Use of Doppler ultrasound in the management of uteroplacental perfusion during cardiopulmonary bypass in pregnancy.

Cardiopulmonary bypass, the extreme of non-obstetric surgery during pregnancy, presents unique challenges to minimize maternal and fetal risk. We present our experience with a woman who was diagnosed with a left atrial myxoma following an ischemic cerebrovascular accident. We discuss clinical management specific to cardiopulmonary bypass during pregnancy and delivery in the context of a multidisciplinary team approach. We recommend using intermittent Doppler ultrasound as a non-invasive real-time assessment of uteroplacental perfusion during non-obstetric surgery in pregnancy. Monitoring of perfusion facilitates active feedback for appropriate in utero resuscitation in these cases.

Meconium staining of amniotic fluid correlates with intestinal peel formation in gastroschisis.

Several studies in animal models demonstrate that peel formation in gastroschisis is due to the accumulation and activation of intestinal waste products (IWP) in the amniotic fluid. We reviewed our recent experience with gastroschisis and asked the following questions: First, does staining of the bowel and amniotic fluid with IWP correlate with intestinal peel formation? Second, what prenatal ultrasound findings indicate that peel formation is occurring in utero? Over two years, 16 neonates were treated for gastroschisis; twelve had been diagnosed by prenatal ultrasound and followed closely. Patients were grouped based on the presence of IWP in the amniotic fluid at the time of delivery (staining or no staining), and outcomes were reviewed. All neonates in the staining group (n=7) had a fibrinous peel present at the time of birth whereas a peel was absent in all neonates in the no-staining group (n=9). Matting of the bowel was seen by prenatal ultrasound in four patients in the staining group (0/8 in the no-staining group) and correlated with peel formation (Fisher's exact test p =0.007). Primary closure was done in 14 of the infants, and two required silo closure. In neonates with gastroschisis, staining of the amniotic fluid and bowel serosa with IWP correlated with intestinal peel formation. The ultrasound findings of matting correlated with both peel formation and staining with IWP. These results suggest that spillage of IWP into the amniotic fluid is one of the factors in peel formation in gastroschisis. Identification of matting of the bowel by prenatal ultrasound indicates formation of a peel.

Adverse and beneficial effects of tocolytic therapy.

In addition to questions raised about the efficacy of many tocolytics, appropriate concern has been voiced about the safety of these potent drugs. Although some degree of risk for adverse effects with drugs promising a strong therapeutic effect can be accepted, caution needs to be exercised when benefits are marginal or unproven. Unfortunately, some of the tocolytics, most notably the betamimetics and magnesium sulfate, have been found to have considerable potential for adverse maternal cardiovascular and respiratory effects. Although less clearly established, the use of indomethacin appears to be associated with increased fetal and neonatal risks. Concerning magnesium sulfate, in addition to the well-known maternal effects, the accumulating evidence showing an increased frequency of adverse outcomes in the fetus and neonate has led to the recommendations to abandon its use entirely as a tocolytic. Given the limitations of our current state of knowledge, nifedipine would appear to be among the more efficacious and safer tocolytics available to use when properly indicated.

Color Doppler ultrasonography for distinguishing myomas from uterine contractions in pregnancy.

OBJECTIVE: To determine the applicability and reliability of color Doppler ultrasonography (US) for distinguishing a uterine myoma from a focal myometrial contraction. STUDY DESIGN: Images from 36 patients with uterine thickenings were classified as myomas when color Doppler US demonstrated no centralized flow with a circumscribed vessel pattern at the border. Thickenings were classified as focal myometrial contractions when there was demonstrable vascular flow throughout the thickening. RESULTS: Using these diagnostic criteria, images from 36 patients were reliably characterized as representing myomas or contractions. The diagnosis was made more reliable by using the lowest velocity settings and exclusion of power Doppler US in nonretroplacental lesions. CONCLUSION: Color Doppler US is a sensitive and reliable tool for distinguishing uterine myomas from focal myometrial contractions.

