Does preeclampsia predict the risk of late postpartum eclampsia?

Objective To investigate potential predictive symptoms of late postpartum eclampsia (LPE). Study Design Retrospective review of patients delivered at a single academic medical center and diagnosed with eclampsia greater than 48 hours postdelivery. Results Among 19 patients with eclampsia, 5 (26%) patients with confirmed eclampsia seized greater than 48 hours after delivery. None of these patients showed evidence of preeclampsia intrapartum or immediately postpartum and none received intrapartum magnesium sulfate. Prior to seizure activity, 4 of 5 (80%) patients had increased blood pressure and 2 of 5 (40%) had central nervous system symptoms (headache and visual changes). Conclusion Gestational hypertension (GHTN) may be a risk factor for LPE. Consideration of seizure prophylaxis for patients with GHTN may facilitate the prevention of LPE.

Early compensatory adaptations in maternal undernourished pregnancies in rats: role of the aquaporins.

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.

Prediction of preterm birth: nonsonographic cervical methods.

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.

AQP1 gene expression is upregulated by arginine vasopressin and cyclic AMP agonists in trophoblast cells.

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.

Adult sequelae of intrauterine growth restriction.

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.

Fetal ST segment heart rate analysis in labor: improvement of intervention criteria using interpolated base deficit.

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.

Cervical neck dislocation associated with the Zavanelli maneuver.

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.

Placental and fetal membrane Nephrin and Neph1 gene expression: response to inflammation.

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.

A randomized controlled trial of prophylactic maneuvers to reduce head-to-body delivery time in patients at risk for shoulder dystocia.

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.

Unopposed orexic pathways in the developing fetus.

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.

Pharmacokinetics of ionized versus total magnesium in subjects with preterm labor and preeclampsia.

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.