Hepatitis viruses: mother to child transmission

The infection by the hepatitis viruses, when appearing during the pregnancy, could result in damages for the infant. However, risks differ according to the implicated virus.Hepatitis B virus infection, for which prevalence varies according to areas, is injurious when the mother is chronic HBsAg carrier. Risk consists of neonate's contamination during the labour, and if contaminated, the neonate becomes a chronic carrier himself in 80 to 90% of cases. When the mother is positive for viral DNA in her serum, transmission rate is estimated at 90%. In the opposite, if the mother is negative for viral DNA in the serum, transmission rate is about 10 to 30%. HBsAg screening is obligatory in France during the sixth month of pregnancy: in case of positivity, serovaccination of the neonate is systematically carried out. Protection rate is 100% if the mother had a low viral load (<150 pg/ml) at the end of pregnancy, and weaker (about 70%) if the mother had a higher level of viral DNA.Transmission risk of hepatitis C virus (HCV) is much lesser, since it is about 5% for a woman who is positive for viral RNA at the end of her pregnancy, and at least 10% if the woman is moreover positive for the HIV. Risk is more important if the woman had an important plasmatic viral load (> 10(5) copies/ml) and if the duration between membrane rupture and delivery is long. Vaginal delivery and breast-feeding are not advised. Neonates from mothers who replicate the HCV at the end of pregnancy are serologically evaluated until 12-15 months of age, in order to determine their possible contamination.Delta virus transmission from mother to infant is exceptional and could be avoided by the HBV serovaccination of the new-born.Intra-utero transmission of hepatitis A virus is very rare, but perinatal transmission could occur. Materno-fetal transmission of hepatitis E virus has been reported, but the virus is essentially dangerous for the mother, resulting in a mortality rate of 15 to 25% if the acute infection occurs during the third trimester of the pregnancy.     

A simple method for calculating risks before DNA analysis.

Calculation of carrier risk of an X linked disease may be performed on a small computer after DNA analysis, but a method for rapid hand estimation of the risk is still useful for a quick check of the results and weighing the relative importance of each element of information, such as the determination of a haplotype. Each risk estimation is a function of a prior risk and the product of likelihood ratios and these terms are derived themselves from parameters such as fitness or the relative mutation rate in male and female gametes. Even if it is often difficult to have strong experimental estimation of these variables, the existence of a normal father or grandfather must be considered whenever male fitness is not null. The likelihood ratio for a woman for not being a carrier, when her father is not affected and her mother has herself a likelihood R for not having the mutated gene, may be expressed as the ratio 2R/(CmR + 1), with Cm being a function of male fitness and relative mutation rate. Cm represents the odds ratio for the mother of a carrier not to be a carrier, given that the father of the known carrier is not affected. This formula can be used recurrently and reduces to 2R/(R + 1) in lethal X linked disease. When likelihood ratios are expressed as an algebraic function, maximum values are easily determined, hence fixing the limits of DNA analysis.     

X-linked intellectual handicap and precocious puberty with obesity in carrier females

Precocious puberty (PP) and intellectual handicap were present in 3 males in 2 generations of a Western Australian family. The 2 obligate carrier women were of normal intelligence but were grossly obese; one died of a cardiomyopathy at 55 years. The youngest affected male was found to have PP at 3 years. His mother was then pregnant, and because of her family history, was aware of the risk to have an affected male. Her mother had given birth to 2 sons with PP. By school age both of these males were mildly intellectually handicapped and this later became moderate. Apart from these 3 affected males, the 2 carriers lost 6 of their other 8 offspring, leaving only one normal woman and her unaffected son. The Fragile X test was negative on all males. This appears to be a new X-linked mental retardation syndrome, and a condition different from true idiopathic PP, or familial PP affecting both sexes, or PP with X-linked dominant inheritance.     

