Optimizing Nutritional Needs of Burn Patients: An Evaluation of Nutritional Assessment Tools, Feeding Strategies, and Their Impact on Patient Outcomes.

BACKGROUND: Optimal nutritional support is essential to the recovery and improved outcomes of burn patients. This review aims to explore existing literature to evaluate nutrition assessment tools, feeding formulations' caloric predictive ability, timing of initiation of feeding, optimal nutritional composition, and caloric intake in burn patients. METHODS: Three databases were searched to glean studies investigating nutrition in acute severe adult burn patient populations in four areas: outcomes based on feeding type and timing, the caloric predictability of nutritional assessment tools, outcomes associated with the composition of feeding formulas, and considerations related to caloric intake. Outcomes of interest included the effects of nutritional assessments using feeding type, nutritional administration timing, formula composition, and caloric intake on mortality rate, length of stay, and infection. RESULTS: A total of 19 studies were included. Nutritional assessment tools were determined to over- or underestimate resting energy expenditure (REE). Milner was the most accurate alternative to indirect calorimetry. Early enteral nutrition in burn patients within 24 hours of admission was preferred. 5 studies evaluated micronutrients and yielded variable results. Low-fat high-carbohydrate diets were the ideal macronutrient composition. Burn patients were shown to receive lower caloric intake than recommended. CONCLUSIONS: Findings showed that while nutritional assessment tools tend to inaccurately estimate REE in burn patients, the ideal alternative to indirect calorimetry is the Milner equation. Several new equations may be worthy alternatives but require further validation. Enteral feeding should be initiated within the first 24 hours of burn injury whenever possible and should contain a high-carbohydrate/low-fat composition.

Revision of an Adult Burn Center's Resuscitation Guideline Leads to Lower Resuscitation Requirements.

In 2018, the institutional burn resuscitation guideline was updated to remove the use of high-dose ascorbic acid (HDAA) therapy, to lower 24-hour resuscitation fluid estimations from 4 to 2 mL/kg/TBSA, and to optimize guidance around appropriate colloid resuscitation. This retrospective study compared the incidence of a composite safety outcome (acute kidney injury, or intra-abdominal hypertension requiring intervention) between the pre-guideline update to post-guideline update. Secondarily, 24-hour resuscitation volumes, hourly urine output, vasopressor use, and mechanical ventilation duration were compared as well. The composite safety outcome was similar between the 2 groups (40% vs 29%; p=0.27), but the post-group showed significantly lower 24-hour resuscitation volumes (3.74 mL/kg/TBSA vs 2.94 mL/kg/TBSA; p<0.01), as well as lower urine output (1.26 mL/kg/hr vs 0.75 mL/kg/hr; p<0.01). There was no difference between the groups with respect to vasopressor use, mechanical ventilation duration, or mortality. This study suggests that a simplified resuscitation protocol without HDAA, combined with a lower starting fluid rate led to significantly lower 24-hour resuscitation volumes without an increase in adverse safety events.

Levothyroxine may not adequately prepare hypothyroid women for controlled ovarian hyperstimulation.

BACKGROUND: Thyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid-treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known. AIMS: To determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes. MATERIALS AND METHODS: Prospective cohort study involving 46 euthyroid (anti-thyroid peroxidase antibody negative) and 16 levothyroxine-replaced women with baseline thyroid-stimulating hormone (TSH) <2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick-up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared. RESULTS: Median serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine-replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine-replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ. CONCLUSION: Adequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.

Prediction on X-ray output of free electron laser based on artificial neural networks.

