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Biomedical subjects

P G Pryde

Publications and source records attributed to P G Pryde.

36 records · Page 2Linked to original sources

Fetal leg and femur/foot length ratio: a marker for trisomy 21.

OBJECTIVE: Our purpose was to determine whether the femur/foot length ratio is useful in the prenatal detection of trisomy 21. STUDY DESIGN: Direct necropsy measurements were analyzed on 436 midgestational fetuses (391 normal, 45 with trisomy 21). Necropsy leg/foot length ratio versus gestational age was found to be significantly different between normal fetuses and those with trisomy 21. On the basis of the necropsy data, 345 midgestational pregnancies were evaluated ultrasonographically for femur/foot length ratio versus gestation age to identify fetuses at risk for trisomy 21. RESULTS: A leg/foot length ratio versus gestation age < or = 2.3 correctly identified 84% of fetuses with trisomy 21 between 110 to 155 days gestation age at necropsy. An ultrasonographic femur/foot length ratio versus gestational age < or = 0.9 had an 18.3 odds ratio risk for trisomy 21 in our high-risk population and correctly identified 71% of fetuses with trisomy 21 (positive predictive value 0.24, negative predictive value 0.98). CONCLUSION: The femur/foot length ratio is an additional ultrasonographic marker for identification of fetuses at increased risk for trisomy 21.

Adult↗

Angiotensin-converting enzyme inhibitor fetopathy.

Angiotensin-converting enzyme (ACE) inhibitors are widely used for controlling hypertension. Their use in women who are pregnant is not without risk to the fetus. We describe three infants exposed in utero to ACE inhibitors who had adverse outcomes. These cases, combined with other reports in the literature, suggest strongly that these drugs are fetotoxic. ACE inhibitor fetopathy is characterized by fetal hypotension, anuria-oligohydramnios, growth restriction, pulmonary hypoplasia, renal tubular dysplasia, and hypocalvaria. Although the true frequency of adverse fetal effects has yet to be determined, because of the debilitating and lethal nature of the fetal damage when it occurs, it is our recommendation that ACE inhibitors not be used in pregnancy, particularly in the second and third trimesters.

Abnormalities, Multiple↗

Fetal drug therapy.

Fetal drug therapy encompasses several areas, including the prevention of external genital masculinization in 21-hydroxylase deficiency syndrome (congenital adrenal hyperplasia), biochemical amelioration of methylmalonic acidemia, and biotin-responsive multiple carboxylase deficiency. The correction of cardiac arrhythmias has become relatively commonplace, and a reduction in the risks of neural tube defects is now possible with the use of preconceptual and early conceptual folic acid. Similarly, fetal function can be altered by the induction of fetal lung maturity using a number of agents; corticosteroids are the most common fetal pharmaceutic agent, and a number of other agents have also been tried. The most common route of administering pharmaceutic agents is through the mother and the placenta, although the direct administration of certain agents is becoming more common.

Female↗

Familial omphalocele: considerations in genetic counseling.

Nonsyndromal omphalocele is generally regarded as a sporadic malformation. Recurrence risk is considered negligible. We report on a patient in whom 5 consecutive pregnancies (by 2 separate nonconsanguineous partners) were complicated by omphalocele as an isolated defect. Neither the patient nor her partners had history of relatives with omphalocele, although the patient's brother and his son had large umbilical hernias requiring repair in infancy. Some familial cases of nonsyndromal omphalocele have been previously reported; most such pedigrees suggest vertical transmission, although there are a few cases with only a single generation involved. In our case, the multigenerational finding of ventral wall hernias makes an autosomal dominant mechanism with variable expressivity a tenable explanation. The collected instances of familial nonsyndromal omphalocele emphasize omphalocele heterogeneity and caution in counseling recurrence risks.

Female↗

Triply discordant triplets: probability, management options, and risks.

The spontaneous occurrence of triplets is rare. With increased utilization of "assisted reproductive technologies," multifetal gestations have become more common. The empiric fetal risk for major malformation is approximately 3%. In a triplet pregnancy each fetus independently carries this risk so that the probability of having at least one malformed fetus is approximately 9%. It is much less likely to have 2 or 3 simultaneously but discordantly malformed fetuses in a multizygotic triplet gestation (.09% and .0027% risk, respectively). We report on the first case, to our knowledge, of an ovulation-stimulated triplet pregnancy complicated by 3-way discordance for major malformations diagnosed in the late second trimester by ultrasound. Fetus A was affected by congenital diaphragmatic hernia and trisomy 21; fetus B had encephalocele, a midline facial defect, and a cleft palate; and fetus C had evidence of unilateral claw hand but an otherwise normal fetal survey. At 19 weeks of gestation, fetus A was found to have spontaneously died, and a selective termination of triplet B was performed. We conclude: (1) the finding of a single major malformation in one fetus should lead to extensive search for malformations in all members of the pregnancy, and (2) the simultaneous occurrence of major malformations in more than one member of a multifetal gestation is a circumstance under which multiple selective termination deserves consideration. In this article we discuss important issues and caveats in the performance of selective termination for abnormal members of multifetal gestations.

