The impact of chorionicity on pregnancy outcome and neurodevelopment at 2 years old among twins born preterm: the EPIPAGE-2 cohort study.

OBJECTIVE: To compare the short- and mid-term outcomes of preterm twins by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: 546 maternity units in France, between March and December 2011. POPULATION: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: First, survival at 2-year corrected age with or without neurosensory impairment, and second, perinatal, short-, and mid-term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. RESULTS: In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2-year follow-up neurodevelopmental results were not significantly different between DC and MC twins. CONCLUSIONS: This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity. TWEETABLE ABSTRACT: Monochorionicity is associated with adverse perinatal outcomes, but outcomes for preterm twins are comparable irrespective of their chorionicity.

[Newborn outcomes after radiofrequency ablation for selective reduction in the complicated monochorionic pregnancies]. / Devenir neurodéveloppemental des nouveau-nés issus de grossesses monochoriales compliquées avec interruption sélective par ablation par radiofréquence.

OBJECTIVE: To describe perinatal data and to evaluate the neonatal neurological outcome of monochorionic twin pregnancies with selective termination by radiofrequency ablation. METHODS: Retrospective data of perinatal data for nine consecutive monochorionic pregnancies eligible for radiofrequency ablation from January 2013 to August 2015 were collected. A prospective observational study of the neurological outcome of nine children was conducted using the Ages & Stages Questionnaire (ASQ), 2nd edition, French version, adapted to the age. RESULTS: The radiofrequency procedures were performed at a mean gestational age (GA) of 21.4 weeks (±7 weeks). The indications for a selective interruption of a pregnancy were: acardiac twin (n=4), brain malformation (n=1), severe intrauterine growth restriction (IUGR) with massive cerebral ischemia in the context of twin-twin transfusion syndrome grade III (n=1), severe selective IUGR associated with a polymalformative syndrome (n=1) and severe selective IUGR (n=2). The mean GA at birth was 36.7 weeks GA (±3.8 weeks). No infant showed neurological neonatal morbidity. Any ASQ area explored was pathological (<-2SD) for the nine children (mean age at follow-up [±SD], 14.8 months [±8.8 months]). CONCLUSION: This work constitutes a preliminary study for developing long-term follow-up and early care programs for those children born subsequent to a radiofrequency ablation for selective reduction.

Gut microbiota analysis reveals a marked shift to bifidobacteria by a starter infant formula containing a synbiotic of bovine milk-derived oligosaccharides and Bifidobacterium animalis subsp. lactis†CNCM I-3446.

Non-digestible milk oligosaccharides were proposed as receptor decoys for pathogens and as nutrients for beneficial gut commensals like bifidobacteria. Bovine milk contains oligosaccharides, some of which are structurally identical or similar to those found in human milk. In a controlled, randomized double-blinded clinical trial we tested the effect of feeding a formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS) generated from whey permeate, containing galacto-oligosaccharides and 3'- and 6'-sialyllactose, and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446. Breastfed infants served as reference group. Compared with a non-supplemented control formula, the test formula showed a similar tolerability and supported a similar growth in healthy newborns followed for 12 weeks. The control, but not the test group, differed from the breast-fed reference group by a higher faecal pH and a significantly higher diversity of the faecal microbiota. In the test group the probiotic B. lactis increased by 100-fold in the stool and was detected in all supplemented infants. BMOS stimulated a marked shift to a bifidobacterium-dominated faecal microbiota via increases in endogenous bifidobacteria (B. longum, B. breve, B. bifidum, B. pseudocatenulatum).

Posture and movement in very preterm infants at term age in and outside the nest.

