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Second Trimester Placental Growth Factor Levels and Placental Histopathology in Low-Risk Nulliparous Pregnancies

Published:February 20, 2021DOI:https://doi.org/10.1016/j.jogc.2021.01.018

      ABSTRACT

      Objective

      Placental growth factor (PlGF) levels are lower at delivery in pregnancies with preeclampsia or fetuses small for gestational age (SGA). These obstetrical complications are typically mediated by placental dysfunction, most commonly related to the specific placental phenotype termed placental maternal vascular malperfusion (MVM). The objective of this study was to determine the relationship between PlGF levels in the second trimester and the development of placental diseases that underlie adverse perinatal outcomes.

      Methods

      We performed a secondary analysis of the prospective Placental Health Study in unselected healthy nulliparous women (n = 773). Maternal demographic data, Doppler ultrasound measurements, and plasma PlGF levels at 15 to 18 weeks gestation were analyzed for association with pregnancy outcomes and placental pathology following delivery.

      Results

      Low PlGF levels in the second trimester (<10th percentile; <72 pg/mL) was associated with preterm delivery (<37 weeks; 26% vs. 6%, P < 0.001; unadjusted odds ratio (OR) 5.75, 95% CI 3.2–10.5), reduced mean birth weight (2998 vs. 3320 g, P < 0.001), SGA deliveries (25% vs. 11%, P = 0.001; OR 2.6, 95% CI 1.5–4.6), and preeclampsia (7% vs. 2%, P = 0.02; OR 4.3, 95% CI 1.5-12.8) relative to normal PlGF levels (≥10th percentile; ≥72 pg/mL). Low PlGF was associated with lower mean placental weight (447 vs. 471 g, P = 0.01), aberrant cord insertion (25% vs. 12%, P = 0.001) and a pathologic diagnosis of MVM (18% vs. 11%, P = 0.04; OR 1.9, 95% CI 1.01–3.55) but not with other placental pathologies.

      Conclusion

      MVM placental pathology and related adverse perinatal outcomes are associated with low PlGF in the early second trimester for healthy nulliparous women.

      RÉSUMÉ

      Objectif

      Le taux de facteur de croissance placentaire (PlGF) est plus faible à l'accouchement en cas de grossesse pré-éclamptique ou d'hypotrophie fœtale. Ces complications obstétricales résultent généralement d'une dysfonction placentaire, qui est le plus souvent liée à un phénotype placentaire en particulier, soit la malperfusion vasculaire d'origine maternelle. L'objectif de cette étude était de déterminer la relation entre le taux de PlGF au deuxième trimestre et l'apparition de maladies placentaires qui sont à l'origine des issues périnatales défavorables.

      Méthodologie

      Nous avons effectué une analyse secondaire de l’étude prospective sur la santé placentaire (Placental Health Study) chez des femmes nullipares en bonne santé non sélectionnées (n = 773). Les données démographiques maternelles, les résultats de l’échographie Doppler et le taux plasmatique de PlGF entre 15 et 18 semaines d'aménorrhée (SA) ont été analysés pour déterminer l'association avec les issues de grossesse et les pathologies placentaires après l'accouchement.

      Résultats

      Un faible taux de PlGF au deuxième trimestre (< 10e percentile; < 72 pg/ml) était associé à l'accouchement prématuré (< 37 SA; 26 % vs 6 %, P < 0,001; rapport de cotes [RC] non ajusté : 5,75; IC à 95 % : 3,2–10,5), à une diminution du poids moyen à la naissance (2 998 g vs 3 320 g, P < 0,001), à l'hypotrophie fœtale à la naissance (25 % vs 11 %, P = 0,001; RC  2,6; IC à 95 % : 1,5–4,6) et à la pré-éclampsie (7 % vs 2 %, P = 0,02; RC : 4,3; IC à 95 % : 1,5–12,8) comparativement à un taux de PlGF normal (≥10e percentile; ≥72 pg/mL). Le faible taux de PlGF, par comparaison à un taux normal, était associé à un poids placentaire moyen moins élevé (447 g vs 471 g, P = 0,01), à une insertion anormale du cordon ombilical (25 % vs 12 %, P = 0,001) et à un diagnostic anatomopathologique de malperfusion vasculaire d'origine maternelle (18 % vs 11 %, P = 0,04; RC : 1,9; IC à 95 % : 1,01–3,55), mais pas à d'autres pathologies placentaires.

      Conclusion

      La malperfusion vasculaire d'origine maternelle et les issues périnatales défavorables connexes sont associées à un faible taux de PlGF au début du deuxième trimestre chez les femmes nullipares en bonne santé.

