Reproductive outcomes in cases of subclinical hypothyroidism and thyroid autoimmunity: a narrative review / Resultados reprodutivos nos casos de hipotireoidismo subclínico e autoimunidade tireoidiana: Uma revisão narrativa

Abstract Thyroid diseases are relatively common in women in the reproductive period. It is currently understood that clinically-evident thyroid disorders may impair ovulation and, consequently, fertility. However, to date it has not been proven that high serum levels of thyroid-stimulating hormone and/or positivity for antithyroid antibodies are associated to a reduction in fertility, mainly in the absence of altered thyroxine levels. The present comprehensive review aims to present current data on the association between subclinical hypothyroidism and/or thyroid autoimmunity and reproductive outcomes.

Resumo As doenças da tireoide são relativamente comuns em mulheres no período reprodutivo. Atualmente, entende-se que distúrbios da tireoide clinicamente evidentes podem prejudicar a ovulação e, consequentemente, a fertilidade. No entanto, não se provou até o presente que níveis séricos altos do hormônio estimulador da tireoide e/ou positividade para anticorpos antitireoidianos estão associados a uma redução na fertilidade, sobretudo na ausência de níveis alterados de tiroxina. Esta revisão narrativa tem como objetivo apresentar dados atuais sobre a associação entre hipotireoidismo subclínico e/ou autoimunidade tireoidiana e resultados reprodutivos.

Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition

ABSTRACT Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95

Association between dietary glycemic index and excess weight in pregnant women in the first trimester of pregnancy / Associação entre o índice glicêmico dietético e o excesso de peso em gestantes no primeiro trimestre de gestação

Abstract Objective To assess the association between dietary glycemic index (GI) and excess weight in pregnant women in the first trimester of pregnancy. Methods A cross-sectional study in a sample of 217 pregnant women was conducted at the maternal-fetal outpatient clinic of the Hospital Geral de Fortaleza, Fortaleza, state of Ceará, Brazil, for routine ultrasound examinations in the period between 11 and 13 weeks + 6 days of gestation.Weight and height were measured and the gestational body mass index (BMI) was calculated. The women were questioned about their usual body weight prior to the gestation, considering the prepregnancy weight. The dietary GI and the glycemic load (GL) of their diets were calculated and split into tertiles. Analysis of variance (ANOVA) or Kruskal-Walls and chi-squared (χ2) statistical tests were employed. A crude logistic regression model and a model adjusted for confounding variables known to influence biological outcomes were constructed. A p-value < 0.05 was considered significant for all tests employed. Results The sample group presented a high percentage of prepregnancy and gestational overweight (39.7% and 40.1%, respectively). InthetertilewiththehigherGIvalue, therewasa lower dietary intake of total fibers (p = 0.005) and of soluble fibers (p = 0.008). In the third tertile, the dietary GI was associated with overweight in pregnant women in the first trimester of gestation, both in the crude model and in the model adjusted for age, total energy intake, and saturated fatty acids. However, this association was not observed in relation to the GL. Conclusion A high dietary GI was associated with excess weight in women in the first trimester of pregnancy.

Resumo Objetivo Avaliar a associação entre índice glicêmico (IG) dietético e presença de excesso de peso em gestantes no primeiro trimestre de gestação. Métodos Estudo transversal realizado com 217 gestantes atendidas no Ambulatório de Medicina Materno-Fetal do Hospital Geral de Fortaleza, Fortaleza, CE, para realização de exames ultrassonográficos de rotina no período entre 11 e 13 semanas e 6 dias de gestação. Peso e altura foram obtidos para o cálculo do índice de massa corporal (IMC) gestacional. As mulheres foram questionadas quanto ao peso corporal habitual anterior à gestação, considerado o peso pré-gestacional. O IG e a carga glicêmica (CG) das suas dietas foram calculados e divididos em tercis. As associações foram investigadas por análise de variância (ANOVA, na sigla em inglês) ou pelos testes Kruskal-Walls e qui-quadrado (χ2). Resultados O grupo tinha alto percentual de excesso de peso pré-gestacional (39,7%) e gestacional (40,1%). Houve menor consumo de fibras totais (p = 0,005) e fibras insolúveis (p = 0,008) no tercil de maior valor de IG. No terceiro tercil, o IG da dieta foi associado ao excesso de peso dasmulheres no primeiro trimestre de gestação, tanto no modelo bruto como no modelo ajustado para idade, consumo total de energia e de ácidos graxos saturados. No entanto, não se observou esta associação emrelação à CG. Conclusão O alto IG da dieta consumida foi associado ao excesso de peso das mulheres no primeiro trimestre da gestação.

Selective screening for thyroid dysfunction in pregnant women: How often do low-risk women cease to be treated following the new guidelines of the American Thyroid Association?

