Third-trimester in utero fetal brain diffusion tensor imaging fiber tractography: a prospective longitudinal characterization of normal white matter tract development.

BACKGROUND: White matter is responsible for inter-neuronal connections throughout the brain that are a driving force in cognitive development. Diffusion tensor imaging (DTI) fiber tractography has been used to evaluate white matter development in the fetal brain; however, longitudinal studies of DTI fiber tractography to assess white matter development in the third trimester are lacking. OBJECTIVE: To characterize in utero longitudinal changes in the fetal brain DTI fiber tracts of normal third-trimester fetuses. MATERIALS AND METHODS: For this single-center prospective longitudinal observational pilot study, we recruited 28 pregnant females with normal third-trimester pregnancies who had routine prenatal ultrasound. MRI of the in utero fetal brain was performed with a Siemens 1.5-tesla (T) Espree scanner at 31 weeks, 33 weeks and 36 weeks of gestation, with 14 DTI tractography parameters quantified in 7 brain regions using DTI-studio version 2.4 (Johns Hopkins University, Baltimore, MD; n=98 measurements). We used multilevel mixed models to examine the relationship between longitudinal changes in DTI measurements and between 98 DTI measurements at 31 weeks and 4 routine fetal brain anatomical biometrics (n=392 assessments). RESULTS: We observed statistically significant decreases in radial diffusivity and apparent diffusion coefficient in 13 of 14 brain regions from 31 weeks to 36 weeks of gestation (P<0.001 for all regions except the genu of the corpus callosum). Significant decreases in radial diffusivity from weeks 33 to 36 and weeks 31 to 36 were seen in the corticospinal tracts, centrum semiovale, posterior limb of the internal capsule, and crus cerebri (P<0.001 for all). When considering all possible combinations of DTI fiber tract measurements and the routine morphological fetal brain biometrics, only 6% (24/392) had a significant association (P<0.05), indicating relative independence of the DTI fiber tract measurements from anatomical biometrics. CONCLUSION: In utero longitudinal changes in fetal brain DTI fiber tractography are quantifiable in normal third-trimester fetuses and are largely independent of morphological brain changes.

Acute kidney injury associated with preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

OBJECTIVE: To determine the prevalence of acute kidney injury (AKI), placental abruption and postpartum hemorrhage in patients with preeclampsia or HELLP syndrome. STUDY DESIGN: A retrospective study of patients with preeclampsia or HELLP syndrome treated at the University of Mississippi Medical Center from January 2000 through December 2010. MAIN OUTCOME MEASURES: Relationships among the obstetric complications of placental abruption, postpartum hemorrhage, and AKI (serum creatinine >107 µmol/L) of women with preeclampsia or HELLP syndrome. Additional analysis was undertaken to explore if there was a correlation between postpartum hemorrhage/placental abruption and the severity of HELLP syndrome according to the Mississippi classification system. RESULTS: Data from 1276 women over 11 years were included in the analysis. 67 of 466 patients (14.4%) with HELLP syndrome and 38 of 810 preeclampsia patients (4.7%) met criteria for AKI. Women with either placental abruption or postpartum hemorrhage had statistically significant increased odds of also having AKI (p < 0.01). Women with HELLP and AKI were also more likely to experience either placental abruption or postpartum hemorrhage. Women with Class 1 HELLP with placental abruption or postpartum hemorrhage were also more likely to have AKI than women with preeclampsia. CONCLUSION: HELLP syndrome, AKI and placental abruption or postpartum hemorrhage appear to be interrelated. AKI occurs more frequently in women with HELLP syndrome with or without associated postpartum hemorrhage and placental abruption.

Tachysystole Following Cervical Ripening and Induction of Labor Is Not Associated with Adverse Outcomes.

