Night shift work undertaken by women and fertility treatment interact to increase prevalence of urogenital anomalies in children.

OBJECTIVE: To investigate the role of maternal night shift work in occurrence of urogenital anomalies in offspring, considering a possible interaction with mode of conception. METHODS: A population-based cohort comprising births in South Australia (1986-2002) was produced via linkage of fertility clinic records, perinatal and birth defects data. This study concerned first births to women in paid employment (n=98 103). Potential exposure to night shift was imputed by applying a job-exposure matrix to recorded occupation. Associations were examined using logistic regression, first for nurses and other night shift workers separately, then combined. An interaction term for night shift work and mode of conception was included in all models, while adjusting for covariates. RESULTS: Associations were similar for nurses and other night shift workers, although only statistically significant for the former when considered separately. A multiplicative interaction was supported: for natural conceptions, maternal night shift work was not associated with offspring urogenital anomalies (OR=0.99, 95% CI 0.84 to 1.15); where a birth arose from fertility treatment, urogenital anomalies were significantly higher among births to all night shift workers compared with day workers (OR=2.07, 95% CI 1.20 to 3.55). This was not due to differences in the type of fertility treatment received. CONCLUSIONS: Women in occupations that probably involved night shift did not have offspring with increased prevalence of urogenital anomalies if they conceived naturally. When night shift workers conceived with fertility treatment, the prevalence of urogenital anomalies was elevated. Possibly these women had the greatest exposure to night shift work, or least tolerance for this work schedule, or heightened sensitivity to hormonal aspects of fertility treatment.

Reproductive technologies and the risk of birth defects.

BACKGROUND: The extent to which birth defects after infertility treatment may be explained by underlying parental factors is uncertain. METHODS: We linked a census of treatment with assisted reproductive technology in South Australia to a registry of births and terminations with a gestation period of at least 20 weeks or a birth weight of at least 400 g and registries of birth defects (including cerebral palsy and terminations for defects at any gestational period). We compared risks of birth defects (diagnosed before a child's fifth birthday) among pregnancies in women who received treatment with assisted reproductive technology, spontaneous pregnancies (i.e., without assisted conception) in women who had a previous birth with assisted conception, pregnancies in women with a record of infertility but no treatment with assisted reproductive technology, and pregnancies in women with no record of infertility. RESULTS: Of the 308,974 births, 6163 resulted from assisted conception. The unadjusted odds ratio for any birth defect in pregnancies involving assisted conception (513 defects, 8.3%) as compared with pregnancies not involving assisted conception (17,546 defects, 5.8%) was 1.47 (95% confidence interval [CI], 1.33 to 1.62); the multivariate-adjusted odds ratio was 1.28 (95% CI, 1.16 to 1.41). The corresponding odds ratios with in vitro fertilization (IVF) (165 birth defects, 7.2%) were 1.26 (95% CI, 1.07 to 1.48) and 1.07 (95% CI, 0.90 to 1.26), and the odds ratios with intracytoplasmic sperm injection (ICSI) (139 defects, 9.9%) were 1.77 (95% CI, 1.47 to 2.12) and 1.57 (95% CI, 1.30 to 1.90). A history of infertility, either with or without assisted conception, was also significantly associated with birth defects. CONCLUSIONS: The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors. The risk of birth defects associated with ICSI remained increased after multivariate adjustment, although the possibility of residual confounding cannot be excluded. (Funded by the National Health and Medical Research Council and the Australian Research Council.).

The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria.

