Publications by authors named "Giancarlo Mari"

60 Publications

Neonatal blood pressure before and after delayed umbilical cord clamping.

J Matern Fetal Neonatal Med 2021 Jan 21:1-5. Epub 2021 Jan 21.

Department of Obstetrics & Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA.

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 -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.
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http://dx.doi.org/10.1080/14767058.2021.1876656DOI Listing
January 2021

Estimated fetal weight and severe neonatal outcomes in preterm prelabor rupture of membranes.

J Perinat Med 2020 Sep;48(7):687-693

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA.

Objectives Our aim was to study the association of clinical variables obtainable before delivery for severe neonatal outcomes (SNO) and develop a clinical tool to calculate the prediction probability of SNO in preterm prelabor rupture of membranes (PPROM). Methods This was a prospective study from October 2015 to May 2018. We included singleton pregnancies with PPROM and an estimated fetal weight (EFW) two weeks before delivery. We excluded those with fetal anomalies or fetal death. We examined the association between SNO and variables obtainable before delivery such as gestational age (GA) at PPROM, EFW, gender, race, body mass index, chorioamnioitis. SNO was defined as having at least one of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, or neonatal death. The most parsimonious logistic regression models was constructed using the best subset selection model approach, and receiver operator curves were utilized to evaluate the prognostic accuracy of these clinical variables for SNO. Results We included 106 pregnancies, 42 had SNO (39.6%). The EFW (area under the receiver operating characteristic curve [AUC]=0.88) and GA at PPROM (AUC=0.83) were significant predictors of SNO. The addition of any of the other variables did not improve the predictive probability of EFW for the prediction of SNO. Conclusions The EFW had the strongest association with SNO in in our study among variables obtainable before delivery. Other variables had no significant effect on the prediction probability of the EFW. Our findings should be validated in larger studies.
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http://dx.doi.org/10.1515/jpm-2019-0474DOI Listing
September 2020

Lack of Fetal Insulin Resistance in Maternal Polycystic Ovary Syndrome.

Reprod Sci 2020 06 28;27(6):1253-1258. Epub 2020 Jan 28.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA.

Polycystic ovary syndrome (PCOS) affects 8-10% of women. NIH criteria for diagnosis include chronic anovulation and evidence of clinical or biochemical hyperandrogenism. PCOS is associated with adverse neonatal outcomes. Our hypothesis is that insulin resistance is increased in fetuses born to women with PCOS. This is a prospective cohort of women who delivered at our institution. Subjects with a body mass index < 20 or ≥ 50 kg/m, multiple gestation, and major fetal malformations were excluded. Maternal blood was collected at admission, and umbilical cord blood was collected after delivery. Serum concentrations of insulin and glucose were measured from each sample. The homeostasis model assessment index of insulin resistance (HOMA-IR) was calculated (plasma glucose (mmol/L) × insulin (μU/mL)/22.5). The HOMA-IR from mothers and fetuses with PCOS was compared with mothers and fetuses without PCOS (controls). Mann-Whitney U test was utilized for statistical analysis. Forty-six women and fetal pairs were included; 28 with PCOS and 18 controls. Maternal insulin (20 [7.7-26.5] vs. 6.6 μU/ml [5.1-7.2]; p = 0.005) and HOMA-IR (3.9 [1.6-4.5] vs. 1.1 [0.9-1.3]; p = 0.01) were increased in the PCOS group. There was no statistical difference in fetal insulin, glucose, or HOMA-IR (p = 0.31) in the umbilical artery (p = 0.10; p = 0.34; p = 0.45, respectively) or the umbilical vein (p = 0.13; p = > 0.99; p = 0.31, respectively). Insulin resistance is present in non-diabetic pregnant women with PCOS, however not in their fetuses. This might explain variations in the occurrence of the adverse neonatal and maternal outcomes reported in PCOS.
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http://dx.doi.org/10.1007/s43032-019-00125-1DOI Listing
June 2020

Uterine artery pulsatility index for the prediction of obstetrical complications in preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2019 Dec 16:1-4. Epub 2019 Dec 16.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA.

Abnormal uterine artery Doppler studies have been associated with an increased risk of preeclampsia, fetal growth restriction (FGR), placental abruption, and fetal demise. These obstetrical complications can affect pregnancies with preterm prelabor rupture of membranes (PPROM). Therefore, our objective was to assess the prediction accuracy of the uterine artery pulsatility index (UtAPI) to detect these complications in pregnancies with PPROM. This was a prospective study of pregnancies complicated by PPROM from October 2015 to May 2018. We included mothers aged 13-46 years old with singleton pregnancies from 23 to 36 + 6 weeks with PPROM. Those without UtAPI measurements and complex fetal anomalies were excluded. Our primary outcome was a composite of obstetrical complications, defined as having one or more of the following: gestational hypertension or preeclampsia, placenta abruption, FGR, or fetal demise. The UtAPI was obtained at the time of enrollment. Logistic regression models with receiver operating curves were used to determine the predictive value of the UtAPI for obstetrical complications. A value of <.05 was considered significant. A total of 103 patients met inclusion criteria, of those 37 (36%) developed an obstetrical complication (FGR = 22 (21.5%); preeclampsia or gestational hypertension = 9 (9%); placental abruption = 8 (8%); fetal demise = 1 (1%)). Six mothers had more than one complication. The UtAPI was not a statistically significant predictor of a composite of obstetrical complications (AUC = 0.61;  = .07) or for any of the individual complications studied. The UtAPI appears to have limited clinical value for the prediction of obstetrical complications previously associated with abnormal uterine artery Doppler indices in pregnancies with PPROM. Larger and more diverse studies are needed to corroborate our findings. An accurate prediction for adverse outcomes in patients with PPROM may help identify those that may benefit from increased surveillance protocols.
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http://dx.doi.org/10.1080/14767058.2019.1702961DOI Listing
December 2019

Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries.

