The Impact of Maternal Body Mass Index and Gestational Age on the Detection of Uterine Contractions by Tocodynamometry: A Retrospective Study.

OBJECTIVE: To examine the impact of maternal body mass index (BMI) and gestational age (GA) on uterine contraction detection by tocodynamometry. METHODS: Gravidas with preterm labor (PTL) complaints who were evaluated by tocodynamometry, discharged from Labor and Delivery triage, and subsequently readmitted for preterm delivery were studied. Forty-six patients in whom contractions were detected (group 1) were compared to 49 women in whom contractions were not detected (group 2) with respect to BMI and GA at both evaluation and delivery. Multivariable logistic regression was used to adjust for confounders. RESULTS: Group 2 had a higher mean BMI (31.7 vs 26.1, P < .001), were more likely to be obese (57.1% vs 19.6%, P < .001), and were more likely to have been evaluated in the mid-trimester (36.7% vs 17.4%, P = .04) compared to group 1. Independent risk factors for the inability of the tocodynamometer to detect contractions were obesity (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.07-0.46) and evaluation in the mid-trimester (OR 0.33, 95% CI 0.13-0.84). CONCLUSION: Our study provides evidence that the effectiveness of tocodynamometry diminishes with increasing maternal BMI. Efficacy of tocodynamometry is also decreased at earlier GA, most pronounced below 25 weeks. To evaluate women with PTL symptoms in the mid-trimester or symptomatic obese women at any GA, a modality other than tocodynamometry could be valuable to more accurately assess uterine activity.

Insulin-like growth factor I receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15.

Most patients with deletion of the distal long arm of chromosome 15 have intrauterine growth retardation and postnatal growth deficiency in addition to developmental abnormalities. It has been proposed that the absence of one copy of the insulin-like growth factor I (IGF-I) receptor gene may play a role in the growth deficiency seen in this syndrome. To address this question we examined IGF-I receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15 (15q26.1-->qter). Quantitative Southern blot analysis of the IGF-I receptor gene was performed on HindIII digests of fibroblast DNA. Radioactivity in the 1.7-kilobase receptor fragment in the two patients was 55% and 51% of the values in controls, consistent with the absence of one copy of the IGF-I receptor gene. IGF-I receptor messenger ribonucleic acid levels were quantitated by a solution hybridization/nuclease protection assay. Receptor messenger ribonucleic acid levels in the two patients were 45% and 52% of the values in controls. Northern blotting demonstrated normal size IGF-I receptor transcripts and affinity crosslinking of [125I]IGF-I to Triton X-100-solubilized fibroblasts demonstrated a normal size receptor in the patients. Analysis of placental membranes prepared from one patient revealed no difference in [125I]IGF-I binding. In the patients' fibroblasts, however, binding of [125I]long [R3]-IGF-I to the IGF-I receptor was significantly reduced, as assessed by the amount of radioactivity competed by the monoclonal antibody alpha IR-3 or insulin and Scatchard analysis of binding data. To assess IGF-I receptor function, stimulation of [alpha-1-14C]-methylaminoisobutyric acid transport and stimulation of [methyl-3H]thymidine incorporation into DNA by a full range of IGF-I concentrations was examined in patient and control fibroblasts. There was a significant decrease in the maximal response to IGF-I in both assays for one of the two patients when data were expressed as fold response over the basal value. However, there was no evidence for impairment of response to IGF-I in either patient's fibroblasts when data were expressed as net stimulation (maximal response minus basal). In conclusion, although IGF-I receptor expression was decreased in fibroblasts from two patients with deletion of the distal long arm of chromosome 15, we were unable to provide conclusive evidence for impairment of the biological response to IGF-I.

The effects of early treatment of hereditary tyrosinemia type I in infancy by orthotopic liver transplantation.

Two infants with hereditary tyrosinemia secondary to fumarylacetoacetate hydrolase (FAH) deficiency underwent orthotopic liver transplantation at 14 and 16 weeks of age due to poor clinical and biochemical response to medical therapy. Prompt clearance of abnormal metabolites with improved mental alertness and appetite occurred with minimal perioperative complications. Both infants tolerated rapid institution of normal diets and have shown progressive growth and development in the first 36 months after transplantation. Early liver transplantation should be considered as an option for infants with certain inherited metabolic disorders with poor prognosis, such as tyrosinemia type I, who fail to respond to medical therapy.

Chromosome deletion 1q42-43.

