First trimester ultrasound of the cerebral lateral ventricles in fetuses with open spina bifida: a retrospective cohort study.

BACKGROUND: Beyond 18 weeks of gestation an increased size of the fetal lateral ventricles is reported in the majority of fetuses with open spina bifida. At 1st trimester, the definition of ventriculomegaly is based on the ratio between the size of the choroid plexus and that of the ventricular space or of the entire fetal head. However, contrary to what is seen from midtrimester, in most fetuses with open spina bifida at 11-13 weeks the amount of fluid in the ventricular system seems to be reduced rather than increased. OBJECTIVE: To compare the biometry of the lateral ventricles at 11+0-13+6 weeks between normal fetuses and those with a confirmed open spina bifida. STUDY DESIGN: Retrospective cohort study including all cases of isolated open spina bifida detected at 11+0-13+6 weeks of gestation over a period of 5 years and a group of structurally normal fetuses attending at our Centre over a period of 1 year for the aneuploidies screening as controls. The transventricular axial views of the fetal brain obtained among cases and controls were extracted from the archive for post-hoc measurement of the cerebral ventricles. The ratios between choroid plexus and lateral ventricle lenghts (CPVLr) and areas (CPVAr), the ratio between the sum of both choroid plexus areas and fetal head area (CPHAr) and the ratio between the mean of choroid plexus lengths and occipito-frontal diameter (CPHLr) were calculated for both groups. Measurements obtained from the two groups were compared, and the association of each parameter with open spina bifida was investigated. RESULTS: Ten fetuses with open spina bifida were compared with 358 controls, showing significantly smaller size of the cerebral ventricles measurements as expressed by larger values of CPVAr (0.72 vs 0.49, p<0.001), CPVLr (0.79 vs 0.70, p<0.001), CPHAr (0.33 vs 0.28, p=0.006) and CPHLr (0.60 vs 0.52, p<0.001) compared with controls. CPVAr was found to be the most accurate predictor of OSB showing an area under the curve of 0.88 with a sensitivity of 90% and a specificity of 82%. CONCLUSIONS: At 11+0-13+6 weeks' gestation open spina bifida is consistently associated with a reduced amount of fluid in the lateral cerebral ventricles of the fetus, as witnessed by significantly increased CPVLr, CPVAr, CPHAr and CPHLr.

Clinical Practice Guidelines and Recommendations by the World Association of Perinatal Medicine and Perinatal Medicine Foundation: Reporting Suspected Findings from Fetal Central Nervous System Examination.

These guidelines follow the mission of the World Association of Perinatal Medicine, in collaboration with the Perinatal Medicine Foundation, which brings together groups and individuals worldwide, with the aim to improve prenatal detection of central nervous system anomalies and the appropriate referral of pregnancies with suspected fetal anomalies. In addition, this document provides further guidance for healthcare practitioners with the goal of standardizing the description of ultrasonographic abnormal findings.

Management of preterm labor: Clinical practice guideline and recommendation by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation.

This practice guideline follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the management of preterm labor. In fact, this document provides further guidance for healthcare practitioners on the appropriate use of examinations with the aim to improve the accuracy in diagnosing preterm labor and allow timely and appropriate administration of tocolytics, antenatal corticosteroids and magnesium sulphate and avoid unnecessary or excessive interventions. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world in the light of scientific literature and serves as a guideline for use in clinical practice.

The "cortical invagination sign": a midtrimester sonographic marker of unilateral cortical focal dysgyria in fetuses with complete agenesis of the corpus callosum.

