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Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate ("rhIGF-1/Risedronate") (n = 33), 12 months of risedronate ("Risedronate") (n = 33), or double placebo ("Placebo") (n = 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p < 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Context: Anorexia nervosa (AN) is a psychiatric illness with considerable morbidity and no approved medical therapies. We have shown that relative androgen deficiency in AN is associated with greater depression and anxiety symptom severity., Objective: To determine whether low-dose testosterone therapy is an effective endocrine-targeted therapy for AN., Design: Double-blind, randomized, placebo-controlled trial., Setting: Clinical research center., Participants: Ninety women, 18 to 45 years, with AN and free testosterone levels below the median for healthy women., Intervention: Transdermal testosterone, 300 μg daily, or placebo patch for 24 weeks., Main Outcome Measures: Primary end point: body mass index (BMI). Secondary end points: depression symptom severity [Hamilton Depression Rating Scale (HAM-D)], anxiety symptom severity [Hamilton Anxiety Rating Scale (HAM-A)], and eating disorder psychopathology and behaviors., Results: Mean BMI increased by 0.0 ± 1.0 kg/m2 in the testosterone group and 0.5 ± 1.1 kg/m2 in the placebo group (P = 0.03) over 24 weeks. At 4 weeks, there was a trend toward a greater decrease in HAM-D score (P = 0.09) in the testosterone vs placebo group. At 24 weeks, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D: -2.9 ± 4.9 (testosterone) vs -3.0 ± 5.0 (placebo), P = 0.72; HAM-A: -4.5 ± 5.3 (testosterone) vs -4.3 ± 4.4 (placebo), P = 0.25]. There were no significant differences in eating disorder scores between groups. Testosterone therapy was safe and well tolerated with no increase in androgenic side effects compared with placebo., Conclusion: Low-dose testosterone therapy for 24 weeks was associated with less weight gain-and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms-compared with placebo in women with AN., (Copyright © 2019 Endocrine Society.)

Context: Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including "atypical" AN [body mass index (BMI) ≥18.5 kg/m2]., Objective: To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum., Design: Cross-sectional observational study., Setting: Clinical research center., Participants: 153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2)., Measures: Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA)., Results: Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone., Conclusions: Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength., (Copyright © 2017 by the Endocrine Society)

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = -[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load-to-strength ratio helps explain increased fracture risk in both low-weight and obese women., (© 2015 American Society for Bone and Mineral Research.)

Heart rate variability (HRV) biofeedback, a technique which encourages slow meditative breathing, was offered to 25 in-patients with various eating disorder diagnoses-anorexia nervosa, bulimia nervosa and binge eating disorder. We found that this modality had no serious side effects, and was subjectively useful to most participants. An enhanced ability to generate highly coherent HRV patterns in patients with recent onset anorexia nervosa was observed.

The period total first abortion rate (TFAR) has been used to estimate the proportion of women who will experience an induced abortion in their reproductive lifetime. It is a hypothetical measure as age-specific rates currently existing will change with time. Instead, a cohort TFAR has been calculated for women born around 1955 using legal-abortion reports in South Australia to calculate first abortion rates for each year of age from 15 years to 44 years for 1971-2000, respectively, and summing these. Yearly fertility rates were also calculated for this cohort to further describe their reproductive experience. Yearly first abortion rates were also calculated for later cohorts born in 1960-1980. The 1955 cohort TFAR was 288.1 per 1,000 women aged 15-44 years. Cumulative first abortion rates at specific ages were higher for subsequent cohorts (e.g., 309.6 per 1,000 at age 40 years for the 1960 cohort). Thus, about 29% of South Australian women born around 1955 and exposed to legal abortion throughout their reproductive lifetime experienced an induced abortion. This proportion would be higher for later cohorts of women born in 1960-1980 (e.g., at least 31% for those born in 1960).

