RESUMO
BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2 = 62%, and 0.59 (95% CI 0.42, 0.82), I2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I2 = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.
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Nascimento Prematuro , Vaginose Bacteriana , Feminino , Humanos , Recém-Nascido , Gravidez , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Metronidazol/uso terapêutico , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Vaginose Bacteriana/tratamento farmacológico , Vaginose Bacteriana/prevenção & controleRESUMO
Bacterial vaginosis (BV) is a common gynaecological condition. Diagnosis of BV is typically based on Amsel criteria, Nugent score and/or bacterial culture. In this study, these conventional methods and two CE-IVD marked quantitative real-time (q)PCR assays were compared with microbiota analysis for the diagnosis of BV. Eighty women were evaluated for BV during two sequential hospital visits by Amsel criteria, Nugent score, culture, the AmpliSens® Florocenosis/Bacterial vaginosis-FRT PCR kit (InterLabService, Moscow, Russia), and the BD MAX™ Vaginal Panel (BD Diagnostics, MD, USA). Microbiota analysis based on amplicon sequencing of the 16S ribosomal RNA gene was used as reference test. The microbiota profile of 36/115 (31%) included cases was associated with BV. Based on microbiota analysis, the sensitivity of detecting BV was 38.9% for culture, 61.15% for Amsel criteria, 63.9% for Nugent score and the BD MAX assay, and 80.6% for the AmpliSens assay, while the specificity of all methods was ≥ 92.4%. Microbiota profiles of the cases with discrepant results between microbiota analysis and the diagnostic methods were variable. All five diagnostic methods missed BV positive cases with a relatively high abundance of the genus Alloscardovia, Bifidobacterium, or Dialister, which were categorised as unspecified dysbiosis by the AmpliSens assay. Compared to Amsel criteria, Nugent score, culture, and the BD MAX assay, the AmpliSens assay was most in agreement with microbiota analysis, indicating that currently, the AmpliSens assay may be the best diagnostic method available to diagnose BV in a routine clinical setting.
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Bactérias/isolamento & purificação , Técnicas Microbiológicas/normas , Microbiota , Vaginose Bacteriana/diagnóstico , Adolescente , Adulto , Bactérias/genética , DNA Bacteriano/genética , Testes Diagnósticos de Rotina , Feminino , Humanos , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real/normas , Sensibilidade e Especificidade , Análise de Sequência de DNA , Vagina/microbiologia , Vaginose Bacteriana/microbiologia , Adulto JovemAssuntos
Cesárea , Tratamento de Ferimentos com Pressão Negativa , Bandagens , Cesárea/efeitos adversos , Feminino , Humanos , GravidezRESUMO
Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Infection/inflammation is responsible for a significant percentage of preterm birth, particularly at early gestations. A recent clinical recommendation by a guidelines group of the Danish Society of Obstetrics and Gynecology advised against the use of clindamycin for the treatment of bacterial vaginosis in pregnancy to reduce the risk of spontaneous preterm birth based on lack of evidence of efficacy. We believe that the evidence for the use of clindamycin for this indication is robust and that this recommendation was reached erroneously on the basis of flawed inclusion criteria: the inclusion of an unpublished study with poorly diagnosed bacterial vaginosis and the exclusion of an important pivotal study on the use of clindamycin in early pregnancy for the prevention of preterm birth. Had these errors been corrected, the conclusions would have been different.
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Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Guias de Prática Clínica como Assunto , Complicações Infecciosas na Gravidez/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Vaginose Bacteriana/tratamento farmacológico , Aborto Espontâneo/microbiologia , Aborto Espontâneo/prevenção & controle , Clindamicina/farmacologia , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Gravidez , Nascimento Prematuro/microbiologia , Projetos de Pesquisa , Vaginose Bacteriana/complicaçõesRESUMO
OBJECTIVE: Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. MATERIALS AND METHODS: Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal biomarkers associated with PTB published from January 2005 to March 2014. RESULTS: Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies) followed by MIP-1ß, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. CONCLUSION: By this systematic review, we conclude that multiplex assays are a potential technological advancement for identifying biomarkers of PTB, although no single or combination of biomarkers could be identified to predict PTB risk.
