Placental protein measurements in complicated pregnancies. I. Intrauterine growth retardation

Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein A (PAPP-A) were measured serially throughout pregnancy in 753 women who had a normal pregnancy when recruited during the second trimester. Thirty-three women were delivered of an infant with low birth-weight and with phenotypic features of intrauterine growth retardation (IUGR). The predictive value of an abnormal (less than 10th centile) hPL result (PVpos) in the identification of IUGR was between 28 and 32%, the sensitivity (36-54%) being greatest at 35 weeks gestation. The predictive value of a normal result (PVneg) was 87-96% at various stages of pregnancy, also greatest at 35 weeks gestation. For SP1, the sensitivity and predictive values were also greatest at 35 weeks gestation (PVpos, 20%; sensitivity, 32%; PVneg, 95%), but for PAPP-A these values were considerably less at all gestations. The trends in levels of hPL, SP1 and PAPP-A observed in individual patients with IUGR were not apparently related to any clinically recognizable feature of the pregnancy or the degree of fetal compromise, irrespective of whether the levels were within or outside the 80% confidence limits of the normal range or whether the levels fell from within the normal range. These data suggest that maternal hPL measurements are superior in the identification of IUGR in samples obtained at 30-35 weeks gestation.     

Placental protein measurements in complicated pregnancies. II. Pregnancy-related hypertension

Summary. Maternal serum levels of pregnancy-associated plasma protein A (PAPP-A), human placental lactogen (hPL) and schwangerschafts-protein 1 (SP1) were measured serially during the second and third trimesters in 753 women with a normal pregnancy when recruited during the second trimester. Thirty-seven pregnancies were complicated by pregnancy-related hypertension after 28 weeks gestation. Maternal levels of PAPP-A and SP1, and trends of levels in individual patients, could generally not be distinguished from those seen in patients with a normal pregnancy, and were unrelated to the time of onset of the disease, its severity or the occurrence of other complications with one exception, in which decreased levels of SP1 and hPL were seen. Mean levels of hPL were significantly lower ( P <0.05) at 35 weeks gestation. These data suggest that the measurement of the placental proteins examined here is of no value in the prediction of occurrence of pregnancy-related hypertension.     

Placental protein measurements in complicated pregnancies. III. Premature labour

Summary. Maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A), human placental lactogen (hPL) and schwangerschafts-protein 1 (SP1) were measured serially during second and third trimester in 753 women with a normal pregnancy when they were recruited to the study. In 24 women spontaneous premature labour occurred before 37 completed weeks and these women had significantly lower mean levels of serum SP1 at 29–31 weeks and at 33–34 weeks gestation but similar mean levels of serum PAPP-A and hPL at all gestations compared with corresponding values in normal pregnancy. The predictive value of an abnormal SP1 result was 5.2% at 29–31 weeks and 10.3% at 33–34 weeks. Furthermore, trends of levels of the three placental proteins in individual patients were similar to those seen in normal pregnancy, and the trends were unrelated to the occurrence of other complications and the time of onset of labour. This study suggests that measurements of the three placental proteins are unlikely to be of any value in the prediction of spontaneous premature labour.     

Placental protein measurements in complicated pregnancies. III. Premature labour

Maternal serum levels of pregnancy-associated plasma protein. A (PAPP-A), human placental lactogen (hPL) and schwangerschafts-protein 1 (SP1) were measured serially during second and third trimester in 753 women with normal pregnancy when they were recruited to the study. In 24 women spontaneous premature labour occurred before 37 completed weeks and these women had significantly lower mean levels of serum SP1 at 29-31 weeks and at 33-34 weeks gestations but similar mean levels of serum PAPP-A and hPL at all gestations compared with corresponding values in normal pregnancy. The predictive value of an abnormal SP1 result was 5.2% at 29-31 weeks and 10.3% at 33-34 weeks. Furthermore, trends of levels of the three placental proteins in individual patients were similar to those seen in normal pregnancy, and the trends were unrelated to the occurrence of other complications and the time of onset of labour. This study suggests that measurements of the three placental proteins are unlikely to be of any value in the prediction of spontaneous premature labour.     

