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Objective: To study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases., Method: Umbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth., Results: The umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease., Conclusion: Umbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period., Competing Interests: Declaration of competing interest All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: The effectiveness of MgSO4 for foetal neuroprotection is acknowledged, but the best time to provide it in relation to birth is a conundrum, and dose schedule is yet unknown. Understanding the determinants of the magnesium levels in cord blood aids in determining the appropriate timing and length of administration., Aim and Objective: To assess the cord blood magnesium concentration in relation to the timing of MgSO4 and delivery. To achieve ROC in relation to optimum level of cord blood magnesium concentration in relation to neonatal outcome variables., Study Design: A prospective observational study conducted in a tertiary care hospital over 2 years in women having preterm delivery from 26 weeks to 33 + 6 weeks, who received Neuroprophylaxis. Cord blood was collected for magnesium level estimation. Baby followed 24 h after delivery. ROC analysis performed for predicting an optimal cut-off for a continuous predictor predicting binary outcome., Results: 85 recruited cases divided into bolus group, bolus + infusion group. The mean cord blood magnesium (n = 85) was 3.8 mg/dl. The AUROC for Gestational Age at Administration predicting Baby Outcome: 0.699, It was statistically significant (p = 0.034). The AUROC for Cord Blood Mg predicting Baby Outcome: 0.606, It was not statistically significant (p = 0.262)., Conclusion: Mean cord blood magnesium levels served as a tool to determine the timing and duration of Neuroprophylaxis. Mean cord blood magnesium of 3.8 mg/dl should be achieved to serve the purpose of Neuroprotection. To achieve this, Bolus followed by Infusion should be administered for at-least 6 h prior to delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Preterm birth (PTB) is one of the most frequent pregnancy complications. It affects millions of babies each year worldwide and is associated with increased morbidity and mortality. PTB-associated alterations in the maternal immune response may have a direct effect on the developing fetal immune system. Having recently shown that B regulatory (Breg) cells are decreased in number and functionally impaired in maternal blood from women delivering preterm, we now addressed the question whether the adaptive immune system is also altered in cord blood (CB) after the onset of PTB. PTB was associated with increased concentrations of IL-6, TNF-α and IL-21 in CB and enhanced IL-6, but decreased IFN-γ and IL-4 in amniotic fluid (AF) samples compared to term delivery (TD). We found no differences in the frequency of CD19 + B cells, CD4 + T cells or CD4+Foxp3+CD25+ T regulatory (Treg) cells in CB cells in PTB vs TD. The frequency of CD86 + B cells was increased, while the percentage of CD24 hi CD38 hi CD19 + Breg and CD1d hi CD5+ Breg cells and the ability of B cells to convert into Breg cells was diminished in PTB compared to TD. CB B cells from PTB secreted more IL-6, TNF-α, IL-9 and IL-2 compared to B cells obtained from term samples. We conclude that, after PTB onset, a shift from immunoregulation towards inflammation takes place in CB cells that are reportedly representative of the fetal compartment. B cells have a substantial contribution herein. This phenomenon might account for the observed enhanced mortality and morbidity in prematurely born infants. Further studies will clarify how to employ this easy-to-obtain information for closely monitoring newborns at risk., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Maternal hypertension may alter physiological parameters, dysregulating the release of hormones such as adipokines, thus influencing the fetal growth course. This study investigated whether hypertensive disorders of pregnancy alter cord blood adipokine levels and correlate these with anthropometric parameters in preterm infants. This is a prospective cohort study with pregnant women < 37-week gestation with and without hypertension and their offspring. Cord blood leptin, adiponectin, and ghrelin were analyzed by LUMINEX®. These adipokines were compared between the groups exposed or not to gestational hypertension using non-parametric statistical tests. The hypertensive pregnancies had significantly higher cord blood leptin (1.00 (IQR 0.67-1.20 ng/mL)) and adiponectin (18.52 (IQR 17.52-25.13 μg/mL)) levels than those without hypertension (0.07 (IQR 0.06-0.08 ng/mL) and 8.13 (IQR 6.50-8.68 μg/mL), respectively, p < 0.0001). The adipokine levels were higher in AGA and SGA infants in the exposed group for both moderate and late preterm. SGA had significantly higher ghrelin levels than the AGA infants. Ghrelin levels were negatively correlated with birth weight (r = - 0.613, p < 0.001), birth length (r = - 0.510, p < 0.001), head circumference (- 0.346, p < 0.002), and gestational age (r = - 0.612, p < 0.001).Conclusions: Our findings demonstrate an increase in adipokine levels in the cord blood of preterm newborn infants exposed to maternal hypertension. What is Known: • Clinical evidence suggests that concentration of the serum adipokines may be affected by risk of hypertension in both adults and pregnant women. • Maternal profile as hypertension alters intrauterine environment and could affect the function of fetal metabolism, impairing fetal growth. What is New: • Gestational hypertension modifies the adipokine profile, with higher rates already present at birth in cord blood samples. • Within the hypertensive group and stratifying for gestation age, ghrelin concentrations were higher in SGA newborns, both in the moderate and late preterm, compared with AGA newborns.

Problem: Vitamin D is well-known for having anti-inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre-term birth. The present study aims to evaluate the impact of fetal cord serum 25-hydroxyvitamin D-mediated signaling in mediating inflammatory responses in placenta during pre-term birth., Method of Study: For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre-term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p-NF-kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study., Results: Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre-term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r = .9368***) and birthweight (r = .9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre-term born babies., Conclusion: Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti-inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre-term birth., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

As endocrine disrupting chemicals, hexachlorocyclohexane (HCH) isomers were reported to impair the intrauterine growth. Although the findings of HCHs with preterm birth were well established, the associations with gestational age were limited. In the present study, we examined whether exposure to HCHs would influence gestational age. The study population included 1028 pregnant women and their offspring who were born in 2014-2015 from a birth cohort in Wuhan, China. Associations of the cord serum HCH levels with gestational age were estimated using generalized linear models. We found higher HCH levels in pregnant women, who were elder, had higher body mass index (BMI) before pregnancy, received higher education, or were exposed to smoking passively. For term birth, the 3rd tertiles of α-HCH and γ-HCH were significantly associated with shorter gestational age [crude β = -1.017, confidence interval (CI): - 2.017, - 0.018 for α-HCH, crude β = -1.068, CI: - 2.067, - 0.070 for γ-HCH], and relationships were similar after adjusted by covariates. Stratified analysis showed positive associations between α-HCH and gestational age for mothers younger than 25 years old (adjusted β = 0.610, CI: 0.061, 1.158), while showing negative relationships for mothers elder than 35 years old (adjusted β = -1.365, CI: -2.414, -0.317). In summary, our results indicated cord serum levels of HCHs were associated with gestational age at birth., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Micronutrients like vitamin B 12 and folate play an important role in nucleic acid metabolism, cell growth, and are important determinants of fetal growth. The present study examined the levels of maternal and cord plasma folate, vitamin B 12 , homocysteine, and their association with birth outcome in women with preeclampsia (PE). This study includes 450 normotensive control (NC) and 350 women with PE. PE women were further classified into women delivering at term (n = 224) and preterm (n = 126). Maternal and cord blood was collected at delivery. The levels of maternal vitamin B 12 (p < 0.05), folate (p < 0.01), and homocysteine (p < 0.01) were higher in the PE group as compared to the NC group. Maternal folate levels were higher in both term and preterm groups, while vitamin B 12 levels were higher only in the preterm group as compared to NC group. In contrast, homocysteine was higher only in the term PE group. Similar changes were also observed in the cord plasma. There was a positive association of maternal plasma homocysteine with systolic (r = 0.151, p = 0.000, n = 578) and diastolic blood pressure (r = 0.213, p = 0.000, n = 578) in the whole cohort. A negative association of maternal folate with systolic blood pressure (r = -0.105, p = 0.048, n = 352) while a positive association with baby weight in the NC group (r = 0.116, p = 0.029, n = 352). The present study suggests that maternal and cord micronutrient levels are altered in women with PE.

