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Background: In the management of shoulder dystocia, fetal head replacement into the uterus has been advocated should delivery attempts remain unsuccessful. Reports of the Zavanelli maneuver have been remarkably optimistic despite the challenges of the procedure. Case: A gravida 3 para 2 (two previous vaginal deliveries of more than 4,500-g infants) with gestational diabetes presented at term. Following a low forceps delivery, shoulder dystocia was encountered and was unable to be relieved with standard maneuvers. A cesarean delivery was performed, shoulders disimpacted, and the infant delivered abdominally. A 4,680-g stillborn infant was delivered with radiologic and autopsy evidence of cervical C5-C6 dislocation. Conclusion: Despite published reports of high success rates and limited fetal consequences, physicians should be aware of adverse consequences including cervical neck trauma associated with use of the Zavanelli maneuver. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of maternal undernutrition (MUN) during pregnancy on fetal and placental weight, amniotic fluid (AF) volume, AF osmolality and ion concentrations at gestational ages E16 and E20. We also quantified protein expression of water channels (aquaporins; AQPs)., Methods: Pregnant rat dams were fed an ad libitum diet (AdLib; n = 6) or were 50% MUN (n = 6) beginning at E10 of gestation. At E16 and E20, we assessed the effect of MUN on fetal and placental weights, AF volume and osmolality, and placental expression of AQP1, 8 and 9. We focused on two uterine positions (proximal and mid-horns) with the extremes of nutrient/oxygen supply. We also separately studied the basal zone (hormone production) and the labyrinth zone (feto-maternal exchange)., Results: We showed that at E16, MUN fetal, and placental weights were unchanged and that, similarly, MUN AF volume, osmolality were comparable to AdLib. At E20, however, MUN fetal and placental zonal weights were significantly decreased. Inversely, due to MUN, maternal and fetal plasma osmolality and Na+ concentrations were significantly increased. Further, MUN AF volume was significantly reduced, while AF osmolality and Na+ concentration were increased at E20., Conclusion: Placental basal zone showed variable changes in AQP expression unrelated to position in the uterus or the gestational age (and thus severity of the fetal/placental growth restriction). In the labyrinth zone, MUN placental AQP1 was significantly decreased, whereas AQP8 and 9 expressions were significantly increased at E16 and E20. Dysregulation of AQPs' expression prior to the occurrence of oligohydramnios may represent a compensatory mechanism under conditions of early MUN.

A short cervix in the second trimester is a powerful predictor of preterm birth risk. Multiple cervical length screens for patients in midpregnancy will likely become the standard of obstetrical care as a result of the development of effective methods (eg, cerclage, progesterone) to prevent early delivery in patients with a short cervix. Because of the high cost and infrastructure requirements, providing multiple cervical length evaluations through transvaginal ultrasound will likely be a significant barrier to universal screening. A cost-effective, low-technology method of cervical length screening is necessary to implement such programs. Available data suggest that digital examination is not sufficiently sensitive and reproducible to reliably screen for short cervix in presymptomatic patients in the mid trimester. New modalities for nonsonographic cervical length assessment (ie, Cervilenz) provide for a cost-effective, sensitive, and reproducible method of screening patients for short cervical length, which deserves further research in comparing its efficacy to sonographic cervical length.

Aquaporins (AQPs) are water channels that regulate water flow in many tissues. As AQP1 is a candidate to regulate placental fluid exchange, we sought to investigate the effect of arginine vasopressin (AVP) and cAMP agonists on AQP1 gene expression in first trimester-derived extravillous cytotrophoblasts (HTR-8/Svneo) and two highly proliferative carcinoma trophoblast-like cell lines but with a number of functional features of the syncytiotrophoblast namely; JAR and JEG-3 cells. Our data demonstrated that AVP (0.1 nM) significantly increased the expression of AQP1 mRNA at 10 h in HTR-8/SVneo and JEG-3 cells (P<0.05). Both SP-cAMP, a membrane-permeable and phosphodiesterase resistant cAMP, and forskolin, an adenylate cyclase stimulator significantly increased AQP1 mRNA expression in all cell lines after 2 h in a dose-dependent manner (P<0.05) with a parallel increase in protein expression. In the time course study, 5 microM of either SP-cAMP or forskolin significantly stimulated AQP1 mRNA expression after 2 h in HTR-8/SVneo cells and after 10 h in JAR and JEG-3 cells. AQP1 protein expression was highest after 20 h in both HTR-8/SVneo and JEG-3 cells (P<0.05). AVP-stimulated cAMP elevation was blocked in the presence of 9-(tetrahydro-2'-furyl) adenine (SQ22536) (100 microM), a cell-permeable adenylate cyclase inhibitor (P<0.05). These results indicate that in trophoblasts-like cells AQP1 gene expression is upregulated by both AVP and cAMP agonists. Furthermore, our data demonstrate that a cAMP-dependent pathway is responsible for the AVP effect on AQP1. Thus, modulation of AQP1 expression by maternal hormones may regulate invasion and fetal-placental-amnion water homeostasis during gestation.

