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Little is understood about child welfare involvement (CWI) in cases where the birth mother has experienced human trafficking.The aim of this study was to explore provider perceptions of the impact of CWI for the trafficked mother.Participants were selected among providers caring for trafficked birth mothers. Semi-structured interviews were conducted with providers and qualitative content analysis was conducted.Interviewees reported reasons for CWI, positive and negative impacts of CWI and provided recommendations for systems improvement.Recommendations from this exploratory study include mechanisms to support trafficked mothers, train hospital social workers, and systems change. During the prenatal period, strategies to support the trafficked mother may include addressing gaps in social determinants of health, ensuring appropriate medical and mental health care, early screening and referral to substance use treatment services, enhancing community support, and working to develop safety plans for survivors and their families. Enhanced engagement of social workers and all providers to improve understanding of the unique complexity of trafficked mothers is needed. Education should include an understanding that judgement of a caretaker's ability to parent should be current and holistic and not reflexive based on history in the electronic medical record. An exploration of the child welfare system itself should also be undertaken to identify and modify discriminatory laws and policies. Finally, efforts to address social determinants of health in the community and enhance the trauma-informed nature of child welfare referrals could improve the lives of trafficked mothers.

Objective To study the incidence and clinical significance of congenital heart defects (CHDs) detected by fetal echocardiography in pregnancies conceived by in vitro fertilization (IVF). Design Cohort study comparing a prospectively maintained database of all fetal echocardiograms from 2012 to 2018 and pooled data from the Connecticut Birth Defects Registry and statewide hospital discharge data. Setting Large tertiary care center. Patient(s) A total of 181,749 live births and 9,252 fetal echocardiograms were analyzed. Fetal echocardiograms in patients with a previous child with a CHD, a family history of CHD, medication exposure, diabetes, anomaly in previous pregnancy, cardiac or other abnormality noted on previous ultrasound, or monochorionic twins were excluded from the final analysis. Intervention(s) Treatment with IVF. Main Outcome Measure(s) Incidence of CHD and odds ratios with 95% confidence intervals (CIs). Infant outcomes for cases of CHD were evaluated for clinically significant disease, defined a priori as disease requiring any medical or surgical intervention or continued follow-up with pediatric cardiology. Result(s) Fetal echocardiography was performed in 2,230 IVF pregnancies, of which 2,040 were without other known risk factors for CHD. The mean gestational age at the time of fetal echocardiography was 22.2 ± 1.4 weeks. The odds ratio for CHD in the IVF group compared with statewide population rates was 1.4 (95% CI 0.9–2.1). CHD was diagnosed in 26 fetuses, of which 21 were clinically insignificant ventricular septal defects. One fetal echocardiogram was concerning for pulmonary stenosis that was not present at birth. Four defects were clinically significant, indicating that 510 fetal echocardiograms were performed for every diagnosis of one clinically significant CHD in the IVF group. Conclusion(s) The incidence of CHD in IVF pregnancies without other risk factors is not significantly different from baseline population rates, and most CHDs diagnosed by fetal echocardiography in this group are clinically insignificant. Routine screening with fetal echocardiography in all IVF pregnancies provides limited utility beyond routine prenatal care and need not be recommended without the presence of other risk factors.

A 26-year-old pregnant woman, with multiple metastatic Ewing sarcoma, presented with a sternal mass that began enlarging during pregnancy. Due to high-risk pregnancy, the patient was discussed in a multidisciplinary meeting and intubation was considered too risky without cardiopulmonary support. Computed tomography showed extrinsic tumor compression of the right ventricle outflow tract. Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) was initiated before general anesthesia, followed by Cesarean section (C-section). VA ECMO was initiated with the patient in the awake position, ECMO support was discontinued when the patient had stable ventilation and hemodynamics. This case represents a unique indication of VA ECMO, during C-section, with maternal and fetal survival.

Objective: The effect of SARS-CoV-2(SV) on the pregnant population is unclear. SV has been associated with significant placental changes, most notably, fetal vascular malperfusion (FVM). The objective of this study is to evaluate placental effects through fetal heart tracings (FHT) among laboring SV+ patients. Study Design: A prospective study including all women delivering at a large urban hospital in Miami, Florida between April 30 - July 31, 2020 was performed. Admitted patients were screened for SV. The FHT in all SV positive cases and SV negative controls 2 hours prior to delivery were evaluated for the presence of late decelerations, severe variable decelerations, loss of variability and persistent tachycardia. Cases and controls were matched for age, race, BMI, gestational age and comorbidities. Two investigators blinded to perinatal outcomes independently evaluated FHTs, and a 3rd resolved discrepancies. Placentas were graded by a perinatal pathologist based on Amsterdam Placental Workshop Group criteria. Result(s): 224 subjects consented to participate. 188 (83.9%) were negative and 36 (16.0%) were positive for SV. Placentas from SV positive participants were more likely to show FVM (P=0.001). FHT for all SV positive patients who underwent labor (n= 26) were compared to 27 paired SV negative controls. Baseline demographic characteristics were not different between the two groups. (Table 1) There was no difference in the rates of absent variability, late decelerations, severe variable decelerations, persistent fetal tachycardia or a composite of any of these abnormal fetal heart rate patterns between the two study groups. (Table 2) Conclusion(s): Despite significant findings on placental pathology, no association was found between SV positivity and abnormal fetal heart tracings during labor. FHT was not a strong indicator of FVM in this cohort. Further studies are needed to fully understand the perinatal effects of the noted placental abnormalities in SV positive pregnant and laboring women. [Formula presented] [Formula presented]Copyright © 2020

