The incidence of tubular carcinoma and mean patient age in this study tend to reflect demographic data seen in previously published series (2,3,7-9). The relatively small mean tumor size and low rate of axillary metastases as well as the high association with both DCIS and ER ⁄ PR positivity are also consistent with prior series (2,7,10-13). Our results compare favorably with recent literature supporting an excellent prognosis and overall low rate of axillary lymph node metastases. In the current study, there were no distant or locoregional recurrences noted, with a median follow-up of over 5 years. The treatment approach for the majority of tubular cancers, which is present in an early stage without clinical evidence of lymph node involvement, is currently unresolved; however, the majority of standard approaches continue to yield excellent results.

Background: SARS-CoV-2 infection triggers a significant maternal inflammatory response. There is a dearth of information regarding whether maternal SARS-CoV-2 infection at admission for delivery or SARS-CoV-2 vaccination triggers an inflammatory response in the fetus. Objective: This study aimed to evaluate fetal inflammatory response to maternal SARS-CoV-2 infection or SARS-CoV-2 vaccination compared to control group. Study Design: A prospective cohort study was performed with a total of 61 pregnant women who presented for delivery at a single medical center (William Beaumont Hospital, Royal Oak, MI). All mothers were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) on admission to Labor and Delivery unit. Three groups were evaluated: 22 pregnant with a positive SARS-CoV-2 test (case group), 23 pregnant women with a negative SARS-CoV-2 test (control group), and 16 pregnant women who had recent SAR-CoV-2 vaccination and a negative SARS-CoV-2 test (vaccine group). At delivery, cord blood was collected to determine the levels of IL-6, C-reactive protein (CRP), and SARS-CoV-2 Nucleocapsid IgG and IgM antibodies. In all cases, the newborn had a negative PCR test or showed no clinical findings consistent with SARS-CoV-2 infection. Results: Mean (SD) IL-6 level was not significantly different for the three groups: case group 9.00 +/- 3.340 pg/ml, control group 5.19 +/- 0.759 pg/ml, and vaccine group 7.11 +/- 2.468 pg/ml (p-value 0.855). Pairwise comparison also revealed no statistical difference for IL-6 concentrations with p-values for case versus control, case versus vaccine, and control versus vaccine = 0.57, 0.91, and 0.74, respectively. Similarly, there were no statistically significant difference in the frequency of elevated IL-6 (> 11 pg/ml) between groups (p-value 0.89). CRP levels across the three groups were not statistically significant different (p-value 0.634). Pairwise comparison of CRP levels among the different groups were also not statistically different. SARS-CoV-2 Nucleocaspid IgG was positive in 12 out of 22 cord blood samples in the case group, 2 out of 23 of the control group (indicating old resolved maternal infection), and 0 out of 16 of the vaccine group. SARS-CoV-2 Nucleocaspid IgM was negative in all cord blood samples of the case group, control group and vaccine group. Limitations: A total number of 61 mothers enrolled in the study which represents a relatively small number of patients. Most patients with positive SARS-CoV-2 PCR were mainly asymptomatic. In addition, our vaccine group received the mRNA-based vaccines (mRNA1273 and BNT162b2). We did not study fetal response to other SARS-CoV-2 vaccines. Conclusion: Neither IL-6 nor CRP indicated increased inflammation in the cord blood of newborns of vaccinated or SARS-CoV-2 infected mothers when the newborn was not infected.

Introduction The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. Objectives Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. Methods Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry. Metabolite set enrichment analysis (MSEA) was used to evaluate altered biochemical pathways due to COVID-19 intrauterine exposure. Logistic regression models were developed using metabolites to predict intrauterine exposure. Results Significant concentration differences between groups (p-value < 0.05) were observed in 19 metabolites. Elevated levels of glucocorticoids, pyruvate, lactate, purine metabolites, phenylalanine, and branched-chain amino acids of valine and isoleucine were discovered in cases while ceramide subclasses were decreased. The top metabolite model including cortisol and ceramide (d18:1/23:0) achieved an Area under the Receiver Operating Characteristics curve (95% CI) = 0.841 (0.725–0.957) for detecting fetal exposure to maternal COVID-19 infection. MSEA highlighted steroidogenesis, pyruvate metabolism, gluconeogenesis, and the Warburg effect as the major perturbed metabolic pathways (p-value < 0.05). These changes indicate fetal increased oxidative metabolism, hyperinsulinemia, and inflammatory response. Conclusion We present fetal biochemical changes related to intrauterine inflammation and altered energy metabolism in cases of mild maternal COVID-19 infection despite the absence of viral infection. Elucidation of the long-term consequences of these findings is imperative considering the large number of exposures in the population. Supplementary Information The online version contains supplementary material available at 10.1007/s11306-023-01988-x.

INTRODUCTION: Research generally focuses on neonatal outcomes when pregnancy is complicated by non-reassuring fetal status. Little attention has been directed to maternal outcomes after such deliveries. METHODS: A retrospective cohort study of 27,886 pregnancies at a single health system evaluated fetal status and postpartum maternal characteristics. Fetal heart tracing, arterial cord pH, maternal blood transfusion, and maternal ICU admission were among the evaluated characteristics. Multivariate logistic regression analyses were performed to assess correlation with markers of fetal well-being and maternal outcomes and adjusted odds ratios (AOR) were derived. RESULTS: Umbilical artery pH less than 7.0 was associated with transfusion (AOR 6.83 [95% CI 2.22–21.0, P<.001]), cesarean delivery (AOR 5.76 [95% CI 3.63–9.15, P<.0001]), and maternal readmission (AOR 12.6 [95% CI 2.26–69.8, P=.0039]). Fetal bradycardia events were associated with increased maternal ICU admission (AOR 3.22 [95% CI 1.23–8.46, P<.017]), transfusion (AOR 2.13 [95% CI 1.26–3.59, P<.005]) and readmission (AOR 4.17 [95% CI 1.16–15.0, P<.029]). Late decelerations were associated with cesarean delivery (AOR 1.65 [95% CI 1.55–1.76, P<.0001]), maternal readmission (AOR 1.24 [95% CI 1.01–1.53, P=.04]), chorioamnionitis (AOR 2.88 [95% CI 2.46–3.37, P<.0001]), and maternal need for antibiotics (AOR 1.89 [95% CI 1.66–2.15, P<.0001]). CONCLUSION: Non-reassuring fetal status is associated with significant risks to the mother as evidenced by significant increases in transfusions, ICU admissions, and readmissions. Obstetricians should remain vigilant after delivery for non-reassuring fetal status and focus on monitoring and optimization of maternal status.