Induction of Labor in Women with Previous Cesarean Section and Unfavorable Cervix: A Retrospective Cohort Study.

Background: The efficacy and safety of a cervical ripening balloon (CRB) in women with a previous cesarean section (CS) and unfavorable Bishop score are still controversial. Methods: A retrospective cohort study was performed across six tertiary hospitals from 2015 to 2019. Women with one previous transverse CS, singleton cephalic term pregnancy and BS < 6 were included if submitted to labor induction with a CRB. The main outcome was the rate of vaginal birth after cesarean (VBAC) after CRB ripening. Secondary outcomes were abnormal composite fetal and maternal outcomes. Results: Of the 265 women included, 57.3% had successful vaginal birth. Augmentation improved vaginal delivery (32.2% vs. 21.2%). Intrapartum analgesia was associated with an increased VBAC rate (58.6% vs. 34.5%). Maternal BMI ≥30 and age ≥40 years increased emergency CS rate (11.8% vs. 28.3% and 7.2 vs. 15.9%). Composite adverse maternal outcome occurred in 4.8% of CRB group women and increased to 17.6% when associated with oxytocin. Uterine rupture occurred in one case (0.4%) in the CRB-oxytocin group. Poorer fetal outcome occurred after emergency CS, if compared to successful VBAC (12.4% vs. 3.3%). Conclusions: In women with a previous CS and unfavorable Bishop score, induction of labor with a CRB can be considered safe and effective.

Operative vacuum vaginal delivery: effect of compliance with recommended checklist.

PURPOSE: Even if the prerequisites and the technique of vacuum extraction are largely established, the role of a checklist in this field has not been tested. To evaluate the role of a checklist implementation on the compliance with the recommended rules in operative vacuum vaginal delivery (OVD) and on maternal and perinatal outcomes. MATERIALS AND METHODS: Retrospective cohort study on OVD between January 2012 and December 2015 at two hospitals with a tradition of teaching of OVD. A checklist for OVD was introduced in 2014. Three rules had to be recorded: fetal head station and position determination, no more than four tractions, and no more than three cup applications. Adverse maternal outcomes included third- and fourth-degree perineal tears. Adverse neonatal outcome included asphyxia, need for neonatal resuscitation, NICU admission, major head injuries, scalp injuries, and bone or brachial plexus injuries. RESULTS: Introduction of a checklist for OVD resulted in an increase in the compliance with the rules (83.3 versus 62.8%, p < .001). Cases in which the rules were respected had lower incidence of third- and fourth-degree perineal lacerations after controlling for episiotomy, nulliparity, and indication for OVD (OR = 0.4, 95% CI 0.18-0.89), but similar rates of failure of OVD (2.1 versus 2.2%, p = 1) and adverse neonatal outcome (10.8 versus 11.7%, p=.71). CONCLUSION: Knowledge and documented compliance with a checklist of recommended rules in OVD may assist in achieving a lower rate of severe perineal and anal sphincter injury but does not alter the success of the procedure or neonatal outcome.

Is perinatal asphyxia predictable?

