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1.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(4): 719-725, 2020 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-32773809

RESUMO

OBJECTIVE: To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance. METHODS: Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ2 tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model. RESULTS: The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 (P < 0.001), the rates ratio was 27.9% (χ2=23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups (P < 0.05). CONCLUSION: The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.


Assuntos
Suplementos Nutricionais , Defeitos do Tubo Neural , Adulto , Pequim , Feminino , Feto , Ácido Fólico , Humanos , Defeitos do Tubo Neural/epidemiologia , Gravidez , Prevalência
2.
Environ Int ; 139: 105688, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32244100

RESUMO

This study examined the associations between concentrations of cobalt (Co), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn) in placental tissue and risks for NTDs with a case-control design consisting of 408 fetuses or newborns with neural tube defects (NTDs) and 593 non-malformed fetuses or newborns. The concentrations of Zn and Fe were determined by inductively coupled plasma-emission spectrometer and the other four elements by inductively coupled plasma-mass spectrometer. Element concentrations were presented in ng/g or µg/g dry weight of placental tissue. The associations between the levels of each of the six ETEs and risk for NTDs were evaluated using multivariable logistic regression, and the associations between overall levels of all six ETEs and risk for NTDs were examined using Bayesian kernel machine regression (BKMR). Concentrations above the median concentration of all participants for an individual element were associated with increased risk for NTDs: Mn, 3.17-fold (95% CI 2.35-4.28); Mo, 3.73-fold (95% CI 2.74-5.07); Se, 3.28-fold (95% CI 2.44-4.42); and Zn, 2.85-fold (95% CI 2.13-3.83), and a decreased risk for Co [OR, 0.18 (95% CI 0.14-0.25)]. The risk for NTDs increased with the increase in the concentrations of Mn, Mo, Se, and Zn, but decreased for Co, in the second, third, and fourth quartiles, respectively, compared to their lowest quartile (all Pstrend < 0.01). In BKMR model, the risk for NTDs increased constantly when the overall exposure levels were higher than the median of the six ETEs as a co-exposure mixture, and the associations between Co, Mn, Se, and Zn and NTD risk remained when the remaining five elements were taken into consideration simultaneously. Taken together, when evaluated individually, higher levels of Mn, Se, and Zn in placental tissue are associated with increased risk for NTDs, while higher levels of Co are associated with decreased risk for NTDs; when examined collectively, the risk of NTDs increases continuously when exposure levels are higher than the median of the six ETE mixture.


Assuntos
Defeitos do Tubo Neural , Selênio , Oligoelementos , Teorema de Bayes , Feminino , Feto , Humanos , Recém-Nascido , Defeitos do Tubo Neural/epidemiologia , Gravidez
4.
Georgian Med News ; (298): 61-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32141851

RESUMO

Until 2015, systematic statistical data on micronutrient deficiency was not available in Georgia, to provide developing national strategy. In the same year, the National Centre for Disease Control and Public Health of Georgia (NCDC) in collaboration with the USA CDC launched the project "Strengthening surveillance of micronutrient deficiency in Georgia". In 2015 we did choose sentinel surveillance approach. For setting nutrition surveillance system 8 sentinel sites (2 sites in each region/children and pregnant health facilities) in four regions of Georgia (Tbilisi, Kakheti, Achara, and Samegrelo) were selected, using the criteria of geographical, social, ethnical, urban/rural, and religion. Also, existing information about malnutrition and dietary habits from the above mentioned regions. The project protocols was approved by the Institutional review board (IRB) at the NCDC and by the Research Review Committee and Ethical review committee of the US CDC. As a result of surveillance system functioning (2016-2019) we reviled that, about 36% out of 1021 studied children U2 (12-23 months) were anemic, 74% of them were identified as iron deficient. Hemoglobin was tested among 963 pregnant women and about 21% of them were found anemic, 57% were iron deficient, and 28% tested positive for folate deficiency. Neural tube defects (NTDs) prevalence per 1000 live births registered in sentinel sites was high 3.7. Our results show that anemia and iron deficiency are prevalent among both pregnant women and children of the specified age group in Georgia. Additionally, folate deficiency was quite common during the1st trimester of pregnancy. Our findings will inform public health policy decision makers to take relevant decisions on required interventions, such as health education, distribution of relevant supplements, and food fortification.