Objective: To compare pregnancy characteristics and outcomes between Aboriginal and non-Aboriginal teenagers. DESIGN, SETTING AND POPULATION: A retrospective cohort study using the perinatal data collection for South Australian births in 1995-1999: 449 Aboriginal and 4,625 non-Aboriginal teenagers., Methods: Comparison of socio-demographic and clinical characteristics, using relative risks., Main Outcome Measures: Rates of pregnancy, smoking during pregnancy, induction, delivery method, preterm and small-for-gestational-age births and perinatal mortality, Results: Aboriginal teenagers have a pregnancy rate more than twice as high as non-Aboriginal, but a smaller proportion of pregnancies are terminated. They have pregnancies earlier, are more likely to be single, to smoke during pregnancy, to have few antenatal visits, to give birth in a country hospital and to have infections and anaemia. They have lower induction and analgesia rates, but a higher caesarean section rate. Their babies are more likely to be small-for-gestational-age and preterm, to have a congenital abnormality, to require special and intensive nursery care and stay longer in hospital. While their perinatal mortality rate has halved since a decade ago, their neonatal death rate is still twice that of non-Aboriginal births., Conclusions: Aboriginal teenagers need special attention. Support in particular is needed for Aboriginal health workers in preconceptional counselling and health promotion programs that build the capacity of the community, eg concerning proper nutrition during pregnancy, smoking cessation, breastfeeding, SIDS prevention, support for early and regular attendance for antenatal care in friendly and culturally appropriate environments. Outreach services and sexual health services for young Aboriginal people also need expansion.

Objectives: To describe trends in teenage pregnancy rates in South Australia and Australia in 1970-2000, and the socio-demographic and clinical characteristics and outcomes of teenage women who gave birth in South Australia in 1995-99., Methods: A descriptive study using population-based legislated South Australian perinatal and abortion data, Australian Medicare and hospital morbidity data on abortions, and birth registration rates from the Australian Bureau of Statistics., Results: The teenage pregnancy rate in South Australia fell in the 1970s and 1980s, increased in the 1990s, but is declining at the turn of the century. Teenage abortions exceeded livebirths annually from 1994, and in 2000 the teenage abortion, birth and pregnancy rates were 22.4,18.3 and 40.8 per 1,000 respectively. The Australian rates, which are an underestimate, follow the South Australian trends and are declining but still much higher than in many western European countries. High socio-economic areas in South Australia have the lowest teenage pregnancy rates but the highest proportion of teenage pregnancies terminated. Teenagers who gave birth were more likely than older women to be Australian-born, Aboriginal, smokers during pregnancy (47% vs. 23%), to attend few antenatal visits, and to have preterm, small-for-gestational-age and low birthweight babies and neonatal deaths. Perinatal mortality has halved among teenagers under 17 years in the past decade., Conclusions and Implications: Births to South Australian teenage women are associated with social disadvantage and relatively poor perinatal outcomes, although these have improved. Current strategies are aimed at reducing the incidence of unplanned teenage pregnancy and improving support for pregnant teenagers.

Objectives: To evaluate a South Australian campaign to promote and implement knowledge that taking adequate folate/folic acid in the periconceptional period can reduce the risk of having a baby with a neural tube defect., Design and Setting: The campaign, conducted in October 1994--August 1995, targeted women of reproductive age and health professionals. Evaluation was by computer-assisted telephone interviews undertaken by random dialling throughout the State before and after the campaign, and by self-administered questionnaires to health professionals and women in the postnatal period., Participants: Women of reproductive age and four groups of health professionals., Main Outcome Measures: Knowledge about folate, folate-rich foods and the periconceptional period; participation of health professionals in advising women about folate; use of periconceptional folic acid supplements; sales of folic acid tablets; and prevalence of neural tube defects., Results: Significant increases in knowledge about folate followed the campaign. Health professionals and women in the postnatal period had higher initial levels of knowledge about folate, which also increased significantly. The proportions of women taking periconceptional folic acid supplements, and of health professionals advising women planning a pregnancy about folate, also increased significantly, and folic acid tablet sales doubled. Total prevalence of neural tube defects declined between 1966 and 1999 from a baseline of 2.0 per 1,000 births to 1.1 per 1,000 births (Poisson regression, P= 0.03; average decline of 1.0% per year)., Conclusions: A short educational campaign with a limited budget ($40,000) can promote folate successfully, but alternative strategies such as food fortification are likely to be needed to achieve adequate periconceptional folate intake for a very high proportion of women.

