Impact of the Covid-19 pandemic on the performance of machine learning algorithms for predicting perioperative mortality.

BACKGROUND: Machine-learning models are susceptible to external influences which can result in performance deterioration. The aim of our study was to elucidate the impact of a sudden shift in covariates, like the one caused by the Covid-19 pandemic, on model performance. METHODS: After ethical approval and registration in Clinical Trials (NCT04092933, initial release 17/09/2019), we developed different models for the prediction of perioperative mortality based on preoperative data: one for the pre-pandemic data period until March 2020, one including data before the pandemic and from the first wave until May 2020, and one that covers the complete period before and during the pandemic until October 2021. We applied XGBoost as well as a Deep Learning neural network (DL). Performance metrics of each model during the different pandemic phases were determined, and XGBoost models were analysed for changes in feature importance. RESULTS: XGBoost and DL provided similar performance on the pre-pandemic data with respect to area under receiver operating characteristic (AUROC, 0.951 vs. 0.942) and area under precision-recall curve (AUPR, 0.144 vs. 0.187). Validation in patient cohorts of the different pandemic waves showed high fluctuations in performance from both AUROC and AUPR for DL, whereas the XGBoost models seemed more stable. Change in variable frequencies with onset of the pandemic were visible in age, ASA score, and the higher proportion of emergency operations, among others. Age consistently showed the highest information gain. Models based on pre-pandemic data performed worse during the first pandemic wave (AUROC 0.914 for XGBoost and DL) whereas models augmented with data from the first wave lacked performance after the first wave (AUROC 0.907 for XGBoost and 0.747 for DL). The deterioration was also visible in AUPR, which worsened by over 50% in both XGBoost and DL in the first phase after re-training. CONCLUSIONS: A sudden shift in data impacts model performance. Re-training the model with updated data may cause degradation in predictive accuracy if the changes are only transient. Too early re-training should therefore be avoided, and close model surveillance is necessary.

Sex-specific issues of central and peripheral arginine-vasopressin concentrations in neurocritical care patients.

BACKGROUND: Arginine-Vasopressin (AVP) is a nonapeptide that exerts multiple functions within the central nervous system and in the blood circulation that might contribute to outcome in critically ill patients. Sex differences have been found for mental and physical effects of AVP. For example, stress response and response due to hemorrhage differ between males and females, at least in animal studies. Data on humans -especially on AVP within the central nervous system (CNS)-are scarce, as cerebrospinal fluid (CSF) which is said to represent central AVP activity, has to be collected by means of invasive procedures. Here we present data on 30 neurocritical care patients where we simultaneously collected blood, CSF and saliva to analyze concentrations in the central and peripheral compartments. PATIENTS AND METHODS: 30 neurocritical care patients were included (13 male, 13 postmenopausal female, 4 premenopausal female) with a median age of 60 years. CSF, plasma and saliva were obtained simultaneously once in each patient and analyzed for AVP concentrations. Correlations between the central compartment represented by CSF, and the peripheral compartment represented by plasma and saliva, were identified. Relations between AVP concentrations and serum sodium and hematocrit were also determined. RESULTS: In the whole patient collective, only very weak to weak correlations could be detected between AVP plasma/CSF, plasma/saliva and CSF/saliva as well as between AVP concentrations in each of the compartments and serum sodium/hematocrit. Regarding the subgroup of postmenopausal females, a significant moderate correlation could be detected for AVP in plasma and CSF and AVP CSF and serum sodium. CONCLUSION: Absolute concentrations of AVP in central and peripheral compartments did not show sex differences. However, correlations between AVP plasma and CSF and AVP CSF and serum sodium in postmenopausal females indicate differences in AVP secretion and AVP response to triggers that deserve further examination.

Mapping Human Fetal Brain Maturation In Vivo Using Quantitative MRI.