The Role in Primary MLC of the non HLA–D/DR Determinant PL3A

To test the influence in primary MLC of the newly PLT defined determinant PL3A (Termijtelen et al. 1980), 11 Dw3/DR3 homozygous individuals were tested in an MLC matrix. Two groups of mutually negative cells were detailed. The results appeared to correlate with the presence of PL3A. Cells from group 2 were stimulated by cells from group 1, but the reverse reactions were negative. A genetic model for this "one way" stimulation, observed in MLC as well as PLT, is discussed. We suggest that PL3A, which causes strong stimulation in PLT, also plays a role in primary MLC.     

HLA DRB1*DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis

A possible causal association between infective dermatitis and HTLV-I infection was reported in 1990 and confirmed in 1992. We now report familial infective dermatitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major histocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune response to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I-seropositive, younger son requires close clinical follow-up. © 1995 Wiley-Liss, Inc.     

Transfusion-related acute lung injury resulting from designated blood transfusion between mother and child: a report of two cases

Transfusion-related acute lung injury (TRALI) is an underdiagnosed serious complication of blood transfusion characterized by the rapid onset of respiratory distress, hypoxia, and noncardiogenic pulmonary edema during or soon after blood transfusion. The presence of anti-HLA and/or antigranulocyte antibodies in the plasma of donors is implicated in the pathogenesis of TRALI. We report 2 cases of TRALI that were caused by designated blood transfusion between mothers and their daughters; one in a 4-month-old girl who received designated packed RBCs donated by her mother and the second in a 78-year-old mother who received blood from her daughter. In both cases, examination of mother's serum revealed panel-reactive cytotoxic HLA antibodies. It is most likely that the mothers were sensitized from earlier pregnancy and produced HLA antibodies against the daughters' paternally derived HLA antigens. Designated blood transfusion between multiparous mothers and children might add an additional transfusion-related risk owing to the higher likelihood of the HLA antibody-antigen specificity between mother and child.     

The fate of filial attachment in juvenile guinea pigs housed apart from the mother

Thirty-five-day-old juvenile guinea pigs exhibited higher levels of plasma cortisol following 60 min of exposure to a novel environment when tested alone than when in the presence of the mother. This effect occurred regardless of whether the offspring had been housed continuously with mother and littermates from birth until testing or had been rehoused with just littermates 1 or 2 days prior to testing. Offspring vocalized more when alone than when in the presence of the mother only if they had been housed continuously with her until testing. In addition, juvenile males reunited with the mother after 1 or 2 days directed sexual behavior toward her. The sexual behavior was not accompanied by a significant change in plasma testosterone levels, though there was an overall suppression of levels following isolation in the novel test environment. The results show that guinea pig mothers maintain the capacity to prevent their offspring from exhibiting a plasma cortisol stress response even when the offspring are well beyond weaning and have been housed apart from her for up to 2 days. This suggests the existence of filial attachment in juveniles under these conditions. Further, juvenile males appear capable of simultaneously directing filial attachment and sexual behavior toward the same female. © 1996 John Wiley & Sons, Inc.     

Brief Focal Psychotherapy with a Pregnant Woman Presenting with Nightmares of Killing Her Baby: A Case Study

This paper reports an 18 session treatment in brief focal psychotherapy of a case that presented with at least two major contra-indications for this type of therapy: 1) childhood deprivation and 2) the danger of intensification of a depressed illness. This paper shows that the recent traumatic event, in this case a highly ambivalent pregnancy, can help to destabilize the armour of a defensive structure, and bring to the surface primitive fears and conflicts which cause severe symptomatology and distress but which become more accessible to the patient's awareness and more amenable to interpretation. The acuteness of the disturbance brought about by the traumatic event increased the patient's motivation and need for treatment, speeding up the therapeutic process. This brief psychotherapy shows the importance of the working through of the patient's intense hostility towards her mother and towards the therapist in the transference, if a solution of murderous feelings towards her baby are to be achieved. As far as technique is concerned, this paper shows that a thorough interpretation of the negative transference from the early stage of therapy, an unusual number of transference/parents interpretations and the working through of the patients's anger and grief about termination seemed to be essential factors correlated with a positive outcome.     

