Search

Objective: To compare the effects of early and delayed cord clamping on the haemoglobin levels of neonates delivered at term., Methods: This randomized controlled trial enrolled pregnant women during the second stage of labour. They were randomized into either the early cord clamping (ECC) group or the delayed cord clamping (DCC) group in the ratio of 1:1. Following delivery of the baby, the umbilical cords of participants in the ECC group were clamped within 30 s of delivery of the neonate while those of participants in the DCC group were clamped after 2 min from the delivery of the neonate. The primary outcome measure was the effect of ECC and DCC on the haemoglobin levels of neonates delivered at term., Results: A total of 270 pregnant women were enrolled in the study. Their baseline sociodemographic and clinical characteristics were similar in both groups. There was no significant difference in the mean haemoglobin level between ECC and DCC groups at birth. The mean haemoglobin level of the neonates at 48 h postpartum was significantly higher in the DCC group than the ECC group., Conclusion: DCC at birth was associated with a significant increase in neonatal haemoglobin levels at 48 h postpartum when compared with ECC. Trial Registration: The trial was registered at Pan African Clinical Trial Registry with approval number PACTR202206735622089., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB., (© 2024. The Author(s).)

Background: To date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS., Methods: In this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants., Results: During the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 - 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 - 1307) rather than in infants without (467 pg/ml, IQR 369 - 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden's Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis., Conclusions: Maximum Youden's index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics., (© 2023. The Author(s).)

Background: Preterm infants are highly vulnerable to infectious disease. While many factors are likely to contribute to this enhanced susceptibility, the immature nature of the preterm immune system is postulated as one key factor., Methods: In our study, we used high-dimensional flow cytometry and cytokine assays to characterise the immune profiles in 25 preterm (range: 30.4-34.1 weeks gestational age) and 25 term infant (range: 37-40 weeks gestational age) cord blood samples., Results: We found that preterm infants exhibit reduced frequencies of monocytes, CD56 bright NK cells, CD8+ T-cells, γδ T-cells and an increased frequency of intermediate monocytes, CD4+ T-cells, central memory CD4+ and CD8+ T-cells, Tregs and transitional B-cells compared to term infants. Pro-inflammatory cytokines IL-1β, IL-6 and IL-17A were lower in preterm infants in addition to chemokines IL-8, eotaxin, MIP-1α and MIP-1β. However, IL-15 and MCP-1 were higher in preterm infants., Conclusion: Overall, we identify key differences in pro-inflammatory immune profiles between preterm and term infants. These findings may help to explain why preterm infants are more susceptible to infectious disease during early life and facilitate the development of targeted interventions to protect this highly vulnerable group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Anderson, Thang, Thanh, Dai, Phan, Nhu, Trang, Trinh, Nguyen, Toan, Harpur, Mulholland, Pellicci, Do and Licciardi.)

Background: Thrombelastometry, allowing timely assessment of global hemostatic function, is increasingly used to guide hemostatic interventions in bleeding patients. Reference values are available for adults and children, including infants but not neonates immediately after birth., Methods: Neonates were grouped as preterm (30 + 0 to 36 + 6 weeks/days) and term (37 + 0 to 39 + 6 weeks/days). Blood samples were drawn from the umbilical cord immediately after cesarean section and analyzed by thrombelastometry. Reference ranges were determined for the extrinsic and intrinsic coagulation pathways, fibrin polymerization, and hyperfibrinolysis detection., Results: All extrinsically activated test parameters, but maximum lysis (P = 0.139) differed significantly between both groups (P ≤ 0.001). Maximum clot firmness in the fibrin polymerization test was comparable (P = 0.141). All intrinsically activated test parameters other than coagulation time (P = 0.537) and maximum lysis (P = 0.888) differed significantly (P < 0.001), and so did all aprotinin-related test parameters (P ≤ 0.001) but maximum lysis (P = 0.851)., Conclusions: This is the first study to identify reference ranges for thrombelastometry in preterm and term neonates immediately after birth. We also report differences in clot initiation and clot strength in neonates born <37 versus ≤40 weeks of gestation, mirroring developmental hemostasis., Impact: Impact: This prospective observational study is the first to present reference ranges in preterm and term infants for all types of commercially available tests of thrombelastometry, notably also including the fibrin polymerization test., Importance: Viscoelastic coagulation assays such as thrombelastometry have become integral to the management of perioperative bleeding by present-day standards. Reference values are available for adults, children, and infants but not for neonates. Key message: Clot initiation and formation was faster and clot strength higher in the term than in the preterm group. Parameters of thrombelastometry obtained from cord blood do not apply interchangeably to preterm and term neonates., (© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.)

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.)

We aimed to assess whether the second-trimester maternal serum markers could be used for the prediction of labour induction success. This prospective study enrolled women planned labour induction at term. Women were assigned to one of two groups: vaginal prostaglandin or balloon dilatation. All patients were evaluated for Bishop score, maternal serum oestriol, human chorionic gonadotropin and progesterone at the time of second-aneuploidy screening. The total successful rate for induction of labour was 63.9% in both groups. Maternal serum oestriol multiple of median (MoM) values were significantly lower among the caesarean section group compared to the vaginal delivery group ( p  < .001). A MoM value of 0.74 for oestriol was associated with a sensitivity of 75.9%, specificity of 41.0%, a positive predictive value of 76.6% and a negative predictive value of 58.0% for a successful induction of labour. Oestriol had a good performance in the prediction of successful induction of labour at term.IMPACT STATEMENT What is already known on this subject? Induction of labour is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Previous studies have reported that a decreased progesterone/oestradiol ratio and increased maternal plasma oestriol levels are associated with successful labour. What the results of this study add? The results of this study showed that second-trimester oestriol multiple of median (MoM) value provide a significant contribution to the efforts of the prediction of successful induction of labour in term pregnancy, having a sensitivity of 69.8%, specificity of 92.4%, positive predictive value of 83.3% and negative predictive value of 82.5%. What the implications are of these findings for clinical practice and/or further research? This finding can be used as an additional method for prediction of labour induction as well as multiparity and Bishop score. This adds new valuable data to the literature which could be used for systematic reviews and for implementing guidelines and protocols on labour induction.

Abstract: The present study was conducted with an attempt to explore the correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.The levels of umbilical cord blood resistin, adiponectin, insulin, growth hormone, leptin, thyrotropin, thyroid hormone (T3, T4), lgM, lgA, lgG, CD4, and CD8 were measured in 180 full-term newborns delivered in hospital from October 2018 to November 2019. The delivery mode, weight, height, and gender at birth were recorded.The levels of resistin, insulin, and growth hormone in umbilical cord blood of newborns delivered vaginally were significantly higher than those born by cesarean section (P < .05), while the levels of adiponectin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable between the 2 groups (P > .05). The levels of resistin, adiponectin, insulin, growth hormone, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 in cord blood of male and female newborns were comparable (P > .05). The newborns with birth weight ≥ 3501 g reported comparable results in the levels of resistin and growth hormone compared with those with birth weight of 3000 to 3500 g (P > .05), but were significantly higher than those with birth weight ≤ 2999 g (P < 0.05). In addition, the levels of adiponectin, insulin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable among the 3 groups (P > .05). Based on Pearson correlation analysis, neonatal umbilical cord blood resistin was positively correlated with adiponectin, leptin, growth hormone, T3, and T4 (r = 0.281, 0.287, 0.321, 0.276, 0.269, P < .05). However, there was no significant correlation between neonatal umbilical cord blood resistin and insulin, TST, lgM, lgA, lgG, CD4, and CD8.The level of serum resistin in neonatal umbilical cord blood was associated with the delivery mode and birth weight, and positively correlated with adiponectin, leptin, growth hormone, T3, and T4. However, no correlation was observed between serum resistin in neonatal umbilical cord blood and insulin, TST, lgM, lgA, lgG, CD4, and CD8., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: The aim of the present study was to evaluate umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (βCTX) levels in term pregnancies with vitamin D deficiency., Materials and Methods: Ninety-two pregnant women between 19 and 35-years-old who delivered at term gestational age were included in the study and divided into deficient ( n  = 32), insufficient ( n  = 30), and normal (control) vitamin D levels ( n  = 30)., Results: Maternal demographic characteristics and biochemical parameters were similar among groups. The mean umbilical cord P1NP level was 221.4 (211.7-231.0, 95%CI) pg/mL in the vitamin D deficiency group, 282.5 (271.2-293.8, 95%CI) pg/mL in the vitamin D insufficiency group, and 280.9 (270.9-290.8, 95%CI) pg/mL in the control group and significantly lower in vitamin D deficiency group than others ( p  < .001). Umbilical cord P1NP level was similar in the vitamin D insufficiency group and control group ( p  = .971). The mean umbilical cord βCTX level was 5530, 9 (5511.5-5550.3, 95%CI) pg/mL in the vitamin D deficiency group, 5516.3 (5498.4-5534.2, 95%CI) pg/mL in the vitamin D insufficiency group, and 5510 (5491.4-5528.5, 95%CI) pg/mL in the control group, which was statistically similar among the groups ( p =  .251)., Conclusion: Our results indicated that vitamin D deficiency during pregnancy affects fetal bone osteoblast activity.