J Drug Alcohol Res 2019 ;8

Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, USA.

Alcohol (ethanol) is one of the most widely consumed drugs. Alcohol consumption by pregnant women may result in a range of fetal abnormalities termed fetal alcohol spectrum disorders (FASDs). The cerebrovascular system is emerging as a critical target of alcohol in the developing brain. We recently showed that three episodes of prenatal alcohol exposure resulting in 80 mg/dL alcohol in maternal blood during mid-pregnancy up-regulated anandamide-induced dilation of fetal cerebral arteries. Moreover, ethanol dilated fetal cerebral arteries via cannabinoid (CB) receptors. Whether a critical role of fetal cerebral artery CB system in responses to alcohol was maintained throughout the gestation, remains unknow.

Main Methods: Pregnant baboons (second trimester equivalent) were subjected to three episodes of either alcohol or control drink infusion via gavage. Cerebral arteries from mothers and near-term female fetuses were pressurized for diameter monitoring.

Key Findings: Near-term fetal and maternal arteries exhibited similar ability to develop myogenic tone, to constrict in presence of 60 mM KCl, and to respond to 10 µM anandamide. Fetal and maternal arteries largely failed to dilate in presence of 63 mM ethanol. No differences were detected between arteries from control and alcohol-exposed baboon donors. Therefore, previously observed ethanol-induced dilation of fetal cerebral arteries and up-regulation of CB components in response to fetal alcohol exposure during mid-pregnancy was transient and disappeared by near-term.
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http://dx.doi.org/10.4303/jdar/236068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497414PMC
January 2019

Middle cerebral artery peak systolic velocity in perinatal cytomegalovirus infection.

J Clin Ultrasound 2019 Jul 20;47(6):372-375. Epub 2019 Feb 20.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, Tennessee.

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.
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http://dx.doi.org/10.1002/jcu.22715DOI Listing
July 2019

Prenatal Alcohol Exposure, Anesthesia, and Fetal Loss in Baboon Model of Pregnancy.

J Drug Alcohol Res 2018 Jun;7

Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Approximately half of pregnant women engage in alcohol consumption some time during pregnancy. On the other hand, a small percentage of pregnant women undergo surgery and anesthesia at some time during pregnancy. In emergencies, anesthesia has to be administered to patients who are under alcohol intoxication. Anesthetic management during pregnancy while patients are intoxicated with alcohol is challenging. Here, we utilized a retrospective analysis of data available from 17 pregnant baboons that underwent anesthesia with alcohol exposure during mid-pregnancy. The analysis was designed to answer three questions: whether maternal vital signs remained stable under anesthesia combined with alcohol, whether maternal vital signs that were routinely monitored under anesthesia could serve as predictor(s) of fetal loss, and what the impact of the combined application of anesthesia and alcohol was on fetal loss. For the purpose of this retrospective analysis, we utilized vital sign (heart and respiratory rates, temperature, oxygen, carbon dioxide, systolic and diastolic blood pressure) and pregnancy outcome (miscarriage versus fetal survival through second trimester-equivalent of human pregnancy) records from 17 pregnant baboons that underwent gastric infusion of either control or alcohol-containing drink under isoflurane anesthesia during the second trimester-equivalent of human pregnancy. Half of the dams underwent a brief prior anesthetic episode for the purpose of gestational age confirmation. Thus, in our analysis, baboons were divided into four groups: "Control" without prior anesthesia, "Control" with prior anesthesia, "Alcohol" without prior anesthesia, and "Alcohol" with prior anesthesia. We did not detect any maternal vital sign in any of the groups that would be predictive of a fetal loss. However, prior anesthesia predisposed dams to the risk of lowering maternal systolic blood pressure and to a significant decrease in maternal oxygen level during the combined application of anesthesia and alcohol. Conceivably, our data showed the largest fetal loss in this group. The disruptive nature of anesthesia and alcohol on maternal vital parameters warns against the use of anesthesia in combination with alcohol during pregnancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333472PMC
June 2018

Serum Anti-Müllerian hormone (AMH) in mothers with polycystic ovary syndrome (PCOS) and their term fetuses.

Syst Biol Reprod Med 2019 Apr 14;65(2):147-154. Epub 2018 Nov 14.

a Department of Obstetrics and Gynecology, Rout Center , University of Tennessee Health Science Center , Memphis , TN , USA.

