH  54,995) C and theConsistent with my hypothesis, maternal fixed effects analyses B compariModels estimating associations between neighborhood greenspace (in quartiles) and SGA show a different pattern of results  than thoGrowing epidemiologic work has examined whether greenspace in a mother’s residential environment during pregnancy reduces her risk of an adverse birth outcome, but results appear mixed ,30,31. RPast findings on the associations between residential greenspace and perinatal health do not converge, with some studies showing more favorable birth outcomes among mothers residing in greener neighborhoods ,33 and oin utero [Contrary to my hypothesis, results on within-mother associations between neighborhood greenspace and SGA, a birth outcome that adjusts for gestational length and gauges infant growth restriction, cannot reject the null. Findings indicate that increases in greenspace may affect birthweight but not the timing of parturition, cohering with some past studies . Reducedin utero . The finThis study advances a small but growing body of research examining heterogeneity in relations between neighborhood greenspace and birth outcomes using maternal sociodemographic characteristics ,40,41,42Given the substantial correlation between low SES and minoritized racial/ethnic identity in the US, socioeconomic characteristics—and not race, per se—may explain the observed protective associations between greenspace and Black births ,38. DescThe current study diverges from past cross-sectional studies of associations between greenspace and perinatal health in several key ways. First, a principal strength of this analysis involves the use of longitudinal data and maternal fixed effects to control for time-invariant maternal characteristics that may confound greenspace–birth outcome associations. Consistent with prior work ,30, I inAnother strength of this study includes the use of the California birth files for years 2005 to 2015 to provide a large and racially diverse sample of mothers. This sample was sufficient to permit theoretically motivated tests of race/ethnicity-specific differences in greenspace–birth outcome associations. Importantly, the analytic sample included over 50,000 NH Black women, who, in the US, exhibit the highest rates of adverse birth outcomes compared to all other racial/ethnic subgroups. Well-documented risk factors for adverse birth outcomes—including exposure to environmental hazards  and heightened stress during pregnancy—disproportionately affect NH Black women ,46. EvidLimitations of this study include a lack of information on the mechanisms by which neighborhood greenspace affects birth outcomes. In addition to reducing stress and improving environmental conditions, research indicates that neighborhood greenspace may increase physical activity and social contacts  ,11. GiveAnother primary limitation of this study includes the use of a home-based, census tract-level measure of residential greenspace, rather than a buffer-based approach . The neighborhood-level measure used in this study may misrepresent the true spatial context through which greenspace influences perinatal health. Measuring greenspace within smaller, buffer-based units around a mother’s home may yield more accurate estimates of greenspace–birth outcome associations. Relatedly, the modifiable areal unit problem (MAUP) ,69, whicTo this end, a shift away from home-based measures and towards mobility-based measures may improve our understanding of whether and how greenspace exposure affects health in the context of everyday life . For exaFinally, this study does not consider the processes through which greenspace changes within a neighborhood over time. As discussed, residential selection may threaten internal validity in studies that rely on cross-sectional data or changes in greenspace induced by moving, as residents may ‘select’ neighborhoods according to preexisting health or social factors ,14. By cInconsistent findings on associations between neighborhood greenspace and birth outcomes may derive from residential self-selection bias in cross-sectional studies or effect modification by maternal sociodemographic characteristics. This study overcomes limitations of previous work by using longitudinal data to analyze within-mother associations between changes in greenspace and birth outcomes overall and by maternal race/ethnicity. Results controlling for unmeasured maternal confounders show that infant birthweight increases among deliveries to NH Black but not NH white, Hispanic, or Asian mothers who experience increases in neighborhood greenspace. These results remain robust to analysis in a restricted sample of mothers who stay in the same neighborhood but experience within-neighborhood changes in greenspace between pregnancies. Such changes more closely mimic, from a methodological perspective, a quasi-experimental design, and, from an applied perspective, a neighborhood-level intervention. These findings suggest that greening initiatives that target historically under-resourced and racially minoritized neighborhoods may reduce persistent racial disparities in birth outcomes, an important step towards promoting health equity across the life course. The replication of results in different study populations and contexts is needed to corroborate the novel evidence presented in this study.


Pre-eclampsia is a pregnancy-related hypertensive disorder with maternal and neonatal complications. Many studies are done regarding the prevalence of pre-eclampsia in Nepal but ascertaining the maternal risk factors and fetal outcomes are important. The aim of this study was to find out the prevalence of pre-eclampsia among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care centre.A descriptive cross-sectional study was conducted among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care hospital from 13 July 2023 to 29 September 2023 after obtaining ethical approval from the Institutional Review Committee. Convenience sampling method was used. Point estimate was calculated at a 95% Confidence Interval.Among 5065 patient, pre-eclampsia was seen in 44 (0.87%) . A total of 16 (36.36%) cases of pre-eclampsia were in the age group 25-29 years and 30 (68.18%) of them were nulliparous. A total of 38 (86.36%) of the newborns of the pre-eclamptic cases had low birth weight. The APGAR score of newborns at the 1 minute after birth was 26 (59.09%) followed by the newborns who needed re-evaluation 16 (36.36%). The APGAR score recorded at 5 minutes showed maximum newborns with normal APGAR score 40 (90.90%).The prevalence of pre-eclampsia among pregnant women was found to be lower than other studies done in similar settings. The non-digitalised hospital records of maternity cases within a duration of 17 months from April 2022 onwards were obtained from the hospital record section after getting ethical approval from the Institutional Review Committee (Reference number: 07(6-11)E-2 080/081). The maternity cases of Nepali origin with no missing information were included. A convenience sampling method was used. The sample size was calculated with the following formula.Where,n = minimum required sample sizeZ = 1.96 at 95% Confidence Interval (CI)p = prevalence taken as 50% for maximum sample size calculationq = 1-pe = margin of error, 2%The calculated minimum required sample size was 2401. After doubling, sample of 4802 was calculated. However, a total of 5065 maternity cases were included in the study.6 The appearance, pulse, grimace, activity and respiratory parameters were scored at 1 and 5 minutes respectively after birth.The study variables were maternal age and parity as risk factors for pre-eclampsia and the fetal viability, birth weight and APGAR scores were considered as fetal outcomes. The parity among the cases was again classified as nulliparous, primiparous and multiparous. The fetal viability was classified as dead or alive newborns; the birth weight of newborns was classified as low birth weight (<2.5 kg), high birth weight (>4 kg) and in between as normal birth weight. The APGAR score recorded was again classified into 3 categories 7-10 , 4-6  and 0-3 (never good requiring immediate attention).Data were entered in Microsoft Excel 2016 and analysed using IBM-SPSS Statistics version 16.0. Point estimate was calculated at a 95% CI were calculated.Among 5065 pregnant women, the distribution of pre-eclampsia was 44 (0.87%) . The mean age among the cases of pre-eclampsia was 30.70±5.09 years. A total of 16 (36.36%) cases were between 25-29 years, 11 (25%) between 35-39 years and only 2 (4.54%) were between 40-44 years. A total of 30 (68.18%) of the cases were nulliparous and 11 (25%) were primiparous .All of the newborns of the pre-eclamptic cases were alive. The mean birth weight of the newborns was 1.84±0.69 years. A total of 38 (86.36%) of the newborns had low birth weight and 6 (13.63%) had normal birth weight. The APGAR score was studied in the first and 5 minutes after birth. A total of 26 (59.09%) of the newborns had APGAR scores between 7-10, 16 (36.36%) had between 4-6 and 2 (4.54%) had between 0-3 in 1 minute after birth. A total of 40 (90.90%) newborns had APGAR scores in between 7-10 and 4 (9.09%) scored between 4-6 in the 5 minute after birth .3 In our sudy, among 5061 pregnant women, 44 (0.87%) had pre-eclampsia which is similar to the study done in Nepal.7Pre-eclampsia is associated with maternal, perinatal and neonatal morbidity and mortality with increased incidence of the disease in developing countries.5 The finding was similar among the pre-eclamptic cases in Uganda as well.8 This age group is the most common age range for marriage and family planning among women which is supported by the highest rate of pregnancy and its associated complications like preeclampsia in this age.This study has found that the distribution of the cases was maximum in age group 25-29 (36.36%). This finding was similar to another retrospective study conducted in Nepal which has also found the highest prevalence of pre-eclampsia in the normal reproductive age group (83.52%). Also, 69.6% of cases of preeclampsia belonged to the age group 20-34 years in a cross-sectional study conducted in Malaysia.4 A similar study done in Saudi Arabia has found that the highest proportion of pre-eclamptic cases (42.0%) were nulliparous.9 The finding was in contrast among the pre-eclamptic cases of Indonesia which reported the distribution of multiparous women being more in the condition.10This study has also found that 68.18% of pre-eclamptic cases were nulliparous, followed by primiparity (25%) and multiparity (6.81%). The nulliparity is also considered an important risk factor for developing the condition.11 It also reported that the risk of fetal demise is over 50% less in cases of mild preeclampsia when compared with severe pre-eclampsia.11 The prevalence of stillbirth was 2.34% among the cases of pre-eclampsia.9 The frequency seemed to increase in the study conducted in Uganda with 12.6% cases of stillbirth in pre-eclamptic women.8As per the outcomes among newborns considered in our study, all of them were alive 44 (100%), and 86.36% had low birth weight. A total of 26 (59.09%) had good APGAR scores in 1 minute which increased to 90.90% at 5 minutes. Studies have found that severe pre-eclampsia represents a significant risk factor for intrauterine fetal demise, with an estimated stillbirth rate being 21 per 1000.12 It supports the hypothesis of placental hypoperfusion due to shallow invasion of fetal trophoblast in pregnancy leading to fetal growth restriction in pre-eclampsia.13 The finding is similar to our study where the highest distribution of low-birth-weight babies was seen among the pre-eclamptic cases.Studies have found that the mean birth weight of babies delivered by mothers who had early onset preeclampsia was lower than those of non-pre-eclamptic across all gestational ages.14 However, similar studies done among pre-eclamptic cases in Indonesia have found that the neonates with normal APGAR score (>7/10) were highly distributed at both 1-minute (80.7%) and 5-minute intervals (94.6%).10 This finding was consistent with the result of our study which reported a higher normal APGAR score at both 1 and 5 minutes in the cases of pre-eclampsia.Studies have found that pre-eclamptic women have infants with lower APGAR scores than healthy women.The limitations of the study are minimum maternal risk factors and newborn outcomes were considered. Thus, a similar study considering various other maternal risk factors such as obesity, blood pressure, blood sugar level, antenatal care facility or any renal or cardiac diseases and fetal outcomes like the fetal size and proportions; haematological and other systemic effects in a larger sample size can be conducted.The prevalence of pre-eclampsia among pregnant women is lesser than in other similar studies done in similar settings.