OBJECTIVE: The objective of this study is to evaluate the use of nests on general movements (GM) and posture in very preterm infants at term age. METHOD: Seventeen high-risk preterm infants-less than 30 weeks of gestation (GA)-underwent a video recording, lying in supine position, with or without nest. Posture, GM quality, and movements made around the child's midline, as well as abrupt movements and frozen postures-in extension or flexion of the four limbs-were analyzed. RESULTS: Nest did not modify quality of GM. Children significantly adopted a curled-up position. The nest system was associated with an increase in movements toward or across the midline, as well as reduction of the hyperextension posture and head rotation movements. Frozen postures in flexion or extension, as well as abrupt movements of the four limbs, were reduced but not significantly. CONCLUSIONS: Nest helps very preterm infants to adopt semi-flexed posture and facilitates movements across the midline and reduces movements of spine hyperextension, without GM global quality modifications.

[Palliative care birth plan: a field of perinatal medicine to build]. / Projets de naissance en soins palliatifs : un domaine de la périnatalité à construire.

Some couples may choose to continue the pregnancy unable to decide for termination of pregnancy. Such situations recently occurred in neonatology units and may lead to neonatal palliative care. Faced with all uncertainties inherent to medicine and the future of the baby, medical teams must inform parents of different possible outcome step by step. Consistency in the reflection and intentionality of the care is essential among all different stakeholders within the same health team to facilitate support of parents up to a possible fatal outcome. This issue in perinatal medicine seems to be to explore how caregivers can contribute in the construction of parenthood in a context of a palliative care birth plan.

Bioactive compounds in human milk and intestinal health and maturity in preterm newborn: an overview.

Premature births are increasing worldwide (about 15 millions per year) due to several reasons (an advanced maternal age, fertility treatments, stress, smoking, nutritional deficiencies) and lead to a high societal overall cost. Among neonatal care procedures, the clinical nutrition practices are essential to promote the development and to minimize the sequelae. Premature newborns are at major risk of death by infections due to the immaturity of their intestine. Human milk provides not only nutrients but also a plethora of biologically active components that are tailored to contribute to the development of the intestinal tract early in postnatal life. Among them, some bioactive molecules exhibit trophic effects (LC­PUFA, sphingomyelin, IGF­I and IGF­II, EGF, insulin, leptin, adiponectin, lactoferrin, lactadherin, probiotics, prebiotics, miRNA) or are part of the intestinal cell membranes (PUFA, LC­PUFA, phospholipids, sphingolipids, cholesterol), others educate the intestine for innate microbial recognition (sCD14, sTLR­2, miRNA), many of them display direct fighting against pathogens (some fatty acids and monoglycerides, some phospholipids and sphingolipids, BSSL, insulin, lactoferrin, sIgAs, MUC­1, lactadherin, probiotics, prebiotics), or contribute to establish the gut microbiota (LC­PUFA, lactoferrin, probiotics, prebiotics). A synergetic action exists between several bioactive molecules. All together these precious agents regulate the maturation of the intestinal mucosal barrier, and might program early in postnatal life the future adult intestinal health. This review lists the main bioactive compounds and addresses their plausible roles and mechanisms of action.

Quality of life of early school-age French children born preterm: a cohort study.

OBJECTIVES: To describe the health-related quality of life (HRQL) of a cohort of children aged 6-10 years who were born preterm; and to determine whether sociodemographic factors, neonatal features and neurocognitive status were affecting their HRQL. STUDY DESIGN: All singleton infants born between 24 and 32 weeks of gestation between January 1997 and December 2001 at the study hospital, who were still alive in 2007 (age 6-10 years), and who had undergone complete clinical paediatric follow-up were included in the study. Maternal and perinatal data were obtained by chart review and regular clinical examination. The 'Battery for Rapid Evaluation of Cognitive Functions' (BREV) was used for cognitive evaluation when children were aged 4-8 years. HRQL data were collected in 2007 using the 'Vécu et Santé Perçue de l'Adolescent et de l'Enfant' (VSP-A) questionnaire (parent version). The HRQL of the preterm children was compared with that of a French reference population. RESULTS: Of 202 children who fulfilled the inclusion criteria, 82 children participated in the study. Their mean age was 7.9 years [standard deviation (SD) 1.4], mean birth weight was 1130.0 g (SD 361.4), 23 children were born before 28 weeks of gestation, 46 were female and 11 had major neurocognitive disorders. These data were not significantly different for the non-respondents (n=120). Parents of preterm children reported a significantly lower perception of HRQL of their child compared with parents of children in the reference population, as reflected by VSP-A global index scores and scores for the 'body image', 'vitality', 'psychological well-being' and 'school performance' dimensions. In multivariate analyses, three factors were found to be significantly associated with at least one dimension in the VSP-A scale in the preterm children: presence of major neurocognitive disorders, negatively correlated with 'vitality', 'relationships with friends', 'physical well-being' and 'school performance' dimensions; maternal parity, positively correlated with the 'psychological well-being' dimension; and socio-economic status of family, positively correlated with the 'relationships with friends' dimension. The maximum R(2) was 15%. CONCLUSION: In addition to neurocognitive disorders, other variables such as socio-economic status of the family have a significant impact on the HRQL of preterm children at 6-10 years of age. Given the low proportion of variability in HRQL explained by the models, there is a need to explore other factors (e.g. environmental).

