Immune Response to SARS-CoV-2 in Vaccine-naive Pregnant Women: Assessment of IgG and IgA Antibody Profile at Delivery and 42 Days Postpartum.

This prospective cohort study assessed the SARS-CoV-2 IgG and IgA Ab profiles at delivery and 42 d postpartum in unvaccinated SARS-CoV-2-positive pregnant women and determined the association with the timing and the clinical course of the infection. A total of 387 vaccine-naive women with confirmed SARS-CoV-2 infection during pregnancy were included. IgG and IgA Abs were detected in maternal blood at delivery and 42 d postpartum using ELISA kits. The relationships between Ab detection and value and clinical features, including the timing of the infection, were analyzed using univariate and multivariate logistic and linear regression models. The mean gestational age at infection was 31 4/7 wk of pregnancy. Symptoms of SARS-CoV-2 infection were present in 88.1% of women. IgG and IgA Abs were detected in 45.7 and 58.9% at delivery, respectively, increasing to 72.7 and 76.8% at 42 d postpartum. Detection of IgG and IgA Abs in maternal blood at delivery was independently associated with symptomatic infection (adjusted odds ratio [OR] 3.13, 95% confidence interval (CI): 1.47-6.69 and adjusted OR 3.62, 95% CI: 1.8-7.26, respectively), but not with the time from positive swab to delivery or gestational age at positive swab. Detection of Abs at 42 d postpartum was also strongly associated with the detection of Abs at delivery (OR 29.97, 95% CI: 10.11-88.82 for IgG and OR 13.09, 95% CI: 6.37-26.9 for IgA). Vaccine-naive pregnant women exhibit a significant and durable immune response to SARS-CoV-2, which is more pronounced in symptomatic women but independent of gestational age at diagnosis or the diagnosis-to-delivery interval.

Uncovering early predictors of cerebral palsy through the application of machine learning: a case-control study.

OBJECTIVE: Cerebral palsy (CP) is a group of neurological disorders with profound implications for children's development. The identification of perinatal risk factors for CP may lead to improved preventive and therapeutic strategies. This study aimed to identify the early predictors of CP using machine learning (ML). DESIGN: This is a retrospective case-control study, using data from the two population-based databases, the Slovenian National Perinatal Information System and the Slovenian Registry of Cerebral Palsy. Multiple ML algorithms were evaluated to identify the best model for predicting CP. SETTING: This is a population-based study of CP and control subjects born into one of Slovenia's 14 maternity wards. PARTICIPANTS: A total of 382 CP cases, born between 2002 and 2017, were identified. Controls were selected at a control-to-case ratio of 3:1, with matched gestational age and birth multiplicity. CP cases with congenital anomalies (n=44) were excluded from the analysis. A total of 338 CP cases and 1014 controls were included in the study. EXPOSURE: 135 variables relating to perinatal and maternal factors. MAIN OUTCOME MEASURES: Receiver operating characteristic (ROC), sensitivity and specificity. RESULTS: The stochastic gradient boosting ML model (271 cases and 812 controls) demonstrated the highest mean ROC value of 0.81 (mean sensitivity=0.46 and mean specificity=0.95). Using this model with the validation dataset (67 cases and 202 controls) resulted in an area under the ROC curve of 0.77 (mean sensitivity=0.27 and mean specificity=0.94). CONCLUSIONS: Our final ML model using early perinatal factors could not reliably predict CP in our cohort. Future studies should evaluate models with additional factors, such as genetic and neuroimaging data.

Successful use of tocilizumab and casirivimab/imdevimab in a twin pregnancy with critical COVID-19 - A case report.

COVID-19 in pregnancy is associated with increased maternal morbidity and mortality as well as higher risk for hospitalization in intensive care unit and mechanical ventilation. We present a 38-year-old 21+5week pregnant unvaccinated woman with twins and critical COVID-19 pneumonia caused by Delta SARS-CoV-2 strain. Because of rapid worsening of respiratory condition despite standard of care treatment with steroids, she received a combination of casirivimab/imdevimab and tocilizumab. After therapy we noticed respiratory improvement and after 10 days she was extubated. Due to selective fetal growth restriction of one of the twins, a planned caesarean section was performed at 34+6 weeks. Presented case indicates favorable outcome and safe use of casirivimab/imdevimab and tocilizumab in critical COVID-19, as no severe or minor signs or symptoms in the case presentation were observed neither in the mother nor in infants during the time of observation.

