Ultrasound surveillance of the cervix during pregnancy in diethylstilbestrol-exposed offspring.

Twenty-three diethylstilbestrol (DES)-exposed patients were evaluated through 27 pregnancies to determine their eligibility for admission to a prospective protocol that combined serial ultrasound surveillance of the lower uterine segment-cervical complex with periodic pelvic examinations to diagnose cervical incompetency. Of these, 21 pregnant women, including seven vaginectomy patients, were matched to 84 low-risk controls to determine the following: 1) the effect of DES exposure on reproductive performance, 2) the efficacy of ultrasound selection of cerclage candidates, and 3) the influence of previous partial vaginectomy on reproductive outcome. Five DES-exposed patients were diagnosed as having cervical incompetency and had cerclages placed. There were no missed diagnoses of cervical incompetency. The DES-exposed patients delivered statistically earlier in gestation than did controls (268 +/- 13 versus 276 +/- 10 days). It was not evident that this difference was important clinically, as there were no neonatal deaths, very low birth weight infants, second-trimester losses, or deliveries before 252 days (36 weeks) among the study patients. Previous vaginectomy did not affect the frequency of the diagnosis of cervical failure or the neonatal outcome. After ultrasound surveillance and treatment for incompetent cervix, a majority of our patients delivered at term without cerclage placement. Therefore, routine cerclage placement is not recommended. Knowledge of the ultrasound criteria for diagnosing cervical incompetency is required.

Management of the diethylstilbestrol-exposed pregnant patient: a prospective study.

Over a 5-year period we have managed 63 diethylstilbestrol-exposed pregnant patients with a standardized protocol requiring weekly cervical examination and decreased physical activity of the patient. Twenty-six patients (42%) underwent a prophylactic cerclage for a history of second-trimester loss or a hypoplastic cervix on initial clinical examination (group I). Thirty-six patients (58%) were followed expectantly (group II). Sixteen patients (44%) in group II demonstrated cervical change and required an emergency cerclage. Twenty-one patients were managed expectantly with no cerclage. The gestational age at delivery for group I was 37.7 +/- 2.80 versus 34.5 +/- 6.9 weeks for patients without a cerclage (p = 0.04). There were no perinatal deaths if a cerclage was performed, whereas there were five deaths (24%) in the group without cerclage. The five deaths occurred at a mean gestational age of 24.40 +/- 4.0 weeks and a mean birth weight of 614.00 +/- 441.73 gm. Patients with a hypoplastic cervix or prior reproductive loss had a better outcome with early cerclage than patients with a normal cervix followed expectantly. We presently lack a reliable method to detect the diethylstilbestrol-exposed patient at greatest risk for perinatal loss. Based on our experience we believe that placement of a cerclage early in pregnancy should be a strong consideration.

[Anti-epileptic agents during pregnancy. A prospective study on the course of pregnancy, malformations and child development]. / Antiepileptika während der Schwangerschaft. Eine prospektive Studie über Schwangerschaftsverlauf, Fehlbildungen und kindliche Entwicklung.

In a prospective controlled study 70 children of females with epilepsy and on anticonvulsant medication during pregnancy were investigated. It was shown that epileptic females had stillbirths more frequently than expected. After delivery particularly children on phenobarbitone are sedated. Due to weak suckling this may lead to inadequate food intake. Withdrawal symptoms manifest in affected children as hyperexcitability lasting for weeks. Children of epileptic women on medication are generally smaller, of lower weight and have smaller heads than children from all control groups. Ingestion of more than one anticonvulsant leads to an even more pronounced reduction of infantile body measurements below the expected mean value. Small malformations are observed more frequently after intrauterine exposition to anticonvulsants than in the control groups. Ingestion of more than one anticonvulsant leads to an increase of the number of small malformations in the child than after single drug therapy. Children of epileptic parents are affected more frequently by large malformations than children of nonepileptic parents.

Pregnancy outcome in 98 women exposed to diethylstilbestrol in utero, their mothers, and unexposed siblings.

