Immune Modifications in Fetal Membranes Overlying the Cervix Precede Parturition in Humans.

In humans, parturition is currently viewed as an intrauterine outbreak of inflammation, accompanied by a massive release of proinflammatory cytokines at the maternal-fetal interface that comprises the maternal decidua, placenta, and fetal membranes. At term, fetal membranes overlying the cervix, the future site of rupture, show altered morphology and are termed the zone of altered morphology (ZAM). These alterations occur in normal fetal membranes during late pregnancy, in preparation for labor. In this study, transcriptome, flow cytometry, electron microscopy, and immunohistochemistry analyses collectively highlight a local shift in gene expression and lymphocyte activation in the ZAM. Just before labor, we show that highly polymorphic HLA-A, -B, and -C determinants of fetal origin are selectively exposed in the ZAM to the maternal immune system. A graft rejection-like program occurs in the ZAM, which involves 1) the activation of cytotoxic decidual NK cells, and 2) the decline of decidual immunotolerant M2-like macrophages. Comparison with a prior cohort of fetal membranes shows that acute inflammation only takes place after these first steps of immune modifications. Our results therefore strongly argue in favor of local immune remodeling at the onset of parturition.

Impact of routine transvaginal ultrasound monitoring of cervical length in twins on administration of antenatal corticosteroids.

OBJECTIVE: To evaluate whether routine measurement of cervical length (CL) by transvaginal ultrasound (TVU) in twin pregnancies can enable identification of women who will give birth before 34 weeks and require antenatal corticosteroids (ACSs), and whether it can limit their administration to women who will give birth later. STUDY DESIGN: Retrospective comparative study in two tertiary referral centers in France. Women with twin gestations followed in two tertiary university hospital maternity units and who delivered from January 1, 2007 to December 31, 2009 were included. In one center, TVU was targeted to women with cases of suspected preterm labor, while the other center used it monthly for all twin pregnancies. The main outcome measure was the administration of a full course of ACS to twins delivered before 34 weeks. RESULTS: Two hundred and seventy women were eligible in the "targeted use" group, and 296 women in the "routine use" group. The rate of administration of at least one full course of ACS for twins born before 34 weeks did not differ between the two groups (85.0% in the targeted use group and 90.0% in the routine use group, P=0.40), but the rate of such administration for those born after 34 weeks was lower in the targeted use group (25.7% vs. 81.2%, P<0.01). On adjusting for confounders using logistic regression modeling, no significant difference in ACS administration before 34 weeks was found between the two groups [adjusted odds ratio (aOR), 0.71, 95% confidence interval (CI), 0.39-1.30]. CONCLUSION: Routine monitoring performed every month of CL with TVU does not affect the rate of administration of ACS to twins born before 34 weeks, but is associated with a higher rate of such administration for those born later in the specific center of the study.

Assessment of the Cervix in Pregnant Women Using Shear Wave Elastography: A Feasibility Study.

The quantitative assessment of the cervix is crucial for the estimation of pre-term delivery risk and the prediction of the success of labor induction. We conducted a cross-sectional study using shear wave elastography based on the supersonic shear imaging technique. The shear wave speed (SWS) of the lower anterior part of the cervix was quantified over an 8-mm region of interest in 157 pregnant women. Cervical SWS is slightly but significantly reduced in patients diagnosed with pre-term labor and in patients who actually delivered pre-term.

Air stepping in response to optic flows that move Toward and Away from the neonate.

To shed further light on the perceptual regulation of newborn stepping, we compared neonatal air stepping in response to optic flows simulating forward or backward displacement with stepping forward on a surface. Twenty-two 3-day-olds performed four 60 s trials in which they stepped forward on a table (Tactile) or in the air in response to a pattern that moved toward (Toward) or away (Away) from them or was static (Static). Significantly more steps were taken in the Tactile and Toward conditions than the Static condition. The Away condition was intermediate to the other conditions. The knee joint activity across the entire trial was significantly greater in the Toward than the Away condition. Within-limb kinematics and between-limb coordination were very similar for steps taken in the air and on the table, particularly in the Toward and Tactile conditions. These findings highlight that visual and tactile stimulation can equally elicit neonatal stepping.

Friend or foe? Early social evaluation of human interactions.