Effect of Prenatal Yoga versus Moderate-Intensity Walking on Cardiorespiratory Adaptation to Acute Psychological Stress: Insights from Non-Invasive Beat-to-Beat Monitoring.

We recently reported enhanced parasympathetic activation at rest throughout pregnancy associated with regular yoga practice. The present study presents a secondary analysis of data collected within a prospective cohort study of 33 pregnant women practicing yoga once weekly throughout pregnancy and 36 controls not involved in formal pregnancy exercise programs. The objective was to assess the impact of prenatal yoga on the autonomic nervous system stress response. Healthy pregnant women with singleton pregnancies were recruited in the first trimester. There was no significant difference in the maternal body mass index (BMI) between the yoga group and the controls (24.06 ± 3.55 vs. 23.74 ± 3.43 kg/m2, p = 0.693). Women practicing yoga were older (28.6 ± 3.9 vs. 31.3 ± 3.5 years, p = 0.005) and more often nulliparous (26 (79%) vs. 18 (50%), p = 0.001). We studied heart rate variability (HRV) parameters in the time domain (SDNN, standard deviation of regular R-R intervals, and RMSSD, square root of mean squared differences of successive R-R intervals) and frequency domain (ln(LF/HF), natural logarithm of low-frequency to high-frequency power), as well as synchronization indices of heart rate, blood pressure and respiration during and immediately following acute psychological stress of a standardized mental challenge test. Measurements were performed once per trimester before and after yoga or a 30 min moderate-intensity walk. Statistical comparison was performed using three-way analyses of variance (p < 0.05 significant). Time domain HRV parameters during and following mental challenge in the yoga group were significantly higher compared to the controls regardless of the trimester (F = 7.22, p = 0.009 for SDNN and F = 9.57, p = 0.003 for RMSSD, respectively). We observed no significant differences in the yoga group vs. the controls in terms of ln(LF/HF) and synchronization indices. Regular prenatal yoga practice was associated with a significantly reduced sympathetic response to mental challenge and quicker recovery after acute psychological stress. These effects persisted throughout pregnancy with regular practice.

The role of lung and cardiac ultrasound for cardiovascular hemodynamic assessment of women with preeclampsia.

Preeclampsia remains the leading cause of maternal morbidity and mortality and is associated with abnormal body fluid homeostasis and cardiovascular dysfunction. Moreover, 2 distinct hemodynamic phenotypes have been described in preeclampsia, which might require different therapeutic approaches. Fluid restriction is mandatory in women at risk of pulmonary edema, whereas additional fluid administration may be required to correct tissue hypoperfusion in women with intravascular volume depletion. As clinical examination alone cannot discriminate among different hemodynamic patterns, optimal management of women with preeclampsia remains challenging. Noninvasive bedside ultrasound has become an important diagnostic and monitoring tool in critically ill patients, and it has been demonstrated that it can also be used in the monitoring of women with preeclampsia. Echocardiography in combination with lung ultrasound provides information on hemodynamic status, cardiac function, lung congestion, and fluid responsiveness and, therefore, could help clinicians identify women at higher risk of life-threatening complications. This review describes the cardiovascular changes in preeclampsia and provides an overview of the ultrasound methodologies that could be efficiently used for better hemodynamic assessment and management of women with preeclampsia.

Maternal Fatigue after Postpartum Anemia Treatment with Intravenous Ferric Carboxymaltose vs. Intravenous Ferric Derisomaltose vs. Oral Ferrous Sulphate: A Randomized Controlled Trial.

