Beneficial Effects of Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 on Mood Imbalance, Self-Confidence, and Breastfeeding in Women during the First Trimester Postpartum.

Background: The post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to postpartum depression (PPD). Objective: The present clinical study assesses the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4 × 109 CFU/day) on the mother's mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized, Double-Blind, Controlled (RDBPC) trial was carried out on 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4 × 109 CFU/day) plus multivitamins and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 using the Edinburgh Postnatal Depression Scale (EPDS) and the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF). Results: At days 45 and 90, the probiotic treatment significantly ameliorated the mothers' mood compared to the control treatment (p < 0.001). Likewise, the breastfeeding quality and the baby's cries significantly improved in the probiotic group (p < 0.001). Conclusions: Microbiota alterations could influence a post-delivery woman's mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates that are able to improve stress resilience in the postpartum period.

Evaluation of umbilical cord pulsatility after vaginal delivery in singleton pregnancies at term.

OBJECTIVES: To define the duration of umbilical cord pulsatility (UCP) after vaginal delivery and to evaluate its possible association with maternal characteristics and obstetric and neonatal variables. STUDY DESIGN: Prospective observational study on women with a singleton pregnancy at term who had a vaginal delivery and cord clamping at the cessation of pulsations. The collection of UCP duration was performed through a stopwatch and by manual palpation of the umbilical cord. Maternal (age, BMI, parity, antepartum hemoglobin), obstetric (pregnancy characteristics, gestational age at delivery, induction of labor, duration of the first, the second and the third stage of labor, post-partum blood loss, umbilical cord length) and neonatal (birthweight, Apgar score, hematocrit, hemoglobin) variables were then compared between two groups: long-term vs. short-term UCP. RESULTS: A total of 102 women were identified. The median duration of UCP after birth was 213 s (IQR 120, 420), corresponding to 3 min and 33 s. The long-term UCP group (n = 51) had a significantly longer duration of third stage of labor (median 12 vs. 8 min, p < 0.001) and a significantly higher birthweight (median 3530 g vs. 3250 g, p = 0.005) compared with the short-term UCP group (n = 51). No differences in the other variables were found between groups. CONCLUSION: For the first time we have reported the duration of UCP after vaginal delivery. An increased duration of UCP is associated with a prolonged duration of third stage of labor and a higher birthweight.

Fetal middle cerebral artery Doppler in late-term pregnancy: a predicting factor for failed induction of labor.

PURPOSE: To study the role of fetal middle cerebral artery (MCA) Doppler evaluated prior to induction of labor in late-term pregnancies, in order to build an ultrasound-based predictive model for failed induction. MATERIALS AND METHODS: A prospective cohort study on 250 nulliparous women carrying singleton late-term pregnancies was conducted. Prior to induction, each patient underwent to an ultrasound evaluation for fetal MCA Doppler. Additional ultrasound parameters such as cervical length (CL), membranes thickness, amniotic fluid index, placental location, and estimated fetal weight (EFW) were collected. According to the type of response, women were divided into three groups: (A) responders within 24 h; (B) responders after 24 h, and (C) no responders. RESULTS: Women who failed to enter active labor showed significantly higher fetal MCA pulsatility index (PI), longer CL and higher EFW. The estimated probability of logistic regression model combining the three variables achieved a sensitivity of 94.2% and a specificity of 86.36% (AUC, 0.926; 95% CI, 0.884 - 0.956, p < .0001) using as decision probability value the cut off >0.1838. CONCLUSIONS: In late-term pregnancies, an ultrasound-based model including cervical length, MCA PI, and EFW achieved a good accuracy in predicting those women who are likely to fail induction of labor.

Maternal anemia effects during pregnancy on male and female fetuses: are there any differences?

OBJECTIVE: Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. STUDY DESIGN: A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb ≤ 11 g/dl and Group B (n = 975) with Hb ≥ 11,1 g/dl. RESULTS: Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). CONCLUSION: Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome.

Corticotropin releasing hormone and Urocortin 2 activate inflammatory pathways in cultured trophoblast cell lines.

