Inducción del parto en gestaciones gemelares: estudio comparativo de oxitocina vs dinoprostona / Induction of labour in twin pregnancies: Comparative study of oxytocin vs. dinoprostone

Introducción: En los últimos años el número de gestaciones gemelares que alcanzan el término se ha incrementado. Aunque la vía vaginal ha demostrado ser una alternativa segura frente a la cesárea cuando el primer feto se encuentra en presentación cefálica, la evidencia disponible sobre los métodos de inducción aplicados a este tipo de gestaciones es limitada. Métodos: Estudio observacional retrospectivo realizado en un hospital de tercer nivel. Se incluyeron 44 gestantes gemelares, con edad gestacional superior a 34 semanas y con el primer gemelo en presentación cefálica, que fueron sometidas a inducción del parto. En 17 casos se utilizaron prostaglandinas vaginales (dinoprostona) y en 27, oxitocina intravenosa. La indicación se realizó aleatoriamente según la práctica clínica diaria. Se compararon los resultados de ambos grupos en seguridad y eficacia. Resultados: No se encontraron diferencias significativas en la tasa de cesárea por fracaso de inducción entre la oxitocina y las prostaglandinas (42,9% vs. 57,1%; p=0,3). Tampoco se encontraron diferencias en complicaciones neonatales ni maternas. Dos gestantes presentaron hemorragia obstétrica, única complicación materna descrita, ambas en el grupo de oxitocina. El 100% de las cesáreas realizadas fueron en gestantes con índices Bishop ≤6. Se encontró un mayor riesgo de cesárea en mujeres con IMC>30kg/m2 (p=0,001) e índice de Bishop previo a la inducción ≤6 (RR: 2,06; p=0,005). Conclusiones: Tanto las prostaglandinas vaginales como la oxitocina intravenosa resultan similares en eficacia, seguridad materna y neonatal, cuando se utilizan en gestaciones gemelares. Un índice de Bishop ≤6 y un IMC >30 se asocian con una mayor probabilidad de inducción fallida.

Introduction: In the last few years the number of twin gestations that reach term has increased. Although vaginal delivery route has proven to be a safe alternative to caesarean section when first foetus is in cephalic presentation, available evidence on induction methods applied to this type of pregnancies is limited. Methods: Retrospective observational study conducted in a tertiary hospital. Forty-four pregnant twins, with gestational age greater than 34weeks, and with the first twin in cephalic presentation, who underwent induction of labour, were included. Vaginal prostaglandins (dinoprostone) were used in 17 cases and intravenous oxytocin in 27 cases, indication was randomised according to daily clinical practice. Results of both groups were compared in terms of safety and efficacy. Results: No significant differences were found in the rate of caesarean section due to induction failure between oxytocin and prostaglandins (42.9% vs. 57.1%; P=.3). No differences were found either in terms of neonatal or maternal complications. Two pregnant women presented obstetric haemorrhage, the only maternal complication described, both in oxytocin group. Higher risk of caesarean section was found in women with BMI >30kg/m2 (P=.001) and pre-induction Bishop's index ≤6 (RR: 2.06) (P=.005). Conclusions: Both vaginal prostaglandins and intravenous oxytocin are similar in efficacy, maternal and neonatal safety when used in twin gestations. Bishop's index ≤6 and BMI >30 are associated with higher probability of induction failure.(AU)

Cardiovascular effects of oxytocin and carbetocin at cesarean section. A prospective double-blind randomized study using noninvasive pulse wave analysis.

