Importance of a multidisciplinary approach and monitoring in fetal warfarin syndrome.

Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow-up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive-related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow-up. Thus, a multidisciplinary approach and long-term monitoring of these patients may be necessary.

HIV exposure does not worsen outcome in stage III necrotizing enterocolitis with current treatment protocols.

BACKGROUND/PURPOSE: The heavy burden of maternal HIV infection in developing countries such as South Africa has resulted in a high prevalence of premature birth and necrotizing enterocolitis (NEC). Uninfected infants born to HIV-infected mothers also demonstrate immune deficiencies. It is, therefore, essential to have a better understanding of how to mitigate HIV as an independent risk factor for surgically treated NEC and to evaluate the relevant contributing factors in the presence of an aggressive strategy of pasteurized breast milk feeding and antiretroviral prophylaxis. METHODS: Infants with stage IIIb NEC presenting over a 4-year period were retrospectively reviewed. HIV-exposed infants were compared with non-HIV-exposed infants. Contributing factors were evaluated and studied by systematic statistical methods to evaluate risk. RESULTS: Twenty percent (17/87) infants were HIV-exposed, and 80% (70/87), unexposed, whereas a further 10 (total, n = 97) had unknown HIV exposure status. Demographics and other perinatal risk factors between the 2 groups were not significantly different other than that HIV-exposed infants received pasteurized breast milk and nonexposed infants received unpasteurized breast milk. There were no statistically significant differences between the groups with respect to disease presentation or severity, surgical findings or type of surgery, postoperative complications, survival, or timing of death. Trends toward higher antenatal steroid exposure and increased postoperative sepsis in the HIV-exposed group (P = .03) were noted but were not related. All HIV-exposed infants received antiretrovirals; there were no significant differences on subanalysis between different antiretroviral regimens. CONCLUSIONS: HIV-exposed infants do not have a more severe disease course nor more adverse outcomes in stage IIIb NEC than unexposed infants. Significant factors were antenatal steroids and post-NEC infective episodes.

Survival, differentiation, and reversal of heroin neurobehavioral teratogenicity in mice by transplanted neural stem cells derived from embryonic stem cells.

Cell therapies in animal models of neurobehavioral defects are normally derived from neural stem cells (NSC) of the developing cortex. However, the clinical feasibility of NSC therapies would be greatly improved by deriving transplanted cells and from a tissue culture source that is self-renewing, containing cells that potentially differentiate into the desired neuronal phenotypes. These cultures can be engineered to contain the appropriate factors to support their therapeutic action and likely evoke lesser immune reactions. In the current study, we employed our model of mice neurobehaviorally impaired via prenatal exposure to heroin, to test the therapeutic efficacy of NSC derived from murine embryonic stem cells culture (ESC). The culture contained elongated bipolar cells, 90% of which are positive for nestin, the intermediate filament protein found in neural precursors. After removal of growth factors, the NSC differentiated into neurons (34.0% +/- 3.8% NF-160 positive), including cholinergic cells (ChAT positive), oligodendrocytes (29.9% +/- 4.2% O(4)), and astrocytes (36.1% +/- 4.7% GFAP positive). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis confirmed the immunocytochemical findings. Mice made deficient in Morris maze behavior by prenatal heroin exposure (10 mg/kg heroin s.c. on gestational days 9-18) were transplanted into the hippocampus region on postnatal day 35 with the ES culture-derived NSC (ES-NSC) labeled with dialkylcarbocyanine (Dil) cell tracker. Dil+ and NF160+ cells were detected in the hippocampal region (50% +/- 8% survival). The transplantation completely restored maze performance to normal; e.g., on day 3, transplantation improved the behavior from the deficient level of 11.9-sec latency to the control of 5.6-sec latency (44.5% improvement).

Reconstrução nasal neonatal na Síndrome do Warfarin Fetal / Neonatal nasal reconstruction in Fetal Warfarin Syndrome

O objetivo deste trabalho é relatar um caso de reconstrução nasal precoce em um paciente com síndrome do Warfarin fetal, onde um paciente de 23 dias com apresentava hipoplasia nasal isolada. O ganho ponderal estava estagnado e não havia possibilidade de introdução de sonda nasoentérica devido à deformidade. Foi realizada rinoplastia aberta com incisão transcolumelar. Dois enxertos de cartilagem tragal foram confeccionados e introduzidos na região da ponta, porção cranial do septo cartilaginoso e alares. O paciente apresentou melhoria da permeabilidade ventilatória, diminuição do ruído inspiratório, ganho de peso e também da forma. Após um ano de seguimento o resultado continuava satisfatório. Concluímos que a intervenção precoce é satisfatória e pode minimizar ou mesmo prevenir procedimentos futuros.

The aim of this work is to report a case of early nasal reconstruction in a 23-day-old patient with fetal Warfarin syndrome and isolated nasal hypoplasia. Weight gain was arrested and the deformity precluded the use of a nasogastric tube. An open rhinoplasty with transcolumellar incision was performed. Two grafts of tragal cartilage were made and introduced in the tip area, cranial portion of the cartilaginous septum, and alar cartilages. The patient presented improved ventilatory permeability, decrease of inspiratory noise, and weight and shape gains. At the one-year follow-up the result was still satisfactory. We concluded that early intervention is satisfactory and may minimize or even prevent future procedures.

Intracranial arteriovenous malformation with maternal carbamazepine use.

1 1/2 month old child born to primigravida mother on prolonged carbamazepine therapy presented with recurrent seizures. The child had abnormal facies and was diagnosed to be having arteriovenous malformation with intracranial hemorrhage on neuroimaging. This case suggests that development of arteriovenous malformation in a child with maternal carbamazepine therapy may occur as a part of clinical profile of 'fetal anticonvulsant syndrome'.