Perinatal Death: Epidemiology and Etiology

Perinatal mortality rate is an important mark to evaluate women and perinatal health care. It is of utmost importance to know causes and the evolution of its two components aiming to improve health care in different fields – sanitary conditions, diagnosis and treatment of infectious disease, immunisations, diagnosing and caring for medical diseases induced by pregnancy or directly related to it, providing skilled birth attendance, preventing birth asphyxia, preventing preterm birth complications and infections. In high-income countries the epidemiology varies mainly with social and economic conditions; in low-income countries, paired with poverty, undernutrition, superstition, lack of medical care, deficient basic sanitary conditions are also found. Also, in rich countries, responsible for 1% of deaths, data are published and improvements evaluated, while in low-income countries responsible for 99% of deaths numbers and causes are unknown, making difficult to implement cost effective interventions, a reason why “stillbirth rates in low-income countries are now where they were in high-income countries 50 to 100 years ago”. Knowledge on causes of death are very important as often what is needed are “simple” measures as improvement of sanitary conditions and immunisation programmes rather than high technologies. About four million babies dye each year in the first 28 days of life and another 3 million dye before birth in the third-trimester, with 98% occurring in low-income and middle income countries and more than 1 million occurring during labour and delivery. Classically stillbirths are the major component of perinatal mortality rate. Causes of death are even more difficult to know. In low-income countries a great proportion of women give birth at home. Worldwide the main causes of stillbirth are asphyxia due to obstructed labour, eclampsia, abruption placenta and umbilical cord complications - making valid the assumption that skilled birth attendance would decrease stillbirth; and infection - chorioamnioitis, syphilis and malaria. In high-income countries placental pathology and infection, congenital anomalies, complications of preterm birth and post term delivery, are the most common. If in low-income countries famine and lack of provisions and health care are common, in high-income countries, advanced maternal age and diabetes, obesity, hypertension, smoking, are frequent findings.

Transmissão do vírus citomegálico através do aleitamento materno em prematuros

RESUMO: Nas últimas quatro décadas, desenvolveram-se vários estudos, dispersos por todo o mundo, visando analisar a importância da transmissão perinatal do CMV pelo leite materno, nos recém-nascidos prematuros e de baixo peso à nascença. Comparando estes estudos, as taxas de incidência de infecção e doença são extremamente variáveis, não havendo consenso entre os autores. Surgiu, assim, a necessidade de realizar a presente dissertação, pioneira ao nível nacional, com o objectivo de determinar a incidência da infecção perinatal citomegálica, transmitida através do aleitamento materno a recémnascidos prematuros, e identificar as suas consequências clínicas. Para a elaboração deste trabalho foram seleccionados todos os recém-nascidos com idade gestacional inferior a 35 semanas e respectivas mães seropositivas para CMV, internados na Unidade de Cuidados Intensivos de Neonatalogia do Hospital de São Francisco Xavier, entre o período de 1 de Outubro de 2010 e 31 Julho de 2011. Foram analisadas as urinas dos recém-nascidos e o leite materno das mães na primeira, sexta e décima segunda semana pós-parto, utilizando a técnica de Nested-PCR e, posteriormente, a PCR em Tempo Real, para determinar a carga viral do leite materno. Constatou-se que a aquisição da infecção perinatal de CMV no recém-nascido prematuro ocorre com alguma frequência (40,5%), sendo muito provável que a via de transmissão em 38,1% destes casos seja o leite materno infectado, não devendo esta ser desvalorizada. Relativamente às consequências clínicas, não foram observadas alterações clínico-laboratoriais associadas à infecção citomegálica. Analisando os factores que condicionam a transmissão da infecção citomegálica perinatal, estabeleceu-se uma correlação entre a carga viral do leite materno e a transmissão do vírus, permitindo deduzir que quanto maior a carga viral, maior o risco de transmissão. Finalmente, os resultados obtidos sugerem que o risco de transmissão da infecção e suas consequências clínicas não justificam a contra-indicação da amamentação, pois esta comporta, também, elevados benefícios. ----------------ABSTRACT: In the last four decades, several studies were developed all over the world to analyze the importance of CMV perinatal transmission through mother´s milk in the preterm and low birthweight newborns. Comparing these studies, the infection and disease incidence rates are extremely variable, without agreement between the authors. The aim of this study, the first of the kind made in Portugal, is to define the rate of perinatal cytomegalovirus infection in preterm newborns via breastfeeding and its clinical consequences. All the newborns with gestational age below 35 weeks and their CMV seropositive mothers, admitted between the October 1, 2010 and July 31, 2011 in the Neonatology Intensive Care Unit of the São Francisco Xavier Hospital, were included in this study. Human breast milk and urine specimens were collected from mothers and their preterms infants around the 1st, 6th and 12th week after delivery and analyzed by Nested-PCR. The PCR in Real Time was used to determine the breast milk viral load. It was found that the CMV perinatal infection in preterm infants occurs in 40,5% of the cases and most likely 38,1% of these were infected via breastmilk and therefore this should not be overlooked. Considering the clinical consequences, no clinical and laboratory changes associated with cytomegalovirus infection were observed. Analyzing the factors that determine the perinatal transmission of the cytomegalovirus, it was established a correlation between breast milk viral load and viral transmission, allowing to conclude that the higher the viral load the greater the risk of transmission. Finally, the obtained results suggest that the risk of CMV infection and its clinical consequences don´t justify the breastfeeding contraindication because it also provides high benefits.

