Adult parent-child relationships: Relationship quality, support, and reciprocity

In accordance with Bengtson's model of intergenerational solidarity (e.g. Bengtson & Roberts, 1991), the interrelations between adult daughters' family values, their perception of the relationship quality with their parents, the support they reported to give to and to receive from their parents, and their perception of reciprocity in intergenerational support exchange were investigated for N = 265 middle-aged women in Germany. It was also asked whether the support given to parents and perceived reciprocity are related to daughters' felt burden as a result of their support. Cross-sectional, self-report data were examined with multiple and multinomial logistic regression analyses. The analyses revealed positive relations between family values, relationship quality, and support to parents. Perceived reciprocity was associated with the exchange of intergenerational support and imbalance in support had negative effects on the relationship quality. Felt burden was predicted by the extent of support and the perceived reciprocity. However, specific correlational patterns depending on the kind of support as well as differences in the importance of mother and father occurred. The findings are discussed against the background of the meaning of family obligations and reciprocity in a Western culture.

Loss to follow-up of HIV-infected women after delivery: The Swiss HIV Cohort Study and the Swiss Mother and Child HIV Cohort Study.

INTRODUCTION HIV-infected pregnant women are very likely to engage in HIV medical care to prevent transmission of HIV to their newborn. After delivery, however, childcare and competing commitments might lead to disengagement from HIV care. The aim of this study was to quantify loss to follow-up (LTFU) from HIV care after delivery and to identify risk factors for LTFU. METHODS We used data on 719 pregnancies within the Swiss HIV Cohort Study from 1996 to 2012 and with information on follow-up visits available. Two LTFU events were defined: no clinical visit for >180 days and no visit for >360 days in the year after delivery. Logistic regression analysis was used to identify risk factors for a LTFU event after delivery. RESULTS Median maternal age at delivery was 32 years (IQR 28-36), 357 (49%) women were black, 280 (39%) white, 56 (8%) Asian and 4% other ethnicities. One hundred and seven (15%) women reported any history of IDU. The majority (524, 73%) of women received their HIV diagnosis before pregnancy, most of those (413, 79%) had lived with diagnosed HIV longer than three years and two-thirds (342, 65%) were already on antiretroviral therapy (ART) at time of conception. Of the 181 women diagnosed during pregnancy by a screening test, 80 (44%) were diagnosed in the first trimester, 67 (37%) in the second and 34 (19%) in the third trimester. Of 357 (69%) women who had been seen in HIV medical care during three months before conception, 93% achieved an undetectable HIV viral load (VL) at delivery. Of 62 (12%) women with the last medical visit more than six months before conception, only 72% achieved an undetectable VL (p=0.001). Overall, 247 (34%) women were LTFU over 180 days in the year after delivery and 86 (12%) women were LTFU over 360 days with 43 (50%) of those women returning. Being LTFU for 180 days was significantly associated with history of intravenous drug use (aOR 1.73, 95% CI 1.09-2.77, p=0.021) and not achieving an undetectable VL at delivery (aOR 1.79, 95% CI 1.03-3.11, p=0.040) after adjusting for maternal age, ethnicity, time of HIV diagnosis and being on ART at conception. CONCLUSIONS Women with a history of IDU and women with a detectable VL at delivery were more likely to be LTFU after delivery. This is of concern regarding their own health, as well as risk for sexual partners and subsequent pregnancies. Further strategies should be developed to enhance retention in medical care beyond pregnancy.

Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus--harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.

Shaping the values of the next generation: Value transmission processes within the family

