Le morti in utero: risultati di un progetto pilota di sorveglianza della mortalità perinatale in Italia (SPItOSS).

OBJECTIVES: to describe the results of a pilot population-based perinatal mortality surveillance system, with regards to stillbirths; to study maternal, obstetric, and foetal characteristics, evaluating risk factors and understanding causes. DESIGN: a cross-sectional study was conducted on incident cases of stillbirths collected by the surveillance system from July 2017 to June 2019 in three Italian Regions (Lombardy, Tuscany, and Sicily). SETTING AND PARTICIPANTS: data on stillbirths, resulting from the in-hospital multidisciplinary audits, organised using the Significant Event Audit methodology, were analysed. According to the World Health Organization (WHO) definitions, the project identified stillbirths as foetuses born dead >=28 weeks of gestation. The WHO International Classification of Diseases-Perinatal Mortality was used to categorise the causes of foetal death. MAIN OUTCOMES MEASURES: maternal characteristics, obstetric and foetal findings were investigated. Unadjusted relative risks and 95% confidence intervals were computed with respect to the background population. Finally, causes of death and contributing maternal conditions have been considered. RESULTS: the maternity and neonatal units of the three participating Regions notified 520 stillbirths, of which 435 cases underwent to the multidisciplinary audit (83.7%); 40.0% of cases occurred in the gestational age range between 36 and 39 weeks. The risk of stillbirth was significantly increased in mothers with foreign citizenship (RR: 1.39; 95%CI: 1.13-1.71), multiple pregnancies (RR: 1.59; 95%CI 1.05-2.42), and pregnancies conceived with assisted reproductive technologies (RR: 2.15; 95%CI 1.45-3.19). The rate of congenital malformations was 6.0%. A diagnosis of foetal growth restriction was reported in 10.3% of cases, although the percentage of dead foetuses weighting <10° centile was at least twice in almost all gestational age periods. Post-mortem and placental histological examinations were carried out in more than 70% and more than 90% of cases, respectively. CONCLUSIONS: the implementation of a population-based surveillance system with high participation rate of maternity units and the use of universally accepted definitions could improve the identification of stillbirth avoidable risk factors and potentially modifiable predisposing maternal conditions, highlighting issues of perinatal assistance in need of improvement.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

Association of intrauterine growth restriction and low birth weight with acute kidney injury in preterm neonates.

BACKGROUND: Preterm birth alters nephrogenesis and reduces the total nephron number. Intrauterine growth restriction (IUGR) seems to worsen nephron loss, but only a few studies have investigated its role in neonatal kidney impairment. We investigated whether IUGR, defined as reduced estimated fetal growth and/or placental flow alterations and low birth weight z-score, increases the risk of developing acute kidney injury (AKI) in very preterm infants. METHODS: We performed a retrospective study including infants born with a birth weight (BW) ≤ 1500 g and/or gestational age (GA) ≤ 32 weeks admitted to our center between January 2016 and December 2021. Neonatal AKI was defined according to the neonatal KDIGO classification based on the decline of urine output and/or creatinine elevation. We used multivariable linear regressions to verify the association between AKI and GA, BW z-score, IUGR definition, and hemodynamically significant patent ductus arteriosus (PDA). RESULTS: We included 282 infants in the analysis, with a median (IQR) GA = 29.4 (27.4, 31.3) weeks, BW = 1150 (870, 1360) g, and BW z-score = - 0.57 (- 1.64, 0.25). AKI was diagnosed in 36 (13%) patients, and 58 (21%) had PDA. AKI was significantly associated with BW z-score (beta (std. error) = - 0.08 (0.03), p = 0.008) and severe IUGR (beta (std. error) = 0.21 (0.08), p = 0.009), after adjusting for GA and PDA. CONCLUSIONS: Our data suggest that low BW z-score and IUGR could represent adjunctive risk factors for kidney impairment in preterm babies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Isolation of single circulating trophoblasts from maternal circulation for noninvasive fetal copy number variant profiling.