Cobalt is an essential trace element and has been suggested to be involved in oxidative stress and inflammatory responses. However, researches have paid little attention to the association between serum cobalt levels during pregnancy and the risk of preterm birth (PTB, <37 week of gestation). The purpose of this study was to determine the association between maternal and umbilical cord serum cobalt concentrations and the risk of PTB. A total of 2951, 3080, and 2698 serum samples were obtained from pregnant women in the first, the second trimester, and the umbilical cord blood, respectively. The tertile levels of ln-transformed cobalt were defined as low, medium and high levels for cobalt respectively. In our study, the rate of PTB (<37 weeks of gestation) was elevated in subjects with low cobalt levels in the first trimester of pregnancy (adjusted OR 1.61, 95% CI: 1.01, 2.58) and the second trimester of pregnancy (adjusted OR 1.62, 95% CI: 1.03, 2.54). The adjusted OR for PTB was 2.46 (95% CI: 1.34, 4.53) among subjects with low cobalt levels and 2.22 (95% CI: 1.19, 4.15) among subjects with medium cobalt levels in the umbilical cord serum. Our findings demonstrated that the lower levels in maternal and umbilical cord serum cobalt were associated with the increased the risk of PTB., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To assess the short and medium-term effects of milking maneuver (MM) compared with early cord clamping for infants born before 37 weeks of pregnancy., Material and Methods: 138 infants between 24+0 and 36+6 weeks of gestation were allocated to MM or early cord clamping. Primary outcomes were the requirement of red blood cell transfusions or phototherapy., Results: Initial hemoglobin was significantly higher in the MM group by 1.675 g/dL (p < 0.05) and initial hematocrit by 5.36% (p < 0.05), but no differences in the need of transfusion during the first 30 days after delivery were found (RR 0.8; 95% CI 0.22-2.85). Peak serum bilirubin was similar in both groups (11,097 ± 3.21 vs. 11,247 ± 3.56 mg/dL, p = 0.837). Phototherapy requirements were higher in the MM group (RR 1.62; 95% CI 1.1-2.38). No differences regarding the need of oral iron supplementation, platelet transfusion, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, periventricular leukomalacia, meconium aspiration syndrome, use of surfactant, days of oxygen supplementation, need of vasopressors, length of stay in the neonatal intensive care unit, or postpartum hemorrhage were found., Conclusion: MM does not reduce the need for red blood cell transfusions and increases phototherapy requirements in preterm infants., (© 2018 S. Karger AG, Basel.)

Background: Preterm birth is still a global burden particularly in Indonesia. The suboptimal concentration of certain micronutrients and heavy metals is hypothesized to play a role in the mechanism of preterm birth., Objective: This study aimed to analyze the micronutrients and heavy metals concentrations between subjects with term and preterm birth., Design: A cross-sectional study was conducted during January-June 2017 in Cipto Mangunkusumo Hospital and Budi Kemuliaan Hospital, Jakarta, Indonesia. Subjects were divided into term and preterm birth groups. The measured outcomes were maternal serum, placental, and blood cord concentration of zinc, copper, iron, selenium, manganese, mercury, lead, AtRA, and 25(OH)D., Results: A total of 51 pregnant women participated in this study. Term group had higher concentration of maternal serum AtRA (0.22 ± 0.07 ng/mL versus 0.12 ± 0.03 ng/mL, p <0.001), higher placental concentration of manganese {0.99 (0.38 - 1.78) μ g/g versus 0.42 ± 0.18 μ g/g, p <0.001}, iron (252.16 ± 170.61 μ g/g versus 78.45 ± 51.73 μ g/g, p <0.001), copper {2.96 ± 1.80 μ g/g versus 1.62 (0.70 - 3.88) μ g/g, p 0.019}, zinc {58.34 (27.88 - 124.05) μ g/g versus 28.41 (1.46 - 137.69) μ g/g, p 0.011}, selenium (0.31 ± 0.31 ng/g versus 0.14 ± 0.20 ng/g, p 0.024), AtRA {21.7 ± 10.69 ng/g versus 0.7 (0.42 - 5.10) ng/g, p <0.001}, and 25(OH)D {75.84 ± 45.12 ng/g versus 18.00 (5 - 88) ng/g, p <0.001}, lower placental concentration of mercury (0.20 ± 0.17 ng/g versus 20.47 ± 41.35 ng/g, p 0.019) and lead (0.02 ± 0.01 ng/g versus 0.81 ± 1.43 ng/g, p 0.009), and higher cord blood concentration of copper {32.20 (16.30 - 69.60) μ g/dL versus 20.60 (5.80 - 53.30) μ g/dL, p 0.006} and AtRA (0.16 ± 0.04 versus 0.07 ± 0.01, p <0.001)., Conclusion: Preterm birth is associated with lower concentrations of micronutrients which play a role in antioxidant mechanism, as well as higher concentration of mercury and lead.