BACKGROUND: Oxytocin is routinely administered after delivery for prophylaxis and treatment of postpartum hemorrhage, but it is associated with considerable cardiovascular side-effects. Carbetocin, a synthetic oxytocin analogue, has a myometrial contraction effect of 60 min when given IV, compared with 16 min for oxytocin. OBJECTIVE: To investigate whether there are differences in cardiovascular effects between oxytocin and carbetocin up to 1 h after treatment. METHODS: Sixty-one healthy pregnant women undergoing elective cesarean section in spinal anesthesia were randomized to receive an IV bolus of either five units (8.3 µg) of oxytocin or 100 µg of carbetocin after delivery of the baby. Heart rate (HR), mean arterial blood pressure, ECG ST index, oxygen saturation (SaO2), and photoplethysmographic digital pulse wave analysis variables were recorded before and at 1, 5, 20, and 60 min after drug administration. Vasopressor use, uterine tonus, total bleeding, and need for additional uterotonics were also assessed. Repeated measurement ANOVA was used for statistical analyses. RESULTS: The drugs had equal vasodilatory and hypotensive effects. Oxytocin, but not carbetocin, caused a decrease in HR at 1 min and a sustained decrease in cardiac left ventricular ejection time. Aggregate vasopressor use was higher in the carbetocin group. Neither drug caused any change in ST index, SaO2, or subjective cardiac symptoms. Uterine tonus, need for additional uterotonics, or total bleeding did not differ significantly between the groups. CONCLUSION: Single doses of oxytocin and carbetocin had similar dilatory effects on vascular tonus, where the difference in aggregate vasopressor use can be attributed to a more persistent hypotensive effect of carbetocin. A transient negative chronotropic and sustained negative inotropic effect occurred after oxytocin. Neither drug showed any alarmingly adverse effects. Differences in drug effects may be attributed to differences in oxytocin and vasopressin receptor signaling pathways.

Three medicinal plants affecting human ovarian cell viability, hormone release, and response to environmental contaminant toluene.

The present study examined the effect of medicinal plants - ginkgo, tribulus (puncture vine), and yucca - on ovarian functions and their response to the toxic influence of toluene. Therefore, we analyzed the effect of toluene with and without these plant extracts on cultured human ovarian granulosa cells. Cell viability and the release of progesterone, insulin-like growth factor I (IGF I), oxytocin, and prostaglandin F (PGF) were analyzed using the trypan blue test, enzyme immunoassay, and enzyme-linked immunosorbent assay, respectively. The ginkgo, tribulus and yucca were able to suppress ovarian cell viability and alter the release of hormones. Toluene suppressed cell viability and the release of PGF, but not of progesterone, IGF-I, or oxytocin. The negative effect of toluene on cell viability was prevented and even reversed by ginkgo and yucca, whereas its effect on PGF was prevented or inverted by all tested plant extracts. These findings (1) demonstrated the direct toxic effect of toluene on ovarian cells, (2) showed the direct effect of some medicinal plants on ovarian cell functions, and (3) demonstrated the ability of these plants to inhibit the effects of toluene and to act as natural protectors against the suppressive effect of toluene on female reproduction.

1,5-Anhydro-D-Fructose Exhibits Satiety Effects via the Activation of Oxytocin Neurons in the Paraventricular Nucleus.

1,5-Anhydro-D-fructose (1,5-AF) is a bioactive monosaccharide that is produced by the glycogenolysis in mammalians and is metabolized to 1,5-anhydro-D-glucitol (1,5-AG). 1,5-AG is used as a marker of glycemic control in diabetes patients. 1,5-AF has a variety of physiological activities, but its effects on energy metabolism, including feeding behavior, are unclarified. The present study examined whether 1,5-AF possesses the effect of satiety. Peroral administration of 1,5-AF, and not of 1,5-AG, suppressed daily food intake. Intracerebroventricular (ICV) administration of 1,5-AF also suppressed feeding. To investigate the neurons targeted by 1,5-AF, we investigated c-Fos expression in the hypothalamus and brain stem. ICV injection of 1,5-AF significantly increased c-Fos positive oxytocin neurons and mRNA expression of oxytocin in the paraventricular nucleus (PVN). Moreover, 1,5-AF increased cytosolic Ca2+ concentration of oxytocin neurons in the PVN. Furthermore, the satiety effect of 1,5-AF was abolished in oxytocin knockout mice. These findings reveal that 1,5-AF activates PVN oxytocin neurons to suppress feeding, indicating its potential as the energy storage monitoring messenger to the hypothalamus for integrative regulation of energy metabolism.

