84 Looking back to move forward; can fetal placental inflammatory response play a role in risk of sepsis and clinical decision making in preterm infant

Primary Subject area Neonatal-Perinatal Medicine Background Sepsis adversely impacts the survival of very low birth weight infants (VLBW), with a mortality risk up to 50%. Its diagnosis in premature infants is challenging. Conversely, prolonged antibiotic use is associated with perilous potential consequences, propelling the need to better identify those at risk of sepsis. The presence of a histological intra-amniotic inflammation (IAI) response may be associated with an increased risk of early onset sepsis (EOS). Currently, it is unknown how the diagnosis of histological IAI impacts the risk of sepsis. Objectives Our research goal is to explore histological fetal and maternal inflammation in the placenta in VLBW infants and to evaluate if specific recommendations about antibiotic management of VLBW infants with histological fetal response can be proposed. Design/Methods Retrospective cohort study of all infants < 1500 g born to a mother with histologically confirmed IAI. Demographic information about the pregnancy, delivery and postnatal course up to 28 days of life was extracted. Descriptive statistical analysis was conducted to compare the characteristics of infants with histological fetal response using χ2 test or Fisher’s exact test and Wilcoxon rank sum test or ANOVA. Results Seventy-three mother-baby pairs were reviewed. EOS prevalence (19%) in our IAI group of VLBW infants is much higher than EOS observed in all VLBW infants from the Canadian Neonatal Network database (below 3%). In our cohort, the majority had fetal inflammatory stage 1 (31.6%) and fetal inflammatory grade 0 (50%). There was no statistically significant distribution amongst the fetal stages or grades. Time to sepsis event analysis showed that the earlier fetal inflammatory grade was associated with positive cultures occurring earlier, while in the later grades there demonstrated longer latency to positive cultures. This trend was also true when looking at the maternal inflammatory stages. Nine infants who had antibiotics discontinued from day of life (DOL) 2-5 developed a positive blood culture ≤ DOL8. Conclusion Our results suggest that the presence of mild fetal inflammatory changes is associated with earlier positive cultures. We hypothesize that later grades may be associated with longer infection exposure leading to prolonged maternal antibiotics, resulting in less EOS. Majority of positive cultures were within the 3-8 day window, suggesting a role of knowing the fetal inflammatory response when deciding duration of antibiotic treatment.

Acute Fetal Response to High-Intensity Interval Training in the Second and Third Trimesters of Pregnancy

The majority of women do not meet the recommended levels of exercise during their pregnancies, frequently due to a lack of time. High-intensity interval training offers a potential solution, providing an effective, time-efficient exercise modality. This exercise modality has not been studied in pregnancy therefore, the objective of this study was to evaluate fetal response to a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy. Fourteen active, healthy women with uncomplicated, singleton pregnancies participated in a high-intensity interval training resistance circuit between 28+0/7 and 32+0/7 weeks. A Borg rating of perceived exertion of 15-17/20 and an estimated heart rate of 80-90% of maternal heart-rate maximum was targeted. Fetal well-being was evaluated continuously with fetal heart-rate tracings and umbilical artery Doppler velocimetry conducted pre-and post-exercise. Fetal heart rate tracings were normal throughout the exercise circuit. Post-exercise, umbilical artery end-diastolic flow was normal and significant decreases were observed in the mean systolic/diastolic ratios, pulsatility indexes and resistance indexes. Therefore, in a small cohort of active pregnant women, a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy appears to be a safe exercise modality with no acute, adverse fetal effects but further study is required. Novelty: • High-Intensity Interval Training, at an intensity in excess of current recommendations, does not appear to be associated with any adverse fetal effects in previously active pregnant women. • High-Intensity Interval Training is an enjoyable and effective exercise modality in previously active pregnant women.

Vitelline Vessel Remnant-Derived Funisitis Is a Sensitive and Specific Predictor of Histological Evidence of Amniotic Fluid Infection

Background 4-11% of umbilical cords contain vitelline vessel remnants (VVRs). A recent study has described neutrophilic inflammation arising from VVRs and suggested an association with amniotic fluid infection (AFI). Methods During routine placental pathology sign-out over a six month period, we identified 70 cords with VVRs. HE-stained sections were re-examined for “VVR-derived funisitis,” which was classified as low or high grade/stage based upon whether neutrophils were present only in Wharton’s jelly near the VVRs or whether neutrophils were also present near the cord’s amniotic surface. The same placentas were also examined for histologic evidence of AFI (maternal response = acute chorionitis or chorioamnionitis vs. fetal response = chorionic vasculitis, umbilical vasculitis, or funisitis vs. both). Results Neutrophilic inflammation arising from VVRs was present in 54.3% (38/70); 15 and 23 lesions were low and high grade/stage, respectively. “VVR-derived funisitis” was strongly associated with histological evidence of AFI elsewhere in the placenta. Its overall sensitivity and specificity were 0.94 and 0.88; when VVR-derived funisitis was high grade/stage or diagnosed in the third trimester, specificity rose to 1.0. Conclusion “VVR-derived funisitis” has a strong association with histological evidence of AFI.