BACKGROUND: The objective of our study was to evaluate the association between perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) with the presence of ante and intrapartum risk factors and/or abnormal fetal heart rate (FHR) findings, in order to improve maternal and neonatal management. METHODS: We did a prospective observational cohort study from a network of four hospitals (one Hub center with neonatal intensive care unit and three level I Spoke centers) between 2014 and 2016. Neonates of gestational age ≥ 35 weeks, birthweight ≥1800 g, without lethal malformations were included if diagnosed with perinatal asphyxia, defined as pH ≤7.0 or Base Excess (BE) ≤ - 12 mMol/L in Umbical Artery (UA) or within 1 h, 10 min Apgar < 5, or need for resuscitation > 10 min. FHR monitoring was classified in three categories according to the American College of Obstetricians and Gynecologists (ACOG). Pregnancies were divided into four classes: 1) low risk; 2) antepartum risk; 3) intrapartum risk; 4) and both ante and intrapartum risk. In the first six hours of life asphyxiated neonates were evaluated using the Thomson score (TS): if TS ≥ 5 neonates were transferred to Hub for further assessment; if TS ≥ 7 hypothermia was indicated. RESULTS: Perinatal asphyxia occurred in 21.5‰ cases (321/14,896) and HIE in 1.1‰ (16/14,896). The total study population was composed of 281 asphyxiated neonates: 68/5152 (1.3%) born at Hub and 213/9744 (2.2%) at Spokes (p < 0.001, OR 0.59, 95% CI 0.45-0.79). 32/213 (15%) neonates were transferred from Spokes to Hub. Overall, 12/281 were treated with hypothermia. HIE occurred in 16/281 (5.7%) neonates: four grade I, eight grade II and four grade III. Incidence of HIE was not different between Hub and Spokes. Pregnancies resulting in asphyxiated neonates were classified as class 1) 1.1%, 2) 52.3%, 3) 3.2%, and 4) 43.4%. Sentinel events occurred in 23.5% of the cases and FHR was category II or III in 50.5% of the cases. 40.2% cases of asphyxia and 18.8% cases of HIE were not preceded by sentinel events or abnormal FHR. CONCLUSIONS: We identified at least one risk factor associated with all cases of HIE and with most cases of perinatal asphyxia. In absence of risk factors, the probability of developing perinatal asphyxia resulted extremely low. FHR monitoring alone is not a reliable tool for detecting the probability of eventual asphyxia.

Delivery and feto-neonatal outcomes of diamniotic twin pregnancies in women with no chronic disease or gestational complications: impact of mode of conception.

Introduction: Autologous and heterologous assisted reproductive technology (ART) conceptions have been on the rise for the last few decades and alongside with that have the rate of multiple pregnancies. Multiple gestations are associated with high odds of gestational complications and, in turn, adverse delivery and feto-neonatal outcomes. Whether ART-conception further increases such elevated risk is still debated. ART is more commonly accessed by older women with chronic diseases, which relate to heightened likelihood of complications. We decided to investigate the influence of autologous and heterologous ART conception compared to spontaneous conception on delivery and feto-neonatal outcomes of diamniotic twin pregnancies in a cohort of healthy women with no chronic conditions or gestational complications.Materials and methods: Retrospective cohort study among diamniotic twin pregnancies in mothers without pregestational or gestational disease. Delivery and feto-neonatal outcomes were compared among three groups according to mode of conception: (1) spontaneous conception (SC, referent group, n = 251 pregnancies), (2) autologous ART-conception (A-ART, n = 87), and (3) heterologous ART-conception (H-ART, n = 22).Results: At adjusted analyses, twin pregnancies conceived by A-ART showed a twofold heightened risk of delivery by urgent/emergent cesarean section, as well as four and sevenfold increase in odds of blood loss >1000 and >1500 mL, respectively. H-ART pregnancies were at fivefold higher risk of undergoing prelabor cesarean section compared to SC, whereas no differences were identified for odds of severe post-partum hemorrhage. Also, A-ART and H-ART gestations displayed fetal and neonatal outcomes similar to SC pregnancies when analysis was adjusted for relevant confounding factors.Conclusion: Our results suggest that both A-ART and H-ART conception associate with increased odds of operative delivery among diamniotic twin pregnancies in healthy mothers with no chronic diseases or gestational complications. Also, a higher risk of severe postpartum hemorrhage appears to relate to A-ART independent of mode of delivery and maternal age. Further studies with larger series of uncomplicated twin pregnancies are warranted to improve our understanding of the relationship of ART to adverse delivery outcomes.

Neonatal hypoxia of the second twin after vaginal delivery of the first twin: what matters?