ABSTRACT Objective: Universal screening for thyroid dysfunction in pregnant women is not recommended by the American Thyroid Association (ATA) or the American Association of Clinical Endocrinologists (AACE). This study evaluated the frequency of pregnant women that would have an indication for levothyroxine (L-T4) according to the new ATA/AACE guidelines among low-risk women without an indication for screening with TSH. Subjects and methods: The sample consisted of 412 pregnant women ranging in age from 18 to 30 years. These women were considered to be at low risk for thyroid dysfunction according to ATA/AACE and would not be candidates for screening with TSH. Anti-thyroid peroxidase antibodies (TPOAb) and TSH were measured. Women who had TSH > 2.5 mIU/L or TPOAb in the first trimester were submitted to subsequent evaluations in the second and third trimester. Results: In the first trimester, none of the pregnant women would have L-T4 therapy "recommended" and treatment would be "considered" in only two. In the second trimester, pregnant women with positive TPOAb or TSH > 2.5 mIU/L in the first trimester (n = 30) were reevaluated. L-T4 treatment would be "recommended" in only one woman and would be "considered" in two others. The 28 women that were not treated in the second trimester were reevaluated in the third trimester, but none of them would have L-T4 "recommended". Conclusion: The findings of the study suggest that selective screening, recommended by ATA/AACE does not result in a significant loss of pregnant women with an indication for L-T4 treatment.

Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study

ABSTRACT Objective: To evaluate the association of isolated hypothyroxinemia in the first trimester with obstetric and neonatal outcomes and iron deficiency. Subjects and methods: The study was prospective. Women who had become pregnant spontaneously were initially selected. Next, anti-thyroid peroxidase antibodies (TPOAb), free T4 (FT4), total T4 (TT4), TSH, and ferritin were measured. TPOAb-positive women were excluded. The final sample consisted of 596 women with serum TSH between 0.1 and 2.5 mIU/l. Hypothyroxinemia was defined as FT4 < 0.86 ng/dL and < 0.92 ng/dL, corresponding to the 5th and 10th percentiles, respectively, and TT4 < 7.8 ng/dL. None of the pregnant women was treated with levothyroxine until the end of pregnancy. Results: The women ranged in age from 18 to 36 years, with a median gestation of 9 weeks. T4 levels were not correlated with BMI or maternal TSH. Isolated hypothyroxinemia was observed in 4.3% (FT4 < 0.86 ng/dL), 9% (FT4 < 0.92 ng/dL), and 7% (TT4 < 7.8 ng/dL) of the pregnant women. The frequencies of obstetric and neonatal outcomes were similar in women with versus without hypothyroxinemia. In women without iron deficiency, 8.4%, 3.9%, and 6.5% had FT4 < 0.92 ng/dl, FT4 < 0.86 ng/dL and TT4 < 7.8 ng/dL, respectively. These frequencies of hypothyroxinemia were significantly higher among women with iron deficiency (20.7%, 14.8% and 17.2%, respectively). Conclusions: This prospective Brazilian study found no association between isolated hypothyroxinemia in the first trimester of gestation and obstetric or neonatal outcomes, but an association was demonstrated with iron deficiency.

Lipoprotein profile modifications during gestation: A current approach to cardiovascular risk surrogate markers and maternal-fetal unit complications / Modificações do perfil lipoproteico durante a gestação: uma abordagem atual demarcadores sugestivos de risco cardiovascular e complicações materno-fetais

Abstract Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports themajor changes that occur in lipoprotein metabolismduring pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications.

Resumo Diversas mudanças ocorrem no metabolismo lipídico durante a gestação em função das alterações hormonais e metabólicas, que são essenciais para satisfazer a demanda nutricional ocasionada pelo desenvolvimento da unidade feto-placentária. O período da gestação apresenta dois momentos distintos que iniciam com acúmulo de gordura principalmente no tecido adiposo materno, e a fase tardia, caracterizada por catabolismo acelerado, com aumento de ácidos graxos na circulação causando hiperlipidemia, principalmente a aquela caracterizada como hipertrigliceridemia. A hiperlipidemia materna pode estar associada ao desenvolvimento de complicações materno-fetais (parto prematuro, pré-eclâmpsia, complicações vasculares) e de doenças cardiovasculares, a longo prazo. O risco pode estar relacionado não apenas ao teor de colesterol contido nas frações lipoprotéicas, mas também ao número e a funcionalidade das partículas lipoproteicas. Esta revisão aborda as principais mudanças que ocorrem no metabolismo lipoproteico durante a gravidez, e que estão associadas ao desenvolvimento de dislipidemias, fenótipo aterogênico e complicações maternofetais.