PURPOSE: This study was aimed at determining if significant uterine tachysystole was associated with adverse fetal or neonatal outcomes during cervical ripening and induction of labor. METHODS: Women undergoing cervical ripening and subsequent labor induction (n = 905) were assessed for tachysystole, defined as ≥6 contractions in each of 2 consecutive 10-minute windows. Women with ≥3 episodes of tachysystole were compared to women with no tachysystole. RESULTS: Over a 5-year period, 70% of the 905 participants (n = 631) had no tachysystole, 143 had 1 or 2 episodes whereas 131 or 15% had ≥3 episodes (p = 0.991). The cesarean delivery rate was lower among those with tachysystole (28.2 vs. 34.1%), but the difference was not significant (p = 0.197). Non-reassuring fetal tracings were more common in the tachysystole group (14.4 vs. 21.4%, p = 0.017), but the Apgar scores at 5 min and the umbilical cord pH and base excess were similar between the 2 groups (p = 0.502, p = 0.435, and p = 0.535, respectively). CONCLUSIONS: Tachysystole was not associated with adverse perinatal outcomes when compared to women with no tachysystole during cervical ripening and induction of labor.

Risks and Benefits of Magnesium Sulfate Tocolysis in Preterm Labor (PTL).

The U.S. Food and Drug Administration issued a drug safety communication on 05/30/2013 recommending "against prolonged use of magnesium sulfate to stop preterm labor (PTL) due to bone changes in exposed babies." In September of 2013, The American Congress of Obstetrics and Gynecologists issued Committee Opinion No. 573 " Magnesium Sulfate Use in Obstetrics" , which supports the short term use of MgSO4 to prolong pregnancy (up to 48 hrs.) to allow for the administration of antenatal corticosteroids." Are these pronouncements by respected organizations short sighted and will potentially result in more harm than good? The FDA safety communication focuses on bone demineralization (a few cases with fractures) with prolonged administration of MgSO4 (beyond 5-7 days). It cites 18 case reports in the Adverse Event Reporting System with an average duration of magnesium exposure of 9.6 weeks (range 8-12 wks). Other epidemiologic studies showed transient changes in bone density which resolved in the short duration of follow up. Interestingly, the report fails to acknowledge the fact that these 18 fetuses were in danger of PTD and the pregnancy was prolonged by 9.6 weeks (e.g. extending 25 weeks to 34.6 wks), thus significantly reducing mortality and morbidity. Evidence does support the efficacy of MgSO4 as a tocolytic medication. The decision to use magnesium, the dosage to administer, the duration of use, and alternative therapies are physician judgments. These decisions should be made based on a reasonable assessment of the risks of the clinical situation (PTL) and the treatments available versus the benefits of significantly prolonging pregnancy.

Maternal hemodynamics by thoracic impedance cardiography for normal pregnancy and the postpartum period.

OBJECTIVE: To establish normative impedance cardiography values for the second half of pregnancy and up to 48 hours postpartum after either vaginal or cesarean delivery. METHODS: A single-center prospective observational institutional review board-approved study of normotensive women (n=168) using thoracic impedance cardiography performed at specific times during gestation. Antepartum testing was performed at three time periods: 20-27 weeks, 28-33 weeks, and 34-40 weeks of gestation. Postpartum testing was undertaken after the immediate puerperium at 6-23 hours and 24-48 hours after vaginal or cesarean delivery. Data analysis was performed using STATA software; data are expressed as mean±standard deviation. RESULTS: All seven of the patient groups studied were comparable with regard to demographic features; 80% of the study participants were African American. Group means obtained between 20 and 40 weeks of gestation and postpartum after vaginal and cesarean delivery fell within the "normal range" of the hemodynamic graph that was developed to associate mean arterial pressure and systemic vascular resistance. The thoracic fluid content group means in both vaginal and cesarean delivery groups were higher than the antepartum patient groups. The thoracic fluid content mean after cesarean delivery at 48 hours is significantly higher than the mean value recorded between 20 and 27 weeks of gestation (P<.05). The systemic vascular resistance systemic vascular resistance means in each of the postpartum groups were significantly higher than the late second-trimester group means recorded at 20-27 weeks of gestation (P<.05). CONCLUSION: The normative values reported in this investigation can be used to interpret and assess similarly tested patients with hypertensive or otherwise complicated pregnancy. LEVEL OF EVIDENCE: III.

