RESUMEN
PROBLEM: Preterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles. Arginines are scarcely studied in relation to PTB and we aimed to investigate arginines (ADMA, SDMA and L-arginine) in women with spontaneous PTB and term birth. METHODS OF THE STUDY: The study was based on data from the population-based, prospective cohort BASIC study conducted in Uppsala County, Sweden, between September 2009 and November 2018. Arginines were analyzed by Ultra-High Performance Liquid Chromatography using plasma samples taken at the onset of labor from women with spontaneous PTB (n = 34) and term birth (n = 45). We also analyzed the inflammation markers CRP, TNF-R1 and TNF-R2 and GDF-15. RESULTS: Women with spontaneous PTB had higher plasma levels of ADMA (p < 0.001), and L-Arginine (p = 0.03). In addition, inflammation marker, TNF-R1 (p = 0.01) was higher in spontaneous PTB compared to term birth. Further, in spontaneous PTB, no significant correlations could be observed when comparing levels of arginines with inflammation markers, except ADMA versus CRP. CONCLUSIONS: These findings provide novel evidence for the potential involvement of arginines in the pathogenesis of spontaneous PTB and it seems that arginine levels at labor vary independently of several inflammatory markers. Further research is warranted to investigate the potential of arginines as therapeutic targets in the prevention and management of spontaneous PTB.
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Arginina , Nacimiento Prematuro , Humanos , Femenino , Arginina/análogos & derivados , Arginina/sangre , Embarazo , Estudios Prospectivos , Adulto , Nacimiento Prematuro/sangre , Suecia , Trabajo de Parto/sangre , Biomarcadores/sangre , Estudios de Cohortes , Recién Nacido , Inflamación/sangreRESUMEN
Background: Postpartum hemorrhage (PPH) is the primary cause of maternal mortality globally, with uterine atony being the predominant contributing factor. However, accurate prediction of PPH in the general population remains challenging due to a lack of reliable biomarkers. Methods: Using retrospective cohort data, we quantified 48 cytokines in plasma samples from 40 women diagnosed with PPH caused by uterine atony. We also analyzed previously reported hemogram and coagulation parameters related to inflammatory response. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to develop predictive models. Established models were further evaluated and temporally validated in a prospective cohort. Results: Fourteen factors showed significant differences between the two groups, among which IL2Rα, IL9, MIP1ß, TNFß, CTACK, prenatal Hb, Lymph%, PLR, and LnSII were selected by LASSO to construct predictive model A. Further, by logistic regression, model B was constructed using prenatal Hb, PLR, IL2Rα, and IL9. The area under the curve (AUC) values of model A in the training set, internal validation set, and temporal validation set were 0.846 (0.757-0.934), 0.846 (0.749-0.930), and 0.875 (0.789-0.961), respectively. And the corresponding AUC values for model B were 0.805 (0.709-0.901), 0.805 (0.701-0.894), and 0.901 (0.824-0.979). Decision curve analysis results showed that both nomograms had a high net benefit for predicting atonic PPH. Conclusion: We identified novel biomarkers and developed predictive models for atonic PPH in women undergoing "low-risk" vaginal delivery, providing immunological insights for further exploration of the mechanism underlying atonic PPH.
