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Hormonal placental function tests for fetal assessment in high risk pregnancies.

BACKGROUND: Biochemical tests of fetal well-being such as placental hormone levels have not always shown direct benefits for mothers and babies. OBJECTIVES: The objective of this review was to assess the effects of measuring placental hormone levels during high risk pregnancies. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and MEDLINE. We also contacted study authors. SELECTION CRITERIA: Adequately controlled trials comparing availability with no availability of hormone placental tests in high risk pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted by two reviewers and this was checked by a colleague. Study authors were contacted for additional information. MAIN RESULTS: Two trials involving 3355 women were included. Methodological quality of the trials was acceptable, but results for only 230 out of 2733 women (abnormal hormone levels) were available from one trial. One trial compared oestriol levels reported promptly with levels measured but not reported. The overall perinatal mortality rate was 30.5 per 1000 live births weighing 500 grams or more. No beneficial effects of oestriol measurement on fetal outcome could be identified (odds ratio of perinatal death 0.87, 95% confidence interval 0.35 to 2.18). For abnormal test results only, the reported oestriol group showed a statistically non-significant trend to less perinatal mortality (odds ratio 0.48, 95% confidence interval 0.15 to 1.60). The other trial compared human placental lactogen measurements reported promptly with measurements not reported until after pregnancy. For abnormal test results, the reported group showed significantly less perinatal mortality with four (3.4%) deaths compared to 17 (15%) in the control group (odds ratio 0.25, 95% confidence interval 0.10 to 0.61). Data from normal test results was not available for this trial. REVIEWER'S CONCLUSIONS: The measurement of human placental lactogen levels may be of some value in high risk pregnancies, but there is not enough evidence to evaluate the use of hormone placental tests generally.

Female↗

What do placental function tests predict? Observations on placental lactogen levels in growth retardation and fetal distress.

Single blood samples were obtained from an unselected population of 527 women between 36 and 40 wk gestation. Serum placental lactogen levels were lower than normal in patients whose infants were growth retarded or developed fetal distress in labor. These associations were independent; the fetal distress group did not contain an excess of subjects with growth retardation. Thus, the results of a biochemical test reflect dynamic aspects of placental function and not simply the overall growth of fetus and placenta.

Female↗

Which is the best placental function test? A comparison of placental lactogen and unconjugated oestriol in the prediction of intrauterine growth retardation.

Serum placental lactogen (hPL) and unconjugated oestriol (E3) levels were measured in 392 women at weekly intervals from 36-40 wk gestation. The levels of both hPL and E3 were reduced in subjects delivering a growth-retarded child. The clinical significance of this observation was similar for the two compounds, with a marginal advantage to hPL. There was a higher incidence of falling levels of hPL and E3 in cases of growth retardation but the finding had very little predictive value in an individual patient.

Adult↗

The dehydroepiandrosterone loading test. III. A possible placental function test.

The dehydroepiandrosterone loading test (DLT) has been used in a small population of normal and high-risk obstetric patients, to date, in an attempt to develop a dynamic test of placental function. In spite of its limited applications, it has shown reliability in discriminating, with statistical significance, between high-risk pregnancies that result in normally grown, undistressed infants, and high-risk pregnancies that result in infants showing signs of placental insufficiency. The present report expands the study population by presenting our data on 40 loading tests performed in 37 high-risk and normal obstetric patients. Results of 19 of these DLT's have been previously reported and are included herein for statistical analysis. The DLT utilizes an excess substrate load of dehydroepiandrosterone to assess the maximum capability of the placenta to convert it to estrogen. Although our previous report did not show false positive or negative results in the conversion rates, the present results (40 DLT's) found two (2 out of 17) false positives (12%) and two (2 out of 19) false negatives (11%). The highly significant correlation between DLT result and pregnancy outcome seen previously was preserved. In addition, the data of another five DLT's in four patients are presented. This group includes a pregnancy with a fetus with multiple congenital malformations, two patients with intrauterine fetal death, and a nonpregnant woman. The results are not included in the statistical analysis, but discussion of these results has interesting pathophysiologic implications.

Dehydroepiandrosterone↗

Early prediction of uteroplacental complications of pregnancy using Doppler ultrasound, placental function tests and combination testing.

In a prospective, blind study of 183 unselected women attending for routine booking scan with a singleton pregnancy at 16-24 weeks' gestation, uteroplacental resistance index, and peripheral levels of alpha-fetoprotein, human chorionic gonadotropin, human placental lactogen, Schwangerswaft protein, pregnancy-associated placental protein A and insulin-like growth factor (IGF) binding protein 1 were measured. High levels of alpha-fetoprotein and IGF 1 binding protein 1 (> 90th centile) were associated with small-for-gestational age babies (< 10th centile) (sensitivity 24% and 22%; specificity 90% and 91%). High levels of alpha-fetoprotein, human chorionic gonadotropin and pregnancy-associated placental protein A (> 90th centile) were associated with one or more of three severe complications of pregnancy: very small-for-gestational age (< 3rd centile), severe proteinuric hypertension or intrauterine death (sensitivity 20%, 20% and 57%; specificity 90%, 95% and 91%, respectively). A uteroplacental resistance index > 90th centile was also associated with small-for-gestational age and severe complications (sensitivity 24% and 50%, specificity 90% and 90%). A combination of resistance index and a placental function test improved the prediction for a group of patients that included any complications (sensitivity 31% and specificity 89%). Doppler ultrasound was a more efficient predictor than individual placental function tests but screening predictions can be improved by combining Doppler parameters and placental protein estimations. Combinations of placental function tests might provide equivalent, or complementary, information. This preliminary work demonstrates the potential value of combining biophysical and biochemical tests to predict complications of pregnancy.