We report evidence that 29-month-old toddlers and 10-month-old preverbal infants discriminate between two agents: a pro-social agent, who performs a positive (comforting) action on a human patient and a negative (harmful) action on an inanimate object, and an anti-social agent, who does the converse. The evidence shows that they prefer the former to the latter even though the agents perform the same bodily movements. Given that humans can cause physical harm to their conspecifics, we discuss this finding in light of the likely adaptive value of the ability to detect harmful human agents.

Neural correlates of infant accent discrimination: an fNIRS study.

The present study investigated the neural correlates of infant discrimination of very similar linguistic varieties (Quebecois and Parisian French) using functional Near InfraRed Spectroscopy. In line with previous behavioral and electrophysiological data, there was no evidence that 3-month-olds discriminated the two regional accents, whereas 5-month-olds did, with the locus of discrimination in left anterior perisylvian regions. These neuroimaging results suggest that a developing language network relying crucially on left perisylvian cortices sustains infants' discrimination of similar linguistic varieties within this early period of infancy.

Vertical and horizontal smooth pursuit eye movements in children with developmental coordination disorder.

AIM: Our aim was to study horizontal and vertical smooth pursuit eye movements in children with developmental coordination disorder (DCD). METHOD: Horizontal and vertical smooth pursuit eye movements of 91 children were studied using electro-oculography: 27 children with DCD (23 males, four females), according to the DSM-IV-TR criteria, and 64 comparison children (26 males, 38 females). All children were 7 to 12 years old (mean 9y, SD 1.5y). Among the group of children with DCD, eight had received intervention. Intervention exercised static and dynamic fixation, saccades, visual strategies, visuospatial abilities, and eye-hand coordination. A smooth pursuit gain index was calculated and statistical comparisons were made between the two groups of children. RESULTS: Horizontal pursuit gain was similar in both populations, but vertical pursuit gain was significantly impaired (p<0.001, after adjusting for age as covariate), i.e. more saccadic in children with DCD (18-99%; n=27, mean 51.6%, median 48.5%, SD 23.2%) than in comparison participants (35-97%; n=63, mean 66.4%, median 65.0%, SD 15.4%). Among the DCD group, the vertical pursuit index was also significantly higher (p=0.009) in the intervention subgroup (29-99%; n=8, mean 69.4%, median 75.5%, SD 28.7%) than in the non-intervention subgroup (18-74%; n=19, mean 44.1%, median 42.5%, SD 15.9%). INTERPRETATION: These results suggest a delay in the maturation of the pursuit system in children with DCD.

Risk factors of superimposed preeclampsia in women with essential chronic hypertension treated before pregnancy.

OBJECTIVE: To determine risk factors of superimposed preeclampsia in women with essential chronic hypertension receiving antihypertensive therapy prior to conception. METHODS: A retrospective study of 211 patients that analyzed risk factors of superimposed preeclampsia at first prenatal visit. Variables with a p<.1 at univariate analysis were included in a logistic regression analysis. P<.05 was considered as significant. RESULTS: Superimposed preeclampsia occurred in 49 (23.2%) women. In logistic regression analysis, previous preeclampsia [OR: 4.05 (1.61-10.16)], and mean arterial blood pressure of 95 mmHg or higher [OR: 4.60 (1.94-10.93)] were associated with increased risk of superimposed preeclampsia. When both variables were present, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for superimposed preeclampsia were 43%, 94%, 70%, 85%, and 7.71 (95% CI: 3.20-18.57), respectively. CONCLUSION: In essential chronic hypertensive women, previous preeclampsia and mean arterial blood pressure of 95 mmHg or higher are associated with increased risks of superimposed preeclampsia.

Insights on NIRS Sensitivity from a Cross-Linguistic Study on the Emergence of Phonological Grammar.