Assuntos
Micronutrientes/deficiência , Defeitos do Tubo Neural/epidemiologia , Anemia Ferropriva/epidemiologia , Criança , Feminino , Deficiência de Ácido Fólico/epidemiologia , Alimentos Fortificados , República da Geórgia/epidemiologia , Humanos , Defeitos do Tubo Neural/sangue , Gravidez , Prevalência
5.
Environ Int ; 137: 105542, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32059143

RESUMO

Rare earth elements (REEs) are ubiquitous in the environment. Animal experiments have shown that many REEs have adverse impacts on the health of fetuses. However, data from humans are scarce. In this study, we examined the associations between concentrations of 10 REEs in maternal serum and the risk for fetal neural tube defects (NTDs). The study included 200 pregnant women with pregnancies affected by NTDs and 400 pregnant women with healthy fetuses/infants. Fifteen REEs in maternal serum were assessed; 10 of them were detectable in over 60% of samples and were included in statistical analyses, including lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), terbium (Tb), dysprosium (Dy), lutetium (Lu), and yttrium (Y). When the elements were considered individually with the use of Logistic regression model, the risk for NTDs increased by 2.78-fold (1.25-6.17) and 4.31-fold (1.93-9.62) for La, and 1.52-fold (0.70-3.31) and 4.73-fold (2.08-10.76) for Ce, in the second and third tertiles, respectively, compared to the lowest concentration tertile. When Bayesian kernel machine regression was used to examine the joint effect of exposure to all 10 REEs, the risk for NTDs increased with overall levels of these REEs and the association between La and NTD risk remained when other nine elements were taken into consideration simultaneously. Taken together, this study shows that the risk for NTDs increases with La concentrations when single REEs are considered and with concentrations of all 10 REEs when these REEs are considered as a co-exposure mixture.


Assuntos
Cério , Metais Terras Raras , Defeitos do Tubo Neural , Teorema de Bayes , Feminino , Feto , Humanos , Lactente , Metais Terras Raras/sangue , Metais Terras Raras/toxicidade , Defeitos do Tubo Neural/epidemiologia , Gravidez , Risco
6.
Nutrients ; 12(1)2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31963665

RESUMO

The United States implemented mandatory fortification of cereal grains with folic acid in 1998 to prevent neural tube defects (NTDs) during pregnancy. The health benefits of folate (vitamin B9) are well documented; however, there are potential risks of exceeding the upper tolerable limit, particularly in vulnerable populations. We conducted a population-based analysis of the Food Fortification Initiative dataset to determine the strength of the evidence regarding reports of decreased NTDs at the national level in response to mandatory folic acid fortification of cereal grains. We found a very weak correlation between NTD prevalence and the level of folic acid fortification, irrespective of the cereal grain fortified (wheat, maize or rice). Stratification of the data based on socioeconomic status (SES) indicated a strong linear relationship between reduced NTDs and better SES. We conclude that national fortification with folic acid is not associated with a significant decrease in the prevalence of NTDs at the population level.


Assuntos
Grão Comestível , Ácido Fólico/administração & dosagem , Alimentos Fortificados , Defeitos do Tubo Neural/prevenção & controle , Bases de Dados Factuais , Feminino , Humanos , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/epidemiologia , Gravidez , Prevalência , Fatores de Proteção , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos
7.
MMWR Morb Mortal Wkly Rep ; 69(1): 1-5, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31917782

RESUMO

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.