Abnormalities, Multiple↗

Spontaneous resolution of nonimmune hydrops fetalis secondary to human parvovirus B19 infection.

Many instances of nonimmune hydrops fetalis ascribed to human parvovirus B19 have been reported. The leading proposed pathophysiologic mechanism of hydrops in affected fetuses is viral invasion of red blood cell progenitors, causing a profound reticulocytopenic fetal anemia. Although the natural history of fetal parvovirus infection remains to be elucidated fully, there have been recent reports of funipuncuture and intrauterine blood transfusions to diagnose and manage this problem. We report two pregnancies in which parvovirus-related hydrops fetalis was observed to resolve without intervention, followed by uncomplicated vaginal deliveries of healthy infants. These observations emphasize the need for further investigation before recommending routine fetal blood transfusion in affected cases.

Adolescent↗

Chorionic villus sampling: transabdominal versus transcervical approach in more than 4000 cases.

OBJECTIVE: To address the evolving trends in the choice of transabdominal or transcervical chorionic villus sampling (CVS) at a teaching hospital and to evaluate the influence of gestational age on the approach chosen. METHODS: We analyzed our CVS data base, which contained information from 1986-1991. The proportions of transabdominal and transcervical CVS were tabulated for each year. In addition, the distribution of the CVS approaches over the various gestational ages was examined. RESULTS: During the study period, 4290 CVS procedures were performed. The rate of the transabdominal technique was stable at about 15% per year except for the first 2 years, when essentially all procedures were transcervical. Use of transabdominal CVS increased with advancing gestational age, from 3.6% at less than 10 weeks' gestation to 97.6% at greater than 14 weeks (chi 2 = 120, P less than .001; r = 0.791). CONCLUSIONS: The choice between the transabdominal and transcervical approach to CVS largely reflects the route emphasized during the physician's training. When choice is based strictly on technical limitations due to placental position, the overall transabdominal CVS rate is approximately 15%. A shift from transcervical to transabdominal CVS occurs with increasing gestational age as the placenta gains bulk and moves away from the cervix. After 14 weeks' gestation, most procedures are performed transabdominally.

Chorionic Villi Sampling↗

Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities.

OBJECTIVE: This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. METHODS: We reviewed all pregnancies complicated by ultrasound-detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." RESULTS: The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. CONCLUSIONS: 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational).

Abortion, Induced↗

Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: I. Clinical issues.

OBJECTIVE: With the intention of preventing the attendant medical, ethical, and legal problems arising from the birth of live-born, anomalous fetuses, we initiated a program offering fetal intracardiac potassium chloride injection as an adjunctive measure in the setting of genetically indicated second-trimester abortion. METHODS: A lethal fetal injection was offered to patients carrying chromosomally or structurally abnormal fetuses at 19-24 weeks' gestation who desired abortion. When the patient elected this procedure, real-time ultrasound guidance was used to inject 3-5 mL of potassium chloride (2 mEq/mL) directly into the fetal cardiac chambers, followed by observation of fetal heart activity to ascertain cessation. Labor was subsequently induced with uterotonic prostaglandins. RESULTS: The procedure caused immediate cessation of fetal heart motion in 20 of 21 cases. There were no maternal complications. No fetuses were live-born. CONCLUSIONS: Direct fetal intracardiac potassium chloride injection effectively causes immediate fetal cardiac arrest. This approach may be adopted in cases of abortion by labor-induction methods at advanced gestations to ensure that the abortus is stillborn.

Abortion, Eugenic↗

Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: II. Ethical issues.

Following the diagnosis of a genetic anomaly, some couples choose to have a legal abortion. However, following later abortions at greater than 20 weeks, the rare but catastrophic occurrence of live births can lead to fractious controversy over neonatal management. To avoid this situation, we have added fetal intracardiac potassium chloride injection to cause fetal cardiac arrest before induction of labor. The ethical issues surrounding such a practice are complex. We support this practice for three reasons: 1) The women's decision for abortion is protected because this practice assures her right for non-interference; 2) potential psychological harm to the patient and other family members is avoided; and 3) the potential for coercive intervention by other health care personnel is eliminated. At least three objections can be raised: 1) All abortions are unjust; 2) newborns and second-trimester fetuses at similar weights with identical defects should be managed in like fashion; and 3) the patient is not entitled to death of the fetus, only to evacuation of the uterine contents. On balance, we believe that our approach is justifiable ethically as it reduces the burden of conflict between the wishes of the patient and those of the neonatal care givers. It should be introduced only in situations in which the likelihood of civil or criminal liability or unwarranted medical intervention is high.