(1) Background: Postpartum anemia is a common maternal complication and is recognized as a cause of impaired quality of life, reduced cognitive abilities, and fatigue. Efficient iron supplementation for the treatment of postpartum anemia is an essential component of high-quality maternal care. The optimal mode of iron supplementation has not been determined yet, whether oral or intravenous. The objective of this study was to compare postpartum anemia treatment with intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate. (2) Methods: A single-center, open-label, randomized controlled trial. Women with hemoglobin < 100 g/L within 48 h postpartum were randomly allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose, or oral ferrous sulfate. Intravenous iron was given in one or two doses, while ferrous sulfate was given as two 80 mg tablets once daily. The primary outcome was maternal fatigue measured by the Multidimensional Fatigue Inventory (MFI) six weeks postpartum. Hemoglobin, ferritin, and transferrin saturation levels were analyzed as secondary outcomes. A Kruskal-Wallis test was used for group comparison (p < 0.05 significant). (3) Results: Three hundred women were included. The MFI score at six weeks postpartum did not differ between groups (median 38 (inter-quartile range (IQR) 29-47) in the ferric carboxymaltose group, median 34 (IQR 26-42) in the ferric derisomaltose group, and median 36 (IQR 25-47) in the ferrous sulfate group; p = 0.26). Participants receiving oral iron had lower levels of hemoglobin (135 (131-139) vs. 134 (129-139) vs. 131 (125-137) g/L; p = 0.008), ferritin (273 (198-377) vs. 187 (155-246) vs. 24 (17-37) µg/L; p < 0.001) and transferrin saturation (34 (28-38) vs. 30 (23-37) vs. 24 (17-37) %; p < 0.001) than those receiving ferric carboxymaltose or ferric derisomaltose. (4) Conclusions: Intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate had similar impacts on maternal fatigue at six weeks postpartum despite improved laboratory parameters in the intravenous groups.

Incidence of postpartum depression after treatment of postpartum anaemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate: A randomized clinical trial.

Objectives: This study aimed to explore whether the type of iron preparation used to treat postpartum anaemia affects the incidence of postpartum depression and whether the risk of postpartum depression is higher in postpartum patients with anaemia who were adequately treated compared to the general postpartum population. Study design: Single-center, open-label, randomized trial. Women were allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Intravenous iron was given in one or two doses, while ferrous sulphate as two 80 mg tablets once daily. Primary outcome was postpartum depression measured by Edinburgh Postnatal Depression Scale (EPDS) six weeks postpartum. Haematological parameters were analyzed as secondary outcomes. Kruskal-Wallis test was used for group comparison (p < 0.05 significant). The chi-square test was applied to compare categorical variables as well as the group of all subjects treated for anaemia in the study with the historical data for the Slovenian postpartum population. Results: Three-hundred women with postpartum anemia (hemoglobin < 100 g/L within 48-hours postpartum) were included between September 2020 and March 2022 in tertiary perinatal center. Most characteristics were similar across groups. EPDS score at six weeks postpartum did not differ between groups. The treatment modality of postpartum anaemia did not have a statistically significant effect on the EPDS score six weeks after treatment (p = 0.10), nor did it have a statistically significant effect on the difference in EPDS scores before and after treatment (p = 0.68). The proportions of participants who scored 10 or more points on the EPDS scores at six weeks postpartum were not statistically different between the groups (p = 0.79). The proportion of participants with an EPDS score of 10 or more at six weeks postpartum in the total study population did not differ significantly from previously reported proportion of postpartum women with EPDS score of 10 or more in the general population (12 % vs. 21 %; p < 0.001). Conclusions: Maternal depression at 6 weeks postpartum did not differ in women treated for postpartum anemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Participants with postpartum anaemia who are adequately treated with either oral or intravenous iron preparations are not at a higher risk of postpartum depression than the general population at six weeks postpartum.

Intrapartum Cesarean Section and Perinatal Outcomes after Epidural Analgesia or Remifentanil-PCA in Breech and Twin Deliveries.

Comparative data on the potential impact of various forms of labor analgesia on the mode of delivery and neonatal complications in vaginal deliveries of singleton breech and twin fetuses are lacking. The present study aimed to determine the associations between type of labor analgesia (epidural analgesia (EA) vs. remifentanil patient-controlled analgesia (PCA)) and intrapartum cesarean sections (CS), and maternal and neonatal adverse outcomes in breech and twin vaginal births. A retrospective analysis of planned vaginal breech and twin deliveries at the Department of Perinatology, University Medical Centre Ljubljana, was performed for the period 2013-2021, using data obtained from the Slovenian National Perinatal Information System. The pre-specified outcomes studied were the rates of CS in labor, postpartum hemorrhage, obstetric anal sphincter injury (OASI), an Apgar score of <7 at 5 min after birth, birth asphyxia, and neonatal intensive care admission. A total of 371 deliveries were analyzed, including 127 term breech and 244 twin births. There were no statistically significant nor clinically relevant differences between the EA and remifentanil-PCA groups in any of the outcomes studied. Our findings suggest that both EA and remifentanil-PCA are safe and comparable in terms of labor outcomes in singleton breech and twin deliveries.