Assuntos
Infecções por HIV/diagnóstico , Defeitos do Tubo Neural/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estados Unidos/epidemiologia , Adulto Jovem
8.
S Afr Med J ; 109(9): 698-703, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31635597

RESUMO

BACKGROUND: Neural tube defects (NTDs) are an important category of birth defect, but surveillance remains inadequate in South Africa. OBJECTIVES: To assess the identification of NTDs at a tertiary hospital using a range of prenatal, perinatal and postnatal data sources, and to estimate the impact of prenatal diagnosis and birth prevalence for the referral area. METHODS: Cases of anencephaly, encephalocele and spina bifida (SB) in a 6-year period were retrospectively identified from 5 data sources covering prenatal, perinatal and postnatal care. These were cross-correlated to avoid duplicate entries and to determine the contribution of different data sources. Details of prenatal diagnosis and termination of pregnancy (TOP) were obtained for 10 years, and birth prevalence over 2 years. RESULTS: During a 6-year period 195 NTDs were identified at a Western Cape Province tertiary hospital. These included 59 (30%) cases of anencephaly, 28 (14%) of encephalocele and 108 (55%) of SB. The majority of NTDs (71%) were detected prenatally, although SB was less commonly diagnosed prenatally than cranial defects (56% v. 88%; p<0.001). Of SB cases ascertained pre- or postnatally, 57% of patients were born alive and 50% discharged alive, but 72% of survivors had not been diagnosed prenatally. Women receiving prenatal diagnosis of any type of NTD before 24 weeks' gestation were nearly always offered TOP, and the majority accepted termination after non-directive counselling. For SB, later prenatal diagnosis was associated with much lower termination rates because the option was less often offered (51% v. 100%; p<0.001), and perhaps less often accepted (57% v. 78%; p=0.06). The estimated NTD birth prevalence for the referral area was 0.76 - 0.80 per 1 000 live births, but perhaps up to 1.18 per 1 000 when considering under-referral of lethal cranial lesions from rural areas. CONCLUSIONS: A substantial number of NTDs can be ascertained from a tertiary hospital environment if multiple data sources are used, even though adding data from the Perinatal Problem Identification Program for outlying health facilities increases detection of lethal defects. Hospital-based surveillance can be considered, especially for SB. Prenatal diagnosis was fairly common and pregnancy termination was often offered and accepted if detected before 24 weeks' gestation. A regional prenatal ultrasound programme, predominantly based in primary care but with ready access to a tertiary centre, can be quite effective, although limited or delayed access to prenatal diagnosis must be addressed.


Assuntos
Anencefalia/epidemiologia , Encefalocele/epidemiologia , Defeitos do Tubo Neural/epidemiologia , Disrafismo Espinal/epidemiologia , Aborto Induzido/estatística & dados numéricos , Anencefalia/diagnóstico , Encefalocele/diagnóstico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Defeitos do Tubo Neural/diagnóstico , Vigilância da População , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Prevalência , Estudos Retrospectivos , África do Sul/epidemiologia , Disrafismo Espinal/diagnóstico , Centros de Atenção Terciária
9.
Nutrients ; 11(10)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581726

RESUMO

Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects (NTDs), but little information is known about its use in Vietnam. It is important that FA supplements start to be taken when planning a pregnancy and continued through the first trimester to prevent NTDs, as the neural tube closes in the first month of pregnancy. However, FA supplementation in Vietnam is usually recommended to commence from the first antenatal visit, which is usually at 16 weeks, and very few women take FA before their first visit. This multicenter study aimed to determine the prevalence of FA supplement use and associated maternal characteristics in Vietnam. FA supplementation was assessed in 2030 singleton pregnant women between 2015 and 2016. In total, 654 (32.2%) women reported taking either supplements containing FA alone or multivitamins containing FA, and 505 (24.9%) reported correctly taking supplements containing FA alone. Women who were aged 30 years or over, had low education levels, had formal employment, and whose current pregnancy was first or unplanned were less likely to supplement with FA. Education programs are needed to encourage FA supplementation when contemplating pregnancy.


