Copy number variants on the X chromosome in women with primary ovarian insufficiency

Objective: To investigate whether submicroscopic copy number variants (CNVs) on the X chromosome can be identified in women with primary ovarian insufficiency (POI), defined as spontaneous secondary amenorrhea before 40 years of age accompanied by follicle-stimulating hormone levels above 40 IU/L on at least two occasions. Design: Analysis of intensity data of single nucleotide polymorphism (SNP) probes generated by genomewide Illumina 370k CNV BeadChips, followed by the validation of identified loci using a custom designed ultra-high-density comparative genomic hybridization array containing 48,325 probes evenly distributed over the X chromosome. Setting: Multicenter genetic cohort study in the Netherlands. Patient(s): 108 Dutch Caucasian women with POI, 97 of whom passed quality control, who had a normal karyogram and absent fragile X premutation, and 235 healthy Dutch Caucasian women as controls. Intervention(s): None. Main Outcome Measure(s): Amount and locus of X chromosomal microdeletions or duplications. Result(s): Intensity differences between SNP probes identify microdeletions and duplications. The initial analysis identified an overrepresentation of deletions in POI patients. Moreover, CNVs in two genes on the Xq21.3 locus (i.e., PCDH11X and TGIF2LX) were statistically significantly associated with the POI phenotype. Mean size of identified CNVs was 262 kb. However, in the validation study the identified putative Xq21.3 deletions samples did not show deviations in intensities in consecutive probes. Conclusion(s): X chromosomal submicroscopic CNVs do not play a major role in Caucasian POI patients. We provide guidelines on how submicroscopic cytogenetic POI research should be conducted. (Fertil Steril (R) 2011;95:1584-8. (C) 2011 by American Society for Reproductive Medicine.)

Post-menopausal hormone therapy reduces autoantibodies to oxidized apolipoprotein B100

The aim of the study was to verify whether post-menopausal hormone replacement therapy (HRT) modifies autoantibody titers against oxidized low-density lipoprotein (LDL) (anti-LDLoxi), against epitopes of oxidized apolipoprotein B100 and common carotid intima-media thickness (IMT) in these women. Sixty-eight women in pre-menopause (PMW) and 216 in post-menopause (POMW) were recruited; eighty-three had undergone HRT for at least 12 months, where 48 received conjugated estrogens alone (EHRT) and 35 received conjugated estrogen and medroxyprogesterone acetate (CHRT). ELISA was used to determine autoantibodies. Lipoprotein lipase (LPL), hepatic lipase (HL), cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities were assayed by radiometric methods. IMT was measured using Doppler ultrasound. Anti-oxidized LDL and anti-D antibodies increased by 40% (p <= 0.003) and 42% (p <= 0.006), respectively, with menopause. There was a surprising and significant 7% reduction in anti-D2 antibody titers with HRT (p <= 0.050), indicating a positive effect of treatment on the immune response to oxidized LDL. Combined HRT decreased activities of HL and LPL. HRT did not change common carotid IMT, which was increased by 32% as expected after menopause (p <= 0.030). This study describes, for the first time, the protective effect of HRT on decreasing autoantibody titers against oxidized apolipoprotein B in LDL.

Morphometric analysis of the urethra of castrated female rats treated with tamoxifen

Objectives: The aim of this study was to evaluate the effects of tamoxifen on the weight and thickness of the urethral epithelium of castrated female rats. Methods: Forty castrated adult female Wistar-Hannover rats were randomly divided into two groups: Group I (n = 20) in which the animals received only the vehicle (propylene glycol) and Group 11 (n = 20) in which the rats received tamoxifen 250 mu g/day by gavage. After 30 days of treatment, all animals were sacrificed and the urethra was immediately removed for weighing. Next, the urethra was divided into the proximal and distal segments, which were fixed in 10% formaldehyde and submitted to routine histological techniques for morphometric study. The data were analyzed using the weighted minimum mean-square error method and Student`s t-test for two independent samples (p < 0.05). Results: There was a significant increase in the mean weight of the urethra in the rats of Group 11 compared to the control group, 32.0 +/- 2.0 mg and 22.0 +/- 1.6 mg, respectively (p < 0.001). The mean thickness of the distal urethral epithelium of the animals treated with tamoxifen was significantly greater than that of the control group, 42.8 +/- 2.0 mu m and 36.6 +/- 1.5 mu m, respectively (p < 0.001). There was no statistically significant difference between the two groups with respect to the epithelial thickness of the proximal urethra (p = 0.514). Conclusion: Treating castrated adult rats with 250 mu g/day of tamoxifen for 30 days may increase the weight of the urethra and the thickness of the distal urethral epithelium. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer

Purpose: To evaluate the microvessel density by comparing the performance of anti-factor VIII-related antigen, anti-CD31 and, anti-CD34 monoclonal antibodies in breast cancer. Methods: Twenty-three postmenopausal women diagnosed with Stage II breast cancer submitted to definitive surgical treatment were evaluated. The monoclonal antibodies used were anti-factor VIII, anti-CD31 and anti-CD34. Microvessels were counted in the areas of highest microvessel density in ten random fields (200 x). The data were analyzed using the Kruskal-Wallis nonparametric test (p < 0.05). Results: Mean microvessel densities with anti-factor VIII, anti-CD31 and anti-CD34 were 4.16 +/- 0.38, 4.09 +/- 0.23 and 6.59 +/- 0.42, respectively. Microvessel density as assessed by anti-CD34 was significantly greater than that detected by anti-CD31 or anti-factor VIII (p < 0.0001). There was no statistically significant difference between anti-CD31 and anti-factor VIII (p = 0.4889). Conclusion: The density of stained microvessels was greater and staining was more intense with anti-CD34 compared to anti-CD31 and anti-factor VII-related antigen.

Workforce trends in specialist and GP obstetric practice in Victoria

OBJECTIVE: To provide a contemporary picture of the general practitioner and specialist obstetric workforce in Victoria.

DESIGN, PARTICIPANTS AND SETTING: Postal census by questionnaire of all 317 Fellows and 961 Diplomates on the Victorian database of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists in September 2003.

MAIN OUTCOME MEASURES: Sex, age and geographical distributions and patterns of retirement from and recruitment to the GP and specialist obstetric workforce in Victoria.

RESULTS: 244 Fellows (77.0%) and 652 Diplomates (67.8%) participated. The average age of Diplomates was 42 years; only 20% were involved in procedural obstetrics. Of GPs practising procedural obstetrics, 56% intended to cease within 7 years. Two-thirds of specialist obstetricians continued to practise obstetrics. Among those ceasing obstetrics, almost half had done so since 2000. Among Fellows ceasing obstetric practice, there is a peak in the 50-60-years age group, but cessation of obstetric practice occurred across all age groups.

CONCLUSION: The proportion of GPs involved in procedural obstetrics has fallen markedly over the past decade, with half of those ceasing practice in the 40-50-years age group. New GPs entering the workforce with the Diploma and overseas doctors are unlikely to meet the procedural workforce shortfall. Attracting the large cohort of doctors aged 40-50 years back to obstetric practice must be a priority. Given the pattern of retirements from obstetrics, there will be insufficient numbers of specialists to maintain current levels of service. The reasons include non-participation in obstetrics by new graduates and international medical graduates, the inadequate number of new graduates, and the predominance of women among specialists aged under 40 years, whose work output tends to be affected by family commitments.

Use of complementary and alternative medicines by a sample of Australian women during pregnancy

Background: The use of complementary and alternative medicines (CAM) is growing in Australia, with women higher users than men. Yet, only a few Australian studies have explored the use of CAM during pregnancy.

Aims: To explore the use of CAM, the types of CAM practitioners consulted, physical symptoms/complaints for which CAM are used by a sample of pregnant Australian women, and women's perceptions of the efficacy of CAM in treating those complaints.

Methods: Three hundred and twenty-one pregnant women, who volunteered for a study exploring women's well-being during pregnancy, completed a self-report questionnaire in their late second/early third trimester.

Results: Seventy-three per cent of women had used at least one kind of complementary therapy in the prior eight weeks of pregnancy. Over one-third of the women had visited at least one alternative medicine practitioner during pregnancy. Approximately one-third of the women reported taking CAM to alleviate a specific physical symptom, with 95.7% of these women reporting they either got completely better or a little bit better with use of CAM; one quarter reported planning to use an alternative therapy to assist with labour preparation. Age, number of physical symptoms experienced, income level and level of education were not associated with greater use of CAM (P < 0.05); however, women reporting more physical symptoms were more likely to consult a CAM practitioner.