Objective: Optimal management of twin deliveries is controversial. We aimed to assess potential risk factors correlated to the development of hypoxia in the second twin after vaginal delivery of the first twin. Study design: This is a retrospective observational study including diamniotic twin pregnancies delivering at our Institution at 35 weeks of gestational age or more, weighing ≥1800 g. Hypoxia was defined as at least one of the following: Apgar score <5 at 10 minute, neonatal resuscitation for >10 minutes, neonatal acidosis (pH ≤7 and/or BE ≥12 mmol/L). Results: A number of 275 diamniotic twin pregnancies met the inclusion criteria and were divided within the following groups: (1) second twin not developing neonatal hypoxia (n = 265); and (2) second twin developing neonatal hypoxia (n = 10). The rate of second twins with neonatal hypoxia during the study period was 3.6% (10/275). Abnormal cardiotocography during the intertwin delivery interval, defined as ACOG category III, was significantly correlated to second twin hypoxia. Of interest, there was no significant difference in the intertwin delivery interval between the study groups. In addition, breech presentation of the second twin did not show to be a risk factor for neonatal hypoxia. None of the second twins developing neonatal hypoxia was reported to have encephalopathy (follow up of at least 24 months). At multivariate analysis, only abnormal cardiotocography was an independent risk factor for second twin hypoxia (OR 17.8, 95% CI 4.1-77.2). Conclusions: In our study, neonatal hypoxia was significantly correlated to abnormal cardiotocography, while intertwin delivery interval was not correlated to the development of this adverse neonatal outcome.

What is the effect of intertwin delivery interval on the outcome of the second twin delivered vaginally?

Objective: Optimal management of twin deliveries is controversial. We aimed to assess if intertwin delivery interval, after vaginal delivery of the first twin, may have an influence on adverse neonatal outcomes of the second twin Study design: This is a retrospective observational study including diamniotic twin pregnancies with vaginal delivery of the first twin, between January 2000 and July 2017. Inclusion criteria were diamniotic pregnancies and vaginal delivery of the first twin. We excluded higher twin order, monoamniotic pregnancies, cesarean delivery of the first twin and patients with missing data. Results: A number of 400 diamniotic twin pregnancies met the inclusion criteria and were divided, considering intertwin delivery interval into (1) ≤30 minutes (n = 365); and (2) >30 minutes (n = 35). Considering the two study groups, maternal and first twin characteristics and outcomes were similar. Second twin reported higher incidence of cesarean section and vacuum delivery, but similar incidence of neonatal adverse outcomes, in case of intertwin interval >30 minutes. At multivariate analysis, a difference between second and first twin weight ≥25% was correlated to neonatal adverse outcome, while we did not found this correlation with a cut-off of 30 minutes. Conclusions: In our study, growth discrepancy between twins was significantly correlated to adverse neonatal outcomes, while intertwin delivery time was not an influencing factor. So, in line with this result, in our clinical practice, we do not use a fixed time in which both twins should be delivered, neither in monochorionic nor in dichorionic pregnancies, when fetal wellbeing was demonstrated during labor.

2D versus 3D real time ultrasound with live xPlane imaging to visualize aortic and ductal arches: comparison between methods.