Assuntos
Suplementos Nutricionais , Deficiência de Ácido Fólico/prevenção & controle , Ácido Fólico/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Defeitos do Tubo Neural/prevenção & controle , Estado Nutricional , Complicações na Gravidez/prevenção & controle , Cuidado Pré-Natal , Adulto , Escolaridade , Emprego , Feminino , Deficiência de Ácido Fólico/diagnóstico , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/fisiopatologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/fisiopatologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Medição de Risco , Fatores de Risco , Vietnã/epidemiologia , Adulto Jovem
10.
Bratisl Lek Listy ; 120(9): 680-685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475554

RESUMO

OBJECTIVES: Neurenteric cysts (NCs) of the central nervous system (CNS) are cystic congenital lesions that may occur anywhere along the neural tube. They are most common in the spinal region, in the lower part of the cervical and upper thoracic spine. Intracranial NCs occur rarely and there are only small series of patients published in literature worldwide. Microsurgical resection is the treatment of choice. We present our experience in treatment of NCs and review of literature. METHODS: Seven patients with NC of CNS who were operated at the Department of Neurosurgery of Comenius University at University Hospital Bratislava within nine years (2010-2018) were included in the study. The series was retrospectively evaluated with an emphasis on symptomatology, surgery and postoperative course. RESULTS: In three of the seven patients, NC was localized intracranially, in the other four, NC was in the spinal canal. In three patients, a complete removal of NC was achieved (2 intracranial NC, 1 spinal NC). In other patients, a portion of the cyst wall was left to prevent the development of a postoperative neurological deficit. After surgery, the neurological symptoms were completely resolved in six patients, while in one patient, they were alleviated. In one patient, a complication occurred during the postoperatove course. There was no recurrence during the follow-up (3-111 months, mean duration 39 months). CONCLUSION: In our series of patients with intracranial and intraspinal tumors, the incidence of NC was higher than presented in the published data. Our own surgical experience has shown that complete tumor resection is not always possible for intimate adherence to the surrounding structures. Leaving a tiny portion of the cyst wall allowed us to achieve good clinical results with no recurrence. Long-term follow-up of patients is required due to the risk of recurrence. However, it can already be stated that an adequate extent of resection leads to good clinical results (Tab. 1, Fig. 4, Ref. 33).


Assuntos
Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/cirurgia , Humanos , Incidência , Procedimentos Neurocirúrgicos , Estudos Retrospectivos
11.
J Pediatr Orthop ; 39(8): e608-e613, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31393300

RESUMO

BACKGROUND: Congenital abnormalities when present, according to VACTERL theory, occur nonrandomly with other congenital anomalies. This study estimates the prevalence of congenital spinal anomalies, and their concurrence with other systemic anomalies. METHODS: A retrospective cohort analysis on Health care Cost and Utilization Project's Kids Inpatient Database (KID), years 2000, 2003, 2006, 2009 was performed. ICD-9 coding identified congenital anomalies of the spine and other body systems. OUTCOME MEASURES: Overall incidence of congenital spinal abnormalities in pediatric patients, and the concurrence of spinal anomaly diagnoses with other organ system anomalies. Frequencies of congenital spine anomalies were estimated using KID hospital-and-year-adjusted weights. Poisson distribution in contingency tables tabulated concurrence of other congenital anomalies, grouped by body system. RESULTS: Of 12,039,432 patients, rates per 100,000 cases were: 9.1 hemivertebra, 4.3 Klippel-Fiel, 56.3 Chiari malformation, 52.6 tethered cord, 83.4 spina bifida, 1.2 absence of vertebra, and 6.2 diastematomyelia. Diastematomyelia had the highest concurrence of other anomalies: 70.1% of diastematomyelia patients had at least one other congenital anomaly. Next, 63.2% of hemivertebra, and 35.2% of Klippel-Fiel patients had concurrent anomalies. Of the other systems deformities cooccuring, cardiac system had the highest concurrent incidence (6.5% overall). In light of VACTERL's definition of a patient being diagnosed with at least 3 VACTERL anomalies, hemivertebra patients had the highest cooccurrence of ≥3 anomalies (31.3%). With detailed analysis of hemivertebra patients, secundum ASD (14.49%), atresia of large intestine (10.2%), renal agenesis (7.43%) frequently cooccured. CONCLUSIONS: Congenital abnormalities of the spine are associated with serious systemic anomalies that may have delayed presentations. These patients continue to be at a very high, and maybe higher than previously thought, risk for comorbidities that can cause devastating perioperative complications if not detected preoperatively, and full MRI workups should be considered in all patients with spinal abnormalities. LEVEL OF EVIDENCE: Level III.