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Biomarcadores , Nascimento Prematuro , Feminino , Humanos , GravidezRESUMO
INTRODUCTION: When complications arise in the delivery room, midwives and obstetricians operate at the interface of life and death, and in rare cases the infant or the mother suffers severe and possibly fatal injuries related to the birth. This descriptive study investigated the numbers and proportions of obstetricians and midwives involved in such traumatic childbirth and explored their experiences with guilt, blame, shame and existential concerns. MATERIAL AND METHODS: A mixed methods study comprising a national survey of Danish obstetricians and midwives and a qualitative interview study with selected survey participants. RESULTS: The response rate was 59% (1237/2098), of which 85% stated that they had been involved in a traumatic childbirth. We formed five categories during the comparative mixed methods analysis: the patient, clinical peers, official complaints, guilt, and existential considerations. Although blame from patients, peers or official authorities was feared (and sometimes experienced), the inner struggles with guilt and existential considerations were dominant. Feelings of guilt were reported by 36-49%, and 50% agreed that the traumatic childbirth had made them think more about the meaning of life. Sixty-five percent felt that they had become a better midwife or doctor due to the traumatic incident. CONCLUSIONS: The results of this large, exploratory study suggest that obstetricians and midwives struggle with issues of blame, guilt and existential concerns in the aftermath of a traumatic childbirth.
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Culpa , Tocologia , Humanos , Parto , Médicos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The importance of the environment on the development of the fetus and infant throughout early life is increasingly recognised. To study such effects, biological samples and accurate data records are required. Based on multiple data collection from a healthy pregnant population, the Odense Childhood Cohort (OCC) study aims to provide new information about the environmental impact on child health by sequential follow-up to 18 years of age among children born between 2010 and 2012. METHODS: A total of 2874 of 6707 pregnancies (43%) were recruited between January 2010 and December 2012. Three hundred seventy-four have since left the study, leaving 2500 active families. The non-participants act as controls contributing data through local registries. Biological material, questionnaires, and registry data were compiled. Anthropometric data and other physical data were collected. RESULTS: Two thousand five hundred families actively participated in the study with 2549 children. Sixty-four per cent of the fathers and 60% and 58% of the mothers, respectively, donated a blood sample at 10 and 28 weeks of gestation. On average, 69% completed questionnaires, 78% of the children were regularly examined, and had a blood sample taken (46%). The participating pregnant women differed from the non-participants in several respects: age, body mass index, smoking, parity, education, and ethnicity. The infants were comparable with respect to gender and mode of delivery. CONCLUSIONS: The OCC provides material for in-depth analysis of environmental and genetic factors that are important for child health and disease. Registry data from non-participating women and infants are available which ensures a high degree of comparable data.
Assuntos
Centros de Saúde Materno-Infantil/estatística & dados numéricos , Serviços de Saúde Materno-Infantil , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Monitoramento Ambiental , Monitoramento Epidemiológico , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Garantia da Qualidade dos Cuidados de Saúde , Características de Residência , Inquéritos e QuestionáriosAssuntos
Antibioticoprofilaxia , Streptococcus agalactiae , Parto Obstétrico , Feminino , Humanos , Parto , GravidezRESUMO
There are few recent data on the prevalence of substance abuse among Danish pregnant women. During 2013, in the Region of Southern Denmark, a cross-sectional, anonymous, screening-based study was conducted among pregnant women attending for routine ultrasound scan at 12 weeks gestation. The women submitted a urine sample and completed a short questionnaire. Urine samples were tested for opiates, cannabis, benzodiazepines, cocaine, methadone, amphetamine and methamphetamine. Positive samples underwent repeat analysis for confirmation. Of 690 pregnant women, 88.1% participated. Overall, 3.6% of women had a positive urine sample confirmed by repeated analysis. The age distribution in women with positive samples did not differ from the entire cohort. Our findings indicate a larger prevalence than anticipated, and that a substantial number of pregnant women with substance abuse are not appropriately referred to the focused specialist center for such women at risk.