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder in women of reproductive age, yet debate over appropriate diagnostic criteria and design limitations with sampling methodology have left some doubt as to the actual prevalence in the community. The objective of this study was to create a representative prevalence estimate of PCOS in the community under the National Institutes of Health (NIH) criteria and the more recent Rotterdam consensus criteria and Androgen Excess Society (AES) criteria. METHODS: A retrospective birth cohort study was carried out in which 728 women born during 1973-1975 in a single maternity hospital were traced and interviewed in adulthood (age = 27-34 year; n = 728). Symptoms of PCOS (hyperandrogenism, menstrual dysfunction and polycystic ovaries) were identified by examination and the presence of polycystic ovaries in those that did not consent to the ultrasound were imputed. RESULTS: The estimated prevalence of PCOS in this birth cohort using the NIH criteria was 8.7 +/- 2.0% (with no need for imputation). Under the Rotterdam criteria, the prevalence was 11.9 +/- 2.4% which increased to 17.8 +/- 2.8% when imputed data were included. Under the AES recommendations, PCOS prevalence was 10.2 +/- 2.2%, and 12.0 +/- 2.4% with the imputed data. Of the women with PCOS, 68-69% did not have a pre-existing diagnosis. CONCLUSIONS: The Rotterdam and AES prevalence estimates were up to twice that obtained with the NIH criteria in this, as well other prevalence studies. In addition, this study also draws attention to the issue of many women with PCOS in the community remaining undiagnosed.

The risk of adverse pregnancy outcomes in women who are overweight or obese.

BACKGROUND: The prevalence of obesity amongst women bearing children in Australia is rising and has important implications for obstetric care. The aim of this study was to assess the prevalence and impact of mothers being overweight and obese in early to mid-pregnancy on maternal, peripartum and neonatal outcomes. METHODS: A secondary analysis was performed on data collected from nulliparous women with a singleton pregnancy enrolled in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS). Women were categorized into three groups according to their body mass index (BMI): normal (BMI 18.5-24.9 kg/m2); overweight (BMI 25-29.9 kg/m2) and; obese (BMI 30-34.9 kg/m2). Obstetric and perinatal outcomes were compared by univariate and multivariate analyses. RESULTS: Of the 1661 women included, 43% were overweight or obese. Obese women were at increased risk of pre-eclampsia (relative risk (RR) 2.99 [95% confidence intervals (CI) 1.88, 4.73], p < 0.0001) and gestational diabetes (RR 2.10 [95%CI 1.17, 3.79], p = 0.01) compared with women with a normal BMI. Obese and overweight women were more likely to be induced and require a caesarean section compared with women of normal BMI (induction - RR 1.33 [95%CI 1.13, 1.57], p = 0.001 and 1.78 [95%CI 1.51, 2.09], p < 0.0001, caesarean section - RR 1.42 [95%CI 1.18, 1.70], p = 0.0002 and 1.63 [95%CI 1.34, 1.99], p < 0.0001). Babies of women who were obese were more likely to be large for gestational age (LFGA) (RR 2.08 [95%CI 1.47, 2.93], p < 0.0001) and macrosomic (RR 4.54 [95%CI 2.01, 10.24], p = 0.0003) compared with those of women with a normal BMI. CONCLUSION: The rate of overweight and obesity is increasing amongst the Australian obstetric population. Women who are overweight and obese have an increased risk of adverse pregnancy outcomes. In particular, obese women are at increased risk of gestational diabetes, pregnancy induced hypertension and pre-eclampsia. Effective preventative strategies are urgently needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00416244.

Borderline gestational diabetes mellitus and pregnancy outcomes.

