Maternal serum alpha-1 antitrypsin levels in spontaneous preterm and term pregnancies.

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.

Cord blood presepsin as a predictor of early-onset neonatal sepsis in term and preterm newborns.

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.

Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses.

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, CD56bright 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-1ß, IL-6 and IL-17A were lower in preterm infants in addition to chemokines IL-8, eotaxin, MIP-1α and MIP-1ß. 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.

Imbalance between inflammatory and regulatory cord blood B cells following pre-term birth.

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 CD24hiCD38hiCD19 + Breg and CD1dhiCD5+ 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.

Correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.

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.

Umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (ßCTX) levels in term pregnancies with vitamin D deficiency.

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 (ßCTX) 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 ßCTX 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.

Relations between second-trimester aneuploidy screening results and prediction of labour induction success in term pregnancies.

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 STATEMENTWhat 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.

The roles played by IL-10, IL-23 and IL-17A in term delivery.

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.

Establishing reference ranges of cord blood: point-of-care hemostatic function assessment in preterm and term neonates.

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.

Delayed Umbilical Cord Clamping After Birth: ACOG Committee Opinion, Number 814.

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 After Birth: ACOG Committee Opinion Summary, Number 814.

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.

Hypocalcaemia and calcium intake in pregnancy: A research protocol for critical analysis of risk factors, maternofoetal outcomes and evaluation of diagnostic methods in a third-category health facility, Cameroon.

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.

Vitamin D in Preterm and Full-Term Infants.

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.

Evaluating the Low-Dose ACTH Stimulation Test in Neonates: Ideal Times for Cortisol Measurement.

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.

Micro-Erythrocyte Sedimentation Rate in Neonatal Sepsis of a Tertiary Hospital: A Descriptive Cross-sectional Study.

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.

Polymorphism of the Oxytocin Receptor (OXTR) Gene Affects the Circulating Oxytocin Receptor Levels in Late-Term Pregnancy in a Turkish Population.

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.

Cell-Free Fetal DNA Increases Prior to Labor at Term and in a Subset of Preterm Births.

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.

Hypoxia-inducible factor-1α, hepcidin and interleukin-6 levels in pregnancies with preterm labour.

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 statementWhat is already known 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 results 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.

Accuracy of the Bilicare™ transcutaneous bilirubinometer as the predischarge screening tool for significant hyperbilirubinemia in healthy term and late preterm neonates.

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, r2 = 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.