This longitudinal study investigated the possible influence of estradiol (E₂), progesterone (P), testosterone (T), cortisol (CORT), and prolactin (PRL) levels on cognitive functioning during late pregnancy and the early postpartum period. The performance of 55 pregnant women on a battery of neuropsychological tests, tested once during the third trimester of pregnancy and once during the early postpartum period, was compared with that of 21 nonpregnant controls matched for age and education. Women in the pregnancy group had significantly lower scores than the controls during both the pre- and postpartum visits on tasks of verbal recall and processing speed. CORT levels were significantly associated, in an inverted-U function, with verbal recall scores at both the pregnancy and at postpartum periods and with spatial abilities at postpartum only. During pregnancy, PRL levels were associated in both a linear and an inverted-U function with scores on tests of paragraph recall and in a linear function with scores on tests of executive function. At postpartum, E₂ and CORT were negatively associated in a linear fashion with attention scores. These findings provide new evidence that fluctuating hormone levels during late pregnancy and early postpartum may modulate selected cognitive abilities.

This study investigated episodic and procedural memory performance in early and late pregnancy. Twenty-six women in the third trimester of pregnancy, 20 women in the first trimester of pregnancy, and 24 nonpregnant controls were administered a battery of verbal and visual episodic memory tasks and two procedural memory tasks. Results indicated that compared to controls, both pregnant groups had reduced scores on immediate and delayed verbal episodic memory tasks, but were unimpaired on visual and procedural memory tasks. Verbal memory differences could not be accounted for by mood state or attention; however, progesterone level accounted for a small amount of the variation. Although memory differences were minor, the perception of memory problems may have implications for everyday living for pregnant women.

We compared 21 postpartum depressed (PPD) women, 22 postpartum nondepressed (PPND) women, and 24 nondepressed, nonpostpartum women on a neuropsychological test battery. Postpartum women presented lower performance on initial learning (Rey Auditory Verbal Learning Test, RAVLT) than did controls. Further, PPD women presented lower performance on Part B of the Trail Making Test than did PPND women and controls. No differences were observed in RAVLT recall or recognition trials, in Greek versions of the Controlled Oral Word Association Test, or in the Ruff 2 and 7 Selective Attention Test. Findings support the hypothesis that postpartum cognitive difficulties could be partially due to postnatal mood problems.

Neocortical plasticity is not usually associated with changes in reproductive function. However, we have shown a six to 10-fold increase in the number of astrocytes labeled with glial fibrillary acidic protein (GFAP) and astrocytic basic fibroblast growth factor or FGF-2 (bFGF) in the cingulate cortex area 2 (Cg2) in postpartum rats, indicative of changes in connectivity in this area. In the present studies, we investigated the necessary and sufficient stimuli for these changes to occur. We show that 3 h of maternal experience combined with a hormonal treatment that mimics late pregnancy induces the astrocytic changes in Cg2 in virgin rats. The extent of these changes was similar to those of postpartum females. Sensitized virgin females did not show any astrocytic changes after 3 h of maternal behavior, suggesting that a similar amount of maternal experience alone is not sufficient to increase astrocytic bFGF- and GFAP-immunoreactivity in Cg2. Consistent with these data, eliminating early maternal experience by removing pups immediately postpartum abolishes the increased bFGF and GFAP protein expression in the cingulate cortex. These results suggest that maternal experience and hormonal state interact to produce astrocytic remodeling in the Cg2. The current results are consistent with a role for the cingulate cortex in maternal responsivity as suggested by early lesion studies in rats and more recent imaging studies in humans.

Although until recently much of the evidence for pregnancy-related deficits in memory was anecdotal or based on self-report, a number of studies have now been conducted that have tested whether these subjective appraisals of memory difficulties reflect objective impairment. However, these studies have failed to yield consistent results. A meta-analysis of the 14 studies that have been conducted over the past 17 years comparing pregnant and/or postpartum women with healthy matched controls on behavioral measures of memory was conducted. The results indicate that pregnant women are significantly impaired on some, but not all, measures of memory, and, specifically, memory measures that place relatively high demands on executive cognitive control may be selectively disrupted. The same specific deficits associated with pregnancy are also observed postpartum. These findings highlight the need for exploration of the etiologies and functional consequences of pregnancy-related memory difficulties and may help to guide the interpretation of neuropsychological data for the purpose of determining cognitive status in individuals who are pregnant or postpartum.

