Temporal, spectral and amplitude characteristics of the Greek fricative /s/ in hearing-impaired and normal-hearing speech.

Fricatives, and especially sibilants, are very frequently misarticulated by speakers with hearing loss. Misarticulations can result in phonemic contrast weakening or loss, compromising intelligibility. The present study focuses on the examination of acoustic characteristics of the Greek alveolar fricative /s/, an articulatorily demanding sound, produced by young adult speakers with profound hearing impairment and with normal hearing. An array of variables was examined using mixed-effects and random forest models aiming to assess the effectiveness of various measures in differentiating hearing-impaired and normal-hearing /s/ production. Significant differences were found in spectral and amplitude measures, but not in temporal measures. In hearing-impaired speech, spectral slope and RMS amplitude had significantly lower values, indicating a more distributed spectrum, suggestive of decreased flow velocity through the fricative constriction. Also, a trend for concentration of energy at lower frequencies was observed suggesting more posterior fricative articulation than normal. Moreover, measures capturing the variation of frequency and amplitude over time revealed different patterns of sibilance development across time than normal, denoting the production of a less well-formed or less sibilant /s/ by speakers with hearing impairment. The investigation of contextual effects on /s/ in hearing-impaired speech showed increased spectral variance, negative skewness and lower kurtosis in the labial (rounded) context /u/ in relation to the nonlabial contexts /i/ and /a/, indicating a more diffuse, less compact spectrum with concentration at high frequencies. Findings are discussed in relation to previous literature on fricative production by speakers with hearing impairment and normal hearing in Greek and other languages.

Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney.

Oxidative stress occurs when there is an imbalance between reactive oxygen species/reactive nitrogen species and antioxidant systems. The interplay between these complex processes is crucial for normal pregnancy and fetal development; however, when oxidative stress predominates, pregnancy related complications and adverse fetal programming such as preterm birth ensues. Understanding how oxidative stress negatively impacts outcomes for the maternal-fetal dyad has allowed for the exploration of antioxidant therapies to prevent and/or mitigate disease progression. In the developing kidney, the negative impact of oxidative stress has also been noted as it relates to the development of hypertension and kidney injury mostly in animal models. Clinical research addressing the implications of oxidative stress in the developing kidney is less developed than that of the neurodevelopmental and respiratory conditions of preterm infants and other vulnerable neonatal groups. Efforts to study the oxidative stress pathway along the continuum of the perinatal period using a team science approach can help to understand the multi-organ dysfunction that the maternal-fetal dyad sustains and guide the investigation of antioxidant therapies to ameliorate the global toxicity. This educational review will provide a comprehensive and multidisciplinary perspective on the impact of oxidative stress during the perinatal period in the development of maternal and fetal/neonatal complications, and implications on developmental programming of accelerated aging and cardiovascular and renal disease for a lifetime.

"Because the resources aren't there, then we fail. We fail as a society": A Qualitative Analysis of Human Trafficking Provider Perceptions of Child Welfare Involvement among Trafficked Mothers.

BACKGROUND: Little is understood about child welfare involvement (CWI) in cases where the birth mother has experienced human trafficking. OBJECTIVES: The aim of this study was to explore provider perceptions of the impact of CWI for the trafficked mother. METHODS: Participants were selected among providers caring for trafficked birth mothers. Semi-structured interviews were conducted with providers and qualitative content analysis was conducted. RESULTS: Interviewees reported reasons for CWI, positive and negative impacts of CWI and provided recommendations for systems improvement. CONCLUSION FOR PRACTICE: 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.

Cesarean section in patient with metastatic Ewing sarcoma requiring VA-ECMO support.

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.

Utility of routine screening fetal echocardiogram in pregnancies conceived by in vitro fertilization.

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.

Placenta Accreta: A Spectrum of Predictable Risk, Diagnosis, and Morbidity.

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.

