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Placental Function: An Epidemiological and Magnetic Resonance Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Obstetrik)
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Placental function is central for normal pregnancy and in many of the major pregnancy disorders. We used magnetic resonance imaging techniques to investigate placental function in normal pregnancy, in early and late preeclampsia and in intrauterine growth restriction. We also investigated maternal body mass index and height, as risk factors for preeclampsia.

A high body mass index and a short maternal stature increase the risk of preeclampsia, of all severities. The association seems especially strong between short stature and early preeclampsia, and a high body mass index and late preeclampsia. (Study I)

Using diffusion-weighted magnetic resonance imaging, we found that the placental perfusion fraction decreases with increasing gestational age in normal pregnancy. Also, the placental perfusion fraction is smaller in early preeclampsia, and larger in late preeclampsia, compared with normal pregnancies. That these differences are in opposite directions, suggests that there are differences in the underlying pathophysiology of early and late preeclampsia. (Study II)

Using magnetic resonance spectroscopy, we found that the phosphodiester spectral intensity fraction and the phosphodiester/phosphomonoester spectral intensity ratio increases with increasing gestational age. Also, we found that the phosphodiester spectral intensity fraction and the phosphodiester/phosphomonoester spectral intensity ratio are higher in early preeclampsia, compared with early normal pregnancy. These findings indicate increased apoptosis with increasing gestational age in normal pregnancy, and increased apoptosis in early preeclampsia. (Study III)

The placental perfusion fraction is smaller in intrauterine growth restriction than in normal pregnancy. Fetal growth, Doppler blood flow in maternal and fetal vessels, infant birth weight and plasma markers of placental function are all correlated to the placental perfusion fraction. The placental perfusion fraction examination seems therefore to offer a fast, direct estimate of the degree of placental dysfunction. (Study IV)

In conclusion: Our findings in studies I-III all support the hypothesis of partly different pathophysiology between early and late preeclampsia, and suggest a strong link between early preeclampsia and placental dysfunction. Study IV shows that the placental perfusion fraction has potential to contribute to the clinical assessment of placental dysfunction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. , 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1066
Keyword [en]
body height, body mass index, early preeclampsia, late preeclampsia, magnetic resonance imaging, placenta, perfusion, IVIM, risk factors, energy metabolism, magnetic resonance spectroscopy, 31P-MRS
National Category
Clinical Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-239294ISBN: 978-91-554-9142-0 (print)OAI: oai:DiVA.org:uu-239294DiVA: diva2:778411
Public defence
2015-02-27, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-02-05 Created: 2014-12-21 Last updated: 2015-03-09
List of papers
1. Maternal Body Mass Index, Height, and Risks of Preeclampsia
Open this publication in new window or tab >>Maternal Body Mass Index, Height, and Risks of Preeclampsia
2012 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 25, no 1, 120-125 p.Article in journal (Refereed) Published
Abstract [en]

Background

There is an association between maternal body mass index (BMI) and preeclampsia, but if BMI has an effect on preeclampsia of all severities is debated. If there is an association between maternal height and preeclampsia of all severities is unknown.

Methods

In this population-based cohort study including 503,179 nulliparous women, we estimated risks of preeclampsia of different severity in short (<164 cm) and tall (≥172 cm) women, using women of average height (164-171 cm) as reference, and in underweight (BMI: ≤18.4kg/m(2)), overweight (BMI: 25.0-29.9 kg/m(2)), obese class I (BMI: 30.0-34.9kg/m(2)) and obese class II-III (BMI: ≥35.0 kg/m(2)) women, using women with normal weight (BMI: 18.5-24.9kg/m(2)) as reference. Severity of preeclampsia was classified as early (<32 weeks), moderately early (32-36 weeks), and late (≥37 weeks) preeclampsia, or severe preeclampsia and mild to moderate preeclampsia, as defined by diagnostic codes.

Results

Short women had increased risks of all types of preeclampsia, but especially of early disease (adjusted odds ratio (OR) 1.3; 95% confidence interval (CI) 1.2-1.5). The risks of all preeclampsia types increased with BMI, but seemed higher for milder than more severe types of preeclampsia. Obesity class II-III was associated with a four-fold increased risk of mild to moderate preeclampsia (adjusted OR 4.0; 95% CI 3.7-4.4).

Conclusion

A short maternal stature and a high BMI increase risks of preeclampsia of all severities. The associations seem especially strong between short stature and severe types of preeclampsia, and high BMI and mild types of preeclampsia.

National Category
Medical and Health Sciences Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-159806 (URN)10.1038/ajh.2011.175 (DOI)000298264800023 ()21976280 (PubMedID)
Available from: 2011-10-10 Created: 2011-10-10 Last updated: 2017-12-08Bibliographically approved
2. Placental perfusion in normal pregnancy and early and late preeclampsia: A magnetic resonance imaging study.
Open this publication in new window or tab >>Placental perfusion in normal pregnancy and early and late preeclampsia: A magnetic resonance imaging study.
Show others...
2014 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 35, no 3, 202-206 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Our primary aim was to investigate if women with early or late preeclampsia have different placental perfusion compared with normal pregnancies. A secondary aim was to investigate if placental perfusion changes with increasing gestational age in normal pregnancy.

