Submitted by Carvalho Cristiane (crisedangelo@yahoo.com.br) on 2012-05-30T12:17:49Z No. of bitstreams: 1 Marcos Nakamura Pereira.pdf: 2337168 bytes, checksum: 8ed5a86601d971398b0db84852aa3df7 (MD5) / Made available in DSpace on 2012-05-30T12:17:49Z (GMT). No. of bitstreams: 1 Marcos Nakamura Pereira.pdf: 2337168 bytes, checksum: 8ed5a86601d971398b0db84852aa3df7 (MD5) / Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil / Este estudo tem por objetivo avaliar o desempenho do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH-SUS) na identificação dos casos de near miss materno ocorridos, em um hospital terciário da cidade do Rio de Janeiro, no ano de 2008. A identificação dos casos se deu pela avaliação dos prontuários médicos das mulheres que apresentaram condições potencialmente ameaçadoras à vida, selecionados a partir da revisão dos sumários de alta hospitalar, sendo este processo considerado o padrão-ouro. A segunda etapa do estudo consistiu no escrutínio das informações contidas no SIH-SUS, através da busca nominal dos casos de near miss materno identificados pela revisão dos prontuários e da seleção das AIHs cujos campos “Diagnóstico Principal”, “Diagnóstico Secundário” e/ou “Procedimento Realizado” apresentassem codificações compatíveis com este agravo, realizando-se então a avaliação das propriedades diagnósticas do SIH-SUS. Após avaliação de 1.170 sumários de internação hospitalar, foram selecionados 228 casos para a revisão dos prontuários. Após revisão das informações contidas nos registros médicos, foram identificados 165 casos de morbidade materna grave, dentre as quais 8 evoluíram com óbito materno, 130 cursaram com situações de morbidade grave não caracterizadas como near miss materno e 27 efetivamente apresentaram-se como casos de near miss materno. Na avaliação inicial do desempenho do SIH-SUS, através da busca nominal das mulheres identificadas com near miss, constatou-se que apenas 16 (59,2%) casos estavam no banco de dados. Acerca da ausência dos outros 11 casos (40.7%) restantes no sistema, foi possível detectar que ao menos 4 (36,3%) deles decorreram pelo não faturamento AIH por haver excedido o limite percentual de cesarianas do hospital. Analisando as propriedades diagnósticas do SIH-SUS, obteve-se sensibilidade de 18,5% (IC95% = 6,3-38,1), valor preditivo positivo de 7,14% (IC95% = 2,36-13,9), especificidade de 94,3 (IC95% = 92,8-95,6) e área sob a curva ROC de 0,56 (IC95% = 0,48-0,63). Considerando os resultados obtidos, em princípio, o SIH-SUS não parece ser boa ferramenta para vigilância do near miss materno. / The aim of this study is to evaluate the performance of the Hospital Information System (SIH) of Brazilian National Health Service in identifying cases of maternal near miss in a tertiary hospital in the city of Rio de Janeiro, during the year of 2008. The identification of such cases was done through evaluation of the medical records of patients who presented with potential life-threatening conditions. The cases were selected after revision of the discharge summaries of those patients; this process is considered gold-standard. The second phase of the study consisted in the scrutiny of the information in the SIH-SUS, through a nominal search of the maternal near miss cases identified from the revision of medical records and selection of the Hospital Admittance Forms (AIH) which the fields “primary diagnosis”, “secondary diagnosis” and/or “performed procedure” presented data compatible with such grievance, thus evaluating the diagnostic properties of the SIH. After evaluation of 1.170 hospital chart summaries, 228 cases were selected for a full chart revision. After revision of the information in the medical charts 165 cases of severe maternal morbidity were identified, among which 8 resulted in maternal death, 130 were cases of severe maternal morbidity not classified as near miss, and 27 were effectively considered maternal near miss cases. In the initial evaluation of the SIH performance through the nominal search of women identified as near miss, it was detected that only 16 (59. 2%) cases were in the database. Regarding the absence of the other 11 (40.7%) remaining cases, it was detected that at least 4 (36.3%) of them resulted from the non-billing of the procedures because the hospital’s cesarean-section percentage limit had been exceeded. An analysis of the diagnostic properties of the SIH showed a 18,5% sensibility (95%CI = 6.3 – 38.1), 7.14% positive predictive value (95%IC = 2.36-15.9), 94.3% specificity (95%CI = 92.8 – 95.6) and area under the ROC curve of 0.56 (95%CI = 0.48 – 0.63). At a first look, considering the results obtained,the SIH does not seem to be a good tool for surveillance of maternal near miss.

