Grandmaternal cells in cord blood.

BACKGROUND: During pregnancy a feto-maternal exchange of cells through the placenta conducts to maternal microchimerism (Mc) in the child and fetal Mc in the mother. Because of this bidirectional traffic of cells, pregnant women have also acquired maternal cells in utero from their mother and could transfer grandmaternal (GdM) cells to their child through the maternal bloodstream during pregnancy. Thus, cord blood (CB) samples could theoretically carry GdMMc. Nevertheless this has never been demonstrated. METHODS: Using Human Leukocyte Antigen (HLA)-specific quantitative PCR assays on three-generation families, we were able to test 28 CB samples from healthy primigravid women for GdMMc in whole blood (WB) and isolated cells (PBMC, T, B, granulocytes, stem cells). FINDINGS: Five CB samples (18%) had GdMMc which could not be confounded with maternal source, with quantities 100 fold lower than maternal Mc in WB and PBMC. Risk of aneuploidies and/or related invasive prenatal procedures significantly correlated with the presence of GdMMc in CB (p=0.024). Significantly decreased HLA compatibility was observed in three-generation families from CB samples carrying GdMMc (p=0.019). INTERPRETATION: Transgenerational transfer of cells could have implications in immunology and evolution. Further analyses will be necessary to evaluate whether GdMMc in CB is a passive or immunologically active transfer and whether invasive prenatal procedures could trigger GdMMc. FUNDING: Provence-Alpes-Côte d'Azur APEX grant # 2012_06549E, 2012_11786F and 2014_03978) and the Foundation for Medical Research (FRM Grant #ING20140129045).

Corrigendum: Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition.

[This corrects the article DOI: 10.3389/fimmu.2021.651399.].

Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition.

Background: Cord blood (CB) samples are increasingly used as a source of hematopoietic stem cells in transplantation settings. Maternal cells have been detected in CB samples and their presence is associated with a better graft outcome. However, we still do not know what influences the presence of maternal microchimerism (MMc) in CB samples and whether their presence influences CB hematopoietic cell composition. Patients and Methods: Here we test whether genetic, biological, anthropometric and/or obstetrical parameters influence the frequency and/or quantity of maternal Mc in CB samples from 55 healthy primigravid women. Mc was evaluated by targeting non-shared, non-inherited Human Leukocyte Antigen (HLA)-specific real-time quantitative PCR in whole blood and four cell subsets (T, B lymphocytes, granulocytes and/or hematopoietic progenitor cells). Furthermore CB samples were analyzed for their cell composition by flow cytometry and categorized according to their microchimeric status. Results: MMc was present in 55% of CB samples in at least one cell subset or whole blood, with levels reaching up to 0.3% of hematopoietic progenitor cells. Two factors were predictive of the presence of MMc in CB samples: high concentrations of maternal serological Pregnancy-Associated-Protein-A at first trimester of pregnancy (p=0.018) and feto-maternal HLA-A and/or -DR compatibility (p=0.009 and p=0.01 respectively). Finally, CB samples positive for MMc were significantly enriched in CD56+ cells compared to CB negative for MMc. Conclusions: We have identified two factors, measurable at early pregnancy, predicting the presence of maternal cells in CB samples at delivery. We have shown that MMc in CB samples could have an influence on the hematopoietic composition of fetal cells. CD56 is the phenotypic marker of natural killer cells (NK) and NK cells are known to be the main effector for graft versus leukemia reactions early after hematopoietic stem cell transplantation. These results emphasize the importance of MMc investigation for CB banking strategies.

Does Assessment of Cervical Phosphorylated Insulin-like Growth Factor Binding Protein-1 by Bedside Vaginal Swab Test Really Predict Preterm Birth?

Preterm birth is the first cause of neonatal mortality and is associated with elevated risks of long-term complications such as neurodevelopmental impairment. Prediction of spontaneous preterm birth, one of the biggest challenges in obstetrics, aims at delaying birth in order to allow corticosteroid therapy and, if necessary, transfer of patient to a higher-level maternity care unit. We aimed to assess the predictive role of phIGFBP-1 (Actim® Partus) diagnostic test on patients at risk of preterm labor, routinely used in our institution. We conducted a retrospective cohort study on 99 patients admitted in the high-risk pregnancy unit of our institution from June 2012 to November 2014. The primary outcome measures were delivery before 34+0 and 37+0 weeks. Data analysis allowed measure of Actim® Partus test sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV), diagnostic efficiency as well as positive and negative likelihood ratios. Actim® Partus test features (Se, Sp, PPV and NPV) were 53.3, 67.9, 23.5 and 88.7% respectively for deliveries occurring ≤ 34+0 weeks and 54.2, 75.4, 55.8, and 74.2%, respectively, for deliveries occurring ≤ 37+0 weeks. Diagnostic efficiency of the test was 65.7% (≤ 34+0 weeks) and 67.7% (≤ 37+0 weeks). Positive likelihood ratios were 1.6 (≤ 34+0 weeks) and 2.2 (≤ 37+0 weeks). Negative likelihood ratios were 0.7 (≤ 34+0 weeks) and 0.6 (≤ 37+0 weeks). Results of our study show that phIGFBP-1 diagnostic test is not accurate enough in predicting preterm birth before 34+0 or 37+0 weeks, and therefore, there is little clinical interest in its everyday use.

Managing pain and anxiety during transabdominal chorionic villus sampling. A noninferiority randomized trial of nitrous oxide vs local anesthesia.

INTRODUCTION: Transabdominal chorionic villus sampling (CVS) is an invasive procedure for prenatal diagnosis reported to be associated with anxiety and pain. In this context, the need for analgesia during CVS has been considered useful. Even though several authors have been interested in pain management during amniocentesis, no study has been published on pain reduction during CVS. Our objective was to evaluate pain and anxiety management during transabdominal CVS using nitrous oxide (N2 O) and local anesthesia. MATERIAL AND METHODS: In a randomized controlled noninferiority trial, self-administered nitrous oxide (N2 O) inhalation (equimolar premix of oxygen and nitrous oxide) was compared with local anesthesia (1% lidocaine) before CVS. Primary outcome was pain and secondary outcome was anxiety, both measured on a visual analog scale 30-60 minutes before, immediately after (5-10 minutes) and 30-60 minutes after CVS. With a statistical power of 90%, type I error of 5% and two-sided test and potential exclusions, a sample size of 96 patients per group was enrolled and randomized. No patient was enrolled before the trial registration date. RESULTS: From 13 March 2013 through 10 February 2015, 192 patients (96 per group) were screened and randomized. Most characteristics were similar across groups. Pain in the N2 O group was 2.65 ± 0.22 vs 3.32 ± 0.26 in local anesthesia group [mean ± standard error of mean  (SEM)]. Mean anxiety in the N2 O group was 3.17 ± 0.27 vs 5.19 ± 0.30 in the local anesthesia group. CONCLUSION: N2 O was as efficient and even superior to local anesthesia for both pain and anxiety reduction during CVS, as the 95% confidence intervals were both below the prespecified noninferiority margin of 0.8 and below zero.