Feto-maternal Ratio Research Articles

Residual curarization in the neonate after Caesarean section

The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d-tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of piperacillin during pregnancy

The pharmacokinetics of piperacillin during pregnancy were investigated. Eight pregnant women received 4 g of piperacillin intravenously before caesarean section. Likewise, five non-pregnant subjects of child bearing age received the same dose before a gynaecological operation. The mean peak plasma concentrations of piperacillin were 87.5 and 172.2 mg/L for the pregnant and non-pregnant patients, respectively. The mean umbilical vein concentration was 9.7 mg/L; the mean umbilical artery concentration was 7.4 mg/L and the amniotic fluid concentration 6.8 mg/L. The feto-maternal ratio at the time of caesarean section was 0.27. Pharmacokinetic parameters of piperacillin indicate larger volumes of distribution and higher clearance rates during pregnancy compared with the non-pregnant state. The altered pharmacokinetics of piperacillin during pregnancy suggest that higher doses may be required for effective treatment of serious infections in pregnant women near term.

Plasma amino acids in appropriate- and small-for-gestational-age fetuses

The fetal plasma amino acid profiles of 28 small-for-gestational-age fetuses were established in umbilical venous blood samples obtained by cordocentesis and the values were compared with those of 62 appropriate-for-gestational age fetuses. In the appropriate-for-gestational-age group fetal levels were significantly correlated with but were higher than the maternal levels, which indicates that amino acids are actively transported by the placenta. In the small-for-gestational-age group, the fetal plasma concentration and the fetomaternal ratio of essential amino acids was decreased and this decrease was significantly correlated with the degree of fetal hypoxemia. There was a variable response (e.g., alanine was increased, whereas serine and tyrosine were decreased) involved with nonessential amino acids. In umbilical venous hypoxemia the plasma ratio of nonessential /essential amino acids was increased, and the maternal plasma concentrations of both essential and nonessential amino acids were increased. These findings suggest that in uteroplacental insufficiency there is intrauterine starvation.

Transplacental transfer of morphine in man

The transplacental transfer of morphine and morphine-3-glucuronide (M3G) was studied in five cases of suspected Rh-isoimmunization. Ultrasound-guided fetal blood sampling from the umbilical vein was carried out as a diagnostic procedure before intrauterine blood transfusion. Morphine was given as a parenteral premedication to the mother at a dose of 0.13-0.20 mg/kg bw. Fetal blood was sampled 5-74 minutes after the morphine administration. These five women were investigated on 14 different occasions. The plasma concentrations of morphine and M3G were measured in blood samples collected simultaneously from mother and fetus. The feto-maternal ratio of morphine was 0.96 at five minutes and remained close to 1.0 in most samples taken later. At 12 minutes the ratio of M3G was less than 0.002 and between 0.2 and 0.6 in the later samples. The feto-maternal plasma ratios of morphine and M3G did not change over the studied period in one woman investigated five times between gestational weeks 26 and 32. This is the first time transplacental transfer of morphine has been quantified in man. Our results demonstrate a rapid transplacental passage and equilibration of morphine between mother and fetus.

Plasma amino acids in appropriate- and small-for-gestational-age fetuses

The fetal plasma amino acid profiles of 28 small-for-gestational-age fetuses were established in umbilical venous blood samples obtained by cordocentesis and the values were compared with those of 62 appropriate-for-gestational age fetuses. In the appropriate-for-gestational-age group fetal levels were significantly correlated with but were higher than the maternal levels, which indicates that amino acids are actively transported by the placenta. In the small-for-gestational-age group, the fetal plasma concentration and the fetomaternal ratio of essential amino acids was decreased and this decrease was significantly correlated with the degree of fetal hypoxemia. There was a variable response (e.g., alanine was increased, whereas serine and tyrosine were decreased) involved with nonessential amino acids. In umbilical venous hypoxemia the plasma ratio of nonessential/essential amino acids was increased, and the maternal plasma concentrations of both essential and nonessential amino acids were increased. These findings suggest that in uteroplacental insufficiency there is intrauterine starvation.

Plasma amino acids in diabetic pregnant rats and in their fetal and adult offspring.