BACKGROUND: The diagnosis of congenital heart defects is challenging, especially for what concerns conotruncal anomalies. Indeed, although the screening techniques of fetal cardiac anomalies have greatly improved, the detection rate of conotruncal anomalies still remains low due to the fact that they are associated with a normal four-chamber view. Therefore, the study aimed to compare real-time three-dimensional echocardiography with live xPlane imaging with two-dimensional (2D) traditional imaging in visualizing ductal and aortic arches during routine echocardiography of the second trimester of gestation. METHODS: This was an observational prospective study including 114 women with uncomplicated, singleton pregnancies. All sonographic studies were performed by two different operators, of them 60 by a first level operator, while 54 by a second level operator. A subanalysis was run in order to evaluate the feasibility and the time needed for the two procedures according to fetal spine position and operator's experience. RESULTS: The measurements with 2D ultrasound were performed in all 114 echocardiographies, while live xPlane imaging was feasible in the 78% of the cases, and this was mainly due to fetal position. The time lapse needed to visualize aortic and ductal arches was significantly lower when using 2D ultrasound compared to live xPlane imaging (29.56 ± 28.5 s vs. 42.5 ± 38.1 s, P = 0.006 for aortic arch; 22.14 ± 17.8 s vs. 37.1 ± 33.8 s, P = 0.001 for ductal arch), also when performing a subanalysis according to operators' experience (P < 0.05 for all comparisons). Feasibility of live xPlane proved to be correlated with the position of the fetal spine and the operator's experience. DISCUSSION: To find a reproducible and standardized method to detect fetal heart defects may bring a great benefit for both patients and operators. In this scenario live xPlane imaging is a novel method to visualize ductal and aortic arches. We found that the position of the fetal spine may affect the feasibility of the method since, when the fetal back is anterior or transverse, the visualization of the correct view of three-vessels and trachea in order to set the reference line properly becomes more challenging. In addition, the fetal spine position influences the duration of the ultrasound examination. Regarding operator's skills and experience, in our study a first level operator was able to perform the complete 2D and xPlane examination in a lower number of cases compared to second level operators. In addition, the time required for the complete examination was higher for first level operators. This means that this technique is based on an adequate operators' expertise.

Influence of weight gain, according to Institute of Medicine 2009 recommendation, on spontaneous preterm delivery in twin pregnancies.

BACKGROUNDS: Maternal total weight gain during pregnancy influences adverse obstetric outcomes in singleton pregnancies. However, its impact in twin gestation is less understood. Our objective was to estimate the influence of total maternal weight gain on preterm delivery in twin pregnancies. METHODS: We conducted a retrospective cohort study including diamniotic twin pregnancies with spontaneous labor delivered at 28 + 0 weeks or later. We analyzed the influence of total weight gain according to Institute of Medicine (IOM) cut-offs on the development of preterm delivery (both less than 34 and 37 weeks). Outcome were compared between under and normal weight gain and between over and normal weight gain separately using Fisher's exact test with Holm-Bonferroni correction. RESULTS: One hundred seventy five women were included in the study and divided into three groups: under (52.0%), normal (41.7%) and overweight gain (6.3%). Normal weight gain was associated with a reduction in the rate of preterm delivery compared to under and over weight gain [less than 34 weeks: under vs. normal OR 4.97 (1.76-14.02), over vs. normal OR 4.53 (0.89-23.08); less than 37 weeks: OR 3.16 (1.66-6.04) and 6.51 (1.30-32.49), respectively]. CONCLUSIONS: Normal weight gain reduces spontaneous preterm delivery compared to over and underweight gain.

Selective IUGR in dichorionic twins: what can Doppler assessment and growth discordancy say about neonatal outcomes?

OBJECTIVE: The aim of the present study was to assess, in a population of dichorionic twin pregnancies with selective growth restriction, the effect of inter-twin differences by use of Doppler velocimetry and fetal growth discordancy on perinatal outcomes. METHODS: This was a retrospective study including dichorionic twin pregnancies from January 2008 to December 2015 at the Department of Obstetrics and Gynecology of Fondazione MBBM. Only dichorionic twin pregnancies affected by selective intrauterine growth restriction (IUGR) delivering at ≥24 weeks were included in the study. RESULTS: We found that twin pregnancies with inter-twin estimated fetal weight (EFW) discordance ≥15% were significantly associated with a higher risk of preterm delivery before 32 (P=0.004) and 34 weeks (P=0.04). Similarly, twin pregnancies with inter-twin abdominal circumference (AC) discordance ≥30° centiles were associated with a higher rate of neonatal intensive care unit (NICU) admission (P=0.02), neonatal resuscitation (P=0.02) and adverse neonatal composite outcome (P=0.04). Of interest, when comparing twin pregnancies according to Doppler study, growth restricted twins had a higher rate of composite neonatal outcome and in multivariate analysis, an abnormal Doppler was an independent risk factor for this outcome. CONCLUSIONS: Our study associated growth discrepancy with specific pregnancy outcomes, according to defined cut-offs. In addition, we demonstrated that an abnormal umbilical artery Doppler is independently associated with a composite neonatal adverse outcome in growth restricted fetuses.