Retroperitoneal lymphatic malformation and transverse testicular ectopia: a unique clinical presentation.

This case report presents a fetal patient diagnosed in utero with a retroperitoneal lymphatic malformation by ultrasound and followed through gestation. At birth the child was noted to have a right inguinal hernia with two palpable testicles. Plan for partial resection and hernia repair with postoperative sclerotherapy was made. At the time of hernia repair, transverse testicular ectopia was diagnosed, and subsequent extraperitoneal transposition orchiopexy was performed following partial resection of the lymphatic malformation. Delayed sclerotherapy in combination with partial resection afforded definitive treatment of the residual lymphatic malformation as the patient demonstrates no recurrence over one year later. This is the first reported case to suggest a direct relationship between transverse testicular ectopia and a retroperitoneal lymphatic malformation.

EXIT procedure: a report of the first three Mississippi cases.

The University of Mississippi Medical Center has initiated a state-of-the-art fetal center. This project involves collaboration between multiple disciplines including anesthesiology, pediatric surgery, maternal-fetal medicine, radiology, neonatology, genetics, pediatric cardiology and other pediatric subspecialties, nursing, and social work. Complicated fetal patients from throughout the southeastern U.S.A. may be referred to this center and benefit from new and innovative interventions that have not been available to this region in the past. The first three EXIT (ex-utero intrapartum treatment) procedures were recently performed at Batson Children's Hospital at the University of Mississippi Medical Center. Our objective is to share our recent experiences with this novel procedure and to detail some of the basics of an EXIT delivery.

Fetal gastroschisis: epidemiological characteristics and pregnancy outcomes in Mississippi.

We describe the epidemiological characteristics and identify maternal-fetal outcomes in pregnancies complicated by gastroschisis. We retrospectively reviewed 115 cases of gastroschisis at the University of Mississippi Medical Center. The incidence of gastroschisis trended upward between 2000 and 2008. Significant proportions of mothers were nonobese, nulliparous, teenagers, smokers, and nonconsumers of alcohol. Infants delivered at > 36 weeks or without sepsis had shorter hospital stay (HS) and interval to full enteral feeding (FEF). The rates of low birth weight (LBW), fetal growth restriction, and spontaneous preterm birth (PTB) were 63%, 45%, and 24%, respectively. Bowel atresia was noted in 9%. Rates of primary closure (25%), neonatal sepsis (29%), fetal death (2%), and infant mortality (4%) were notable. Median HS and interval to FEF were 40 and 30 days, respectively. The incidence of gastroschisis is increasing in Mississippi. Sepsis, LBW, and PTB are key determinants of poor infant outcomes.

Prediction of placenta accreta by ultrasonography and color Doppler imaging.

OBJECTIVE: To determine the accuracy of ultrasound and color flow Doppler to diagnose placenta accreta. METHODS: Respectively, ultrasound images consistent with signs of placenta accreta (concomitant previa, numerous vascular lacunae, absent lower uterine segment between bladder-placenta, turbulent or complicated blood flow at the uteroplacental interface) were correlated with findings at the time of surgery and pathologic examination. RESULTS: Over 64 months, 12 cases with suspected placenta accreta by ultrasound were studied. The median gestational age at first diagnosis was 25 weeks and 92% had a previa while all had at least one previous cesarean delivery. At surgery, 83% (10/12) had an adherent placenta requiring hysterectomy (eight accreta, one increta, and one percreta). There were two false positives (one complete previa, one low-lying placenta with vasa previa). Nine of 12 women (75%) required blood transfusions due to a mean hematocrit nadir of 22.7 ± 4.6%. The mean number of packed red blood cell units transfused was 4.9 ± 4.7 units (range 2-17 units). CONCLUSION: Sonography coupled with color-flow Doppler appears helpful in allowing antenatal diagnosis of accreta.