Objective Placenta accreta is a feared pathology, in part, because prenatal diagnosis is imperfect. It is not known whether clinical risk factors or sonographic features equally predict the entire graded pathological spectrum of placental overinvasion disease nor whether clinical outcomes differ along the spectrum. Study Design We conducted a mixed methods retrospective study of a cohort of women screened sonographically for placenta accreta, cross-referenced against cases identified by pathological diagnosis (N = 416). Demographic, diagnostic, and outcome information were compared across the spectrum of invasive placentation: percreta, increta, accreta, and focal accreta not requiring hysterectomy. The t-test, chi-square, Mann–Whitney, and Kruskal–Wallis tests were used for statistical analysis across groups. Results As the depth of invasion decreased, risk factors for placental overinvasion were less common, especially placenta previa and previous cesarean. There was also reduced anticipation by sonographic examination of the placenta. Rates of adverse outcomes were lower among women with focal accreta compared with those with deeper invasion. Conclusion As the depth of invasion decreases, clinical risk factors and sonographic evaluation are less reliable in the antenatal prediction of placenta accreta. The potential for unanticipated morbidity underscores the need for improved diagnostic tools for placenta accreta spectrum.

To describe the treatment and subsequent pregnancy outcomes in patients with cesarean scar pregnancies at a single institution over 5 years.This is a case series of all cesarean scar pregnancies diagnosed from May 2013 to March 2018 at Yale-New Haven Hospital. Data were collected on each patient using electronic medical record review and included patient demographics; medical, surgical, and obstetric history; pregnancy characteristics; treatment modalities used; response to therapy; complications; and subsequent pregnancy outcomes.Thirty cases of cesarean scar pregnancies were diagnosed in 26 patients, including one recurrence in one patient and three recurrences in another. Forty-six percent of cesarean scar pregnancies were in Hispanic women. The median number of prior cesarean deliveries was two. Mean gestational age at the time of diagnosis was 46 days (SD±10). Fetal cardiac activity was detected in 18 cases. Three patients initially were erroneously diagnosed with a viable intrauterine pregnancy and failed medical termination. Others opted for termination through systemic methotrexate alone (n=4), systemic and local methotrexate (n=12), systemic and local methotrexate with potassium chloride injected into the gestational sac (n=3), potassium chloride injection with laparotomy and wedge resection (n=1), methotrexate with bilateral uterine artery embolization (n=2), or intrauterine balloon (n=4). Five patients who underwent expectant management or methotrexate therapy had retained products of conception and required hysteroscopy and curettage. One patient opted for hysterectomy after failed curettage. After complete resolution of cesarean scar pregnancies, there were 10 subsequent spontaneous conceptions in eight patients, including four recurrent cesarean scar pregnancies, four term pregnancies, and one spontaneous abortion. One viable normally located pregnancy is ongoing.There is a wide array of treatment modalities available for cesarean scar pregnancies. Women with a cesarean scar pregnancy are at risk for its recurrence in the future, although normal pregnancy after a cesarean scar pregnancy is also possible. Safe outcomes depend on timely diagnosis and multidisciplinary care by skilled clinicians.

Problem Women with antiphospholipid syndrome (APS) are at increased risk of recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies (aPL) directly alter trophoblast function. Treatment with low molecular weight heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of aPL and LMWH. Method of study A human first trimester trophoblast cell line (HTR8) and primary trophoblast cultures were treated with or without aPL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion of inflammatory cytokines and angiogenic factors were measured by ELISA. Results Vitamin D alone or in combination with LMWH attenuated the aPL-induced trophoblast inflammatory response in the HTR8 cells and primary cultures. While vitamin D did not have any impact on aPL-mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH-induced sFlt-1 release. Conclusion LMWH in combination with vitamin D may be more beneficial than single-agent therapy by preventing aPL-induced trophoblast inflammation and reversing LMWH-induced sFlt-1 secretion.

Objective To describe the sonographic features and pregnancy outcomes of placental mesenchymal dysplasia (PMD), an entity often misdiagnosed as molar pregnancy. Methods We reviewed PMD cases from our institution and performed a systematic review of the existing literature. Inclusion criteria for the review were diagnosis of PMD as defined by placental pathology, description of placental morphology on antenatal ultrasound and reporting of pregnancy outcomes. Results We found three cases of PMD at our institution. Patient 1 had elevated human chorionic gonadotropin (hCG) and an enlarged, hydropic placenta at 13 weeks, suggestive of a molar pregnancy. Patient 2 also had elevated hCG with large, vascular placental lakes on ultrasound suggesting placenta accreta or molar pregnancy. Case 3 involved placentomegaly and fetal anomalies suggestive of Beckwith–Wiedemann syndrome. From the literature review, 61 cases met the inclusion criteria. The most common sonographic features included enlarged (50%) and cystic (80%) placenta with dilated chorionic vessels. Biochemical aneuploidy screening abnormalities were relatively common as were fetal anomalies, Beckwith–Wiedemann syndrome and other genetic abnormalities. Pregnancy complications included intrauterine growth restriction (IUGR; 33%), intrauterine fetal death (IUFD; 13%), and preterm labor (33%). Pregnancies without fetal anomalies, IUGR, IUFD or preterm labor had normal neonatal outcomes despite PMD (9%). Conclusions The differential diagnosis of PMD includes molar pregnancy and other placental vascular anomalies. PMD is associated with adverse pregnancy outcome, so heightened surveillance with genetic evaluation, serial growth scans and third-trimester assessment of wellbeing should be considered. PMD must be differentiated from gestational trophoblastic disease because management and outcomes differ. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Problem Women with antiphospholipid antibodies (aPL) are at risk of miscarriage and pre-eclampsia, obstetrical disorders associated with reduced trophoblast invasion and spiral artery transformation. aPL target the placenta by binding beta2-glycoprotein I (β2GPI) on the trophoblast. In this study, we determined whether aPL alter the trophoblast secretion of angiogenic factors and evaluated the effect of low molecular weight heparin (LMWH) on this response. Method of study First-trimester trophoblast was treated with anti-β2GPI antibodies with or without LMWH. Angiogenic factor secretion was measured by enzyme-linked immunosorbent assay. Results Trophoblast cells produced more vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), and soluble endoglin following exposure to anti-β2GPI Abs, and this occurred in both a MyD88-dependent and MyD88-independent manner. LMWH was unable to reverse the effects of the anti-β2GPI Abs on trophoblast VEGF secretion, but enhanced PlGF. Strikingly, LMWH upregulated soluble fms-like tyrosine kinase receptor-1 (sFlt-1) secretion independently of aPL. Conclusion This study demonstrates that aPL perturb the secretion of trophoblast angiogenic factors. LMWH does not reverse this effect but exacerbates sFlt-1 secretion, a potent anti-angiogenic factor. These findings may help to explain why women with antiphospholipid syndrome, who are treated with heparin to prevent early pregnancy loss, remain at increased risk of developing late obstetrical complications, such as pre-eclampsia.