BACKGROUND: The impact of borderline gestational diabetes mellitus (BGDM), defined as a positive oral glucose challenge test (OGCT) and normal oral glucose tolerance test (OGTT), on maternal and infant health is unclear. We assessed maternal and infant health outcomes in women with BGDM and compared these to women who had a normal OGCT screen for gestational diabetes. METHODS: We compared demographic, obstetric and neonatal outcomes between women participating in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS) who had BGDM and who screened negative on OGCT. RESULTS: Women who had BGDM were older (mean difference 1.3 years, [95% confidence interval (CI) 0.3, 2.2], p = 0.01) and more likely to be obese (27.1% vs 14.1%, relative risk (RR) 1.92, [95% CI 1.41, 2.62], p < 0.0001) than women who screened negative on OGCT. The risk of adverse maternal outcome overall was higher (12.9% vs 8.1%, RR 1.59, [95% CI 1.00, 2.52], p = 0.05) in women with BGDM compared with women with a normal OGCT. Women with BGDM were more likely to develop pregnancy induced hypertension (17.9% vs 11.8%, RR 1.51, [95% CI 1.03, 2.20], p = 0.03), have a caesarean for fetal distress (17.1% vs 10.5%, RR 1.63, [95% CI 1.10, 2.41], p = 0.01), and require a longer postnatal hospital stay (mean difference 0.4 day, [95% CI 0.1, 0.7], p = 0.01) than those with a normal glucose tolerance.Infants born to BGDM mothers were more likely to be born preterm (10.7% vs 6.4%, RR 1.68, [95% CI 1.00, 2.80], p = 0.05), have macrosomia (birthweight > or =4.5 kg) (4.3% vs 1.7%, RR 2.53, [95% CI 1.06, 6.03], p = 0.04), be admitted to the neonatal intensive care unit (NICU) (6.5% vs 3.0%, RR 2.18, [95% CI 1.09, 4.36], p = 0.03) or the neonatal nursery (40.3% vs 28.4%, RR 1.42, [95% CI 1.14, 1.76], p = 0.002), and have a longer hospital stay (p = 0.001). More infants in the BGDM group had Sarnat stage 2 or 3 neonatal encephalopathy (12.9% vs 7.8%, RR 1.65, [95% CI 1.04, 2.63], p = 0.03). CONCLUSION: Women with BGDM and their infants had an increased risk of adverse health outcomes compared with women with a negative OGCT. Intervention strategies to reduce the risks for these women and their infants need evaluation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00416244.

Costs and consequences of treatment for mild gestational diabetes mellitus - evaluation from the ACHOIS randomised trial.

BACKGROUND: Recommended best practice is that economic evaluation of health care interventions should be integral with randomised clinical trials. We performed a cost-consequence analysis of treating women with mild gestational diabetes mellitus by dietary advice, blood glucose monitoring and insulin therapy as needed compared with routine pregnancy care, using patient-level data from a multi-centre randomised clinical trial. METHODS: Women with a singleton pregnancy who had mild gestational diabetes diagnosed by an oral glucose-tolerance test between 24 and 34 weeks' gestation and their infants were included. Clinical outcomes and outpatient costs derived from all women and infants in the trial. Inpatient costs derived from women and infants attending the hospital contributing the largest number of enrolments (26.1%), and charges to women and their families derived from a subsample of participants from that hospital (in 2002 Australian dollars). Occasions of service and health outcomes were adjusted for maternal age, ethnicity and parity. Analysis of variance was used with bootstrapping to confirm results. Primary clinical outcomes were serious perinatal complications; admission to neonatal nursery; jaundice requiring phototherapy; induction of labour and caesarean delivery. Economic outcome measures were outpatient and inpatient costs, and charges to women and their families. RESULTS: For every 100 women with a singleton pregnancy and positive oral glucose tolerance test who were offered treatment for mild gestational diabetes mellitus in addition to routine obstetric care, $53,985 additional direct costs were incurred at the obstetric hospital, $6,521 additional charges were incurred by women and their families, 9.7 additional women experienced induction of labour, and 8.6 more babies were admitted to a neonatal nursery. However, 2.2 fewer babies experienced serious perinatal complication and 1.0 fewer babies experienced perinatal death. The incremental cost per additional serious perinatal complication prevented was $27,503, per perinatal death prevented was $60,506 and per discounted life-year gained was $2,988. CONCLUSION: It is likely that the general public in high-income countries such as Australia would find reductions in perinatal mortality and in serious perinatal complications sufficient to justify additional health service and personal monetary charges. Over the whole lifespan, the incremental cost per extra life-year gained is highly favourable. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12606000294550.

Neonatal adrenal function after repeat dose prenatal corticosteroids: a randomized controlled trial.

