The hidden mortality of congenital diaphragmatic hernia: a 20-year review.

AIMS: The true mortality associated with congenital diaphragmatic hernia (CDH) is hidden because survival analyses do not include fetuses with CDH. A retrospective review of all postmortems (PMs) with a diagnosis of CDH over a 20-year period was carried out to highlight this hidden mortality and also measure the nature and number of associated anomalies. METHODS: Postmortem case record details were reviewed for the period January 1986 to December 2005. Data were collected on live birth, stillbirth, therapeutic abortion, and spontaneous abortion. RESULTS: There was a decline in the annual number of PMs during the period of the study. The median for the four 5-year intervals being 609 (570-657), 528 (488-565), 515 (413-537), and 373 (357-388). A total of 130 PMs were identified, which included a diagnosis of CDH; 97 (75%) were left sided, 22 (17%) were right sided, and 11 (8%) were bilateral. There were 69 live births, 46 therapeutic abortions, 10 stillbirths, and 5 intrauterine deaths; 22% were right sided/bilateral in the live and therapeutic abortion groups, whereas 53% were right sided/bilateral in the latter 2 groups. Of 130, 82 (63%) had major associated anomalies, and 50% of these had at least 1 further major anomaly. The commonest categories of anomalies were cardiac (30), gastrointestinal/abdominal wall defect (28), and neural tube defects (25). CONCLUSIONS: The true incidence of CDH is considerably higher than that seen in neonatal surgical practice. The decline in number of PMs in our region will exacerbate the underestimation of the true incidence. There is a higher incidence of right-sided/bilateral hernias and more than one major anomaly in those who die in utero.

Reversible chronic pulmonary fibrosis associated with MMF in a pediatric patient: a case report.

We describe a case of chronic mineralizing pulmonary elastosis in a seven-yr-old boy following DD renal transplantation for Wilms tumour. Fourteen months post-transplantation he developed respiratory symptoms with lung biopsy demonstrating chronic mineralizing pulmonary elastosis thought to be secondary to immunosuppression with MMF. Symptomatic resolution occurred following MMF cessation.

Foregut duplication cyst of the pharynx.

INTRODUCTION: Foregut duplication cysts are heterotrophic rests of foregut-derived epithelium which are usually found in the abdomen and thorax; rarely are they found in the head and neck. CASE REPORT: We describe the case of a pharyngeal foregut duplication cyst presenting with airway obstruction in a neonate. We also review the pathology, investigation and management of this rare condition. DISCUSSION: The occurrence of a foregut duplication cyst in the head and neck region mandates vigilance with respect to the airway. Magnetic resonance imaging is a useful part of pre-operative evaluation but cannot be relied upon for definitive diagnosis. Although foregut duplication cysts are benign lesions, definitive cure ultimately requires surgical excision, and this is often the means by which a definitive diagnosis is made. The prognosis for these lesions is excellent, with no reports in the literature of recurrence following excision.

Fatal and near-fatal encephalopathy with hyponatraemia in two siblings with fluticasone-induced adrenal suppression.

AIM: To document previously unreported acute effects of adrenal insufficiency. METHODS: We describe two siblings who presented acutely with hyponatraemia and cerebral oedema following prolonged treatment with high dose inhaled fluticasone. RESULTS: A girl aged 5.5 years presented with vomiting, headache, visual impairment and seizures. She was hyponatraemic but not hypoglycaemic. Her conscious level continued to deteriorate and she died, post mortem examination showing small adrenal glands and cerebral oedema. Four weeks later her 7-year-old brother presented with similar symptoms. Assessment showed hyponatraemia with cerebral oedema. His illness responded to intensive care. A diagnosis of adrenal insufficiency was made retrospectively in both cases. The siblings had been receiving Fluticasone propionate (FP) in doses of up to 2000 microg/day for several years. CONCLUSION: We believe that the hyponatraemia and cerebral oedema was related to cortisol deficiency, leading to impaired excretion of water. We emphasize the need for careful cerebral monitoring in acute adrenal insufficiency presenting with impaired consciousness.

Placental and maternal serum inhibin-A and activin-A levels in Down's syndrome pregnancies.

