Neonatal blood pressure before and after delayed umbilical cord clamping.

OBJECTIVE: To describe values of blood pressure (BP) before and after delayed cord clamping (DCC) in healthy term neonates born to low risk pregnancies, examine differences in the temporal patterns of BP during this transition, and assess potential correlation of these parameters with maternal and perinatal clinical and demographic variables. METHODS: Prospective observational study of term infants eligible for DCC born vaginally from uncomplicated pregnancies. Neonatal BP was estimated noninvasively before DCC, at 30 min and 24 h of life. Median, minimum, maximum, mean and standard deviation, as well as percentiles for BP values were calculated. Pearson correlation assessed the correlation between demographic and clinical variables and BP measurements. Spearman correlation studied the association between BP parameters prior to DCC and Apgar scores. Repeated measures ANOVA and Tukey post hoc analyses were used to compare BP measurements over time. A p-value of <.05 was considered significant. RESULTS: A total of 54 patients were included. Mean neonatal birthweight was 3185 g and gestational age 39/3 weeks. The mean values for the systolic, diastolic, and mean BP prior to DCC were 97 ± 24.9 mmHg, 58 ± 21.9 mmHg and 67 ± 27.7 mmHg respectively. A statistically significant difference was detected when comparing BP values obtained before DCC with those measured afterwards (Figure 1). A positive correlation was found between SBP and MAP prior to DCC and Apgar scores at 1 min.[Figure: see text]. CONCLUSION: We describe novel values of BP before DCC in healthy term infants following vaginal delivery. Data suggest that neonates whose cord is clamped in a delayed fashion experience an increase blood pressures immediately after birth, followed by a significant drop within 30 min to levels that remain unchanged at 24 h of life. BP values obtained after DCC in our study are similar to those found by previous authors. Further studies are needed to determine the clinical significance of these findings and assess the potential of BP prior to DCC to evaluate immediate postnatal adaptation. LIMITATIONS: Results generalizability may have been limited by varying degrees of neonatal resuscitation, inability to perform more than one measurement before cord clamping ensued, as well as an unequal distribution of self-reported race in our cohort. Also, noninvasive BP estimates have proven less accurate that invasive methods. Finally, our cohort was comprised by a relatively small sample and larger studies will be required to corroborate our findings.

Middle cerebral artery peak systolic velocity in perinatal cytomegalovirus infection.

A middle cerebral artery peak systolic velocity value (MCA-PSV) persistently greater than 1.5 times the median of the normal population is utilized to detect moderate and severe anemia in fetuses at risk. Cytomegalovirus (CMV) is the most common perinatal infection and can cause fetal anemia. We present four cases with CMV perinatal infection. Although their MCA-PSV values were the highest recorded in normal as well as in anemic fetuses, only two of them developed moderate or severe anemia. These findings suggest that high MCA-PSV values in cases with perinatal CMV infection may have a different pathophysiologic mechanism than anemia.

Cell free fetal DNA to triage antenatal rhesus immune globulin: Is it really cost-effective in the United States?

OBJECTIVE: To compare the efficacy and costs of three different strategies of antenatal rhesus immune globulin (RhIG) administration in a US population. METHODS: A decision tree analysis was undertaken for universal antenatal RhIG administration based on RhD serologic paternity testing, universal administration without paternity, and selective antenatal RhIG administration using cell free fetal DNA (cfDNA) for RHD fetal typing. Rates of alloimmunization were calculated. Charges were determined for laboratory testing and obstetrical and neonatal treatments for the first pregnancy and cases of alloimmunization in the following pregnancy. RESULTS: The largest number of new RhD alloimmunization cases resulted from a strategy of universal RhIG that included paternity. Fewer cases resulted from a selective strategy; the least number of cases were associated with a universal approach that discounted paternity. When the costs of first pregnancies and alloimmunized second pregnancies were combined, a universal strategy that excludes paternity had the least costs followed by a selective strategy followed by a universal strategy that included paternity. CONCLUSION: The use of cfDNA to determine the selective use of antenatal RhIG would not be cost-effective in the United States. Universal antenatal RhIG without paternity is more effective in preventing new cases of alloimmunization than the current ACOG guideline.

Fetal anemia.

The diagnosis and management of fetal anemia has been at the forefront of advances in the fields of fetal physiology, immunology, fetal imaging, and fetal therapy among others. Alloimmunization and parvovirus infection are the leading cause of fetal anemia in the United States. The middle cerebral artery peak systolic velocity (MCA-PSV) diagnoses fetal anemia. Its discovery is considered one of the most important achievements in fetal medicine. Accumulation of experience in recent years as well as refinement of surgical techniques have led to safer invasive procedures. It is expected that long term follow-up of affected pregnancies, continues to reflect all these improvements in care. It is also expected that treatment of other less common causes of fetal anemia becomes more frequently reported and that the management principles of fetal anemia are successfully applied to other fetal pathologies.

Is mean platelet volume a better biomarker in pre-eclampsia?

