Elevated C-reactive protein levels during first trimester of pregnancy are indicative of preeclampsia and intrauterine growth restriction

Abstract

C-reactive protein (CRP) is a marker of tissue damage and inflammation. Maternal levels of CRP are elevated in overt preeclampsia, but there is still debate about its use as a predictive marker for preeclampsia during the first and second trimesters of pregnancy. In this study, we measured CRP levels during the first trimester of pregnancy in women who later developed preeclampsia or gave birth to a growth-restricted baby. In total, 107 women from a low-risk population participated in the study, six women developed preeclampsia and nine gave birth to a growth-restricted baby. Although there is a large overlap in measured CRP levels between the three groups, mean CRP levels were significantly elevated in women who later developed preeclampsia (P=0.031) or delivered a growth-restricted baby (P=0.041) when compared with women from the control group, matched for maternal and gestational age, parity, and gravidity. This study shows that in a low-risk population, CRP levels are already elevated between weeks 10 and 14 in pregnant women who develop preeclampsia or deliver a growth-restricted baby.

Introduction

Common pregnancy disorders include hypertensive disorders of pregnancy, gestational diabetes, and premature birth. Maternal health is especially affected when preeclampsia or more severe complications such as eclampsia or HELLP develop. These syndromes substantially contribute to maternal morbidity and mortality. Symptoms of preeclampsia include hypertension and proteinuria, and preeclampsia are associated with general endothelial dysfunction (Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy, 2000). Preeclampsia is associated with an increased risk of intrauterine growth restriction (IUGR), although most preeclamptic patients do not give birth to a growth-restricted baby (Xiong et al., 1999).

In recent years, much focus has been put on the detection of pregnancy disorders before the symptoms actually occur. Both preeclampsia and IUGR share similar defects in placental development and function. Besides a shallow trophoblast invasion leading to poor placental perfusion (Meekins et al., 1994, Sheppard and Bonnar, 1981), preeclampsia and IUGR are also associated with high levels of apoptosis in the placenta (Erel et al., 2001, Leung et al., 2001). At present, Doppler analysis at the 24th week of pregnancy, or screening of circulating pregnancy-associated proteins in maternal plasma or serum, can be used to indicate which women are at risk to develop maternal-fetal pathologies such as preeclampsia or IUGR (Chien et al., 2000, Reis et al., 2002, Zimmermann et al., 1997). Circulating markers potentially useful in early pregnancy, i.e. at the presymptomatic stage, share a restricted but common feature indicative of placental production and function.

In this respect, C-reactive protein (CRP), being a sensitive marker of tissue damage and inflammation, can be a potential marker. Plasma CRP levels rise in cases of acute infection, malignancy, and inflammatory diseases. CRP can bind to chromatin, released from apoptotic or necrotic cells, and to small nuclear ribonucleoprotein particles. It has been proposed that CRP acts as a scavenger and is responsible for the clearance of membranes and nuclear antigens (DuClos, 1996). It has been suggested that CRP, in accordance with its proposed function, may play a role in eliciting the inflammatory response characteristics of preeclampsia (Redman et al., 1999). Recently, it has been demonstrated that CRP enhanced opsonization, and phagocytosis of apoptotic cells is specific for and restricted to apoptotic cells. Once cells have become necrotic, the effect of CRP is lacking (Gershov et al., 2000). CRP is elevated in women with overt preeclampsia (Teran et al., 2001), but there is still debate about its potential use as an early marker for preeclampsia. Wolf et al. (2001) showed elevated CRP levels during the first trimester in women who subsequently develop preeclampsia, whereas Savvidou et al. (2002) showed that late second trimester CRP levels were not associated with preeclampsia. In this study, we investigated whether CRP levels are elevated during the first trimester in women from a low-risk population who subsequently develop preeclampsia or deliver a growth-restricted baby.