Prenatal identification of small-for-gestational age and risk of neonatal morbidity and stillbirth.

OBJECTIVE: To assess whether prenatal identification of small-for-gestational age (SGA) was associated with lower rates of the primary composite outcome of stillbirth, death in the delivery room or neonatal complications, and secondary outcomes of the composite outcome according to gestational age at delivery, stillbirth and low 5-min Apgar score. METHODS: This historical cohort study included women who had a singleton delivery (≥ 32 weeks) between 1994 and 2011 at one of 247 French maternity units. We excluded pregnancies terminated medically, infants with malformations or with missing data on estimated fetal weight or birth weight, and women with missing delivery data. Among the 24 946 infants born SGA (< 5th percentile), we compared those who had been identified as such prenatally (n = 5093; 20%), with those who had not (n = 19 853; 80%). The main outcome was a composite variable defined as stillbirth or death in the delivery room, or transfer to a neonatal department either immediately or during the neonatal stay in the obstetrics ward. Secondary outcomes were the composite outcome according to gestational age at delivery (32 to < 35 weeks; 35 to < 37 weeks, 37 to < 40 weeks, or ≥ 40 weeks), stillbirth and low 5-min Apgar score (≤ 4 and < 7). RESULTS: The mean ± SD birth weight was 2449.1 ± 368.3 g. The rate of the main composite outcome was higher in the group identified prenatally as SGA compared with non-identified SGA fetuses (39.5% vs 13.5%; adjusted relative risk (aRR), 1.29; 95% CI, 1.21-1.38). This association was not observed in the subgroups delivered before 37 weeks. The stillbirth rate was lower in fetuses with prenatal suspicion of SGA (aRR, 0.47; 95% CI, 0.27-0.79), while the 5-min Apgar score did not differ between the two groups. The a-posteriori study power with α = 0.05 was 99%. CONCLUSION: Prenatal identification of SGA was not associated with lower fetal or neonatal morbidity overall, although it was associated with a lower rate of stillbirth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Malformations of cortical development: New surgical advances.

Epilepsy related to malformations of cortical development is frequently drug resistant or requires heavy medication, therefore surgery is key in their management. The role of stereotactic surgery has recently changed the diagnosis and treatment of focal cortical dysplasias (FCD), hypothalamic hamartomas (HH) and periventricular nodular heterotopias (PNH). In HH, radiosurgery using Gammaknife® leads to 60 % of seizure control and is associated with excellent neuropsychological results without significant endocrine function impairment. The seizure control rate is even higher (more than 80 %) with monopolar multiple stereotactic thermocoagulations and Laser interstitial Thermal Therapy (LiTT). While the first technique is associated with a 2 % complications rate (but with excellent neuropsychological outcomes), the latest has up to 22 % side effects in some series. All three of these techniques have encouraging results, but controlled studies are still lacking to provide evidence-based new therapeutic algorithms. With regard to the PNH, surgical management has long been limited by the depth of the lesions and their close anatomical relations with the functional brain connectome. Stereotactic approaches required to perform a SEEG, to locate the part of the PNH responsible for the seizure onset, are later followed by a stereotactic lesioning procedure, therefore doubling the bleeding risk. That is why SEEG-guided radiofrequency-thermocoagulation (SEEG guided-RF-TC), which makes it possible to perform these two steps in a single procedure, was considered as a promising option. A recent meta-analysis confirmed this intuition and reported 38 % of seizure-free patients and 81 % of responders with only 0.3 % of complications, making this approach the first treatment line, followed by LiTT. Among the multiple advances in the FCD identification by non-invasive investigations, a new modality of per-operative diagnostic procedure, the three-dimensional electrocorticography may lead to simplify the preoperative investigation and enhance the accuracy of FCD delineation. Evidence is nevertheless still insufficient to validate this promising concept. Conventional surgical resection has also been concerned by significant conceptual advances during the past few years, in particular with the development of the hodotopic approach, initially in oncologic surgery. Associated with a better understanding of neuroplasticity in epilepsy and the setting up of functional mapping during SEEG or during awake surgery, the possibility of surgical resections grew up. A short-term perspective in this field, when surgical resection remains impossible, would be to target crucial nodes of the epileptic network, distinct from the core functional connectome.

Semiology of insular lobe seizures.