AIM: Platelet activation and destruction is a well recognized feature of pre-eclampsia, but the current literature is contradictory regarding the role of mean platelet volume (MPV) in the diagnosis of this condition. We investigated whether MPV, compared with other routine laboratory markers such as platelet count, is a more significant biomarker of pre-eclampsia, giving special attention to the intrapartum period. METHODS: Biochemical and hematological markers along pregnancy including MPV were compared retrospectively between pre-eclampsia and matched controls. Laboratory marker data were compared using independent t-test. A logistic regression model was used to compare the strength of the associations of MPV and other routine markers such as platelet count with pre-eclampsia. Receiver operating characteristic curves were plotted. RESULTS: There were a total of 150 cases of pre-eclampsia and 297 controls. In the pre-eclampsia group, there were 60 cases of mild pre-eclampsia (40.0%); 84, severe (56.0%); and six of eclampsia (4.0%). MPV was significantly higher in the pre-eclampsia than in the control group (11.3 ± 1.0 vs 10.1 ± 0.8 fL, P = 0.002). On multivariate analysis, MPV was the only statistically significant biomarker of pre-eclampsia (OR, 4.5; 95%CI: 1.5-13.7), and severe pre-eclampsia (OR, 6.2; 95%CI: 1.6-24.6); performing superiorly to platelet count. CONCLUSIONS: Mean platelet volume is a more significant biomarker of pre-eclampsia. It is more significantly associated with this condition than other routinely measured laboratory markers such as platelet count. MPV is routinely obtained on complete blood cell count and its utilization in the assessment of pre-eclampsia in a clinical setting should continue to be evaluated.

Exploring the Pharmacokinetic Profile of Remifentanil in Mid-Trimester Gestations Undergoing Fetal Intervention Procedures.

Background: Indications for surgery during pregnancy have increased. Specifically fetal interventions have increased from conditions that were considered lethal like twin-twin transfusion syndrome and severe fetal anemia to non-lethal conditions like myelomeningocele. The optimal anesthetic agent for in utero surgery is yet to be determined. Success of the procedure is often dictated by the efficacy of the anesthetic to immobilize the fetus without over-sedating mom. Remifentanil is used as preferred agent due to its short half-life however pharmacokinetics in pregnancy is unknown. Objective: To determine the pharmacokinetic parameters of remifentanil in a mid-trimester pregnant patient population undergoing fetal intervention. Study Design: A validated liquid chromatography assay with ultraviolet absorbance was employed to estimate maternal serum remifentanil levels. Blood samples were obtained at baseline and at selected time points: 5, 15, 30, 45, 60 min after the beginning of the remifentanil infusion and at 15, 30, and 60 min post end of infusion. Results: Ten pregnant patients were enrolled in the study however only eight patients had sampling obtained at all time points. The mean gestational age was 22.2 (±2.7) weeks, maternal age was 27.8 (±5.1) years and body mass index was 29.6 (±6.3). After receiving a continuous infusion of remifentanil, mean total dose was 975.3 µg, Cmin was 2.0 ng/mL and Cmax was 8.4 ng/mL. A two-compartment model best described the plasma remifentanil data. Mean pharmacokinetic parameters were: volume of distribution (Vdc) = 124.6 L (16.2-530.8 L), maternal remifentanil total clearance (Clt) = 170.7 L/h (17.7-486.9 L/h), and half-life (t½) = 0.6 h (0.2-0.9 h). The maternal remifentanil area under the curve (AUC) ranged from 2.7 to 21.7 µg/L*h. The mean alpha-acidic glycoprotein was 124.8 mg/dL (81.3-149.8). Conclusion: The pharmacokinetic profile of remifentanil in pregnant women is similar to previously reported general population profiles. This data did provide potential rationale for the clinical observations why when remifentanil is dosed based on non-pregnant guidelines, it did not uniformly provide adequate fetal immobilization as per anecdotal perception of operating fetal surgeons. These findings are important for the development of further clinical studies to optimize dosing for surgery during pregnancy including the estimation of placental transfer and total fetal exposure.

Differences in clinical presentation and pregnancy outcomes in antepartum preeclampsia and new-onset postpartum preeclampsia: Are these the same disorder?

OBJECTIVE: New-onset postpartum preeclampsia is a poorly defined condition that accounts for a significant percentage of eclampsia cases. It is unclear whether new-onset postpartum preeclampsia is a different disorder from or belongs to the same spectrum of classic antepartum preeclampsia. The objective of this study was to compare the clinical presentation and pregnancy outcomes of antepartum preeclampsia and new-onset postpartum preeclampsia. METHODS: A retrospective study including 92 patients with antepartum preeclampsia and 92 patients with new-onset postpartum preeclampsia was performed. Clinical presentation and pregnancy outcomes were compared. Chi-square test was used to analyze categorical variables, and independent t-test and Mann-Whitney U-test for numerical variables. P-values of <0.05 were used to indicate statistical signifi cance. RESULTS: Patients with antepartum preeclampsia and new-onset postpartum preeclampsia differ significantly in profile, symptoms at presentation, laboratory markers and pregnancy outcomes. CONCLUSION: New-onset postpartum preeclampsia has a distinct patient profile and clinical presentation than antepartum preeclampsia, suggesting they may represent different disorders. Characterization of a patient profile with increased risk of developing this condition will help clinicians to identify patients at risk and provide early and targeted interventions to decrease the morbidity associated with this condition.

