title: Individual risk assessment of adverse pregnancy outcome by multivariate regression analysis may serve as basis for drug intervention studies: retrospective analysis of 426 high-risk patients including ethical aspects.
abstract: OBJECTIVE
  To identify patients at very high risk for adverse pregnancy outcome (APO) at the 20- to 23-week scan and to assess the effectiveness of Aspirin (ASS) and low molecular weight heparin (LMWH) starting after this examination.
  
  
  METHODS
  By applying an algorithm based on multivariate logistic regression analysis using the parameters maternal age, parity, body mass index (BMI), mean pulsatility index of both uterine arteries (meanPI), presence of uni- or bilateral notch, and depth of notch (mean notch index (meanNI), we retrospectively calculated the individual risk for APO of 21,302 singleton pregnancies. We isolated a subgroup of 426 patients with the highest calculated probability for APO (cpAPO > 27.8 %). 147 had been treated with ASS; 73 with LMWH, 15 patients with a combination of ASS and LMWH, and 191 patients had not received anticoagulants.
  
  
  RESULTS
  Administration of ASS starting after 20 gestational weeks in comparison to non-treated patients significantly reduced the frequency of intrauterine/neonatal death (IUD/NND), preeclampsia <33 weeks (PE < 33), and preterm delivery <33 weeks (PD < 33), while the frequency of IUGR showed a tendency to be elevated (P = 0.061). The subgroup of high-risk patients treated with LMWH was characterised by a higher a priori risk for APO and showed no significant reduction of any form of APO but an increased frequency of PE.
  