BACKGROUND AND PURPOSE: On the basis of a single multidynamic multiecho sequence acquisition, SyMRI generates a variety of quantitative image data that can characterize tissue-specific properties. The aim of this retrospective study was to evaluate the feasibility of SyMRI for the qualitative and quantitative assessment of fetal brain maturation. MATERIALS AND METHODS: In 52 fetuses, multidynamic multiecho sequence acquisitions were available. SyMRI was used to perform multidynamic multiecho-based postprocessing. Fetal brain maturity was scored qualitatively on the basis of SyMRI-generated MR imaging data. The results were compared with conventionally acquired T1-weighted/T2-weighted contrasts as a standard of reference. Myelin-related changes in T1-/T2-relaxation time/relaxation rate, proton density, and MR imaging signal intensity of the developing fetal brain stem were measured. A Pearson correlation analysis was used to detect correlations between the following: 1) the gestational age at MR imaging and the fetal brain maturity score, and 2) the gestational age at MR imaging and the quantitative measurements. RESULTS: SyMRI provided images of sufficient quality in 12/52 (23.08%) (range, 23 + 6-34 + 0) fetal multidynamic multiecho sequence acquisitions. The fetal brain maturity score positively correlated with gestational age at MR imaging (SyMRI: r = 0.915, P < .001/standard of reference: r = 0.966, P < .001). Myelination-related changes in the T2 relaxation time/T2 relaxation rate of the medulla oblongata significantly correlated with gestational age at MR imaging (T2-relaxation time: r = -0.739, P = .006/T2-relaxation rate: r = 0.790, P = .002). CONCLUSIONS: Fetal motion limits the applicability of multidynamic multiecho-based postprocessing. However, SyMRI-generated image data of sufficient quality enable the qualitative assessment of maturity-related changes of the fetal brain. In addition, quantitative T2 relaxation time/T2 relaxation rate mapping characterizes myelin-related changes of the brain stem prenatally. This approach, if successful, opens novel possibilities for the evaluation of structural and biochemical aspects of fetal brain maturation.

Characterization of phenotypic spectrum of fetal heterotaxy syndrome by combining ultrasound and magnetic resonance imaging.

OBJECTIVE: Heterotaxy or isomerism of the atrial appendages is a congenital disorder with variable presentation, associated with both cardiac and non-cardiac anomalies, which may have a serious impact on fetal outcome. The aim of this exploratory study was to assess the value of fetal magnetic resonance imaging (MRI), as a complementary tool to ultrasound, for describing the morphological spectrum encountered in heterotaxy. METHODS: This retrospective study included 27 fetuses that underwent fetal MRI following prenatal suspicion of heterotaxy on ultrasound from 1998 to 2019 in a tertiary referral center. Heterotaxy was classified as left atrial isomerism (LAI) or right atrial isomerism (RAI) based on fetal echocardiography (FE) examination. In addition to routine prenatal ultrasound, fetal MRI was offered routinely to enhance the diagnosis of non-cardiac anomalies, which might have been missed on ultrasound. Prenatal findings on ultrasound, FE and MRI were reviewed systematically and compared with those of postnatal imaging and autopsy reports. RESULTS: Twenty-seven fetuses with heterotaxy and cardiovascular pathology, of which 19 (70%) had LAI and eight (30%) had RAI, were included. Seven (7/19 (37%)) fetuses with LAI had normal intracardiac anatomy, whereas all fetuses with RAI had a cardiac malformation. All 27 fetuses had non-cardiac anomalies on fetal MRI, including situs and splenic anomalies. In 12/19 (63%) fetuses with LAI, a specific abnormal configuration of the liver was observed on MRI. In three fetuses, fetal MRI revealed signs of total anomalous pulmonary venous connection obstruction. An abnormal bronchial tree pattern was suspected on prenatal MRI in 6/19 (32%) fetuses with LAI and 3/8 (38%) fetuses with RAI. CONCLUSIONS: Visualization on MRI of non-cardiac anomalies in fetuses with suspected heterotaxy is feasible and can assist the complex diagnosis of this condition, despite its limitations. This modality potentially enables differentiation of less severe cases from more complex ones, which may have a poorer prognosis. Fetal MRI can assist in prenatal counseling and planning postnatal management. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Beyond Isolated and Associated: A Novel Fetal MR Imaging-Based Scoring System Helps in the Prenatal Prognostication of Callosal Agenesis.