Genetic counseling in Becker type X-linked muscular dystrophy. II: Practical considerations

A frequent problem of genetic counseling in Becker muscular dystrophy (BMD) is the differential diagnosis between BMD and the autosomal recessive benign limb-girdle muscular dystrophy (LGMD) if the pedigree pattern is not typical of X-linkage. In this situation, the a priori probability that a woman and her husband may be heterozygotes for LGMD can be shown to be 80 mu/a (mu = mutation rate in BMD; a = incidence ratio between BMD and LGMD). In addition, the age-corrected serum creatine kinase (CK) values of all female relatives are also important for the risk calculation of a woman being carrier of BMD.     

Incest: the Pathological Taboo

ABSTRACT: The little boy wants to kill his mother so as to have his mother all to himself. The little girl attempts to push her mother away so as to enjoy her father on her own. This is the oedipus complex, generally accepted as inevitable, even normal. The terminology, however, has not been chosen at random: a complex is a symptom pointing to an illness (depression-neurosis-psychosis) which needs treatment. George Dubai, a psychoanalyst from Geneva has put the cat among the pigeons by asking: why accept the fatality of the oedipus complex which gives so much pain to humanity? He states the following:‘The oedipus complex would not develop if parents could accept fully the incestuous feelings of their small child towards them and vice versa’. Dubai attacks the taboo… with a plea for love.     

HLA-G and vertical mother-to-child transmission of human papillomavirus infection

Role of host factors in transmission of human papillomavirus (HPV)-infection from mother to her offspring is not known. Our aim was to study whether human leukocyte antigen (HLA)-G allele concordance among the mother–child pairs could facilitate vertical transmission of HPV, because HLA-G may contribute to immune tolerance in pregnancy. Altogether, 310 mother-child pairs were included from the Finnish Family HPV study. Overall, nine different HLA-G alleles were identified. The HLA-G genotype concordance of G¹01:01:01/01:04:01 increased the risk of high risk (HR)-HPV genotype positivity in cord blood and infant’s oral mucosa. The mother-child concordance of G¹01:01:02/01:01:02 increased the risk of oral HPV positivity with HR-HPV genotypes both in the mother and offspring; OR 2.45 (95%CI 1.24–4.85). Discordant HLA-G allele for G¹01:04:01 and for G¹01:06 was significantly associated with infant’s oral low risk (LR)-HPV at birth, OR 3.07 (95%CI 1.01–9.36) and OR 5.19 (95%CI 1.22–22.03), respectively. HLA-G had no association with HPV genotype-specific concordance between the mother and child at birth nor influence on perinatal HPV status of the child. Taken together, our results show that HLA-G molecules have a role in predicting the newborn’s likelihood for oral HPV infection at birth.     

An unusual connective tissue disease in mother and son: A “new” type of Ehlers-Danlos syndrome?

A 23-year-old woman and her 2 1/2-year-old son both had large hernias, positional foot deformities, abnormal thoracic shape, asthma, and severe eczematoid dermatitis. Their facial appearance was quite similar and included asymmetry with prominent nasal bridge and small jaw. In addition, the mother had severe thoracolumbar kyphoscolosis and "cigarette paper" scars over her legs. She died after rupture of a thoracic aortic aneurysm and was found on postmortem examination to have cystic medionecrosis of the aorta and myxomatous degeneration and elongation of the mitral and tricuspid valves. The family history was otherwise negative; there was no consanguinity. The connective tissue disease in this mother and her son appears to be a previously unrecognized dominantly-inherited disorder with some similarity to classical Ehlers-Danlos syndrome.     

Immunogenicity and protective efficacy of low dose recombinant DNA hepatitis B vaccine in normal and high-risk neonates.