After the early attempts of intra-operative electrocorticography and insulectomy in the 1950s, the notion of insular lobe seizures was largely forgotten for decades. It is only since the late 1990s that the recent technique of stereo-electroencephalography (SEEG) enabled preoperative diagnosis of insular origin seizures and thus gave rise to a renewed interest for this ill-defined electroclinical entity. Owing to the multiple functional roles of insula and its extensive connectivity with adjacent as well as distant brain structures, insular lobe seizures present with a combination or series of diverse subjective and objective symptoms. In this review, we summarize current knowledge on the semiology of insular origin seizures. The following two distinct forms of clinical presentation have been recognized: 1) Seizures with predominant insulo-perisylvian symptoms, most notably paraesthesia and cervico-laryngeal discomfort. The former typically involves a large/bilateral cutaneous territory and can be perceived as cold, hot, or painful sensations. The latter ranges from slight dyspnea to strong sensation of strangulation. Other symptoms include epigastric discomfort/nausea, hypersalivation, auditory, vestibular, gustatory, and aphasic symptoms. 2) Nocturnal hyperkinetic seizures with/without tonic elevation of upper limbs, masquerading as fronto-mesial seizures. Patients are usually not fully aware of their symptoms despite preserved contact and organized behavior to others. Ipsilateral eye blinking can be observed. These two patterns often occur in succession or simultaneously. This characteristic combination and progression of ictal symptoms orients us strongly towards an insular origin of seizure, a better understanding of which is a crucial key to further optimize modern SEEG strategy.

Resective surgery in tuberous Sclerosis complex, from Penfield to 2018: A critical review.

Medically treated patients suffering from tuberous sclerosis complex (TSC) have less than 30% chance of achieving a sustained remission. Both the international TSC consensus conference in 2012, and the panel of European experts in 2012 and 2018 have concluded that surgery should be considered for medically refractory TSC patients. However, surgery remains currently underutilized in TSC. Case series, meta-analyses and guidelines all agree that a 50 to 60% chance of long-term seizure freedom can be achieved after surgery in TSC patients and a presurgical work-up should be done as early as possible after failure of two appropriate AEDs. The presence of infantile spasms, the second most common seizure type in TSC, had initially been a barrier to surgical planning but is now no longer considered a contraindication for surgery in TSC patients. TSC patients undergoing presurgical evaluation range from those with few tubers and good anatomo-electro-clinical correlations to patients with a significant "tuber burden" in whom the limits of the epileptogenic zone is much more difficult to define. Direct surgery is often possible in patients with a good electro-clinical and MRI correlation. For more complex cases, invasive monitoring is often mandatory and bilateral investigations can be necessary. Multiple non-invasive tools have been shown to be helpful in determining the placement of these invasive electrodes and in planning the resection scheme. Additionally, at an individual level, multimodality imaging can assist in identifying the epileptogenic zone. Increased availability of investigations that can be performed without sedation in young and/or cognitively impaired children such as MEG and HR EEG would most probably be of great benefit in the TSC population. Of those selected for invasive EEG, rates of seizure freedom following surgery are close to cases where invasive monitoring is not required, strengthening the important and efficient role of intracranial investigations in drug-resistant TSC associated epilepsy.

[Pediatric outcome after selective feticide for 30 complicated monochorionic twin pregnancies]. / Suivi pédiatrique de 30 grossesses gémellaires monochoriales consécutives traitées par fœticide sélectif.

OBJECTIVES: To describe perinatal and pediatric outcome after selective feticide for complicated monochorionic twin pregnancy. PATIENTS AND METHODS: We reviewed all consecutive cases of umbilical cord occlusion performed for complicated monochorionic twin pregnancy over a 16-year period. Pediatric follow-up was based on medical records and updated by phone calls to the parents. RESULTS: Thirty procedures were performed. Indications were: twin-to-twin transfusion syndrome (TTTS) progressing despite serial amniodrainage (n=12) ; twin reversed arterial perfusion (n=9) ; selective growth restriction (n=5) ; severe discordant structural anomalies (n=4). Mean gestational age at procedure was 21.8±3.1gestational weeks (GW) and 31.8±4.8 GW at birth. Overall survival rate was 87%, i.e. 83%, 100%, 60% and 100% for each indication, respectively. Mean pediatric follow-up was 5years (range: 6months to 15years). Medical charts and parents declared normal development in 88% of surviving children, i.e. 67%, 100%, 100%, and 100% for each indication. Cross-comparison between the four groups revealed that in the TTTS group, gestational age at procedure was more advanced (P=0.01) while delivery was slightly earlier (P=0.1), and pediatric development was poorer (P=0.02). DISCUSSION AND CONCLUSION: Pediatric outcome after selective feticide appeared to be poorer for TTTS progressing despite serial amniodrainage than for other indications.

