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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.

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 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 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.

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.

Fetal malformations are more frequent in twins than in singletons. The aim of our study was to define the influence of a malformed twin on di-chorionic pregnancy outcomes. We performed a retrospective cohort study of di-chorionic pregnancies delivered between 2000 and 2015. Exclusion criteria were: both twins affected by fetal malformations, double intra-uterine fetal death in pregnancies without fetal malformation, selective feticide and therapeutic pregnancy termination. We compared maternal and fetal outcomes of di-chorionic pregnancies not complicated by fetal malformations with pregnancies affected by a single malformed fetus with conservative management. We included 642 di-chorionic pregnancies: 56 (case group, 8.7%) with one twin affected by a malformation (20 minor, 36 major ones), 586 (control group, 91.3%) without fetal malformation. No differences were found on maternal and not malformed co-twin outcomes when compared to pregnancies with no malformation; case vs control group presented similar rates of preeclampsia (8.9% vs. 10.8%, respectively), intrauterine growth restriction (7.1% vs. 9.4%) and composite adverse neonatal outcomes (19.6% vs. 15.1%). No case of fetal death in not malformed co-twin was reported. Expectant management could be a safe option for both mother and co-twin in case of di-chorionic twin pregnancy complicated by only one malformed fetus.

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

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

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

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 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 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 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.

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.

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 95minutes (range 10-510minutes). 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

Study design. aEuro integral 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 aEuroS < a parts per thousand currency sign aEuroS7.10 or base excess (BE) aEuroS < a parts per thousand currency sign aEuroS--12 in a multivariate model.Results. aEuro integral Head-to-body interval was timed and recorded in 789 deliveries. The mean head-to-body interval was 88 aEuroS +/-+/- aEuroS61 s. Although head-to-body interval was significantly correlated to umbilical artery pH (p aEuroS== aEuroS0.02), 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 aEuroS < a parts per thousand currency sign aEuroS7.10 and/or BE aEuroS < a parts per thousand currency sign aEuroS--12 were significantly related to abnormal fetal heart rate tracing during the second stage (p aEuroS== aEuroS0.012) and operative vaginal delivery (p aEuroS== aEuroS0.045), but not to head-to-body interval (p aEuroS== aEuroS0.25). Shoulder dystocia occurred in three cases (0.38%%).Conclusion. aEuro integral A ''two-step'' approach to birth does not significantly increase the risk of neonatal acidemia.

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. (BIRTH 38:1 March 2011)

OBJECTIVE: We investigated whether gestational age at glucocorticoids administration in very preterm premature rupture of membranes (PROM) affects the occurrence of neonatal cerebral white matter damage (WMD). METHODS: In a cohort of singleton neonates born at 24.0-33.6 weeks after PROM who underwent at least one full course of glucocorticoids (n = 130), we compared the gestational age at first and last course of glucocorticoids between those who developed WMD (n = 8) and those who did not (n = 122) after adjusting for gestational age at PROM using logistic regression with P < 0.05 considered significant. RESULTS: Gestational age at first course of glucocorticoids (P = 0.2), at last course of glucocorticoids (P = 0.2) and at delivery (P = 0.2), were not significantly different between those who developed WMD and those who did not. Although latency between PROM and first course of glucocorticoids was protective against WMD (P = 0.02), the significance was lost after controlling for gestational age at PROM, which was significantly lower in cases that developed WMD (P < 0.01). CONCLUSIONS: In very preterm PROM, the beneficial effect of glucocorticoids on occurrence of WMD is not related to gestational age at steroid administration.

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.

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.

Objective: To evaluate predictors of umbilical artery acidemia in term neonates with low Apgar score. Study design: From a cohort of term singleton deliveries over a 13-year period, we selected neonates with 5-min Apgar score

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.