A low dose of recombinant DNA hepatitis B vaccine (HB-VAX II, MSD) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in normal and high-risk neonates born from HBsAg carrier mothers. A dose of 2.5 micrograms recombinant vaccine was injected intramuscularly at 0, 1, 2 and 12 months of age to 30 newborns from HBsAg negative mother (group I), 30 from HBeAg negative/HBsAg carrier mother (group II) and 30 from HBeAg positive/HBsAg carrier mother (group III). The incidence of persistent HBsAg carrier infants at 13 months of age was 0, 0, and 30.4 percent in groups I, II and III, respectively. The protective efficacy in high risk infants in group III was 65.7 percent. The seroconversion at month 4, after the third dose of vaccination was 96.3, 95.7 and 100 percent in group I, group II and group III, respectively. After a booster dose of vaccination at 12 months of age, the seroconversion rose to 100 percent at month 13 in all three groups. The geometric mean titer (GMT) of anti-HBs antibody at 13 months of age were 2,092, 1,657 and 1,938 mIU/ml in group I, group II and group III, respectively. It is concluded that the low dose (2.5 micrograms) recombinant hepatitis B vaccine using alone is effective in prevention of perinatal HBV transmission in low risk infants (groups I and II), but it is less effective in high risk infants (group III).(ABSTRACT TRUNCATED AT 250 WORDS)     

Psychosocial issues and outcomes in maternal PKU

Elevated phenylalanine (Phe) levels in pregnant women with PKU are teratogenic. Fetal damage due to elevated maternal Phe levels during pregnancy is known as maternal phenylketonuria (MPKU). The risk of birth defects in MPKU, including global developmental delays, microcephaly, congenital heart disease, and low birth weight, can be dramatically reduced by controlling Phe levels during pregnancy (metabolic control). Phe levels should be maintained in the range of 120–360 μmol/L, ideally starting before pregnancy begins (i.e., when planning a pregnancy). If control is not achieved before pregnancy (e.g., if the pregnancy was unplanned), good outcomes are still possible if metabolic control is established by 8 weeks of pregnancy. Unfortunately, metabolic control before and during pregnancy can be poor. As well, many mothers stop treatment after pregnancy, which can decrease the mother’s ability to focus on her child and increase her risk of behavioral and psychological problems. This can have a negative effect on the home environment. Many factors affect adherence to the strict diet used to control Phe levels, including poor access to medical care, lack of reimbursement for medical foods (in some regions, such as parts of the United States), practical difficulties with implementing the diet, financial constraints, demographics, and psychosocial issues. A comprehensive treatment approach that begins prior to pregnancy and continues after the infant is born may help to improve the management of MPKU. This approach should include education of girls about MPKU at an early age, interventions to prevent unplanned pregnancies, psychosocial support, improved treatment access and reimbursement for medical foods, and treatment guidelines. Treatments such as sapropterin may also have a role in improving metabolic control during pregnancy.     

Environmental features determining successful rearing in the mutant mouse staggerer

The mutant mouse staggerer is unable to rear her pups to weaning unless special precautions are taken. The following environmental conditions were found to contribute to compensate for the maternal behavioral deficits of the staggerer: (1) the foster pups used in a constraining box to stimulate the lactating staggerer mother are 4 days old. (2) The mother is enforced to stay in close physical contact with these pups for at least 12 hours immediately after delivery. (3) The staggerer pups are transferred to a normal lactating mother to suckle her for the first 12 hours of life.     

5个中间型β-地中海贫血家系临床结果分析

目的了解现行PCR-RDB法对中间型β-地贫基因诊断的准确性。方法对5个中间型β-地贫家系进行血常规、血红蛋白电泳和β-地贫基因的PCR-RDB法检测,并用长链PCR法检测家系1和家系2中的先证者及母亲的β-地贫基因的缺失突变。结果 5例先证者HbF含量均增高,其中2例为轻度贫血,3例为中度贫血;4例先证者PCR-RDB法结果为杂合子与其表现的临床症状不符,1例先证者PCR-RDB结果为纯合子与父母基因检测结果不符;先证者1及其母亲长链PCR法显示阴性,先证者2及其母亲长链PCR法均为东南亚（SEA）缺失型HPFH。结论若在产前诊断时仅用PCR-RDB法检测β-地贫基因,会造成缺失型β-地贫基因漏诊,引起一系列严重的社会问题。     