Knowledge of x-ray free electron lasers' (XFELs) pulse characteristics delivered to a sample is crucial for ensuring high-quality x-rays for scientific experiments. XFELs' self-amplified spontaneous emission process causes spatial and spectral variations in x-ray pulses entering a sample, which leads to measurement uncertainties for experiments relying on multiple XFEL pulses. Accurate in-situ measurements of x-ray wavefront and energy spectrum incident upon a sample poses challenges. Here we address this by developing a virtual diagnostics framework using an artificial neural network (ANN) to predict x-ray photon beam properties from electron beam properties. We recorded XFEL electron parameters while adjusting the accelerator's configurations and measured the resulting x-ray wavefront and energy spectrum shot-to-shot. Training the ANN with this data enables effective prediction of single-shot or average x-ray beam output based on XFEL undulator and electron parameters. This demonstrates the potential of utilizing ANNs for virtual diagnostics linking XFEL electron and photon beam properties.

'The dark before the dawn': the 2021 British Thoracic Society Audit of the treatment of tobacco dependency in acute trusts.

Smoking remains the single largest cause of preventable death, disability and health inequality. Smoking tobacco directly contributes to over 500 000 hospital admissions each year, making hospitals an important location to optimise treatment for tobacco dependency. The third British Thoracic Society Tobacco Dependency Audit was undertaken to determine how effectively national standards for treating tobacco-dependent smokers have been implemented and assess if any progress has been made from previous audits. Data on 14579 patients from 119 hospitals revealed 21% of patients were current smokers, 45% were offered very brief advice and 5% prescribed combination nicotine replacement therapy or varenicline. Only 9% completed a consultation with a specialist tobacco dependency practitioner during their inpatient stay and fewer than 1% of smokers were abstinent at 4 weeks following discharge. Clinical leadership of tobacco dependency services was deficient, and staff were ill equipped in supporting current smokers in their efforts to quit with only 50% of trusts offering regular smoking cessation training. There has been little meaningful improvement from previous audits and there remains woefully inadequate provision of tobacco dependency treatment for patients who smoke. The National Health Service (NHS) Long Term Plan has committed substantial, new funding to the NHS to ensure every patient that smokes admitted to hospital will be offered evidence-based support and treatment for tobacco dependency. The findings of this audit highlight the urgency with which this programme must be implemented to tackle the greatest cause of premature death in the UK and to achieve the wider well-recognised benefits for the healthcare system.

Successful live birth following a short course of glucocorticoid suppression in a patient with autoimmune polyglandular syndrome type 2 and premature ovarian insufficiency: A case report.

A 32-year-old nulliparous woman with premature ovarian insufficiency POI and autoimmune polyglandular syndrome type 2 (APS-2), presented to our fertility center with a 2.5-year history of amenorrhoea. Controlled ovarian hyperstimulation (COH), with high dose gonadotropins, failed to promote antral follicle growth. The patient was given a short, 4-week course of 2 mg dexamethasone prior to a repeat COH cycle, which resulted in the retrieval of good oocyte numbers and eventual live birth from a thawed embryo transfer.

Relationship Between Preexisting Functional Mobility Impairments and Burn Treatment Outcomes.

Burn severity is determined by total body surface area affected, temperature of source, and duration of exposure. Patients with impaired mobility are less capable of avoiding hazards and escaping traumatic injuries. Additionally, patients with impaired mobility frequently suffer from other comorbid conditions and have specialized needs, which can complicate their acute treatment. This study was a retrospective electronic medical records review of all adult patients, aged 18 years and older with a preexisting mobility impairment, admitted as inpatients to a single burn center for treatment of burn-related injuries from January 1, 2009, to December 31, 2019. The 10-year review of 1520 adult burn admissions meeting the initial criteria of inpatient admission and burn injury revealed 174 patients with documentation supporting preexisting functional mobility impairment (11%). Surprisingly, patients' overall lengths of stays were consistent with all burn populations at 0.81 days per % TBSA, with the average length of stay being 6.7 days. The demographic data were consistent with national burn registry data as male, Caucasian, and older, with mean age of 61.1 years. Demographic data and details of hospital course focusing on treatment, complications, and outcomes were extracted and analyzed. There is a paucity of literature describing the needs of this unique burn population. Burn-injured patients with preexisting mobility impairments suffer from similar mechanisms of injury. By identifying attributes unique to this population, we hope to develop specialized prevention education and treatment protocols.