OBJECTIVE: Do repeat prenatal corticosteroids suppress neonatal cortisol concentrations? STUDY DESIGN: Randomized controlled trial of women given weekly repeat corticosteroids or saline placebo, while at risk of preterm birth, until 32 weeks' gestation. RESULTS: Cord serum cortisol concentrations in infants exposed to repeat corticosteroids were similar compared with infants exposed to a single course of corticosteroids (mean difference -26 nmol/L (95% CI -57, 5 nmol/L, P = .10), as were prestress salivary cortisol concentrations on day 3 (median 16.5 vs 15.3 nmol/L, P = .96). The adrenal response to a stressor on day 3 was lower in the repeat corticosteroid group compared with the single course group (median 11.9 vs 21.4 nmol/L, P = .02). Cortisol concentrations were lower in the repeat corticosteroid group on day 7 (median 11.7 vs 18.2 nmol/L, P = .04), but not on days 14 and 21. CONCLUSION: The short- or long-term clinical impact, if any, of these changes in adrenal function needs to be determined.

Perinatal outcomes by mode of assisted conception and sub-fertility in an Australian data linkage cohort.

BACKGROUND: Fertility treatment is associated with increased risk of major birth defects, which varies between in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), and is significantly reduced by embryo freezing. We therefore examined a range of additional perinatal outcomes for these exposures. METHODS: All patients in South Australia receiving assisted conception between Jan 1986-Dec 2002 were linked to the state-wide perinatal collection (all births/stillbirths ≥20 weeks gestation or 400 g birth weight, n = 306 995). We examined stillbirth, mean birth weight, low birth weight (<2500 g, <1500 g), small size for gestational age (<10th percentile, <3rd percentile), large size for gestational age (>90th percentile), preterm birth (32-<37 weeks, <32 weeks gestation), postterm birth (≥41 weeks gestation), Apgar <7 at 5 minutes and neonatal death. RESULTS: Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn (OR = 1.82, 95% Confidence Interval (CI) 1.34-2.48), while survivors as a group were comprehensively disadvantaged at birth, including lower birth weight (-109 g, CI -129--89), very low birth weight (OR = 2.74, CI 2.19-3.43), very preterm birth (OR = 2.30, CI 1.82-2.90) and neonatal death (OR = 2.04, CI 1.27-3.26). Outcomes varied by type of assisted conception. Very low and low birth weight, very preterm and preterm birth, and neonatal death were markedly more common in singleton births from IVF and to a lesser degree, in births from ICSI. Using frozen-embryos eliminated all significant adverse outcomes associated with ICSI but not with IVF. However, frozen-embryo cycles were also associated with increased risk of macrosomia for IVF and ICSI singletons (OR = 1.36, CI 1.02-1.82; OR = 1.55, CI 1.05-2.28). Infertility status without treatment was also associated with adverse outcomes. CONCLUSIONS: Births after assisted conception show an extensive range of compromised outcomes that vary by treatment modality, that are substantially reduced after embryo freezing, but which co-occur with an increased risk of macrosomia.

Intergenerational associations of chronic disease and polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. OBJECTIVE: To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. DESIGN, SETTING AND PARTICIPANTS: Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant. RESULTS AND CONCLUSIONS: Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47), and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76). Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88) and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70). Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations.

Assessing agreement between point of care and pathology laboratory results for INR: experiences from the Point of Care Testing in General Practice Trial.

AIMS: To assess the level of agreement between international normalised ratio (INR) results obtained from pathology laboratories and point of care testing (PoCT) devices used in a general practice setting. METHODS: INR pathology results were collected from multiple pathology laboratories and CoaguChek S PoCT devices over a 6 month period. Agreement was assessed using both clinically relevant agreement and the Bland Altman method. RESULTS: Analysis was based on 1664 dual measurements collected on 417 patients from 26 general practices across Australia. The percentage of dual measurements satisfying the expanded and narrow agreement criteria were 91% and 89%, respectively. The mean difference in results and the 95% limits of agreement depended on the average INR result: mean difference = -0.30 + 0.08 x average; 95% limits of agreement = -0.30 + 0.08 x average +/- 0.77. CONCLUSIONS: The current study provides further evidence that PoCT is an acceptable alternative to pathology laboratory testing in a general practice setting. The Bland Altman method is a useful and flexible tool for assessing agreement. Limits of agreement should be reported in future method comparison studies to assist clinicians in patient management.