Assuntos
Comunicação Interatrial/epidemiologia , Atresia Intestinal/epidemiologia , Anormalidades Musculoesqueléticas/epidemiologia , Defeitos do Tubo Neural/epidemiologia , Escoliose/epidemiologia , Coluna Vertebral/anormalidades , Adolescente , Criança , Pré-Escolar , Comorbidade , Anormalidades Congênitas/epidemiologia , Bases de Dados Factuais , Humanos , Incidência , Lactente , Recém-Nascido , Intestino Grosso/anormalidades , Rim/anormalidades , Nefropatias/congênito , Nefropatias/epidemiologia , Síndrome de Klippel-Feil/epidemiologia , Prevalência , Estudos Retrospectivos , Adulto Jovem
12.
BMC Res Notes ; 12(1): 495, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399144

RESUMO

OBJECTIVE: Although infant mortality because of birth defect has increased in both developed and developing countries, had not got attention like other health issues at national, regional, or local levels. Documenting the risk factors that influence the occurrence of birth defects and its seasonality will help to inform the community and to develop preventive strategies for the country. RESULTS: Factors associated with higher likelihood of a major structural birth defects included maternal age; neonates born from women living in urban; and in Dega; history of fever during pregnancy; intake of herbal medicine; and drinking alcohol. Counselling for pregnancy preparation and folic acid supplementation was found protective for the likelihood of birth defect.


Assuntos
Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Anormalidades Congênitas/epidemiologia , Anormalidades Musculoesqueléticas/epidemiologia , Defeitos do Tubo Neural/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Fenda Labial/etiologia , Fenda Labial/prevenção & controle , Fissura Palatina/etiologia , Fissura Palatina/prevenção & controle , Anormalidades Congênitas/etiologia , Anormalidades Congênitas/prevenção & controle , Países em Desenvolvimento , Suplementos Nutricionais , Etiópia/epidemiologia , Feminino , Febre/complicações , Ácido Fólico/administração & dosagem , Humanos , Lactente , Recém-Nascido , Masculino , Idade Materna , Anormalidades Musculoesqueléticas/etiologia , Anormalidades Musculoesqueléticas/prevenção & controle , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/prevenção & controle , Parto , Gravidez , Encaminhamento e Consulta , Fatores de Risco , Estações do Ano , População Urbana
14.
N Engl J Med ; 381(9): 827-840, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31329379

RESUMO

BACKGROUND: A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies. METHODS: We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals. RESULTS: From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, -0.13 to 0.87). CONCLUSIONS: The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.).


Assuntos
Antirretrovirais/efeitos adversos , Anormalidades Congênitas/epidemiologia , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamente , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Botsuana/epidemiologia , Quimioterapia Combinada , Feminino , Feto/efeitos dos fármacos , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Recém-Nascido , Defeitos do Tubo Neural/epidemiologia , Vigilância da População , Gravidez , Prevalência , Fatores Socioeconômicos
15.
Drug Metab Dispos ; 47(8): 890-898, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31167838

