Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study.

OBJECTIVE: To assess the contribution of maternal factors to major birth defects after in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and natural conception. DESIGN: Retrospective cohort study in South Australia for the period January 1986 to December 2002. SETTING: A whole of population study. POPULATION: A census of all IVF and ICSI linked to registries for births, pregnancy terminations, and birth defects (diagnosed before a child's fifth birthday). METHODS: Odds ratios (ORs) for birth defects were calculated among IVF, ICSI, and natural conceptions for maternal age, parity, pre-pregnancy BMI, smoking, pre-existing diseases, and conditions in pregnancy, with adjustment for confounding factors. MAIN OUTCOME MEASURES: Birth defects classified by International Classification of Diseases (ninth revision) and British Paediatric Association (ICD9-BPA) codes. RESULTS: There were 2211 IVF, 1399 ICSI, and 301 060 naturally conceived births. The unadjusted prevalence of any birth defect was 7.1, 9.9, and 5.7% in the IVF, ICSI, and natural conception groups, respectively. As expected, the risk of birth defects increased with maternal age among the natural conceptions. In contrast, for IVF and ICSI combined, relative to natural conceptions, births to women aged ≤29 years had a higher risk (adjusted odds ratio, aOR 1.42; 95% confidence interval, 95% CI 1.04-1.94), births to women aged 35-39 years had no difference in risk (aOR 1.01; 95% CI 0.74-1.37), and births to women aged ≥40 years had a lower risk of defects (aOR 0.45; 95% CI 0.22-0.92). Defects were also elevated for nulliparity, anaemia, and urinary tract infection in births after ICSI, but not after IVF. CONCLUSIONS: The usual age-birth defect relationship is reversed in births after IVF and ICSI, and the associations for other maternal factors and defects vary between IVF and ICSI. TWEETABLE ABSTRACT: Risk of birth defects in women over 40 years is lower after infertility treatment than for natural conceptions.

Core food intakes of Australian children aged 9-10 years: nutrients, daily servings and diet quality in a community cross-sectional sample.

BACKGROUND: The present study aimed to evaluate core food intakes in 9-10-year-old Australian children by considering adequacy of nutrient intakes, comparing servings of core food groups with Australian recommendations and scoring overall diet quality. METHODS: Children from an established community-based cohort study completed a semi-quantitative food frequency questionnaire. Daily intakes of energy, macronutrients, micronutrients, servings of core (i.e. nutrient-rich) foods and a diet quality index were calculated and compared with appropriate standards. Sex and socio-economic differences were examined. RESULTS: The 436 children participating were from low to high socio-economic status families. As a group, over half of the children met estimated average requirements for key macro- and micronutrients, with the exception of fibre (inadequate in 41% of boys and 24% of girls). Children obtained 55% of their daily energy from core foods. Most children had fewer than the recommended servings of vegetables (91%) and meat/alternatives (99.8%), whereas boys generally ate fewer servings of grains and cereals than recommended (87%), and girls ate fewer servings of dairy (83%). Diet quality scores indicated room for improvement (median score of 26 for boys and 25 for girls, out of a maximum of 73 points). CONCLUSIONS: As a group, a large proportion of children were able to meet their daily nutrient requirements. However, achieving this through noncore foods meant that diets were high in salt, saturated fat and sugar; more servings of core foods and greater dietary diversity would be preferable. These results suggest that families need more support to optimise dietary patterns of children in this age group.

Growth trajectories in early childhood, their relationship with antenatal and postnatal factors, and development of obesity by age 9 years: results from an Australian birth cohort study.