Abstract: Research on human values within the family focuses on value congruence between the family members (Knafo & Schwartz, 2004), based on the assumption that transmission of values is part of a child’s socialization process. Within the family, values are not only implicitly transmitted through this process but also explicitly conveyed through the educational goals of parents (Grusec et al., 2000; Knafo & Schwartz, 2003; 2004, 2009). However, there is a lack of empirical evidence on the role of family characteristics in the value transmission process, especially for families with young children. Thus, the study presented had multiple aims: Firstly, it analyzed the congruency between mothers’ and fathers’ values and their value-based educational goals. Secondly, it examined the influence of mothers’ and fathers’ socio-demographic characteristics on their educational goals. Thirdly, it analyzed the differences in parental educational goals in families with daughters and families with sons. Finally, it examined the congruency between children’s values and the value-based educational goals of their parents. The value transmission process within families with young children was analyzed using data from complete families (child, mother and father) in Switzerland (N = 265). The survey of children consisted of 139 boys and 126 girls aged between 7 and 9 years. Parents’ values and parental educational goals were assessed using the Portrait Value Questionnaire (PVQ-21) (Schwartz, 2005). Children’s’ values were assessed using the Picture-Based Value Survey for Children (PBVS-C) (Döring et al., 2010). Regarding the role of the family context in the process of shaping children’s values, the results of the study show that, on average, parents are similar not only with respect to their value profiles but also with regard to their notion as to which values they would like to transmit to their children. Our findings also suggest that children’s values at an early age are shaped more strongly by mothers’ values than by fathers’ values. Moreover, our results show differences in value transmission with respect to the child’s gender. In particular, they suggest that value transmission within the family has a greater influence on female than on male offspring.

Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood

We report on a female who is compound heterozygote for two new point mutations in the CYP19 gene. The allele inherited from her mother presented a base pair deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele inherited from her father showed a point mutation from G-->A at the splicing point (canonical GT to mutational AT) between exon and intron 3. This mutation ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase deficiency was already suspected because of the marked virilization occurring prepartum in the mother, and the diagnosis was confirmed shortly after birth. Extremely low levels of serum estrogens were found in contrast to high levels of androgens. Ultrasonographic follow-up studies revealed persistently enlarged ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day) given for 50 days at the age of 3 6/12 yr resulted in normalization of serum gonadotropin levels, regression of ovarian size, and increase of whole body and lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size returned to pretreatment levels shortly (150 days) after cessation of E2 therapy. Therefore, we recommend that affected females be treated with low-dose E2 in amounts sufficient to result in physiological prepubertal E2 concentrations using an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted throughout childhood and puberty to ensure normal skeletal maturation and adequate adolescent growth spurt, normal accretion of bone mineral density, and, at the appropriate age, female secondary sex maturation.

Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data

Background There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women. Objective The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity. Method We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS). Results Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85–3.6] and 2.5 (95% CI 1.4–4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy. Conclusion Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women.

Pregnancy and delivery outcomes of HIV infected women in Switzerland 2003-2008

Rates of vertical HIV transmission between mother and child are low, allowing many HIV positive women to have children with near impunity. In this study, data from the Swiss Mother and Child HIV Cohort Study were used to describe maternal characteristics and their association with pregnancy outcomes in HIV positive women.

Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

GH mutant (R77C) in a pedigree presenting with the delay of growth and pubertal development: structural analysis of the mutant and evaluation of the biological activity

A heterozygous missense mutation in the GH-1 gene converting codon 77 from arginine (R) to cysteine (C), which was previously reported to have some GH antagonistic effect, was identified in a Syrian family. The index patient, a boy, was referred for assessment of his short stature (-2.5 SDS) at the age of 6 years. His mother and grandfather were also carrying the same mutation, but did not differ in adult height from the other unaffected family members. Hormonal examination in all affected subjects revealed increased basal GH, low IGF-I concentrations, and subnormal IGF-I response in generation test leading to the diagnosis of partial GH insensitivity. However, GH receptor gene (GHR) sequencing demonstrated no abnormalities. As other family members carrying the GH-R77C form showed similar alterations at the hormonal level, but presented with normal final height, no GH therapy was given to the boy, but he was followed through his pubertal development which was delayed. At the age of 20 years he reached his final height, which was normal within his parental target height. Functional characterization of the GH-R77C, assessed through activation of Jak2/Stat5 pathway, revealed no differences in the bioactivity between wild-type-GH (wt-GH) and GH-R77C. Detailed structural analysis indicated that the structure of GH-R77C, in terms of disulfide bond formation, is almost identical to that of the wt-GH despite the introduced mutation (Cys77). Previous studies from our group demonstrated a reduced capability of GH-R77C to induce GHR/GH-binding protein (GHBP) gene transcription rate when compared with wt-GH. Therefore, reduced GHR/GHBP expression might well be the possible cause for the partial GH insensitivity found in our patients. In addition, this group of patients deserve further attention because they could represent a distinct clinical entity underlining that an altered GH peptide may also have a direct impact on GHR/GHBP gene expression causing partial GH insensitivity. This might be responsible for the delay of growth and pubertal development. Finally, we clearly demonstrate that GH-R77C is not invariably associated with short stature, but that great care needs to be taken in ascribing growth failure to various heterozygous mutations affecting the GH-IGF axis and that careful functional studies are mandatory.