Abortion, Eugenic↗

Biodistribution, with high uptake by the reproductive tract, of an intraperitoneally infused radiohalogenated steroidal estrogen-receptor ligand.

We infused [123I]16 alpha-(123I)-iodo-estradiol ([123I]E2) intraperitoneally (i.p.) into swine to study its biodistribution and to explore the i.p. use of radiohalogenated steroid estrogen-receptor (ER) ligands as a potential option for diagnosing and treating intra-abdominal, retroperitoneal, and distant sites of advanced ER-rich malignancies. Fifty to 80% of the radiolabel was absorbed from the peritoneal cavity within 30 minutes, and 30 to 50% of the infused radiolabel was excreted in the urine within 2 hr. The rate of biliary clearance was maximal within 25 minutes. At 3 hr, the ER-rich reproductive tract had greater than 63 times the concentration of radiolabel in blood; the former was blocked by non-labeled competitors for ER. Uptake by non-ER-rich tissues, compared to blood, ranged from 0.7:1 (heart and lungs) to 16:1 (spleen); the omentum, however, exhibited a concentration as high as 64:1, which was not blocked by non-labeled ER ligands. Uptake by ER-rich target tissue remained high when charcoal was used to prevent reabsorption of radiolabel from the digestive tract after its biliary excretion, and when the products of biliary excretion were removed by catheterization of the common bile duct. Neither charcoal nor exteriorization of bile appeared to affect urinary clearance of the radiolabel over the time course of the experiments. Taken together with the recent development of syntheses that yield radiohalogenated sex steroid receptor ligands of high specific activity, our findings are encouraging for the potential application of radiolabeled ligands as i.p. administered pharmaceuticals. The advantage of the i.p. route is that it provides direct uptake of the pharmaceutical by free-floating clusters and individual cancer cells in ascitic fluid, as well as delivery via the circulation to vascularized intra- and/or extraperitoneal metastases.

Abdomen↗

Severe oligohydramnios with intact membranes: an indication for diagnostic amnioinfusion.

OBJECTIVE: To quantify the improvement in ultrasonographic fetal imaging following diagnostic amnioinfusion for the indication of unexplained midtrimester oligohydramnios. METHODS: Patients referred for unexplained midtrimester oligohydramnios were retrospectively reviewed. Videotapes of those undergoing diagnostic antenatal amnioinfusion were analyzed for quality of visualization of routinely imaged structures before and after the infusion procedure. RESULTS: The overall rate of adequate visualization of fetal structures improved from 50.98 to 76.79% (p < 0.0001). In fetuses having preinfusion-identified obstructive uropathy, there was improvement in identification of associated anomalies from 11.8 to 31.3%. CONCLUSIONS: Several authors have suggested that diagnostic amnioinfusion can facilitate fetal imaging and increase diagnostic precision in the setting of unexplained severe oligohydramnios. We have quantified the improvement in the rate of optimal visualization of fetal structures which likely translates, in experienced hands, into this observed improved diagnostic precision. Of particular importance is the improvement in appreciation of associated anomalies in cases of obstructive uropathy in which such findings may determine whether or not invasive fetal therapy is indicated.

Abnormalities, Multiple↗

Viable pregnancies after diagnosis of trisomy 16 by CVS: lethal aneuploidy compartmentalized to the trophoblast.

Increasing utilization of chorionic villus sampling (CVS) has lead to the discovery that the placenta can karyotypically be a very heterogeneous organ, and chromosomal mosaicism within the placental can confuse cytogenetic interpretation. Recently, confined placental mosaicism (confined regions of aneuploidy in the otherwise normal diploid placental and fetus) has been described involving a number of chromosomal abnormalities. Fetal trisomy 16 is considered uniformly lethal early in gestation. However, we present 3 cases of nonmosaic trisomy 16 confined regionally to the placenta. We discuss the possible etiology, impact on the developing fetus, and suggest an approach to the workup and evaluation of cases where the karyotype obtained on CVS is not compatible with the findings on ultrasound.

Adult↗

Ultrasound-detected free-floating particles in amniotic fluid: correlation with maternal serum alpha-fetoprotein.