Cesarean delivery rates and obstetric culture - an Italian register-based study.

INTRODUCTION: Cesarean delivery rates are rising due to multiple factors, including less use of operative vaginal delivery and vaginal birth after cesarean delivery, which often reflect local obstetric practices. Objectives of the study were to analyze the relations between cesarean delivery, these practices, and perinatal outcomes. MATERIAL AND METHODS: We included all deliveries in the 72 hospitals of Lombardia, a region in northern Italy, during the year 2013. The delivery certificate was used as data source. Pearson's correlation coefficient and logistic regression were used for statistical analysis. RESULTS: We included 87 896 deliveries. The number of deliveries per hospital ranged from 140 to 6123. The rate of cesarean delivery was 28.3% (range 9.9-86.4%), operative vaginal delivery 4.7% (range 0.2-10.0%), and vaginal birth after cesarean 17.3% (range 0-79.2%). We found a significant inverse correlation between rates of overall cesarean delivery and operative vaginal delivery (r = -0.25, p = 0.04). The correlation between rate of overall cesarean delivery and vaginal birth after cesarean was also inverse and significant (r = -0.57, p < 0.001). There was no association between overall cesarean delivery rate and the rates of Apgar score at 5 min <7 in term and late preterm neonates (r = -0.92, p = 0.46) and of perinatal mortality (r = -0.19, p = 0.13), respectively. The associations were independent of hospital volume of activity. CONCLUSIONS: An obstetric practice that encourages vaginal instrumental delivery in delayed second stage of labor or vaginal birth after previous cesarean delivery, could reduce the rising cesarean delivery rate. This will require a change in obstetric culture, continuing education of healthcare providers, and leadership.

Effect of oxytocin during labor on neonatal acidemia.

OBJECTIVE: To assess the factors affecting neonatal acidemia, including occurrence of tachysystole/hypertonus in fetuses exposed to oxytocin during labour and with continuously-monitored fetal heart rate (FHR) tracings. METHODS: Prospective observational study of all women with term pregnancies who received oxytocin for induction/augmentation of labour. FHR tracings were prospectively classified using ACOG classification. Independent predictors of neonatal acidemia were identified using multivariate linear regression with p < 0.05 considered significant. RESULTS: We included 430 women, 236 of whom (54.9%) had spontaneous onset of labour. The duration of active phase of the second stage of labour and the presence of abnormal FHR tracing during labour were significantly associated with UA pH (p < 0.001) and BE (p < 0.001), while maximum dose of oxytocin (p < 0.17; p < 0.7) and tachysystole (p < 0.9; p < 0.8) were not. At logistic regression, the duration of active phase of the second stage of labour was independently predictive of neonatal acidemia (p < 0.009) while abnormal FHR tracing approached significance (p < 0.088). CONCLUSIONS: In women receiving oxytocin during labour, the duration of active phase of the second stage of labour correlates with neonatal acidemia, whereas maximum dose of oxytocin, duration of oxytocin administration and occurrence of tachysystole during labour do not.

Prenatal treatment prevents learning deficit in Down syndrome model.