Effects of mesotocin manipulation on the behavior of male and female common waxbills.

The oxytocin family of neuropeptides is implicated in the regulation of sociality across vertebrates. Non-mammalian homologs of oxytocin, such as isotocin in fish and mesotocin in amphibians, reptiles and birds, all play crucial roles modulating social and reproductive behavior. In this study, we exogenously manipulated the mesotocinergic system in a highly social bird, the common waxbill Estrild astrild, and tested the effects on affiliative and aggressive behavior by performing tests of competition over food. Birds treated with mesotocin decreased almost all the behaviors we studied (movement, feeding, allopreening), while birds treated with an oxytocin antagonist showed a reduction only in social behaviors (aggressions and allopreening). We also found two sex-specific effects: mesotocin reduced allopreening more in males than females, and the oxytocin antagonist reduced aggressiveness only in females. Our results suggest sex-specific effects in the modulation of affiliative and aggressive behaviors via mesotocinergic pathways.

Oxytocin receptor antagonism during early vocal learning reduces song preference and imitation in zebra finches.

In species with vocal learning, acquiring species-typical vocalizations relies on early social orienting. In songbirds, for example, learning song requires dynamic social interactions with a "tutor" during an early sensitive period. Here, we hypothesized that the attentional and motivational processes that support song learning recruit the oxytocin system, which is well-understood to play a role in social orienting in other species. Juvenile male zebra finches naïve to song were each tutored by two unfamiliar adult males. Before exposure to one tutor, juveniles were injected subcutaneously with oxytocin receptor antagonist (OTA; ornithine vasotocin) and before exposure to the other, saline (control). Treatment with OTA reduced behaviors associated with approach and attention during tutoring sessions. Using a novel operant paradigm to measure preference while balancing exposure to the two tutor songs, we showed that the juveniles preferred to hear the song of the control tutor. Their adult songs more closely resembled the control tutor's song, and the magnitude of this difference was predicted by early preference for control over OTA song. Overall, oxytocin antagonism during exposure to a tutor seemed to bias juveniles against that tutor and his song. Our results suggest that oxytocin receptors are important for socially-guided vocal learning.

Dynamic modulation of pulsatile activities of oxytocin neurons in lactating wild-type mice.

Breastfeeding, which is essential for the survival of mammalian infants, is critically mediated by pulsatile secretion of the pituitary hormone oxytocin from the central oxytocin neurons located in the paraventricular and supraoptic hypothalamic nuclei of mothers. Despite its importance, the molecular and neural circuit mechanisms of the milk ejection reflex remain poorly understood, in part because a mouse model to study lactation was only recently established. In our previous study, we successfully introduced fiber photometry-based chronic imaging of the pulsatile activities of oxytocin neurons during lactation. However, the necessity of Cre recombinase-based double knock-in mice substantially compromised the use of various Cre-dependent neuroscience toolkits. To overcome this obstacle, we developed a simple Cre-free method for monitoring oxytocin neurons by an adeno-associated virus vector driving GCaMP6s under a 2.6 kb mouse oxytocin mini-promoter. Using this method, we monitored calcium ion transients of oxytocin neurons in the paraventricular nucleus in wild-type C57BL/6N and ICR mothers without genetic crossing. By combining this method with video recordings of mothers and pups, we found that the pulsatile activities of oxytocin neurons require physical mother-pup contact for the milk ejection reflex. Notably, the frequencies of photometric signals were dynamically modulated by mother-pup reunions after isolation and during natural weaning stages. Collectively, the present study illuminates the temporal dynamics of pulsatile activities of oxytocin neurons in wild-type mice and provides a tool to characterize maternal oxytocin functions.

Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context.