OBJECTIVE: To develop a multi-step workflow for the isolation of circulating extravillous trophoblasts (cEVTs) by describing the key steps enabling a semi-automated process, including a proprietary algorithm for fetal cell origin genetic confirmation and copy number variant (CNV) detection. METHODS: Determination of the limit of detection (LoD) for submicroscopic CNV was performed by serial experiments with genomic DNA and single cells from Coriell cell line biobank with known imbalances of different sizes. A pregnancy population of 372 women was prospectively enrolled and blindly analyzed to evaluate the current workflow. RESULTS: An LoD of 800 Kb was demonstrated with Coriell cell lines. This level of resolution was confirmed in the clinical cohort with the identification of a pathogenic CNV of 800 Kb, also detected by chromosomal microarray. The mean number of recovered cEVTs was 3.5 cells per sample with a significant reverse linear trend between gestational age and cEVT recovery rate and number of recovered cEVTs. In twin pregnanices, evaluation of zygosity, fetal sex and copy number profiling was performed in each individual cell. CONCLUSION: Our semi-automated methodology for the isolation and single-cell analysis of cEVTS supports the feasibility of a cell-based noninvasive prenatal test for fetal genomic profiling.

Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.

Acute spontaneous non-hemorrhagic adrenal infarction in pregnancy: case-report and literature review.

Unilateral non-hemorrhagic adrenal infarction (NHAI) is a very uncommon cause of acute abdomen in pregnancy. Diagnosis is highly challenging due to its rarity, heterogeneity of clinical presentation, and inconclusiveness of the initial workup. Timely recognition is pivotal to ensuring optimal outcomes. Here we describe a case of spontaneous unilateral NHAI diagnosed in a singleton pregnant woman at 32 weeks' gestation at our centre and provide the findings of an extensive literature review on the topic. We identified 22 articles describing 31 NHAI cases in 30 obstetric patients: NHAI occurs more frequently on the right side and in the third trimester, and diagnosis is formulated more than 24 h after clinical presentation in 50% of cases; second-level imaging is always necessary to reach a definitive diagnosis and start appropriate treatment. A high degree of clinical suspicion is needed to promptly recognize NHAI in pregnancy, thus allowing appropriate multidisciplinary management and timely treatment initiation. Promotion of knowledge and awareness of NHAI as a potential cause of acute abdomen in pregnancy is mandatory to improve clinical practice and, ultimately, perinatal outcomes.

Endometriosis-related spontaneous hemoperitoneum in pregnancy: A case series.

Endometriosis can be associated with adverse pregnancy outcomes. We report six cases of endometriosis-related spontaneous hemoperitoneum diagnosed in pregnant and postpartum women over 13 years. Spontaneous hemoperitoneum in pregnancy mainly occurred in the second half of gestation. All women presented with acute abdominal pain; four of them needed an emergent surgery, two were managed expectantly. The median estimated blood loss was 4250 ml, four women required massive transfusion. Three out of six women had a known history of endometriosis, all of them had histologically confirmed endometriosis after surgery. No maternal or perinatal deaths occurred. In one case, reticence to perform a computed tomography scan led to delayed diagnosis. Since delay can lead to lethal consequences, high levels of suspicion for spontaneous hemoperitoneum should be maintained in cases of severe abdominal pain, even with a woman's negative history of endometriosis. Improved knowledge and regular interdisciplinary meetings are pivotal to ameliorate outcomes.

Development and validation of a predictive model to identify the active phase of labor.

BACKGROUND: The diagnosis of the active phase of labor is a crucial clinical decision, thus requiring an accurate assessment. This study aimed to build and to validate a predictive model, based on maternal signs and symptoms to identify a cervical dilatation ≥4 cm. METHODS: A prospective study was conducted from May to September 2018 in a II Level Maternity Unit (development data), and from May to September 2019 in a I Level Maternity Unit (validation data). Women with singleton, term pregnancy, cephalic presentation and presence of contractions were consecutively enrolled during the initial assessment to diagnose the stage of labor. Women < 18 years old, with language barrier or induction of labor were excluded. A nomogram for the calculation of the predictions of cervical dilatation ≥4 cm on the ground of 11 maternal signs and symptoms was obtained from a multivariate logistic model. The predictive performance of the model was investigated by internal and external validation. RESULTS: A total of 288 assessments were analyzed. All maternal signs and symptoms showed a significant impact on increasing the probability of cervical dilatation ≥4 cm. In the final logistic model, "Rhythm" (OR 6.26), "Duration" (OR 8.15) of contractions and "Show" (OR 4.29) confirmed their significance while, unexpectedly, "Frequency" of contractions had no impact. The area under the ROC curve in the model of the uterine activity was 0.865 (development data) and 0.927 (validation data), with an increment to 0.905 and 0.956, respectively, when adding maternal signs. The Brier Score error in the model of the uterine activity was 0.140 (development data) and 0.097 (validation data), with a decrement to 0.121 and 0.092, respectively, when adding maternal signs. CONCLUSION: Our predictive model showed a good performance. The introduction of a non-invasive tool might assist midwives in the decision-making process, avoiding interventions and thus offering an evidenced-base care.