OBJECTIVE: Embryo implantation and parturition are recognized as inflammatory events involving endocrine and immune system. NF-kB and MAPK are two transcription factor families involved in inflammation. A possible role of neuroendocrine mechanism in early pregnancy and delivery was proposed for the neuropeptides related to corticotropin releasing hormones (CRH), named Urocortins (Ucns). Experimental and clinical studies support a role for CRH, Ucn, Ucn2 and Ucn3 in the endocrine/immune modulation of inflammation in human trophoblast; however the intracellular mechanisms are not yet recognized. The aim of the present study was to evaluate which of these neuropeptides modulate NF-kB or MAPKs pathways. STUDY DESIGN: In Jeg-3 placental cell line the effect of CRH, Ucn, Ucn2 or Ucn3 on NF-kB and MAPKs pathways were evaluated using Western blot analysis. RESULTS: CRH induced the phosphorylation of MAPK subunits; Ucn2 was able to induce the phosphorylation of both NF-kB and MAPK subunits. Ucn and Ucn3 had no effects on these pathways. CONCLUSIONS: These data provide novel information on inflammatory process in trophoblast cells: Ucn2 is a potent pro-inflammatory neuropeptide via NF-kB and MAPK pathways and CRH via MAPK, and CRH and Ucn2 network participates in the inflammatory mechanisms of pregnancy and parturition.

Term histologic chorioamnionitis: a heterogeneous condition.

A histologic response of histologic chorioamnionitis (HCA) is defined as an intrauterine inflammatory condition characterized by acute granulocyte infiltration into the fetal-maternal or the fetal tissues. Prevalence of HCA is inversely correlated with gestational age, occurring in 50% of preterm birth and in up to 20% of deliveries at term. Regardless of these standard definitions, understanding HCA is challenging as it reflects a heterogeneous condition. A histologic response of HCA from term placentas often does not correspond to a clinical presentation; in this context, the present review aims to analyze main characteristics of this condition, in particular focusing on mechanisms and birth outcomes.

Urocortin 2 role in placental and myometrial inflammatory mechanisms at parturition.

The purpose of the study was to investigate urocortin (Ucn)2 involvement in placental and myometrial inflammatory pathways associated with parturition by evaluating: 1) Ucn2 and its receptor, CRH-receptor type 2 (CRH-R2), expression in laboring/nonlaboring human gestational tissues and in mouse utero-placental tissues approaching delivery; and 2) Ucn2 effect on myometrial contractility and on the expression of inflammatory mediators (prostaglandin F2α receptor and cytokines) and regulation of Ucn2 by TNF-α in cultured myometrial cell line. Placenta (n = 16), fetal membranes (n = 16), and myometrium (n = 22) were obtained from healthy pregnant women delivering at term by vaginal/elective caesarean delivery and from timed-pregnant mice on days 16-19. Expression of Ucn2/CRH-R2 in human/mouse tissues and inflammatory mediators in myometrial cell lines were measured by RT-PCR or ELISA, mouse Ucn2/CRH-R2 protein localization by immunohistochemistry. Ucn2 but not CRH-R2 was up-regulated (P < .05) in all human tissues in labor (compared with before labor) and increased significantly (P < .01) in mouse placenta approaching delivery. Ucn2 was up-regulated by TNF-α via nuclear factor-κB (NF-kB) in myometrium cell lines (P < .05 or P < .01 on the basis of treatment doses) and increased proinflammatory mediators and prostaglandin F (PGF2α) receptor expression (P < .05) via CRH-R2, without a direct effect on contractility. Placental and myometrial Ucn2 may play a role in the endocrine-inflammatory processes of parturition, representing a potential target for treating inflammation-induced obstetric complications.

Histologic chorioamnionitis: different histologic features at different gestational ages.

OBJECTIVE: The aim of this study was to investigate the rate of the different histological chorioamnionitis (HCA) grade in relation to the gestational age in term and preterm delivery. METHODS: Three hundred and ninety-two women with singleton pregnancy with spontaneous onset of labor either prematurely or at term, with histologic diagnosis of HCA, were enrolled. Placentas were classified as: deciduitis and/or histologic chorioamnionitis within the membranes (HCA1); amnionitis or inflammation of the chorionic plate without funisitis (HCA2); and histologic chorioamnionitis with funisitis (HCA3). Microbiological culture was performed on both placental and fetal membrane samples. RESULTS: HCA1 was more frequent in women delivering at term than in preterm (p < 0.001). HCA2 was more represented in women delivering between 32 and 36 weeks (p < 0.001) and HCA3 occurred more frequently in those delivering within 32 weeks (p < 0.001). The positive bacterial culture was higher (p = 0.008) in presence of HCA3 in comparison with HCA1 and HCA2. CONCLUSIONS: This study showed a significantly different distribution of HCA grades in relation to gestational age at delivery. HCA may represent the expression of different subtending etiologies and may also reflect specific immune competence of gestational tissues at different gestational ages, strengthening as pregnancy advances.