Neu-Laxova syndrome: a prenatal diagnosis.

Neu-Laxova syndrome is a rare autosomal recessive congenital disorder. Prenatal diagnosis is possible via second trimester ultrasonography. Characteristic ultrasound findings include hydramnios, severe intrauterine growth restriction, craniofacial and CNS anomalies, limb contractures, skin lymphedema, skin restrictions, and akinesia. Fewer than 70 cases have been reported, and no survival beyond six months of age is known with most neonatal deaths occurring within the first few days of life. Overall, this is a lethal condition after birth secondary to severe lung hypoplasia and brain anomalies. Herein we report a recent case from our institution with prenatal diagnosis.

A randomized clinical trial comparing vaginal misoprostol versus cervical Foley plus oral misoprostol for cervical ripening and labor induction.

We compared labor induced by vaginal misoprostol versus a supracervical Foley catheter and oral misoprostol. Singleton pregnancies at > or = 24 weeks' gestation were randomized to either an initial 25-microg dose of intravaginal misoprostol, followed by 50-microg intravaginal doses at 3- to 6-hour intervals, or a supracervical Foley balloon and 100 microg of oral misoprostol at 4- to 6-hour intervals. Primary outcome was time from induction to delivery. One hundred twenty-six women were randomized to vaginal misoprostol alone (group I) and 106 women to Foley and oral misoprostol (group II). The groups were similar in age, weight, gestational age, parity, indication for induction of labor, and oxytocin use. Cesarean delivery rates at 37% and cesarean indications were similar ( P = 0.25). The time from induction to delivery in group II (12.9 hours) was significantly shorter than that in group I (17.8 hours, P < 0.001). Uterine tachysystole occurred less often in the vaginal misoprostol group (21% versus 39%, P = 0.015). Compared with vaginal misoprostol, delivery within 24 hours was significantly more likely with a Foley balloon and oral misoprostol. The use of terbutaline and peripartum outcomes were similar in the two groups.

Risk factors for cesarean delivery in preterm, term and post-term patients undergoing induction of labor with an unfavorable cervix.

BACKGROUND/AIMS: To identify risk factors for cesarean delivery in patients with an unfavorable cervix undergoing an indicated induction of labor. METHODS: This is a secondary analysis of combined data from three prospective randomized trials comparing cervical ripening methods in singleton pregnancies with an unfavorable cervix seeking to identify risk factors for cesarean delivery. RESULTS: Nine hundred and five women underwent an induction of labor for a variety of indications. Gestational age ranged from 27.0-42.8 weeks (mean of 37.8 weeks) and initial Bishop's score from 0-6 (mean 2.5). There were 613 vaginal deliveries (67.7%) and 292 cesarean deliveries (32.2%). Factors associated with an increased risk for cesarean delivery included nulliparous status, Bishop's score 40 and diabetes mellitus. CONCLUSIONS: Risk factors for cesarean delivery in women undergoing an indicated induction include a low Bishop's score, high BMI, nulliparity and diabetes.

Postpartum plasma exchange as adjunctive therapy for severe acute fatty liver of pregnancy.

Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic compromise that poses significant fetal-maternal risk. Plasma exchange (PEX) is an effective bridge therapy to sustain liver function and enable hepatocellular regeneration to occur in nonpregnant patients following acute decompensation of a chronic liver disease or while awaiting liver transplantation. The application of PEX for patients with AFLP is a novel concept; since 1988 we have utilized postpartum PEX (PPEX) as adjunctive medical therapy for six patients with severe AFLP. Before PPEX initiation, four patients had signs and symptoms of encephalopathy, three required ventilatory support, five had advanced liver insufficiency, and all six were developing renal failure. PPEX was initiated 2-8 days following delivery and repeated (two to four times, mean = 3) at 24-48-h intervals thereafter. All patients responded with composite clinical (symptoms/signs) and laboratory improvement; the average length of hospitalization following final PPEX for five of six patients was 7 days. No significant PPEX-related complications occurred. PPEX utilization in patients with severe AFLP may enhance maternal recovery by preventing secondary sequelae from hepatic insufficiency until spontaneous healing can occur. Further study appears to be indicated to validate a role for PPEX as supportive therapy for puerperal patients with AFLP suffering multiorgan failure.

Pregnancy loss after first trimester viability in women with sickle cell trait: a preliminary report.

BACKGROUND: Traditionally, sickle cell trait has not been associated with a higher risk of fetal death, but we noted several, which led us to assess all such pregnancies. METHODS: In this retrospective study, 131 patients with sickle cell trait were analyzed over a two-year period. The Institutional Review Board approved the collection of deidentified data. RESULTS: Subjects were African-American with an average age of 23.9 years, and average gestational age at delivery of 30.1 weeks. There were 10 (8.13%) intrauterine fetal deaths (IUFDs), and one neonatal death. Ascending amniotic fluid infection was noted in 50% and 92% meconium histocytes. All placentas had sickling in the intervillous space and the decidual vessels. CONCLUSIONS: Sickling in the decidual vessels and poor placental perfusion may play a role in pregnancy loss in excess of what has previously been reported. A cohort control study appears to be in order. NARRATIVE: Pregnant women with sickle cell trait are thought not to have increased maternal or fetal mortality/morbidity. Over a two year period, we studied 131 women with this hemoglobinopathy and found that 10.6% had intrauterine growth retardation (IUGR), 8.4% preterm premature rupture of the membranes, 8.1% intrauterine fetal demise (n = 10) at most occurring at 16 to 24 weeks, and one neonatal death. Amniotic fluid infection was noted in 50%, and meconium histocytes indicating intrauterine hypoxia were noted, as was unsuspected sickling in the placental vasculature. Based on this case series, sickle cell trait may not be as benign for the fetus as was previously thought.

Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison.

OBJECTIVE: To compare glycemic control and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with metformin vs. insulin. STUDY DESIGN: Women with GDM not controlled with diet and exercise were randomized to metformin (n = 32) or insulin (n = 31). The levels of glycemic control as well as maternal/neonatal complications were evaluated. RESULTS: The mean (+/- SD) fasting and 2-hour postprandial blood glucose did not differ statistically between the 2 treatment groups. No patient failed metformin and required insulin. The majority (27/32) were easily controlled on the initial dosage (500 mg twice a day). Gestational age at entry and delivery (p = 0.077, 0.412) were similar. The difference in the rate of cesarean delivery was not statistically significant between the 2 groups (p = 0.102). Neonatal statistics were also not different between the metformin and insulin groups: birth weight, Apgar score at 5 minutes, respiratory distress syndrome, hyperbilirubinemia, neonatal hypoglycemia and neonatal intensive care unit admission (p = 0.144-0.373). CONCLUSION: Based on these preliminary data, metformin appears to be an effective alternative to insulin in the treatment of GDM.

Prenatal diagnoses and outcomes of congenital diaphragmatic hernia.

