Digit Ratio (2D:4D) in Newborns: Influences of Prenatal Testosterone and Maternal Environment

Introduction: The 2D:4D digit ratio is sexually-dimorphic, probably due to testosterone action through the perinatal period. We characterize the 2D:4D ratio in newborn (NB) infants, in between the pre- and postnatal surges of testosterone, and relate it to the mother's 2D:4D and to testosterone levels in the amniotic fluid (AF). Subjects and methods: Testosterone was assayed in samples of maternal plasma and AF collected at amniocentesis. Shortly after birth, 106 NBs and their mothers were measured for 2D:4D ratio. Results: NB males had lower mean 2D:4D ratios than females but this dimorphism was significant only for the left hand (males: 0.927; females: 0.950; p=0.004). Mothers who had sons had lower 2D:4D ratios than those who had daughters and the mother's 2D:4D were higher than those of NBs regardless of sex. Both hands of NB females were negatively correlated with AF testosterone and positively correlated with the mother's 2D:4D, but males showed no significant associations. Maternal plasma testosterone also showed a negative weak correlation with NB's digit ratio in both sexes. Conclusions: Sexual dimorphism at birth was only significant for the left hand, in contrast with reports of greater right hand dimorphism, suggesting that postnatal testosterone is determinant for 2D:4D stabilization. The lower 2D:4D ratios in mothers who had sons support claims that hormone levels in parents are influential for determining their children's sex. NB female's digit ratio, but not males', was associated to the level of AF testosterone. The mother's 2D:4D ratios were positively correlated with their daughters' 2D:4D, but the same was not observed for male NBs, suggesting that prenatal testosterone levels in male fetus lead their 2D:4D ratios to stray from their mothers' with high individual variability.

Confined Placental Mosaicism in Chorionic Vilus Sampling - Case Report

Objectives: Chorionic Vilus Sampling (CVS) has several advantages over amniocentesis: it may be performed at an earlier gestational age, the results are quicker to obtain and there’s a lower miscarriage risk – 1%. However, the higher prevalence of discrepant fetal and vilus sampling material’s karyotype findings is a disadvantage of this technique – 0.5%. This is caused, amongst other causes, by placental mosaicism which consists of two genetically different cell lines. There are three types of placental mosaicism according to the abnormal cell line location: Type I – in the cytotrophoblast; Type II – in the vilus’ stroma; Type III – in both the above locations. Material and Methods: We present a case report about a 36-year-old pregnant woman going through our Department’s 1st trimester combined screening program; a CVS was performed, which showed Confined Placental Mosaicism (CPM). Results and Conclusion: Although the pregnant woman was in the low-risk group for aneuploidy, the patient wanted the cytogenetic study to be performed in order to reduce maternal anxiety. CVS was performed at the gestational age of 12 weeks + 5 days and the karyotype was 47XY+2/46XY. For the correct interpretation of this data an amniocentesis was performed at the gestational age of 15 weeks + 6 days, which showed a 46XY karyotype. We therefore conclude that the cytogenetic analysis of the CVS was the result of a CPM. A careful follow-up including fetal echocardiogram and seriated ultrasonographic monitoring was used to safely exclude malformations and fetal growth restriction. We verified no occurences throughout pregnancy, delivery and perinatal period. CVS practice was recently implemented in our country and has many advantages over amniocentesis. Besides the fact that an earlier gestational age usually means less affective bonding to the fetus and therefore makes medical termination of pregnancy somewhat less difficult, one should consider specific situations like the one reported in which CPM may be diagnosed. This condition is associated with increased risk of fetal growth restriction, so the clinician should be aware of the need for a more careful follow-up, since perinatal complications, which should be anticipated and treated, can be expected in 16-21% of these cases.

Perinatal Care in Portugal: Effects of 15 Years of a Regionalized System

AIM: To share information on the organization of perinatal care in Portugal. METHODS: Data were derived from the Programme of the National Committee for Mother and Child Health 1989, National Institute for Statistics, and Eurostat. RESULTS: In 1989, perinatal care in Portugal was reformed: the closure was proposed of maternity units with less than 1500 deliveries per year; hospitals were classified as level I (no deliveries), II (low-risk deliveries, intermediate care units) or III (high-risk deliveries, intensive care units), and functional coordinating units responsible for liaison between local health centres and hospitals were established. A nationwide system of neonatal transport began in 1987, and in 1990 postgraduate courses on neonatology were initiated. With this reform, in-hospital deliveries increased from 74% before the reform to 99% after. Maternal death rate decreased from 9.2/100,000 deliveries in 1989 to 5.3 in 2003 and, in the same period, the perinatal mortality rate decreased from 16.4 to 6.6/1000 (live births + stillborn with > or = 22 wk gestational age), the neonatal mortality rate decreased from 8.1 to 2.7/1000 live births, and the infant mortality rate from 12.2/1000 live births to 4/1000. CONCLUSION: Regionalization of perinatal care and neonatal transport are key factors for a successful perinatal health system.