Prior iodine exposure and impact on thyroid function during controlled ovarian hyperstimulation: A prospective study.

AIMS: Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH. METHODS: One-hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4-2.5 mIU/L) planning their first COH cycle were subdivided according to iodine supplementation (nil, <6 months, ≥6 months) and compared to levothyroxine (LT4)-treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded. RESULTS: TSH increased during COH for those women taking iodine supplements for ≥6 months (P = 0.025). One quarter recorded a TSH level >2.5 mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4-dependent controls (P = 0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine (P < 0.0001) or supplemented for ≥6 months (P < 0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for <6 months were four times more likely to achieve a live birth than women taking iodine for longer. CONCLUSIONS: Women taking iodine supplements for ≥6 months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4-dependent patients.

Understanding the anatomy of a malpractice suit. In the United States this is a doctor's best defence.

In the United States, the majority of physicians have been sued and those who have not, will be. Defendants share the notion that the lawsuit is totally fallacious. To be fallacious, the outcome of a medical intervention must be an unpreventable random maloccurrence. This is the only alternative to a medical error. The conflict over outcomes that are random and outcomes that are medical errors results in 46,000 malpractice suits every year in the USA. The burden of proof is a preponderance of evidence, but this is insufficient to do more than just infer, not prove, a relationship between the medical intervention and the outcome. Plaintiffs, generally, prove a malpractice case using inductive reasoning. Inductive reasoning leaves much to intuition. They use inductive reasoning because, by definition, preponderance of evidence, also, leaves much to intuition. Deductive reasoning is objective and there is no place for intuition. With deductive reasoning, the burden of proof is now sufficient to distinguish whether or not the cause relates to the effect with 95% confidence. A model for deductive reasoning in malpractice which is completely consistent with the scientific method is presented. This should and would derail frivolous lawsuits.

Dapsone as an Effective Treatment for Arthritis Secondary to Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a disorder of the terminal follicular epithelium in the apocrine sweat glands. Chronic relapsing inflammation, mucopurulent discharge, and progressive scarring frequently involving the axillary and inguinoperineal area characterize HS. Reactive arthritis is associated with chronic infections, such as HS, although joint involvement is uncommon. Treatment is based on the eradication of the underling infection. Whereas skin lesions may improve with antibiotic therapy, the arthritis of HS is often unresponsive to therapy. Various therapies have been tried in HS, including nonsteroidal antiinflammatory drugs, colchicine, mesalamine, dapsone, and TNF inhibitors. A case of severe, debilitating arthritis associated with HS that responded to dapsone is reported. This case demonstrates the difficulty of successful treatment of HS as well as of the associated arthritis.

Retrospective cohort study on preparation regimens for frozen embryo transfer.