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits the endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using a serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch influence not only current hormonal and brain responses but also later responses. Namely, touch from a male to his female romantic partner enhanced her subsequent OT release for touch from an unfamiliar stranger, yet females' OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial social interaction. In the subsequent interaction, precuneus and parietal-temporal cortex pathways tracked time- and context-dependent variables in an OT-dependent manner. This OT-dependent cortical modulation included a region of the medial prefrontal cortex that also covaried with plasma cortisol, suggesting an influence on stress responses. These findings demonstrate that modulation between hormones and the brain during human social interactions can flexibly adapt to features of social context over time.

Functional modular networks identify the pivotal genes associated with morphine addiction and potential drug therapies.

BACKGROUND: Chronic morphine usage induces lasting molecular and microcellular adaptations in distinct brain areas, resulting in addiction-related behavioural abnormalities, drug-seeking, and relapse. Nonetheless, the mechanisms of action of the genes responsible for morphine addiction have not been exhaustively studied. METHODS: We obtained morphine addiction-related datasets from the Gene Expression Omnibus (GEO) database and screened for Differentially Expressed Genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) functional modularity constructs were analyzed for genes associated with clinical traits. Venn diagrams were filtered for intersecting common DEGs (CDEGs). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for functional annotation. Protein-protein interaction network (PPI) and CytoHubba were used to screen for hub genes. Potential treatments for morphine addiction were figured out with the help of an online database. RESULTS: Sixty-five common differential genes linked to morphine addiction were identified, and functional enrichment analysis showed that they were primarily involved in ion channel activity, protein transport, the oxytocin signalling pathway, neuroactive ligand-receptor interactions, and other signalling pathways. Based on the PPI network, ten hub genes (CHN2, OLIG2, UGT8A, CACNB2, TIMP3, FKBP5, ZBTB16, TSC22D3, ISL1, and SLC2A1) were checked. In the data set GSE7762, all of the Area Under Curve (AUC) values for the hub gene Receiver Operating Characteristic (ROC) curves were greater than 0.8. We also used the DGIdb database to look for eight small-molecule drugs that might be useful for treating morphine addiction. CONCLUSIONS: The hub genes are crucial genes associated with morphine addiction in the mouse striatum. The oxytocin signalling pathway may play a vital role in developing morphine addiction.

Cephalic version by moxibustion for breech presentation.

