Luiz Kulay Júnior

Obstetric and perinatal effects of active and/or passive smoking during pregnancy

CONTEXT Cigarette smoke, whether inhaled voluntarily or not, causes damage to the mother-infant pair. The antenatal period may present the best opportunity for performing effective anti-smoking campaigns. OBJECTIVE To study the obstetric and perinatal effects of smoking on pregnancy and the infant. TYPE OF STUDY Prospective study, interviewing pregnant women who were randomly selected at the maternity hospital as they were being discharged after giving birth. SETTING Hospital Municipal Vereador José Storópolli, São Paulo, Brazil. METHODS 758 patients were interviewed regarding smoke inhalation before being discharged from the maternity hospital. The groups were formed by 42 active smokers, 272 passive smokers, 108 who inhaled smoke both actively and passively, and 336 non-smokers. The groups were compared regarding age, parity, school education, incidence of spontaneous abortion, rate of caesarian births, average gestational age at birth, rate of low birth weight and adequacy of weight in relation to the gestational age of newborn infants. For all variables we considered p < 0.05 as statistically significant. RESULTS There was a high rate (55.7%) of pregnant smokers, including 5.5% active, 35.9% passive and 14.3% active-passive smokers. Active and active-passive smokers were older and had higher parity. Active smokers had lower education levels and higher rates of previous spontaneous abortion. The weights of newborn babies were lower for smoking mothers. DISCUSSION The study was performed among patients that were mostly of low economic, social and cultural levels, thus possibly explaining the high incidence of smokers. Worse still was that 35.9% of the non-smokers were actually passive smokers. These rates we report were similar to those from the literature. The typical receptiveness of teenage girls to unrestricted advertising in the media contributes towards an early start to acquiring the habit of smoking, including during pregnancy in our country. We emphasize the difficulties in quantifying exposure to cigarettes even among active smokers. CONCLUSIONS Cigarette smoke, whether inhaled voluntarily or not, has an unfavorable effect on the mother-infant pair.

Ação da Betametasona em Ratas Prenhes: Impacto sobre os Níveis de Corticosterona e Glândulas Adrenais Maternas e Fetais

Purpose: the repetitive use of antenatal corticosteroid therapy for acceleration of fetal lung maturation has been common in cases at risk of preterm delivery. We studied the corticosterone levels at term and the morphologic aspects in the maternal and fetal adrenal glands submitted to the effect of betamethasone in the second half of rat pregnancy in order to verify its consequences. Methods: thirty female pregnant rats were divided into three groups of ten animals each. Group I received betamethasone on the 11th, 12th, 18th and 19th day of pregnancy. Group II received distilled water on the same days (control group). Group III did not receive any drug (stress control group). All rats were sacrificed on the 20th day of pregnancy when plasma corticosterone levels of dams were assessed and the maternal and fetal adrenal glands were studied by light microscopy. Results: plasma corticosterone level of dams was lower in the group treated with betamethasone (4.8 mg/dL) when compared with the control groups (17.7 and 26.8 mg/dL). The light microscopy study revealed cytoplasmatic vacuolation in the fasciculate zone in the maternal and fetal adrenal glands, which indicates adrenal suppression. Conclusions: the antenatal repetitive and prolonged use of corticosteroids in pregnant rats for acceleration of lung fetal maturation causes maternal and fetal adrenal suppression.

Estudo comparativo entre marcadores ultra-sonográficos morfológicos preditores de parto pré-termo: sinal do afunilamento do colo e ausência do eco glandular endocervical

OBJECTIVE: To verify if different morphological ultrasonographic markers such as the funneling sign and the cervical gland area can be predictors of spontaneous premature delivery in pregnant women between 21 and 24 weeks of gestation. MATERIALS AND METHODS: This was a prospective cross-sectional study in which 361 women with 21 to 24 weeks of gestation were examined by transvaginal ultrasonography. The gestational age at delivery was later checked by telephone or mail. RESULTS: Spontaneous preterm delivery (SPD) occurred in 5% of the patients. Cervical funneling occurred in 4.2% of the women and in 22.2% of those who had SPD. This finding was correlated to preterm delivery (p < 0.001; relative risk of 6.68). Absence of a hypoechoic area peripheral to the cervical canal consistent with endocervical epithelium glands, namely endocervical glandular echo (EGE) feature, was detected in 2.8% of all patients and in 44.4% of those who developed spontaneous preterm labor. There was a statistically significant association of this feature to SPD (p < 0.001; relative risk of 28.57). Multivariance logistic regression analysis showed that this was the feature with strongest correlation with SPD, when compared to cervical funneling. CONCLUSION: Prediction of SPD through ultrasound features should observe biometrical and morphological signs such as absence of EGE. This is a new and important ultrasound finding that can be considered a predictor of risk for SPD, and should be confirmed in future multicentric trials.

