A mass shooting at Port Arthur, Tasmania, Australia: a study of its impact on early pregnancy losses using a conception time-based methodology.

STUDY QUESTION: Does an acute calamity in a community cause early miscarriage and is this association the same for male and female fetuses? SUMMARY ANSWER: Estimated losses of 29.5% of first trimester pregnancies in the affected region could be associated with an acute calamity, with no statistically significant difference in estimated losses by fetal sex. WHAT IS KNOWN ALREADY: There are very few studies on the impact of a calamity on early pregnancy loss and its differential effects on male and female fetuses. A decline in the human sex ratio at birth associated with the events of 9/11 in New York has been documented. STUDY DESIGN, SIZE, DURATION: This is a retrospective descriptive study of birth register data in Tasmania, Australia, from 1991 to 1997, covering the period in which the calamity occurred. The register contains data on all pregnancies that proceeded to >20 weeks gestation. The conception date was calculated by subtracting gestational age from birth date. We estimated that 40 318 pregnancies were conceived in the period 1991-1996 inclusive. These were aggregated to 4-weekly blocks classified by region and sex. PARTICIPANTS/MATERIALS, SETTING, METHODS: The acute calamity was at Port Arthur, Tasmania, Australia. On 28 April 1996, a gunman opened fire on visitors and staff in a tourist cafe. A very stressful 20 h period, ended with 35 people dead and 22 injured. A negative binomial regression model was used to assess the association between this calamity and pregnancy loss. This loss is evidenced by a shortfall in the registration of pregnancies that were in their first trimester at the time of the calamity. MAIN RESULTS AND THE ROLE OF CHANCE: We estimated a shortfall of 29.5% or 229 registered pregnancies among those in the first trimester at the time of the calamity (P < 0.001), in the region surrounding the calamity site. There was no sex effect in this shortfall (P = 0.911). There was no corresponding shortfall in other parts of Tasmania (P = 0.349). LIMITATIONS, REASONS FOR CAUTION: The study is descriptive and cannot produce causal inferences. These first trimester miscarriages are estimated statistically and it is understood that gestational age is an estimate. The use of maternal residential postcodes at birth as a surrogate for geographic area or space assumes that the mother has not moved into the postcode area after the calamity and before the reporting of a birth. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study suggest that calamities bring about significant pregnancy loss affecting both sexes. The methodology presented of inferring conception date from birth date and using this for analysis, provides a more accurate assessment of first trimester pregnancy losses than raw birth data or sex ratio at birth.

Management of subsequent pregnancy after an unexplained stillbirth.

PURPOSE: To review the management of pregnancy after an unexplained stillbirth. EPIDEMIOLOGY: Approximately 1 in 200 pregnancies will end in stillbirth, of which about one-third will remain unexplained. Unexplained stillbirth is the largest single contributor to perinatal mortality. Subsequent pregnancies do not appear to have an increased risk of stillbirth, but are characterized by increased rates of intervention (induction of labor, elective cesarean section) and iatrogenic adverse outcomes (low birth weight, prematurity, emergency cesarean section and post-partum hemorrhage). CONCLUSIONS: There is no level-one evidence to guide management in this situation. Pre-pregnancy counseling is very important to detect and correct potential risk factors such as obesity, smoking and maternal disease. As timely delivery is the mainstay of management, early accurate determination of gestational age is vital. There is controversy regarding the pattern of surveillance, but evidence exists only for ultrasound and not for regular non-stress testing, nor formal fetal movement charting. There is an urgent need for more studies in this important area.

Diagnosis of and screening for cytomegalovirus infection in pregnant women.

