Objective: To anlysis the efficacy and safety of cut-umbilical cord milking (C-UCM) compared with immediate cord clamping in preventing anemia and iron deficiency among term cesarean-delivered newborns. Methods: A total of 485 pregnant women planning to deliver by cesarean section were recruited in this randomized controlled trial in Hunan Maternal and Child Health Hospital and Liuyang Maternal and Child Health Care Hospital from July 2016 to April 2019. A block randomization was conducted to evenly allocate them to the controlled group and the C-UCM group. In the controlled group, the cord was clamped within 30 seconds as routine. In the C-UCM group, the cord was first clamped at 25 cm from the newborn\'s navel, and then the blood in the cord was gently squeezed into the newborn\'s body until the cord became white and shriveled. The cord was clamped twice at 2-3 cm from the newborn\'s navel subsequently. Neonatal jaundice, hyperbilirubinemia and polycythemia were monitored before discharge. After the newborns discharged, their hemoglobin, red blood cell count, hematocrit (at the age of 1, 6 and 12 months) and serum ferritin (at the age of 6 and 12 months) were followed up; body length and weight were measured; and information about their feeding and iron supplementation were collected (at the age of 1, 6, 12 and 18 months). The two groups were compared by t test, Mann-Whitney U test, χ² test, or Fisher exact probability method. The hospital was set as a random item, and the mixed effects regression model was used to evaluate the effect of C-UCM on relevant indicators of cesarean-delivered newborns. Results: There were 244 women in the C-UCM group with an average age of (31.9±4.4) years, and 241 in the control group with an average age of (31.8±4.2) years (P>0.05). There was no statistically significant difference between the C-UCM group and the control group at 1, 6 and 12 months of age in hemoglobin [(123.6±14.5) vs (122.2±14.5) g/L, (115.3±9.4) vs (114.1±8.5) g/L, (115.6±9.6) vs (116.1±12.6) g/L] or anemia incidence rate [15.2% (17/112) vs 18.4% (19/103), 22.7% (34/150) vs 26.8% (44/164), 22.3% (25/112) vs 19.5% (22/113)] (all P>0.05). There was no statistically significant difference between the two groups at 6 and 12 months of age in serum ferritin [M (Q1, Q3), 39.9 (24.9, 61.8) vs 43.6 (25.2, 100.9) μg/L, 40.3 (25.4, 259.2) vs 40.3 (26.4, 167.6) μg/L)] or iron deficiency incidence rate [6.1% (5/82) vs 4.2% (3/72), 6.7% (5/75) vs 3.8% (3/80)] (all P>0.05). There were also no significant difference between the two groups in other indicators, such as the Z-score of weight-for-length, the incidence of neonatal jaundice, and the incidence of neonatal hyperbilirubinemia (all P>0.05). After adjusting for the relevant covariates, there were still no significant effects of C-UCM on these outcomes above. Conclusions: Compared to immediate cord clamping, the intervention of gently squeezing 25 cm of the cord does not significantly reduce the risk of anemia or iron deficiency in term cesarean-delivered newborns, nor does it have a significant impact on infant growth and development. Yet this intervention does not increase the risk of jaundice or hyperbilirubinemia in newborns as well.
目的： 分析断脐后捋挤脐血（C-UCM）预防足月剖宫产儿贫血和铁缺乏的有效性和安全性。 方法： 本随机对照试验纳入2016年7月至2019年4月湖南省妇幼保健院和浏阳市妇幼保健院剖宫产孕妇485名，采用区组随机分组将其等比例分配至对照组和C-UCM组。对照组按照临床常规在30 s内完成结扎断脐，C-UCM组在距新生儿肚脐25 cm处行初次结扎断脐，而后轻柔捋挤该段脐带中的血液至新生儿体内、待脐带发白变瘪后再在距肚脐2~3 cm处行二次结扎断脐。新生儿出院前监测黄疸、高胆红素血症和红细胞增多症情况；出院后随访并检测血红蛋白、红细胞计数和红细胞压积（1、6和12月龄）和血清铁蛋白（6和12月龄），测量身长、体重，询问喂养和补铁情况（1、6、12和18月龄），并比较上述指标在两组间差异。将医院设为随机项，采用混合效应回归模型评价C-UCM对剖宫产儿相关指标的影响。 结果： 485名孕妇年龄为（31.8±4.3）岁；对照组241名，年龄为（31.8±4.2）岁，C-UCM组244名，年龄为（31.9±4.4）岁，两组年龄差异无统计学意义（P>0.05）。C-UCM组和对照组新生儿1、6和12月龄血红蛋白水平［（123.6±14.5）比（122.2±14.5）g/L、（115.3±9.4）比（114.1±8.5）g/L、（115.6±9.6）比（116.1±12.6）g/L］和贫血发生率［15.2%（17/112）比18.4%（19/103）、22.7%（34/150）比26.8%（44/164）、22.3%（25/112）比19.5%（22/113）］差异无统计学意义（均P>0.05）。C-UCM组和对照组6和12月龄血清铁蛋白水平［M（Q1，Q3）］［39.9（24.9，61.8）比43.6（25.2，100.9）μg/L，40.3（25.4，259.2）比40.3（26.4，167.6）μg/L］和铁缺乏发生率［6.1%（5/82）比4.2%（3/72）、6.7%（5/75）比3.8%（3/80）］差异均无统计学意义（均P>0.05）。两组间身长别体重Z评分、新生儿黄疸和新生儿高胆红素血症发生率等差异均无统计学意义（均P>0.05）。调整相关协变量后仍未见C-UCM对上述结局有影响（均P>0.05）。 结论： 与立即钳夹脐带相比，未见断脐后轻柔捋挤25 cm脐带血的干预方法降低足月剖宫产儿贫血和铁缺乏的发生风险，未见影响婴儿生长发育，但也未见其增加新生儿黄疸和高胆红素血症发生风险。.