BACKGROUND: Breech presentation at term can cause complications during birth and increase the chance of caesarean section. Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) at the acupuncture point Bladder 67 (BL67) (Chinese name Zhiyin), located at the tip of the fifth toe, has been proposed as a way of changing breech presentation to cephalic presentation. This is an update of a review first published in 2005 and last published in 2012. OBJECTIVES: To examine the effectiveness and safety of moxibustion on changing the presentation of an unborn baby in the breech position, the need for external cephalic version (ECV), mode of birth, and perinatal morbidity and mortality. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, and conference proceedings), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) (4 November 2021). We also searched MEDLINE, CINAHL, AMED, Embase and MIDIRS (inception to 3 November 2021), and the reference lists of retrieved studies. SELECTION CRITERIA: The inclusion criteria were published and unpublished randomised or quasi-randomised controlled trials comparing moxibustion either alone or in combination with other techniques (e.g. acupuncture or postural techniques) with a control group (no moxibustion) or other methods (e.g. acupuncture, postural techniques) in women with a singleton breech presentation. DATA COLLECTION AND ANALYSIS: Two review authors independently determined trial eligibility, assessed trial quality, and extracted data. Outcome measures were baby's presentation at birth, need for ECV, mode of birth, perinatal morbidity and mortality, maternal complications and maternal satisfaction, and adverse events. We assessed the certainty of the evidence using the GRADE approach.   MAIN RESULTS: This updated review includes 13 studies (2181 women), of which six trials are new. Most studies used adequate methods for random sequence generation and allocation concealment. Blinding of participants and personnel is challenging with a manual therapy intervention; however, the use of objective outcomes meant that the lack of blinding was unlikely to affect the results. Most studies reported little or no loss to follow-up, and few trial protocols were available. One study that was terminated early was judged as high risk for other sources of bias. Meta-analysis showed that compared to usual care alone, the combination of moxibustion plus usual care probably reduces the chance of non-cephalic presentation at birth (7 trials, 1152 women; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.78 to 0.99, I2 = 38%; moderate-certainty evidence), but the evidence is very uncertain about the effect of moxibustion plus usual care on the need for ECV (4 trials, 692 women; RR 0.62, 95% CI 0.32 to 1.21, I2 = 78%; low-certainty evidence) because the CIs included both appreciable benefit and moderate harm. Adding moxibustion to usual care probably has little to no effect on the chance of caesarean section (6 trials, 1030 women; RR 0.94, 95% CI 0.83 to 1.05, I2 = 0%; moderate-certainty evidence). The evidence is very uncertain about the effect of moxibustion plus usual care on the the chance of premature rupture of membranes (3 trials, 402 women; RR 1.31, 95% CI 0.17 to 10.21, I2 = 59%; low-certainty evidence) because there were very few data. Moxibustion plus usual care probably reduces the use of oxytocin (1 trial, 260 women; RR 0.28, 95% CI 0.13 to 0.60; moderate-certainty evidence). The evidence is very uncertain about the chance of cord blood pH less than 7.1 (1 trial, 212 women; RR 3.00, 95% CI 0.32 to 28.38; low-certainty evidence) because there were very few data. We are very uncertain whether the combination of moxibustion plus usual care increases the chance of adverse events (including nausea, unpleasant odour, abdominal pain and uterine contractions; intervention: 27/65, control: 0/57), as only one study presented data in a way that could be reanalysed (122 women; RR 48.33, 95% CI 3.01 to 774.86; very low-certainty evidence). When moxibustion plus usual care was compared with sham moxibustion plus usual care, we found that moxibustion probably reduces the chance of non-cephalic presentation at birth (1 trial, 272 women; RR 0.74, 95% CI 0.58 to 0.95; moderate-certainty evidence) and probably results in little to no effect on the rate of caesarean section (1 trial, 272 women; RR 0.84, 95% CI 0.68 to 1.04; moderate-certainty evidence). No study that compared moxibustion plus usual care with sham moxibustion plus usual care reported on the clinically important outcomes of need for ECV, premature rupture of membranes, use of oxytocin, and cord blood pH less than 7.1, and one trial that reported adverse events reported data for the whole sample. When moxibustion was combined with acupuncture and usual care, there was very little evidence about the effect of the combination on non-cephalic presentation at birth (1 trial, 226 women; RR 0.73, 95% CI 0.57 to 0.94) and at the end of treatment (2 trials, 254 women; RR 0.73, 95% CI 0.57 to 0.93), and on the need for ECV (1 trial, 14 women; RR 0.45, 95% CI 0.07 to 3.01). There was very little evidence about whether moxibustion plus acupuncture plus usual care reduced the chance of caesarean section (2 trials, 240 women; RR 0.80, 95% CI 0.65 to 0.99) or pre-eclampsia (1 trial, 14 women; RR 5.00, 95% CI 0.24 to 104.15). The certainty of the evidence for this comparison was not assessed. AUTHORS' CONCLUSIONS: We found moderate-certainty evidence that moxibustion plus usual care probably reduces the chance of non-cephalic presentation at birth, but uncertain evidence about the need for ECV. Moderate-certainty evidence from one study shows that moxibustion plus usual care probably reduces the use of oxytocin before or during labour. However, moxibustion plus usual care probably results in little to no difference in the rate of caesarean section, and we are uncertain about its effects on the chance of premature rupture of membranes and cord blood pH less than 7.1.  Adverse events were inadequately reported in most trials.

The optimal induction timing in prelabor rupture of membranes: a retrospective study.