Background: The immune system significantly participates in the development of the successful delivery process. The roles played by cytokine molecules in the induction of term delivery are yet to be clarified. The aim of this project was to explore the serum levels of interleukin-10 (IL-10), IL-17A, and IL-23 in the mothers with term and prolonged pregnancy and their infants., Materials and Methods: In this study, 60 samples were collected from either mothers with term and prolonged pregnancy or their infants, collectively 240 samples. Serum levels of IL-10, IL-17A and IL-23 were explored using enzyme linked immunosorbent assay (ELISA) technique., Results: IL-10 serum levels significantly decreased in the neonates with prolonged pregnancy when compared to their mothers. Serum levels of IL-23 were increased either in term or prolonged pregnancy neonates when compared to their corresponded mothers. Serum levels of IL-10 and IL-23 significantly decreased and increased, respectively, in the female in comparison to male in the prolonged pregnancy neonates. IL-10 also significantly decreased in the term mothers who had higher gravidity., Conclusion: Although, IL-17A does not play a key role in the delivery mechanism, IL-10 and IL-23 may be considered as potential factors in the modulation of term delivery.

Context: Low-dose adrenocorticotropic hormone stimulation testing (LDST) can be used to diagnose central adrenal insufficiency. However, uncertainty remains over optimal times to draw serum cortisol levels., Objective: To determine optimal times to draw serum cortisol levels for the LDST in neonates., Design: A retrospective chart review of LDSTs performed on neonates from January 1, 2009 to September 30, 2017., Setting: Children's Hospital of Eastern Ontario (CHEO), a tertiary-care outborn pediatric center., Patients: Forty-nine patients were included: 23 (46.9%) born at term, 12 (24.5%) born very preterm to late preterm, and 14 (28.6%) born extremely preterm., Intervention: Cortisol levels were drawn at baseline and 15, 30, and 60 minutes following administration of Cortrosyn 1 mcg/kg (maximum dose 1 mcg)., Main Outcome Measure: Timing of peak cortisol level and marginal value of drawing a second and third cortisol sample at 15, 30, or 60 minutes was determined., Results: Cortisol peaked at 15-, 30-, and 60-minute sampling times for 4%, 27%, and 69% of patients, respectively. The probability that a failed LDST changes to a pass by adding a 15- or 30-minute sample to the superior 60 minute sample is 5.6% (1% to 25.8%) and 11% (3.1% to 32.6%), respectively, for a cortisol pass threshold of 18.1mcg/dL (500 nmol/L)., Conclusions: In contrast to studies of older children, we found that the majority of neonatal LDST cortisol peaks occurred at the 60-minute sampling time with the addition of a 30-minute sample providing substantial benefit. It is questionable if a 15-minute sample provides any benefit, making a case to revise LDST protocols to sample cortisol later for neonates., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Delayed umbilical cord clamping appears to be beneficial for term and preterm infants. In term infants, delayed umbilical cord clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcomes. There is a small increase in the incidence of jaundice that requires phototherapy in term infants undergoing delayed umbilical cord clamping. Consequently, obstetrician-gynecologists and other obstetric care providers adopting delayed umbilical cord clamping in term infants should ensure that mechanisms are in place to monitor and treat neonatal jaundice. In preterm infants, delayed umbilical cord clamping is associated with significant neonatal benefits, including improved transitional circulation, better establishment of red blood cell volume, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage. Delayed umbilical cord clamping was not associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor was it associated with a difference in postpartum hemoglobin levels or the need for blood transfusion. Given the benefits to most newborns and concordant with other professional organizations, the American College of Obstetricians and Gynecologists now recommends a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30-60 seconds after birth. The ability to provide delayed umbilical cord clamping may vary among institutions and settings; decisions in those circumstances are best made by the team caring for the mother-infant dyad.

Delayed umbilical cord clamping appears to be beneficial for term and preterm infants. In term infants, delayed umbilical cord clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcomes. There is a small increase in the incidence of jaundice that requires phototherapy in term infants undergoing delayed umbilical cord clamping. Consequently, obstetrician-gynecologists and other obstetric care providers adopting delayed umbilical cord clamping in term infants should ensure that mechanisms are in place to monitor and treat neonatal jaundice. In preterm infants, delayed umbilical cord clamping is associated with significant neonatal benefits, including improved transitional circulation, better establishment of red blood cell volume, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage. Delayed umbilical cord clamping was not associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor was it associated with a difference in postpartum hemoglobin levels or the need for blood transfusion. Given the benefits to most newborns and concordant with other professional organizations, the American College of Obstetricians and Gynecologists now recommends a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30-60 seconds after birth. The ability to provide delayed umbilical cord clamping may vary among institutions and settings; decisions in those circumstances are best made by the team caring for the mother-infant dyad.

Introduction: Hypocalcaemia in pregnancy remains a major health issue, particularly in the developing world where daily calcium intakes are suboptimal. This electrolyte imbalance can lead to severe maternofoetal and childhood consequences. Calcium supplementation, amongst others, contributes significantly to meeting calcium demands in pregnancy. With ionised calcaemia as the gold standard for diagnosis, total calcaemia and albumin-corrected calcaemia in other pathological states have been found to overestimate the burden of hypocalcaemia. The main objectives of this study are to describe the blood calcium level (total, albumin corrected, and ionised calcaemia) and associated maternofoetal outcomes while identifying determinants of calcium supplementation and ionised hypocalcaemia. This study will also evaluate the sensitivity and specificity of albumin corrected calcaemia as a diagnostic tool for hypocalcaemia (ionised calcaemia as the gold standard) among pregnant women in the Nkongsamba Regional Hospital, Cameroon., Methods: Our study will target a total of 1067 term pregnant women who shall be included consecutively into the study as they arrive the maternity of the Nkongsamba Regional Hospital for their last antenatal care visit. Data shall be collected using a semi-structured interview-administered questionnaire and blood samples collected for total plasma calcium, albumin and serum ionized calcium assays. Additional data will be collected at birth (maternal and foetal variables; foetal outcomes evaluated as secondary outcomes). Total calcaemia and albuminemia shall be measured by atomic absorption spectrophotometry, while ionised calcaemia will be measured by ion-selective electrode potentiometry(using MSLEA15-H electrolyte analyzer) per standard BIOLABO and MSLEA15 protocols, respectively. Data will be analysed using the statistical softwares epi-Info version 7.2.2.16 and STATA version 16., Expected Research Outcome: This study will present a more precise estimate of the burden of hypocalcaemia in late pregnancy as well as identify and analyse the different factors associated with calcium supplementation and ionised hypocalcaemia among term pregnant women in a developing world setting. Maternofoetal outcomes associated with hypocalcaemia will be determined as well as the sensitivity and specificity of total and albumin-corrected calcaemia in diagnosing hypocalcaemia. Our findings will contribute significantly to designing or strengthening interventions to control this electrolyte imbalance., Competing Interests: The authors have declared that no competing interests exist.