UNLABELLED: Down syndrome is the most common genetic cause of mental retardation. Active fragments of neurotrophic factors release by astrocyte under the stimulation of vasoactive intestinal peptide, NAPVSIPQ (NAP) and SALLRSIPA (SAL) respectively, have shown therapeutic potential for developmental delay and learning deficits. Previous work demonstrated that NAP+SAL prevent developmental delay and glial deficit in Ts65Dn that is a well-characterized mouse model for Down syndrome. The objective of this study is to evaluate if prenatal treatment with these peptides prevents the learning deficit in the Ts65Dn mice. Pregnant Ts65Dn female and control pregnant females were randomly treated (intraperitoneal injection) on pregnancy days 8 through 12 with saline (placebo) or peptides (NAP 20 µg +SAL 20 µg) daily. Learning was assessed in the offspring (8-10 months) using the Morris Watermaze, which measures the latency to find the hidden platform (decrease in latency denotes learning). The investigators were blinded to the prenatal treatment and genotype. Pups were genotyped as trisomic (Down syndrome) or euploid (control) after completion of all tests. STATISTICAL ANALYSIS: two-way ANOVA followed by Neuman-Keuls test for multiple comparisons, P<0.05 was used to denote statistical significance. Trisomic mice who prenatally received placebo (Down syndrome-placebo; n = 11) did not demonstrate learning over the five day period. DS mice that were prenatally exposed to peptides (Down syndrome-peptides; n = 10) learned significantly better than Down syndrome-placebo (p<0.01), and similar to control-placebo (n = 33) and control-peptide (n = 30). In conclusion prenatal treatment with the neuroprotective peptides (NAP+SAL) prevented learning deficits in a Down syndrome model. These findings highlight a possibility for the prevention of sequelae in Down syndrome and suggest a potential pregnancy intervention that may improve outcome.

Comparative analysis of cesarean delivery rates over a 10-year period in a single Institution using 10-class classification.

OBJECTIVE: To evaluate the variables associated with changes in cesarean delivery (CD) rates in a University Hospital with standardized and unchanged protocols of care. METHODS: Retrospective analysis of consecutive deliveries between two triennia 10 years apart. The Robson classification of CD was used, and the analysis focused on factors affecting Robson's classes 1 and 2 combined (term singleton cephalic nulliparae) and class 5 (previous CD). RESULTS: A total of 8237 deliveries occurred in the 1st period, and 8420 in the 2nd. CD increased from 12.5 to 18% (p < 0.001). Robson's classes 1 and 2 combined contributed more than other classes to CD rates (32 vs 36%; p < 0.001). At multivariate analysis, BMI (Odds ratio [OR]: 1.08; 95% CI: 1.06-1.1) and maternal age (OR: 1.06; 95% CI: 1.05-1.08) were independently related to CD. In Robson class 5, the rate of CD increased from 34 to 46%, p < 0.001, mostly due to an increase in elective CD (39 vs 67.5%; p < 0.001). At multivariate analysis, BMI (OR: 1.06 95% CI: 1.02-1.1) and more than one previous CD (OR: 18.7; 95% CI: 9.6-36.4) were independently related to CD. CONCLUSIONS: BMI and maternal age are independent factors associated to the increasing rate of CD in nulliparae with spontaneous or induced labor at term. In women with previous CD, BMI and more than one previous CD are factors associated with the increasing rate of CD.

Can placental histology establish the timing of meconium passage during labor?

OBJECTIVE: To evaluate the relation between duration of placental exposure to recently passed meconium in vivo and histological evidence of meconium uptake by macrophages. DESIGN: Retrospective cohort. SETTING: University hospital. POPULATION: A total of 44 term deliveries of singleton infants with moderate or thick meconium had placental examination and documented timing of meconium appearance after membrane rupture. METHODS: Placentas were examined to assess the extent of meconium uptake by macrophages based on location in the amniochorionic membranes, chorionic plate and umbilical cord, and the intensity of uptake, based on the number of macrophages per field. An arbitrary score of severity of uptake was also created by multiplying the intensity of meconium uptake (number of meconium-laden macrophages) by the extent in the three placental areas. Twenty cases of singleton term pregnancy with clear amniotic fluid throughout labor and at delivery were included as negative controls. MAIN OUTCOME MEASURES: Relation between interval of meconium exposure in vivo and uptake by macrophages. RESULTS: The median interval from meconium appearance to delivery was 95 minutes (range 10-510 minutes). The median score of severity of meconium uptake was significantly higher than in the negative controls. There was no correlation between the interval of meconium appearance to delivery and score of severity of meconium uptake (p=0.76). Inflammatory lesions were present in 12 (27%) of 44 cases and vascular lesions in 11 (25%) of 44. CONCLUSIONS: Duration of placental exposure to meconium in vivo was not related to meconium uptake by macrophages where exposure was <8.5 hours.