BACKGROUND: Agenesis of the corpus callosum is associated with several malformations of cortical development. Recently, features of focal cortical dysgyria have been described in fetuses with agenesis of the corpus callosum. OBJECTIVE: This study aimed to describe the "cortical invagination sign," a specific sonographic feature of focal cortical dysgyria, which is consistently seen at midtrimester axial brain ultrasound in fetuses with complete agenesis of the corpus callosum. STUDY DESIGN: This was a retrospective analysis of prospectively collected data from 2018 to 2021, including patients referred to 5 fetal medicine centers in the second trimester of pregnancy (19 0/7 to 22 0/7 weeks of gestation) with suspected complete agenesis of the corpus callosum. All cases with the diagnosis of complete agenesis of the corpus callosum were submitted to an axial sonographic assessment of the fetal brain on the transventricular plane. In this scanning section, the mesial profile of both cerebral hemispheres at the level of the frontal-parietal cortex was investigated. In this area, the operator looked for an abnormal invagination of the cortical surface along the widened interhemispheric fissure, which was referred to as the "cortical invagination sign." All fetuses were submitted to dedicated antenatal magnetic resonance imaging to reassess the ultrasound findings. Cases with additional brain anomalies, which did not involve the cortex, were excluded. The final diagnosis was confirmed at postnatal brain magnetic resonance imaging or postmortem examination, for cases undergoing termination of pregnancy. The primary outcome of this study was to evaluate the presence and laterality of the "cortical invagination sign" in fetuses with complete agenesis of the corpus callosum at antenatal ultrasound and magnetic resonance imaging. RESULTS: During the study period, 64 cases of complete agenesis of the corpus callosum were included; of those cases, 50 (78.1%) resulted in termination of pregnancy, and 14 (21.9%) resulted in a live birth. The "cortical invagination sign" was detected at ultrasound in 13 of 64 cases (20.3%) and at targeted brain magnetic resonance imaging in 2 additional cases (23.4%), all of which were electively terminated. Moreover, the "cortical invagination sign" was found to be exclusively unilateral and on the left cerebral hemisphere in all the cases. There was a predominant number, although nonsignificant, of male fetuses (80.0% of cases; P=.06) in the group of complete agenesis of the corpus callosum with the "cortical invagination sign." CONCLUSION: The "cortical invagination sign" is a specific marker of focal cortical dysgyria, which seems to characterize at midtrimester of pregnancy in a large group of fetuses with complete agenesis of the corpus callosum. The etiology, pathophysiology, and prognostic significance of this finding remain to be elucidated.

Association between the cervical sliding sign and successful induction of labor in women with an unfavorable cervix: A prospective observational study.

OBJECTIVES: To evaluate the role of the cervical sliding sign (CSS) in the prediction of the outcome of induction of labor (IOL). STUDY DESIGN: Two-center prospective observational cohort study involving a non-consecutive series of uncomplicated singleton term pregnancies, planned for IOL, with a fetus in cephalic presentation and unfavorable cervix as defined by a Bishop score ≤ 6. The Bishop score was evaluated by transvaginal digital examination and the cervical length and CSS by transvaginal ultrasound. The presence of CSS was defined as the sliding of the anterior cervical lip on the posterior one under gentle pressure of the transvaginal probe. The primary outcome of the study was successful vaginal delivery within 24 h. The secondary outcome was the induction-to-active-labor time. The interobserver agreement for the CSS was also evaluated. RESULTS: Over a period of 12 months, 179 women were included. The CSS was found in 86 (48.0 %) patients and was associated with an increased likelihood of vaginal delivery within 24 h (60/86 or 69.8 % vs 27/93 or 29.0 %, P < 0.001) and a shorter induction-to-active-labor time (954 ± 618 min vs 1416 ± 660 min, P < 0.001). Multivariable regression analysis showed that the CSS was an independent predictor of vaginal delivery within 24 h (aOR 5.37, 95 % CI 2.26-12.75) and shorter induction-to-active-labor time interval (HR 1.81, 95 % CI 1.19-2.74). The interobserver variability based on intraclass correlation coefficient for the CSS was excellent (ICC = 0.90). CONCLUSION: In women undergoing IOL with an unfavorable cervix, the CSS is associated with a higher frequency of vaginal delivery within 24 h and a shorter induction-to-active-labor time.

The sonographic measurement of the ratio between the fetal head circumference and the obstetrical conjugate is accurate in predicting the risk of labor arrest: results from a multicenter prospective study.

