Diabetes mellitus (DM) during pregnancy causes congenital malformation, macrosomia, respiratory distress syndrome, and other abnormalities in neonates, but whether maternal DM affects the neonatal innate immune system is unknown. Therefore we aimed to reveal the influence of DM in pregnancy on the toll-like receptor (TLR)-mediated innate immune response in neonates. Cord blood was collected after full-term vaginal or cesarean delivery and classified into a DM group (n=8) and non-DM (control) group (n=7). Mononuclear cells were harvested from cord blood by using density gradient centrifugation, after which anti-CD14 magnetic beads were used to isolate monocytes from the mononuclear population. After monocytes were cultured with lipopolysaccharide (TLR4 ligand), flagellin (TLR5 ligand), Pam3CSK4 (TLR1/TLR2 ligand), zymosan (TLR2/TLR6 ligand), or macrophage-activating lipopeptide (TLR2/TLR6 ligand) for 12h, the cytokine levels (interleukin [IL]-8, IL-6, IL-1β, IL-10, tumor necrosis factor alpha and IL-12) in the culture supernatants were measured. Compared with the control group, the DM group had higher concentrations of IL-8 (P=0.01) and tumor necrosis factor alpha (P=0.02) after monocyte cultures were stimulated with Pam3CSK4 and higher concentrations of IL-8 (P=0.01) after flagellin treatment. In contrast, stimulation with lipopolysaccharide, zymosan, or macrophage-activating lipopeptide did not lead to any difference in cytokine profiles between the two groups. These data indicate that maternal DM induces excessive inflammatory activation in neonates via a TLR5- or TLR1/2-mediated innate immune response.
A primagravida, 23-years-old patient was referred to our hospital at the 38th week of pregnancy. The initial ultrasound (18 wks) reported oligohydramnios but fetal anatomy, karyotype (46, XY) and growth parameters were otherwise normal. The parents of the baby were healthy and unrelated and none of them had ophthalmic anomalies. At 26 weeks of pregnancy, an improper development of the skull bones, heart malformation, multiple cysts in both kidneys and dilated ureter were diagnosed by ultrasound.At the 38 week of gestation a 3600 g boy was delivered by Cesarean section (Apgar scores was 1). The child died soon after birth due to respiratory insufficiency. Autopsy confirmed the presence of bilateral anophthalmia. The hypoplastic thoracic cage contained a right hypoplastic lung and complete agenesis of the left one. There was also malformation of the cardio-vessel tissues presenting in the manner of Tetralogy of Fallot and along with a void of the atrial valve, pulmonary artery atresia was present. Within the urinary tract there were bilaterally polycystic dysplastic renals. No diaphragmatic hernia was present.STRA6-related mutations are inherited in an autosomal recessive manner requiring both mother and father to be a carrier of the mutation. The diagnosis of MWS was confirmed by the genetic identification of two STRA6 heterozygous deleterious mutations. This child was compound heterozygote for a previously reported missense mutation (c.878C > T [p.Pro293Leu] inherited from his father, and for a novel frameshift mutation (c.50_52delACTinsCC [p. Asp18Aalaf*54]) which produced a premature stop codon which was inherited from the mother.
Objectives: To study the course and outcome of fetuses with congenital Atrial Ventricular Block (AVB) over a 10-year period in a single centre. Methods: Retrospective study of all cases diagnosed prenatally with AVB of 2nd and 3rd degree between 2002 and 2012. All prenatal records, pre and postnatal echocardiographic reports, as well as follow-up data were reviewed. The clinical characteristics and outcome of fetal AVB were evaluated and compared with the data in the literature including the use of corticosteroids prenatally. Results: 91 cases of congenital AVB were referred to our unit over 10 years of which 62 cases were eligible for analysis and formed our study group. Associated congenital heart defect (CHD) was found in 17/62 (27.4%), maternal anti-bodies (AB) were present in 42/62 (67.7%). Fetal hydrops was present in 3 (4.8%) cases. Pregnancy was terminated in 12 (19.3%) cases including 8 and 2 cases with CHD and hydrops respectively. Among the 49 (79.3%) live-born neonates 4 (8.2%) died before 28 days of life, all had associated CHD, one needed to be paced at 2 years and died at 2.6 years of cardiac failure due to congestive cardiomyopathy. The only predictive factor for neonatal death was the association of CHD (OR for mortality: 15.6 [3.4; 78.4}, p < 10-4). 41 (63%) babies had a permanent pacemaker implanted. Mean (+/− SD) age at placement was 8.4 +/− 1.4 months. Congestive cardiomyopathy occurred in four cases. The median (interquartile range) age at follow up in our series was 3.4 (1.4-7.4) years. Among women with antibodies, twenty (44.4%) women received corticosteroids, sympathomimetics or both type of medication in 17 (37.8%), 1 (2.2%) and 2 (4.4%) cases respectively. No difference in outcome was found between these treatment groups. Conclusions: The most important prognostic factor for AVB is association with CHD. The treatment of congenital AVB remains a questionable intervention. A multicentre, randomized, controlled trial is recommended.
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