Pregnancy and Delivery Outcomes in Women With Persistent Versus Resolved Low-Lying Placenta in the Late Third Trimester.

OBJECTIVES: The safest mode of delivery in low-lying placenta is debatable. Little is known about outcomes in low-lying placenta resolved during the late third trimester. We compare outcomes of women with persistent versus resolved low-lying placenta. METHODS: A retrospective analysis on a prospective cohort of women with low-lying placenta confirmed at 28-30 weeks sonography (01/2009 to 03/2018). Women were followed up serially every 2 to 3 weeks until delivery to assess the placental edge-to-internal os distance (IOD), and included if scan was performed within 28 days before delivery. RESULTS: There were 86 women: in 21 the low-lying placenta resolved, whereas in 65 persisted (n = 15 IOD 1-10 mm, n = 50 IOD 11-20 mm). Antepartum bleeding associated with higher rates of urgent cesarean delivery in 1-10 mm (P = .041) but not in 11-20 mm (P = 1.000) and >20 mm (P = .333). Among women with IOD >10 mm allowed to labor, vaginal delivery occurred in 76.7% (11-20 mm) and 94.1% (>20 mm) (P = .155), with no difference according to parity (70% and 80% in multiparas, P = .696; 60% and 72.7% in nulliparas, P = .698). Severe PPH (P = .922) and hemoglobin drop (P = .109) were similar among groups. Women with IOD 11-20 mm and >20 mm and vaginal delivery bled less than women with similarly located placenta and cesarean delivery (P = .009 and P = .048). CONCLUSIONS: Women with IOD >10 mm have high chances of deliver vaginally with no further increase of their hemorrhagic risk. Success of vaginal delivery is independent of parity and antepartum bleeding. Labor should be managed in an adequate hospital setting.

The effect of clamped and unclamped umbilical cord samples on blood gas analysis.

PURPOSE: Delayed cord clamping for at least 60 s is recommended to improve neonatal outcomes. The aim of this study is to evaluate whether there are differences in cord BGA between samples collected after double clamping the cord or without clamping the cord, when blood collection occurs within 60 s from birth in both groups. METHODS: A cross-sectional study was carried out, collecting data from 6884 high-risk women who were divided into two groups based on the method of cord sampling (clamped vs unclamped). RESULTS: There were significant decrease in pH and BE values into unclamped group compared with the clamped group. This difference remained significant when considering pathological blood gas analysis parameters, with a higher percentage of pathological pH or BE values in the unclamped group. CONCLUSION: Samples from the unclamped cord alter the acid-base parameters compared to collection from the clamped cord; however, this difference does not appear to be of clinical relevance. Findings could be due to the large sample size, which allowed to achieve a high power and to investigate very small numerical changes between groups, leading to a statistically significant difference in pH and BE between samples even when we could not appreciate any clinical relevant difference of pH or BE between groups. When blood gas analysis is indicated, the priority should be given to the timing of blood collection to allow reliable results, to assess newborns status at birth and intervene when needed.

Pro-inflammatory cytokines favor the emergence of ETV6-RUNX1-positive pre-leukemic cells in a model of mesenchymal niche.