We report a case of Alagille syndrome in which sonographic examination revealed the presence of angulation of the fetal spine due to vertebral fusion as well as tetralogy of Fallot. Histologic examination after pregnancy termination revealed the presence of agenesis of the gallbladder with a paucity of intrahepatic bile ducts, leading to the diagnosis of Alagille syndrome. In the presence of cardiac and axial skeletal anomalies, attention should be paid to the fetal gallbladder, whose absence would signal a diagnosis of Alagille syndrome.

The fluorescent probe 4',6-diamidino-2-phenylindole (DAPI), extensively used with nucleic acids, has also recently been used with membranes and proteins (Favilla et al., Biophys. Chem., 46 (1993) 217-226 and Mazzini et al., Biophys. Chem. 52 (1994) 145-156, respectively). The spectroscopic changes of DAPI observed, namely a considerable enhancement of fluorescence, induced circular dichroism (CD) and absorbance spectral shifts, have been exploited to study the binding of this dye to both native and alkali denatured pepsin. Fluorescence and CD titrations show that nearly two molecules of DAPI bind to either native or alkali denatured pepsin with pH and ionic strength dependent Kd values, whereas absorbance titrations evidentiate an interaction characterized by a lower affinity and a larger number of binding sites. Therefore two kinds of interaction are proposed: a specific one, involving both hydrophobic and electrostatic forces; and a non-specific one, involving surface protein negative charges only. Finally, the behaviour of DAPI as a competitive inhibitor and the remarkable effect of pepstatin A, a specific inhibitor of pepsin, on both the CD and fluorescence spectra of DAPI in the presence of pepsin, show the involvement of the protein active site in the interaction.

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.

To evaluate whether peptides given to adult mice with Down syndrome prevent learning deficits, and to delineate the mechanisms behind the protective effect.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.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).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.

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 95minutes (range 10-510minutes). 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

To evaluate whether treatment with neuroprotective peptides to young adult mice prenatally exposed to alcohol reverses alcohol-induced learning deficits in a mouse model of fetal alcohol syndrome, whether the mechanism involves the N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid type A (GABAA) receptors, and whether it is related to glial cells.C57Bl6/J mice were treated with alcohol (0.03 ml/g) or placebo on gestational day 8. On day 40, male mice exposed to alcohol in utero were treated daily for 10 days with D-NAPVSIPQ and D-SALLRSIPA (n=20) or placebo (n=13); and control offspring were treated with placebo (n=46), with the treatment blinded. Learning evaluation began after 3 days using the Morris watermaze and the T-maze. The hippocampus, cortex, and cerebellum were isolated. Expression of NR2A, NR2B, GABAAbeta3, GABAAalpha5, vasoactive intestinal peptide (VIP), activity-dependent neuroprotective protein, and glial fibrillary acidic protein was measured using calibrator-normalized relative real-time polymerase chain reaction. Statistical analysis included analysis of variance and Fisher's protected least significant difference.Treatment with D-NAPVSIPQ and D-SALLRSIPA reversed the alcohol-induced learning deficit in both learning tests as well as the NR2A and NR2B down-regulation in the hippocampus and the up-regulation of NR2A in the cortex and NR2B in the cortex and cerebellum (all P.05). No significant differences were found in GABAA expression. Moreover, the peptides changed activity-dependent neuroprotective protein expression in the cortex (P=.016) but not the down-regulation of VIP (P=.883), probably because the peptides are downstream from VIP.Alcohol-induced learning deficit was reversed and expression of NR2A and NR2B was restored in the hippocampus and cortex of young adult mice treated with D-NAPVSIPQ and D-SALLRSIPA. Given the role of NMDA receptors in learning, this may explain in part the mechanism of prevention of alcohol-induced learning deficits by D-NAPVSIPQ and D-SALLRSIPA.

