Peripartum and postpartum outcomes in uncomplicated term pregnancy following ART: a retrospective cohort study from two Italian obstetric units.

STUDY QUESTION: Do singleton uncomplicated term pregnancies conceived by assisted reproductive technology (ART) have adverse peripartum and postpartum outcomes? SUMMARY ANSWER: Term pregnancies following ART, even if uncomplicated until birth, have a higher risk of retained placenta and postpartum hemorrhage (PPH). WHAT IS KNOWN ALREADY: There is consistent evidence that pregnancies following ART have higher incidence of complications during pregnancy. However, few studies specifically investigated birth outcomes in ART term pregnancies. STUDY DESIGN SIZE DURATION: A retrospective cohort study was conducted on 14 415 deliveries at two university tertiary care obstetric units. Clinical data were extracted by reviewing obstetric records of all deliveries from 1 January 2010 to 31 December 2014, in a standardized electronic database regarding the mother's health before and during pregnancy, complications during pregnancy and at birth, and neonatal outcome. PARTICIPANTS/MATERIALS SETTING METHODS: Following an accurate evaluation of exclusion criteria (multiparity, maternal pre-pregnancy diseases, prior uterine surgery, fetal malformations, intrauterine deaths, elective cesarean section and pregnancy complications), the group of uncomplicated singleton term pregnancies from autologous ART conception by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (n = 188) was compared with a maternal age and body mass index (BMI) matched group of spontaneous pregnancies (n = 1168). Cases of intrauterine insemination (IUI) (n = 14) and ovulation induction with timed intercourse (n = 18) were not included. Labor, delivery and postpartum outcomes were evaluated. Odds ratios (OR) were adjusted with multivariable logistic regression to maternal age, BMI, nationality and gestational age at birth. MAIN RESULTS AND THE ROLE OF CHANCE: The age of women in the final analysis ranged from 25 to 45 years, while BMI ranged from 17 to 34 kg/m2. Uncomplicated term pregnancies with ART conception had a higher risk of operative delivery (adjusted OR 1.40, 95% confidence interval (CI) 1.01-1.95), retained placenta (adjusted OR 2.63, 95% CI 1.31-5.26) and PPH (adjusted OR 2.86 95% CI 1.37-5.99). Conversely, ART conception did not increase the risk of induced labor (adjusted OR 1.18, 95% CI 0.85-1.65). However, patients that conceived by ART and underwent labor induction had a higher risk of failed induction compared with the control group (adjusted OR 2.53, 95% CI 1.23-5.21). Infants born after ART had a similar birthweight, Apgar score and arterial blood pH compared with spontaneously-conceived ones. LIMITATIONS REASONS FOR CAUTION: The database lacked specific information about causes of infertility, smoking habit, family income and details on ART (fresh versus frozen cycle, IVF versus ICSI), limiting, in part, our analysis of the results. However, only autologous IVF/ICSI pregnancies were included in order to prevent bias related to conception by oocyte/embryo donation. In vivo conception ART cases were excluded because they were too few to allow comparison with IVF/ICSI. Nevertheless, the inclusion of only uncomplicated pregnancies provides a highly homogeneous and still representative population sample. Study sample is representative of a well-resourced obstetric facility in a high-income country, limiting to some extent the generalizability of study results. WIDER IMPLICATIONS OF THE FINDINGS: Pregnancies conceived by autologous ART that proceed uncomplicated until term may require counseling about the risk of placental retention with PPH. STUDY FUNDING/COMPETING INTERESTS: The authors have no conflict of interest and funding to declare.

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.

Preimplantation and prenatal diagnosis, wrongful birth and wrongful life: a global view of bioethical and legal controversies.

