Intrauterine diagnosis and treatment of fetal goitrous hypothyroidism.

Newborn screening programs for the detection of congenital hypothyroidism have dramatically shortened the time before treatment is begun. However, concern still exists about central nervous system sequelae which may persist due to a period of untreated intrauterine hypothyroidism. Presence of polyhydramnios led to the ultrasound diagnosis of a fetal goiter. Hypothyroidism was confirmed at 34 weeks gestation by percutaneous fetal blood sampling, which revealed an elevated TSH (186 mU/L) and a low T4 (19.3 nmol/L). Intraamniotic fluid injections of 500 micrograms levothyroxine sodium (T4) every 10-14 days increased fetal serum T4 (59.2 nmol/L), decreased fetal serum TSH (14 mU/L), decreased amniotic fluid TSH, and decreased the size of the fetal goiter. The infant was born at term without perinatal complications. Thyroid function studies on cord blood were normal (T4, 109.4 nmol/L; TSH, 1.3 mU/L), and the infant was discharged on oral T4. Follow-up examination at age 6 weeks revealed that the infant was developmentally normal and clinically and chemically euthyroid. Intrauterine T4 therapy can suppress fetal TSH and treat fetal hypothyroidism despite hypothyroid levels of serum T3. Highly sensitive TSH assays may allow the use of amniotic fluid TSH as a marker for fetal hypothyroidism.

Fetal recoil during labor to evaluate fetal well-being when heart rate monitoring is not informative.

BACKGROUND: Fetal movement is a predictor of fetal well-being. Fetal movement in response to a stimulation (fetal recoil) has been tested, and all fetuses that demonstrated recoil had umbilical arterial blood pH at least 7.20. CASES: We used fetal recoil to allow labor in three women with fetal heart tracings that were not informative. In all three, Apgar scores or umbilical artery pH values confirmed normal fetal acid-base status at birth. CONCLUSION: Fetal recoil is a potentially useful method to assess fetal status when fetal heart rate monitoring is not informative.

Aggressive therapeutic amniocentesis for treatment of twin-twin transfusion syndrome.

Acute severe twin-twin transfusion syndrome occurs in about 1% of monochorionic twin gestations. In the most severe form, acute hydramnios develops in the recipient twin's sac and fetal hydrops may be present. The donor twin is anemic and oligohydramnios is present, so that the donor appears "stuck" in a cocoon made by its adherent amnion. In this report, aggressive therapeutic amniocentesis restored amniotic fluid volume to normal in both sacs in all pregnancies. Fetal hydrops resolved in three of five (60%) of the fetuses affected. Pregnancy was extended a mean 80 +/- 33 days (+/- 2 SD) and perinatal survival was 79%. These findings contrast dramatically with the virtual 100% mortality reported in the literature with no therapy. Repeated aggressive amniocentesis effectively reversed the physiology of twin-twin transfusion syndrome and should be the treatment of choice for acute hydramnios, which previously had no recommended therapy.

Fetal transfusion with real-time ultrasound guidance.

A technique of fetal transfusion using sonographic guidance for needle placement is described. Sixteen patients underwent a total of 43 transfusions. The fetal mortality risk appears to be lower than that encountered in fluoroscopy-directed transfusions. Fetal irradiation has been dramatically reduced from an average of 2.2 rads per transfusion to 0.29 rads per transfusion. The technique allows very precise placement of a needle within the uterus or fetus. We have used it in difficult cases for amniocentesis. The technique could also be adapted to other problems requiring accurate placement of a needle within the body, such as biopsy of masses or aspiration of cysts.

Relationship of fetal hemoglobin and oxygen content to lactate concentration in Rh isoimmunized pregnancies.

Fetal blood samples were obtained fetoscopically from 32 Rh isoimmunized pregnancies at 18-32 weeks' gestation, and the hemoglobin concentration, plasma lactate concentration, and oxygen content were measured. When the hemoglobin concentration was more than 8 g/dL, the umbilical arterial and venous lactate concentrations were equal. Abnormal elevations of lactate were found in the umbilical artery at hemoglobin concentrations below 8 g/dL (oxygen content 2 mmol/L) and in the umbilical vein at hemoglobin concentrations below 4 g/dL (oxygen content 2 mmol/L); the arterial lactate values were higher than the venous. These results show that lactate is produced by the human fetus stressed by anemic hypoxia and suggest that compensatory cardiovascular mechanisms are unable to maintain adequate oxygenation to all tissues when the umbilical venous oxygen content falls below 2 mmol/L.