Humoral hypercalcemia of pregnancy treated with bisphosphonates

SUMMARY Hypercalcemia can be hazardous during pregnancy, most cases being due to primary hyperparathyroidism. We report a case of hypercalcemia with suppressed PTH levels necessitating treatment with bisphosphonates during pregnancy. A 38-year-old woman at the 26th week gestation was admitted because of symptomatic hypercalcemia. She did not take any medication that could influence her calcium levels. Physical examination was unremarkable. Laboratory tests on admission were: calcium 12.7 mg/dL (8.5-10.5 mg/dL), phosphorus 1.8 mg/dL (2.5-4.5 mg/dL) and PTH on 3 consecutive tests 1.2, 1.3 and 1.2 pg/mL (15-65 pg/mL). Her 24h urine calcium was 900 mg, 25-OH-D 40 ng/mL (30-58 ng/mL) and 1,25-OH-D 99 pg/mL (80-146 for women in the third trimester). Abdominal ultrasound revealed multiple hypervascular liver lesions consistent with hemangiomas by MRI. Breast and neck ultrasound were normal, and chest CT revealed few non-significant 0.3-0.7 cm pulmonary nodules with no change after an interval of 3 months. She was treated with isotonic saline, loop diuretics and calcitonin. Despite this treatment, calcium levels remained high (14.1 mg/dL), and pamidronate was initiated. On 35th week gestation, she underwent a cesarean section complicated by hypocalcemia of the newborn. Eight weeks after delivery, her calcium levels are 9.4 mg/dL and PTH 18 mg/dL. According to the extensive workup and the post-partum normalization of PTH and calcium levels, we conclude that excessive secretion of placental PTHrP was the cause of hypercalcemia in this patient. No significant adverse effect of bisphosphonate on the mother or baby were seen at the short term follow up.

Impact of the Use of Different Diagnostic Criteria in the Prevalence of Dyslipidemia in Pregnant Women / Impacto do Uso de Diferentes Critérios Diagnósticos na Prevalência de Dislipidemia em Gestantes

Abstract Background: There is a physiologic elevation of total cholesterol (TC) and triglycerides (TG) during pregnancy. Some authors define dyslipidemia (DLP) in pregnant women when TC, LDL and TG concentrations are above the 95th percentile (p95%) and HDL concentration is below the 5th percentile (P5%) for gestational age (GA). Objective: To compare the prevalence of DLP in pregnant women using percentiles criteria with the V Brazilian Guidelines on Dyslipidemia and the association with maternal and fetal outcomes. Results: Pregnant women with high-risk conditions, aged 18-50 years, and at least one lipid profile during pregnancy was classified as the presence of DLP by two diagnostic criteria. Clinical and laboratorial data of mothers and newborns were evaluated. Conclusion: 433 pregnant women aged 32.9 ± 6.5 years were studied. Most (54.6%) had lipid profile collected during third trimester. The prevalence of any lipid abnormalities according to the criteria of the National Guidelines was 83.8%: TC ≥ 200 mg/dL was found in 49.9%; LDL ≥ 160 mg/dL, in 14.3%, HDL ≤ 50 mg/dL in 44.4% and TG ≥ 150 mg/dL in 65.3%. Any changes of lipid according to percentiles criteria was found in 19.6%: elevation above the P95% for TC was found in 0.7%; for LDL, 1.7%; for TG 6.4% and HDL lower than the P5% in 13%. The frequency of comorbidity: hypertension, diabetes, smoking, obesity and preeclampsia was similar among pregnant women when DLP was compared by both criteria. Conclusion: The prevalence of DLP during pregnancy varies significantly depending on the criteria used, however none demonstrated superiority in association with comorbidities.

Resumo Fundamento: Durante a gestação ocorrem, fisiologicamente, elevações do colesterol total (CT) e triglicerídios (TG). Alguns autores definem dislipidemia (DLP) gestacional quando as concentrações de CT, LDL e TG são superiores ao percentil 95 (P95%) e de HDL, inferiores ao percentil 5 (P5%) para a idade gestacional. Objetivo: Comparar a prevalência da DLP em gestantes conforme critério por percentis com o da V Diretriz Brasileira de Dislipidemia e avaliar a associação com desfechos materno-fetais. Métodos: Gestantes com patologias de alto risco, idade entre 18 a 50 anos, e, pelo menos um perfil lipídico durante a gestação foram classificadas quanto à presença de DLP por dois critérios. Dados clínicos e laboratoriais das mães e neonatos foram avaliados. Resultados: Estudou-se 433 gestantes com idade de 32,9 ± 6,5 anos. A maioria (54,6%) teve o perfil lipídico coletado no terceiro trimestre. A prevalência de quaisquer das alterações lipídicas, conforme os critérios da Diretriz Nacional, foi de 83,8%: CT ≥ 200 mg/dL foi encontrado em 49,9%; LDL ≥ 160 mg/dL, em 14,3%, HDL ≤ 50 mg/dL em 44,4% e TG ≥ 150 mg/dL, em 65,3%. Quaisquer das alterações lipídicas pelo critério dos percentis foi encontrada em 19,6%: sendo que elevação superior ao P95% para CT foi encontrada em 0,7%; para LDL, em 1,7%; para TG, em 6,4% e inferiores ao P5% para o HDL em 13%. A frequência das comorbidades: hipertensão, diabetes, tabagismo, obesidade e pré-eclâmpsia foi semelhante entre as gestantes quando se comparou DLP pelos dois critérios. Conclusão: A prevalência de DLP na gestação variou significativamente conforme o critério utilizado, entretanto nenhum demonstrou superioridade na associação com comorbidades.

Resultados perinatales de las pacientes con anemia a la captación del embarazo (enero 2015-diciembre 2016) / Perinatal Outcomes of Patients with Anemia at the Beginning of Pregnancy (January 2015-December 2016)

Introducción: la anemia durante el embarazo se produce como resultado de deficiencias nutricionales y constituye un problema de salud. Es una de las afecciones coincidentes con más frecuencia en el embarazo. Objetivo: describir los resultados perinatales en pacientes con diagnóstico de anemia en el momento de la captación del embarazo. Métodos: se realizó un estudio observacional, descriptivo, longitudinal y prospectivo, en 543 pacientes con anemia atendidas en la consulta de nutrición del Hospital Ginecobstétrico Eusebio Hernández Pérez de La Habana, Cuba, desde enero de 2015 hasta diciembre de 2016. La recolección de la información se realizó mediante entrevista, examen físico, las investigaciones diagnósticas realizadas y las historias clínicas. Resultados: casi la mitad de las pacientes estuvieron representadas por las adolescentes y las mayores de 35 años (45,4 por ciento). Las multíparas iniciaron la gestación con anemia para un 36,6 por ciento. Las nulíparas presentaron infecciones durante el embarazo para un 59,2 por ciento. El 83,9 por ciento de las pacientes con partos anteriores tenían un periodo intergenésico corto. El parto antes del término y el recién nacido con bajo peso al nacer estuvo presente en 15,4 por ciento. No hubo mortalidad materno-fetal. Hubo tres muertes neonatales precoces. Conclusiones: la multiparidad y el período intergenésico corto fueron antecedentes frecuentes en las gestantes con anemia en la captación. La prematuridad y el bajo peso al nacer fueron bajas y no se produjeron muertes maternas ni fetales. La mortalidad perinatal fue a expensas de los recién nacidos menores de siete días(AU)

Introduction: Anemia during pregnancy occurs as a result of nutritional deficiencies and is a health problem. It is one of the most frequently encountered conditions in pregnancy. Objective: Describe the perinatal outcomes in patients with anemia at the beginning of pregnancy. Methods: An observational, descriptive, longitudinal and prospective study was conducted in 543 patients with anemia treated at the nutrition clinic of the Eusebio Hernández Pérez Ginecobstetric Hospital, Havana, Cuba, from January 2015 to December 2016. The collection of information was made through interview, physical examination, diagnostic investigations and clinical records. Results: Almost half of the patients were represented by adolescents and those over 35 (45.4 percent). The multiparous women started gestation with anemia (36.6 percent). Nulliparous women had infections during pregnancy (59.2 percent).83.9 percent of the patients with previous deliveries had short intergenic period. Preterm birth and low birth weight newborns were present in 15.4 percent. There was no maternal-fetal mortality but only three early neonatal deaths. Conclusions: Multiparity and short intergenic period were frequent antecedents in pregnant women with anemia at the beginning of pregnancy. Prematurity and low birth weight incidence were low and there were no maternal or fetal deaths. Perinatal mortality was at the expense of infants younger than seven days(AU)

Identification of Matrix Metalloproteinase-2 and 9 as Biomarker of Intrahepatic Cholestasis of Pregnancy

ABSTRACT Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transaminase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population.

Evolución de una vasculitis renal asociada a anticuerpos anti-citoplasma de neutrófilos (ANCA) durante un embarazo: caso clínico / Antineutrophil cytoplasmic antibody (ANCA) associated renal vasculitis and pregnancy: report of one case

ANCA mediated vasculitis mainly occur between the fourth and fifth decade of life; therefore, it is very uncommon to see pregnant patients with the disease. Vasculitis may affect significantly the course of pregnancy; in turn pregnancy can change the course of vasculitis. We report a 20 years old woman with ANCA-mediated renal vasculitis lasting 10 years who consulted with a pregnancy of 15 weeks. She was in remission and had amenorrhea attributed to ovarian toxicity due to cyclophosphamide. Pregnancy had an uneventful course with spontaneous delivery at the 37th week, giving birth to a healthy newborn. Proteinuria increased during the course of pregnancy with a mild deterioration of kidney function. During the year after delivery, she had nephrotic proteinuria and a worsening of renal function.

Cetoacidosis diabética normoglicémica en el embarazo: caso clínico / Normoglycemic diabetic ketoacidosis in pregnancy: report of one case

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

Asociación de nivel bajo de PAPP-A en primer trimestre con resultados obstétricos adversos / Association of low PAPP-A level in the first trimester with adverse obstetric outcomes