Umbilical cord serum ionized magnesium level and total pediatric mortality.

OBJECTIVE: To estimate whether higher magnesium levels in umbilical cord blood at delivery are associated with increased total pediatric (fetal + neonatal + postneonatal) mortality. METHODS: During the Magnesium and Neurologic Endpoints Trial, in addition to randomizing mothers having preterm labor into arms containing magnesium sulfate, other tocolytic agents, or saline controls, we obtained biologic specimens at delivery, including umbilical cord venous blood on which was determined the serum ionized magnesium level using the AVL 988-4 analyzer (Graz, Austria). Laboratory results were then matched with the pediatric mortalities. The study power was based on the anticipated reductions in neonatal intraventricular hemorrhage related to magnesium usage from 18.9% to 4.4%. For alpha =.05, 1-beta (power)=80%, two tailed, the total number of infants needed would be 140. RESULTS: Of 149 mothers who gave permission for randomization, ionized magnesium levels were available for 82 children. Seven deaths occurred (one immediately before delivery, three as neonates, and three in the postneonatal period). The median level of ionized magnesium among the seven dead children was 0.76 mmol/L; among the 75 survivors, the median level of ionized magnesium was 0.55 mmol/L (Mann-Whitney U test, P =.03). Using multivariable logistic regression analysis, the association remained statistically significant when controlling for possible confounding factors (adjusted odds ratio 7.7, 95% confidence interval 1.2, 47.6, P =.03). CONCLUSION: These findings of a dose response between serum ionized magnesium and deaths in children increase our concern about the improper use of tocolytic magnesium.

An overview of the possible relationship between antenatal pharmacologic magnesium and cerebral palsy.

Magnesium sulfate is currently being used in obstetric practice for either eclamptic seizure prophylaxis or for tocolysis, in some countries. Evidence for its use in preeclampsia is credible, whereas the evidence for its use as a tocolytic is limited, if not absent. Of interest, the findings of two epidemiologic studies have suggested a third possible use for antenatal pharmacologic magnesium sulfate, namely, as a neuroprotectant against the later development of cerebral palsy in the newborn. In support of this hypothesis are laboratory data, much of which have to do with the modulation of cellular membrane receptors. Unfortunately, during the Magnesium and Neurologic Endpoints Trial (MagNET), while attempting to confirm the neuroprotective effect of magnesium sulfate, the occurrence of excess total pediatric mortality in those children exposed to magnesium led to early termination of the trial. Nonetheless, despite the alarming findings in MagNET, it is conceivable that exposures to doses of magnesium sulfate less than those often used for aggressive tocolysis may be neuroprotective without being lethal. Other randomized controlled trials now underway may answer this important question.

Perinatal death and tocolytic magnesium sulfate.

OBJECTIVE: To determine whether there is a significant association between perinatal mortality and exposure to total doses of tocolytic magnesium sulfate larger than 48 g. METHODS: We did a case-control study in which cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, chi(2) test, Student t test, Mann-Whitney U test, multivariable logistic regression, and Cochrane-Armitage trend test. RESULTS: Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4. 7; 95% confidence interval 1.1, 20.0; P =.035). Using the Cochrane-Armitage trend test, we found that a significant dose response was present (P =.03), but one that was most consistent with a threshold effect. CONCLUSION: Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700-1249 g.

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.

Hyperemesis gravidarum. Effects on fetal outcome.

