Metabolomic profile of umbilical cord blood plasma from early and late intrauterine growth restricted (IUGR) neonates with and without signs of brain vasodilation

PLoS ONE

Volumn 8, Issue 12, 2013, Pages

  Sanz Cortés, Magdalena ^a   Carbajo, Rodrigo J ^b   Crispi, Fatima ^a   Figueras, Francesc ^a   Pineda Lucena, Antonio ^b   Gratacós, Eduard ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

^b CENTRO DE INVESTIGACIÓN PRÍNCIPE FELIPE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ACETONE; AMOXICILLIN PLUS CLAVULANIC ACID; AMPICILLIN; CHOLINE; CREATINE; ERYTHROMYCIN; GENTAMICIN; GLUCOSE; GLUTAMINE; LEUCINE; MAGNESIUM SULFATE; PENICILLIN DERIVATIVE; PHENYLALANINE; TYROSINE; UNSATURATED FATTY ACID; VALINE; VERY LOW DENSITY LIPOPROTEIN;

ADULT; ARTICLE; BIRTH WEIGHT; BLOOD SAMPLING; BRAIN METABOLISM; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; DELIVERY; DISEASE SEVERITY; DOPPLER ECHOGRAPHY; ECHOGRAPH; FEMALE; FETUS; GESTATIONAL AGE; HUMAN; INTRAUTERINE GROWTH RETARDATION; MALE; METABOLIC PARAMETERS; METABOLITE; METABOLOMICS; NEWBORN; NUCLEAR MAGNETIC RESONANCE SPECTROMETER; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PREECLAMPSIA; PROSPECTIVE STUDY; PROTON NUCLEAR MAGNETIC RESONANCE; REFERENCE VALUE; UMBILICAL ARTERY; UMBILICAL CORD BLOOD; VASODILATATION;

BRAIN; ECHOENCEPHALOGRAPHY; FATS, UNSATURATED; FEMALE; FETAL GROWTH RETARDATION; HUMANS; INFANT, NEWBORN; LIPOPROTEINS, VLDL; MAGNETIC RESONANCE SPECTROSCOPY; MALE; METABOLOME; METABOLOMICS; VASODILATION;

EID: 84891821361     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0080121     Document Type: Article

References (79)