BACKGROUND: Labor arrest is estimated to account for approximately one-third of all primary cesarean deliveries, and is associated with an increased risk of adverse maternal and perinatal outcomes. One of the main causes is the mismatch between the size of the birth canal and that of the fetus, a condition usually referred to as cephalopelvic disproportion. OBJECTIVE: This study aimed to describe a new ultrasound predictor of labor arrest leading to cesarean delivery because of suspected cephalopelvic disproportion. STUDY DESIGN: This was a multicenter prospective study conducted at 3 maternity units from January 2021 to January 2022. A nonconsecutive series of singleton pregnancies with cephalic-presenting fetuses, gestational age of 34 weeks+0 days or above, and no contraindication to vaginal delivery attending at the antenatal clinics of each institution were considered eligible. Between 34+0 and 38+0 weeks of gestation, all eligible patients were submitted to transabdominal 2D ultrasound measurement of the obstetrical conjugate. On admission to the labor ward, the fetal head circumference was measured on the standard transthalamic plane by transabdominal ultrasound. The primary outcome of the study was the accuracy of the ratio between the fetal head circumference and the obstetrical conjugate measurement (ie, head circumference/obstetrical conjugate ratio) in predicting the occurrence of cesarean delivery secondary to labor arrest. The secondary outcome was the relationship between the head circumference/obstetrical conjugate ratio and labor duration. RESULTS: A total of 263 women were included. Cesarean delivery for labor arrest was performed in 7.6% (20/263) of the included cases and was associated with more frequent use of epidural analgesia (95.0% vs 45.7%; P<.001), longer second stage of labor (193 [120-240] vs 34.0 [13.8-66.5] minutes; P=.002), shorter obstetrical conjugate (111 [108-114] vs 121 [116-125] mm; P<.001), higher head circumference/obstetrical conjugate ratio (3.2 [3.2-3.35] vs 2.9 [2.8-3.0]; P<.001), and higher birthweight (3678 [3501-3916] vs 3352 [3095-3680] g; P=.003) compared with vaginal delivery. At logistic regression analysis, the head circumference/obstetrical conjugate ratio expressed as Z-score was the only parameter independently associated with risk of cesarean delivery for labor arrest (odds ratio, 8.8; 95% confidence interval, 3.6-21.7) and had higher accuracy in predicting cesarean delivery compared with the accuracy of fetal head circumference and obstetrical conjugate alone, with an area under the curve of 0.91 (95% confidence interval, 81.7-99.5; P<.001). A positive correlation between the head circumference/obstetrical conjugate ratio and length of the second stage of labor was found (Pearson coefficient, 0.16; P=.018). CONCLUSION: Our study, conducted on an unselected low-risk population, demonstrated that the head circumference/obstetrical conjugate ratio is a reliable antenatal predictor of labor arrest leading to cesarean delivery.

First trimester examination of fetal anatomy: clinical practice guideline by the World Association of Perinatal Medicine (WAPM) and the Perinatal Medicine Foundation (PMF).

This recommendation document follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation. We aim to bring together groups and individuals throughout the world for precise standardization to implement the ultrasound evaluation of the fetus in the first trimester of pregnancy and improve the early detection of anomalies and the clinical management of the pregnancy. The aim is to present a document that includes statements and recommendations on the standard evaluation of the fetal anatomy in the first trimester, based on quality evidence in the peer-reviewed literature as well as the experience of perinatal experts around the world.

The use of antenatal corticosteroids for fetal maturation: clinical practice guideline by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine foundation.

This practice guideline follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the use of antenatal corticosteroids (ACS) for fetal maturation. In fact, this document provides further guidance for healthcare practitioners on the appropriate use of ACS with the aim to increase the timely administration and avoid unnecessary or excessive use. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world and serves as a guideline for use in clinical practice.

Automatic measurement of head-perineum distance during intrapartum ultrasound: description of the technique and preliminary results.

OBJECTIVES: To evaluate the accuracy and reliability of a new ultrasound technique for the automatic assessment of the head-perineum distance (HPD) during childbirth. METHODS: HPD was measured on a total of 40 acquisition sessions in 30 laboring women both automatically by an innovative algorithm and manually by trained sonographers, assumed as gold standard. RESULTS: A significant correlation was found between manual and automatic measurements (Intra-CC = 0.994). High values of the coefficient of determination (r2=0.98) and low residual errors: RMSE = 2.01 mm (4.9%) were found. CONCLUSION: The automatic algorithm for the assessment of the HPD represents a reliable technique.