Problem Preeclampsia is associated with hyperuricemia, which correlates with the disease severity. Levels of circulating uric acid increase before the clinical manifestations, suggesting they may be causally related. Uric acid, or monosodium urate (MSU), activates the Nod-like receptor, Nalp3, leading to inflammasome activation and IL-1β processing. Since preeclampsia is associated with placental immune/inflammatory dysregulation, we sought to determine in the trophoblast, the presence of the Nalp3 inflammasome, and the effect of MSU on its activation.

Over the past decade, gastroschisis has become an antenatal diagnosis. Rarely, the bladder is found to be extracorporeal in the third trimester. Although there are several case reports, no case series exists to suggest the prognosis for these infants. Here, we present a case of bladder herniation in a fetus with gastroschisis and a literature review. The fetus presented in this case report was diagnosed at 18 weeks, at which time the bladder was in situ. At 34 weeks, the bladder had herniated through the abdominal wall defect. A review of the literature suggests that bladder herniation in right-sided gastroschisis is not associated with any additional long-term morbidity or mortality. The herniation typically develops between 30 and 35 weeks. Regardless of renal findings on sonography, these infants do well postoperatively. Interestingly, most cases occur in female infants.

Premature birth before 37 weeks of gestation is a significant public health problem. Each year, 4.5 million premature infants are born worldwide. Despite extensive research and a variety of interventions, the rate of preterm birth has steadily increased over the past 20 years and reached a high of 12.8% in 2006. The etiology of most preterm births remains elusive and is likely multifactorial, with many pathophysiological pathways involved, such as excessive stretching, oxidative stress, decidual hemorrhage, and infection. Genomics and proteomics have emerged to provide a better comprehension of the pathophysiological conditions leading to preterm birth, thereby providing a perspective for improving neonatal outcome.

OBJECTIVE To evaluate the ability of microbiologic and pathologic examination of the placenta to accurately diagnose intraamniotic infection and inflammation. METHODS One hundred eighty-three women with a clinically indicated amniocentesis were enrolled prospectively. We applied our analysis to 56 women with evidence of preterm labor or preterm premature rupture of membranes who delivered within 48 hours of amniotic fluid testing results. Twenty-three patients, assessed for fetal lung maturity in the third trimester, served as controls. Amniotic fluid was cultured for aerobic, anaerobic, Ureaplasma, and Mycoplasma species. We used mass spectrometry to assess the degree of intraamniotic inflammation (Mass Restricted scoring). After delivery, microbiologic and histologic studies of the placenta were performed. These results were interpreted in comparison with the direct microbiologic and inflammatory analysis of the amniotic fluid. A sample size of 45 patients was required to show a test accuracy of 80% or more. RESULTS Ninety-two percent of women with positive amniotic fluid cultures tested with at least one positive placenta culture. Eighty percent of women who had negative amniotic fluid cultures also tested with a positive placenta culture. The accuracy of placental cultures in predicting amniotic fluid infection varied from 44% to 57%. Placental pathology showed an accuracy of only 58% in diagnosing intraamniotic inflammation. CONCLUSION Placental microbiologic and histologic studies poorly reflect the infectious and inflammatory status of the amniotic fluid. Results of such studies should be interpreted with caution in the management and future counseling of women with preterm labor or preterm premature rupture of membranes. LEVEL OF EVIDENCE II.

BACKGROUND: Mullerian anomalies are associated with adverse pregnancy outcomes. We discuss pregnancy in anomalous uteri, with a focus on uterine didelphys, in the setting of a prior cesarean delivery. CASE(S): A 30-year-old woman, gravida 2 para 1001, presented in latent labor at 40 1/7 weeks of gestation. Her first pregnancy was in the right horn of a didelphic uterus and resulted in a cesarean delivery in the setting of chorioamnionitis remote from delivery. The current pregnancy was in the left horn and resulted in a vacuum-assisted vaginal delivery after spontaneous labor. CONCLUSION: There is sparse literature on a trial of labor after cesarean delivery in a uterine didelphys.

Progesterone is a steroid hormone that plays an integral role in each step of human pregnancy. In early pregnancy, progesterone produced by the corpus luteum is critical to the maintenance of early pregnancy until the placenta takes over this function at 7 to 9 weeks of gestation, hence its name (pro-gestational steroid hormone). The role of progesterone in later pregnancy, however, is less clear. It has been proposed that progesterone may be important in maintaining uterine quiescence in the latter half of pregnancy by limiting the production of stimulatory prostaglandins and inhabiting the expression of contraction-associated protein genes within the myometrium. Although systemic progesterone withdrawl may not correlate directly with the onset of labour in humans, there is increasing evidence to suggest that progesterone exerts its influence indirectly via a 'functional' withdrawl at the level of the uterus. The molecular mechanisms by which progesterone is able to maintain uterine quiescence and prevent preterm birth in some high-risk women are not clear. Six putative mechanisms have been proposed in the literature by both US and other investigators and are explored in this review.

