Probe motion during mid-trimester fetal anomaly scan in the clinical setting: A prospective observational study.

INTRODUCTION: This study aims to investigate probe motion during full mid-trimester anomaly scans. METHODS: We undertook a prospective, observational study of obstetric sonographers at a UK University Teaching Hospital. We collected prospectively full-length video recordings of routine second-trimester anomaly scans synchronized with probe trajectory tracking data during the scan. Videos were reviewed and trajectories analyzed using duration, path metrics (path length, velocity, acceleration, jerk, and volume) and angular metrics (spectral arc, angular area, angular velocity, angular acceleration, and angular jerk). These trajectories were then compared according to the participant level of expertise, fetal presentation, and patient BMI. RESULTS: A total of 17 anomaly scans were recorded. The average velocity of the probe was 12.9 ± 3.4 mm/s for the consultants versus 24.6 ± 5.7 mm/s for the fellows (p = 0.02), the average acceleration 170.4 ± 26.3 mm/s2 versus 328.9 ± 62.7 mm/s2 (p = 0.02), and the average jerk 7491.7 ± 1056.1 mm/s3 versus 14944.1 ± 3146.3 mm/s3 (p = 0.02), the working volume 9.106 ± 4.106 mm3 versus 29.106 ± 11.106 mm3 (p = 0.03), respectively. The angular metrics were not significantly different according to the participant level of expertise, the fetal presentation, or to patients BMI. CONCLUSION: Some differences in the probe path metrics (velocity, acceleration, jerk and working volume) were noticed according to operator's level.

Prediction of spontaneous preterm birth in women with previous full dilatation cesarean delivery.

BACKGROUND: A previous term (≥37 weeks' gestation), full-dilatation cesarean delivery is associated with an increased risk for a subsequent spontaneous preterm birth. The mechanism is unknown. We hypothesized that the cesarean delivery scar characteristics and scar position relative to the internal cervical os may compromise cervical function, thereby leading to shortening of the cervical length and spontaneous preterm birth. OBJECTIVE: This study aimed to determine the relationship of cesarean delivery scar characteristics and position, assessed by transvaginal ultrasound, in pregnant women with previous full-dilatation cesarean delivery with the risk of shortening cervical length and spontaneous preterm birth. STUDY DESIGN: This was a single-center, prospective cohort study of singleton pregnant women (14 to 24 weeks' gestation) with a previous term full-dilatation cesarean delivery who attended a high-risk preterm birth surveillance clinic (2017-2021). Women underwent transvaginal ultrasound assessment of cervical length, cesarean delivery scar distance relative to the internal cervical os, and scar niche parameters using a reproducible transvaginal ultrasound technique. Spontaneous preterm birth prophylactic interventions (vaginal cervical cerclage or vaginal progesterone) were offered for short cervical length (≤25 mm) and to women with a history of spontaneous preterm birth or late miscarriage after full-dilatation cesarean delivery. The primary outcome was spontaneous preterm birth; secondary outcomes included short cervical length and a need for prophylactic interventions. A multivariable logistic regression analysis was used to develop multiparameter models that combined cesarean delivery scar parameters, cervical length, history of full-dilatation cesarean delivery, and maternal characteristics. The predictive performance of models was examined using the area under the receiver operating characteristics curve and the detection rate at various fixed false positive rates. The optimal cutoff for cesarean delivery scar distance to best predict a short cervical length and spontaneous preterm birth was analyzed. RESULTS: Cesarean delivery scars were visualized in 90.5% (220/243) of the included women. The spontaneous preterm birth rate was 4.1% (10/243), and 12.8% (31/243) of women developed a short cervical length. A history- (n=4) or ultrasound-indicated (n=19) cervical cerclage was performed in 23 of 243 (9.5%) women; among those, 2 (8.7%) spontaneously delivered prematurely. A multiparameter model based on absolute scar distance from the internal os best predicted spontaneous preterm birth (area under the receiver operating characteristics curve, 0.73; 95% confidence interval, 0.57-0.89; detection rate of 60% for a fixed 25% false positive rate). Models based on the relative anatomic position of the cesarean delivery scar to the internal os and the cesarean delivery scar position with niche parameters (length, depth, and width) best predicted the development of a short cervical length (area under the receiver operating characteristics curve, 0.79 [95% confidence interval, 0.71-0.87]; and 0.81 [95% confidence interval, 0.73-0.89], respectively; detection rate of 73% at a fixed 25% false positive rate). Spontaneous preterm birth was significantly more likely when the cesarean delivery scar was <5.0 mm above or below the internal os (adjusted odds ratio, 6.87; 95% confidence interval, 1.34-58; P =.035). CONCLUSION: In pregnancies following a full-dilatation cesarean delivery, cesarean delivery scar characteristics and distance from the internal os identified women who were at risk for spontaneous preterm birth and developing short cervical length. Overall, the spontaneous preterm birth rate was low, but it was significantly increased among women with a scar located <5.0 mm above or below the internal cervical os. Shortening of cervical length was strongly associated with a low scar position. Our novel findings indicate that a low cesarean delivery scar can compromise the functional integrity of the internal cervical os, leading to cervical shortening and/or spontaneous preterm birth. Assessment of the cesarean delivery scar characteristics and position seem to have use in preterm birth clinical surveillance among women with a previous, full-dilatation cesarean delivery and could better identify women who would benefit from prophylactic interventions.