We report on a newborn male and a female of 3 years 9 months with de novo 1q42 or 43-qter deletions. These cases are compared with ten other reported cases.

A paternally derived inverted duplication of 7q with evidence of a telomeric deletion.

We report on a de novo constitutional rearrangement involving the long arm of chromosome 7 in a second trimester fetus with the karyotype of 46,XX, inv dup del (7)(pter-q36::q36-q21.2:) pat. Both a large duplication (q21.2-q36) and a small deletion (within q36) were confirmed by FISH studies. DNA analysis on the family showed that the abnormal chromosome was derived from a single paternal homolog. A mechanism is proposed in light of this finding. The phenotype at autopsy was consistent with reported cases of similar duplications in chromosome 7 in that hydrocephalus, a depressed nasal bridge, low set ears, microretrognathia and a short neck were present.

Sexual discordance in monozygotic twins.

We report on monozygotic (MZ) twins who were discordant for phenotypic sex and Ullrich-Turner syndrome (UTS). The nonviable female was hydropic with cystic hygromas, ventricular septal defect, bicuspid aortic valve, polysplenia, intestinal malrotation, and small ovaries. The male was phenotypically normal. The monochorionic, diamniotic placenta had hydropic changes limited to the UTS infant's side. Skin samples from the infants and blood from their parents were obtained for cytogenetic and molecular analysis. Karyotypes of the twins were 45,X and 46,XY. Quinacrine polymorphisms on 7 chromosomes and RFLP analysis at 8 loci showed complete identity. MZ twins discordant for phenotypic sex have been described previously. Most of these show evidence of mosaicism in a 45,X patient with a normal 46,XY cell line, and a normal 46,XY male. While the issue of mosaicism in our case cannot be fully resolved, no mosaicism was found in 50 cells analyzed cytogenetically from each culture or by PCR analysis of a Y-specific sequence. The twins probably originated from either postzygotic nondisjunction or anaphase lag, followed or accompanied by twinning. The discordant placental morphology suggests an embryonic origin of at least part of the placental mesenchymal core.

Engraftment following in utero bone marrow transplantation for globoid cell leukodystrophy.

To date, in utero bone marrow transplantation (BMT) has had limited success, largely because of poor donor engraftment. The poor engraftment is probably the result of performing the procedure late in gestation after significant fetal immunocompetence has developed and/or transplanting insufficient numbers of donor hematopoietic stem cells for competing successfully with ongoing fetal hematopoiesis. To overcome these problems, we performed in utero BMT on a fetus with globoid cell leukodystrophy during the first trimester of gestation using selected paternal bone marrow stem (CD34+) cells. CD34 selection allowed a substantially greater number of stem cells to be transplanted. Although the fetus died 7 weeks after the procedure (during the 20th week of gestation), full donor engraftment was established. Moreover, the cause of death appeared to be overwhelming donor engraftment and leukostasis with paternal myeloid cells infiltrating most tissues. The ability of in utero BMT to produce this degree of engraftment provides great promise for the use of this approach in the treatment of a variety of inherited disorders that can be diagnosed prenatally.

Fetal vibro-acoustic stimulation: magnitude and duration of fetal heart rate accelerations as a marker of fetal health.

The relationship between intrapartum fetal acid-base status and fetal heart rate (FHR) response to vibro-acoustic stimulation was investigated in 100 patients. Fetal heart rate responses were classified into three groups: acceleration of 15 or more beats per minute lasting 15 or more seconds, acceleration of ten or more beats per minute lasting 10 seconds but less than 15 beats per minute and 15 seconds, or no acceleration. The mean fetal scalp blood pH was 7.29 in both groups with acceleratory responses, and such responses were highly predictive (98-100%) of scalp pH 7.20 or above. The mean pH value for the no-acceleration group (7.22) was significantly lower than the mean pH value for both groups with an acceleratory response (P less than .05), and the lack of response to the stimulus detected 90-100% of fetuses with a pH below 7.20. This sensitivity was reduced to 45% in the detection of fetuses with pH less than 7.25.

Isolated fetal ascites detected by sonography: an unusual presentation of Turner syndrome.

The prenatal sonographic diagnosis of Turner syndrome usually depends upon the discovery of a cystic hygroma or nonimmune hydrops fetalis. This report describes isolated fetal ascites as a newly recognized presentation of the disorder. Intrapartum fetal paracentesis permitted atraumatic vaginal birth. The etiology of the ascites in this case was congenital intestinal lymphangiectasia, consistent with the generalized lymphatic hypoplasia previously described in Turner syndrome.

