Management and outcome of fetomaternal Rh alloimmunization in twin pregnancies.

Between 1987 and 1996, nine twin pregnancies with fetomaternal Rh alloimmunization were delivered at our institution. Eight pregnancies were dizygotic, and the fetal blood groups were different in 3 cases. The remaining pregnancy was monozygotic and monochorionic-diamniotic. Intravenous fetal exchange transfusion was performed in five pregnancies, up to five times in each twin in one pregnancy. No fetal death occurred. The average gestational age at birth was 35 (range 33-37) weeks. The hemoglobin level was 13.2 (range 9.2-16.5) g/dl. Fetomaternal Rh alloimmunization in twin pregnancy is according to zygosity; each fetus has to be treated separately, except in case of transplacental communication.

Acromegalic pregnancy associated with a Beckwith-Wiedemann fetus.

BACKGROUND: Beckwith-Wiedemann syndrome is a rare serious condition with a high rate of malignant tumors. A relationship between Beckwith-Wiedemann syndrome and insulin-like growth factor (IGF) II gene located at the level of the 11p15 chromosomic region has been demonstrated. CASE: An acromegalic woman (elevated IGF I serum levels) undergoing pregnancy with a Beckwith-Wiedemann fetus is reported. We therefore reviewed data about this association and particularly fetal growth, and analyzed fetal blood samples for IGF I and II. CONCLUSION: We conclude that this association (i.e. Beckwith-Wiedemann syndrome and acromegaly) is independent, and point out that IGF I and II might be very high in the Beckwith-Wiedemann fetus.

Neonatal infection with Streptococcus milleri.

Streptococcus milleri is a known commensal of the female genitourinary tract, but its pathogenicity in neonates has been reported in only a few cases. During a period of one year in an obstetrical unit, Streptococcus milleri was isolated from nine neonates and from one foetus after a spontaneous abortion. In seven of the nine newborns, neonatal infection was assessed and Streptococcus milleri was the lone pathogen involved, associated with positive blood or vaginal cultures in four mothers. Because Streptococcus milleri requires special conditions for identification, it is probably underestimated as a cause of neonatal infection and septic abortion.

PCR-based determination of Rhc and RhE status of fetuses at risk of Rhc and RhE haemolytic disease.

After anti-RhD, anti-Rhc is the most important red cell alloantibody which can cause haemolytic disease of the newborn (HDN) when the mother is Rhc-negative and the fetus Rhc-positive. We report here the development of polymerase chain reaction (PCR) assays which detect the presence of the Rhc alleles in amniotic cells by the use of allele-specific primers (ASP). It is expected that such determination will help in the management of pregnancies at risk of Rhc haemolytic disease. In the course of this study we have similarly performed PCR-ASP experiments to detect fetal RHE alleles since, in rare cases, anti-RhE can also cause HDN.

Improved detection of human papillomavirus types 16 and 18 in cervical scrapes by a multiplex polymerase chain reaction: a 4% prevalence among 120 French women with normal cytology.

BACKGROUND: Cancer of the cervix is still a deadly disease. Since the finding of an association between human papillomavirus (HPV) and cervical carcinoma, the development of a reliable means of detecting viral DNA in cervical scrapes has become a priority. We have used the polymerase chain reaction to detect DNA from HPV types 16 and 18 in cervical scrapes. EXPERIMENTAL DESIGN: We designed a protocol that minimizes manipulation steps and improves control of the reaction. Our technique involves elaboration of a unique reaction mixture (core reagent) containing all reagents except Taq polymerase. Each cervical sample from controls and patients treated during the same experiment, received an aliquot of this core reagent, with the DNA polymerase added just before dispensing. The results of the amplification are visualized on a polyacrylamide gel stained with ethidium bromide. Positive results for viral DNA are confirmed by restriction mapping of the amplified products. We used HeLa cells as the positive control for HPV 18 and negative control for HPV 16 and SiHa cells for the reciprocal controls. As an internal control, we used a target in the exon 3 of the human embryonic myosin heavy chain gene. RESULTS: The polymerase chain reaction in our experiments assure a sensitivity at least equal to two copies of target per cell. We analyzed 120 cervical smears with normal cytology; only 4% gave a positive result for HPV 16. We did not detect any HPV 18 DNA. CONCLUSIONS: This prevalence, which is among the lowest reported in the literature to date, supports the concept that HPV detection may have value in aiding the prevention of cervical cancer.

The use of the antiprogestin RU486 (mifepristone) as an abortifacient in early pregnancy--clinical and pathological findings; predictive factors for efficacy.

