Haemolytic Disease of the Newborn

Mollison, P. L.; Cutbush, Marie

doi:10.1136/bmj.1.4599.364-a

Cited by 16 publications

(16 citation statements)

References 5 publications

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“…There was no significant difference between the bilirubin content of tissues superfused with medium containing bilirubin at a con- infants was recognized over a century ago (23) there was some delay before the recognition that bilirubin is the neurotoxic agent responsible for the severe neurological damage associated with icterus gravis in the newborn (24). The mechanism of this neurotoxicity, however, remains uncertain.…”

Section: Resultsmentioning

confidence: 97%

The Effects of Bilirubin on Brain Energy Metabolism during Normoxia and Hypoxia: An in Vitro Study Using 31P Nuclear Magnetic Resonance Spectroscopy

et al. 1988

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ABSTRACX. Available evidence from in vitro studies suggests that the neurotoxic effects of bilirubin may be exacerbated by, or even require, additional factors such as hypoxia or asphyxia. The aim herein was to use 31P nuclear magnetic resonance spectroscopy to study the effects of bilirubin on brain energy metabolism in vitro under conditions of normoxia and hypoxia.nuclear magnetic resonance spectra were acquired from guinea pig cerebral hemisphere slices during superfusion with solutions containing bilirubin and albumin in 5:l molar ratio. The effects of bilirubin at concentrations between 400 nmollliter and 120 pmollliter were studied under normoxic conditions. Bilirubin caused no apparent disruption in brain energy metabolism during normoxia. The combined effects of bilirubin (40 pmollliter) and hypoxia were studied. Hypoxia alone led to a steady state reduction in the phosphocreatine to inorganic phosphate peak-height ratio to 0.30 (0.27-0.32) [mean (range) n = 31. Bilirubin (40 pmollliter) in the presence of hypoxia caused a further reduction in the phosphocreatine to inorganic phosphate ratio to 0.18 (0.17-0.20) [mean (range) n = 3, p < 0.01, analysis of variance] which was rapidly reversed on returning to normoxia. These results demonstrate that bilirubin at the concentration studied requires hypoxia, in addition, to cause a measurable disturbance of brain energy metabolism. The nature of this interaction is unknown, but it may reflect the effect of intracellular acidosis on bilirubin solubility or the oxygen dependence of brain mitochondrial bilirubin oxidase. (Pediatr Res 23: 569-573, 1988) Abbreviations NMRS, 3 1 p h o~p h o r~~ nuclear magnetic resonance spectroscopy PCr, phosphocreatine Pi, inorganic phosphate FID, free induction decay NPT, nucleoside triphosphate Although the prevention of Rhesus-hemolytic disease has curtailed the incidence of severe jaundice in term newborn infants, the potential neurotoxicity of bilirubin is still a common and important concern, especially in the care of infants born pre-

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Section: Resultsmentioning

confidence: 97%

The Effects of Bilirubin on Brain Energy Metabolism during Normoxia and Hypoxia: An in Vitro Study Using 31P Nuclear Magnetic Resonance Spectroscopy

et al. 1988

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“…22 Today, alloimmunisation against the D antigen (RH1) is still the most common cause of HDFN. 23 However, alloantibodies other than anti-D antibodies have also emerged as important triggers of severe clinical reactions. In particular, anti-c (anti-RH4) in the Rh system and anti-K (anti-KEL1) in the Kell system are the next most common causes of HDFN, while Rh antigens C (RH2) and E (RH5) only occasionally result in severe HDFN.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy

Gutensohn¹,

Müller

Thomann

et al. 2010

BJOG

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Objective The aim of the study was to determine the sensitivity, specificity and accuracy of noninvasive tests for the fetal rhesus CcEc (RHCE) alleles C, c and E in early pregnancy.Design A prospective clinical trial was carried out to evaluate diagnostic accuracy.Setting Women were recruited at four centres specialising in prenatal diagnosis. Peripheral blood and amniotic fluid samples were obtained and sent to a single laboratory for analysis.Sample A total of 233 tests (46 for C, 87 for c and 100 for E) were performed on 181 specimens obtained from pregnant women at weeks 12 to 28 (median week 16) of gestation.Methods Following automated extraction of fetal DNA from maternal plasma, two different real-time polymerase chain reaction (PCR) protocols were used for the detection of the C, c and E alleles of RHCE. The results of the PCR were compared with genotyping results for the amniotic fluid.Main outcome measures Failure rate, sensitivity, specificity and accuracy were the main outcome measures.Results Unequivocal results were obtained for all specimens. With the first PCR protocol, the sensitivity was 100% for C, 38% for c and 59% for E. In contrast, with the second protocol, the sensitivity for C, c and E was 100%. The specificity for all assays was found to be between 99% and 100%.Conclusions A highly accurate protocol has been identified for the detection of fetal RHCE alleles in maternal plasma in early pregnancy. This noninvasive approach can be considered as a useful test in the management of pregnancies with anti-c, anti-E or anti-C alloimmunisation.

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“…We predict that glycan antigens, which remain polymorphic, will have features allowing them to avoid being targeted by the female immune system by interrupting one or more of the above-mentioned three operational requirements of incompatibility by immunity. For example, anti-A and anti-B blood group antibodies tend to be large IgM molecules, which diffuse much less freely into the female reproductive tract and across the placenta (30).…”

Section: Discussionmentioning

confidence: 99%

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

Ghaderi

Springer

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(−/−) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-offunction alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-offunction allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines.glycan antigen | sialic acid | xeno-antigens

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Haemolytic Disease of the Newborn

Cited by 16 publications

References 5 publications

The Effects of Bilirubin on Brain Energy Metabolism during Normoxia and Hypoxia: An in Vitro Study Using 31P Nuclear Magnetic Resonance Spectroscopy

The Effects of Bilirubin on Brain Energy Metabolism during Normoxia and Hypoxia: An in Vitro Study Using 31P Nuclear Magnetic Resonance Spectroscopy

Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy

Sexual selection by female immunity against paternal antigens can fix loss of function alleles

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