Fetal intrauterine growth restriction has been associated with adult disease in both human epidemiologic studies and in animal models. In some cases, intrauterine deprivation programs the fetus to develop increased appetite and obesity, hypertension, and diabetes as an adult. Although the mechanisms responsible for fetal programming remain poorly understood, both anatomic and functional (cell signaling) changes have been described in affected individuals. In some animal models, aspects of fetal programming can be reversed postnatally; however, at the present time, the best strategy for avoiding the adult consequences of fetal growth restriction is prevention.

Water arrives in the mammalian gestation from the maternal circulation across the placenta. It then circulates between the fetal water compartments, including the fetal body compartments, the placenta and the amniotic fluid. Amniotic fluid is created by the flow of fluid from the fetal lung and bladder. A major pathway for amniotic fluid resorption is fetal swallowing; however in many cases the amounts of fluid produced and absorbed do not balance. A second resorption pathway, the intramembranous pathway (across the amnion to the fetal circulation), has been proposed to explain the maintenance of normal amniotic fluid volume. Amniotic fluid volume is thus a function both of the amount of water transferred to the gestation across the placental membrane, and the flux of water across the amnion. Membrane water flux is a function of the water permeability of the membrane; available data suggests that the amnion is the structure limiting intramembranous water flow. In the placenta, the syncytiotrophoblast is likely to be responsible for limiting water flow across the placenta. In human tissues, placental trophoblast membrane permeability increases with gestational age, suggesting a mechanism for the increased water flow necessary in late gestation. Membrane water flow can be driven by both hydrostatic and osmotic forces. Changes in both osmotic/oncotic and hydrostatic forces in the placenta my alter maternal-fetal water flow. A normal amniotic fluid volume is critical for normal fetal growth and development. The study of amniotic fluid volume regulation may yield important insights into the mechanisms used by the fetus to maintain water homeostasis. Knowledge of these mechanisms may allow novel treatments for amniotic fluid volume abnormalities with resultant improvement in clinical outcome.

Water arrives in the mammalian gestation from the maternal circulation across the placenta. It then circulates between the fetal water compartments, including the fetal body compartments, the placenta and the amniotic fluid. Amniotic fluid is created by the flow of fluid from the fetal lung and bladder. A major pathway for amniotic fluid resorption is fetal swallowing; however, in many cases the amounts of fluid produced and absorbed do not balance. A second resorption pathway, the intramembranous pathway (across the amnion to the fetal circulation), has been proposed to explain the maintenance of normal amniotic fluid volume. Amniotic fluid volume is thus a function both of the amount of water transferred to the gestation across the placental membrane, and the flux of water across the amnion. Water flux across biologic membranes may be driven by osmotic or hydrostatic forces; existing data suggest that intramembranous flow in humans is driven by the osmotic difference between the amniotic fluid and the fetal serum. The driving force for placental flow is more controversial, and both forces may be in effect. The mechanism(s) responsible for regulating water flow to and from the amniotic fluid is unknown. In other parts of the body, notably the kidney, water flux is regulated by the expression of aquaporin water channels on the cell membrane. We hypothesize that aquaporins have a role in regulating water flux across both the amnion and the placenta, and present evidence in support of this theory. Current knowledge of gestational water flow is sufficient to allow prediction of fetal outcome when water flow is abnormal, as in twin-twin transfusion syndrome. Further insight into these mechanisms may allow novel treatments for amniotic fluid volume abnormalities with resultant improvement in clinical outcome.