Each language has a unique set of phonemic categories and phonotactic rules which determine permissible sound sequences in that language. Behavioral research demonstrates that one's native language shapes the perception of both sound categories and sound sequences in adults, and neuroimaging results further indicate that the processing of native phonemes and phonotactics involves a left-dominant perisylvian brain network. Recent work using a novel technique, functional Near InfraRed Spectroscopy (NIRS), has suggested that a left-dominant network becomes evident toward the end of the first year of life as infants process phonemic contrasts. The present research project attempted to assess whether the same pattern would be seen for native phonotactics. We measured brain responses in Japanese- and French-learning infants to two contrasts: Abuna vs. Abna (a phonotactic contrast that is native in French, but not in Japanese) and Abuna vs. Abuuna (a vowel length contrast that is native in Japanese, but not in French). Results did not show a significant response to either contrast in either group, unlike both previous behavioral research on phonotactic processing and NIRS work on phonemic processing. To understand these null results, we performed similar NIRS experiments with Japanese adult participants. These data suggest that the infant null results arise from an interaction of multiple factors, involving the suitability of the experimental paradigm for NIRS measurements and stimulus perceptibility. We discuss the challenges facing this novel technique, particularly focusing on the optimal stimulus presentation which could yield strong enough hemodynamic responses when using the change detection paradigm.

(Non)words, (non)words, (non)words: evidence for a protolexicon during the first year of life.

Previous research with artificial language learning paradigms has shown that infants are sensitive to statistical cues to word boundaries (Saffran, Aslin & Newport, 1996) and that they can use these cues to extract word-like units (Saffran, 2001). However, it is unknown whether infants use statistical information to construct a receptive lexicon when acquiring their native language. In order to investigate this issue, we rely on the fact that besides real words a statistical algorithm extracts sound sequences that are highly frequent in infant-directed speech but constitute nonwords. In three experiments, we use a preferential listening paradigm to test French-learning 11-month-old infants' recognition of highly frequent disyllabic sequences from their native language. In Experiments 1 and 2, we use nonword stimuli and find that infants listen longer to high-frequency than to low-frequency sequences. In Experiment 3, we compare high-frequency nonwords to real words in the same frequency range, and find that infants show no preference. Thus, at 11 months, French-learning infants recognize highly frequent sound sequences from their native language and fail to differentiate between words and nonwords among these sequences. These results are evidence that they have used statistical information to extract word candidates from their input and stored them in a 'protolexicon', containing both words and nonwords.

Assessing signal-driven mechanisms in neonates: brain responses to temporally and spectrally different sounds.

Past studies have found that, in adults, the acoustic properties of sound signals (such as fast versus slow temporal features) differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns' brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS) and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb) in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

Functional screening of TLRs in human amniotic epithelial cells.

Intrauterine infection is a major cause of spontaneous preterm birth. Amniotic epithelial cells represent the first line of defense against intra-amniotic bacteria. We hypothesize that this epithelial cell barrier is able to recognize and respond to pathogens through the function of TLRs, which are crucial regulators of the innate immune system. In this study, we describe the expression of transcripts for TLR1-TLR10 in human amniotic epithelial cells. We show that amniotic epithelial cells express functional TLR5, TLR6/2, and TLR4. Activation by TLR5 and TLR6/2 agonists produces IL-6 and IL-8, concomitantly with the activation of NF-κB signaling pathway, matrix metalloproteinase-9 induction, and PTGS2 expression. In contrast, TLR4 activation reduced amniotic epithelial cell viability and induced cell apoptosis evidenced by an elevated Bax/Bcl-2 ratio and cleavage of caspase-3. These data suggest specific TLR-mediated functions in human amniotic epithelial cells for initiating different immune responses, which ultimately may lead to preterm birth.

Subtypes of developmental coordination disorder: research on their nature and etiology.

Children with Developmental Coordination Disorder (DCD) are a group embracing clumsiness and developmental dyspraxia. Our study provides a better understanding of the nature of DCD and its etiology, and identifies subtypes of dyspraxia. Forty-three children with DCD (5-15 years) were enrolled on the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV-TR]; American Psychiatric Association, 2000) criteria. Extensive standardized evaluations were conducted. We distinguished from two patterns of "pure" developmental dyspraxia: ideomotor and visual-spatial/visual-constructional, and mix dyspraxia with more co-morbidities. Our study provides a better understanding of the nature of DCD, and sheds light on its etiology and brain dysfunction, so as to identify subtypes of developmental DCD/dyspraxia with specific clinical criteria.

Vascularization of the placenta and the sub-placental myometrium: feasibility and reproducibility of a three-dimensional power Doppler ultrasound quantification technique. A pilot study.