Resultado do Obstétrico de Gravidezes Gemelares Resultantes de Fecundação in Vitro, Microinjeção e Estimulação da Ovulação em Comparação com Espontâneas

Introduction: Uncontrolled studies suggest that twins conceived by in vitro fertilization have increased rates of preterm birth and low birth weight and would warrant increased antenatal monitoring. The objective of this study was to compare the obstetric outcome of twin pregnancies conceived by in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) and ovulation induction with those conceived spontaneously. Methods: All twin deliveries achieved by IVF/ICSI (n=235) and ovulation induction (n=68) from September 1994 through December 2010 were evaluated. Both groups and an additional control group who conceived spontaneously (n=997) and was delivered during the same time period were compared with each other. Results: In univariate analysis, patients who conceived with the assistance of IVF/ICSI had a significantly higher risk of being older (p=0.01), nulliparous (p=0.01), having hypertensive disorders (p=0.012), gestational diabetes mellitus (p=0.031), cesarean section (p=0.008) and lower gestational age at birth, compared with the control group. Newborns had similar birthweights in all groups (2229±544g; 2102±619g; 2251±553g). Spontaneous pregnancies had a higher risk of being monochorionic 38.4% versus 16.2% and 10.2% (p=0.01). Multivariate analysis however showed that patients who conceived with the assistance of IVF/ICSI only had a higher risk of gestational diabetes (OR=1.91,95%CI 1.168-3.120; p=0.01). Conclusions: Our study shows that twin pregnancies conceived with the assistance of IVF/ICSI had a higher risk of gestacional diabetes and a lower gestacional age at birth. Birthweights were similar, as was the incidence of perinatal death, low birth weight infants, and congenital malformations.

A Mortalidade Perinatal na Maternidade Dr. Alfredo da Costa em 1999

Os autores avaliam a mortalidade perinatal no ano de 1999, na Maternidade Dr. Alfredo da Costa, utilizando a metodologia proposta por Wigglesworth. Procuram identificar os factores com ela associados no sentido de reduzir as causas evitáveis.

Epilepsy and Cerebral Palsy: Characteristics and Trends in Children Born in 1976 - 1998

Background: Although epilepsy is common in children with cerebral palsy (CP), no data exists on prevalence rates of CP and epilepsy. Aims: To describe epilepsy in children with CP, and to examine the association between epilepsy and neonatal characteristics, associated impairments and CP subtypes. Methods: Data on 9654 children with CP born between 1976 and 1998 and registered in 17 European registers belonging to the SCPE network (Surveillance of Cerebral Palsy in Europe)were analyzed. Results: A total of 3424 (35%) children had a history of epilepsy. Among them, seventy-two percent were on medication at time of registration. Epilepsy was more frequent in children with a dyskinetic or bilateral spastic type and with other associated impairments. The prevalence of CP with epilepsy was 0.69 (99% CI, 0.66e0.72) per 1000 live births and followed a quadratic trend with an increase from 1976 to 1983 and a decrease afterwards. Neonatal characteristics independently associated with epilepsy were the presence of a brain malformation or a syndrome, a term or moderately preterm birth compared with a very premature birth, and signs of perinatal distress including neonatal seizures, neonatal ventilation and admission to a neonatal care unit. Conclusions: The prevalence of CP with epilepsy followed a quadratic trend in 1976e1998 and mirrored that of the prevalence of CP during this period. The observed relationship between epilepsy and associated impairments was expected; however it requires longitudinal studies to be better understood.