Objective Term labor is associated with global thinning of the myometrium. We hypothesized that a thickened myometrium at the time of preterm premature rupture of membranes (PPROM) predicts less myometrial wall stress and, consequently, a longer latency interval. Study design Myometrial thickness was measured prospectively in 76 pregnant women enrolled in the following groups: PPROM (n=28, mean [range], gestational age [GA]: 29.5 weeks [w] [21.0 w-33.0 w]), preterm nonlabor control group (P-CTR), (n=21, GA: 27.5 w [23.0 w-32.0 w]) and term nonlabor control (T-CTR) (n=27, GA: 38.6 w [37.0 w-41.6 w]). All PPROM women had oligohydramnios (AFI: 1.4 cm [0.0 cm-5.1 cm]). MT was measured ultrasonographically at the midanterior, fundal, posterior, and lower uterine segment wall in cases and controls with an intraoperator variability Results Women in the PPROM group displayed uniform thickness of the uterine body (mean ± SEM, anterior: 10.6 ± 0.6 mm, fundal: 10.7 ± 0.7 mm, posterior: 8.9 ± 0.5 mm, P =.078). At midanterior site the myometrium of the PPROM group was thicker compared to both P-CTR ( P P =.025) groups. This difference was preserved at the fundus (PPROM vs P-CTR, P P =.015). There was a positive correlation between fundal MT and latency period ( r =0.43, P =0.02) that persisted after adjusting for GA ( P =.04). A fundal MT less than 12.1 mm was 93.7% sensitive and 63.6% specific for the identification of women whose latency period was less than 120 hours. Conclusion Significant thickening of the anterior and fundal walls of the uterus follows PPROM. A thick myometrium in nonlaboring patients with PPROM is associated with longer latency interval. Sonographic evaluation of MT may represent an alternative clinical tool for the prediction of a short latency interval in women with PPROM.

Objective The purpose of this study was to assess the validity of vaginal fetal fibronectin as a screening test for spontaneous preterm birth in patients with cervical cerclage. Study design A historic cohort of 117 patients who underwent cervical cerclage placement between 1996 and 2002 were identified. All patients were followed up in a maternal-fetal medicine faculty practice in a university setting. Serial fetal fibronectin samples of vaginal secretions were collected every 2 to 3 weeks, starting at 22 weeks of gestation and continuing until 32 weeks or delivery, whichever came first. Results There were 81 singleton, 23 twin, 12 triplet, and 1 quadruplet pregnancies. There were 61 ultrasound-indicated, 47 prophylactic, and 9 emergency cerclages that were placed. Most cerclages were of the modified Shirodkar type (95%) with a median gestational age at cerclage placement of 16.6 weeks. Overall, 33.3% of gestations were delivered spontaneously before 37 weeks of gestation; 17.1% of gestations were delivered spontaneously before 34 weeks. For deliveries within 2 weeks and 3 weeks of a single fetal fibronectin assessment, the test had a sensitivity of 50% and 48.3%, a specificity of 90% and 91.1%, a positive predictive value of 16.3% and 28.6%, and a negative predictive value of 97.9% and 96%, respectively. Subgroup analysis by number of fetuses (singleton, twin, and higher order multiple gestations) revealed similar values. For delivery before 34 weeks of gestation, fetal fibronectin had a sensitivity of 50%, a specificity of 78.4%, a positive predictive value of 33.3%, and a negative predictive value of 88%. Conclusion This study is the first to evaluate the use of vaginal fetal fibronectin assessments to screen for preterm birth in patients who had undergone cervical cerclage procedures. We conclude that this test has similar validity to predict spontaneous preterm delivery in these high-risk pregnancies, as in previously published cohorts.

Objectives Induction of fetal demise before second-trimester termination is performed for a number of reasons. One method for inducing fetal demise is via sonographically guided intracardiac potassium chloride (KCl) injection. We performed a retrospective cohort study to determine the efficacy and safety of intracardiac KCl injection as a method of second-trimester induced fetal demise. Methods We reviewed records from patients who were referred for induced fetal demise from October 2002 to October 2011. We excluded patients undergoing selective fetal reduction in multiple gestations. Procedural complications, the dose of KCl, and the number of failed procedures were determined. Results Of the 192 completed procedures, 191 were successful (99.5%). The median gestational age at termination was 22 weeks (range, 15.4–24.9 weeks), and most terminations were surgical (68.0%). Major indications for termination were fetal anomalies (41.6%), unwanted pregnancy (20.8%), and aneuploidy (15.7%). The median dose of KCl was 10 mL (range, 3–40 mL). We found a significant correlation between the dose of KCl and estimated fetal weight. There was no significant correlation between the dose of KCl and body mass index or gestational age. We had 1 maternal complication of a seizure after needle placement but before KCl injection. Conclusions Intracardiac KCl injection is an effective and safe method for induced fetal demise.

The occurrence of a psoas abscess after a spontaneous vaginal delivery is a rare postpartum complication with a significant mortality risk.A 17-year-old primiparous patient presented 3 weeks after an uncomplicated spontaneous vaginal delivery with fever refractory to antibiotics. Imaging revealed the patient to have a 4x4-cm abscess of the right iliopsoas muscle. The patient underwent drainage of the abscess along with the administration of intravenous antibiotics.Prompt recognition of and subsequent effective treatment for a psoas abscess are crucial to avoid potential long-term morbidity and even mortality.