1. Bernstein IM, Horbar JD, Badger GJ, Ohlsson A, Golan A (2000) Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. The Vermont Oxford Network. Am J Obstet Gynecol 182: 198-206. doi:10.1016/S0002-9378(00)70513-8. PubMed: 10649179.
2. McCowan LM, Harding JE, Stewart AW (2000) Umbilical artery Doppler studies in small for gestational age babies reflect disease severity. BJOG 107: 916-925. doi:10.1111/j.1471-0528.2000.tb11092.x. PubMed: 10901565.
3. Figueras F, Eixarch E, Gratacos E, Gardosi J (2008) Predictiveness of antenatal umbilical artery Doppler for adverse pregnancy outcome in small-for-gestational-age babies according to customised birthweight centiles: population-based study. BJOG 115: 590-594. doi:10.1111/j.1471-0528.2008.01670.x. PubMed: 18333939.
4. Cruz-Lemini M, Crispi F, Van Mieghem T, Pedraza D, Cruz-Martínez R et al. (2012) Risk of perinatal death in early-onset intrauterine growth restriction according to gestational age and cardiovascular Doppler indices: a multicenter study. Fetal Diagn Ther 32: 116-122. doi:10.1159/000333001. PubMed: 22777088.
5. Barker DJ (1995) Fetal origins of coronary heart disease. BMJ 311: 171-174. doi:10.1136/bmj.311.6998.171. PubMed: 7613432.
6. Arcangeli T, Thilaganathan B, Hooper R, Khan KS, Bhide A (2012) Neurodevelopmental delay in small babies at term. A systematic review. Ultrasound Obstet Gynecol.
7. Kaijser M, Bonamy AK, Akre O, Cnattingius S, Granath F et al. (2008) Perinatal risk factors for ischemic heart disease: disentangling the roles of birth weight and preterm birth. Circulation 117: 405-410. doi:10.1161/ CIRCULATIONAHA.107.710715. PubMed: 18172034.
8. Palinski W, Napoli C (2008) Impaired fetal growth, cardiovascular disease, and the need to move on. Circulation 117: 341-343. doi: 10.1161/CIRCULATIONAHA.107.750133. PubMed: 18212299.
9. Hoyert DL, Mathews TJ, Menacker F, Strobino DM, Guyer B (2006) Annual summary of vital statistics: 2004. Pediatrics 117: 168-183. doi: 10.1542/peds.2005-2587. PubMed: 16396875.
10. Baschat AA (2011) Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol 37: 501-514. doi:10.1002/uog.9008. PubMed: 21520312.
11. Hecher K, Bilardo CM, Stigter RH, Ville Y, Hackelöer BJ et al. (2001) Monitoring of fetuses with intrauterine growth restriction: a longitudinal study. Ultrasound Obstet Gynecol 18: 564-570. doi:10.1046/j.0960- 7692.2001.00590.x. PubMed: 11844190.
12. Bilardo CM, Wolf H, Stigter RH, Ville Y, Baez E et al. (2004) Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction. Ultrasound Obstet Gynecol 23: 119-125. doi:10.1002/uog.965. PubMed: 14770389.
13. Figueras F, Eixarch E, Meler E, Iraola A, Figueras J et al. (2008) Small-for-gestational-age fetuses with normal umbilical artery Doppler have suboptimal perinatal and neurodevelopmental outcome. Eur J Obstet Gynecol Reprod Biol 136: 34-38. doi:10.1016/j.ejogrb.2007.02.016. PubMed: 17434250.
14. Miller J, Turan S, Baschat AA (2008) Fetal growth restriction. Semin Perinatol 32: 274-280. doi:10.1053/j.semperi.2008.04.010. PubMed: 18652928.
15. Figueras F, Oros D, Cruz-Martinez R, Padilla N, Hernandez-Andrade E et al. (2009) Neurobehavior in term, small-for-gestational age infants with normal placental function. Pediatrics 124: e934-e941. doi:10.1542/peds.2008-3346. PubMed: 19858151.
16. Cruz-Martínez R, Figueras F, Hernandez-Andrade E, Oros D, Gratacos E (2011) Fetal brain Doppler to predict cesarean delivery for nonreassuring fetal status in term small-for-gestational-age fetuses. Obstet Gynecol 117: 618-626. doi:10.1097/AOG.0b013e31820b0884. PubMed: 21343765.
17. Severi FM, Bocchi C, Visentin A, Falco P, Cobellis L et al. (2002) Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 19: 225-228. doi:10.1046/j.1469-0705.2002.00652.x. PubMed: 11896941.
18. Hershkovitz R, Kingdom JC, Geary M, Rodeck CH (2000) Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 15: 209-212. doi:10.1046/j.1469-0705.2000.00079.x. PubMed: 10846776.
19. Oros D, Figueras F, Cruz-Martinez R, Padilla N, Meler E et al. (2010) Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 35: 456-461. doi:10.1002/uog.7588. PubMed: 20178115.
20. Hecher K, Snijders R, Campbell S, Nicolaides K (1995) Fetal venous, intracardiac, and arterial blood flow measurements in intrauterine growth retardation: relationship with fetal blood gases. Am J Obstet Gynecol 173: 10-15. doi:10.1016/0002-9378(95)90161-2. PubMed: 7631665.
