Is thrombophilia associated with placenta‐mediated pregnancy complications? A prospective cohort study: reply

Abstract

We thank Drs Kjellberg and Hellgren for their letter and for pointing our that the results of their study are consistent with our findings. Space limitations prevented us from more detailed reporting of the methods and results of our systematic review. We are familiar with the study by Kjellberg et al., as it was one of the seven full-text articles [1][2][3][4][5][6][7] that were retrieved in the systematic review process. Their report was independently assessed by two reviewers (M.R. and N.L.) and then discussed, leading to the conclusion that the study was not eligible, owing to its design. That is, the 'case-cohort' design did not meet the first of three eligibility criteria that were established a priori for our meta-analysis; studies had to enroll unselected pregnant women in the first or second trimester of pregnancy. Although 6003 women were screened for their study, 'every fifth woman who tested negative for activated protein C resistance was selected as a control'.Although this study could not be included in our formal meta-analysis, we agree with the comments of Kjellberg and Hellgren that the consistency of the findings between their study and ours lends additional support for the conclusion that an association does not exist between the factor V Leiden mutation or the prothrombin gene mutation and placenta-mediated pregnancy complications.It is also worth pointing out that the proportion of small-for-gestational-age children is a more clinically relevant outcome than mean differences in birth weight between exposed and unexposed groups. One could imagine scenarios where there are no mean differences between two exposed groups, yet the exposure leads to severe small for gestational age birth in an important proportion of patients without significantly influencing the mean birth weight in the exposed group.

Exploratory analysis of thrombophilic risk markers in histology-defined placental thromboembolism.

“…PTE was found in 30% of histological specimens arguing for an important role in the etiology of RPL. However, no profound association of established thrombophilic risk factors with histology-defined placental thromboembolism was observed which might help to explain discrepant results reported so far 1 2 3 4 5 .…”

Effects of low‐molecular‐weight heparin and aspirin in recurrent pre‐eclampsia: A stratified cohort study

“…Cumulative observational scientific literature suggests weak associations between thrombophilia and placenta-mediated pregnancy complications including severe pre-eclampsia, SGA, and abruption. 21,22 There is no definitive evidence that placental thrombosis is a major contributor to placenta-mediated pregnancy complications. Placental abruption is a bleeding complication.…”

“…Administration of LDA and LMWH does not decrease the risk of placental abruption, intrauterine death, or SGA. Cumulative observational scientific literature suggests weak associations between thrombophilia and placenta‐mediated pregnancy complications including severe pre‐eclampsia, SGA, and abruption 21,22 . There is no definitive evidence that placental thrombosis is a major contributor to placenta‐mediated pregnancy complications.…”

Abruptio placentae y trombofilia hereditaria

“…En un meta-análisis que incluyó estudios prospectivos de cohorte no se observó incremento del riesgo de DPPNI en pacientes portadoras de Factor V de Leiden (FV Leiden) ni con la mutación de la protrombina G20210A7. En este sentido, un estudio de cohorte realizado en Canadá que incluyó 7343 mujeres embarazadas no seleccionadas que se siguieron prospectivamente y se testeo TH luego de parto se detectó 6.9% de prevalencia de TH y no se vieron diferencias en la incidencia de DPPNI entre las portadoras de TH vs la que no presentaban 8 . Contrariamente, otros meta-análisis han mostrado una asociación modesta entre FV Leiden y Protrombina G20210A y las complicaciones mediadas por la placenta dentro de las cuales se incluye el DPPNI [9][10][11][12] .…”