Intrauterine growth in twin pregnancies: prediction of fetal growth retardation

In 80 consecutive twin pregnancies, prenatal measurements of fetal biparietal diameter (BPD) and abdominal diameter were made and growth curves were calculated using routine ultrasound examinations. Nineteen percent of the infants were growth retarded. Growth retardation was found in both fetuses in four pregnancies and in one fetus in 22 other pregnancies. Linear regression analysis between birth weight and gestational age showed the standard deviation of birth weight to be proportional to gestational age. A more linear growth curve also was found when the mean fetal weight was calculated by use of the BPD and abdominal diameter measurements in the formula developed for singletons. The estimated weight compared with birth weight in 62 twins who had ultrasound examinations less than seven days before delivery showed a significant correlation (r = 0.89, P less than .001) with a coefficient of variation of 12.4%. The identification of intrauterine growth retardation (IUGR) in twin pregnancies by ultrasound had a sensitivity of 62%, a specificity of 98%, and a predictive value of positive and negative test of 93% and 83%, respectively.     

Coagulation and fibrinolysis in pregnancies complicated by fetal growth retardation.

Saline extracts were made from portions of 17 normal placentae and from 8 placentae from pregnancies complicated by fetal growth retardation, but not hypertension. The ability of these extracts to inhibit urokinase-induced fibrinolysis was measured using a fibrin plate technique. Placental extracts from pregnancies complicated by fetal growth retardation exhibited greater inhibition of urokinase-induced fibrinolysis. There was no evidence of disseminated intravascular coagulation in these patients, but certain coagulation factors in the peripheral blood were raised.     

Essential fatty acids in pregnancies complicated by intrauterine growth retardation.

The relative fatty acid composition of lecithin was measured in maternal and cord blood serum in human pregnancies at risk for intrauterine growth retardation (IUGR) (n = 28) as compared to controls (n = 20). In the IUGR cases (n = 13) linoleic acid was lower in maternal samples but higher in cord blood, oleic acid was elevated in both whereas docosohexaenoic acid was lower. Essential fatty acid composition of lecithin was found to be different in IUGR.     

Changes in platelet function in pregnancies complicated by fetal growth retardation.

Platelet function was investigated in three patients with severely decreased fetal growth rates detected by ultrasound scanning. Only one patient had hypertension, which was mild and developed after decreased fetal growth and altered platelet responses had been detected. Much higher concentrations of platelet-activating factor (PAF) (20-500 nM) were required to stimulate maximal platelet aggregation in all three patients compared with the concentrations of PAF (5-10 nM) required in control pregnancies of similar gestational age. In a fourth patient, platelet desensitisation was observed 5 weeks before the detection of decreased fetal growth. These results are similar to those observed in women with hypertensive disorders of pregnancy, and indicate that there may be a similar change in platelet function in gestational hypertension and in fetal growth retardation, although the clinical manifestations are different.     

Fetal blood flow in pregnancies complicated by intrauterine growth retardation

A noninvasive pulsed Doppler ultrasound technique was used to characterize blood flow in the descending thoracic aorta and the intra-abdominal part of the umbilical vein in 159 fetuses suspected of intrauterine growth retardation (IUGR) on the basis of ultrasound fetometry. From this group, 74 infants with IUGR (defined as gestational age-related birth weight of 2 standard deviations [SD] or more below the population mean) were born. The blood flow results were not available to the clinicians managing the pregnancies. Blood flow mean velocity in the fetal aorta was lower, pulsatility index and rising slope higher, and umbilical volume flow and umbilical flow per 100 g placental tissue were lower in the pregnancies with IUGR than in 21 normal pregnancies. The waveform of the maximum aortic velocity envelope was related to operative delivery for fetal distress, Apgar score, and umbilical cord blood pH. The pulsatility index and the configurational assessment of the diastolic part of the waveform were combined to form a new concept, the blood flow class. The blood flow class was abnormal in 57% of the fetuses classified as having IUGR at birth and in 93% of those growth-retarded fetuses who subsequently developed signs of fetal distress requiring operative delivery. Waveform analysis, in terms of blood flow class, seems to be a useful tool in the surveillance of fetuses when IUGR is suspected. Abnormal blood flow class is a marker of fetal distress and probably gives an earlier indication than antenatal nonstressed cardiotocography. The results of this study point to a strong association between IUGR and impaired fetal blood flow. The aortic volume blood flow, unlike waveform analysis, does not seem to be a variable sensitive enough to predict fetal outcome in the individual pregnancy.     

