Lower Extremity Blood Flow Velocity in Obese versus Nonobese Pregnant Women.

OBJECTIVE: Obesity and pregnancy are risk factors for venous thromboembolism (VTE). In nonpregnant individuals, abdominal obesity is associated with venous insufficiency. This study aimed to compare venous Doppler volume flow and velocity in the lower extremities of obese versus nonobese women. STUDY DESIGN: A prospective cohort study was performed. Duplex ultrasound examined bilateral lower extremity venous flow and velocity (time-averaged mean velocity, TAMV). Flow was analyzed at the superficial femoral (SFV), distal external iliac (DEI), common femoral, profunda femoris, and popliteal veins. Mann-Whitney U-test, Spearman's correlation, and chi-square tests were used, with a significance of p < 0.05. RESULTS: Left SFV TAMV and volume flow were higher in the obese group (5.1 [4.1-5.7] vs. 2.8 [1.7-3.4] cm/second; p < 0.001) and (89 [73-119] vs. 48 [26-62] cm/minute; p = 0.005). Significant differences were noted for right DEI flow (obese 326 [221-833] vs. nonobese 182 [104-355] cm/minute; p = 0.049). The right femoral profunda flow was also higher in obese (49 [40-93] cm/minute) compared with nonobese (31 [22-52] cm/minute; p = 0.041). CONCLUSION: Volume flow and TAMV in the lower extremities of obese gravidas are higher compared with nonobese ones. Thus, the increased risk of VTE among obese pregnant women may not be caused by venous stasis.

Hemostatic Resuscitation in Peripartum Hysterectomy Pre- and Postmassive Transfusion Protocol Initiation.

Background Massive transfusion protocols (MTPs) have been examined in trauma. The exact ratio of packed red blood cells (PRBC) to other blood replacement components in hemostatic resuscitation in obstetrics has not been well defined. Objective The objective of this study was to evaluate hemostatic resuscitation in peripartum hysterectomy comparing pre- and postinstitution of a MTP. Study Design We conducted a retrospective, descriptive study of women undergoing peripartum hysterectomies from January 2002 to January 2015 who received ≥ 4 units of PRBC. Individuals were grouped into either a pre-MTP institution group or a post-MTP institution group. The post-MTP group was subdivided into those who had the protocol activated (MTP) versus not activated (no MTP). Primary outcomes were estimated blood loss (EBL) and need for blood product replacement. The secondary outcome was a composite of maternal morbidity, including need for mechanical ventilation, venous thromboembolism, pulmonary edema, acute kidney injury, and postpartum infection. A Mann-Whitney U test was used to compare continuous variables, and a chi-squared test was used for categorical variables with significance of p < 0.05. Results Of the 165 women who had a peripartum hysterectomy during the study period, 62 received four units or more of PRBC. No significant differences were noted in EBL or blood product replacement between the pre-MTP (n = 39) and post-MTP (n = 23) groups. Similarly, the MTP (n = 6) and no MTP (n = 17) subgroups showed no significant difference between EBL and overall blood product replacement. Significant differences were seen in transfusion of individual blood products, such as fresh frozen plasma (FFP) (MTP = 4, no MTP = 2; p = 0.02) and platelets (plts) (MTP = 6, no MTP = 0; p = 0.03). The use of high ratio replacement therapy for both plasma and plts was more common in the MTP group (FFP/PRBC ratio [MTP = 0.5, no MTP = 0.3; p = 0.02]; plts/PRBC ratio [MTP = 0.7, no MTP = 0; p = 0.03]). There were no differences in the secondary outcome between pre- and post-MTP or MTP and no MTP. Conclusion Initiation of the MTP did result in an increase in transfusion of FFP and plts intraoperatively. At our institution, the MTP is underutilized, but it appears that providers are more cognizant of the use of high transfusion ratios.