Amino acid profiles and total amino-acid concentrations are established in nonfasting plasma of pregnant control, mildly diabetic and severely diabetic rats, and of their fetal and adult offspring. In pregnant rats at day 20 of gestation plasma amino acids can be regarded as normal in mildly diabetic mothers, but are significantly decreased in severely diabetic mothers. In fetuses of control rats, amino acid levels are twice as high as in the mother (fetomaternal ratio 2.0); in the fetuses of mildly diabetic mothers they are significantly lower than normal (fetomaternal ratio 1.3); in the fetuses of severely diabetic mothers they are also significantly lower than normal but with a normal fetomaternal ratio (fetomaternal ratio 2.0). In adult offspring of mildly diabetic mothers the concentration of almost all amino acids as well as that of total amino acid pool is significantly lower than in the controls; in the offspring of severely diabetic mothers they can be regarded as normal. No specific amino acid or group of amino acids can be held responsible for any of these changes, since all differences with control values display an overall effect, involving all or almost all amino acids.

Tryptophan Availability and Fetal Behavioral States

Behavioral state instability in growth-retarded fetuses might be related to a decrease in serotonine production. Tryptophan maternal and cord blood values after elective cesarean section have been investigated by means of high performance liquid chromatography in 20 growth-retarded fetuses due to pregnancy-induced hypertension (PIH) and 20 normal pregnancies as control group. The feto-maternal ratio of tryptophan is significantly higher in normal fetuses than in PIH growth-retarded fetuses (p less than 0.001). Behavioral states have been determined 1 week and just before cesarean section. Values of 1F, 2F, 3F and 4F differ in the 2 groups (p less than 0.001). A higher percentage of non-coincidences (p less than 0.001) and state interruptions (p less than 0.001) is found in PIH fetuses. A significant correlation is demonstrated between the increase of non-coincidences and decrease in the feto-maternal Trp ratio (p less than 0.001).

Placental transfer of flunitrazepam following intramuscular administration during labour.

After a single intramuscular dose of flunitrazepam 0.015 mg kg-1 (n = 14) in women 37 to 41 weeks pregnant, the concentrations in the umbilical artery and amniotic fluid were significantly lower than in maternal venous plasma. Although the difference between the maternal venous and umbilical venous plasma concentrations was not significant, the mean fetomaternal ratio was 0.7. The plasma protein binding of flunitrazepam was 80 +/- 4% in the mother and 79 +/- 5% in the umbilical circulation. Both mothers and midwives subjectively estimated intramuscular flunitrazepam as a valuable sedative-anxiolytic agent during the first stage of labour.

Obstetric analgesia. Clinical pharmacokinetic considerations.

All drugs used in obstetric analgesia are more or less lipophilic, their site of action is in the central nervous system, and they have good membrane penetrability in the fetomaternal unit. Thus the dose and method of administration as well as the duration of treatment are important clinical determinants of drug effects in the fetus and newborn. In the past, too much emphasis has been placed on fetomaternal blood concentration ratios of different agents; it is now appreciated that the extent of fetal tissue distribution and the neonatal elimination rate are pharmacokinetically much more important. Extensive fetal tissue distribution is reflected in a low fetomaternal drug concentration ratio, which may be followed by prolonged neonatal elimination of the drug. Currently, the most effective and safest method for obstetric analgesia is regional epidural administration of bupivacaine or lignocaine (lidocaine); only low doses are needed and the newborn is able to handle these agents efficiently. On the basis of pharmacokinetic and neurobehavioural assessments, inhalational anaesthetic agents appear to be more attractive than pethidine (meperidine) or benzodiazepines. Intermittent administration and fast pulmonary elimination of inhalational agents ensure that long-lasting residual effects are unlikely to occur. The kinetics of epidural and intrathecal opiates explain the problems associated with their use in obstetrics. Among the newer drugs used in obstetric analgesia, the properties of meptazinol and isoflurane appear interesting and these agents warrant further study. All drugs used in obstetric analgesia have a potentially detrimental effect on the neonate and, therefore, knowledge of fetal and neonatal pharmacokinetics is of importance to the clinician.