Use of drugs during pregnancy: benefit and cost

As mudanças são freqüentes no mercado de medicamentos, o que influencia o padrão de prescrição e automedicação. Na maior parte das vezes, não são conhecidos os efeitos adversos dos produtos novos em relação à gestação. Assim, é oportuno avaliar e conhecer quais fármacos são consumidos na gravidez, período de vulnerabilidade única para a vida fetal. Esse foi o trabalho de Fonseca et al. Estima-se que 10% ou mais dos defeitos congênitos são resultantes da exposição materna a drogas. Por este motivo, a Food and Drug Administration (FDA) classifica todas elas em categorias de risco. Muitas drogas não têm sido avaliadas em estudos clínicos – e, provavelmente, não o serão por questões éticas. Em estudo de revisão de literatura sobre a farmacogenética dos defeitos congênitos, com foco sobre a necessidade de ensaio genotípico materno preditivo, os autores concluem que os indivíduos variam em como metabolizam drogas e manipulam exposições ambientais tóxicas. Em usuárias crônicas de medicamentos, não existe técnica disponível que possa identificar aquelas de risco de dismorfose. Os polimorfismos de gene para uma determinada enzima específica podem resultar numa ausência ou redução no nível da atividade enzimática, ou em nenhuma mudança, com pouco efeito sobre a estrutura/função dos produtos do gene, mas eles não estão associados ao fenótipo clínico, tanto para a mãe como para o feto. Outros polimorfismos podem ser apenas marcadores. A eficácia e a toxicidade das drogas usadas pelas grávidas podem ser difíceis de serem preditas pelas alterações em muitos parâmetros fisiológicos e pela variação das atividades enzimáticas no metabolismo das drogas, ditadas pela presença da placenta e do feto. Efflux transporters têm sido detectados em elevado nível dentro do tecido placentário, limitando potencialmente a exposição fetal a xenobióticos. O ajustamento de dose de drogas antiepilépticas, antidepressivas e antiinfecciosas administradas durante a gravidez tem sido requisitado devido a estas mudanças no metabolismo e à disposição das drogas. Morgan conclui que a extensão da exposição fetal à droga administrada ao organismo materno depende de numerosos fatores – em particular dos mecanismos de eliminação materno-fetal e da permeabilidade placentária. Refere que, na gravidez, a proteína plasmática carreadora de certas drogas está reduzida, em razão da redução na concentração da albumina sérica. Devido ao aumento do trabalho cardíaco na gravidez, há elevação de 50% no fluxo plasmático renal efetivo, nível de filtração glomerular e clearance de creatinina.

Ação crônica do ácido acetilsalicílico na prenhez da rata

The purpose of the present study was to evaluate the effects of acetylsalicylic acid (ASA) on the pregnancy of female albino rats. We used 60 pregnant female rats which were divided into six groups of ten cache. All the animals received daily by gavage, from the 5th (day zero) until the 20th day of pregnancy, 1 ml of the following: Group I - only distilled water (control); Group II - 0.2% aqueous solution of carboxymethylcellulose (vehicle); Groups III, IV, V and VI - 1, 10, 100 and 400 mg/kg body weight respectively, of ASA diluted in 0.2% carboxymethylcellulose solution. The animals were weighed on days 0, 7, 14 and 20 of pregnancy. Our results showed that the animals treated with 100 mg of ASA presented a reduction in the number of live newborns. The animals treated with 400 mg/kg/day presented not only a reduction in the number of live newborns but also decrease in maternal, newborn and placental weight.