BACKGROUND: Prenatal diagnosis based on different technologies is increasingly used in developed countries and has become a common strategy in obstetric practice. The tests are crucial in enabling mothers to make informed decisions about the possibility of terminating pregnancy. They have generated numerous bioethical and legal controversies in the field of 'wrongful life' claims (action brought by or on behalf of a child against the mother or other people, claiming that he or she has to endure a not-worth-living existence) and 'wrongful birth' claims (action brought by the mother or parents against the physician for being burdened with an unwanted, often disabled child, which could have been avoided). OBJECTIVE AND RATIONALE: The possibility which exists nowadays to intervene actively by programming and deciding the phases linked to procreation and birth has raised several questions worldwide. The mother's right to self-determination could be an end but whether or not this right is absolute is debatable. Freedom could, with time, act as a barrier that obstructs intrusion into other people's lives and their personal choices. Therapeutic choices may be manageable in a liberal sense, and the sanctity of life can be inflected in a secular sense. These sensitive issues and the various points of view to be considered have motivated this review. SEARCH METHODS: Literature searches were conducted on relevant demographic, social science and medical science databases (SocINDEX, Econlit, PopLine, Medline, Embase and Current Contents) and via other sources. Searches focused on subjects related to bioethical and legal controversies in the field of preimplantation and prenatal diagnosis, wrongful birth and wrongful life. A review of the international state of law was carried out, focusing attention on the peculiar issue of wrongful life and investigating the different jurisdictional solutions of wrongful life claims in a comparative survey. OUTCOMES: Courts around the world are generally reluctant to acknowledge wrongful life claims due to their ethical and legal implications, such as existence as an injury, the right not to be born, the nature of the harm suffered and non-existence as an alternative to a disabled life. Most countries have rejected such actions while at the same time approving those for wrongful birth. Some countries, such as France with a law passed in March 2002, have definitively excluded Wrongful Life action. Only in the Netherlands and in three states of the USA (California, Washington and New Jersey) Wrongful Life actions are allowed. In other countries, such as Belgium, legislation is unclear because, despite a first decision of the Court allowing Wrongful Life action, the case is still in progress. There is a complete lack of case law regarding wrongful conception, wrongful birth and wrongful life in a few countries, such as Estonia. WIDER IMPLICATIONS: The themes of 'wrongful birth' and 'wrongful life' are charged with perplexing ethical dilemmas and raise delicate legal questions. These have met, in various countries and on certain occasions, with different solutions and have triggered ethical and juridical debate. The damage case scenarios result from a lack of information or diagnosis prior to the birth, which deprives the mother of the chance to terminate the pregnancy.

Twin pregnancies after assisted reproductive technologies: the role of maternal age on pregnancy outcome.

OBJECTIVES: Our aim was to investigate whether advanced maternal age (≥40years) still impairs the outcome of twin pregnancies after assisted reproductive techniques (ART). STUDY DESIGN: The retrospective observational study evaluated 430 nulliparous dichorionic diamniotic twin pregnancies conceived with ART. The population was divided into women <40 years old (Group A, n=265) and ≥40 years old (Group B, n=165). RESULTS: Gestational diabetes mellitus and gestational hypertension/preeclampsia were significantly more frequent in nulliparous twin pregnancies after ART ≥40years compared to <40years (p=0.021 and p<0.001, respectively). In univariate analysis of twin pregnancies after ART, there was only a trend of higher incidence of total preterm birth (PB) rate within mother aged ≥40 years old (p=0.104). However, Group A showed higher rate of spontaneous preterm birth (SPB) <37 weeks, whereas Group B showed significantly higher rate of iatrogenic PB <37 weeks of gestation (p=0.023 and p=0.001, respectively). For delivery <32 weeks of gestation, the rate of SPB in Group A was significantly higher (p=0.002). A higher incidence of PB was observed in Group B after heterologous treatment (p<0.001). Despite this, the absolute prevalence of PB in the entire population is higher in Group A, both after autologous (22.5%) and heterologous (25%) ART treatment, than in Group B (10.1% vs 21.4%). CONCLUSIONS: Our data indicate that nulliparous twin pregnancies conceived with ART in mothers ≥40 years old did not show significantly higher incidence of PB, even if an increased rate of iatrogenic PB <37 weeks is showed.

Endocrinology of human parturition.

The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. The "final common pathway" to delivery is composed by inflammatory and endocrine interactive paths that tip the balance in favor of coordinated uterine contractility and cervical dilation. These mechanisms involve a shift from progesterone to estrogen dominance, CRH action, increased sensitivity to oxytocin, gap junction formation, and increased prostaglandins activity. Complementary changes in the cervix involve a decrease in progesterone dominance and the actions of prostaglandins and relaxin, via connective tissue alterations, leading to cervical softening and dilation. Neuronal, hormonal, inflammatory and immune pathways participate in initiation of labor and the utero-placental unit plays a major role in the synthesis and release of parturition mediators.

Expression, localization and control of activin A release from human umbilical vein endothelial cells.

Activin-A is a member of the TGFß superfamily found in maternal and umbilical cord blood throughout gestation. We investigated whether human umbilical vein endothelial cells (HUVEC) express activin-A in vivo and tested the effects of vasoactive (endothelin-1), pro-inflammatory (interferon-γ, interleukin-8) and anti-inflammatory (dexamethasone, urocortin) factors on activin-A release by isolated HUVEC in vitro. Activin ßA subunit protein and mRNA were strongly localized in the endothelial cells of umbilical veins and were also detectable in scattered cells of the cord connective tissue. Dimeric activin-A was detected in the HUVEC culture medium at picomolar concentrations. Activin-A release by HUVEC decreased after cell incubation with urocortin (p < 0.01), whereas no effect was observed with interleukin-8, interferon-γ, endothelin-1 or dexamethasone. In summary, activin-A is present in the human umbilical vein endothelium in vivo and is produced and released by isolated HUVEC. Activin-A secretion is inhibited in vitro by urocortin, a neuropeptide with predominantly anti-inflammatory action.