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Complicações na Gravidez/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Cromatografia de Afinidade , Dinamarca/epidemiologia , Feminino , Humanos , Projetos Piloto , Gravidez , Prevalência , Adulto JovemRESUMO
BACKGROUND: In recent decades there have been advances in the options for prenatal screening. Screening programmes for Down syndrome are well established in many countries. It is important that pregnant women are well informed about the benefits and risks of screening. A variety of interventions has been introduced to support pregnant women in their choice of prenatal screening. OBJECTIVE: To summarize the literature using randomized controlled trials to compare the effects of different interventions to provide pregnant women with the information necessary to make an informed choice about screening for Down syndrome. DESIGN: Systematic review METHODS: A systematic search was performed using the PUBMED and EMBASE databases. The search terms included MeSH terms and free text and were combined by Boolean terms (AND, OR) with no restriction on language or time. MAIN OUTCOME MEASURES: Knowledge, informed choice, patient satisfaction, anxiety, depression, conflict and worries. RESULTS: Twelve studies were included in the review. All were characterised by having one or more interventions designed to improve the level of information about prenatal screening for Down syndrome. A positive effect on knowledge and satisfaction from the information received was found in the majority of the studies. The studies were heterogeneous with respect to interventions, methodology and outcome measurements. CONCLUSIONS: Interventions aimed at providing pregnant women with specific information about prenatal screening for Down syndrome can improve their ability to make an informed choice.
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Síndrome de Down/diagnóstico , Educação de Pacientes como Assunto/métodos , Diagnóstico Pré-Natal , Lista de Checagem , Aconselhamento , Tomada de Decisões , Feminino , Humanos , Gravidez , Resultado do TratamentoRESUMO
INTRODUCTION: The aim of this study was to evaluate the effect of an eHealth intervention (interactive website) on pregnant women's ability to make an informed choice about Down syndrome screening. MATERIAL AND METHODS: The study was designed as a randomized controlled trial with allocation to an intervention group and a control group in a ratio of 1:1. Subsequent subgroup analysis was conducted. Participants were recruited from 5 August 2013 to 25 April 2014 at Odense University Hospital, Denmark. Inclusion criteria were: pregnant women aged ≥18 years who were invited to participate in Down syndrome screening. Exclusion criteria were: high risk of abortion, psycho-socially vulnerable women, late referral, inability to speak Danish and women declining to participate. The primary outcome was informed choice about Down syndrome screening. The Multidimensional Measure of Informed Choice was used to assess whether the choice was informed or uninformed. RESULTS: A total of 1150 participants were included in the study, of which 910 (79%) completed the questionnaire. Only a minority (30% of the women in the intervention group) actually used the website. There was no significant difference in the groups with respect to making an informed choice. The mean knowledge scores were significantly higher for those in the intervention group who used the intervention. CONCLUSIONS: An interactive website with information about Down syndrome screening had no direct effect on making an informed choice. However, the majority of the pregnant women who used the website were satisfied with the website and would recommend it to others.
Assuntos
Comportamento de Escolha , Síndrome de Down/diagnóstico , Diagnóstico Pré-Natal , Adulto , Dinamarca , Feminino , Humanos , Gravidez , Inquéritos e Questionários , TelemedicinaRESUMO
PURPOSE OF REVIEW: Vitamin D status (which is involved in glucose homeostasis) is related to gestational diabetes mellitus (GDM). GDM is characterized by increased resistance to and impaired secretion of insulin and results in higher risk of adverse pregnancy outcomes including operative delivery, macrosomia, shoulder dystocia and neonatal hypoglycemia. Women with GDM and their babies are at increased risk for developing type II diabetes. RECENT FINDINGS: International definitions of vitamin D deficiency and normality are inconsistent. Vitamin D deficiency is common in pregnant women particularly those with poor diets and who have dark skins living in temperate climes with lack of exposure to sunlight. SUMMARY: Few interventional studies indicate that supplementation optimizes maternal vitamin D status or improves maternal glucose metabolism. Observational studies about maternal vitamin D status and risk of GDM are conflicting. This could be because of measurement of vitamin D or differences in population characteristics such as ethnicity, geographic location, gestational age at sampling and diagnostic criteria for GDM. Good-quality randomized controlled trials are required to determine whether vitamin D supplementation decreases the risk of GDM or improves glucose tolerance in diabetic women.