Previous work has suggested that DHEA supplementation may have adverse cognitive effects in elderly women. This article analyzed 24-h measurements of DHEA, DHEAS, and cortisol to determine if cognitive decrease with treatment is mediated by DHEA's impact on endogenous cortisol. It was found that DHEA administration increased cortisol at several hours during the day. In the treatment group, cortisol was positively associated with cognition at study completion. An increase in negative associations between DHEA(S) levels and cognition was found at completion. Increased cortisol does not explain the cognitive deficits associated with DHEA, suggesting a direct negative effect of exogenous DHEA on cognition.

Steroidal hormones are increasingly recognized as highly relevant in multiple aspects of brain functioning. While basic science has actively worked to advance understanding of fundamental steroid mechanisms within the brain, investigation of the neurobehavioral outcomes of reproductive hormone actions on the human brain has received less attention. We argue that the dramatic steroidal hormone changes seen in human reproduction must be systematically studied and may provide novel explanations of cognitive and mood disorders associated with reproductive events. This chapter provides a review of current literature establishing a role for a variety of steroids on neuroactivity, and evidence from a variety of observational and experimental paradigms linking hormones and clinical aspects of cognition and mood in humans. The specific hormonal changes of pregnancy are described and discussed in relation to concomitant alterations in cognition and mood across the peri-natal period. A review of studies that have systematically observed cognitive and affective changes both during pregnancy and the post-partum period is presented, as well as new data that follow a small cohort of women for an extended period of time after delivery. We conclude that women may show specific areas of cognitive changes during and after pregnancy, notably deficits in verbal learning and memory. Mood appears to be impacted as well. While steroidal hormones show a pattern of associations with mood during and after pregnancy, no such pattern is evident for cognition. The embryonic state of our knowledge regarding reproductive hormones and neurobehavioral functioning is evident, as are the scientific and public health reasons to redress this lacuna.

The effects of pregnancy on cognition and mood were examined using a repeated-measures design. Nineteen women, average age 33, were tested with a comprehensive neuropsychological battery during their last 2 months of pregnancy and again within 2 months of delivery. Blood samples were obtained from all subjects and assayed for a variety of steroid hormones implicated in cognitive and mood functioning. Most participants also completed several self-report measures of mood. In comparison with performance after delivery, women showed significantly more impairment in aspects of verbal memory during pregnancy and also tended to report more negative mood states. Memory deficits were not explained by mood disturbances. No hormone assayed consistently related to cognitive performance during pregnancy. During pregnancy, higher levels of progesterone (P) were associated with greater mood disturbances and higher levels of dehydroepiandrosterone (DHEA) with better mood. After delivery, testosterone (T) was strongly and consistently associated with greater reported mood disturbances. Our results confirm a peripartal memory deficit, which cannot be explained by the dramatic rise in circulating steroid hormones, or by mood status during pregnancy. Steroidal hormones, namely P, DHEA and T, appear to play a role in mood disturbances during, and after, pregnancy. Studies beginning earlier in pregnancy and continuing for an extended period of time after delivery are needed to confirm and expand these observations.

Two questions regarding findings from the Women's Health Initiative are (1) What is the effect of various hormonal regimens including selective estrogen receptor modulators? and (2) Is the negative effect on cognitive functioning related to the older age (65+ years) of the women? This study addresses these two questions in a short-term randomized trial of the effects of raloxifene versus alendronate on cognition. The study found only one significant interaction where the raloxifene and alendronate group changed differently across the two testing occasions. Hence, raloxifene does not have any impact, positive or negative, on short-term cognitive functioning when compared to alendronate.

Hyperemesis gravidarum (HG) is a condition of severe, intractable nausea and vomiting during pregnancy. It has long been held that HG is a psychosomatic illness reflective of a long-term psychological trait, that is, conversion disorder. We investigated this possibility by conducting a two-phase study:(1) a comparison of women with (n = 9) and without (n = 10) HG during pregnancy and (2) a comparison of nonpregnant women who did (n = 10) and did not (n = 12) have HG during their most recent pregnancies. The pattern of findings differed between experiments 1 and 2. During pregnancy, women with HG scored significantly higher on three scales associated with conversion disorder (all p values <0.01) than did women without HG. There were no significant differences between HG subjects and controls after pregnancy. We find no support for the theory that HG is a psychosomatic condition. Rather, it appears to be a complex interaction of biological, psychological, and sociocultural factors.

OBJECTIVE To provide exploratory analyses of associations between levels of several sex hormones and cognitive performance in elderly women. BACKGROUND Sex steroid hormones are implicated in the cognitive processes of the adult brain. Comparing cognitive performance across or between conditions associated with different hormone levels, such as phases of the menstrual cycle, surgical menopause, and estrogen replacement therapy suggests conditions with higher levels of estrogen are associated with better verbal memory and possibly worse visuospatial ability. METHOD The authors measured circulating sex hormone levels in 39 highly educated, nondemented, predominantly white elderly women. Levels were correlated with neuropsychological performance, controlling for age, education, frequency of prior testing, use of estrogen replacement, and depression. RESULTS High estradiol levels were associated with better delayed verbal memory and retrieval efficiency, whereas low levels were associated with better immediate and delayed visual memory. Levels of testosterone were related positively to verbal fluency. Levels of progesterone and androstenedione were unrelated to cognitive performance. CONCLUSIONS Both estrogen and testosterone showed associations with cognitive performance. Estrogen may enhance, and depress, specific cognitive skills.

Fluctuating endogenous and exogenous estrogens influence cognition in women. In this study, cognitive functioning in elderly women was examined by applying methodology used in understanding the effects of chronic estrogen exposure on hormone-sensitive tissue other than the brain. An index, combining menstrual, reproductive, and physical markers associated with estrogen levels, was developed for elderly, nondemented, predominantly Caucasian women (n = 87). This index related to better performance on two verbal factors, one attentional and one global in nature. Findings suggest that estrogen exposure across the life span plays a role in brain aging. Possible physiological mechanisms for this effect are discussed.

BackgroundAbiraterone and docetaxel are both approved treatments for men with metastatic castration-resistant prostate cancer (mCRPC). Abiraterone pre-docetaxel is currently undergoing evaluation in a phase III study. In vitro studies indicate that taxanes may act by disrupting androgen receptor signalling. We hypothesised that prior abiraterone exposure would adversely impact docetaxel efficacy.Patients and methodsWe retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone, using Prostate Cancer Working Group and radiological criteria.ResultsOf the 54 patients treated with abiraterone, 35 subsequently received docetaxel. Docetaxel resulted in a prostate-specific antigen (PSA) decline of ≥50% in nine patients [26%, 95% confidence interval (CI) 13% to 43%], with a median time to PSA progression of 4.6 months (95% CI 4.2% to 5.9%). PSA declines ≥30% were achieved by 13 patients (37%, 95% CI 22% to 55%). The median overall survival was 12.5 months (95% CI 10.6-19.4). All patients who failed to achieve a PSA fall on abiraterone and were deemed abiraterone-refractory were also docetaxel-refractory (N = 8). In the 24 patients with radiologically evaluable disease, partial responses were reported in four patients (11%), none of whom were abiraterone-refractory.ConclusionThe activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.

Purpose: Accurate superficial dosimetry in breast cancer treatment is critical for the evaluation of the cosmetic and recurrence free survival. It is often believed that treatment planning systems (TPS) may not be able to provide accurate dosimetry in buildup region as it is not properly modeled in most TPS. Breast dosimetry in various treatment techniques; tangential, field-in field, electronic compensator and IMRT are studied using EBT2 film and compared with TPS. Methods: A humanoid unsliced phantom was chosen for this study. Multiple layers of superflab bolus were placed on the breast for EBT2 film dosimetry. Treatment plans were generated using 4 techniques with 2 different grid sizes (1×1 and 2.5×2.5 mm(2)) to provide optimum dose distribution using AAA algorithm. Films were exposed with selected techniques and analyzed after 24 hrs. A calibration curve for dose versus pixel values was also generated at the same day as of the phantom measurement. The calculated dose and image data are imported to in-house software developed using Visual C++, and the dose profiles on the film positions were collected. The calculated profiles were stretched to match their resolutions to that of film dosimetry. Results: At 6 mm and 11 mm depths, film dosimetry showed good agreement with the TPS calculation. On the other hand, the measured dose at 3 mm depth was higher than calculation by 15-30% for all techniques. For tangential and IMRT techniques, the calculation with 1×1 mm(2) grid size showed smaller difference than 2.5×2.5 mm(2) grid size. Conclusions: It is concluded that TPS do not provide accurate dosimetry in the buildup region as verified by EBT2 film for all treatment techniques. For all cases TPS and measured dose are in agreement from 6 mm in depths but differ at shallower depths. Grid size does play role in dose calculation. This work was supported by the JSPS Core-to-Core Program No. 23003.