Understanding spontaneous preterm birth: from underlying mechanisms to predictive and preventive interventions.

Preterm birth is defined as birth before 37 weeks' gestational age. With an incidence of 7% to 11%, it is one of the major causes of perinatal mortality and morbidity. Preterm birth is considered a clinical syndrome, which arises from different pathological processes that activate prematurely one or more components of the mechanisms leading to parturition. The premature activation of labor may be caused by multiple pathological conditions; in particular a deregulation of the immune system and an exaggeration of inflammatory processes represent common central mechanisms. The complex pathogenesis, the main risk factors and the different therapeutic options will be described in the present review. Since its incidence is still increasing in the last decades, the goal is to improve the primary and secondary prevention.

Weight gain regardless of pre-pregnancy BMI and influence of fetal gender in response to labor induction in postdate pregnancy.

OBJECTIVE: To evaluate whether maternal weight and body mass index (BMI) and their increase throughout pregnancy are associated with the response to labor induction in postdate pregnancies. METHODS: A total of 376 nulliparous women carrying singleton postdate pregnancies with unfavorable cervix were enrolled. We considered as primary outcome vaginal delivery within 24 h after induction, and outcomes were divided into responders (n = 258) and non-responders (n = 107) to the induction of labor to perform the statistical analyses. RESULTS: In the total population of study, women who successfully delivered within 24 h differed significantly from the remaining patients in terms of maternal weight gain (p = 0.009) and BMI increase (p = 0.02) during pregnancy. In addition, males were significantly more (p = 0.005) than females among newborns of women not responding to induction of labor. In the multivariate analysis, maternal weight gain and fetal sex significantly influenced the induction response. The occurrence of a failed induction of labor was more likely in patients presenting a greater maternal weight gain (cut-off 12 kg) and male fetus. CONCLUSION: Weight gain over 12 kg regardless of pre-pregnancy weight and male fetal gender are two novel potential risk factors for the prediction of failure to induction of labor in postdate pregnancy.

The obstetric syndromes: clinical relevance of placental hormones.

Preterm delivery, preeclampsia and intrauterine growth restriction are the major diseases of pregnancy. A key role in their pathogenesis is played by the placenta, which is the source of hormones and other important regulatory molecules providing the metabolic and endocrine homeostasis of the fetal-placental unit. Since obstetric syndromes are characterized by important maternal and neonatal morbidity and mortality worldwide, numerous efforts have been made over the years to prevent and treat them. Due to their complex pathogenesis, however, the therapy is poor and not very effective. Therefore, great emphasis is currently given to the prevention of these diseases through the identification of biochemical and biophysical markers, among which placental factors play a crucial role. The increasing knowledge of the role of placental molecules can indeed lead to the development of new therapeutic and diagnostic tools.

Histologic chorioamnionitis at term: implications for the progress of labor and neonatal wellbeing.

OBJECTIVE: The aim of the present study was to evaluate: i) the rate of histologic chorioamnionitis in relation to the onset of labor and mode of delivery; ii) influence of clinical parameters on the risk of histologic chorioamnionitis in laboring women; iii) neonatal outcome in relation to histologic chorioamnionitis. METHODS: A cohort study was conducted on 395 healthy women at term, with singleton uneventful pregnancy, of which 195 with spontaneous onset of labor and 200 with elective cesarean section. All placentas, collected after delivery, were examined for the diagnosis of histologic chorioamnionitis. Mode of delivery, presence of bacterial infection of placenta and membranes, maternal clinical parameters and neonatal outcome were recorded. RESULTS: The rate of histologic chorioamnionitis in women with spontaneous onset of labor was significantly higher than in those experiencing elective cesarean section (28.7% vs. 11.5%). Nulliparity and the duration of labor were independent variables associated with acute histologic chorioamnionitis. The presence of histologic chorioamnionitis did not affect neonatal outcome. CONCLUSIONS: The present study showed a highest rate of histological chorionamniositis in women delivering after spontaneous onset of term labor, although the mode of delivery either vaginally or by emergency cesarean section was not influenced by the presence of this pathological condition.

Fetal gender effects on induction of labor in postdate pregnancies.