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.

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.

Uterine fibroids affect pregnancy outcome in women over 30 years old: role of other risk factors.

OBJECTIVE: To evaluate the pregnancy outcome in women >30 years old with uterine fibroids also considering other possible concomitant risk factors. METHODS: A multicentric, observational and retrospective study was conducted. All women were asked to complete a questionnaire while they were in hospital and the outcome of pregnancy was investigated. RESULTS: Women with uterine fibroids before pregnancy were more frequently >35 years old and in their clinical history before pregnancy showed more pelvic pain, polliachiuria, previous pelvic surgery, hypermenorrhea and dysmenorrhea, than control women (p < 0.0001). During pregnancy patients with uterine fibroids showed significantly more threatened preterm birth (PTB) and PTB, weight gain, hyperemesis, gestational hypertension and post-partum bleeding and showed more often requirement for emergency cesarean section (p < 0.0001). The multivariate logistic regression model used for evaluating the effect of clinical parameters on outcome of pregnancy showed that age >35 years, pelvic pain, work, weight gain, hyperemesis, threatened miscarriage and threatened PTB were significantly correlated with unfavorable pregnancy outcome , independently of the presence of uterine fibroids (p < 0.0001). CONCLUSIONS: The present study confirming a more frequent negative pregnancy outcome in presence of uterine fibroids, showed that other risk factors may affect pregnancy and delivery outcome in women aging >30 years old.

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.

Ultrasound estimated fetal weight slightly below the median is associated with increased risk of spontaneous preterm birth.

BACKGROUND: This study investigates the possible relationship between ultrasound estimated fetal weight (EFW) at third trimester and the risk of preterm birth following spontaneous preterm labor in otherwise uncomplicated pregnancies. METHODS: We performed a nested case-control study including 281 cases of spontaneous preterm labor with preterm delivery in the third trimester and 3372 matched controls within a cohort of 6207 consecutive pregnant women. Pregnancies with fetal growth restriction (birth weight <10th centile of population-based normograms) or fetal anomalies were not included. EFW was calculated by using Hadlock's formula and converted to fetal gender adjusted multiples of median (MoM) for each gestational age. RESULTS: EFW correlated with birth weight (r = 0.959, p < 0.0001) and was lower in preterm than in control fetuses (p < 0.0001). The odds ratios (95% confidence intervals) for preterm birth for fetuses below 0.9 MoM, 0.85 MoM, 0.80 MoM, and 0.75 MoM of EFW were, respectively, 4.6 (3.6-5.9), 5.7 (4.3-7.5), 8.5 (5.9-12.1), and 11.2 (6.8-18.3). The independent relationship between preterm birth and lower EFW was confirmed in multivariate analysis with adjustment for potential confounders, such as maternal age, parity, and fetal gender. CONCLUSION: In asymptomatic women between 28 and 36 weeks of gestation, an EFW lower than 0.90 MoM increases by 4.6 times the risk of spontaneous preterm birth, and the risk increases proportionally to the degree of weight reduction.

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).

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.

Serum activin A levels are lower in tubal than intrauterine spontaneously conceived pregnancies.

OBJECTIVE: To measure serum activin A levels together with progesterone and hCG, in women with overt clinical signs and symptoms of ectopic pregnancy (EP) and, in gestational age-matched intrauterine pregnancy (IUP). DESIGN: Retrospective case-control study. SETTING: Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy. POPULATION: The study group was composed by 30 women with an EP; the control group was composed by 30 women with a sonographic evidence of a single spontaneous IUP. METHODS: Clinical examination; transvaginal ultrasound scan; hCG, progesterone and activin-A measurements; laparoscopy; uterine curettage; histological examination. MAIN OUTCOME MEASURE: Pregnancy outcome; sensitivity and specificity of hCG, progesterone, and activin A for EP. RESULTS: Serum hCG levels did not differ significantly between tubal EP and IUP, while P concentrations were significantly (P < 0.001) lower in tubal EP than IUP. Serum levels of activin A were significantly (P < 0.0001) lower in tubal EP than in IUP and, at the cutoff 0.43 ng/mL achieved a sensitivity of 96.7% and a specificity of 100% for EP. CONCLUSION: Activin A secretion in EP is reduced and measurement of its serum levels may have the potential clinical advantage to signal the presence of EP.

Efficacy of vaginal danazol treatment in women with menorrhagia during fertile age.

