Ultrasound prediction of fetal macrosomia in pregnancies complicated by diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of ultrasound in identifying fetuses with macrosomia in pregnancies complicated by gestational or pregestational diabetes. METHODS: Medline, Embase and Cochrane databases were searched. Inclusion criteria were singleton pregnancies complicated by diabetes undergoing third-trimester ultrasound evaluation. The index test was represented by ultrasound estimation of fetal macrosomia (estimated fetal weight EFW or abdominal circumference AC >90th or 95th percentile). Subgroup analyses were also performed. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were computed using the hierarchical summary receiver-operating characteristics model. RESULTS: Twenty studies were included in the systematic review including 8,530 pregnancies complicated by diabetes. Ultrasound showed an overall moderate accuracy in identifying fetuses with macrosomia with a sensitivity of 71.2 % (95 % CI 63.1-78.2), a specificity of 88.6 % (95 % CI 83.9-92.0). The interval between ultrasound and birth of two weeks showed the highest sensitivity and specificity (71.6 %, 95 % CI 47.9-87.3 and 91.7, 95 % CI 86.2-95.5). EFW sensitivity and specificity were 76.6 % (95 % CI 70.1-82.3) and 82.9 % (95 % CI 80.9-84.8), while AC 84.8 % (95 % CI 78.2-90.0) and 73.7 % (95 % CI 71.0-76.4). CONCLUSIONS: Ultrasound demonstrates an overall good diagnostic accuracy in detecting fetal macrosomia in pregnancies with diabetes.

A national survey on current practice of ultrasound in labor ward.

OBJECTIVES: Use of ultrasonography has been suggested as an accurate adjunct to clinical evaluation of fetal position and station during labor. There are no available reports concerning its actual use in delivery wards. The aim of this survey was to evaluate the current practice regarding the use of ultrasonography during labor. METHODS: A questionnaire was sent to members of the Italian Society of Ultrasound in Obstetrics and Gynecology employed in delivery wards. The qFeuestionnaire was made up of 22 questions evaluating participant characteristics and the current use of ultrasound in labor in their hospital of employment. The answers were grouped according to participant characteristics. RESULTS: A total of 200 participants replied. Ultrasound was considered useful before an operative vaginal delivery by 59.6 % of respondents, while 51.8 and 52.5 % considered it useful in the management of prolonged first and second stages of labor, respectively. The major indication for ultrasound use during labor was the assessment of fetal occiput position. The major difficulties in its application were the perceived lack of training and the complexity of the ultrasound equipment use. Participants that reported fewer difficulties were those employed in hospitals with a higher number of deliveries or having delivery units with more years of experience using ultrasound in labor, or those who had attended specific training courses. CONCLUSIONS: The results indicate that, despite the reported evidence of a higher accuracy of ultrasound compared to clinical evaluation in assessing fetal position and station, its use is still limited, even amongst maternal-fetal medicine practitioners specialized in ultrasonography.

Third Trimester Myocardial Performance Index in Fetuses from Women with Hyperglycemia in Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: The myocardial performance index (MPI) has been proposed to evaluate cardiac dysfunction in newborns from diabetic mothers. Although MPI is routinely assessed in newborns, its role in the evaluation of fetuses from women with hyperglycemia in pregnancy (HIP) is still under evaluation. We aimed to evaluate the differences in third trimester fetal MPI in pregnant women with hyperglycemia compared to healthy controls. MATERIALS AND METHODS: Seven electronic databases were searched for all studies assessing women with HIP who underwent evaluation of fetal left MPI during pregnancy compared to a control group. The summary measures were reported as mean differences (MD) in the mean fetal left MPI between women with HIP and healthy controls, with a 95 % confidence interval (CI). A post hoc subgroup analysis based on the type of HIP - pregestational diabetes, GDM, or gestational impaired glucose tolerance (GIGT) - was performed as an additional analysis. RESULTS: 14 studies assessing 1326 fetuses (580 from women with HIP and 746 from controls) were included. Women with HIP had a significantly higher mean left fetal MPI compared to controls (MD 0.08; 95 %CI: 0.05 to 0.11; p < 0.00 001). Subgroup analysis according to the type of HIP concurred with the overall analysis for women with DM (MD 0.07; 95 %CI: 0.01 to 0.13; p = 0.02) and for women with GDM (MD 0.012; 95 %CI: 0.07 to 0.17; p < 0.00 001) but not for women with GIGT (MD -0.01, 95 % CI -0.28 to 0.27; p = 0.96). CONCLUSION: Fetal left MPI is increased in pregnancies with HIP appearing as a potential marker of cardiac dysfunction.

