Combining 2nd-Trimester Maternal Serum Homocysteine Levels and Uterine Artery Doppler for Prediction of Preeclampsia and Isolated Intrauterine Growth Restriction

Abstract

Aim: To evaluate the efficacy of a combined 2nd-trimester maternal serum homocysteine and uterine artery Doppler screening at 20 weeks of gestation for complications of pregnancy: preeclampsia, isolated intrauterine growth restriction (IUGR), placental abruption, and stillbirths. Methods: Consecutive singleton pregnancies without previous risk factors who had homocysteine measured as part of a serum-screening program for trisomy 21 had uterine artery Doppler performed. Sensitivity, specificity, positive and negative predictive values, odds ratio, and positive and negative likelihood ratios for the subsequent development of preeclampsia, isolated IUGR, placental abruption, stillbirth, and preterm delivery were calculated for the following methods (1) homocysteine cutoff level 6.3 µmol/l (95th centile); (2) on Doppler ultrasound bilateral notches with a mean resistance index (RI) >0.55 (50th centile), all unilateral notches with a mean RI >0.65 (80th centile), and absence of notches with a mean RI >0.7 (95th centile), and (3) Doppler ultrasound notch evaluation (bilateral, unilateral, absence as in method 2) combined with the homocysteine cutof level of 6.3 µmol/l. Results: By using a logistic regression model, methods 1 and 2 predicted preeclampsia (p < 0.001), isolated IUGR (p < 0.01), and ‘any complication’ (p < 0.01). The sensitivity for prediction of preeclampsia using the combined method (3) was 61.3% for a false-positive rate of 2%, better than that for isolated IUGR (54%) below the 5th centile and ‘any complication’(56%). Conclusion: This prospective study confirms the potential of a combined method of elevated homocysteine and uterine artery Doppler screening for preeclampsia, isolated IUGR, and any obstetric complication.

Circulating levels of homocysteine in preeclamptic women

“…In contrast, other studies detected no differences in midtrimester maternal circulating level of homocysteine between women who developed preeclampsia and normal pregnant women 15,[18][19][20] .…”

Serum markers for predicting pre-eclampsia

“…A prospective study assessed uterine artery Doppler measurements at 20 weeks gestation in combination with midtrimester maternal serum homocysteine levels in the prediction of pre-eclampsia. Sensitivity for predicting pre-eclampsia of 60% was observed, with a false-positive rate of 3% (Onalan et al, 2006).…”

“…Earlier, a case-control study reported increased homocysteine levels at early midtrimester in women with subsequent severe and non-severe pre-eclampsia (Cotter et al, 2003). In contrast, other studies detected no difference in midtrimester homocysteine serum levels between women who developed pre-eclampsia and controls (Yu et al, 2004;Onalan et al, 2006;D'Anna et al, 2004). The contradictory results undermine the potential of homocysteine as a marker for subsequent pre-eclampsia.…”

Effect of Homocysteine Concentration in Early Pregnancy on Gestational Hypertensive Disorders and Other Pregnancy Outcomes

“…Consequently, a number of studies have evaluated the relationship between tHcy and pregnancy outcome to find out whether increased tHcy is associated with adverse pregnancy outcomes, and if so, whether the relationship is causal. Increased tHcy has been associated with an increased risk of preeclampsia (2)(3)(4)(5)(6)(7)(8)(9)(10), intrauterine growth restriction (3,7 ), abruptio placenta (7 ), stillbirth (2,7 ), and miscarriage (11 ). Systematic reviews generally support the positive association between tHcy and placenta-mediated conditions, including pregnancy loss, preeclampsia, and abruption (1,12,13 ).…”