BACKGROUND: Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels.
METHODS: Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category.
RESULTS: We observed a significant interaction between pre-pregnancy BMI category and prenatal maternal depressive symptoms with cord blood omega-3 (F(4,379) = 6.21, p < .0001, adj. R2 = 0.05). Stratified models revealed an association between prenatal maternal depressive symptoms with lower cord blood omega-3 levels only among individuals with pre-pregnancy OWOB (β = -0.06, 95% CI = -0.11, -0.02; F (2,208) = 4.00, p < .05, adj R2 = 0.03). No associations were observed among non-OWOB participants.
CONCLUSIONS: Findings suggest maternal-placental transfer of omega-3 may represent one pathway by which maternal metabolic and mental health impacts infant development.

UNASSIGNED: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations.
UNASSIGNED: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504).
UNASSIGNED: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts.
UNASSIGNED: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers.
UNASSIGNED: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.

UNASSIGNED: Umbilical cord pH (UC-pH) level is an important objective indicator of intrapartum fetal hypoxia and is used to predict neonatal morbidity and mortality. A UC-pH value of less than 7.00 is often defined as a threshold for severe acidosis, but existing evidence is divergent and largely based on UC-pH measurements from selected populations; consequently, the results are challenging to interpret.
UNASSIGNED: To investigate the association between UC-pH levels and the risk of adverse neonatal outcomes in a national setting with universal UC-pH measurement.
UNASSIGNED: This national, population-based cohort study included all liveborn, singleton, full-term infants without malformations born in Denmark from January 1, 2012, to December 31, 2018. Data were analyzed from January 1, 2023, to March 1, 2024.
UNASSIGNED: Umbilical cord pH level categorized as less than 7.00, 7.00 to 7.09, 7.10 to 7.19 and 7.20 to 7.50 (reference group).
UNASSIGNED: The primary outcome was a composite of severe adverse neonatal outcomes: neonatal death, therapeutic hypothermia, mechanical ventilation, treatment with inhaled nitric oxide, or seizures. Secondary outcomes were individual components of the primary outcome, Apgar score, respiratory outcomes, and hypoglycemia. Data are presented as adjusted risk ratios (ARRs) with 95% CIs.
UNASSIGNED: Among the 340 431 infants included, mean (SD) gestational age was 39.9 (1.6) weeks; mean (SD) birth weight was 3561 (480) g; and 51.3% were male. Umbilical cord pH of less than 7.20 was observed more often among infants with a gestational age of 40 or 41 weeks (31.6%-33.6% compared with 18.2%-20.2% at a gestational age of 39 weeks) and among male infants (53.9%-55.4% vs 44.6%-46.1% among female infants). Compared with the pH reference group (576 of 253 540 [0.2%]), the risk for the primary outcome was increased for the groups with UC-pH levels of less than 7.00 (171 of 1743 [9.8%]), 7.00 to 7.09 (101 of 11 904 [0.8%]), and 7.10 to 7.19 (259 of 73 244 [0.4%]). Comparable patterns were observed for the individual outcomes, except for neonatal death, which was only increased in the group with UC-pH levels of less than 7.10. The risk of treatment with continuous positive airway pressure was increased when UC-pH levels were less than 7.20, and the risk of hypoglycemia was 21.5% if UC-pH levels were less than 7.10.
UNASSIGNED: In this cohort study of 340 431 newborn infants, results support and extend previous studies indicating a higher risk of adverse outcomes even at UC-pH levels above 7.00. The threshold for more intensive observation and treatment may be reconsidered.