OBJECTIVE: To describe the prenatal diagnoses and clinical outcomes of congenital diaphragmatic hernia (CDH). METHODS: A retrospective case series was developed by reviewing 16,983 ultrasounds performed between March 2003 and January 2006 for the prenatal diagnosis of CDH. Medical records of each mother/infant pair were reviewed for demographic information, ultrasound findings, obstetric management, and outcomes. RESULTS: Nineteen fetuses were diagnosed with CDH. Only one was lost to follow-up. Median gestational age at diagnosis was 28.4W (range 17.6-36.6). Fifteen cases (79%) were left sided, 3 (16%) were right-sided, and 1 (5%) was bilateral. Seven fetuses (39%) had additional abnormalities, the most common being a single umbilical artery. Ten patients (52.6%) underwent amniocentesis for karyotype; none were aneuploid. Three patients developed hydramnios. All 18 infants were liveborn. Seven infants (39%) died shortly after birth, 6 (33%) underwent surgery with subsequent discharge, and 5 (28%) were transferred to another center. Three of these died after transfer. CONCLUSION: Prenatal diagnosis of CDH portends a poor prognosis. Thirty-nine percent of infants with this diagnosis (7/18) did not survive to undergo surgery or transfer to another facility and overall mortality was 56% (10/18). Targeted ultrasonography, extensive counseling of parents, and delivery at a tertiary care center is recommended.

Thrombotic thrombocytopenic purpura masquerading as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in late pregnancy.

BACKGROUND: Thrombotic thrombocytopenic purpura rarely presents during late pregnancy or immediately postpartum. This report describes the clinical course of a patient considered to have hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome but later determined to have thrombotic thrombocytopenic purpura. CASE: At 37 weeks of gestation, a multiparous woman was diagnosed with HELLP syndrome. She received high-dose dexamethasone, magnesium, antihypertensives, and platelets before delivery. Over the next 36 hours, renal function acutely worsened and death ensued. One week after death a plasma ADAMTS13 activity of 4% was reported. CONCLUSION: Thrombotic thrombocytopenic purpura can mimic HELLP syndrome late in gestation. Lack of response to dexamethasone within 12-24 hours and atypical relationships among laboratory values are two clues that thrombotic thrombocytopenic purpura may be the underlying pathology and that plasma exchange is emergently needed.

Pregnancy loss after first-trimester viability in women with sickle cell trait: time for a reappraisal?

OBJECTIVE: The purpose of this study was to evaluate the obstetric outcomes and pathologic findings in women with sickle cell trait. STUDY DESIGN: In this retrospective case control study, pregnant women with sickle cell trait were studied over a 4-year period (2001-2005). The women who were delivered at > 16 weeks of gestation were compared with a cohort group of subjects with normal hemoglobin levels, and the placentas were sent for pathologic evaluation. RESULTS: A total of 180 pregnancies were studied with a like number of control patients. Subjects who had sickle cell trait demonstrated shorter average duration of pregnancy (233 +/- 45 days vs 255 +/- 34 days; P < .001) and lower birth weight (2114 +/- 1093 g vs 2672 +/- 942 g; P < .001). The rate of fetal death was significantly higher among study group patients (3.5% vs 9.7%; P = .015) when compared with the control group. Additionally, in study women, acute ascending amniotic infection and meconium histiocytosis were noted much more frequently. Sickling in the intervillous space and decidual vessels that were not associated with artifactual change was also found among patients sickle cell trait. CONCLUSION: Patients with sickle cell trait appear to be at increased risk for fetal loss compared with women with normal hemoglobin levels, and placental abnormalities may play a causal role.

Neonatal organ dysfunction among newborns at gestational age 34 weeks and umbilical arterial pH<7.00.

PURPOSE: Among newborns at 34 weeks or more with umbilical arterial pH<7.00, we endeavoured to determine the pH threshold and risk factors for neonatal organ injury within 72 hours of birth. STUDY DESIGN: Retrospectively, all non-anomalous newborns delivered over 6 years near term with a low pH were identified. Each case of a newborn with injury was compared with the next four neonates with a pH below 7.00 and no injury. A receiver-operating characteristic (ROC) curve and unconditional logistic regression was used. RESULTS: Of the 87 newborns with pathologic acidosis, 16% had neonatal organ system injury. Inspection of the ROC curve indicates that a pH of 6.92 is the threshold that identifies newborns who will have damage to organs. Unconditional logistic regression analysis indicates that the significant risk factors for morbidity were an Apgar score or=37 weeks, pH