Parental experience following perinatal death: exploring the issues to make progress.

OBJECTIVES: This study was performed to understand the parental attitudes, needs and ethical issues associated with perinatal death, to assist in the development of interventions for bereaved families. STUDY DESIGN: We conducted a qualitative descriptive survey of parental experiences with perinatal death. We developed a questionnaire based on the Delphi method, conducted semi-directed interviews or asked subjects to return the questionnaire by post. As a secondary analysis, we examined whether certain ethical principles (i.e., the concepts of beneficence, nonmaleficence, autonomy, and justice) were encountered by the study participants. The study population consisted of families who had experienced perinatal death in the maternity department of a French university hospital, as well as members of bereaved parent support groups. RESULTS: Six of the 12 parents who participated in the survey were members of a support group. Responses were analyzed according to precise objectives and grouped according to key themes. In particular, we studied deaths that occurred during neonatal palliative care and deaths relating to multiple pregnancies. Parents expressed opinions about the caregivers' practices (e.g., which practices were beneficial and detrimental). Half of the parents did not feel that their feelings and decisions were respected according to ethical principles. Understanding the experience of parents allows staff to reconsider and change their practices. CONCLUSIONS: By understanding parents' feelings toward neonatal death, caregivers can better assist with the grieving process. Our study reveals parents' attitudes toward the ethical decision-making process and shows that it is difficult for perinatal medicine caregivers to respect parents' autonomy.

Preterm birth affects dorsal-stream functioning even after age 6.

With increasing numbers of preterm infants surviving, the impact of preterm birth on later cognitive development presents a major interest. This study investigates the impact of preterm birth on later dorsal- and ventral-stream functioning. An atypical pattern of performance was found for preterm children relative to full-term controls, but in the dorsal-drawing task only. These findings suggest that the number of gestational weeks does affect dorsal-stream functioning, even after more than 6 years of favorable environmental conditions in healthy preterm children.

Congenital laryngeal cyst: benefits of prenatal diagnosis and multidisciplinary perinatal management.

Congenital laryngeal cysts are rare and can cause upper airway obstruction if they are misdiagnosed. We describe a case of large vallecular cyst diagnosed at 33 weeks of gestation. The purpose of an early diagnosis is to establish a careful perinatal management. If the airway is compromised, a multidisciplinary medical team is necessary to perform emergency immediate tracheostomy. Elective delivery should be always carried out in a tertiary referral center.

[Imaging of neonatal neurological disorders]. / Imagerie des désordres neurologiques néonataux.

Neonatal brain disorders consist of a wide chapter including brain malformations, hypoxic-ischemic encephalopathy, intracranial infections, perinatal trauma and metabolic encephalopathies. The aim of this review paper is to describe the main imaging modalities (ultrasonography, CT, MRI) that are used extensively for the diagnosis of neonatal brain disorders, with their respective advantages and limitations, to illustrate and describe the main brain lesions encountered in the neonatal period, particularly with MRI since its role has increased over the recent years. We will focus on hypoxic-ischemic encephalopathy, materno-fetal infections, metabolic encephalopathies and stroke, those four conditions being the most frequent so far. Imaging modalities, especially MRI, by showing the extent of brain damage, are part of the prognostic factors in cases of infective causes and of hypoxic-ischemic origin. MRI is also very efficient in showing brain damage as atrophy and white matter abnormalities suggestive of an underlying abnormal brain of metabolic origin.