Conclusion: Findings highlight the substantial use of CAM during pregnancy and the need to have all health professionals adequately informed about such therapies during this life stage.

Prevalence and cost of musculoskeletal disorders: a population-based, public hospital system healthcare consumption approach.

Objective: To use a population-level, public-hospital approach to compare the prevalence and cost of musculoskeletal diseases (MSD) with other clinical specialties.

Methods: A healthcare utilization survey of 4 million individual records over 4 years, from all major public hospitals in the state of Victoria (estimated population 4.8 million residents in 2000/01) from 1997/98 to 2000/01. Main outcome measures were inpatient episodes of care, bed-days, and outpatient clinic encounters. MSD was defined as the combination of orthopedics and rheumatology.

Results: After obstetrics, MSD was the most frequent outpatient service, with orthopedics accounting for 9.9% of all visits in 2000/01. The proportion of MSD outpatient encounters (on average 11.6% of the total) was constant over the study period. Among 26 medical specialties, MSD had the sixth highest number of inpatient episodes (6.2% in 2000/01), following renal dialysis (14.6%), general surgery (8.2%), obstetrics (7.6%), gastroenterology (7.1%), and general medicine (6.7%). MSD was the fifth highest consumer of bed-days, occupying on average 7.7% of all beds per annum in the period 1997/98 to 2000/01, behind psychiatry (10.1%), respiratory medicine (8.5%), rehabilitation (8.3%), and general medicine (7.8%). MSD was the third most-costly discipline in 2000/01, with total costs of over A dollars 169 million (9.7% of total inpatient costs that year), behind respiratory medicine (11.6%) and general surgery (11.5%).

Conclusion: Compared to other diseases, MSD consumes a substantial proportion of healthcare resources in Victorian public hospitals. These data have important implications for allocation of healthcare resources, clinical care pathways, and prevention strategies.

Adolescent depressive symptoms and subsequent pregnancy, pregnancy completion and pregnancy termination in young adulthood : findings from the Victorian Adolescent Health Cohort Study

Study Objective: To examine relationships between depressive symptoms in adolescence (14-18 years of age) and becoming pregnant, completing a pregnancy (live birth) and terminating a pregnancy in young adulthood (21-24 years of age).

Participants and Design: Data from 1000 females were drawn from a larger sample of 1943 young Australians participating in a longitudinal study of adolescent health and development, followed across 8 waves from adolescence (waves 1-6) to young adulthood (waves 7 and 8).

Setting: Victoria, Australia.

Main Outcome Measures: Pregnancy, pregnancy completion and pregnancy termination between 21-24 years of age.

Results: We observed a twofold increase in the odds of becoming pregnant in those reporting persisting patterns of depressive symptoms during adolescence (2þ waves); however, after staged adjustment for adolescent antisocial behaviour, drug use and socioeconomic disadvantage, there was no evidence of association. Of particular note, and consistent with previous research, adolescent antisocial and drug use behavior were strongly associated with becoming pregnant and pregnancy termination in young adulthood.

Conclusions: Adolescent antisocial and drug use behavior, not depressive symptoms, independently predict pregnancy outcomes in young adulthood.

Interventions designed to promote exclusive breastfeeding in high-income countries: a systematic review

Worldwide, women fail to reach the recommended exclusive breastfeeding target of 6 months postpartum. The objective of this study was to present a conceptual and methodological synthesis of interventions designed to promote exclusive breastfeeding to 6 months in high-income countries.

The transition to motherhood: towards a broader understanding of perinatal distress

A substantial body of research has focused on maternal perinatal mood and wellbeing, with the focus predominantly being on depression, and to a lesser extent, anxiety. Perinatal maternal stress has also been investigated recently, but to a far lesser extent. The present paper questions whether the term 'perinatal distress' accurately captures the range of challenges experienced by women during the perinatal period, when the scope of 'distress' is limited to the experience of depression and anxiety alone.