Congenital cystic lesions of the lung in fetuses are rare. The most common malformations of the lower respiratory tract are congenital cystic adenomatoid malformation and bronchopulmonary sequestration. With the increased use of obstetric ultrasound, cystic lung lesions are detected more often antenatally, which allows for proper planning of peripartum and neonatal management. This article discusses a range of diagnostic and management options.

OBJECTIVE To test the hypothesis that myometrial thickness predicts the success of external cephalic version. METHODS Abdominal ultrasonographic scans were performed in 114 consecutive pregnant women with breech singletons before an external cephalic version maneuver. Myometrial thickness was measured by a standardized protocol at three sites: the lower segment, midanterior wall, and the fundal uterine wall. Independent variables analyzed in conjunction with myometrial thickness were: maternal age, parity, body mass index, abdominal wall thickness, estimated fetal weight, amniotic fluid index, placental thickness and location, fetal spine position, breech type, and delivery outcomes such as final mode of delivery and birth weight. RESULTS Successful version was associated with a thicker ultrasonographic fundal myometrium (unsuccessful: 6.7 [5.5-8.4] compared with successful: 7.4 [6.6-9.7] mm, P=.037). Multivariate regression analysis showed that increased fundal myometrial thickness, high amniotic fluid index, and nonfrank breech presentation were the strongest independent predictors of external cephalic version success (P

The diagnosis of uterine dehiscence in the early second trimester by ultrasonography is rare and its effect on pregnancy outcome is unclear.An asymptomatic woman presented for anatomy survey in the 19th week of pregnancy. Uterine dehiscence at the site of previous hysterotomy was diagnosed by ultrasound scan. She was admitted to the hospital for expectant management and eventually opted for termination of pregnancy in the 22nd week of pregnancy. Termination was performed by classical hysterotomy without any complications.Given the increasing cesarean delivery rate and improvements in ultrasound technology, obstetricians should expect to face the management dilemma of antenatally diagnosed uterine dehiscence. The risks of expectant management compared with termination remain theoretical, and timing of delivery and methods of termination are important questions to consider.

There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-α, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal–fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor.

PROBLEM Women with antiphospholipid antibodies (aPL) are at risk of miscarriage and pre-eclampsia, obstetrical disorders associated with reduced trophoblast invasion and spiral artery transformation. aPL target the placenta by binding beta(2) -glycoprotein I (β(2) GPI) on the trophoblast. In this study, we determined whether aPL alter the trophoblast secretion of angiogenic factors and evaluated the effect of low molecular weight heparin (LMWH) on this response. METHOD OF STUDY First-trimester trophoblast was treated with anti-β(2) GPI antibodies with or without LMWH. Angiogenic factor secretion was measured by enzyme-linked immunosorbent assay. RESULTS Trophoblast cells produced more vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), and soluble endoglin following exposure to anti-β(2) GPI Abs, and this occurred in both a MyD88-dependent and MyD88-independent manner. LMWH was unable to reverse the effects of the anti-β(2) GPI Abs on trophoblast VEGF secretion, but enhanced PlGF. Strikingly, LMWH upregulated soluble fms-like tyrosine kinase receptor-1 (sFlt-1) secretion independently of aPL. CONCLUSION This study demonstrates that aPL perturb the secretion of trophoblast angiogenic factors. LMWH does not reverse this effect but exacerbates sFlt-1 secretion, a potent anti-angiogenic factor. These findings may help to explain why women with antiphospholipid syndrome, who are treated with heparin to prevent early pregnancy loss, remain at increased risk of developing late obstetrical complications, such as pre-eclampsia.

To compare the incidence of wound complications between suture and staple skin closure after cesarean delivery.This prospective, randomized clinical trial conducted at three hospitals in the United States between 2010 and 2012 included women undergoing cesarean delivery at 23 weeks of gestation or greater through a low-transverse skin incision. Women were randomized to closure of the skin incision with suture or staples after stratifying by body mass index and primary compared with repeat cesarean delivery. The primary outcome was incidence of wound complications, predefined as a composite of infection, hematoma, seroma, separation of 1 cm or longer, or readmission for wound complications. Analysis was according to the intention-to-treat principle; results were stratified by randomization group and adjusted for hospital by including it as a covariate.A total of 746 women were randomized, 370 to suture and 376 to staple closure. The median gestational age was 39 weeks. Fifty-eight women (7.8%) had wound complications-4.9% in the suture group and 10.6% in the staple group (adjusted odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23-0.78); this was largely the result of the decreased incidence of wound separation in the respective groups (1.6% compared with 7.4%; adjusted OR 0.20, 95% CI 0.07-0.51).Suture closure of the skin incision at cesarean delivery is associated with a 57% decrease in wound complications compared with staple closure.Clinicaltrials.gov, www.clinicaltrials.gov, NCT01211600.I.

Objective We sought to characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta, or percreta shares features of epithelial-to-mesenchymal transition. Study Design We analyzed gestational age-matched serum samples from 90 pregnant women with either complete placenta previa (n = 45) or uncomplicated pregnancies (n = 45). Vascular endothelial growth factor (VEGF), placental growth factor, and soluble form of fms-like-tyrosine-kinase-1 were immunoassayed. VEGF and phosphotyrosine immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7. Results Women with previa and invasive placentation (accreta, n=5; increta, n=6; percreta, n=2) had lower systemic VEGF (invasive previa: median 0.8 [0.02-3.4] vs control 6.5 [2.7-10.5] pg/mL, P = .02). VEGF and phosphotyrosine immunostaining predominated in the invasive extravillous trophoblasts that coexpressed vimentin and cytokeratin-7, an epithelial-to-mesenchymal transition feature and tumorlike cell phenotype. Conclusion Lower systemic free VEGF and a switch of the interstitial extravillous trophoblasts to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion.