BACKGROUND AND PURPOSE: Although "corpus callosum agenesis" is an umbrella term for multiple entities, prenatal counseling is based reductively on the presence (associated) or absence (isolated) of additional abnormalities. Our aim was to test the applicability of a fetal MR neuroimaging score in a cohort of fetuses with prenatally diagnosed isolated corpus callosum agenesis and associated corpus callosum agenesis and correlate it with neurodevelopmental outcomes. MATERIALS AND METHODS: We performed a single-center retrospective analysis of a cohort of cases of consecutive corpus callosum agenesis collected between January 2011 and July 2019. Cases were scored by 2 raters, and interater agreement was calculated. Outcome was assessed by standardized testing (Bayley Scales of Infant and Toddler Development, Kaufman Assessment Battery for Children) or a structured telephone interview and correlated with scores using 2-way ANOVA. RESULTS: We included 137 cases (74 cases of isolated corpus callosum agenesis), imaged at a mean of 27 gestational weeks. Interrater agreement was excellent (0.98). Scores were higher in associated corpus callosum agenesis (P < .0001) without a significant score difference between complete and partial corpus callosum agenesis (P = .38). Outcome was assessed in 42 children with isolated corpus callosum agenesis and 9 with associated corpus callosum agenesis (mean age, 3.1 years). MR imaging scores correctly predicted developmental outcome in 90.7% of patients with isolated corpus callosum agenesis, improving neurodevelopmental risk stratification in corpus callosum agenesis. CONCLUSIONS: The scoring system is very reproducible and can differentiate isolated corpus callosum agenesis and associated isolated corpus callosum agenesis (significantly higher scores) but not between partial and complete corpus callosum agenesis. Scores correlated with outcome in isolated corpus callosum agenesis, but there were too few associated postnatal cases of isolated corpus callosum agenesis to draw conclusions in this group.

Comparison of the colon with T1 breath-hold vs T1 free-breathing-A retrospective fetal MRI study.

OBJECTIVES: Fetal magnetic resonance imaging (MRI) plays an increasingly important role in the prenatal diagnosis of gastrointestinal abnormalities. During gestation, the bowel develops T1-weighted hyperintensity due to meconium formation. Currently used T1-weighted sequences are performed in maternal breath-hold (BH) technique, which may take up to 20 s. The free-breathing (FB) T1-weighted 3D radial VIBE (volumetric interpolated breath-hold examination) sequence requires no breath-hold, improving patient comfort. This study aimed to address how well the FB acquisition technique can visualize large bowel structures compared to the routinely performed breath-hold sequence. METHODS: Forty-seven fetal MRI studies between 21 and 36 weeks of gestation without abdominal pathologies on prenatal MRI and ultrasound were included. All fetal scans were performed using a Philips Ingenia 1.5 T MRI. Coronal T1-weighted BH and FB sequences without fat suppression were compared. The following acquisition parameters were used (T1, FB): resolution 1.137 mm, 1.004 mm; matrix size 288 × 288, 448 × 448; FOV 328 mm, 450 mm; TR 81-132 ms, 3.47 ms; TE 4.6 ms, 1.47 ms. Due to the necessity of the breath-hold the duration of the sequence could not exceed 20 s (mean duration of the T1-weighted BH sequence 15.17 s, and mean duration of the FB sequence 26.42 s). In all examined fetuses the following structures were evaluated with respect to their visibility (0-not visible, 1-partially visible, 2-clearly visible): rectum, sigmoid, descending, transverse and ascending colon, cecum. Furthermore, motion artifacts were assessed (0-none, 1-intermediate, 2-severe motion artifacts), and the signal intensity (SI) ratio between maternal fat and fetal rectum SI was calculated. RESULTS: No significant differences in the visibility of sigmoid and colon between BH and FB were detected, only the cecum could be seen slightly better (in 29.8 % of cases) using BH technique. Motion artifacts were similar between BH and FB. There was a non-significant SI difference (p = 0.68) in the rectum, with a higher SI in the BH sequence. CONCLUSIONS: The FB acquisition technique compared to T1 using BH is equal regarding visibility of bowel structures and artifacts. Due to non-inferiority to the BH technique, the FB sequence is a good alternative in cases where BH cannot be performed. As the FB sequence further allows for thinner slices with a good signal, even small bowel loops may be visualized.