BACKGROUND: Using natural killer (NK) cells to treat hematopoietic and solid tumors has great promise. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells provide an \"off-the-shelf\" solution.
METHODS: In this study, we developed two CAR-NK cells targeting PD-L1 derived from lentiviral transduction of human umbilical cord blood (UCB)-CD34+ cells and UCB-CD34+-derived NK cells. The transduction efficiencies and in vitro cytotoxic functions including degranulation, cytokine production, and cancer cell necrosis of both resultants PD-L1 CAR-NK cells were tested in vitro on two different PD-L1 low and high-expressing solid tumor cell lines.
RESULTS: Differentiated CAR‑modified UCB-CD34+ cells exhibited enhanced transduction efficiency. The expression of anti-PD-L1 CAR significantly (P < 0.05) enhanced the cytotoxicity of differentiated CAR‑modified UCB-CD34+ cells and CAR-modified UCB-CD34+-derived NK cells against PD-L1 high-expressing tumor cell line. In addition, CAR-modified UCB-CD34+-derived NK cells significantly (P < 0.05) restored the tumor-killing ability of exhausted PD-1 high T cells.
CONCLUSIONS: Considering the more efficient transduction in stem cells and the possibility of producing CAR-NK cell products with higher yields, this approach is recommended for studies in the field of CAR-NK cells. Also, a pre-clinical study is now necessary to evaluate the safety and efficacy of these two CAR-NK cells individually and in combination with other therapeutic approaches.

UNASSIGNED: Production of anti-phosphatidylserine (anti-PS) antibodies has been associated with malaria and can aggravate pathology. How these autoantibodies develop during early childhood in a malaria context is not known. We examined levels of anti-PS IgG and IgM antibodies in a longitudinal cohort of mother-baby pairs during birth, in the infants at 2.5, 6 months, and in mothers and their babies at 9 months postpartum.
UNASSIGNED: There was no difference between levels of anti-PS IgG in cord blood and the mothers\' peripheral blood at birth. However, anti-PS IgM levels were significantly higher in the mothers compared to the infants\' cord blood, and IgM levels were steadily increasing during the first 9 months of the infants\' life. In infants that had the highest anti-PS IgM levels at birth, there was a decline until 6 months with a rise at 9 months. Infants that possessed high anti-PS IgG at birth also exhibited a progressive decline in levels. When anti-PS were correlated to different fractions of B-cells, there were several correlations with P. falciparum specific atypical B cells both at birth and at 2.5 months for the infants, especially for anti-PS IgM. Anti-PS also correlated strongly to C1q-fixing antibodies at birth.
UNASSIGNED: These results show that anti-PS IgG acquired by mothers could be transferred transplacentally and that IgM antibodies targeting PS are acquired during the first year of life. These results have increased the knowledge about autoimmune responses associated with infections in early life and is critical for a comprehensive understanding of malaria vaccine functionality in endemic areas.

