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Am J Perinatol 2015; 32(12): 1185-1190
DOI: 10.1055/s-0035-1552932
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Angiogenic and Antiangiogenic Factors in Preterm Neonates Born to Mothers with and without Preeclampsia

Cláudia R. Hentges
1   Department of Pediatrics, Newborn Section, Universidade Federal do Rio Grande do Sul and Hospital de Clínicas de Porto Alegre, Porto Alegre-RS, Brazil
,
Rita C. Silveira
1   Department of Pediatrics, Newborn Section, Universidade Federal do Rio Grande do Sul and Hospital de Clínicas de Porto Alegre, Porto Alegre-RS, Brazil
,
Renato S. Procianoy
1   Department of Pediatrics, Newborn Section, Universidade Federal do Rio Grande do Sul and Hospital de Clínicas de Porto Alegre, Porto Alegre-RS, Brazil
› Author Affiliations
Further Information

Publication History

09 February 2015

06 April 2015

Publication Date:
22 May 2015 (online)

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Abstract

Background Angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborns remains unknown.

Objective This study aims to measure vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels in preterm neonates born to mothers with PE.

Methods Neonates with birth weight < 2,000 g and gestational age ≤ 34 weeks were included and divided into the following two groups: born to mothers with PE and without PE. Blood was collected from neonates within the first 72 hours of life. VEGF and sFlt-1 levels were measured using the enzyme-linked immunosorbent assay method.

Results A total of 88 neonates were included (37 born to mothers with PE and 51 born to mothers without PE), with a mean gestational age of 29.12 ± 2.96 weeks and birth weight of 1,223.80 ± 417.48 g. In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age.

Conclusion Higher sFlt-1 and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction.

Keywords

angiogenic factors - preeclampsia - prematurity - VEGF - sFlt-1 - antiangiogenic factors
 