The study objective was to determine the prevalence of LBW and immediate (within 24 hours) birth outcomes of LBW neonates born to pre-eclamptic women at Moi Teaching and Referral Hospital (MTRH), Kenya.a descriptive cross-sectional study was conducted among 364 participants (346 singletons and 9 twins) born to pre-eclamptic women at MTRH. A study tool was used to gather data on birth weight and neonatal outcomes. Data was cleaned, coded and entered into SPSS version 22 for analysis. Descriptive statistics were computed for the prevalence of LBW and immediate neonatal outcomes.the study found an LBW prevalence of 180(49.5%) and prematurity of 81(45%). Of the LBW neonates (n=180), 162(90%) were alive and 18(10%) were stillbirths. Their immediate morbidities were, birth asphyxia 51(28.7%), neonatal jaundice 38(21%), hypothermia 18(7.9%) and neonatal sepsis 1(0.7%). Of the neonates that were born alive; 107(59.2%) were admitted to level II nursery care, 53(29.5%) were rooming in with their mothers and 20(11.3%) died within 24 hours.preeclampsia contributes to LBW, nursery admissions and morbidity/mortality of neonates necessitating the need for neonatal units' preparedness for prompt and appropriate management to avert death. More. (2018) .et al. (2020) [et al.(2019) [Congruent to our study findings, other studies have reported birth asphyxia as the leading cause of neonatal morbidity among neonates born to pre-eclamptic women owing to lung immaturity and insufficient surfactant production ,25,31. I. (2020)  that rep. (2020) ,37. Our l.(2019)  that estLimitations: this study was carried out at a national referral hospital that had a possible bias of admitting high-risk pregnancies referred from other regions in the country hence the findings may not be generalizable. In addition, the study included twins who may not share the same risk factors as the singletons.This study was carried out at a national referral hospital that had a possible bias of admitting high-risk pregnancies referred from other regions in the country hence the findings may not be generalizable. In addition, the study included twins who may not share the same risk factors as the singletons. Preeclampsia contributes to LBW, nursery admissions, and morbidity/mortality of neonates necessitating the need for neonatal units’ preparedness for prompt and appropriate management to avert death.Preeclampsia contributes to stillbirth, low birth weight, prematurity, and morbidity due to uteroplacental insufficiency.The findings of low birth weight (49%), prematurity (45%), and fresh stillbirth (9%) among pre-eclamptic women at MTRH, Kenya.


Extrauterine growth restriction (EUGR) is common among very low birth weight (VLBW) infants and associated with poor neurodevelopmental outcomes. There are two types of EUGR definitions  and many growth charts for monitoring postnatal growth. Aims of our study were 1) to compare the rate of small for gestational rate (SGA) and EUGR in a population of VLBW infants, both according to different growth charts  and different definitions; 2) to identify risk factors for EUGR.This is a single centre retrospective observational study, including all VLBW infants born between January 2009 and December 2018. Anthropometric measures were obtained at birth and at discharge and presented as z-scores according to three growth charts . Maternal, clinical and nutritional data were retrieved from clinical records.cross sectional-EUGR: Fenton 33.5%, INeS charts 40.9%, Intergrowth-21 23.8%, p 0.001; longitudinal-EUGR (loss of 1SDS): Fenton 15%, INeS charts 20.4%, Intergrowth 4%, p <0.001). In our population a longer time to reach 100 ml/kg/day of enteral feeding increased of 18% the risk of longitudinal EUGR. Late onset sepsis and retinopathy of prematurity were associated with an increased risk of longitudinal EUGR, although not significantly, while having a preeclamptic mother was associated with a reduced risk.228 VLBW were included. Percentage of SGA did not change significantly according to the three different growth charts . Prevalence of EUGR was significantly higher when INeS and Fenton charts were used, compared to Intergrowth charts regardless of EUGR-definition (We confirmed a wide variability of EUGR rates when using different charts and definitions, highlighting that Intergrowth-21 charts identify less EUGR when compared to INeS and Fenton charts. Standardized criteria for defining EUGR are warranted in order to facilitate comparisons between studies and to improve the nutritional management of VLBW infants. Adequate growth of preterm infants remains a challenge for neonatologists. Extrauterine growth restriction (EUGR), defined as poor growth during hospitalization, is common both in preterm and very low birth weight babies (VLBW). Many factors are known to influence EUGR such as periods of inadequate nutrition, feeding intolerance and a range of morbidities associated with preterm birth  . Moreoveth centile, independently of birthweight or (2) longitudinal as weight loss between birth and a given time with different standard deviation thresholds (ΔSDS) [Current EUGR definitions can be classified in (1) cross-sectional as weight at a given time <10s (ΔSDS) . Moreoves (ΔSDS) .In cross-sectional charts, assessment is based on intrauterine growth standards and does not reflect the adaptation of premature infants to extrauterine life. The most used cross-sectional growth chart is Fenton’s , derivedst Project was a prospective, longitudinal, multicentre, multi-ethnic study with strict selection criteria and it describes optimal rather than average growth of preterm infants.The most recently developed charts with a longitudinal approach are the Intergrowth-21 . The IntPrevious studies showed that the rate of neonates either classified as small for gestational age (SGA) or as having EUGR changes remarkably when assessed with different charts –12, and cross-sectional versus longitudinal). Secondary aim was to identify maternal, neonatal and nutritional factors associated with EUGR in our VLBW population.The primary aim of the present study was to describe the differences of prevalence of SGA and EUGR among very low birth weight (VLBW) infants born in an Italian referral hospital, according to the three growth charts most commonly used in Italy  and according to EUGR different definitions , a public tertiary level university hospital with approximately 1600 births annually. The study was approved by our Institutional Board Review (RC 09/2020) which waived consent for retrospective data access from medical records. Data were fully anonymised before data analysis. Our study population included infants with a birthweight ≤1500 g born between the 1st Project growth standards, the Intergrowth 21st Project newborn charts were used to derive the birth weight z-scores and the Intergrowth 21st Project postnatal growth charts were used to derive the z-scores at discharge.Clinical and growth data were retrospectively collected from hospital records. The anthropometric measures of VLBW infants were captured at birth and discharge. The discharge criteria are as follows: cardiorespiratory stability in room air, good and regular growth in the last week and feeding autonomy since at least the last 48–72 hours. Infants who had been transferred to other hospitals after 33 weeks of postmenstrual age have also been included in our analysis. The discharge criteria in this case are the same, except for feeding autonomy. Birth and growth data were presented as centiles (Standard Deviation Score or z-score) according to the three reference standards . For the Intergrowth 21th percentile of the chart used. EUGR was defined as cross-sectional-EUGR if the weight was below the 10th percentile at discharge, whereas longitudinal-EUGR if