No single diagnostic test for cytomegalovirus (CMV) infection is currently available for pregnant women at all stages of gestation. Improved accuracy in estimating the timing of primary infections can be used to identify women at higher risk of giving birth to congenitally infected infants. A diagnostic algorithm utilizing immunoglobulin G (IgG), IgM, and IgG avidity was used to prospectively screen serum from 600 pregnant women enrolled from two groups: < or =20 weeks gestation (n = 396) or >20 weeks gestation (n = 204). PCR testing of urine and/or blood was performed on all seropositive women (n = 341). The majority (56.8%) of women were CMV IgG seropositive, with 5.5% being also CMV IgM positive. In the IgM-positive women, 1.2% had a low-avidity IgG, indicating a primary CMV infection and a high risk of intrauterine transmission. Two infants with asymptomatic CMV infection were born of mothers who had seroconverted in the second trimester of pregnancy. Baseline, age-stratified CMV serostatus was established from 1,018 blood donors. Baseline seropositivity from a blood donor population increased with age from 34.9% seroprevalence at less than 20 years of age to 72% seroprevalence at 50 years of age. Women at high risk of intrauterine transmission of CMV were identified at all stages of gestation. Women infected with CMV during late gestation may be more likely to transmit the virus, so failure to detect seroconversions in late gestation may result in failure to detect infected neonates.

Vibroacoustic stimulation for fetal assessment in labour in the presence of a nonreassuring fetal heart rate trace.

BACKGROUND: Fetal vibroacoustic stimulation is a simple, non-invasive technique where a device is placed on the maternal abdomen over the region of the fetal head and sound is emitted at a predetermined level for several seconds. It is hypothesized that the resultant startle reflex in the fetus and subsequent fetal heart rate acceleration or transient tachycardia following vibroacoustic stimulation provide reassurance of fetal well-being. This technique has been proposed as a tool to assess fetal well-being in the presence of a non-reassuring cardiotocographic trace during the first and second stages of labour. OBJECTIVES: To evaluate the clinical effectiveness and safety of vibroacoustic stimulation in the assessment of fetal well-being during labour, compared with mock or no stimulation for women with a singleton pregnancy exhibiting a non-reassuring fetal heart rate pattern. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 September 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (January 1966 to January 2005), EMBASE (January 1966 to January 2005) and reference lists of all retrieved articles. We sought unpublished trials and abstracts submitted to major international congresses and contacted expert informants. SELECTION CRITERIA: All published and unpublished randomised trials that compared maternal and fetal/neonatal/infant outcomes when vibroacoustic stimulation was used to evaluate fetal status in the presence of a non-reassuring cardiotocographic trace during labour, compared with mock or no stimulation. DATA COLLECTION AND ANALYSIS: Two independent review authors identified potential studies from the literature search and assessed them for methodological quality and appropriateness of inclusion, using a data extraction form. Attempts to contact study authors for additional information were unsuccessful. MAIN RESULTS: The search strategies yielded six studies for consideration of inclusion. However, none of these studies fulfilled the requirements for inclusion in this review. AUTHORS' CONCLUSIONS: There are currently no randomised controlled trials that address the safety and efficacy of vibroacoustic stimulation used to assess fetal well-being in labour in the presence of a non-reassuring cardiotocographic trace. Although vibroacoustic stimulation has been proposed as a simple, non-invasive tool for assessment of fetal well-being, there is insufficient evidence from randomised trials on which to base recommendations for use of vibroacoustic stimulation in the evaluation of fetal well-being in labour in the presence of a non-reassuring cardiotocographic trace.

Breast cancer in premenopausal women: recurrence and survival rates and relationship to hormone replacement therapy.

OBJECTIVES: To determine any association between hormonal replacement therapy (HRT) usage and breast cancer recurrence and survival rates in women who were premenopausal at the time of diagnosis of breast cancer. METHODS: The study group comprised 524 women who were diagnosed with breast cancer when they were premenopausal. Of these, 277 women reached menopause before recurrence of the disease, being lost to follow-up, or reaching the end of the study. In this group, 119 women took HRT to control menopausal symptoms. The majority took combined continuous estrogen-progestin treatment. Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes, and to death from primary tumor were compared between HRT users and non-users. RESULTS: Women who used HRT after their menopause had an adjusted relative risk of recurrence or new breast cancer of 0.75 (95% confidence interval (CI), 0.29-1.95) compared to that of non-users. The relative risk of death from all causes was 0.36 (95% CI, 0.11-1.16) and that of death from primary tumor was 0.24 (95% CI, 0.05-1.14). CONCLUSION: HRT use in women who were premenopausal at the diagnosis of primary invasive breast cancer is not associated with worse outcomes in terms of breast cancer recurrence or mortality.