Five distinct lactate dehydrogenase isoenzymes have been described. We sought to illustrate the specific amniotic fluid lactate dehydrogenase isoenzyme activity profiles in women with intra-amniotic infection.Amniotic fluid was retrieved from 82 women who were stratified in the following groups: (1) positive amniotic fluid cultures (n = 23 women; gestational age, 26 weeks [range, 21-32 weeks]); (2) negative amniotic fluid cultures (n = 22 women; gestational age, 30 weeks [range, 16-36 weeks]); (3) second trimester control (normal genetic karyotype; n = 17 women; gestational age, 18 weeks [range, 16-22 weeks]); and (4) third trimester control (fetal lung maturity testing; n = 20 women; gestational age, 36 weeks [range, 31-38 weeks]). The optical density of each isoform was determined relative to a standard with 5 known lactate dehydrogenase isoenzyme activities. Total lactate dehydrogenase activity was measured by the clinical laboratory immediately after retrieval and by a kinetic UV spectrophotometric assay at the time of the isoelectric focusing.Infection increased total lactate dehydrogenase activity: positive amniotic fluid cultures (median, 762.4 [range, 169.3-3374.8]) vs negative amniotic fluid cultures (median, 203.7 [range, 57.8-1939.3]; U/L; P.001]). Lactate dehydrogenase isoform profiling identified significant and specific increases in lactate dehydrogenase isoforms 3, 4 (P.01), and 5 (P.05) in positive amniotic fluid cultures compared to the negative amniotic fluid cultures group. A selective up-regulation in lactate dehydrogenase isoform 5 was identified at term in healthy subjects.Intra-amniotic infection is characterized by an increase in the activities of lactate dehydrogenase isoforms 3, 4, and 5; advancing gestational age demonstrates an up-regulation of isoform 5 only.

Objective Elevation of total serum inhibin A and activin A has been interpreted as evidence of placental dysfunction in women who develop pre-eclampsia. We sought to evaluate serum and urine levels of inhibin A and free activin A in normal and hypertensive pregnancies. Study design Inhibin A and free activin A were measured by immunoassay in simultaneously collected serum and urine samples from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n = 11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams urine creatinine, and fractional excretions were calculated. Results Serum and urine inhibin A were increased and fractional excretion was decreased in pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in severe pre-eclampsia, compared with other gravidas. The only difference observed in free activin A was a decrease in serum free activin A in chronic hypertension, compared with severe pre-eclampsia and pregnant control women. Urine inhibin A showed the greatest discrimination between severe pre-eclampsia and pregnant control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity, 87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90 pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7-459.5) of a clinically indicated delivery due to pre-eclampsia. Conclusion Serum and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin A may have application in the diagnosis and management of pre-eclampsia. Those with chronic hypertension have lower serum but not urine free activin A levels, compared with severe pre-eclampsia and mild pre-eclampsia.

Four proteomic biomarkers (human neutrophil peptide 1 [HNP1], HNP2 [defensins], calgranulin C [Cal-C], and Cal-A) characterize the fingerprint of intra-amniotic inflammation (IAI). We compared proteomic technology using surfaced-enhanced laser desorption-ionization-time of flight (SELDI-TOF) mass spectrometry to enzyme-linked immunosorbent assay (ELISA) for detection of these biomarkers. Amniocentesis was performed on 48 women enrolled in two groups: those with intact membranes ( n = 27; gestational age [GA], 26.0 ± 0.8 weeks) and those with preterm premature rupture of the membranes (PPROM; n = 21; GA, 28.4 ± 0.9 weeks). Paired abdominal amniotic fluids (aAFs)-vaginal AFs (vAFs) were analyzed in PPROM women. Quantitative aspects of HNP1-3, Cal-C, Cal-A, and calprotectin (a complex of Cal-A with Cal-B) were assessed by ELISA. SELDI-TOF mass spectrometry tracings from 16/48 (33.3%) aAFs and 13/17 (88.2%) vAFs were consistent with IAI (three or four biomarkers present). IAI (by SELDI-TOF mass spectrometry) was associated with increased HNP1-3 and Cal-C measured by ELISA. However, immunoassays detected Cal-A in only 4 of the AFs even though its specific SELDI-TOF mass spectrometry peak was identified in 19/48 AFs. Calprotectin immunoreactivity was decreased in AFs retrieved from women with IAI ( P = 0.01). In conclusion, IAI is associated with increased HNP1-3 levels. In the absence of isoform-specific ELISAs, mass spectrometry remains the only way to discriminate the HNP biomarker isoforms. Monomeric Cal-A is not reliably estimated by specific ELISA as it binds to Cal-B to form the calprotectin complex. Cal-C was reliably measured by SELDI-TOF mass spectrometry or specific ELISA.