Head-to-body delivery interval using 'two-step' approach in vaginal deliveries: effect on umbilical artery pH.

OBJECTIVE: To assess the duration of head-to-body interval using a 'two-step' approach to delivery that include waiting for the next contraction to deliver the shoulders; and its effect on umbilical artery pH and neonatal outcome. STUDY DESIGN: Prospective observational study on vaginal deliveries with singleton cephalic fetuses at term from June to December 2005. Clinical variables were evaluated in reference to umbilical artery pH and evidence of neonatal acidemia, defined as pH  ≤ 7.10 or base excess (BE) ≤ -12 in a multivariate model. RESULTS: Head-to-body interval was timed and recorded in 789 deliveries. The mean head-to-body interval was 88 ± 61 s. Although head-to-body interval was significantly correlated to umbilical artery pH (p = 0.02), the decline in umbilical artery pH in relation to the head-to-body interval was clinically not significant (0.0078 units for every additional minute of the interval). At the multivariate analysis, umbilical artery pH  ≤ 7.10 and/or BE  ≤ -12 were significantly related to abnormal fetal heart rate tracing during the second stage (p = 0.012) and operative vaginal delivery (p = 0.045), but not to head-to-body interval (p = 0.25). Shoulder dystocia occurred in three cases (0.38%). CONCLUSION: A 'two-step' approach to birth does not significantly increase the risk of neonatal acidemia.

Variability in rate of cervical dilation in nulliparous women at term.

BACKGROUND: Cervical dilatation is commonly documented on a partogram indicating the expected rate of progress of labor. Although deviations from such a line can be used to indicate abnormal progress, what constitutes the "normal" rate of cervical dilation is still largely unknown. The objectives of this study were to assess the variability of the rate of cervical dilation in nulliparous women and to determine whether the rate of labor was independent of dilation on admission. METHODS: We analyzed a cohort of consecutive nulliparous women with spontaneous labor at term and singleton fetuses in cephalic presentation. Exclusion criteria were gestational age less than 37 weeks, induction of labor, or the presence of a uterine scar. Management of labor was standardized using set protocols of care. Active labor was diagnosed as regular contractions every 10 minutes or less, lasting more than 40 seconds, with cervical effacement more than 80 percent and dilation of 2 cm. Vaginal examinations were performed by a dedicated midwife every 2 hours. Amniotomy was performed for slow progress or arrest of dilation over 2 hours. Oxytocin was administered for arrest of cervical dilation for 2 hours with membranes ruptured. Data pertaining to cases ending in cesarean delivery were included up to the time of cesarean section. RESULTS: The study sample comprised 1,119 women at 39.7 ± 1.1 weeks with an average duration of labor of 4.1 ± 2.4 hours. The rate of oxytocin use was 27 percent and of epidural analgesia 5 percent. The rate of oxytocin use was inversely related to cervical dilation on admission. Cesarean delivery was performed in 6 percent of women. Duration of labor at each centimeter of cervical dilation on admission showed a broad distribution (e.g., at 4 cm: median = 5.5, range: 0.8-12.5 hr). The rate of labor progression (expressed as the slope of the dilation-vs-time curve) was approximately 1.5 cm/hr, and it was essentially independent of cervical dilation on admission (r = 0.034, p = 0.267). A deceleration phase seemed to be present toward the end of the active phase of labor (approximately 9 cm). CONCLUSION: In our setting, the rate of labor in nulliparous women at term was highly variable, and it did not appear to be affected by cervical dilation on admission.