Objectives: To assess the role of aquaporins (AQPs) in the regulation of amniotic fluid (AF) volume, we determined AF volume and composition and placental and fetal membrane AQP expression throughout the second half of murine gestation., Methods: Pregnant CD1 mice were sacrificed at e10-19 and AF volume and composition determined. Placenta and fetal membranes were screened for AQP gene expression. AQP gene expression was quantified by real-time RT PCR and protein location determined by immunohistochemistry. Changes in AF volume were correlated with AQP expression., Results: Both membranes and placenta demonstrated expression of AQP1, -3, -8 and -9. Advancing gestation was associated with increased AF volume from e10 to e16, with a marked decrease in AF volume from e16 to e19. By immunohistochemistry, AQP1 was localized to placental vessels and AQP3 to trophoblast. AF volume was negatively correlated with fetal membrane AQP1 and placental AQP1 and AQP9 expression, and positively correlated with placental AQP3 expression., Conclusion: Changes in AQPs with advancing gestation, and their correlation with AF volume, suggest a role in mediating placental and membrane water flow and ultimately AF volume. AQP1 appears to regulate fetal membrane water flow, and AQP3 is a likely candidate for the regulation of placental water flow.

Objective: The addition of ST waveform analysis (STAN, Neoventa, Sweden) to fetal heart rate (FHR) tracings has been demonstrated to improve fetal outcome and reduce operative delivery rates, though the actual level of fetal acidosis at which STAN indicates intervention has not been assessed. We sought to determine if FHR ST segment analysis recommends intervention at appropriate levels of fetal acidosis., Methods: FHR tracings of 10 acidotic and 10 non-acidotic infants with FHR tracings having a minimum of one STAN flag were retrospectively analyzed. Fetal base deficit (BD) was calculated by interpolation throughout the FHR tracing and STAN 'action' and 'ignore' flags assigned a fetal BD value. A secondary analysis was performed with a revised interpretation of FHR reassuring status., Results: The mean (+/-SD) BD of the first STAN action was significantly greater than the first 'ignore' (4.0+/-2.1 vs. 3.0+/-0.8 mmol/L, p<0.05). Clarified STAN criteria for reassuring vs. non-reassuring FHR resulted in a first action BD of 6.0+/-2.0 mmol/L with 90% sensitivity and 100% specificity for prediction of fetal acidosis., Conclusion: The STAN monitor discriminates increasing levels of fetal BD. With clarification of the criteria for reassuring FHR, the calculated BDs of action flags are an appropriate threshold for emergent intervention, successfully predict acidotic fetuses, and avoid unnecessary intervention.

Objective: Fetal and amniotic fluid (AF) proteins (eg, alpha fetoprotein [AFP]) are measurable in the maternal circulation. Elevated maternal serum AFP levels indicate a risk for fetal anomalies or for obstetrical complications that are often associated with inflammation (eg, preterm labor). However, little is known of the mechanism of protein exchange between the fetus, AF, and maternal circulation. Nephrin and Neph1 are cell membrane proteins that restrict glomerular protein filtration and which are differentially expressed with renal inflammation. We sought to investigate whether nephrin and Neph1 were expressed in placenta and fetal membranes, and whether inflammation modified the expression., Methods: Pregnant rats at 18 days' gestation were injected with lipopolysacchride (LPS) or control saline intraperitoneally (IP) and killed at 1, 6, and 12 hours after injection. Placenta and fetal membranes were obtained and real-time polymerase chain reaction (PCR) performed for determination of nephrin and Neph1 levels., Results: Nephrin and Neph1 were expressed in both placenta and fetal membranes. Following maternal LPS administration, nephrin mRNA significantly increased in the membranes (0.22 +/- 0.02 to 0.51 +/- 0.050, P <.05), while Neph1 expression significantly declined in the placenta (0.19 +/- 0.05 to 0.10 +/- 0.01, P <.05)., Conclusion: Fetal membranes and placenta of the rat express mRNA for the protein barriers nephrin and Neph 1, suggesting a role in the regulation of protein transfer from the fetus to mother. Under basal conditions, AF AFP transfer across fetal membranes may account for maternal serum AFP levels, whereas gestational inflammatory conditions (eg, preterm labor, threatened abortion) may augment AFP transfer across the placenta.

Objective: To assess whether prophylactic use of the McRoberts maneuver and suprapubic pressure decreased the head-to-body time, as a proxy for shoulder dystocia, in at-risk patients., Methods: Patients with estimated fetal weights over 3800 g were randomized to undergo the McRoberts maneuver and suprapubic pressure before delivery of the fetal head (prophylactic maneuvers) or to undergo maneuvers only after delivery of the head, if necessary (controls). A total of 185 patients were enrolled in the study. After exclusions (eg, abdominal delivery), there were 128 evaluable vaginal deliveries. The study had the power to detect a 30% difference in head-to-body time between groups., Results: Head-to-body delivery times did not differ between the prophylactic and control patients (24 +/- 18 seconds versus 27 +/- 20 seconds, P =.38). In addition, the two groups did not differ in rates of admission of the infant to the special care nursery or in birth injuries. There was a significant increase in the risk of delivering by cesarean for patients randomized to the use of prophylactic maneuvers., Conclusion: This study does not support the hypothesis that prophylactic use of the McRoberts maneuver and suprapubic pressure speeds delivery in a population of patients at increased risk for shoulder dystocia.