We sought to identify the use of vaginal amniotic fluid (vAF) glucose measurements in predicting infection of the amniotic fluid retrieved by transabdominal amniocentesis (aAF) in women with preterm premature rupture of the membranes (PPROM).Fluid was retrieved by aAF was retreived from 35 consecutive women with PPROM on whom an amniocentesis was clinically indicated to rule out intra-amniotic infection/inflammation and successfully completed. aAF was cultured for aerobic, anaerobic bacteria, Ureaplasma and Mycoplasma species. Clinical laboratory analysis for aAF included glucose concentration, Gram stain, lactate dehydrogenase, and white and red blood cell count. vAF was analyzed only for glucose concentration. Glucose concentration for the paired abdominal-vaginal AF samples (aAF-vAF) was determined by using well-established clinical and research laboratory methods. At the end of enrollment we stratified our patients into 2 groups: (1) positive microbial cultures (+)AFC (n = 17, gestational age [GA]: 27.3 +/- 0.7 weeks) or (2) negative microbial cultures (-)AFC (n = 18, GA: 31.3 +/- 0.5 weeks). Cohen kappa measure of concordance and receiver operating characteristic (ROC) curve analysis were used to test the ability of the vaginal "pool" glucose measurements to discriminate between women with positive or negative AF cultures.Women with (+)AFC ruptured and delivered at an earlier GA compared with the (-)AFC group (p.001). The latency period was similar (P = .35). There was a significant linear correlation between aAF and vAF glucose concentrations (r = 0.783, P.001). Women with intra-amniotic infection (IAI) had significantly lower aAF [mean +/- SEM (+)AFC: 11.4 +/- 3.2 vs (-)AFC 23.0 +/- 2.8 mg/dL, P = .01] and vAF glucose levels [(+)AFC: 10.1 +/- 2.8 vs (-)AFC: 19.8 +/- 2.9 mg/dL, P = .02] compared with the noninfected group. Cohen kappa measure of concordance indicated "substantial" agreement between aAF and vAF glucose measurements (kappa = 0.719, 95% CI = 0.491-0.947). The sensitivity of the vAF glucose level to detect IAI ranged from 82% to 47%, whereas specificity ranged from 100% to 56% depending on the threshold we used. A vaginal "pool" (vAF) glucose measurement less than 5 mg/dL had 47.1% sensitivity, 100% specificity, 100% positive predictive value, 66.7% negative predictive value, and 74.2% accuracy in identifying women with (+)AFC.Vaginal glucose determination is a readily available, inexpensive, rapid AF marker that can be measured practically in any clinical laboratory. vAF glucose measurements less than 5 mg/dL have predictive value, but low sensitivity for detection of IAI.

inflammatory response compared to infections with a single microbial species Antonette Dulay, Catalin Buhimschi, Lydia Shook, Guomao Zhao, Mert Bahtiyar, Christian Pettker, Anna Sfakianaki, Heather Lipkind, Sonya Abdel-Razeq, Irina Buhimschi Yale University, Ob/Gyn & Reprod. Sci., New Haven, CT OBJECTIVE: Amniotic fluid (AF) TLR2 mediated innate immune signaling occurs following their engagement by Gram positive (GP), Mycoplasma and Ureaplasma spp. TLR4 recognizes Gram negative (GN) microbial ligands. Because cross-talk among TLR2 and TLR4 may generate a differential immune reaction, we explored in vivo and in vitro the intensity of an inflammatory response elicited by single vs mixed spp. STUDY DESIGN: We studied 133 preterm AF samples from amniocentesis in the following groups: single GN species (n 37, GA 26 3w), single GP (n 24, GA 26 3w), Mycoplasma or Ureaplasma (n 30, GA 26 4w), mixed TLR2 ligands (n 10, GA 26 2w), and mixed TLR2 and TLR4 ligands (n 32, GA 25 1w). IL6, TNF , IL8, and the anti-inflammatory IL10 were assessed by ELISA. Data was corrected for GA. A HEK293 Blue-4 cell line was used to address specific ligand effects with particular focus on TLR4 activation. HEK cells were incubated (n 5) with TLR4 (LPS), TLR2 (Lipoteichoic acid [LTA], Pam3Cys [PAM], Mycoplasma FSL-1) & mixed ligand groups (LPS PAM, LPS FSL-1, PAM LTA). RESULTS: In vivo, compared to all other possible combinations, single GN infections had the highest AF IL6, IL8, TNF and IL10 levels (P .001). There was no difference in the inflammatory response among various single TLR2 engaging spp. Conversely, mixed GPs augmented all cytokine responses at levels above single TLR2-engaging spp. (P .016). When GNs cohabitate in AF with GP microbes the cytokine response is above that elicited by single or mixed GPs but less than GNs alone (all P .05). In vitro, LPS induced the highest TLR4 activation (P .001), with the lowest response seen for FSL. LPS response was significantly dampened by PAM (12-fold decrease) and FSL-1 (10-fold decrease). LTA PAM gave a 2-fold increase in cell activation over either alone (all P .05). CONCLUSION: GN bacteria generate a robust AF inflammatory response, that could be either potentiated or dampened through their interaction with various GPs or Ureaplasma/Mycoplasma spp.

gestation. Neonatal evaluation revealed left knee over extension and reactive TPHA with titer 1:10240. Radiographic evaluation disclosed dislocation of left knee joint. After benzathine penicillin administration and close reduction of left knee with cast fixation. The neonate was discharged smoothly. Congenital dislocation of knee is a rare condition which estimated about 0.017 in 1,000 births. The etiology remains unclear but supposes contracture of the quadriceps femoris muscle with variable deformity of anterior cruciate ligament. Congenital syphilis may present demineralization and osseous destruction of long bone. Joint dislocation was never reported in congenital syphilis in literature. Fetus with maternal syphilis should examine the joint of four extremities with prenatal ultrasound carefully.

