The influence of prenatal diagnosis on postnatal outcome in patients with structural congenital heart disease

Examination of the fetal heart has become an established part of mid-trimester anomaly scanning. Along side this has emerged the ability to diagnose congenital heart disease in the fetus with accuracy. Despite this, the development of screening programmes to look for fetal cardiac disease has only been partially successful. Furthermore, when detected, there seems to be little survival advantage associated with prenatal diagnosis. Demonstrating such an advantage is complicated by the nature of fetal cardiac disease, which tends to be severe and is often associated with extra-cardiac abnormalities. More selective studies, mostly involving small numbers of cases, are now beginning to demonstrate both improved survival and reduced morbidity in prenatally diagnosed infants presenting to cardiac intensive care units compared to those with a postnatal diagnosis. Copyright © 2004 John Wiley & Sons, Ltd.     

Cardiac and extra-cardiac anomalies as indicators for trisomies 13 and 18: A prenatal ultrasound study

The purpose of the present study was to establish sonographic markers for prenatal diagnosis of trisomies 13 and 18. Retrospective analysis of sonographic morphology was therefore carried out in seven fetuses with trisomy 13, and 16 fetuses with trisomy 18. Gestational age ranged between 17 and 39 weeks (median 28 weeks). Polyhydramnios and symmetrical growth retardation were present in 14 of 23 fetuses. A cardiac anomaly was diagnosed in all 23 fetuses, the majority representing a ventricular septal defect (n = 8) or double outlet right ventricle (n = 8). Extra-cardiac anomalies were characterized by a high incidence of limb deformities (polydactyly, clenched hands, club feet; n = 15) and omphalocele (n = 7). We conclude that the combined appearance of cardiac and extra-cardiac anomalies should prompt fetal karyotyping. Cardiac anomalies in combination with fetal limb deformities and omphalocele are suspicious for trisomies 13 and 18.     

True trisomy 15 mosaicism,detected by amniocentesis at 12 weeks of gestation and fetal echocardiography

A case of mosaicism of trisomy 15, with two-thirds of the cells trisomic, was detected at 12 weeks of gestation in amniotic fluid cell cultures obtained with the filtration technique. Ultrasound examination at 13 weeks showed a nodule protruding into the amniotic cavity which was speculated to be remnants of a co-twin, causing the trisomic cell line. At 20 weeks of gestation, a malformation scan (level III) was normal, but supplementary fetal echocardiography revealed a severe cardiac defect (mitral atresia and a ventricular septal defect). Fetal lymphocytes obtained by cordocentesis showed trisomy 15 mosaicism, but only in 5 per cent of the mitoses. After termination, the same percentage of trisomy 15 mosaicism was found in cells from skin and tendon as in the original early amniocentesis. No sign of earlier twinning was found in the placenta or membranes. We conclude that mosaicism in early amniotic fluid obtained by the filter technique in this case reflected the true karyotype accurately and that supplementary echocardiography added significantly to the interpretation of the clinical implications.     

Effectiveness of tiger moth (Lepidoptera, Arctiidae) chemical defenses against an insectivorous bat (Eptesicus fuscus)

Summary. Adult tiger moths exhibit a wide range of palatabilities to the insectivorous big brown bat Eptesicus fuscus. Much of this variation is due to plant allelochemics ingested and sequestered from their larval food. By using a comparative approach involving 15 species from six tribes and two subfamilies of the Arctiidae we have shown that tiger moths feeding on cardiac glycoside-containing plants often contain highly effective natural feeding deterrents. Feeding on pyrrolizidine alkaloid-containing plants is also an effective deterrent to predation by bats but less so than feeding on plants rich in cardiac glycosides. Moths feeding on plants containing iridoid glycosides and/or moths likely to contain biogenic amines were the least deterrent. By manipulating the diet of several tiger moth species we were able to adjust their degree of palatability and link it to the levels of cardiac glycosides or pyrrolizidine alkaloids in their food. We argue that intense selective pressure provided by vertebrate predators including bats has driven the tiger moths to sequester more and more potent deterrents against them and to acquire a suite of morphology characteristics and behaviors that advertise their noxious taste.     