We investigated antepartum and intrapartum risk factors for neonatal encephalopathy (NE) in term infants. We performed a case-controlled study in which characteristics of singleton term infants who developed NE from 1993 to 2003 were compared with those of randomly selected controls. Antenatal risk factors (including obesity, diabetes, thyroid dysfunction, previous cesarean delivery, preeclampsia, fetal growth restriction, abnormal amniotic fluid volume, and abnormal fetal heart rate [FHR] tracing before labor) and intrapartum risk factors (acute intrapartum sentinel events and other risk factors like suspicious or ominous FHR tracing and clinical chorioamnionitis) were related to occurrence of NE. From the study cohort of 30,580 infants, 27 (0.09%) developed NE and were compared with 100 controls. Neonates with encephalopathy had more frequent antepartum (74% versus 18%, p

Objective To study the relationship between prenatal ultrasound features and postnatal course of meconium peritonitis. Study Design We reviewed our cohort of cases of meconium peritonitis (MP) (n = 13/37, 225 pregnancies or 0.3/1000) as well as those published in the English literature with prenatal ultrasonographic findings and postnatal follow-up (n = 56). The total number of cases (n = 69) was divided into 4 grades of progressive severity based on the number of pertinent sonographic findings: grade 0, isolated intra-abdominal calcifications (n = 18); grade 1, intra-abdominal calcifications and ascites (n = 17) or pseudocyst (n = 2) or bowel dilatation (n = 6); grade 2, two associated findings (n = 20); and grade 3, all sonographic features (n = 6). Presence of polyhydramnios was also recorded. Prenatal predictors of need for neonatal surgery and risk of neonatal death were identified using Chi-square and Fisher exact test, with P < 0.05 considered significant. Results Neonatal surgical intervention was required in 0% (0/18) of newborns with grade 0 MP; in 52% (13/25) of those with grade 1; in 80% (16/20) with grade 2; and in 100% (6/6) with grade 3 MP (P < 0.001, Chi-square for trend). Moreover, neonatal surgery was more frequent in the presence than absence of polyhydramnios [69% (18/26) vs 37% (16/43); P = 0.007]. Neonatal mortality was 6% (4/69; 3 after surgery and 1 for premature delivery) and it was confined to the subgroup with polyhydramnios (4/26, 15%). Conclusions Prenatal sonographic features are related to postnatal outcome. Persistently isolated intra-abdominal calcifications have an excellent outcome. Delivery in a tertiary care center is recommended when calcifications are associated with other sonographic findings. Copyright © 2007 John Wiley & Sons, Ltd.

Objective. To compare the risk of uterine rupture between a cohort of women with previous low-transverse cesarean section (CS) and a cohort with intact uterus. Methods. All women with a singleton pregnancy and previous low-transverse CS requiring induction of labor from January 1, 1992 to December 30, 2001 (n = 310) were compared with a cohort of women with intact uterus undergoing induction of labor during the same study period (n = 5420). Protocols of induction using prostaglandin E-2 gel and oxytocin infusion were consistent within groups, but differed between the previous CS and the intact uterus group. Results. Uterine rupture occurred in 0.3% in the previous CS group vs. 0.03% in the intact uterus group (p = 0.37). Logistic regression analysis showed no significant difference in rate of uterine rupture between the previous CS vs. intact uterus group (p = 0.16) after controlling for maternal age, parity, gestational age at delivery, Bishop score on admission, use of prostaglandin and oxytocin, and birth weight. Our study had adequate power to detect a 0.38% difference in rate of uterine rupture between the two groups (alpha = 0.05, beta = 0.80). Conclusion. Induction of labor is not associated with significantly higher rates of uterine rupture among women with previous low-transverse CS compared with women with intact uterus provided a consistent protocol with strict intervention criteria is adopted.