Normal human brainstem development in vivo: a quantitative fetal MRI study.

OBJECTIVES: To characterize spatiotemporal growth differences of prenatal brainstem substructures and cerebellum, using linear biometry and planimetry on fetal magnetic resonance imaging (MRI). METHODS: In this retrospective study, we included fetuses with normal brain and a precise midsagittal T2-weighted brain MRI sequence obtained between May 2003 and April 2019. The cross-sectional area, rostrocaudal diameter and anteroposterior diameter of the midbrain, pons (basis pontis and pontine tegmentum), medulla oblongata and cerebellar vermis, as well as the transverse cerebellar diameter, were quantified by a single observer. The diameters were also assessed by a second observer to test inter-rater variability. RESULTS: We included 161 fetuses with normal brain and a precise midsagittal MRI sequence, examined at a mean ± SD gestational age of 25.7 ± 5.4 (range, 14 + 0 to 39 + 2) weeks. All substructures of the fetal brainstem and the cerebellum could be measured consistently (mean ± SD interobserver intraclass correlation coefficient, 0.933 ± 0.065). We provide reference data for diameters and areas of the brainstem and cerebellum in the second and third trimesters. There was a significant quadratic relationship between vermian area and gestational age, and all other measured parameters showed a significant linear growth pattern within the observed period (P < 0.001). A significant change in the relative proportions of the brainstem substructures occurred between the beginning of the second trimester and the end of the third trimester, with an increase in the area of the pons (P < 0.001) and a decrease in that of the midbrain (P < 0.001), relative to the total brainstem area. CONCLUSIONS: The substructures of the fetal brainstem follow a distinct spatiotemporal growth pattern, characterized by a relative increase in the pons and decrease in the midbrain, between 15 and 40 weeks of gestation. Caution is needed when interpreting fetal brainstem appearance during the early second trimester, as the brainstem proportions differ significantly from the adult morphology. The reference data provided herein should help to increase diagnostic accuracy in detecting disorders of defective hindbrain segmentation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal ovarian cysts: development and neonatal outcome.

INTRODUCTION: The aim of the study was to evaluate the outcome of fetal ovarian cysts in relation to their size and ultrasonic appearance. METHODS: We retrospectively analysed pre- and postnatal charts of 61 infants with a prenatal diagnosis of ovarian cysts between 1991 and 2000. RESULTS: In a total of 61 fetuses 65 ovarian cysts were detected by transabdominal ultrasound: 35 (57 %) cysts on the left side, 22 (36 %) on the right side and 4 fetuses (7 %) had bilateral cysts. Three patients with uncomplicated cysts were lost to follow-up and one fetus with bilateral cysts died in the 27th week of gestation. In 17 cysts treatment was necessary. 14 cysts (all complicated) were operated after delivery because of persistence or enlargement. The histological results were either follicular or theca lutein cysts in 12 cases, one lymphangioma and one teratoma. Two cysts were aspirated in utero and one after delivery. In the remaining 40 fetuses, 43 cysts where only controlled by ultrasound. 8 cysts regressed before delivery and 35 cysts after delivery independent of their sonographic appearance. The mean diameter of cysts that required treatment was significantly different from the mean diameter of cysts that resolved spontaneously (6.8 [SD 2.4] cm vs. 3.3 [SD 0.8] cm; p < 0.01). CONCLUSION: Complicated cysts which do not regress should be treated either by laparotomy or laparoscopically after delivery. Uncomplicated cysts which exceed 5 cm could be treated by in utero aspiration or aspiration after delivery to avoid further complications. Cysts smaller than 5 cm, presenting the tendency to regress, should be left untouched independent of their sonographic appearance.

Dandy-Walker malformation as sonographic marker for fetal triploidy.