Bosque Aleatorio Basado en Rasgos Tiempo-Frecuencia de la VFC Fetal para la Identificación de Actividad Uterina en Fetos a Término y Pretérmino

The aim of this work was to discriminate periods of contraction and periods of rest during labor by implementing a random forest classifier based on time-frequency features of the fetal heart rate variability (fHRV) from term and preterm fetuses. fHRV signals from term (PT = 38) and preterm (PP = 25) fetuses were analyzed during active labor. The signals were segmented with respect to the presence or absence of uterine activity. Subsequently, time-frequency indices of fHRV such as flow (0 °, 45 ° and 90 °) and energy (very low, low and high frequency) were calculated. The classifier obtained an area under the ROC curve of 0.87 and 0.88, for PT and PP respectively. Our results suggest that for both groups (PT and PP), there is a different cardiac dynamic between periods of contraction and periods of rest. Therefore, it is important to distinguish between the two periods to adequately characterize the fetal response to labor.

Immunological assessment of SARS-CoV-2 Infection in Pregnancy From Diagnosis to Delivery: A multicentre prospective observational study

Objective We profile the maternal and fetal response to SARS-CoV-2 infection in symptomatic and asymptomatic pregnant women and make an assessment of passive immunity to the neonate, Design Multicentre prospective study. Setting Dublin, Ireland Methods RT-PCR for viral RNA via a nasopharyngeal swab was performed using the Cobas SARS-CoV-2 6800 platform. Maternal, and fetal serological antibody response, via umbilical cord bloods, was measured using both the Elecsys® immunoassay, Abbott SARS-CoV-2 IgG Assay and the IgM Architect assay. Main outcome Measure Prevalence of RT PCR positive SARS-CoV-2. Assessment of IgM and IgG anti-SARS-CoV-2 serology antibodies. Results Ten of twenty three symptomatic women had SARS-CoV-2 RNA in a nasopharyngeal swab. Five (5/23, 21.7%) demonstrated serological evidence of anti-SARS-CoV-2 IgG antibodies and seven (30.4%, 7/23) were positive for IgM antibodies. In the asymptomatic cohort, the prevalence of SARS-CoV-2 infection in RNA was 0.16% (1/608). IgG SARS-CoV-2 antibodies were detected in 1·67% (10/598, 95% CI 0·8%-3·1%) and IgM in 3·51% (21/598, 95% CI 2·3–5·5%). Nine women had repeat testing between post baseline. Four (4/9, 44%) remained IgM positive, one IgG positive. IgG anti SARS-CoV-2 antibodies were detectable in cord bloods from babies born to five seropositive women who delivered during the study. Conclusion Using two independent serological assays, we present a comprehensive illustration of the antibody response to SARS-CoV-2 in pregnancy, and show a low prevalence of asymptomatic SARS-CoV-2. Transplacental migration of anti-SARS-CoV-2 antibodies was identified in cord blood of women who demonstrated antenatal anti-SARS-CoV-2 antibodies, raising the possibility of passive immunity.

Extended multi-drug maternal therapy for refractory supraventricular tachycardia in premature hydrops fetalis

Background Fetal supraventricular tachycardia (SVT) is a reversible cause of fetal hydrops, with better outcomes if detected early and reverted in utero. Modern imaging allows accurate diagnosis and maternal anti-arrhythmic therapy can be practiced ensuring in utero cardioversion. Case presentation We present a case of preterm fetal hydrops due to SVT successfully reverted in utero by multidrug maternal therapy. The mother presented to our tertiary care hospital at 32 weeks’ gestation with a fetal heart rate of 229 beats/min with evidence of mild fetal pericardial effusion and ascites. Under strict maternal monitoring, the treatment was started with parenteral digoxin. Flecainide, sotalol and amiodarone were introduced sequentially based on the response until cardioversion was achieved at 35 weeks with no maternal side effects. She labored spontaneously and delivered a 2.6 kg baby boy 4 days after the successful cardioversion. The baby was discharged home on day 7 on oral amiodarone with outpatient follow-up. Digoxin monotherapy failed in our case, possibly due to evidence of hydrops and a sequential multi-drug therapy was required for an extended duration of up to 2 weeks to achieve cardioversion successfully. Conclusions Our report suggests that multi-drug therapy is more successful in cases of SVT with fetal hydrops, titrated according to fetal response and maternal tolerance, although a prolonged period of therapy might be required to achieve the desired clinical effect.

Fetal Renal Echogenicity Associated with Maternal Focal Segmental Glomerulosclerosis: The Effect of Transplacental Transmission of Permeability Factor suPAR

We report a case of a pregnant woman with nephrotic syndrome due to biopsy-proven focal segmental glomerulosclerosis (FSGS) whose fetus developed echogenic kidneys and severe oligohydramnios by 27 weeks of gestation. Maternal treatment with prednisone resulted in normalization of the amniotic fluid indices and resolution of fetal renal echogenicity. The newborn was noted to have transient renal dysfunction and proteinuria, resolving by 6 weeks postpartum. The transplacental passage of permeability factors is postulated to have caused both the fetal and newborn renal presentation, with significantly elevated levels of soluble urokinase-type plasminogen activator receptor (suPAR) noted in the cord blood. This case documents the transplacental maternal-fetal transmission of suPAR, demonstrating the potential for maternal-fetal transmission of deleterious, disease-causing entities, and adds to the differential diagnosis of fetal echogenic kidneys. Further, this is the first documentation of a fetal response to maternal systemic therapy.