ETV6-RUNX1 (E/R) fusion gene, arising in utero from translocation t(12;21)(p13:q22), is the most frequent alteration in childhood acute lymphoblastic leukemia (ALL). However, E/R is insufficient to cause overt leukemia since it generates a clinically silent pre-leukemic clone which persists in the bone marrow but fails to out-compete normal progenitors. Conversely, pre-leukemic cells show increased susceptibility to transformation following additional genetic insults. Infections/inflammation are the most accredited triggers for mutations accumulation and leukemic transformation in E/R+ pre-leukemic cells. However, precisely how E/R and inflammation interact in promoting leukemia is still poorly understood. Here we demonstrate that IL6/TNFα/ILß pro-inflammatory cytokines cooperate with BM-MSC in promoting the emergence of E/R+ Ba/F3 over their normal counterparts by differentially affecting their proliferation and survival. Moreover, IL6/TNFα/ILß-stimulated BM-MSC strongly attract E/R+ Ba/F3 in a CXCR2-dependent manner. Interestingly, E/R-expressing human CD34+ IL7R+ progenitors, a putative population for leukemia initiation during development, were preserved in the presence of BM-MSC and IL6/TNFα/ILß compared to their normal counterparts. Finally, the extent of DNA damage increases within the inflamed niche in both control and E/R-expressing Ba/F3, potentially leading to transformation in the apoptosis-resistant pre-leukemic clone. Overall, our data provide new mechanistic insights into childhood ALL pathogenesis.

Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo.

Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche. CB ossicles were regularly observed upon transplantation. Compared with BM ossicles, CB ossicles showed a predominance of red marrow over yellow marrow, as demonstrated by histomorphological analyses and the number of hematopoietic cells isolated within ossicles. Marrow cavities from CB and BM ossicles included donor-derived CD146-expressing osteoprogenitors and host-derived mature hematopoietic cells, clonogenic lineage-committed progenitors and HSCs. Furthermore, human CD34+ cells transplanted into ossicle-bearing mice engrafted and maintained human HSCs in the niche. Our data indicate that CB-BFs are able to recapitulate the conditions by which the bone marrow microenvironment is formed and establish complete HSC niches, which are functionally supportive of hematopoietic tissue.

ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic leukemic cells.

B-cell precursor-acute lymphoblastic leukemia modulates the bone marrow (BM) niche to become leukemia-supporting and chemo-protective by reprogramming the stromal microenvironment. New therapies targeting the interplay between leukemia and stroma can help improve disease outcome. We identified ActivinA, a TGF-ß family member with a well-described role in promoting several solid malignancies, as a factor favoring leukemia that could represent a new potential target for therapy. ActivinA resulted over-expressed in the leukemic BM and its production was strongly induced in mesenchymal stromal cells after culture with leukemic cells. Moreover, MSCs isolated from BM of leukemic patients showed an intrinsic ability to secrete higher amounts of ActivinA compared to their normal counterparts. The pro-inflammatory leukemic BM microenvironment synergized with leukemic cells to induce stromal-derived ActivinA. Gene expression analysis of ActivinA-treated leukemic cells showed that this protein was able to significantly influence motility-associated pathways. Interestingly, ActivinA promoted random motility and CXCL12-driven migration of leukemic cells, even at suboptimal chemokine concentrations, characterizing the leukemic niche. Conversely, ActivinA severely impaired CXCL12-induced migration of healthy CD34+ cells. This opposite effect can be explained by the ability of ActivinA to increase intracellular calcium only in leukemic cells, boosting cytoskeleton dynamics through a higher rate of actin polymerization. Moreover, by stimulating the invasiveness of the leukemic cells, ActivinA was found to be a leukemia-promoting factor. Importantly, the ability of ActivinA to enhance BM engraftment and the metastatic potential of leukemic cells was confirmed in a xenograft mouse model of the disease. Overall, ActivinA was seen to be a key factor in conferring a migratory advantage to leukemic cells over healthy hematopoiesis within the leukemic niche.

Characteristics of patients with cervical cancer during pregnancy: a multicenter matched cohort study. An initiative from the International Network on Cancer, Infertility and Pregnancy.