BACKGROUND: In an era where around one in four children in the United Kingdom, the United States, and Australia are overweight or obese, the development of obesity in early life needs to be better understood. We aimed to identify groups of children with distinct trajectories of growth in infancy and early childhood, to examine any association between these trajectories and body size at age 9, and to assess the relative influence of antenatal and postnatal exposures on growth trajectories. DESIGN: Prospective Australian birth cohort study. SUBJECTS AND METHODS: In total, 557 children with serial height and weight measurements from birth to 9 years were included in the study. Latent class growth models were used to derive distinct groups of growth trajectories from birth to age 3½ years. Multivariable logistic regression models were used to explore antenatal and postnatal predictors of growth trajectory groups, and multivariable linear and logistic regression models were used to examine the relationships between growth trajectory groups and body size at age 9 years. RESULTS: We identified four discrete growth trajectories from birth to age 3½ years, characterised as low, intermediate, high, or accelerating growth. Relative to the intermediate growth group, the low group had reduced z-body mass index (BMI) (-0.75 s.d.; 95% confidence interval (CI) -1.02, -0.47), and the high and accelerating groups were associated with increased body size at age 9 years (high: z-BMI 0.70 s.d.; 95% CI 0.49, 0.62; accelerating: z-BMI 1.64 s.d.; 95% CI 1.16, 2.11). Of the antenatal and postnatal exposures considered, the most important differentiating factor was maternal obesity in early pregnancy, associated with a near quadrupling of risk of membership of the accelerating growth trajectory group compared with the intermediate growth group (odds ratio (OR) 3.72; 95% CI 1.15, 12.05). CONCLUSIONS: Efforts to prevent childhood obesity may need to be embedded within population-wide strategies that also pay attention to healthy weight for women in their reproductive years.

Sleep disturbances in a community-based sample of women with polycystic ovary syndrome.

STUDY QUESTION: Is there an excess of sleep disturbances in women with polycystic ovary syndrome (PCOS) in a community-based sample? STUDY ANSWER: Sleep disturbances are almost twice as common in women with PCOS compared with women of similar age without PCOS, with the association slightly accounted for by body weight and, to a greater extent, by depressive symptoms. WHAT IS KNOWN ALREADY: There is an excess of sleep-disordered breathing in clinical samples of women with PCOS, after accounting for their profile of body weight. Poor sleep patterns increase insulin resistance and thus may exacerbate PCOS symptoms and longer-term risk of metabolic disease. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 724 women, comprising 74% of a cohort study established retrospectively when women were around age 30 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Comparisons were made between 87 women with PCOS, diagnosed using the Rotterdam criteria, and 637 women without this diagnosis in Adelaide, South Australia. Differences in sleep disturbances, assessed using a modified version of the Jenkins questionnaire, were investigated using ordered logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Sleep disturbances were twice as common in women with PCOS compared with those without. Specifically, PCOS was associated with increasing occurrence of difficulty falling asleep (odds ratio (OR) 1.94, 95% confidence interval (CI) 1.28-2.95); this association was attenuated but still statistically significant after accounting for BMI and depressive symptoms. Increasing occurrence of difficulty maintaining sleep (OR 1.92 95% CI 1.12-3.31) was mediated by obesity and depressive symptoms, together. Other factors did not change these findings. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of the study means that the direction of associations between PCOS and sleep disturbances is unclear, although bi-directionality for the mediators is likely based on data in the wider literature. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that assessment and management of both sleep and mental health problems in women with PCOS should be undertaken. Longitudinal data would be valuable to see how poor sleep affects longer-term health profiles.

Maternal body size prior to pregnancy, gestational diabetes and weight gain: associations with insulin resistance in children at 9-10 years.

AIMS: To investigate whether maternal body size pre-pregnancy, gestational diabetes and weight gain are independently associated with subsequent insulin resistance in children; and to examine the potential mediating role of child's body size in any associations. METHODS: At 9-10 years, 443 children took part in a follow-up of a prospective cohort. Of those, 163 children elected to provide a fasting blood sample and child insulin resistance was estimated by homeostasis model assessment. Generalized linear models with log link function and Gaussian family were used to assess associations with antenatal exposures. Potential confounders were considered as well as the role of the child's size. RESULTS: Prior to pregnancy, 23% of mothers were overweight and another 17% obese. All women were screened for gestational diabetes, with 6% diagnosed. On average, women gained an estimated 14 kg during pregnancy. Gestational diabetes was positively associated with child insulin resistance. In addition, maternal pre-pregnancy body mass index (BMI) was associated with child insulin resistance in a non-linear manner: a positive, progressive association was observed until BMI of 30 kg/m² was reached, but not thereafter. Estimated gestational weight gain was not associated with child insulin resistance. These findings were not accounted for by size of the child at birth or at 9-10 years. CONCLUSIONS: Maternal body size prior to pregnancy is positively associated with increases in child insulin resistance, at least until the 'obese' category is reached. This is independent of gestational diabetes and not mediated by body size of the child, suggesting genetic and/or developmental programming origins.

