The use of human placental lactogen,oxytocinase and estriol in twin pregnancies with intrauterine growth retardation

In 38 twin pregnancies human placental lactogen (HPL) and oxytocinase were measured in serum and estriol in urine. Eleven women carried light-for-dates (LFD) twins (birth weight less than P₅), and 27 had appropriate-for-dates twins (birth weight greater than p₅). We investigated if intrauterine growth retardation in these patients could be detected either by the biochemical measurements or by clinical examination. The values of oxytocinase and estriol were not related to fetal weight. A serum level of HPL of 12 mg/l after 34 wk of gestation proved to be helpful in the detection of LFD twins. The predictive value of a positive test was 64% ($\text{7}\text{11}$) and of a negative test 84% ($\text{21}\text{25}$). Eight LFD twins were suspected clinically. If clinical examination and HPL measurements were used in conjunction all LFD twins could have been suspected before birth.     

An endocrine model for the diagnosis of intrauterine growth retardation as demonstrated by the determination of total estrogen and pregnandiol 24-hour urinary excretion in 222 at risk pregnancies.

A reliable method for surveillance of chronic impairment of nutritive placental function is described. The techniques are simple, tested for their reliability, without need for isotopes or special apparatus and hence inexpensive. Using 222 pregnancies at risk it is shown that the simultaneous determination of a fetal (estrogen) and a placental (pregnandiol) parameter makes the early diagnosis of intrauterine growth retardation possible. Estrogen diagnosis alone has a reliability of 90.1% with 1.8% falsely pathological and 8.1% falsely normal findings (Tab. I). Simultaneous pregnandiol determinations increase the number of falsely pathological findings to 8.1% but reduce that of falsely normal ones to 2.7%. No small for date (SGA) infants are found here. It consists of 5 cases of imminent (3 times actual) premature delivery and one postmature one. Hence our technique indicates the risk of intrauterine growth retardation in all cases but not the risk of premature or postmature delivery. Early diagnosis (from week 20) indicates that impairment of placental function as indicated by decreased pregnandiol excretion, occurs weeks or months earlier than decreased estrogen excretion (Fig. 1). This can be explained only by assuming that the rate of estrogen excretion is usually not dependent on the placenta but on the capacity of the fetal adrenals and liver. Thus our results indirectly confirm those of others who claim that the fetus can synthetize estrogen precursors without the need for placental pregnenolon by using acetate. Thus it appears that the synthetic pathway is independent of the placenta at the beginning plays a quantitative role also. Since the placenta can form aromatic compounds even when its nutritive function is severely impaired, our finding is further proof that estrogen excretion reflects fetal and not fetoplacental well-being. It follows that pathological estrogen excretion indicates fetal injury that has already occurred. The requirement that a sensitive parameter of placental function be hence determined in time is met by pregnandiol assays. Low pregnandiol excretion often precedes low estrogen excretion which leads to a SGA infant, indicating that pregnandiol excretion is closely correlated to placental nutritive function. Synthetic reactions in the fetus require energy and hence depend on the placenta. Normal estrogen excretion frequently observed in the presence of prolonged decreased pregnandiol excretion must hence indicate that the fetus can compensate for placental insufficiency. In the placenta this can be demonstrated by hyperplasia of the capillaries. This is reflected in the undulating excretion of pregnandiol (Fig. 1), where compensation (new vessel formation) and depression (lesion of vessels) make these contradictory placental processes "visible". The functional unity of the fetus and the placenta is finally also demonstrated by the fact that each prolonged compensatory phase of the placenta is reponded to by the fetus with a clearly compensatory excretion of estrogen (Fig. 1)...     

Serotonin, 5-hiaa, total estrogen and pregnanediol excretion in urine during therapeutic saline abortion.

In 24 patients, who underwent therapeutic abortion for various reasons between the 17th and 26th week of pregnancy, urinary excretion of serotonin, 5-HIAA, total estrogens, and pregnanediol were measured before, during and after the intra-amniotic injection of hypertonic saline. 20% hypertonic saline solution (160-500 ml) was given by transabdominal injection over a period of 5 min. The four hormones or metabolites were measured during six periods: I; 12-24 hrs, and II: 0-12 hrs before saline administration, III: 0-12 hrs after saline administration, IV: 0-12 hrs during aborion, V: 0-12 hrs and VI: 12-24 hrs after abortion. The results point to the active participation of serotonin in the process of fetal expulsion, as serotonin was increased by over 100% (from 20-22 to 43-47 mu-g/12 hrs) during periods III-IV, and its metabolite 5-HIAA, too, increased by nearly 60% (from 2.4-2.5 to 3.3-3.9 mg/12 hrs). They decreased during the post-abortive periods V-VI. On the other hand, total estrogens decreased only slowly, but continuously, during all 6 periods (4.9, 4.3, 3.4, 3.1, 1.8 and 1.4 mg/12 hrs). Pregnanediol, beginning with 12 mg/12 hrs showed a slight increase during periods III-IV (14.5 and 15.6 mg/12 hrs) and a decrease during periods V-VI (8.0 and 5.8 mg/12 hrs). These findings are interpreted as indicating the disruption of feto-placental function affecting estrogens during periods III-VI. They might demonstrate an accelerated hydrogenation of progesterone into pregnanediol during periods III-IV, followed by a sharp decreased in progesterone/pregnanediol production during periods V-VI.     