Prevention of learning deficit in a Down syndrome model.

OBJECTIVE: To evaluate whether peptides given to adult mice with Down syndrome prevent learning deficits, and to delineate the mechanisms behind the protective effect. METHODS: Ts65Dn mice were treated for 9 days with peptides D-NAPVSIPQ (NAP)+D-SALLRSIPA (SAL) or placebo, and wild-type animals were treated with placebo. Beginning on treatment day 4, the mice were tested for learning using the Morris watermaze. Probe tests for long-term memory were performed on treatment day 9 and 10 days after treatment stopped. Open-field testing was performed before and after the treatment. Calibrator-normalized relative real-time polymerase chain reaction (PCR) with glyceraldehyde-3-phosphate dehydrogenase (GAPD) standardization was performed on the whole brain and hippocampus for activity-dependent neuroprotective protein, vasoactive intestinal peptide (VIP), glial fibrillary acidic protein (GFAP), NR2B, NR2A, and γ-aminobutyric acid type A (GABAA)-α5. Statistics included analysis of variance and the Fisher protected least significant difference, with P<.05 significant. RESULTS: The Ts65Dn plus placebo animals did not learn over the 5-day period compared with the controls (P<.001). The Ts65Dn +(D-NAP+D-SAL) learned significantly better than the Ts65Dn plus placebo (P<.05), and they retained learning similar to controls on treatment day 9, but not after 10 days of no treatment. Treatment with D-NAP+D-SAL prevented the Ts65Dn hyperactivity. Adult administration of D-NAP+D-SAL prevented changes in activity-dependent neuroprotective protein, intestinal peptide, and NR2B with levels similar to controls (all P<.05). CONCLUSION: Adult treatment with D-NAP+D-SAL prevented learning deficit in Ts65Dn, a model of Down syndrome. Possible mechanisms of action include reversal of vasoactive intestinal peptide and activity-dependent neuroprotective protein dysregulation, as well as increasing expression of NR2B, thus facilitating learning.

Treatment with neuropeptides attenuates c-fos expression in a mouse model of fetal alcohol syndrome.

Fetal alcohol syndrome (FAS) is the most common nongenetic cause of mental retardation and is characterized by neurodevelopmental anomalies. C-FOS is a cellular marker of transcriptional activity in the stress-signal pathway. Previously, we showed the treatment with NAP (NAPVSIPQ) + SAL (SALLRSIPA) reversed the learning deficit after prenatal alcohol exposure in FAS. Our objective was to evaluate if the mechanism of actions of NAP + SAL involves the stress-signal pathway differentiating C-FOS expression in mouse brains after prenatal alcohol exposure. C57Bl6/J mice were treated with alcohol (0.03 mL/g) or placebo on gestational day 8. On postnatal day 40, in utero alcohol-exposed males were treated via gavage with 40 µg D-NAP and 40 µg D-SAL ( N = 6) or placebo ( N = 4); controls were gavaged with placebo daily ( N = 12). After learning evaluation, hippocampus, cerebellum, and cortex were isolated. Calibrator-normalized relative real-time polymerase chain reaction and Western blot analysis were performed. Statistics included analysis of variance and post hoc Fisher analysis. Adult treatment with NAP + SAL restored the down-regulation of C-FOS in the hippocampus after prenatal alcohol exposure ( P < 0.05), but not in the cerebellum. There was no difference in C-FOS expression in the cortex. Adult treatment with NAP + SAL restored the down-regulation of C-FOS expression in hippocampus attenuating the alcohol-induced alteration of the stress-signal pathway.