Intrauterine growth retardation

Fetal growth retardation ranks third after prematurity and malformations as a cause of perinatal deaths. Antenatal fetal monitoring (biochemical testing of fetoplacental function plus cardiotocography) has emerged as the most important means of reduction in the number of stillbirths and improvement in the quality of survival of infants who are born alive. Clinical acumen combined with biochemical and/or ultrasonographic testing will identify no more than 70% of growth retarded fetuses. However, not all small for dates fetuses are at risk, and many doomed to die in utero are not by definition, growth retarded. It should be the obstetrician's aim to identify the fetus at risk of death from hypoxia whether growth retarded or not. Biochemical and ultrasonographic methods of testing are not truly comparable, since some aim to identify the growth retarded fetus, irrespective of his state of health, whereas others aim to detect fetoplacental dysfunction, irrespective of whether or not the fetus is growth retarded. With present methods of antenatal diagnosis and treatment and timing of delivery determined by nonstressed cardiotocography, the physical and intellectual prognosis of growth retarded infants is most satisfactory; follow-up studies have shown that only about 2% of these infants are severely handicapped.     

Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation

Previous studies using two-dimensional chest radiographs have found a significant correlation between prematurity, fetal growth retardation, and the size of the maternal heart. Accordingly, we evaluated maternal left ventricular size and function by M-mode echocardiography near the end of gestation in 42 women with suspected fetal growth retardation and in 79 women whose pregnancies were normal. No significant differences were found between the two groups, implying that maternal left ventricular size and function is adequate in pregnancies complicated by "idiopathic" fetal growth retardation.     

Secretion of prolactin and insulin-like growth factor I by decidual explant cultures from pregnancies complicated by intrauterine growth retardation.

OBJECTIVES: Prolactin and insulin-like growth factor I secretion elsewhere in the uterus have been shown to decrease when tissue-specific growth is limited. We investigated their secretion by decidual explant cultures from pregnancies complicated by fetal intrauterine growth retardation. STUDY DESIGN: Explant cultures from 13 pregnancies complicated by intrauterine growth retardation and 12 control pregnancies were established in minimal essential medium and media was harvested after 24 hours of culture. Prolactin and insulin-like growth factor I concentrations were determined by radioimmunoassay. Total protein in the media was also measured. Data were analyzed by analyses of variance and linear regression. RESULTS: Decidual prolactin secretion in the pregnancies with intrauterine growth retardation was reduced to 109 +/- 31 ng/100 mg tissue per 24 hours compared with 254 +/- 51 ng in the controls (p = 0.01). Insulin-like growth factor I secretion was reduced to 1.9 +/- 0.6 ng/100 mg tissue per 24 hours from 7.1 +/- 0.9 ng/100 mg in the controls (p < 0.0001). Total protein secretion did not differ between the two groups. Decidual prolactin and insulin-like growth factor I secretion had a highly significant positive correlation (r = 0.71, p = 0.0001). CONCLUSIONS: Our data show that two protein hormones secreted by the maternal decidua are dramatically reduced in intrauterine growth retardation and warrant further investigation into their roles in the intrauterine environment.     

Intrauterine growth retardation: obstetrical aspects.

We have just begun our study of fetal growth retardation. Prenatal influences upon fetal growth are poorly understood and little studied. One may list multiple etiologies, catalogue numerous physiologic processes, and still not know in any given child what went wrong. The questions far exceed our preliminary answers. How does maternal undernutrition significantly effect the fetal "parasite?" Is the syndrome of intrauterine growth retardation a manifestation of a host versus graft phenomenon, with "runting" in the offspring? Are deficits in cell number and size unalterable? Can these deficits be overcome with good postnatal care? How can we better detect the fetus who is undergoing deprivation in utero? What altered biochemical processes exist? Can we reverse such abnormal influences in utero and prevent their consequences to the fetus? Certainly there are numerous additional areas for investigation and thought.     

Maternal-fetal glucose gradient in normal pregnancies and in pregnancies complicated by alloimmunization and fetal growth retardation

Maternal and fetal glucose concentrations were measured simultaneously in 54 pregnancies in which fetal blood sampling was conducted between 18 and 34 weeks gestation. Twenty-five pregnancies were normal (group 1), 13 were complicated by fetomaternal alloimmunization (group 2), and 16 by intrauterine growth retardation (group 3). The maternal glucose concentration was similar in the three groups. The fetal glucose level was significantly lower in growth-retarded (mean = 2.7 mmol/L) than in normal pregnancies (mean = 3.5 mmol/L). There was a statistically significant gradient between maternal and fetal glucose concentrations in groups 1 and 3, but no gradient was found in group 2. Maternal and fetal glucose concentrations were significantly correlated in all groups, but the correlations were distinct. For a given maternal glucose concentration, fetal glucose was higher in patients with alloimmunization and lower in patients with intrauterine growth retardation than in normal pregnancies. In patients with intrauterine growth retardation, fetal PO2 correlated positively with fetal glucose and inversely with maternal fetal glucose gradient.