OBJECTIVE: To assess the feasibility of placental and myometrial vascularization quantification using 3D power Doppler ultrasonography. METHODS: 3D standardized acquisition was performed in the mid part of the utero-placental unit, once, in 38 patients undergoing normal pregnancies between 15 and 39 weeks. Vascularization parameters (VI, FI, and VFI) of placentae and myometrium were measured. Intra and inter-observer, as well as inter-acquisition reproducibility were evaluated. RESULTS: Intra-class Correlation Coefficient of vascularization measurements were at least 0.94 for intra-observer, 0.92 for inter-observer, and 0.56 for inter-acquisition reproducibility. There was no significant difference for placental measurements for VI, FI and VFI between the second trimester and the third trimester pregnancies. Concerning the myometrium, we observed no significant difference between second and third trimester for FI. However, VI (28.090 vs. 19.374) and VFI (17.691 vs. 11.336) was significantly lower in the third trimester (p < 0.01). CONCLUSION: 3D quantification of placental and myometrial vascular parameters is feasible with a high intra and inter-observer reproducibility. Evaluating a potential myometrial vascular impairment appears to be as relevant as studying the placenta alone and might be of great clinical interest. We believe that this technique should therefore be evaluated in clinical observational studies.

Active versus expectant management for preterm prelabor rupture of membranes at 34-36 weeks of completed gestation: comparison of maternal and neonatal outcomes.

OBJECTIVE: To compare maternal and neonatal outcomes in deliveries managed by a policy of expectant management and active management of women with preterm prelabor rupture of membranes (pPROM), at 34-36 completed weeks of gestation. DESIGN: Retrospective multicenter cohort study. SETTING: Three tertiary care teaching hospitals in France. POPULATION: Women with pPROM were identified from the databases of three perinatal centers. METHODS: Maternal and neonatal complications were compared according to the hospital policy in effect at pPROM--expectant or active management. MAIN OUTCOME MEASURES: Clinical chorioamnionitis, neonatal morbidity including neonatal infection, respiratory problems, and metabolic disorders. RESULTS: During the seven-year study period, 634 women were admitted for pPROM at 34-36 completed weeks of gestation, 241 of whom were included in the study: 126 in the group with a policy of expectant management and 115 in the active management group. The incidence of clinical chorioamnionitis was 4.8% in the former and 0.9% in the latter (p = 0.07). Neonatal oxygen was still needed at 24 hours significantly more often in the active than in the expectant management group (7.0 vs. 1.6%, p = 0.05). However, after adjustment for gestational age at birth, only delivery at 34 weeks of gestation remained associated with the need for neonatal oxygen at 24 hours. The rate of hypoglycemia or hypocalcemia was 5.6% in the expectant management group versus 12.3% in the active management group (p = 0.07). There were no neonatal deaths. CONCLUSION: A policy of active management, especially at 34 weeks of gestation, was associated with greater neonatal morbidity, whereas an expectant management policy tended to be associated with an increased rate of clinical chorioamnionitis.

Secreted surfactant protein A from fetal membranes induces stress fibers in cultured human myometrial cells.

In the present study, we investigated the ability of human fetal membranes (amnion and choriodecidua) to regulate human maternal uterine cell functions through the secretion of surfactant protein (SP)-A and SP-D at the end of pregnancy. We detected the expression of both SP-A (SP-A1 and SP-A2) and SP-D by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed that human fetal membranes expressed both SP-A and SP-D. By Western blot analysis, we demonstrated that SP-A protein expression was predominant in choriodecidua, whereas the amnion predominantly expressed SP-D. Only the secretion of SP-A was evidenced in the culture supernatants of amnion and choriodecidua explants by immunodot blot and confirmed by Western blot. Exogenous human purified SP-A induced stress fiber formation in cultured human myometrial cells via a pathway involving Rho-kinase. Conditioned medium from choriodecidua and amnion explants mimicked the SP-A effect. Treatment of myometrial cells with SP-A-depleted conditioned medium from choriodecidua or amnion explants failed to change the actin dynamic. These data indicate that SP-A released by human fetal membranes is able to exert a paracrine regulation of F-actin filament organization in myometrial cells.

Study of fetal tracheal fluid velocities using Doppler ultrasound.

OBJECTIVE: To characterize tracheal fluid flow during fetal breathing movements by Doppler ultrasound. STUDY DESIGN: To use pulsed Doppler to measure flow velocity during inspiration and expiration in a cross-sectional study of 15 normal fetuses and determine the correlation, if any, between flow velocity and gestational age. RESULTS: Cyclic respiratory profiles - both regular and irregular - were observed. Intratracheal flow velocity was very elevated during inspiration, ranging from 10 to 80 cm/s and from 5 to 20 cm/s during expiration. CONCLUSION: This technique enables the noninvasive semiquantitative evaluation of fetal breathing movements. This Doppler application opens the field for future studies to characterize the extent of pulmonary hypoplasia.