We sought to determine serum AMH levels in the maternal circulation, and the umbilical artery and vein, in normal women and women with PCOS, and their neonates at time of delivery. This represents a cross-sectional study of 57 pregnant patients who presented to the labor and delivery suite and subsequently delivered. We obtained maternal, as well as fetal blood from both, umbilical artery and vein. We measured serum concentrations of estradiol, AMH, testosterone and FSH. A total of 30 patients delivered a female and 27 a male neonate. Of them, 18/30 and 18/27 had a diagnosis of PCOS by NIH criteria. Mean age, BMI, weight gain in pregnancy, and gestational age did not differ between the two groups of mothers. AMH serum levels were statistically higher in women with PCOS (p < 0.005) and in their fetuses, independently of gender. Testosterone was higher in women with PCOS (p < 0.001), but there was no PCOS-related difference in their fetuses. FSH levels were significantly lower in PCOS than non-PCOS mothers carrying a male (p = 0.022), but not a female, fetus. AMH was positively correlated with maternal serum testosterone (p = 0.001) and negatively with fetal serum FSH (p < 0.026). In PCOS pregnancies, AMH was negatively correlated with maternal BMI (p = 0.019), menstrual cycle length (p = 0.035), and fetal uterine vein FSH (p = 0.021). In conclusion, at time of delivery, fetuses of women with PCOS had higher AMH levels and similar testosterone levels compared to fetuses from non-PCOS mothers, irrespective of gender. Our results may help explaining developmental differences in offspring of PCOS women.
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http://dx.doi.org/10.1080/19396368.2018.1537385DOI Listing
April 2019

Bilateral salpingectomy versus bilateral partial salpingectomy during cesarean delivery.

Int J Womens Health 2018 23;10:649-653. Epub 2018 Oct 23.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA,

Objective: To compare surgical outcomes in patients undergoing bilateral salpingectomy (salpingectomy group) with those who had partial salpingectomy (partial salpingectomy group) during cesarean delivery.

Materials And Methods: A chart review from July 2015 to November 2016 was performed. We included women who had sterilization during cesarean delivery. We excluded sterilization by occlusive methods. Our primary outcomes were total operative time and a composite score of transfusion rate, internal organ injury, hospital readmission, and endometritis. Secondary outcomes included menstrual abnormalities, pelvic pain, quality of life assessment, and regrets rate. We compared these outcomes between women in the salpingectomy and partial salpingectomy groups. Chi-squared, Fisher's exact, test, and Mann-Whitney were utilized for statistical analysis where appropriate. A <0.05 was considered significant.

Results: We included a total of 160 pregnancies. Of these, 41 were in the salpingectomy and 119 in the partial salpingectomy group. The median total operative time was longer for the salpingectomy group (62 [IQR 54, 71] vs 60 minutes [IQR 46, 72]; =0.03). The composite of surgical complications (19.5% vs 12.6%; =0.28) was not significantly different between our study groups. Menstrual irregularities (≥0.99), quality of life (≥0.99), dyspareunia (≥0.99), dysmenorrhea (=0.36), and regrets (≥0.99) were not different between groups.

Conclusion: Salpingectomy during cesarean delivery increased the median operative time by 2 minutes and may not be associated with an increased risk of surgical complications. We acknowledge the need for larger multi-center trials to corroborate our outcomes.
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http://dx.doi.org/10.2147/IJWH.S180329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204850PMC
October 2018

Fetal pulmonary artery acceleration/ejection time prognostic accuracy for respiratory complications in preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2020 Jun 26;33(12):2054-2058. Epub 2018 Nov 26.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA.

To determine the prognostic accuracy of the fetal pulmonary artery acceleration time/ejection time (PATET) for the prediction of neonatal respiratory complications (NRCs) in pregnancies with preterm premature rupture of membranes (PPROM). This is a prospective cohort of singleton pregnancies complicated by PPROM managed in our institution from October 2015 to April 2018. Inclusion criteria included mothers from 13 to 46 years of age and singleton pregnancies with PATET measurements <7 days prior to delivery. PATET was obtained by placing the Doppler caliper in the main pulmonary artery proximal to the bifurcation of this vessel. NRC was defined as: need for ventilatory support, respiratory distress syndrome (RDS), or lung hypoplasia. Logistic regression models and area under the receiver operating characteristic curves (ROC) were utilized to determine the prognostic accuracy of PATET and gestational age for NRC and RDS. Of 95 patients included, 46 had NRC (RDS = 33). PATET was a significant predictor of NRC (AUC 0.74; 95%CI: 0.61-0.83;  < .001) and RDS (AUC 0.69; 95%CI: 0.57-0.80;  = .021) in PPROM. Gestational age at delivery and gestational age at PPROM were also significantly associated with NRC and RDS. Their predictive accuracy for NRC was 0.87 and 0.84, and for RDS 0.85 and 0.86, respectively. PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited as gestational age is a better predictor of these outcomes. NRCs are common in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). We aim to determine the prognostic accuracy of the fetal PATET for the prediction of neonatal NRC in these pregnancies. Our results indicate that PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited, as gestational age is a better predictor of these outcomes.
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http://dx.doi.org/10.1080/14767058.2018.1536744DOI Listing
June 2020

Fetal anemia.

Minerva Ginecol 2019 Apr 11;71(2):97-112. Epub 2018 Oct 11.