Objectives: To investigate whether the levels of angiogenic factors in cord blood are associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants with maternal preeclampsia., Study Design: This retrospective cohort study included 199 singleton infants (gestational age < 32 weeks), including the preeclampsia group (59 infants) with severe/moderate BPD (24 infants) or no/mild BPD (35 infants) and the no preeclampsia group (140 infants)., Main Outcomes Measures: The levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin, and placental growth factor (PlGF) in cord blood were measured and compared among the study groups., Results: The soluble endoglin level and the ratio of (sFlt-1 + soluble endoglin) to PlGF were significantly higher in the preeclampsia group than in the no preeclampsia group (P < .05). Among preterm infants with maternal preeclampsia, both of these parameters were also significantly higher in the severe/moderate BPD group than the no/mild BPD group (P < .05). Receiver operator curve analysis revealed that increased cord blood soluble endoglin was predictive of severe or moderate BPD in preterm infants with maternal preeclampsia (area under the curve 0.73). Gestational age (adjusted odds ratio [OR] 0.25; P < .001) and high soluble endoglin level in cord blood (>3420 pg/mL) (adjusted OR 11.9; P = .006) were significant risk factors for the development of severe or moderate BPD in the preeclampsia group according to multivariate logistic regression analysis., Conclusion: Increased cord blood soluble endoglin is associated with the development of severe or moderate BPD in preterm infants with maternal preeclampsia., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the clinical application of the new Hologic quantitative foetal fibronectin (qfFN) bedside test for the prediction of spontaneous preterm birth (sPTB) in patients with symptoms suggestive of spontaneous threatened preterm labour (sPTL)., Methods: A prospective observational study with 154 pregnant women presenting signs and symptoms of sPTL was conducted. These women were subjected to a qfFN test between 22 and 35 weeks of gestation For each cut-off threshold, the ability to predict sPTB at within 14 days of conducting the test and <37 weeks was assessed by calculating the positive predictive value (PPV), negative predictive value (NPV), likelihood ratios, odds ratios, sensitivity, and specificity., Results: For the outcome of delivery within 14 days of the test, qfFN <10 ng/mL had a 100% NPV and >200 ng/mL produced a 50.0% PPV; thus, qfFN added enhanced discrimination between high- and low-risk patients. The overall rate of sPTB (<37) was 13.3% (16/120), which increased progressively with increasing levels of fFN, with rates of 9.8% (8/81), 11.5% (3/26), 14.2% (1/7), 50% (3/6) within the 4 categories (fFN 0-9, 10-49, 50-200, 200+) respectively., Conclusions: The use of the qfFN testing in symptomatic patients allowed for more accurate identification of women at risk of sPTB and thus more directed management., (© 2017 S. Karger AG, Basel.)

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Some evidence suggests that low maternal vitamin D status adversely affects perinatal health but few studies have examined cord blood vitamin D status. This project aimed to determine the association between the cord blood concentration of 25-hydroxyvitamin D [25(OH)D] and neonatal outcomes., Methods: A nested case-control study was conducted in Quebec City, Canada from 2005 to 2010. Included were 83 cases of low birthweight (LBW; <2500 g), 301 cases of small for gestational age (SGA; <10th percentile), 223 cases of preterm birth (PTB; <37 weeks' gestation), and 1027 controls. Levels of 25(OH)D were determined by chemiluminescence immunoassay. Adjusted odds ratios (OR) and 95 % confidence intervals (CI) were estimated with logistic regression., Results: Cord blood [25(OH)D] <50 nmol/L was associated with a lower risk of LBW compared to [25(OH)D] ≥75 nmol/L (OR 0.47 95 % CI 0.23-0.97). For 25(OH)D levels 50-75 nmol/L, a significant association was not demonstrated (OR 0.58, 95 % CI 0.34-1.01). No significant associations were observed between [25(OH)D] and either SGA or PTB after adjustment., Conclusions: Although our findings suggest that [25(OH)D] <50 nmol/L is associated with reduced risk of having a LBW infant, prenatal vitamin D recommendations require an examination of the literature that considers the full spectrum of maternal and neonatal outcomes.

Objective: Evaluate the effect of Hepatitis B vaccine (HepB) on C-reactive protein (CRP) levels in healthy term infants., Study Design: A prospective controlled study in an academic medical center serving an inner city community. Subjects were singleton, term and late pre-term infants delivered vaginally with normal physical examination and without risk factors for or signs of sepsis. CRP levels were measured in cord blood and at the time of newborn genetic screening. The early HepB group received HepB within a few hours after birth. The late HepB group had HepB delayed until after the repeat CRP., Result: One hundred and eighty-two infants were enrolled (94 early HepB, 88 late HepB) with similar demographic features in each group. Neither the mean cord CRP (early HepB, 0.24±0.23 vs late HepB, 0.30±0.68 mg l(-1), P=0.37) nor the median of the repeat CRP (early HepB, 2.6 (interquartile range, 1.18 to 7.03) vs late HepB, 1.7 (interquartile range, 0.73 to 5.8) mg l(-1), P=0.14) showed significant differences between the two groups., Conclusion: HepB does not affect CRP levels in healthy term infants.

Objective: To develop a reliable and validated tool for prediction of spontaneous preterm birth (sPTB) in symptomatic women that incorporates quantitative measurements of fetal fibronectin (qfFN) and other relevant risk factors., Methods: Data were analyzed that had been collected prospectively from 382 women who presented at an emergency assessment unit between 22 + 0 and 35 + 6 weeks' gestation with symptoms of preterm labor. Clinicians were blinded to qfFN although they were aware of qualitative fFN results. Parametric survival models for sPTB, with time-updated covariates, were developed for combinations of predictors and the best was selected using the Akaike and Bayesian information criteria. The model was developed on the first 190 consecutive women and validated on the subsequent 192. The estimated probability of delivery before 30, 34 or 37 weeks' gestation and within 2 or 4 weeks of testing was calculated for each patient and was compared to actual event rates. Predictive statistics were calculated to compare training and validation sets., Results: The final model that was selected used qfFN and previous sPTB/preterm prelabor rupture of membranes (PPROM) as predictors. Predictive statistics were similar for training and validation sets and there was good agreement between expected and observed sPTB for all outcomes. Areas under the receiver-operating characteristics curves ranged from 0.77 to 0.88, indicating accurate prediction across all five delivery outcomes., Conclusions: sPTB in symptomatic women can be predicted accurately using a model combining qfFN and previous sPTB/PPROM. Clinicians can use this model, which has been incorporated into an App (QUiPP), to determine accurately a woman's risk of sPTB and potentially tailor management decisions appropriately., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: In recent years, much attention has been given to infants born prematurely, at 34 0/7 to 36 6/7 weeks of gestation (WG), which have been classified as 'late preterm'. Neonates from that subgroup are less physiologically and metabolically mature than term infants. The aim of the study was to determine whether infants born at 34WG can be classified as 'late preterm' or 'preterm' newborns., Material and Methods: A total of 141 newborns were included in the study: 25 born ≤ 33WG, 53 late-preterm newborns, and 63 term infants. Cord-blood neutrophil gelatinase-associated lipocalin (NGAL) and creatinine concentrations were measured in all newborns. Also, the incidence of clinical complications in the early adaptive period during hospitalization was evaluated., Results: Higher NGAL concentration was noted among preterm newborns as compared to late-preterm neonates (p < 0.05), and term newborns (p < 0.05), especially in children born at 34WG as compared to 35WG (p < 0.001). However, no differences in NGAL concentration were found between neonates born at 35WG and 36WG, as well as children born at 36WG and term infants. A relationship between umbilical NGAL levels and gestational age was observed. Additionally, a statistically significant difference was found in the incidence of respiratory distress syndrome (p < 0.05) and infections (p < 0.05) among neonates born at 34WG as compared to 35WG., Conclusions: Late preterm neonates should be defined as 'preterm' between 35 0/7 and 36 6/7 WG. Infants born at 34WG should be included in the preterm group.