Antepartum evaluation of the obstetric conjugate at transabdominal 2D ultrasound: A feasibility study.

INTRODUCTION: The obstetric conjugate represents the shortest anteroposterior diameter of the birth canal and it reflects the capacity of the pelvic inlet to allow the passage and the engagement of the fetal head. The antepartum evaluation of this parameter may be attempted at digital examination to predict the risk of cephalopelvic disproportion, but the accuracy of clinical pelvimetry is notoriously poor. The aim of our study was to describe the sonographic measurement of the obstetric conjugate at transabdominal 2D-ultrasound and to assess its reproducibility. MATERIAL AND METHODS: This is a prospective cohort study conducted at a tertiary University hospital. A non-consecutive series of pregnant women with uncomplicated singleton pregnancies attending the antenatal clinic for routine booking from 34 weeks of gestation onward were included. The ultrasound probe was longitudinally placed above the level of the symphysis and the interpubic fibrocartilaginous disk was visualized. Then the promontory was identified as the most prominent segment of the sacral vertebral column. The obstetric conjugate was measured as the distance between the inner edge of the interpubic disk and the promontory. The inter- and intraobserver repeatability of this measurement was calculated using the intraclass correlation coefficient (ICC) and the Bland-Altman method. RESULTS: In all, 119 women were considered eligible for the study; of these, 111/119 (93.3%) women were included in the analysis with a median gestational age of 36.0 (35.0-37.0) weeks. The mean obstetric conjugate measurement was 11.4 ± 0.93 mm for the first operator and 11.4 ± 0.91 mm for the second operator. The overall interobserver ICC was 0.95 (95% [confidence interval] CI 0.92-0.96) and the overall intraobserver ICC was 0.97 (95% CI 0.96-0.98). Limits of agreement ranged from -0.84 to 0.80 for interobserver measures and from -0.64 to 0.62 for intraobserver measures. The degree of reliability was also analyzed for women with a body mass index ≥30 and for women with a gestational age ≥37 weeks. The inter- and intraobserver ICCs were respectively 0.97 (95% CI 0.90-0.98) and 0.98 (0.95-0.99) in the former group and 0.96 (95% CI 0.93-0.98) and 0.97 (95% CI 0.95-0.98) in the latter group. CONCLUSIONS: Our study demonstrated that among pregnant women at term gestation, sonographic measurement of the obstetric conjugate is feasible and reproducible.

Three-Dimensional Sonographic Evaluation of the Position of the Fetal Conus Medullaris at First Trimester.

OBJECTIVE: The objective of this study was to assess the position of the conus medullaris (CM) at the first trimester 3D ultrasound in a cohort of structurally normal fetuses. METHODS: This was a multicenter prospective study involving a consecutive series of structurally normal fetuses between 11 and 13 weeks of gestation (CRL between 45 and 84 mm). All fetuses were submitted to 3D transvaginal ultrasound using a sagittal view of the spine as the starting plane of acquisition. At offline analysis, the position of the CM was evaluated by 2 independent operators with a quantitative and a qualitative method: (1) the distance between the most caudal part of the CM and the distal end of the coccyx (CMCd) was measured; (2) a line perpendicular to the fetal spine joining the tip of the CM to the anterior abdominal wall was traced to determine the level of this line in relation to the umbilical cord insertion (conus to abdomen line, CAL). Interobserver agreement for the CCMd was evaluated. Linear regression analysis was used to determine the association between the CMCd and CRL, and a normal range was computed based on the best-fit model. The absence of congenital anomalies was confirmed in all cases after birth. RESULTS: In the study period between December 2019 and March 2020, 143 fetuses were recruited. In 130 fetuses (90.9%), the visualization of the CM was feasible. The mean value of the CMCd was 1.09 ± 0.16 cm. The 95% limits of agreement for the interobserver variability in measurement of the CMCd were 0.24 and 0.26 cm. The interobserver variability based on the intra-class correlation coefficient (ICC) for the CCMd was good (ICC = 0.81). We found a positive linear relationship between the CCMd and CRL. In all these fetuses, the CAL encountered the abdominal wall at or above the level of the cord insertion. CONCLUSION: In normal fetuses, the assessment of the CM position is feasible at the first trimester 3D ultrasound with a good interobserver agreement. The CM level was never found below the fetal umbilical cord insertion, while the CMCd was noted to increase according to the gestational age, confirming the "ascension" of the CM during fetal life.