The aim of the study was to investigate whether serum hypoxia-inducible factor-1alpha (HIF-1α), hepcidin and interleukin-6 (IL-6) concentrations differed between threatened preterm labour (TPL) and uncomplicated pregnancies. This study was conducted on 54 women with TDL pregnancies and 26 healthy pregnant women. The TPL group was further divided into two subgroups according to the gestational age at delivery. Patients who gave birth within 48-72 h after the hospitalisation were referred to as preterm delivery (PD) and who gave birth at ≥37 weeks were referred to as term delivery (TD). Maternal levels of serum HIF-1α, hepcidin and IL-6 were measured with the use of enzyme-linked immunosorbent assay kits. The mean maternal serum HIF-1α, hepcidin and IL-6 levels of PD were significantly higher than TD ( p  < .001*) and control group ( p  < .001*). The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group ( p =.058, p  = .064). The mean maternal serum IL-6 level of TD was significantly higher than the control group ( p  < .001*). A negative correlation was found between serum concentration of HIF1α, hepcidin, IL-6 with the gestational week of delivery ( r  = -0.421, p  < .01* for HIF-1α; r  = -0.578, p  < .01* for hepcidin and r  = -0.435, p  < .01* for IL-6). High levels of HIF-1α, hepcidin and IL-6 may have potential to be used as biomarkers for the differentiation of PD and TD.Impact statement What is already know n on this subject? It is known that hypoxia-inducible factor-1alpha (HIF-1α) is a hypoxia marker and hepcidin and interleukin-6 (IL-6) increase in inflammation. Our study is the comparison of maternal serum HIF-1α, hepcidin and IL-6 levels between the TPL group (TD and PD) and healthy control group. What the result s of this study add? The present study demonstrates that serum HIF-1α, hepcidin and IL-6 levels were significantly higher in TPD group than uncomplicated group. The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group. What the implications are of these findings for clinical practice and/or further research? High levels of HIF-1α, hepcidin and IL-6 may be biomarkers in the determination of true preterm labour within the TPL group.

Introduction: Neonatal sepsis is the most important cause of morbidity and mortality among low birth weight and preterm babies in developing countries. The main objective of this study is to find the level of micro-Erythrocyte sedimentation rate in neonatal sepsis., Methods: This is a descriptive cross-sectional study conducted at the neonatal unit over six months period (November 2019 to April 2020). All preterm, term and post-term babies with neonatal sepsisdelivered at Kathmandu Medical College Teaching Hospital were enrolled. Ethical clearance was received from the Institutional Review Committee of Kathmandu Medical College (Ref: 181020191). Convenient sampling method was applied and statistical analysis was done with Statistical package for social sciences 19 version., Results: Out of 75 babies, confirm sepsis is 13 (17.3%), probable sepsis is 40 (53.4%) and suspected sepsis is 22 (29.2%). Micro-Erythrocyte sedimentation level is elevated (≥15mm in 1st hr) in 25 (33.3%) babies with a mean micro-Erythrocyte sedimentation level 9.32±5.4 (2-18) mm in 1st hr. The elevated micro- Erythrocyte sedimentation level was seen in relation to sepsis types and C-reactive protein., Conclusions: The bedside micro-Erythrocyte sedimentation level aids in the diagnosis of neonatal sepsis.

Cell-free fetal DNA in the maternal circulation has been associated with the onset of labor at term. Moreover, clinical studies have suggested that cell-free fetal DNA has value to predict pregnancy complications such as spontaneous preterm labor leading to preterm birth. However, a mechanistic link between cell-free fetal DNA and preterm labor and birth has not been established. Herein, using an allogeneic mouse model in which a paternal green fluorescent protein (GFP) can be tracked in the fetuses, we established that cell-free fetal DNA (Egfp) concentrations were higher in late gestation compared to mid-pregnancy and were maintained at increased levels during the onset of labor at term, followed by a rapid decrease after birth. A positive correlation between cell-free fetal DNA concentrations and the number of GFP-positive pups was also observed. The increase in cell-free fetal DNA concentrations prior to labor at term was not linked to a surge in any specific cytokine/chemokine; yet, specific chemokines (i.e., CCL2, CCL7, and CXCL2) increased as gestation progressed and maintained elevated levels in the postpartum period. In addition, cell-free fetal DNA concentrations increased prior to systemic inflammation-induced preterm birth, which was associated with a strong cytokine response in the maternal circulation. However, cell-free fetal DNA concentrations were not increased prior to intra-amniotic inflammation-induced preterm birth, but in this model, a mild inflammatory response was observed in the maternal circulation. Collectively, these findings suggest that an elevation in cell-free fetal DNA concentrations in the maternal circulation precedes the physiological process of labor at term and the pathological process of preterm labor linked with systemic inflammation, but not that associated with intra-amniotic inflammation.

Vitamin D is necessary for the active (transcellular) absorption of calcium and for skeletal health. Inadequate vitamin D in infants leads to increased risks of poor bone mineralization and ultimately rickets. Rickets is uncommon in full-term infants with a much higher risk in very premature infants. However, the primary cause of rickets in premature infants is a deficiency of calcium and phosphorus, not vitamin D. Available research, as well as most guidelines, recommend an intake of 400 IU daily of vitamin D as adequate for bone health in preterm and full-term infants. Higher doses have not been consistently shown to have specific clinical benefits for healthy infants. There are no strong data to support either routine testing of serum 25-hydroxyvitamin D or targeting high serum 25-hydroxyvitamin D levels (e.g., 30 ng/mL) in healthy preterm or full-term infants. Vitamin D is commonly provided to infants via drops for breastfed babies or via infant formula, although alternative dosing approaches exist for breastfed infants, which some families may prefer. These include the use of drops placed on the mother's breast, dissolvable doses, and high maternal doses (approximately 6,400 IU daily). Infant formula contains vitamin D, and most infants will reach an intake from formula of about 400 IU daily within the first 2 months of life if they are consuming routine cow milk-based formula. Although vitamin D toxicity is very uncommon, caution should be used to avoid extremely concentrated high doses found in some commercially available drops. Infants with liver or kidney disease may need special attention to vitamin D intake and status. Further research is needed to define the role of vitamin D in non-bone health outcomes of infants and to identify methods to enhance compliance with current recommendations for vitamin D intake in infants., (© 2020 S. Karger AG, Basel.)

Introduction: Postterm and late-term pregnancies still remain a serious health problem, and underlying exact mechanisms are not fully elucidated. These mechanisms are influenced by many factors., Objective: The aim of this study was to investigate the relationship between plasma oxytocin and oxytocin receptor levels and oxytocin receptor polymorphisms in term and late-term pregnant women., Methods: Sixty-eight singleton pregnant women with late-term pregnancy and 83 singleton pregnant women with term parturition were included in this study. A comparison was performed between pregnancies and neonates born at term (37 0/7 and 41 6/7 weeks' gestation). Plasma oxytocin, oxytocin receptor, estradiol, and progesterone levels were measured by using enzyme-linked immunosorbent assay kits. TaqMan® SNP Genotyping Assays and qPCR ProbesMaster were used to investigate the polymorphisms of rs237911, rs2228485, rs53576, and rs2254298., Results: There was not any difference in gene distributions of 4 common single-nucleotide polymorphisms of oxytocin receptor of rs237911, rs2228485, rs53576, and rs2254298 between subjects in late-term and term pregnancy groups. With rs53576 of the GG genotype, serum oxytocin levels were 21.50 ± 10.69 (ng/L) in the late-term group and 62.71 ± 18.01 (ng/L) in the term group (p = 0.049). Oxytocin receptor levels in the late-term and term pregnancy groups of the GG genotype were 17.92 ± 8.15 (pg/mL) and 45.77 ± 11.66 (pg/mL), respectively (p = 0.046)., Conclusion: Our findings suggest that the rs53576 oxytocin receptor single-nucleotide polymorphism is associated with late-term pregnancy through acting by direct modulation of oxytocin and oxytocin receptor levels., (© 2020 S. Karger AG, Basel.)