The objective of this study was to analyse the levels of inhibin-A and activin-A in maternal serum and placental tissue from Down's syndrome (DS) pregnancies. Inhibin-A and activin-A levels were determined by specific immunoassays and individual results were expressed as multiples of the control median (MoM) at the appropriate gestation. Immunohistochemistry was used to localize inhibin alpha and beta(A)-subunits in a selection of placental sections. In DS pregnancies, median inhibin-A levels were found to be significantly elevated to 1.46 MoM (P< 0.05) in placental extracts, and 2.06 MoM (P< 0.0001) in maternal serum, when compared with uncomplicated pregnancies. Median activin-A MoMs were also elevated in placental extracts and maternal serum to 1.62 MoM (P< 0.01), and 1.26 MoM (P< 0.05), respectively. Immunohistochemistry revealed that the alpha subunit of inhibin-A and the beta(A)subunit of inhibin-A and activin-A were mainly localized to the trophoblastic layer of placental villi. Semiquantitative studies of staining intensity revealed a trend towards stronger staining of placental trophoblasts and stroma of DS tissues, although this was statistically significant only for beta(A)subunit staining of trophoblasts (P< 0.05). These results support the hypothesis that maternal serum levels of inhibin-A and activin-A are elevated due to increased production in the placenta, and increased immunostaining of trophoblasts suggests that this may be due to increased production in the trophoblasts.

Benign symptomatic thymic tumors.

Benign tumors of the thymic gland are relatively rare. Although most of these lesions are asymptomatic in nature, they may result in respiratory distress. This report describes 2 cases of benign thymic tumors presenting with respiratory symptoms that resolved after operative excision.

Post-mortem findings in fetal and neonatal congenital diaphragmatic hernia.

Analyses of survival data of neonates born with congenital diaphragmatic hernia (CDH) can be misleading. There is a hidden mortality only apparent when fetuses with CDH are included in the analysis. A retrospective review of all post mortems with a diagnosis of CDH in the West of Scotland over a 10-year period was carried out. Congenital anomalies were identified and heart and lung weights were compared with controls (infants dying of non-cardiorespiratory causes). 70 Pm reports were studied. Major congenital anomalies were present in 53% (18/ 47 live born, 19/23 not live born). Neural tube defects, cardiac and chromosomal anomalies were the most common. Antenatal detection rate was 17% in live-born infants. In infants dying within the first week of life lung weights showed severe pulmonary hypoplasia, but heart weights were within the normal range. Detailed antenatal scanning needs to be considered if the detection rate for CDH is to improve in this region.

Placental synthesis of oestriol in Down's syndrome pregnancies.

In the second trimester, oestriol is synthesized in the placenta and secreted into the maternal circulation. 16alpha-hydroxy dehydroepiandrosterone sulphate (16alpha-OH-DHEAS) is formed in the fetal liver by hydroxylation of dehydroepiandrosterone sulphate (DHEAS) and transported to the placenta where it undergoes desulphation by steroid sulphatase (STS) and aromatization to oestriol. Maternal serum levels of unconjugated oestriol (UE3) are lower in Down's syndrome pregnancies than in unaffected pregnancies in the second trimester. The underlying cause of this variation was investigated in placenta, fetal liver, maternal serum and amniotic fluid from Down's syndrome pregnancies by measuring the levels of UE3, DHEAS and STS in appropriate tissues and in corresponding samples from unaffected pregnancies. UE3 levels, expressed as multiples of the control median at the appropriate gestation (MOM), were lower in placental tissue (0.52 MOM), maternal serum (0.65 MOM) and amniotic fluid (0.61 MOM) than in unaffected pregnancies. There was a significant correlation between placental and maternal serum levels of UE3 in the Down's syndrome cases. The median STS activity in placental tissue from Down's syndrome pregnancies (1.14 MOM) was not significantly different from that of the control pregnancies (1. 01 MOM), suggesting that placental turnover of the fetal precursor DHEAS is not reduced. However, levels of DHEAS were reduced in maternal serum (0.69 MOM), placental tissue (0.54 MOM) and fetal liver (0.65 MOM) from Down's syndrome pregnancies. Thus, a diminished supply of the fetal precursor DHEAS may be the cause of the decreased placental production of UE3 in Down's syndrome pregnancies in the second trimester.

Infant cerebellar gray and white matter fatty acids in relation to age and diet.

There is little evidence as to the fatty acid composition of the cerebellum in infancy and it remains uncertain whether milk diet can influence its composition. We therefore examined cerebellar gray and white matter of infants less than 6 month old who had died unexpectedly. The fatty acid content of 33 gray and 21 white matter specimens from infants born at term and 6 gray and 5 white matter specimens from preterm infants was assessed by gas chromatographic/mass spectrometric analysis. Infants were grouped according to whether they had received human or manufactured formula milk. Whereas cerebellar cortex docosahexaenoic acid (DHA, 22:6n-3) concentrations were significantly lower (P<0.01) in the formula-fed than breast-fed infants, no differences existed between the term (n = 10) and preterm (n = 5) Synthetic Milk Adapted [corrected] (SMA) formula-fed infants. Cerebellar white matter DHA concentrations were similarly lower (P<0.01) in the SMA formula-fed infants (n = 8) than in an age-matched breast-fed group. Low concentrations of cerebellar white matter lignoceric (24:0) and nervonic acid (24:1n-9) in two 7-wk-old preterm infants appeared to correlate with postgestational rather than chronological age. Dietary long-chain polyunsaturated fatty acids, particularly DHA, are probably essential for normal development of the infant cerebellum.