Objectives: To determine the contribution of maternal smoking to preterm birth (< 37 weeks' gestation), small for gestational age (SGA, birthweight < 10th percentile for gestational age) and low birthweight (< 2500 g) among Aboriginal and non-Aboriginal births in South Australia., Design: Retrospective cohort analysis of population-based perinatal data., Setting: The State of South Australia, population 1.5 million., Participants: 36059 women (of whom 851 were Aboriginal women) who had singleton births in 1998-1999., Main Outcome Measures: Relative risks and population-attributable risks of preterm birth, SGA and low birthweight from smoking in the second half of pregnancy, by age and Aboriginality., Results: Aboriginal women had a higher rate of smoking in pregnancy than non-Aboriginal women (57.8% v 24.0% at the first antenatal visit) and high rates for all age groups, while the rates decreased with age among non-Aboriginal women. Heavy smoking increased with age, and Aboriginal women were heavier smokers. Women who smoked had elevated relative risks of preterm birth (1.64), SGA (2.28) and low birthweight (2.52), and all these showed a dose-response relationship. Among Aboriginal (versus non-Aboriginal) births, population-attributable risks were significantly higher for SGA (48% v 21%, and 59% for births to Aboriginal teenagers), low birthweight (35% v 23%) and preterm birth (20% v 11%)., Conclusions: Health promotion programs, with a focus on smoking cessation and reducing uptake of smoking, need to be implemented in an appropriate cultural context, especially among young Aboriginal women. Such a program is being developed in South Australia.

The objective of this study was to determine whether women who have experienced an unexplained stillbirth have a higher risk of adverse perinatal outcomes in subsequent births. We compared 316 subsequent births to women with a previous unexplained stillbirth, with 3160 births to women with no previous history of stillbirth, matched by year of birth, in the period 1987-1997, from the South Australian perinatal database, using logistic regression analysis. There was no increase in the rate of stillbirth and no statistically significant increase in the rate of perinatal death (OR 1.62 [95%CI 0.63-4.20]) or neonatal death, although larger studies are needed to confirm this. However, after adjusting for age, parity, and hospital category of birth, women who had a previous stillbirth had increased incidences in subsequent births of abnormal glucose tolerance or gestational diabetes (a fourfold increase); induction of labour and elective Caesarean section; fetal distress and postpartum haemorrhage; and forceps and emergency Caesarean delivery and preterm birth, which were independent of induction of labour. Gestational age at birth and birthweight were also significantly reduced, suggesting a need for close monitoring of their future pregnancies.

Year 5 of the Massachusetts Behavioral Health Program was a transition to management by a new private managed care organization. Fifty-eight providers interviewed for an ongoing panel survey reported slightly lower levels of quality, access, utilization, and length of stay than a year earlier. Relationships with providers and advocates improved after an initial difficult period, while consumer and family involvement at all levels remained low. The greatest changes in managed care appeared to take place during the initial transition from fee-for-service care, but intractable problems continue, and full participation of stake-holders seems difficult to achieve.

