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J Psychosom Res ; 127: 109840, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677548


OBJECTIVE: Inflammatory bowel disease (IBD) is often diagnosed in women in their reproductive years of life and therefore children are born to mothers with IBD. Health outcomes of children born to mothers with IBD seem favorable. However, little is known about the quality of life related to their health compared to children born to healthy mothers. Therefore, our first objective was to investigate the effect of having IBD during pregnancy on the health-related quality of life (HRQoL) of children born to mothers with IBD in the first 5 years of age compared to children born to healthy mothers. Secondly, we studied the effect of the different IBD related factors on the HRQoL. METHODS: We prospectively followed 264 women with IBD, who visited the preconception outpatient clinic at our tertiary health center in the Netherlands from April 2013 through November 2016. Women of children aged 1-5 years were approached to fill in a 43-item validated TNO-AZL Preschool Children Quality of Life questionnaire (TAPQOL) to assess HRQoL (Fekkes et al., 2000; Bunge et al., 2005 [1,2]). Outcomes were compared to children of mothers without IBD. RESULTS: One-hundred-eighty-two women completed the TAPQOL questionnaire. In total 182 children of mothers with IBD were included [median age 3.0 years (IQR 2-4)]. From 70 healthy mothers, 70 children were included as controls. There was no significant difference in the HRQoL between children who were and were not born to mothers with IBD (P = .18). Also, no effect of the different IBD related factors was found. CONCLUSION: In this study, we found no effect of having IBD during pregnancy on the health-related quality of life of children in the first 5 years of life.

J Crohns Colitis ; 13(1): 1-2, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30272119
Expert Rev Gastroenterol Hepatol ; 12(8): 811-818, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29972674


INTRODUCTION: Relapse of inflammatory bowel disease (IBD) during conception and pregnancy has been associated with a negative pregnancy outcome. Therefore, it is advised to maintain drugs in order to prevent relapse. The effect of drugs, which cross the placenta, on children who have been exposed during pregnancy will be discussed in this review. Areas covered: A literature search was performed using the following search terms: inflammatory bowel disease, pregnancy, infant, antitumor necrosis factor alpha, infliximab, adalimumab, golimumab, certolizumab, anti-integrins, vedolizumab, anti-interleukin (IL)-12/23 ustekinumab, placenta, vaccination. Other studies were identified by using references from articles identified through our original literature search. The occurrence of unfavorable pregnancy outcome and congenital malformations does not seem to be increased after exposure to anti-TNFα, but the effects on the developing immune system are largely unknown. For anti-integrins and anti IL-12/23, the numbers of exposed pregnancies are too small to draw any conclusions. Expert commentary: Follow-up of the developing immune system in children exposed to these drugs seems warranted, preferably in a prospective study design.

Anticorpos Monoclonais/efeitos adversos , Sistema Imunitário/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal , Terapia Biológica/efeitos adversos , Transporte Biológico , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Sistema Imunitário/embriologia , Sistema Imunitário/imunologia , Lactente , Doenças Inflamatórias Intestinais/imunologia , Integrinas/antagonistas & inibidores , Integrinas/imunologia , Troca Materno-Fetal , Placenta/metabolismo , Cuidado Pré-Concepcional , Complicações na Gravidez/imunologia , Resultado da Gravidez , Cuidado Pré-Natal , Efeitos Tardios da Exposição Pré-Natal/imunologia , Prevenção Secundária , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
Lancet ; 390(10097): 871-881, 2017 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-28711318


BACKGROUND: Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. METHODS: We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with, number NCT00854932. FINDINGS: Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI -4·6 to 4·8) in the intention-to-treat analysis (5 [0·6%] of 866 neonates in the procalcitonin group vs 4 [0·5%] of 844 neonates in the standard group) and 0·1% (-5·2 to 5·3) in the per-protocol analysis (5 [0·7%] of 745 neonates in the procalcitonin group vs 4 [0·6%] of 663 neonates in the standard group). INTERPRETATION: Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death. FUNDING: The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.