Fetal ascitic fluid: a new source of lymphocytes for rapid chromosomal analysis.

BACKGROUND: The cells found in ascites can be processed like amniotic fluid for fetal karyotyping. We have characterized these cells and used them for a rapid cytogenetic result. CASES: Three patients presented with massive fetal ascites detected by sonography. Samples of ascitic fluid were obtained at fetal paracentesis. Cells from the fluid were cultured using standard methods for fetal blood, and were compared with fetal blood lymphocytes and amniocytes. The length of time in culture, chromosome morphology, and mitotic index of ascitic fluid cells were equivalent to those of fetal blood. In the third case, we performed immunophenotyping on the ascitic fluid cells. CONCLUSION: Ascitic fluid contains lymphocytes that permit rapid chromosomal analysis within 96 hours.

Fetal genitourinary tract anomalies: evaluation, operative correction, and follow-up.

The prenatal diagnosis of a genitourinary anomaly was made in 53 fetuses. Sonographic findings, antenatal course, and postnatal treatment and outcomes were examined. No interventional therapy was undertaken in utero, and the natural history could be examined in the 44 of 53 (83%) who did not electively terminate their pregnancies. Twenty-three of the total 53 (43%) had unilateral disease and 30 (57%) had bilateral involvement. Thirty-five of 53 (66%) survived, with 22 undergoing operative therapy postnatally. In all but one of the 35 survivors, the anomaly was isolated to the genitourinary tract, and the majority of surviving fetuses had unilateral disease. Oligohydramnios was present in only three of 35 survivors, and none had severe oligohydramnios. Nine of 53 women underwent termination of pregnancy and nine others experienced a neonatal death. All 18 of their fetuses had bilateral disease, with oligohydramnios present in 14 (78%). All five fetuses with chromosomal abnormalities were found in this group of 18. The majority of fetuses with a genitourinary anomaly will do well postnatally. Pulmonary hypoplasia, extrarenal anomalies, and chromosomal defects are frequent findings in the minority with poor outcomes. A multidisciplinary approach to management of the pregnancy with a fetal genitourinary tract anomaly is essential to optimize outcome.

A prospective comparison of hourly and quarter-hourly oxytocin dose increase intervals for the induction of labor at term.

Fifty-two women undergoing labor induction and vaginal delivery at term were randomized between two oxytocin infusion protocols, involving hourly versus quarter-hourly increases in dose. Potential differences were sought of duration of labor, amount of uterine activity generated, and amount of oxytocin required. Starting at 0.5 mU/minute, oxytocin infusion was increased regularly in small increments every hour or every 15 minutes, according to group assignment. No differences were observed in potentially confounding clinical and demographic factors between the groups, including time to ruptured membranes. There were no clinically or statistically significant differences found for the duration of any phase or stage of labor, quantitative assessment of uterine activity, incidence of hyperstimulation, or neonatal outcome. The average dose of oxytocin used was lower in the hourly than in the quarter-hourly, protocol (4.4 versus 6.7 mU/minute; P less than .005). Significantly fewer patients on the hourly protocol required a maximum infusion rate exceeding 8 mU/minute (P less than .05). More patients on the hourly protocol either had oxytocin discontinued completely or were maintained at 4 mU/minute or less during the active phase of labor (P less than .05 and P less than .001, respectively). We conclude that a slower rate of increase in oxytocin administration via continuous infusion results in no prolongation of any phase of induced labor, while permitting lower infusion rates of the drug.

Prediction of birth weight by ultrasound in the third trimester.

OBJECTIVE: To compare the accuracy of predicted birth weight by the gestation-adjusted projection method using ultrasonographic measurements obtained just before and at term. METHODS: The study group comprised patients with singleton pregnancies who underwent sonograms between 34.0 and 36.9 weeks' gestation (period 1) and at 37 weeks and beyond (period 2). The mean error in birth weight prediction, absolute birth weight error, and signed and absolute percent errors were compared with paired t tests. Thus, each patient served as her own control. RESULTS: The study included 138 patients undergoing 276 sonograms. The mean absolute error of the predicted birth weight was smaller for period 1 than for period 2 (197 +/- 167 g compared with 235 +/- 209 g, P =.019). The mean absolute percent error was 6.2 +/- 5.2% for period 1 compared with 7.4 +/- 6.3% for period 2 (P =.019). These same trends were observed when fetuses with suspected growth abnormalities were examined separately. Averaging data from both gestational periods did not improve the prediction of birth weight. CONCLUSION: Sonograms between 34.0 and 36. 9 weeks' gestation allow for more accurate prediction of birth weight than sonograms later in gestation. Though these differences are small and not clinically significant, this study indicates that serial sonograms in the late third trimester do not improve the ability to predict birth weight, even in abnormally grown fetuses. A single sonogram between 34 and 37 weeks' gestation is recommended for prediction of birth weight.