Department of Obstetrics and Gynecology, Health Sciences Center, University of Tennessee, Memphis, TN, USA.

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.
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http://dx.doi.org/10.23736/S0026-4784.18.04334-4DOI Listing
April 2019

Uterine artery flow velocity waveforms before and after delivery in hypertensive disorders of pregnancy near term.

Hypertens Pregnancy 2018 Aug 18;37(3):131-136. Epub 2018 Jul 18.

a Department of Obstetrics and Gynecology , University of Tennessee Health Science Center , Memphis , TN , USA.

Objective: To compare the uterine artery pulsatility index (UtAPI-AP) before labor and immediate postpartum (UtAPI-PP) in hypertensive disorders of pregnancy (HTNP) and normotensives near term.

Methods: Pregnancies ≥36 weeks admitted for labor induction in our institution from October 2015 to October 2017 were included. We excluded active labor, multiple gestations, fetal demise, and those with inadequate uterine artery sampling. Our primary outcome was to compare the UtAPI-AP and UtAPI-PP between subjects with HTNP (gestational hypertension, preeclampsia with and without severe features) and normotensive participants. Our secondary outcomes were to compare the UtAPI-AP and UtAPI-PP by subgroups (severe HNTP, non-severe HTNP, and controls) and the UtAPI-PP in participants while on MgSO and after its discontinuation. A linear regression model was applied to test the above associations. A P < .05 was considered significant.

Results: We included 108 women (HTNP = 71; controls = 37). The UtAPI-AP was higher in the HTNP group (.85 ± .3 vs. .71 ± .2; P < .001); however, the UtAPI-PP was not different between groups (1.11 ± .3 vs. 1.16 ± .4; P = .46). The UtAPI-AP was higher in the severe HTNP group than controls (P = .004), but there was no significant difference in the UtAPI-PP between subgroups. Our results remained unchanged after adjusting for confounders. The UtAPI while on MgSO and after its discontinuation was similar (P =  >.99).

Conclusion: The increased UtAPI in patients with HTNP resolves soon after delivery. MgSO does not seem to have an effect on the UtAPI postpartum.
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http://dx.doi.org/10.1080/10641955.2018.1493495DOI Listing
August 2018

A conceptual framework for the impact of obesity on risk of cesarean delivery.

Am J Obstet Gynecol 2018 10 11;219(4):356-363. Epub 2018 Jun 11.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center College of Medicine, Memphis, TN.

Cesarean deliveries accounted for 32.2% of nearly 4 million births in the United States in 2014. Obesity affects a third of reproductive-age women and is associated with worse cesarean delivery outcomes. Studies have shown that increasing maternal body mass index correlates linearly with cesarean delivery rates, but little is known about the potential mediating and moderating mechanisms. Thus, a conceptual framework for understanding how obesity correlates with risk of cesarean delivery is crucial to determining safe ways to reduce the cesarean delivery rate among obese gravidas. Based on an extensive review and synthesis of the literature, we present a conceptual framework that posits how obesity may operate through several pathways to lead to a cesarean delivery. Our framework explores the complexity of obesity as an exposure that operates through potential mediating pathways, a moderator of cesarean delivery risk, and a covariate with other cesarean delivery risk factors. Among nulliparas, obesity appears to operate through 3 main proximal mediating mechanisms to increase risk of cesarean delivery including: (1) preexisting comorbidities and obstetric complications; (2) a slower progression of first-stage labor, potentially increasing the risk of cesarean delivery secondary to failure to progress; and (3) a prolongation of pregnancy, which is associated with risk of maternal postdates. For multiparas, a fourth proximal mediator of prior uterine scar may also increase cesarean delivery risk. Distal mediating mechanisms, which operate through one of the proximal mechanisms, may include an induction of labor or planned prelabor cesarean delivery. Obesity may also moderate the likelihood of cesarean delivery by interacting with clinician-level or hospital-level factors. Future research should assess the validity of this framework and seek to understand the relative contributions of each potential pathway between obesity and cesarean delivery. This will allow for evidence-based recommendations to reduce preventable cesareans among obese women by targeting modifiable mediators and moderators of the relationship between obesity and increased risk of cesarean delivery.
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http://dx.doi.org/10.1016/j.ajog.2018.06.006DOI Listing
October 2018

Factors Associated With Improvements in Mortality and Morbidity Rates of Very-Low-Birth-Weight Infants: A Cohort Study.

Glob Pediatr Health 2018 6;5:2333794X18765366. Epub 2018 Apr 6.

University of Tennessee Health Science Center, Memphis, TN, USA.