Cesarean Scar Pregnancy, Incidence, and Recurrence: Five-Year Experience at a Single Tertiary Care Referral Center.

OBJECTIVE: To describe the treatment and subsequent pregnancy outcomes in patients with cesarean scar pregnancies at a single institution over 5 years. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Coarticulatory dynamics in Greek disyllables produced by young adults with and without hearing loss.

Hearing loss affects both speech perception and production with detrimental effects on various speech characteristics including coarticulatory dynamics. The aim of the present study is to explore consonant-to-vowel (C-to-V) and vowel-to-vowel (V-to-V) coarticulation in magnitude, direction and temporal extent in the speech of young adult male and female speakers of Greek with normal hearing (NH) and hearing impairment (HI). Nine intelligible speakers with profound HI, using conventional hearing aids, and five speakers with NH produced /pV1CV2/ disyllables, with the point vowels /i, a, u/ and the consonants /p, t, s/, stressed either on the first or the second syllable. Formant frequencies F1 and F2 were measured in order to examine C-to-V effects at vowel midpoint and V-to-V effects at vowel onset, midpoint and offset. The acoustic and statistical analyses revealed similarities but also significant differences regarding coarticulatory patterns of the two groups. Interestingly, prevalence of anticipatory coarticulation effects in alveolar contexts was observed for speakers with HI. Findings are interpreted on account of possible differences in articulation strategies between the two groups and with reference to current coarticulatory models.

Acoustic characteristics of vowels produced by Greek intelligible speakers with profound hearing impairment I: Examination of vowel space.

PURPOSE: The study examines F1, F2 and F3 formant frequencies of vowels produced by six Greek intelligible speakers with profound hearing impairment and six speakers with normal hearing (three male and three female in each group). METHOD: The formant frequencies are measured in words of the form /'pVCV/ where V = /i, , , , u/ and C = /p, t, k, s/. The study examines differences in formant frequencies between the two groups and as a function of gender. Three measures are calculated to examine the area of the vowel space and differences along the F1 and F2 axes between the groups and genders. RESULT: The results show that the vowel space produced by the speakers with hearing impairment is considerably reduced. Greater reduction was evident for F2 compared to F1. Restricted formant frequency ranges and relatively large variation along F1 and/or F2 for selected vowels resulted in overlap among vowel categories. F3 frequencies were systematically lower and showed greater variation for the speakers with hearing impairment. CONCLUSION: The paper discusses findings with reference to perceptual and production constraints affecting the speech of individuals with hearing impairment.

Acoustic characteristics of vowels produced by Greek intelligible speakers with profound hearing impairment II: The influence of stress and context.

PURPOSE: The present paper examines the influence of stress and context on selected acoustic characteristics of vowels produced by six adult Greek intelligible speakers with profound hearing impairment and six speakers with normal hearing (three males and three females in each group). METHOD: F1, F2 and F3 formant frequencies and the duration of vowels are measured in words of the form /(')pVCV/ with V = /i, ɛ, ɐ, ɔ, u/ and C = /p, t, k, s/. Variation in these parameters due to context and stress is reported for the two genders. A co-articulatory measure and three measures that examine the area of the vowel space and differences along the F1 and F2 axes are calculated. RESULT: The results show a reduction of the vowel space in the unstressed condition for both groups, while vowel duration was found to be significantly longer in this condition for the speakers with hearing impairment. In addition, smaller C-to-V carryover co-articulatory effects were found for the speakers with hearing impairment. CONCLUSION: Findings are discussed within the framework of perceptual and production constraints in hearing impairment and with reference to current models of co-articulation.

Uterine didelphys and vaginal birth after cesarean delivery.

BACKGROUND: Müllerian 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.

Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast.

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.

Suture compared with staple skin closure after cesarean delivery: a randomized controlled trial.

OBJECTIVE: To compare the incidence of wound complications between suture and staple skin closure after cesarean delivery. METHODS: 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. RESULTS: 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). CONCLUSIONS: Suture closure of the skin incision at cesarean delivery is associated with a 57% decrease in wound complications compared with staple closure. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT01211600. LEVEL OF EVIDENCE: I.