Antibacterianos/administração & dosagem , Calcitonina/sangue , Tomada de Decisões , Sepse/sangue , Sepse/tratamento farmacológico , Biomarcadores/sangue , Monitoramento de Medicamentos/métodos , Diagnóstico Precoce , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/sangue , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/tratamento farmacológico , Internacionalidade , Masculino , Sepse/diagnóstico , Fatores de Tempo , Resultado do Tratamento
J Clin Immunol ; 36(3): 195-203, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26931784


PURPOSE: Complete interferon-γ receptor 1 (IFN-γR1) deficiency is a primary immunodeficiency causing predisposition to severe infection due to intracellular pathogens. Only 36 cases have been reported worldwide. The purpose of this article is to describe a large novel deletion found in 3 related cases, which resulted in the complete removal of the IFNGR1 gene. METHODS: Whole blood from three patients was stimulated with lipopolysaccharide (LPS) and IFN-γ to determine production of tumor necrosis factor (TNF), interleukin-12 p40 (IL-12p40) and IL-10. Expression of IFN-γR1 on the cell membrane of patients' monocytes was assessed using flow cytometry. IFNGR1 transcript was analyzed in RNA and the gene and adjacent regions were analyzed in DNA. Finally, IL22RA2 transcript levels were analyzed in whole blood cells and dendritic cells. RESULTS: There was no expression of the IFN-γR1 on the monocytes. Consistent with this finding, there was no IFN-γ response in the whole blood assay as measured by effect on LPS-induced IL-12p40, TNF and IL-10 production. A 119.227 nt homozygous deletion on chromosome 6q23.3 was identified, removing the IFNGR1 gene completely and ending 117 nt upstream of the transcription start of the IL22RA2 gene. Transcript levels of IL22RA2 were similar in patient and control. CONCLUSIONS: We identified the first large genomic deletion of IFNGR1 causing complete IFN-γR1 deficiency. Despite the deletion ending very close to the IL22RA2 gene, it does not appear to affect IL22RA2 transcription and, therefore, may not have any additional clinical consequence.

Deleção de Genes , Síndromes de Imunodeficiência/genética , Infecções Oportunistas/genética , RNA Mensageiro/genética , Receptores de Interferon/genética , Receptores de Interleucina/genética , Adulto , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/imunologia , Células Sanguíneas/patologia , Pré-Escolar , Cromossomos Humanos Par 6 , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Regulação da Expressão Gênica , Homozigoto , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/fisiopatologia , Lactente , Interferon gama/farmacologia , Interleucina-10/genética , Interleucina-10/imunologia , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/imunologia , Lipopolissacarídeos/farmacologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/fisiopatologia , Linhagem , Cultura Primária de Células , RNA Mensageiro/imunologia , Receptores de Interferon/deficiência , Receptores de Interferon/imunologia , Receptores de Interleucina/imunologia , Análise de Sequência de DNA , Transcrição Genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
Ned Tijdschr Geneeskd ; 157(41): A6250, 2013.
Artigo em Holandês | MEDLINE | ID: mdl-24103134


Only 10-15% of neonates with congenital cytomegalovirus infection have symptoms at birth. The most common symptoms are intrauterine growth retardation, microcephaly, petechiae, jaundice, hepatosplenomegaly, intracranial abnormalities, ophthalmological abnormalities and hearing loss. Symptomatic and asymptomatic CMV infections can both have long-term effects. CMV infection during pregnancy is diagnosed using a blood test and possible testing of the amniotic fluid for viral DNA. Infection of the fetus may be prevented by treating the mother with CMV hyperimmune globulin. In the neonate a diagnosis can be made by viral culture or PCR in urine. PCR in saliva could be an alternative. Blood testing is of limited value. If symptoms of CMV infection occur in the neonate, such as petechiae, microcephaly, central nervous system abnormalities, sensorineural hearing loss or chorioretinitis, antiviral treatment should be considered. Long-term follow-up is advisable because of the possibility of delayed-onset hearing loss and chorioretinitis.

Infecções por Citomegalovirus/congênito , Perda Auditiva Neurossensorial/virologia , Líquido Amniótico/virologia , Antivirais/uso terapêutico , Coriorretinite/congênito , Coriorretinite/virologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , DNA Viral/análise , Feminino , Perda Auditiva Neurossensorial/congênito , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle