Ultrasound detection of placental insufficiency in women with elevated second trimester serum alpha-fetoprotein or human chorionic gonadotropin.

OBJECTIVE We evaluated the role of placental morphology ultrasound and uterine artery Doppler in predicting adverse perinatal outcomes in women with unexplained elevated serum alpha-fetoprotein (AFP) or human chorionic gonadotropin (hCG) levels in the second trimester of pregnancy. METHODS Women with a serum AFP > 2.0 MoM (n = 83) or serum hCG > 2.5 MoM (n = 68) had placental imaging at 19-23 weeks' gestation. Abnormal placental morphology (i.e., a maximum thickness of > 4 cm or > 50% of length) and abnormal uterine artery Doppler [UTAD] (mean pulsatility index > 1.45) were related to placental complications of pregnancy. Relative risks were derived for all women. Likelihood ratios were derived for the subset (55/83) in the group with elevated AFP who had no medical and/or obstetrical risk factors. RESULTS Compared with elevated serumh CG, an elevated serum AFP was associated with higher rates of perinatal mortality (15.6% vs. 4.3%), preterm birth at < 32 weeks' gestation (26.5% vs. 7.3%), small-for-gestational age (SGA) birth weight < 10th centile (24.1% vs. 10.3%) and severe intrauterine growth restriction (IUGR) (8.4% vs. 2.8%). Thirty-seven (44.5%) women with elevated serum AFP had an adverse perinatal outcome, and 23 of these women (67%) had no prior medical and/or obstetric risk factors. Abnormal tests of placental function were more common in the elevated serum AFP group than in the hCG group (UTAD 30.1% vs. 11.6%; placental morphology 30.2% vs. 16.2%). Abnormal UTAD and abnormal placental morphology had similar positive likelihood ratios for a range of adverse perinatal events in the elevated AFP group (1.3-4.4) and were increased when both tests were abnormal (likelihood ratio 5.0 for preeclampsia, 4.5 for preterm delivery < 32 weeks, 4.9 for intrauterine fetal demise). In the elevated hCG group abnormal UTAD and abnormal placental morphology predicted SGA (likelihood ratios 5.2 and 4.9) and IUGR (likelihood ratios 4.7 and 7.3) but did not predict preeclampsia or preterm birth. CONCLUSION Assessment of placental function using either morphology or UTAD at 19-23 weeks' gestation identifies a subset of women at increased risk of adverse perinatal events with an elevated serum AFP. These tests have more limited value in women with an elevated serum hCG because of the lower prevalence of adverse perinatal events.

[1]  B. Harlow,et al.  The role of Doppler velocimetry in the structurally normal second‐trimester fetus with elevated levels of maternal serum α‐fetoprotein , 1994, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[2]  R. Frydman,et al.  Prediction of Preeclampsia or Intrauterine Growth Restriction by Second Trimester Serum Screening and Uterine Doppler Velocimetry , 2004, Fetal Diagnosis and Therapy.

[3]  E. Thom,et al.  Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes. , 2004, American journal of obstetrics and gynecology.

[4]  F. Malone,et al.  First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial). , 2004, American journal of obstetrics and gynecology.

[5]  D. Nyberg,et al.  Elevated maternal serum alpha-fetoprotein levels and midtrimester placental abnormalities in relation to subsequent adverse pregnancy outcomes. , 1992, American journal of obstetrics and gynecology.

[6]  J. Pell,et al.  Pregnancy-Associated Plasma Protein A and Alpha-fetoprotein and Prediction of Adverse Perinatal Outcome , 2006, Obstetrics and gynecology.

[7]  Sequential Pathways of Testing After First-Trimester Screening for Trisomy 21 , 2004, Obstetrics and gynecology.

[8]  Gynecologists.  ACOG PRACTICE BULLETIN , 2009 .

[9]  Tianhua Huang,et al.  Association between second-trimester isolated high maternal serum maternal serum human chorionic gonadotropin levels and obstetric complications in singleton and twin pregnancies. , 2003, American journal of obstetrics and gynecology.

[10]  J. Kingdom,et al.  Prognostic value of placental ultrasound in pregnancies complicated by absent end-diastolic flow velocity in the umbilical arteries. , 2004, Placenta.

[11]  F. Malone,et al.  Quad Screen as a Predictor of Adverse Pregnancy Outcome , 2005, Obstetrics and gynecology.

[12]  J. Kingdom,et al.  Second-trimester prediction of severe placental complications in women with combined elevations in alpha-fetoprotein and human chorionic gonadotrophin. , 2006, American journal of obstetrics and gynecology.

[13]  Tianhua Huang,et al.  Double-positive maternal serum screening results for down syndrome and open neural tube defects: An indicator for fetal structural or chromosomal abnormalities and adverse obstetric outcomes. , 2002, American journal of obstetrics and gynecology.

[14]  First-trimester placentation and the risk of antepartum stillbirth. , 2004 .

[15]  J. Kingdom,et al.  Determinants of adverse perinatal outcome in high-risk women with abnormal uterine artery Doppler images. , 2008, American journal of obstetrics and gynecology.

[16]  E. Jauniaux,et al.  Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies. , 2003, The American journal of pathology.

[17]  C. Sibley,et al.  Denudations as paracellular routes for alphafetoprotein and creatinine across the human syncytiotrophoblast. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[18]  E. Jauniaux,et al.  Ultrasonographic investigation of placental morphologic characteristics and size during the second trimester of pregnancy. , 1994, American journal of obstetrics and gynecology.

[19]  Gordon C. S. Smith,et al.  Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. , 2002, The Journal of clinical endocrinology and metabolism.

[20]  J. Rankin,et al.  The changing prevalence of neural tube defects: a population-based study in the north of England, 1984-96. Northern Congenital Abnormality Survey Steering Group. , 2000, Paediatric and perinatal epidemiology.

[21]  E. Hook,et al.  Second-trimester maternal serum alpha-fetoprotein levels and the risk of subsequent fetal death. , 1991, The New England journal of medicine.

[22]  F. Goffinet,et al.  A population‐based evaluation of the impact of antenatal screening for Down's syndrome in France, 1981–2000 , 2004, BJOG: an International Journal of Obstetrics and Gynaecology.

[23]  J. Kingdom,et al.  Ultrasound detection of placental insufficiency in women with ‘unexplained’ abnormal maternal serum screening results , 2005, Clinical genetics.

[24]  I. Crocker,et al.  Altered cell kinetics in cultured placental villous explants in pregnancies complicated by pre‐eclampsia and intrauterine growth restriction , 2004, The Journal of pathology.

[25]  I. Bernstein,et al.  Uterine artery Doppler velocimetry in the detection of adverse obstetric outcomes in women with unexplained elevated maternal serum alpha-fetoprotein levels. , 1995, American journal of obstetrics and gynecology.

[26]  K. Nicolaides,et al.  Correlation of ultrasound and pathologic findings of placental anomalies in pregnancies with elevated maternal serum alpha-fetoprotein. , 1990, European journal of obstetrics, gynecology, and reproductive biology.

[27]  K. Nicolaides,et al.  One‐Stage Screening for Pregnancy Complications by Color Doppler Assessment of the Uterine Arteries at 23 Weeks' Gestation , 2000, Obstetrics and gynecology.

[28]  A. Rudnicka,et al.  First-trimester or second-trimester screening, or both, for Down's syndrome. , 2005, The New England journal of medicine.