Is precarious employment associated with women remaining childless until age 35 years? Results from an Australian birth cohort study.

STUDY QUESTION: Does time in casual employment (while not studying full time) affect the likelihood of a woman having a child by age 35? SUMMARY ANSWER: Duration of time spent in casual employment is associated with an increased likelihood of childlessness at age 35 years, irrespective of socio-economic background as indicated by educational level. WHAT IS KNOWN ALREADY: Precarious employment conditions have become increasingly prevalent in recent decades in Western countries. The relationship between precarious employment conditions and age at first childbirth has been examined in several European countries with varying results. STUDY DESIGN, SIZE, DURATION: A retrospective cross-sectional component (n = 663) was added to an existing study based on a cohort of women born during 1973-1975. An event history calendar instrument was used to obtain data regarding a range of life domains over a 20-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using data from the Life Journeys of Young Women Project carried out in Adelaide, South Australia, Cox proportional hazards models were applied to investigate the research questions. MAIN RESULTS AND THE ROLE OF CHANCE: The likelihood of childbirth by around age 35 was reduced for every year spent in casual employment, irrespective of socioeconomic status, partner's education and parents' birthplace. The likelihood was reduced by 8, 23 and 35% for 1, 3 and 5 years spent in casual employment, respectively. LIMITATIONS, REASONS FOR CAUTION: Women with longer employment histories (and greater age at first birth) had more opportunities for errors in recall, but it is unlikely that such errors were systematic and led to bias in the results. While we included variables reflecting partner's education and length of time with a live-in partner, partner's employment histories were not taken into account. WIDER IMPLICATIONS OF THE FINDINGS: Duration of time spent in casual employment is associated with an increased likelihood of childlessness at age 35 years, and this association is present across the spectrum of socioeconomic status. We suggest that upstream labour market reforms could be considered in order to reduce barriers to childbearing.

Growth in early life and the development of obesity by age 9 years: are there critical periods and a role for an early life stressor?

OBJECTIVE: Rapid growth, possibly occurring in critical periods in early life, may be important for the development of obesity. It is unknown whether this is influenced by postnatal exposures such as age-relevant sources of stress. Frequent house moves may be one such stressor. We aimed to examine if there is a period of growth in early life critical for the development of child obesity by age 9 years and assess the role of house moves in modifying any relationships between early life growth and obesity at age 9 years. DESIGN: Prospective Australian birth cohort study. SUBJECTS: In all, 392 children with serial body size measurements from birth to age 9 years. METHODS: Standardized body mass index (z-BMI) was available for six time points (spanning birth to 3½ years), and the total number of house moves between birth and 3½ years. The outcomes considered were z-BMI and % body fat (%BF) at age 9 years. Linear regression models were used to estimate the effects of serial measurements of z-BMI and number of house moves on the outcomes. RESULTS: Life-course plots showed that z-BMI at 3½ years was a statistically significant predictor of z-BMI at 9 years (ß=0.80; standard error (s.e.), 0.04), whereas z-BMI at 9 months (ß=-1.13; s.e., 0.40) and 3½ years (ß=4.82; s.e., 0.42) were significant predictors of %BF at age 9 years. There were statistically significant interactions between the number of house moves and change in z-BMI between 9 and 12 months, such that ≥ 3 house moves in early life amplified the detrimental effects of earlier rapid growth on both body size and composition at age 9 years. CONCLUSION: In the absence of evidence for a single critical period, efforts to prevent overweight and obesity are required throughout childhood. In addition, modifiable postnatal stressors may exacerbate effects of early growth on obesity in later childhood.

Parental work schedules and child overweight and obesity.