Encefalopatia Hipóxico-Isquémica por Asfixia Perinatal: Evolução a Curto e Longo Prazo

Introdução: A encefalopatia hipoxico-isquémica (EHI) é uma causa importante de mortalidade e morbilidade a longo prazo. Estima-se que anualmente ocorram 1 a 8 casos /1000 nascimentos. A asfixia perinatal mantida é a causa mais frequente de EHI. Objectivo: Avaliar a evolução a curto e longo prazo de crianças com EHI devido a asfixia perinatal. Metodologia: Estudo prospectivo histórico. População: Recém-nascidos (RN) consecutivos, nascidos na maternidade do HDE, com idade gestacional ≥ 37 semanas, admitidos na UCIN com os diagnósticos de EHI e asfixia perinatal, sem anomalias congénitas major. Período: 04/04/2001 – 31/12/2010. Variáveis: morbilidade, sobrevivência e sequelas. Covariáveis: peso ao nascer, idade gestacional, índice de Apgar, eventos peri-parto e tipo de parto. Resultados: Dos 19365 nados-vivos (NV), foram incluídos 28 RN (incidência 1,4/1000). Características da amostra: 68 % do sexo masculino; peso médio ao nascer 3180 g, mediana da idade gestacional 39,4 semanas. Índice de Apgar: moda ao 1º, 5º e 10º minuto, respectivamente 2, 5 e 7. Eventos peri-parto mais frequentes: líquido amniótico meconial (46,4%), alterações cardiotocográficas (50%) e circular cervical apertada (10,7%). Em 67,8% dos casos, foi realizada cesariana de emergência. Todos os RN necessitaram de manobras de reanimação. Desenvolveram EHI: ligeira 12 (42,9%), moderada 7 (25%) e grave 9 (32,1%). Ocorreram convulsões em 66% dos RN e disfunção multiorgânica em 12 RN (42,9%). Dos exames de imagem, a ecografia transfontanelar (ECOTF) foi realizada em 89,3% dos casos, o electroencefalograma (EEG) em 67,9% e a RMN em 32,1%. A ECOTF revelou alterações sugestivas de EHI em todos os casos; o EEG evidenciou anomalia da actividade eléctrica em 73,7% e a RMN revelou achados compatíveis com EHI em 100%. Houve 3 óbitos. Dos sobreviventes, 75% foram seguidos em consulta hospitalar, apresentando como sequelas graves paralisia cerebral (22,2%), atraso global do desenvolvimento (16,6%), epilepsia (11,1%), surdez neurossensorial (5,6%) e hemiparésia (5,6%). Conclusões: A incidência de EHI por asfixia foi 1,4/1000 NV. Verificou-se EHI ligeira em 42,8% dos casos. A mortalidade foi de 14,3%. Nos 18 casos seguidos, 38,9% não apresentavam sequelas ou tinham sequelas ligeiras. Apenas um caso foi submetido a hipotermia, sendo esta uma terapêutica promissora.

Perinatal Bacterial Infection: Screenning of Vertical Transmitted Infections

Perinatal bacterial infection may be caused by any microorganism colonizing the vaginal tract. Neonatologists and paediatricians are especially concerned about group B Stretpococcus (GBS). However, Enterobactereacea, mainly E.coli and Proteus, are also responsible for infection. GBS screening may be accomplished in over 90% of pregnant women. In our maternity in 2007-2008, 85% of the mothers had been screened. Screening and prophylaxis were responsible for a decreasing incidence of neonatal infection - from 0.6/1000 to 0.15/1000 live births in Portugal, from 2002 to 2007. However there are some difficulties related to screening. In the second Portuguese study 16/57 NB with early-onset infection (28%) were born to “negative” mothers. Several factors illustrate how difficult is to draw national screening policies: a wide range of carrier’s state rate throughout a country - in Portugal from 12% to 30%. The success of any screening policy may also be affected by additional technical and organizational problems. In countries where home delivery is a tradition or a trend intrapartum GBS prophylaxis requires a very well organized assistance.. Moreover factors usually accepted as protective are not so effective. In the Portuguese study 24/57 infected newborns (42%) were delivery by caesarean section. Another subject deals with the workload in the postnatal ward generated by deficient compliance to the guidelines a problem not confirm by a study of our group. Decreasing the importance of GBS, highlight the importance of E. coli in perinatal infection. From the 16 340 registrations of the National Registry 1676 were newborns with mother-related infection. Applying the same reasoning to E.coli as to GBS and Listeria monocytogenes – that is considering all of them are of maternal origin - 6.7% of these infections were due to E. coli, 4.6% to SGB and 0.5% to Listeria monocytogenes. In conclusion screening and prophylaxis may be not the best way to prevent all GBS neonatal infections but by now it is the only available procedure. The other bacteria continue to demand a high suspicion level and immediate intervention.