RESUMO

Preliminary analysis of ongoing birth surveillance study identified evidence of potential increased risk for neural tube defects (NTDs) in newborns associated with exposure to dolutegravir at the time of conception. Folate deficiency is a common cause of NTDs. Dolutegravir and other HIV integrase inhibitor drugs were evaluated in vitro for inhibition of folate transport pathways: proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and folate receptor α (FRα)-mediated endocytosis. Inhibition of folate transport was extrapolated to the clinic by using established approaches for transporters in intestine, distribution tissues, and basolateral and apical membranes of renal proximal tubules (2017 FDA Guidance). The positive controls, methotrexate and pemetrexed, demonstrated clinically relevant inhibition of PCFT, RFC, and FRα in folate absorption, distribution, and renal sparing. Valproic acid was used as a negative control that elicits folate-independent NTDs; valproic acid did not inhibit PCFT, RFC, or FRα At clinical doses and exposures, the observed in vitro inhibition of FRα by dolutegravir and cabotegravir was not flagged as clinically relevant; PCFT and RFC inhibition was not observed in vitro. Bictegravir inhibited both PCFT and FRα, but the observed inhibition did not reach the criteria for clinical relevance. Elvitegravir and raltegravir inhibited PCFT, but only raltegravir inhibition of intestinal PCFT was flagged as potentially clinically relevant at the highest 1.2-g dose (not the 400-mg dose). These studies showed that dolutegravir is not a clinical inhibitor of folate transport pathways, and it is not predicted to elicit clinical decreases in maternal and fetal folate levels. Clinically relevant HIV integrase inhibitor drug class effect on folate transport pathways was not observed. SIGNIFICANCE STATEMENT: Preliminary analysis of ongoing birth surveillance study identified evidence of potential increased risk for neural tube defects (NTDs) in newborns associated with exposure to the HIV integrase inhibitor dolutegravir at the time of conception; folate deficiency is a common cause of NTDs. Dolutegravir and other HIV integrase inhibitor drugs were evaluated in vitro for inhibition of the major folate transport pathways: proton-coupled folate transporter, reduced folate carrier, and folate receptor α-mediated endocytosis. The present studies showed that dolutegravir is not a clinical inhibitor of folate transport pathways, and it is not predicted to elicit clinical decreases in maternal and fetal folate levels. Furthermore, clinically relevant HIV integrase inhibitor drug class effect on folate transport pathways was not observed.


Assuntos
Ácido Fólico/metabolismo , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Animais , Cães , Endocitose/efeitos dos fármacos , Ensaios Enzimáticos , Feminino , Receptor 1 de Folato/metabolismo , Ácido Fólico/sangue , Deficiência de Ácido Fólico/induzido quimicamente , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Recém-Nascido , Células Madin Darby de Rim Canino , Exposição Materna/efeitos adversos , Troca Materno-Fetal , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/etiologia , Gravidez , Transportador de Folato Acoplado a Próton/metabolismo , Proteína Carregadora de Folato Reduzido/metabolismo , Medição de Risco
16.
Nutrients ; 11(5)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109064

RESUMO

Most professional and international organizations recommend folic acid supplementation for women planning pregnancy. Various studies have shown high levels of non-compliance with this recommendation. This study aimed to identify sociodemographic characteristics related to this compliance. The analyses were based on 16,809 women from the French nationwide ELFE cohort (Etude Longitudinale Française depuis l'Enfance). Folic acid supplementation was assessed at delivery, and sociodemographic characteristics were collected at two months postpartum. The association between sociodemographic characteristics and compliance with recommendations on folic acid supplementation (no supplementation, periconceptional supplementation, and supplementation only after the periconceptional period) was examined using multivariate multinomial logistic regression. Only 26% of French women received folic acid supplementation during the periconceptional period, 10% of women received supplementation after the periconceptional period, and 64% received no supplementation. Young maternal age, low education level, low family income, multiparity, single parenthood, maternal unemployment, maternal overweight, and smoking during pregnancy were related to lower likelihood of folic acid supplementation during the periconceptional period compared to no supplementation. These associations were not explained by unplanned pregnancy. Immigrant and underweight women were more likely to receive folic acid supplementation after the periconceptional period. Our study confirms great social disparities in France regarding the compliance with the recommendations on folic acid supplementation.