21. Cruz-Martinez R, Figueras F, Oros D, Padilla N, Meler E et al. (2009) Cerebral blood perfusion and neurobehavioral performance in full-term small-for-gestational-age fetuses. Am J Obstet Gynecol 201: 474: e471-e477. PubMed: 19631930.
22. Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB (2004) Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol 22: 245-252. doi:10.1016/j.tibtech.2004.03.007. PubMed: 15109811.
23. Allen J, Davey HM, Broadhurst D, Heald JK, Rowland JJ et al. (2003) High-throughput classification of yeast mutants for functional genomics using metabolic footprinting. Nat Biotechnol 21: 692-696. doi:10.1038/nbt823. PubMed: 12740584.
24. Romero R, Espinoza J, Gotsch F, Kusanovic JP, Friel LA et al. (2006) The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome. BJOG 113 Suppl 3: 118-135. doi:10.1111/j.1471-0528.2006.01150.x. PubMed: 17206980.
25. Favretto D, Cosmi E, Ragazzi E, Visentin S, Tucci M et al. (2012) Cord blood metabolomic profiling in intrauterine growth restriction. Anal Bioanal Chem 402: 1109-1121. doi:10.1007/s00216-011-5540-z. PubMed: 22101423.
26. Ivorra C, García-Vicent C, Chaves FJ, Monleón D, Morales JM et al. (2012) Metabolomic profiling in blood from umbilical cords of low birth weight newborns. J Transl Med 10: 142. doi: 10.1186/1479-5876-10-142. PubMed: 22776444.
27. Robinson HP, Fleming JE (1975) A critical evaluation of sonar "crown-rump length" measurements. Br J Obstet Gynaecol 82: 702-710. doi: 10.1111/j.1471-0528.1975.tb00710.x. PubMed: 1182090.
28. Figueras F, Meler E, Iraola A, Eixarch E, Coll O et al. (2008) Customized birthweight standards for a Spanish population. Eur J Obstet Gynecol Reprod Biol 136: 20-24. doi:10.1016/j.ejogrb.2006.12.015. PubMed: 17287065.
29. Arduini D, Rizzo G (1990) Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med 18: 165-172. doi:10.1515/jpme.1990.18.3.165. PubMed: 2200862.
30. Baschat AA, Gembruch U (2003) The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol 21: 124-127. doi:10.1002/uog.20. PubMed: 12601831.
31. Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E et al. (2007) Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2: 2692-2703. doi:10.1038/nprot.2007.376. PubMed: 18007604.
32. Bernini P, Bertini I, Luchinat C, Nincheri P, Staderini S et al. (2011) Standard operating procedures for pre-analytical handling of blood and urine for metabolomic studies and biobanks. J Biomol NMR 49: 231-243. doi:10.1007/s10858-011-9489-1. PubMed: 21380509.
33. Meiboom S, Gill D (1958) Modified spin echo method for measuring nuclear relaxation times. Review of Scientific Instruments 29: 688-691. doi:10.1063/1.1716296.
34. Nicholson JK, Foxall PJ, Spraul M, Farrant RD, Lindon JC (1995) 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma. Anal Chem 67: 793-811. doi:10.1021/ac00101a004. PubMed: 7762816.
35. Lindon JC (2010) Biofluids studied by NMR spectroscopy. Encyclopedia of Spectroscopy and Spectrometry. Elsevier. p. 128.
36. Barton RH, Waterman D, Bonner FW, Holmes E, Clarke R et al. (2010) The influence of EDTA and citrate anticoagulant addition to human plasma on information recovery from NMR-based metabolic profiling studies. Mol Biosyst 6(1): 215-224. doi:10.1039/b907021d. PubMed: 20024083.
37. Story L, Damodaram MS, Allsop JM, McGuinness A, Patel A et al. (2011) Brain metabolism in fetal intrauterine growth restriction: a proton magnetic resonance spectroscopy study. Am J Obstet Gynecol 205: 483: e481-e488. PubMed: 21861969.
38. Leduc L, Delvin E, Ouellet A, Garofalo C, Grenier E et al. (2011) Oxidized low-density lipoproteins in cord blood from neonates with intra-uterine growth restriction. Eur J Obstet Gynecol Reprod Biol 156: 46-49. doi:10.1016/j.ejogrb.2011.01.007. PubMed: 21324580.
39. Pecks U, Brieger M, Schiessl B, Bauerschlag DO, Piroth D et al. (2012) Maternal and fetal cord blood lipids in intrauterine growth restriction. J Perinat Med 40: 287-296. PubMed: 22505508.
40. Pecks U, Caspers R, Schiessl B, Bauerschlag D, Piroth D et al. (2012) The evaluation of the oxidative state of low-density lipoproteins in intrauterine growth restriction and preeclampsia. Hypertens Pregnancy 31: 156-165. doi:10.3109/10641955.2010.544805. PubMed: 21250891.