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.

Induced Labor– Is There an Increased Risk of Perinatal Infection?

Objectives: To assess induced labor-associated perinatal infection risk at Hospital D.Estefânia from January to June of 2010 at Hospital de D. Estefânia’s delivery rooms, reviewing the indications for inducing labor as well as the techniques used. Material and Methods: Performing an historical prospective study searching the clinical processes as well as the mother and newborn’s computer database from January to June of 2010. An exposed and an unexposed group were created; the first group comprises pregnant women and their newborns whose labor was induced. The unexposed group is constituted by newborns and pregnant women whose labor was spontaneous. Labor induction was performed using intra-vaginal prostaglandins in women who didn’t start it spontaneously; perinatal infection was defined either clinically or using blood tests. The gestational age was ≥ 37 weeks for both groups. 19 variables were studied for both groups. Results: A total of 190 mother-newborn pairs were included: 55 in the exposed group and 135 in the unexposed group. 3 cases of perinatal infection were reported, two in the exposed group and one in the unexposed group. Preliminary data resulted in a perinatal infection rate of 3.6% in the exposed group and 0.7% in the unexposed group; preliminary data suggest that the risk of perinatal infection may be increased in up to 5-fold when labor is inducted. Conclusions: A larger series of patients and a multivariable analysis using logistic regression are both necessary in order to perform a more thorough assessment of labor induction’s role in perinatal infection risk. One must also try to distinguish labor inducing- and clinical practicesrelated factors.

Regionalización del Cuidado Perinatal en Portugal - Resultados

Lo Servicio Nacional de Salud en Portugal fue criado en 1979, universal e gratis. Las primeras UCIN surgieran en 1980, en 1985 fue criada la Sociedad Portuguesa de Neonatología, en 1987 lo sistema de transporte neonatal, en mismo año fue nominada una Comisión de Peritos en Perinatología. En 1989 fue nominado el Comité Nacional de la Mujer y del niño y empezó la Reforma de los cuidados de salud perinatal. Era un programa de 9 años en etapas de 3 años que incluía el ccierre de Hospitales con menos de 1500 partos/año, categorización de los hospitales en niveles de cuidados e la creación de Unidades Coordinadoras entre Centros de Salud y Hospitales. Las UCIN y Intermedios neonatales fueran equipados y definido el número necesario de obstetras, pediatras y enfermeras e fue hecha formación en Cuidados Intensivos Neonatales. Los Centros de Salud no tienen partos e controlan el embarazo normal; los hospitales Nivel I no tienen partos; los de Nivel II tienen partos normales y de bajo riesgo, por lo menos 1500/año, obstetras, Unidad de Cuidados Intermedios, Pediatras con formación en neonatología, ventilación por períodos cortos. Los Hospitales de Nivel III tienen partos de bajo y alto riesgo, obstetras y neonatólogos, UCIN, formación en obstetricia y neonatología e investigación. Las UCIN tienen ventilación de longa duración, nutrición parenteral, cuidados de recién nacidos con menos de 1500g, condiciones quirúrgicas, son centros de enseñanza e investigación. Deben tener neonatólogos y pediatras con competencia en neonatología 24h por día, 1.5 camas /1000 partos, 1 enfermera para 2 logares de intensivos – 2,5 enfermeras por cada cama de intensivos - deben estar localizadas en maternidades con >3000 partos. Hay también reglas para translado para nível III pré-natal y pós-natal. Lo impacto fue que la tasa de partos hospitalares aumentó hasta 99% la mortalidad fetal e fetal tardia disminuiu hasta 3,7 e 2,5/1000 NV+MN, la mortalidad perinatal con más de 28 semanas para 4,6/1000 NV+ MN, la neonatal para 2,4/1000NV e la infantil para 3,6. Las mejores condiciones socioeconómicas y nivel de educación pueden justificar parte de estos resultados pero la organización de los cuidado perinatales fue ciertamente una grande razón de mejoría.

Why and How Was Regionalization of Perinatal Care Accomplished in Portugal?

