Congenital thyrotoxicosis in premature infants

OBJECTIVES Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex. DESIGN and PATIENTS The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays. RESULTS Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25-36 week) and median B Wt was 1.96 kg (0.50-2.62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1-16 days) and mean age at commencement of treatment was 12 days (7-26 days). Two infants received propylthiouracil and five received a combination of carbimazole and propranolol. Pour became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supplementation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort. CONCLUSIONS This is a large series of extremely small and premature infants with neonatal thyrotoxicosis. Presentation was nonspecific. The diagnosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme law birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recognition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.

Myocardial abnormalities in hypertensive patients with normal and abnormal left ventricular filling: a study of ultrasound tissue characterization and strain

Abnormal left ventricular (LV) filling is common, but not universal, in hypertensive LV hypertrophy (LVH). We sought to elucidate the relative contributions of myocardial structural changes, loading and hypertrophy to LV dysfunction in 113 patients: 85 with hypertensive LVH and 28 controls without LVH and with normal filling. Patients with normal dobutamine stress echocardiography and no history of coronary artery disease were selected, in order to exclude a contribution from ischaemia or scar. Abnormal LV filling was identified in 65 LVH patients, based on Doppler measurement of transmitral filling and annular velocities. All patients underwent grey-scale and colour tissue Doppler imaging from three apical views, which were stored and analysed off line. Integrated backscatter (113) and strain rate imaging were used to detect changes in structure and function; average cyclic variation of 113, strain rate and peak systolic strain were calculated by averaging each segment. Calibrated 113 intensity, corrected for pericardial 113 intensity, was measured in the septum and posterior wall from the parasternal long-axis view. Patients with LVH differed significantly from controls with respect to all backscatter and strain parameters, irrespective of the presence or absence of abnormal LV filling. LVH patients with and without abnormal LV filling differed with regard to age, LV mass and incidence of diabetes mellitus, but also showed significant differences in cyclic variation (P < 0.01), calibrated 113 in the posterior wall (P < 0.05) and strain rate (P < 0.01), although blood pressure, heart rate and LV systolic function were similar. Multivariate logistic regression analysis demonstrated that age, LV mass index and calibrated IB in the posterior wall were independent determinants of abnormal LV filling in patients with LVH. Thus structural and functional abnormalities can be detected in hypertensive patients with LVH with and without abnormal LV filling. In addition to age and LVH, structural (not functional) abnormalities are likely to contribute to abnormal LV filling, and may be an early sign of LV damage. 113 is useful for the detection of myocardial abnormalities in patients with hypertensive LVH.

Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities

Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where the response of the lung to Pseudomonas aeruginosa is exaggerated as a consequence of processes mediated by the product of the CF gene, CFTR. Of importance to any gene-replacement strategy for treatment of CF is the identification of the cell type(s) within the lung milieu that need to be corrected and an indication whether this is sufficient to restore a normal inflammatory response and bacterial clearance. We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages. Following chronic pulmonary infection with P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR showed an improvement in pathogen clearance and inflammatory markers compared with control CF animals. Additionally, these data indicate the general role for epithelial cell-mediated events in the response of the lung to bacterial pathogens and the importance of CFTR in mediating these processes.

Surgical programme at Royal Alexandra Hospital, Sydney, for Papua New Guinea children with congenital heart disease, 1978-1994

Objective : To report the history of the Royal Alexandra Hospital for Children (RAHC) Papua New Guinea (PNG) cardiac surgical programme and describe the selection, preoperative clinical features and postoperative outcome of children with congenital heart disease managed by the programme. Methods : Details for each of the PNG cardiac patients admitted to RAHC following selection by visiting cardiologists between 1978 and 1994 were entered into a database, and analysed and interpreted. Results : A congenital heart defect was confirmed in 165 of the 170 children selected. The male to female ratio was 1:1 and the mean age on admission to RAHC was 5.5 years. Almost all of the children for whom data were available (98%) had a weight for age and 41% had a height for age less than the 3rd centile. One-sixth had delayed milestones. A large number were tachypnoeic, in heart failure, or had pulmonary hypertension on admission. Ventricular septal defect and tetralogy of Fallot were the commonest defects, and lesions such as aortic stenosis, coarctation of the aorta and transposition of the great arteries were absent or rare. Thirty-one (19%) of the children selected initially did not receive surgery because of pulmonary hypertension, or because the lesions did not fall within the programme guidelines for operation. One hundred and twenty-nine children had corrective and four had palliative procedures. Half of the operated children had postoperative complications. Eight children died, all following open-heart procedures, giving a case fatality rate of 6%. Preoperative tachypnoea, hepatomegaly, cardiac failure and pulmonary hypertension were strongly associated with poor outcome. Conclusions : The programme was an arduous exercise for all organizations concerned, but achieved comparatively good short-term outcomes. The experience gained should assist in planning for similar programmes.

Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls

Abnormalities of calcium and vitamin D metabolism in cystic fibrosis (CF) are well documented. We tested the hypothesis that alterations in calcium metabolism are related to vitamin D deficiency, and that bone resorption is increased relative to accretion in patients with CF. Calcitropic hormones, electrolytes, osteocalcin (OC) and bone alkaline phosphatase (BAP), (markers of bone mineralisation), urinary deoxypyridinoline [total (t) Dpd, a marker of bone resorption] and lumbar spine bone mineral density (LS BMD), expressed as a z-score, were measured in 149 (81 M) CF and 141 (61 M) control children aged 5.3-10.99 years, adolescents aged 11-17.99 years and adults aged 18-55.9 years. Data were analysed by multiple regression to adjust for age. In patients, FEV1% predicted and CRP (as disease severity markers), genotype and pancreatic status (PS) were recorded. The distribution of PTH differed between groups (P

Suspected acute toxoplasmosis in pregnant women

OBJECTIVE: To determine the prevalence of reagent serology for suspected acute toxoplasmosis in pregnant women and to describe clinical, laboratory and therapeutic profiles of mothers and their children. METHODS: A retrospective study was conducted with IgM-anti-Toxoplasma gondii-reagent pregnant women and their children who attended the public health system in the state of Paraná, Southern Brazil, from January 2001 to December 2003. Information were obtained from clinical, laboratory (ELISA IgM/IgG) and ultrasonographic data and from interviews with the mothers. To test the homogeneity of the IgM indices in relation to the treatment used, the Pearson's Chi-square test was applied. Comparisons were considered significant at a 5% level. RESULTS: Two hundred and ninety (1.0%) cases of suspected IgM-reagent infection were documented, with a prevalence of 10.7 IgM-reagent women per 1,000 births. Prenatal care started within the first 12 weeks for 214/290; 146/204 were asymptomatic. Frequent complaints included headaches, visual disturbance and myalgia. Ultrasonography revealed abnormalities in 13 of 204 pregnancies. Chemoprophylaxis was administered to 112/227; a single ELISA test supported most decisions to begin treatment. Pregnant women with IgM indices =2.000 tended to be treated more often. Among exposed children, 44/208 were serologically followed up and all were IgG-reagent, and three IgM-reagent cases showed clinical symptoms. CONCLUSIONS: The existence of pregnant women with laboratorially suspected acute toxoplasmosis who were not properly followed up, and of fetuses that were not adequately monitored, shows that basic aspects of the prenatal care are not being systematically observed. There is need of implementing a surveillance system of pregnant women and their children exposed to T. gondii.

Missed opportunities for congenital syphilis and HIV perinatal transmission prevention

OBJECTIVE: To estimate the prevalence of missed opportunities for congenital syphilis and HIV prevention in pregnant women who had access to prenatal care and to assess factors associated to non-testing of these infections. METHODS: Cross-sectional study comprising a randomly selected sample of 2,145 puerperal women who were admitted in maternity hospitals for delivery or curettage and had attended at least one prenatal care visit, in Brazil between 1999 and 2000. No syphilis and/or anti-HIV testing during pregnancy was a marker for missed prevention opportunity. Women who were not tested for either or both were compared to those who had at least one syphilis and one anti-HIV testing performed during pregnancy (reference category). The prevalence of missed prevention opportunity was estimated for each category with 95% confidence intervals. Factors independently associated with missed prevention opportunity were assessed through multinomial logistic regression. RESULTS: The prevalence of missed prevention opportunity for syphilis or anti-HIV was 41.2% and 56.0%, respectively. The multivariate analysis showed that race/skin color (non-white), schooling (<8 years), marital status (single), income (<3 monthly minimum wages), having sex during pregnancy, history of syphilis prior to the current pregnancy, number of prenatal care visits (<6), and last prenatal visit before the third trimester of gestation were associated with an increased risk of missed prevention opportunity. A negative association with missed prevention opportunity was found between marital status (single), prenatal care site (hospital) and first prenatal visit in the third trimester of gestation. CONCLUSIONS: High rates of non-tested women indicate failures in preventive and control actions for HIV infection and congenital syphilis. Pregnant women have been discontinuing prenatal care at an early stage and are failing to undergo prenatal screening for HIV and syphilis.

Congenital cytomegalovirus infection: occurrence in two socioeconomically distinct populations of a developing country

In São Paulo, Brazil, between November 1980 and July 1982, 1614 newborns of middle socioeconomic background and 1156 newborns of low socioeconomic background were examined for the occurrence of congenital cytomegalovirus (CMV) infection by isolation of virus from urine samples or detection of specific anti-CMV IgM in umbilical cord serum tested by immunofluorescence. In the low socioeconomic population prevalence of CMV complement-fixing antibodies in mothers was 84.4%(151/179) and the incidence of congenital infection assessed by virus isolation 0.98% (5/508), as compared with 0.46% (3/648) in the group of newborns tested by detection of specific anti-CMV IgM in umbilical cord-serum. In middle socioeconomic level population prevalence of CMV complement-fixing antibodies in mothers was 66.5% (284/427) and the incidence of CMV congenital infection was 0.39% (2/518) in the group of newborns screened by virus isolation and 0.18% (2/1096) in the group tested by detection of specific anti-CMV IgM. In the present study none of the 12 congenitally infected newborns presented clinical apparent disease at birth.