Background  Wirral University Teaching Hospital is a large district general hospital situated on the Wirral Peninsula, UK. Because of the district's geographical and demographic characteristics, Wirral is an ideal location for population-based studies. Information on community paediatric referrals, case mix and outcomes is scarce. We took advantage of our situation to conduct an epidemiological study of referrals to community paediatrics in Wirral. A companion paper examines referrals to general paediatricians during the same period. Methods  A prospective observational study of community paediatric outpatient referrals between 1 February and 31 May 2006 for all children under the age of 15 offered a new patient appointment during the study period. The study was conducted using the same methodology as a previous population-based study of community paediatric outpatients in Northampton, UK in 1998. We compared our results with this previous study. Results  The referral rate was 10.1 per 1000 children under 15 per annum. School nurses and health visitors made nearly half the referrals, with general practitioners referring most of the remainder. Compared with the Northampton study, more children were seen by consultants. Case mix showed a shift towards behavioural and neurodevelopmental disorders, with less general paediatrics. Attention deficit hyperactivity disorder was the commonest disorder seen (28.2%), a significant increase from the previous study (3.4%)(P < 0.01). Autism spectrum disorder showed little change (8.1% vs. 9.6%; NS). The Wirral study showed significantly more follow-up compared with the Northampton. Conclusions  This population-based study gives a unique insight into the epidemiology of referrals to community paediatricians in the UK in 2006 and how these differ from those recorded in a different UK district in 1998.

OBJECTIVE We examined whether adult women's intention for future pregnancy predicted actual pregnancies occurring in a 2-year follow-up study. METHODS Data are from the Central Pennsylvania Women's Health Study population-based longitudinal survey of women ages 18-45 (n = 1,420). The analytic sample consists of 889 nonpregnant women who had reproductive capacity. Intention for future pregnancy was ascertained at baseline, and women were re-interviewed 2 years later to document interval pregnancies. The impact of pregnancy intention on subsequent pregnancy was analyzed using multiple logistic regression adjusting for relevant covariates. RESULTS At baseline, 46% of women were considering a future pregnancy. One hundred thirty-seven women became pregnant during the 2-year study; of these pregnancies, 83% were intended (occurring in women considering a future pregnancy at baseline) and 17% were unintended (occurring in women not considering a future pregnancy at baseline). Pregnancies occurred in 28% of women who at baseline were considering future pregnancy and 5% of women not considering pregnancy. In adjusted analysis, baseline pregnancy intention was predictive of with pregnancy occurrence in women ages 25-34 (adjusted odds ratio [OR], 4.19; 95% confidence interval [CI], 2.20-7.97) and ages 35-45 (adjusted OR, 26.89; 95% CI, 9.05-79.93), but not in women ages 18-24. CONCLUSIONS In this prospective study, pregnancy intention was strongly associated with pregnancy incidence over a 2-year follow-up period among women ages 25 and older, suggesting that pregnancy intentions could be used to identify women at greater risk of pregnancy. Future investigation is needed to confirm these findings and to explore the reasons why pregnancy intentions were not predictive for women ages 18-24.