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Biomarcadores , Citocinas , Hemorragia Posparto , Humanos , Femenino , Embarazo , Biomarcadores/sangre , Hemorragia Posparto/sangre , Hemorragia Posparto/diagnóstico , Hemorragia Posparto/etiología , Adulto , Citocinas/sangre , Estudios Retrospectivos , Inercia Uterina/sangre , Estudios Prospectivos , Trabajo de Parto/sangreRESUMEN
OBJECTIVE: To look into the effects of different anesthesia methods on the labor process and the expression of serum estrogen and progesterone in primiparas with painless labor. METHODS: 60 primiparas receiving painless labor were selected as the research objects, and they were divided into either a Spinal & Continuous epidural anesthesia group (n = 30) or a continuous epidural anesthesia group (n = 30), anesthesia is administered using the corresponding anesthesia method. The authors compared serum estrogen and progesterone, inflammatory index expression, pain degree and neonatal health status in different periods. RESULTS: At T2 and T3, serum P, LH, FSH and E2 levels in the Spinal & Continuous epidural anesthesia group were signally lower than those in the Spinal & Continuous epidural anesthesia group (p < 0.05). Spinal & Continuous epidural anesthesia group harbored faster onset and longer duration of sensory block and motor block than the Continuous epidural anesthesia group (p < 0.05). SAS and SDS scores of the Spinal & Continuous epidural anesthesia group were clearly lower than those of the Continuous epidural anesthesia group (p < 0.05). VAS score and serum TNF-α, IL-6 levels of pregnant women in the Spinal & Continuous epidural anesthesia group were memorably lower than those in the Continuous epidural anesthesia group at T2 and T3 (p < 0.05). The total incidence of postoperative complications in the Spinal & Continuous epidural anesthesia group was distinctively lower than that in the Continuous epidural anesthesia group (p < 0.05). CONCLUSION: Spinal anesthesia combined with continuous epidural anesthesia has a better anesthesia effect in the painless labor of primiparas, which can effectually ameliorate the labor process and the expression of serum estrogen and progesterone.
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Anestesia Epidural , Estrógenos , Periodo Posparto , Progesterona , Humanos , Femenino , Embarazo , Progesterona/sangre , Anestesia Epidural/métodos , Adulto , Estrógenos/sangre , Periodo Posparto/sangre , Trabajo de Parto/sangre , Anestesia Raquidea/métodos , Anestesia Obstétrica/métodos , Adulto Joven , Factores de Tiempo , Dimensión del Dolor , Paridad , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
INTRODUCTION: Epidural analgesia has been associated with intrapartum maternal fever development. Epidural-related maternal fever (ERMF) is believed to be based on a non-infectious inflammatory reaction. Circulating cell-free mitochondrial deoxyribonucleic acid (mtDNA) is one of the possible triggers of sterile inflammatory processes; however, a connection has not been investigated so far. Therefore, this study aimed to investigate cell-free mtDNA alterations in women in labour with ERMF in comparison with non-febrile women. MATERIAL AND METHODS: A total of 60 women in labour were assessed for maternal temperature every 4 h and blood samples were obtained at the beginning and after delivery. Depending on the analgesia and the development of fever (axillary temperature ≥ 37.5 °C), the women were allocated either to the group of no epidural analgesia (n = 17), to epidural analgesia no fever (n = 34) or to ERMF (n = 9). Circulating cell-free mtDNA was analysed in the maternal plasma for the primary outcome whereas secondary outcomes include the evaluation of inflammatory cytokine release, as well as placental inflammatory signs. RESULTS: Of the women with epidural analgesia, 20% (n = 9) developed ERMF and demonstrated a decrease of circulating mtDNA levels during labour (p = 0.04), but a trend towards higher free nuclear DNA. Furthermore, women with maternal pyrexia showed a 1.5 fold increased level of Interleukin-6 during labour. A correlation was found between premature rupture of membranes and ERMF. CONCLUSIONS: The pilot trial revealed an evident obstetric anaesthesia phenomenon of maternal fever due to epidural analgesia in 20% of women in labour, demonstrating counterregulated free mtDNA and nDNA. Further work is urgently required to understand the connections between the ERMF occurrence and circulating cell-free mtDNA as a potential source of sterile inflammation. TRIAL REGISTRATION: NCT0405223 on clinicaltrials.gov (registered on 25/07/2019).