41. Lin G, Liu C, Feng C, Fan Z, Dai Z et al. (2012) Metabolomic analysis reveals differences in umbilical vein plasma metabolites between normal and growth-restricted fetal pigs during late gestation. J Nutr 142: 990-998. doi:10.3945/jn.111.153411. PubMed: 22513987.
42. Kaser S, Ebenbichler CF, Wolf HJ, Sandhofer A, Stanzl U et al. (2001) Lipoprotein profile and cholesteryl ester transfer protein in neonates. Metabolism 50: 723-728. doi:10.1053/meta.2001.23307. PubMed: 11398152.
43. Alvino G, Cozzi V, Radaelli T, Ortega H, Herrera E et al. (2008) Maternal and fetal fatty acid profile in normal and intrauterine growth restriction pregnancies with and without preeclampsia. Pediatr Res 64: 615-620. doi:10.1203/PDR.0b013e31818702a2. PubMed: 19034199.
44. Matorras R, Perteagudo L, Nieto A, Sanjurjo P (1994) Intrauterine growth retardation and plasma fatty acids in the mother and the fetus. Eur J Obstet Gynecol Reprod Biol 57: 189-193. doi: 10.1016/0028-2243(94)90299-2. PubMed: 7713295.
45. Raff H, Bruder ED, Jankowski BM, Goodfriend TL (2000) Neonatal hypoxic hyperlipidemia in the rat: effects on aldosterone and corticosterone synthesis in vitro. Am J Physiol Regul Integr Comp Physiol 278: R663-R668. PubMed: 10712286.
46. Horgan RP, Broadhurst DI, Dunn WB, Brown M, Heazell AE et al. (2010) Changes in the metabolic footprint of placental explant-conditioned medium cultured in different oxygen tensions from placentas of small for gestational age and normal pregnancies. Placenta 31: 893-901. doi:10.1016/j.placenta.2010. 07.002. PubMed: 20708797.
47. Mordasini R, Klose G, Greten H (1978) Secondary type II hyperlipoproteinemia in patients with anorexia nervosa. Metabolism 27: 71-79. doi:10.1016/0026-0495(78)90125-7. PubMed: 201820.
48. Arden MR, Weiselberg EC, Nussbaum MP, Shenker IR, Jacobson MS (1990) Effect of weight restoration on the dyslipoproteinemia of anorexia nervosa. J Adolesc Health Care 11: 199-202. doi: 10.1016/0197-0070(90)90348-6. PubMed: 2358386.
49. Yaffee S, Gold A, Sampugna J (1980) Effects of prolonged starvation on plasma free fatty acid levels and fatty acid composition of myocardial total lipids in the rat. J Nutr 110: 2490-2496. PubMed: 7441376.
50. Regnault TR, Teng C, de Vrijer B, Galan HL, Wilkening RB et al. (2010) The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation. Exp Biol Med (Maywood) 235: 999-1006. PubMed: 20576742.
51. Marconi AM, Paolini C, Buscaglia M, Zerbe G, Battaglia FC et al. (1996) The impact of gestational age and fetal growth on the maternal-fetal glucose concentration difference. Obstet Gynecol 87: 937-942. doi:10.1016/0029-7844(96) 00048-8. PubMed: 8649702.
52. Engineer N, Kumar S (2010) Perinatal variables and neonatal outcomes in severely growth restricted preterm fetuses. Acta Obstet Gynecol Scand 89: 1174-1181. doi:10.3109/00016349.2010.501370. PubMed: 20804344.
53. Tea I, Le Gall G, Küster A, Guignard N, Alexandre-Gouabau MC et al. (2012) 1H-NMR-based metabolic profiling of maternal and umbilical cord blood indicates altered materno-foetal nutrient exchange in preterm infants. PLOS ONE 7: e29947. doi:10.1371/journal.pone.0029947. PubMed: 22291897.
54. Marconi AM, Ronzoni S, Vailati S, Bozzetti P, Morabito A et al. (2009) Neonatal morbidity and mortality in intrauterine growth restricted (IUGR) pregnancies is predicated upon prenatal diagnosis of clinical severity. Reprod Sci 16: 373-379. doi:10.1177/1933719108327591. PubMed: 19087980.
55. Neu J (2001) Glutamine in the fetus and critically ill low birth weight neonate: metabolism and mechanism of action. J Nutr 131: 2585S-2589S; discussion: 11533317.
56. Kuhn KS, Schuhmann K, Stehle P, Darmaun D, Fürst P (1999) Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production. Am J Clin Nutr 70: 484-489. PubMed: 10500016.
57. Darmaun D, Roig JC, Auestad N, Sager BK, Neu J (1997) Glutamine metabolism in very low birth weight infants. Pediatr Res 41: 391-396. doi:10.1203/00006450-199703000-00015. PubMed: 9078541.
58. Muhlbacher F, Kapadia CR, Colpoys MF, Smith RJ, Wilmore DW (1984) Effects of glucocorticoids on glutamine metabolism in skeletal muscle. Am J Physiol 247: E75-E83. PubMed: 6146264.
59. Ardawi MS, Jamal YS (1990) Glutamine metabolism in skeletal muscle of glucocorticoid-treated rats. Clin Sci (Lond) 79: 139-147. PubMed: 1975227.