Station at onset of active labor in nulliparous patients and risk of cesarean delivery.

OBJECTIVE: To determine whether term nulliparas with an unengaged vertex presentation at onset of active labor have a higher risk for cesarean delivery. METHODS: A retrospective cohort of 1250 randomly chosen nulliparous patients at 37-42 weeks' gestation who delivered between 1988 and 1989 were selected. Four hundred forty-seven patients were excluded because of nonvertex presentation, cesarean delivery before active phase of labor, multiple gestation, delivery at less than 37 weeks' or greater than 42 weeks' gestation, induction of labor, or missing charts. For the purpose of this study, active labor was defined as regular contractions with cervical dilatation of at least 3 cm. The station at onset of active labor was recorded. Engagement was considered to be at station 0 or below. RESULTS: Of the 803 patients in the study group, 567 presented unengaged and 236 patients presented engaged. The cesarean rates differed significantly between the two groups: 14% of those unengaged compared with 5% of those engaged (chi2 = 11.9, P < .001). After adjusting for confounding variables, engagement at the time of onset of active labor was associated with lower risk of cesarean delivery (odds ratio .512, 95% confidence interval .285, .922). CONCLUSION: Eighty-six percent of nulliparas with an unengaged vertex at onset of active labor delivered vaginally. Engaged vertex at the onset of active labor was associated with a lower risk of cesarean delivery.

What can be learned from cordocentesis?

Cordocentesis is a well-accepted procedure that is widely practiced by experienced perinatologists. Its facile and safe access to the fetal circulation has broadened the spectrum of congenital disorders diagnosed prenatally. Some fetal disease states can now be identified and treated earlier, directly, more quickly, and more effectively than before, resulting in improved patient care. Although cordocentesis has been embraced by the perinatal community, it is, by definition, a technique of obtaining a fetal blood sample. A prerequisite for the procedure to exert its full impact on perinatal care is a highly capable clinical laboratory. The facility must be aware of the commonly requested fetal serologic, hematologic, and serum chemistry studies, as well as their normal values. Efforts must be made to perform fetal blood studies rapidly and reliably on small specimens. Laboratory personnel should be familiar with the indications and pitfalls of these tests and those that are best referred to a specialty laboratory. A general understanding of the perinatologist's needs and concerns will lead to a cooperative working relationship between clinician and laboratory. In this manner, we will truly discover what can be learned from cordocentesis.

Evaluation of elevations in maternal serum alpha-fetoprotein: a review.

Maternal serum AFP screening has had significant clinical impact on reducing unrecognized anencephaly and open neural tube defects at delivery. In addition, a growing number of other associations with maternal serum AFP elevations have become apparent since antepartum screening has become commonplace. We present in this review a clinically oriented approach to understanding the physiologic basis of maternal serum AFP elevations, both true- and false-positives. Compartmentalization of etiology, fetal and maternal, and routes of communication, amniotic fluid and placenta, allows a more logical approach to developing a differential diagnosis in this group of patients. In evaluating an elevation in maternal serum AFP, it is first necessary to consider the amount of fetal production by confirming the gestational age of the fetus and the number of fetuses present. Adjustments for maternal factors (weight, race, diabetes) must also be made. Fetal developmental defects which may lead primarily to leakage of the fetal proteins into the surrounding amniotic fluid with secondary elevations of maternal serum AFP enter into the differential diagnosis. The placenta itself is probably not a production source of AFP, but when the placenta is abnormal, a greater amount of AFP may be transported to the maternal circulation. Although our thoughts frequently do turn first to an increased maternal serum AFP reflecting an increased AFP concentration in the amniotic cavity with greater transference "across the membranes," in fact a far more common etiology is an increased transfer from the fetal circulation to the maternal via the fetal-maternal interface within the placenta. This is supported by the simple fact that the vast majority of maternal serum AFP elevations are not associated with amniotic fluid AFP elevations; the amniotic fluid AFP concentrations are usually normal. Thus, in circumstances where the fetal anatomy is grossly normal and there is not another explanation for elevations in maternal serum AFP, the placenta, either secondary to providing increased areas of transport or in providing an abnormal endothelial barrier, allows for greater transfer of fetal serum, and thus AFP, into the maternal compartment. An abnormal placenta is also a likely explanation for the increased risk of adverse pregnancy outcome that is associated with increased maternal serum AFP elevations for which no obvious etiology is found. The case herein reported suggests that an abnormal placenta which provides an altered interface for AFP flow between the fetal and maternal circulations may in fact be the etiology of the significant elevations of maternal serum AFP seen in cases of triploidy.(ABSTRACT TRUNCATED AT 400 WORDS)

