Regulation of amniotic fluid volume.

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.

Amniotic fluid water dynamics.

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.

Placental and membrane aquaporin water channels: correlation with amniotic fluid volume and composition.

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.

Clavicle fracture in labor: risk factors and associated morbidities.

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.

Intrapartum screen for diabetes in patients without prenatal care: use of labor admission serum glucose.

OBJECTIVE: For patients presenting in labor with no prenatal care, a rapid screening test for gestational diabetes would potentially aid in decisions for tocolysis (e.g., preterm patients) and mode of delivery (e.g., large for gestational age). We sought to determine whether a labor admission serum glucose is of predictive value in the diagnosis of gestational diabetes. METHODS: We obtained labor admission glucose values for laboring patients and compared these with 1-h (50-g) postglucola (1 degree PG) screens obtained at 24 to 32 weeks' gestation. Diabetics being treated with insulin were excluded from the study. Labor admission serum glucose values were compared to 1 degrees PG values by linear regression. Sensitivity and specificity of admission glucose for identification of a positive 1 degree PG (140 mg/dl) were evaluated by a receiver operator curve (ROC). RESULTS: A total of 98 patients with both 1 degree PG screens and labor admission glucose were identified. Linear regression showed no significant correlation of labor admission glucose and 1 degree PG values (r = 0.13; P = 0.9). The ROC failed to demonstrate an optimal admission random glucose cutoff value for diagnosis of diabetes. CONCLUSIONS: In laboring patients without insulin-requiring diabetes, labor admission glucose does not predict an abnormal 1 degree PG and thus does not aid in labor management of patients with suboptimal prenatal care.

Objective definition of shoulder dystocia: a prospective evaluation.

OBJECTIVE: The current study was undertaken to validate the objective definition of shoulder dystocia in a prospectively evaluated group of patients. STUDY DESIGN: Selected vaginal deliveries from January 1995 to December 1996 (N = 722) were evaluated for head-to-body delivery time and use of ancillary obstetric maneuvers. Charts were reviewed for perinatal and outcome data. RESULTS: Ninety-nine deliveries were complicated by shoulder dystocia and 623 deliveries had no shoulder dystocia. The objective definition described infants with lower 1-minute Apgar scores and increased birth weight. All fetal injuries were in the shoulder dystocia group. Duration of the second stage was significantly associated with a diagnosis of shoulder dystocia. The risk of shoulder dystocia was increased with maternal diabetes, but it was not correlated with birth weight in diabetics. CONCLUSIONS: The objective definition of shoulder dystocia identified a group of patients with an increased birth weight and risk of fetal injuries. The use of an objective definition will assist the evaluation of prophylactic and treatment proposals for shoulder dystocia.

Omphalocele with absent radial ray (ORR): a case with diploid-triploid mixoploidy.

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.

Anomalous inferior and superior venae cavae with oculoauriculovertebral defect: review of Goldenhar complex and malformations of left-right asymmetry.

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.

Occipital encephalocele and MURCS association: case report and review of central nervous system anomalies in MURCS patients.

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.

Ratio of choroid plexus circumference to ventricular circumference in the diagnosis of fetal hydrocephalus.

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.

Transcervical sonography: an investigational technique for visualization of the embryo.

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.

Pregnancy and congenital heart disease.

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 prospective trial of the femur length to abdominal circumference ratio to predict the outcome of preterm labor.

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.

A patient with an interstitial deletion of the proximal portion of the long arm of chromosome 4.

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.

A comparison of ritodrine, terbutaline, and magnesium sulfate for the suppression of preterm labor.

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.