Made available in DSpace on 2012-09-06T01:11:06Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 1291.pdf: 1062166 bytes, checksum: f9a5c964726f24cc4d45694a3bdb1763 (MD5) Previous issue date: 1994 / O objetivo deste trabalho foi analisar a tendência e o perfil epidemiológico da mortalidade materna no município do Rio de janeiro e nas suas áreas de planejamento no período de 1960 a 1990 e subsidiar o planejamento de ações de assistência a saúde reprodutiva feminina. As fontes de dados foram as publicações e listagens da Secretaria de Estado de Saúde no período de 1960-1978 e o Sistema de Informação de Mortalidade do Ministério de Saúde, de 1979 em diante. Os dados sobre nascidos vivos procedem dos Anuários estatísticos e das estatísticas do Registros Civil do IBGE. As analises foram realizadas agrupando-se os dados em períodos quinquenais. Resultado Destaca-se a queda de 70% da mortalidade materna que passou de 180,14 para 52,41 óbitos maternos por 100.000 nascidos vivos(nv), considerando todo o período de 30 anos. Nossas taxas de mortalidade mesmo sem correção da subnotificação e do subregistro, encontram-se em patamares semelhantes aos dos países desenvolvido nas década de 50/60. Observou-se também uma mudança no perfil de causas. No início da década de 60,as hemorragias que ocupavam o primeiro lugar, hoje correspondem a terceira causa mais frequente. Atualmente, a principal causa de morte materna é a toxemia, seguida das complicações puerperais. Ao desagregarmos as taxas do município por áreas de residência, a Área de Planejamento 2 (AP2), de maior poder aquisitivo, apresentou a menor taxa média do período, 60,34 óbitos maternos por 100.000 nv. A maior taxa foi registrada na AP1 , que reúne as regiões administrativas do Centro e área Portuária e deve-se provavelmente a invasão de óbitos de outras regiões e municípios. Notou-se ainda uma maior mortalidade nas faixas etárias extremas. Discutiu-se também o impacto da queda da fecundidade na mortalidade materna. / The objective of this study was to analyze trends and epidemiological profile of maternal mortality in the municipality of Rio de Janeiro and sub-areas in the period 1960-1990 and contribute to planning the assistance to women's reproductive health. Data sources were the publications and list of the Secretary of State for Health in the period 1960-1978 and the Mortality Data System of the Ministry of Health, from 1979 onwards. Live births data were from the Annual Report of Statistics and Civil records of IBGE. Analyses were performed by grouping the data into five-year periods. Results The study highlights the decline of 70% of maternal mortality, which increased from 180.14 to 52.41 deaths per 100,000 live births (lb), considering the whole period of 30 years. Our mortality rates, even without correction of underreporting, are similar to developed countries in the decade of 50/60. We also noticed a change in the profile of causes. In the early 60's, hemorrhage that occupied the first cause, now represent the third most frequent cause. Currently, the leading cause of maternal death is toxemia, followed by puerperal complications. When we analyzed rates by area of residence, Planning Area 2 (AP2), that had the highest social- economic level, had the lowest mean mortality rate for the period, 60.34 deaths per 100,000 live births. The highest rate was observed in AP1, corresponding to the administrative regions of Central and Harbour area and is happened probably due to invasion of deaths from other regions and municipalities. It was noted a higher mortality even in extreme ages. It was also discussed the fertility impact in maternal mortality reduction.

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-11-13T14:19:06Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao Josy Pinho.pdf: 1226133 bytes, checksum: eb4114659ac7eea459d334e4f15bb04f (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-11-13T14:19:16Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao Josy Pinho.pdf: 1226133 bytes, checksum: eb4114659ac7eea459d334e4f15bb04f (MD5) / Made available in DSpace on 2017-11-13T14:19:16Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao Josy Pinho.pdf: 1226133 bytes, checksum: eb4114659ac7eea459d334e4f15bb04f (MD5) Previous issue date: 2017 / Viva Rio / Objetivo: Análise da morbidade materna grave (near miss materno), por meio de revisão sistemática de estudos no Brasil. Métodos: Foram examinados estudos que relataram dados quantitativos, causas e fatores associados à morbidade materna grave (near miss materno). A busca foi feita pelos sites MEDLINE e LILACS, sendo as palavras-chave: maternal near miss or severe maternal morbidity and Brazil. Foram extraídos dados utilizando-se um protocolo pré-definido (autor, ano, desenho do estudo, população estudada, cenário e contexto, análise estatística, critérios de near miss e resultados). A razão de near miss e os indicadores derivados foram descritos ou estimados, quando não relatados. Resultados: Identificamos 55 estudos, a maioria de desenho transversal (32). Predominaram estudos (40) de base hospitalar (local ou nacional); outros usaram sistemas de informação de saúde ou