Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case control study

Aims: To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. Methods: An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (F1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. Results: There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lowerApgar score at 5 min, and presented a higher rate of earlyonset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. Conclusions: After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.

Information and risk management during the first trimester care for pregnant women: Some reflections about the ethical challenges and the legal framework in Switzerland. [L'information et la gestion des risques dans le suivi de la grossesse lors du 1er trimestre : quelques réflexions sur le défi éthique et le cadre légal en Suisse.]

The progress in prenatal medicine raises complex questions with respect to the physician-patient relationship. The physician needs to reconcile medical aspects, ethical principles as well as judicial norms. Already, during the first trimester, the physician has to put into practice the schedule combining for each individual pregnancy physical, laboratory and other appropriate exams. Physicians are under the obligation to inform in a clear and comprehensive way without creating unnecessary anxiety for their patients. Legal requirements include informed consent, the respect for the patient's right to self-determination, and compliance with the Swiss federal law on genetic testing, especially with its articles on prenatal screening and diagnosis. This article discusses the complexity of obstetrical practice when it comes to delivering adequate information within the scope of ethical and legal requirements in Switzerland. L'évolution de la médecine prénatale soulève des enjeux complexes dans la relation médecin-patient. Il s'agit de concilier à la fois les aspects médicaux, les principes éthiques et les normes juridiques. Dès le premier trimestre de la grossesse le médecin doit poser le cadre du suivi et des examens appropriés pour chaque grossesse. Son devoir est d'informer de manière claire et précise sans inquiéter inutilement, en respectant l'exigence légale d'un consentement éclairé et plus largement le droit de la patiente à l'autodétermination ainsi que le cadre de la loi fédérale suisse sur l'analyse génétique humaine dans le domaine du dépistage et du diagnostic prénatal. Cet article discute de la complexité de l'information et de l'application des principes éthiques et légaux dans la pratique obstétricale en Suisse.

Valproic acid monotherapy in pregnancy and major congenital malformations.

BACKGROUND: The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited. METHODS: We first combined data from eight published cohort studies (1565 pregnancies in which the women were exposed to valproic acid, among which 118 major malformations were observed) and identified 14 malformations that were significantly more common among the offspring of women who had received valproic acid during the first trimester. We then assessed the associations between use of valproic acid during the first trimester and these 14 malformations by performing a case-control study with the use of the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic-study database, which is derived from population-based congenital-anomaly registries. Registrations (i.e., pregnancy outcomes with malformations included in EUROCAT) with any of these 14 malformations were compared with two control groups, one consisting of infants with malformations not previously linked to valproic acid use (control group 1), and one consisting of infants with chromosomal abnormalities (control group 2). The data set included 98,075 live births, stillbirths, or terminations with malformations among 3.8 million births in 14 European countries from 1995 through 2005. RESULTS: Exposure to valproic acid monotherapy was recorded for a total of 180 registrations, with 122 registrations in the case group, 45 in control group 1, and 13 in control group 2. As compared with no use of an antiepileptic drug during the first trimester (control group 1), use of valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations under consideration; the adjusted odds ratios were as follows: spina bifida, 12.7 (95% confidence interval [CI], 7.7 to 20.7); atrial septal defect, 2.5 (95% CI, 1.4 to 4.4); cleft palate, 5.2 (95% CI, 2.8 to 9.9); hypospadias, 4.8 (95% CI, 2.9 to 8.1); polydactyly, 2.2 (95% CI, 1.0 to 4.5); and craniosynostosis, 6.8 (95% CI, 1.8 to 18.8). Results for exposure to valproic acid were similar to results for exposure to other antiepileptic drugs. CONCLUSIONS: The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs.

Is screening for fetal anomalies reliable in HIV-infected pregnant women? A multicentre study.