Background: The Bilicare™ is a new device that measures transcutaneous bilirubin (TcB) level at the ear pinna. There are only few studies which have evaluated its accuracy in clinical practice. Objective: This study aims to determine the accuracy of Bilicare™ as a predischarge screening tool in late preterm and term neonates and to define the optimal cutoff point for determining the need to measure total serum bilirubin (TSB). Methods: The 35 weeks' gestation or more and healthy neonates who underwent predischarge TSB measurement were enrolled. Bilicare™ TcB was measured within 30 minutes of blood sampling. Paired TcB and TSB data were analyzed. Results: We collected 214 paired samples. Mean age (SD) at TcB measurement was 57.17 (7.47) hours. Mean TSB (SD) was 9.79 (2.83) mg/dL. TcB showed a significant correlation with TSB ( r  = 0.84, r 2  = 0.7). The mean difference (SD) between TcB and TSB was 0.7 (0.21) mg/dL (95%CI 0.49-0.91). TcB tended to overestimate TSB level at the TSB values of <12 mg/dL but underestimate at the higher TSB level. The accuracy of using TcB values to detect neonates who required phototherapy was 92.5%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 78.3, 94.2, 62.1, and 97.3%, respectively. If TcB +3 mg/dL was applied as a cutoff point, the sensitivity, specificity, PPV, and NPV were 100, 53.9, 20.7, and 100%, respectively. Conclusions: Bilicare™ TcB and TSB measurements were well correlated. The TcB level +3 mg/dL could detect all neonates who had significant hyperbilirubinemia requiring phototherapy during their birth hospitalization.

Objective: To examine inflammatory mediators in three fetomaternal biological compartments to inform theory related to the fetal and maternal inflammatory contributions to parturition at term and preterm., Methods: We conducted a cross-sectional study of amniotic fluid, cord blood, and maternal plasma from women with singleton pregnancies. Women had one of four conditions: term labor (n=11), term not in labor (n=13), spontaneous preterm birth with intact membranes (preterm birth; n=13), or preterm prelabor rupture of membranes (PROM; n=8). We measured two damage-associated molecular pattern markers (high-mobility group box-1 [HMGB1] and uric acid) and two acute phase response markers (interleukin [IL]-6 and C-reactive protein [CRP]) using enzyme-linked immunosorbent assay. The distribution of each analyte within amniotic fluid, cord blood, and maternal plasma across the four conditions (term not in labor, term labor, preterm birth, and preterm PROM) were calculated. To explore whether there were distributional differences in each analyte across each of the four labor conditions, we used a nonparametric Kruskal-Wallis test. For analytes that differed across groups, we further compared distributions by labor group (term labor vs term not in labor, and preterm PROM vs preterm birth)., Results: Fetal compartments (amniotic fluid and cord blood) showed higher HMGB1 in term labor vs term not in labor and preterm PROM vs preterm birth. Amniotic fluid IL-6, cord blood CRP and cord blood uric acid were higher in term vs term not in labor. Cord blood uric acid was higher in preterm PROM vs preterm birth. Only maternal plasma IL-6 was higher in term labor vs term not in labor., Conclusion: Accumulation of HMGB1 and an overall increase in inflammation observed on the fetal side, but not the maternal side, may be signals of parturition. Understanding fetal-derived proparturition inflammatory signals at term and preterm, especially in preterm PROM, might provide fetal-specific biomarkers and identify underlying mechanisms and targets for interventions to reduce the risk of preterm birth and preterm PROM.

Cytokines are the main factors involved in the normal functions of the placenta and delivery process. The aim of this project was to compare serum levels of interleukin-8 (IL-8), IL-6, tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) in term and prolonged-pregnancy mothers and their neonates. This study was performed on 240 participants including 60 term and prolonged-pregnancy neonates and their corresponding mothers. Serum levels of IL-8, IL-6, TNF-α and TGF-β were evaluated by the enzyme-linked immunosorbent assay technique. The results revealed that IL-8 serum levels were significantly lower in the prolonged-pregnancy mothers and their neonates when compared with term mothers and their neonates. Data analysis also revealed a negative correlation between TGF-β and age of prolonged-pregnancy mothers. A poor positive correlation between IL-6 and head circumference of term neonates was also observed. IL-8 may play crucial roles in the process of on-time delivery and age may significantly affect TGF-β production in prolonged-pregnancy mothers. Pro-inflammatory cytokines, such as IL-6, can also be considered as main factors involved in fetal growth.

Exosomes are membrane-bound nanovesicles that transport molecular signals between cells. This study determined changes in maternal plasma exosome proteomics contents in term and preterm births. Maternal plasma (MP) samples were collected from group 1: term not in labor (TNIL, n = 13); group 2: term in labor (TL, n = 11); group 3: preterm premature rupture of membranes (pPROM, n = 8); and group 4: preterm birth (PTB, n = 13). Exosomes isolated from plasma by differential density centrifugation followed by size exclusion chromatography were characterized by morphology (electron microscopy), quantity and size (nanoparticle tracking analysis), and markers (western blot). A quantitative, information-independent acquisition [sequential windowed acquisition of all theoretical mass spectra (SWATH-MS)] approach was used to determine the protein profile in exosomes. Ingenuity Pathway Analysis determined pathways associated with the protein profile identified in exosomes. MP exosomes were spherical, had a mean diameter of 120 nm, and were positive for exosomal proteins CD63 and TSG101 irrespective of pregnancy status. No distinct changes in exosome quantities were seen in maternal circulation across the groups. SWATH-MS identified 72 statistically significant proteins across the groups studied. Bioinformatics analysis showed the proteins within the exosomes in TNIL, TL, pPROM, and PTB target pathways mainly associated with inflammatory and metabolic signals. Exosomal data suggest that homeostatic imbalances, specifically inflammatory and endocrine signaling, might disrupt pregnancy maintenance resulting in labor-related changes both at term and preterm. Reflection of physiologic changes in exosomes is suggestive of its usefulness as biomarkers and cellular function indicators., (Copyright © 2019 Endocrine Society.)