pesquisas nacionais de saúde. Diferentes definições e terminologias para “near miss” foram adotadas. A Razão de near miss materno variou de 2,4/ 1000 NV a 188,4/ 1000 NV, dependendo dos critérios e do cenário epidemiológico. O índice de mortalidade near miss materno variou entre 3,3% e 32,2%. Doenças hipertensivas e hemorrágicas foram as morbidades mais comuns. As causas indiretas vêm aumentando nos últimos anos. A ausência de cuidados pré-natais e outras demoras nos cuidados de saúde foram associados ao near miss, como também fatores sociodemográficos (cor da pele não branca, adolescência/ idade≥35 anos, baixo nível de escolaridade). Conclusão: O near miss materno no Brasil está associado a iniquidades e demoras na assistência à saúde. Existem grandes diferenças entre as regiões e de acordo com a classificação/ definição usada nos estudos. Os casos de near miss devem ser monitorados rotineiramente em unidades de saúde. Pesquisas futuras sobre casos de near miss materno devem usar os critérios da OMS e expandir o conceito de morbidade materna / Objective: Analysis of severe maternal morbidity (maternal near miss), through systematic review of studies in Brazil. Methods: We examined studies that reported quantitative data, causes, and associated factors on severe maternal morbidity (maternal near miss). The search was through MEDLINE and LILACS, and keywords were: maternal near miss or severe maternal morbidity and Brazil. We extracted data, using a pre-defined protocol (author, year, study design, population studied, setting and context, statistical analysis, criteria of near miss, and results). Near miss ratios, and near miss indicators were described or estimated, when not reported. Results: We identified 55 studies, mainly cross-sectional (32). Most of them (35) were health facility-based (local or national); others used health information systems or national health surveys. Different definitions and terminologies for maternal near miss were adopted. Near miss ratio ranged from 2,4/1000 LB to 188,4/1000 LB, depending on criteria and epidemiological scenario. Mortality index for maternal near miss ranged from 3.3%-32.2%. Hypertensive diseases and hemorrhage were the commonest morbidities. Indirect causes have been increasing in last years. Absence of prenatal care and other delays in health care were associated with near miss, as sociodemographic factors (skin color, adolescence and age > 35 years, low educational level). Conclusion: Maternal near miss in Brazil is associated with health iniquities and delays in health care. Large differences exist between regions and depending on the classification/setting of the studies. Near miss cases should be surveyed routinely in health facilities. Future research on maternal near misses should use WHO criteria and expand the concept of maternal morbidity

Abstract The first aim of this randomized, placebo-controlled and double-blind study was to investigate whether low-dose aspirin therapy, started prior to controlled ovarian hyperstimulation, improves ovarian stimulation response, uterine haemodynamics and clinical pregnancy rates in unselected patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The second aim was to examine if the maternal serum placental proteome is different in IVF/ICSI pregnancies compared with spontaneous pregnancies, and whether low-dose aspirin modifies maternal serum placental protein expression and uteroplacental haemodynamics during the first half of pregnancy. Finally, the effect of low-dose aspirin therapy on the incidence of hypertensive pregnancy complications among women who became pregnant after IVF/ICSI was investigated. Low-dose aspirin therapy did not increase the number of oocytes retrieved, the total number of embryos or number of top-quality embryos, endometrial thickness or uterine haemodynamics on the day of embryo transfer (ET) or clinical pregnancy rates compared with placebo-treated IVF/ICSI women. On the day of ET, low-dose aspirin did not affect UtA vascular impedance, but the incidence of non-optimal uterine artery haemodynamics (UtA PI≥3.0) was statistically significantly lower (p<0.05) in the aspirin group compared with the placebo group. In the placebo-treated IVF/ICSI patients, maternal serum proteome analysis showed altered protein expression compared with women with spontaneous pregnancies. Between aspirin- and placebo-treated IVF/ICSI patients, proteome analysis showed a unique and distinct pattern of differentially expressed proteins including extra-cellular matrix, complement and transport proteins. At 6 weeks’ gestation, arcuate artery PI and at 18 weeks’ gestation, UtA PI values were lower (p<0.05) in the aspirin group than in the placebo group. In conclusion, low-dose aspirin therapy, when started concomitantly with controlled ovarian hyperstimulation, did not improve ovarian responsiveness, uterine receptivity, pregnancy outcome in unselected IVF/ICSI women or affect UtA vascular impedance on the day of ET. Low-dose aspirin modified the early placentation process and reduced uteroplacental vascular impedance in mid-pregnancy, but did not decrease the incidence of hypertensive pregnancy