OBJECTIVE: Term prelabour rupture of membrane (PROM) occurs in 8% of term deliveries, but it is unclear when to initiate induction. Our objective was to assess the optimal timing of oxytocin induction in the management of term PROM in terms of maternal and neonatal outcomes. METHODS: A retrospective cohort study was performed at a single tertiary care center from 2010 to 2020. All singleton pregnancies with PROM beyond 37 weeks gestation, without regular uterine contractions, were included. Eligible women were divided into three groups according to the timing of oxytocin induction (≤12; 12-24; ≥24 h) following PROM. RESULTS: Of 9,443 women presented with the term PROM, 1676 were included. They were classified according to the timing of oxytocin induction initiation following PROM: 1,127 within 12 h; 285 within 12-24 h; 264 after 24 h. There were no significant differences in baseline demographic characteristics between groups. Women who presented at our emergency department were induced earlier delivered significantly sooner than those who received oxytocin later (45 vs. 28.2 vs. 23.2 h, respectively, p < .001. Maternal infection rate was similar and unrelated to oxytocin starting time. Induction at <12 h from PROM was associated with reduced rate of antibiotic administration compared with other timings (26.8% vs. 38.6% vs. 33.33%, respectively; p < .001), and the same was found for neonatal composite adverse outcomes (RR = 1.27, p = .0307). CONCLUSION: In term PROM, early induction (within 12 h of PROM) may be recommended to reduce the time-do-delivery interval and increase the delivery rate within 24 h. It may be of economic significance and improve women satisfaction. Furthermore, early induction may also improve neonatal outcomes, without worsening maternal outcomes.

[Oxytocin and vasopressin: sexual differences and clinical implications]. / Oxitocina y vasopresina: diferencias sexuales y sus implicaciones clínicas.

Oxytocin and vasopressin share a similar chemical structure but have different functions. Both hormones are produced in different brain areas, are transported through the hypophyseal portal system, pass to the anterior hypophysis, and released to reach their target organs. These hormones also act as neuromodulators, where its receptors are found in the lateral septum, the middle amygdala, the hippocampus, the hypothalamus, and the brain stem. These brain structures regulate socio-sexual behaviors in vertebrates. Moreover, the oxytocinergic and the vasopressin systems are sexually different. The sexual steroids promote oxytocin release and the oxytocin receptor synthesis, as well as promoting or inhibiting vasopressin release and its receptor genetic transcription. Both neuropeptides are involved in social recognition, male-female pair bonding, aggression, and cognition. Furthermore, the disruption or malfunctioning of the oxytocin and vasopressin systems adds to the causes of some psychiatric disorders like depression, schizophrenia, autism, and borderline personality.

La oxitocina y la vasopresina son similares en estructura química, pero difieren en sus funciones. Ambas se producen en diversas áreas del cerebro, se transportan a través del sistema porta hipofisario a la hipófisis anterior y se distribuyen a sus órganos blanco actuando como hormonas. Estas fungen también como neurorreguladores, con receptores dispersos en el septum lateral, la amígdala central, el hipocampo, el hipotálamo y el tronco encefálico, estructuras asociadas a la conducta sociosexual en todos los vertebrados. Los sistemas vasopresinérgico y oxitocinérgico difieren entre los cerebros femenino y masculino. Aunado a esto, los esteroides sexuales intervienen en la expresión de los genes para oxitocina, la síntesis de sus receptores y su liberación. Además, promueven o inhiben la transcripción de los genes para vasopresina. Ambos neuropéptidos participan en el reconocimiento social, el vínculo de pareja, la cognición y la agresión. La disrupción de los sistemas de estos neuromoduladores se suma a las causas de algunos desórdenes psiquiátricos, como la depresión, la esquizofrenia, el autismo y la personalidad limítrofe. Esta revisión está enfocada a describir las diferencias entre géneros, tanto de la síntesis, como la distribución de los receptores y los efectos que generan la oxitocina y la vasopresina en la conducta para comprender la prevalencia, la sintomatología y la respuesta a los tratamientos a dichas patologías.

Novel Risk Variants in the Oxytocin Receptor Gene (OXTR) Possibly Linked to and Associated with Familial Type 2 Diabetes.