OBJECTIVE: Studies in school-age children have consistently shown a positive association between maternal paid work hours and child obesity. However, there is conflicting evidence about the impact of maternal work hours scheduled at nonstandard times (for example, evenings, nights or weekends), and no previous examination of paternal work schedules and child weight. We examined the associations between maternal, paternal and combined parental paid work schedules and overweight/obesity in children at age 9 years. METHODS: Data were analysed from the most recent follow-up of 9-year-old children (n=434) in an Australian birth cohort study. Children were measured and classified as overweight/obese using the International Obesity Taskforce body mass index cutoff points. Current working conditions of parents were obtained from a structured interview with the primary caregiver. Logistic regression analyses were used to investigate the effect of parental work schedules on child overweight/obesity with adjustment for a range of sociodemographic and household factors associated with parental employment and child weight. RESULTS: At 9 years of age, 99 children (22.8%) were overweight or obese. When parental work schedules were examined separately, child overweight/obesity was significantly associated with paternal nonstandard work schedules (adjusted odds ratio (OR) 1.97, 95% confidence interval (CI) 1.08-3.61). There was no association with any type of maternal work schedule. We also found an association between child overweight/obesity and circumstances in which both parents worked nonstandard schedules; however, this was of borderline statistical significance in the adjusted models (adjusted OR 2.26, 95% CI 0.99-5.16). CONCLUSION: Work hours scheduled at nonstandard times, when worked by the father or both parents, were associated with child overweight and obesity. These findings indicate the potential importance of fathers' paid work arrangements for child overweight/obesity, which until recently has largely been ignored.

Birthweight and thinness at birth independently predict symptoms of polycystic ovary syndrome in adulthood.

BACKGROUND: The aetiology of polycystic ovary syndrome (PCOS) is unknown and contested. While it has been suggested that PCOS could have origins in perturbed development, epidemiological findings have been inconclusive. We aimed to examine potential fetal origins of PCOS. METHODS: A retrospective birth cohort of 948 singleton female babies born at one hospital in South Australia in 1973-1975 was assembled. Birth characteristics were obtained from hospital records and PCOS symptoms were identified through interview and clinical examination when women were ~30 years old. Based on the combination of PCOS symptoms, women formed seven outcome groups. A multinomial logistic regression analysis was used to investigate associations between birth characteristics and these outcome groups. RESULTS: After adjusting for gestational age, two distinct birth characteristics were associated with two PCOS symptom groups. Each 100 g increase in birthweight increased the risk of hyperandrogenism (as a single symptom) in adulthood by 5% [relative risk ratio: 1.05, 95% confidence interval (CI): 1.01-1.09]. In contrast, each one unit increase in the ponderal index at birth decreased the risk of all three key PCOS symptoms (hyperandrogenism, menstrual dysfunction and polycystic ovaries) by 21% (0.79, 95% CI: 0.66-0.93). CONCLUSIONS: These results suggest two discrete fetal programming pathways (related to high birthweight and to thinness at birth) are operating. Our findings point to differing aetiologies for symptom clusters, and inform the debate over symptoms that best represent the disorder.

Assisted reproductive technologies: a hierarchy of risks for conception, pregnancy outcomes and treatment decisions.

The use of assisted reproductive technologies (ART) for the treatment of infertility has grown exponentially over the last 20 years, and now accounts for 4% of all births in Australia, and over 1 m births annually around the globe. There is consistent reporting of increased risk of adverse perinatal outcomes and birth defects following infertility treatment. However, change in practice has been stymied by critical knowledge gaps with regards to (a) the relative contribution of patient and treatment factors to adverse outcomes, (b) the independent contribution of specific contemporary treatments and treatment combinations to outcomes, (c) the impact of innovations in laboratory and clinical practice on treatment success and observed risk and (d) changes over time in patient characteristics. Here we summarize key findings from the South Australian Birth Cohort, which is a whole-of-population cohort of over 300,000 births from 1986 to 2002. Relative to spontaneous conceptions, singletons from assisted conception were more likely to be stillborn [odds ratio (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 (OR=2109 g; 95% CI 2129-289), very low birth weight (OR=2.74; 95% CI 2.19-3.43), very preterm birth (OR=2.30; 95% CI 1.82-2.90) and neonatal death (OR=2.04; 95% CI 1.27-3.26). Major birth defects, including cardiac, urogenital and musculoskeletal defects are doubled after fresh ICSI cycles, which is a particular concern as ICSI now accounts for 70% of all treatment cycles globally. Future study is needed to provide contemporary, precise evidence to inform patient and clinic decision making, and generate knowledge for future innovation in ART laboratory methods and clinical practice, thereby optimizing treatment and health outcomes while reducing adverse events.