Antenatal detection of cystic hygroma.

Ultrasonographic evaluation, as a routine component of prenatal care, has significantly contributed to in utero assessment of pregnancy status. The detection of fetal abnormalities by ultrasound, however, has raised clinical questions and created parental dilemmas concerning the outcomes of such pregnancies. A relatively frequent anomaly observed on routine ultrasonographic examination is the posterior nuchal cystic hygroma. We report the prenatal detection of 16 cases of cystic hygromata and an analysis of a survey of the world's literature including an additional 155 cases. The information available from these 171 cases allows a clearer picture of the prognosis for fetuses in whom posterior cystic hygroma is detected in utero. Regarding outcome, 73.2 per cent of cases were terminated at the parents' request; 37 cases (22.6 per cent) resulted in fetal death in utero prior to any intervention. Only 7 per cent of continuing pregnancies resulted in live-born infants. Of the 142 cases with available cytogenetic findings, 22 per cent had normal karyotypes; 58 per cent had a karyotype associated with Turner syndrome phenotype; while autosomal trisomies and various structural abnormalities made up the remaining 20 per cent. Even among those fetuses with normal chromosomes, various physical anomalies were detected. Fetal hydrops was present in 66 per cent of the 102 cases with pertinent information. For those fetuses demonstrating cystic hygroma and normal karyotypes, Mendelian syndromes must be considered in the differential diagnosis. Alpha-fetoprotein evaluation of both maternal serum and amniotic fluid was not helpful in determining prognosis of these fetuses. The ultrasonographic finding of a posterior nuchal cystic hygroma, with or without accompanying fetal hydrops, is a valid indicator for a poor outcome of such pregnancies.

Prenatal diagnosis by chorionic villus sampling.

The future of chorionic villus sampling can only be envisioned in the light of current knowledge. Amniocentesis will undoubtedly continue to hold an important place in prenatal diagnosis and has recently assumed greater importance in diagnosing neural tube defects and Down syndrome through widespread maternal serum alpha-fetoprotein screening. Patients now have a choice in prenatal diagnostic procedures for most genetic disorders. Many are already choosing chorionic villus sampling despite the questions that remain regarding risks and diagnostic accuracy. Risk figures for miscarriages due to the procedure and for intrauterine infection are especially needed. The issues of maternal contamination in laboratory analyses and chromosomal mosaicism that may not be present in the fetus are also of prime importance. Collaborative efforts continue to answer these and other questions so that in the future patients will be better able to make informed decisions regarding prenatal diagnosis.

Oxytocin for the induction of labor.

The obstetric benefits and dangers of using oxytocin to promote uterine activity have long been appreciated. The induction of labor should be undertaken when the positive reasons for delivery outweigh the risks of allowing the pregnancy to continue. Over the years, recognition of the pharmacokinetics of oxytocin has led to modifications in how it is administered for the induction of labor. Most would agree that it should be used in the lowest possible dose that will provide a safe as well as efficacious process of labor for both patients: the woman and her fetus. The sensitivity of the uterus to oxytocin varies with gestational age and from individual to individual. Likewise, each fetus exhibits its own tolerance to the effects of this drug. Close surveillance of each patient's uterine activity response and labor curve and of her fetus's heart rate response is an essential part of the induction of labor.

Basic concepts in molecular (DNA) diagnosis.

There has been an explosion of new information in molecular biology that will change the ways in which we practice medicine in the future. These laboratory advances in disease detection at the DNA level are quickly finding clinical application in prenatal diagnosis. An understanding of some basic concepts of DNA laboratory techniques and their applications is increasingly important in obstetrics and gynecology today.