      Keywords

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      REFERENCES

        • Drewlo S
        • Levytska K
        • Sobel M
        • et al.
        Heparin promotes soluble VEGF receptor expression in human placental villi to impair endothelial VEGF signaling.
        J Thromb Haemost. 2011; 9: 2486-2497
        • Redman CWG
        • Staff AC
        Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.
        Am J Obstet Gynecol. 2015; 213 (S9.e1–11)
        • Levine RJ
        • Maynard SE
        • Qian C
        • et al.
        Circulating angiogenic factors and the risk of preeclampsia.
        N Engl J Med. 2004; 350: 672-683
        • Taylor RN
        • Grimwood J
        • Taylor RS
        • et al.
        Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies.
        Am J Obstet Gynecol. 2003; 188: 177-182
        • Wright E
        • Audette MC
        • Ye XY
        • et al.
        Maternal vascular malperfusion and adverse perinatal outcomes in low-risk nulliparous women.
        Obstet Gynecol. 2017; 130: 1112-1120
        • Korzeniewski SJ
        • Romero R
        • Chaiworapongsa T
        • et al.
        Maternal plasma angiogenic index-1 (placental growth factor/soluble vascular endothelial growth factor receptor-1) is a biomarker for the burden of placental lesions consistent with uteroplacental underperfusion: a longitudinal case-cohort study.
        Am J Obstet Gynecol. 2016; 214 (629.e1–17)
        • Redline RW
        Classification of placental lesions.
        Am J Obstet Gynecol. 2015; 213 (S21–8)
        • Soto E
        • Romero R
        • Kusanovic JP
        • et al.
        Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion.
        J Matern Fetal Neonatal Med. 2012; 25: 498-507
        • Novac MV
        • Niculescu M
        • Manolea MM
        • et al.
        Placental findings in pregnancies complicated with IUGR - histopathological and immunohistochemical analysis.
        Rom J Morphol Embryol. 2018; 59: 715-720
        • Triunfo S
        • Lobmaier S
        • Parra-Saavedra M
        • et al.
        Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion.
        Placenta. 2014; 35: 398-403
        • Rolnik DL
        • Wright D
        • Poon LC
        • et al.
        Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.
        N Engl J Med. 2017; 377: 613-622
        • Rodger MA
        • Gris JC
        • de Vries JIP
        • et al.
        Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials.
        Lancet. 2016; 388: 2629-2641
        • Rana S
        • Powe CE
        • Salahuddin S
        • et al.
        Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia.
        Circulation. 2012; 125: 911-919
        • Gómez O
        • Figueras F
        • Fernández S
        • et al.
        Reference ranges for uterine artery mean pulsatility index at 11-41 weeks of gestation.
        Ultrasound Obstet Gynecol. 2008; 32: 128-132
      1. ACOG practice bulletin no. 202: gestational hypertension and preeclampsia.
        Obstet Gynecol. 2019; 133: e1-e25
        • Gardosi J
        • Chang A
        • Kalyan B
        • et al.
        Customised antenatal growth charts.
        Lancet. 1992; 339: 283-287
        • Khong TY
        • Mooney EE
        • Ariel I
        • et al.
        Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group consensus statement.
        Arch Pathol Lab Med. 2016; 140: 698-713
        • Odibo AO
        • Patel KR
        • Spitalnik A
        • et al.
        Placental pathology, first-trimester biomarkers and adverse pregnancy outcomes.
        J Perinatol. 2014; 34: 186-191
        • Benton SJ
        • McCowan LM
        • Heazell AEP
        • et al.
        Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction.
        Placenta. 2016; 42: 1-8
        • Mijal RS
        • Holzman CB
        • Rana S
        • et al.
        Mid-pregnancy levels of angiogenic markers as indicators of pathways to preterm delivery.
        J Matern Fetal Neonatal Med. 2012; 25: 1135-1141
        • Jauniaux E
        • Hempstock J
        • Greenwold N
        • et al.
        Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies.
        Am J Pathol. 2003; 162: 115-125
        • Wat JM
        • Audette M
        • Kingdom JC
        Molecular actions of heparin and their implications in preventing preeclampsia.
        J Thromb Haemost. 2018; 16: 1510-1522
        • McLaughlin K
        • Nadeem L
        • Wat J
        • et al.
        Low molecular weight heparin promotes transcription and release of placental growth factor from endothelial cells.
        Am J Physiol Heart Circ Physiol. 2020; 318: H1008-H1017
        • McLaughlin K
        • Baczyk D
        • Potts A
        • et al.
        Low molecular weight heparin improves endothelial function in pregnant women at high risk of preeclampsia.
        Hypertension. 2017; 69: 180-188
        • Makris A
        • Yeung KR
        • Lim SM
        • et al.
        Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in nonhuman primates.
        Hypertension. 2016; 67: 1263-1272
        • Kingdom JCP
        • Walker M
        • Proctor LK
        • et al.
        Unfractionated heparin for second trimester placental insufficiency: a pilot randomized trial.
        J Thromb Haemost. 2011; 9: 1483-1492
        • Triunfo S
        • Crovetto F
        • Crispi F
        • et al.
        Association of first-trimester angiogenic factors with placental histological findings in late-onset preeclampsia.
        Placenta. 2016; 42: 44-50