Management of pregnancies with suspected intrauterine growth retardation in Sweden. Results of a questionnaire

BACKGROUND: Diagnosis and management of intrauterine growth retardation during pregnancy remain a major challenge in obstetric care. The objective of this survey was to evaluate the routine clinical management of pregnancies with suspected intrauterine growth retardation at obstetric departments in Sweden. METHODS: In 1997, a questionnaire was sent to all 59 obstetric departments in Sweden. Forty-two departments, caring for 83% of all deliveries in Sweden, replied. Four major topics were addressed: definition and diagnosis of intrauterine growth retardation; magnitude of the problem; clinical management; use of Doppler ultrasound in clinical decision-making. RESULTS: Intrauterine growth retardation is diagnosed by a combination of serial fundal height measurements and ultrasonic fetal biometry at 40 departments, two departments perform routine fetal biometry at 32 weeks. The diagnosis is most often made at 32-36 gestational weeks. Five departments use 1.5 s.d. below the mean as cut-off point for diagnosis of small for gestational age fetuses; 35 departments use mean - 2 s.d. and two departments mean - 2.5 s.d. Intrauterine growth retardation is suspected in 1.6-6.3% pregnancies. About 19% of patients with suspected intrauterine growth retardation are hospitalized. On average, 63% of all small-for-gestational age babies are diagnosed prenatally. Thirty-nine out of 42 obstetric departments use formalized management protocols. All departments use cardiotocography, repeat ultrasound scans and Doppler ultrasound for antenatal surveillance. CONCLUSIONS: In Swedish obstetric units, the diagnostic procedures and methods of fetal surveillance in pregnancies suspected of intrauterine growth retardation are more or less uniform. Doppler examination of umbilical artery is used at all responding departments and is considered a valuable asset in clinical decision-making.     

Platelets and intrauterine growth retardation in pre-eclampsia.

In pre-eclampsia, but not essential hypertension of pregnancy, reduced maternal levels of circulating platelets were found to correlate with intrauterine growth retardation. This suggests that disseminated intravascular coagulation and fibrin deposition contribute to the placental damage of pre-eclampsia.     

Determination of immunoglobulins IgG, IgM and IgA in maternal serum in patients with intrauterine growth retardation

Immunoglobulin IgG, IgM, and IgA were analysed in maternal serum of 33 patients with intrauterine growth retardation and 30 patients without hypotrophic newborns. The estimations of the immunoglobulins were carried out by means of single radial immunodiffusion according to Mancini and coworkers. There were no significant differences between both groups of patients. Therefore IgG, IgM, and IgA are no additional parameters for estimation of the placental function of the 3rd trimester of pregnancy.     

The evaluation of serum estradiol, progesterone, testosterone concentrations and urinary estrogen excretion level for the monitoring indices of follicular maturation

We have evaluated serum estradiol, progesterone, testosterone, and urinary estrogen excretion in 24 hour urine samples to monitor indices of follicular maturation. The serum steroid levels were determined with the direct radioimmunoassay kit. The urinary estrogen level was measured with the estrogen micrometering kit using hemagglutination inhibition reaction. Moreover, relationships between these steroid levels and the follicular size measured with ultrasound were analyzed. The serum estradiol concentration and the estrogen excretion in 24 hour urine samples mostly showed a continuous increase during the late follicular phase, and had a positive correlation to the maximum follicular diameter of the leading follicle (MxFD) and to the total of the maximum diameter of the follicles (TFD). The serum progesterone concentration showed a remarkable increase especially on the day of the LH surge onset in many cases, and had a significant (p less than 0.01) correlation to MxFD but not to TFD. The serum testosterone concentration, however, showed neither a specific tendency on its daily change nor a correlation with the follicular size. These results indicated that the serum estradiol and progesterone, and the urinary estrogen excretion can be utilized as indices of follicular maturation.     

HCS, estriol and oxytocinase in maternal serum and neonatal condition in high risk pregnancies.

In order to find a reliable index of fetal wellbeing, maternal estriol, hCS and oxytocinase levels were related with condition of the neonate. Fifty six high risk pregnancies were studied. Estriol and hCS were determined by specific radioimmunoassay and oxytocinase with a colorimetric method. The condition of the newborn was evaluated by the APGAR score. Neonates were divided into two groups, depressed (APGAR score 0-6) and vigorous (APGAR score 7-10). When the mean birthweights of both groups were statistically different, maternal estriol levels were corrected to avoid the influencing factor of newborn weight. Mean maternal estriol level corresponding to vigorous newborns was 46.73 ng/ml. This value was statistically higher than that corresponding to the group of depressed newborns, which was 26.25 ng/ml (Fig. 1). The mean birthweight of depressed infants (2,382.75 g) was statistically lower than that of the vigorous group (3,044.75 g). The corrected mean maternal estriol values of vigorous neonates (45.44 ng/ml) was different from that of depressed ones (25.14 ng/ml) (Fig. 2). When patients were divided according to maternal diseases (diabetes, vascular pathology, Rh sensitization) serum estriol levels of the mother were statistically different according to the Apgar score of the newborns. There was no significant difference between serum hCS and oxytocinase levels of mothers with depressed and vigorous newborns. Discarding fetal weight as an influencing factor in maternal hormone level, our results indicate the suitability of maternal serum estriol determinations to predict condition of the newborns in high risk pregnancies.     