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Analgesia Epidural , ADN Mitocondrial , Fiebre , Humanos , Femenino , ADN Mitocondrial/sangre , Proyectos Piloto , Embarazo , Adulto , Fiebre/sangre , Analgesia Obstétrica , Trabajo de Parto/sangre , Ácidos Nucleicos Libres de Células/sangreRESUMEN
Background: Increased maternal cortisol secretion has been observed during pregnancy and labor. However, due to the limitations in diagnostic methods, the dynamic change of cortisol during the short period between threatened labor and labor is unknown. In this study, we aim to evaluate the changes in serum cortisol during late pregnancy and full-term labor initiation, verifying if cortisol could serve as a biomarker for the diagnosis of labor initiation from threatened labor. Methods: This cross-sectional onsite study involved 564 participants of 6 different gestational stages (C: Control; T1: Trimester 1; T3: Trimester 3; E: expectant; TL: threatened labor; L: labor), all patients in the E, TL, and L groups were at full term. The serum cortisol concentration was quantified with a point-of-care test (POCT), and the gestation, age, parity, and BMI of participants were documented. Morning serum cortisol was collected between 8:00 and 10:00 a.m., except for the TL and L group women who were tested upon arrival or during latent labor. With cortisol levels or all five variables, L was distinguished from TL using machine learning algorithms. Results: Significant elevation of cortisol concentration was observed between T1 and T3, or TL and L group (P< 0.001). Women belonging to the E and TL group showed similar gestation week and cortisol levels. Diagnosis of labor initiation using cortisol levels (cutoff = 21.46 µg/dL) yielded sensitivity, specificity, and AUC of 86.50%, 88.60%, and 0.934. With additional variables, a higher specificity (89.29%) was achieved. The diagnostic accuracy of all methods ranged from 85.93% to 87.90%. Conclusion: Serum cortisol could serve as a potential biomarker for diagnosis of L form TL. The rapid onsite detection of serum cortisol with POCT could facilitate medical decision-making for admission and special treatments, either as an additional parameter or when other technical platforms are not available.
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Biomarcadores , Hidrocortisona , Humanos , Femenino , Embarazo , Estudios Transversales , Hidrocortisona/sangre , Adulto , Biomarcadores/sangre , Trabajo de Parto/sangre , Inicio del Trabajo de Parto/sangre , Adulto Joven , Edad GestacionalRESUMEN
The complex physiologic process of parturition includes the onset of labor, which requires the orchestrated stimulation of a common pathway involving uterine contractility, cervical ripening, and chorioamniotic membrane activation. However, the labor-specific processes taking place in these tissues have limited use as predictive biomarkers unless they can be probed in non-invasive samples, such as the peripheral blood. Herein, we utilized a transcriptomic dataset to assess labor-specific changes in the peripheral blood of women who delivered at term. We identified a set of genes that were differentially expressed with labor and enriched for immunological processes, and these gene expression changes were strongly correlated with results from prior studies, providing in silico validation of our findings. We then identified significant correlations between labor-specific transcriptomic changes in the maternal circulation and those detected in the chorioamniotic membranes, myometrium, and cervix of women at term, demonstrating that tissue-specific labor signatures are partly mirrored in the peripheral blood. Finally, we demonstrated a significant overlap between the peripheral blood transcriptomic changes in term parturition and those observed in asymptomatic women, prior to the diagnosis of preterm prelabor rupture of the membranes, who ultimately delivered preterm. Collectively, we provide evidence that the normal process of labor at term is characterized by a unique immunological expression signature, which may serve as a useful tool for assessing labor status and for potentially identifying women at risk for preterm birth.