[Macrocephaly-capillary malformation. A neonatal case]. / Le syndrome macrocéphalie - malformation capillaire. Intérêt du diagnostic en période néonatale.

UNLABELLED: Macrocephaly-cutis marmorata telangiectatica congenita is a multiple congenital anomaly syndrome first described in 1997 in children with macrocephaly, cutis marmorata telangiectatica congenita, and several other abnormalities. Since 2007, this syndrome has been renamed macrocephaly-capillary malformation. CASE REPORT: The pregnancy was marked by polyhydramnios associated with fetal macrosomia and macrocephaly. Clinical examination of the newborn confirmed overgrowth, macrocephaly, and found skin abnormalities with diffuse marbled skin, filtrum and upper lip vascular anomaly, and several superficial capillary malformations on the chest and abdomen, partial bilateral syndactyly between the 2nd and 3rd toes, and right hemi-hypertrophy of the body. Brain magnetic resonance imaging showed moderate right hemimegalencephaly. Radiological examination of the skeleton showed asymmetry of the limbs. At 8 months, the medical follow-up confirmed the diagnosis and its neurosurgical treatment of hydrocephalus secondary to an Arnold Chiari malformation. DISCUSSION: The patient reported herein presented macrocephaly-capillary malformation syndrome characterized by macrocephaly and more than two of the main reported findings comprising cutis marmorata, superficial vascular anomaly, syndactyly, and body asymmetry. We describe the major components of this multiple malformative syndrome that is rarely reported in the pediatric literature, especially in newborns. This syndrome should be detected early because medical multidisciplinary follow-up is necessary to prevent different complications (neurological, orthopedic, or oncologic).

[Favourable outcome after fetoscopic laser surgery for twin-twin transfusion syndrome: experience of an emerging centre]. / Résultats favorables d'une équipe émergente dans le traitement du syndrome transfuseur-transfusé par photocoagulation-laser.

OBJECTIVES: Our objective was to report perinatal outcome during the first three years of an emerging centre for laser photocoagulation in twin-twin transfusion syndrome (TTTS) and to compare with outcome observed earlier in the same centre when management consisted in recurrent amniodrainage. PATIENTS AND METHODS: We conducted a single centre retrospective study. We compared perinatal outcome of 19 consecutive cases of mid trimester TTTS managed by amniodrainage over a 10-year period with 49 cases of TTTS managed by laser photocoagulation over a 3-year period. RESULTS: Laser photocoagulation increased survival rate at birth (P=0.02) and at postnatal day 28 (P=0.01). Neurologic and cardiologic complications did not differ significantly (P=0.5 and P=0.3 respectively). We observed a significant increase in survival of the donor after laser coagulation at birth (P=0.04). DISCUSSION AND CONCLUSION: Our study demonstrated better outcome after laser photocoagulation. Early results of an emerging centre appeared comparable to those of more experienced centres.

[Congenital diaphragmatic hernia - mechanisms of pulmonary hypoplasia]. / Hernie congénitale du diaphragme : mécanismes de l'hypoplasie pulmonaire.

Congenital diaphragmatic hernia (CDH) is a common cause of severe neonatal respiratory distress. Mortality and morbidity are determined by the amount of pulmonary hypoplasia (PH) that occurs and by the development of therapy-resistant pulmonary hypertension. The pathogenesis and aetiology of CDH and its associated anomalies are still largely unknown despite all research efforts. The pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. PH, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Our understanding of CDH has also been aided by basic research with the use of dietary, teratogen-induced, and knockout models of CDH. These studies indicate that lung hypoplasia may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. Recent data reveal the role of disruption of a retinoid-signalling pathway in the pathogenesis of CDH. Although multifactorial inheritance may best explain most cases of CDH in humans, much has been learned about the genetic factors that play a role in the development of CDH by studies of patients with CDH caused by specific genetic syndromes and chromosome anomalies. More research is warranted to improve our understanding of normal and abnormal lung development in relation to CDH. Such investigations will help in the design of new treatment strategies to improve the natural course or even to prevent this anomaly.

[A study of the metabolic pathways of vitamin A in the fetal human lung]. / Étude de la voie métabolique de la vitamine A dans le poumon fœtal humain.