complications. / Tiivistelmä Keinoalkuisten hedelmöityshoitojen seurauksena keskimäärin reilu kolmannes naisista tulee raskaaksi hoitokertaa kohti. Näissä raskauksissa äidin seerumista määritettyjen istukkaperäisten merkkiaineiden pitoisuuksissa on eroavaisuuksia verrattuna spontaanisti raskaaksi tulleiden naisten seerumipitoisuuksiin ensimmäisen ja toisen raskauskolmanneksen aikana. Pre-eklampsian eli raskausmyrkytyksen riski on myös lisääntynyt. Syyksi arvellaan istukan verisuonipuuston poikkeavaa kehitystä. Pre-eklampsiaan liitetään intravaskulaarisen prostasykliinin ja tromboksaanin epätasapaino, joka johtaa verihiutaleiden aggregaation lisääntymiseen ja verisuonten supistumiseen. Matala-annoksinen asetyylisalisyylihappo (ASA) vähentää tromboksaanituotantoa ja korjaa tromboksaani- ja prostasykliinituotannon epätasapainoa, mutta sen ei ole todettu merkittävästi vähentävän näiden raskauskomplikaatioiden esiintyvyyttä edes riskiryhmillä, kun lääkitys on aloitettu toisen raskauskolmanneksen aikana. Tämän satunnaistetun ja plasebo-kontrolloidun kaksoissokkotutkimuksen tavoitteena oli tutkia keinoalkuisia hedelmöityshoitoja saavilla naisilla matala-annoksisen ASA-hoidon (100 mg/vrk) merkitystä munasarjojen stimulaatiovasteeseen, alkion kiinnittymiseen, istukan muodostumiseen ja kehittymiseen sekä lääkehoidon vaikutusta kohdun, istukan ja sikiön verenkiertoon, kun lääkitys aloitettiin munasarjojen stimulaatiohoidon alkaessa. Lisätavoitteena oli selvittää, onko lapsettomuushoitoja saavien naisten raskauksissa todettavissa spesifinen istukkaproteomiikkalöydös (istukan tuottamat valkuaisaineet) verrattuna spontaanisti raskaaksi tulleisiin naisiin ja voidaanko siihen vaikuttaa matala-annoksisella ASA-hoidolla. Toisena lisätavoitteena oli selvittää matala-annoksisen ASA-hoidon vaikutus pre-eklampsian esiintyvyyteen loppuraskaudessa. Matala-annoksinen asetyylisalisyylihappo (ASA) ei paranna keinoalkuisten hedelmöityshoitojen hoitotuloksia eikä vaikuta kohdun verenkiertoon tai kohdun limakalvon paksuuteen ultraäänellä arvioituna alkion siirtopäivänä. Matala-annoksista ASA-hoitoa käyttäneiden potilaiden ryhmässä todettiin kuitenkin merkitsevästi vähemmän naisia, joilla oli huonoa hoitotulosta keinoalkuisissa hedelmöityshoidoissa ennakoiva korkea molemminpuolinen kohtuvaltimoiden verenvirtausvastus alkion siirtopäivänä verrattuna plasebo-ryhmään. Raskaaksi tulleilla naisilla, jotka käyttivät matala-annoksista ASA-hoitoa, todettiin kohdun verenvirtausvastus matalammaksi alku- ja keskiraskaudessa verrattuna plasebo-ryhmän naisiin. Istukkaproteomiikkatutkimusten mukaan varhaisistukan proteiinituotanto on erilainen keinoalkuisissa raskauksissa verrattuna spontaanisti alkaneisiin raskauksiin ja siihen voidaan vaikuttaa matala-annoksisella ASA-hoidolla. Pre-eklampsian ja sikiön kasvunhidastuman esiintyvyydessä ei ryhmien välillä todettu eroa. Matala-annoksinen ASA-hoito aloitettuna ennen raskautta munasarjojen stimulaatiohoidon alkaessa ei paranna munasarjojen vastetta lapsettomuushoidoissa käytettäville hormonihoidoille, raskauslukuja eikä kohdun verenkiertoa alkion siirtopäivänä. Hoidon todettiin kuitenkin vaikuttavan varhaisistukan kehittymiseen sekä parantavan kohdun verenkierto alku- ja keskiraskaudessa viitaten istukan verisuonipuuston parempaan kehittymiseen. Matala-annoksinen ASA-hoito ei vähentänyt istukkaperäisten raskauskomplikaatioiden esiintymistä.

Background: The Veterans Health Administration (VHA) encourages depression screening and treatment for pregnant veterans; however, rates of depression symptoms and treatment utilization during pregnancy have not been well-studied. Methods: We used data from the Maternity Care Coordination for Women Veterans cohort study. Specifically, our aims were to: 1) examine rates and correlates of depression symptoms in a sample of pregnant veterans; 2) understand mental health care treatment utilization and explore the experiences of veterans accessing mental health care at the VHA during pregnancy; and 3) examine VHA mental health provider's perspectives on depression screening and treatment in the perinatal period. Findings: Depression symptoms were present in 28% of pregnant veterans in our sample. Social support and employment decreased odds of symptoms; history of anxiety, antidepressant use, and active duty service resulted in increased odds of symptoms. Nearly 70% of women veterans with prenatal depression symptoms received at least one mental health visit or antidepressant prescription during pregnancy. However, symptomatic pregnant women without a history of depression were less likely to receive care. Mental health providers identified absence of screening protocols and referral procedures and variability in risk/benefit conversations surrounding antidepressant use as areas of weakness for VHA mental health care during the perinatal period. Conclusions: Depression symptoms were present in nearly one in every three pregnant veterans. Depression treatment during pregnancy is complex, requiring individualized care. Policies for depression screening, referrals to providers, and medication review could be better encouraged to improve standardized care across the VHA.