Study protocol: asking questions about alcohol in pregnancy (AQUA): a longitudinal cohort study of fetal effects of low to moderate alcohol exposure

Despite extensive research, a direct correlation between low to moderate prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders has been elusive. Conflicting results are attributed to a lack of accurate and detailed data on PAE and incomplete information on contributing factors. The public health effectiveness of policies recommending complete abstinence from alcohol during pregnancy is challenged by the high frequency of unplanned pregnancies, where many women consumed some alcohol prior to pregnancy recognition. There is a need for research evidence emphasizing timing and dosage of PAE and its effects on child development.

The impact of maternal smoking during pregnancy on depressive and anxiety behaviors in children: the Norwegian Mother and Child Cohort Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is associated with multiple adverse childhood outcomes including externalizing behaviors. However, the association between MSDP and internalizing (anxiety and depressive) behaviors in offspring has received less investigation. We aimed to assess the association between MSDP and childhood internalizing (anxiety and depressive) behaviors in a very large, well-characterized cohort study. METHODS: We assessed the association between MSDP and internalizing behaviors in offspring utilizing information drawn from 90,040 mother-child pairs enrolled in the Norwegian Mother and Child Cohort Study. Mothers reported smoking information, including status and frequency of smoking, twice during pregnancy. Mothers also reported their child's internalizing behaviors at 18 months, 36 months, and 5 years. Associations between MSDP and childhood internalizing behaviors, including dose-response and timing of smoking in pregnancy, were assessed at each time point. RESULTS: MSDP was associated with increased internalizing behaviors when offspring were aged 18 months (B = 0.11, P <0.001) and 36 months (B = 0.06, P <0.01), adjusting for numerous potential confounders. Higher rates of smoking (e.g., >20 cigarettes per day) were associated with higher levels of internalizing behaviors. Maternal smoking during early pregnancy appeared to be the critical period for exposure. CONCLUSIONS: We found evidence supporting a potential role for MSDP in increasing internalizing (anxiety and depressive) behaviors in offspring. We also found evidence supportive of a possible causal relationship, including dose-dependency and support for a predominant role of early pregnancy exposure. Further investigation utilizing genetically informed designs are warranted to assess this association.

Maternal creatine homeostasis is altered during gestation in the spiny mouse: is this a metabolic adaptation to pregnancy?

BACKGROUND: Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse. METHODS: Plasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis. RESULTS: Plasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P < 0.001, P < 0.05, respectively). Pregnancy resulted in increased lean tissue (P < 0.01), kidney (P < 0.01), liver (P < 0.01) and heart (P < 0.05) mass at term. CrT1 expression was increased in the heart (P < 0.05) and skeletal muscle (P < 0.05) at term compared to non-pregnant tissues, and creatine content of the heart (P < 0.05) and kidney (P < 0.001) were also increased at this time. CrT1 mRNA expression was down-regulated in the liver (<0.01) and brain (<0.01) of pregnant spiny mice at term. Renal AGAT mRNA (P < 0.01) and protein (P < 0.05) expression were both significantly up-regulated at term, with decreased expression of AGAT mRNA (<0.01) and GAMT protein (<0.05) observed in the term pregnant heart. Brain AGAT (<0.01) and GAMT (<0.001) mRNA expression were also decreased at term. CONCLUSION: Change of maternal creatine status (increased creatine synthesis and reduced creatine excretion) may be a necessary adjustment of maternal physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus.

Exploring Heideggerian hermeneutic phenomenology: a perfect fit for midwifery research

BACKGROUND: Heideggerian hermeneutic phenomenology has been used widely to understand the meaning of lived experiences in health research. For midwifery scholars this approach enables deep understanding of women's and midwives' lived experiences of specific phenomena. However, for beginning researchers this is not a methodology for the faint hearted. It requires a period of deep immersion to come to terms with at times impenetrable language and perplexing concepts. OBJECTIVES: This paper aims to assist midwives to untangle and examine some of the choices they face when they first come to terms with an understanding of this methodology and highlights the methodology's capacity to reveal midwifery authenticity and holistic practice. DISCUSSION: The illumination of a selection of various concepts underpinning hermeneutic phenomenology will inform midwives considering this methodology as suitable framework for exploring contemporary midwifery phenomena.