Spontaneous loss of a co-twin and the risk of birth defects after assisted conception.

The study of very early pregnancy loss is impractical in the general population, but possible amongst infertility patients receiving carefully monitored treatments. We examined the association between fetal loss and the risk of birth defects in the surviving co-twin in a retrospective cohort study of infertility patients within an infertility clinic in South Australia from January 1986 to December 2002, linked to population registries for births, terminations and birth defects. The study population consisted of a total of 5683 births. Births from singleton pregnancies without loss were compared with survivors from (1) pregnancies with an empty fetal sac at 6-8 weeks after embryo transfer, (2) fetal loss subsequent to 8-week ultrasound and (3) multiple pregnancy continuing to birth. Odds ratios (OR) for birth defects were calculated with adjustment for confounders. Amongst infertility patients, the prevalence of birth defects was 7.9% for all twin pregnancies without fetal loss compared with 14.6% in pregnancies in which there had been an empty sac at ultrasound, and 11.6% for pregnancies with fetal loss after 6-8 weeks. Compared with singleton pregnancies without loss, the presence of an empty sac was associated with an increased risk of any defect (OR=1.90, 95% confidence intervals (CI)=1.09-3.30) and with multiple defects (OR=2.87, 95% CI=1.31-6.28). Twin pregnancies continuing to birth without loss were not associated with an overall increased prevalence of defects. We conclude that the observed loss of a co-twin by 6-8 weeks of pregnancy is related to the risk of major birth defects in the survivor.

The autonomic control of heart rate and insulin resistance in young adults.

The pathophysiology of insulin resistance is unclear. A link between increased heart rate (HR) and insulin resistance suggests an association with sympathetic nervous system activity. To further evaluate this, we examined autonomic activity using spectral analysis of HR variability (HRV), which provides a measure of cardiac sympathovagal modulation, and related this to insulin sensitivity (Si) in 137 men and women (20 yr old). The HRV spectrum displays 2 major peaks: a high-frequency peak, reflecting vagal activity, and a low-frequency peak caused by vagal and sympathetic activity. The high-to-low ratio (HLratio) reflects sympathovagal balance. Si was measured, using the i.v. glucose tolerance test with minimal modeling, and HR data was derived from a 15-min supine electrocardiogram. Women were more insulin resistant than men (Si, 3.94 vs. 5.09 10(4) min(-1)/per pmol x L; P = 0.002), had higher HR (59 vs. 56 beats/min, P = 0.019), but had a higher HLratio (2.04 vs. 1.31, P = 0.001). In men (but not women), Si correlated with HR (r = -0.410, P = 0.001) and measures of HRV: HLratio (r = 0.291, P = 0.002) independently of body mass index. In conclusion, Si correlates with cardiac sympathovagal balance in men, but not women, suggesting gender differences in the autonomic modulation of insulin resistance.

The relationship between birth weight and blood pressure amplifies from childhood to adulthood.