UNASSIGNED: Vitamins A and D are essential for the health of pregnant women and infants. Nevertheless, the relationship between umbilical cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants remains uncertain.
UNASSIGNED: This cohort study aims to examine the relationship between cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants aged 0-6 months.
UNASSIGNED: 140 singleton mother-infant pairs were recruited in total. Questionnaires were used to collect maternal and infant information, and liquid chromatography was utilized to quantify the levels of vitamins A and D in the umbilical cord blood. Anthropometric measurements were conducted at birth, at 3 and 6 months of age, and the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HAZ), and BMI-for-age z-score (BMIZ) were calculated. Univariate and multivariate linear regression models were used for the analysis.
UNASSIGNED: The average concentration of vitamins A and D in cord blood was 0.58 ± 0.20 μmol/L and 34.07 ± 13.35 nmol/L, both below the normal range for children. After adjusting for confounding factors, vitamin A levels in cord blood positively correlated with HAZ growth in infants aged 3-6 months (β= 0.75, P < 0.01) while vitamin D levels negatively correlated with LAZ growth (β= -0.01, P = 0.01) and positively correlated with BMIZ growth (β= 0.02, P < 0.01).
UNASSIGNED: Higher Vitamin A levels at birth promote HAZ growth in infants aged 3-6 months while higher vitamin D levels at birth promote BMIZ growth in infants aged 3-6 months.
UNASSIGNED: https://register.clinicaltrials.gov, identifier NCT04017286.

The current study aimed to explore the combined and individual effects of vitamin D (VitD) status in three trimesters during pregnancy and cord blood (CB) on child growth trajectories from birth to 4 years of age. Pregnant women (n = 1100) were recruited between 2013 and 2016 in the Shanghai Birth Cohort (SBC) Study. A total of 959 mother-child dyads were included. VitD status was measured by LC-MS/MS at three trimesters (T1, T2, T3) and CB. Children\'s weight, length/height, and head circumference were assessed at birth, 42 days, 6, 12, 24 months, and 4 years of age, and standardized into z-scores [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HCZ) and weight-for-length z-score (WLZ)]. Using the group-based trajectory model (GBTM), the trajectories of the four growth parameters were categorized into discrete groups. The generalized estimating equation (GEE) was employed to analyze the mixed effect of 25(OH)D throughout pregnancy on growth trajectories. The association between 25(OH)D status and each growth trajectory group was examined by multivariable logistic regression. Each 10 ng/mL increase in 25(OH) throughout three trimesters was not associated with four anthropometric parameters. Each 10 ng/mL increase in VitD in T3 was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.75; 95% CI: 0.62, 0.91; p < 0.01). Each 10 ng/mL increase in VitD in CB was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.57; 95% CI: 0.43, 0.76; p < 0.01). No significant association was found between maternal or CB VitD and LAZ or HCZ. Three trimesters\' VitD throughout pregnancy had no persistent effect on the offspring\'s growth trajectory. However, higher VitD status in the third trimester and CB related to a lower risk of high-increasing WAZ from birth to 4 years of age. Elevated VitD levels in late pregnancy and cord blood may protect against continuous early-life weight growth at high levels.

BACKGROUND: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP.
METHODS: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions.
RESULTS: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk.
CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP.
BACKGROUND: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

UNASSIGNED: Malnourished pregnant women are at increased risk of micronutrient deficiency. We assessed the vitamin B12 status in both malnourished and normally nourished pregnant women and their neonates. Additionally, we studied the association between maternal B12 levels, cord B12 levels and neonatal anthropometry.
UNASSIGNED: This cross-sectional study enrolled 63 malnourished and 63 normally nourished mothers and neonates. Maternal and cord blood samples were collected at the time of delivery for estimation of vitamin B12 levels. Maternal and cord vitamin B12 levels were compared using the Mann-Whitney U test. Neonatal anthropometry was correlated with maternal and cord B12 levels using Spearman\'s correlation. Data were analyzed using SPSS version 25.
UNASSIGNED: Mean maternal age was 26.58 yrs. The median cord B12 levels were lower than the maternal B12 levels. Maternal B12 levels showed a strong positive correlation with cord B12 levels (rho = 0.879; p < 0.001). Maternal (p < 0.001) and cord (p < 0.001) vitamin B12 levels were significantly lower in the malnourished group than in the normally nourished group. In malnourished group, 66.8% mothers and 95.2% neonates were Vitamin B12 deficient, whereas 1.5% mothers and 4.7% neonates were vitamin B12 deficient in normally nourished group. In the malnourished group, maternal B12 levels were positively correlated with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p =0.008), whereas cord B12 levels were positively correlated with birth weight in the normally nourished group. (rho 0.277 p= 0.028).
UNASSIGNED: High rates of vitamin B12 deficiency were observed in malnourished mothers and neonates. There was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.