A Novel Mutation in ACTG2 Gene in Mother with Chronic Intestinal Pseudoobstruction and Fetus with Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

Background. A novel mutation in the ACTG2 gene is described in a pregnant patient followed up for chronic intestinal pseudoobstruction (CIPO) during pregnancy and her fetus with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS). Case. 24-year-old gravida 1 para 1 with CIPO and persistent nausea and vomiting in pregnancy, admitted at 28 weeks of gestation. Ultrasound revealed a fetus measuring greater than the 95th percentile, polyhydramnios, and megacystis. At delivery, the newborn was noted to have an enlarged bladder, microcolon, and intolerance of oral intake. Genetic testing of mother and child revealed a novel mutation in the ACTG2 gene (C632F>A, p.R211Q). Conclusion. This is the first case in the literature describing a novel mutation in ACTG2 associated with visceral myopathy affecting both mother and fetus/neonate. Visceral myopathy should be included in the differential diagnosis of megacystis diagnosed by ultrasound, and suspicion should increase with family history of CIPO or MMIHS.

Perinatal Outcomes after Short versus Prolonged Indomethacin for Tocolysis in Women with Preterm Labor.

Objective Indomethacin tocolysis is generally limited to 48 hours. Indomethacin has been administered for longer durations to prolong gestation in extreme prematurity. Our aim is to compare perinatal outcomes after a prolonged course, > 48 hours versus ≤ 48 hours in preterm labor. Methods A retrospective chart review of women admitted with preterm labor < 32 weeks gestation who received indomethacin for tocolysis. The primary maternal outcome was latency from admission until delivery. The primary neonatal outcome was a composite of severe neonatal morbidities. Results A total of 73 women were included: 32 (43.8%) received indomethacin for > 48 hours (prolonged) and 41 (56.2%) for ≤ 48 hours (standard). Prolonged group started on indomethacin at an earlier gestational age compared with standard group (23.9 [23.1-27.3] vs. 25.7 [23.8-28.5] weeks, p = 0.03). Latency from admission until delivery was longer in the prolonged group versus the standard group (1.8 [1.1-3] vs. 0.4 [0.1-0.8] weeks, p < 0.001). Prolonged use was not associated with increased risk of the composite neonatal outcome; however, there was a trend for more necrotizing enterocolitis. Conclusion A prolonged course of indomethacin may be an option for women with preterm labor at risk of extreme prematurity; it may also be associated with higher risks of some adverse neonatal outcomes.

Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes.

STUDY HYPOTHESIS: In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. STUDY FINDING: We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation. WHAT IS KNOWN ALREADY: Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups. MAIN RESULTS AND THE ROLE OF CHANCE: Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence. LIMITATIONS, REASONS FOR CAUTION: Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM. WIDER IMPLICATIONS OF THE FINDINGS: Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome. STUDY FUNDING AND COMPETING INTERESTS: This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of Texas Medical Branch at Galveston and funds to Dr M. Kacerovský from the Ministry of Health Czech Republic (UHHK, 001799906). The authors report no conflict of interest.

Fetal DNA methylation of autism spectrum disorders candidate genes: association with spontaneous preterm birth.

OBJECTIVE: Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth. STUDY DESIGN: A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD. DNA methylation in fetal leukocyte DNA in 4 of these genes (OXTR, SHANK3, BCL2, and RORA) was associated with PTB in a previous study. This study evaluated DNA methylation, transcription (reverse transcription polymerase chain reaction), and translation patterns (immunostaining and Western blot) in fetal membrane from term labor (n = 14), term not in labor (TNIL; n = 29), and spontaneous preterm birth (PTB; n = 27). Statistical analysis was performed with analysis of variance; a probability value of < .05 was significant. RESULTS: Higher methylation of the OXTR promoter was seen in fetal membranes from PTB, compared with term labor or TNIL. No other gene showed any methylation differences among groups. Expression of OXTR was not different among groups, but the 70 kDa OXTR protein was seen only in PTB, and immunostaining was more intense in PTB amniocytes than term labor or TNIL. CONCLUSION: Among the 4 genes that were studied, fetal membranes from PTB demonstrate differences in OXTR methylation and regulation and expression, which suggest that epigenetic alteration of this gene in fetal membrane may likely be indicating an in utero programing of this gene and serve as a surrogate in a subset of PTB. The usefulness of OXTR hypermethylation as a surrogate for a link to ASD should be further evaluated in longitudinal and in vitro studies.