INTRODUCTION: Retinoic acid plays an essential role in lung development and is involved in all stages of embryogenesis and morphogenesis. We aimed to determine whether the human foetal lung is able to synthesize retinoic acid. METHODS: ADH3, RALDH1 and CYP26B1 RNA were studied by qualitative and semi-quantitative RT-PCR in human lungs at different stages of development. In human alveolar epithelial cells (lines A549), RAR beta (induced by retinoic acid) was quantified, after treatment by retinol, by q-PCR at 24h and 48 h. RESULTS: The expression of the RNA of ADH3, RALDH1 and CYP26B1 was detected for each of the four stages studied and in the A549 cell line. Only the level of RALDH1 RNA changed during the course of lung development. In the A549 cell line, treatment by retinol induced transcription of the RAR beta gene at 24 and 48 hours. CONCLUSION: The presence of ADH3, RALDH1 and CYP26B1 during the four stages of normal lung development and in the A549 cell line, as well as the capacity to convert retinol to retinoic acid in these cells, indicate that foetal human lung has the ability to regulate the supply of vitamin A from the pseudoglandular stage.

Prenatal diagnosis of lobar bronchial atresia.

We report three cases of fetal lobar bronchial atresia referred to our Fetal Medicine Center during the mid-trimester of pregnancy over the last 15 years. Lobar bronchial atresia can mimic a main stem bronchial atresia on mid-trimester ultrasound examination as it induces extensive lobar enlargement, major mediastinal shift and eversion of the diaphragm. It was associated with severe pulmonary hypoplasia in all three cases, even though polyhydramnios and ascites were absent in two. Termination of pregnancy was performed at parental request after extensive counseling in each of the cases and necropsy confirmed one or two enlarged lung lobes leading to major compression of the remaining lobe(s) of the ipsilateral lung, the contralateral lung and the heart. No other anomalies were observed and the karyotype was normal in all cases.

[Congenital lobar emphysema: a rare etiology of hyperechoic lung]. / Une étiologie rare de poumon hyperéchogène: l'emphysème lobaire géant congénital.

Lobar congenital emphysema is a rare pulmonary malformation corresponding to progressive overinflation of a pulmonary lobe secondary to partial bronchial obstruction. Prenatal diagnosis is mainly based on lung hyperechoic area. Sonographic features are not specific highlighting the interest of fetal MRI or postnatal tomodensitometry. This case report describes prenatal detection including pitfalls and postnatal management.

Expression of retinoid receptors during rabbit lung development.

Rabbit lung is often used to study the pathophysiology of some congenital anomalies affecting the lung because its development is very comparable with that of human. Retinoids and the molecular transducers of the retinoic signal play a crucial role in mammalian lung development. In the rabbit, the molecular retinoic pathway has so far been poorly studied. As a first step in elucidating this process, we aimed to identify the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We cloned a part of the nuclear receptors (RARs and RXRs), and we used reverse transcription - polymerase chain reaction (RT-PCR) and immunohistochemistry assays to demonstrate the presence of RAR (α,ß) and RXR (α, ß) at all stages of rabbit lung development. Our results initiate further analysis into the molecular and genetic functions of retinoids during normal and pathological rabbit lung development including the surgical model of congenital diaphragmatic hernia.

Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study.

OBJECTIVES: To describe the true incidence, prenatal detection rate and fetal outcome of congenital diaphragmatic hernia (CDH) in a systematically registered population over an 18-year period and to determine any change in trends over time. METHODS: This was a retrospective study of all cases of CDH registered in the Central-Eastern France Birth Defects Registry from 1986 to 2003. All fetuses and infants up to 1 year of age diagnosed with CDH were registered, including miscarriages later than 22 weeks of gestation, stillbirths and terminations of pregnancy (TOP). Routine prenatal screening consisted of three ultrasound examinations and there was no upper limit of gestational age for TOP. RESULTS: Five hundred and one cases of CDH were identified from a total of 1 835 022 live births (2.7 cases per 10 000 live births). The overall prenatal detection rate was 54%. There was a significant increase over time in the detection rate mainly for associated CDH and left-sided CDH (P < 0.0001), and in the proportion of neonates delivered in tertiary centers (P < 0.0001). The overall survival rate at discharge was 47% and this increased significantly over time for isolated CDH (P = 0.04), whereas it was lower and remained stable for associated CDH (P = 0.64). The TOP rate for isolated CDH did not vary significantly in contrast to that for associated CDH cases in which the TOP rate increased over time, progressively replacing the neonatal death rate (P = 0.01). CONCLUSIONS: Over an 18-year period, this large population-based study demonstrated increasing prenatal detection rates for associated CDH and left-sided CDH and confirmed an increasing survival rate mainly for isolated CDH.