ANTECEDENTES: La PAPP-A es una proteína utilizada en obstetricia de forma rutinaria para el cribado de aneuploidías de primer trimestre. En los últimos años se está conociendo más acerca de su papel en la función placentaria. Diversos estudios están mostrando una asociación entre un nivel bajo de PAPP-A y distintos eventos obstétricos. OBJETIVO: Establecer una asociación entre PAPP-A baja y eventos obstétricos adversos. MÉTODO: Estudio retrospectivo de casos y controles anidado en una cohorte. Se han recogido las gestaciones únicas con PAPP-A inferior a percentil 5 en primer trimestre durante 2 años. Se ha recogido de la misma cohorte un grupo control, en proporción 2:1. Se compara mediante análisis estadístico la incidencia de eventos obstétricos adversos de cada grupo. RESULTADOS: Se incluyó un total de 285 pacientes en el grupo de casos y 570 pacientes en el grupo control. Se observó un aumento significativo en el grupo de casos de la incidencia de prematuridad, restricción del crecimiento, hipertensión gestacional y diabetes gestacional. Se ha correlacionado la PAPP-A baja con varios eventos obstétricos adversos, incluyendo prematuridad (OR 4,27), diabetes gestacional (OR 2,40), restricción del crecimiento (OR 2,36) e hipertensión gestacional (OR 2,22). No se observó relación con el resto de eventos obstétricos adversos. CONCLUSIÓN: Un nivel de PAPP-A bajo se asocia con aumentos significativos de prematuridad, diabetes gestacional, restricción del crecimiento e hipertensión gestacional.

BACKGROUND: PAPP-A is a placental protein used in obstetrics as a first trimester marker in aneuploidy screening. In the last few years we are knowing more about its placental function. Some studies are showing a association between low PAPP-A and obstetrical adverse events. AIM: Establish an association between low PAPP-A an obstetrical adverse events. METHOD: This is a retrospective nested case-control study. We identified each singleton pregnancy with a normal phenotype and a low PAPP-A (under percentile 5) in the last 2 years, and match it with a control group of the same population in a 2:1 proportion. It was compared the incidence of each obstetrical adverse outcomes with statistical analysis. RESULTS: We found 285 patients in the case group and match it with 570 patients from control group. It was observed a significative increase in the incidence of prematurity, intrauterine growth restriction, gestational hypertension and gestational diabetes. A low PAPP-A level was correlated with some obstetrical adverse events, like prematurity (OR 4.27), gestational diabetes (OR 2.40), intrauterine growth restriction (OR 2.36) and gestational hypertension (OR 2.22). We observe no correlation with the rest of outcomes. CONCLUSIONS: A low PAPP-A level is related with significative increases of prematurity, gestational diabetes, intrauterine growth restriction and gestational hypertension.

Ovarian hyperstimulation syndrome in a spontaneous singleton pregnancy / Síndrome da hiperestimulação ovariana em gestação única e espontânea

ABSTRACT The ovarian hyperstimulation syndrome is the combination of increased ovarian volume, due to the presence of multiple cysts and vascular hyperpermeability, with subsequent hypovolemia and hemoconcentration. We report a case of spontaneous syndrome in a singleton pregnancy. This was a spontaneous pregnancy with 12 weeks of gestational age. The pregnancy was uneventful until 11 weeks of gestational age. After that, the pregnant woman complained of progressive abdominal distention associated with abdominal discomfort. She did not report other symptoms. In the first trimester, a routine ultrasonography showed enlarged ovaries, multiples cysts and ascites. Upon admission, the patient was hemodynamically stable, her serum β-hCG was 24,487mIU/mL, thyroid-stimulating hormone was 2.2µUI/mL and free T4 was 1.8ng/dL. All results were within normal parameters. However, levels of estradiol were high (10,562pg/mL). During hospitalization, she received albumin, furosemide and prophylactic dose of enoxaparin. The patient was discharged on the sixth hospital day.

RESUMO A síndrome de hiperestimulação ovariana é a combinação do aumento dos ovários, devido à presença de múltiplos cistos e de hiperpermeabilidade vascular, com subsequente hipovolemia e hemoconcentração. Relata-se um caso de síndrome espontânea em uma gestação única. Trata-se de gravidez espontânea com 12 semanas de idade gestacional. A gravidez ocorreu sem intercorrências até 11 semanas de idade gestacional. Após, a gestante passou a se queixar de distensão abdominal progressiva, associada com desconforto abdominal. A paciente não relatava outros sintomas. A ultrassonografia de rotina no primeiro trimestre mostrou ovários aumentados com múltiplos cistos e ascite. No momento da internação, a paciente apresentava-se hemodinamicamente estável, com β-hCG sérico de 24.487mUI/mL, hormônio estimulante da tireoide de 2,2µUI/m e T4 livre de 1,8ng/dL, ou seja, valores dentro dos parâmetros normais. Porém, os níveis de estradiol estavam elevados (10.562pg/mL). Durante a internação, a paciente recebeu albumina, furosemida e enoxaparina profilática. A alta hospitalar ocorreu no sexto dia de internação.

IL-6 and IL-10 levels in the umbilical cord blood of newborns with a history of crack/cocaine exposure in utero: a comparative study / Níveis de IL-6 e IL-10 no sangue de cordão umbilical de recém-nascidos com história de exposição intrauterina ao crack/cocaína: um estudo comparativo