Quality of life of breast cancer survivors: the impact of hormonal replacement therapy.

OBJECTIVES: The aims of this non-randomized qualitative study were to compare the quality of life (QOL) of breast cancer survivors who received hormone replacement therapy (HRT) and those who did not, and to describe the impact of breast cancer on their social, physical, psychological and spiritual domains. A QOL self-evaluation questionnaire was used to determine the most important concerns and changes described by women that affected, or were likely to affect, their QOL as a result of breast cancer. METHODS: In total, 220 patients who had finished treatment for breast cancer were contacted; 190 agreed to participate, of whom 123 (64.8%) completed and returned their questionnaires, which comprised demographic data, Quality of Life Breast Cancer Version Questionnaire and Quality of Life Self Evaluation Questionnaire. The results for women taking HRT were compared with results for those who were not. RESULTS: There were no significant differences in time between surgery for breast cancer and the survey, age at last birthday, number of pregnancies and live births, employment, breast cancer surgery and adjuvant therapy between HRT and non-HRT groups. No differences were found in the social, physical, psychological and spiritual domains between the two groups; however, significant differences were found between survival time and quality of life in some domains. During the study, none of the 123 women developed a recurrence of their breast cancer. CONCLUSION: There were no significant differences in any demographic variables between the users of HRT and the non-users. The same level of QOL was observed between HRT and non-HRT groups in the four domains of well-being. The majority of women with breast cancer recovered to a near normal level of QOL after a 4-year adjustment period, and lead fulfilling lives. This adjustment period cannot be quantified, as individual factors such as emotional, social and financial concerns will differ for each individual.

Maternal stress and obstetric and infant outcomes: epidemiological findings and neuroendocrine mechanisms.

This review examines the associations between antenatal maternal stress and obstetric and infant outcomes using preterm delivery as the key outcome indicator. This was done by means of a Medline search focusing predominantly on prospective, controlled studies which investigated both the associated epidemiological factors and putative neuroendocrine mechanisms. There is evidence from a number of United States studies in economically deprived African American women for an association between perceived maternal life event (LE) stress and preterm delivery. The findings from the European studies are conflicting, partly because they combine outcome measures ie. preterm delivery and low birth weight. However the three largest Scandinavian epidemiological studies examining preterm delivery and controlling for confounders such as smoking, age and obstetric history, have confirmed this association. These studies taken together suggest that this may be a robust finding not limited to socioeconomically deprived African American samples and independent of other significant risk factors. Two small prospective studies examining the relationship between the hypothalamic-pituitary-adrenal (HPA) axis, psychosocial status and premature delivery have reported a significant association between a set of adverse psychosocial factors on the one hand, and levels of adrenocorticotrophic hormone (ACTH), corticotrophin releasing hormone (CRH) and cortisol levels, and on the other hand, a significant correlation between CRH levels and premature delivery. Clearly, these findings remain preliminary and indicate a complex relationship between perceived stress in pregnancy, the HPA axis and premature delivery. The impact of antenatal maternal stress on infant temperament and psychopathology remains to be examined more fully in prospective controlled trials.

Interaciones entre nutrientes y factores peptidos de crecimiento, en el desarrollo reparacion y funcionamiento de la mucosa intestinal / Nutrition and restitution of bowel mucosa