The oxytocin system is well-known for its role in social bonding and reproduction. Recently, the oxytocin system was found to play other metabolic roles such as regulation of food intake, peripheral glucose uptake, and insulin sensitivity. Variants in OXTR gene have been associated with overeating, increased cardiovascular risk, and type 2 diabetes (T2D). We tested 20 microarray-derived single nucleotide polymorphisms in the OXTR gene in 212 Italian families with rich family history for T2D and found four novel and one previously reported variant suggestively significant for linkage and association with the risk of T2D. Our study has shed some light into the genetics of susceptibility to T2D at least in Italian families.

Cervical dilatation at diagnosis of active phase of labour determines the mode of delivery and peripartum outcomes: a retrospective study in a single tertiary centre in Malaysia.

BACKGROUND: There is an increasing trend of Caesarean section rate in Malaysia. Limited evidence demonstrated the benefits of changing the demarcation of the active phase of labour. METHODS: This was a retrospective study of 3980 singletons, term pregnancy, spontaneous labouring women between 2015 and 2019 comparing outcomes between those with cervical dilation of 4 versus 6 cm at diagnosis of the active phase of labour. RESULTS: A total of 3403 (85.5%) women had cervical dilatation of 4 cm, and 577 (14.5%) at 6 cm upon diagnosis of the active phase of labour. Women in 4 cm group were significantly heavier at delivery (p = 0.015) but significantly more multiparous women were in 6 cm group (p < 0.001). There were significantly fewer women in the 6 cm group who needed oxytocin infusion (p < 0.001) and epidural analgesia (p < 0.001) with significantly lower caesarean section rate (p < 0.001) done for fetal distress and poor progress (p < 0.001 both). The mean duration from diagnosis of the active phase of labour until delivery was significantly shorter in the 6 cm group (p < 0.001) with lighter mean birth weight (p = 0.019) and fewer neonates with arterial cord pH < 7.20 (p = 0.047) requiring neonatal intensive care unit admissions (p = 0.01). Multiparity (AOR = 0.488, p < 0.001), oxytocin augmentation (AOR = 0.487, p < 0.001) and active phase of labour diagnosed at 6 cm (AOR = 0.337, p < 0.001) reduced the risk of caesarean delivery. Caesarean delivery increased the risk of neonatal intensive care admission by 27% (AOR = 1.73, p < 0.001). CONCLUSIONS: Active phase of labour at 6 cm cervical dilatation is associated with reduced primary caesarean delivery rate, labour intervention, shorter labour duration and fewer neonatal complications.

Oxytocin receptor (OXTR) is a risk gene for polycystic ovarian syndrome.

OBJECTIVE: Oxytocin (OXT) controls appetite, promotes diet-induced energy expenditure, and may protect against obesity. Furthermore, the oxytocin system controls ovarian follicle luteinization and steroidogenesis as well as adrenal steroidogenesis, which if impaired might lead to anovulation and hyperandrogenism, signs found in women with polycystic ovarian syndrome (PCOS). PCOS is a common complex endocrine disorder of reproductive-age women, and it often presents with impaired glucose metabolism, insulin resistance (IR), and type 2 diabetes (T2D). The oxytocin receptor gene (OXTR) may confer a risk for PCOS, conceivably through dysregulation of metabolism, ovarian follicle maturation, and ovarian and adrenal steroidogenesis. Therefore, we aimed to investigate whether OXTR variants confer risk for PCOS. SUBJECTS AND METHODS: In 212 Italian subjects with T2D and PCOS, we have analyzed 22 single nucleotide polymorphisms (SNPs) within the OXTR gene for linkage to and/or linkage disequilibrium (LD, i.e., association) with PCOS. We tested whether the significant risk variants were independent or part of an LD block. RESULTS: We found 5 independent variants significantly linked to/in LD with PCOS within the peninsular families. CONCLUSIONS: This is the first study to report OXTR as a novel risk gene in PCOS. Functional and replication studies are needed to confirm these results.