Assuntos
Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/prevenção & controle , Fenômenos Fisiológicos da Nutrição Pré-Natal , Adulto , Criança , Feminino , França , Humanos , Gravidez , Fatores Socioeconômicos , Adulto Jovem
17.
Ann Intern Med ; 170(9): 614-625, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30934067

RESUMO

Background: Dolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception. Objective: To project clinical outcomes of ART policies for women of child-bearing potential in South Africa. Design: Model of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach). Data Sources: Published data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women). Target Population: 3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children. Time Horizon: 5 years. Perspective: Societal. Intervention: EFV, DTG, and WHO approach. Outcome Measures: Deaths among women and children, sexual and pediatric HIV transmissions, and NTDs. Results of Base-Case Analysis: Compared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths). Results of Sensitivity Analysis: Women's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater. Limitation: Uncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses. Conclusion: Although NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential. Primary Funding Source: National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Massachusetts General Hospital; and Harvard University Center for AIDS Research.


Assuntos
Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Adolescente , Adulto , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/epidemiologia , Humanos , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Contracepção Reversível de Longo Prazo , Pessoa de Meia-Idade , Modelos Teóricos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , África do Sul/epidemiologia , Adulto Jovem
18.
J Acquir Immune Defic Syndr ; 81(4): 481-486, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31021990

RESUMO

BACKGROUND: Dolutegravir, an integrase strand transfer inhibitor (InSTI), is a major antiretroviral agent for HIV infection. Its use is promising, especially in low- and middle-income countries, because of a high resistance barrier and a good safety profile. Very recently, a World Health Organization safety signal has been raised regarding neural tube defects after the first-trimester exposure. Furthermore, to date, the experience is limited regarding the use of the other InSTI drugs (raltegravir and elvitegravir) during pregnancy. Our objective is to analyze the safety of InSTI drugs in pregnant women. SETTING: Nation-wide database cohort analysis. METHODS: We evaluated the risk of major birth defects according to EUROCAT classification in pregnant women, which had had a first-trimester exposure to dolutegravir, raltegravir, or elvitegravir. RESULTS: We found a major birth defect rate of 1.9% in the general population between 2012 and 2016. As InSTI drugs are not used as first-line therapy in pregnant women, we found a very low exposure in this population. Among 49, 240, and 70 pregnancy outcomes exposed to dolutegravir, raltegravir, and elvitegravir, respectively, during the first trimester, there were 2, 3, and 1 major birth defects, respectively. There was no case of neural tube defect. CONCLUSIONS: Drug exposure to InSTI is limited in our nation-wide database. Nevertheless, our data do not support a pharmacovigilance signal on neural tube defects in women exposed to dolutegravir, raltegravir or elvitegravir during pregnancy. Owing to a small number of pregnancy outcomes, these results need to be confirmed with further studies.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Gravidez/efeitos dos fármacos , Adulto , Antirretrovirais/efeitos adversos , Estudos de Coortes , Anormalidades Congênitas/epidemiologia , Farmacorresistência Viral/efeitos dos fármacos , Feminino , França , Infecções por HIV/complicações , Inibidores de Integrase de HIV/efeitos adversos , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Defeitos do Tubo Neural/epidemiologia , Farmacovigilância , Quinolonas/uso terapêutico , Raltegravir Potássico/uso terapêutico , Resultado do Tratamento , Adulto Jovem
19.
BJOG ; 126(9): 1127-1133, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31006176