Diversas evidencias demuestran que el estado nutricional general, de ciertos nutrientes (zinc y glutamina, por ejemplo) y algunos factores tróficos de crecimiento (como la hormona de crecimiento, el factor de crecimiento 1 similar a la insulina, el factor de crecimiento de los queratinocitos y el péptido 2 similar al glucagón), tienen interacciones que son importantes para el desarrollo y funcionamiento de la mucosa intestinal. Un estado nutricionai adecuado es indispensable para la síntesis del factor endógeno de crecimiento en el intestino y otros tejidos, y es también mediador importante de la respuesta orgánica a la administración de factor exógeno de crecimiento. Los factores de crecimiento, tanto el sintetizado de modo endógeno, como el administrado en forma exógena, regulan en forma positiva la captación y utilización de nutrientes en la mucosa intestinal, el músculo esquelético y otros órganos, los datos que surgen de estudios, tanto en animales como en seres humanos indican, que la combinación de algunos factores de crecimiento con ciertos nutrientes pueden incrementar el desarrollo, adaptación y reparación de la mucosa intestinal. Se requieren estudios adicionales para determinar cuáles son los mecanismos básicos de las interacciones entre nutrientes y factores de crecimiento, así como la seguridad y eficacia de tratamientos con combinaciones específicas de nutrientes y factores de crecimiento recombinantes. Los resultados de tales investigaciones deberán definir nuevos métodos para el soporte del tracto intestinal en casos de síndrome de intestino corto (SUS, sigla en inglés), enfermedad catabólica y desnutrición

Glutamine and the gastrointestinal tract.

The amino acid glutamine has become one of the most intensively studied nutrients in the field of nutrition and metabolic support. A variety of studies in cell culture systems, animal models of gut mucosal atrophy, injury/repair and adaptation and a limited number of clinical trials demonstrate trophic and cytoprotective effects of glutamine in small bowel and colonic mucosal cells. Although the routine clinical use of glutamine-enriched parenteral and enteral nutrient solutions remains controversial, available data demonstrate both the safety and metabolic and clinical efficacy of glutamine treatment in selected patient groups. Basic investigations are elucidating underlying mechanisms of glutamine action in intestinal cells. These will inform preclinical and clinical investigations designed to determine glutamine efficacy in selected gastrointestinal disorders. Emerging clinical trials will further define the utility of adjunctive glutamine supplementation as a component of specialized nutrition support in gastrointestinal disease.

Interactions between nutrients and peptide growth factors in intestinal growth, repair, and function.

Several lines of evidence demonstrate that general nutritional status, specific nutrients (eg, zinc, glutamine), and certain trophic growth factors (eg, growth hormone, insulin-like growth factor I, keratinocyte growth factor, and glucagon-like peptide-2) have important interactions relevant for intestinal growth and function. Adequate nutritional status is critical for endogenous growth factor synthesis in the gut and other tissues and is an important mediator of organ responsiveness to exogenous growth factor administration. Both endogenously synthesized and exogenously administered growth factors upregulate nutrient uptake and utilization by gut mucosa, skeletal muscle, and other organs. Emerging data from both animal and human studies indicate that combinations of selected growth factors and specific nutrients may improve the growth, adaptation, and repair of the intestinal mucosa. Additional studies to determine basic mechanisms of nutrient-growth factor interactions and the safety and efficacy of treatment with combinations of specific nutrients and recombinant growth factors are needed. Results of these investigations should define new methods for support of the intestinal tract during short bowel syndrome (SBS), catabolic illness, and malnutrition.

Freezing survival by isolated Malpighian tubules of the New Zealand alpine weta Hemideina maori.

The ability of isolated Malpighian tubules from a freeze-tolerant insect, the New Zealand alpine weta (Hemideina maori), to withstand freezing was assessed by measuring post-freeze membrane potentials and rates of fluid secretion. The hemolymph of cold-acclimated Hemideina maori was found to contain relatively high concentrations of the cryoprotectants trehalose (>300 mmol l-1) and proline (41 mmol l-1). Survival of isolated Malpighian tubules was correspondingly high when a high concentration of trehalose was present in the bathing saline. Tubules allowed to recover for 20 min from a 1 h freeze to -5 degrees C in saline containing 400 mmol l-1 trehalose had a basolateral membrane potential of -53 mV compared with a potential of -63 mV in tubules not exposed to a freeze/thaw cycle. Fluid secretion in tubules that had experienced a freeze/thaw cycle in saline containing 400 mmol l-1 trehalose was 9.9+/-2.6 nl h-1 compared with 18.7+/-5.0 nl h-1 (means +/- s.e.m., N=18) in tubules that had not been frozen. Tubules frozen in saline containing a lower concentration of trehalose (200 mmol l-1) or in glucose (400 mmol l-1) showed a similar ability to survive freezing to -5 degrees C. In contrast, freezing for 1 h at -5 degrees C in saline containing 400 mmol l-1 sucrose produced a 57 % decrease in membrane potential and an 88 % decrease in secretion rate. Tubules held in saline lacking high concentrations of sugars showed no survival after freezing to -5 degrees C for 1 h. When frozen to -15 degrees C, tubules appeared to survive best in saline with the highest trehalose concentration (400 mmol l-1). Freezing damage was not simply the result of exposure to cold, since tubules chilled (unfrozen) to -5 degrees C for 1 h were not compromised even when the bathing saline lacked a high sugar concentration. Exposure of tubules to a combination of low temperature and high osmolality mimicked damage caused by actual freezing: the membrane potential showed a 60 % recovery when the test was performed in saline containing trehalose, but showed no recovery in saline containing sucrose.