Evaluation of the biological activity of a growth hormone (GH) mutant (R77C) and its impact on GH responsiveness and stature

CONTEXT AND OBJECTIVE: A single missense mutation in the GH-1 gene converting codon 77 from arginine (R) to cysteine (C) yields a mutant GH-R77C peptide, which was described as natural GH antagonist. DESIGN, SETTING, AND PATIENTS: Heterozygosity for GH-R77C/wt-GH was identified in a Syrian family. The index patient, a boy, was referred for assessment of his short stature (-2.5 SD score) and partial GH insensitivity was diagnosed. His mother and grandfather were also carrying the same mutation and showed partial GH insensitivity with modest short stature. INTERVENTIONS AND RESULTS: Functional characterization of the GH-R77C was performed through studies of GH receptor binding and activation of Janus kinase 2/Stat5 pathway. No differences in the binding affinity and bioactivity between wt-GH and GH-R77C were found. Similarly, cell viability and proliferation after expression of both GH peptides in AtT-20 cells were identical. Quantitative confocal microscopy analysis revealed no significant difference in the extent of subcellular colocalization between wt-GH and GH-R77C with endoplasmic reticulum, Golgi, or secretory vesicles. Furthermore studies demonstrated a reduced capability of GH-R77C to induce GHR/GHBP gene transcription rate when compared with wt-GH. CONCLUSION: Reduced GH receptor/GH-binding protein expression might be a possible cause for the partial GH insensitivity with delay in growth and pubertal development found in our patients. In addition, this group of patients deserves further attention because they could represent a distinct clinical entity underlining that an altered GH peptide may also have a direct impact on GHR/GHBP gene expression causing partial GH insensitivity.

Leukaemia and pregnancy

In summary, the management of women diagnosed with leukaemia in pregnancy needs an interdisciplinary approach, including a careful oncological work-up as well as close monitoring of the pregnancy until delivery and beyond. Patients with acute leukaemias normally must receive anti-leukaemic treatment at full dosage prior to delivery, except for selected women diagnosed very close to term. Treatment should be avoided in the first trimester. The prognosis of pregnant women with acute leukaemia corresponds to that of an age-matched and diagnosis-matched non-pregnant cohort of patients, provided appropriate treatment is given. If given as of the second trimester, the typical chemotherapy regimes used for acute leukaemias imply acceptable acute toxicities to the fetus, with a somewhat increased risk of premature birth or developmental retardation, but no clear evidence of late sequelae in children and adolescents who were exposed to cytostatic agents whilst in utero. In chronic leukaemias and MDS, treatment may often be delayed until after delivery. In CML targeted therapy with imatinib mesylate is safe as of the second trimester, and possibly even before. Obstetric care and monitoring of women with leukaemia are essential throughout the pregnancy to ensure the best possible outcome for mother and child.

Management of early aggressive rheumatoid arthritis during pregnancy and lactation

This survey outlines the problems of drug therapy in women with early aggressive rheumatoid arthritis (RA) who desire children, are pregnant, or are lactating. Solutions for treatment that benefit the mother and do not harm the fetus or the breast-fed child are discussed. The most effective immunosuppressive drugs alone or in combination are contraindicated during pregnancy and, to a lesser degree, also during lactation. Judicious timing of therapy is therefore necessary, aiming at fast remission of symptoms with the most effective therapy and maintaining quiescent disease with drugs compatible with pregnancy or lactation.