Milkweeds,monarch butterflies and the ecological significance of cardenolides

Summary The contribution of Miriam Rothschild to the monarch cardenolide story is reviewed in the light of the 1914 challenge by the evolutionary biologist, E.B. Poulton for North American chemists to explain the chemical basis of unpalatability in monarch butterflies and their milkweed host plants. This challenge had lain unaccepted for nearly 50 years until Miriam Rothschild took up the gauntlet and showed with the help of many able colleagues that monarchs are aposematically coloured because they sequester toxic cardenolides from milkweed host plants for use as a defence against predators. By virtue of Dr Rothschild's inspiration and industry, and subsequently that of Lincoln Brower and his colleagues, this tritrophic interaction has become a familiar paradigm for the evolution of chemical defences and warning colouration. We now know that the cardenolide contents of different milkweeds vary quantitatively, qualitatively and spatially, both within and among species and we are starting to appreciate the implications of such variation. However, as Dr Rothschild has pointed out in her publications, cardenolides have sometimes blinded us to reality and it is curious how little evidence there is for a defensive function to cardenolides in plants — especially against adapted specialists such as the monarch. Thus the review will conclude with a discussion of the significance of temporal variation and induction of cardenolide production in plants, the lethal plant defence paradox and an emphasis on the dynamics of the cardenolide-mediated interaction between milkweeds and monarch larvae.     

Responses of three mouse species to deterrent chemicals in the monarch butterfly. I. Taste and toxicity tests using artificial diets laced with digitoxin or monocrotaline

Summary Of three common mouse species at the Mexican overwintering sites of the monarch butterfly, onlyPeromyscus melanotis eats monarchs. We hypothesized thatP. aztecus andReithrodontomys sumichrasti reject monarchs because they are more sensitive to the bitter taste and/or toxic effects of the cardiac glycosides (CGs) and pyrrolizidine alkaloids (PAs) in the butterflies. Two-choice preference tests revealed no difference in taste avoidance thresholds to free base and N-oxide forms of the PA, monocrotaline, but very different avoidance thresholds to the CG, digitoxin. Avoidance thresholds forR. sumichrasti andP. aztecus were, in respective order, 1020 and 34 times less than that forP. melanotis. We also tested the toxic sensitivity of juvenile mice by chronically feeding diets containing digitoxin or monocrotaline at concentrations similar to those used in the preference tests. No species developed CG toxicity, but bothP. melanotis andP. aztecus developed moderate PA toxicity (R. sumichrasti was not tested for PA toxicity).P. aztecus grew more slowly and manyP. melanotis had hepatic metabolic lesions. Thus, the three mouse species responded very differently to the taste and toxic properties of CGs and PAs at ecologically relevant concentrations: 1) CGs were taste rejected by all species exceptP. melanotis, while PAs were not; and 2) PAs were toxic, while CGs were not.     

Fetal bradyarrhythmia: Diagnosis and outcome

Seventeen patients were referred to our ultrasound unit because of fetal bradyarrhythmia (<100 bpm). Duration of pregnancy varied between 21 and 40 weeks. Bradyarrhythmia was diagnosed as atrioventricular block (n = 12), mild sinus bradycardia (n = 3), and irregular bradycardia (n = 2). The association with maternal collagen disease was 29 per cent and with cardiac structural defects 59 per cent. The overall mortality was 41 per cent. There were three abnormal karyotypes (17 per cent) and four cases of cardiac compromise (23 per cent). Prognosis depends on the nature of the bradyarrhythmia and recognition of associated pathology such as cardiac structural defects, abnormal karyotype and degree of cardiac compromise.     

Molecular studies on the ouabain binding site of the Na+, K+-ATPase in milkweed butterflies

Summary. The Na⁺, K⁺-ATPase of the Monarch butterfly (Danaus plexippus) is insensitive to the inhibition by cardiac glycosides due to an amino acid replacement: histidine instead of asparagine at position 122 of the α-subunit representing the ouabain binding site. By PCR amplification of the DNA sequence of this site, a PCR product of 270 bp was obtained from DNA extracted from Danainae species (Danaus plexippus, D. chrysippus, D. gillipus, D. philene, D. genutia, Tirumala hamata, Euploea spp., Parantica weiskei, P. melusine), Sphingidae (Daphnis nerii) and mimics of milkweed butterflies (Hypolimnas missipus, Limenitis archippus and L. arthemis, Nymphalidae). Analysis of the nucleotide sequences revealed that the single point mutation in the ouabain binding domain (AAC-Asn for CAC-His) was present only in Danaus plexippus, but not in the other species investigated. Since these milkweed butterflies also store cardenolides, other structural modifications of the Na⁺, K⁺-ATPase may have occurred or other strategies of cardenolide tolerance have been developed. Received 15 May 2000; accepted 29 June 2000