Background: Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups., Methods and Results: Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.61% (range 0.15-4.8) vs 0.3% (0.032-2.23) p = 0.0001 and in neonates <32 weeks of gestational age (GA) compared to those ≥32 wks GA: 0.95% (range 0.18-4.8) and 0.36% (0.15-3.2) respectively p = 0.0025. The majority of CD34+ cells co-expressed CD71 antigen (p<0.05 preterm vs term) and grew in vitro large BFU-E, mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45- resulted more represented in preterm samples compared to term, conversely, Side Population (SP) did not show any difference between the two group. The absolute number of preterm colonies (CFCs/10microL) resulted higher compared to term (p = 0.004) and these progenitors were able to grow until the third generation maintaining an higher proportion of CD34+ cells (p = 0.0017). The number of colony also inversely correlated with the gestational age (Pearson r = -0.3001 p<0.0168)., Conclusions: We found no differences in the isolation and expansion capacity of Endothelial Colony Forming Cells (ECFCs) from cord blood of term and preterm neonates: both groups grew in vitro large number of endothelial cells until the third generation and showed a transitional phenotype between mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and CD144)The presence, in the cord blood of preterm babies, of high number of immature hematopoietic progenitors and endothelial/mesenchymal stem cells with high proliferative potential makes this tissue an important source of cells for developing new cells therapies.

Aim: To assess effects of umbilical cord milking (UCM) on early blood pressure stabilization, hemoglobin (Hb), as well as incidence of transfusion and complications in preterm infants., Methods: This meta-analysis was conducted by searching the Pubmed, EMBASE and Cochrane Library (until July 2014) databases. Any clinical trials, including randomized control trials, comparing UCM to immediate cord clamping (ICC) were analyzed., Results: Six studies were included in this meta-analysis. In total, 292 preterm infants were treated with UCM, while 295 received ICC. Compared to ICC, UCM increased initial Hb significantly by 1.84 g/dL (weighted mean difference; 95%CI: 0.91-2.76; P < 0.0001) and decreased the incidence of transfusion with a pooled risk ratio of 0.74 (95%CI: 0.61-0.90; P = 0.002). Incidence of necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH) and mortality were significantly lower with UCM compared with ICC. Apgar score and temperature were not significantly different between the two groups., Conclusions: By facilitating the early stabilization of blood pressure, UCM at preterm birth was found to be comparatively safe and associated with lower blood transfusion exposure and lower incidence of IVH, NEC and death., (© 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.)

Background: The clinical significance of TGFβ isoforms in cord blood is not well understood., Methods: We obtained cord blood samples from 37 term infants and 85 preterm infants who were born in several clinical settings. The serum levels of 3 TGFβ isoforms and of the other 17 cytokines in cord blood were investigated using cytometric bead array technology., Results: Very high levels of TGFβ1 and TGFβ2 isoforms compared to the level of other cytokines were found; mean levels were 44,180 and 1871pg/mL, respectively. The levels of all 3 isoforms of TGFβ were significantly correlated with birth weight, and the levels of TGFβ1 and TGFβ3 were correlated with gestational age. The levels of TGFβ1 and β2 isoforms were strongly correlated with each other, but not with levels of other cytokines. The levels of TGFβ1 and TGFβ2 were significantly higher in male infants and significantly lower in infants with fetal growth restriction. The prevalence of chronic lung disease was related to a low level of TGFβ1, and that of patent ductus arteriosus was related to a high level of TGFβ1 in preterm infants., Conclusions: TGFβ1 and TGFβ2 appeared to play a significant role in physiological and pathological conditions in the fetus. TGFβ isoform levels appear to be regulated independently of those of other cytokines and do not appear to be influenced by inflammation in the fetal period. The role of TGFβ3 in cord blood and the postnatal chronological changes of the TGFβ isoforms should be investigated in the future., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD)., Study Design: Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences., Results: Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI., Conclusion: Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Retinopathy of prematurity (ROP) is the leading cause of blindness in preterm infants. In this study, we investigated the cytokine levels in cord blood of normal preterm neonates and preterm infants developed ROP. Serum levels of 10 cytokines in umbilical cord blood were measured by multiplex protein arrays from 62 healthy preterm neonates and 30 preterm neonate cases who developed ROP at later stage. Results showed that serum levels of cytokines including interleukin 7 (IL-7), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1α), and macrophage inflammatory protein 1 beta (MIP-1β) were significantly increased in cases who developed ROP than in healthy preterm neonates (3.5-fold, 3.2-fold, 3.4-fold, and 2.1-fold, respectively), whereas levels of these four cytokines did not reveal any significant differences between healthy preterm infants and normal infants. When comparing the expression of cytokines in ROP patients with different clinical parameters, ROP cases whose gestational age at delivery earlier than 29.0 weeks demonstrated increased levels of MCP-1 and MIP-1β than those later than 29.0 weeks (p < 0.05). Also, ROP cases with birth weight less than 1.28 kg revealed significantly higher level of MIP-1β than those who were heavier than 1.28 kg (p < 0.05). These data indicated that levels of IL-7, MCP-1, MIP-1α, and MIP-1β were associated with increased risk of ROP, in which MIP-1β may be further correlated with the severity of ROP., (© 2014 APMIS. Published by John Wiley & Sons Ltd.)

