Maternal serum inhibin-A and activin-A levels in the first trimester of pregnancies developing pre-eclampsia.
OBJECTIVE
To evaluate whether measurement of maternal serum inhibin-A and activin-A at 11 + 0 to 13 + 6 weeks of gestation, alone or in combination with second-trimester uterine artery pulsatility measured by Doppler velocimetry, is useful in predicting those women who will develop pre-eclampsia.


METHODS
This was a nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage time for the maternal serum. Samples were collected as part of a first-trimester prenatal chromosomal anomaly screening program. Activin-A and inhibin-A were measured using a commercial enzyme-linked immunosorbent assay and the clinical outcomes were blinded to the operator. All the patients underwent uterine artery Doppler flow velocimetry to measure the mean pulsatility index at 22-24 weeks' gestation.


RESULTS
In total there were 64 cases with pre-eclampsia, with 34 delivering prior to 35 weeks of gestation. The control group included 240 cases. In the control group the levels of activin-A and inhibin-A did not change across the narrow gestational window and the median levels were 2.16 ng/mL and 231.13 pg/mL, respectively. In the pre-eclamptic group levels of activin-A and inhibin-A were significantly increased, at 2.52 ng/mL and 286.64 pg/mL (1.24 multiples of the median (MoM) and 1.17 MoM, respectively). There was no difference in the median MoM in those delivering prior to 35 weeks and those delivering later. At cut-offs of the 90(th) centile of normal, activin-A and inhibin-A levels would have identified 20% and 35%, respectively, of cases that would develop pre-eclampsia. When combined with uterine artery Doppler, activin-A measurement could have increased the detection rate from 55% to 63% and inhibin-A measurement could have increased it to 68% at a 5% false positive rate.


CONCLUSIONS
Although increased in the first trimester, levels of activin-A and inhibin-A are probably too low to make a significant contribution to screening for pre-eclampsia at this time.
Spencer
K
K
Prenatal Screening Unit, Clinical Biochemistry Department, King George Hospital, Goodmayes, London, UK. KevinSpencer1@aol.com
Cowans
N J
NJ
Nicolaides
K H
KH
D028341:Activins / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D028322:Inhibin-beta Subunits / Q000097:blood*; D017078:Laser-Doppler Flowmetry; D011225:Pre-Eclampsia / Q000175:diagnosis*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011673:Pulsatile Flow; D012680:Sensitivity and Specificity; D018615:Ultrasonography, Doppler, Color / Q000379:methods; D014599:Uterus / Q000098:blood supply*
D015415:Biomarkers; C422405:activin A; C103008:inhibin beta A subunit; D028341:Activins; D028322:Inhibin-beta Subunits