. The objective of this study was to determine factors contributing to improvements in infant mortality rates (IMR) and composite morbidity-mortality in very-low-birth-weight (VLBW) infants after initiating a new perinatal program in 2009 at Regional One Health (ROH). VLBW infants account for 67% of infant deaths. . This is a pre-/postintervention cohort study of prospectively gathered data. . VLBW infants delivered at ROH during the 2004 to 2015 study period. . ROH is a Regional Perinatal Center affiliated with the University of Tennessee Health Science Center. . We studied 2364 consecutive VLBW infants. Multivariate models were applied to determine factors contributing significantly to the reduction in the outcome measures as well as trends over time. . Primary outcomes were IMR and composite morbidity-mortality rates. Standardized, risk-adjusted mortality and composite morbidity ratios were also reported as defined by the Vermont Oxford Network. . Mortality declined from 15.5% in Pre-Implementation to 13.1% in Post-Implementation ( = .093), corresponding to an 18% reduction in odds. The combined factors of composite morbidity-mortality rate decreased from 55.7% in Pre-Implementation to 43.9% in Post-Implementation ( < .0001), representing a 38% reduction in odds. Standardized, risk-adjusted mortality and composite morbidity ratios improved during the study period from 20% above to 20% below the expected rate. Increases in the administration of antenatal steroids, surfactant administration, cesarean delivery, and perhaps other programmatic changes that were observational and unaccounted in the model were associated with improvements in outcome measures. . Decreased mortality and composite morbidity-mortality in VLBW infants delivered at ROH were found following the initiation of a new perinatal program.
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http://dx.doi.org/10.1177/2333794X18765366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894905PMC
April 2018

The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy.

Reprod Sci 2018 07 5;25(7):1116-1123. Epub 2017 Oct 5.

1 Department of Obstetrics and Gynecology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.

Prenatal alcohol exposure often results in an array of fetal developmental abnormalities termed fetal alcohol spectrum disorders (FASDs). Despite the high prevalence of FASDs, the pathophysiology of fetal damage by alcohol remains poorly understood. One of the major obstacles in studying fetal development in response to alcohol exposure is the inability to standardize the amount, pattern of alcohol consumption, and peak blood alcohol levels in pregnant mothers. In the present study, we used Doppler ultrasonography to assess fetal growth and cardiovascular parameters in response to alcohol exposure in pregnant baboons. Baboons were subjected to gastric alcohol infusion 3 times during the second trimester equivalent to human pregnancy, with maternal blood alcohol levels reaching 80 mg/dL within 30 to 60 minutes following alcohol infusion. The control group received a drink that was isocaloric to the alcohol-containing one. Doppler ultrasonography was used for longitudinal assessment of fetal biometric parameters and fetal cardiovascular indices. Fetal abdominal and head circumferences, but not femur length, were significantly decreased in alcohol-exposed fetuses near term. Peak systolic velocity of anterior and middle cerebral arteries decreased during episodes of alcohol intoxication, but there was no difference in Doppler indices between groups near term. Acute alcohol intoxication affected fetal cerebral blood flow independent of changes in the fetal cardiac output. Unlike fetal growth parameters, changes in vascular indices did not persist over gestation. In summary, alcohol effects on fetal growth and on fetal vascular function have different time courses.
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http://dx.doi.org/10.1177/1933719117734317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346348PMC
July 2018

Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors.

Alcohol 2017 06 18;61:51-61. Epub 2017 May 18.

Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address:

Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.
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http://dx.doi.org/10.1016/j.alcohol.2017.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517095PMC
June 2017

Technique for bilateral salpingectomy at the time of Cesarean delivery: a case series.

Contraception 2017 May 3;95(5):509-511. Epub 2017 Mar 3.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, 853 Jefferson Ave # E102, Memphis, TN 38013.

The American Congress of Obstetricians and Gynecologists and the Society of Gynecologic Oncology endorse bilateral salpingectomy for ovarian cancer prevention. We describe a bilateral salpingectomy technique in 23 patients during Cesarean delivery. Operative time, hospital length of stay and complications are reported. Bilateral salpingectomy during Cesarean delivery appears feasible.
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http://dx.doi.org/10.1016/j.contraception.2017.02.021DOI Listing
May 2017

Effects of selective reduced uterine perfusion pressure in pregnant rats.

Placenta 2015 Dec 28;36(12):1450-4. Epub 2015 Oct 28.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, 853 Jefferson Ave, Room E102., Memphis, 38163, TN, USA.

Introduction: To assess the effects of selective reduced uterine perfusion pressure (SRUPP) in pregnant rats.

Methods: 20 pregnant Sprague-Dawley rats were allocated either to an intervention group, exposed to SRUPP (n = 10) or a control group, exposed to sham surgery (n = 10). Such procedures were performed on gestational day (GD) 14. The Mean arterial pressure (MAP) was measured on GD14 (before surgery) and GD20. We measured 18 h proteinuria on GD20. On GD21, mean fetal (MFW) and placental (MPW) weights were obtained. Oxidative stress and angiogenic markers were measured in placental tissue and urine. Mann Whitney U or Independent samples T test were used when appropriate. A two-sided P < 0.05 indicated statistical significance.

Results: MAP on GD20 was higher in the intervention group (109 ± 1.7 mmHg) when compared with the control group (83 ± 1.5 mmHg) (P = 0.002). There was no significant difference in urinary protein excretion (117 ± 3.1 mg/24 h versus 136 mg ± 2.8/24 h, P = 0.18), MFW (4.14 ± 0.05 versus 4.39 ± 0.04 g, P = 0.19) or MPW (0.43 ± 0.008 versus 0.44 ± 0.006 g, P = 0.73) between the intervention and the control groups, respectively. The oxidative stress was increased; whereas, the sFLT1 expression was not increased when the SRUPP group was compared with controls.