Pre-eclampsia and placenta accreta have opposite histological features of placentation. This study set out to test the hypotheses that the sex ratios in these two pregnancy complications are opposite and that these conditions are mutually exclusive. A population-based database covering all deliveries in South Australia between 1986 and 1995 and the hospital-based obstetric database of the Adelaide Women's and Children's Hospital, covering 8549 births between 1993 and 1995, were used to ascertain the sex ratios in singleton pregnancies and the sex ratios in those pregnancies in which there was retained placenta, hypertension in pregnancy, or pre-eclampsia. The likelihood of independence of occurrence or mutual exclusivity of retained placenta and hypertension in pregnancy or pre-eclampsia were also examined. The male:female sex ratio in the South Australian population was 1.077. In pregnancies with hypertension in pregnancy it was 1.165 (P<0.001) and in pregnancies with retained placenta it was 0.883 (P<0.0001). There was a trend to an increased sex ratio in pre-eclamptic pregnancy (1.248 in primigravid and 1.092 in multigravid women) but there was insufficient power to detect significance (P=0.207 and 0.470, respectively). Neither hypertension in pregnancy nor pre-eclampsia were mutually exclusive of placenta accreta: hypertensive disorders of pregnancy and placenta accreta occurred independently of each other. Our findings suggest that sex-linked antigens are unlikely to influence maternofetal interactions consistently to give rise to one but not the other pregnancy complication.

Objectives: To describe the impact of rubella immunisation on the incidence of rubella, congenital rubella syndrome and rubella-related terminations of pregnancy in South Australia, and to identify factors associated with a re-emerging problem., Design and Methods: A population-based descriptive study using data from South Australian notifications of disease, births and terminations of pregnancy, the rubella immunisation programme, antenatal rubella antibody screening and paediatric hospital case records., Setting: South Australia (population 1.48 million people; 20,000 births per year)., Main Outcome Measures: Incidence of rubella (age-sex specific), congenital rubella syndrome and rubella-related terminations of pregnancy; antenatal rubella sero-positive rates; rubella immunisation uptake rates., Results: Rubella notification rates in 1990-1996 were significantly higher for males than females for ages 15-34 years. There were five cases of congenital rubella syndrome notified in 1980-1996 compared with at least 20 confirmed or compatible cases in 1965-1979. Rubella-related terminations of pregnancy are now rare, with the last termination for maternal rubella being in 1993. The antenatal rubella sero-positive rate in 1995 was 96.7%, but was significantly lower among Asian women born overseas (78.6% among those 30 years or older). Vaccination uptake rates in schoolgirls decreased between 1990 and 1994 (91.2% to 86.9%)., Conclusions: Since the introduction of rubella immunisation, the incidence of rubella infection among women of reproductive age, and of rubella-related terminations, has fallen. Congenital rubella syndrome has not been notified since 1990 but its risk persists with a recent increase in rubella notifications, a fall in school immunisation rates, a relatively low antenatal sero-positive rate among older Asian women born overseas and the trend towards giving birth at older ages. Effective immunisation programmes must be maintained, particularly in schools and for young children and migrant women.

The oral retinoids isotretinoin and etretinate are uniquely effective in the treatment of severe cystic acne and keratinisation disorders. Because of their known teratogenicity, there are strict prescription guidelines, but exposure during pregnancy still occurs. A dedicated effort by women and their clinicians is required, involving patient selection, education and informed consent, detailed contraceptive counselling, and careful monitoring and management, including pregnancy testing before commencement of therapy.

The oral retinoids, isotretinoin and etretinate, are highly teratogenic drugs which have been available in Australia since 1985 because of their unique effectiveness in severe cystic acne, psoriasis and other keratinization disorders. Only dermatologists can prescribe them, but in spite of strict guidelines by the manufacturers and the College of Dermatologists, exposed pregnancies have occurred. We attempted to determine the circumstances of exposure to these drugs for the 18 pregnancies terminated in South Australia in 1985-1993, using questionnaires to medical practitioners who notified the terminations under legislation. The main reason for their occurrence was the lack of compliance with the use of effective contraception by the women. In South Australia, some prescriptions of oral retinoids by unauthorized doctors have been dispensed during this period. Using statistics on prescriptions dispensed, an estimate was made of 1 termination of pregnancy for 319 courses of treatment for women with isotretinoin. Extension of guidelines for prescription and more detailed counselling in relation to the use of contraception are recommended. It is also suggested that doctors intending to recommend terminations obtain consent to discuss exposure with the dermatologists concerned, who may not be aware of the exposed pregnancy.