Wellbeing Forecasting in Postpartum Anemia Patients.

Postpartum anemia is a very common maternal health problem and remains a persistent public health issue globally. It negatively affects maternal mood and could lead to depression, increased fatigue, and decreased cognitive abilities. It can and should be treated by restoring iron stores. However, in most health systems, there is typically a six-week gap between birth and the follow-up postpartum visit. Risks of postpartum maternal complications are usually assessed shortly after birth by clinicians intuitively, taking into account psychosocial and physical factors, such as the presence of anemia and the type of iron supplementation. In this paper, we investigate the possibility of using machine-learning algorithms to more reliably forecast three parameters related to patient wellbeing, namely depression (measured by Edinburgh Postnatal Depression Scale-EPDS), overall tiredness, and physical tiredness (both measured by Multidimensional Fatigue Inventory-MFI). Data from 261 patients were used to train the forecasting models for each of the three parameters, and they outperformed the baseline models that always predicted the mean values of the training data. The mean average error of the elastic net regression model for predicting the EPDS score (with values ranging from 0 to 19) was 2.3 and outperformed the baseline, which already hints at the clinical usefulness of using such a model. We further investigated what features are the most important for this prediction, where the EDPS score and both tiredness indexes at birth turned out to be by far the most prominent prediction features. Our study indicates that the machine-learning model approach has the potential for use in clinical practice to predict the onset of depression and severe fatigue in anemic patients postpartum and potentially improve the detection and management of postpartum depression and fatigue.

Ethical Dilemmas in Neonatal Care at the Limit of Viability.

Advances in neonatal care have pushed the limit of viability to incrementally lower gestations over the last decades. However, surviving extremely premature neonates are prone to long-term neurodevelopmental handicaps. This makes ethics a crucial dimension of periviable birth management. At 22 weeks, survival ranges from 1 to 15%, and profound disabilities in survivors are common. Consequently, there is no beneficence-based obligation to offer any aggressive perinatal management. At 23 weeks, survival ranges from 8 to 54%, and survival without severe handicap ranges from 7 to 23%. If fetal indication for cesarean delivery appears, the procedure may be offered when neonatal resuscitation is planned. At a gestational age ≥24 weeks, up to 51% neonates are expected to survive the neonatal period. Survival without profound neurologic disability ranges from 12 to 38%. Beneficence-based obligation to intervene is reasonable at these gestations. Nevertheless, autonomy of parents should also be respected, and parental consent should be sought prior to any intervention. Optimal counselling of parents involves harmonized cooperation of obstetric and neonatal care providers. Every fetus/neonate and every pregnant woman are different and have the right to be considered individually when treatment decisions are being made.

Physical fitness trajectories from childhood to adolescence in extremely preterm children: A longitudinal cohort study.

OBJECTIVE: Cohort studies on physical fitness (PF) in former extremely preterm children are scarce and yield conflicting results. Therefore, this study aimed to assess the effect of extremely preterm birth on PF in school-age with a focus on bronchopulmonary dysplasia (BPD). METHODS: Eighty school-aged children were enrolled in the longitudinal cohort study. Fifty were born extremely preterm (

Comparison of Four Intrapartum Cardiotocography Classifications for Predicting Neonatal Acidemia at Birth.