Objective: Erythropoietin - a hormone regulating erythropoiesis - is a biomarker of chronic fetal hypoxia. High erythropoietin levels in fetal plasma and amniotic fluid are associated with increased risk of adverse neonatal outcome. Since the risk of perinatal morbidity and mortality is increased in pregnancies beyond 41 gestational weeks, we evaluated erythropoietin levels in amniotic fluid and umbilical cord serum in apparently low-risk term (≥ 37 gestational weeks) and prolonged pregnancies (≥ 41 gestational weeks) with labor induction., Study Design: This prospective cohort study comprised 93 singleton pregnancies at 37 +0 -42 +1 gestational weeks, of which prolonged pregnancies numbered 63 (67.7%). Amniotic fluid samples were collected at time of labor induction by amniotomy. Umbilical cord blood samples for evaluation of pH, base excess, and umbilical cord serum erythropoietin were collected at birth. Erythropoietin levels were measured by immunochemiluminometric assay. Normal value of amniotic fluid erythropoietin level was defined as ≤ 3 IU/L, and abnormal value as ≥ 27 IU/L. Normal umbilical cord serum erythropoietin was defined as < 40 IU/L. Data on maternal pregnancy and delivery characteristics and short-term neonatal outcomes such as Apgar score were obtained from the hospital charts. Associations were calculated using Spearman's rank correlation coefficient. The Chi-square test, Fisher's exact test and the Mann-Whitney U test were utilized to determine differences in the study groups., Results: Amniotic fluid erythropoietin levels correlated with gestational age (r = 0.261, p = 0.012) and were higher among prolonged pregnancies as compared to term pregnancies (p = 0.005). There were 78 (83.9%) vaginal deliveries, and among these erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum (r = 0.513, p < 0.000). Umbilical cord serum erythropoietin levels correlated with gestational age among vaginal deliveries (r = 0.250, p = 0.027). Erythropoietin levels in amniotic fluid and umbilical cord serum did not correlate with umbilical artery pH or base excess, or other adverse pregnancy outcome., Conclusions: In vaginal deliveries erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum. Erythropoietin levels correlated with gestational age, probably due to weakening placental function and relative hypoxemia occurring in advanced gestation. However, in this relatively low-risk study population erythropoietin was not related to adverse delivery outcome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Our study aimed to study regulatory T cells (Tregs) and their expression of CD45RA, HLA-DR, and CD39 in preterm and full-term infants. In an observational study, we used a three-color flow cytometry for determination of Tregs and their expression of CD45RA, HLA-DR, and CD39 in preterm and full-term infants. The percentages of CD4 + CD25 +high Foxp3 + , CD39 + Tregs, HLA-DR + Tregs and the expression of Foxp3 + in CD4 + CD25 +high Foxp3 Tregs cells were significantly lower in neonates when compared to healthy adult controls. The levels of naïve resting Tregs (CD45RA + Tregs) were significantly higher in neonates than controls. The percentages of CD4 + CD25 +high Foxp3 + Tregs, total CD4 + CD25 + and CD4 + CD25 +high were significantly higher in preterm infants when compared to the full-term group. Moreover, CD45RA + Tregs were significantly higher in preterm than in term infants. We found significant inverse correlations between the gestational age and the levels of both Tregs (r = - 0.395, p = 0.017) and CD45RA + Tregs (r = - 0.422, p = 0.010). Relative to full-term, the frequencies, and phenotypes of Tregs were affected by prematurity. A larger longitudinal study with a sufficient number of newborns is needed to investigate the Treg pool of term and preterm infants thoroughly and to explore the association between the Treg pool and clinical variables.

Background: C-reactive protein (CRP) is used to assist the diagnosis and monitoring of newborn infection. Little is known about CRP activity after birth in the absence of infection., Objective: The aim of this work was to describe postnatal CRP responses in the first days of life in asymptomatic infants with a negative blood culture., Methods: Data were collected from infants who had a blood culture taken at <72 h of age in a UK maternity hospital. All CRP values and their time from birth were recorded. Infants with signs of infection, positive blood culture, or major congenital anomalies were excluded. Infants were analysed by gestation (greater or less than 37 weeks). Normalised CRP curves were generated by linear interpolation and centile curves were derived. Comparisons of median CRP values between groups were made by Mann-Whitney U test at 24, 36, and 48 h., Results: During the study period a total of 219 babies were screened. After exclusions, 73 infants (58 term, 15 preterm) were analysed. In asymptomatic term neonates the CRP (mg/L) peaked at 9.4 after 34.6 h. In preterm babies the CRP peak was 1.75 at 43 h. The median (IQR) values were higher in the term group at 24 and 36 h: 2.5 (1-10.5) versus 0 (0-2.2; p = 0.02) and 3 (0-8.6) versus 0 (0-2.8; p = 0.031)., Conclusions: A CRP rise was demonstrated in term and preterm infants without evidence of infection. This rise was greatest in term infants. CRP values must be interpreted in the context of an infant's clinical condition and not used alone to guide clinical decision making., (© 2019 S. Karger AG, Basel.)

Children born at early term (37 0/7 to 38 6/7 weeks' gestation) are at an increased risk for long-term respiratory, cardiovascular, neurological, and developmental morbidities as compared with children born at full term (39 0/7 to 40 6/7 weeks' gestation). In this population-based cohort analysis, we sought to evaluate the long-term hematological morbidity of early-term born children. The cohort consisted of 223,242 term singleton deliveries. Hospitalizations of the offspring up to 18 years of age involving hematological morbidity were evaluated, including hereditary and acquired anemias, immunodeficiency disorders, coagulation disorders, white blood cell disorders, cytopenias, polycythemia, and myelodysplastic syndrome. Hematological hospitalizations were significantly more common in children delivered at early term as compared with those born at later gestational ages. A Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of hematological-related hospitalizations in the early-term born group (logrank p < 0.001). Using a Cox regression model, early-term delivery was found to be an independent risk factor for childhood hematological morbidity with an adjusted hazard ratio of 1.15 (95%CI 1.01-1.30, p=0.027).Conclusion: Early-term delivery appears to be independently associated with pediatric long-term hematological morbidity of the offspring. What is Known? • It has been shown that children born at early term are at increased risk for short-term adverse outcomes including perinatal mortality. • Early-term infants are also at increased risk for long-term morbidity, mainly respiratory. What is New? • Early-term delivery is also independently associated with long-term hematological morbidity of the offspring.

The progressive adaptations in carbohydrate and lipid metabolism during canine pregnancy are reflected in the concentrations of glucose, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB). The levels of these metabolites in the bitch likely affect fetal concentrations and the composition of amniotic and allantoic fluids (AMF and ALF, respectively). We studied 31 canine parturitions (Cesarean sections) and found that glucose, NEFA and BHB concentrations were significantly higher in maternal serum than in AMF or ALF. Glucose levels in maternal serum, AMF and ALF were closely related (R 2  ≥ 0.821, P < 0.0001) as well as serum and AMF BHB levels (R 2  = 0.661, P < 0.0001). In maternal serum, increases in NEFA were associated with increased BHB, and both were negatively related to glucose (P ≤ 0.010). To estimate the effect of the metabolic burden of pregnancy, we evaluated these variables in relation to the dam's body weight and to the ratio of litter weight to the dam's body weight (LW/BW). Maternal serum glucose was not influenced by LW/BW, but it was lower in small than in large/giant bitches. Small breed dogs and those with >10% LW/BW had significantly higher serum NEFA and BHB concentrations. Glucose in AMF and ALF was independent of LW/BW (P ≥ 0.399). AMF NEFA was lower and BHB higher, if LW/BW was >10% (P ≤ 0.048). In conclusion, the extent of the metabolic load of pregnancy in bitches depends on breed size and on the ratio of litter weight to dam's body weight. Maternal concentrations of glucose, BHB and NEFA determine the concentrations of these metabolites in fetal fluids., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To determine if umbilical cord milking is detrimental in compromised term/near-term infants., Study Design: A retrospective analysis of infants with abnormal cord gases (cord arterial or venous pH of ≤ 7.1 or base deficit > -12). We collected maternal risk factors, cord management, birth, and neonatal outcomes during hospitalization., Result: We found 157 infants who met the criteria for abnormal cord gases. Thirty-six of those had umbilical cord milking at delivery. There was no significant difference in neonatal outcomes, but fewer infants in the cord milking group needed resuscitation (38 vs. 56%, p = 0.07) and ongoing respiratory support (19 vs. 31%, p = 0.16) compared to the immediate clamping group., Conclusions: While not significant, infants who received cord milking at birth needed less resuscitation and ongoing respiratory support. This study suggests that umbilical cord milking appears to be a safe therapy when acidosis is present and when resuscitation is needed.