OBJECTIVE: To evaluate the clinical efficacy and patient satisfaction of danazol delivered vaginally as treatment for young women with menorrhagia. DESIGN: Prospective study. SETTING: University of Siena, Siena, Italy. PATIENT(S): Women with menorrhagia (n = 55; age range 25-35 years) after ultrasound and hysteroscopy. INTERVENTION(S): Low-dose danazol (200 mg/day) was daily administered by vaginal route for 6 months. MAIN OUTCOME MEASURE(S): Before and every month during the treatment women were requested: 1) to keep a diary of menstrual bleeding and to rate blood loss on a visual analog scale from 0 (no blood loss) to 10 (gushing-type bleeding); 2) to record side effects and their satisfaction with the therapy. Transvaginal ultrasound, blood count, serum chemistries, and serum concentration of LH, FSH, E(2), TSH, FT(3), FT(4), and PRL were evaluated before and after 6 months. RESULT(S): The severity of blood loss was significantly reduced in all of the women after 2 months of treatment. Uterine volume was significantly reduced, and hematocrit, hemoglobin, and red blood cell count increased in all of the women after 6 months. The medical treatment did not affect hormonal parameters, and menstrual cycle remained unaffected; few local vaginal adverse effects were recorded. CONCLUSION(S): Vaginal danazol resulted in effective medical treatment in young women with menorrhagia, and, because of a lack of significant adverse effects, it may be proposed as an alternative treatment.

The increase of blood flow in the fetal middle cerebral artery correlates with the onset of labor at term.

The objective of this cohort study is to evaluate the relationship between blood flow resistance in the fetal middle cerebral artery (MCA) and the beginning of spontaneous labor. A group of consecutive women (n = 664) with a singleton pregnancy was submitted to Doppler examination of fetal MCA between 24 and 41 weeks' gestation (median, 35 weeks). The study population was later divided into 2 groups according to the MCA pulsatility index (PI), expressed in multiples of the median (MoM) for each gestation week. The median time elapsed between the Doppler examination and the onset of spontaneous labor (which eventually occurred in 302 women, of whom 291 were at term) was significantly shorter in the group with MCA PI <0.74 MoM (5.5 days; interquartile interval, 2-10 days) than in the group with MCA PI >or=0.74 MoM (22.5 days; interquartile interval, 5-37.5 days; P < .001). Survival analysis and Cox regression confirmed that the MCA PI was independently associated with the number of days elapsed from Doppler to spontaneous labor (P < .001; Exp[B], 2.77; 95% confidence interval, 1.95-3.90) after correction for birth weight and umbilical artery PI. The present data suggest that, at term of pregnancy, a gestation-independent decrease of fetal cerebral vascular resistance precedes the onset of spontaneous labor.

Prenatal diagnosis and multidisciplinary approach to the congenital gingival granular cell tumor.

OBJECTIVE: Congenital gingival granular cell tumor (CGCT) is a rare benign lesion appearing at birth on the alveolar median ridge of the maxilla. Etiology is still unclear because spontaneous regression of the lesion is rare. METHODS: The present report describes 2 cases of neonatal CGCT, highlighting benefits of ultrasonography to treatment of the prenatally diagnosed lesion. RESULTS: The patients immediately underwent surgical exeresis. Pathology revealed a tumor of large polyedric cells with vacuolar central nuclei and eosinophil granular cytoplasm. CONCLUSIONS: Prenatal diagnosis is fundamental in the therapeutic approach to CGCT: ultrasonography methodologies allow diagnosis of the lesion in the uterus at the 36th gestational week, thus also allowing planning of delivery and, immediately later, the surgical treatment. That permits planning of delivery in a third-level center with considerable benefit for both the mother and the newborn.

Low-molecular-weight heparin improves the performance of uterine artery Doppler velocimetry to predict preeclampsia and small-for-gestational age infant in women with gestational hypertension.

This study investigated whether a short course of subcutaneous low-molecular-weight heparin (LMWH) might modify the performance of uterine artery Doppler to predict preeclampsia and small-for-gestational age (SGA) newborns in a high-risk population. A controlled, open-labeled study included 94 women with gestational hypertension and 30 healthy women enrolled at 24 to 26 weeks gestation. Doppler evaluation of uterine arteries resistance index (RI) was performed before and after a two-week course of LMWH (enoxaparin, 4000 IU/d, n = 56 hypertensive patients) or no treatment (n = 38 hypertensive women and 30 healthy controls). There was a significant decrease of uterine artery RI after LMWH (p < 0.001, paired Student's t-test), whereas the untreated hypertensive patients and the healthy control group showed no change between the two Doppler evaluations. The change induced by LMWH was restricted to women with normal outcome, whose RI decreased from (mean +/- standard error) 0.62 +/- 0.01 to 0.56 +/- 0.01 (p < 0.0001). By consequence, the second RI measurement, performed after LMWH administration, had fewer false positive results and higher positive likelihood ratios (LR+) to predict both preeclampsia (LR + 5.91) and SGA (LR + 4.69) compared with the first Doppler examination (LR + 1.97 and 2.22, respectively). Thus, LMWH improved the performance of uterine artery RI to predict preeclampsia and SGA in women with gestational hypertension.