First-trimester NRBC Count in Maternal Circulation : Correlation with Doppler Ultrasound Studies
Medical Genetics (AM,AK,EK) and First Department of Obstetrics and Gynecology (AS,AP,YK,PA,AA), Athens University School of Medicine, Athens, Greece
Correspondence to: Dr. Ariadni Mavrou, Associate Professor of Genetics, Medical Genetics, Athens University School of Medicine, "Aghia Sofia" Children's Hospital, Thivon & Levadias, 11521 Athens, Greece. E-mail: ariamav{at}hol.gr
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Summary |
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Key Words: intrauterine growth restriction preeclampsia nucleated red blood cells screening Doppler ultrasound
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Introduction |
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Doppler ultrasound studies have shown that impaired placental perfusion at 2224 weeks of gestation is associated with high impedance to flow in the uterine arteries, which is characterized by the presence of an early diastolic notch in the waveform of these vessels (Harrington et al. 1996; Frusca et al. 1997
). Therefore, Doppler ultrasound examination of the uterine arteries can be used to identify a group of pregnancies at high risk for subsequent development of PET/IUGR.
Recently, it has been demonstrated that fetal cells, as well as fetal DNA, in maternal circulation in weeks 22 and 23 of gestation precede the onset of PET, suggesting that impaired placental perfusion is associated with an increase in fetomaternal trafficking (Holzgreve et al. 1998,2000
; Lo et al 1999
; Al-Mufti et al. 2000a
,b
; Zhong et al. 2002
).
Because PET is a major cause of fetal and maternal morbidity and mortality, it is important to develop a predictive screening test early in pregnancy so that we can anticipate pregnancies at high risk for this complication.
This is a preliminary study aimed at determining whether the number of nucleated red blood cells (NRBCs) in maternal circulation during the first trimester of pregnancy could identify pregnancies that will have an anomalous Doppler finding during the second trimester.
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Materials and Methods |
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Follow-up scans in weeks 22 and 23 of pregnancy were obtained for 46 of the 85 originally tested cases. Details of the pregnancy outcomes were available from the patients' files. PET was diagnosed as maternal blood pressure >140/90 mmHg with positive protein on reagent strip urinalysis of urine protein collection >300 mg/24 hr.
The diagnosis of IUGR was made if the birth weight was below the fifth percentile of the normal range of gestation.
Methods
Mononuclear cells were isolated by density gradient centrifugation with Histopaque 1083, magnetically labeled with CD71 antibody to the transferrin receptor, and positively selected using magnetic automated cell sorting. Isolated cells were next stained with May/Grunwald/Giemsa and NRBCs were identified and enumerated by morphology under a light microscope.
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Results |
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Discussion |
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Previous studies demonstrated a correlation between the number of NRBCs and abnormal uterine artery Doppler ultrasound in women who develop PET/IUGR during the second trimester of pregnancy (Holzgreve et al. 1998,2000
; Al-Mufti et al. 2000a
,b
). The present report, which must be considered preliminary because only seven of the 46 women tested continued to have high-impedance blood flow during the second trimester and only two of the seven developed PET or IUGR, indicates that the number of NRBCs in the maternal circulation during the first trimester cannot be used as a second-line screening to identify pregnancies at high risk for PET/IUGR. There was one case with high NRBC number and subsequent delivery of an IUGR baby, but this finding is not sufficient to establish a possible correlation and more pregnancies complicated by PET/IUGR must be tested to confirm this finding.
The NRBCs detected in our study must be both fetal and maternal, but we did not attempt to identify their origin because of the low cell numbers. However, it has been postulated that the increase in the number of fetal NRBCs during pregnancy precedes the increase in the number of maternal NRBCs (Al-Mufti et al. 2000a). In addition, female carriers of the ß-thalassemia trait were excluded from the study because we had previously demonstrated that under the stress of pregnancy, carriers of the ß-thalassemia trait produce and release into the circulation a significant number of NRBCs (Mavrou et al. 2003
).
High-impedance blood flow in the uterine arteries in the first trimester may be due to an unfinished process of trophoblastic invasion, most likely to be completed successfully by 2224 weeks. This may explain why the Doppler findings normalized during the second trimester.
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Footnotes |
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Received for publication May 18, 2004; accepted September 15, 2004
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Literature Cited |
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