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Parto/sangre , Nacimiento Prematuro/sangre , Transcriptoma/fisiología , Adulto , Cuello del Útero/química , Membranas Extraembrionarias/química , Femenino , Rotura Prematura de Membranas Fetales/sangre , Humanos , Inflamación/sangre , Inflamación/inmunología , Trabajo de Parto/sangre , Trabajo de Parto/inmunología , Miometrio/química , EmbarazoRESUMEN
OBJECTIVE: This pilot study evaluated the relationship between maternal and neonatal R- and S-methadone and R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) exposure and the severity of neonatal abstinence syndrome (NAS). The use of dried blood spots (DBS) as an alternative for plasma in assessing methadone and EDDP was also assessed. STUDY DESIGN: Women receiving methadone for medication assisted treatment of opioid use disorder during pregnancy were eligible for recruitment. Plasma and DBS samples were collected from mothers during labor, from cord blood, and from newborns during genetic screen. R-/S-methadone and EDDP were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). Associations between methadone exposure, neonatal morphine requirements, and severity of NAS were examined. RESULTS: Twenty women and infants completed the study. Maternal methadone dose at delivery was 112 mg/day (range = 60-180 mg/day). Sixteen neonates experienced NAS requiring morphine; three also required phenobarbital. Higher cord blood concentrations of R-methadone, R- and S-EDDP were associated with higher maximum doses of morphine (p < 0.05). CONCLUSION: Maternal methadone and cord blood concentration at delivery are variable and may be potential markers of neonatal abstinence syndrome.
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Analgésicos Opioides/sangre , Pruebas con Sangre Seca , Metadona/sangre , Síndrome de Abstinencia Neonatal/sangre , Pirrolidinas/sangre , Analgésicos Opioides/uso terapéutico , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Recién Nacido , Trabajo de Parto/sangre , Metadona/uso terapéutico , Morfina/uso terapéutico , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Fenobarbital/uso terapéutico , EmbarazoAsunto(s)
Trabajo de Parto/sangre , Factor de Crecimiento Placentario/sangre , Placenta/irrigación sanguínea , Citrato de Sildenafil/uso terapéutico , Vasodilatadores/uso terapéutico , Adulto , Extracción Obstétrica/estadística & datos numéricos , Femenino , Sufrimiento Fetal/epidemiología , Sufrimiento Fetal/terapia , Humanos , Estimación de Kaplan-Meier , Embarazo , Modelos de Riesgos Proporcionales , Nacimiento a Término , Resultado del TratamientoRESUMEN
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.
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Ácidos Nucleicos Libres de Células/sangre , Trabajo de Parto/sangre , Trabajo de Parto Prematuro/sangre , Nacimiento Prematuro/sangre , Nacimiento a Término/sangre , Animales , Quimiocinas/sangre , Citocinas/sangre , Femenino , Ratones , Parto/sangre , EmbarazoRESUMEN
The purpose of this study was to determine whether timing of the initiating event of spontaneous labor (either uterine contractions with intact fetal membranes or rupture of membranes prior to labor (PROM)) is associated with maternal viral infection. It was a prospective case control study of women with either spontaneous labor or PROM occurring < 37 weeks' gestation ("cases") or at term ("controls"). An initial unbiased screen for viruses was performed with next-generation sequencing (NGS) in serum pooled from eight cases delivered by C/S and represents a range of gestational ages, membrane rupture status, and presence or absence of chorioamnionitis. Custom PCR was used to query individual patient samples from the original cohort. The NGS screen generated 15 million reads. Seven unique viral sequences were detected in two cases, all identified as torque teno virus (TTV), an ubiquitous DNA anellovirus of no known pathogenicity. Using nested and semi-nested PCR, sera from 72 patients (47 cases and 25 matched controls, stratified by ROM status) were screened for the 3 subtypes of anelloviruses (TTV, TTMDV, or TTMV). These were found in 43/47 cases (91%) and 16/25 controls (64%) (p = 0.012, OR = 5.9 (95% CI = 1.4-29.9)). In logistic regression, pregnant women with at least one type of anellovirus were more likely to experience preterm labor than those with no anellovirus (p = 0.03, aOR = 4.6, CI = 1.2-18.7). Among women experiencing a spontaneous initiating event of labor, TTV virus was more likely to be present in the serum of preterm than term patients. TTV may have a role in determining the timing of parturition.