OBJECTIVE: To study perinatal outcomes in pregnancies complicated by hyperemesis gravidarum (HG) as compared to controls. STUDY DESIGN: Between 1984 and 1991, 138 patients were diagnosed with HG according to Fairweather's criteria. Subjects were stratified into groups of mild and severe HG according to the presence of at least one of the following criteria: ketonuria, increased blood urea nitrogen and hematocrit, and/or abnormal electrolytes. All patients without HG on whom records were available and who delivered during the study period were included as controls. Multiple gestations and stillbirths were excluded from the analysis. Student's t test and X2 were used for statistical analysis. RESULTS: Demographic data were not significantly different between the groups. Forty patients were diagnosed as having mild HG and 98 patients as having severe; 12,335 patients were defined as controls. Mean fetal birth weights were 3,110, 3,093, and 3,160 g in the mild, severe and control groups, respectively. The incidence of congenital anomalies was 2.5%, 2.0% and 1.6%, respectively. The incidence of prematurity was 17.5%, 11.2% and 10.7% in mild and severe HG and controls, respectively. None of the outcome variables for mild or severe HG were significantly different as compared to the controls. Differences in other neonatal outcomes, including frequency of five-minute Apgar score < 7 and neonatal intensive care unit admissions, were not significantly different between the three groups. CONCLUSION: In contrast to previous reports, this study demonstrated that fetuses of gravidas admitted for HG are not at increased risk of growth retardation, congenital anomalies or prematurity. No beneficial effect on pregnancy outcome was detected.

Gastroschisis: can antenatal ultrasound predict infant outcomes?

OBJECTIVE: To test previously proposed but unproven antenatal ultrasound prognostic criteria in fetal gastroschisis. METHODS: Thirty consecutive gastroschisis-affected pregnancies and their outcomes were reviewed retrospectively. Data were tabulated by review of antenatal ultrasound videotapes, with blinded comparison to indicators of short- and long-term infant outcomes obtained from the medical records. Criteria of previous reports were applied to these data, focusing on their ability to prognosticate effectively. RESULTS: Applying a criterion of 10 mm bowel dilatation proved minimally useful in prognosticating infant outcomes. However, a stricter 17-mm criterion for clinically important bowel dilatation provided prognostic information, with remarkable improvement in specificity (75 versus 37%) and positive predictive value (55 versus 37%) for infant morbidity, with comparatively little loss of sensitivity (71 versus 85%). CONCLUSIONS: Bowel dilated more than 17 mm on antenatal ultrasound appears to be associated with increased short- and long-term infant morbidity. Whether this finding warrants obstetric intervention in the preterm gastroschisis-affected pregnancy with substantial bowel dilatation remains to be determined.

Constriction of the umbilical cord leading to fetal death. A report of three cases.

Constriction of the umbilical cord is characterized by localized absence of Wharton's jelly, leading to narrowing of the cord, thickening of the vascular walls and narrowing of the vascular lumens. This may result in a compromised fetal blood supply, leading to fetal anoxia and eventual fetal death. Approximately 50 cases have been reported in the world literature over the last three centuries. Three cases of umbilical cord constriction leading to intrauterine fetal demise are reported. Two of the patients presented during the late second trimester with loss of sensation of fetal movements. Intrauterine fetal demise was diagnosed, and autopsy revealed constricted umbilical cords associated with torsion. The third patient is unique in that fetal death was precipitated by a routine, technically uncomplicated, transplacental amniocentesis procedure performed in the early second trimester. At the time of termination of the pregnancy we found marked stenosis with torsion over a 1-cm segment of the umbilical cord juxtaposed against the fetal insertion site. Umbilical cord constriction is a rare, almost invariably fatal condition, usually undiagnosed antenatally. In case 3, disruption of the placenta by amniocentesis may have initiated a terminal event in a fetus already compromised by a cord constriction. Three possible mechanisms could have contributed to the fetal death after amniocentesis in the presence of cord constriction: acute vasospasm, acute oligohydramnios and uterine contraction, or an obliterating thrombus.

In utero surgical treatment of fetal obstructive uropathy: a new comprehensive approach to identify appropriate candidates for vesicoamniotic shunt therapy.