OBJECTIVE: To assess the impact of HIV infection on the reliability of the first-trimester screening for Down syndrome, using free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency, and of the second-trimester screening for neural tube defects, using alpha-fetoprotein. PATIENTS AND METHODS: Multicentre study comparing the multiples of the median of markers for Down syndrome and neural tube defect screening among 214 HIV-infected pregnant women and 856 HIV-negative controls undergoing a first-trimester Down syndrome screening test, and 209 HIV-positive women and 836 HIV-negative controls with a risk evaluation for neural tube defect. The influence of treatment, chronic hepatitis and HIV disease characteristics were also evaluated. RESULTS: Multiples of the median medians for pregnancy-associated plasma protein-A and beta-human chorionic gonadotrophin were lower in HIV-positive women than controls (0.88 vs. 1.05 and 0.84 vs. 1.09, respectively; P < 0.005), but these differences had no impact on risk estimation; no differences were observed for the other markers. No association was found between HIV disease characteristics, antiretroviral treatment use at the time of screening or chronic hepatitis and marker levels. CONCLUSION: Screening for Down syndrome during the first trimester and for neural tube defect during the second trimester is accurate for HIV-infected women and should be offered, similar to HIV-negative women.

Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case control study

Aims: To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. Methods: An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (F1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. Results: There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lowerApgar score at 5 min, and presented a higher rate of earlyonset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. Conclusions: After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.

Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case control study

Aims: To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. Methods: An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (F1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. Results: There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lowerApgar score at 5 min, and presented a higher rate of earlyonset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. Conclusions: After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.

Consequences of gestational stress on GABAergic modulation of respiratory activity in developing newborn pups.

The GABAergic system modulates respiratory activity and undergoes substantial changes during early life. Because this maturation process is sensitive to stress, we tested the hypothesis that gestational stress (GS) alters development of GABAergic modulation of respiratory control in rat pups. The respiratory responses to the selective GABAA receptor agonist muscimol were compared between pups born to dams subjected to GS (bright light and predator odor; 20 min/day from G9 to G19) or maintained under standard (control) conditions. Respiratory activity was measured on 1 and 4 days old pups of both sexes using in vivo (whole body plethysmography) and in vitro (isolated brainstem-spinal cord preparation) approaches. In intact pups, muscimol injection (0.75 mg/kg; i.p.) depressed minute ventilation; this response was less in GS pups, and at P4, muscimol augmented minute ventilation in GS females. Bath application of muscimol (0.01-0.5 μM) onto brainstem preparations decreased inspiratory (C4) burst frequency and amplitude in a dose-dependent manner; the responsiveness decreased with age. However, GS had limited effects on these results. We conclude that the results obtained in vivo are consistent with our hypothesis and show that GS delays maturation of GABAergic modulation of respiratory activity. The differences in the results observed between experimental approaches (in vivo versus in vitro) indicate that the effect of prenatal stress on maturation of GABAergic modulation of respiratory control mainly affects the peripheral/metabolic components of the respiratory control system.

Neonatal lupus erythematosus with congenital heart block and severe heart failure due to myocarditis and endocardititis of the mitral valve.

We report a case of neonatal lupus erythematosus (NLE) with congenital heart block and severe myocardial failure, which was followed from the 25th week of gestation because of fetal bradycardia. The child was delivered at the 37th week of gestation by elective cesarean section because of echocardiographically documented heart enlargement, pericardial effusion and moderate insufficiency of the mitral and tricuspid valves. In spite of immediate pacing, intubation and supportive treatment, the newborn developed progressive heart failure. Echocardiography showed endocarditis of the mitral valve and diffuse myocarditis. The heart failure resolved under steroid treatment. Our experience supports the early use of steroids in treating myocarditis due to NLE. Intrauterine steroid treatment in the presence of fetal hydrops and congenital heart block is discussed.