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Infecciones por Virus ADN/sangre , Infecciones por Virus ADN/diagnóstico , Rotura Prematura de Membranas Fetales/sangre , Rotura Prematura de Membranas Fetales/virología , Trabajo de Parto/sangre , Adulto , Estudios de Casos y Controles , Infecciones por Virus ADN/genética , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Embarazo , Estudios Prospectivos , Torque teno virusRESUMEN
BACKGROUND: Rotational thromboelastometry (ROTEM®) is a point-of-care coagulation test. Reference ranges in non-labouring women have recently been established from a cohort of women presenting for elective caesarean delivery using the recommended minimum sample size of 120. This study aimed to present baseline parameters for labouring and non-labouring women and to compare the mean values of these ROTEM® parameters. METHODS: Ethical approval was granted for an opt-out recruitment approach for labouring women and written consent was obtained from non-labouring women (data published previously). ROTEM® testing was performed in these two cohorts at term gestation. Women with any condition affecting coagulation were excluded. ROTEM® Delta reference ranges were derived by calculating the 2.5 and 97.5 percentiles for INTEM/EXTEM/FIBTEM amplitude at 5 min (A5), coagulation time (CT), maximum clot firmness (MCF) and clot formation time (CFT). RESULTS: One hundred and twenty-one labouring and 132 non-labouring women met inclusion criteria. The mean values for selected ROTEM® parameters for labouring and non-labouring women respectively were: FIBTEM A5, 21.05 and 19.7â¯mm (P=0.008); EXTEM A5, 54.8 and 53.2â¯mm (P=0.025); and EXTEM CT, 52.2 and 53.7â¯s (P=0.049). Significant differences between the groups were observed in measures of clotting onset and clot firmness. CONCLUSIONS: We demonstrated a significant decrease in the mean time-to-clotting onset in labouring women compared with non-labouring women. Mean values for measures of clot firmness were greater in labouring women. In comparison to previously established ROTEM® baseline parameters for non-labouring women, this study provides evidence that there is greater hyper-coagulability in labouring women.
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Trabajo de Parto/sangre , Pruebas en el Punto de Atención , Embarazo/sangre , Tromboelastografía/métodos , Adulto , Femenino , Humanos , Valores de ReferenciaRESUMEN
BACKGROUND: To reduce the number of new HIV infections among children, retesting of HIV negative pregnant women in labor to identify new infections and instituting appropriate modified obstetrics practices (MOP) has a huge role to play. AIMS AND OBJECTIVES: This study evaluated the HIV sero-positivity in labor among pregnant women who earlier tested negative in antenatal clinic, associated risk factors and the corresponding rate of mother-to-child transmission of HIV infection. METHODS: This was a prospective observational study where pregnant women in labor who had earlier tested HIV negative in the antenatal clinic at Imo State University Teaching Hospital Orlu, Imo state, Nigeria, were retested. The infants of the women who seroconverted were tested for HIV infection at 6 weeks using Deoxyribonucleic acid polymerase chain reaction (DNA PCR) by collecting Dried Blood Sample. This study was conducted from October 2015 to March 2016. RESULT: Out of the 163 patients studied, 6 demonstrated HIV seroconversion giving a seroconversion rate of 3.7%. Deliveries from the seroconverted patients were 5 live births and 1 intrauterine fetal death. All the 5 live babies tested HIV negative at 6 weeks of age. Predictors of seroconversion in late pregnancy include spouse's HIV status and number of other sexual partners. CONCLUSION: Retesting of HIV negative pregnant women in labor to identify new infections and instituting appropriate modified obstetrics practices has a huge role to play in the prevention of mother to child transmission of HIV infection.
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Infecciones por VIH/diagnóstico , Infecciones por VIH/transmisión , Seropositividad para VIH/sangre , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Trabajo de Parto/sangre , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/virología , Adulto , Anticuerpos Antivirales/sangre , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Seropositividad para VIH/epidemiología , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Tamizaje Masivo/métodos , Nigeria/epidemiología , Parto , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Estudios Prospectivos , Factores de Riesgo , SeroconversiónRESUMEN
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.