Objectives: To study the normal oxygen saturation trends and fetomaternal correlates in healthy term newborns within 30 min of life born by normal vaginal delivery (NVD) and elective cesarean section (CS)., Materials and Methods: A cross-sectional study was conducted on 200 healthy term newborns born by NVD and elective CS at a tertiary care centre. Routine care as per the Neonatal Resuscitation Program (NRP) 2015 (Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, et al. Part 13: neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132:S543-60) protocol was given and pre-ductal arterial oxygen saturation was assessed by pulse oximetry at different intervals after birth., Results: The mean peripheral oxygen saturation (SpO2) was 85.4%, 90.8%, 94.1%, 95.7%, 96.7% and 97.4% at 5, 10, 15, 20, 25 and 30 min, respectively, after birth. Higher mean SpO2 was observed in NVD compared to elective CS (P<0.005). The mean time for SpO2 to reach >90% was 9.13 min in NVD and 12.31 min in elective CS (P<0.001). Maternal hemoglobin (Hb) (r=-0.15; P<0.01), birth weight (r=-0.125; P<0.05) and Apgar at 10 min (r=0.33; P<0.001) were significantly correlated with SpO2 of newborns at 10 min of life., Conclusion: Our study defines normal SpO2 levels in healthy term newborns in the first 30 min of life born by NVD and elective CS. Babies born by NVD had significantly higher SpO2 levels and attained SpO2 >90% faster than those born by elective CS. Maternal Hb, birth weight and Apgar at 10 min were significant factors affecting SpO2 levels of newborns at 10 min of life.

Objective: We performed the present study to investigate the feto-maternal osmotic relationship at term with the hypothesis that, in contrast to the literature, maternal plasma osmolality is lower than fetal levels. In a previous study, we found that maternal plasma sodium at delivery was consistently lower than the sodium in the umbilical artery. Our aim was to corroborate these results with analysis of osmolality., Methods: Blood was sampled from 30 women immediately before cesarean section and from the umbilical artery and vein before cord clamping and osmolality, sodium and albumin were analyzed., Results: Maternal osmolality was (mean; 95% confidence interval) 287.0 (285.8-288.2) mOsmkg/kg, arterial cord osmolality was 289.4 (287.9-291.0) mOsm/kg and venous cord osmolality was 287.3 (286.0-288.5) mOsm/kg. The paired difference between maternal and umbilical arterial osmolality was mean (SD) -2.4 (3.3) mOsm/kg (P<0.001), between maternal and umbilical vein -0.3 (3.0) mOsm/kg (P=0.63) and between umbilical artery and vein -2.1 (2.8) mOsm/kg (P<0.001)., Conclusion: Maternal osmolality was significantly lower than arterial cord osmolality confirming our previous results. The feto-maternal osmotic gradient favors water transport from the mother to the fetus and may increase the fetal risk of water intoxication when the mother ingests or is administered large volumes of electrolyte free solutions.

Background: Ghrelin, leptin and insulin, generally considered as regulators of energy homeostasis of the organism may be related to fetal and early postnatal growth. Numerous studies have confirmed the presence of these hormones in the cells of the fetus indicating their importance in development at early stages of life., Methods: This study analyzed active and total ghrelin by radioimmunoassay (RIA), leptin and insulin concentrations by enzyme-linked immunosorbent assay (ELISA) in 65 cord blood samples, from term newborns, and measured the birth anthropometric parameters [birth weight (BW), head circumference, chest, stomach, thigh and arm circumference]., Results: Active ghrelin (AG) concentrations correlated negatively with BW, head circumference, stomach and thigh circumference. When divided by gender, AG correlated negatively with males' BW, stomach and thigh circumference. Females' head circumference correlated negatively with AG. Cord leptin correlated positively with arm circumference. When divided by gender, cord leptin was positively associated with BW and stomach circumference in male newborns and with thigh and arm circumference in female newborns. Insulin concentrations tended to correlate positively with BW in male newborns., Conclusions: In summary, it was confirmed that cord blood ghrelin, leptin and insulin correlate with anthropometric parameters at birth. This study showed a negative correlation of AG with anthropometric parameters, which may emphasize that this hormone is an indicator of growth restriction. This is in contrast to cord leptin and insulin, which are more connected with overgrowth. Taking all the results into consideration, the metabolic status of the fetus and newborn is an essential component in understanding the regulation of perinatal development.

Background: Although delayed cord clamping (DCC) is a recent WHO recommendation, early cord clamping (ECC) is still a routine practice in many countries. Limited researches studied the effect of delayed cord clamping on oxidative stress in term neonates; In this study we aim to assess the influence of cord clamping either early or late on oxidative stress in term neonates and to evaluate the association of oxidative stress and cord blood lipids., Methods: One-hundred mothers and their term neonates were included in the present study. Umbilical cord blood samples were collected from the umbilical vein and umbilical artery immediately following labor., Results: Total cholesterol, total triglycerides and phospholipids levels were significantly higher in the ECC group than the DCC group (p < 0.001 in all). Plasma total antioxidant status was higher in the DCC group than the ECC group (p < 0.001). While, plasma hydroperoxides were lower in the DCC group than the ECC group (p < 0.001). Levels of erythrocytes catalase cytosol, superoxide dismutase and glutathione peroxidase were significantly higher in the DCC group than the ECC group (p < 0.001)., Conclusion: DCC was associated with a decrease in cord blood lipids and an augmented antioxidant activity. This suggests the protective effect of DCC on the future health of the term neonates and supports the application of DCC in active management of 3rd stage of labor in term neonates.

The onset of labour in rodents and in humans is associated with physiological inflammation which is manifested by infiltration of activated maternal peripheral leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to immunophenotype mPLs throughout gestation and labour, both term and preterm. Peripheral blood was collected from non-pregnant women and pregnant women in the 1st, 2nd and 3rd trimesters. Samples were also collected from women in active labour at term (TL) or preterm (PTL) and compared with women term not-in-labour (TNIL) and preterm not-in-labour (PTNIL). Different leukocyte populations were identified by surface markers such as CD45, CD14, CD15, CD3, CD4, CD8, CD19 and CD56. Their activation status was measured by the expression levels of CD11b, CD44, CD55, CD181 and CD192 proteins. Of all circulating CD45+ leukocytes, we detected significant increases in CD15+ granulocytes (i) in pregnant women versus non-pregnant; (ii) in TL women versus TNIL and versus pregnant women in the 1st/2nd/3rd trimester; (iii) in PTL women versus PTNIL. TL was characterized by (iv) increased expressions of CD11b, CD55 and CD192 on granulocytes; (v) increased mean fluorescent intensity (MFI) of CD55 and CD192 on monocytes; (vi) increased CD44 MFI on CD3+ lymphocytes as compared to late gestation. In summary, we have identified sub-populations of mPLs that are specifically activated in association with gestation (granulocytes) or with the onset of labour (granulocytes, monocytes and lymphocytes). Additionally, beta regression analysis created a set of reference values to rank this association between immune markers of pregnancy and to identify activation status with potential prognostic and diagnostic capability., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Purpose: Preterm birth (PTB) is a complex trait with strong genetic background, whose etiology is not fully understood. It was recently suggested that pregnancy duration is affected by fetal genetic variation even more than by the maternal genome. Vitamin D receptor (VDR) is involved in embryonic implantation and fertility. We studied the association between both maternal and neonatal vitamin D receptor (VDR) genetic variation and PTB., Methods: Maternal and fetal (umbilical cord) DNA was isolated from Jewish Israeli idiopathic preterm newborns (24-36 weeks, n = 146) and control term newborns (>37 weeks, n = 229). Maternal and fetal VDR polymorphisms (FokI, ApaI, BsmI, TaqI) were analyzed by restriction fragment length polymorphism analysis. Using SPSS analysis to correlate VDR genotypes with phenotypic variation: pregnancy duration, preterm birth and spontaneous miscarriages, adjusted for gravidity, parity and gender of newborn., Results: Women homozygous to VDR ApaI (AA) genotype had significant twofold increase risk for PTB [OR 1.973, (CI) 1.183-3.289, p = 0.009] compared to heterozygous women. Male newborns had significant (p < 0.05) 1.73-fold increase of PTB. Women with history of previous (≥1) spontaneous miscarriage had a significant increased risk for PTB if their newborn carried either of the VDR BsmI homozygous (BB or bb) genotypes compared to the heterozygous (Bb) genotype [OR 6.857, (CI) 1.273-36.934, p = 0.018 and OR 9.231, (CI) 1.753-48.618, p = 0.008, respectively], or VDR ApaI homozygous (AA or aa) genotype compared to heterozygous (Aa) genotype [OR 4.33, (CI) 1.029-18.257, p = 0.046 and OR 7.2, (CI) 1.34-38.917, p = 0.021, respectively]., Conclusions: We show association between maternal and fetal VDR genotype variants with PTB.