Family interactions in IVF families: change over the transition to parenthood

Objective: This article presents a study of the change over time in the family interactions of couples who conceived through in-vitro fertilisation (IVF). Background: Observational methods are rarely used to study family interactions in families who used assisted reproductive techniques, but these methods are crucial for taking account of the communication that occurs in interactions with infants. Methods: Thirty-one couples expecting their first child were seen during the fifth month of pregnancy and when the child was nine months old. Family interactions were recorded in pre- and postnatal versions of the Lausanne Trilogue Play situation. Measures of marital satisfaction and parent-to-foetus/baby attachment or 'bonding' were also used to assess family relational dynamics. Results: Results showed that family alliance, marital satisfaction and parental attachment scores in the IVF sample were all similar to or higher than those in the reference sample during pregnancy. However, at nine months postnatally, the family alliance scores were lower. While marital satisfaction decreased over the period and parent-baby attachment increased, the family alliance scores were unstable, as no association was observed between the pre- and postnatal scores. In addition, neither prenatal marital satisfaction nor parent-foetus attachment predicted the postnatal family alliance. Conclusion: The change in the family alliance over the transition to parenthood appears to be specific to our IVF sample. Given that postnatal family functioning could not be predicted by prenatal family functioning, our observational data underline the importance of offering postnatal support to these families.

Quantitative morphometry analysis of the fetal brain using clinical MR imaging

In vivo fetal magnetic resonance imaging provides aunique approach for the study of early human braindevelopment [1]. In utero cerebral morphometry couldpotentially be used as a marker of the cerebralmaturation and help to distinguish between normal andabnormal development in ambiguous situations. However,this quantitative approach is a major challenge becauseof the movement of the fetus inside the amniotic cavity,the poor spatial resolution provided by very fast MRIsequences and the partial volume effect. Extensiveefforts are made to deal with the reconstruction ofhigh-resolution 3D fetal volumes based on severalacquisitions with lower resolution [2,3,4]. Frameworkswere developed for the segmentation of specific regionsof the fetal brain such as posterior fossa, brainstem orgerminal matrix [5,6], or for the entire brain tissue[7,8], applying the Expectation-Maximization MarkovRandom Field (EM-MRF) framework. However, many of theseprevious works focused on the young fetus (i.e. before 24weeks) and use anatomical atlas priors to segment thedifferent tissue or regions. As most of the gyraldevelopment takes place after the 24th week, acomprehensive and clinically meaningful study of thefetal brain should not dismiss the third trimester ofgestation. To cope with the rapidly changing appearanceof the developing brain, some authors proposed a dynamicatlas [8]. To our opinion, this approach however faces arisk of circularity: each brain will be analyzed /deformed using the template of its biological age,potentially biasing the effective developmental delay.Here, we expand our previous work [9] to proposepost-processing pipeline without prior that allow acomprehensive set of morphometric measurement devoted toclinical application. Data set & Methods: Prenatal MRimaging was performed with a 1-T system (GE MedicalSystems, Milwaukee) using single shot fast spin echo(ssFSE) sequences (TR 7000 ms, TE 180 ms, FOV 40 x 40 cm,slice thickness 5.4mm, in plane spatial resolution1.09mm). For each fetus, 6 axial volumes shifted by 1 mmwere acquired under motherâeuro?s sedation (about 1min pervolume). First, each volume is segmentedsemi-automatically using region-growing algorithms toextract fetal brain from surrounding maternal tissues.Inhomogeneity intensity correction [10] and linearintensity normalization are then performed. Brain tissues(CSF, GM and WM) are then segmented based on thelow-resolution volumes as presented in [9]. Ahigh-resolution image with isotropic voxel size of 1.09mm is created as proposed in [2] and using B-splines forthe scattered data interpolation [11]. Basal gangliasegmentation is performed using a levet setimplementation on the high-resolution volume [12]. Theresulting white matter image is then binarized and givenas an input in FreeSurfer software(http://surfer.nmr.mgh.harvard.edu) to providetopologically accurate three-dimensional reconstructionsof the fetal brain according to the local intensitygradient. References: [1] Guibaud, Prenatal Diagnosis29(4) (2009). [2] Rousseau, Acad. Rad. 13(9), 2006. [3]Jiang, IEEE TMI 2007. [4] Warfield IADB, MICCAI 2009. [5]Claude, IEEE Trans. Bio. Eng. 51(4) 2004. [6] Habas,MICCAI 2008. [7] Bertelsen, ISMRM 2009. [8] Habas,Neuroimage 53(2) 2010. [9] Bach Cuadra, IADB, MICCAI2009. [10] Styner, IEEE TMI 19(39 (2000). [11] Lee, IEEETrans. Visual. And Comp. Graph. 3(3), 1997. [12] BachCuadra, ISMRM 2010.