BACKGROUND: Treatment of cervical cancer during pregnancy is often complex and challenging. This study aimed to analyze current patterns of practice in the management of pregnant patients diagnosed with cervical cancer. METHODS: This was a matched cohort study comprising patients managed for cervical cancer during pregnancy from six European centers. Patient information was retrieved from the dataset of the International Network for Cancer, Infertility and Pregnancy from 1990 to 2012. Each center matched its patients with two non-pregnant controls for age (±5 years) and International Federation of Gynecology and Obstetrics (FIGO) 2009 stage. Information on age, histological type, grade, lymphovascular space invasion, stage, tumor size, method of diagnosis, site of recurrence, delivery, date of recurrence, and date of death was recorded. Progression-free survival was compared using multivariable Cox proportional hazards regression. RESULTS: A total of 132 pregnant patients and 256 controls were analyzed. The pregnant patients (median age 34 years, range 21-43) were diagnosed at a median gestational age of 18.4 weeks of pregnancy (range 7-39). Stage distribution during pregnancy was 14.4% for stage IA, 47.0% for IB1, 18.9% for IB2, and 19.7% for II-IV. For treatment during pregnancy, 17.4% of the patients underwent surgery, 16.7% received neoadjuvant chemotherapy, 26.5% delayed their treatment, 12.9% had a premature delivery, and 26.5% had their pregnancy terminated. Median follow-up was 84 months (67 months for pregnant and 95 months for non-pregnant patients). The unadjusted hazard ratio of pregnancy for progression-free survival was 1.18 (95% confidence interval 0.74 to 1.88). CONCLUSION: Surgery and chemotherapy is increasingly used in the management of pregnant patients with cervical cancer and prognosis is similar to that of non-pregnant patients.

Tetrasomy 18p: The challenges of noninvasive prenatal testing and combined test.

Circulating cell-free DNA, having no procedural risk of miscarriage, is the most suitable sample for a noninvasive prenatal testing (NIPT). Here we report on a boy, who came to our attention for hypotonia and psychomotor delay when he was 16 months old. During the pregnancy his mother performed a NIPT that resulted compatible with the presence of trisomy 18. A confirmatory invasive procedure has been proposed, but not performed, because the family preferred to follow a conservative line. A series of ultrasound excluded the presence of any major malformations. Genetic tests, performed after birth, revealed the presence of a tetrasomy 18p with an extra isochromosome 18p. Our report wants to underline the importance of an invasive procedure and consequent cytogenetic analysis in case of NIPT results indicating autosomal trisomies because under it may hide the presence of other structural chromosomal anomalies. These conditions are normally not visible at prenatal ultrasound or using combined test (CT) and the only identifiable not invasive sign could be the results of high risk at NIPT.

Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities.

Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antiviral agents, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes. Using multiple models of CMV infection in the developing mouse brain, we show that subcutaneous low-dose VCD suppresses CMV by reducing the level of virus available for entry into the brain and by acting directly within the brain to block virus replication and dispersal. VCD during the first 3 weeks of life restored timely acquisition of neurological milestones in neonatal male and female mice and rescued long-term motor and behavioral outcomes in juvenile male mice. CMV-mediated brain defects, including decreased brain size, cerebellar hypoplasia, and neuronal loss, were substantially attenuated by VCD. No adverse side effects on neurodevelopment of uninfected control mice receiving VCD were detected. Treatment of CMV-infected human fetal astrocytes with VCD reduced both viral infectivity and replication by blocking viral particle attachment to the cell, a mechanism that differs from available anti-CMV drugs. These data suggest that VCD during critical periods of neurodevelopment can effectively suppress CMV replication in the brain and safely improve both immediate and long-term neurological outcomes.SIGNIFICANCE STATEMENT Cytomegalovirus (CMV) can irreversibly damage the developing brain. No anti-CMV drugs are available for use during fetal development, and treatment during the neonatal period has substantial limitations. We studied the anti-CMV actions of valnoctamide (VCD), a psychiatric sedative that appears to lack teratogenicity and toxicity, in the newborn mouse brain, a developmental period that parallels that of an early second-trimester human fetus. In infected mice, subcutaneous VCD reaches the brain and suppresses viral replication within the CNS, rescuing the animals from CMV-induced brain defects and neurological problems. Treatment of uninfected control animals exerts no detectable adverse effects. VCD also blocks CMV replication in human fetal brain cells.

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

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

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

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

A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus.

BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).

Early Prenatal MRI of Cervical "Abortive" Myelocystocele: Case Report and Review of the Literature.

Cervical abortive myelocistocele is a very rare congenital malformation. In this case report, we describe the prenatal magnetic resonance imaging (MRI) of such entity in a 20-week gestational age fetus, whose imaging features showed to be different from the only other previous prenatal report. We underscored the value of fetal MR for counseling and prognosis, especially when assessing the integrity of the spinal cord.