Correspondence
Thrombophilia Polymorphisms and Intrauterine Growth Restriction
N Engl J Med 2002; 347:1530-1531November 7, 2002
- Article
To the Editor:
Infante-Rivard et al. (July 4 issue)1 found no association between thrombophilic mutations and intrauterine growth restriction defined by a birth weight below the 10th percentile, as we2 and others3,4 have demonstrated, and they found an unexpectedly low rate of placental infarcts. Although the authors note that we used the 5th percentile for defining fetal growth restriction,2 they did not address other important differences between our study and their own.
The authors report that the mean (±SD) birth weight was 2393.5±606.2 g and that 83 percent of the mothers delivered between 36 and 40 weeks of gestation. Among our 44 newborns with growth restriction, the mean birth weight was 1387 g, and 64 percent of the mothers delivered at less than 36 weeks of gestation. The use of the 10th percentile in the definition for the primary analysis results in the inclusion of many constitutionally small fetuses with none of the clinically significant risks associated with growth restriction.5 Conversely, the combination of prematurity and growth restriction carries a high risk of serious long-term sequelae.5 Different study criteria may explain the fact that Infante-Rivard et al. did not find an association with thrombophilic mutations.
5 ReferencesMichael J. Kupferminc, M.D.
Ariel Many, M.D.
Joseph B. Lessing, M.D.
Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel
tmcobgyn@tasmc.health. gov. il 1
Infante-Rivard C ,Rivard G-E ,Yotov WV , et al. Absence of association of thrombophilia polymorphisms with intrauterine growth restriction. N Engl J Med 2002;347:19-25
Full Text | Web of Science | Medline2
Kupferminc MJ ,Eldor A ,Steinman N , et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999;340:9-13[Erratum, N Engl J Med 1999;341:384.]
Full Text | Web of Science | Medline3
Martinelli P ,Grandone E ,Colaizzo D , et al. Familial thrombophilia and the occurrence of fetal growth restriction. Haematologica 2001;86:428-431
Web of Science | Medline4
Grandone E ,Margaglione M ,Colaizzo D , et al. Lower birth-weight in neonates of mothers carrying factor V G1691A and factor II A(20210) mutations. Haematologica 2002;87:177-181
Web of Science | Medline5
Resnik R . Intrauterine growth restriction. Obstet Gynecol 2002;99:490-496
CrossRef | Web of Science | Medline
To the Editor:
Infante-Rivard and colleagues did not specify whether women with known causes of intrauterine growth restriction (such as diabetes, hypertension, other diseases, or prolonged and multiple pregnancies) were included in their study. Moreover, no information was given about the types of malformations included, the fetal karyotype, or transplacental infections, which may influence birth weight. Up to 19.5 percent of fetuses with intrauterine growth restriction may have chromosomal abnormalities, 11.5 percent may have structural malformations, and 6.2 percent may have proven congenital infections.1
1 ReferencesElvira Grandone, M.D.
Istituto di Ricovero e Cura a Carattere Scientifico, 71013 San Giovanni Rotondo, Italy
grandone@katamail.com Maurizio Margaglione, M.D.
University of Foggia, 71100 Foggia, ItalyAuthor/Editor Response
The authors reply:
To the Editor: Kupferminc et al. underscore the fact that the 44 newborns with intrauterine growth restriction in their study were different in terms of birth weight, gestational age, and percentile of birth weight from the newborns we studied — which could explain the discrepancies between their results and ours. As we reported, our results in analyses using the 5th percentile as the cutoff for growth restriction were not different from those obtained in analyses using the 10th percentile as the cutoff. Our study included 60 newborns with a birth weight below 1500 g; their mean gestational age was 31.3 weeks. There were also 19 controls who weighed less than 1500 g at birth. The prevalence of the maternal MTHFR C677T polymorphism (one or two copies) was lower among these newborns than among the controls; one mother of a newborn with growth restriction had the factor V Leiden mutation (one copy), as compared with no mothers of controls; and two mothers of newborns with growth restriction had the prothrombin G20210A polymorphism (one copy), as compared with no mothers of controls. These results are compatible with our overall results. That we had an “unexpectedly low rate of placental infarcts” is a surprising comment, given that most of the few available studies of placental lesions and intrauterine growth restriction have found no difference in the prevalence of lesions between women with and without thrombophilia.1-3
Grandone and Margaglione ask about known causes of intrauterine growth restriction (such as diabetes and hypertension). We included all newborns with intrauterine growth restriction born at our hospital during a defined period; however, adjustment for maternal diseases associated with intrauterine growth restriction in the analysis comparing newborns with growth restrictions and controls did not change our results. We should have noted that all newborns with clinically detectable and important malformations at birth were excluded.
3 ReferencesClaire Infante-Rivard, M.D., Ph.D.
McGill University, Montreal, QC H3A 1A3, Canada
claire.infante-rivard@mcgill. ca Georges-Etienne Rivard, M.D.
Robert Gauthier, M.D.
Hôpital Sainte-Justine, Montreal, QC H3T 1C5, Canada1
Wisotzkey JD ,Bayliss P ,Rutherford E ,Bell T . Placental genotyping of the factor V Leiden, prothrombin 20210A and the methylenetetrahydrofolate reductase (MTHFR) C677T alleles in IUGR pregnancies. Thromb Haemost 1999;81:844-845
Web of Science | Medline2
Mousa HA ,Alfirevicl Z . Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Hum Reprod 2000;15:1830-1833
CrossRef | Web of Science | Medline3
Sikkema JM ,Franx A ,Bruinse HW ,van der Wijk NG ,de Valk HW ,Nikkels PGJ . Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia. Placenta 2002;23:337-342
CrossRef | Web of Science | Medline
- Citing Articles (5)
Citing Articles
1
Catherine S. Gibson, Alastair H. MacLennan, William M. Hague, Eric A. Haan, Kevin Priest, Annabelle Chan, Gustaaf A. Dekker. (2005) Associations between inherited thrombophilias, gestational age, and cerebral palsy. American Journal of Obstetrics and Gynecology 193:4, 1437.e1-1437.e12
CrossRef2
M. P. M. De Maat, M. W. J. C. Jansen, E. T. M. Hille, H. L. Vos, K. W. M. Bloemenkamp, S. Buitendijk, F. M. Helmerhorst, J. W. Wladimiroff, R. M. Bertina, C. J. M. De Groot. (2004) Preeclampsia and its interaction with common variants in thrombophilia genes. Journal of Thrombosis and Haemostasis 2:9, 1588-1593
CrossRef3
M. J. Paidas, D.-H. W. Ku, M.-J. Lee, C. J. Lockwood, Y. S. Arkel. (2004) Pregnant patients with thrombophilia and subsequent adverse pregnancy outcomes have a decreased first trimester response to thrombomodulin in an activated partial thromboplastin time (APTT) system. Journal of Thrombosis and Haemostasis 2:5, 840-841
CrossRef4
Iris Schrijver, Tiffanee J. Lenzi, Carol D. Jones, Marla J. Lay, Maurice L. Druzin, James L. Zehnder. (2003) Prothrombin Gene Variants in Non-Caucasians with Fetal Loss and Intrauterine Growth Retardation. The Journal of Molecular Diagnostics 5:4, 250-253
CrossRef5
(2003) Current Awareness in prenatal diagnosis. Prenatal Diagnosis 23:2, 179-185
CrossRef