Prenatal diagnosis and management of nonimmune hydrops fetalis.

We examined the incidence, aetiological factors and outcome in 40 cases of nonimmune hydrops fetalis (NIH) and suggest a rational approach to management. The incidence of NIH was 1 in 830 deliveries during the last 10-year period. In spite of extensive antenatal and postnatal investigation no cause could be established in 14 (35%) cases. A probable aetiological factor was found in 65% of cases. These included viral infection (7), cardiovascular (6), twin-to-twin transfusion (3), chromosomal abnormality (3), other malformation syndromes (4), renal dysplasia (1), laryngeal atresia (1) and severe fetomaternal haemorrhage (1). Five of the 40 fetuses survived, 2 treated antenatally for tachyarrhythmia, 2 had spontaneous resolution and the fifth fetus had repeated intrauterine transfusions because of human parvovirus B19-induced anaemia. After diagnosis of nonimmune hydrops fetalis, early referral to a tertiary centre is to be encouraged for investigation and provision of intensive perinatal care. Investigation allows parents to be counselled appropriately that the mortality is no longer 100% and a steadily growing number may be amenable to some form of fetal therapy.

CT-guided 14-G cutting needle lung biopsy in children: safe and effective.

CT-guided percutaneous lung biopsy was performed in children with chronic respiratory disease to obtain samples for histological examination. An automatic cutting device with a 14-G needle was used with one or two cores obtained in each procedure. Seven procedures were performed in six children, mostly with local anaesthesia. Adequate tissue was obtained in all cases. Although a small pneumothorax and/or haemothorax occurred in most procedures, these were usually visible only on CT and did not require active management. A larger pneumothorax in one child also resolved with conservative management. Percutaneous CT-guided 14-G automatic cutting-needle biopsy of lung parenchyma in children is a minimally invasive alternative to open-lung biopsy with no complications in our series.

Intrauterine growth restriction is associated with persistent juxtamedullary expression of renin in the fetal kidney.

BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production. METHODS: Immunohistochemistry and in situ hybridization were employed to localize renin-containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17). RESULTS: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered. CONCLUSIONS: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life.

Determination of low concentrations of potentially toxic elements in human liver from newborns and infants.

One hundred and fifty-seven liver samples from newborns and infants who had died from sudden infant death syndrome (SIDS) or other known causes have been analysed by ICP-MS for Ag, Cd, Co, Pb and Sb. The median concentrations found were: 15.4 (Ag), 2.9 (Cd), 15.9 (Co), 65.2 (Pb) and 1.8 (Sb) ng g-1 wet mass. There was no measurable difference in the concentrations of any of these elements between the SIDS and non-SIDS groups. The validity of the results was assessed by analysis of appropriate reference materials, interlaboratory comparison and isotope dilution analysis. The instrumental limits of detection were 0.25 (Ag), 0.14 (Cd), 0.21 (Co), 3.8 (Pb) and 0.38 (Sb) ng g-1 wet mass. The limits of detection of the method depend on the reagent blank and the extent of background contamination.

Infant growth and aorta total lipid fatty acids.

Abnormal fetal and infant growth have increasingly been correlated with adult onset cardiovascular disease. To date, there is little known about the lipid fatty acid profiles in infant cardiovascular tissue. Therefore, we analysed total lipid fatty acids from thoracic and abdominal aorta intima and media from 24 normally grown sudden infant death syndrome cases. Aorta from small for gestational age (n = 2), failure to thrive from birth (n = 3), and premature (n = 1) infants were also examined. Dihomo-gamma-linolenic acid (C20:3n-6) and oleic acid (C18:1n-9) concentrations were significantly lower in the thoracic than in the abdominal aorta. Similar dietary related differences were found in the subgroup (n = 15) of infants fed on formula milks. Both abdominal and thoracic intimal arachidonic (C20:4n-6) to dihomo-gamma-linolenic acid ratios were greater in the infants with retarded growth after birth than in their normally grown counterparts. Growth restriction in infancy might disrupt the normal accretion of vascular endothelial polyunsaturated fatty acids.