Elevated serum triiodothyronine and intellectual and motor disability with paroxysmal dyskinesia caused by a monocarboxylate transporter 8 gene mutation

Monocarboxylate transporter 8 (MCT8 or SLC16A2) is important for the neuronal uptake of triiodothyronine (T3) in its function as a specific and active transporter of thyroid hormones across the cell membrane, thus being essential for human brain development. We report on a German male with Allan-Herndon-Dudley syndrome presenting with severe intellectual and motor disability, paroxysmal dyskinesia combined with truncal muscular hypotonia, and peripheral muscular hypertonia at his current age of 9 years. Additionally, the patient has a lesion in the left putamen region revealed by magnetic resonance imaging and elevated serum T3 levels. The male appeared to have a hemizygous mutation (R271H) in the MCT8 gene that was sequenced directly from genomic DNA and occurred de novo in the maternal germline, as both his mother and his sister were not carriers of the mutation. Ruling out a common polymorphism, 50 normal individuals of the same ethnic background did not harbour the mutation. The identified MCT8 gene mutation (R271H) is very likely to be the genetic cause for neuronal hypothyroidism despite elevated serum T3 levels.

Facial esthetics in children with unilateral cleft lip and palate 3 years after alveolar bonegrafting combined with rhinoplasty between 2 and 4 years of age

OBJECTIVES To evaluate facial esthetics in patients with unilateral cleft lip and palate (UCLP) after alveolar bone grafting combined with rhinoplasty between 2 and 4 years of age. DESIGN Retrospective case-control study. SETTING The Department of Pediatric Surgery, Institute of Mother and Child, Warsaw, Poland. MATERIAL AND METHODS Photographs of full faces and cropped images of five nasolabial components: nasal deviation, nasal form, nasal profile, vermillion border, and inferior view were assessed by 5 professional and 14 layraters in 29 children (23 boys and 6 girls; mean age = 5.3 years, SD 0.5; Early-grafted group) and 30 children (20 boys and 10 girls; mean age = 5.5 years, SD 1.0; Non-grafted group) with complete unilateral cleft lip and palate repaired with a one-stage closure. The groups differed regarding the timing of alveolar bone grafting: in the Early-grafted group, alveolar bone grafting in combination with rhinoplasty (ABG-R) was performed between 2 and 4 years of age (mean age = 2.3 years; SD 0.6); in the Non-grafted group, the alveolar defect was grafted after 9 years of age. No primary nose correction was carried out in any group. To rate esthetics, a modified five-grade esthetic index of Asher-McDade was used, where grade 1 means the most esthetic and grade 5 - the least esthetic outcome. RESULTS Esthetics of full faces and of all nasolabial elements in the Early-grafted group was significantly better than in Non-grafted group. The scores in the Early-grafted group ranged from 2.30 to 2.66 points, whereas in the Non-grafted group ranged from 2.66 to 3.17 points. All intergroup differences were statistically significant (p < 0.05). CONCLUSIONS Three years post-operatively, early alveolar bone grafting combined with rhinoplasty is favorable for facial esthetics in children with UCLP, but a longer follow-up is needed to assess whether the improvement was permanent.

Current insights into thrombotic microangiopathies: Thrombotic thrombocytopenic purpura and pregnancy.

The complex relation between thrombotic thrombocytopenic purpura (TTP) and pregnancy is concisely reviewed. Pregnancy is a very strong trigger for acute disease manifestation in patients with hereditary TTP caused by double heterozygous or homozygous mutations of ADAMTS13 (ADisintegrin And Metalloprotease with ThromboSpondin type 1 domains, no. 13). In several affected women disease onset during their first pregnancy leads to the diagnosis of hereditary TTP. Without plasma treatment mother and especially fetus are at high risk of dying. The relapse risk during a next pregnancy is almost 100% but regular plasma transfusion starting in early pregnancy will prevent acute TTP flare-up and may result in successful pregnancy outcome. Pregnancy may also constitute a mild risk factor for the onset of acute acquired TTP caused by autoantibody-mediated severe ADAMTS13 deficiency. Women having survived acute acquired TTP may not be at very high risk of TTP relapse during an ensuing next pregnancy but seem to have an elevated risk of preeclampsia. Monitoring of ADAMTS13 activity and inhibitor titre during pregnancy may help to guide management and to avoid disease recurrence. Finally, TTP needs to be distinguished from the much more frequent hypertensive pregnancy complications, preeclampsia and especially HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet count) syndrome.