PMID- 37473584
OWN - NLM
STAT- MEDLINE
DCOM- 20230915
LR  - 20230919
IS  - 1872-7603 (Electronic)
IS  - 0165-0378 (Linking)
VI  - 159
DP  - 2023 Sep
TI  - Poor glucose control and markers of placental dysfunction correlate with 
      increased circulating fetal microchimerism in diabetic pregnancies.
PG  - 104114
LID - S0165-0378(23)00320-0 [pii]
LID - 10.1016/j.jri.2023.104114 [doi]
AB  - Fetal microchimerism (FMc) arises during pregnancy as fetal cells enter maternal 
      circulation and remain decades postpartum. Circulating FMc is increased in 
      preeclampsia, fetal growth restriction, and as we recently showed, is associated 
      with biomarkers of placental dysfunction in normotensive term pregnancies. 
      Diabetes mellitus (DM) also correlates with placental dysfunction. We hypothesize 
      that poor glucose control and markers of placental dysfunction are associated 
      with increased circulating FMc in diabetic pregnancies. We included 122 
      pregnancies preceding active labor (pregestational DM, n = 77, gestational DM 
      (GDM), n = 45) between 2001 and 2017. Maternal and fetal samples were genotyped 
      for various human leukocyte antigen (HLA) loci, and other polymorphisms to 
      identify fetus-specific alleles. We used validated polymerase chain reaction 
      (PCR) assays to quantify FMc in maternal peripheral blood buffy coat. Negative 
      binomial regression with adjustment for confounders was used to assess FMc 
      quantity. In pregestational DM, increased circulating FMc correlated with 
      elevation of HbA1c (>/= 6.0 %) (detection rate ratio (DRR) = 4.9, p = 0.010) and a 
      1000 pg/mL rise in the anti-angiogenic biomarker soluble fms-like tyrosine 
      kinase-1 (sFlt-1) (DRR = 1.1, p = 0.011). In GDM, increased FMc correlated with 
      elevated 2-hour oral glucose tolerance test results (DRR = 2.3, p = 0.046) and 
      birthweight < 10th or > 90th percentile (DRR = 4.2, p = 0.049). These findings 
      support our novel hypothesis that FMc correlates with poor glucose control and 
      various aspects of placental dysfunction in DM. Whether increased FMc in 
      pregnancies with poor glucose control and placental dysfunction contributes to 
      the risk of preeclampsia in diabetic pregnancies and to the increased risk of 
      chronic cardiovascular disease later in life remains to be investigated.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Fjeldstad, Heidi E
AU  - Fjeldstad HE
AD  - Faculty of Medicine, University of Oslo, Norway; Division of Obstetrics and 
      Gynaecology, Oslo University Hospital, Oslo, Norway. Electronic address: 
      h.e.fjeldstad@studmed.uio.no.
FAU - Jacobsen, Daniel P
AU  - Jacobsen DP
AD  - Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway.
FAU - Johnsen, Guro M
AU  - Johnsen GM
AD  - Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway.
FAU - Sugulle, Meryam
AU  - Sugulle M
AD  - Faculty of Medicine, University of Oslo, Norway; Division of Obstetrics and 
      Gynaecology, Oslo University Hospital, Oslo, Norway.
FAU - Chae, Angel
AU  - Chae A
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      USA; Department of Obstetrics and Gynecology Research Division, University of 
      Washington, Seattle, WA, USA.
FAU - Kanaan, Sami B
AU  - Kanaan SB
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      USA; Chimerocyte, Inc., Seattle, WA, USA.
FAU - Gammill, Hilary S
AU  - Gammill HS
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      USA; Department of Obstetrics and Gynecology Research Division, University of 
      Washington, Seattle, WA, USA.
FAU - Staff, Anne Cathrine
AU  - Staff AC
AD  - Faculty of Medicine, University of Oslo, Norway; Division of Obstetrics and 
      Gynaecology, Oslo University Hospital, Oslo, Norway.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230716
PL  - Ireland
TA  - J Reprod Immunol
JT  - Journal of reproductive immunology
JID - 8001906
RN  - 0 (Blood Glucose)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Pregnancy
MH  - Female
MH  - Humans
MH  - Placenta
MH  - *Pre-Eclampsia
MH  - Blood Glucose
MH  - Chimerism
MH  - Fetus
MH  - *Placenta Diseases
MH  - Vascular Endothelial Growth Factor Receptor-1
MH  - Biomarkers
MH  - *Diabetes Mellitus
OTO - NOTNLM
OT  - Abnormal birthweight
OT  - Diabetes mellitus
OT  - Fetal microchimerism
OT  - Placental dysfunction
OT  - Poor glucose control
OT  - Soluble fms-like tyrosine kinase-1
COIS- Declaration of Competing Interest Roche Diagnostics donated in-kind reagents for 
      analysis of the placenta-related biomarkers (sFlt-1 and PlGF). Chimerocyte Inc., 
      of which Sami B. Kanaan is founder, generated some of the microchimerism data in 
      a blinded fashion. Neither Roche Diagnostics nor Chimerocyte had any further 
      involvement in collection or interpretation of data, writing of the manuscript, 
      or the decision to submit the article for publication. The remaining authors 
      declare no other conflicts of interest.
EDAT- 2023/07/21 01:12
MHDA- 2023/09/15 06:43
CRDT- 2023/07/20 18:04
PHST- 2023/04/04 00:00 [received]
PHST- 2023/07/04 00:00 [revised]
PHST- 2023/07/13 00:00 [accepted]
PHST- 2023/09/15 06:43 [medline]
PHST- 2023/07/21 01:12 [pubmed]
PHST- 2023/07/20 18:04 [entrez]
AID - S0165-0378(23)00320-0 [pii]
AID - 10.1016/j.jri.2023.104114 [doi]
PST - ppublish
SO  - J Reprod Immunol. 2023 Sep;159:104114. doi: 10.1016/j.jri.2023.104114. Epub 2023 
      Jul 16.