Objective: The objective of this study is to determine the impact of postnatal age on the bias between transcutaneous (TcB) and total serum bilirubin (TSB), and evaluate a TcB screening protocol., Study Design: Preterm and term infants had paired TcB and TSB performed on days 1 to 3 of life; a subset of preterm infants had measurements on days 4 to 7. Sensitivity and specificity of TcB (plotted on an age-specific TSB nomogram) for prediction of high-intermediate (HIR) or high-risk TSB were calculated., Results: Median TcB bias was 2.6 and 2.5 mg dl -1 for term and preterm infants in the first 3 days of life, respectively. However, median bias was 2.2 mg dl -1 for preterm infants at 4 to 7 days of life. TcB in preterm infants predicted HIR or high-risk TSB with 94% sensitivity and 56% specificity., Conclusion: TcB screening protocols developed for term infants can be used for late preterm infants in the first 3 days of life.

Objective: To determine the postnatal course of neurosteroid levels in relation to gender, mode of delivery and the extent of skin-to-skin (STS) contact during the first days of life in healthy term newborns., Study Design: Prospective observational study of 39 neonates in which parents recorded total duration of STS in the first 2 days and nine neurosteroids (dehydroepiandrosterone-sulfate, progesterone, pregnenolone, pregnenolone-sulfate, allopregnanolone, isopregnanolone, epipregnanolone, pregnanolone and pregnanolone-sulfate) were assayed from blood samples at birth and at 1-2 days of age., Results: All nine neurosteroid levels declined significantly during the first 2 days of life. Gender did not significantly affect the change in neurosteroid levels. The decline in neurosteroid levels was generally more pronounced in vaginal deliveries, and there was a trend toward a larger decline with more exposure to STS., Conclusion: Ongoing studies may better characterize the role of neurosteroids and the influence of STS in more critically ill and premature neonates.

Objective: To compare maternal, cord blood erythropoietin (EPO), and copeptin levels in low-risk term deliveries which are complicated by meconium-stained amniotic fluid (MSAF) to those with clear amniotic fluid. Also, to evaluate the relations between these markers and cord blood pH values., Methods: Low-risk term pregnant women with MSAF at an active phase of labor were defined as the study group (n = 39). Pregnant women with clear amniotic fluid were selected for the control group (n = 41). The two groups were matched for age, body mass index and gestational age. Maternal, cord blood EPO and copeptin levels with cord blood pH values were also measured., Results: Maternal, cord blood EPO, and copeptin levels of study and control groups were 42.6 ± 9.0 versus 40.7 ± 9.2, 134.2 (20.5-834.6) versus 38.4 (10.3-114.2), 4.9 (0.1-31.1) versus 4.0 (3.1-28.4), and 4.7 (2.6-25.5) versus 3.6 (2.0-23.2), respectively. The differences were statistically significant for cord blood EPO, maternal and cord blood copeptin levels (p < 0.001, p = 0.004, p < 0.001, respectively). The study group had a statistically and significantly lower cord blood pH values (7.25 ± 0.05 versus 7.34 ± 0.04, p < 0.001). Moreover, cord blood EPO and maternal and cord blood copeptin levels were inversely correlated with cord blood pH values in the study group (p < 0.001, p = 0.005, and p = 0.009, respectively)., Conclusion: We suggest that higher cord blood EPO and maternal and cord blood copeptin levels may be an indicator of fetal acidosis in low-risk term deliveries complicated by MSAF.

Objective: The objective of the study was to measure the effects of a 5-min delay (DCC) versus immediate cord clamping (ICC) on residual placental blood volume (RPBV) at birth, and hemoglobin and serum bilirubin at 24 to 48 h of age., Study Design: In this prospective randomized controlled trial, 73 women with term (37 to 41 weeks) singleton fetuses were randomized to DCC (⩾5 min; n=37) or ICC (<20 s; n=36)., Results: Maternal and infant demographics were not different between the groups. Mean cord clamping time was 303±121 (DCC) versus 23±59 (ICC) s (P<0.001) with 10 protocol violations. Cord milking was the proxy for DCC (n=11) when the provider could not wait. Infants randomized to DCC compared with ICC had significantly less RPBV (20.0 versus 30.8 ml kg -1 , P<0.001), higher hemoglobin levels (19.4 versus 17.8 g dl -1 , P=0.002) at 24 to 48 h, with no difference in bilirubin levels., Conclusion: Term infants had early hematological advantage of DCC without increases in hyperbilirubinemia or symptomatic polycythemia.

Background: The use of transcutaneous bilirubin (TcB) as a screening tool, based on relevant population-specific nomogram, or proxy for total serum bilirubin (TSB) levels in assessing the risk of subsequent hyperbilirubinemia is supported by several clinical guidelines on the management of neonatal hyperbilirubinemia. However, while TcB has been found to significantly over-estimate TSB in neonates of African-American ancestry, with variations across TcB devices, no nomogram has been specifically reported for this racial group. This study therefore set out to develop TcB nomograms for healthy late pre-term and term black African neonates derived from two widely used bilirubinometers., Methods: A retrospective analysis of 12,377 TcB measurements obtained from 6,373 neonates in the first postnatal week, over a period of 48 months using Bilichek and JM-103 bilirubinometers. TcB percentiles were computed from hour-specific TcB values and nomograms developed for each of the screening devices. Predictive ability of the 75th and 95th percentiles to detect significant hyperbilirubinemia was evaluated between 24-96 hours of age. The 95th percentile curve was compared with those from other populations., Results: The velocity of TcB rise at 75th and 95th percentiles was generally higher with JM-103 than Bilichek. Both percentiles also peaked at higher TcB levels with JM-103. The 95th percentile for both instruments showed a downward trend as from approximately 114 hours. Both instruments had high negative predictive values across the selected time-epochs and lower discriminatory ability than reported in non-black populations., Conclusions: The predictive utility of TcB as a potential screening tool varies across devices in black African neonates with or without risk of significant hyperbilirubinemia, and lower than levels reported in non-black populations. Equipment-specific nomograms should be considered for TcB monitoring in this racial population where TSB is not routinely available., Competing Interests: The authors have declared that no competing interests exist.

Background: In very-low-birth-weight infants IGF-I plays an important role in postnatal growth restriction and is probably also involved in growth restriction in childhood. We compared IGF-I and its relation to growth in early childhood in very-low-birth-weight infants and term appropriate for gestational age born infants., Methods: We included 41 very-low-birth-weight and 64 term infants. Anthropometry was performed at all visits to the outpatient clinic. IGF-I and insulin were measured in blood samples taken at 6 months and 2 years corrected age (very-low-birth-weight children) and at 3 months, 1 and 2 years (term children)., Results: Over the first 2 years of life growth parameters are lower in very-low-birth-weight children compared to term children, but the difference in length decreases significantly. During the first 2 years of life IGF-I is higher in very-low-birth-weight children compared to term children. In both groups there is a significant relationship between IGF-I and (change in) length and weight over the first 2 years of life and between insulin and change in total body fat., Conclusions: Considering the relation of IGF-I to growth and the decrease in difference in length, higher IGF-I levels in very-low-birth-weight infants in early childhood probably have an important role in catch-up growth in length., Competing Interests: The authors have declared that no competing interests exist.