  • References

  • 1 Silasi M, Cohen B, Karumanchi SA, Rana S. Abnormal placentation, angiogenic factors, and the pathogenesis of preeclampsia. Obstet Gynecol Clin North Am 2010; 37 (2) 239-253
    CrossrefPubMedSearch in Google Scholar
  • 2 Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension 2005; 46 (5) 1077-1085
    CrossrefPubMedSearch in Google Scholar
  • 3 Muy-Rivera M, Vadachkoria S, Woelk GB, Qiu C, Mahomed K, Williams MA. Maternal plasma VEGF, sVEGF-R1, and PlGF concentrations in preeclamptic and normotensive pregnant Zimbabwean women. Physiol Res 2005; 54 (6) 611-622
    PubMedSearch in Google Scholar
  • 4 Cerdeira AS, Karumanchi SA. Angiogenic factors in preeclampsia and related disorders. Cold Spring Harb Perspect Med 2012; 2 (11) pii: a006585
    PubMedSearch in Google Scholar
  • 5 Ribatti D. The discovery of the placental growth factor and its role in angiogenesis: a historical review. Angiogenesis 2008; 11 (3) 215-221
    CrossrefPubMedSearch in Google Scholar
  • 6 Hentges CR, Silveira RC, Ferrelli RS, Procianoy RS. Influence of maternal pre-eclampsia on VEGF/PlGF heterodimer levels in preterm infants. J Matern Fetal Neonatal Med 2014; 14: 1-6
    PubMedSearch in Google Scholar
  • 7 Catarino C, Rebelo I, Belo L , et al. Fetal and maternal angiogenic/anti-angiogenic factors in normal and preeclamptic pregnancy. Growth Factors 2009; 27 (6) 345-351
    CrossrefPubMedSearch in Google Scholar
  • 8 Staff AC, Braekke K, Harsem NK, Lyberg T, Holthe MR. Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during preeclampsia. Eur J Obstet Gynecol Reprod Biol 2005; 122 (1) 33-39
    CrossrefPubMedSearch in Google Scholar
  • 9 Rana S, Karumanchi SA, Levine RJ , et al. Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia. Hypertension 2007; 50 (1) 137-142
    CrossrefPubMedSearch in Google Scholar
  • 10 Erez O, Romero R, Espinoza J , et al. The change in concentrations of angiogenic and antiangiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J Matern Fetal Neonatal Med 2008; 21 (5) 279-287
    CrossrefPubMedSearch in Google Scholar
  • 11 Maynard SE, Min JY, Merchan J , et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003; 111 (5) 649-658
    CrossrefPubMedSearch in Google Scholar
  • 12 Levine RJ, Maynard SE, Qian C , et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004; 350 (7) 672-683
    CrossrefPubMedSearch in Google Scholar
  • 13 Vatten LJ, Eskild A, Nilsen TI, Jeansson S, Jenum PA, Staff AC. Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia. Am J Obstet Gynecol 2007; 196 (3) 239.e1-239.e6
    CrossrefPubMedSearch in Google Scholar
  • 14 Troisi R, Braekke K, Harsem NK, Hyer M, Hoover RN, Staff AC. Blood pressure augmentation and maternal circulating concentrations of angiogenic factors at delivery in preeclamptic and uncomplicated pregnancies. Am J Obstet Gynecol 2008; 199 (6) 653.e1-653.e10
    CrossrefPubMedSearch in Google Scholar
  • 15 Levine RJ, Lam C, Qian C , et al; CPEP Study Group. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 2006; 355 (10) 992-1005
    CrossrefPubMedSearch in Google Scholar
  • 16 Staff AC, Harsem NK, Braekke K, Hyer M, Hoover RN, Troisi R. Maternal, gestational and neonatal characteristics and maternal angiogenic factors in normotensive pregnancies. Eur J Obstet Gynecol Reprod Biol 2009; 143 (1) 29-33
    CrossrefPubMedSearch in Google Scholar
  • 17 Sunderji S, Gaziano E, Wothe D , et al. Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol 2010; 202 (1) 40.e1-40.e7
    CrossrefPubMedSearch in Google Scholar
  • 18 Furuya M, Kurasawa K, Nagahama K , et al. Disrupted balance of angiogenic and antiangiogenic signalings in preeclampsia. J Pregnancy 2011; 2011: 123717
    PubMedSearch in Google Scholar
  • 19 Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365 (9461) 785-799
    CrossrefPubMedSearch in Google Scholar
  • 20 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996; 87 (2) 163-168
    CrossrefPubMedSearch in Google Scholar
  • 21 Zin A, Florêncio T, Fortes Filho JB , et al; Brazilian Society of Pediatrics, Brazilian Council of Ophthalmology and Brazilian Society of Pediatric Ophthalmology. Brazilian guidelines proposal for screening and treatment of retinopathy of prematurity (ROP). Arq Bras Oftalmol 2007; 70 (5) 875-883