RESUMO

BACKGROUND: At the end of the 1980s, several studies suggested a potential increased risk of neural tube defects (NTDs) with ovulation induction/fertility drugs, especially with clomiphene citrate (CC). A previous meta-analysis of observational studies evaluating the risk of NTDs associated with the use of CC performed in 1995 found a risk ratio of 1.08 (95% CI 0.76-1.51). Since then, additional studies have been published and the risk of NTDs associated with periconceptional CC exposure may have changed. OBJECTIVE: To perform an updated quantitative meta-analysis of the risk of NTDs associated with periconceptional CC exposure. SEARCH STRATEGY: MEDLINE, Web of Science, and Scopus were searched (October 2018). SELECTION CRITERIA: Comparative cohort and case-control studies investigating the risk of NTDs after periconceptional CC exposure. DATA COLLECTION AND ANALYSIS: Pooled effect sizes with corresponding 95% CIs were calculated using random effects models, comparing the risk of NTDs between pregnancies exposed and not exposed to CC. MAIN RESULTS: Thirteen studies met the inclusion criteria, totalling 218 819 pregnancies. Periconceptional exposure to CC was not significantly associated with an increased risk of NTDs (pooled odds ratio 1.21, 95% CI 0.88-1.66). No heterogeneity between studies was observed (I2  = 26%). A funnel plot and asymmetry test were not suggestive of publication bias. CONCLUSION: Our meta-analysis confirms that exposure to CC before or in early pregnancy was associated with a 21% increased risk of NTD in relation to CC exposure; however, this increased risk is not statistically significant. TWEETABLE ABSTRACT: A new meta-analysis finds that clomiphene citrate exposure before or in early pregnancy is not associated with an increased risk of NTDs.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Clomifeno/efeitos adversos , Fármacos para a Fertilidade Feminina/efeitos adversos , Exposição Materna/efeitos adversos , Defeitos do Tubo Neural/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Infertilidade Feminina/tratamento farmacológico , Defeitos do Tubo Neural/induzido quimicamente , Estudos Observacionais como Assunto , Razão de Chances , Indução da Ovulação/métodos , Gravidez , Fatores de Risco
20.
Paediatr Perinat Epidemiol ; 33(2): 145-153, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30920008

RESUMO

BACKGROUND: We sought to assess the recent trend in NTD prevalence at birth in the post-folic acid food fortification era and to identify the maternal risk factors associated with that trend. METHODS: We carried out a population-based study of all livebirths and stillbirths (including late pregnancy terminations) delivered in hospitals in Canada (excluding Quebec) from 2004 to 2015 (n = 3 439 330). We examined NTD birth prevalence by year, multiple pregnancy, maternal age, parity, pregestational diabetes, chronic illness, and problematic substance use. Poisson regression was used to quantify the association between spina bifida and cranial defects and maternal characteristics and other risk factors. RESULTS: We identified 1517 non-chromosomal NTDs, yielding a birth prevalence of 4.4 per 10 000 total births. NTD prevalence rose from 3.6 in 2004 to 4.6 per 10 000 in 2015 (Ptrend  = 0.03). Among NTD subtypes, only spina bifida showed a temporal increase (Ptrend  = 0.03). Birth prevalence of spina bifida was higher among younger mothers, those with type 2 diabetes (rate ratio (RR) 3.74, 95% confidence interval (CI) 2.21, 6.35), chronic illness (RR 3.16, 95% CI 1.97, 5.07), and problematic substance use (RR 1.88, 95% CI 1.31, 2.71). Adjusting for risk factors attenuated the significant temporal trend in spina bifida (unadjusted average annual prevalence ratio (aAAPR) 1.016, 95% CI 1.001, 1.032; adjusted AAPR 1.014, 95% CI 0.998, 1.029). CONCLUSIONS: Increases in the frequency of maternal risk factors such as pregestational diabetes mellitus, substance use, and chronic illness may be partly responsible for the recent rise in NTDs, particularly spina bifida.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Ácido Fólico/uso terapêutico , Mães , Defeitos do Tubo Neural/epidemiologia , Gravidez em Diabéticas/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Canadá/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Recém-Nascido , Idade Materna , Defeitos do Tubo Neural/etiologia , Vigilância da População , Gravidez , Gravidez em Diabéticas/fisiopatologia , Prevalência , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
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