First trimester screening for pre-eclampsia and targeted aspirin prophylaxis: a cost-effectiveness cohort study.

OBJECTIVE: Investigate cost-effectiveness of first trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in comparison with standard care. DESIGN: Retrospective observational study. SETTING: London tertiary hospital. POPULATION: 5957 pregnancies screened for pre-eclampsia using the National Institute for Health and Care Excellence (NICE) method. METHODS: Differences in pregnancy outcomes between those who developed pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia were compared by the Kruskal-Wallis and Chi-square tests. The FMF algorithm was applied retrospectively to the cohort. A decision analytic model was used to estimate costs and outcomes for pregnancies screened using NICE and those screened using the FMF algorithm. The decision point probabilities were calculated using the included cohort. MAIN OUTCOME MEASURES: Incremental healthcare costs and QALY gained per pregnancy screened. RESULTS: Of 5957 pregnancies, 12.8% and 15.9% were screen-positive for development of pre-eclampsia using the NICE and FMF methods, respectively. Of those who were screen-positive by NICE recommendations, aspirin was not prescribed in 25%. Across the three groups, namely, pregnancies without pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia there was a statistically significant trend in rates of emergency caesarean (respectively 21%, 43% and 71.4%; P < 0.001), admission to neonatal intensive care unit (NICU) (5.9%, 9.4%, 41%; P < 0.001) and length of stay in NICU. The FMF algorithm was associated with seven fewer cases of preterm pre-eclampsia, cost saving of £9.06 and QALY gain of 0.00006/pregnancy screened. CONCLUSIONS: Using a conservative approach, application of the FMF algorithm achieved clinical benefit and an economic cost saving.

Do differences in diagnostic criteria for late fetal growth restriction matter?

BACKGROUND: Criteria for diagnosis of fetal growth restriction differ widely according to national and international guidelines, and further heterogeneity arises from the use of different biometric and Doppler reference charts, making the diagnosis of fetal growth restriction highly variable. OBJECTIVE: This study aimed to compare fetal growth restriction definitions between Delphi consensus and Society for Maternal-Fetal Medicine definitions, using different standards/charts for fetal biometry and different reference ranges for Doppler velocimetry parameters. STUDY DESIGN: From the TRUFFLE 2 feasibility study (856 women with singleton pregnancy at 32+0 to 36+6 weeks of gestation and at risk of fetal growth restriction), we selected 564 women with available mid-pregnancy biometry. For the comparison, we used standards/charts for estimated fetal weight and abdominal circumference from Hadlock, INTERGROWTH-21st, and GROW and Chitty. Percentiles for umbilical artery pulsatility index and its ratios with middle cerebral artery pulsatility index were calculated using Arduini and Ebbing reference charts. Sensitivity and specificity for low birthweight and adverse perinatal outcome were evaluated. RESULTS: Different combinations of definitions and reference charts identified substantially different proportions of fetuses within our population as having fetal growth restriction, varying from 38% (with Delphi consensus definition, INTERGROWTH-21st biometric standards, and Arduini Doppler reference ranges) to 93% (with Society for Maternal-Fetal Medicine definition and Hadlock biometric standards). None of the different combinations tested appeared effective, with relative risk for birthweight <10th percentile between 1.4 and 2.1. Birthweight <10th percentile was observed most frequently when selection was made with the GROW/Chitty charts, slightly less with the Hadlock standard, and least frequently with the INTERGROWTH-21st standard. Using the Ebbing Doppler reference ranges resulted in a far higher proportion identified as having fetal growth restriction compared with the Arduini Doppler reference ranges, whereas Delphi consensus definition with Ebbing Doppler reference ranges produced similar results to those of the Society for Maternal-Fetal Medicine definition. Application of Delphi consensus definition with Arduini Doppler reference ranges was significantly associated with adverse perinatal outcome, with any biometric standards/charts. The Society for Maternal-Fetal Medicine definition could not accurately detect adverse perinatal outcome irrespective of estimated fetal weight standard/chart used. CONCLUSION: Different combinations of fetal growth restriction definitions, biometry standards/charts, and Doppler reference ranges identify different proportions of fetuses with fetal growth restriction. The difference in adverse perinatal outcome may be modest, but can have a significant impact in terms of rate of intervention.

Second trimester abnormal uterine artery Dopplers and adverse obstetric and neonatal outcomes when PAPP-a is normal.

OBJECTIVES: To explore the association between abnormal uterine artery Dopplers (combined PI > 2.5) - with normal PAPP-A - and adverse obstetric/neonatal outcomes. METHODS: This was a retrospective cohort study of 800 patients between 1 March 2019 - 23 November 2021 in a tertiary UK hospital, where it is routine to measure uterine artery Dopplers of all pregnancies during their anomaly scans. 400 nulliparous women/birthing people with complete data were included. 400 nulliparous controls scanned in the same time frame (1.5 years) with normal PAPP-A and uterine artery Dopplers were matched for age and BMI. Outcomes included: mode of birth, postpartum complications, birth weight/centile, Apgar score, gestational age at delivery, neonatal unit admission, and clinical neonatal hypoglycemia. Multivariable analysis was used. RESULTS: Compared to controls, pregnancies with abnormal uterine artery Dopplers and normal PAPP-A were at increased risk of induction (46.5% vs 35.5%, p = .042), cesarean section (46.0% vs 38.0%, p = .002), emergency cesarean section (35.0% vs 26.5%, p = .009), and pre-eclampsia 5.8% vs 2.5%, p = .021). Their babies were more likely to be admitted to the neonatal unit - mostly for prematurity (15.3% vs 6.3%, p = .0004), hypoglycemia (4.0% vs 1.0%, p = .007), be small for gestational age (26.5% vs 11.5%, p = .0001), had intrauterine growth restriction (10.8% vs 1.3%, p = .0001), and be born prematurely (10.0% vs 3.5%, p = .002). Routine measurement of uterine artery Dopplers increased the detection rate of small for gestational age fetuses by 15.1%. Over half of the babies admitted with neonatal hypoglycemia in pregnancies with abnormal uterine artery Dopplers had an unexplained cause. CONCLUSIONS: Pregnancies with abnormal uterine Dopplers are not only at increased risk of pre-eclampsia and small for gestational age fetuses/intrauterine growth restriction, but are also at increased risk of emergency cesarean section and adverse neonatal outcomes. The increased incidence of neonatal hypoglycemia is likely driven to some degree by prematurity and placental complications, but possibly also by undiagnosed glucose dysmetabolism. This may warrant routine measurement of uterine artery Dopplers in all pregnancies (regardless of risk), where feasible, to aid antenatal management and counseling.

What are the novel findings of this work?Pregnancies with abnormal uterine artery Dopplers at the time of the anomaly scan and normal PAPP-A are at increased risk of having pre-eclampsia, small for gestational age fetuses, emergency cesarean, neonatal unit admission (including but not limited to prematurity), and neonatal hypoglycemia.What are the clinical implications of this work?Due to the significantly increased risk of adverse maternal and neonatal outcomes in first time mothers with increased uterine artery Dopplers despite normal PAPP-A, ultrasound assessment of placental function should be offered to all during their anomaly scans, subject to resources, to aid antenatal management and counseling. Further research is needed into undiagnosed diabetes.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSION: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Training in Obstetric Ultrasound Biometry: Results from a Multicenter Reproducibility Study.

OBJECTIVES: To assess the intra- and interobserver reproducibility of fetal biometry measurements obtained by trainee (junior) and experienced sonographers (senior) in the contest of two training programs in obstetric ultrasound. METHODS: This was a prospective study on 192 women recruited ensuring an even distribution throughout gestation (18-41 weeks), at University College London Hospital (UCLH), England (87 cases), and at Maternité Regionale Universitaire de Nancy (MRUN), France (105 cases). The training took place in two training centers with experience in ultrasound training and subspecialist training in fetal medicine. Measurements for head circumference (HC), abdominal circumference (AC), and femur length (FL) were obtained twice by junior and senior sonographers, blind to their own and each other's measurements. Differences between and within sonographers were expressed in millimeters and as a percentage of fetal dimensions. Reproducibility was assessed using Bland-Altman plots. RESULTS: Reproducibility was overall high with 95% confidence intervals (CI) within <6% for intraobserver and <8% for interobserver reproducibility. Intraobserver reproducibility was lower within junior than within senior sonographers' measurements for HC (95% CI: <4% versus <3%) and FL (95% CI: <6% and < 5%). Intraobserver reproducibility was similar between the two centers/training programs (AC 95% CI: <6%). Cumulative interobserver reproducibility in both centers was similar to the reproducibility within a single site (95% CI: <5%, <8%, and <7% for HC, AC, and FL, respectively). CONCLUSIONS: Reproducibility of fetal biometry measurement was high in centers with structured training programs regardless of sonographers' experience. Reproducibility was higher in sonographers who completed the training.

Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with COVID-19 in pregnancy: the INTERCOVID study.