Perinatal autopsy: its clinical value.

The clinical value of the routine autopsy was studied in 172 sequential cases of perinatal deaths. Of these cases 139 (81%) were autopsied including 52 fetal deaths and 87 neonatal deaths. The clinically assigned cause of death was compared with the cause of death as identified by the autopsy. In 26% (nine fetal and 27 neonatal deaths) the autopsy was the sole means of establishing the cause of death. A need for specific genetic counseling or evaluation was identified in 62 of the 139 perinatal deaths. In 30 (48%) cases the autopsy was the sole source of information highlighting this need. The autopsy is an important clinical tool providing useful information to the perinatal clinician. Besides providing specific causes of death, it can correct clinical impressions and identify genetic factors that require further assessment and counseling.

Absence of maternal side effects from prostaglandins used for cervical ripening.

Prostaglandin E2 vaginal suppositories were found to have associated maternal and fetal side effects no different than those in women undergoing spontaneous labor or labor induced with oxytocin.

Intracervical prostaglandin E2 gel. Safety for outpatient cervical ripening before induction of labor.

Cervical ripening prior to induction of labor is often necessary for medical complications of pregnancy. We proposed to prospectively determine the safety of administering prostaglandin E2 (PGE2) gel intracervically in an outpatient setting. Four hundred forty-six patients underwent 515 gel procedures as outpatients. Trained perinatal nurses placed 0.5 mg of PGE2, prepared in a standard methylcellulose base, in the intracervical canal. The PGE2 dose was administered every two hours for a total of three doses if labor did not start. The patient was sent home two hours after the last dose if she was not in active labor. Labor started in 90 patients (20%) during the gel procedure; they were admitted to the labor-and-delivery unit. The remaining patients were discharged. Eighty-eight patients (20%) were later admitted in active labor prior to scheduled induction. One patient (0.02%) was found to have occasional prolonged decelerations on admission and underwent a cesarean section two hours after admission; the Apgar scores were 8 and 9 and the arterial pH, 7.21. Hyperstimulation with excessive intrauterine activity caused significant deceleration of the fetal heart rate in four patients (0.8%), two of whom required transfer to the labor-and-delivery unit but none of whom needed a cesarean section for fetal distress. PGE2 gel can be administered safely intracervically as an outpatient procedure by trained perinatal nurses.

Intra-uterine shunting procedures.

Modern realtime ultrasound equipment and interpretation have presented physicians with a new type of patient, i.e. the fetus. The fetus suffers all the diseases we know as birth defects, but in their formative stages. Two conditions, namely obstructive uropathy and obstructive hydrocephalus, appear to be amenable in some cases to treatment in utero. Animal models for these conditions have been developed and the first attempts to treat the disorders in humans have been made. While many questions remain unanswered, some initial observations and conclusions can be drawn from this experience.

Congenital hydrocephalus: treatment in utero.

Congenital hydrocephalus occurs in about 1 in every 1,000 live births. Is is rarely lethal but frequently severely handicapping. It can be diagnosed by ultrasound as early as 20 weeks of gestation. When not accompanied by other serious malformations, it may be amenable to treatment in utero. Experimental treatment by shunting the lateral ventricle to the amnion has been shown to control ventricular enlargement during fetal life. The mental development of treated babies has, however, been disappointing. At this time no in utero treatment of fetal hydrocephalus is being done.

Measurement of human fetoplacental blood volume in erythroblastosis fetalis.

The fetoplacental blood volume of the human fetus was measured with the change in hematocrit at the time of intravascular transfusion for severe erythroblastosis. A total of 121 measurements were made between 18 and 31 weeks' gestation. The volume ranged from 117 ml/kg at 18 weeks to 93.1 ml/kg at 31 weeks. These values compare closely with those reported for the sheep fetus and, when they are extrapolated to term, are similar to the blood volume of human newborns plus the residual placental blood volume.

Changes in cervical compliance at parturition independent of uterine activity.