Fetal swallowing has important roles in fetal gastrointestinal development, and perhaps fetal somatic growth and maturation. Ingestive behavioral responses must develop in utero to provide for acquisition of water and food intake during the neonatal period. At birth, the rat, ovine and human fetus have developed mechanisms to acquire food via intact mechanisms of taste, suckling and swallowing. Our preliminary studies suggest that in sheep and likely in human fetuses, putative orexic-mediated ingestive responses are present near term gestation. We hypothesize that both orexic (appetite) and satiety mechanisms develop during the last third of gestation and the related neurotransmitters involved in this process are functional. The potential in utero imprinting of orexic mechanisms may influence infant, childhood and ultimately adult appetite "set-points". Thus, dysfunctional appetite, and perhaps obesity, may result from maternal environmental influences during critical stages of development.

Objective: Intravenous magnesium sulfate is widely used in obstetrics for the treatment of both preterm labor and preeclampsia. Although therapeutic levels of total magnesium have been proposed, the levels remain controversial. Because the active form of magnesium is the free or ionized form, it is essential to determine whether ionized magnesium and total magnesium levels are highly correlated in vivo. We sought to examine the correlation between ionized magnesium and total magnesium under basal and therapeutic conditions and to define the initiation and elimination pharmacokinetics of both forms during intravenous magnesium sulfate infusion., Study Design: Twenty-four singleton pregnant patients who were candidates for magnesium sulfate were studied (preterm labor, 15; preeclampsia, 9). Serial blood samples were taken before the magnesium sulfate infusion, during the first 4 hours after the initiation of magnesium sulfate infusion and for 4 hours after the discontinuation of the infusion., Results: Baseline levels of total magnesium and ionized magnesium were not different between patients with preterm labor and with preeclampsia. Among patients with preeclampsia, although not patients with preterm labor, the initial apparent volume of distribution was significantly smaller for total magnesium than for ionized magnesium (16,397 +/- 1441 vs 23,856 +/- 2745 mL, respectively; P =.03), and the elimination half-life was greater for total magnesium as compared to ionized magnesium (707 +/- 160 vs 313 +/- 29 minutes;P <.05). Linear regression analysis demonstrated a lack of correlation between ionized magnesium and total magnesium during the pretreatment period and during the steady state infusion for both preterm labor and preeclampsia., Conclusion: The measurement of total magnesium may not be adequate for the titration of therapeutic magnesium infusions in patients with preeclampsia or preterm labor because of the lack of correlation between total magnesium and the physiologically active ionized magnesium. Further studies may determine whether the measurement of ionized magnesium is a superior method for following the adequacy and safety of the treatment of preeclampsia and preterm labor.

Objective: Neonatal clavicle fracture has been previously reported to occur in association with shoulder dystocia, suggesting liability on behalf of the obstetrician. However, clavicle fracture is often inconsistently diagnosed, and shoulder dystocia commonly subjectively defined. Using a formal pediatric diagnosis protocol and an objective definition of shoulder dystocia, we sought to determine the incidence, antecedents, and associated morbidities of clavicle fracture and the potential association with shoulder dystocia., Study Design: All deliveries at Harbor-UCLA Medical Center complicated by clavicle fracture from January 1996 to March 1999 were studied. Deliveries with clavicle fracture were compared to all vaginal deliveries during this period., Results: Among 4297 deliveries, twenty-six were complicated by clavicle fracture (0.5%). Clavicle fracture was significantly associated with increased maternal age and birth weight greater than 4 kg, though not associated with shoulder dystocia or operative vaginal delivery. Clavicle fracture was associated with meconium passage and with neonatal orthopedic abnormalities., Conclusion: Neonatal clavicle fracture is associated with infant birth weight greater than 4 kg, but not with the occurrence of objectively defined shoulder dystocia. However, infants with clavicle fracture may be at increased risk for additional complications.

We observed omphalocele, absence of radii, hypoplasia of one humerus, a hemivertebra, and syndactyly in a stillborn male at 22 weeks of gestation. Craniofacial and genitourinary abnormalities were absent. DNA measurement by flow cytometry on a paraffin-embedded autopsy specimen showed 32% triploid cells. ORR (omphalocele-radial ray) complex appears to be a consistent combination, and diploid-triploid mixoploidy may be one of its causes.