A NOVEL MODEL OF MATERNAL HYPOAMINOACIDEMIA

Chronic hyperglucagonemia produces persistent hypoaminoacidemia (HA). Glucagon does not cross the placenta; therefore, the effects of low maternal amino acids on the fetus could be studied. Alzet pumps delivered glucagon (0.25 mg/d) s.c. in 8 rats fed ad lib from d. 14 to 20 of gestation. Ten controls were sham-operated. Blood was obtained prior to implantation, at d. 3, and before delivery for total amino acids (α-amino nitrogen), glucose, and insulin. Four dams (HA-A) had weight gain and caloric intake comparable to controls; the other 4 (HA-B) gained no weight and had 1/3 lower caloric intake. Glucose cone. declined comparably from d. 14 to 20 in all groups. Insulin was unaffected in HA-A, but decreased in HA-B.Fetal weight on day 20 was 4.01±0.37 g in controls (n=102), 3.90±0.51 in HA-A (45), but 3.05±0.27 in HA-B (48). Fetal glucose and insulin levels were similar as were fetal amino acid levels. The latter resulted in higher feto-maternal ratios in both HA groups (p <0.001). Thus, hypoaminoacidemia in mothers with normal weight gain did not affect fetal weight due to the ability of the conceptus to maintain total amino acid levels.

Trace metals in postdate pregnancy.

Maternal and cord serum calcium, copper, iron and zinc concentrations were analyzed in 20 women with a postdate pregnancy. The control group consisted of 20 parturients with delivery at term and their newborns. Serum free estriol (E3) was also determined. Maternal serum copper, zinc and E3 were statistically significantly lower, while cord serum copper and fetomaternal ratio of zinc were significantly higher in the study group than in the control group. Further, a positive correlation between E3 and maternal serum copper level (r = 0.63) was found.

CONTINUOUS MINI‐INFUSION OF BUPIVACAINE INTO THE EPIDURAL SPACE DURING LABOR

Mini-infusion of 0.25 per cent bupivacaine plain into the epidural space was used in 16 healthy women for pain relief during labor. After a loading dose, continuous administration was ensured by using an automatic pump at an infusion rate of 5 or 8 ml per hour. Maternal venous blood concentrations of bupivacaine were determined 20, 40, and 60 minutes after the loading dose. Further samples were taken hourly until delivery. Fetal blood concentrations were determined from fetal scalp blood during mini-infusion, and from umbilical venous blood at delivery. Maternal blood levels averaged 206 ng/ml. The maximum concentration (604 ng/ml) did not exceed 30 per cent of the toxic level. The blood concentration of bupivacaine did not tend to increase during the course of continuous infusion. Tachyphylaxis could not be detected statistically. The fetal blood concentration during blockade averaged 58 ng/ml, giving a feto-maternal ratio of 0.28. The neonatal-maternal ratio, calculated from the umbilical venous blood, was 0.32. With a shift of the acid-base status towards acidosis in the neonate, the ration of bupivacaine slightly increased. Absence of maternal hypotension as well as absence of fetal heart irregularities during infusion may be attributed to the low and stable blood concentration of bupivacaine. The mean Apgar score was 9.5 at one minute and 9.9 at five minutes. The maternal arterial acid-base balance at delivery was normal. The fetal acid-base status at delivery showed wide variation, without any relation to the Apgar score or the total dose of bupivacaine. It is concluded that continuous mini-infusion of bupivacaine by means of an automatic pump has advantages over intermittent administration.

Feto-maternal amino acid patterns and cyclic AMP in the human placenta with abnormal pregnancies, particularly with SFD.

To clarify the causes of SFD from the view-point of placental function, investigations were made on feto-maternal amino acid circumstances and on how cyclic AMP behaves in the placenta, particularly in relation to the transport of amino acid across the placenta. Amino acids were measured by gas liquid chromatography (hydrogen-flame ion detector), c-AMP by the binding protein method, adenyl cyclase activity by Krishna's method, and proteins by Lowry's method. Results show: (1) The levels of maternal amino acids were indistinctive between the SFD group and the normal pregnancy group. (2) The feto-maternal ratio of amino acid concentrations (f/m ratio) was lower in the SFD group than in the normal control. (3) The level of c-AMP in the placenta was lower in the SFD group than in the control. (4) The lower level of placenta c-AMP in the SFD placenta seems partly attributable to the decreased adenyl cyclase activity. (5) There was a positive correlation (gamma=0.61) between the content of c-AMP in the placenta and the f/m ratio of amino acid concentrations. These findings suggest a decline in placental active transport of acids in SFD; adenyl cyclase and c-AMP in the placenta presumably play a key role in such course.