WAPM-World Association of Perinatal Medicine Practice Guidelines: Fetal central nervous system examination.

These practice guidelines follow the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the ultrasound assessment of the fetal Central Nervous System (CNS) anatomy. In fact, this document provides further guidance for healthcare practitioners for the evaluation of the fetal CNS during the mid-trimester ultrasound scan with the aim to increase the ability in evaluating normal fetal anatomy. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world, and serves as a guideline for use in clinical practice.

Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019.

BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes. CONCLUSION: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.

In-hospital mortality in the emergency department: clinical and etiological differences between early and late deaths among patients awaiting admission.

OBJECTIVE: Given that there are no studies on diseases that occur by waiting for hospitalization, we aimed to evaluate the main causes of death in the emergency room (ER) and their relationship with overcrowding. METHODS: Patients who died in the ER in the past 2 years (pediatrics and trauma victims excluded) were divided into two groups: patients who died within 6 hours of arrival (emergency department [ED] group) and patients who died later (LD group). We compared the causes of death, total vital signs, diagnostic tests performed, and therapy between the groups. We assessed for possible correlation between the number of monthly deaths per group and four variables of overcrowding: number of patients treated per month, waiting time before medical visit (W-Time), mean intervention time (I-Time), and number of patients admitted to the ward per month (NPA). RESULTS: During the two years, 175 patients had died in our ER (52% in ED group and 48% in LD group). The total time spent in the ER was, respectively, 2.9±0.2 hours for ED group and 17.9± 1.5 hours for LD group. The more frequent cause of death was cardiovascular syndrome (30%) in ED group and sepsis (27%) and acute respiratory failure (27%) in LD group. Positive correlations between number of monthly deaths and W-Time (R2 0.51, P<0.001), I-Time (R2 0.73, P< 0.0001), and NPA (R2 0.37, P<0.01) were found only in LD group. CONCLUSION: Patients with sepsis and acute respiratory failure die after a long stay in the ER, and the risk increases with overcrowding. A fast-track pathway should be considered for hospital admission of critical patients.

Hyperechoic amniotic membranes in patients with preterm premature rupture of membranes (p-PROM) and pregnancy outcome.

OBJECTIVES: The early identification of women with preterm premature rupture of membranes (p-PROM) who are at higher risk of imminent delivery remains challenging. The aim of our study was to evaluate if an increased echogenicity of the amniotic membranes may represent a sonographic marker of impending delivery in women with p-PROM. METHODS: This was a prospective study including women with singleton pregnancies and diagnosis of p-PROM between 22 and 37 gestational weeks. A sonographic examination was performed within 24 h from the hospital admission and the appearance of the amniotic membranes close to the internal os was specifically evaluated. The membranes were defined as hyperechoic when their echogenicity was similar to that of the fetal bones or normoechoic in the other cases. The primary aim of the study was to compare the admission to spontaneous onset of labor interval and the pregnancy outcome between the cases of p-PROM with and without hyperechoic membranes. RESULTS: Overall, 45 women fulfilled the inclusion criteria with similar characteristics at admission. In women with hyperechoic membranes, the admission to spontaneous onset of labor interval was significantly shorter (11.5 [5.3-25.0] vs. 3.0 [1.5-9.0] p=0.04) compared to women with normo-echoic membranes. At binomial logistic regression after adjustment for GA at hospital admission, the presence of hyperechoic membranes was found as the only independent predictor of spontaneous onset of labor ≤72 h (aOR: 6.1; 95% CI: 1.0-36.9). CONCLUSIONS: The presence of hyperechoic membranes is associated with a 6-fold higher incidence of spontaneous onset of labor within 72 h independently from the gestational age at p-PROM.

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.