the weight loss was more than respectively 1 SDS (moderate) and 2 SDS (severe) between birth and discharge.Neonates were defined as SGA if their birthweight was below the 10Pregnancy complications (intra-uterine growth restriction (IUGR), gestational diabetes, preeclampsia), antenatal steroid administration (complete prophylaxis-2 doses), and delivery mode; gender, gestational age at birth, Apgar score, morbidities related to prematurity , late-onset sepsis (LOS), necrotizing enterocolitis), time (days) to regain birthweight, duration of parenteral nutrition (PN), days for achieving 100 ml/kg/day of enteral feeding and feeding with maternal milk were all recorded.Bronchopulmonary dysplasia or chronic lung disease (BPD/CLD) was defined as moderate/severe according to Jobe’s classification  if therelongitudinal-EUGR definition since it seems to better predict the auxological long-term outcome [For the analysis of EUGR risk factors in our population, we used the  outcome  and psyc outcome ,17. More outcome . Weight Descriptive analysis was conducted calculating frequency and percentage for categorical variables and median and Interquartile Range (IQR) for continuous variables.th percentile of the chart used and the total of newborns. We calculated, also, the EUGR percentage using the three definitions above mentioned: number of children with 1) weight below the 10th percentile on discharge , 2) weight loss > 1 SDS , and 3) weight loss > 2 SDS between birth and discharge , on the total of newborns, for all charts used.We evaluated the percentage of SGA as the ratio between the number of children whose birthweight was below the 10Chi square test or exact Fisher test were used to evaluate the association between two categorical variables while Wilcoxon Mann Whitney non parametric test was applied to verify the difference in the distribution of a continuous variable between the categories of a dichotomous variable.To identify EUGR risk factors, we used a backward selection logistic model adjusted for SGA at birth, sex and time to regain birthweight. Clinical data and anthropometric measures, both maternal and neonatal, were included as independent variables. A p-value<0.05 was considered as statistically significant. All statistical analysis was performed using SAS software, Version 9.4 .Considering α = 0.05 and presuming EUGR prevalence at discharge of 72%, according to longitudinal EUGR definition and using INeS charts , with a Between 2009 and 2018, 266 VLBW infant were admitted to our NICU. Thirty-eight newborns were excluded for the following reasons: 24 died, 4 were transferred to other hospitals before 33 weeks of postmenstrual age, 9 had chromosomal abnormalities or major congenital abnormalities and 1 had no available data.Hence, 228 VLBW were included in the study.cross-sectional-EUGR and longitudinal-EUGR-1 definitions, both INeS and Fenton charts estimated a statistically significantly higher prevalence of EUGR when compared to Intergrowth charts. On the contrary, EUGR prevalence when defined as longitudinal-EUGR-2 did not significantly change according to reference growth chart , took a higher median time to reach 100 ml/kg/day of enteral feeds and to regain birthweight. Some morbidities were significantly higher in the EUGR VLBW including LOS and ROP, while there were no differences regarding NEC and BPD .In the multivariate analysis, independently of birthweight, gender and time to regain birthweight, the risk of being EUGR was higher, although not significantly, if VLBW experienced a LOS (OR: 2.28–95%CI: 0.67–7.79), and ROP (OR 2.36–95%CI 0.94–5.94). Longer time to reach 100 ml/kg/day of enteral feeding was significantly associated with longitudinal EUGR (OR: 1.18–95%CI: 1.04–1.34). On the contrary, in our study having a mother who suffered from preeclampsia significantly reduced the risk of EUGR at discharge .cross-sectional and a longitudinal-EUGR-1 definition. At multivariate analyses, LOS and a longer time for reaching 100 ml/kg/day enteral feeding were associated with a higher risk of EUGR at discharge, while maternal preeclampsia reduced this risk.In our study we found that rates of EUGR varied significantly according to charts and definitions used, resulting higher when using INeS charts both when applying a st growth charts [In line with other studies, in our population frequency of SGA was higher, though not significantly so, when using the Intergrowth-21h charts ,10,18. TOn the contrary, when using Intergrowth-21th charts, EUGR prevalence was lower when compared to Fenton and INeS charts, both with the cross-sectional and the longitudinal definition. This result is consistent with previous studies ,10,18–20Ideal growth for preterm babies is far from being clearly defined. One of the widely accepted goals of neonatal nutritional care is to try to replicate the intrauterine growth as close as possible  and, forThese trends to lower rates of EUGR when using Intergrowth-21 charts have been reported by several other studies, both for cross sectional EUGR definition ,10 and llongitudinal-EUGR definition , changes. EUGR rates from NICUs of high-income countries similar to ours, evaluated at discharge, varied from 17% to 77.2% for the cross-sectional EUGR [longitudinal-1 definition [longitudinal-2 EUGR [Our study was done because knowing and monitoring the prevalence of EUGR in our Unit, is considered to be a quality measure of care for preterm infants . In our nal EUGR ,24–26, ffinition ,28 and fl-2 EUGR –29.When looking for risk factors, we confirmed that the characteristics of the study population are determinant to EUGR at discharge. The degree of longitudinal EUGR is influenced by birth weight z score: the lower the birthweight centile, the lower the probability to lose 1 or 2 SDS ,28,30. IIndependently of the above factors, in our population we found that LOS and ROP more than doubled the risk for EUGR, although not statistically significant. In other studies ,30,32,34In our analyses longer time to reach 100 ml/kg/day of enteral feeding was found to be a potential risk factor. Again, this may be an indirect sign of severity of illness, as increasing oral nutrition may be harder in sick infants. Intervention studies showed that optimising nutrition (such as introducing guidelines for increasing feeds and weaning PN) reduced the incidence of EUGR –39.In our study it was surprising to find a negative association between preeclampsia and EUGR risk. As far as we know, no other study reported this association up to now. However, Gonzalez-Garcia et al showed that in a Spanish cohort of preterm babies, IUGR, which is known to be frequently associated with preeclampsia, was negatively associated with longitudinal EUGR . This asLimitations of our study are inherent to the retrospective observational nature of the study. Our cohort is small and includes a wide range of gestational ages and birthweight categories. Another limitation may lie in the choice of discharge as a time point for assessing EUGR, as there is a wide range of time of evaluation and a long time passes between birth and discharge. Considering these two time points (birth and discharge) for evaluation of growth, we are not able to identify when loss of z-score occurred most often. As this study was conducted in a single medical centre, generalization of the data is limited. Moreover, residual confounding cannot be ruled out.In conclusion, our study confirms a wide variability of EUGR rates when using different charts and definitions. It highlights the need to standardize criteria and the evaluation method for EUGR, which would facilitate comparisons between studies and help to improve nutrition in neonatal units and to perform studies on its long term implication.S1 Table(DOCX)Click here for additional data file.