The role of ultrasound in the diagnosis and management of postpartum hemorrhage.

Postpartum hemorrhage (PPH) is the leading cause of death or severe morbidity for the mother after delivery. As a consequence healthcare staff working in the delivery room should be trained to perform a prompt diagnosis and adequate management of PPH. Uneventful outcome is induced correct identification of the underlying cause of hemorrhage. Ultrasound is a promising technique for the prompt diagnosis of PPH etiology. Indeed, it is easily available, with relatively low cost, not using ionizing radiation, and can be used in different settings including the labor room, the operating theater and at the bedside of an affected women. In order to be effective Obstetricians should have an adequate knowledge of postpartum ultrasonography. In this article, we will review the sonographic findings occurring in PPH, in the differential diagnosis of the underlying cause of hemorrhage, that include retained placenta, morbidly adherent placenta, rupture of the uterus uterine, vascular anomalies of the uterine arteries and uterine inversion. We will also provide an algorithm to manage PPH according to the ultrasonographic findings.

Fetal brain biometry and cortical development after maternal SARS-CoV-2 infection in pregnancy: A prospective case-control study.

OBJECTIVES: To assess cerebral growth and the development of fetal cortex using neurosonography in fetuses from pregnancies experiencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) according to infection timing. METHODS: Pregnancies with by SARS-CoV-2 during first and second trimesters were prospectively studied and matched with unaffected controls. Enclosed women underwent neurosonography at 30-34 weeks of gestation and corpus callosum (CC) and cerebellar vermis (CV) lengths measured. Further Sylvian fissure (SF), insula. Parieto-occipital fissure (POF), and calcarine sulci fissures (CSF) depths were obtained. The ultrasonographic variables considered were normalized with fetal head size. RESULTS: One hundred and seventy four consecutive pregnancies experiencing SARS COV 2 infection (81 before 14 weeks and 93 later) and 131 not affected pregnancies were considered. General and pregnancy characteristics were similar between the three groups of women. No significant differences existed in CC and CV lengths across groups. Similarly, insula, SF, POF And CSF depth did not result changed in fetuses of affected mothers. CONCLUSIONS: SARS-CoV-2 infection does nor resulted associate with differential fetal cortical development or brain growth in mildly symptomatic pregnant women. This information may be useful to reassure infected mothers on the health of their fetuses.

Ectrodactyly-ectodermal dysplasia-clefting syndrome. Prenatal prospective ultrasound diagnosis.

OBJECTIVE: Prenatal diagnosis of the Ectrodactyly-Ectodermal dysplasia-clefting (EEC) syndrome has been based upon the detection of ectrodactyly, in association with facial clefting and/or positive family history. Our aim is to describe other ultrasonographic features indicating the presuntive diagnosis, regardless of genetic diagnosis, especially in cases of negative family history. MATERIALS AND METHODS: A case report and a review of the literature was assessed. RESULTS: Our case report showed a singleton foetus "lobster claw" deformities of hands and feet. Paternal history revealed bilateral agenesia of two fingers. Through literature, 15 case reports of prenatal diagnosis of EEC syndrome were found, 14 of which were eligible for our systematic review. The 33% of cases (5/15) had a familiar history of EEC, thus, we found one case of consanguinity of parents. Anomalies EEC-related were recognized in the 40% of cases (6/15). An association with genitourinary anomalies was found in 30% (5/15) of them. CONCLUSIONS: A strong suspicion of final diagnosis of EEC may be done in the presence of ectrodactyly, facial clefting and urinary malformation especially in cases of negative family history. More attention should be given to a genetic counseling, especially to understand a possible relation to other genetic syndromes.

BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status.

BACKGROUND: Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. METHODS: Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. RESULTS: We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ2 = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ2 = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027-20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084-42.476; p = 0.041). CONCLUSIONS: In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

Obstetric A&E unit admission and hospitalization for obstetrical management during COVID-19 pandemic in a third-level hospital of southern Italy.

BACKGROUND: The COronaVIrus Disease 2019 (COVID-19) has spread in Italy since February 2020, inducing the government to call for lockdown of any activity, apart primary needs, during the months March-May 2020. During the lockdown, a reduction of admissions and hospitalizations for ischemic diseases was noticed. Purpose of this study was to observe if there has been the same reduction trend in Accident & Emergency (A&E) unit admissions also for obstetric-gynecological conditions. METHODS: Medical records and electronic clinical databases were searched for all patients who were admitted to the obstetric A&E department or hospitalized at the Gynecology and Obstetrics Unit of University hospital of Naples Federico II, during the quarter March-May in the years 2019 and 2020. The mean ± standard deviation (SD) of monthly admission to the obstetric A&E department and hospitalization of the year 2020 was compared with that of the year 2019, using the unpaired T test with α error set to 0.05 and 95% confidence intervals (95% CI). RESULTS: Admissions were 1483 in the year 2020 and 1786 in 2019. Of total, 1225 (37.5%) women were hospitalized: 583 in the year 2020, 642 in 2019. Mean ± SD of patients monthly admitted to our obstetric A&E department was 494 ± 33.7 in the year 2020, and 595.3 ± 30.9 in 2019, with a mean difference of - 101.3 (95% CI - 103.5 to - 99.1; p < 0.0001). Mean ± SD of patients monthly hospitalized to our department was 194 ± 19.1 in the year 2020, 213.7 ± 4.7 in 2019, with a mean difference of - 19.7 (95% CI - 23.8 to - 15.6; p < 0.0001). CONCLUSION: A significant decrease in the mean of monthly admissions and hospitalizations during the COVID-19 pandemic when compared to the previous year was found also for obstetric-gynecological conditions. Further studies are necessary to assess COVID-19 impact and to take the most appropriate countermeasures.

Preliminary Characterization of the Epigenetic Modulation in the Human Mesenchymal Stem Cells during Chondrogenic Process.

Regenerative medicine represents a growing hot topic in biomedical sciences, aiming at setting out novel therapeutic strategies to repair or regenerate damaged tissues and organs. For this perspective, human mesenchymal stem cells (hMSCs) play a key role in tissue regeneration, having the potential to differentiate into many cell types, including chondrocytes. Accordingly, in the last few years, researchers have focused on several in vitro strategies to optimize hMSC differentiation protocols, including those relying on epigenetic manipulations that, in turn, lead to the modulation of gene expression patterns. Therefore, in the present study, we investigated the role of the class II histone deacetylase (HDAC) inhibitor, MC1568, in the hMSCs-derived chondrogenesis. The hMSCs we used for this work were the hMSCs obtained from the amniotic fluid, given their greater differentiation capacity. Our preliminary data documented that MC1568 drove both the improvement and acceleration of hMSCs chondrogenic differentiation in vitro, since the differentiation process in MC1568-treated cells took place in about seven days, much less than that normally observed, namely 21 days. Collectively, these preliminary data might shed light on the validity of such a new differentiative protocol, in order to better assess the potential role of the epigenetic modulation in the process of the hypertrophic cartilage formation, which represents the starting point for endochondral ossification.

Noninvasive screening for congenital heart defects using a serum metabolomics approach.