Donor insemination: attitudes of parents towards disclosure.

OBJECTIVE: To determine attitudes of parents of children conceived by donor insemination to telling the children of their origin. DESIGN: Questionnaire survey, in 1992-1993, of parents who had had a child by donor insemination at four New South Wales clinics from 1979 to 1990. SETTING: Three hospital-based clinics (two public, one private) and a private clinic service. PARTICIPANTS: 276 families who altogether had had 420 children by donor insemination. MAIN OUTCOME MEASURES: Number of children told that they had been conceived by donor insemination; parents' intentions, before conceiving and after the birth, of informing the child; and whether other people were informed of the child's origin. RESULTS: Of 393 families who could be contacted, 353 agreed to participate and 276 (70%) replied to the questionnaire. Only 22 of the 420 children (5.2%) had been informed of their origin. Before conceiving, 18% of parents (49/273) planned to tell the child. Seventy-one per cent of families (182/257) had told others of the origin of the child, but 94% (241/257) had not told the child. Of the 29% of families (75/257) who had not told others of the child's origins, none had told the child. As the children grow older, more parents decide not to tell them of their origin. CONCLUSIONS: Most parents of children conceived by donor insemination do not plan to tell their child, but most of these parents have told others, creating the potential for accidental disclosure. Because of the small number of children who are told of their origin, there may not be a need for government-regulated donor registers, provided donor insemination units maintain a high standard of record-keeping.

Adjunctive therapies in nutritional support.

The need for new therapeutic approaches to improve the metabolic and clinical efficacy of nutritional therapy has been increasingly emphasized. The field of nutrition support of catabolic, malnourished, or hospitalized patients is rapidly evolving in response to the beneficial effects observed with adjunctive therapies in animal models and in emerging clinical investigations. Enteral nutrition is being increasingly administered, and enteral diets are being tested to improve gut structure and function. Adjunctive therapies in enteral and parenteral nutrition are being actively investigated. These include administration of recombinant growth factors and anabolic steroid hormones (e.g., growth hormone, oxandrolone); conditionally essential amino acids (e.g., arginine, glutamine); novel lipid products (e.g., structured lipids, fish oils); nutrient antioxidants (e.g., vitamins C and E); and combinations of these approaches. It is likely that current methods of enteral and parenteral nutrition support will evolve in response to the results of these research studies.

Glutamine: from basic science to clinical applications.

Glutamine (Gln) has been one of the most intensively studied nutrients in the field of nutrition support in recent years. Interest in provision of Gln derives from animal studies in models of catabolic stress, primarily in rats. Enteral or parenteral Gln supplementation improved organ function and/or survival in most of these investigations. These studies have also supported the concept that Gln is a critical nutrient for the gut mucosa and immune cells. Recent molecular and protein chemistry studies are beginning to define the basic mechanism involved in Gln action in the gut, liver and other cells and organs. Double-blind prospective clinical investigations to date suggest that Gln-enriched parenteral or enteral feedings are generally safe and effective in catabolic patients. Intravenous Gln (either as the L-amino acid or as Gln-dipeptides) has been shown to increase plasma Gln levels, exert protein anabolic effects, improve gut structure and/or function and reduce important indices of morbidity, including infection rates and length of hospital stay in selected patients subgroups. Additional blinded studies of Gln administration in catabolic patients and increasing clinical experience with Gln-enriched nutrient products will determine whether routine Gln supplementation should be given in nutrition support, and to whom. Taken together, the data obtained over the past decade or so of intensive research on Gln nutrition demonstrate that this amino acid is an important dietary nutrient and is probably conditionally essential in humans in certain catabolic conditions.