OBJECTIVE: To determine delivery outcome in women undergoing induction of labor for postdate pregnancy in relation to fetal gender. STUDY DESIGN: A total of 365 nulliparous and 127 multiparous women carrying singleton postdate pregnancies with unfavorable cervix were enrolled. Clinical characteristics and delivery outcome were analyzed in relation to fetal gender. RESULTS: Women carrying male fetuses showed higher rate of caesarean section than those carrying females, in both nulliparous and multiparous women. Moreover, women carrying male fetuses presented more frequently with (i) interval between induction of labor and delivery >24 hours (P < .0002); (ii) augmentation of labor after cervical ripening (P < .0391); (iii) meconium-stained liquor (P< .0126); and (iv) higher neonatal weight (P < .0011) than those carrying females. CONCLUSION: Male fetuses are more likely to be associated with higher rates of cesarean section. In maternal fetal medicine, gender differences may add prognostic information on the delivery outcome in women induced for postdate pregnancy.

Activin A and its regulatory molecules in placenta and fetal membranes of women with preterm premature rupture of the membranes associated with acute chorioamnionitis.

UNLABELLED: LABELED PROBLEM: To investigate regulation of activin A and related molecules in placenta/fetal membranes from preterm premature rupture of membranes (pPROM) associated with acute chorioamnionitis (ACA). METHOD OF STUDY: Tissues were obtained from women with spontaneous preterm deliveries (PTD), pPROM without ACA, pPROM with ACA. Activin A, follistatin, and nodal and cripto mRNA were measured by RT-PCR. RESULTS: Activin A mRNA was up-regulated in tissues from pPROM, in presence or absence of HCA, respect to PTD and in pPROM with ACA respect to pPROM without ACA. Follistatin mRNA expression did not differ between the groups. In placenta, nodal mRNA showed the same trend of activin A, while cripto was down-regulated in pPROM with ACA than other groups. Nodal and cripto were not expressed by fetal membranes. CONCLUSION: The study shows the involvement of activin A pathway in pPROM with ACA. Further studies will focus on its role in placental immune functions.

Correlation with placental kisspeptin in postterm pregnancy and apoptosis.

Postterm pregnancy represents a condition associated with trophoblast apoptosis. Kisspeptin is a peptide able to induce apoptosis by a specific receptor, GPR54, through the upregulation of proapoptotic genes. The aims of the study were to evaluate (1) the messenger RNA (mRNA) expression of kisspeptin, GPR54, Bax/Bcl2, and p21 in postterm placentas and (2) kisspeptin ability to act on apoptosis in the third trimester placental explants. Placental specimens were collected from spontaneous term and postterm delivery and kisspeptin, GPR54, Bax/Bcl2, and p21 mRNA expression levels were analyzed by real-time polymerase chain reaction. Placental explants, collected from elective term cesarean sections, treated with different doses of kisspeptin were analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of all the genes studied in postterm placentas were significantly higher than in-term placentas. Kisspeptin-induced apoptosis in placental explants with a dose-dependent effect, and TUNEL assay demonstrated the kisspeptin involvement in the apoptotic placental processes. Our present findings led us to hypothesize that kisspeptin may represent a placental proapoptotic agent acting in physiological and/or pathological pregnancy conditions in which placental apoptosis mechanisms are increased.

Neuroendocrine aspects of placenta and pregnancy.

Placenta plays a central role in the regulation of physiological mechanisms of pregnancy, and in particular is the organ of communication between mother and fetus. This action is also related to its ability to produce hormones, growth factors and cytokines during the progression of pregnancy, and in response to stimuli such as stress and inflammation/infection. In the last years the understanding of the physiological and pathological functions of human placenta revealed the hypersecretion of hormones in presence of gestational diseases and raised the question whether this mechanism is cause of disorders of pregnancy, or part of an adaptive response of placenta to resolve adverse conditions. However, there are evidences indicating that changes of placental hormone secretion may have clinical usefulness, since they are measurable in biological fluids, and may be used as predictive markers or prognostic tools. Of particular interest is the role of corticotropin releasing hormone, urocortins and activins in the maintaining physiological pregnancy and in the pathogenesis of diseases (preterm birth and preeclampsia).

The identification of high risk pregnancy: a new challenge in obstetrics.

Preterm delivery (PTD) and pre-eclampsia (PE) represent the main "obstetric syndromes," caused by multiple conditions, and characterized by complex pathogenesis. Nonetheless, recent evidences attest that deregulation of the immune system and exaggeration of inflammatory processes, taking place in the feto-placental unit, represent common central mechanisms occurring in both diseases. Tertiary prevention represents the only intervention to prevent PTD, but its incidence is still increasing. Advances in secondary prevention, focusing on risk factors and possible markers, are necessary.