Pregnancy outcomes in women with HIV type-1 receiving a lopinavir/ritonavir-containing regimen.

BACKGROUND: The pregnancy-related adverse effects of antiretroviral therapy (ART) have yielded discordant results, which could be explained in part by the heterogeneity of ART protocols. The objective of our study was to explore whether lopinavir/ritonavir (LPV/r) exposure during pregnancy is associated with adverse outcomes. METHODS: Data on 100 consecutive HIV type-1 (HIV-1)-infected women receiving LPV/r during pregnancy and who delivered after 15 weeks gestational age (GA) between January 2003 and June 2007 in a single centre were analysed. For each HIV-1-infected woman, two uninfected women matched by age, parity and geographical origin were selected among patients delivering during the same period. Preterm delivery (PTD), vasculoplacental complications, gestational glucose intolerance and post-partum complication rates were compared between cases and controls. Factors associated with PTD and post-partum complications were assessed in HIV-1-infected women by a logistic regression model. RESULTS: Rates of vasculoplacental complication and gestational glucose intolerance were not higher among HIV-1-infected women than in controls. PTD was higher in HIV-1-infected women (21%) than in controls (10%; P<0.01). In HIV-1-infected women, PTD was associated with HIV-1 RNA level > or =50 copies/ml at delivery (adjusted odds ratio 6.15, 95% confidence interval 1.83-20.63; P=0.003). No association was found between occurrence of PTD and LPV/r exposure before 14 weeks GA. CONCLUSIONS: In this population of HIV-1-infected pregnant women receiving LPV/r, the risk of PTD was higher than in HIV-1-uninfected controls. As PTD risk was not associated with early exposure to LPV/r, these data support current guidelines to initiate ART earlier in pregnancy.

Prediction of clinical infection in women with preterm labour with intact membranes: a score based on ultrasonographic, clinical and biological markers.

OBJECTIVE: To predict maternal and neonatal clinical infection at admission in women hospitalized for preterm labour (PTL) with intact membranes. STUDY DESIGN: Prospective study of 371 women hospitalized for preterm labour with intact membranes. The primary outcome was clinical infection, defined by clinical chorioamnionitis at delivery or early-onset neonatal infection. RESULTS: Clinical infection was identified in 21 cases (5.7%) and was associated with earlier gestational age at admission for PTL, elevated maternal C-reactive protein (CRP) and white blood cell count (WBC), shorter cervical length, and a cervical funnelling on ultrasound. We used ROC curves to determine the cut-off values that minimized the number of false positives and false negatives. The cut-off points chosen were 30 weeks for gestational age at admission, 25 mm for cervical length, 8 mg/l for CRP and 12,000 c/mm(3) for WBC. Each of these variables was assigned a weight on the basis of the adjusted odds ratios in a clinical infection risk score (CIRS). We set a threshold corresponding to a specificity close to 90%, and calculated the positive and negative predictive values and likelihood ratios of each marker and of the CIRS. The CIRS had a sensitivity of 61.9%, while the sensitivity of the other markers ranged from 19.0% to 42.9%. Internal cross-validation was used to estimate the performance of the CIRS in new subjects. The diagnostic values found remained close to the initial values. CONCLUSION: A clinical infection risk score built from data known at admission for preterm labour helps to identify women and newborns at high risk of clinical infection.

Neonatal stepping in relation to terrestrial optic flow.

This experiment examined whether newborn stepping, a primitive form of bipedal locomotion, could be modulated by optical flow. Forty-eight 3-day-old infants were exposed to optical flows that were projected onto a horizontal surface above which the infants were suspended. Significantly more air steps were elicited by exposure to a terrestrial optical flow specifying forward translation than by a rotating optical flow or a static optical pattern. Thus, a rudimentary coupling between optical flow and stepping is present at birth, suggesting a precocious capacity in the newborn to perceive and utilize visual information specifying self-motion. The findings may help the early diagnosis of infants with visual or visual-motor deficits and the development of visually based interventions for disabled infants.