The growing body of evidence for a Developmental Origin of Health and Diseases (DOHaD) emphasizes the need to assess the role of fetal and neonatal factors in canine overweight which affects nearly 40% of adult dogs. The purpose of the current study was to examine the association between birth weight and subcutaneous fat thickness (SFT) at adulthood, measured by ultrasonography, in a population of purebred Labrador dogs. We used a linear mixed-effects model by adjusting for sex, age, neuter status and the anatomical sites of SFT measurements . The results suggest that, as in other species, dogs with the lowest birth weights have a greater thickness of subcutaneous fat at adulthood than the others. These findings highlight the importance of fetal life in adult health in the canine species. They suggest that birth weight is an important health indicator of long-term impact. It should be considered in particular in overweight management plans: puppies born with low birth weight should be identified as being at higher risk of overweight and their owners should be encouraged to enter their dogs in specific weight control plans from an early stage in life.Overweight affects nearly 40% of dogs. The objective of this study was to explore the hypothesis of the Developmental Origins of Health and Disease through the association between birth weight and adiposity in adult dogs. The association between body condition score (BCS) and subcutaneous fat thickness (SFT), measured in the flanks, abdomen and lumbar regions, was assessed in a population 88 adult Labradors (>1 year). Significant positive moderate correlations between BCS and SFT were described. A linear mixed-effects model was used to investigate the association between birth weight and SFT by adjusting for sex, age, neuter status and the anatomical site of the measurement. The results showed that SFT values increased with age and were higher in sterilized than in entire dogs. In addition, SFT values were higher in the lumbar region compared to the other anatomical sites. Finally, the model revealed a significant association between SFT and birth weight, suggesting that, as in other species, dogs with the lowest birth weights have thicker subcutaneous fat at adulthood than the others. The assessment of visceral adipose tissue and the relative importance of birth weight among the numerous risk factors of overweight remains to be explored in dogs. In the canine species, overweight affects nearly 40% of dogs ,2,3,4,5 Since the 1980s and the development the “Barker hypothesis”, suggesting an impact of early life events on the risk of diseases in adulthood, a growing body of epidemiological and experimental data have supported the Developmental Origins of Health and Disease (DOHaD) in humans ,14,15,16The objective of this study was to explore further the association between birth weight and adiposity at adulthood, assessed through the SFT, in a Labrador dog population.The study population was 88 adult (>1 year), purebred Labradors, born in one breeding kennel . At the time of examination, they were either active, retired or breeding assistance dogs and they are housed in volunteer families. Age, sex and neuter status were recorded and weights at birth were extracted from the kennel database.For each dog, adiposity was estimated through two different methods. First, the body condition score (BCS) was assessed jointly by two operators, through palpation and visual observation, using the 9-point scale developed by Laflamme , i.e., fp value < 0.05 and statistical uncertainty was assessed by calculating the 95% confidence intervals (95% CI).The information collected was transferred into an Excel spreadsheet . Then, statistical analysis and graphical representations were performed using R software, version 4.2.1  and the After a description of the population studied , the relThen, the interplay between birth weight and SFT values was investigated by fitting a linear mixed regression model with SFT as response variable. Explanatory variables included birth weight , the animal’s sex , age , neuter status (neutered/entire) and location (abdomen/flanks/lumbar region). Dog identification was introduced as a random term to deal with the repetition of the individuals (three locations per dog). Starting with the full model (SFT~Location + Birth weight + Neuter status + Sex + Age), a backward selection based on Akaike’s Information Criterion (AIC) was applied to select the most parsimonious model. At the end of the backward selection, interactions between birth weight and location as well as between birth weight and age were tested by running models with and without the interaction term. The normal probability plot of residuals and the plot of residuals versus predicted values were generated to check whether the assumptions of normality and homogeneity of variance had been fulfilled. The estimated marginal means of SFT were obtained from this model and pairwise comparisons were performed using Tukey’s Honest Significant Difference method. n = 9, n = 27, n = 25, n = 17, n = 8 and n = 2, for BCS levels 4, 5, 6, 7, 8 and 9, respectively; Among the 88 adult Labradors included in the present study, ages ranged from 1.1 to 9.6 years (median: 3.4 years) with 28 young dogs (≤2 years), 29 adults (2–5 years) and 31 old dogs (≥5 years). Sex distribution was 6 (6.8%) entire males, 34 (38.6%) entire females, 17 (19.3%) neutered males and 31 (35.2%) spayed females. BCS varied between 4 and 9 (p < 0.001). For each site, SFT significantly increased with BCS , varied between 0.8 and 35.6 mm . It was also higher for sterilized dogs  than for entire dogs  and in the lumbar region compared with the two other locations . Finally, the estimated marginal mean of SFT was higher for dogs with birth weights below the median compared to those with higher birth weights . Individuals with the lightest birth weights had thicker fat deposits whatever the site of measurement  contrary to BCS, its use in livestock (pigs ,43, smalBCS is a semi-quantitative subjective parameter for body composition whereas SFT is more quantitative and objective. Nevertheless, both criteria were correlated in the present work, as in previous studies ,48,49. AThe main objective of this paper was to assess whether birth weight belongs to the variation factors of SFT at adulthood: adult dogs with the lightest weights at birth exhibited higher values of SFT at all locations and at all ages. This finding is in agreement with the literature indicating the maternal programming of adiposity at adulthood by low birth weight ,60,61. GAs the interaction between birth weight and location was not significant, birth weight can be considered as a determinant of later subcutaneous fat deposition but without any impact on its distribution pattern. Our results are in contradiction with previous work on humans indicating a more truncal distribution of subcutaneous fat in adults with low birth weight . This miThese findings highlight the importance of fetal life in adult health in the canine species. They suggest that birth weight is an important health criterion of long-term impact. It should be considered in particular in overweight management plans: puppies born with low birth weight should be identified as having a higher risk of overweight and their owners should be encouraged to involve the dog in a specific weight control plan early in life. In addition, it would be wise to consider training pet owners who currently tend to underestimate the adiposity of their animal ,71. ThisMaternal programming in the canine species is therefore a public health issue that requires the involvement of all stakeholders: breeders are responsible for newborns and for passing on the value of birth weight to owners; veterinarians need to pay attention to birth weight as a significant health outcome even in adulthood; and owners need to be aware of this risk factor for overweight and seriously follow a weight management plan. In addition to birth weight, further studies are required to assess the influence of neonatal events and namely early growth on overweight risk at adulthood.Many other factors suggested or demonstrated to have effects on adiposity in dogs cannot be explored in the current study which aim was to demonstrate the impact of birth weight. For example, inadequate diet or a lack of physical activity are known risk factors of dog overweight ,72. In aTo conclude, this work suggests that birth weight, interesting parameter to predict neonatal life, is also an important health indicator of long-term impact associated with adiposity at adulthood. Thus, it should be considered in overweight management plans: puppies born with low birth weight should be identified as being at higher risk of overweight and their owners should be encouraged to enter their dogs in specific weight control plans from an early stage in life. In the future, it may also be of interest to consider and evaluate the effect of early growth that may accentuate or temper the effect of birth weight on adult adiposity.