The objective of this study was to determine the rate of ultrasound-detected free-floating particles in amniotic fluid during the early second trimester and their relationship with maternal serum alpha-fetoprotein (MSAFP) in patients with normal amniotic fluid alpha-fetoprotein (AFAFP). Ninety-eight consecutive patients undergoing second-trimester amniocentesis for various indications were prospectively studied. Before undergoing amniocentesis, each patient had a level II ultrasound examination and evaluation of the presence of free-floating particles. A subjective estimate of the particle amount and measurement of the size of the largest particle seen were made. Patients were stratified into three groups according to their MSAFP level (low, normal, high). Statistical significance of results was assessed by analysis of variance and multiple comparison procedure, and by nonparametric procedures, as appropriate. MSAFPs (mean +/- 1 SD) were 0.41 +/- 0.18 and 4.88 +/- 2.22 multiples of the median for the low and the high groups, respectively. All AFAFPs were within normal limits. Ninety-four percent of patients with high MSAFP had free-floating particles in amniotic fluid as compared to 43% in the low and normal groups (p < 0.01). Patients with high MSAFP had significantly greater density and size of particles. The presence of ultrasound-detected free-floating particles in amniotic fluid of normal patients during the early second trimester may preclude its use as a reliable indicator for fetal lung maturity, or suggest that the source of these particles may differ by trimester. High MSAFP is significantly correlated with the ultrasonographic appearance of free-floating particles, as well as with larger size and higher amount.

Adult↗

Technical aspects of transcervical chorionic villus sampling.

Following the 1990 FDA approval of the Trophocan catheter for use in transcervical chorionic villus sampling (CVS), an increasing number of US physicians have begun offering the procedure. To obtain privileges to perform CVS, some states such as California have enacted legislation requiring the performance of a certain number of CVS procedures in pregnancies in which the patient has already chosen first-trimester abortion. This practice is not universally feasible for legal, logistic, or financial reasons. We describe our approach to training in a busy reproductive genetics service. The physician initially trains by performing amniocentesis to optimize skills in ultrasound-directed needle guidance and placement. During this initial period, he or she also assists in performing transabdominal CVS procedures. The initial transcervical CVS cases should be performed in those situations requiring minimal catheter manipulation, or in those individuals undergoing CVS in the setting of spontaneous abortion. Cases of increasing difficulty should only be performed as skill and familiarity increase. For a physician already skilled and experienced in ultrasound-guided invasive procedures, sequential periods of observation at a busy center allows him or her to become familiar with the common pitfalls in performing transcervical CVS, and thus avoid them. Using this approach, we have performed over 5,000 CVS procedures and trained 6 reproductive genetics fellows in transcervical CVS.

Cervix Uteri↗

Sonographic screening for trisomy 21: fetal humerus:foot length ratio, a useful new marker.

We have analyzed morphometric measurements from midgestational fetal necropsies and shown that arm and foot lengths are linear relationships versus gestational age (GA). Using foot length as the GA determinant, we found that the ratio of arm:foot length was also a linear relationship and was decreased in trisomy 21 fetuses when compared to age-matched normals. Based on these laboratory findings, we prospectively evaluated the use of the humerus:foot length ratio as a sonographic screening tool for identification of fetuses at risk for trisomy 21. Humerus length, foot length and the humerus:foot length ratio were found to be linear relationships vs. gestational age in both the normal and trisomy 21 populations. However, the regressions for the humerus:foot length ratio were significantly different between normals and Down's fetuses (p < 0.001). We found that a humerus:foot length ratio < or = 0.85 correctly identified 47% of our trisomy 21 fetuses (spec = 0.92, PPV = 0.25, NPV = 0.97). When compared to women > or = 35 years old in our high risk population, a humerus:foot length ratio < or = 0.85 carried an odds ratio of 52.7 (99% CL = 9.72-285.23) for trisomy 21.

Adult↗

Platelet activating factor-acetylhydrolase activity following chorionic villus sampling and amniocentesis.

OBJECTIVE: Platelet activating factor (PAF) is essential for embryonic development and is a potent vasodilator. It increases vascular permeability and stimulates prostaglandin E2 (PGE2) production. Platelet activating factor-acetylhydrolase (PAF-AH), the enzyme that degrades PAF, is synthesized by decidual macrophages. The aim of this study was to test the hypothesis that chorionic villus sampling (CVS) and/or amniocentesis might cause an increase in maternal PAF-AH activity. METHODS: Maternal plasma PAF-AH activity was evaluated before and after genetic amniocentesis (N = 13) and transcervical CVS (N = 29). A control group (N = 9) was evaluated to study the effects of venipuncture. RESULTS: Chorionic villus sampling caused a significant elevation in PAF-AH activity (P < .0005). No changes were noted in PAF-AH activity in the amniocentesis or the control group. CONCLUSIONS: Chorionic villus sampling causes subclinical release of PAF-AH, possibly from the decidual macrophages. Increased PAF-AH activity might result in decreased PAF levels, which might lead to vasoconstriction in the placental circulation due to lack of the vasodilator effects of PAF and possibly PGE2. This mechanism might explain the increased risk for fetal limb reduction noted with CVS performed at very early gestational ages.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