HCG, HPL, oestradiol, progesterone and AFP in serum in patients with threatened abortion.

The predictive value of various biochemical methods for monitoring early risk pregnancies has been compared in 65 cases of threatened abortion. Estimation of human chorionic gonadotropin (HCG), human placental lactogen (HPL), progesterone, oestradiol and alpha-fetoprotein (AFP) in serum were made by radioimmunoassays. Values below the normal range predicted abortion in 79, 81, 89, 92 and 38 per cent of patients, while normal values confirmed continuation of pregnancy with an accuracy of 71, 61, 60, 68 and 30 per cent respectively. Thus predictions from oestradiol and progesterone were at least as reliable as those from the protein hormones, while AFP proved to be unsuitable for this purpose. Combination of two variables gave even more reliable results. Due to individual and diurnal variation, however, abortion in the third and fourth month could not be definitely assumed at values above 5 IU HCG/ml, 5 ng progesterone/ml or 200 pg oestradiol/ml.     

The evaluation of the methods used in the diagnosis of intrauterine growth retardation

Several methods used in the diagnosis of intrauterine growth retardation (IUGR) were evaluated with epidemiologic techniques. The strong effect of IUGR prevalence on the positive predictive and false-positive values of these methods is discussed. If correctly used, the combination of clinical measurements and perinatal risk factors can have a predictive power as high as any of the other more sophisticated techniques. The data reviewed show that at present biparietal diameter measurements, nonstress test/oxytocin challenge test or hormone values do not contribute to a better IUGR prediction than when the above mentioned methods are applied. For IUGR detection, ultrasound evaluation should include ratios of anthropometric measurements and may be complemented with amniotic fluid volume assessment. It is suggested that these procedures be reserved to a selected high risk population. Efforts should be made to evaluate new technologies through randomized controlled trials before they are introduced to the general population, particularly in developing countries.     

胎儿宫内生长迟缓孕妇静脉血及其新生儿脐血一氧化氮水平测定的临床意义

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正常妊娠及胎儿宫内生长迟缓母血脐动静脉血中胰岛素和血糖的变化

目的检测胰岛素、血糖在正常妊娠和胎儿宫内生长迟缓(IUGR)的母血和脐动静脉血中的变化。方法正常妊娠要求终止妊娠采用引产和自然分娩者107例,足月妊娠合并IUGR者32例。采用放射免疫法测定胰岛素值,血糖测定采用葡萄糖氧化酶法。结果母血中胰岛素值在28周无明显变化,28周时达高峰,之后随孕周的增加而减少,至妊娠末期又达一较高水平;脐动脉血中胰岛素水平逐渐增高,至36周达峰值,以后降而复升;脐静脉血中胰岛素水平无规律性变化。血糖值无明显变化。IUGR母血中胰岛素和血糖与正常晚期妊娠组比较无明显变化,而脐动静脉血中胰岛素及血糖值有明显差异(P＜0.01)。结论IUGR时脐动静脉血胰岛素和血糖值降低,说明胰岛素和血糖在调节胎儿生长、发育方面起重要作用。     

Oligoamnios and intrauterine growth retardation. Apropos of 2 cases

The authors report two cases of oligoamnios associated with growth retardation. They wish to demonstrate how important the monitoring of the pregnancy is, from a clinical and sonographic standpoint, in order to screen, among others, an oligoamnios, frequently associated with a fetal malformation, and prepare to receive the child in a suitable obstetric-pediatric environment.     

Maternal hyperoxygenation in the treatment of intrauterine growth retardation.

OBJECTIVE: In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated. STUDY DESIGN: Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery. RESULTS: Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively. CONCLUSION: Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation.     

Radioimmunoassay of serum SP 1 and HPL in normal and abnormal pregnancies.

Serum concentrations of the pregnancy-specific beta 1-glycoprotein (SP 1) and human placental lactogen (HPL) were measured by radioimmunoassay in 372 blood samples obtained from 40 women in the second half of a normal singleton pregnancy. The mean level of SP 1 steadily increased from 40 micrograms/ml in the 22nd week of pregnancy to 168 micrograms/ml in the 36th week of gestation and thereafter reached a plateau. The half-life of SP 1 during the first week after delivery was about 39 h. The clinical value of SP 1 in comparison to HPL estimations was assessed in a prospective study of a few high risk pregnancies. There were no significant differences between serum SP 1 and HPL levels in pregnancies complicated by preeclampsia with or without intrauterine growth retardation and in twin pregnancies. Serum HPL and SP 1 levels were equally effective in predicting placental insufficiency with fetal growth retardation.