Risk of placental abruption in first‐degree relatives of index patients

To the Editor: Evidence for a genetic background behind placental abruption comes from two different sources. Firstly, the recurrence rate of placental abruption is as high as 11% (1–4) and this increase in risk appears not to be explained solely on the basis of environmental factors such as smoking and drug abuse. Secondly, genetic studies involving the use of a candidate gene approach have shown a positive association between polymorphisms of the nitric oxide synthase gene and placental abruption (5). Similarly, the observed high prevalence of thrombophilia among women with placental abruption supports the idea of a genetic background behind the disease (6–9). As far as we are aware, there are no studies on twins, sib pairs, or pedigrees of women who have already experienced placental abruption in pregnancy to support conclusively the theory of a genetic background. This study was designed to evaluate the rate of placental abruption in the first-degree relatives of index patients. Women (n1⁄4 160) with singleton pregnancies complicated by placental abruption, who gave birth at Kuopio University Hospital in 1989–2001 were identified from the Birth Registry Data of Kuopio University Hospital as index patients and contacted. The pregnancy histories of index patients and their relatives were reviewed and pedigrees were drawn. Information on the health status and the number of the births among the relatives was obtained from the index patients (n1⁄4 129), either in a face to face interview or by telephone. When the index patients’ knowledge turned out to be vague, she was asked to contact her first-degree relatives and the information was subsequently confirmed by another phone call. The first-degree relatives, i.e. mothers and sisters, were also interviewed in cases of placental abruption. Not all index patients could be reached, because of change of location (n1⁄4 22), refusal to respond (n1⁄4 6), or death (n1⁄4 3; one had coarctatio aortae, one had intracerebral hemorrhage, and one died of cardiac failure). All those who participated in this study gave informed consent. Diagnosis of placental abruption was based on clinical examination and ultrasonography, as previously described (1). The rate of placental abruption in first-degree relatives was compared with that in the general obstetric population (n1⁄4 29,605), the population frequency being 1 in 175 in singleton pregnancies. Placental abruption recurred in 10 index patients, and the risk of placental abruption in their firstdegree relatives was assessed separately. Differences between study groups and controls were tested for significance by Fisher’s exact test. Statistical significance was set at p1⁄4 0.05, and odds ratios and their 95% confidence intervals (CIs) were determined (10). Index patients (n1⁄4 129) had a total of 380 births and they had 214 sisters, of whom 169 had a total of 412 births. Mothers (n1⁄4 129) of index patients had a total of 528 births. Placental abruption recurred in 10 patients, who had a total of 42 births, and they had 12 sisters, of whom 10 had a total of 25 births. The mothers (n1⁄4 10) of recurrent placental abruption patients had a total of 38 births. There were two fetal deaths and four preterm births before the 30th week of gestation in those who did not respond (n1⁄4 6). Of those who could not be contacted because of change of location (n1⁄4 22), four had experienced stillbirth, and overall, these missed cases covered the clinical spectrum normally seen in placental abruption (1). Placental abruption was experienced by 0.5% of the parous sisters (2/412) and 0.4% of the mothers (2/528) of the index patients. The pooled risk per delivery was 0.4% in the first-degree relatives (4/940), which figure is statistically similar (p1⁄4 0.34) to that (170/29,605) seen in the general obstetric population (0.6%; 95% CI: 0.48–0.66%). However, in the subgroup of women with recurrent abruption (n1⁄4 10), the sisters’ and mothers’ risks of abruption were 4.0% (1/25) and 2.6% (1/38), the odds ratios and 95% CIs being 6.9 (0.94–51.7) for the sisters and 4.7 (0.64–34.5) for the mothers. In this subgroup, the Clin Genet 2004: 66: 244–246 Copyright # Blackwell Munksgaard 2004 Printed in Denmark. All rights reserved CLINICAL GENETICS doi: 10.1111/j.1399-0004.2004.00294.x