  
  CONCLUSIONS
  Individual assessment of risk for APO by applying a simple algorithm based on biometrical/biographical as well as sonographic parameters may serve as basis for drug intervention studies. The administration of ASS in high-risk patients starting after 20 gestational weeks reduced the frequency of most of the severe forms of adverse pregnancy outcome in high-risk patients. A complication-reducing effect of LMWH starting after 20 weeks of gestation in patients could not be proven. From an ethical point of view, it may not be justified any more to preclude high-risk patients from administration of ASS or to perform studies of ASS against placebo.
authors: Center for Prenatal Diagnosis and Human Genetics, Free University of Berlin, Kurfuerstendamm 199, 10719 Berlin, Germany. bedaktari@t-online.de
authors: Rolf
authors: R
authors: Becker
authors: Thomas
authors: T
authors: Keller
authors: Holger
authors: H
authors: Kiesewetter
authors: Heiner
authors: H
authors: Fangerau
authors: Uta
authors: U
authors: Bittner
mesh_terms: D000465:Algorithms; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D005260:Female; D005313:Fetal Death / Q000517:prevention & control; D005317:Fetal Growth Retardation / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D008423:Maternal Age; D010298:Parity; D011225:Pre-Eclampsia / Q000517:prevention & control; D011247:Pregnancy; D011248:Pregnancy Complications / Q000517:prevention & control*; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000517:prevention & control; D011673:Pulsatile Flow; D012189:Retrospective Studies; D018570:Risk Assessment; D014463:Ultrasonography; D055988:Uterine Artery / Q000000981:diagnostic imaging
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D001241:Aspirin
references: BMJ. 2011 Apr 07;342:d1875
references: 21474517
references: Int J Gynaecol Obstet. 1999 Apr;65(1):93-6
references: 10390112
references: Eur J Obstet Gynecol Reprod Biol. 2004 Feb 10;112(2):142-4
references: 14746947
references: J Postgrad Med. 2011 Apr-Jun;57(2):91-5
references: 21654128
references: Bull Med Ethics. 2002 Oct;(182):17-23
references: 14983848
references: Obstet Gynecol Surv. 2011 Apr;66(4):225-39
references: 21756405
references: Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004659
references: 17443552
references: Obstet Gynecol. 2010 Aug;116(2 Pt 1):402-414
references: 20664402
references: Thromb Haemost. 2011 Dec;106(6):1053-61
references: 21946915
references: Blood. 2011 Nov 3;118(18):4780-8
references: 21868576
references: Ultrasound Obstet Gynecol. 2003 Sep;22(3):233-9
references: 12942493
references: N Engl J Med. 2002 Jul 4;347(1):19-25
references: 12097536
references: Eur J Obstet Gynecol Reprod Biol. 1998 Sep;80(1):49-54
references: 9758259
references: Am J Obstet Gynecol. 2009 Feb;200(2):151.e1-9; discussion e1-5
references: 19070828
references: Prenat Diagn. 2011 Oct;31(10):990-4
references: 21744367
references: Obstet Gynecol. 1986 Nov;68(5):649-53
references: 2945132
references: Obstet Gynecol. 2008 Aug;112(2 Pt 1):320-4
references: 18669729
references: Fetal Diagn Ther. 2011;30(4):250-65
references: 22067258
references: Obstet Gynecol. 2010 Jan;115(1):14-20
references: 20027028
references: Semin Thromb Hemost. 2011 Mar;37(2):118-24
references: 21370211
references: Ultrasound Obstet Gynecol. 2009 Jan;33(1):23-33
references: 19090499
references: Prenat Diagn. 2012 Jun;32(6):550-6
references: 22517407
references: BJOG. 2002 Feb;109(2):161-7
references: 11888098
references: BJOG. 2006 May;113(5):580-9
references: 16579806
references: Hypertens Pregnancy. 2006;25(2):115-27
references: 16867918
references: Blood. 2012 Apr 5;119(14):3269-75
references: 22289887
references: Obstet Gynecol. 2001 Nov;98(5 Pt 1):861-6
references: 11704184
references: Prenat Diagn. 2011 Dec;31(12):1141-6
references: 22034048
references: Fetal Diagn Ther. 2012;31(3):141-6
references: 22441437
references: Ultrasound Obstet Gynecol. 2010 Jun;35(6):680-7
references: 20205159
references: Geburtshilfe Frauenheilkd. 1996 Oct;56(10):550-8
references: 9036070
references: Ultrasound Obstet Gynecol. 2010 Jun;35(6):662-70
references: 20232288
references: Placenta. 2011 Aug;32(8):598-602
references: 21652068
references: Obstet Gynecol. 2009 Jun;113(6):1206-1216
references: 19461414
references: Obstet Gynecol. 2010 Jan;115(1):5-13
references: 20027027
references: PLoS One. 2011;6(7):e21564
references: 21799738
references: J Obstet Gynaecol Can. 2009 Sep;31(9):818-826
references: 19941706
references: Obstet Gynecol. 2008 Aug;112(2 Pt 1):359-72
references: 18669736
references: Prenat Diagn. 2011 Jan;31(1):66-74
references: 21210481
references: J Thromb Haemost. 2004 Jul;2(7):1194-5
references: 15219211
references: Best Pract Res Clin Obstet Gynaecol. 2011 Aug;25(4):419-33
references: 21454131
references: Placenta. 2011 Feb;32 Suppl:S42-8
references: 21257082
references: Am J Obstet Gynecol. 2003 Oct;189(4):1173-7
references: 14586374
references: Thromb Res. 2011 Feb;127 Suppl 3:S76-80
references: 21262448
references: Fetal Diagn Ther. 2010;27(2):78-86
references: 20093804
references: Clinics (Sao Paulo). 2005 Oct;60(5):407-14
references: 16254678
references: Blood Coagul Fibrinolysis. 2011 Mar;22(2):123-6
references: 21192252
references: Lancet. 2007 May 26;369(9575):1791-1798
references: 17512048
references: BJOG. 2003 May;110(5):475-84
references: 12742332
references: BJOG. 2003 May;110(5):485-91
references: 12742333
references: Lancet. 1986 Jan 4;1(8471):1-3
references: 2867260
references: Lancet. 1983 Mar 26;1(8326 Pt 1):675-7
references: 6132039
references: J Perinat Med. 2011 Nov;39(6):667-72
references: 21919546
references: J Perinat Med. 2002;30(5):388-94
references: 12442602
references: J Matern Fetal Neonatal Med. 2011 Aug;24(8):1042-5
references: 21231837
references: Obstet Gynecol. 2005 Jan;105(1):182-92
references: 15625161