Portuguese health care system was created in 1979. It is universal and for free. Expenses are supported by the State through taxes. The modern perinatal care system started by the end of 1970. The first neonatal intensive care units were created in 1980, the Portuguese Neonatal Society in 1985 and the National Neonatal Transport System in 1987. Until the seventies of twentieth century and even during eighties there were more than 200 hospitals with deliveries, a great part without obstetrician or paediatrician, a great percentage of pregnancies had no prenatal care, there were few neonatal intensive care units and perinatal mortality rate was one of the highest in the European countries. In 1987 an Experts Committee was nominated by the Health Ministry aiming to collect and analyse data on perinatal care and to suggest improvements. The Report resulting from this work is the main document on which is based the reform. The reform was a 9 years program in 3 years stages aiming to close hospitals with less than 1500 deliveries/year, to reclassify hospitals, to create Coordinating Units between health centres and hospitals, to equip neonatal intensive and intermediate care units, to define needs of obstetricians, paediatricians and nurses for each centre and to promote specialised training in neonatology for paediatricians and nurses. Levels of perinatal care were defined as well as localization of each level of hospital according to the number of deliveries in one geographic area, geographic difficulties and existing routes and connections. Steps for opening and closure of different levels of hospitals were very well programmed. The organization, capacities, number of obstetricians, neonatologists and nurses as well as equipment for each level of care was defined. Rules for pregnant women and newborns transfer from level II to level III hospitals were also well described. A specific training is neonatology was created starting in 1990. This organization resulted in an impressive decrease in mortality rates at all levels and still it is the policy we have today.

Perinatal Outcome and Change in Body Mass Index in Mothers of Dichorionic Twins: a Longitudinal Cohort Study

We used a prospective cohort to analyze the effect of change in BMI rather than change in weight, in mothers carrying dichorionic twins from a population that did not receive any dietary intervention. A total of 269 mothers (150 nulliparas and 119 multiparas) were evaluated. The average change (%) from the pre-gravid BMI was 7.2+/-6.1, 17.4+/-8.2, and 28.7+/-10.8, at 12-14, 22-25, and 30-34 weeks, respectively, without difference between nulliparas and multiparas. The comparison between maternities below or above the average change from the pregravid BMI failed to demonstrate an advantage (in terms of total twin birthweight and gestational age) of an above average change from the pregravid BMI, even when the lower versus upper quartiles were compared. Our observations reached different conclusions regarding the recommended universal dietary intervention in twin gestations. A cautious approach is advocated towards seemingly harmless excess weight gain, as normal weight women may turn overweight, or even obese, by the end of pregnancy, and be exposed to the untoward effects of obesity on future health and body image.

Late Stillbirth: a Ten Year Cohort Study

Introduction: Late fetal death is a desolating event that inspite the effort to implement new surveillance protocols in perinatal continues to defy our clinical pratice. Objective: To examine etiological factors contributing to main causes and conditions associated with fetal death in late pregnancies over a 10-year period. Methods: Retrospective cohort analysis of 208 late singleton stillbirth delived in a tertiary-perinatal referral maternity over a 10-year period. Clinical charts, laboratory data and feto-placental pathology findings were systematically reviewed. Results: The incidence of late fetal demise was 3.5 per 1000 pregnancies. No significant trend in the incidence of stillbirth was demonstrated during the study period. Stillbirth was intrapartum in 12 (5.8%) cases and 72 (35%) were term pregnancies. Fourteen percent of cases were undersurveilled pregnancies. Mean gestacional age at diagnosis was 34 weeks. The primary cause of death was fetal, it was present in 59 cases, 25% were considered small for gestational age. Stillbirths were unexplained in 24.5% of cases. Maternal medical disorders were identified in 21%. Hypertensive disorders were frequent and associated with early gestacional age (p = 0.028). Conclusion: There was no change in the incidence of late stillbirth during the 10 years under evaluation. The incidence was 3.5 ‰ which was identical to that described in developed countries. About one quarter of the stillbirths was unexplained. The most frequent maternal pathology was chronic hypertension.

Incontinentia Pigmenti in the Neonatal Period

Incontinentia pigmenti (IP) is a rare multisystem disease, X linked dominant disorder. As all X linked dominant diseases, it is usually male-lethal. Female newborn admitted to the neonatal intensive care unit on the fi rst day of life was diagnosed as having probable herpetic infection with vesicular skin lesions distributed on upper right limb and inferior limbs. Family history showed that her 22-year-old mother had hypopigmented lesions on the lower limbs and her 13-month-old sister had hyperpigmented lesions on the trunk and limbs. In newborns, herpes infection emerges as the principal diagnosis of vesicular rash, due to the importance of precocious diagnosis and treatment. Other hypothesis must be considered in a newborn with vesicobullous rash, such as IP.