Preterm birth is the single most important and persistent of obstetrical problems, accounting for three-fourths of nonanomalous neonatal deaths and nearly half of cases of congenital neurological disability. A short cervical length (CL), noted on transvaginal ultrasonography (TVU), has proved to be one of the best predictors of preterm birth. A recent meta-analysis found cerclage to be potentially beneficial in a mixed group of high- and low-risk women if the CL was less than 25 mm. The present trial, a retrospective cohort study, enrolled 67 women having a CL of 25 mm or less on TVU, performed at approximately 16-25 weeks' gestation. None had a history of preterm birth or mid-trimester loss. Thirty-one of the women had cerclage placement, while 36 were managed solely by rest. Women undergoing cerclage placement had a significantly lower gestational age at the time of TVU as well as shorter cervical length, but the 2 management groups did not differ with regard to rates of prior cervical surgery. Gestational age at delivery was similar in the 2 groups. Rates of delivery before 35 weeks' gestational age were 16% in the cerclage group and 5.5% in the control group. No significant association between cerclage and the risk of delivery before 35 weeks was noted after controlling for gestational age at the time of TVU and initial CL. There was, however, significant correlation between CL and gestational age at delivery. The interval from TVU to delivery was longer in the cerclage group, but no significant group difference in the interval to delivery was apparent after controlling for gestational age and cervical length. The investigators conclude from these findings that cervical cerclage does not improve pregnancy outcomes in low-risk women whose CL early in the second trimester is no greater than 25 mm. It remains possible that such women will benefit from other interventions such as a vaginal pessary or progesterone therapy.

in infants with asphyxia Cristina Plevani, Ilaria Pozzi, Anna Locatelli, Silvia Malguzzi, Gaia Kullmann, Maddalena Incerti, Giuseppe Paterlini MBBM Foundation, University of Milano-Bicocca, Obstetrics and Gynecology, Monza, Italy, MBBM Foundation, San Gerardo Hospital, Neonatology, Monza, Italy OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) occurs in the first days of life in asphyxiated term neonates. Our objective is to identify markers predictive of moderate-severe HIE and long term adverse neurodevelopmental outcome (ANDO) among neonates with asphyxia. STUDY DESIGN: All term asphyxiated neonates (umbilical artery (UA) pH 7.0 or base excess (BE) -16 or Apgar 5 at 5 min or need of intubation or prolonged resuscitation at birth) inborn between January 2004 and June 2011 were prospectively admitted to a clinical and instrumental monitoring protocol and at least 12 months follow-up. Data on antenatal, intrapartum risk factors, placental histology and neonatal outcome were collected. HIE was defined as mild, moderate and severe according to modified SarnatSOR 145) and UA BE (p 0.04; OR 0.7) were independently related to moderate-severe HIE and ANDO. CONCLUSION: Among neonates with asphyxia, the risk of developing moderate-severe HIE or ANDO is predicted by perinatal factors, i.e. need for intubation and UA BE. Neither antenatal and intrapartum risk factors nor placental histology are helpful to identify these outcomes.

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

Our objective was to evaluate whether brain-derived neurotrophic factor (BDNF) expression is affected by prenatal alcohol exposure and whether the neuroprotective effects of the vasoactive intestinal peptide (VIP)-related peptides, NAPVSIPQ (NAP) and SALLRSIPA (SAL), are mediated through BDNF.Using a well-characterized fetal alcohol syndrome (FAS) model, timed pregnant C57BL6/J mice were treated on gestational day (E) 8 with alcohol (0.03 mL/g), placebo, or alcohol plus (NAP plus SAL). Embryos were harvested at 6 hours (E8), 24 hours (E9), and 10 days (E18) and pups at postnatal day 40. Calibrator-normalized relative real time polymerase chain reaction was performed to quantify BDNF with hypoxanthine phosphoribosyl transferase-1 standardization.BDNF expression was lower in the alcohol-exposed embryos than in controls at 6 hours and higher at 24 hours and 10 days (all P.05). Pretreatment with NAP plus SAL prevented the alcohol-induced rise in BDNF expression (P.05) at 24 hours and 10 days after alcohol exposure. We found no difference between alcohol and control in young-adults' brain (P.05).NAP plus SAL treatment prevented alcohol-induced changes in BDNF expression 24 hours and 10 days after alcohol exposure in mouse embryos. This may explain, at least in part, the peptides' prevention of neurodevelopmental anomalies in FAS.