The reproductive capability and labor complications of 98 women exposed to diethylstilbestrol (DES) in utero were compared with those of 3 separate control groups. The controls consisted of 167 age-matched, normal women, 20 siblings not exposed to DES who had achieved pregnancy, and their mothers. Spontaneous abortion, ectopic pregnancy, incompetent cervix, and premature labor occurred significantly more often in the DES-exposed population than in the normal controls. The controls also achieved a higher percentage of desired pregnancies overall; this was statistically significant (89.6 versus 75.0%, P less than .001). When compared with their mothers, however, the DES-exposed population achieved a greater percentage of desired, viable pregnancies (75.6 versus 67.0%, P less than .001). The unexposed siblings of the DES women achieved a higher percentage of desired, viable pregnancies than did their exposed sisters (86.9 versus 73.6%, P = .274), but less than the normal population (86.9 versus 89.6%).

Pregnancy outcome in women exposed to diethylstilbestrol in utero.

The presence of anomalies in vagina, cervix, and uterine body of women exposed to diethylstilbestrol in utero has provoked interest and concern regarding the reproductive potential of these women. To expand and to evaluate better better the current knowledge in this matter, the outcomes of the pregnancies of exposed women registered in the Stilbestrol Clinic at the Stanford University Medical Center were examined. The results were combined with the published results of similar examinations of other institutions and a summation of all available data is presented. Although it is evident that the majority (79%) of exposed women who have become pregnant and not regularly sought abortion have obtained at least one living infant, the incidence of spontaneous abortion and preterm delivery has consistently been found to be greater in exposed women than in unexposed control women. One of every 30 pregnancies reported in exposed patients has been ectopically located. Additionally, there is suggestive evidence that exposed women with teratologic changes have a higher incidence of pregnancy loss than those without such changes. However, few of these observations can boast statistical validity and statistical validation of the same observation by separate investigators has not been obtained. Moreover, none of th teratologic changes in exposed patients has been seen to preclude normal pregnancy and term delivery.

PIP: Current knowledge regarding the pregnancy outcome for women exposed to DES (diethylstilbestrol) in utero is presented using information from a follow-up study of patients at the Stanford Stilbestrol Clinic and from other published data from similar studies. 2/3 of all women exposed to DES in utero have teratologic changes in the vagina, cervix, and/or uterine cavity, leading to a question as to the reproductive capacity of these women. A compilation of the study material revealed a doubled incidence of spontaneous abortion, a 3-fold increase in the incidence of preterm delivery, and a substantially greater occurrence of ectopic pregnancy in exposed women when compared to unexposed women. These findings were true for all and for the 1st pregnancies. Exposed patients had obtained at least 1 surviving infant in only approximately 80% of all cases whereas unexposed patients had done so in 95% of all instances. It is not clear whether teratologic changes in any part of the reproductive tract of exposed patients have an influence on pregnancy outcome. None of the vaginal, cervical, uterine, or tubal changes alone or in any combination was found to preclude a term intrauterine pregnancy and delivery of a viable infant. It is emphasized that the relevant study literature was minimal and incomplete.

Reproductive failure and cervical incompetence in women exposed to diethylstilbestrol.

Exposure to diethylstilbestrol in utero is recognized to be associated with a wide range of developmental abnormalities in the female genital tract, the most prominent being adenocarcinoma of the vagina. Recently anatomic anomalies have been discovered with increasing frequency. This case illustrates the association of exposure to diethylstilbestrol, cervical incompetence, and poor reproductive history, and stresses the importance of early evaluation.

Incompetent cervix in a hormone-exposed offspring.

Intensive interest has focused on DES-exposed men and women since the first reports on this in the early 1970s. We are presenting here what we feel is the first case of incompetent cervix in a DES-exposed female. It is hoped that this will stimulate further interest in the functional as well as anatomic problems which these individuals experience.

Letter: Role of the G.P. in major medical decisions.

PIP: In the past 12 months I have seen 4 patients with unexpected incompetence of the internal os of the cervix uteri. This resulted in extreme premature labor and a perinatal death on each occasion. In each case, the patient had previously undergone therapeutic abortion by means of the intraamniotic injection of (PGF2alpha) prostaglandin F2alpha. Cervical damage at the time of PG abortion has been noted by several users of this method and PGF2alpha seems to be particularly involved. Whilst most authorities would agree that such a method of terminating pregnancy is far safer than hysterotomy, I wish to draw attention to what is possibly a sequel to this procedure. I wonder whether cervical encirclage should be performed routinely when a history of previous therapeutic abortion using PGF2alpha is obtained?^ieng