The objective of this study was to examine the pregnancy outcomes from frozen embryo transfer (FET) cycles using different endometrial preparation regimens, compared to ovulation induction with letrozole (letrozole OI). A retrospective cohort study was conducted at a fertility centre in Sydney, Australia, on 6060 FET cycles. The cycles were stratified into one of four ways to achieve endometrial preparation. These were either a natural, letrozole OI, OI with follicle-stimulating hormone (FSH OI) or a programmed cycle. The primary outcome was live birth rate (LBR) per embryo transfer. Secondary outcomes included clinical pregnancy and biochemical pregnancy rates, adverse events including miscarriage, ectopic pregnancy, stillbirth, neonatal death and multiple births. Ovarian stimulation parameters were also analysed including the time taken to reach the luteal phase and the number of blood or urine tests required for monitoring the cycle. The results of the study showed that the LBR following letrozole OI cycles was higher when compared to natural cycles (odds ratio (OR): 1.27 (1.07-1.49)) and programmed cycles (OR: 2.36 (1.67-3.34)). There was no significant difference between letrozole OI and FSH OI LBR (OR: 0.99 (0.76-1.28)). An improved LBR with letrozole OI compared to natural cycles was maintained when only women with a normal length cycle were considered (OR: 1.44 (1.10-1.89)). There was a significant reduction in miscarriage rates when letrozole OI was compared to programmed cycles (OR: 0.46 (0.26-0.83)). It was therefore concluded that the use of letrozole OI for endometrial preparation in an FET cycle may be associated with higher LBR and lower miscarriage rate, compared to using a programmed cycle. LAY SUMMARY: Couples suffering from infertility frequently try to conceive following the transfer of an embryo which has been frozen during an in vitro fertilisation cycle. Embryos will only lead to a pregnancy if the woman's womb lining has particular characteristics that allow it to accept the embryo. Despite the thousands of frozen embryo transfer cycles carried out across the world, it is not known how best to prepare a woman's lining so it has these particular characteristics. This study looked at the pregnancy outcomes of 6060 cycles to compare four different ways to prepare a woman's womb lining. These included relying on a woman's natural menstrual cycle, or using an oral medication called letrozole, or injectable medicine called follicle-stimulating hormone, or oestrogen and progesterone hormonal medications. The comparison found that using letrozole before transfer of a frozen embryo may be associated with higher rates of a live birth for some women.

Low Levels of Vitamin D Promote Memory B Cells in Lupus.

Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse is a spontaneous model of lupus and Sjögren's syndrome, characterized by increased Th17 cells and peripheral B cell expansion. Vitamin D3 has anti-inflammatory properties, reduces Th17 cells and impairs B cell differentiation/activation. Therefore, we assessed how varying amounts of vitamin D3 affected lupus-like disease in the Act1-/- mouse. Methods: Act1-/- mice were fed either low/restricted (0 IU/kg), normal (2 IU/kg), or high/supplemented (10 IU/kg) vitamin D3 chow for 9 weeks, after which lupus-like features were analyzed. Results: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction specifically promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients. Conclusion: Low levels of vitamin D3 are associated with elevated levels of memory B cells in an animal model of lupus and well-controlled SLE patients.

Intractable hypercalcaemia during pregnancy and the postpartum secondary to pathogenic variants in CYP24A1.

SUMMARY: Parathyroid-independent hypercalcaemia of pregnancy, due to biallelic loss of function of the P450 enzyme CYP24A1, the principal inactivator of 1,25(OH)2D results in hypervitaminosis D, hypercalcaemia and hypercalciuria. We report two cases of this disorder, with intractable hypercalcaemia, one occurring during gestation and into the postpartum, and the other in the postpartum period. Case 1, a 47-year-old woman with a twin pregnancy conceived by embryo transfer, presented with hypercalcaemia at 23 weeks gestation with subnormal serum parathyroid hormone (PTH) and normal serum 25-OH D levels. She was admitted to hospital at 31 weeks gestation with pregnancy-induced hypertension, gestational diabetes and increasing hypercalcaemia. Caesarean section at 34 weeks gestation delivered two healthy females weighing 2.13 kg and 2.51 kg. At delivery, the patient's serum calcium level was 2.90 mmol/L. Postpartum severe hypercalcaemia was treated successfully with Denosumab 60 mg SCI, given on two occasions. CYP24A1 testing revealed she was compound heterozygous for pathogenic variants c.427_429delGAA, (p.Glu143del) and c.1186C>T, (p.Arg396Trp). Case 2, a 36-year-old woman presented 4 days after the delivery of healthy twins with dyspnoea, bradycardia, severe headaches, hypertension and generalized tonic-clonic seizures after an uneventful pregnancy. She was hypercalcaemic with a suppressed PTH, normal 25(OH)D, and elevated 1,25(OH)2D levels. Her symptoms partially responded to i.v. saline and corticosteroids in the short term but bisphosphonates such as Pamidronate and Zoledronic acid did not result in sustained improvement. Denosumab 120 mg SCI successfully treated the hypercalcaemia which resolved completely 2 months post-partum. CYP24A1 testing revealed she was homozygous for the pathogenic variant c.427_429delGAA, (p.Glu143del). LEARNING POINTS: Hypercalcaemia in pregnancy can be associated with considerable morbidity with few options available for management. In non-PTH-related hypercalcaemia the diagnosis of CYP24A1 deficiency should be considered. Making a definitive diagnosis of CYP24A1 deficiency by genetic testing delays the diagnosis, while the availability of serum 24,25-dihydroxyvitamin D (24,25(OH)2D) will expedite a diagnosis. In pregnant women with CYP24A1 deficiency hypercalcaemia can worsen in the post-partum period and is more likely to occur with twin pregnancies but generally resolves within 2-3 months. Therapeutic alternatives are limited in pregnancy and their effectiveness is short-lived and mostly ineffective. Denosumab used in both our patients after delivery was the most effective agent normalizing calcium and may have benefit as a long-term therapeutic agent in preventing complications in patients with CYP24A1 deficiency.