Assessing agreement between point of care and laboratory results for lipid testing from a clinical perspective.

OBJECTIVES: Investigate agreement between lipid pathology results from point-of-care testing (PoCT) devices and laboratories. DESIGN AND METHODS: Agreement was assessed using the Bland-Altman method. RESULTS: : Mean difference (limits of agreement) were: -0.28 mmol/L (-1.04, 0.48) for total cholesterol, -0.09 mmol/L, (-0.55, 0.36) for HDL-C. Median difference (nonparametric limits of agreement) were 0.07 mmol/L, (-0.40, 3.04) for triglycerides. CONCLUSIONS: The clinical acceptability of the variation between lipid PoCT and laboratory test results is debatable but our work provides baseline data for further research.

Effectiveness of point-of-care testing for therapeutic control of chronic conditions: results from the PoCT in General Practice Trial.

OBJECTIVE: To compare the clinical effectiveness of point-of-care testing (PoCT) and that of pathology laboratory testing, as measured by therapeutic control in chronic conditions. DESIGN: Multicentre, cluster randomised controlled trial using non-inferiority analysis. SETTING: 53 Australian general practices in urban, rural and remote areas across three Australian states, September 2005 to February 2007. PARTICIPANTS: 4968 patients with established type 1 or type 2 diabetes, established hyperlipidaemia, or taking anticoagulant therapy. INTERVENTION: The intervention group (3010 patients in 30 practices) had blood and urine samples tested by PoCT devices in their general practices, and the control group (1958 patients in 23 practices) had samples tested by their usual pathology laboratories. MAIN OUTCOME MEASURES: The proportion of patients and of tests with results in the target range, and change in test results from baseline. RESULTS: For the proportion of patients with results in the target range, PoCT was found to be non-inferior to pathology laboratory testing for measuring glycated haemoglobin (HbA(1c)), urine albumin, albumin-creatinine ratio (ACR), total cholesterol and triglyceride levels but not for high-density lipoprotein (HDL) cholesterol level and international normalised ratio (INR). For the proportion of tests with results in the target range, PoCT was found to be non-inferior to pathology laboratory testing for measuring all variables except HDL cholesterol. For the proportion of patients showing an improvement in their test result from baseline, PoCT was non-inferior to pathology laboratory testing for HbA(1c), total cholesterol and triglyceride levels, but not for HDL cholesterol level. CONCLUSIONS: This study provides important evidence for those considering the introduction of PoCT into general practice. For all tests except INR and HDL cholesterol, the PoCT approach demonstrated the same or better clinical effectiveness than pathology laboratory testing. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12612607000628448.

Dietary composition of pregnant women is related to size of the baby at birth.

The fetal origins theory of adult disease suggests that term infants who are small for their gestational age have an increased susceptibility to chronic disease in adulthood as a consequence of physiologic adaptations to undernutrition during fetal life. Consistent evidence for an influence of women's dietary composition during pregnancy on growth of their babies is lacking, despite robust effects in animal experiments. We undertook a prospective observational study of 557 women aged 18-41 y, living in Adelaide, South Australia. Diet was assessed in early and late pregnancy using an FFQ. In early pregnancy, medians for energy intake, the proportion of energy derived from protein and from carbohydrate were 9.0 MJ, 17 and 48%, respectively. In late pregnancy the corresponding medians were 9.2 MJ, 16 and 49%. In early pregnancy, the percentage of energy derived from protein was positively associated with birth weight (P = 0.02) and placental weight (P = 0.07), independently of energy intake and weight gain during pregnancy, and after adjustment for potential confounders, including maternal age, parity, and smoking. Effects were stronger among women (n = 429) who had reliable data, based on prespecified criteria including the plausibility of dietary data when referenced against estimated energy expenditure. In addition, for this subgroup, the percentage of energy from carbohydrate in early and late pregnancy was negatively associated with ponderal index of the baby, and a specific effect of protein from dairy sources was identified. These data support the proposition that maternal dietary composition has an effect on fetal growth. Maternal diet in Western societies may therefore be important for the long-term health of the child.