    CrossrefPubMedSearch in Google Scholar
  • 22 Pieh C, Agostini H, Buschbeck C , et al. VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants: relationship to retinopathy of prematurity. Br J Ophthalmol 2008; 92 (5) 689-693
    CrossrefPubMedSearch in Google Scholar
  • 23 Eklund A. Beeswarm: The bee swarm plot, an alternative to stripchart. R package version 0.1.1, 2011. Available at: http://CRAN.R-project.org/package=beeswarm . Accessed February 2, 2015
    PubMed
  • 24 Boutsikou T, Malamitsi-Puchner A, Economou E, Boutsikou M, Puchner KP, Hassiakos D. Soluble vascular endothelial growth factor receptor-1 in intrauterine growth restricted fetuses and neonates. Early Hum Dev 2006; 82 (4) 235-239
    CrossrefPubMedSearch in Google Scholar
  • 25 van Beem RT, Verloop RE, Kleijer M , et al. Blood outgrowth endothelial cells from cord blood and peripheral blood: angiogenesis-related characteristics in vitro. J Thromb Haemost 2009; 7 (1) 217-226
    CrossrefPubMedSearch in Google Scholar
  • 26 Khan I, Zhang L, Mohammed M , et al. Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils. J Inflamm Res 2015; 8: 1-8
    PubMedSearch in Google Scholar
  • 27 Mashiloane CD, Moodley J. Induction or caesarean section for preterm pre-eclampsia?. J Obstet Gynaecol 2002; 22 (4) 353-356
    CrossrefPubMedSearch in Google Scholar
  • 28 Zhang Y, Li W, Xiao J, Chen S. The complication and mode of delivery in Chinese women with severe preeclampsia: a retrospective study. Hypertens Pregnancy 2014; 33 (3) 283-290
    CrossrefPubMedSearch in Google Scholar
  • 29 Jelin AC, Cheng YW, Shaffer BL, Kaimal AJ, Little SE, Caughey AB. Early-onset preeclampsia and neonatal outcomes. J Matern Fetal Neonatal Med 2010; 23 (5) 389-392
    CrossrefPubMedSearch in Google Scholar
  • 30 Wang A, Holston AM, Yu KF , et al. Circulating anti-angiogenic factors during hypertensive pregnancy and increased risk of respiratory distress syndrome in preterm neonates. J Matern Fetal Neonatal Med 2012; 25 (8) 1447-1452
    CrossrefPubMedSearch in Google Scholar
  • 31 Ozkan H, Cetinkaya M, Koksal N. Increased incidence of bronchopulmonary dysplasia in preterm infants exposed to preeclampsia. J Matern Fetal Neonatal Med 2012; 25 (12) 2681-2685
    CrossrefPubMedSearch in Google Scholar
  • 32 Tang JR, Karumanchi SA, Seedorf G, Markham N, Abman SH. Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 2012; 302 (1) L36-L46
    CrossrefPubMedSearch in Google Scholar
  • 33 Hansen AR, Barnés CM, Folkman J, McElrath TF. Maternal preeclampsia predicts the development of bronchopulmonary dysplasia. J Pediatr 2010; 156 (4) 532-536
    CrossrefPubMedSearch in Google Scholar
  • 34 Ozkan H, Cetinkaya M, Koksal N, Ozmen A, Yıldız M. Maternal preeclampsia is associated with an increased risk of retinopathy of prematurity. J Perinat Med 2011; 39 (5) 523-527
    PubMedSearch in Google Scholar
  • 35 Tsao PN, Wei SC, Su YN, Chou HC, Chen CY, Hsieh WS. Excess soluble fms-like tyrosine kinase 1 and low platelet counts in premature neonates of preeclamptic mothers. Pediatrics 2005; 116 (2) 468-472
    CrossrefPubMedSearch in Google Scholar
  • 36 Procianoy RS, Silveira RC, Mussi-Pinhata MM , et al; Brazilian Network on Neonatal Research. Sepsis and neutropenia in very low birth weight infants delivered of mothers with preeclampsia. J Pediatr 2010; 157 (3) 434-438 , 438.e1
    Search in Google Scholar
  • 37 Åsvold BO, Vatten LJ, Romundstad PR, Jenum PA, Karumanchi SA, Eskild A. Angiogenic factors in maternal circulation and the risk of severe fetal growth restriction. Am J Epidemiol 2011; 173 (6) 630-639
    CrossrefPubMedSearch in Google Scholar
  • 38 Taki A, Abe M, Komaki M , et al. Expression of angiogenesis-related factors and inflammatory cytokines in placenta and umbilical vessels in pregnancies with preeclampsia and chorioamnionitis/funisitis. Congenit Anom (Kyoto) 2012; 52 (2) 97-103
    CrossrefPubMedSearch in Google Scholar
  • 39 Malamitsi-Puchner A, Boutsikou T, Economou E , et al. Vascular endothelial growth factor and placenta growth factor in intrauterine growth-restricted fetuses and neonates. Mediators Inflamm 2005; 2005 (5) 293-297
    CrossrefPubMedSearch in Google Scholar