Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohortsBMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h5948 (Published 17 November 2015) Cite this as: BMJ 2015;351:h5948
All rapid responses
Re: Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts
To the Editor,
As a physician assistant student who is interested in the field of obstetrics, a question arose, while reading this article, about screening for preeclampsia in the general population. The article states routine blood pressure measurements between 20 and 36 weeks’ gestation can contribute to the prediction of preeclampsia and its associated adverse outcomes of preterm birth and small for gestational age (1). Since preeclampsia does not manifest itself until after 20 weeks’ gestation, is there any screening tool that can be implemented earlier to predict the development of the disease?
According to the U.S. Preventive Services Task Force (USPSTF), there is no recommended screening for preeclampsia at anytime during pregnancy. The USPSTF is currently in “Step 2” of developing a recommendation for screening, which means they are reviewing the evidence after proposing a research plan (2). There is difficulty in developing a screening tool that is sensitive and specific enough for the general obstetrical population for the development of preeclampsia.
Another article discusses the measurement of angiogenic factors (or proteins) in the maternal blood and urine early in pregnancy as a predictor of preeclampsia. These factors include vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) that can be present weeks to months before the pathophysiologic hallmarks of the disease are present. The World Health Organization (WHO) has initiated a large prospective research study to evaluate the usefulness of measuring maternal angiogenic factors for the prediction of preeclampsia in women at any time during pregnancy (3).
As the previously mentioned screening of measuring maternal angiogenic factors appears promising, it is important to note that these tests are still heavily under investigation and are not available to the general population yet. It is also important to note that if these tests do become available, they will most likely be expensive, making them unavailable to many lower income or uninsured pregnant women. A screening test should be cheap, rapid, easily available, and noninvasive in order to be of any value for the general population. According to the American College of Obstetricians and Gynecologists (ACOG), taking a detailed medical history and assessing for risk factors is currently the best and only recommended screening approach for preeclampsia in the first trimester of pregnancy. ACOG states that current predictive tests for preeclampsia may cause more harm than good because they have a low positive predictive value (4). Determining which women possess certain risk factors early in pregnancy is important so the appropriate monitoring can be initiated and a referral to a specialist can be considered.
1. Macdonald-Wallis C, Silverwood RJ, de Stavola BL, et al. Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: Development and validation in two general population cohorts. BMJ. 2015;351:h5948
2. Final Research Plan: Preeclampsia: Screening. U.S. Preventive Services Task Force. January 2015. http://www.uspreventiveservicestaskforce.org/Page/Document/final-researc...
3. Norwitz, E. (2016). Prediction of preeclampsia. In C.J. Lockwood (Ed.), UpToDate. Retrieved from http://www.uptodate.com/contents/prediction-of-preeclampsia
4. First-trimester risk assessment for early-onset preeclampsia. Committee Opinion No. 638. American College of Obstetricians and Gynecologists. Obstet Gynecol 2015;126:e25–7
Competing interests: No competing interests
An English physiologist and Greek obstetrician described two of the three key elements of the pathophysiology of preeclampsia in some remarkable experiments in the early 1950’s (1). Kenneth Franklin and John Sophian noticed blanching of the kidneys with redistribution of the renal blood flow from the cortex to the medulla, and, oliguria after inflating balloons in rabbit uteri . Denervating the kidneys abolished the “uterorenal reflex”. They did not study the sensory mechanism in the uterus.
Recent studies demonstrate similarities between the narrowing of uterine arterioles in preeclampsia, and, similar narrowing in different gynaecological syndromes including chronic pelvic pain with, or without, endometriosis, vulvodynia, irritative bladder and bowel syndromes, adenomyosis etc. (Fig. 1a-b). In both there is irregular hyperplasia of the tunica media and intima. In the gynaecological syndromes this is associated with circumferential layers of injured, abnormal nerve profiles (2, Fig B). These abnormal nerve profiles may express purinergic “stretch” receptors that elicit the “uterorenal reflex” in preeclampsia (3). In the obstetric syndromes that include preeclampsia, there are no circumferential nerves because the arterioles elongate to reach the placental bed during pregnancy whereas the nerves do not (4, Fig A). Injuries to nulliparous uterine nerves result from physical efforts during defaecation and evacuation of the uterus and result in release of cytokines that cause (a) regrowth of abnormal, injured nerves, and, (b) hyperplasia of adjacent tissues including denervated arteriolar walls (2).
The clinical associations of preeclampsia including age, nulliparity, diabetes mellitus, hydatidiform mole, multiple pregnancy, polyhydramnios , pre-existing renal disease, fetal hydrops, etc are largely explained in “early-onset” and “late-onset” preeclampsia by perivascular and myometrial reinnervation respectively (3, 4)). Predicting preeclampsia with some precision may become possible once the prior sources of neural injury and pathophysiology of the preeclamptic syndromes are fully understood.