Evaluation of lung function abnormalities prevalence in poultry workers

Introduction - Poultry workers can be at an increased risk of occupational respiratory diseases, like asthma, chronic obstructive pulmonary disease and extrinsic allergic alveolitis. Spirometry screening is fundamental to early diagnosis trough the identification of related ventilatory defects. Purpose - We aimed to assess the prevalence of lung function abnormalities in poultry workers.

Ascaris lumbricoides in neonate: evidence of congenital transmission of intestinal nematodes

Clinical and epidemiological study of a forty-days-old infant with a diarrheic condition and insufficient development led to the coprological diagnosis of ascariasis and possible congenital infection. Specific treatment with levamizole, resulted in clinical and parasitological cure, in addition to gain of weight up to normal levels. Maternal parasitism had been diagnosed two months before labor and proved beyond doubt during the ensuing epidemiological inquiry.

PCR in the First Oropharynx Aspirate of the Newborn: A Possible Source for Identification of Congenital Infection Agents

We present a case of prenatal diagnosis of congenital rubella. After birth, in addition to traditional serologic and clinical examinations to confirm the infection, we could identify the virus in the "first fluid aspirated from the oropharynx of the newborn", using polimerase chain reaction (PCR). We propose that this first oropharynx fluid (collected routinely immediately after birth) could be used as a source for identification of various congenital infection agents, which may not always be easily identified by current methods

A survey of congenital Chagas’ disease, carried out at three Health Institutions in São Paulo City, Brazil

The congenital transmission of Chagas’ disease was evaluated in 57 pregnant women with Chagas’ disease and their 58 offspring. The patients were selected from three Health Institutions in São Paulo City. The maternal clinical forms of Chagas’ disease were: indeterminate (47.4%), cardiac (43.8%) and digestive (8.8%); 55 were born in endemic areas and two in São Paulo City. The transmission of Chagas’ disease at fetal level was confirmed in three (5.17%) of the 58 cases studied and one probably case of congenital Chagas’ disease. Two infected infants were born to chagasic women with HIV infection and were diagnosed by parasitolological assays (microhematocrit, quantitative buffy coat-QBC or artificial xenodiagnosis). In both cases the placenta revealed T. cruzi and HIV p24 antigens detected by immunohistochemistry. In one case, a 14-week old abortus, the diagnosis of congenital T. cruzi infection was confirmed by immunohistochemistry. The other probable infection, a 30-week old stillborn, the parasites were found in the placenta and umbilical cord. The Western blot method using trypomastigote excreted/secreted antigens of T. cruzi (TESA) was positive for IgG antibodies in 54/55 newborns and for IgM in 1/55 newborns. One of the two newborns with circulating parasites had no detectable IgG or IgM antibodies. The assessment of IgG antibodies in the sera of pregnant women and their newborns was performed by ELISA using two different T. cruzi antigens: an alkaline extract of epimastigotes (EAE) and trypomastigote excreted/secreted antigens (TESA). The analysis showed a linear correlation between maternal and newborn IgG antibody titers at birth.

Congenital cytomegalovirus infection in a neonatal intensive care unit in Brazil evaluated by PCR and association with perinatal aspects

Cytomegalovirus (CMV) infection is the most common congenital infection, affecting 0.4% to 2.3% newborns. Most of them are asymptomatic at birth, but later 10% develop handicaps, mainly neurological disturbances. Our aim was to determine the prevalence of CMV shed in urine of newborns from a neonatal intensive care unit using the polymerase chain reaction (PCR) and correlate positive cases to some perinatal aspects. Urine samples obtained at first week of life were processed according to a PCR protocol. Perinatal data were collected retrospectively from medical records. Twenty of the 292 cases (6.8%) were CMV-DNA positive. There was no statistical difference between newborns with and without CMV congenital infection concerning birth weight (p=0.11), gestational age (p=0.11), Apgar scores in the first and fifth minutes of life (p=0.99 and 0.16), mother's age (p=0.67) and gestational history. Moreover, CMV congenital infection was neither related to gender (p=0.55) nor to low weight (<2,500g) at birth (p=0.13). This high prevalence of CMV congenital infection (6.8%) could be due to the high sensitivity of PCR technique, the low socioeconomic level of studied population or the severe clinical status of these newborns.

Congenital Chagas disease of second generation in Santiago, Chile. Report of two cases

Congenital Chagas disease (CChD) has been reported in different countries, mostly in Latin America. In 1987 a fatal case of CChD of second generation (CChDSG) was published. Within a period of six months - 1989-1990 - two cases of CChDSG were diagnosed and studied in the city of Santiago. Two premature newborns, sons of two sisters, with moderate liver and spleen enlargement, were found to have positive serology for Chagas disease and xenodiagnoses. The mothers, urban residents all their lives, without antecedents of triatomine bugs contact or blood transfusions, showed positive serology and xenodiagnoses. Their mother (grandmother of the infants), lived 20 years in a Northern rural Chagas disease endemic locality, in a triatomine infested house. Afterwards, she moved to Santiago, where she married and has resided up to now. Serology and xenodiagnoses were also positive. All the Trypanosoma cruzi infected individuals were successfully treated with nifurtimox.