Multivariable logistic regression took into account the variables potentially related to the risk of hypertensive complications in pregnancy (maternal age, body mass index, parity, previous preterm delivery, smoking, and fetal gender). In these models, membership in group A (compared with groups B and C) remained predictive of hypertensive complications, as did the categorical variable that stratified cases by degree of placental disruption in each of the 3 groups (Table 3). This analysis was unchanged after controlling for gestational age at prenatal diagnosis and the volume of cases performed by each operator.
We considered needle size and single- versus double-needle sampling for group A (CVS) and the effect of multiple sampling attempts in all groups (Table 4). No differences were observed with respect to subsequent gestational hypertension or preeclampsia, except for the higher risk in group A cases associated with the 19-gauge (ie, intermediate size) sampling needle, the larger of the 2 needles used in the single-needle method of sampling. The significance of this finding is unclear because of the small sample size in this cell.
Our study found a potential relationship between the degree of placental disruption during the late first trimester and the subsequent manifestation of maternal hypertensive complications. A greater likelihood of gestational hypertension or preeclampsia was noted as the degree of placental disruption increased. These observations are intriguing because placental dysfunction is a credible precondition among women who develop hypertensive disorders in pregnancy. Pertinent to the current study are the theoretic antecedents of preeclampsia, which include abnormalities in placental penetration of the uterine decidua followed by incomplete spiral artery proliferation. Because spiral artery remodeling occurs during the “second wave” of trophoblast invasion (at 14–16 weeks of gestation), the narrow window during which prenatal diagnosis was performed in this trial (13–14 weeks) makes plausible at least a temporal relationship to these theories.4
An aberrant maternal immune response to fetal antigens has also been implicated as an alternative mechanism that may contribute to the development of preeclampsia.4 To the extent that an abnormal maternal immune response to paternally derived antigens might play a role in the etiology of preeclampsia, placental disruption at 13–14 weeks could certainly release fetal material into the maternal circulation. Studies showing increased maternal serum alpha-fetoprotein levels after prenatal diagnosis indicate the possibility of increased fetal-maternal transfer following certain procedures.5,6
Reduced uterine blood flow and placental ischemia have also been proposed as elements of preeclampsia pathophysiology. Disruption of the placenta during prenatal diagnosis, with focal hemorrhage and subsequent inflammation, could theoretically inhibit the spiral arteriolar widening, contributing to reduced placental perfusion and initiating a cascade of additional effects that include oxidative stress and endothelial cell dysfunction.4 Various animal models of preeclampsia have intentionally employed early perturbations of placental or uterine perfusion to provoke preeclampsia-like conditions. This has been accomplished in rats by creating an imbalance in vasoactive mediators responsible for placental perfusion or by directly reducing uterine blood flow with secondary reduction of placental and fetal growth.7,8
Despite the novelty of the association reported herein, we are mindful of significant limitations related to our analysis. Misclassification could have occurred, given that the original trial was not designed to explore gestational hypertension/preeclampsia as a primary endpoint, and diagnoses were not confirmed by chart review. The approximate doubling of the incidence of hypertensive complications noted in group A still resulted in an absolute rate that was low (< 6%) and within an expected range for similar populations of pregnant women. Thus, the immediate clinical significance of our finding, even if confirmed, may be limited. Our observations cannot be extrapolated to either CVS or amniocentesis performed in their usual time frames of 10–12 and 15–21 weeks, respectively. Nor has preeclampsia been linked to CVS or amniocentesis in prior trials for which maternal data were provided.2,9,10 However, a clinically relevant question that our analysis does prompt is the advisability of transplacental sampling when the alternative of not traversing the placenta exists. Some authors have empirically recommended avoiding the placenta during amniocentesis to minimize the risk of fetal complications.11,12 Although this strategy would seem intuitive, clear support for this practice cannot be found.13–19 In fact, it has been alternatively suggested that traversing the placenta to obtain amniotic fluid may actually reduce the procedure-related risk of miscarriage by limiting the likelihood of postprocedure leaking, especially during early midtrimester procedures.19 In support are data from the current study (Table 2), with lower rates of amniotic fluid leakage being observed in group B versus group C cases. Defining both maternal and fetal risks is of interest because the demand for prenatal diagnosis at 13–14 weeks is likely to increase in response to proliferation of first-trimester screening using nuchal translucency and serum analytes.20
In conclusion, our results support a potential relationship between late first-trimester placental disruption and subsequent gestational hypertension/preeclampsia. It is pivotal in pursuing this idea to broaden the scope and definition of placental disruption to include additional causes unrelated to prenatal diagnosis, such as occult or overt placental trauma, ischemia, or inflammation.
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Besides the authors, the members of The Randomized Trial of Early Amniocentesis and Transabdominal CVS (EATA) investigative group are as follows: Rigshospitalet, Genetic Center: J. Bang, W. Keller, A. Meyer, M. Vad, B. Binzer, A. G. Sidenius, S. Lindstrøm, S. Flint, K. Sundberg, and L. Sperling; Chromosome Laboratory: C. Lundsteen and A. M. Lind; Hvidovre Hospital: S. Smidt-Jensen; Drexel University College of Medicine: G. Davis, M. DiVito, and M. McGee; Baylor College of Medicine: R. Carpenter, J. Dungan, and A. Burke; Northwestern University Medical School: N. A. Ginsberg, C. Dougherty, and K. DeMarco; Fetal Diagnostic Center, Evanston Hospital of Northwestern University Medical School: S. MacGregor, K. Blum, E. Leeth, and J. Weimer; Cedars-Sinai Medical Center: D. E. Carlson (deceased), J. Williams, D. Krakow, C. A. Walla, W. Herbert, K. Wendt, and N. Greene; Magee-Women's Hospital: W. A Hogge, E. Smith, and K. Ventura; UCLA Center for the Health Sciences: S. Beverly; University of Tennessee, Memphis: L. Shulman, S. Elias, O. Phillips, L. Seely, and P. King; Wayne State University: M. Evans, D. Duquette, E. Krivchenia, and P. Devers; Yale University: J. Copel, R. Bahado-Singh, M. DiMaio, and S. Turk; McMaster University Medical Center: J. Smith, M. L. Beecroft, G. White, N. Brown, M. Huggins, and V. Freeman; BC Women's Hospital: D. Shaw and S. Soanes; Prenatal Diagnosis of Northern California Medical Group: K. Kahl and M. Palmer; University of Maryland, Baltimore: K. Frayer; Mt Sinai School of Medicine, New York: R. Desnick, K. Eddleman, J. Stone, R. Zinberg, and J. Robinowitz; The George Washington University Biostatistics Center: B. Fisher, K. Poydence, P. Van, and N. Boone; The National Institute of Child Health and Human Development: F. de la Cruz and J. Hanson; Danish Centre for Evaluation and Health Technology Assessment, National Board of Health, Denmark: F. Børlum Kristensen. Cited Here...