Maternal serum protein S forms in pregnancies complicated by intrauterine growth restriction.

OBJECTIVES: The clinical relevance of protein S deficiency in pregnant women remains controversial. Major debate exists regarding which parameter (total protein S antigen, free protein S antigen or functional protein S) should be evaluated in order to define protein S deficiency. The present study aimed to identify which of these parameters correlate with intrauterine growth restriction (IUGR). STUDY DESIGN: A retrospective case-control study of women with IUGR (n=27) and healthy controls (n=123) in the third trimester of pregnancy. RESULTS: The maternal serum of women in the IUGR group had significantly lower levels of functional and free protein S compared with the control group: 54.07 ± 24.72% vs 65.20 ± 17.95% (p<0.005) and 42.88 ± 11.01% vs 56.64 ± 13.30% (p<0.0001), respectively. No significant correlation was found between total protein S and IUGR. CONCLUSIONS: Levels of functional and free protein S are correlated with IUGR.

Carbetocin versus oxytocin after caesarean section: similar efficacy but reduced pain perception in women with high risk of postpartum haemorrhage.

OBJECTIVE: To compare the effectiveness of carbetocin with oxytocin with respect to maintain adequate uterine tone and to reduce the incidence and severity of postpartum haemorrhage. Moreover safety, adverse effects and the need of additional medications were evaluated. METHODS: Prospective controlled clinical trial. We compared the effect of a single dose of carbetocin (n = 55) with oxytocin infusion (n = 55) in a women population undergoing to elective caesarean section with regional subarachnoid anaesthesia with at least one risk factor for postpartum haemorrhage. RESULTS: The mean ± SD of postoperative pain in the day of surgery in carbetocin group was significantly lower than in oxytocin group and remained significant till the third day after caesarean section. In the day of surgery and the first day after surgery, women of carbetocin group who needed analgesic drugs were significantly lower than women of oxytocin group. The differences of diuresis and of diuretic drugs need were not statistically significant between the two groups. CONCLUSIONS: A single carbetocin injection is efficacious and safe on the maintenance of uterine tone and on the limitation of blood losses, in peri- and in postoperative period. In addition, carbetocin was able to reduce pain perception during postoperative days improving quality life of women.

Maternal risk factors for preterm birth: a country-based population analysis.

OBJECTIVE: The aim of this study was to identify maternal risk factors for spontaneous preterm birth (PTB) compared to delivery at term, in order to recognize high risk women and to provide a global overview of the Italian situation. STUDY DESIGN: A multicenter, observational and retrospective, cross-sectional study was designed. The study population comprised 7634 women recruited in 9 different University Maternity Hospitals in Italy. The main criteria for inclusion were: women having had vaginal preterm or term spontaneous delivery in each participating centre during the study period. The records related to deliveries occurring between April and December 2008. A multivariable logistic regression was employed to identify independent predictors of spontaneous preterm birth. Odds ratios (ORs) and 95% confidence intervals (95% CI) were reported with two-tailed probability (p) values. Statistical calculations were carried out using SAS version 9.1. A two-tailed p-value of 0.05 was used to define statistical significant results. RESULTS: A significant increased risk of PTB was found in women with BMI>25 (OR=1.662; 95% CI=1.033-2.676; p-value=0.0365) and in women employed in heavy work (OR=1.947; 95% CI=1.182-3.207; p-value=0.0089). Moreover there was a significant association between PTB and previous reproductive history. In fact a history of previous abortion (OR=1.954; 95% CI=1.162-3.285; p-value=0.0116) or previous cesarean section (OR=2.904; 95% CI=1.066-7.910; p-value=0.0371) was positively correlated to the increased risk of PTB and an important statistically significant association was calculated between PTB and previous pre-term delivery (OR=3.412; 95% CI=1.342-8.676; p-value=0.0099). All the other covariates examined as potential risk factors for PTB were not found to be statistically significantly related (p-value>0.05). CONCLUSIONS: The present study, applied to a substantial sample of Italian population, demonstrates that there are peculiar risk factors for spontaneous PTB in the Italian population examined. It shows an association between preterm delivery and certain maternal factors as: BMI, employment, previous abortions, previous PTBs and previous cesarean section.