Fetal triploidy is a frequent reason for early abortion, and only few fetuses survive into the second trimester of pregnancy. Common sonographic markers for triploidy in the second trimester are severe asymmetric growth restriction (triploidy of maternal origin) and partial molar changes of the placenta (triploidy of paternal origin), together with structural fetal malformations. We report prenatal sonographic findings of thirteen triploid fetuses between 18 and 34 weeks' gestational age (eleven fetuses with 69, XXX, and two fetuses with 69, XXY). Intrauterine growth restriction (11/13 fetuses), oligohydramnios (8/13), bilateral cerebral ventriculomegaly (6/13), structural heart defects (4/13), and Dandy-Walker malformation or Dandy-Walker variant (4/13) were the most frequent findings. We conclude that the Dandy-Walker malformation and Dandy-Walker variant should be considered as additional sonographic markers for fetal triploidy.

Correlation between serum testosterone levels and peripartal mood states.

BACKGROUND: We conducted a prospective study at the Department of Obstetrics and Gynecology, University Hospital of Vienna to investigate associations between serum testosterone levels and maternal peripartal mood states. METHODS: Two hundred and fifty-two pregnant women at term (38 to 40 weeks' gestation) took part in the study. Blood samples for plasma testosterone levels and other biochemicals were obtained prepartum, and on the 1st and 3rd day postpartum. Mood was assessed with the McNair Profile of Mood States (POMS) at term pregnancy and daily from the first day after delivery until discharge from the hospital. RESULTS: The final study population consisted of 193 women. Serum testosterone levels correlated significantly with maternal depression scores, both pre- and post partum (at term r=0.148, p=0.04; 1st day postpartum r=0.156, p=0.03; and 2nd day postpartum r=0.186, p=0.02, respectively). Testosterone concentrations also correlated with anger prepartum (r=0.164, p=0.02) and on the third day after delivery (r=0.188, p=0.02). No significant correlation between testosterone concentration and fatigue and vigor both pre- and post partum, respectively were found. CONCLUSION: Serum testosterone levels correlate with depression and anger in the first postpartum days.

High levels of reticulated platelets and thrombopoietin characterize fetal thrombopoiesis.

To characterize fetal thrombopoiesis, we determined plasma thrombopoietin (TPO) and glycocalicin levels, platelet counts and reticulated platelets (RP) of fetuses and compared them with the respective values of their mothers. Percutaneous umbilical vein sampling in abnormal pregnancies revealed twofold higher thrombopoietin levels and 20-fold higher reticulated platelet counts, but lower levels of glycocalicin in fetuses compared with their mothers (P < 0.05). Neither the expression of platelet glycoprotein Ib and IIb on platelets nor the platelet counts were different between mothers and their fetuses. These data indicate enhanced thrombopoiesis and/or increased platelet turnover in fetuses.

Immunoglobulin administration to fetuses with anemia due to alloimmunization to D.

BACKGROUND: The purpose of this study was to examine fetal tolerance of high-dose intravenous immunoglobulin (IVIG), given directly at the time of intravascular transfusion, and its effects on fetal hemolysis and pregnancy outcome in the setting of alloimmunization to D. STUDY DESIGN AND METHODS: Thirteen consecutive D+ fetuses requiring transfusion for maternal alloimmunization received high-dose IVIG (1.0 g/kg) and red cell transfusions. Twenty-four previous, consecutive fetuses with maternal anti-D served as controls. The schedules for subsequent transfusions were the same in the two groups. RESULTS: High-dose IVIG was well tolerated by all fetuses. In the IVIG group, daily decreases in hematocrit were smaller than those in controls after the second administration of IVIG (mean hematocrit decrease, 0.72 percent/day vs. 1.45 percent/day; p = 0.007). No significant difference was found in the total number of fetal transfusions, the gestational age at delivery, the duration of neonatal intensive care, the number of neonates requiring postnatal transfusion therapy, and perinatal mortality. CONCLUSION: In this small pilot study, direct administration to fetuses of IVIG with red cell transfusions was well tolerated and appeared to have a beneficial effect on fetal hemolysis.

Twenty-four cordocenteses in one woman.