Suplementação com aditivos nutricionais e minerais orgânicos no desempenho de bezerros Nelore recém-desmamados em pastagem

Resumo: O objetivo deste trabalho foi avaliar o desempenho de bezerros Nelore recém-desmamados em resposta à suplementação com aditivos nutricionais e minerais orgânicos no sal mineral proteinado, em pastagem de Urochloa brizantha 'Marandu', na época seca. Foram utilizados 112 bezerros com idade entre 7-8 meses e com 252±24 kg. Os animais foram divididos em pastos sob lotação rotativa e receberam os tratamentos: sal mineral proteinado (controle); e sal mineral proteinado com minerais na forma orgânica, com monensina ou com óleos funcionais. A cada ciclo de pastejo, foram calculados o consumo de suplemento, o ganho de peso e a eficiência; coletadas amostras de sangue para análise de minerais; e feitas ultrassonografias de carcaça. O consumo do tratamento com monensina foi inferior ao dos demais (0,47 kg por dia); os consumos dos tratamentos controle (0,82 kg por dia) e com óleo (0,8 kg por dia) foram semelhantes; e o do tratamento com minerais orgânicos foi superior ao dos outros (0,92 kg por dia). Diferenças entre os tratamentos não foram observadas para ganho de peso (0,123 kg por dia) e para eficiência (0,161). A área de olho de lombo (46,81 cm2) e a espessura de gordura subcutânea (0,77 mm) não diferiram significativamente entre os tratamentos. A adição de monensina diminui o consumo do suplemento, o que pode significar menor ingestão de proteína e prejuízo ao desempenho dos animais.

La biologie moléculaire est-elle utile au praticien [Is molecular biology useful to the practitioner?]

The relative importance of molecular biology in clinical practice is often underestimated. However, numerous procedures in clinical diagnosis and new therapeutic drugs have resulted from basic molecular research. Furthermore, understanding of the physiological and physiopathological mechanisms underlying several human diseases has been improved by the results of basic molecular research. For example, cloning of the gene encoding leptin has provided spectacular insights into the understanding of the mechanisms involved in the control of food intake and body weight maintenance in man. In cystic fibrosis, the cloning and identification of several mutations in the gene encoding the chloride channel transmembrane regulator (CFTR) have resolved several important issues in clinical practice: cystic fibrosis constitutes a molecular defect of a single gene. There is a strong correlation between the clinical manifestations or the severity of the disease (phenotype) with the type of mutations present in the CFTR gene (genotype). More recently, identification of mutations in the gene encoding a subunit of the renal sodium channel in the Liddle syndrome has provided important insight into the physiopathological understanding of mechanisms involved in this form of hereditary hypertension. Salt retention and secondary high blood pressure are the result of constitutive activation of the renal sodium channel by mutations in the gene encoding the renal sodium channel. It is speculated that less severe mutations in this channel could result in a less severe form of hypertension which may correspond to patients suffering from high blood pressure with low plasma renin activity. Several tools, most notably PCR, are derived from molecular research and are used in everyday practice, i.e. in prenatal diagnosis and in the diagnosis of several infectious diseases including tuberculosis and hepatitis. Finally, the production of recombinant proteins at lower cost and with fewer side effects is used in everyday clinical practice. Gene therapy remains an extraordinary challenge in correcting severe hereditary or acquired diseases. The use of genetically modified animal cell lines producing growth factors, insulin or erythropoetin, which are subsequently encapsulated and transferred to man, represents an attractive approach for gene therapy.

Congenital tracheal anomalies.