A new animal model has been developed to measure intrinsic changes of cerivcal compliance during spontaneous parturition or exposure to hormonal manipulation. Intermittent measurements of cervical compliance and continous measurements of uterine and cervical pressure were made during the last month of gestation of nine pregnant ewes. Cervical compliance increased abruptly and dramatically during spontanous and dexamethasone-induced parturition. Maternal progesterone supplementation at parturition inhibited uterine contractions but not the increase in cervical compliance, demonstrating the independence of the two events. The cervix was found to contract rhythmically and vigorously with a gradual decrease in activity as parturition approached.

Twin-twin transfusion syndrome.

Twin-twin transfusion syndrome associated with acute polyhydramnios in one sac and severe oligohydramnios in the other, which characteristically is diagnosed between 18 and 28 weeks, is associated with a high mortality rate for the involved twins. Patients who are managed without intervention have essentially 100% perinatal mortality. Nineteen patients with this diagnosis were treated at Good Samaritan Medical Center over a 5-year period. Because of the known perinatal mortality and because of early experiences with the twin-twin transfusion syndrome, we began to actively intervene in such patients with various modes of therapy. As experience was gained, it was found that repeated therapeutic amniocenteses, if performed before severe maternal abdominal distention or labor, appears to be beneficial.

Comparison of uterotrophic and vascular effects of estradiol-17beta and estriol in the mature organism.

Estradiol-17beta (E2) has been considered the most potent of the natural estrogens in terms of uterine growth and vasodilatation. As a result of studies of uterine growth in rodents, estriol (E3) has been considered an "impeded" estrogen. In this study, direct comparisons of the actions of E2 and E3 on the sheep uterus were made in nonpregnant, oophorectomized ewes by using bilateral uterine artery catheters and electromagnetic flow transducers. Intra-arterial injections of E2 or E3 had equal growth-promoting and vascular effects. There were slight but statistically significant differences in the time course of vasodilatation. Estriol induced a more prolonged dilatation than did estradiol.

Stimulus summation and tachyphylaxis in estrogen response in sheep.

The response of the uterine circulation to estrogen has been extensively studied. Estrogen is the most potent vasodilator of the uterine bed. The magnitude of the vascular response depends on both the dose of estrogen used and the duration of exposure to estrogen. In this study, the relationship between the arterial concentration of estrogen, the duration and pattern of exposure, and the response was studied. This is a complex relationship, but one that is consistent with accepted models of estrogen-target tissue interaction. It was also shown that prolonged, high-concentration exposure results in tachyphylaxis.

Twin-twin transfusion syndrome: the surgical removal of one twin as a treatment option.

The twin-twin transfusion syndrome, associated with acute polyhydramnios in the 18th to 28th week of gestation, has a high perinatal mortality rate. Patients managed without intervention have essentially a 100% mortality rate for the involved twins. Different methods of intervention have been described, including therapeutic amniocentesis, selective feticide, and placental vessel puncture. In this case report we describe selective removal of one twin at 21 weeks of gestation by hysterotomy in a patient with the twin-twin transfusion syndrome.

PIP: The twin-twin transfusion syndrome, associated with acute polyhydramnios in weeks 18-28 of gestations has a high perinatal mortality rate. Patients managed without intervention have essentially a 100% mortality rate for the involved twins. Different methods of intervention have been described, including therapeutic amniocentesis, selective feticide, and placental vessel puncture. In this case report, the authors describe the selective removal of 1 twin at 21 weeks of gestation by hysterotomy in a patient with twin-twin transfusion syndrome.

Fetal goitrous hypothyroidism. A new diagnostic and therapeutic approach.

We present a first case in whom fetal hypothyroidism with goiter was both successfully diagnosed and treated in utero. An obstetrical sonogram at 33 weeks revealed a bilobed fetal neck mass, compatible with enlarged thyroid gland, associated with neck hyperextension, reduced gastric fluid, and polyhydramnios. Umbilical blood sampling after volume reduction amniocentesis confirmed fetal hypothyroidism with a euthyroid mother. Fetal T4 measured 1.3 micrograms/dl, free T4 0.3 ng/dl, and thyroid-stimulating hormone 186 microU. Intraamniotic levothyroxine, 500 micrograms, was given twice with a 14-day interval. The head flexed, gastric fluid increased, and amniotic fluid levels returned to normal. Prenatal (36 weeks) and neonatal blood sampling demonstrated return to euthyroid indices. Ultrasonic estimates of thyroid volume decreased by over 50%. Vaginal delivery at 39 weeks was uncomplicated. The newborn appeared normal and is being maintained on thyroid replacement therapy.