PURPOSE National dispensing data for subsidized prescription medicines have recently been approved for linkage to the population-based health datasets in Western Australia (WA), creating the capacity to study how these medicines are used and their impact on pregnancy outcomes. METHODS Pregnancy events were identified in the Hospital Morbidity Data System from 2002 to 2005 (N = 164,278 admissions; N = 98,265 women) and linked to the midwives' notification system (MNS), the registry of births and deaths, the Western Australian birth defects registry and the pharmaceutical benefit scheme. Dispensing records were extracted for each pregnancy event (N = 1,276,084 dispenses). RESULTS There were 106,074 births, 1527 ectopic pregnancies and 25,180 terminations of pregnancy. Dispensed medicines were linked to 28.0% of the pregnancy events. Multiple birth pregnancies were 50% more likely to be dispensed a medicine in the first trimester. As parity increased, so did the likelihood of a medicine being dispensed in pregnancy. Women who were dispensed a medicine were twice as likely to smoke during pregnancy and were 14% more likely to have a registered birth defect. During the first trimester, medicines from category D or X of the risk of drug use in pregnancy were dispensed to 2.1% of all pregnancy events. The WHO ATC 'Psychoanaleptics' category was dispensed to 3.8% of all pregnancy events. CONCLUSION Linkage of dispensing data to pregnancy events is feasible and this approach to post-marketing surveillance will add to the resources available in Australia to investigate pregnancy outcomes in relation to the safe use of prescribed medicines in pregnancy.

OBJECTIVES Study of outcomes of pregnancy in women with congenital heart disease. MATERIAL AND METHODS The cardiac state during and after pregnancy was analysed in 173 women (mean age 28 years, range 21-41) referred for fetal echocardiography and evaluation of maternal heart during 201 pregnancies. Acyanotic lesions were present in 152 women (100 operated), in 175 pregnancies; cyanotic lesions in 21, all operated, in 26 pregnancies. Eighteen patients in 20 pregnancies (9.9% pregnancies) presented an increased risk due to severe arrhythmias or relevant residual hemodynamic lesions (risk group). RESULTS Complications related to heart defects occurred in 9/201 (4.5%), pregnancies: in 6/175 (3.4%) pregnancies with acyanotic lesions, in 3/26 (11.5%) with cyanotic lesions and in 9/20 pregnancies of the risk group (45%), with a statistically significant difference with respect to the non-risk group. Two cases had serious tachyarrhythmias, five worsened hemodynamic state or cyanosis, one had hemorrhage post-partum on anticoagulants and one died of a rupture of isthmic aneurysm post-coarctectomy. Prematurity occurred in 19.2% of pregnancies with cyanotic and 5.7% with acyanotic lesions. There were 6/201 recurrences of cardiac anomaly (3%). CONCLUSIONS Patients with uncomplicated heart disease had normal course of pregnancy, while complications due to serious arrhythmias or residual hemodynamical lesions and cyanosis occurred in 4.5% of pregnancies and, mainly in 45% of those with increased risk. Thorough evaluation of the cardiologic risk is mandatory for a correct counseling of women planning pregnancy.

There is a lack of profound research on the experiences of a new pregnancy following a subsequent late termination of pregnancy (TOP). Results from late pregnancy losses indicate that women do grieve even during a new pregnancy and therefore the process of bonding can be affected. 56 women were investigated within the project "psychosocial counselling in the context of prenatal diagnosis," which recruited 512 patients. Results on the experience of a new pregnancy after late TOP will be presented. In general women experienced a normal level of bereavement 2 years after TOP (PGS), but 11-21% showed significant symptoms of distress (BSI). 50% were aware of the terminated pregnancy furthermore and they felt an emotional distance to their unborn child. This is remarkable because most subsequent pregnancies were planned and desired. Many patients showed feelings of fear, worries and uncertainties. Time since TOP and new conception was not predictive of feelings during pregnancy. If a pregnant woman had a TOP because of fetal anomaly in the preceding pregnancy this should be taken into account during medical care. If symptoms of distress are persisting there is an indication for additional care. The intention is to release the patient and to support a sound relationship between mother and child.

Pregnancy history formulae usually provide only summaries of numbers of pregnancies and births. Different pregnancy outcomes and their sequence are not captured. A new pregnancy history formula is proposed where one number provides information on parity, gravidity, sequence, gestation and outcome of pregnancies. For instance, 914 represents the history of a woman having had three pregnancies, where '9' represents a term first birth,'1', a miscarriage and '4', a preterm perinatal death in the third pregnancy. This formula could be used in medical records or perinatal databases.