The hypothalamo-neurohypophysial model has been studied for many years. Of note, when the axons of the magnocellular, peptidergic neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) are transected or crushed, varying degrees of polydipsia and polyuria ensue as the result of measurable losses of vasopressin (AVP) within the organism's circulation. Following insult, these hypothalamic cells show a remarkable capacity to reorganize themselves within the proximal areas of the infundibular stalk and median eminence and form what has come to be known as a new 'mini neural lobe' . While the surviving neurons sprout new projections toward the level of the external zone, vascular hypertrophy is marked throughout the new neurohypophysis and new neurohemal contacts have been identified (at the ultrastructural level) associated with these vessels. In parallel with this vascular hypertrophy is a measurable re-release of vasopressin into the circulation. This new 'mini neural lobe' now has the morphological and physiological appearance of an intact neural lobe and is capable of releasing AVP in response to changes in water balance. While the ability of these axons to reorganize is more characteristic of the peripheral nervous system (PNS), this model system provides an unique opportunity to study axonal regeneration of the central nervous system (CNS). Not only the mechanisms underlying the restoration of AVP function following axotomy but the extent to which various magnocellular neuron populations are involved in the regenerative process may also be analyzed. Before attempting to identify putative markers associated with this regenerative process, it was necessary to carefully characterize the system following axonal injury. Using Sprague Dawley rats, we repeated previous physiological studies which had examined the intake of water and output of urine following hypophysectomy. In addition, we also correlated the restoration of water balance with the return of AVP release, as measured by radioimmunoassay. These data defined a temporal framework in which magnocellular AVP regeneration occurs. As a result of repeating these physiological studies, we noted several inconsistencies between other previously published work. First, the time course of AVP recovery did not agree with other published results, nor did the first appearance of AVP immunoreactivity . We did not observe a complete recovery of water balance as previously reported and the degree of magnocellular death was inconsistent with other reports. In light of these many conflicting observations between several historical reports and our own results, we did a basic physiological re-characterization of the hypothalamo-neurohypohysial system following hypophysectomy. By means of immunohistochemistry, we also demonstrated the re-appearance of AVP within the new the 'mini neural lobe ' concomitant with the increased appearance of synapsin I, a marker associated with the presence of mature and presumably functioning synapses to be no sooner than 28 days following surgical removal of the hypophysis. Immunocytochemistry was also used in conjunction with retrograde fluorescent labeling to extend the previous studies and include a 2-D analysis of cell survival throughout the PVN and SON following hypophysectomy or neurohypophysectomy. As reported previously, magnocellular neuronal loss is greater within the SON, particularly the hypophysectomized subject, and less so within the PVN; again with the greater loss in the PVN of the hypophysectomized animal. Based upon our observations and other recent reports, we suggest the possibility that some cells of the hypothalamo-neurohypophysial system or some other extrahypothalamic cell population may be capable of expressing vasopressin in response to neurohypophysectomy. We provide initial evidence that glial cells of the third ventricle may indeed be involved. Finally, one of the ultimate goals of using this as a model system of CNS regeneration is to understand the underlying mechanisms and components essential to central nervous tissue regeneration. Toward that end I have been involved with the initial studies to optimize an adenovirus delivery system which will be capable of incorporating various putative neurotransmitter and/or peptide anti-sense messages, being injected into the neurohypophysis and transported back into the cells of the hypothalamo-neurohypophysial system. Once these antisense sequences are expressed by the cells following axotomy, the sequence of expression of various proteins in response to injury may be elucidated.