[Prenatal screening of kidney pelvis ectasia, frequently caused by vesico-ureteral reflux detected after birth. Analysis of a series of 159 cases in 4 years at a maternal-child unit]. / Le dépistage anténatal des ectasies pyéliques, souvent dues à un reflux vésico-urétéral dépisté après la naissance. Analyse d'une série de 159 dépistages en 4 ans dans une unité mère-enfant.

UNLABELLED: To describe the pre- and post-natal management of vesico-ureteric reflux in a prospective study of babies presenting with vesico-ureteric reflux suspected from pre-natal ultrasonography in a tertiary paediatric center. PATIENTS AND METHODS: Between 1997 and 2001, 35 children (25 boys and 10 girls) with were vesico-ureteric reflux followed for 12 to 36 months after the pre-natal detection of urinary tract anomalies. Ultrasound examination was realized at the 5th of life, retrograde cystography at the 15th if the renal pelvic dilatation measured at least 10 mm of diameter. In 11 the reflux was bilateral and 46 refluxing units were reviewed. RESULTS: According to the international classification of, 7% vesico-ureteric reflux were grade I, 20.5% were grade II, 32% were grade III, 18% were grade IV, 22.5% were grade V. Fourteen patients (17 refluxing units) underwent ureteric-reimplantation. Four total and two partial nephrectomics were carried out in patients < 2 years old; in 8 patients the VUR resolved spontaneously. Of the latter, 7 patients (ten refluxing grade III-IV units) are still being followed and awaiting a decision on treatment. CONCLUSION: This study confirms the predominance of boys in those with antenatally suspected vesico-ureteric reflux. The spontaneous resolution or improvement during the first 3 years of life was apparent in most cases, even in those with severe reflux (grade III-V).

[MRI and in utero ventriculomegaly]. / IRM et ventriculomégalie in utero.

Ventriculomegaly constitutes the major indication of fetal brain MRI. MRI is therefore of utmost importance to look for a cause through the depiction of criteria of malformations and through the definition of criteria of destructive lesions. Malformations and destructive lesions are the most common causes of ventricular dilatation. Some challenging points are worth mentioning in term of mechanism with the challenge of hydrocephalus (in term of increased in intracranial pressure) and of isolated ventriculomegaly. The image itself is also challenging since a similar image may be of different origin. In term of natural history of fetal brain injury an irregular, nodular aspect of the ventricular wall and/or the germinal matrix is often the only pathologic MRI finding that is known to be of clastic origin. In term of prognosis the challenge is represented by the isolated mild ventriculomegaly, the literature being quite confusing. The purpose of this review paper is to highlight the underlying mechanisms and pathophysiology of ventricular dilatation based on results from the literature as well as from personal experience.

[Early cerebral MRI in preterm infants: correlations with EEG and outcome]. / Intérêt de la réalisation d'une IRM cérébrale précoce chez le prématuré: corrélation avec l'EEG et le devenir.

AIM OF THE STUDY: Assess the potential benefits of performing an early cerebral MRI to evaluate the gravity of cerebral lesions among premature neonates at risk of neurologic sequels and establish correlations between EEG findings, abnormal neuroimaging findings and neurodevelopment. METHODS: A MRI was performed in 34 premature newborn babies with abnormal neurological clinical signs, and/or with two abnormal EEG and/or with two abnormal cerebral ultrasound scans. The mean age and the adjusted age of our population were 5 weeks (range 1-11 weeks) and 35 weeks of adjusted age (range 29-40 weeks) respectively. The neuroimaging findings were correlated to the results of three EEGs (recorded before 15 days old, between 15 days and one month old, and after the first month of life) and to neurodevelopment. RESULTS: Two statically significant correlations were found between: 1) the severity of brain injuries observed in MRI and the results of the latest EEG (sensitivity 100%, specificity 60%), 2) the severity of brain injuries observed in MRI and abnormal neurodevelopment (sensitivity 75%, specificity 80%). There was no correlation between the abnormal development and the results of EEG recordings. CONCLUSION: Early cerebral MRI is justified in a selected premature population. It is useful for the diagnosis, the evaluation of the severity of brain injury and for the management of these children. The correlation with EEGs traces allows the detection of the majority of prematures babies that will develop sequels.