Potassium chloride-induced fetal demise: a retrospective cohort study of efficacy and safety.

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.

Congenital cystic lesions of the lung: congenital cystic adenomatoid malformation and bronchopulmonary sequestration.

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.

Pravastatin does not prevent antiphospholipid antibody-mediated changes in human first trimester trophoblast function.

STUDY QUESTION: What is the effect of pravastatin on antiphospholipid antibody (aPL) modulation of human first trimester trophoblast function? SUMMARY ANSWER: Pravastatin does not prevent the effects of aPL on human first trimester trophoblast cell function. WHAT IS KNOWN ALREADY: Antiphospholipid syndrome (APS) is associated with recurrent pregnancy loss and late pregnancy complications, such as pre-eclampsia, owing to direct targeting of the placenta by aPL. While treatment with heparin reduces the rate of pregnancy loss, the risk for severe pre-eclampsia remains high. Thus, there is a need to find alternative treatments for the prenatal management of patients with APS. Statins have recently been shown to prevent aPL-mediated fetal loss in mice but their effects on a human pregnancy model of APS have not yet been studied. DESIGN, DATA COLLECTION, METHODS: The human first trimester trophoblast cell line, HTR8, and human first trimester trophoblast primary cultures were incubated with or without a mouse anti-human beta 2 glycoprotein I (ß(2)GPI) monoclonal antibody in the presence or absence of pravastatin. Cytokine and angiogenic factor secretion were measured by enzyme-linked immunosorbent assay and multiplex analysis. Cell migration was measured using a colorimetric two-chamber migration assay. MAIN FINDINGS: Using the human first trimester trophoblast cell line, HTR8, pravastatin significantly augmented, compared with no treatment, aPL-dependent secretion of interleukin (IL)-8 (P< 0.05), IL-1ß (P< 0.05) and soluble endoglin (P< 0.01) but had no effect on aPL-induced up-regulation of vascular endothelial growth factor, placenta growth factor or growth-related oncogene alpha secretion. Furthermore, pravastatin alone limited basal HTR8 cell migration (P< 0.01), and did not mitigate the adverse effect of aPL on trophoblast migration. Pravastatin also had no impact on the secretion of pro-inflammatory cytokines and angiogenic factors by primary human first trimester trophoblast cells exposed to aPL. LIMITATIONS AND WIDER IMPLICATIONS OF THE FINDINGS: While our in vitro findings suggest that pravastatin may not be effective in preventing pregnancy complications in patients with APS, the in vivo condition may be more complex, and thus, more studies are needed to determine the effectiveness of pravastatin in the prevention of aPL-associated pregnancy complications in humans. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the American Heart Association.

Ultrasonographic evaluation of myometrial thickness and prediction of a successful external cephalic version.

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<.001). A fundal myometrial thickness greater than 6.75 mm and an amniotic fluid index greater than 12 cm were each associated with successful external cephalic versions (fundal myometrial thickness: odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.2, P=.029; amniotic fluid index: OR 2.8, 95% CI 1.3-6.0, P=.008). Combining the two variables resulted in an absolute risk reduction for a failed version of 27.6% (95% CI 7.1-48.1) and a number needed to treat of four (95% CI 2.1-14.2). CONCLUSION: Fundal myometrial thickness and amniotic fluid index contribute to success of external cephalic version and their evaluation can be easily incorporated in algorithms before the procedure. LEVEL OF EVIDENCE: III.

Uterine dehiscence in early second trimester.

BACKGROUND: The diagnosis of uterine dehiscence in the early second trimester by ultrasonography is rare and its effect on pregnancy outcome is unclear. CASE: 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. CONCLUSION: 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.

Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor.

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.

Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin.

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 (ß(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-ß(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-ß(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-ß(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.