Introduction Prenatal cocaine exposure (PCE) is associated with neurobehavioral problems during childhood and adolescence. Early activation of the inflammatory response may contribute to such changes. Our aim was to compare inflammatory markers (IL-6 and IL-10) both in umbilical cord blood and in maternal peripheral blood at delivery between newborns with history of crack/cocaine exposure in utero and non-exposed newborns. Methods In this cross-sectional study, 57 newborns with a history of crack/cocaine exposure in utero (EN) and 99 non-exposed newborns (NEN) were compared for IL-6 and IL-10 levels. Sociodemographic and perinatal data, maternal psychopathology, consumption of nicotine and other substances were systematically collected in cases and controls. Results After adjusting for potential confounders, mean IL-6 was significantly higher in EN than in NEN (10,208.54, 95% confidence interval [95%CI] 1,328.54-19,088.55 vs. 2,323.03, 95%CI 1,484.64-3,161.21; p = 0.007; generalized linear model [GLM]). Mean IL-10 was also significantly higher in EN than in NEN (432.22, 95%CI 51.44-812.88 vs. 75.52, 95%CI 5.64-145.39, p = 0.014; GLM). Adjusted postpartum measures of IL-6 were significantly higher in mothers with a history of crack/cocaine use (25,160.05, 95%CI 10,958.15-39,361.99 vs. 8,902.14, 95%CI 5,774.97-12,029.32; p = 0.007; GLM), with no significant differences for IL-10. There was no correlation between maternal and neonatal cytokine levels (Spearman test, p ≥ 0.28 for all measures). Conclusions IL-6 and IL-10 might be early biomarkers of PCE in newborns. These findings could help to elucidate neurobiological pathways underlying neurodevelopmental changes and broaden the range of possibilities for early intervention.

Introdução A exposição pré-natal à cocaína está associada a problemas neurocomportamentais durante a infância e adolescência. A ativação precoce da resposta inflamatória pode contribuir para tais alterações. Nosso objetivo foi comparar marcadores inflamatórios (IL-6 e IL-10) no sangue do cordão umbilical e no sangue periférico materno na hora do parto, entre recém-nascidos expostos ao crack intraútero e recém-nascidos não expostos. Métodos Neste estudo transversal, 57 recém-nascidos expostos ao crack intraútero (RNE) e 99 recém-nascidos não expostos (RNNE) foram comparados quanto aos níveis de IL-6 e IL-10. Dados sociodemográficos e perinatais, psicopatologia materna, consumo de nicotina e outras substâncias foram sistematicamente coletados em casos e controles. Resultados Após o ajuste para potenciais confundidores, a média de IL-6 foi significativamente maior nos RNE em comparação aos RNNE [10.208,54, intervalo de confiança (IC95%) 1.328,54-19.088,55 versus2.323,03, IC95% 1.484,64-3.161,21; p = 0,007; modelo linear generalizado (MLG)]. A média ajustada de IL-10 foi significativamente maior nos RNE do que nos RNNE (432,2189, IC95% 51,44-812,88 versus 75,52, IC95% 5,64-145,39, p = 0,014; MLG). Medidas pós-parto ajustadas de IL-6 foram significativamente maiores nas mães que usaram de crack/cocaína (25.160,05, IC95% 10.958,15-39.361,99 versus 8.902,14, IC95% 5.774,97-12.029,32; p = 0,007; MLG), sem diferenças significativas para IL-10. Não houve correlação entre níveis maternos e neonatais de citocinas (teste de Spearman, p ≥ 0,28 para todas as medidas). Conclusões IL-6 e IL-10 podem ser biomarcadores precoces da exposição pré-natal a cocaína em recém-nascidos. Esses resultados podem ajudar a elucidar as vias neurobiológicas subjacentes a alterações do desenvolvimento e aumentar a gama de possibilidades para intervenção precoce.

Management of gestational hypothyroidism: results of a Brazilian survey

Objectives Evaluate the management of hypothyroidism in fertile-aged and pregnant women and compare these practices to the recommendations of the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Latin American Thyroid Society, published in 2013. Materials and methods In the first trimester of 2014, SBEM made available to all members an electronic questionnaire based on clinical scenarios in the management of gestational hypothyroidism. The responses of 406 physicians, most of them endocrinologists, were analyzed. Results Eighty-one per cent of the endocrinologists screen all their pregnant patients for thyroid dysfunction, mostly during the pregestational period or after the first prenatal visit. Following screening, 82% of the respondents initiate treatment when TSH levels are > 2.5 mIU/L while 67% monitor their pregnant patients even if TSH was normal on first trimester screening. For hypothyroid women who are planning pregnancy, 96% of the clinicians are aware of the importance of adjusting the levothyroxine (LT4) dose as soon as pregnancy is confirmed. However, opinions diverge with respect to adjusting the LT4 dose before or after reassessing thyroid function. The most widely used tests for monitoring pregnant women in use of LT4 are TSH and free T4 (62%) or TSH alone (21%). Unanimously, the treatment goal is to achieve the target TSH level for each trimester of gestation. Conclusion The recommendations of the consensus statements are incorporated into the respondents’ clinical practice. It is noteworthy that the great majority of the clinicians favor universal screening.