60. Nugent JL, Wareing M, Palin V, Sibley CP, Baker PN et al. (2013) Chronic glucocorticoid exposure potentiates placental chorionic plate artery constriction: implications for aberrant fetoplacental vascular resistance in fetal growth restriction. Endocrinology 154: 876-887. doi: 10.1210/en.2012-1927. PubMed: 23295737.
61. Sloboda DM, Newnham JP, Challis JR (2000) Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term. J Endocrinol 165: 79-91. doi:10.1677/joe.0.1650079. PubMed: 10750038.
62. Dessì A, Atzori L, Noto A, Visser GH, Gazzolo D et al. (2011) Metabolomics in newborns with intrauterine growth retardation (IUGR): urine reveals markers of metabolic syndrome. J Matern Fetal Neonatal Med 24 Suppl 2: 35-39. doi:10.3109/14767058.2011.605868. PubMed: 21767100.
63. Paolini CL, Marconi AM, Ronzoni S, Di Noio M, Fennessey PV et al. (2001) Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab 86: 5427-5432. doi:10.1210/jc.86.11.5427. PubMed: 11701717.
64. Eixarch E, Meler E, Iraola A, Illa M, Crispi F et al. (2008) Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 32: 894-899. doi:10.1002/uog.6249. PubMed: 19035538.
65. Geva R, Eshel R, Leitner Y, Fattal-Valevski A, Harel S (2006) Memory functions of children born with asymmetric intrauterine growth restriction. Brain Res 1117: 186-194. doi:10.1016/j.brainres.2006.08.004. PubMed: 16962082.
66. Leitner Y, Fattal-Valevski A, Geva R, Eshel R, Toledano-Alhadef H et al. (2007) Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study. J Child Neurol 22: 580-587. doi:10.1177/0883073807302605. PubMed: 17690065.
67. Cetin I, Corbetta C, Sereni LP, Marconi AM, Bozzetti P et al. (1990) Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis. Am J Obstet Gynecol 162: 253-261. doi:10.1016/0002-9378(90)90860-A. PubMed: 2301500.
68. Palova S, Charvat J, Masopust J, Klapkova E, Kvapil M (2007) Changes in the plasma amino acid profile in anorexia nervosa. J Int Med Res 35: 389-394. doi:10.1177/147323000703500314. PubMed: 17593868.
69. Hiroshige K, Sonta T, Suda T, Kanegae K, Ohtani A (2001) Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis. Nephrol Dial Transplant 16: 1856-1862. doi:10.1093/ndt/16.9.1856. PubMed: 11522870.
70. You YN, Short KR, Jourdan M, Klaus KA, Walrand S et al. (2009) The effect of high glucocorticoid administration and food restriction on rodent skeletal muscle mitochondrial function and protein metabolism. PLOS ONE 4: e5283. doi:10.1371/journal.pone.0005283. PubMed: 19381333.
71. Elia M, Farrell R, Ilic V, Smith R, Williamson DH (1980) The removal of infused leucine after injury, starvation and other conditions in man. Clin Sci (Lond) 59: 275-283. PubMed: 7428295.
72. Zeisel SH, Niculescu MD (2006) Perinatal choline influences brain structure and function. Nutr Rev 64: 197-203. doi:10.1111/j.1753-4887.2006. tb00202.x. PubMed: 16673755.
73. Sheard NF, Tayek JA, Bistrian BR, Blackburn GL, Zeisel SH (1986) Plasma choline concentration in humans fed parenterally. Am J Clin Nutr 43: 219-224. PubMed: 3080867.
74. Ilcol YO, Yilmaz Z, Ulus IH (2003) Serum free and phospholipid-bound choline decrease after surgery and methylprednisolone administration in dogs. Neurosci Lett 339: 195-198. doi:10.1016/S0304-3940(03)00035-1. PubMed: 12633886.
75. Montoya DA, White AM, Williams CL, Blusztajn JK, Meck WH et al. (2000) Prenatal choline exposure alters hippocampal responsiveness to cholinergic stimulation in adulthood. Brain Res. Dev Brain Res 123: 25-32. doi:10.1016/S0165-3806(00)00075-4.
76. Nurk E, Refsum H, Bjelland I, Drevon CA, Tell GS et al. (2012) Plasma free choline, betaine and cognitive performance: the Hordaland Health Study. Br J Nutr: 1-9. PubMed: 22717142.
77. Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E et al. (2010) Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation 121: 2427-2436. doi:10.1161/CIRCULATIONAHA.110.937995. PubMed: 20497977.
78. Crispi FF, Cruz-Lemini M, Bartrons J, Bijnens B, Gratacos E (2012) Cardiovascular programming in children born small for gestational age and relationship with prenatal signs of severity. Am J Obstet Gynecol, 207: 121.e1. PubMed: 22717268.
79. Figueras F, Cruz-Martinez R, Sanz-Cortes M, Arranz A, Illa M et al. (2011) Neurobehavioral outcomes in preterm, growth-restricted infants with and without prenatal advanced signs of brain-sparing. Ultrasound Obstet Gynecol 38: 288-294. doi:10.1002/uog.9041. PubMed: 21557369.