CRG-CeO2-0.5 and CRG-CeO2-1 composites were prepared by compositing CeO2 to CRG + CeO2 at a weight ratio of 0.5:100 and 1:100, respectively. The physicochemical and structural properties of these compounds were studied and compared with pristine CRG. Upon incorporation of CeO2 nanoparticles into the CRG matrix, significant reductions in hydrogel degradation were observed. In addition, it was noted that CRG-CeO2 exhibited better antibacterial and hemostatic properties than CRG hydrogel without CeO2 NPs. The biocompatibility of the materials was tested using the NIH 3T3 cell line, and all samples were found to be nontoxic. Particularly, CRG-CeO2-1 demonstrated superior hemostatic effects, biocompatibility, and a lower degradation rate since more CeO2 NPs were present in the CRG matrix. Therefore, CRG-CeO2-1 has the potential to be used as a hemostatic agent and wound dressing.In this study, a novel absorbable hemostatic agent was developed using carrageenan (CRG) as a natural polymer and cerium oxide nanoparticles (CeO When such situations arise, materials that stop bleeding and dressings that enhance wound healing are required. Studies have shown that the application of hemostatic dressings can reduce mortality rates and speed up wound healing. Besides their capability of stopping bleeding rapidly, they are also capable of protecting against infection. Various materials have been reported to possess favorable characteristics in bleeding management. A variety of hemostatic materials are commercially available, including zeolite powder (ZLP) , silica 3−) .There are many types of antibacterial agents available, including antibiotics, nanoparticles , cationic organic agents, and others, which are applied to combat bacterial infections . Antibio2 NPs) are considered highly promising for wound healing applications due to their exceptional properties as antioxidants, anti-inflammatory agents, antibacterial agents, and stimulators of angiogenesis [Recently, nanomaterials have attracted considerable attention due to their unique properties resulting from higher surface-to-volume ratios . Nanomatogenesis . Their iogenesis . Moreove2 NPs in conjunction with other hydrogels. Zhao et al. developed an alginate (ALG) hydrogel that contained different amounts of green-synthesized CeO2 NPs to enhance wound healing. NPs of CeO2 were synthesized with curcumin as a capping agent, and ALG-CeO2 composites were crosslinked with calcium chloride as the crosslinking agent. The researchers have provided evidence to support the efficacy of these composites in promoting wound healing, suggesting their potential as highly effective wound dressing materials utilizing hydrogels [2 NPs exhibit strong antibacterial properties [A variety of composite materials have been prepared using CRG in conjunction with other types of NPs or CeOydrogels . A studyydrogels . Composioperties . Furtheroperties .2 composite biomaterial that was crosslinked using glutaraldehyde (GA). The CRG-CeO2 composite exhibited suitable physicochemical properties, biocompatibility, hemostatic effect, and antibacterial behavior, suggesting that it could be used as a promising hemostatic and wound-healing agent in the future.Therefore, our study aimed to synthesize a novel CRG-CeO2 NPs) was bought from US Research Nanomaterials. Glutaraldehyde 25% solution in water was supplied from Titrachem. HCl fuming 37% also was purchased from Merck . The chemicals used were all analytical grade.Calcium chloride hydrate and κ-carrageenan were purchased from Sigma Aldrich . Cerium oxide nanopowder (CeO2) sponges, 0.025 g of CRG powder was added to 5 mL of deionized water. Afterwards, the solution was placed into an oil bath at 70 °C for 30 min until completely dissolved. In subsequent steps, various amounts of CeO2 NPs—0, 0.5, and 1 wt.% (relative to CRG)—were dispersed in deionized water using a sonicator and separately added to the CRG solutions and stirred in the dark, as shown in In order to prepare carrageenan (CRG) sponges and carrageenan-cerium oxide nanoparticles  operating at 20 kV. Prior to characterizing the samples, they were all sputter-coated with gold. In order to conduct SEM analysis of CeO2 NPs, a small quantity of NPs was disseminated in ethanol and subjected to sonication in an ice bath. Subsequently, the resulting suspension was deposited onto an aluminum substrate and allowed to air dry. ImageJ 1.52v software was utilized to determine the pore size of each group. Photos were taken from ten randomly selected areas of each sample.The surface morphology images of CRG and CRG-CeOX-ray diffraction analysis (XRD) was performed using an X-ray diffractometer .−1.FTIR analysis was carried out using a Fourier transform infrared spectrophotometer  in the range 400–4000 cm2 composite scaffolds were investigated by immersing them in PBS at 37 °C for designated time intervals , the weight of swelling hydrogels was measured until equilibrium was reached. Based on Equation (1), the swelling percentage was determined.Wt represents the weight of the swollen sample at a predetermined time, while W0 represents the weight of the sample at the beginning of the study.The swelling and degradation behaviours of CRG and CRG-CeOntervals . The eff2 composite scaffolds was performed according to ASTM F1635-16, which is widely used in order to assess the degradation of hydrogels. To determine how the hydrogel degraded in PBS at 37 °C, the weight change of the sample was determined in intervals of 1, 3, and 5 days. A degradation percentage was calculated using Equation (2).Wt represents the weight of the degraded sample at a specific time, while W0 represents the weight of the sample at the start. Both swelling and degeneration were assessed using three replicates.The degradation of the CRG and CRG-CeO2) to 100 µL of blood at a concentration of 0.2 M. The CRG, CRG-CeO2-0.5, and CRG-CeO2-1 scaffolds, as well as the gauze  as a positive control, were cut into cylindrical sections (5 mm × 8 mm) and 50 µL of recalcified whole blood solution was added to them. The samples and the positive control were incubated at various intervals of 30 s, 60 s, 90 s, and 120 s. Subsequently, 10 mL of deionized water was carefully added so as not to disturb the clot, and 8 mL of the solution was centrifuged at 3000 rpm for one minute. In the next step, the supernatant was placed in an incubator for one hour. After this time, the absorbance of 2 mL of the samples and the control was determined using a UV-Vis spectrophotometer at a wavelength of 540 nm.The determination of the blood clotting index (BCI) was performed according to a method that had been used previously . Recalci2-0.5, and CRG-CeO2-1 scaffolds. A study was conducted on two bacteria, including Gram-negative Escherichia coli  and Gram-positive Staphylococcus aureus . As a first step, 14 g of nutrient agar (QUELAB) was suspended in 500 mL deionized water and stirred for 15 min to obtain a medium culture. Following this, the agar solution was autoclaved for two hours at 121 °C. Upon completion of this procedure, the solution was poured into a 10 cm Petri dish. Following solidification, fresh cultures of the bacteria E. coli and S. aureus were smeared evenly on the agar medium using sterile swabs. CRG, CRG-CeO2-0.5, and CRG-CeO2-1 samples were placed aseptically on the agar surface and incubated for 24 h at 37 °C. The inhibition zones for each sample, if present, were determined and documented after the incubation time. As a positive control, vancomycin antibiotic discs  were used.Agar disk diffusion was used to determine the antibacterial activity of the CRG, CRG-CeONIH 3T3 cells were obtained from the National Cell Bank of Iran . An RPMI-1640 medium  supplemented with 10% Fetal Bovine Serum (FBS) and 100 IU per milliliter streptomycin  was used for cell cultivation.2-0.5, and CRG-CeO2-1 scaffolds. A minimum of three replications were conducted for each type of sample (each sample weighs approximately 0.01 g). Following previous studies [4 cells per well. Seed cells were treated for one and three days with an extracted medium derived from sterilized hydrogel—RPMI-1640 medium containing 10% FBS. After 1 and 3 days, 10 μL of MTT  was added to the wells, followed by an incubation period of 4 h at 37 °C. Afterwards, the solutions were removed from the wells and 100 μL DMSO was added to each well, allowing the crystals to dissolve for one hour. The absorbance of the solution was determined at 570 nm with a plate reader.An MTT assay was conducted to determine the viability of cells on the CRG, CRG-CeO studies , the samp < 0.05, ** p < 0.01, and *** p < 0.001.Graph Pad Prism 8  was used to perform all statistical analyses. Analyses were conducted using one-way or two-way ANOVA, depending on the experimental design. The results were expressed as mean ± standard deviation. The significance levels were defined as * 2-0.5, CRG-CeO2-1 scaffolds, and CeO2 NPs. 2 NPs are in the nanoscale and have a size distribution from 15–30 nm. According to low-magnification images, all samples appear to be connected and well structured. Additionally, high-magnification images of both CRG-CeO2 composite scaffolds indicate that CeO2 NPs were well distributed within CRG hydrogels. Depending on the type of sample, the pore size range varied between 40 and 200 μm. This figure illustrates that pristine CRG hydrogel has pores ranging from 60 to 190 μm, with an average size of 135.69 ± 29.3 µm. However, as can be seen, the addition of 0.5% and 1% CeO2 NPs significantly reduced the average pore diameter of the CRG-CeO2-0.5 and CRG-CeO2-1 composite scaffolds, respectively, to 103.02 ± 30.04 µm and 60.5 ± 12.8 µm compared to the pristine CRG. This is attributed to the electrostatic interaction between negatively charged CRG polysaccharides and positively charged CeO2 NPs, which is consistent with previous findings [2 NPs from 0.5 to 1%, the hydrogel became more compact, and pores became smaller. Furthermore, CeO2 NPs may function as crosslinking agents, so altering the amount of CeO2 NPs can alter the degree of crosslinking. Eventually, this interferes with the growth of ice crystals during the freezing stage, resulting in a reduced pore size on the scaffolds when they are frozen.findings ,33. By i2 composite hydrogels, respectively. 2-0.5 and CRG-CeO2-1 scaffolds. According to the EDS mapping that was performed for both the CRG-CeO2-0.5 and CRG-CeO2-1 composite hydrogels, CeO2 NPs were distributed evenly throughout them.As shown in 2 hydrogels occurred through a reaction between the hydroxyl group of CRG and the aldehyde group of GA. Predicted mechanisms of the crosslinking reaction are in good agreement with previous studies [2 NPs as well as their chemical functionality. 2-0.5, and CRG-CeO2-1 scaffolds. It can be seen that scaffolds containing CRG exhibit a board band in the 3200–3400 cm−1 region due to stretching vibrations within O-H groups and hydrogen bonds [−1 to 3600 cm−1 of width becomes a boundary and intensifies, which is attributed to the formation of both intramolecular and intermolecular hydrogen bonds [−1 and 2850 cm−1 were observed, which are related to the C-H stretching bands [−1, and -O-SO3 stretching vibrations occur at D-galactose-4-sulfate (G4S) at 844 cm−1 and D-galactose-2-sulfate (DA2S) at 801 cm−1, respectively [2-0.5, and CRG-CeO2-1 exhibited these peaks [−1 and 934 cm−1 regions would result in vibrations in the CC, COC, and OH groups in the CRG structure. There will also be demonstrations of the formation of hydrogen bonds between CeO2 NPs and CRG, as well as GA crosslinking [−1 is associated with a metal–oxygen bond. It is apparent from the results that the addition of CeO2 NPs intensified peaks at 1066 cm−1 and 860 cm−1 due to the stretching vibration of Ce-O as well, which is specific to CeO2 NPs [As shown in  studies . An FTIRen bonds ,36. Baseng bands ,38. Moreectively ,40,41,42se peaks ,40,41,42slinking . In accoXRD was used to determine the crystallinity and phase composition of all CRG, CRG-CeO2-0.5, and CRG-CeO2-1 scaffolds. 