Gestational Age-specific Cut-off Values Are Needed for Diagnosis of Subclinical Hypothyroidism in Early Pregnancy

During the first trimester of pregnancy, thyroid-stimulating hormone (TSH) >2.5 mIU/L has been suggested as the universal criterion for subclinical hypothyroidism. However, TSH levels change continuously during pregnancy, even in the first trimester. Therefore the use of a fixed cut-off value for TSH may result in a different diagnosis rate of subclinical hypothyroidism according to gestational age. The objective of this study was to obtain the normal reference range of TSH during the first trimester in Korean gravida and to determine the diagnosis rate of subclinical hypothyroidism using the fixed cut-off value (TSH >2.5 mIU/L). The study population consisted of pregnant women who were measured for TSH during the first trimester of pregnancy (n=492) and nonpregnant women (n=984). Median concentration of TSH in pregnant women was lower than in non-pregnant women. There was a continuous decrease of median TSH concentration during the first trimester of pregnancy (median TSH concentration: 1.82 mIU/L for 3+0 to 6+6 weeks; 1.53 mIU/L for 7+0 to 7+6 weeks; and 1.05 mIU/L for 8+0 to 13+6 weeks). Using the fixed cut-off value of TSH >2.5 mIU/L, the diagnosis rate of subclinical hypothyroidism decreased significantly according to the gestational age (GA) at TSH (25% in 3+0 to 6+6 weeks, 13% in 7+0 to 7+6 weeks, and 9% for 8+0 to 13+6 weeks, P<0.001), whereas the diagnosis rate was 5% in all GA with the use of a GA-specific cut-off value (P=0.995). Therefore, GA-specific criteria might be more appropriate for the diagnosis of subclinical hypothyroidism.

Postpartum glucose tolerance status 6 to 12 weeks after gestational diabetes mellitus: a Brazilian cohort / Reavaliação do estado glicêmico 6 a 12 semanas após o diabetes melito gestacional: uma coorte brasileira

Objectives: The aims of this study were to estimate the local rate of postpartum diabetes screening after gestational diabetes mellitus (GDM) pregnancies, and to identify clinical variables associated with retesting rates and with the persistence of decreased glucose tolerance. Subjects and methods: Prospective cohort of GDM women with prenatal delivery at a specialized center, from November 2009 to May 2012. All women were advised to schedule a 6 weeks postpartum 75-g oral glucose tolerance test (OGTT). Results: Of the 209 women included, 108 (51.7%) returned to be tested with fasting plasma glucose (n = 14), OGTT (n = 93) or random glucose (n = 1). Return was associated with lower parity rate (2 vs. 3, p < 0.001) and higher pregnancy 2-h OGTT (165 vs. 155 mg/dL, p = 0.034), but not with socio-demographic characteristics. Four women (3.7%) had diabetes, 22 (20.4%) had impaired fasting glucose or impaired glucose tolerance. Persistent hyperglycemia was associated with a positive family history of diabetes (relative risk - RR 2.41, p = 0.050), diagnostic 2-h OGTT in pregnancy (RR 1.01, p = 0.045), insulin use during pregnancy (RR 2.37, p = 0.014), and cesarean section (RR 2.61, p = 0.015). Conclusions: Even though postpartum abnormalities were frequent in GDM, rates of postpartum diabetes screening were undesirably low. As no specific clinical profile defines who will adhere to postpartum testing, it is essential to encourage all women to reevaluate their glucose status, particularly those with a family history of diabetes and more severe hyperglycemia. Arq Bras Endocrinol Metab. 2014;58(2):197-204 .

Objetivos: Os objetivos foram estimar a taxa de reavaliação de diabetes pós-parto em mulheres com diabetes melito gestacional (DMG) e identificar fatores associados ao retorno e à persistência das alterações glicêmicas. Sujeitos e métodos: Coorte prospectiva de mulheres com DMG atendidas em ambulatório de pré-natal especializado, de novembro de 2009 a maio de 2012. Todas foram orientadas a agendar o teste oral de tolerância à glicose (TOTG) a partir da sexta semana pós-parto. Resultados: Das 209 mulheres arroladas na gestação, 108 (51,7%) foram avaliadas após o parto: 14 com glicemia de jejum, 93 com o TOTG e uma com glicemia ao acaso. O retorno para reavaliação foi associado com menor paridade (2 vs. 3, p < 0,001) e com glicemia de 2-h mais elevada no TOTG diagnóstico (165 vs. 155 mg/dL, p = 0,034). Diabetes foi diagnosticado em quatro mulheres (3,7%) e pré-diabetes em 22 (20,4%). Análise multivariada evidenciou que a história familiar de diabetes (risco relativo – RR 2,41, p = 0,050), a glicemia de 2 horas no TOTG da gestação (RR 1,01, p = 0,045), o uso de insulina na gestação (RR 2,37, p = 0,014) e a taxa de cesariana (RR 2,61, p = 0,015) foram os fatores associados à persistência da hiperglicemia. Conclusões: O retorno para reavaliação foi baixo, embora as alterações glicêmicas tenham sido frequentes. Como não houve fatores que indiquem quais mulheres retornarão, estratégias para aumentar a adesão são necessárias, especialmente quando há história familiar ou o DMG foi mais grave. Arq Bras Endocrinol Metab. 2014;58(2):197-204 .