RU486, a potent antiprogesterone steroid was administered to 124 women requesting therapeutic abortion. All were less than 49 days from their last menstrual period. Ten of these subjects (Group I) received high doses of RU486 in a decremental dose regimen (400, 300, 200 and 100 mg/day) over 4 successive days and 14 received 50 mg/day for 7 days (Group II). A further 50 subjects (Group III) received 100 mg/day for seven days and the remaining 50 subjects (Group IV) received 450 mg in a single dose. In the first three groups, half the daily dose was given in the morning and the remainder in the evening. Blood was collected before, and on Days 4 and 7 and then once a week after commencing therapy until disappearance of circulating beta HCG. In addition to beta HCG, estradiol-17 beta (E2), progesterone (P), cortisol, and various metabolic and hematological parameters were measured. Plasma RU486 concentrations were also assayed in Group II, III and IV subjects on Day 7 of therapy and in some cases on Days 14 and 21. Ultrasonography was performed in all cases on Day 1 and on Day 14. All the patients bled within five days following RU486 administration, for 1 to 21 days. A complete abortion occurred in 60% in Group I, 50% in Group II, 86% in Group III, and 80% in Group IV. The difference between the last two groups and the first two was significant at p less than 0.01. The non-responders were submitted to a uterine vacuum aspiration. A stepwise discriminant analysis was performed and indicated that the best predictors of the outcome of therapy were beta HCG values and the gestational sac diameter. With these criteria, the prediction was accurate in 86.4% of the cases. The best results were obtained in the cases where the ultrasonic measurement of gestational sac was under 10 mm in diameter and the initial beta HCG values under 15,000 mIU/ml. Among the observed side effects were moderate pelvic cramps (20.9%), nausea (27%), fainting (4.8%); 61.3% of the women complained of fatigue. Heavy bleeding occurred in 15.3% of the women but only one of them required blood transfusion. In the patients with complete abortion, beta HCG values decreased to below 500 mIU/ml by Day 14 (but in 11 cases values fell below 2,000 mIU/ml only by Day 21). Plasma estradiol and progesterone also fell. Cortisol levels increased during therapy especially in subjects of Group I, but returned to basal values after termination of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Moclobemide excretion in human breast milk.

1. Six lactating white women, aged 24-36 years, received a single oral dose of 300 mg moclobemide, between 09.00 h and 11.00 h, 3 to 5 days after the delivery of a full term neonate. 2. Complete milk collections were obtained before, 3, 6, 9, 12 and 24 h after drug administration by means of a breast pump. Venous blood samples were drawn before, and 0.5, 1, 3, 4.5, 6, 9, 12, 24 h post-dosing. 3. Moclobemide, and its major metabolite (Ro 12-8095) were measured in milk and plasma samples using h.p.l.c. The active metabolite (Ro 12-5637) could only be detected in plasma. 4. Moclobemide and its metabolites were not detectable in 24 h plasma samples. Cmax, tmax and t1/2 for moclobemide were (mean +/- s.d.) 2.70 +/- 1.24 mg l-1, 2.03 +/- 1.19 h and 2.26 +/- 0.26 h, respectively. 5. The concentrations of moclobemide and Ro 12-8095 in milk were highest at 3 h after drug administration and the drug and metabolite were not detectable after 12 h. Ro 12-5637 was not detected in any milk sample. The percentages of the dose excreted as moclobemide and Ro 12-8095 were (mean +/- s.d.) 0.057 +/- 0.020% and 0.031 +/- 0.011%, respectively. An average 3.5 kg breast-fed neonate would therefore be exposed to only a 0.05 mg kg-1 moclobemide dose (approximately 1% of the maternal dose on the mg kg-1 basis). The low amount of moclobemide excreted into breast milk is unlikely to be hazardous to suckling infants.

Collection of placental blood with a view to hemopoietic reconstitution.

Collection of placental blood in a sterile and closed system is a simple, safe and efficient procedure. One hundred and fifty eight units of fetal blood were collected by applying the same requirements of quality and safety as those defined for blood products in blood banks. No adverse effects were seen in mothers or their newborns.

Two hundred intrauterine exchange transfusions in severe blood incompatibilities.

Two hundred intrauterine exchange transfusions were performed under local anesthesia in 107 cases of blood incompatibilities (60 fetuses with severe anemia and 47 with hydrops). Under sonographic guidance, depending on fetal and placental position, an optimal puncturing site was selected along the umbilical vein: placental insertion, fetal insertion, or fetal intraabdominal segment. Tests were immediately performed to confirm fetal origin of blood obtained and estimate hemoglobin level. Blood used for exchange transfusion was compatible with maternal blood and had a hematocrit value of 75%. Exchange transfusion was continued until a hemoglobin level of 16 gm/dl was reached. This procedure was first associated with intraperitoneal transfusions and was subsequently used independently once a month to maintain an adequate hemoglobin level. In 4 fetuses with hydrops, antenatal regression of this sign was observed in 33 cases (70.2%). Overall outcome of 107 fetuses after exchanges was 84 living neonates (78.5%), 15 deaths in utero, and eight neonatal deaths. The survival rate was 91.6% for fetuses without hydrops and 61.7% for those with hydrops. The advantage of exchange transfusion appears to be rapid and efficient correction of anemia with elimination of incompatible fetal red blood cells.

Maternal-fetal transfer of fluoride in pregnant women.