OBJECTIVES: We present a new approach to prenatal evaluation and prediction of renal function and long-term outcomes for fetuses considered candidates for in utero surgery. STUDY DESIGN: A review of 34 cases of obstructive uropathies was made, with analysis of our approach to prenatal evaluation, the predictive value of urinary electrolytes and protein analysis in identifying renal dysplasia, and the outcomes of cases with and without in utero surgical intervention. RESULTS: Ten of 11 pregnancies that were terminated had dysplasia; one female had cloacal dysgenesis. In three of eight unshunted cases megacystis resolved after vesicocentesis. Eight of 15 shunted fetuses survived. Of those predicted to have good postnatal outcome, six of six demonstrated good postnatal renal function. Of those predicted to have poor outcomes, two of two had poor postnatal renal function and dysplasia. Seven of 15 shunted fetuses died, four of four predicted to have dysplasia were confirmed, and three died of nonrenal causes. CONCLUSIONS: Our prenatal approach successfully differentiated fetuses with underlying renal dysplasia from those without irreversible damage who subsequently benefited from in utero vesicoamniotic shunt placement.

Prenatal diagnosis of sirenomelus with color Doppler ultrasonography.

Sirenomelus is an invariably lethal congenital anomaly characterized by complete or nearly complete fusion of the lower extremities that occurs in 1 of 60,000 births. In about 50% of cases this condition cannot be diagnosed prenatally because of the associated oligohydramnios that precludes a detailed examination of the fetus. We present a case of sirenomelus in which prenatal diagnosis was aided by color Doppler ultrasonography; visualization of the vitelline artery as a single, large intraabdominal vessel that did not branch in the fetal pelvis but rather coursed ventrally into the umbilical cord proved to be diagnostic of this rare condition. Color Doppler flow ultrasonography is a valuable tool for the prenatal diagnosis of sirenomelus.

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.

Prenatal diagnosis of umbilical cord pseudocyst.

The association between umbilical cord anomalies and chromosomal abnormalities has received little attention in the literature. In this report, we present two cases of umbilical cord pseudocyst incidentally detected by ultrasound prior to genetic amniocentesis performed for the indication of advanced maternal age. In the first case it was only the initial abnormal finding in a 21-week fetus ultimately found to have a trisomy 18. In the second case, detected at 26 weeks, the karyotype was normal and a healthy normal neonate was delivered at term. The finding of a umbilical cord cystic mass during prenatal sonographic examination should alert the clinician to the increased risk of aneuploidy.

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.

Septic shock and sepsis syndrome in obstetric patients.

Septic shock is a life-threatening clinical syndrome that, despite its rare occurrence in obstetrics, remains a leading cause of maternal mortality. Its pathophysiology is explained by a profound systemic response to a complex variety of host cellular and humoral mediators elaborated after exposure to microbial toxins. Early recognition, prompt diagnostic workup, and immediate initiation of therapy improve outcomes. Therefore, recent publications have popularized the concept of the "sepsis syndrome," a preshock list of clinical criteria associated with progressive sepsis. Needed diagnostic studies should never be withheld because of "pregnancy concerns." With critically ill patients, the risk-to-benefit ratio supports the use of these diagnostic studies in almost all circumstances. Standard therapy is directed principally at restoring tissue perfusion by intravascular volume expansion and in some instances vasoactive pharmacological intervention. Simultaneously, identification of the source of infection and commencement of appropriate empiric antibiotic treatment are critical. In some cases, surgical abscess drainage or debridement of infected necrotic tissue will need to be considered. Novel approaches to treatment that attempt to reduce the systemic response to microbial toxins are promising and under active investigation. Pregnancy-specific considerations include the following: 1) initial signs or symptoms of septic shock may be masked by normal physiologic alterations of pregnancy; 2) a mixed polymicrobial group of organisms, consistent with lower genital tract flora, should be anticipated; and 3) initial therapy should be directed at maternal concerns since adverse fetal effects are most likely the result of maternal decompensation.

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.