OBJECTIVE: Heart anomalies represent nearly one-third of all congenital anomalies. They are currently diagnosed using ultrasound. However, there is a strong need for a more accurate and less operator-dependent screening method. Here we report a metabolomics characterization of maternal serum in order to describe a metabolomic fingerprint representative of heart congenital anomalies. METHODS: Metabolomic profiles were obtained from serum of 350 mothers (280 controls and 70 cases). Nine classification models were built and optimized. An ensemble model was built based on the results from the individual models. RESULTS: The ensemble machine learning model correctly classified all cases and controls. Malonic, 3-hydroxybutyric and methyl glutaric acid, urea, androstenedione, fructose, tocopherol, leucine, and putrescine were determined as the most relevant metabolites in class separation. CONCLUSION: The metabolomic signature of second trimester maternal serum from pregnancies affected by a fetal heart anomaly is quantifiably different from that of a normal pregnancy. Maternal serum metabolomics is a promising tool for the accurate and sensitive screening of such congenital defects. Moreover, the revelation of the associated metabolites and their respective biochemical pathways allows a better understanding of the overall pathophysiology of affected pregnancies.

An integrated approach based on advanced CTG parameters and Doppler measurements for late growth restriction management.

BACKGROUND: The clinical diagnosis of late Fetal Growth Restriction (FGR) involves the integration of Doppler ultrasound data and Fetal Heart Rate (FHR) monitoring through computer assisted computerized cardiotocography (cCTG). The aim of the study was to evaluate the diagnostic power of combined Doppler and cCTG parameters by contrasting late FGR -and healthy controls. METHODS: The study was conducted from January 2018 to May 2020. Only pregnant women who had the last Doppler measurement obtained within 1 week before delivery and cCTG performed within 24 h before delivery were included in the study. Two hundred forty-nine pregnant women fulfilling the inclusion criteria were enrolled in the study; 95 were confirmed as late FGR and 154 were included in the control group. RESULTS: Among the extracted cCTG parameters, Delta Index, Short Term Variability (STV), Long Term Variability (LTV), Acceleration and Deceleration Phase Rectified Slope (APRS, DPRS) values were lower in the late FGR participants compared to the control group. In the FGR cohort, Delta, STV, APRS, and DPRS were found different when stratifying by MCA_PI (MCA_PI <5th centile or > 5th centile). STV and DPRS were the only parameters to be found different when stratifying by (UA_PI >95th centile or UA_PI <95th centile). Additionally, we measured the predictive power of cCTG parameters toward the identification of associated Doppler measures using figures of merit extracted from ROC curves. The AUC of ROC curves were accurate for STV (0,70), Delta (0,68), APRS (0,65) and DPRS (0,71) when UA_PI values were > 95th centile while, the accuracy attributable to the prediction of MCA_PI was 0.76, 0.77, 0.73, and 0.76 for STV, Delta, APRS, and DPRS, respectively. An association of UA_PI>95th centile and MCA_PI<5th centile with higher risk for NICU admission, was observed, while CPR < 5th centile resulted not associated with any perinatal outcome. Values of STV, Delta, APRS, DPRS were significantly lower for FGR neonates admitted to NICU, compared with the uncomplicated FGR cohort. CONCLUSIONS: The results of this study show the contribution of advanced cCTG parameters and fetal Doppler to the identification of late FGR and the association of those parameters with the risk for NICU admission. TRIAL REGISTRATION: Retrospectively registered.

Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study.

INTRODUCTION: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction. MATERIAL AND METHODS: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data. RESULTS: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001). CONCLUSIONS: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

INTRODUCTION: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. METHODS: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission). RESULTS: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. CONCLUSION: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.

First trimester detection of fetal open spina bifida using BS/BSOB ratio.

BACKGROUND: Despite the well-known second trimester ultrasound signs, current possibilities of in utero surgical repair of open spina bifida require a timely detection of the spine defect. OBJECTIVE: To evaluate the diagnostic accuracy of the ratio between brain stem (BS) diameter and its distance to the occipital bone (BSOB) (BS/BSOB ratio) in the detection of fetuses with open spina bifida at first trimester ultrasound. METHODS: A systematic review and meta-analysis of diagnostic accuracy was performed by searching seven electronic databases from their inception to February 2019 for all studies assessing the association between BS/BSOB ratio and diagnosis of spine bifida. Diagnostic accuracy of BS/BSOB ratio in prenatal diagnosis of spine bifida was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR + and LR-), and area under the curve (AUC) on SROC curves. RESULTS: Four studies, including 17,598 fetuses with 23 cases of open spina bifida, were included in the meta-analysis. BS/BSOB ratio showed pooled sensitivity of 0.70 (95% CI 0.47-0.87; I2 = 78.3%), specificity of 1.00 (95% CI 0.99-1.0; I2 = 99.2%), LR + and LR- of 51.44 (95% CI 9.53-277.64; I2 = 85.5%) and 0.23 (95% CI 0.04-1.17; I2 = 64.8%), respectively, and an AUC of 0.9649. CONCLUSION: First trimester BS/BSOB ratio has a high diagnostic accuracy in detecting fetuses with open spina bifida.