Objective: To compare diagnostic values of four intrapartum cardiotocography (CTG) classifications in predicting neonatal acidemia at birth. Methods: Retrospective case-control study. Forty-three CTG traces with an umbilical artery pH < 7.00 (study group) and 43 traces with a pH ≥ 7.00 (control group) were analyzed. Inclusion criteria were singleton pregnancy, cephalic presentation, admission to labour ward during active phase of first stage of labour, and gestational age 37+0 to 41+6 weeks. Exclusion criteria were suspected intrauterine growth restriction, oligohydramnios, polyhydramnios, pregestational or gestational insulin-dependent diabetes mellitus, and preeclampsia. Last 30-60 minutes before delivery of CTG traces was classified retrospectively according to four classification systems-International Federation of Gynecology and Obstetrics (FIGO), Royal College of Obstetricians and Gynaecologists (RCOG), National Institute of Child Health and Human Development (NICHD), and the 5-tier system by Parer and Ikeda. Predictive value of each classification for neonatal acidemia was assessed using receiver operating characteristics (ROC) analysis. Results: FIGO, RCOG, and NICHD classifications predicted neonatal acidemia with areas under the ROC curves (AUC) of 0.73, 95% confidence interval (CI) 0.63-0.84; 0.72, 95% CI 0.60-0.83; and 0.69, 95% CI 0.57-0.80, respectively. The five-tier system by Parer and Ikeda had significantly better predictive value with an AUC of 0.96, 95% CI 0.91-1.00. Conclusions: The 5-tier classification system proposed by Parer and Ikeda for assessing CTG in labour was superior to FIGO, RCOG, and NICHD intrapartum CTG classifications in predicting severe neonatal acidemia at birth.

Comparison of Neonatal Morbidity and Mortality Following Spontaneous and Medically Indicated Preterm Births: A Retrospective Population-Based Study Using Data from the Slovenian National Perinatal Information System 2013-2018.

BACKGROUND This retrospective population-based study analyzed data from the Slovenian National Perinatal Information System (NPIS) between 2013 and 2018 to compare neonatal morbidity and mortality following spontaneous and medically indicated preterm births. MATERIAL AND METHODS Retrospective population-based cohort. Entries to the NPIS database were searched by gestational age (GA) <37 weeks in Slovenia between 2013 and 2018. Of 9200 (6252 following spontaneous birth, 2948 following medically indicated) neonates included, 1358 were born at extremely to very preterm GA (998 following spontaneous birth, 360 following medically indicated). Logistic regression analysis was used to examine the association between neonatal mortality and composite severe neonatal morbidity and preterm birth type (spontaneous vs medically indicated) controlling for potential confounding variables. Analysis was first performed for all preterm births (GA 22 0/7 to 36 6/7) and later only for extremely to very preterm births (GA 22 0/7 to 31 6/7). RESULTS Neonatal mortality was significantly lower following spontaneous preterm birth at extremely to very preterm GA (odds ratio [OR] 0.34; 95% confidence interval [CI] [0.14, 0.81]), while there was no association in all preterm births group (OR 0.56; 95% CI [0.26, 1.20]). No significant correlation between preterm birth type and neonatal morbidity was found (OR 0.76; 95% CI [0.54, 1.09] for all preterm births and OR 0.71; 95% CI [0.47, 1.07] for extremely to very preterm births). CONCLUSIONS In this population study from Slovenia between 2013 and 2018, medically indicated preterm births at <32 weeks of GA were associated with significantly increased neonatal mortality but not neonatal morbidity.

Mixed Intervillositis in SARS-CoV-2 Infection Associated with Fetal Death: A Case Report.

Maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been shown in epidemiological studies to be associated with an increased risk of stillbirth. Several histopathologic features of placental SARS-CoV-2 infection have been proposed as potential causes of fetal death. We present a case of an otherwise healthy G3P1 women with mild symptoms of SARS-CoV-2 infection at 23 6/7 weeks of gestation. At 25 2/7 weeks, she presented with signs and symptoms of preterm labor and decreased fetal movements. Fetal death was diagnosed at admission. Placental pathology showed pronounced placental mixed intervillositis. Inflammatory infiltrate caused extreme narrowing of intervillous space leading to placental malfunction and fetal death. Placental tissue SARS-CoV-2 infection was confirmed by positive immunohistochemistry staining of syncytiotrophoblasts with spike protein antibody. The case presented suggests that SARS-CoV-2 associated inflammatory placental changes pose an elevated risk for the fetus.