Act1 is a negative regulator in T and B cells via direct inhibition of STAT3.

Although Act1 (adaptor for IL-17 receptors) is necessary for IL-17-mediated inflammatory responses, Act1- (but not Il17ra-, Il17rc-, or Il17rb-) deficient mice develop spontaneous SLE- and Sjögren's-like diseases. Here, we show that Act1 functions as a negative regulator in T and B cells via direct inhibition of STAT3. Mass spectrometry analysis detected an Act1-STAT3 complex, deficiency of Act1 (but not Il17ra-, Il17rc-, or Il17rb) results in hyper IL-23- and IL-21-induced STAT3 activation in T and B cells, respectively. IL-23R deletion or blockade of IL-21 ameliorates SLE- and Sjögren's-like diseases in Act1-/- mice. Act1 deficiency results in hyperactivated follicular Th17 cells with elevated IL-21 expression, which promotes T-B cell interaction for B cell expansion and antibody production. Moreover, anti-IL-21 ameliorates the SLE- and Sjögren's-like diseases in Act1-deficient mice. Thus, IL-21 blocking antibody might be an effective therapy for treating SLE- and Sjögren's-like syndrome in patients containing Act1 mutation.

Healing Animals in an Antibiotic Age: Veterinary Drugs and the Professionalism Crisis, 1945-1970.

Between 1945 and 1970, the introduction of antibiotics in agriculture forced veterinarians to articulate the boundaries of their professional identity. While veterinarians welcomed the new aid to arrest infectious diseases of livestock, they worried as farmers took animal healing into their own hands without veterinary supervision, and resented the competition from retail outlets that sold the drugs. Veterinary antibiotics also set off heated debates within the field about whether the profession should position itself as preventers or healers of disease, debates that were akin to the kinds of professional discourses among physicians and pharmacists in the same period. By calling attention to the social context that helped facilitate an increasing reliance on the veterinary antibiotics, this article helps explain the sources of present-day overuse of such antibiotics in American agriculture.