Objective: The aim of the study is to determine if umbilical cord serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and myeloperoxidase (MPO), in pregnancies at risk for preterm birth (PTB), are associated with neonatal morbidities and/or altered neurodevelopmental outcomes in the children., Study Design: Umbilical cord serum samples were collected at birth from 400 newborns delivered within a multicenter randomized controlled trial of repeated versus single course of antenatal corticosteroids (ACs), in women at increased risk for PTB. Newborns were followed through discharge and were evaluated between 36 and 42 months corrected age with neurological examination and Bayley Scales of Infant Development. Umbilical cord serum concentrations of IL-6, CRP, and MPO were determined using enzyme-linked immunoassays. Multivariate logistic regression analyses explored the relationship between umbilical cord serum IL-6, CRP, and MPO levels, adverse newborn outcomes, and PTB < 32 weeks of gestational age (GA)., Results: Univariate analysis revealed that umbilical cord IL-6 above the 75th percentile was associated with increased respiratory distress syndrome (RDS) and chronic lung disease (CLD), but not with necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), or neonatal sepsis; however, this association was not significant after adjusting for GA at delivery and treatment group. No significant associations between CRP or MPO and RDS, CLD, NEC, sepsis, or IVH were evident. Regression analysis revealed that CRP above the 75th percentile was associated with a decreased risk of CLD (odds ratio, 0.10; 95% confidence interval, 0.02-0.41). No associations between umbilical cord IL-6, CRP, or MPO and MDI < 70 or PDI < 70 were evident. Umbilical cord serum concentrations of IL-6, CRP, and MPO, above the 75th percentile, were associated with more frequent PTB < 32 weeks of GA., Conclusion: Elevated umbilical cord serum concentration of CRP is associated with reduced risk for CLD even after adjusting for GA at delivery. Occurrence of levels > 75th percentile of IL-6, CRP, and MPO in umbilical cord serum was associated with PTB < 32 weeks of GA. Elevated umbilical cord serum concentrations of IL-6, CRP, and MPO at birth were not associated with poor neurodevelopmental outcomes., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To develop classification models of demographic/clinical factors and biomarker data from spontaneous preterm birth in African Americans and Caucasians., Design: Secondary analysis of biomarker data using multivariate adaptive regression splines (MARS), a supervised machine learning algorithm method., Setting: Analysis of data on 36 biomarkers from 191 women was reduced by MARS to develop predictive models for preterm birth in African Americans and Caucasians., Samples: Maternal plasma, cord plasma collected at admission for preterm or term labor and amniotic fluid at delivery., Methods: Data were partitioned into training and testing sets. Variable importance, a relative indicator (0-100%) and area under the receiver operating characteristic curve (AUC) characterized results., Results: Multivariate adaptive regression splines generated models for combined and racially stratified biomarker data. Clinical and demographic data did not contribute to the model. Racial stratification of data produced distinct models in all three compartments. In African Americans maternal plasma samples IL-1RA, TNF-α, angiopoietin 2, TNFRI, IL-5, MIP1α, IL-1β and TGF-α modeled preterm birth (AUC train: 0.98, AUC test: 0.86). In Caucasians TNFR1, ICAM-1 and IL-1RA contributed to the model (AUC train: 0.84, AUC test: 0.68). African Americans cord plasma samples produced IL-12P70, IL-8 (AUC train: 0.82, AUC test: 0.66). Cord plasma in Caucasians modeled IGFII, PDGFBB, TGF-β1 , IL-12P70, and TIMP1 (AUC train: 0.99, AUC test: 0.82). Amniotic fluid in African Americans modeled FasL, TNFRII, RANTES, KGF, IGFI (AUC train: 0.95, AUC test: 0.89) and in Caucasians, TNF-α, MCP3, TGF-β3 , TNFR1 and angiopoietin 2 (AUC train: 0.94 AUC test: 0.79)., Conclusions: Multivariate adaptive regression splines models multiple biomarkers associated with preterm birth and demonstrated racial disparity., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Epidemiological and experimental studies indicate that early vascular dysfunction occurs in low-birth-weight subjects, especially preterm (PT) infants. We recently reported impaired angiogenic activity of endothelial colony-forming cells (ECFCs) in this condition. We hypothesized that ECFC dysfunction in PT might result from premature senescence and investigated the underlying mechanisms. Compared with ECFCs from term neonates (n = 18), ECFCs isolated from PT (n = 29) display an accelerated senescence sustained by growth arrest and increased senescence-associated β-galactosidase activity. Increased p16(INK4a) expression, in the absence of telomere shortening, indicates that premature PT-ECFC aging results from stress-induced senescence. SIRT1 level, a nicotinamide adenine dinucleotide-dependent deacetylase with anti-aging activities, is dramatically decreased in PT-ECFCs and correlated with gestational age. SIRT1 deficiency is subsequent to epigenetic silencing of its promoter. Transient SIRT1 overexpression or chemical induction by resveratrol treatment reverses senescence phenotype, and rescues in vitro PT-ECFC angiogenic defect in a SIRT1-dependent manner. SIRT1 overexpression also restores PT-ECFC capacity for neovessel formation in vivo. We thus demonstrate that decreased expression of SIRT1 drives accelerated senescence of PT-ECFCs, and acts as a critical determinant of the PT-ECFC angiogenic defect. These findings lay new grounds for understanding the increased cardiovascular risk in individuals born prematurely and open perspectives for therapeutic strategy.

Objective: Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that are particularly abundant in umbilical cord blood. We sought to determine whether ECFC abundance in cord blood is associated with maternal body-mass index (BMI) in nonpathologic pregnancies., Study Design: We measured the level of ECFCs in the cord blood of neonates (n = 27) born from non-obese healthy mothers with nonpathologic pregnancies and examined whether ECFC abundance correlated with maternal BMI. We also examined the effect of maternal BMI on ECFC phenotype and function using angiogenic and vasculogenic assays., Results: We observed variation in ECFC abundance among subjects and found a positive correlation between prepregnancy maternal BMI and ECFC content (r = 0.51, P = .007), which was independent of other obstetric factors. Despite this variation, ECFC phenotype and functionality were deemed normal and highly similar between subjects with maternal BMI <25 kg/m(2) and BMI between 25-30 kg/m(2), including the ability to form vascular networks in vivo., Conclusions: This study underlines the need to consider maternal BMI as a potential confounding factor for cord blood levels of ECFCs in future comparative studies between healthy and pathologic pregnancies., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Data concerning the effects of phthalate exposure on preterm delivery and fetal growth are limited in humans. In this paper, we assessed the relationship between 15 phthalate levels in cord blood and preterm delivery and fetal growth parameters in 207 Chinese women going into labor. Exposure to phthalates except DCHP was associated with gestational age reduction and preterm delivery (p<0.05). There were associations between phthalates and fetal growth parameters, many of which disappeared when analyses were adjusted for gestational age, especially in male infants (Only DEEP was associated with birth weight; DEP, DNHP, BBP, DNP with abdominal circumference; DEP, DBP, DCHP, DEHP with femur length in female infants. And DPP, DBEP was associated with birth length in male infants. p<0.05). This study indicates that prenatal exposure to phthalates is associated with younger gestational age and preterm delivery. Also, phthalate exposure may adversely affect fetal growth parameters via gestational age reduction and preterm delivery with a significant gender effect.

Steroids are important markers in pregnancy. Although estimating their levels separately in umbilical arterial (UA) and venous blood (UV) enable more precise insights into the functioning fetoplacental unit compared to using mixed umbilical blood (UM), selective aspiration of UA and UV is technically more demanding than collecting UM. We measured the levels of 67 unconjugated steroids and steroid polar conjugates in UA and UV using GC-MS in 80 women giving birth within weeks 28 to 42 of gestation. The samples were sorted into three groups: women entering labor within weeks 28-32 (group A, n=19), weeks 33-37 (group B, n=19), and weeks 38-42 (group C, n=42) of gestation, respectively. The preterm labors were due to pathologies unrelated to steroid status. Most unconjugated steroids exhibited pronounced arteriovenous differences (AVD). The AVD were less distinct in more stable steroid conjugates. Most steroids positively correlate with gestational age, but unconjugated 5beta-reduced pregnanes show negative correlations, as do testosterone and androstenediol, substrates for the placental synthesis of estrogens. Tight correlations between steroids in UA and UV indicate that steroid measurements in UA, UV and UM can be accurately derived from each other, which is important for the diagnostics of steroid related diseases in newborns.