Sexual Intercourse for Induction of Spontaneous Onset of Labor: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Sexual intercourse during pregnancy is commonly believed to trigger the onset of contractions and, therefore, labor. However, in low-risk pregnancies, there is neither association with preterm birth, premature rupture of membranes, or low birth weight, nor with spontaneous onset of labor at term. AIM: To evaluate the effectiveness of sexual intercourse for spontaneous onset of labor at term in singleton pregnancies. METHODS: The systematic search was conducted using electronic databases from inception of each database to June 2019. Review of articles also included the abstracts of all references retrieved from the search. Inclusion criteria were randomized controlled trials comparing sexual intercourse in singleton low-risk pregnancies at term with controls (either reduced number of coitus or no coitus) for spontaneous onset of labor. Estimates were pooled using random-effects meta-analysis. MAIN OUTCOME MEASURES: The primary outcome was the incidence of spontaneous onset of labor. The summary measures were reported as summary relative risk with 95% CI using the random-effects model of DerSimonian and Laird. RESULTS: Data extracted from 3 trials, including 1,483 women with singleton pregnancy at term and cephalic presentation, were analyzed. Women who were randomized in the sexual intercourse group had similar incidence of spontaneous onset of labor compared with control subjects (0.82% vs 0.80%; relative risk 1.02, 95% CI 0.98-1.07). CLINICAL IMPLICATION: Sexual intercourse should not be restricted in low-risk term pregnancies. Further studies are needed to properly evaluate the impact of orgasm, penetration, condom use, frequency of intercourse and other factors on induction of labor at term. STRENGTH & LIMITATIONS: Our study has several strengths. The three included trials had low risk of allocation bias; intention-to-treat analysis was used; this is the first meta-analysis on this issue so far. Limitations mainly depend on the design of the included studies. Firstly, compliance to the protocol relied on self-reporting by patients; in addition, not all the features of sexual intercourse could be adequately assessed (orgasm, nipple stimulation, sexual positions, etc.). CONCLUSION: In women with singleton, cephalic, low-risk pregnancies, sexual intercourse at term does not significantly increase the incidence of spontaneous onset of labor. Carbone L, De Vivo V, Saccone G, et al. Sexual Intercourse for Induction of Spontaneous Onset of Labor: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Sex Med 2019;16:1787-1795.

Serum metallome in pregnant women and the relationship with congenital malformations of the central nervous system: a case-control study.

BACKGROUND: Congenital malformations of the central nervous system (CNS) consist of a wide range of birth defects of multifactorial origin. METHODS: Concentrations of 44 metals were determined by Inductively Coupled Plasma Mass Spectrometry in serum of 111 mothers in the second trimester of pregnancy who carried a malformed fetus and compared them with serum concentrations of the same metals in 90 mothers with a normally developed fetus at the same week of pregnancy. Data are reported as means ± standard deviations. RESULTS: We found a direct relationship between congenital defects of the CNS and maternal serum concentration of aluminum: it was statistically higher in women carrying a fetus with this class of malformation, compared both to mothers carrying a fetus with another class of malformation (6.45 ± 15.15 µg/L Vs 1.44 ± 4.21 µg/L, p < 0.0006) and to Controls (i.e. mothers carrying a normally-developed fetus) (6.45 ± 15.15 µg/L Vs 0.11 ± 0.51 µg/L, p < 0.0006). Moreover, Aluminum abundances were below the limit of detection in the majority of control samples. CONCLUSION: CAluminum may play a role in the onset of central nervous system malformations, although the exact Aluminum species and related specific type of malformation needs further elucidation.