Journal Article↗

From biochemical to biophysical placental function tests in fetal surveillance.

Radioimmunoassays of human placental lactogen and estriol levels in the maternal plasma, ultrasound biometry of the abdominal diameter (AD), pulsed Doppler measurements of uteroplacental arteries, the common carotid artery (CCA), and the umbilical artery (UA) and fetal heart rate monitoring were simultaneously performed in 219 risk pregnancies from 26 weeks' onward at regular intervals. The prognostic value of all tests to predict small for gestational age infants (SGA) and fetal distress was evaluated simultaneously. Receiver operator characteristic allowed the simultaneous comparison of all methods: The AD was most predictive for early detection of SGA, even more than uteroplacental blood flow. Fetal blood flow redistribution expressed as a ratio of the resistance index of CCA/UA was the most significant test for detection of fetal distress later in pregnancy, even more than antenatal cardiotocography. Considering cutoff levels used in clinical routine, the sensitivity and specificity of the fetal AD in detecting intrauterine growth retardation more than 28 days before birth, were 71 and 81%, respectively. Pulsed Doppler measurements of CCA/UA less than 7 days before the delivery had a sensitivity and specificity of 83 and 90%, respectively. Our results demonstrate the historical change in fetal surveillance within one study group: If accurate routine ultrasound is available, the use of biochemical placental function tests is not justified, a procedure that is already accepted in nearly all perinatal centers. Fetal cerebral versus umbilical blood flow measurements should be applied as a tool to measure fetal blood flow redistribution in small fetuses to predict most precisely the risk for poor outcome and perinatal hypoxia.

Estriol↗

Placental function test, clinical and biochemical parameters in diabetic pregnancy complicated by retinopathy.

The pregnancy in specific-beta 1-glycoprotein (SP1) has been characterized as a beta 1 electrophoretic mobile glycoprotein with a molecular weight of 90,000 daltons. SP1 is known to be synthesized by the trophoblast. The measurement of this protein has been shown to be useful as a placental function test. At present, we have compared maternal SP1 serum levels in diabetic pregnancies between White classes A to D on the one hand and R, F on the other. A total of 37 uncomplicated pregnancies in healthy women and 32 of insulin-dependent pregnant diabetic women were examined between completed gestational weeks 8 and 41. In the diabetic group there were eleven women with diabetic retinopathy. Maternal SP1 serum levels were estimated by single radial immunodiffusion using a monospecific antiserum. In the results were integrated maternal and neonatal data such as glycemic control, glycosylated hemoglobin and insulin requirements. In each group there was a significant rise in maternal SP1 serum values in the second and the third trimester, when compared with values in the first trimester (p less than 0.01). Between the 34th and the 37th gestational week we found significantly lower SP1 values (p less than 0.05) in the retinopathic group (104.2 +/- 28.7 mg/l) in comparison with the control group (149.9 +/- 61.0 mg/l) and non-retinopathic group (139.1 +/- 41.7 mg/l).

Adult↗

Neurology and behaviour of growth-retarded neonates. Relation to biochemical placental function tests in late pregnancy.

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were done in a prospective study on 29 pregnancies in which intrauterine growth retardation was diagnosed in the third trimester by the gravidogram method and/or serial ultrasound measurements of the fetal biparietal diameter. The series was divided into 2 growth-retarded groups: (i) severe growth retardation with birth weight less than -2 SD from the mean for gestational age (N = 14); (ii) moderate growth retardation with birth weight between -1 and -2 SD from the mean for gestational age (N = 15). These were compared with a control group of 18 normal pregnancies and infants. A modified Prechtl neurological examination and the Brazelton Neonatal Behavioural Assessment Scale (NBAS) were done in the neonatal period at full-term age. Both categories of growth-retarded infants showed lower muscle tonus than the controls. The severely growth-retarded infants showed fewer optimal items in the neurological examination; they also showed poorer capacity for orientation to external stimuli, inferior motor function, and less physiological stability in NBAS than the controls. The abnormal biochemical placental tests were significantly correlated to low Apgar scores (urinary oestriol), to low excitability (S-CAP) and to poor motor function (S-HCS). The neurological and behavioural condition of the neonate seemed to be more closely associated to the extent of growth retardation than to the occurrence of abnormal biochemical placental tests.

Adult↗