In contrast to cleft lip and palate, which are common1, median mandibular clefts are extremely rare2 and show broad variation in severity. There may be associated anomalies, such as lower lip hemangioma3, cleft palate4, facial anomalies5-7, cervical dermoid cyst, abnormal hyoid bone (fissure or agenesis)7, 8, malformation of the laryngeal cartilage9 and aplasia of the epiglottis, cardiac malformation6, 7, 9 and chromosomal abnormalities, which can worsen the neonatal prognosis and therefore need to be known before delivery. Anomalies of the pharynx and larynx in particular can be responsible for respiratory distress and therefore require specific management immediately after birth. To our knowledge, there has been no previous description of prenatal diagnosis of a labio-mandibular cleft. We report a case of median cleft of the lower lip and mandible, and bifid tongue, detected by ultrasound during the third trimester of pregnancy. The patient was a healthy, 22-year-old woman. Fetal ultrasound examination at 32 weeks of gestation revealed a 2.5-mm-wide and 10-mm-long cleft of the lower lip, with a 5.8-mm bone defect of the lower jaw (Figure 1a). The anterior portion of the tongue was bifid (Figure 1b). The malformation was imaged by three-dimensional (3D) surface reconstruction (Figure 1c). Fetal echocardiography was normal. Amniocentesis revealed a normal karyotype. Prenatal ultrasound assessment of the mandibular cleft at 32 weeks of gestation: (a) two-dimensional (2D) image of the frontal view of the chin showing the cleft of the lip and chin; (b) 2D image of the cross-sectional view of the floor of the mouth showing bifid tongue; and (c) three-dimensional reconstruction of the face showing the cleft of the lip and chin. (d) T2-weighted magnetic resonance image of the frontal section showing bifid tongue at 35 weeks. Further explorations were made to make sure there was no ear, nose and throat (ENT) malformation. Fetal magnetic resonance imaging (MRI) (Figure 1d) showed no significant brain anomaly, with particular attention paid to the midline, and showed that the tongue cleft extended from the tip to the base. The hypopharynx and the trachea were visible, and no anomaly was detected. A 2780-g female infant was delivered vaginally at 40 weeks of gestation, with Apgar scores of 8, 9 and 10 at 1, 5 and 10 min, respectively, and was immediately transferred to the pediatric intensive care unit. The child was breathing normally and the pharynx and larynx were normal. The sucking reflex was present but of variable quality without false passage. Examination of the neonate revealed a cleft of the lower lip involving the chin and the mandible, a bifid tongue attached to the floor of the mouth and an inflamed median cervical cyst. There was no facial dysmorphia or associated malformation (Figures 2a and 2b). Postnatal appearance before and after surgery. (a) Examination on postnatal day 2: bifid tongue (arrow) and cleft of the lip and chin (dashed arrow). (b) Examination on postnatal day 2: cleft of the lip and chin (arrow) and median cervical cyst (dashed arrow). (c) Appearance 2 months postoperatively. (d) Appearance at the 22-month follow up. Three weeks after birth, the neonate underwent surgery with cheiloplasty, tongue repair, mandibular osteosynthesis and correction of a median cervical fistula. Surgical follow-up was uneventful with an excellent esthetic result (Figures 2c and d) and a satisfactory functional outcome. The aim of antenatal support is to eliminate associated malformations, especially ENT anomalies, which can be life-threatening and thus need specific care, with pediatric ENT specialists in attendance during labor. Fetal MRI seems to be more informative than ultrasound examination when exploring anomalies of the base of the tongue and of the pharynx and larynx. Karyotyping and specialized ultrasound screening for other morphological anomalies should be performed. Multidisciplinary management is needed because the prognosis, although mainly functional (speech and swallowing), is also esthetic and therefore psychological. Follow up should be conducted by a team including maxillofacial surgeons, pediatric plastic surgeons, speech therapists, orthodontists, physiotherapists and psychologists10. A. Vincent-Rohfritsch*, O. Anselem*, G. Grangé*, C. Benard*, G. Viot*, P. Lalau , A. E. Millischer-Bellaïche , P. Hornoy , M. Mitrofanoff§, V. Tsatsaris*, * APHP, Maternité Port-Royal, Hôpital Cochin-Saint-Vincent-de-Paul, Université Paris-Descartes, Paris, France, Service de Gynécologie-Obstétrique, Centre Hospitalier de Lagny Marne-la-Vallée, Lagny, France, APHP, Service de Radiologie Pédiatrique, Hôpital Cochin-Saint-Vincent-de-Paul, Université Paris-Descartes, Paris, France, § APHP, Service de Chirurgie Maxillo-faciale et Stomatologie Pédiatrique, Hôpital Necker-Enfants Malades, Université Paris-Descartes, Paris, France
Vaccination in pregnancy has been shown to be effective for the prevention of influenza and pertussis in infants, providing support for similar strategies to prevent group B streptococcus and respiratory syncytial virus infections that represent a large burden in pediatric population.This review addresses the principle of maternal immunization, efficacy and safety of both pertussis and seasonal influenza vaccines and presents available data on group B streptococcus and respiratory syncytial virus that are in development for administration during pregnancy.Complementary data is needed to help in understanding pertussis vaccine mechanisms, improving influenza vaccine efficacy and addressing the interference phenomenon which is when maternal antibodies interfere with the infant vaccine response. Several knowledge gaps need to be filled in group B streptococcus and respiratory syncytial virus vaccines research.
It is now well established that maternal serum markers are often abnormal in fetal trisomy 21. Their determination is recommended for prenatal screening and pregnancy follow-up. However, mechanisms leading to abnormal maternal serum levels of such markers are still debated. Our objective was to help clinicians and scientists unravel the pathophysiology of these markers via a review of the main studies published in this field, both in vivo and in vitro, focusing on the six most widely used markers (hCG, its free subunit hCGβ, PAPP-A, AFP, uE3, and inhibin A) as well as cell-free feto-placental DNA. Analysis of the literature shows that mechanisms underlying each marker's regulation are multiple and not necessarily directly linked with the supernumerary chromosome 21. The crucial involvement of the placenta is also highlighted, which could be defective in one or several of its functions (turnover and apoptosis, endocrine production, and feto-maternal exchanges and transfer). These defects were neither constant nor specific for trisomy 21, and might be more or less pronounced, reflecting a high variability in placental immaturity and alteration. This explains why maternal serum markers can lack both specificity and sensitivity, and are thus restricted to screening.