Background: 16S rRNA-based genomic analyses have revolutionized our understanding of infectious diseases. Many cases which were recognized as "idiopathic" are now known to have an infectious etiology. Here, we present a proof-of-concept study to examine the microbial link between intra-amniotic infection (IAI) and early-onset neonatal sepsis (EONS)., Results: Using culture independent methods, we analyzed paired amniotic fluid (AF) and cord blood (CB) samples from 36 singleton pregnancies complicated by preterm birth (PTB), IAI, and/or EONS. PTB cases were grouped as 1) Group 1- neonatal blood culture-positive EONS (n=6). 2) Group 2- neonatal blood culture-negative presumed EONS with positive IAI (n=16). 3) Group 3- neonatal blood culture-negative presumed EONS with no IAI (n=7); 4) Group 4- no EONS or IAI (n=7). In addition, samples from term healthy deliveries (n=8) served as technical controls. A total of 31 species (15 non-redundant) were identified in AF, of which only 1/3 were cultivated. Significantly fewer microorganisms were detected in CB, with a total of 18 species (7 non-redundant) identified, of which only 2 (Escherichia coli, Streptococcus agalactiae) were cultivated. Of those, Bergeyella, Fusobacterium nucleatum, and Sneathia sanguinegens had not been detected in EONS before. The novel species identified in AF by PCR include Peptoniphilus harei and Lachnospiraceae sp. The majority (72%) of CB species were also detected in the matching AF, with E. coli and F. nucleatum as the most prevalent. The 16S rRNA sequences of paired AF and CB were 99.9-100% identical, while no identical sequences were found between different pregnancies., Conclusions: Previously unrecognized, uncultivated or difficult-to-cultivate species are implicated in EONS. Microbial species in paired AF and CB likely share the same infectious origin. Given its prevalence in EONS, F. nucleatum should be placed on the same importance scale as E. coli.

Aim: We hypothesized that circulating apelin concentrations in preterm babies might be linked with retinopathy of prematurity (ROP), similar to IGF-1 levels., Patients & Methods: A total of 97 infants born with a gestational age before 32 weeks in 2007-2009 were screened for ROP at the Gata Haydarpasa Hospital (Turkey). Fourteen of them with classified ROP stage 3-5 comprised our study group., Results: The non-ROP group had higher apelin and IGF-1 levels than ROP neonates at birth. After 4-6 weeks, postnatal ROP subjects had lower apelin and IGF-1 levels than non-ROP controls. At the end of the study, the change in apelin levels was positively correlated with the change in IGF-1 levels (r = 0.852; p = 0.01)., Conclusion: We suggested that the pathogenesis of ROP, which is regarded as a neovascular retinal disorder, includes variations in the levels of apelin and IGF-1.

Objective: The objective of the study was to investigate whether concentrations of chemokines in the umbilical cord blood of neonates are affected by delivery via cesarean section., Study Design: Umbilical cord blood was obtained from 116 singleton late-preterm and full-term neonates without infections, born to healthy pregnant women. Concentrations of chemokines - MIP-1α (CCL3), MIP-1β 1 (CCL4), RANTES (CCL5), GRO-α (CXCL1) and ENA-78 (CXCL5) - were measured by ELISA. Logistic regression was used to investigate regression relationships between the occurrence of neonatal chemokines concentrations in umbilical cord blood and mode and time of delivery., Results: Concentrations of CXC chemokines in late-preterm neonates were the same as those in term neonates. RANTES concentrations in late-preterm cord blood were significantly lower than concentrations in term cord blood. Concentrations of the CC chemokine - RANTES (CCL5) - were noted to be lower in neonates born to cesarean section than in neonates born vaginally. Any anesthetic taken by the mothers during cesarean section did not affect CC chemokine production in the cord blood of full-term neonates. In a logistic regression model including gestational age as a variable, late-preterm delivery was associated with RANTES concentrations (OR = 3.8). After adjustment for variable mode of delivery in regression model, RANTES concentration (OR = 4.75)., Conclusion: Both late-preterm and cesarean delivery are essential risk factors of low RANTES (CCL5) concentrations in the umbilical cord blood.

Problem: This study investigates whether affectivity differs between mothers delivering preterm and term and whether maternal and umbilical cord serum cytokines differ between these groups. Further, whether there are associations between mothers' emotions and maternal and cord cytokines at preterm and term birth., Method of Study: Twenty-seven mothers delivering preterm and 37 mothers delivering at term reported positive/negative affect and previous depressive symptoms during pregnancy. Blood samples from mothers in labor and cord samples (23 preterm and 33 term) were analyzed for cytokines., Results: Maternal IL-8 was lower at preterm delivery compared with term. In the preterm group only, associations were found between negative emotions and maternal IL-6, IL-8 and cord IL-6, IL-8, IL-10, IL-13, and IL-18., Conclusion: The findings indicate associations in preterm delivery between negative emotions and both maternal and neonate immune activity. Future studies should investigate whether such associations are part of the etiology of preterm delivery., (© 2011 John Wiley & Sons A/S.)

Objective: To document racial disparity in biomarker concentrations in maternal/fetal plasma and amniotic fluid between African Americans and European Americans with spontaneous preterm birth (PTB; cases) and normal term birth (controls), and their contribution to distinct pathophysiological pathways of PTB., Design: Nested case-control study., Setting: The Perinatal Research Center, Nashville, Tennessee, USA., Sample: Maternal and fetal plasma and amniotic fluid samples were collected from 105 cases (59 African American and 46 European American) and 86 controls (40 African American and 46 European American)., Methods: Thirty-six biomarkers were analysed using the protein microarray approach., Main Outcome Measures: Differences in biomarker concentrations between cases and controls of different races in maternal, fetal and intra-amniotic compartments, and the risk of PTB. Dysregulated biomarker-induced PTB pathways associated with PTB in each race were determined using ingenuity pathway analysis (IPA)., Results: Racial disparity was observed in biomarker concentrations in each compartment between cases and controls: amniotic fluid, IL8 and MIP1α differed between case and controls in European Americans, whereas ANGPT2, Eotaxin, ICAM-1, IL-1β, IL1RA, RANTES and TNFα differed between case and controls in African Americans. In both races the FAS ligand, MCP-3 and TNFR-I differed between cases and controls. For fetal plasma, ANGPT2, Eotaxin, FGF basic, ICAM-1, IGF-I, IL10, IL-1β, IL2, IP10 KGF, MCP-3, MIP1α, PDGF-BB, TGFα, TGFβ1, TIMP1, TNFα, TNFR-I, TNFR-II and VEGF differed between cases and controls in European Americans, whereas only MMP7 differed between cases and controls in African Americans. IL-8 differed between cases and controls in both races. For maternal plasma, IL1RA, MMP7 and VEGF differed between cases and controls in European Americans, whereas ANGPT2, FGF basic, IL-1β, IL5, IL6R, KGF, MCP-3, MIP1α, TIMP1 and TNFα differed between cases and controls in African Americans. ANG, IL8 and TNFR-I differed between cases and controls in both races., Conclusions: We conclude that: (1) biomarker concentrations in maternal, fetal and intra-amniotic compartments differ between cases and controls; (2) there is racial disparity in the biomarker profile in each of the compartments; (3) substantial numbers of dysregulated fetal plasma biomarkers contribute to PTB in European Americans, whereas maternal plasma biomarkers contribute to PTB in African Americans; and (4) both inflammation and haematological functions are associated with PTB in European Americans, but maternal proinflammatory changes dominate PTB in African Americans. Biomarker analyses document racial disparity and the distinct pathophysiological contributions from different compartments that can determine pregnancy outcome., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Objective: Human umbilical cord blood (hUCB) is rich in stem cells. The CD45(+)/CD34(+) coexpression in hUCB is a marker of hemopoietic progenitor cells. The objective of this study is to compare the coexpression of hUCB CD45(+)/CD34(+) cells in preterm (PT) and full-term (FT) neonates., Methods: We studied the coexpression of hUCB CD45(+)/CD34(+) cells in PT and FT neonates. The study included 25 PT (29-36 weeks gestation) and 25 FT (37-41) neonates delivered at Ain Shams University, Maternity Hospital. Absolute mononuclear layer cord blood CD45(+)/CD34(+) cell count were measured by flow cytometry. Morbidity was assessed for 12 of the studied 25 PT infants, using Morbidity Assessment Index for Newborns score., Results: The absolute CD45(+)/CD34(+) count did not differ between PT and FT infants: Z =  -0.485, p = 0.63. There was no correlation between absolute cell count and GA (r = 0.013, p = 0.9) for all 50 neonates. Mode of delivery did not affect the absolute count in the PT infants: Z  =  -0.6, p  = 0.57. There was no correlation between the degree of morbidity and absolute cell count in PT neonates; r = 0.13, p = 0.69., Conclusion: The absolute cell count is not affected by gestational age and did not relate to morbidity scores in the studied PT infants. Further, wide-scale work will be needed to study CD45(+)/CD34(+) count in hUCB in sick PT neonates.