Feto-maternal concentrations of diazepam and W-demethyldiazepam after intra-amniotic diazepam injection.

Ten milligrams of diazepam were injected intraamniotically in 8 mothers prior to therapeutic abortion between 12 and 19 weeks. The diazepam concentrations in the maternal plasma were comparable to those found after the same intramuscular diazepam dose to the mother. The concentration of diazepam in the amniotic fluid 12 to 18 hours after the injection was no longer significantly higher than in the maternal plasma. The concentrations of diazepam in the fetal plasma, liver and brain were comparable to the concentrations resulting from a 10 mg intramuscular diazepam dose to the mother about 2 hours before legal abortion. The feto-maternal ratio of diazepam was of same magnitude as after the intramuscular application to the mother. The results indicate that the disappearance of diazepam from the amniotic fluid in this stage of pregnancy occurs extraplacentally, through the mambranes into the uterine circulation. In the treatment of a fetus with drugs having properties similar to diazepam, intra-amniotic administration is no better than intramuscular administration to the mother.

Fréquence et importance des hémorragies fœto-maternelles par amniocentèse précoce

Amniocentesis is a technic to which it is now made more and more reference, even when feto-maternal incompatibility is not involved, for many various indications and at variable chronology along pregnancy. Our study concerns the risk developing Rh immunization among Rh negative women, undergoing amniocentesis early in pregnancy. 233 women had 243 amniocentesis between 16 and 21 weeks of pregnancy. Fetal cells in the maternal circulation were searched for using the Kleihauer's acid elution technic. In 154 cases, the Kleihauer's method was also used just before the amniocentesis, in order to run out a spontaneous foeto-maternal haemorrhage and to correlate the 25 (16,2%) transplacental haemorrhage reported to amniocentesis. When ever the result was positive, we observed a feto-maternal ratio varying from 1/20 000 to 100/20 000 but it is very difficult at this early period of fetal life to assure a precise volume of blood from this ratio. Placental localization preceeding amniocentesis does not seem minimizing the risk of bleeding. Althrough the occurence of a fetal bleeding seems to be more frequent in cases where blood can be demonstrated in the amniotic fluid (8/25 = 32%) than in cases it is not, the estimated volume of the foeto-maternal haemorrhage is not related to the presence or absence of blood in the amniotic cavity. In 3 cases the intra-amniotic blood was tested by the Kleihauer's method. In two instances there was a mixture of adult and fetal cells. In the 3rd case only fetal cells were present. In this last case, as in 17/25 bloody amniotic fluid (68%) no feto-maternal haemorrhage could be demonstrated. The risk of Rh immunization commands prophylaxis. In such Rh negative women, we inject intravenously a 85 mug dose of anti-D immunoglobulin, soon after performing amniocentesis, what ever the result of Kleihauer test is positive or negative.

Free aminoacids and alpha-aminoacid nitrogen in cord and maternal sera at delivery and in nonpregnant women.

Serum levels of alpha aminoacid nitrogen and free aminoacids were studied in forty-two newborns, their mothers and in ten non-pregnant healthy women. The alpha aminoacid nitrogen was raised in the cord and maternal sera as compared with the value in the sera of non-pregnant women. The highest levels were seen in the immature babies. Taurine was spotted in more mothers and newborns as compared to non-pregnant women. The levels of many of the aminoacids in sera were highest in the newborns and lowest in the non-pregnant women. The feto-maternal ratio for essential aminoacids was elevated in the fullterm babies and lowest in the immatures while the reverse were the findings for non-essential aminoacids. The role played by the growing placenta with advancing gestation in raising the fetal and to some extent maternal aminoacids and alpha aminoacid nitrogen is discussed.