We report on 2 consecutive pregnancies in a woman with a history of neonatal death secondary to Rhesus alloimmunization. Her first subsequent pregnancy was complicated by fetal hydrops at 20 weeks of gestation. The fetus received a total of 11 intrauterine transfusions, and was delivered at 38 weeks. In the patient's next pregnancy, the fetus developed hydrops at 18 weeks of gestation. Thirteen intrauterine transfusions were given to correct fetal anemia, and a healthy baby was delivered at 38 weeks of gestational age. Continuation of intravascular transfusion therapy may represent a reasonable alternative to selective premature delivery even in cases with highly aggressive maternal Rhesus alloimmunization.

Unfused amnion and chorion after 14 weeks of gestation: associated fetal structural and chromosomal abnormalities.

OBJECTIVE: To assess possible associations between delayed chorioamniotic fusion after the end of the first trimester and fetal structural and/or chromosomal abnormalities. DESIGN: We prospectively studied 492 fetuses from high-risk pregnancies between 14 and 18 weeks of gestation by transabdominal ultrasonography. Of these, 60 (12%) had unfused amnion and chorion. RESULTS: No additional abnormalities were detected in 28/60 fetuses (47%). Karyotyping was performed in 27/28 cases, and one fetus had trisomy 13 (4%). Ten of 24 fetuses (42%) of this group attending a second mid-trimester scan after 18 weeks of gestation had abnormal sonographic findings not noted at the initial scan. Thirty-two of 60 (53%) fetuses had additional abnormalities at the initial scan: cystic hygroma (n = 12), increased nuchal translucency (n = 10) and other abnormalities (n = 10). Karyotyping revealed aneuploidy in 13 of 28 fetuses (46%) tested: trisomy 21 (n = 5), Turner's syndrome (n = 3), trisomy 18 (n = 3) and trisomy 13 (n = 2). Additional fetal abnormalities were detected only at the second scan after 18 weeks of gestation in three of eight fetuses (38%). CONCLUSIONS: These preliminary data suggest that the sonographic finding of unfused amnion and chorion after 14 weeks of gestation may be associated with fetal structural and/or chromosomal abnormalities.

Ultrasound evaluation of fetal spine length between 14 and 24 weeks of gestation.

The objective of our study was to establish a nomogram of fetal spine length in the second trimester of pregnancy by using two and three-dimensional ultrasound. Fetal spine length was measured prospectively by means of transabdominal ultrasonography in 114 normal singleton pregnancies between 14 and 24 weeks of gestation. Regression analyses were performed on spine length, gestational age, biparietal diameter and femur length. Supplementary three-dimensional ultrasound to assess fetal spine length was performed in 75 cases. Fetal spine length, as a function of gestational age, was expressed by the following regression equation: spine length (mm) = -47.2 + 7.16 x gestational age (weeks), with a Pearson correlation coefficient of R(2)=0.956. The results of the measurements revealed no difference between two and three-dimensional ultrasound. Our study defines the normal limits of fetal spinal length in the second trimester of pregnancy and demonstrates a high correlation between spinal length, gestational age, biparietal diameter and femur length. However, there are still too few prenatal research data to say whether and to what extent an assessment of fetal spine length at this stage of pregnancy can be used for prenatal diagnosis of congenital syndromes, which, among other manifestations, are marked by fetal spine lengthening or shortening.

Three-dimensional ultrasonographic imaging of fetal tooth buds for characterization of facial clefts.

The purpose of this prospective study was to investigate whether the antenatal characterization of fetal facial clefts can be improved by three-dimensional ultrasonographic visualization of fetal tooth buds. Between January 1996 and June 1998, seventeen consecutive fetuses with facial clefts were examined for fetal maxillary tooth buds in the cleft area using three-dimensional multiplanar reconstruction. It was possible in all cases to classify the clefts either as cleft lip alone or unilateral cleft lip and palate or bilateral cleft lip and palate. Three-dimensional computed tomography and histological jaw sections of three stillborn infants were produced in order to examine the correlation between the sonographic, radiographical and histological findings. The prenatal characterization of the facial clefts by means of a visualization of the tooth buds showed to be accurate postnatally in all cases. The sonographic proof of tooth buds might gain increasing importance as this technique seems to facilitate and improve the prenatal classification of suspected facial clefts.