Chronic use of indinavir in albino rat pregnancy (Rattus norvegicus albinus, Rodentia, Mammalia): biological assay.

Aim:  Assess possible adverse effects of the chronic use of indinavir during pregnancy in a rat model.

Avaliação da medida do comprimento do colo e da ausência do eco glandular endocervical para predição do parto pré-termo

OBJETIVO: verificar a prevalencia do sinal eco glandular endocervical (EGE) e o comprimento cervical menor ou igual a 20 mm em gestantes entre a 21a e a 24a semana e comparar estes sinais ecograficos como fatores indicadores de parto pre-termo espontâneo. METODOS: estudo prospectivo transversal no qual foram incluidas 361 gestantes da populacao geral, para realizacao de exame ultra-sonografico em idade gestacional entre a 21a a 24a semana. Os criterios de exclusao do estudo foram malformacoes mullerianas, gestacoes multiplas, malformacoes fetais, obito fetal, alteracoes da quantidade de liquido amniotico, placenta com insercao segmentar, antecedentes de cirurgia no colo uterino (conizacao, amputacao, cerclagem) e procedimentos cirurgicos durante a gestacao. Apos a realizacao do exame ultra-sonografico obstetrico morfologico efetuado por via abdominal, seguiu-se o exame ecografico por via vaginal para observacao de uma faixa hipoecoica ou hiperecoica adjacente ao canal endocervical correpondente as glândulas do epitelio endocervical (EGE) e mensuracao do comprimento cervical. As variaveis qualitativas sao representadas por frequencia absoluta e relativa, ao passo que as variaveis quantitativas, por media, desvio-padrao, mediana e valores minimo e maximo. A associacao entre as variaveis qualitativas foi avaliada pelo teste c2 ou teste exato de Fisher. Para cada variavel estudada, foi calculado o risco relativo seguido do intervalo com 95% de confianca. A tecnica de analise de regressao logistica univariada foi utilizada para verificar, entre as variaveis estudadas, quais foram indicativas de parto pre-termo espontâneo. O nivel de significância adotado foi de 95% (alfa = 5%) e descritivos (p) iguais ou inferiores a 0,05 foram considerados significantes. RESULTADOS: a incidencia do parto pre-termo espontâneo foi de 5,0%. O comprimento do colo uterino revelou-se igual ou inferior a 20 mm em 3,3% da populacao estudada e em 27,8% das pacientes que apresentaram parto pre-termo espontâneo. A ausencia do EGE foi detectada em 2,8% das pacientes estudadas e em 44,4% das pacientes que evoluiram para parto pre-termo espontâneo. A associacao entre ausencia do EGE e presenca do colo curto revelou-se estatisticamente significante (p<0,001). A ausencia do EGE teve forte associacao com parto pre-termo espontâneo e risco relativo de 28,57, com intervalo de confianca (IC 95%) 14,40-56,68. A medida do comprimento cervical inferior a 20 mm tambem apresentou associacao com parto pre-termo espontâneo (p<0,001), com risco relativo de 11,27 e IC 95% de 4,79-26,53. CONCLUSAO: a nao visualizacao do EGE endocervical constitui parâmetro morfologico ultra-sonografico novo e util na predicao do parto pre-termo espontâneo nas gestacoes unicas da populacao geral. Os resultados deste trabalho indicam uma tendencia clara da marcante importância da ausencia do EGE como indicador do risco para parto pre-termo espontâneo, a ser confirmada em pesquisas multicentricas futuras.

Índices veno-arteriais para predição da acidemia fetal ao nascimento em gestações com insuficiência placentária