Sinergia em Investigação Clínica: Mais do Que a Soma das Partes

A propósito do estudo “Early high calcium and phosphorus intake by parenteral nutrition prevents short-term bone strength decline in preterm infants”, de colaboração entre a UCIN do HDE, os Serviços Farmacêuticos do HDE e estudantes da Licenciatura de Dietética e Nutrição da ESTeSL, foi realçada a vantagem da sinergia multiprofissional multicêntrica em investigação clínica: a investigação foi possível sem depender de financiamento, dado que o dispendioso equipamento de ultrassonografia quantitativa pertence à ESTeSL; a UCIN beneficiou de investigação com a colaboração de investigadores externos (estudantes ESTeSL) dedicados em exclusividade ao projecto; estes, por sua vez, beneficiaram da aprendizagem em investigação de qualidade; o estudo ao ser publicado em revista internacional indexada (J Pediatr Gastroenterol Nutr.), proporcionou o enriquecimento curricular às instituições (HDE e ESTeSL) e aos investigadores (estudantes, médicos e farmacêutica) envolvidos.

Valores de Referência de Robustez Óssea: Avaliados Próximo ao Nascimento por Ultrassonografia Quantitativa em Recém-Nascidos de Termo e Pré-Termo

Objectivo: Estabelecer valores de referência da robustez óssea nos primeiros dias de vida, em recém-nascidos de termo e pré-termo adequados para a idade de gestação nascidos em Portugal. Métodos: Foi medida a velocidade do som (VdS) (m/s) por ultrassonografia quantitativa, numa amostra sistemática de recém-nascidos adequados para a idade de gestação, de termo e pré-termo, respectivamente nos primeiros dois e cinco dias após o nascimento. Foi avaliada a homogeneidade de valores entre géneros e entre grupos de idade de gestação. Resultados: A amostra constou de 158 recém-nascidos, 34 de termo e 124 pré-termo (idade de gestação entre 26 a 41 semanas), com peso de nascimento de 595 g a 4195 g, 84 do sexo masculino (53,2%) e 20 gémeos (10,8%). A média da VdS aumenta significativamente com a idade de gestação. São providenciados valores de referência da VdS para os percentis 10, 25, 50, 75 e 90, para grupos de idade de gestação, sem distinção para o género. Conclusão: São disponibilizados valores de referência de VdS nos primeiros dias de vida, de recém-nascidos adequados para a idade de gestação, de termo e pré-termo, nascidos em Portugal. Estes valores reflectem a robustez óssea intrauterina e servem de referência basal para estudos evolutivos realizados em Portugal.

Prospective Risk of Intrauterine Death of Monochorionic-Diamniotic Twins

OBJECTIVE: The purpose of this study was to calculate the prospective risk of fetal death in monochorionic-diamniotic twins. STUDY DESIGN: We evaluated 193 monochorionic diamniotic twin pregnancies that were followed and delivered after 24 weeks. Surveillance included cardiotocography and sonography performed at least once weekly. The prospective risk of fetal death was calculated as the total number of deaths at the beginning of the gestational period divided by the number of continuing pregnancies at or beyond that period. RESULTS: The fetal death rate was 5 of 193 pregnancies (2.6%; 95% CI, 1.1, 5.9); the prospective risk of stillbirth per pregnancy after 32 weeks of gestation was 1.2% (95% CI, 0.3% - 4.2%). CONCLUSION: Under intensive surveillance, the prospective risk of fetal death in monochorionic-diamniotic pregnancies after 32 weeks of gestation is much lower than reported and does not support a policy of elective preterm delivery.

Transmissão do Citomegalovírus no Leite Materno nos Recém-Nascidos Pré-Termos ou Muito Baixo Peso

A infecção pós-natal a citomegalovírus (CMV) nos recém-nascidos pré termos (RNPT) ou muito baixo peso (MBP) pode cursar com doença grave. Para avaliar a transmissão do CMV no leite materno, no RNPT ou MBP, a infecção e o prognóstico a longo prazo, efectuamos uma pesquisa online no motor de busca OVID (consultando a Pubmed, Medline e a Medscape) de Janeiro de 1982 a Agosto de 2011. Os estudos que incluíam a infecção congénita foram excluídos. Incluímos cerca de 30 estudos para análise. A taxa de infecção materna assintomática é elevada (média 81%) e a transmissão do CMV no LM varia entre 66-97,2% das mães CMV-IgC positivas com subsequente positividade nos RN entre 5.7 – 58.6%. Sendo as taxas de infecção sintomática (0-34,5%) e/ou de doença grave (0-13,8%) muito variáveis de estudo para estudo. A longo prazo pode cursar com perturbações do neurodesenvolvimento e morbilidade importantes, sem compromisso auditivo. Em relação à inactivação do CMV pode-se optar por pasteurizar ou congelar o LM, com eficácia/benefício/custo variável. As recomendações actuais são variáveis e pouco directivas, deixando nalguns casos ao critério individual.

Food Allergy and Anaphylaxis in Infants and Preschool-Age Children

Food allergy (FA) prevalence data in infants and preschool-age children are sparse, and proposed risk factors lack confirmation. In this study, 19 children’s day care centers (DCC) from 2 main Portuguese cities were selected after stratification and cluster analysis. An ISAAC’s (International Study of Asthma and Allergies in Childhood) derived health questionnaire was applied to a sample of children attending DCCs. Outcomes were FA parental report and anaphylaxis. Logistic regression was used to explore potential risk factors for reported FA. From the 2228 distributed questionnaires, 1217 were included in the analysis (54.6%). Children’s median age was 3.5 years, and 10.8% were described as ever having had FA. Current FA was reported in 5.7%. Three (0.2%) reports compatible with anaphylaxis were identified. Reported parental history of FA, personal history of atopic dermatitis, and preterm birth increased the odds for reported current FA. A high prevalence of parental-perceived FA in preschool-age children was identified. Risk factor identification may enhance better prevention.

Nutrição Entérica na Criança Nascida Pré-Termo: Revisão do Consenso Nacional

Na presente actualização da recomendação sobre nutrição entérica no recém-nascido pré-termo, da Secção de Neonatologia da Sociedade Portuguesa de Pediatria, é dada especial relevância às necessidades nutricionais do recém-nascido pré-termo, aspetos particulares da nutrição entérica durante o internamento na unidade neonatal, nomeadamente em relação ao momento de iniciar a nutrição entérica, como progredir, modo de administração, especificidades do leite humano pré-termo, sua fortificação, nutrição em situações particulares e nutrição após alta hospitalar. É incluída informação sobre a composição das fórmulas especiais, fortificante e suplemento proteico do leite humano comercializados em Portugal.

Biological and Physiological Markers of Tactile Sensorial Processing in Healthy Newborns

The main objective of this review is to provide a descriptive analysis of the biological and physiological markers of tactile sensorial processing in healthy, full-term newborns. Research articles were selected according to the following study design criteria: (a) tactile stimulation for touch sense as an independent variable; (b) having at least one biological or physiological variable as a dependent variable; and (c) the group of participants were characterized as full-term and healthy newborns; a mixed group of full-term newborns and preterm newborns; or premature newborns with appropriate-weight-for-gestational age and without clinical differences or considered to have a normal, healthy somatosensory system. Studies were then grouped according to the dependent variable type, and only those that met the aforementioned three major criteria were described. Cortisol level, growth measures, and urinary catecholamine, serotonin, and melatonin levels were reported as biological-marker candidates for tactile sensorial processing. Heart rate, body temperature, skin-conductance activity, and vagal reactivity were described as neurovegetative-marker candidates. Somatosensory evoked potentials, somatosensory evoked magnetic fields, and functional neuroimaging data also were included.

Electrohysterogram signal component cataloging with spectral and time-frequency methods

The Electrohysterogram (EHG) is a new instrument for pregnancy monitoring. It measures the uterine muscle electrical signal, which is closely related with uterine contractions. The EHG is described as a viable alternative and a more precise instrument than the currently most widely used method for the description of uterine contractions: the external tocogram. The EHG has also been indicated as a promising tool in the assessment of preterm delivery risk. This work intends to contribute towards the EHG characterization through the inventory of its components which are: • Contractions; • Labor contractions; • Alvarez waves; • Fetal movements; • Long Duration Low Frequency Waves; The instruments used for cataloging were: Spectral Analysis, parametric and non-parametric, energy estimators, time-frequency methods and the tocogram annotated by expert physicians. The EHG and respective tocograms were obtained from the Icelandic 16-electrode Electrohysterogram Database. 288 components were classified. There is not a component database of this type available for consultation. The spectral analysis module and power estimation was added to Uterine Explorer, an EHG analysis software developed in FCT-UNL. The importance of this component database is related to the need to improve the understanding of the EHG which is a relatively complex signal, as well as contributing towards the detection of preterm birth. Preterm birth accounts for 10% of all births and is one of the most relevant obstetric conditions. Despite the technological and scientific advances in perinatal medicine, in developed countries, prematurity is the major cause of neonatal death. Although various risk factors such as previous preterm births, infection, uterine malformations, multiple gestation and short uterine cervix in second trimester, have been associated with this condition, its etiology remains unknown [1][2][3].