BACKGROUND: Among nonpregnant individuals, diabetes mellitus and high body mass index increase the risk of COVID-19 and its severity. OBJECTIVE: This study aimed to determine whether diabetes mellitus and high body mass index are risk factors for COVID-19 in pregnancy and whether gestational diabetes mellitus is associated with COVID-19 diagnosis. STUDY DESIGN: INTERCOVID was a multinational study conducted between March 2020 and February 2021 in 43 institutions from 18 countries, enrolling 2184 pregnant women aged ≥18 years; a total of 2071 women were included in the analyses. For each woman diagnosed with COVID-19, 2 nondiagnosed women delivering or initiating antenatal care at the same institution were also enrolled. The main exposures were preexisting diabetes mellitus, high body mass index (overweight or obesity was defined as a body mass index ≥25 kg/m2), and gestational diabetes mellitus in pregnancy. The main outcome was a confirmed diagnosis of COVID-19 based on a real-time polymerase chain reaction test, antigen test, antibody test, radiological pulmonary findings, or ≥2 predefined COVID-19 symptoms at any time during pregnancy or delivery. Relationships of exposures and COVID-19 diagnosis were assessed using generalized linear models with a Poisson distribution and log link function, with robust standard errors to account for model misspecification. Furthermore, we conducted sensitivity analyses: (1) restricted to those with a real-time polymerase chain reaction test or an antigen test in the last week of pregnancy, (2) restricted to those with a real-time polymerase chain reaction test or an antigen test during the entire pregnancy, (3) generating values for missing data using multiple imputation, and (4) analyses controlling for month of enrollment. In addition, among women who were diagnosed with COVID-19, we examined whether having gestational diabetes mellitus, diabetes mellitus, or high body mass index increased the risk of having symptomatic vs asymptomatic COVID-19. RESULTS: COVID-19 was associated with preexisting diabetes mellitus (risk ratio, 1.94; 95% confidence interval, 1.55-2.42), overweight or obesity (risk ratio, 1.20; 95% confidence interval, 1.06-1.37), and gestational diabetes mellitus (risk ratio, 1.21; 95% confidence interval, 0.99-1.46). The gestational diabetes mellitus association was specifically among women requiring insulin, whether they were of normal weight (risk ratio, 1.79; 95% confidence interval, 1.06-3.01) or overweight or obese (risk ratio, 1.77; 95% confidence interval, 1.28-2.45). A somewhat stronger association with COVID-19 diagnosis was observed among women with preexisting diabetes mellitus, whether they were of normal weight (risk ratio, 1.93; 95% confidence interval, 1.18-3.17) or overweight or obese (risk ratio, 2.32; 95% confidence interval, 1.82-2.97). When the sample was restricted to those with a real-time polymerase chain reaction test or an antigen test in the week before delivery or during the entire pregnancy, including missing variables using imputation or controlling for month of enrollment, the observed associations were comparable. CONCLUSION: Diabetes mellitus and overweight or obesity were risk factors for COVID-19 diagnosis in pregnancy, and insulin-dependent gestational diabetes mellitus was associated with the disease. Therefore, it is essential that women with these comorbidities are vaccinated.

A preliminary study on a novel bioaugmentation technique enhancing lactic acid production by mixed cultures fermentation.

The paper is a preliminary study on the selection of lactic acid producing microorganisms from a mixed microbial population via bioaugmentation. The bioaugmentation technique is based on pH sudden variations occurring in sequential batch steps of a dark fermentation process applied to simple substrates. Different conditions are tested and compared. The structure of microbial communities and concentrations of metabolic intermediates are analyzed to study the possible substrate conversion routes. Obtained results indicate that the initial mixed culture produced a lactic acid percentage of 5% in terms of CODLA/CODPRODUCTS. In the most favourable conditions, the selected culture produced a lactic acid percentage of 59%. The analysis of the composition of microbial communities before and after the bioaugmentation processes, indicates that lactic acid production mainly results from the population change to bacteria belonging to the genus Bacillus. Indeed, the relative abundance of Bacilli increased from 0.67%, to 8.40% during the bioaugmentation cycle.

Carbon catabolite repression occurrence in photo fermentation of ethanol-rich substrates.

The paper investigates the phenomenon of Carbon Catabolite Repression occurring during photo fermentation of ethanol-rich effluents, which usually contain ethanol as main carbon source, and glycerol as secondary one. The study was conducted using mixed phototrophic cultures, adopting, as substrate, the effluent produced by the alcoholic fermentation of sugar cane bagasse. In order to elucidate the phenomenon, experimental tests were carried out using two different ethanol to glycerol ratios. Results were compared with those resulting from pure ethanol and glycerol conversion. According to the obtained data, as a result of Carbon Catabolite Repression occurrence, the presence of glycerol negatively affects hydrogen production. Indeed, part of the ethanol source is converted to biomass and polyhydroxybutyrate rather than to hydrogen. In more details, the presence of glycerol determines a drop of the hydrogen production, which goes from 12 % to 32 %, according to the ethanol/glycerol ratio, compared to the production obtained from fermentation of ethanol alone. Therefore, to promote the hydrogen production, it is advisable to apply strategies to produce low glycerol concentrations in the ethanol production stage.