Human platelet antigen genotypes in Turkish and Caucasian blood donors in Germany

Exposition to allogenic human platelet antigens (HPAs) can lead to antibody formation causing neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura or platelet (PLT) transfusion refractoriness. The frequencies of HPA differ between ethnical groups which could be associated with different potential alloimmunization risk. The Turkish population is the largest ethnic minority group living in Germany. However, no data are available about the HPA frequency among Turkish population. We compared the frequency of HPA between Caucasian and Turkish blood donors. DNA from blood samples of 119 Caucasian and 117 Turkish blood donors was isolated. The genotype of HPA-1, -2, -3 -4, -5 and -15 was determined using a commercialized polymerase chain reaction kit with sequence-specific primers. In Turkish blood donors, the gene frequencies of HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/5b and -15a/15b were 0.863/0.137, 0.868/0.133, 0.607/0.393, 0.996/0.004, 0.893/0.107 and 0.474/0.256, respectively. In Caucasians, we observed 0.798/0.202, 0.908/0.092, 0.567/0.432, 1.000/0.000, 0.916/0.084 and 0.517/0.483 for HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/5b and -15a/15b, respectively. No statistically significant difference between genotypes in these populations could be observed. Due to the similar distribution of HPA genotypes in both ethnical groups, no increased risk of NAIT for children of mixed couples or of post-transfusion purpura or PLT transfusion refractoriness secondary to antibodies to HPAs for recipients of PLT concentrates from blood donors of the other ethnicity is given.     

Juvenile onset Huntington disease resulting from a very large maternal expansion

We report a 5(1/2)-year-old girl with a maternal family history of Huntington disease (HD), who presented clinically with unbalanced gait, impaired speech, and increasing difficulty with fine motor control. Onset of symptoms began at the age of 3(1/2) years. The suspected diagnosis of juvenile HD, based upon her family history, was confirmed by DNA analysis. At age 7, the patient died secondary to complications of her underlying disorder. Juvenile-onset Huntington disease is uncommon, predominantly transmitted by fathers and is always associated with very large expansions of the CAG repeat. Interestingly, this patient inherited a large CAG size expansion from her mother, who herself had symptoms of HD at the age of 18. Molecular analysis revealed that the mother had 70 CAG repeats whereas our patient had approximately 130 CAG repeats. This is the largest reported CAG expansion from a maternal transmission that has been confirmed molecularly and it demonstrates that very large expansions can also occur through the maternal lineage.     

Transgenerational sex-specific impact of preconception stress on the development of dendritic spines and dendritic length in the medial prefrontal cortex

Perinatal adverse experience programs social and emotional behavioral traits and is a major risk factor for the development of behavioral and psychiatric disorders. Little information is available on how adversity to the mother prior to her first pregnancy (preconception stress, PCS) may affect brain structural development, which may underlie behavioral dysfunction in the offspring. Moreover, little is known about possible sex-dependent consequences of PCS in the offspring. This study examined spine number/density and dendritic length/complexity of layer II/III pyramidal neurons in the anterior cingulate (ACd), prelimbic/infralimbic (PL/IL) and orbitofrontal cortex (OFC) of male and female rats born to mothers exposed to unpredictable variable stress at different time points prior to reproduction. Our main findings are that in line with our hypothesis adversity to the mother before her pregnancy results in highly complex changes in neuronal morphology in the medial prefrontal, but not in the orbitofrontal cortical regions of her future offspring that persist into adulthood. Moreover, our study revealed that (1) in the PCS2 group (offspring of dams mated two weeks after stress) spine numbers and dendritic length and complexity were increased in response to PCS in the ACd and PL/IL, (2) these regional effects depended on the temporal proximity of adversity and conception, (3) in the ACd of the PCS2 group only males and the left hemispheres were affected. We speculate that these transgenerational brain structural changes are mediated by stress-induced epigenetic (re)programming of future gene activity in the oocyte.