2 scaffolds in PBS. The weight of all samples increased within the first few hours of immersion. The weight then started to decrease and then started to level off after a certain period of time. It can be seen that incorporating CeO2 into CRG results in a decrease in swelling behavior when compared to neat CRG. This decrease in swelling behavior is attributed to the increased crosslinking density of the polymer matrix due to the incorporation of CeO2 NPs. This improved crosslinking leads to a more rigid polymer network with fewer voids, resulting in a decrease in swelling behavior. The SEM images in 2-1 has a more compact structure with a smaller pore size as compared to CRG-CeO2-0.5 and CRG hydrogels. Thus, their initial amounts of PBS were reduced in total, which was in accordance with the swelling capability study shown in 2-0.5 and CRG-CeO2-1 exhibit a lower degradation rate and weight loss value, as shown in 2-1 hydrogels lost 20% of their original weight, which is about 50% less than the weight loss associated with the neat CRG scaffold after five days. The incorporation of CeO2 NPs into CRG matrix, with an increasing amount from 0.5 to 1, is attributed to the increased crosslinking density as well as to a decrease in weight loss during incubation.Compared to CRG, both CRG-CeOHydrogel-based wound dressings are a promising candidate for wound dressing, as they provide moist conditions that speed up the healing process. To facilitate the production of new ECM on the skin, scaffolds should be capable of absorbing water between 100 and 800 times their dry weight. Such a scaffold should also be able to maintain its shape and structural integrity in the presence of moisture, providing an effective substrate for cell adhesion and growth. The polysaccharides such as CRG , chitosa2-0.5, and CRG-CeO2-1, displayed a lower BCI. CRG-CeO2-0.5 and CRG-CeO2-1, however, demonstrated lower BCI values than CRG, indicating that they have greater hemostatic properties than CRG. Accordingly, the introduction of CeO2 NPs into the CRG matrix resulted in a lower BCI rate and an improved clotting index rate in comparison to neat CRG. All samples and controls showed a downward trend in BCI as the incubation time was extended from 30 s to 120 s. The combination of all factors, including their highly porous structure, swelling properties, rapid blood adsorption, and excellent in vitro blood clotting effect, makes them ideal hemostatic materials.The blood clotting capability of materials was assessed using a dynamic whole-blood clotting test, where a solution with a higher absorbance value indicates a slower clotting rate. As a control group, gauze was utilized as a traditional hemostatic agent. 2 NPs into CRG resulted in improved stability, making CRG particularly suitable for hemostatic applications. The porous and three-dimensional architecture of the scaffold, as well as the coagulation capability of both CRG and CeO2 NPs, allow it to absorb and retain blood as well as prevent bleeding. Meanwhile, CRG contains high levels of hydroxyl groups, thus making them hydrophilic biomaterials that may be helpful in surface wetting and adhesion and consequently control bleeding [Currently, CRG is used widely as wound dressings due to its ability to absorb pseudo-extracellular fluid . Previoubleeding ,53.S. aureus and E. coli. These two kinds of bacteria were chosen because they are among the top five pathogens associated with diabetic and non-diabetic wound infections [2 NPs after 24 h of incubation with E. coli and S. aureus bacteria. Observations indicate that both CRG-CeO2-0.5 and CRG-CeO2-1 demonstrate antibacterial properties, whereas CRG does not show antibacterial properties. According to our findings, CRG-CeO2 hydrogels containing a higher concentration of CeO2 NPs demonstrated greater activity than hydrogels containing a lower concentration of CeO2 NPs.The antibacterial properties of the composite scaffolds were investigated against fections . Figure 2 NPs remain on the surface of bacteria for a long time rather than penetrating their membranes, resulting in the blockage of the membranes of bacteria. Following this, NPs may have a detrimental effect on the viscosity of the membrane, impair the specific ionic pumps, and cause a significant disruption in transport exchange between the bacterial cell and the solution [2 NPs may be capable of attacking proteins after they bind to the outer membrane of a bacterial cell [2 NPs can physically damage bacterial membranes, especially in Gram-positive bacteria, due to their irregular structure [The mechanism can be explained by the fact that positively charged NPs were adsorbed onto the membranes of negatively charged Gram-positive and Gram-negative bacteria as a result of electrostatic interactions. In this way, CeOsolution . As a seial cell ,56. Moretructure ,57.2-0.5, and CRG-CeO2-1 was conducted using the NIH 3T3 cell line. NIH 3T3 cells seeded in 96-well plates were treated with an extracted solution separately derived from the scaffolds. As shown in 2 NPs, CRG-CeO2-0.5 and CRG-CeO2-1 demonstrated a higher degree of cell viability, which is in line with previous studies [2 NPs were released into the culture medium after 24 h and 72 h, leading to an increase in metabolic rate and decreased production of reactive oxygen species (ROS) [2-1 scaffolds showed an insignificant loss of cell viability on day 3, possibly due to the overexpression of pro-inflammatory factors that may affect cellular function [2 NPs are known to be highly biocompatible, making them ideal for biomedical applications as well as wound healing [2 NPs in concentrations ranging from 0 to 1% are cytotoxic [2 NPs at these concentrations, suggesting that CeO2 NPs at these levels have no toxic effects on cells [2 NPs. Nourmohammadi et al. utilized CRG as a capping agent to prepare CeO2 NPs in an environmentally friendly manner [2 were produced in spherical shapes with an average diameter of 34 nm [2 NPs with concentrations ranging from 0 to 500 µg/mL were evaluated for their cytotoxicity on WEHI 164 cells. In general, CeO2 NPs appeared to have a very low cytotoxic effect on WEHI 164 cells, which makes them suitable for a variety of biomedical applications [An evaluation of the cytotoxicity of scaffolds made from CRG, CRG-CeO studies ,58. CeO2es (ROS) ,59. Howefunction . Severalfunction ,61. Furt healing ,62. An iytotoxic . Based oon cells . CRG cany manner . NPs of of 34 nm . Synthesications .2 NPs show great promise, as they are capable of effective wound closure, tissue regeneration, and scar reduction [2 NPs exhibit great potential as a nanomaterial for wound healing purposes, as they possess the ability to promote wound closure, facilitate tissue regeneration, and minimize scarring. NP-incorporated hydrogels hold significant potential as versatile dressings for wound healing, offering wide-ranging application possibilities [Multifunctional hydrogels could be suitable as wound healing agents . CRG is eduction . Incorpoeduction . CeO2 NPbilities . Variousbilities . GA is cbilities . Due to bilities . A key abilities .2 NPs that have hemostatic properties, antibacterial properties, and high biocompatibility. To accomplish this, various weight percentages of CeO2 NPs—0, 0.5, and 1% (relative to CRG)—were incorporated into the CRG hydrogel. Based on SEM results, electrostatic interactions between positively charged CeO2 NPs and negatively charged CRG resulted in the formation of a compact hydrogel structure, with smaller pores, when a higher amount of NPs was added. Pores present in the biopolymer matrix contribute significantly to the healing process by facilitating cell filtration, promoting high permeability, and allowing oxygen and nutrients to diffuse [2 NPs into CRG, the swelling percentage was reduced, which may be attributed to a reduction in available void spaces between polymeric chains. Furthermore, the degradation rate is also decreased as a result of this reduction in free volume between macromolecular chains [This study aimed to develop and create multifunctional biomaterials based on CRG and CeO diffuse . Studies diffuse . Water r diffuse . By incor chains .2 hydrogels demonstrate favorable characteristics for multifunctional applications and can serve effectively as hemostatic and wound healing agents while preserving structural integrity. In future investigations, a series of in vivo experiments will be conducted to further understand the effectiveness of hydrogels.Local hemostatic agents have several benefits in the medical field. These type of agents effectively enhance blood preservation by minimizing fluid loss, expediting the process of hemostasis, limiting the potential negative consequences associated with systemic hemostatic medications, and saving valuable transfusion blood supplies. In recent years, significant efforts have been put into creating high-tech dressings that actively induce or promote hemostasis beyond just absorbency . Chen et2 scaffolds by freeze-drying and crosslinking them with GA. SEM micrographs showed interconnected pores with pore sizes of around 136, 103, and 60 µm for CRG, CRG-CeO2-0.5, and CRG-CeO2-1, respectively, indicating a more compact structure after incorporating CeO2 NPs into the CRG matrix. Incorporating CeO2 NPs into the CRG matrix enhanced hemostatic performance, as demonstrated by the BCI. The BCI test indicated that CRG-CeO2-0.5 and CRG-CeO2-1 scaffolds have hemostatic activity comparable to CRG and gauze . There is evidence that CeO2 NPs enhance antibacterial activity in CRG-CeO2 hydrogels; however, CeO2 NPs concentration influences pore size, degradation, and swelling behaviors. The in vitro results also revealed that both CRG-CeO2-0.5 and CRG-CeO2-1 showed high cell viability and nontoxic behavior compared to the results obtained with CRG and control samples. According to these findings, the incorporation of CeO2 NPs into CRG hydrogels could lead to the development of hemostatic agents that are antibacterial in nature.In this study, we produced CRG and CRG-CeO