The objective of the study was to evaluate longitudinally the in vivo changes in myometrial thickness (MT) during gestation in patients carrying twin gestations in relation to pregnancy outcome.Serial abdominal ultrasounds were performed prospectively in 92 patients carrying twin gestations through each trimester. Ninety-seven patients pregnant with singletons served as controls. For twins, the primary endpoint was spontaneous delivery at less than 35 weeks' gestational age (GA). The myometrium was defined sonographically as the echohomogeneous layer between the serosa and the decidua and was measured at the anterior, fundal, and lower uterine segment (LUS) walls. The estimated fetal weight, maximum vertical pocket of amniotic fluid, and placental thickness were also assessed ultrasonographically at the same time as the MT and served as estimates for the contribution of each to the uterine volume. In twins, cervical length measurements were performed transvaginally, as clinically indicated. Data analysis included 2-way analysis of variance and linear, nonlinear, and multivariate regression.A total of 41.3% of twin pregnancies (38 of 92) delivered preterm (35 weeks). There were no significant changes in measurements at the anterior and fundal site over time throughout pregnancy and no differences in these sites between twin and singleton gestations. Conversely, in both twins and singletons, there was a significant and gradual thinning of the LUS myometrium during gestation. In the absence of uterine contractions or symptoms of preterm labor, twins that delivered preterm had a significantly thinner LUS at an earlier gestation, compared with twins that delivered at term (P.001), suggesting that LUS thinning occurred earlier in these cases. There was a significant correlation between cervical length and LUS thinning during gestation in twins that delivered 35 weeks GA or later (r = 0.352; P.001) but not in those that delivered preterm (35 weeks GA; r = 0.125; P = .326).Twin pregnancy is characterized by a significant, selective, and gradual thinning of the LUS during gestation, which does not occur in the anterior and fundal myometrium. Thinning of the LUS occurs earlier in twin pregnancies destined to deliver preterm. These observations suggest that similar to the cervix, the LUS changes dynamically during twin pregnancy and that this too may be assessed through ultrasound imaging.

It has been shown that hypoxia leads to alterations in maternal serum levels of vascular endothelial growth factor (VEGF). In this study, we sought to test the hypothesis that chronic hypoxia increases maternal serum levels of VEGF, which in turn cause measurable changes in the viscoelastic properties of the rat uterine cervix.Timed-pregnant adult Sprague-Dawley rats were exposed to hypoxia beginning on day 17 of gestation (term = day 22). The following groups of animals were studied: (1) nonpregnant controls (NP, n = 6); (2) normoxia 21% fraction of inspired oxygen (FiO2) (NMX, n = 6); and (3) severe hypoxia 10% FiO2 (HPX; n = 5). A hypoxic chamber was used to assure consistent hypoxic environment. Animals were killed on day 21 of gestation (before labor). Maternal blood was collected immediately following anesthesia and prior to euthanasia. Free serum levels of VEGF were measured by highly specific immunoassays. Tensile strength properties of the cervix were assessed using a stretching regimen designed to mimic labor. Physical parameters measured were: indicators of viscoelasticity (slope; measure of stiffness), plasticity (yield point [YP]; moment the tissue changes its properties from elastic to plastic), strength (break point [BP]; moment of tissue disruption), and displacement at YP (marks the duration of the viscoelastic phase of the stretching) and BP (a measure of the strength of the material). Data were normalized to the dry weight of the cervix.Hypoxia is associated with increased serum levels of VEGF compared to NP or NMX groups (P = .001). Cervical stiffness was lower in NMX, compared with NP animals (P = .004), and was not significantly influenced by hypoxia (P.05). Overall there was a significant inverse correlation between slope and maternal serum levels of VEGF (r = -0.85, P.001). The force required to reach YP was significantly higher for the NP, compared with NMX and HPX groups (P = .004). Hypoxia did not alter the force required to reach the YP (NMX vs HPX, P.05). Conversely, hypoxia significantly decreased the displacement at YP, indicating a shortening of the elastic phase (NMX vs HPX, P = .021). There was a significant inverse correlation between maternal serum levels of VEGF and the displacement at YP (r = -0.68, P = .002). In vivo, hypoxia decreased the force required to reached the BP (NMX vs HPX, P = .025), but there was no correlation between the levels of maternal serum VEGF and this indicator (r = -0.35, P = .170).Chronic hypoxia induces measurable changes in maternal serum levels of VEGF and tensile properties of the rat cervix, specifically a shortening of the elastic phase. Hypoxia decreases the cervical strength to stretch and predisposes to rupture, but this effect seems to be unrelated to maternal serum levels of VEGF.

MECHANISM BY WHICH FIRST TRIMESTER BLEEDING CAUSES ABORTION VICTORIA SNEGOVSKIKH, ERIC HODGSON, ANNA SFAKIANAKI, EDMUND FUNAI, YUEHONG MA, SETH GULLER, MIZANUR RAHMAN, CATALIN BUHIMSCHI, IRINA BUHIMSCHI, ERROL NORWITZ, Yale University, New Haven, Connecticut OBJECTIVE: Bleeding in the first trimester is associated with spontaneous pregnancy loss, but whether this bleeding causes the abortion or is simply a sign of an already unsuccessful implantation is not clear. Adequate production of hCG by syncytiotrophoblast is critical to the maintenance of early pregnancy by sustaining progesterone production by the corpus luteum. We propose that bleeding may cause abortion by interfering with hCG-progesterone signalling. This study investigates the effect of thrombin on hCG production by syncytiotrophoblast in vitro. STUDY DESIGN: Term placentae were collected from elective cesarean deliveries and cytotrophoblast cells isolated by enzymatic digestion and purified using Percoll gradient. As previously described, cells were cultured in Basal Dulbecco’s medium containing 5% fetal calf serum for 3-4 days at which time syncytiotrophoblast formation was evident. Cells were cultured in fresh serum-free medium and stimulated with or without thrombin (2.5 IU/mL) for 24h. Levels of hCG in conditioned supernatant were measured by specific ELISA and corrected for protein content. Data were analyzed by ANOVA and Chi square tests. RESULTS: Thrombin significantly suppressed hCG levels in conditioned supernatant of cultured syncytiotrophoblast from 40.8 7.5 to 20.7 3.7 mIU/mg of protein per 24h (mean SEM; n 6; p 0.038) (Figure).