Donor insemination: effects on parents.

OBJECTIVE: To examine the psychosocial effects of donor insemination on couples. DESIGN: Questionnaire survey of couples who had a child by donor insemination at four NSW clinics over a 15-year period. RESULTS: Forty-seven per cent of couples thought their marriage had improved, while 3% thought their marriage had deteriorated as a result of having a child by donor insemination. Seventy-six per cent felt it had a positive personal effect and almost all couples had no regrets about having a child this way. Over 90% of respondents felt very close to these children. In those who also had children not conceived by donor insemination (60 couples), men were significantly closer to their children by donor insemination than to their "other" children (P < 0.001). There was a significant sex difference in perceptions of the child's resemblance (P < 0.0001): 61% of women thought their child conceived by donor insemination resembled their partner, while 89% of men thought the child resembled their partner. Twenty-one per cent of couples were concerned about having to tell the child about donor insemination. CONCLUSION: Donor insemination can have positive psychosocial effects on couples and close relationships exist between the parents and their children conceived by donor insemination. The concern about the physical appearance of children conceived by donor insemination can be allayed by our finding that the majority of couples see a resemblance between the child and their partner.

Continuous intrapartum fetal monitoring: a prospective randomized comparison of 2 types of fetal scalp electrode.

This trial was conducted to compare 2 commonly used fetal scalp electrodes with regard to ease of use, frequency and extent of neonatal injury and quality of cardiotocographic record. A randomized design was employed to study a group of 106 patients divided between a Surgicraft Copeland clip fetal scalp electrode (52 patients) and a Meditrace spiral single helix scalp electrode (54 patients). Patients were eligible for trial entry if they required an intrapartum fetal scalp electrode, at term with a singleton cephalic pregnancy. Ease of application was rated by the operator using a linear analogue score. Unidentified traces were reviewed independently for quality by 2 obstetricians and neonates were examined on day-2 postpartum for injury. The Meditrace spiral fetal scalp electrode was significantly easier to apply (unpaired t-test p < 0.02). It also obtained higher ratings for trace quality (unpaired t-test p < 0.02). There were no serious neonatal injuries and no difference was found between the 2 electrodes in this regard.

Vaginal delivery after caesarean section.

In a prospective study of 318 consecutive pregnancies complicated by previous Caesarean section, 193 (61%) had an elective repeat Caesarean section, 125 (39%) had a trial of labour and 80 (64%) of these women achieved a vaginal delivery. The incidence of uterine rupture was 0.8% (1 of 125). The vaginal delivery rate was not influenced by the indication for the first Caesarean section (including cephalopelvic disproportion), birth-weight, health insurance status, use of epidural analgesia or oxytocin in labour. Perinatal morbidity was unaffected by the mode of delivery and maternal morbidity was comparable following elective and emergency repeat Caesarean section. Patients having a vaginal deliver spent significantly less time in hospital. We conclude that vaginal delivery after lower segment Caesarean section is safe and should be considered in most patients after a critical review of the indication for the first Caesarean section.

The use of clearplan home ovulation detection kits in unexplained and male factor infertility.

One hundred and five couples with unexplained infertility and 43 couples whose infertility was thought to be due to reduced sperm motility were recruited. The median duration of infertility was 36 months (range 12-168). Couples were randomly allocated to either using Clearplan home ovulation detection kits for 3 cycles or were advised about the optimal time during their menstrual cycle to achieve a pregnancy. The clinical details of the 2 groups were similar. In couples with unexplained infertility over the study period 10 (20.4%) in the Clearplan group and 9 (16%) in the control group conceived with 58% of pregnancies occurring in the first cycle. In couples with reduced sperm motility, the results were disappointing with only 2 (8%) pregnancies in the Clearplan group and 2 (11.1%) in the controls. Assisted reproduction technology may not be justified as the first line of management in patients with unexplained infertility.