Discussion: SRUPP is associated with an increase in maternal MAP and oxidative stress and therefore it may become a useful tool in the study of pregnancy-related hypertensive disorders.
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http://dx.doi.org/10.1016/j.placenta.2015.10.017DOI Listing
December 2015

Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia--diagnosis and management.

Am J Obstet Gynecol 2015 Jun 27;212(6):697-710. Epub 2015 Mar 27.

Society for Maternal-Fetal Medicine, 409 12 St. SW, Washington, DC 20024, USA.

Objective: We sought to provide evidence-based guidelines for the diagnosis and management of fetal anemia.

Methods: A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and the Cochrane Library. The search was restricted to English-language articles published from 1966 through May 2014. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion. Evidence reports and published guidelines were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was used for defining the strength of recommendations and rating the quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence.

Results And Recommendations: We recommend the following: (1) middle cerebral artery peak systolic velocity (MCA-PSV) measured by ultrasound Doppler interrogation be used as the primary technique to detect fetal anemia; (2) amniotic fluid delta OD450 not be used to diagnosis fetal anemia; (3) MCA-PSV assessment be reserved for those patients who are at risk of having an anemic fetus (proper technique for MCA-PSV evaluation includes assessment of the middle cerebral artery close to its origin, ideally at a zero degree angle without angle correction); (4) if a fetus is deemed at significant risk for severe fetal anemia (MCA greater than 1.5 multiples of the median or hydropic), fetal blood sampling be performed with preparation for an intrauterine transfusion, unless the pregnancy is at a gestational age when the risks associated with delivery are considered to be less than those associated with the procedure; (5) if a fetus is deemed at significant risk for severe fetal anemia, the patient be referred to a center with expertise in invasive fetal therapy; (6) MCA-PSV be considered to determine the timing of a second transfusion in fetuses with anemia, and, alternatively, a predicted decline in fetal hemoglobin may be used for timing the second procedure; and (7) pregnancies with a fetus at significant risk for fetal anemia be delivered at 37-38 weeks of gestation unless indications develop prior to this time.
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http://dx.doi.org/10.1016/j.ajog.2015.01.059DOI Listing
June 2015

Lactate in cord blood and its relation to fetal gluconeogenesis in at term deliveries.

Early Hum Dev 2015 Mar 3;91(3):165-8. Epub 2015 Feb 3.

Division of Perinatal Medicine, Policlinico Abano Terme, Abano Terme, Italy.

Background: In the human fetus, an increased lactate and glucose level can be anticipated when hypoxia and stress are present and is likely to be a function of both anaerobic metabolism and catecholamine-mediated glycogenolysis/glycolysis.

Aim: We assessed if measurement of lactate in cord artery blood after vaginal and cesarean delivery may predict glucose concentration.

Study Design: Umbilical artery cord blood lactacidemia, acidemia, and glucose concentration was tested by 'mini-lab' Radiometer ABL90 FLEX analyzers (Radiometer®, Copenhagen, Denmark) after vaginal delivery (VD), spontaneous (n=493) and by vacuum extractor (n=41) or by cesarean delivery (CD), elective (n=120) and emergency (n=68) in at term, vigorous neonates delivered from March to December 2012 at the 2nd level maternity ward of Policlinico Abano Terme, Abano Terme (Italy).

Results: Cord blood lactacidemia and glucose levels were significantly higher in VD by vacuum extractor than in all other groups (5.32±1.96mmol/L, p=0.050 and 103.6±30.5mg/dL, p<0.001, respectively) and significantly lower in elective CD group (1.77±0.99mmol/L, p<0.001 and 69.8±13.0mg/dL, p<0.001). The cord blood lactate concentration was significantly and positively correlated with glucose levels (r=0.434, p<0.001), but significantly and negatively correlated with pH (r=-0,662, p<0.001), NaHCO3(-) (r=-0,802, p<0.001), and base excess (BE) (r=-0,698, p<0.001). However, in multivariate linear regression analysis, only BE, PaCO2 and cord blood lactate were significant predictive variables (R(2)=0.410; p<0.001) of glucose levels at birth.

Conclusion: Cord blood artery lactate and glucose concentration are significantly and positively correlated at birth in healthy, at term vaginally and cesarean delivered neonates, but BE is the best indicator of activated fetal gluconeogenesis.
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http://dx.doi.org/10.1016/j.earlhumdev.2015.01.003DOI Listing
March 2015

Predicting fetal lung maturity using the fetal pulmonary artery Doppler wave acceleration/ejection time ratio.

Fetal Diagn Ther 2014 13;36(3):208-14. Epub 2014 Aug 13.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, Tenn., USA.

Objective: To determine whether the acceleration/ejection time ratio of the fetal main pulmonary artery Doppler waveform (PATET) can accurately predict the results of fetal lung maturity testing in amniotic fluid.

Methods: We prospectively studied pregnant women attending our ultrasound unit for clinically indicated fetal lung maturity testing. An ultrasound examination that included measurement of the PATET was performed before the results of the amniocentesis were reported. The results of the PATET and the surfactant/albumin ratio were compared, and a receiver operating characteristic curve was used to determine the PATET cutoff with the optimal sensitivity and specificity for predicting surfactant/albumin ratio results. p < 0.05 was considered statistically significant.