We observed a girl with an interrupted, left inferior vena cava with hemiazygous continuation, bilateral superior venae cavae, heart defects, and sacral agenesis. She had macrostomia and bilateral ear tags and pits, as in oculoauriculovertebral defect. Maternal diabetes was present. The combination, which we call OAV-heterotaxia complex, supports the view that some cases of oculoauriculovertebral defect may be part of a midline field defect of blastogenesis.

The combination of MURCS association (Müllerian duct and renal agenesis, upper limb and rib anomalies) and occipital encephalocele occurred in a stillborn girl of 41 weeks gestation. The malformations are compatible with a defect in the organization of the paraxial mesoderm that gives rise to occipital, cervical, and thoracic somites and adjoining intermediate mesoderm. These structures contribute to the occipital bone, cervical spine, upper limbs, and urogenital system. Brain imaging may be useful in assessing MURCS patients, if cranial malformations prove to be clinically important in these individuals.

Objective: To establish normative measures of the biologic growth of fetal choroid plexus circumference (CPC) and ventricular circumference (VC) in normal pregnant women., Study Design: We studied 185 women with uncomplicated pregnancies ranging in gestational age from 14 to 26 weeks and undergoing ultrasound examination for genetic amniocentesis. CPC and VC were measured with a transverse scan of the fetal head to establish normative values. Following establishment of CPC/VC ratios for normocephalic fetuses, an additional eight fetuses with suspected ventriculomegaly at the time of routine ultrasound were scanned., Results: Of the 185 fetuses for normal pregnancies who met the criteria for this study, all were normocephalic at birth. Of the eight fetuses who were suspected to have ventriculomegaly on ultrasound, all were diagnosed as moderately to severely hydrocephalic on autopsy after second-trimester termination., Conclusion: The CPC/VC ratio is able to unequivocally distinguish between the overtly hydrocephalic and normocephalic fetus. The results of this study suggest that CPC and VC measurements may be valuable when hydrocephalus is suspected and there are equivocal ventricular/hemispheric width measurements.

A catheter-based, miniature ultrasound transducer, operating at a frequency of 12.5 MHz, was introduced transcervically into the uterine cavity of 18 pregnant women about to undergo first-trimester abortion. Transcervical sonography showed the yolk sac and embryonic structures, such as brain vesicles, limb buds, liver, spinal canal, and umbilical cord with blood flow, in eight embryos at 5-8 menstrual weeks of age. As an investigational technique, catheter-assisted transcervical sonography offers a new diagnostic approach to imaging of the first-trimester human embryo.

Congenital heart disease as a complicating factor in pregnancy has assumed increasing clinical importance because improved techniques of surgical repair have resulted in a larger proportion of affected women living to the reproductive age. The most serious forms are those associated with pulmonary hypertension (such as the Eisenmenger syndrome), which carry a prohibitively high risk of maternal death. Complex forms of cyanotic heart disease, of which the commonest is the tetralogy of Fallot, are only slightly less dangerous. It has recently been recognized that children born to women with congenital heart disease are at increased risk of having cardiac defects; fetal echocardiography is therefore an important diagnostic test. Optimal care of the pregnant woman with congenital heart disease is best provided by a team consisting of internist-cardiologist, obstetrician-perinatologist, obstetric anesthesiologist, and ultrasonographer-echocardiographer.

A patient with a proximal deletion of the long arm of chromosome 4 is presented. This patient and 6 others previously described appear to have similar findings of moderate to severe developmental delay, small size, small hands and feet, and similar facial appearance. These patients appear to be quite different from those with more distal 4q deletions.

Ritodrine, terbutaline, and magnesium sulfate have all been used in the United States as tocolytic drugs. Studies have shown each of these drugs to be effective in suppressing preterm labor. The current study was undertaken in order to compare their relative safety and efficacy and to evaluate the effectiveness of a second drug when the first-used drug failed to stop contractions. No differences in efficacy could be demonstrated between the drugs; however, there was a marked difference in the incidence of maternal side effects. Because of an unacceptable level of side effects, we have stopped the use of terbutaline at our institution.

Femur length to abdominal circumference ratio was used to predict the adequacy of fetal growth for patients undergoing treatment for preterm labor. When quantitated in this way, no correlation could be found between fetal growth and effectiveness of tocolytic therapy. Despite its correlation in retrospective studies, poor fetal growth was not correlated with preterm delivery to any measurable extent in this prospective trial.