This cohort study investigates culturally invariant, nonlinear associations of birth weight percentiles and gestational age with later cognitive performance. Are birth weight percentiles and gestational age nonlinearly associated with cognitive performance?z scores until the z score equaled the 69th percentile, with a subsequent plateau. In contrast, every week of gestation was significantly associated with increased IQ, but the strongest association was observed in the very preterm range, before 32 weeks gestation.In this cohort study of 4 longitudinal cohorts with 30 643 pooled participants, IQ was associated with increasing birth weight Using the 10th birth weight percentile to estimate low cognitive performance does not adequately represent the nonlinear association between the 2 constructs. Birth weight percentiles (BWPs) are often dichotomized at the 10th percentile and show statistically significant association with later cognitive performance, for both preterm and term-born children. However, research testing nonlinear associations between BWPs and cognitive performance is scarce.To investigate culturally invariant, nonlinear associations of BWPs and gestational age with later cognitive performance.In this cohort study, participants with valid neonatal and cognitive data were combined from 4 observational cohorts, including the Millennium Cohort Study, the National Longitudinal Survey of Youth 1979 Child and Young Adult cohort, Growing Up in Ireland, and the Longitudinal Study of Australian Children, with children born between 2000 and 2002, 1980 and 2010, 2007 and 2008, and 2003 and 2004, respectively. Neonatal data were parent reported before age 1 year. At approximately 5 years of age, multiple cognitive tests were performed. Follow-up at 5 years of age was the predominant focus. Data were analyzed July 17, 2023.The parent-reported neonatal data were used to calculate BWPs according to the Fenton growth chart.z standardized separately within each cohort.Scores for IQ were created from multiple measures of cognition, which were Of 30 643 participants , 7.5% were born preterm (before 37 weeks gestation) and 92.5% were term born (between 37 and 42 weeks gestation). In the pooled data using multivariate adaptive regression splines, IQ linearly increased by 4.2 points as BWPs increased from the first to the 69th percentile before completely plateauing. For gestational age, IQ linearly increased by 1.3 points per week up until 32 weeks, with the association reducing to 0.3 points per week after 32 weeks. The association of BWP with IQ was not moderated by gestational age. For term-born infants, the estimated IQ score was only clinically meaningfully lower than average when birth weight was below the third percentile. Consistent results were found when instead using multivariable regression where gestational age and BWPs were categorized into groups.In this cohort study, lower BWPs and gestational age were independently associated with lower IQ. For term-born infants, a cutoff of the third percentile would be more appropriate than the traditionally used 10th percentile when the aim is estimating meaningful cognitive differences. Alternatively, if one assumes a linear relationship between BWP and IQ, then for the 10th percentile to be a clinically useful, binary predictor of IQ, it should be associated with a standardized difference of at least 0.2 (3 IQ points).Being born small for gestational age (SGA), often defined as a birth weight percentile (BWP) of lower than 10% for gestation, has been repeatedly shown to be associated with lower scores on intelligence tests (IQ)—an important predictor of a variety of long-term outcomes such as academic and occupational achievement, as well as physical healthz scores (BWZS). Indeed, it has been shown that improved developmental outcomes are associated with increasing BWPs.8 However, analyses using continuous measures of relative birth weight that test for linear associations assume that there are no areas in the distribution where IQ scores substantially increase, plateau, or even decrease,9 assuming that the 100th BWP is optimal. As infants weighing above the 90th percentile have been found to have substantially higher risk of asphyxia and malignant neoplasms,10 increasingly higher BWPs may be associated with lower IQ, indicating a nonlinear association. Indeed, 1 study reported the optimal BWP for educational outcomes at the 66th percentile, with a subsequent decline in educational performance if BWP was higher.8 However there are contrasting findings, including no reduction in school performance from the 80th to the 100th BWP11 or that children with a BWP above 90% have higher IQs than those between the 50th and 90th percentiles.12The alternative is to consider continuous measures of relative birth weight such as BWPs or birth weight 13 This is due to evidence that SGA status in preterm infants may more often result from intrauterine growth restriction, whereas SGA status in those born at term may more often result from being constitutionally small.14 However, a meta-analysis found that the relative IQ difference between SGA and appropriate for gestational age individuals to be of largely similar magnitude for those born preterm and at term.3 Unknown is whether this is equally true for those born VP specifically.It has also been hypothesized that SGA/lower BWP’s negative association with IQ may be greater for infants born moderately/late preterm  or very preterm  relative to term born (between 37 and 42 weeks gestation).The aim of this cohort study was 2-fold. First, to test whether IQ increases as BWP increases and whether the association is nonlinear. Second, to determine whether the association between BWP and IQ differs by term-born, MLP, and VP status.16 the Longitudinal Study of Australian Children (LSAC) from the Commonwealth of Australia,18 the National Longitudinal Survey of Youth 1979 (NLSY79) Child and Young Adult cohort from the US,20 and the Growing Up in Ireland study (GUI) from the Republic of Ireland.22 Included participants from the MCS, LSAC, NLSY79 Child and Young Adult cohort, and GUI were born between 2000 and 2002, 2003 and 2004, 1980 and 2010, and 2007 and 2008, respectively. All studies were reviewed by institutional review boards or ethics committees, and written informed consent was collected from parents.26 All data are open access and, except for the NLSY79 Child and Young Adult cohort, thought to be nationally representative.27 This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.Data from 4 large, longitudinal cohorts from high-income, English-speaking countries were pooled together. These included the Millennium Cohort Study (MCS) from the UK,29 However, the GUI data are grouped together for infants with birth weights lower than 2500 g, while for all other participants it is to the nearest 100 g. Because BWPs could therefore not be accurately calculated for these participants with lower birth weights, they were excluded. Furthermore, in all cohorts, participants with a gestation equal to or greater than 42 weeks were removed.In all cohorts, gestational age and birth weight information was collected from the primary caregiver at the first wave of data collection. In the MCS, this has been subsequently verified by matching the data to official birth records, finding them to be highly accurate, within 100 g in 92% of cases and within a week of gestation in 94% of cases.30 The Fenton reference uses data from 3 986 456 infants from multiple countries to develop an international growth chart that identifies the average birth weight at each gestational week. Participants with BWPs lower than 0.003% (z score <−4) or greater than 0.998% (z score >4) were removed, as these likely reflect reporting errors.31Using gestational age, birth weight, and the participants’ sex, the Fenton reference was used to determine BWZS.z score standardized separately in each cohort.To develop a full-scale IQ score, scores on standardized cognitive tests that broadly assessed crystallized and fluid intelligence were combined. Once scores for fluid and crystallized intelligence were calculated, the average of the 2 scores was taken as to calculate a full-scale IQ score, which was 33 In the LSAC, the Wechsler Intelligence Scale for Children, Fourth Edition’s Matrix Reasoning test was administered.35 In the NLSY79 Child and Young Adult cohort, the principal component of the Peabody Individual Achievement Test’s Mathematics and Reading Recognition was used.36 In the GUI, the BAS Picture Similarities test was used.32All cognitive tests were measured at approximately 5 years of age, with the exception of fluid intelligence measured at 7 years of age in the LSAC. To assess fluid intelligence in the MCS, the principal component of scores on the British Ability Scales (BAS) Picture Similarities and Pattern Construction tests was taken.32 In the LSAC, the Peabody Picture Vocabulary Test, Third Edition was used,37 whereas in the NLSY79 Child and Young Adult cohort the revised Peabody Picture Vocabulary Test was used.38To measure crystallized intelligence, the MCS and GUI used BAS’s Naming Vocabulary test.12 Confounders were child sex, English as the primary language for the child, maternal age, maternal height, maternal weight, maternal marital status, parity, maternal education, the household income, and cohort. All confounders were measured at the nearest assessment to birth, except for the child’s primary language, which was assessed at age 5 years.Potentially confounding factors were based on those used in similar past studies and which were harmonizable across all cohorts.z scores at 5 years of age. Birth weight z scores were used rather than BWPs because BWZS are naturally centered, which is advantageous for testing interactions.39 