Results: Forty-three patients were included in this study. The receiver operating characteristic curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93% (95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58-96%) for predicting immature surfactant/albumin ratio results.

Conclusion: The PATET may provide a noninvasive means of determining fetal lung maturity with acceptable levels of sensitivity, specificity, and predictive values.
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http://dx.doi.org/10.1159/000358299DOI Listing
June 2015

A novel translational model of percutaneous fetoscopic endoluminal tracheal occlusion - baboons (Papio spp.).

Fetal Diagn Ther 2014 30;35(2):92-100. Epub 2014 Jan 30.

Division of Maternal and Fetal Medicine, University of Tennessee Health Science Center, Memphis, Tenn., USA.

Introduction: Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications.

Material And Methods: Seven non-human primates underwent two subsequent surgeries: the first, the FETO in the experimental group (n = 3) or sham operation in the control animals (S-FETO, n = 4) at 132-142 days of gestation (dGA); the second, the reversal of occlusion or sham operation at 162 ± 5 dGA. Maternal stress axis, complete blood count, and biochemical parameters were evaluated and newborn tracheal radiography was performed.

Results: The average pregnancy duration and neonatal weights in the FETO group did not differ from the animals in the S-FETO group. There was no bleeding or premature fetal membrane rupture during the procedures in any of the baboons. The maximal tracheal width was 7.02 ± 0.6 mm in the FETO versus 5.46 ± 0.6 mm in S-FETO group.

Discussion: This is the very first report of a successful FETO model in non-human primates. Similarities to human tracheomegaly were for the first time documented in any model studied.
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http://dx.doi.org/10.1159/000357139DOI Listing
November 2014

The effect of cesarean delivery skin incision approach in morbidly obese women on the rate of classical hysterotomy.

J Pregnancy 2013 20;2013:890296. Epub 2013 Nov 20.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, 853 Jefferson Avenue Suite E102, Memphis, TN 38163, USA.

Objective: To assess the risk of classical hysterotomy and surgical morbidity among women with a body mass index (BMI) greater than 40 kg/m² who underwent a supraumbilical incision at the time of cesarean delivery.

Methods: We conducted a retrospective cohort study in women having a BMI greater than 40 kg/m² who underwent a cesarean delivery of a live, singleton pregnancy from 2007 to 2011 at a single tertiary care institution. Intraoperative and postoperative outcomes were compared between patients undergoing supraumbilical vertical (cohort, n = 45) or Pfannenstiel (controls, n = 90) skin incisions.

Results: Women undergoing supraumbilical incisions had a higher risk of classical hysterotomy (OR, 24.6; 95% CI, 9.0-66.8), surgical drain placement (OR, 6.5; 95% CI, 2.6-16.2), estimated blood loss greater than 1 liter (OR, 3.4; 95% CI, 1.4-8.4), and longer operative time (97 ± 38 minutes versus 68 ± 30 minutes; P < .001) when compared to subjects with Pfannenstiel incisions (controls). There was no difference in the risk of wound complication between women undergoing supraumbilical or Pfannenstiel incisions (OR, 2.7; 95% CI, 0.9-8.0).

Conclusion: In women with a BMI above 40 kg/m², supraumbilical incision at the time of cesarean delivery is associated with a greater risk of classical hysterotomy and operative morbidity.
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http://dx.doi.org/10.1155/2013/890296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853441PMC
March 2014

Eclampsia characteristics and outcomes: a comparison of two eras.

J Pregnancy 2013 7;2013:826045. Epub 2013 Apr 7.

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Objective: To describe the trends in incidence, characteristics, and outcomes of women with eclampsia.

Methods: We reviewed and abstracted data from medical records of all women diagnosed with eclampsia in our institution from August 1998 to April 2011. In addition to overall characteristics and outcomes, the cases were stratified by onset: antenatal versus postnatal and early (<32 weeks of gestation) versus late antenatal cases (≥32 weeks of gestation). Comparisons were made using chi-square, Fisher's exact, Mann-Whitney U, and t-tests. A two-sided P < 0.05 was considered statistically significant.

Results: We identified 87 eclampsia cases out of 59,388 deliveries; 62 cases were diagnosed before delivery, and 25 had a postnatal onset. Among the 62 antenatal cases, 41 were diagnosed before 32 weeks and 21 at or after 32 weeks of gestation. Antenatal cases had higher systolic (P = 0.03) and diastolic (P = 0.01) blood pressures, more abnormal dipstick-test proteinuria (P = 0.002), and lower platelet counts (P ≤ 0.001) than postnatal cases. Early eclampsia cases were complicated more often with HELLP syndrome than late eclampsia cases (P = 0.007).

Conclusion: The occurrence of eclampsia has decreased over time. The earlier the onset is, the worse the outcome appears to be.
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http://dx.doi.org/10.1155/2013/826045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649178PMC
September 2013

Topics in perinatal genitourinary system ultrasound evaluation.

Ultrasound Q 2011 Dec;27(4):229-54

Department of Radiology, University of Tennessee Health Science Center, Memphis, TN, USA.