OBJECTIVE: to investigate whether it is possible to predict acidemia at birth in pregnancies with placental insufficiency using venous-arterial indices: pulsatility index for vein (PIV) of the ductus venosus (DV) over PI of the middle cerebral artery (MCA) and PIV of the DV over PI of the umbilical artery, and establish cut-off values for this prediction. PATIENTS AND METHODS: this was a prospective cross-sectional study involving forty-seven patients with placental insufficiency (umbilical artery resistance and pulsatility indices above the 95th percentile for gestational age) who were submitted to Dopplervelocimetry in the last 24 hours before delivery. All pregnancies were singleton, over 26 weeks of age and without structural or chromosome anomalies. Arterial cord blood was obtained for gasometry immediately after birth. Acidemia was defined as umbilical arterial pH < 7.20 in the absence of uterine contractions and pH < 7.15 in the presence of contractions. Metabolic or mixed acidemia at birth were considered pathological. A ROC curve was calculated for the venous-arterial indices: PIV DV/PI umbilical artery (UA) and PIV DV/PI MCA. A cut-off value was established and sensitivity, specificity, accuracy, positive and negative predictive values and positive and negative likelihood ratios were calculated. RESULTS: The DV/UA PI index was not a good predictor of acidemia at birth. The DV/MCA PI index was related to acidemia at birth (area under the curve 0,785, p = 0,004). The cut-off value was: 0,582, sensitivity 66,7%, specificity 77,1 and accuracy 74,5%. CONCLUSION: the PIV DV/PI MCA ratio is adequate for predicting acidemia at birth in pregnancies with placental insufficiency. The cut-off value was: 0,582.

Avaliação do Desenvolvimento de Embriões Bovinos Pós-Biópsia: um Modelo para Treinamento

Purpose: to develop an animal model for the study of, and training in, bovine biopsies. Methods: cow ovaries were obtained from a slaughterhouse and transported to the laboratory where the oocytes were aspirated, maturated and submitted to in vitro fertilization. On the 5th day after fertilization, the embryos were biopsied, with the zona pellucida being opened with a cutting blade fitted to the light microscope. One or two blastomeres were removed from the embryos and left in coculture for three additional days. After this time, embryo development was evaluated in comparison to a control group by morphological study and cell counts using specific staining for nuclei. Results: forty of the 57 biopsied embryos reached the blastocyst stage (70.2%) and hatching was observed in 11 (27.5%). Forty-two blastocysts were obtained in the control group (73.7%) and 11 of them hatched (26.2%). Cell counts showed no significant differences between groups. Conclusions: we conclude that the proposed protocol is technically feasible and supplies a good number of embryos because of the easy technique for obtaining bovine oocytes, thus representing a method that could be adopted for training.

Análise morfológica dos fígados e rins no binômio materno-fetal após tratamento de ratas prenhes com Ritonavir durante toda a prenhez

OBJETIVO: avaliar os efeitos da administracao cronica de tres diferentes doses de Ritonavir nos figados e rins de ratas prenhes e seus conceptos do ponto de vista morfologico. METODOS: Quarenta ratas albinas EPM-1 Wistar, prenhes, foram aleatoriamente divididas em quatro grupos: Contr (controle do veiculo) e tres grupos experimentais, Exp20, Exp60 e Exp180, que receberam, respectivamente, 20, 60 e 180 mg/kg por dia de Ritonavir por via oral. A droga e o veiculo (propilenoglicol) foram administrados por gavagem, desde o primeiro ate o 20o dia da prenhez. No ultimo dia do experimento, todos os animais foram anestesiados e sacrificados. Em seguida, fragmentos dos figados e rins maternos e fetais foram coletados e preparados para analise em microscopia de luz. RESULTADOS: nao observamos nenhuma alteracao morfologica nas visceras estudadas nos Grupos Contr e Exp20. No Grupo Exp60, encontramos, no figado materno, hepatocitos com sinais de atrofia e de apoptose (eosinofilia citoplasmatica e nucleos picnoticos) e vasodilatacao marcante dos capilares sinusoides (congestao). No rim materno, encontramos areas eosinofilicas e nucleos hipercromaticos na parede dos tubulos contorcidos proximais. O figado e rins maternos do Grupo Exp180 tiveram alteracoes morfologicas mais intensas do que no Grupo Exp60. Nao observamos alteracoes histomorfologicas nos figados e rins fetais em todos os grupos, o que pode ser decorrente da acao protetora da glicoproteina P. CONCLUSOES: nossos resultados mostram que a administracao de Ritonavir a ratas prenhes causou alteracoes morfologicas nos figados e rins maternos em doses mais altas que a convencional. Ja a ausencia de anormalidades nos orgaos fetais pode ser explicada pelo papel protetor da glicoproteina P.