A Systematic Review of Methodology Used in Studies Aimed at Creating Charts of Fetal Brain Structures.

Ultrasound-based assessment of the fetal nervous system is routinely recommended at the time of the mid-trimester anatomy scan or at different gestations based on clinical indications. This review evaluates the methodological quality of studies aimed at creating charts for fetal brain structures obtained by ultrasound, as poor methodology could explain substantial variability in percentiles reported. Electronic databases (MEDLINE, EMBASE, Cochrane Library, and Web of Science) were searched from January 1970 to January 2021 to select studies on singleton fetuses, where the main aim was to construct charts on one or more clinically relevant structures obtained in the axial plane: parieto-occipital fissure, Sylvian fissure, anterior ventricle, posterior ventricle, transcerebellar diameter, and cisterna magna. Studies were scored against 29 predefined methodological quality criteria to identify the risk of bias. In total, 42 studies met the inclusion criteria, providing data for 45,626 fetuses. Substantial heterogeneity was identified in the methodological quality of included studies, and this may explain the high variability in centiles reported. In 80% of the studies, a high risk of bias was found in more than 50% of the domains scored. In conclusion, charts to be used in clinical practice and research should have an optimal study design in order to minimise the risk of bias and to allow comparison between different studies. We propose to use charts from studies with the highest methodological quality.

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Quality control of fetal biometric evaluation and Doppler ultrasound.

In recent years quality control in obstetric ultrasound has become recommended and an essential component of obstetric scanning. This is to minimize the inaccuracy and variability related to fetal measurements, to provide an effective quality assurance system to sonographers to certify their practice and decrease the impact of medical litigations. For a quality control system in obstetric ultrasound to be useful clinically, multiple strategies need to be employed: certified training, practical standardization exercise, image storing, qualitative and quantitative quality control. Qualitative quality control consists of the evaluation of images obtained for fetal biometry and Doppler scans using an objective score against predefined criteria. Quantitative quality control consists of analyzing quantitatively the performance of a sonographer and the impact on measurements values. Quantitative analysis could be performed either using estimates of intraobserver or interobserver reproducibility of plane acquisition and caliper placements.

CRAFT (Cerclage after full dilatation caesarean section): protocol of a mixed methods study investigating the role of previous in-labour caesarean section in preterm birth risk.

BACKGROUND: Full dilatation caesarean sections are associated with recurrent early spontaneous preterm birth and late miscarriage. The risk following first stage caesarean sections, are less well defined, but appears to be increased in late-first stage of labour. The mechanism for this increased risk of late miscarriage and early spontaneous preterm birth in these women is unknown and there are uncertainties with regards to clinical management. Current predictive models of preterm birth (based on transvaginal ultrasound and quantitative fetal fibronectin) have not been validated in these women and it is unknown whether the threshold to define a short cervix (≤25 mm) is reliable in predicting the risk of preterm birth. In addition the efficacy of standard treatments or whether benefit may be derived from prophylactic interventions such as a cervical cerclage is unknown. METHODS: There are three distinct components to the CRAFT project (CRAFT-OBS, CRAFT-RCT and CRAFT-IMG). CRAFT-OBS: Observational Study; To evaluate subsequent pregnancy risk of preterm birth in women with a prior caesarean section in established labour. This prospective study of cervical length and quantitative fetal fibronectin data will establish a predictive model of preterm birth. CRAFT-RCT: Randomised controlled trial arm; To assess treatment for short cervix in women at high risk of preterm birth following a fully dilated caesarean section. CRAFT-IMG: Imaging sub-study; To evaluate the use of MRI and transvaginal ultrasound imaging of micro and macrostructural cervical features which may predispose to preterm birth in women with a previous fully dilated caesarean section, such as scar position and niche. DISCUSSION: The CRAFT project will quantify the risk of preterm birth or late miscarriage in women with previous in-labour caesarean section, define the best management and shed light on pathological mechanisms so as to improve the care we offer to women and their babies. TRIAL REGISTRATION: CRAFT was prospectively registered on 25th November 2019 with the ISRCTN registry ( https://doi.org/10.1186/ISRCTN15068651 ).