Congenital tracheal lesions are rare, but important, causes of morbidity in infants and children. Consequently, experience in their management is limited and dispersed. Given its small diameter, the juvenile trachea is obstructed easily by various natural causes, or following a surgical intervention. The diagnosis of a congenital, tracheal, obstructive anomaly is based on a high degree of suspicion in infants and children with respiratory distress accompanied by retraction. In this article, the authors discuss the various causes of these conditions, their diagnostic features, and the treatment possibilities.

Modificaciones en el consumo de tabaco durante la gestación y el posparto

Objetivo: Averiguar el consumo de tabaco y las modificaciones del hábito durante la gestación, y observar las recaídas después del parto. Personas y método: Estudio descriptivo transversal, realizado en el PASSIR «Casagemas», Badalona, desde febrero de 2006 a septiembre de 2007. Se incluyó a 115 gestantes que acudieron a la consulta de control prenatal en el tercer trimestre de gestación, y se excluyeron las que no fumaban al inicio de la gestación. Se recogieron variables sociodemográficas y las relacionadas con el hábito tabáquico a través de un cuestionario en la gestación y otro en el posparto. Resultados: Dejaron de fumar el 26% (30) de las gestantes, y las que continuaron fumando redujeron el consumo de una media de 19,2 (DE= 6,7) a 7,2 (DE= 6) cigarrillos/día. Se observaron diferencias en el abandono del tabaco en aquellas que fumaban un menor número de cigarrillos (p <0,001), en las que iniciaron el tabaquismo más tarde y en las de mayor edad (p= 0,013). Al año del parto, seguían fumando el 73% (70) de las mujeres, y habían recaído en el hábito el 39,2% (11) de las que lo habían abandonado en la gestación. Las mujeres que no fumaban lactaron a sus hijos un 76,9% (20), mientras que las que fumaban lo hicieron un 57,1% (40). La duración media de la lactancia fue inferior en las mujeres que fumaron en el posparto (2,81 meses [DE= 3,4]) en relación con las que no lo hicieron (4,96 meses [DE= 4,1]; p= 0,01). Conclusiones: La tasa de abandono del tabaco durante el embarazo es aún muy baja, y el índice de recaída del hábito tabáquico en el posparto, elevada.

Modificaciones en el consumo de tabaco durante la gestación y el posparto

Objetivo: Averiguar el consumo de tabaco y las modificaciones del hábito durante la gestación, y observar las recaídas después del parto. Personas y método: Estudio descriptivo transversal, realizado en el PASSIR «Casagemas», Badalona, desde febrero de 2006 a septiembre de 2007. Se incluyó a 115 gestantes que acudieron a la consulta de control prenatal en el tercer trimestre de gestación, y se excluyeron las que no fumaban al inicio de la gestación. Se recogieron variables sociodemográficas y las relacionadas con el hábito tabáquico a través de un cuestionario en la gestación y otro en el posparto. Resultados: Dejaron de fumar el 26% (30) de las gestantes, y las que continuaron fumando redujeron el consumo de una media de 19,2 (DE= 6,7) a 7,2 (DE= 6) cigarrillos/día. Se observaron diferencias en el abandono del tabaco en aquellas que fumaban un menor número de cigarrillos (p <0,001), en las que iniciaron el tabaquismo más tarde y en las de mayor edad (p= 0,013). Al año del parto, seguían fumando el 73% (70) de las mujeres, y habían recaído en el hábito el 39,2% (11) de las que lo habían abandonado en la gestación. Las mujeres que no fumaban lactaron a sus hijos un 76,9% (20), mientras que las que fumaban lo hicieron un 57,1% (40). La duración media de la lactancia fue inferior en las mujeres que fumaron en el posparto (2,81 meses [DE= 3,4]) en relación con las que no lo hicieron (4,96 meses [DE= 4,1]; p= 0,01). Conclusiones: La tasa de abandono del tabaco durante el embarazo es aún muy baja, y el índice de recaída del hábito tabáquico en el posparto, elevada.