Ultrasound is a helpful imaging tool for triaging and in most instances making a definitive diagnosis of abnormalities of the fetal and neonatal genitourinary systems. Ultrasound can define an abnormality found in a fetus or neonate as definitively related to the genitourinary system, guiding further workups. Ultrasound can be used to assuage clinical concern by showing normal anatomic findings or variants that can simulate abnormality. This article discusses necessary information to aid in ultrasound diagnosis in various areas of the perinatal genitourinary system including the kidneys, bladder, and genital system. It discusses some adrenal findings that may help in these diagnoses.
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http://dx.doi.org/10.1097/RUQ.0b013e318239c710DOI Listing
December 2011

The MCA Doppler and its role in the evaluation of fetal anemia and fetal growth restriction.

Clin Perinatol 2011 Mar;38(1):83-102, vi

Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, 853 Jefferson Avenue, Memphis, TN 38103, USA.

Doppler velocimetry of the middle cerebral artery (MCA) has played a major role in fetal medicine for the last 23 years, both in intrauterine growth-restricted (IUGR) and anemic fetuses. Its utility in the diagnosis and management of cases of fetal anemia was initially demonstrated in cases of red cell alloimmunization and later extended to other types of anemia. In addition, MCA Doppler studies are crucial in the evaluation of IUGR fetuses. This article is a review of the role of the MCA in these 2 conditions.
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http://dx.doi.org/10.1016/j.clp.2010.12.003DOI Listing
March 2011

Middle cerebral artery Doppler for managing fetal anemia.

Clin Obstet Gynecol 2010 Dec;53(4):851-7

University of Tennessee Health Science Center, Department of Obstetrics and Gynecology, Memphis, Tennessee, USA.

The measurement of the middle cerebral artery peak systolic velocity, a noninvasive technique, has become the standard for the diagnosis of fetal anemia. The middle cerebral artery peak systolic velocity is used because of its ease of measurement and its high sensitivity in predicting anemia. This diagnostic tool should only be used with fetuses at risk for anemia and in medical centers with adequate training in the technique.
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http://dx.doi.org/10.1097/GRF.0b013e3181fbaf6dDOI Listing
December 2010

Surgical management of unusual cardiac tumors in infants and children.

World J Pediatr Congenit Heart Surg 2010 Jul;1(2):211-6

University of Tennessee Medical Group/Le Bonheur Children's Medical Center, Memphis, Tennessee.

While most primary tumors of the heart are histologically benign, they are significant space-occupying lesions with serious functional implications for the heart and lungs. Herein, we highlight our experience with the surgical management of selected cardiac tumors in the pediatric population between 2008 and 2010. (1) Intrapericardial teratomas in the fetus can produce fatal tamponade from compression by the attendant pericardial effusion, and a critical life-saving maneuver preoperatively is to drain the effusion prenatally, followed by an expeditious resection after birth. (2) Rhabdomyomas, the most common of the pediatric cardiac tumors, can be intracavitary, large, and associated with the mitral subvalvular apparatus. (3) Cardiac fibromas should be aggressively resected or at least debulked, especially given their propensity for dysrrhythmias. The key to success is as complete a resection as possible, but not at the expense of other normal structures. (4) Complex nonobstructive hypertrophic myopathy can be thought of as a type of neoplastic overgrowth, and aggressive resection of even midcavitary obstructive lesions should be considered as a viable alternative to primary transplantation.
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http://dx.doi.org/10.1177/2150135110372527DOI Listing
July 2010

Surgical management of intrapericardial teratoma in the fetus.

J Pediatr 2010 May 20;156(5):848-9, 849.e1. Epub 2010 Mar 20.

Division of Pediatric Cardiovascular Surgery, University of Tennessee Health Sciences Center/Le Bonheur Children's Medical Center, Memphis, TN 38103, USA.

Intrapericardial teratomas often present as life-threatening problems when diagnosed during fetal life. They are large lesions that compress the heart and lungs and can result in tamponade if not treated expeditiously. We present a case of a large teratoma that was managed by prenatal pericardiocentesis followed by surgical resection.
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http://dx.doi.org/10.1016/j.jpeds.2010.01.016DOI Listing
May 2010

Fetal transfusion: the spectrum of clinical research in the past year.

Curr Opin Obstet Gynecol 2010 Apr;22(2):155-8

University of Tennessee Health Science Center, Department of Obstetrics and Gynecology, Memphis, Tennessee, USA.

Purpose Of Review: Our goal is to review recent articles that examine the current state of fetal transfusion therapy from technique to education.

Recent Findings: Even as technology facilitates physicians' diagnosis and treatment of rare disorders requiring fetal transfusion therapy, longstanding questions remain such as the use of intravascular versus intraperitoneal transfusion sites. However, the recent progress seen with molecular techniques, disease markers, and mathematical models demonstrates that despite unanswered questions, there is much to be hopeful about in improving our understanding of fetal transfusions and their application to a variety of diseases.

Summary: Systematic and collaborative approaches to studying low-frequency disorders treatable by fetal transfusions are necessary. Continued refinement of techniques should improve the timeliness and accuracy of diagnosis, as well as assist in determining the appropriate timing, site, and duration of treatments.
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http://dx.doi.org/10.1097/GCO.0b013e32833723b5DOI Listing
April 2010