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Líquido Amniótico/química , Sangre Fetal/química , Mediadores de Inflamación/análisis , Trabajo de Parto/sangre , Parto/sangre , Adulto , Estudios Transversales , Femenino , Rotura Prematura de Membranas Fetales/sangre , Humanos , Trabajo de Parto Prematuro/sangre , Embarazo , Nacimiento a Término/sangreRESUMEN
BACKGROUND: Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies. METHODS: An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects. RESULTS: Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin. CONCLUSIONS: Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does.
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Trabajo de Parto/sangre , Oxitocina/sangre , Parto/sangre , Embarazo/sangre , Femenino , Humanos , Oxitócicos , Oxitocina/líquido cefalorraquídeoRESUMEN
AIM: Changes in glucose levels during labor have not been sufficiently investigated in pregnant women. Using real-time continuous glucose monitoring, we aimed to assess glucose kinetics during labor among pregnant women with gestational diabetes mellitus (PwGDM), and those with normal glucose tolerance (PwNGT). METHODS: Japanese PwGDM and PwNGT who had planned a transvaginal delivery at Okayama University Hospital were enrolled. The correlation between changes in glucose levels during labor among the PwGDM and PwNGT groups at four time periods was assessed: (i) active phase of 1st stage of labor; (ii) 2nd stage of labor; (iii) postpartum 0-12 h; and (iv) postpartum 12-48 h. RESULTS: In total, 18 and 22 PwGDM and PwNGT, respectively, were enrolled. During labor, both groups had similar changes in glucose levels over time, which peaked during period 3. The main effect of glucose level changes was the labor period (P < 0.001), not the presence of gestational diabetes mellitus. Furthermore, differences in glucose levels in the PwGDM group were observed between periods 1 and 2 (P = 0.037), 1 and 3 (P = 0.024), 3 and 4 (P = 0.005); differences in glucose levels in the PwNGT group were observed between periods 3 and 4 (P = 0.024). CONCLUSION: During labor, both PwGDM and PwNGT groups showed similar changes in glucose levels over time. During delivery, the PwGDM who regularly measured their own glucose levels could be managed using the same nutritional management methods as those for PwNGT.
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Glucemia/fisiología , Diabetes Gestacional/sangre , Trabajo de Parto/sangre , Adulto , Automonitorización de la Glucosa Sanguínea , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Cinética , EmbarazoRESUMEN
BACKGROUND: Hemostasis is the dynamic equilibrium between coagulation and fibrinolysis. During pregnancy, the balance shifts toward a hypercoagulative state; however placental abruption and abnormal placentations may lead to rapidly evolving coagulopathy characterized by the increased activation of procoagulant pathways. These processes can result in hypofibrinogenemia, with fibrinogen levels dropping to 2 g/L or less and an associated increased risk of post-partum hemorrhage. The aim of the present study was to evaluate the concordance between two methods of functional fibrinogen measurement: the Thromboelastography (TEG) method (also known as FLEV) vs. the Clauss method. Three patient groups were considered: healthy volunteers; non-pathological pregnant patients; and pregnant patients who went on to develop postpartum hemorrhage. METHODS: A prospective observational study. Inclusion criteria were: healthy volunteer women of childbearing age, non-pathological pregnant women at term, and pregnant hemorrhagic patients subjected to elective or urgent caesarean section (CS), with blood loss exceeding 1000 mL. Exclusion criteria were age < 18 years, a history of coagulopathy, and treatment with contraceptives, anticoagulants, or antiplatelet agents. RESULTS: Bland-Altman plots showed a significant overestimation with the FLEV method in all three patient groups: bias was - 133.36 mg/dL for healthy volunteers (95% IC: - 257.84; - 8.88. Critical difference: 124.48); - 56.30 mg/dL for healthy pregnant patients (95% IC: - 225.53; 112.93. Critical difference: 169.23); and - 159.05 mg/dL for hemorrhagic pregnant patients (95% IC: - 333.24; 15.148. Critical difference: 174.19). Regression analyses detected a linear correlation between FLEV and Clauss for healthy volunteers, healthy pregnant patients, and hemorrhagic pregnant patients (R2 0.27, p value = 0.002; R2 0.31, p value = 0.001; R2 0.35, p value = 0.001, respectively). ANOVA revealed a statistically significant difference in fibrinogen concentration between all three patients groups when assayed using the Clauss method (p value < 0.001 for all the comparisons), but no statistically significant difference between the two patients groups of pregnant women when using the FLEV method. CONCLUSIONS: The FLEV method does not provide a valid alternative to the Clauss method due to the problem of fibrinogen overestimation, and for this reason it should not be recommended for the evaluation of patients with an increased risk of hypofibrinogenemia.