Background: Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants., Objective: Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH., Methodology: Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry., Principal Findings: Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants., Conclusion: The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates.

Background: Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns., Methodology/principal Findings: We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (P<0.001). Western blot concurred in determining that EONS babies had conspicuous Hp&HpRP bands in cord blood ("switch-on pattern") as opposed to non-EONS newborns who had near-absent "switch-off pattern" (P<0.001). Fetal Hp phenotype independently impacted Hp&HpRP. A bayesian latent-class analysis (LCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage., Conclusions/significance: Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth.

Recent studies reveal that salivary cortisol measurements accurately reflect blood cortisol levels in older children and adults; yet, the relationship between the two values in premature infants has not been established. This study explores the use of salivary cortisol as an accurate measure of adrenal steroid concentrations in premature infants to provide a reliable and less invasive tool for investigating hormonal stress response. Premature infants (n=51) were recruited, with saliva and blood collected immediately after birth, and cortisol levels measured by radioimmunoassay. A linear relationship emerged between cord plasma and salivary cortisol values in the 102 paired samples [(salivary cortisol) = 0.546 +/- 0.192 x (plasma cortisol), r = 0.481 and p = 0.0003]. Findings demonstrated that salivary and plasma cortisol levels were correlated in premature infants. This information will be useful in future studies that assess use of salivary cortisol to evaluate neonatal stress axis function.

While elevated levels of proinflammatory cytokines are clearly associated with preterm birth, the relation between cytokines and fetal growth is unclear. The authors examined associations between umbilical cord serum cytokine concentrations and risk of small-for-gestational-age (SGA) and preterm birth. This cross-sectional analysis was nested within a National Institute of Child Health and Human Development-University of Alabama population-based cohort study of high-risk prenatal care patients in Jefferson County, Alabama. Patients were enrolled between 1985 and 1988. For 370 singletons, umbilical cord serum concentrations of interferon gamma (IFN-gamma), tumor necrosis factor alpha, and interleukins 12p70, 4, and 10 were determined. Associations between each cytokine and SGA and preterm delivery were evaluated using log binomial regression. Increasing log concentration of tumor necrosis factor alpha was associated with an increased risk of preterm birth (risk ratio (RR) = 2.00, 95% confidence interval (CI): 1.31, 3.06). IFN-gamma was associated with a decreased risk of SGA birth (RR = 0.78, 95% CI: 0.61, 1.01). After stratification for preterm birth status, the association between IFN-gamma concentration and SGA birth was pronounced among preterm babies (RR = 0.56, 95% CI: 0.31, 1.01). The observations regarding IFN-gamma, which is involved in the activation of adaptive immune responses and regulation of trophoblast function, suggest that IFN-gamma levels at birth may be related to fetal growth restriction.

One collectin (mannan-binding lectin, MBL) and three ficolins (M-ficolin/ficolin-1, L-ficolin/ficolin-2 and H-ficolin/ficolin-3) share the capability to activate complement via the lectin pathway. This property depends on the ability of these lectins to form complexes with MBL-associated serine proteases (MASPs), particularly MASP-2. We report the results of an investigation of cord blood MASP-2 concentrations in a large, ethnically homogeneous cohort (n=1788) of neonates. The median value of MASP-2 in cord sera was determined to be 93 ng/ml (range <25-812). Serum MASP-2 concentrations correlated with gestational age and birthweight and were significantly lower in premature babies and other pre-term babies compared with term babies. Neonates with MASP-2 concentrations below 42 ng/ml were deemed to be MASP-2 deficient. That group had a shorter mean gestational age and a higher incidence of premature and low birthweight babies, but not of perinatal infections when compared with the others. Indeed, there was a trend towards higher MASP-2 concentrations amongst babies with infections. Among 362 samples tested for the D120G single nucleotide polymorphism (SNP) of the MASP2 gene, no homozygote for that mutation was found. Heterozygosity for this allele significantly influenced the protein concentration, but not the lectin pathway of complement activity (MBL-MASP-2 complex activity). Moreover, no association of this SNP was apparent with prematurity, low birthweight or perinatal infections.

Background & Objective: Low birth weight (LBW) babies are a vulnerable group and represent two outcomes--preterm birth (preterm LBW) and term with intrauterine growth retardation (term LBW). LBW babies are considered to have low nutrient reserve, but the extent of deficiency as compared to the normal babies and the differences between preterm LBW and term LBW are unclear. This study was carried out to look at key anthropometric, biochemical and clinical (ABC) parameters of LBW babies, both preterm and term, in comparison to a control group of term normal weight babies., Methods: A group of 500 babies was selected at birth from a tertiary care teaching hospital and categorized into LBW (n = 251) with preterm LBW (n = 59), term LBW (n = 192) and term controls (n = 249). Two controls were dropped as tests could not be performed in the available cord blood sample. Key anthropometric and biochemical parameters were measured. Socio-economic status, age, parity, height and pre-delivery haemoglobin of the mothers were also recorded., Results: The maternal characteristics were comparable in the three groups. Socio-economically, majority of them belonged to lower middle or upper lower class (Class III and IV) representing the non affluent. All the anthropometric measurements and nutrients measured namely total protein, albumin, cholesterol, triglycerides, calcium, magnesium, zinc and iron were significantly lower in LBW babies compared to term control babies. These values were lowest in preterm LBW followed by term LBW. Total iron binding capacity (TIBC) showed inverse association with iron. Some of the babies including control babies had protein, albumin, calcium and iron below the normal range and mean albumin, calcium and iron levels were below the normal range in all the three subsets., Interpretation & Conclusion: Preterm and term LBW babies are born with significantly lower nutrient reserves at birth compared to term control babies. Normal weight babies from the non affluent sections also have low nutrients especially albumin, calcium and iron. As these levels are liable to be further lowered by recurrent infections and inappropriate feeding habits, nutritional surveillance, extra feeding and supplements like calcium and iron are recommended for such vulnerable babies to promote optimum growth and to prevent deficiencies. This is important as currently, there are no clear or uniform recommendations for extra feeding and nutrient supplements to LBW babies and no supplements other than exclusive breast feeding are recommended for term normal birth weight babies. Extra nutritional inputs for LBW and selected non affluent babies along with care of the prospective and prenatal mothers for ensuring adequate transfer of nutrients to the offspring seem necessary. Such interventions can be integrated with the existing health care programmes to reach all the beneficiaries.