[Professional divers: analysis of critical issues and proposal of a health protocol for work fitness]. / Il lavoratore subacqueo: analisi delle criticità e proposto di un protocollo sanitario per l'idoneità al lavoro.

INTRODUCTION: From many years now, thanks to the development of modern diving techniques, there has been a rapid spread of diving activities everywhere. In fact, divers are ever more numerous both among the Armed Forces and civilians who dive for work, like fishing, biological research and archeology. AIM: The aim of the study was to propose a health protocol for work fitness of professional divers keeping in mind the peculiar work activity, existing Italian legislation that is almost out of date and the technical and scientific evolution in this occupational field. METHOD: We performed an analysis of the most frequently occurring diseases among professional divers and of the clinical investigation and imaging techniques used for work fitness assessment of professional divers. RESULTS: From analysis of the health protocol recommended by D.M. 13 January 1979 (Ministerial Decree), that is most used by occupational health physician, several critical issues emerged. Very often the clinical investigation and imaging techniques still used are almost obsolete, ignoring the execution of simple and inexpensive investigations that are more useful for work fitness assessment. CONCLUSIONS: Considering the out-dated legislation concerning diving disciplines, it is necessary to draw up a common health protocol that takes into account clinical and scientific knowledge and skills acquired in this area. This protocol's aim is to propose a useful tool for occupational health physicians who work in this sector.

Three-dimensional Doppler sonography in asymptomatic and symptomatic women after medical termination of pregnancy.

OBJECTIVES: To characterize the 3D Doppler sonographic appearance of the uterine cavity in asymptomatic and symptomatic women after administration of mifepristone and misoprostol for medical termination of pregnancy. METHODS: A prospective observational study was performed. Women admitted for medical termination of pregnancy underwent transvaginal sonography 15 days after the procedure. Volumes were acquired, and offline analyses of the 3D vascularization indices were performed. Outcomes were collected at the follow-up scan and by telephone after the termination. Women were subclassified as asymptomatic or symptomatic according to the presence/absence of fever, vaginal bleeding, abdominal/pelvic pain, and infections. Spotting was defined as any episodic vaginal bleeding that was less than an expected menstruation and not regarded as a symptom. RESULTS: A total of 104 women who underwent medical termination of pregnancy between 6 and 9 weeks' gestation were enrolled in the study. The termination procedure was successful in 98% of cases; among them, 9 women (8.6%) were symptomatic due to bleeding. Two asymptomatic women required surgery; 1 had sonographic evidence of suspected retained products of conception (endometrial thickness ≥ 15 mm or power Doppler vascularization presence). Fifty-seven women (55%) presented with retained products of conception. All the women with suspected retained products regained normal menses; of these, 3 symptomatic women with retained products (2.9%) underwent a 1-month sonographic follow-up. The symptomatic status was not associated with endometrial thickness, 3D intrauterine mass volume, or 2-dimensional (2D) and 3D power Doppler appearances. CONCLUSIONS: The necessity of surgery after medical termination of pregnancy cannot be predicted by sonography. In cases with sonographic evidence of suspected retained products of conception, endometrial thickness, 2D Doppler findings, and the 3D vascularization indices correlated poorly with bleeding symptoms. Long-term follow-up should be considered in symptomatic women, and it can avoid any unnecessary surgical intervention.