Biochemical markers of trisomy 21 and the pathophysiology of Down's syndrome pregnancies.

Using biochemical and immunocytochemical methods, we have investigated endogenous levels of various markers in tissues obtained from 67 Down's syndrome pregnancies after therapeutic abortion in the second trimester and in corresponding tissues from unaffected abortuses. Alpha-fetoprotein (AFP), intact and free beta human chorionic gonadotrophin (hCG), pregnancy-specific beta-1 glycoprotein (SP-1), placental alkaline phosphatase (PALP), pregnancy-associated plasma protein A (PAPP-A), and gamma glutamyl transferase (GGT) were investigated in placental tissue; AFP and GGT in fetal liver; and GGT in fetal intestine. The results indicate that maternal serum levels of placental products reflect those found in the placenta: intact hCG, free beta hCG, and SP-1 levels were elevated in Down's syndrome pregnancies, while PAPP-A and PALP levels were little changed. This suggests that membrane passage of these markers is not affected but there is altered synthesis of hCG and SP-1. AFP levels were strikingly elevated in placental homogenates and unchanged in liver homogenates from Down's syndrome pregnancies, while the levels in maternal serum were reduced, pointing to a possible transport defect specific to AFP. GGT levels were high in placenta and liver from Down's syndrome pregnancies but low in fetal intestine.

Batten disease in the west of Scotland 1974-1995 including five cases of the juvenile form with granular osmiophilic deposits.

We report on 12 children with neuronal ceroid lipofuscinosis (NCL) diagnosed between 1974-1995 in the West of Scotland. Diagnosis was made on the basis of clinical, electrophysiological, radiological and pathological examination including electron microscopy (EM) in all cases. Incidence was calculated on the basis of the year of diagnosis and the live birth rate. Six cases were infantile and 6 juvenile NCL derived from a total of 10 families. No cases of late infantile or early juvenile NCL were identified. All cases were typical in clinical description. Cumulative incidence was 1.61/100,000 live births (0.87 and 0.73/100,000 live births for juvenile and infantile NCL respectively). There was significant delay in diagnosis of the juvenile form of NCL. EM findings were unusual in the juvenile group in that 5 of 6 cases exhibited granular osmiophilic deposits (GROD) rather than typical fingerprint inclusion bodies. Four of these 5 cases also failed to show vacuolation of lymphocytes. Thus, in the West of Scotland, the distribution of NCL cases by type and by EM findings is unusual, and suggests a distinct genetic variant of juvenile NCL, possibly allelic to infantile NCL.

Atypical mycobacterial infection in childhood: a "surgical disease'.

Atypical mycobacterial (AMB) infection is an important cause of lymph node enlargement in children. Over the period, January 1992 to December 1993, 17 patients with lymphadenitis because of AMB infection were treated at the Royal Hospital for Sick Children in Glasgow. These case notes of the patients were reviewed. The mean age at presentation was 5.37 years (range 1.5-10.6 years). The patients had a short history (1-11 weeks) of unilateral single focus, usually cervicofacial (16/17), disease. The tuberculin skin test was not helpful in diagnosis (negative in 14/15). Primary excision was curative (11/11). Incision and drainage of an abscess or drainage with partial excision led to chronically discharging sinus in all cases (6/6). AMB were not always seen on staining (11/17) of drained or excised material and cultures were negative in eight cases. The diagnosis in the remaining patients was made on the basis of clinical features and particular histopathological patterns. We are currently assessing the use of polymerase chain reaction (PCR) techniques for making the diagnosis in non-cultured cases.

Demonstration of renin gene expression in nephroblastoma by in situ hybridization.

Most patients with nephroblastoma have high levels of plasma renin and some are hypertensive. Blood pressure falls after removal of the affected kidney, suggesting that nephroblastoma is associated with renin production either by the tumour or by the kidney. In this study, direct evidence was sought of renin gene expression in nephroblastoma using in situ hybridization. Digoxigenin-labelled riboprobes and an immunoperoxidase technique were used to detect cells containing renin mRNA: this showed renin gene expression in 9 out of 12 cases. There were positive cells within metanephric blastema and in occasional neoplastic glomeruloid structures, confirming that in seven cases nephroblastoma tumour cells expressed the renin gene. However, renin gene expression was also demonstrated in perivascular cells of uncertain lineage in seven cases; in five cases there was evidence of renin gene expression in both tumour cells and perivascular cells. The latter finding raises the possibility that some of the cells expressing the renin gene could be stromal cells. It is concluded that nephroblastomas contain cells that express the renin gene and that some are tumour cells, while other perivascular cells may be stromal cells.