To test for nonlinear associations and to determine feature selection, multivariate adaptive regression splines (MARS) in the R package earth were used.40 As such, BWZS and gestational age were tested for “hinges,” where the association with IQ changes in strength and/or direction. For feature selection, MARS will only include features , if they considerably improve the model fit, as determined by cross-validation. In cross-validation, 5 folds (subsets) of the data were created. Iteratively, 4 folds of the data were used to train models with a varying number of features, then tested on the fifth fold. The optimal model was determined by the highest mean R2 for the fifth fold .All analyses were performed in R, version 4.1.1 (R Foundation). The primary analysis tested BWZS, gestational age centered on 40 weeks, cohort, their interaction terms, and the aforementioned confounders as factors associated with IQ z scores were categorized into 6 groups . Gestational age was categorized into 3 groups: VP, MLP, and term born. The regression model included these categorical variables, their interaction terms, and the aforementioned confounders as factors associated with IQ z score at 5 years of age. From the regression results, estimated marginal means were calculated and contrasted as to test for the association of BWP with IQ within each gestation group, which was adjusted for multiple comparisons using the false discovery rate.41 The multivariable regression was 2-sided with P < .05 indicating statistical significance.Rather than using MARS, a multivariable regression was performed as a secondary analysis with BWPs and gestational age categorized into traditional groups. The BWPs based on the Fenton z scores of −0.2 , −0.5 , or −0.8  were thought to be equivalent to a small, medium, or large reduction in absolute IQ, respectively.42Finally, the coefficients of the MARS analysis were used to determine what combination of gestational age and BWZS would be associated with reduction of IQ scores by a clinically meaningful amount. Estimated IQ 43 Three percent of covariate data was imputed, with 77% of participants having no missing covariate data. Five imputed data sets were used for the multivariable regression, while a single version of the imputed data was used in the MARS analysis.Analyses only included participants with full data on IQ and BWZS, while missing confounder data were imputed by multiple chained equations.In the included sample, there were 30 643 participants with valid IQ scores at age 5 years and BWZS. Further perinatal and sociodemographic factors by cohort are summarized in z = 0.50 (69th BWP)  . For eve with IQ .z scores of the 75th to 90th BWP reference group were not statistically significantly different from any other BWP group.Following the MARS analysis, the analysis was repeated using multivariable regression (eTable 3 in z score reduction (IQ z <−0.2) was associated with a BWZS less than −1.9 (BWP <3%). Comparatively, a medium reduction in IQ (IQ z score <−0.5) was associated with birth at 33 weeks gestation and with a very small BWZS of –4 (BWP <0.001%). Alternatively, if an infant was born with a BWZS of 0.50 (69th BWP) or above, the estimated IQ Z score was below −0.5 when the infant was born at less than 27 weeks of gestation. Finally, large reductions in IQ were not associated with gestational age until the infant was born at 29 weeks and with a very small BWZS of −4, or if the infant was born at 25 weeks and with a BWZS of −0.85. The results from the MARS analysis indicated that above or below the 10th percentile (z = −1.28) would differentiate IQ scores in the normal range from a small IQ reduction, when the infant was born at approximately 34 weeks of gestation.From the MARS analysis, estimated IQ scores were calculated based on BWZS and gestational age, determining when IQ scores were associated with small, medium, or large reductions . For an This study investigated the association of relative birth weight and gestational age with IQ scores in 4 longitudinal cohorts. It was found that IQ scores increased with BWZS until an optimal BWZS of 0.50 (69th BWP), after which there was no association between BWZS and IQ. Independent of BWZS, IQ scores particularly increased from 25 weeks until 32 weeks of gestation with scores continuing to increase, but at a slower rate, up until 41 weeks. It was found that there was no evidence for a turning point where increasing BWZS became negatively associated with IQ performance, nor was there evidence for BWZS interacting with gestational age as a multiplicative risk effect.11 Furthermore, the present MARS results suggested no reduction in IQ above the 69th BWP, which was similarly found in the multivariable regression where within each gestation group , those in the 75th to 90th BWP range did not significantly differ on IQ to those in the 90% or higher. Thus, the present results are more in concordance with the Dutch study where no significant differences above the 80th percentile were found, relative to the Australian study where education scores subsequently declined.11 At the lower end of the BWP range, for both term borns and those born MLP, participants in the lowest 10% BWP range had significantly lower IQ than their respective 75th to 90th percentile reference groups, consistent with results indicating SGA is associated with lower cognitive performance.3 However, the clinical relevance of this association should be considered. As indicated in z score below −0.2, equivalent to an IQ score of 97, until their BWP is less than the third percentile. This indicates that while dichotomizing at the 10th percentile may find significant IQ differences among term borns, the estimated IQ of SGA term borns will often not be low enough to be of specific concern for clinicians, policymakers, or parents. Regarding VP participants, the 90% and higher BWP group has the highest estimated marginal means within the VP sample, which may suggest that being particularly large for gestational age is a protective factor for IQ of those born VP in a similar way to past findings regarding mortality.44 However, no BWP group significantly differed on IQ to those in the 75th to 90th percentile reference group. A lack of significant differences within the VP sample may arise due to lack of statistical power; this should be addressed in future research via the combination of multiple cohorts that specifically recruit those born VP, rather than only using population-based birth cohorts.45The results mostly indicated that “large is good” for IQ. The MARS result indicated that the 69th BWP or above is optimal for IQ, while the multivariable regression using categorical groups similarly indicated that term borns in the 75th to 90th BWP range had the optimal cognitive outcomes. These results are similar to the 66th and 80th percentiles reported previously in Australian and Dutch studies looking at educational outcomes.z score) increase before reducing in strength to 0.3 IQ points (0.02 z score) per week after 32 weeks gestation. This is largely concordant with a previous study in Germany and the UK, where IQ increased by 2.3 points per week until 34 weeks before a complete plateau.46 When the overall magnitude of IQ differences between those born VP and term borns is considered, the difference reported herein is smaller than those reported in meta-analyses of cohort studies but larger than those reported from registry studies. Meta-analyses of cohort studies have reported IQ z score differences between those born VP and term borns of 0.8647 and 0.78,7 respectively. In contrast, a Danish registry study using a sibling-matched approach indicated a much smaller difference at just 0.25 for adolescent boys born between 28 and 31 weeks gestation.48 By uniquely testing for nonlinear associations, the current study indicates that at 32 weeks of gestation the estimated IQ z score was −0.13, which then changed dramatically due to the hinge point to approximately −0.50 at 28 weeks. Additional methodological differences should be considered, including the use of multiple different cognitive tests rather than using a fully validated IQ test or that proxy scores were not calculated for participants unable to take part due to impairments. Because participants with lower gestational ages were more likely to have impairments that prevented them from completing the test, the present estimate of the IQ difference between those born VP and term borns may be an underestimation of the true population difference.49Furthermore, every week of gestation was associated with a 1.3 IQ point (0.09 28 and a week of gestation.29 This also meant that we could not investigate potentially important neonatal morbidities for IQ, such as intraventricular hemorrhage or bronchopulmonary dysplasia,47 or differentiate constitutionally small infants from those with intrauterine growth restriction, which may be stronger evidence of pathology.51 However, the relative effect sizes of neonatal morbidities have been found to be smaller than socioenvironmental factors.7 While socioenvironmental factors were thoroughly controlled for, there may be further potentially important confounding factors such as familial dietary patterns that should be considered.52 Overall, gestational age and relative birth weight should potentially be thought of as early and easily measurable indicators that an infant is at risk for lowered childhood IQ and potentially beyond, given reports of stable associations between preterm birth and SGA with IQ differences into adulthood.53Rather than using hospital records, birth weight and gestational age were parent reported. However, in the year after birth, more than 90% of parents can accurately recall their child’s birth weight within 100 gIn this cohort study of 4 large, longitudinal cohorts, increasing BWP was associated with increased IQ until a plateau at the 69th BWP, and this association was independent of gestational age’s association with IQ. When considering both factors additively, being born at 34 weeks gestation and below the 10th BWP was associated with a small IQ reduction. For term borns, a lower BWP cutoff at or below the third BWP was associated with a similarly small IQ reduction.