This article reports the results of a study on the relationship between cord blood levels of erythropoietin and periventricular leukomalacia. Cord blood was obtained from 19 infants with gestational age between 27 and 32 weeks. Cystic periventricular leukomalacia was seen in 4 of them. Erythropoietin levels were not different between those with and those without periventricular leukomalacia.

Background: Infants born term have substantially elevated plasma concentrations of the endogenous nitric oxide synthase antagonist asymmetrical dimethylarginine (ADMA) that normalize with growth. The plasma levels of ADMA in preterm newborns are unknown., Subjects and Methods: Plasma concentrations of ADMA, symmetrical dimethylarginine (SDMA) and L-arginine were analyzed from venous umbilical cord blood samples of 19 preterm and 21 term infants by high performance liquid chromatography., Results: Male preterm newborns (n=11) had higher ADMA (median [95% confidence interval (CI)]: 1.90 [1.73-2.10] micromol/l) than females born preterm (n=8; 1.57 [1.24-1.69] micromol/l; p<0.005). In term born males (n=10) and females (n=11) ADMA was significantly lower than in preterm male infants (all p<0.005), and without sex differences. SDMA and L-arginine concentrations were comparable between all groups. ADMA correlated inversely with body weight in male preterm newborns (r=-0.67; p<0.03)., Conclusion: Male neonates delivered preterm have significantly higher umbilical cord venous plasma concentrations of ADMA compared to female neonates and infants born term. The sex difference and the time course of elevated ADMA may play a role in development and warrant further investigation.

Objective: The aim of this study was to characterize the lymphocyte and the hematopoietic stem and progenitor cell (HPC) subsets of cryopreserved premature cord blood (PCB) compared to term cord blood (TCB) by flow cytometry, to study the influence of birth conditions, and to assess its availability for transplantation., Materials and Methods: Four-color flow cytometric analysis was performed on 43 PCB and 40 TCB cryopreserved samples using a panel of 24 different mAbs, directed against lymphoid and HPC surface markers. The CB volume was estimated by the weight of the newborn to determine the absolute MNC and CD34(+) cell content/CB sample. Clinical and obstetrical data were recovered. Statistical comparisons and a multiple regression analysis were performed., Results: No consistent differences were found in the mononuclear cell (MNC) or CD34(+) cell concentration (x10(6)/L) between PCB and TCB. The percentage of primitive HPC (CD34(+)CD38(-), CD34(+)CD38(-)CD90(-)HLA-DR(-), CD34(+)CD38(-)CD90(-)HLA-DR(+)) and primitive lymphoid progenitors (CD34(+)CD7(+), CD34(+)CD7(+)CD19(-)CD117(-)) were higher in PCB than in TCB. Correspondingly, TCB had an increased percentage of committed HPC. No sample of PCB contained >2 x 10(7) MNC/kg (and only 48% had >1 x 10(5) CD34(+) cells) for a recipient of 20 kg body wt, as the minimum threshold recommended for CB transplantation. Obstetrical factors modulated mainly lymphocyte subsets and fewer HPC subpopulations. Acute fetal distress increased CD34(+) cells, especially the immature subsets. Maternal treatment with dexamethasone and intrauterine growth retardation decreased CD3(+) cells. No other obstetrical factors played a detrimental effect on CB cells if used for transplantation., Conclusion: PCB is richer in immature cells both in lymphocyte and HPC populations, and its use for transplantation, at least in special cases, should be reconsidered.

Objective: Osteopenia is a frequent condition in preterm infants. This prospective study was designed to assess the relationship between cord blood insulin-like growth factor-I (IGF-I) levels and bone mineralization in healthy premature infants., Methods: Twenty preterm infants (ten males and ten females) were studied. We determined the bone mineral density (BMD) and bone mineral content (BMC) of healthy premature infants by dual-energy X-ray absorptiometry and also studied the correlation between IGF-I and other parameters and the influence of cord blood IGF-I concentrations on bone mineralization in these infants., Results: The mean concentration of IGF-I was 13.6 +/- 16.9 ng/ml and BMD and BMC were 0.249 +/- 0.06 g/cm2 and 3.09 +/- 1.18 g, respectively. Cord serum levels of IGF-I had significantly positive correlations with BMD (r = 0.605, p = 0.008), but not BMC (r = 0.242, p = 0.367). In stepwise regression analysis, IGF-I emerged as a significant predictor of BMD (beta = 0.595, p = 0.015) contributing to 35.4% of its variability., Conclusion: We found a relationship between cord blood IGF-I and BMD in preterm neonates, suggesting that even within an unremarkable population, IGF-I might be important to ensuring bone health.

Background: To compare procalcitonin (PCT) concentrations between maternal blood and levels in umbilical cord or venous blood of neonates who were born with or without infection., Methods: Forty-six women with singleton pregnancies, complicated by premature rupture of membranes, preterm delivery and/or chorioamnionitis, were enrolled in this study. The study group comprised 15 patients and their infected newborns. The control group consisted of 31 women and their healthy newborns. We compared PCT concentrations between maternal, umbilical cord and neonatal serum, in both study and control groups. Additionally, PCT levels were compared between the corresponding compartments., Results: PCT concentrations in the umbilical cord and venous blood in infected newborns, but not in non-infected neonates, were significantly higher than maternal serum PCT levels. PCT concentrations of mothers who delivered infected newborns were comparable to those in the controls. However, PCT concentrations in the umbilical cord and in the venous blood of the infected newborns were higher than in healthy newborns., Conclusion: Measurement of maternal PCT concentration during labor does not contribute to early prediction of infection in the neonate. However, umbilical cord PCT concentrations, as well as its neonatal venous levels on the second day of life, seem to be related to intrauterine infection, and may be a useful tool in the diagnosis of early neonatal infection.

Many of the published reports of reference values in neonates are found in older medical literature. Recognition of abnormalities in blood cell morphology and hematologic parameters depend on well-established normative data; it is essential that each neonatal medical unit have its own reference ranges. We give the umbilical cord blood complete blood count reference values from 142 healthy, appropriate for gestational age (AGA) newborns and 58 small for gestational age (SGA) newborns (term and preterm). Our data, obtained by automated blood cell counter analysis of umbilical cord blood samples taken at birth, are comparable to other previously published data. The correlation between previous data and our reference data confirms that in term AGA newborns, values for red blood cells, hemoglobin, and hematocrit are higher and mean corpuscular volume values lower than in preterm AGA newborns. Also, we found that platelet levels are reduced in SGA newborns, in accordance with the literature. These findings further support the fact that preterm SGA infants are truly growth restricted, whereas term SGA infants are most likely small but otherwise healthy babies.