METHODS: The study population included thirteen women with preeclampsia (five with early and eight with late preeclampsia) and nineteen women with normal pregnancy (ten with early and nine with late pregnancy). Early was defined as <34 weeks and late as ≥34 weeks gestation. All women underwent a magnetic resonance imaging (MRI) examination including a diffusion weighted sequence at 1.5 T. The perfusion fraction was calculated.

RESULTS: Women with early preeclampsia had a smaller placental perfusion fraction (p = 0.001) and women with late preeclampsia had a larger placental perfusion fraction (p = 0.011), compared to women with normal pregnancies at the corresponding gestational age. The placental perfusion fraction decreased with increasing gestational age in normal pregnancies (p = 0.001).

CONCLUSION: Both early and late preeclampsia differ in placental perfusion from normal pregnant women. Observed differences are however in the opposite direction, suggesting differences in pathophysiology. Placental perfusion decreases with increasing gestational age in normal pregnancy.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-221884 (URN)10.1016/j.placenta.2014.01.008 (DOI)000333495900008 ()24529946 (PubMedID)
Available from: 2014-04-07 Created: 2014-04-07 Last updated: 2017-12-05Bibliographically approved
3. In vivo(31)P-MR spectroscopy in normal pregnancy, early and late preeclampsia: A study of placental metabolism
Open this publication in new window or tab >>In vivo(31)P-MR spectroscopy in normal pregnancy, early and late preeclampsia: A study of placental metabolism
Show others...
2014 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 35, no 5, 318-323 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Preeclampsia affects about 3% of pregnancies and the placenta is believed to play a major role in its pathophysiology. Lately, the role of the placenta has been hypothesised to be more pronounced in preeclampsia of early (<34 weeks) rather than late (≥34 weeks) onset. (31)P Magnetic Resonance Spectroscopy (MRS) enables non-invasive, in vivo studies of placental metabolism. Our aim was to study placental energy and membrane metabolism in women with normal pregnancies and those with early and late onset preeclampsia.

METHODS: The study population included fourteen women with preeclampsia (five with early onset and nine with late onset preeclampsia) and sixteen women with normal pregnancy (seven with early and nine with late pregnancy). All women underwent a (31)P-MRS examination of the placenta.

RESULTS: The phosphodiester (PDE) spectral intensity fraction of the total (31)P signal and the phosphodiester/phosphomonoester (PDE/PME) spectral intensity ratio was higher in early onset preeclampsia than in early normal pregnancy (p = 0.03 and p = 0.02). In normal pregnancy the PDE spectral intensity fraction and the PDE/PME spectral intensity ratio increased with increasing gestational age (p = 0.006 and p = 0.001).

DISCUSSION: Since PDE and PME are related to cell membrane degradation and formation, respectively, our findings indicate increased cell degradation and maybe also decreased cell proliferation in early onset preeclampsia compared to early normal pregnancy, and with increasing gestational age in normal pregnancy.

CONCLUSIONS: Our findings could be explained by increased apoptosis due to ischaemia in early onset preeclampsia and also increased apoptosis with increasing gestational age in normal pregnancy.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-221881 (URN)10.1016/j.placenta.2014.02.005 (DOI)000335614500006 ()24612844 (PubMedID)
Available from: 2014-04-07 Created: 2014-04-07 Last updated: 2017-12-05Bibliographically approved
4. MRI estimated placental perfusion in fetal growth assessment
Open this publication in new window or tab >>MRI estimated placental perfusion in fetal growth assessment
Show others...
2015 (English)In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 46, no 6, 700-705 p.Article in journal (Refereed) Published
Abstract [en]

Objective

This study aimed to evaluate placental perfusion fraction estimated by magnetic resonance imaging (MRI) in vivo as a marker of placental function.

Methods

The study population included 35 pregnant women, of whom 13 had preeclampsia, examined at gestational weeks 22 to 40. Each woman underwent, within a 24 hour period: a MRI diffusion-weighted sequence (from which we calculated the placental perfusion fraction); venous blood sampling; and an ultrasound examination including estimation of fetal weight, amniotic fluid index and Doppler velocity measurements. We compared the perfusion fraction in pregnancies with and without fetal growth restriction and estimated correlations between the perfusion fraction and ultrasound estimates and plasma markers with linear regression. The associations between the placental perfusion fraction and ultrasound estimates were modified by the presence of preeclampsia (p < 0.05) and therefore we included an interaction term between preeclampsia and the covariates in the models.

Results

The median placental perfusion fraction in pregnancies with and without fetal growth restriction was 21% and 32%, respectively (p = 0.005). The correlations between the placental perfusion fraction and ultrasound estimates and plasma markers were highly significant (p-values 0.002 to 0.0001). The highest coefficient of determination (R2= 0.56) for placental perfusion fraction was found for a model including pulsatility index in ductus venosus, plasma level of sFlt1, estimated fetal weight and presence of preeclampsia.

Conclusion

The placental perfusion fraction has potential to contribute to the clinical assessment in cases of placental insufficiency.

Keyword
Intrauterine growth restriction, Small for gestational age, Magnetic resonance imaging, Placenta, Perfusion, Perfusion fraction
National Category
Obstetrics, Gynecology and Reproductive Medicine Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-239293 (URN)10.1002/uog.14786 (DOI)000365855700011 ()25640054 (PubMedID)
Funder
Swedish Research Council, 2014-3561
Available from: 2014-12-21 Created: 2014-12-21 Last updated: 2017-12-05Bibliographically approved

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