Prevention of respiratory syncytial virus infections

Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia), and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.

Characterization of newborns with nonimmune hydrops fetalis admitted to a neonatal intensive care unit

PURPOSE: To determine the incidence and characteristics of nonimmune hydrops fetalis in the newborn population. METHOD: A retrospective study of the period between 1996 and 2000, including all newborns with a prenatal or early neonatal diagnosis of nonimmune hydrops fetalis, based on clinical history, physical examination, and laboratory evaluation. The following were analyzed: prenatal follow-up, delivery type, gender, birth weight, gestational age, presence of perinatal asphyxia, nutritional classification, etiopathic diagnosis, length of hospital stay, mortality, and age at death. RESULTS: A total of 47 newborns with hydrops fetalis (0.42% of live births), 18 (38.3%) with the immune form and 29 (61.7%) with the nonimmune form, were selected for study. The incidence of nonimmune hydrops fetalis was 1 per 414 neonates. Data was obtained from 21 newborns, with the following characteristics: 19 (90.5%) were suspected from prenatal diagnosis, 18 (85.7%) were born by cesarean delivery, 15 (71.4%) were female, and 10 (47.6%) were asphyxiated. The average weight was 2665.9 g, and the average gestational age was 35 3/7 weeks; 14 (66.6%) were preterm; 18 (85.0 %) appropriate delivery time; and 3 (14.3%) were large for gestational age. The etiopathic diagnosis was determined for 62%, which included cardiovascular (19.0%), infectious (9.5%), placental (4.8%), hematologic (4.7%), genitourinary (4.8%), and tumoral causes (4.8%), and there was a combination of causes in 9.5%. The etiology was classified as idiopathic in 38%. The length of hospital stay was 26.6 ± 23.6 days, and the mortality rate was 52.4%. CONCLUSIONS: The establishment of a suitable etiopathic diagnosis associated with prenatal detection of nonimmune hydrops fetalis can be an important step in reducing the neonatal mortality rate from this condition.

Peri-intraventricular hemorrhage in newborns weighing less than 1500 grams: comparative analysis between 2 institutions

PURPOSE: This study aims to characterize the peri-intraventricular hemorrhages in the neonatal period in very low birth weight newborns in 2 institutions that provide neonatal tertiary assistance. METHOD: This was a comparative and observational study in 2 neonatal intensive care units, the Maternity Hospital of Campinas and the "Centro de Atenção Integrada à Saúde da Mulher" of the State University of Campinas, from December 01, 1998 to November 30, 1999. We examined 187 newborns for peri-intraventricular hemorrhages, using transfontanel ultrasound (76 and 11 respectively at the first and second unit), and classified them into 4 grades. We observed their gender, intrauterine growth, weight, and gestational age at birth. RESULTS: We diagnosed 34 cases of peri-intraventricular hemorrhages (13 and 21, respectively), and both groups differed as to the birth weight and the adequacy of weight to the gestational age at birth. There was no difference in the prevalence or extent of peri-intraventricular hemorrhages among cases. There was a statistically significant occurrence of lower birth weight at gestational ages of less than 30 weeks. CONCLUSIONS: The prevalence of peri-intraventricular hemorrhages in our study was compared to that reported in the world literature. Although the cases of the second institution had a smaller mean birth weight, the prevalence of peri-intraventricular hemorrhages was similar to that at the first institution, probably because in the first one, 69% of the gestational ages of the neonates with hemorrhage were less than 30 weeks as compared to 48% in the second one. We stress the importance of the ultrasonographic method for diagnosing peri-intraventricular hemorrhages in very low birth weight newborns.

Autoimmune diseases and pregnancy: analysis of a series of cases

BACKGROUND: An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. METHODS: The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. RESULTS: The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid function over the years and first trimester miscarriage, suffered a second miscarriage despite clinical stability and antibody regression. CONCLUSIONS: As described in literature, the authors found a strong association between autoimmune disease and obstetric complications, especially with systemic lupus erythematosus, antiphospholipid syndrome and autoimmune thyroiditis.