Comparison of Oxytocin vs. Carbetocin Uterotonic Activity after Caesarean Delivery Assessed by Electrohysterography: A Randomised Trial.

Electrohysterography has been used for monitoring uterine contractility in pregnancy and labour. Effective uterine contractility is crucial for preventing postpartum haemorrhage. The objective of our study was to compare postpartum electrohysterograms in women receiving oxytocin vs. carbetocin for postpartum haemorrhage prevention after caesarean delivery. The trial is registered at ClinicalTrials.gov with the identifier NCT04201665. We included 64 healthy women with uncomplicated singleton pregnancies at term scheduled for caesarean section after one previous caesarean section. After surgery, a 15 min electrohysterogram was obtained after which women were randomised to receive either five IU of oxytocin intravenously or 100 µg of carbetocin intramuscularly. A 30 min electrohysterogram was performed two hours after drug application. Changes in power density spectrum peak frequency of electrohysterogram pseudo-bursts were analysed. A significant reduction in power density spectrum peak frequency in the first two hours was observed after carbetocin but not after oxytocin (median = 0.07 (interquartile range (IQR): 0.87 Hz) compared to median = -0.63 (IQR: 0.20) Hz; p = 0.004). Electrohysterography can be used for objective comparison of uterotonic effects. We found significantly higher power density spectrum peak frequency two hours after oxytocin compared to carbetocin.

Effect of Prenatal Yoga on Heart Rate Variability and Cardio-Respiratory Synchronization: A Prospective Cohort Study.

The objective was to assess the effects of prenatal yoga on heart rate variability (HRV) and cardio-respiratory synchronization, used as proxies of autonomic nervous system activity. Sixty-nine healthy pregnant women were included; 33 in a yoga group attending at least one 90-min yoga class weekly throughout pregnancy, and 36 controls not involved in formal pregnancy exercise programs. Measurements of the time domain (SDNN, standard deviation of regular R-R intervals, and RMSSD, square root of mean squared differences of successive R-R intervals) and frequency domain (ln(LF/HF), natural logarithm of low-frequency to high-frequency power) HRV indices, as well as cardio-respiratory synchronization indexes were performed once per trimester before and after yoga or 30-min moderate-intensity walk. A statistical comparison was performed using a three-way analysis of the variance (p < 0.05 significant). Both the time domain and frequency domain HRV indices showed significant shifts towards parasympathetic dominance following yoga when compared to the controls throughout pregnancy (p = 0.002 for SDNN, p < 0.001 for RMSSD, and p = 0.006 for ln(LF/HF), respectively). There was a statistically non-significant trend towards higher synchronization between respiratory frequency and heart rate following yoga vs. controls (p = 0.057). Regular prenatal yoga was associated with enhanced parasympathetic activation persisting throughout pregnancy.

Protective Effect of Lactobacillus crispatus against Vaginal Colonization with Group B Streptococci in the Third Trimester of Pregnancy.

Background: A normal vaginal microbiota may protect the vaginal mucosa from colonization by potentially pathogenic bacteria, including group B streptococci (GBS). The aim of this study was to investigate the association between colonization with GBS and the presence of specific vaginal microbiota isolated from vaginal swabs in the third trimester of pregnancy. Methods: A semiquantitative culture of 1860 vaginal swabs from consecutive pregnant women in their third trimester was analyzed. The dominant bacteria, including lactobacilli, were identified using MALDI-TOF mass spectrometry. An enrichment culture for GBS was performed on the swabs. GBS colonization correlated with the bacteria isolated at the same time. Results: Lactobacilluscrispatus was isolated in 27.5% of the cultures, followed by L. jensenii (13.9%), L. gasseri (12.6%), and L. iners (10.1%). The presence of lactobacilli as a group, and of L. crispatus, inversely correlated with GBS colonization (OR = 0.44 and OR = 0.5, respectively; both with p < 0.001). Other microorganisms, including Gardnerella vaginalis, mixed aerobic bacteria and yeasts, were not associated with GBS colonization. Conclusions: Lactobacilli, especially L. crispatus, may prevent GBS colonization in pregnancy. Maintaining a normal vaginal microbiota could be an effective method for the antibiotic-free prevention of invasive GBS infections in neonates.