OBJECTIVE: To investigate relationships between birth characteristics and blood pressure at age 20 years and to assess whether effects of birth weight on blood pressure are amplified from childhood to adulthood. DESIGN: A longitudinal study of 584 men and women from Adelaide, Australia, examined previously at 8 years and followed up at age 20 years. RESULTS: Birth weight was negatively associated with systolic pressure at age 20 years in men (regression coefficient 2.6 mmHg per kg; 95% confidence interval 0.7, 4.4) and women (regression coefficient 4.6 mmHg per kg; 95% confidence interval 2.9, 6.4), after adjustment for current weight There was an interaction with current size (P = 0.05 for men and P = 0.09 for women), such that effects were enhanced among individuals with relatively high weight or weight for height. Shortness at birth, thinness at birth, and low birth weight relative to placental weight were also associated with elevated systolic pressure at age 20 years. Effects of birth weight on blood pressure were stronger at age 20 than at age 8 years (P < 0.01 for men and P = 0.03 for women). This was not due simply to increased variability of blood pressure in adulthood. There were greater rises in blood pressure with age among individuals of relatively low birth weight. CONCLUSIONS: These findings are further evidence that poor fetal growth is associated with elevated blood pressure in later life. The results support the hypothesis that the relationship is amplified with increasing age.

Assessment and evaluation of child health associates.

More than 20 studies have been carried out of child health associates to assess their knowledge, training, and practice; their ability to interpret and integrate data; their cognitive knowledge and psychomotor and interpersonal skills; and their competence and effectiveness as a primary health care providers. The results of the assessment and evaluation studies of child health associates indicate that they can determine the health status and manage the health care of patients in ambulatory settings and in the newborn nursery with a degree of skill and competence approaching that of pediatricians. Child health associates can provide comprehensive primary health care for more than 90% of children seen in these settings. The high degree of acceptance of child health associates by families and their demonstrated proficiency and cost-effectiveness document that they can be an important source of primary health care for most children.

Origins of fetal growth restriction.

Regulation of growth of the fetus and its placenta begins before pregnancy. Early in pregnancy the mother sets the rate of growth of the fetus on a trajectory, which may be modified by events later in pregnancy. Low maternal weight for height, history of previous small babies, maternal undernutrition, pregnancy disorders, e.g. pre-eclampsia, are associated with low birthweight. Maternal smoking is a major factor in developed countries; infections and undernutrition in developing countries.Recently, there has been emphasis on adverse long-term outcomes including ischaemic heart disease, hypertension and diabetes associated with poor fetal growth. Experimental studies in animals show that some of these outcomes can readily be induced by restriction of fetal growth. Progress in determining successful treatments to improve the growth of the fetus has lagged behind these epidemiological and experimental findings. However, nutrient supplements improve growth in undernourished women and smoking cessation also improves fetal size and outcome.

Estimated and measured blood alcohol levels in the night-time driving population.

The aim of this study was to compare drivers' subjective estimates of their blood alcohol concentration (BAC) with their measured BAC. As part of a night-time survey of drinking and driving in the Adelaide metropolitan area, 13 951 drivers were approached at intersections between 10 p.m. and 3 a.m. and asked to provide a breath alcohol sample. In addition, drivers were given a reply-paid mail questionnaire which sought their own estimate of their BAC. The 5765 replies were compared with the measured BACs. It was found that drivers with low measured BACs tended to over-estimate their BAC while drivers with high BACs tended to under-estimate; the error in the estimates increased as measured BAC increased. These errors were similar for males and females and did not vary with age group. These results emphasize the need for the wider adoption of reliable means by which people can assess their own BAC more accurately.

The effect of random breath testing on perception of likelihood of apprehension and on illegal drink-driving.

This study examines the links between random breath testing (RBT), driver perception of the likelihood of apprehension if illegally drink-driving, and drink-driving behaviour in Adelaide, South Australia. It is based on information gained from surveys of night-time drivers in metropolitan Adelaide, during 1987, 1989 and 1991. Overall, about 25% of the sample in each year thought that illegal drink-driving was likely to result in apprehension. This perception was consistently lower for males and for those aged less than 30 years than for their counterparts, however, there was evidence that it increased with exposure to RBT, notably when that exposure was recent. Also, compared with other drivers, fewer drivers who thought that apprehension was likely had an illegal blood alcohol concentration (BAC) when surveyed, or reported that they would be likely to drive if they thought that they had an illegal BAC. However, the majority of drivers who thought that detection was unlikely also reported that they would be unlikely to drink-drive. These results suggest the need for some re-direction of current RBT activities.