Maternal race and neonatal outcomes after elective repeat cesarean delivery.

OBJECTIVE: To determine the effect of race in the risks of prematurity-related complications (PRC) after elective repeat cesarean delivery (ERCD). METHODS: The NCHS-CDC Database for the U.S. (2004-2008) was used. ERCD cases were included. Exclusion criteria were multiple gestation, trial of labor, fetal anomalies, history of diabetes and/or hypertension. PRC analyzed were: Apgar score, assisted ventilation, intensive care admission, surfactant use, antibiotic use, seizures. Regression analysis was performed to calculate the odds ratio (OR) of these variables. Deliveries at 36-40 weeks were studied with 40 weeks as reference. RESULTS: Totally, 785,340 ERCDs were performed between 36 and 40 weeks. For the overall population, there was not difference in adverse outcomes between 39 and 40 weeks. The rates of PRC were significantly higher in newborns at 38 compared to 39 weeks, with similar findings in sub-analysis of whites. For African-Americans, the rate of PRC was not significantly different at 38 compared to 39 weeks. CONCLUSIONS: We report increased rates of PRC after ERCD before 39 weeks, similar findings from smaller hospital-based studies. For African-American newborns, there was no further decrease in PRC after 38 weeks suggesting earlier maturation of these fetuses. The study does not propose changing the current 39 weeks threshold for ERCD.

Serial intrauterine transfusions for a hydropic fetus with severe anemia and thrombocytopenia caused by parvovirus: lessons learned.

Introduction Fetal exsanguination is a rare complication of cordocentesis. Successful correction of fetal thrombocytopenia is essential for the reduction of risks. Case Report A 25-year-old, gravida 3, P2-0-0-0-2, was referred at 27 weeks of gestation for evaluation of newly diagnosed nonimmune hydrops secondary to parvovirus infection. Despite the use of ancillary platelet transfusions to correct the severe fetal thrombocytopenia, prolonged bleeding from the cord puncture site still occurred, necessitating five intrauterine transfusions to ultimately correct the fetal anemia. Conclusions The use of a smaller-diameter procedure needle, correction of the fetal thrombocytopenia early in the procedure, and external cord compression with the ultrasound transducer were ultimately successful measures in allowing for minimal loss of transfused red cells from the intravascular compartment.

Management and prevention of red cell alloimmunization in pregnancy: a systematic review.

OBJECTIVE: To evaluate the application of new technologies to the management of the red cell alloimmunized pregnancy. DATA SOURCES: We searched three computerized databases for studies that described treatment or prevention of alloimmunization in pregnancy (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials [1990 to July 2012]). The text words and MeSH included Rhesus alloimmunization, Rhesus isoimmunization, Rhesus prophylaxis, Rhesus disease, red cell alloimmunization, red cell isoimmunization, and intrauterine transfusion. METHODS OF STUDY SELECTION: Of the 2,264 studies initially identified, 246 were chosen after limiting the review to those articles published in English and crossreferencing to eliminate duplication. TABULATION, INTEGRATION, AND RESULTS: Both authors independently reviewed the articles to eliminate publications involving less than six patients. Special emphasis was given to publications that have appeared since 2008. CONCLUSION: Quantitative polymerase chain reaction can be used instead of serology to more accurately determine the paternal RHD zygosity. In the case of unknown or a heterozygous paternal RHD genotype, new DNA techniques now make it possible to diagnose the fetal blood type through cell-free fetal DNA in maternal plasma. Serial Doppler assessment of the peak systolic velocity in the middle cerebral artery is now the standard to detect fetal anemia and determine the need for the first intrauterine transfusion. Assessment of the peak systolic velocity in the middle cerebral artery can be used to time the second transfusion, but its use to decide when to perform subsequent procedures awaits further study. New data suggest normal neurologic outcome in 94% of cases after intrauterine transfusion, although severe hydrops fetalis may be associated with a higher risk of impairment. Recombinant Rh immune globulin is on the horizon. Cell-free fetal DNA for fetal RHD genotyping may be used in the future to decide which patients should receive antenatal Rh immune globulin.

An overview of first-trimester screening for chromosomal abnormalities.

The last decade has witnessed the transformation of first-trimester Down syndrome screening from an aspiration to a clinical reality. First-trimester screening now equals or exceeds the diagnostic accuracy of conventional midtrimester screen while realizing an important desire of pregnant women for early diagnosis. Beyond the obvious benefits to individual patients, this accomplishment emphatically affirms the centrality and value of clinical research.