Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study.
Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti-β2 glycoprotein-I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well-established.



The purpose of this study was to assess the risk of obstetric complications in women with primary antiphospholipid syndrome that is associated with specific antibody profile.



The Pregnancy In Women With Antiphospholipid Syndrome study is a multicenter, retrospective, cohort study. Diagnosis and classification of antiphospholipid syndrome were based on the 2006 International revised criteria. All women included in the study had at least 1 clinical criteria for antiphospholipid syndrome, were positive for at least 1 antiphospholipid antibody (anticardiolipin antibodies, anti-β2 glycoprotein-I, and/or lupus anticoagulant), and were treated with low-dose aspirin and prophylactic low molecular weight heparin from the first trimester. Only singleton pregnancies with primary antiphospholipid syndrome were included. The primary outcome was live birth, defined as any delivery of a live infant after 22 weeks gestation. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction, and stillbirth. We planned to assess the outcomes that are associated with the various antibody profile (test result for lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein-I).



There were 750 singleton pregnancies with primary antiphospholipid syndrome in the study cohort: 54 (7.2%) were positive for lupus anticoagulant only; 458 (61.0%) were positive for anticardiolipin antibodies only; 128 (17.1%) were positive for anti-β2 glycoprotein-I only; 90 (12.0%) were double positive and lupus anticoagulant negative, and 20 (2.7%) were triple positive. The incidence of live birth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared with women with only 1 antibody positive test results, women with multiple antibody positive results had a significantly lower live birth rate (40.9% vs 56.6%; adjusted odds ratio, 0.71; 95% confidence interval, 0.51-0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; adjusted odds ratio, 1.56; 95% confidence interval, 1.22-1.95) and with severe features (22.7% vs 13.8%, adjusted odds ratio, 1.66; 95% confidence interval, 1.19-2.49), of intrauterine growth restriction (53.6% vs 40.8%; adjusted odds ratio, 2.31; 95% confidence interval, 1.17-2.61) and of stillbirth (36.4% vs 21.7%; adjusted odds ratio, 2.67; 95% confidence interval, 1.22-2.94). In women with only 1 positive test result, women with anti-β2 glycoprotein-I positivity present alone had a significantly lower live birth rate (47.7% vs 56.3% vs 79.6%; P<.01) and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; P<.01) and with severe features (17.2% vs 14.4% vs 0%; P=.02), intrauterine growth restriction (48.4% vs 40.1% vs 25.9%; P<.01), and stillbirth (29.7% vs 21.2% vs 7.4%; P<.01) compared with women with anticardiolipin antibodies and with women with lupus anticoagulant present alone, respectively. In the group of women with >1 antibody positivity, triple-positive women had a lower live birth rate (30% vs 43.3%; adjusted odds ratio,0.69; 95% confidence interval, 0.22-0.91) and a higher incidence of intrauterine growth restriction (70.0% vs 50.0%; adjusted odds ratio,2.40; 95% confidence interval, 1.15-2.99) compared with double positive and lupus anticoagulant negative women.



In singleton pregnancies with primary antiphospholipid syndrome, anticardiolipin antibody is the most common sole antiphospholipid antibody present, but anti-β2 glycoprotein-I is the one associated with the lowest live birth rate and highest incidence of preeclampsia, intrauterine growth restriction, and stillbirth, compared with the presence of anticardiolipin antibodies or lupus anticoagulant alone. Women with primary antiphospholipid syndrome have an increased risk of obstetric complications and lower live birth rate when <1 antiphospholipid antibody is present. Despite therapy with low-dose aspirin and prophylactic low molecular weight heparin, the chance of a liveborn neonate is only 30% for triple-positive women.
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), Rome, Italy. Electronic address: gabriele.saccone.1990@gmail.com.
Gabriele
G
Saccone
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA.
Vincenzo
V
Berghella
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), Rome, Italy.
Giuseppe Maria
GM
Maruotti
Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), Rome, Italy; Department of Obstetrics and Gynecology, University of Parma, Parma, Italy.
Tullio
T
Ghi
Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), Rome, Italy; Department of Obstetrics and Gynecology, Università Roma Tor Vergata, Rome, Italy.
Giuseppe
G
Rizzo
Department of Medical Surgical Sciences, Division of Obstetrics and Prenatal Medicine, St Orsola Malpighi Hospital, University of Bologna, Bologna, Italy.
Giuliana
G
Simonazzi
Department of Medical Surgical Sciences, Division of Obstetrics and Prenatal Medicine, St Orsola Malpighi Hospital, University of Bologna, Bologna, Italy.
Nicola
N
Rizzo
Department of Obstetrics & Gynecology, University of Modena and Reggio Emilia, Modena, Italy.
Fabio
F
Facchinetti
Department of Obstetrics and Gynecology, University of Parma, Parma, Italy.
Andrea
A
Dall'Asta
Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), Rome, Italy; Department of Woman's and Child's Health, University of Padua, Padua, Italy.
Silvia
S
Visentin
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), Rome, Italy.
Laura
L
Sarno
Department of Gynaecology and Obstetrics, School of Medicine, University of Udine, Udine, Italy.
Serena
S
Xodo
Department of Medical Surgical Sciences, Division of Obstetrics and Prenatal Medicine, St Orsola Malpighi Hospital, University of Bologna, Bologna, Italy.
Dalila
D
Bernabini
Department of Obstetrics & Gynecology, University of Modena and Reggio Emilia, Modena, Italy.
Francesca
F
Monari
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA.
Amanda
A
Roman
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD.
Ahizechukwu Chigoziem
AC
Eke
Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy.
Ariela
A
Hoxha
Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy.
Amelia
A
Ruffatti
Stanford Prevention Research Center, School of Medicine, Stanford University, Stanford, CA.
Ewoud
E
Schuit
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG), Rome, Italy.
Pasquale
P
Martinelli
D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D000925:Anticoagulants / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000175:diagnosis / Q000453:epidemiology*; D001241:Aspirin / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology; D006495:Heparin, Low-Molecular-Weight; D006801:Humans; D007558:Italy / Q000453:epidemiology; D050498:Live Birth / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011225:Pre-Eclampsia / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000453:epidemiology; D012189:Retrospective Studies; D050497:Stillbirth / Q000453:epidemiology; D053482:beta 2-Glycoprotein I / Q000276:immunology
D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D010975:Platelet Aggregation Inhibitors; D053482:beta 2-Glycoprotein I; D001241:Aspirin
antiphospholipid antibody; autoimmune disorder; preeclampsia; preterm birth; thrombophilia