Induction of labor at full-term in pregnant women with uncomplicated singleton pregnancy: A systematic review and meta-analysis of randomized trials.

INTRODUCTION: The lowest incidence of perinatal morbidity and mortality occurs around 39-40 weeks. Therefore, some have advocated induction of uncomplicated singleton gestations once they reach full-term. The aim of the study was to evaluate the risk of cesarean delivery, and any maternal and perinatal effects of a policy of induction of labor in women with full-term uncomplicated singleton gestations. MATERIAL AND METHODS: We performed an electronic search from inception of each database to August 2018. All results were then limited to randomized trial. No restrictions for language or geographic location were applied. Inclusion criteria were randomized clinical trials of asymptomatic women with uncomplicated, singleton gestations at full-term (ie, between 39+0 and 40+6  weeks) who were randomized to either planned induction of labor or control (ie, expectant management). Only trials on asymptomatic singleton gestations without premature rupture of membranes or any other indications for induction evaluating the effectiveness of planned induction of labor in full-term singleton gestations were included. The primary outcome was the incidence of cesarean delivery. RESULTS: Seven randomized clinical trials, including 7598 participants were analyzed. Three studies enrolled only women with favorable cervix, defined as a Bishop score of ≥5 in nulliparous women or ≥4 in multiparous women. One trial included only women aged 35 years or older. Women randomized to the planned induction of labor, received scheduled induction usually at 39+0 to 39+6  weeks of gestation, whereas women in the control group received expectant management usually until 41-42 weeks of gestation, or earlier if medically indicated. Methods of induction usually included cervical ripening, with either misoprostol or Foley catheter, in conjunction with or followed by oxytocin for women with unfavorable cervix, and oxytocin and artificial rupture of membranes for those with favorable cervix. Five trials also used artificial rupture of membranes as a method for induction. Uncomplicated full-term singleton gestations that were randomized to receive induction of labor had similar incidence of cesarean delivery compared with controls (18.6% vs 21.4%; relative risk 0.96, 95% CI 0.78-1.19). Regarding neonatal outcomes, induction of labor at full-term was associated with a significantly lower rate of meconium-stained amniotic fluid (4.0% vs 13.5%; relative risk 0.32, 95% CI 0.18-0.57), and lower mean birthweight (mean difference -98.96 g, 95% CI -126.29 to -71.63) compared with the control group. There were no between-group differences in other adverse neonatal outcomes. CONCLUSIONS: Induction of labor at about 39 weeks is not associated with increased risk of cesarean delivery.

Fetal heart rate monitoring and neonatal outcome in a population of early- and late-onset intrauterine growth restriction.

AIM: The early-onset intrauterine growth restriction (IUGR) is associated with severe placental insufficiency and Doppler abnormalities. The late-onset IUGR is associated with mild placental insufficiency and normal Doppler velocimetry. The computerized cardiotocographic (cCTG) monitoring is used to evaluate the fetal well-being in pregnancies complicated by IUGR. Our aim was to investigate the cardiotocographic characteristics of IUGR fetuses and to identify every cCTG difference between Healthy and IUGR fetuses. METHODS: Four hundred thirty pregnant women were enrolled starting from the 28th week of gestation until the time of delivery: 200 healthy and 230 IUGR fetuses. Fetal heart rate (FHR) baseline (FHR), short-term variability (STV), long-term irregularity (LTI), delta, interval index (II), approximate entropy (ApEn), high frequency (HF), low frequency (LF), movement frequency (MF), LF/(HF + MF) ratio (LF/(HF + MF)) and number of decelerations were examined. Newborn baby data were also collected. RESULTS: The parameters of short- and medium-term variability discriminate between IUGR and healthy fetuses before 36 weeks including FHR, STV, LTI and delta discriminate between each subgroup of IUGR were compared to each one of the other two (P < 0.05). CONCLUSION: cCTG is a useful tool for the evaluation of chronic hypoxemia, which causes a delay in the maturation of all components of the autonomic and central nervous system. However, cCTG requires integration with fetal ultrasound and Doppler vessels evaluation to improve the ability to predict the neonatal outcome.

Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study.

BACKGROUND: Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti-ß2 glycoprotein-I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well-established. OBJECTIVE: The purpose of this study was to assess the risk of obstetric complications in women with primary antiphospholipid syndrome that is associated with specific antibody profile. STUDY DESIGN: The Pregnancy In Women With Antiphospholipid Syndrome study is a multicenter, retrospective, cohort study. Diagnosis and classification of antiphospholipid syndrome were based on the 2006 International revised criteria. All women included in the study had at least 1 clinical criteria for antiphospholipid syndrome, were positive for at least 1 antiphospholipid antibody (anticardiolipin antibodies, anti-ß2 glycoprotein-I, and/or lupus anticoagulant), and were treated with low-dose aspirin and prophylactic low molecular weight heparin from the first trimester. Only singleton pregnancies with primary antiphospholipid syndrome were included. The primary outcome was live birth, defined as any delivery of a live infant after 22 weeks gestation. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction, and stillbirth. We planned to assess the outcomes that are associated with the various antibody profile (test result for lupus anticoagulant, anticardiolipin antibodies, and anti-ß2 glycoprotein-I). RESULTS: There were 750 singleton pregnancies with primary antiphospholipid syndrome in the study cohort: 54 (7.2%) were positive for lupus anticoagulant only; 458 (61.0%) were positive for anticardiolipin antibodies only; 128 (17.1%) were positive for anti-ß2 glycoprotein-I only; 90 (12.0%) were double positive and lupus anticoagulant negative, and 20 (2.7%) were triple positive. The incidence of live birth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared with women with only 1 antibody positive test results, women with multiple antibody positive results had a significantly lower live birth rate (40.9% vs 56.6%; adjusted odds ratio, 0.71; 95% confidence interval, 0.51-0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; adjusted odds ratio, 1.56; 95% confidence interval, 1.22-1.95) and with severe features (22.7% vs 13.8%, adjusted odds ratio, 1.66; 95% confidence interval, 1.19-2.49), of intrauterine growth restriction (53.6% vs 40.8%; adjusted odds ratio, 2.31; 95% confidence interval, 1.17-2.61) and of stillbirth (36.4% vs 21.7%; adjusted odds ratio, 2.67; 95% confidence interval, 1.22-2.94). In women with only 1 positive test result, women with anti-ß2 glycoprotein-I positivity present alone had a significantly lower live birth rate (47.7% vs 56.3% vs 79.6%; P<.01) and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; P<.01) and with severe features (17.2% vs 14.4% vs 0%; P=.02), intrauterine growth restriction (48.4% vs 40.1% vs 25.9%; P<.01), and stillbirth (29.7% vs 21.2% vs 7.4%; P<.01) compared with women with anticardiolipin antibodies and with women with lupus anticoagulant present alone, respectively. In the group of women with >1 antibody positivity, triple-positive women had a lower live birth rate (30% vs 43.3%; adjusted odds ratio,0.69; 95% confidence interval, 0.22-0.91) and a higher incidence of intrauterine growth restriction (70.0% vs 50.0%; adjusted odds ratio,2.40; 95% confidence interval, 1.15-2.99) compared with double positive and lupus anticoagulant negative women. CONCLUSION: In singleton pregnancies with primary antiphospholipid syndrome, anticardiolipin antibody is the most common sole antiphospholipid antibody present, but anti-ß2 glycoprotein-I is the one associated with the lowest live birth rate and highest incidence of preeclampsia, intrauterine growth restriction, and stillbirth, compared with the presence of anticardiolipin antibodies or lupus anticoagulant alone. Women with primary antiphospholipid syndrome have an increased risk of obstetric complications and lower live birth rate when <1 antiphospholipid antibody is present. Despite therapy with low-dose aspirin and prophylactic low molecular weight heparin, the chance of a liveborn neonate is only 30% for triple-positive women.