OBJECTIVE To investigate the outcome of pregnancy in women after surgical treatment of tubal pregnancy and measures to improve the rate of successful postoperative pregnancy. METHODS A retrospective study was conducted among 424 women who underwent surgical treatment for tubal pregnancy between Jan 1999 and Jan 2004. All patients desiring a second pregnancy were followed up for 18-72 months for the outcome. Cumulative fertility and recurrence curve were compared and calculated by life-table. RESULTS Of the 424 women with tubal pregnancy, 177 (41.7%) had intrauterine pregnancy after the operation, while 102 (24.1%) had recurrent ectopic pregnancy. Among the 177 women with intrauterine pregnancy, 85 (48.02%) became pregnant within 6 months after the operation, 133 (75.14%) within one year, and the cumulative intrauterine pregnancy rate approached 94.92% within 2 years. But among the 102 women with recurrent ectopic pregnancy, only 10 (9.8%) were pregnant within 6 months after the operation, and 49 (48.04%) within 18 months, with a cumulative ectopic pregnancy rate of 67.65%. CONCLUSION For women receiving surgery for ectopic pregnancy, the chance for intrauterine pregnancy can be the greatest within 6 months after operation and reduced markedly after 2 years, when recurrent ectopic pregnancy can be likely. Early plans for pregnancy and hydrotubation following the surgery may prove beneficial for raising the chances for postoperative intrauterine pregnancy.

The pregnant woman experiences physiological changes to support fetal growth and development. Particularly the physiological changes of the liver are the results of the increment of estrogens and progesterone during the pregnancy, and also the hemodynamics changes.(hemodilution). Telangiectasia may appear in up to 60% of normal pregnancies. Liver function test (LFT) abnormalities occurs in 3% of the pregnancies, and the Preeclampsia is the most frequent cause. Most of the articles agree that in normal pregnancy the LFT are either normal or slightly increase o decrease but within normal range. Thus, an increase in serum ALT, AST and GGT activities and serum bilirubin and total bile acid concentration during pregnancy may be pathologic and should prompt further evaluation. In the same way the serum albumin levels is significantly low and the serum alkaline phosphatase concentrations are considerably higher and are a normal component of the pregnancy , and if they are within normal range, do not usually indicate the presence of liver disease. The prothrombine time and the partial prothrombine time remain unchanged during pregnancy and serum fibrinogen increase in late pregnancy. Most of the articles related to plasma lipids in pregnancy agree that cholesterol. Triglyceride and lipoprotein increase during pregnancy. Use of gestational age of the pregnancy are the best guide to the differential diagnosis of liver disease in the pregnancy.

The management of pregnant patients with essential thrombocythemia (ET) and polycythemia vera (PV) may be problematic. In the literature there are approximately 300 cases of pregnancies reported in ET and less than 50 pregnancies reported in PV. To reduce the effect of reporting bias, we selected articles with either > 10 pregnancies or at least six patients, and here report on the outcome of 195 pregnancies in ET and 36 pregnancies in PV patients. The live birth rate was approximately 60% in ET and 58% in PV. Spontaneous abortion during the first trimester was the most frequent fetal complication, occurring in 31% of ET pregnancies and in 22% of PV pregnancies, respectively. Major maternal complications were more frequent in PV compared with ET (44.4 versus 7.7%). Treatment with low-dose aspirin during pregnancy in ET seemed to reduce complications and also seemed beneficial during pregnancy in PV. In high-risk pregnancies, the additional use of low molecular weight heparin and/or interferon alpha should be considered. This article also describes a registry for an observational study concerning pregnancy in chronic Philadelphia chromosome-negative myeloproliferative disorders within the European LeukemiaNet. A potential management algorithm for pregnancies in ET or PV is also provided.

The Kearn-Sayre's syndrome is an uncommon, non-hereditary disease which belongs to the group of mitochondrial myopathy. The characteristic symptoms of this syndrome often appear before the age of 20. In this report we describe the outcome of primigravid pregnancy of a 33 year old woman with early diagnosed Kearn-Sayre's syndrome.