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Diabetes Gestacional/sangue , Deficiência de Vitamina D/sangue , Vitamina D/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Gestacional/etiologia , Diabetes Gestacional/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Insulina/metabolismo , Secreção de Insulina , Estado Nutricional , Estudos Observacionais como Assunto , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Luz Solar , Vitamina D/administração & dosagem , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
OBJECTIVE: To examine whether a 3-day training course in motivational interviewing, which is an approach to helping people to change, could improve the communication skills of obstetric healthcare professionals in their interaction with obese pregnant women. DESIGN: Intervention study. SETTING: The Region of Southern Denmark. METHODS: Eleven obstetric healthcare professionals working with obese pregnant women underwent a 3-day course in motivational interviewing techniques and were assessed before and after training to measure the impact on their overall performance as well as the effect on specific behavioral techniques observed during interviews. FINDINGS: With a few exceptions, the participants changed their behavior appropriate to the motivational interviewing technique. The participants made more interventions towards the principles of motivational interviewing (adherent and nonadherent interventions). Furthermore, the participants asked fewer closed and more open questions before training in motivational interview. In the assessment of proficiency and competency, most of the participants scored higher after the training in motivational interviewing. CONCLUSIONS: Training in motivational interviewing improves healthcare professionals' proficiency and competency when communicating with obese pregnant women, albeit that the effect was not universal.
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Competência Clínica , Comportamentos Relacionados com a Saúde , Pessoal de Saúde/educação , Entrevista Motivacional/métodos , Obstetrícia/educação , Adulto , Feminino , Humanos , Masculino , Obesidade/terapia , Gravidez , Complicações na Gravidez/terapiaRESUMO
OBJECTIVES: To study the effects of lifestyle intervention in pregnancy on weight retention 6 months postpartum among obese women from the "Lifestyle in Pregnancy" (LiP) study, and to determine associations between breastfeeding with postpartum maternal weight. DESIGN: Six months postpartum follow up after a randomized controlled intervention trial. SETTING: Two university hospitals in Denmark. POPULATION: A total of 360 women with pregestational body mass index ≥30 kg/m(2) . METHODS: The intervention involved lifestyle changes (diet and exercise) during pregnancy. The control group received routine pregnancy care. Both groups received standard postnatal care. MAIN OUTCOME MEASURES: Gestational weight gain, postpartum weight retention and breastfeeding. RESULTS: Follow up was completed in 238 women of whom 46% in the intervention group and 57% in the control group had retained weight 6 months postpartum (p = 0.088). Women with gestational weight gain ≤9 kg, (recommended by the Institute of Medicine), retained less postpartum weight compared with those who exceeded 9 kg (median -0.7 vs. 1.5, p < 0.001). Ninety-two percent in both weight gain groups initiated breastfeeding. The number of breastfeeding mothers was higher among women with postpartum weight retention ≤5 kg compared with those with weight retention > 5 kg (94% vs. 85%, p = 0.034). CONCLUSIONS: We could not detect sustained weight control at 6 months postpartum despite a lower gestational weight gain for obese women during pregnancy who received a lifestyle intervention rather than standard care. Women who adhered to gestational weight gain recommendations had significantly lower postpartum weight retention. Breastfeeding for 6 months was negatively associated with postpartum weight retention.
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Aleitamento Materno , Obesidade/terapia , Período Pós-Parto , Complicações na Gravidez/terapia , Cuidado Pré-Natal/métodos , Redução de Peso , Programas de Redução de Peso/métodos , Aleitamento Materno/estatística & dados numéricos , Dietoterapia , Terapia por Exercício , Feminino , Seguimentos , Humanos , Estilo de Vida , Modelos Lineares , Gravidez , Resultado do Tratamento , Aumento de PesoRESUMO
The manuscript disputes the exclusive mono-infectious way of thinking, which presumes that for every infection only one pathogen is responsible and sufficient, when infectious vectors, close contact and reduced immunity meet. In situations involving heavily colonized anatomical sites such an approach often ends in insoluble contradictions. Upon critical reflection and evaluation of 20 years research on spatial organization of vaginal microbiota it is apparent, that in some situations, pathogens may act and operate in permanent, structurally organized consortia, whereas its individual components may be innocuous and innocent, failing to express any pathogenic effect. In these cases, consortia are the true pathogens responsible for many infectious conditions, which usually remain unrecognized as long as improperly diagnosed. The structure of such consortia can be unraveled using ribosomal fluorescence in situ hybridization (FISH). FISH methodology, that not only offers an ex vivo opportunity to recognize bacterial species, but provides unique physical insight into their specific role in the pathogenesis of polymicrobial infections. Ribosomal FISH technique applied to both, women with bacterial vaginosis (BV) and their male partners, has added significantly to our understanding of the pathogenesis of this condition and contributed to appreciating the mechanisms of polymicrobial, community-based infection, potentially leading to therapeutic advances.