We sought to examine the concordance of two suicidal ideation items from the Patient Health Questionnaire-9 (PHQ-9) and the Edinburgh Postnatal Depression Scale (EPDS), to evaluate the prevalence of suicidal ideation among pregnant women, and to assess the co-occurrence of suicidal ideation with antepartum depressive symptoms. A cross-sectional study was conducted among 1,517 pregnant women attending prenatal care clinics in Lima, Peru. Item 9 of the PHQ-9 assesses suicidal ideation over the last 14 days while item 10 of the EPDS assesses suicidal ideation in the past 7 days. The two suicidal ideation items have a high concordance rate (84.2 %) but a moderate agreement (the Cohen's kappa = 0.42). Based on the PHQ-9 and the EPDS, 15.8 and 8.8 % of participants screened positive for suicidal ideation, respectively. Assessed by the PHQ-9, 51 % of participants with suicidal ideation had probable depression. In prenatal care clinics, screening for suicidal ideation is needed for women with and without depressive symptoms. Future studies are needed to identify additional predictors of antepartum suicidality, determine the appropriate duration of reporting period for suicidal ideation screening, and assess the percentage of individuals with positive responses to the two suicidal ideation items at high risk of planning and attempting suicide. / This research was supported by an award from the National Institutes of Health (NIH), the Eunice Kennedy Shriver Institute of Child Health and Human Development (R01-HD-059835). The NIH had no further role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors wish to thank the dedicated staff members of Asociacion Civil Proyectos en Salud (PROESA), Peru and Instituto Especializado Materno Perinatal, Peru for their expert technical assistance with this research. The authors would like to thank Kathy Brenner for her help with revising this manuscript. / Revisión por pares

<p>Uprkos op&scaron;te prihvaćenom stavu da u trudnoći lekove treba izbegavati, veliki broj trudnica tokom trudnoće uzima lekove sa manje ili vi&scaron;e opravdanja. Primena lekova u trudnoći zahteva dodatnu patnju, jer se mora voditi računa o zdravlju majke i zdravlju jo&scaron; nerođenog&nbsp; deteta. Većina lekova koji nalaze primenu u trudnoći, nisu ispitani u kontrolisanim studijama na trudnicama, već se njihov uticaj naljudski fetus, bazira na predpostavkama i kliničkim istraživanjima na životinjama. Odsustvo studija dovodi do toga da se trudnicama obično prepisuju lekovi u dozi za odrasle osobe, koje ne prate fiziolo&scaron;ke promene u trudnoći. Tokom trudnoće u telu trudnica dolazi do promena u funkciji organa i organskih sistema, a zbog nastalih promena menja se i sudbina leka u organizmu. Sistemske bolesti trudnice poput hipertenzije i dijabetesa dovode do hemodinamskih promena i utiču na nastanak patolo&scaron;kih promena posteljice, &scaron;to sve zajedno menja farmakokinetiku lekova i njihov transplacentrarni transport. Ukupno 75 trudnica je uključeno u studiju i podeljeno u tri grupe: zdrave trudnice-kontrolna grupa (n=31), trudnice sa hipertenzijom (n=30) i trudnice sa dijabetesom (n=14). Sve trudnice su u premedikaciji primile iste lekove koji su deo standardne kliničke&nbsp; procedure. Trudnice su primile jednu dozu diazepama intramuskularnom injekcijom (10mg/2ml), a intravenski su primile pojedinačne doze cefuroksima (1,5g), metoklopramida (10mg/2ml) i ranitidina (50mg/2ml). Od svakog para majka-dete ukupno je analizirano po 5 uzoraka. Uzorci krvi od majke uzimani su u tri vremenske tačke: nakon davanja leka, u momentu ekstrakcije deteta i nakon porođaja. Uzorci&nbsp; krvi&nbsp; deteta&nbsp; uzimani su&nbsp; nakon&nbsp; porođaja iz pupčane vene i arterije. Prikupljeni uzorci plazme analizirani su metodom tečne hromatografije visokih performansi (HPLC). Istraživanje je pokazalo da lekovi&nbsp; primenjeni u premedikaciji&nbsp; carskog reza prolaze transplacentarnu membranu i da se ni jedan&nbsp; od&nbsp; lekova&nbsp; primenjenih&nbsp; u studiji nije akumulirao u fetusu i nije imao neželjeno dejsvo na novorođenče. Cefuroksim, ranitidin i metoklopramid pokazali su nizak feto-maternalni transfer, dok je diazepam pokazao visok&nbsp; feto-maternalni transfer. Izmerene koncentracije cefuroksima u plazmi trudnica u momentu porođaja bile su &ge;8 &mu;g/ml, &scaron;to je koncentracija veća od MIC za većinu patogena odgovornih za nastavak infekcija u aku&scaron;erstvu. Koncentracije cefuroksima u fetalnoj plazmi bile su &ge;4&mu;g/ml &scaron;to je veće od&nbsp; MIC koncentracija za veliki broj patogena. Gestacijska starost trudnoće nije uticala na obim prolaska cefuroksima&nbsp; kroz placentu, koji je prolazi uglavnom pasivnom difuzijom. Farmakokinetski parametri cefuroksima razlikovali su se kod hipertenzivnih i dijabetičnih trudnica, u odnosu kontrolnu grupu, ali ove bolesti nisu imale značajan uticaj na smanjenje terapijske efikasnosti cefuroksima. Farmakokinetika cefuroksima kod hipertenzivnih&nbsp; trudnica&nbsp; ukazala je na bržu eliminaciju cefuroksima iz krvi majke i na veću distribuciju leka u okolna tkiva. U dijabetičnoj grupi trudnica i novorođenčadi koncentracije cefuroksima su bile vi&scaron;e u odnosu na druge ispitivane grupe, dok je feto-maternalni odnos bio niži, &scaron;to ukazuje na postojanje strukturalne i funkcionalne pomenu posteljice u dijabetesu. Hipertenzija i dijabetes trudnica nisu imali uticaj na prodor ranitidina kroz placentu. Hipertenzija i dijabetes trudnica nisu uticali na većinu farmakokinetskih