Asunto(s)
Coagulación Sanguínea/fisiología , Fibrinógeno/metabolismo , Trabajo de Parto/sangre , Embarazo/sangre , Tromboelastografía/métodos , Adulto , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Pruebas de Coagulación Sanguínea/métodos , Cesárea , Femenino , Humanos , Estudios ProspectivosRESUMEN
The mechanism of human labour remains poorly understood, limiting our ability to manage complications of parturition such as preterm labour and induction of labour. In this study we have investigated the effect of labour on plasma metabolites immediately following delivery, comparing cord and maternal plasma taken from women who laboured spontaneously and delivered vaginally with women who were delivered via elective caesarean section and did not labour. Samples were analysed using ultra high-performance liquid chromatography-tandem mass spectrometry. Welch's two-sample t-test was used to identify any significant differences. Of 826 metabolites measured, 26.9% (222/826) were significantly altered in maternal plasma and 21.1% (174/826) in cord plasma. Labour involves changes in many maternal organs and poses acute metabolic demands in the uterus and in the fetus and these are reflected in our results. While a proportion of these differences are likely to be secondary to the physiological demands of labour itself, these results present a comprehensive picture of the metabolome in the maternal and fetal circulations at the time of delivery and can be used to guide future studies. We discuss potential causal pathways for labour including endocannabinoids, ceramides, sphingolipids and steroids. Further work is necessary to confirm the specific pathways involved in the spontaneous onset of labour.
Asunto(s)
Trabajo de Parto/sangre , Metaboloma , Madres , Adulto , Análisis Químico de la Sangre , Femenino , Feto , Humanos , Trabajo de Parto/metabolismo , Lactonas/química , Metabolómica , Persona de Mediana Edad , Proyectos Piloto , Embarazo , Adulto JovenRESUMEN
OBJECTIVE: To study the association between bloody amniotic fluid (BAF) during labor and adverse pregnancy outcomes. STUDY DESIGN: In the last 10 years we have implemented an institutional protocol that mandates obstetricians/midwives to report their subjective impression of the color of amniotic fluid (clear, meconium stained, bloody) during labor. The medical records, and neonatal charts of all singleton deliveries ≥ 370/7 weeks between 2008-2018 were reviewed. The cohort was divided into two groups: clear AF (Clear group) and BAF (BAF group). Cases with meconium stained AF were excluded. The primary outcome was a composite of the following complications: umbilical Ph ≤ 7.1, seizures, hypoxic-ischemic encephalopathy, intra-ventricular hemorrhage, periventricular leukomalacia, hypoglycemia, hypothermia, mechanical ventilation, meconium aspiration syndrome, RDS, NEC, phototherapy, sepsis, or transfusion. RESULTS: Overall, 21,300 deliveries were reviewed, 20,983 (98.5%) in the Clear group and 317 (1.5%) in the BAF group. The rate of the primary outcome did not differ between the BAF (2.2%) and the Clear (2.1%) groups. The rate of placental abruption (both clinically and hystopathologically) did not differ between the groups (3.2% vs. 1.9% and 1.6% vs. 0.6%, respectively). BAF was associated with higher rates of labor induction (p = 0.002), assisted vaginal deliveries (p = 0.04), cesarean deliveries (p = 0.03), and lower birth weights (p = 0.03). CONCLUSION: BAF observed in labor was not associated with composite adverse neonatal outcome, nor with placental abruption. BAF was associated with higher rates of labor induction, assisted vaginal deliveries, cesarean deliveries, and lower birth weights. These findings may assist obstetricians and neonatologists in the interpretation of BAF observed in labor.