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Nascimento Prematuro , Vaginose Bacteriana , Clindamicina , Feminino , Humanos , Recém-Nascido , Trabalho de Parto Prematuro , GravidezRESUMO
OBJECTIVE: To examine the experience of women with a pre-pregnant BMI >30 kg/m², in their encounters with healthcare professionals during pregnancy. DESIGN: Qualitative study using a phenomenological methodology approach. SETTING: Face-to-face interviews with pregnant women in their own home who were referred from their general practitioner to specialist antenatal follow-up at their local hospital. SAMPLE: Sixteen women with pre-pregnant BMI >30 kg/m². METHODS: Qualitative in-depth interviews. Participant's experiences of their encounters with health care professionals were recorded verbatim, transcribed and analysed using a phenomenological approach. RESULTS: Two main themes were identified, an accusatorial response from healthcare professionals and a lack of advice and helpful information on how being obese and pregnant might affect the women's health and that of their child. CONCLUSIONS: Pregnant women with obesity may experience prejudice from healthcare professionals. These women felt they were treated with a lack of respect, an accusatorial response, and the feeling that information which could have been helpful was not forthcoming. Communication between obese pregnant woman and healthcare professionals appears to be lacking. Improved training in communication skills, less judgemental behaviour and better dissemination of information from healthcare professionals working with pregnant women with obesity are needed.
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Atitude do Pessoal de Saúde , Obesidade/complicações , Preconceito , Relações Profissional-Paciente , Adulto , Imagem Corporal , Índice de Massa Corporal , Feminino , Pessoal de Saúde , Humanos , Tocologia , Gravidez , Complicações na Gravidez , Pesquisa Qualitativa , Mulheres , Saúde da MulherRESUMO
INTRODUCTION: Phthalates freely cross the placenta and have the potential to influence pregnancy outcomes, with evidence of an increased incidence of preterm birth, low birth weight, pregnancy loss, and gestational diabetes. There is no regulation of phthalate concentrations in medications, which is often found in enteric coatings. Ingestion of phthalate containing medication during pregnancy may result in materno-fetal harm. AREAS COVERED: Phthalate subtypes, sources of phthalate exposure, mechanisms of phthalate toxicity, associations between phthalate exposure and incidence of preterm birth, low birth weight, fetal growth, gestational diabetes, and placental development. EXPERT OPINION: There is robust evidence to link exposure to phthalates in medical products including preterm birth, gestational diabetes, pregnancy-induced hypertension, and miscarriage. Nevertheless, future studies need to address standardization to avoid the heterogeneity of current studies. In future, the use of naturally occurring biopolymers may be safer, and the role of vitamin D as an immune modulator also has promise.
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Aborto Espontâneo , Diabetes Gestacional , Nascimento Prematuro , Gravidez , Humanos , Recém-Nascido , Feminino , Placenta , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Exposição Materna , Resultado da GravidezRESUMO
The impact of maternal vitamin D status in pregnancy on the extraskeletal health of the offspring has become a "hot topic" with a potential for cost-beneficial prevention. The objective of this study was to systematically review the level I and II evidence. PubMed, Embase and Cochrane databases were searched using the MeSH terms "vitamin D" AND "pregnancy" until 1 January 2012. The search was limited to randomized controlled trials (evidence level I) and observational studies (evidence level II) in humans and in the English language. Papers reporting on vitamin D supplementation in combination with other supplements, or not reporting on 25OHD or outcomes of the offspring were excluded. Six randomized controlled trials and 24 observational studies were finally included. In randomized controlled studies, vitamin D supplementation resulted in increased birthweight in one study, but showed no effect in five other studies. In cohort and case-control studies, higher vitamin D intake, or higher 25OHD, was associated with increased birthweight in large studies only, and modified by vitamin D receptor polymorphisms and by race (U-shaped in Caucasians in one unconfirmed study). The risks of HIV mother-to-child transmission, rhinitis symptoms and eczema were lower. Data were conflicting on the effect on respiratory infections and wheezing, whereas U-shaped associations to inhalant allergen-specific IgE at five years and to schizophrenia were reported in unconfirmed studies. The risk of type 1 diabetes at 15 years was lower or unchanged. It is concluded that observational studies suggest an effect of vitamin D on several outcomes. U-Shaped associations warrant caution.