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.

Background: Parturition at term and preterm is characterized by sterile inflammatory processes occurring in the absence of infection whereby peripheral leukocytes infiltrate gestational tissues in response to chemotactic signals. In response to a homing signal, recruited leukocytes undergo diapedesis and extravasate through capillaries, migrating into stromal tissue. There they interact with resident immune and stromal cells to produce a mixture of matrix metalloproteinases, prostaglandins and cytokines including interleukin-1β (IL-1β) and IL-6 that in turn transform the uterus from pregnancy to parturition. Since migration is an early parturitional event our purpose was to study the migration of maternal peripheral blood leukocytes in response to a standard chemotactic signal during several different conditions of late pregnancy., Methods: We used a cross-sectional observational study design. Subjects were (sTL) spontaneous normal labour delivered vaginally at term, (TNL) elective caesarean section at term without labour, (PTL) preterm in labour, (PTNL) preterm not in labour, (TPTL) threatened preterm labour, and (pPROM) preterm with premature rupture of membranes. Leukocytes (100,000) obtained by venipuncture and chemotactic factor isolated from term labour fetal membranes were placed in the upper and lower halves, respectively, of a Boyden chamber separated by a filter with 3μm pores. Migrated leukocytes were assessed by flow cytometry. The number of leukocytes that migrated in 90 min was the primary outcome measure., Results: Increased numbers of leukocytes from peripheral blood of women in labour (TL or PTL) or soon to go into labour (PPROM) migrated towards a chemotactic signal than did leukocytes from women not in labour (TNL, PTNL, or TPTL) (p < 0.0001). All pPROM delivered within 7d; TPTL delivered >30d. Receiver operating characteristic curve parameters indicated the cut-off point for delivery within 7d to be 37,082 leukocytes with sensitivity 78.1%, specificity 88.9%, positive predictive value 91.4%, negative predictive value 72.7%, and area under the curve 0.83., Conclusion: Leukocyte migration to a fetal membrane signal varies in a predictable fashion during various clinical situations of late gestation. This principle has the potential to be improved to become a clinical test to predict delivery.

Background: Reticulocyte haemoglobin content, i.e., the reticulocyte equivalent (Ret-He), seems to be a promising parameter for the detection of iron deficiency (ID) in neonates because it can be obtained as part of a reticulocyte count, with no additional blood loss and at no extra cost. Due to the short life span of reticulocytes, Ret-He reflects current iron availability for erythropoiesis more accurately than other common erythrocyte indices., Objective: We aimed to evaluate postnatal changes in Ret-He within the first days after birth in term and preterm infants with the hypothesis that preterm infants experience a more pronounced postnatal reduction in Ret-He when compared to term infants., Methods: We conducted retrospective analyses of clinically indicated blood samples. Paired t test and mixed regression modelling were used., Results: In total, 805 blood samples obtained from 207 term and 295 preterm infants were analysed. Ret-He decreased by 1.5 pg per day (regression coefficient [95% CI] -1.5 [-1.8 to -1.2] pg, p < 0.0001). This drop was more significant in preterm infants (regression coefficient -2.2 [-2.6 to -1.8] pg, p < 0.0001) than in term infants (regression coefficient -0.8 [-1.3 to -0.2] pg, p < 0.01, pinteraction < 0.0001)., Conclusion: Ret-He declined within the first days after birth. The observed changes with postnatal age were more pronounced in preterm than in term infants. Further studies are needed to evaluate if these changes are due to developing ID or other causes., (© 2017 S. Karger AG, Basel.)

Objective: To develop normative ranges for citrate-modified and heparinase-modified thromboelastography (TEG) in term neonates., Design: Prospective observational study., Setting: An outborn neonatal and cardiac intensive care unit in a free-standing academic children's hospital., Patients: Thirty term neonates were enrolled as control subjects. Seventeen infants with clinically documented bleeding requiring blood transfusion were enrolled in the comparison group., Main Outcome Measures: Citrate-modified and heparinase-modified TEG parameters were calculated from blood specimens drawn via peripheral arterial stick or arterial line., Results: TEG in neonates differs from older children and adults; clotting time (R) and clot kinetics (K) values are generally lower while fibrinolysis or rate of clot breakdown (LY30) and coagulation index (CI) are often higher in neonates. TEG values in term neonates calculated as median (Q1-Q3) are as follows: R 4.150 (3.200-6.200), K 1.550 (1.200-1.800), α angle (α) 70.100 (66.000-72.900), maximum amplitude (MA) 61.850 (59.400-66.000), LY30 1.050 (0.100-1.600) and CI 1.950 (0.100 to 2.900). Cut points selected for optimal predictive value for bleeding using receiver operating curve analyses were R>6.3 (sensitivity 82.4%, specificity 80%); K>2.5 (sensitivity 82.4%, specificity 96.7%); α<59 (sensitivity 82.4%, specificity 96.7%); MA<57 (sensitivity 82.4%, specificity 86.7%); CI<-0.15 (sensitivity 88.2%, specificity 83.3%)., Conclusions: The reference ranges and cut points for citrate-modified and heparinase-modified TEG can be used to diagnose and evaluate coagulopathy in term neonates., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Delayed umbilical cord clamping appears to be beneficial for term and preterm infants. In term infants, delayed umbilical cord clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcomes. There is a small increase in jaundice that requires phototherapy in this group of infants. Consequently, health care providers adopting delayed umbilical cord clamping in term infants should ensure that mechanisms are in place to monitor for and treat neonatal jaundice. In preterm infants, delayed umbilical cord clamping is associated with significant neonatal benefits, including improved transitional circulation, better establishment of red blood cell volume, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage. Delayed umbilical cord clamping was not associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor was it associated with a difference in postpartum hemoglobin levels or the need for blood transfusion. Given the benefits to most newborns and concordant with other professional organizations, the American College of Obstetricians and Gynecologists now recommends a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30-60 seconds after birth. The ability to provide delayed umbilical cord clamping may vary among institutions and settings; decisions in those circumstances are best made by the team caring for the mother-infant dyad.

Background: The club cell 10-kDa protein (CC10) is a homeostatic protein that is produced in the lung, diffuses into the blood, and is then excreted into the urine and stool. CC10 is known to have anti-inflammatory properties and to have lower endogenous production in preterm infants., Objectives: As recombinant human CC10 (rhCC10) is being studied in preterm infants to reduce lung injury, understanding CC10 levels in term infants with normal lungs is needed to establish appropriate target dosing ranges., Methods: Serum, urine, and stool samples were collected from 24 healthy full-term infants, and CC10 levels were measured. Levels in term infants were then compared to those in preterm infants who were examined in our previous studies., Results: The mean gestational age and birth weight of the term infants were 38.8 ±1.1 weeks and 3,257 ± 513 g, respectively. The mean gestational age of the preterm infants was 26.8 ± 1.4 weeks. The median serum [CC10] levels with minimum and maximum values in term infants (214.2 ng/mL [34.1, 428.1]) were >7-fold higher than in preterm infants (27.5 ng/mL [8.0, 760.0]; p < 0.05). A significant correlation was found between [CC10] in urine and stool as well as between gestational age and stool [CC10] (p < 0.05)., Conclusions: CC10 is detectable in serum, urine, and stool in healthy term infants, with levels significantly higher than in preterm infants. This provides important data for ongoing therapeutic intervention trials with rhCC10 in high-risk preterm infants., (© 2016 S. Karger AG, Basel.)