Elevated anti-Mullerian hormone in lean women may not indicate polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder with clinical features shared with functional hypogonadotrophic hypogonadism (FHH). AIM: To investigate the usefulness of an elevated (>40 pmol/L) anti-Mullerian hormone (AMH) in identifying PCOS and distinguishing PCOS from FHH. MATERIALS AND METHODS: 141 patients with an elevated AMH and body mass index either <20 kg/m2 (lean) or >30 kg/m2 (obese) were selected and three subgroups analysed - obese, lean, lean with suspected FHH. FHH was diagnosed clinically, incorporating diet, weight and exercise history; confirmatory tests included pituitary MRIs, progestin challenges and endometrial thickness measurements. PCOS features of oligo/anovulation, polycystic ovarian morphology (PCOm) and hyperandrogenism were determined by clinical history, pelvic ultrasound, free androgen index and physical examination, respectively. Features of PCOS and blood levels of AMH, follicle-stimulating hormone, luteinising hormone, sex hormone binding globulin (SHBG) and testosterone were compared between subgroups. RESULTS: Of 141 patients with elevated AMH, 76 were obese and 65 lean. Greater than one-third of lean women had the clinical picture of FHH. Elevated AMH predicted PCOm and menstrual irregularity across all subgroups but uniquely associated with hyperandrogenism in the obese. Median AMH levels were similar among FHH and non-FHH women. Median SHBG levels were significantly higher (111 ± 73 vs 56 ± 31, P < 0.001) in lean women with FHH compared to those without FHH. CONCLUSIONS: PCOS and FHH share common features of elevated AMH levels, oligo-anovulation and polycystic ovarian morphology. AMH did not assist in differentiating FHH from PCOS. A higher SHBG level shows promise as a discriminatory finding in FHH.

ASSERT trial - How to assess the safety and efficacy of a high frequency rTMS in postpartum depression ? A multicenter, double blinded, randomized, placebo-controlled clinical trial.

BACKGROUND: Postpartum Depression affects a considerable number of women worldwide. This condition inflicts severe consequences to mother and child health. Thus far, available treatments have low response and high relapse rates. We designed this trial to evaluate a safe and more efficacious innovative therapy. AIMS: To report a feasible and ethical study design to assess the safety and efficacy of a high frequency repetitive Transcranial Magnetic Stimulation 10 Hz (rTMS) compared to sham rTMS in women with moderate to severe Post-Partum Depression using standard treatment (sertraline).To conduct an ancillary, exploratory, randomized, active controlled, double blind study with a hypothesis to assess the safety and efficacy of 10 Hz rTMS compared to sertraline. METHODS: A multicenter, parallel arm, randomized, placebo-controlled, double-blind design to assess safety and efficacy of 10 Hz rTMS compared to sham.An ancillary study will be conducted with parallel arm, randomized, active controlled and double dummy design to assess safety and efficacy of 10 Hz rTMS compared to sertraline.

Ovulatory disorders are an independent risk factor for pregnancy complications in women receiving assisted reproduction treatments.

BACKGROUND: Conception using assisted reproduction treatments (ART) has been associated with an increased risk of pregnancy complications. It is uncertain if this is caused by ART directly, or is an association of the underlying factors causing infertility. AIMS: We assessed the relationship between assisted conception (AC) and maternal or fetal complications in a large retrospective cohort study. In a nested cohort of women receiving infertility treatment, we determined if such risk rests predominantly with certain causes of infertility. MATERIALS AND METHODS: Retrospective database analysis of 50 381 women delivering a singleton pregnancy in four public hospital obstetric units in western Sydney, and a nested cohort of 508 women receiving ART at a single fertility centre, in whom the cause of infertility was known. RESULTS: A total of 1727 pregnancies followed AC; 48 654 were spontaneous conceptions. Adjusted for age, body mass index and smoking, AC was associated with increased risk of preterm delivery (OR 1.73, 95% CI 1.50-2.02), hypertension (OR 1.55, 95% CI 1.34-1.82) and diabetes (OR 1.51, 95% CI 1.30-1.75). In the nested cohort, ovulatory dysfunction was present in 145 women and 336 had infertility despite normal ovulatory function. Ovulatory dysfunction was associated with increased risk of diabetes (OR 2.94, 95% CI 1.72-5.02) and hypertension (OR 2.40, 95% CI 1.15-5.00) compared to women with normal ovulatory function. CONCLUSIONS: Assisted conception is associated with increased risk of pregnancy complications. This risk appears greatest for women whose underlying infertility involves ovulatory dysfunction. Such disorders probably predispose towards diabetes and hypertension, which is then exacerbated by pregnancy.