Gas chromatography was used to measure the maternal and fetal plasma inorganic fluoride values at term in 91 women. They were assigned to one of four groups: group A were untreated controls; group B received a single daily dose of 1.5 mg of fluoride (as calcium fluoride) during the final trimester of pregnancy; group C was given a single dose of 1.5 mg of fluoride (as sodium fluoride) and group D was given 2 daily doses of fluoride (as sodium fluoride) totaling 1.5 mg. There was a significant difference between the cord plasma fluoride levels of the newborns in the untreated group (mean: 27.8 micrograms/l) and that of the combined supplemented groups B, C and D (mean: 58.3 micrograms/l). There was no difference between the average fluoride levels in the three supplemented groups. There was no significant effect of maternal age, infant birth weight, gestation or diet during pregnancy on the cord plasma fluoride level. These results indicate that fluoride supplementation during the final trimester of pregnancy will significantly elevate cord plasma fluoride concentrations.

[In utero treatment of fetal tachycardias with a digitalis-beta blocker combination. Apropos of 2 cases]. / Traitement in utero des tachycardies foetales par l'association digitalique-bêta-bloquant. A propos de deux cas.

The authors report two cases of fetal tachycardia treated in utero by digitalis (Digoxin) and a beta-blocker (Sotalol). The first case did well on treatment but the second case gave rise to difficulties in treatment both before and after delivery. A study of the literature and an analysis of our findings makes it possible for us to point out the following: echotomography is valuable in screening for fetal cardiac rhythm troubles and echocardiography is useful to work out the cause and to follow the progress of the case, this condition can be treated in utero and Sotalol, a beta-blocker, is valuable in overcoming the troubles of the rhythm, it is difficult to follow up the treatment by relying on maternal blood levels of the drugs used, finally the cause of the abnormal rhythm possibly alters the expectation of success from the treatment.

Autoimmunity, fetal losses, lupus anticoagulant: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco-obstetrical expression?

Among the various autoantibodies commonly found in women with systemic lupus erythematosus, the so-called lupus anticoagulant has been described in association with fetal losses. Recently, women with repeated spontaneous abortions and lupus anticoagulant, but no apparent systemic lupus erythematosus have been described. We have studied prospectively the possible connections between fetal losses and autoimmunity in a large control study of 130 idiopathic habitual aborters. These non-pregnant patients without any antecedent autoimmune disease were explored for the presence for autoantibodies especially lupus anticoagulant. Ten percent of the patients exhibit an antithromboplastin antibody (lupus anticoagulant) and half of this group possesses a striking association of biological manifestations of autoimmunity. In conclusion, two points appear: firstly, statistical correlation is demonstrated between antithromboplastin antibody and habitual abortion; secondly, doubt remains about the significance of the association between autoimmunity, fetal losses and antithromboplastin: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco-obstetrical expression.

[Immunological disorders of coagulation in habitual abortion. Prospective study]. / Désordres immunologiques de la coagulation dans la maladie abortive. Etude prospective.

The physiopathological role of antithromboplastin-type circulating anticoagulants in habitual abortion may be envisaged since the presence of antithromboplastin has been reported in most studies on women at high risk of abortion. To avoid a possible statistical bias, we conducted a prospective study in a sufficiently large group of women with habitual abortion (n = 99) compared with a control group of women with normal fecundity (n = 50). In addition, all women were investigated for lupus symptoms. The circulating antibody was detected by the diluted thromboplastin time and activated cephalin time methods. The results were considered positive when the patient/control diluted thromboplastin time ratio was 1.2 and/or when the increase in activated cephalin time was not corrected by a control plasma. In the patients' group, 10 women (10%) had an anti-thromboplastin type circulating anticoagulant, whereas no circulating anticoagulant could be detected in the control group. Three women with circulating anticoagulant had signs of systemic lupus erythematosus. None of the patients presented with Soulier-Boffa syndrome. These data have established a significant correlation between habitual abortion and circulating anticoagulant whilst avoiding statistical bias. Our results suggest that women with idiopathic habitual abortion should be subjected to systematic immunological exploration and that a small number of them should be followed attentively.

[Preliminary study on transplacental transfer of fluoride. Apropos of 41 mother-infant couples]. / Etude préliminaire sur le passage transplacentaire du fluor. A propos de 41 couples mère-enfant.

Comparing the levels of ionised fluoride in the serum of maternal blood at the time of delivery and cord blood shows that there is a good correlation between the two levels (r = 0.66). This makes it possible to say that fluoride is transferred easily across the placenta. The transfer is not influenced by the parity of the age of the mother nor by epidural anaesthesia, nor by the Apgar score. It does, however, correlate with the duration of the pregnancy.

[Detection during pregnancy of massive fetomaternal transfusion. A life saved by adherence to a protocol]. / Dépistage en cours de grossesse d'une hémorragie foeto-maternelle massive. Une vie sauvée par un protocole.

A case of massive feto-maternal haemorrhage which was discovered by chance in the 34th week of pregnancy is described in detail. This case is characterised by: total absence of clinical, electrical and echographic abnormalities, a part from the fetus being very anaemic; the saving of the very anaemic newborn baby because of the performance of caesarean section; although the pregnant woman was Rh negative, giving her large doses of IgG and anti-D prophylactically seems to have protected her from Rh immunisation. The authors conclude with the special value that they have found using the Kleihauer test. This is a simple, reproducible, low-cost laboratory examination. They suggest that it should be used mainly in the last third of pregnancy and may be even routinely.