Clinical features and neuroradiological findings of mitochondrial pathology in six neonates.

OBJECTS: We hoped to itemize the clinical and neuroradiological features of six neonates with mitochondrial disorders. METHODS: We examined a case series of six neonates. The diagnosis of mitochondrial cytopathy was made on the basis of spectrophotometric measurements of respiratory chain enzyme activities in skeletal muscle biopsy specimens. Magnetic resonance (MR) imaging was performed in all cases. CONCLUSIONS: The antenatal onset in five cases and the lack of any symptom-free interval are suggestive of fetal expression of the disease. No specific symptoms were found: arthrogryposis congenita multiplex in one, progressive hepatocellular dysfunction in three, encephalomyelopathy and cardiomyopathy in four. Complex I deficiency was found in three patients, while one patients had a defect of complex IV and the last a combined defect of complexes I and IV. Neuroradiological findings were either cerebral atrophy or white matter abnormalities of the brain stem in all cases but one and gave additional information, because clinical symptoms are not quite specific. The combination of clinical and MRI findings in neonatal cases can rule out hypoxic ischemic encephalopathy, which suggests an additional screening method to look for mitochondrial disorder.

Preterm premature rupture of membrane and twin-to-twin transfusion syndrome before 20 weeks: a favourable outcome.

We describe a monochorionic twin gestation with a severe twin-to-twin transfusion syndrome associated with a preterm premature rupture of membranes at 20 weeks of gestation in the polyhydramniotic sac. The pregnancy was managed expectantly and outcome was favourable for the 2 neonates. We discuss how these two severe pathologies seem to counteract each other by compensations of their symptoms.

Ultrasonographic evaluation of cervical length in pregnancies complicated by preterm premature rupture of membranes.

OBJECTIVE: To evaluate the usefulness of transvaginal ultrasonography in the determination of the risk of preterm delivery and chorioamnionitis in pregnancies affected by preterm premature rupture of membranes preterm premature rupture of membranes. DESIGN: One hundred and one singleton pregnancies with preterm premature rupture of membranes were included in this prospective study over a 3-year period. Patients underwent cervical length measurement by transvaginal ultrasonography at admission and thereafter, in the absence of chorioamnionitis, were managed expectantly. RESULTS: The median time interval between admission and delivery (latency period) was 48 h. A cervical length of less than 20 mm was associated with a significant risk of early delivery (mean latency period was 59.44 +/- 159.93 h vs. 240.94 +/- 364.67; P < 0.05). There was no relation between cervical length and occurrence of chorioamnionitis or neonatal sepsis. CONCLUSIONS: These data suggest that the use of transvaginal ultrasonography for cervical length measurement during preterm premature rupture of membranes may predict an early delivery but cannot anticipate the risk of chorioamnionitis or neonatal sepsis.

An automated computer system to support ultra high throughput SNP genotyping.

Celera Genomics has constructed an automated computer system to support ultra high-throughput SNP genotyping that satisfies the increasing demand that disease association studies are placing on current genotyping facilities. This system consists of the seamless integration of target SNP selection, automated oligo design, in silico assay quality validation, laboratory management of samples, reagents and plates, automated allele calling, optional manual review of autocalls, regular status reports, and linkage disequilibrium analysis. Celera has proven the system by generating over 2.5 million genotypes from more than 10,000 SNPs, and is approaching the target capacity of over 10,000 genotypes per machine per hour using limited human intervention with state of the art laboratory hardware.