Objective: To determine the sensitivity of antenatal screening methods for neural tube defects in population-based screening in South Australia in 1986-1991, and whether ultrasound can replace serum alpha-fetoprotein screening in terms of achieving an equivalent level of sensitivity., Design and Setting: Ascertainment of all births and terminations of pregnancy with neural tube defects from multiple sources for 1986-1991 in South Australia. Serum and amniotic fluid alpha-fetoprotein results were obtained from the only laboratory performing the tests as a Statewide antenatal screening programme, and information on ultrasound screening from case notifications, hospital case records and medical practitioners who cared for the women., Subjects: All 243 births and terminations of pregnancy with neural tube defects in South Australia in 1986-1991., Main Outcome Measures: The sensitivity of individual screening methods and of all methods used, particularly for spina bifida., Results: For pregnancies with neural tube defects screened by any method (serum alpha-fetoprotein, ultrasound or amniocentesis), 86% sensitivity was achieved. Ultrasound screening for anencephaly achieved 100% sensitivity even in low risk pregnancies, compared with 92% for serum alpha-fetoprotein. For spina bifida, the sensitivity of ultrasound screening increased with the level of risk in pregnancy: it was 60% in low risk pregnancies, which was equivalent to that of serum alpha-fetoprotein screening (64%); 89% in high risk pregnancies and 100% for women referred for confirmation of a suspected spina bifida by another ultrasonographer (chi 1(2) for trend = 23.49, P < 0.0001). Ultrasound screening in high risk pregnancies for spina bifida achieved higher sensitivity in teaching hospitals compared with other ultrasound services in the State (97% vs 65%), but sensitivity was equivalent for low risk pregnancies. It is estimated that, had the serum screening programme not been in place, the level of sensitivity achieved for spina bifida by ultrasound and amniocentesis would have been 62% compared with the actual situation of 76% with the programme in existence, a difference of nearly 15% (95% CI 2.5 to 26.7) (chi 1(2) = 5.45, P = 0.02)., Conclusions: Antenatal screening for neural tube defects in South Australia achieved a higher level of sensitivity with the maternal serum alpha-fetoprotein programme in place. We conclude that the serum screening programme should continue in South Australia pending a significant improvement in the sensitivity of routine ultrasound screening for spina bifida.

Objective: To determine trends in total prevalence of neural tube defects in South Australia during 1966-91, the impact of prenatal diagnosis on birth prevalence, and the effectiveness of prenatal screening for neural tube defects in 1986-91., Design: All births and terminations of pregnancy affected by neural tube defects and information on prenatal screening were ascertained from multiple sources including the South Australian perinatal and abortion statistics collections, birth defects register, and state maternal serum alpha fetoprotein screening programme., Setting: Southern Australia., Subjects: All 1058 births and terminations of pregnancy affected by neural tube defects in 1966-91., Main Outcome Measures: Total prevalence and birth prevalence of individual and all neural tube defects. The proportion of screened cases detected prenatally., Results: Total prevalence of neural tube defects during 1966-91 was 2.01/1000 births with no upward or downward trend. However, birth prevalence fell significantly (by 5.1% a year), with an 84% reduction from 2.29/1000 births in 1966 to 0.35/1000 in 1991 (relative risk = 0.16, 95% confidence interval 0.07 to 0.34). The fall was 96% for anencephaly and 82% for spina bifida. 85% of defects, both open and closed, were detected before 28 weeks' gestation in women screened by serum alpha fetoprotein or mid-trimester ultrasonography, or both, in 1986-91 (99.0% for anencephaly and 75.7% for spina bifida)., Conclusions: While the total prevalence of neural tube defects in South Australia remained stable, prenatal diagnosis and termination of pregnancy resulted in an 84% fall in birth prevalence during 1966-91. Screening detected over four fifths of cases in 1986-91.