(1) Sophian GJ
Toxaemias of Pregnancy.
Butterworth & Co. Ltd., 1953.
(2) Atwal G, du Plessis D, Armstrong G, Slade R, Quinn M.
Uterine innervation after hysterectomy for chronic pelvic pain with, and without,
Am J Obstet Gynecol. 2005; 193(5):1650-5.
(3) Quinn MJ.
Pre-eclampsia - The "uterine reinnervation" view.
Med Hypoth 2014; 83(5):575-9.
(4) Quinn MJ.
Preeclampsia: two placental phenotypes, one etiology.
Am J Obstet Gynecol. 2014; 211(3):313-4.
Competing interests: No competing interests
To the Editor:
Macdonald-Wallis et al. conducted an outstanding work concluding that blood pressure measurements from 28 weeks onwards improve predictive models for pre-eclampsia based on blood pressure in early pregnancy and other risk factors. These results might have important implications for pre-eclampsia screening schedule.
In their models, the authors include a number of maternal predictors (i.e. BMI before pregnancy, height, age ≥35, parity, smoking, essential hypertension, previous gestational hypertension, diabetes, previous gestational diabetes, and non-white ethnicity) on the basis of previous evidence of their association with pre-eclampsia, the plausibility to routinely collect the data in clinical practice, and the potential generalizability to different settings, including low and middle-income countries. Physical activity before and during pregnancy has been inversely associated with the risk of developing pre-eclampsia (both in animal and human[3-6] models) and preterm birth, and might be routinely collected in clinical practice. Although this association in humans is still controversial and requires further research[9,10], different reviews highlight several mechanisms by which physical activity might reduce the risk of pre-eclampsia[11,12], such as preventing placenta alterations through stimulation of placental growth and vascularity; reducing oxidative stress and stimulating antioxidant defense; diminishing autoimmune response and inflammation; reversing maternal endothelial dysfunction; and preventing several medical conditions that can predispose to the development of pre-eclampsia (hypertension and other cardiovascular diseases, type 2 diabetes mellitus, obesity, thrombophilia, etc.). Since both the ALSPAC and SWS projects collected self-reported physical activity data, it would be of interest to know whether the addition of physical activity (e.g. being physically active or not) before and/or during pregnancy might contribute, to any extent, to enhancing the predictive capacity of the models and whether their predictive capacity is equal in physically active and inactive women.
1. Macdonald-Wallis C, Silverwood RJ, de Stavola BL, et al. Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts. BMJ 2015;351:h5948.
2. Falcao S, Bisotto S, Michel C, et al. Exercise training can attenuate pre-eclampsia-like features in an animal model. J Hypertens 2010;28:2446-53.
3. Magnus P, Trogstad L, Owe KM, Olsen SF, Nystad W. Recreational physical activity and the risk of pre-eclampsia: a prospective cohort of Norwegian women. Am J Epidemiol 2008;168:952-7.
4. Sorensen TK, Williams MA, Lee IM, Dashow EE, Thompson ML, Luthy DA. Recreational physical activity during pregnancy and risk of pre-eclampsia. Hypertension 2003;41:1273-80.
5. Saftlas AF, Logsden-Sackett N, Wang W, Woolson R, Bracken MB. Work, leisure-time physical activity, and risk of pre-eclampsia and gestational hypertension. Am J Epidemiol 2004;160:758-65.
6. Rudra CB, Sorensen TK, Luthy DA, Williams MA. A prospective analysis of recreational physical activity and pre-eclampsia risk. Med Sci Sports Exerc 2008;40:1581-8.
7. Juhl M, Andersen PK, Olsen J, et al. Physical exercise during pregnancy and the risk of preterm birth: a study within the Danish National Birth Cohort. Am J Epidemiol 2008;167:859-66.
8. Evenson KR, Wen F. Measuring physical activity among pregnant women using a structured one-week recall questionnaire: evidence for validity and reliability. Int J Behav Nutr Phys Act 2010;7:21.
9. Osterdal ML, Strom M, Klemmensen AK, et al. Does leisure time physical activity in early pregnancy protect against pre-eclampsia? Prospective cohort in Danish women. BJOG 2009;116:98-107.
10. Kasawara KT, do Nascimento SL, Costa ML, Surita FG, e Silva JL. Exercise and physical activity in the prevention of pre-eclampsia: systematic review. Acta Obstet Gynecol Scand 2012;91:1147-57.
11. Weissgerber TL, Wolfe LA, Davies GA. The role of regular physical activity in pre-eclampsia prevention. Med Sci Sports Exerc 2004;36:2024-31.
12. Genest DS, Falcao S, Gutkowska J, Lavoie JL. Impact of exercise training on pre-eclampsia: potential preventive mechanisms. Hypertension 2012;60:1104-9.
Competing interests: No competing interests