Asunto(s)
Desprendimiento Prematuro de la Placenta/epidemiología , Líquido Amniótico , Parto Obstétrico/estadística & datos numéricos , Trabajo de Parto/sangre , Complicaciones del Trabajo de Parto/epidemiología , Desprendimiento Prematuro de la Placenta/etiología , Adulto , Femenino , Humanos , Recién Nacido , Trabajo de Parto Inducido/estadística & datos numéricos , Complicaciones del Trabajo de Parto/sangre , Complicaciones del Trabajo de Parto/etiología , Embarazo , Resultado del Embarazo , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Hyponatremia during labor and delivery may result in severe maternal and neonatal sequelae. Our aim was to describe the direct effect of hyponatremia in labor on pregnancy outcome. METHODS: A case series of parturients diagnosed with hyponatremia during labor and their neonates. Clinical presentation, laboratory workup, and maternal and neonatal outcomes are presented. RESULTS: Four parturients and their corresponding six neonates were diagnosed with hyponatremia. Of these, two cases were caused by water intoxication and two were preeclampsia induced. While two were identified due to maternal or neonatal symptoms, two were diagnosed by routine laboratory testing. In all cases, low maternal sodium resulted in similarly low neonatal sodium. Neonatal symptoms included respiratory distress syndrome (RDS), lethargy, and jaundice. CONCLUSION: Psychogenic drinking during labor and preeclampsia may predispose to maternal hyponatremia, resulting in neonatal hyponatremia. Early recognition and treatment can prevent further maternal deterioration and adverse neonatal sequelae.
Asunto(s)
Hiponatremia/etiología , Enfermedades del Recién Nacido/etiología , Preeclampsia/fisiopatología , Intoxicación por Agua/complicaciones , Adulto , Anestesia Epidural/efectos adversos , Femenino , Humanos , Hiponatremia/sangre , Hiponatremia/terapia , Síndrome de Secreción Inadecuada de ADH/complicaciones , Recién Nacido , Enfermedades del Recién Nacido/sangre , Enfermedades del Recién Nacido/terapia , Trabajo de Parto/sangre , Trabajo de Parto/fisiología , Masculino , Persona de Mediana Edad , Embarazo , Resultado del EmbarazoRESUMEN
Prior to and during the process of human labor, maternal circulating leukocytes infiltrate the maternal-fetal interface (choriodecidua) and become activated resembling choriodecidual leukocytes. Since, there is no evidence comparing maternal circulating and choriodecidual leukocytes, herein, we characterized their transcriptome and explored the biological processes enriched in choriodecidual leukocytes. From women undergoing spontaneous term labor we isolated circulating and choriodecidual leukocytes, performed microarray analysis (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up-regulated genes. We found 270 genes up-regulated and only 17 genes down-regulated in choriodecidual leukocytes compared to maternal circulating leukocytes. The most up-regulated genes were CCL18, GPNMB, SEPP1, FN1, RNASE1, SPP1, C1QC, and PLTP. The biological processes enriched in choriodecidual leukocytes were cell migration and regulation of immune response, chemotaxis, and humoral immune responses. Our results show striking differences between the transcriptome of choriodecidual and maternal circulating leukocytes. Choriodecidual leukocytes are enriched in immune mediators implicated in the spontaneous process of labor at term.