parametara ranitidina, mada je zabeleženo smanjenje volumena distribucije u ovim grupama trudnica, &scaron;to bi moglo da ukazuje na njihovu hemodinamsku nestabilnost i povećanje slobodne frakcije ranitidina. Koncentracija metoklopramida bila veća u krvi majki u odnosu na krv fetusa. Transport metoklopramida iz fetusa ka majci bio je dominantniji, a naročito u hipertenzivnoj i dijabetičnoj grupi trudnica. Hipertenzija i dijabetes trudnica uticali su na zadržavanje metoklopramida u fetusu. Koncentracije dijazepama u majčinoj i fetalnoj krvi bile su vi&scaron;e u kontrolnoj i hipertenzivnoj grupi trudnica. Hipertenzija i dijabetes trudnica povećavaju&nbsp; transfer diazepama kroz placentu, povećanjem koncentracije slobodnih masnih kiselina, steroidnih hormona, smanjenjem vezivnog kapaciteta potencijalna opasnost od neželjenog dejstva diazepama i njegovih metabolita na fetus i novorođenče. Ova doktorska studija ukazuju na potrebu obimnijih farmakokinetskih istraživanja kako na zdravim tako i na bolesnim trudnicama, koja će dati zaključke utvrđene na dokazima i pomoći u individualnom terapijskom pristupu svakoj trudnici.</p> / <p>In spite of&nbsp; the widespread opinion&nbsp; that&nbsp; drugs should be avoided in pregnancy, a great number of&nbsp; pregnant&nbsp; women&nbsp; take drugs with more or less justification.&nbsp; Administration of drugs in pregnancy requires additional attention because the health of&nbsp; both the mother and&nbsp; her unborn child must be protected. Majority of drugs administered in pregnancy have not been tested&nbsp; within the controlled studies performed on pregnant women, but&nbsp; their effect on the human foetus is based on assumptions and clinical trials performed on animals. This absence of studies results in the situation that pregnant&nbsp; women are usually prescribed drugs in a dose&nbsp; for adults, which does not take into account the physiological changes happening in pregnancy. During pregnancy, the pregnant woman&rsquo;s body undergoes changes in the<br />functions of organs and organ systems. These changes further affect the destiny of a&nbsp; drug in the organism. In pregnant women, systemic diseases such as hypertension&nbsp;&nbsp; and diabetes mellitus lead to hemodynamic changes and cause pathological&nbsp; changes in placenta, thus changing the pharmacokinetics of drugs and their transplacental transport. The study sample consisted of 75 pregnant women, who were divided into three groups as follows: the control group included healthy pregnant&nbsp; women (n=31), a group of pregnant women&nbsp; with&nbsp; hypertension (n=30) and&nbsp; a group of&nbsp; those&nbsp; with&nbsp; diabetes mellitus (n=14). All of them were administered the same drugs as a part of standard clinical procedure in premedication. The pregnant women received a single dose of diazepam by intramuscular injection (10mg/ml), and individual doses of cefuroxime (1.5mg), metoclopramide (10mg/2ml) and ranitidine (50mg/2ml). Five samples taken from each mother-infant pair were analyzed. Blood samples were taken from the mother three times: after drug administration, at the moment of extraction of baby and after delivery. Baby&rsquo;s blood samples were taken from the umbilical cord vein and artery after delivery. Plasma samples were analyzed by the method of high-performance liquid chromatography (HPLC). The research has shown that drugs administered in premedication of caesarean section went through the transplacental membrane and that none of the tested drugs accumulated in the foetus and had an adverse effect on the newborn. Cefuroxime, ranitidine and metoclopramide were shown to have a low transfer between the mother and her foetus, whereas diazepam showed a high foetal-maternal transfer. Cefuroxime concentrations measured in the pregnant woman&rsquo;s and foetal plasma at the moment of delivery were &ge;8&mu;g/ml and &ge;4&mu;g/ml, respectively, that&nbsp; being above the minimum inhibitory concentration (MIC) for most pathogens responsible for the development of infection in obstetrics. Gestational age had no effect on the range of cefuroxime flow through the placenta, which happens mostly by&nbsp; passive diffusion. Pharmacokinetic parameters of cefuroxime differed in the pregnant&nbsp; women having hypertension and diabetes mellitus from the controls; however, these diseases did not significantly reduce the therapeutic efficacy of cefuroxime. Pharmacokinetics of cefuroxime indicated faster elimination of&nbsp; cefuroxime into the maternal blood and greater distribution of the drug into the surrounding tissues in the hypertensive pregnant women. In the group consisting of pregnant women and newborns having diabetes, the cefuroxime concentrations were higher than in other groups, whereas foetal-maternal relation was lower, which suggests the presence of structural and functional change in the placenta in diabetes. Hypertension and diabetes mellitus had no affect either on the flow of ranitidine through the placenta in the pregnant women or on&nbsp; the&nbsp; majority of pharmacokinetic parameters of ranitidine, although a certain reduction in the volume&nbsp; of distribution was recorded in these groups of pregnant women, which could suggest their hemodynamic instability and increased free fractions of ranitidine. The concentration of metocloporamide was higher in the maternal blood than in the&nbsp; foetal blood, and&nbsp; the transport of metocloporamide from the foetus towards the mother was more dominant, particularly