Glicemia de jejum do primeiro trimestre e fatores de risco de gestantes com diagnóstico de diabetes melito gestacional / First trimester fasting glycemia and risk factors of pregnant women diagnosed with gestational diabetes mellitus

OBJETIVO: Avaliar a incidência de repercussões materno-fetais e controle glicêmico em gestantes com diagnóstico de Diabetes Melito Gestacional (DMG) tendo como corte a glicemia de jejum de 85 mg/dL no primeiro trimestre e correlacionar com fatores de risco. MÉTODOS: Foram revisados os prontuários das gestantes acompanhadas no ambulatório de Pré-Natal de Alto Risco (PNAR) no período de janeiro de 2011 a março de 2012 e selecionadas aquelas com diagnóstico de DMG para contato e verificação do cartão de pré-natal. Foram colhidos dados de idade, paridade, glicemia de jejum do primeiro trimestre, valor do Teste Oral de Tolerância à Glicose (TOTG), Índice de Massa Corpórea (IMC), via de parto, forma de controle, repercussões fetais e fatores de risco para DMG. A análise estatística foi realizada no software PSPP 0.6.2 e consistiu de análise descritiva de frequências, teste do χ2 para variáveis categóricas, teste t de Student para amostras independentes e teste de Pearson para as correlações com nível de significância de 5%. RESULTADOS: Das 408 gestantes atendidas, 105 tinham diagnóstico de Diabetes Melito Gestacional (DMG) e 71 tinham prontuários completos ou responderam ao contato para fornecer as informações faltantes. No grupo DMG-jejum <85, (com glicemia de jejum <85 mg/dL na primeira consulta no primeiro trimestre) foram incluídas 29 gestantes (40,8%) e no grupo DMG-jejum>85 (glicemia de jejum >85 mg/dL na primeira consulta, no primeiro trimestre) 42 gestantes (59,1%). Observou-se que poucas pacientes (5 no grupo DMG-jejum <85 e 3 no grupo DMG-jejum>85) não apresentavam fatores de risco para DMG. Houve maior frequência da necessidade de controle com insulina nas pacientes do grupo DMG-jejum >85. Não houve diferença significativa quanto às repercussões fetais e via de parto entre os grupos. CONCLUSÃO: A glicemia de jejum do primeiro trimestre, tendo como ponto de corte o valor 85 mg/dL, isoladamente, ou associado a fatores de risco, não seria bom preditor isolado de repercussões materno-fetais do DMG.

PURPOSE: To evaluate the incidence of maternal and fetal repercussions and glycemic control in women with Gestational Diabetes Mellitus (GDM) using a fasting glucose of 85 mg/dL in the first trimester as a cut-off point and to correlate it with risk factors. METHODS: The medical records of pregnant women followed in the outpatient antenatal high-risk service (PNAR) of HRAN from January 2011 to March 2012 were reviewed and those women diagnosed with GDM were selected for contact and for prenatal card verification. We collected data of age, parity, fasting glucose during the first quarter, the value of the Oral Glucose Tolerance Test (OGTT), Body Mass Index (BMI), mode of delivery, form of control, effects and fetal risk factors for GDM. Statistical analysis was performed using the PSPP 0.6.2 software and consisted of descriptive analysis of frequencies, χ2 test for categorical variables, Student's t-test for independent samples, and Pearson test for correlations, with the level of significance set at 5%. RESULTS: From 408 pregnant women enrolled, 105 were diagnosed with GDM and 71 had complete records or answered to the contact in order to provide the missing information. The GDM-fasting <85 (fasting glucose <85 mg/dL at the first prenatal visit, in the first trimester) group consisted of 29 (40.8%) women and the GDM-fasting >85 (fasting glucose >85 mg/dL at the first prenatal visit, in the first trimester) consisted of 42 (59.1%) women. It was observed that few patients (five in the GDM-fasting <85 group and three in the GDM-fasting >85 group) had no risk factors for GDM. There was a major need for control with insulin in patients of the GDM-fasting >85 group. There was no significant difference related to fetal impact or mode of delivery between the groups. CONCLUSIONS: The first trimester fasting glycemia, with a cut-off value of 85 mg/dL alone or associated with risk factors, does not seem to be a good single predictor of the maternal-fetal effects of GDM.

Tumor estromal esclerosante de ovário associado à síndrome de Meigs e gestação: relato de caso / Sclerosing stromal tumor of the ovary associated with a Meigs' syndrome and pregnancy: a case report

O tumor estromal esclerosante de ovário é uma neoplasia benigna extremamente rara, mais frequente em mulheres jovens e sem sintomas específicos na maioria dos casos. Menos de 150 casos foram descritos, dos quais 8 diagnosticados durante a gestação. Neste relato, documentamos a associação entre tumor estromal esclerosante de ovário, síndrome de Meigs e elevação dos níveis de CA-125 em gravidez a termo.

The sclerosing stromal tumor of the ovary is an extremely rare benign tumor more common in young women and without specific symptoms in most cases. Less than 150 cases have been described, of which 8 were diagnosed during pregnancy. In this report, we describe the association between sclerosing stromal tumor of the ovary, Meigs' syndrome and elevated levels of CA-125 in term pregnancy.