in&nbsp; the&nbsp; group of&nbsp; hypertensive and diabetic&nbsp;&nbsp;&nbsp; pregnant women. Metoclopramide tended to retain in the foetuses of mothers having&nbsp; hypertension and diabetes. The concentrations of diazepam in maternal and foetal blood were higher in the controls&nbsp; and hypertensive&nbsp; pregnant&nbsp; women. Hypertension and diabetes in pregnant&nbsp; women increase the transfer of diazepam through the placenta by increasing the concentration of free fatty acids and steroid hormones and by reducing the binding capacity of carrier proteins and the concentration of plasma&nbsp;&nbsp; proteins, thus increasing the potential danger of adverse effects of diazepam and its metabolites on the foetus and the newborn. This doctoral study suggests the necessity for more extensive pharmacokinetic research including both healthy and affected pregnant women that would lead to conclusions based on evidence and help to develop individual therapeutic approach to each pregnant woman.</p>

Background: One in ten people in the U.S. are affected by a substance use disorder (SUD), roughly one third of whom are women. Rates of unintended pregnancy are higher in this population than in the general public. Little is understood about how women with SUD use prescription contraception and think about pregnancy. Methods: By analyzing Medicaid claims data and conducting qualitative interviews with women with SUD, this doctoral thesis seeks to: 1) compare any use of and consistent, continued coverage by prescription contraceptives between women with and without SUD; 2) determine the extent to which SUD is associated with pregnancy, abortion, and adverse feto-maternal outcomes in women who use prescription contraception; and 3) explore facilitators of and barriers to contraceptive utilization by women with SUD, using qualitative interviews. Results: Compared to women without SUD, women with SUD are less likely to use any prescription contraceptive, particularly long-acting reversible methods. Among women who do use long-acting methods, SUD is associated with less continued, consistent coverage by a prescription contraceptive. Among women who use contraception, SUD is also associated with increased odds of abortion. When interviewed, women with SUD report fatalistic attitudes towards pregnancy planning, and have difficulty conceptualizing how susceptibility to pregnancy may change over time. Women with SUD also report that pregnancy has substantial impact on their drug treatment prospects. Conclusions: This study is the first to examine contraceptive utilization by women with SUD who are enrolled in Medicaid or state-subsidized insurance. Our study may help to inform clinical practice and policy development to improve the reproductive health and wellbeing of women with SUD.

Background: Migraine headache is a chronic pain condition that affects 20% of women of reproductive age, and is often treated with triptans. Triptans are serotonin 1B, 1D, and 1F receptor agonists that act as vasoconstrictors and inhibitors of the trigeminal cervical complex as well as peripheral neurons; they cross the blood brain barrier and placenta, and as such are plausible neurodevelopmental teratogens. No studies have examined risk of neurodevelopmental problems in children with prenatal triptan exposure. This dissertation had three aims: (1) to examine risk of behavioral problems in children using in the presence of time-varying confounding by concomitant medication use; (2) to examine risk of temperamental, motor, and communication disturbances associated with prenatal triptans exposure, adjusting for unmeasured confounding by migraine type and severity; and (3) to examine changes in neurodevelopment over time associated with prenatal triptan exposure. Methods: This dissertation used data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort including more than 100,000 women recruited during their first prenatal ultrasound visit. Aims 1 and 3 used marginal structural models to assess the risk of (1) neurodevelopmental problems at age 36 months (Aim 1), or (2) change in risk of neurodevelopmental problems from 18 to 36 months (Aim 3) associated with prenatal triptan exposure. Aim 2 used propensity matching and calibration to adjust for unmeasured confounding by migraine type, severity, and attitudes towards medication use in pregnancy. Neurodevelopmental outcome measures included the Child Behavior Checklist (CBCL), the Emotionality, Activity, and Temperament Scale (EAS), and the Ages and Stages Questionnaire (ASQ). Exposure to triptans was ascertained by self-report. Results: Prenatal triptan exposure was associated with greater externalizing behavior problems at 18 and 36 months, as well as greater increases in emotionality and activity from 18 to 36 months. We observed no association between triptan exposure and motor skills or communication problems; triptan use during pregnancy was associated with migraine severity but not migraine type, and adjustment for unmeasured migraine characteristics moved effect estimates towards the null. Conclusions: Prenatal triptan exposure is associated with externalizing-type behaviors and temperament in children, while migraine itself is associated with internalizing-type behaviors and temperament. The use of concomitant medications and the severity of the underlying condition both exerted substantial influence on observed effect estimates, and should be considered in any future studies of triptan medication use in pregnancy.