Antenatal sildenafil citrate treatment increases offspring blood pressure in the placental-specific Igf2 knockout mouse model of FGR.

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring (P < 0.05) and reduced glucose sensitivity in both WT (P < 0.01) and P0 (P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life.NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.

The effects of myo-inositol and probiotic supplementation in a high-fat-fed preclinical model of glucose intolerance in pregnancy.

Glucose intolerance during pregnancy - a major driver of gestational diabetes mellitus (GDM) - has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.

Prenatal anxiety and obstetric decisions among pregnant women in Wuhan and Chongqing during the COVID-19 outbreak: a cross-sectional study.

OBJECTIVES: To investigate the mental status of pregnant women and to determine their obstetric decisions during the COVID-19 outbreak. DESIGN: Cross-sectional study. SETTING: Two cities in China--Wuhan (epicentre) and Chongqing (a less affected city). POPULATION: A total of 1947 pregnant women. METHODS: We collected demographic, pregnancy and epidemic information from our pregnant subjects, along with their attitudes towards COVID-19 (using a self-constructed five-point scale). The Self-Rating Anxiety Scale (SAS) was used to assess anxiety status. Obstetric decision-making was also evaluated. The differences between cities in all of the above factors were compared and the factors that influenced anxiety levels were identified by multivariable analysis. MAIN OUTCOME MEASURES: Anxiety status and its influencing factors. Obstetric decision-making. RESULTS: Differences were observed between cities in some background characteristics and women's attitudes towards COVID-19 in Wuhan were more extreme. More women in Wuhan felt anxious (24.5 versus 10.4%). Factors that influenced anxiety also included household income, subjective symptom and attitudes. Overall, obstetric decisions also revealed city-based differences; these decisions mainly concerned hospital preference, time of prenatal care or delivery, mode of delivery and infant feeding. CONCLUSIONS: The outbreak aggravated prenatal anxiety and the associated factors could be targets for psychological care. In parallel, key obstetric decision-making changed, emphasising the need for pertinent professional advice. Special support is essential for pregnant mothers during epidemics. TWEETABLE ABSTRACT: The COVID-19 outbreak increased pregnant women's anxiety and affected their decision-making.

Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial.

OBJECTIVES: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR. METHODS: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' gestation or delivery. Maternal blood pressure (BP), heart rate (HR), augmentation index, pulse wave velocity (PWV), cardiac output, stroke volume (SV) and total peripheral resistance were recorded before randomization, 1-2 h and 48-72 h post-randomization, and 24-48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction. RESULTS: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m2 (95% CI, -11.00 to -0.50 mL/m2 ) vs 0.00 mL/m2 (95% CI, -5.00 to 4.00 mL/m2 ); P = 0.056). CONCLUSIONS: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

OBJECTIVE: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. DESIGN: A randomised placebo-controlled trial. SETTING: Thirteen maternal-fetal medicine units across New Zealand and Australia. POPULATION: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. METHODS: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). MAIN OUTCOME MEASURES: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia. RESULTS: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75). CONCLUSIONS: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing. TWEETABLE ABSTRACT: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

The relationship between maternal 25-hydroxyvitamin D status in pregnancy and childhood adiposity and allergy: an observational study.

BACKGROUND: Vitamin D insufficiency (defined as <75 nmol l-1) is widespread among pregnant women around the world and has been proposed to influence offspring outcomes in childhood and into adult life, including adiposity and allergy. Disorders, including asthma and eczema, are on the rise among children. Our aim was to investigate the relationship between maternal 25-hydroxyvitamin D status in pregnancy and offspring adiposity, asthma and eczema in childhood. SUBJECTS AND METHODS: Maternal 25-hydroxyvitamin D concentrations were analysed in serum samples collected at 15 weeks' gestation from 1710 participants of the prospective Screening for Pregnancy Endpoints cohort study. The offspring of 1208 mothers were followed up at age 5-6 years. Data collected included height, weight, percentage body fat (PBF, measured by bioimpedance) and history of asthma and eczema. Multivariable analysis controlled for maternal body mass index (BMI), age and sex of the child and season of serum sampling. RESULTS: Complete data were available for 922 mother-child pairs. Each 10 nmol l-1 increase in maternal 25-hydroxyvitamin D concentration at 15 weeks' gestation was associated with a decrease in offspring PBF of 0.2% (95% confidence interval 0.04-0.36%, P=0.01) after adjustment for confounders but was not related to child BMI z-score. Maternal mean (±s.d.) 25-hydroxyvitamin D concentration was similar in children who did and did not have asthma (71.7±26.1 vs 73.3±27.1 nmol l-1, P=0.5), severe asthma (68.6±28.6 vs 73.3±26.8 nmol l-1, P=0.2) and eczema (71.9±27.0 vs 73.2±27.0 nmol l-1, P=0.5). CONCLUSIONS: The finding of a relationship between maternal vitamin D status and adiposity in childhood is important, particularly because vitamin D insufficiency in pregnancy is highly prevalent. The association between maternal vitamin D supplementation in pregnancy and adiposity in the offspring merits examination in randomised controlled trials.

STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): an international consortium of randomised placebo-controlled trials.

BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. DISCUSSION: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis. TRIAL REGISTRATIONS: New Zealand and Australia: ACTRN12612000584831 . Registered 30/05/2012. Canada: NCT02442492 . Registered 05/05/2015. Ireland: CT 900/572/1 . Registered 15/07/2015. The Netherlands: NCT02277132 . Registered 29/09/2014. United Kingdom: ISRCTN39133303 . Registered 31/07/2014.

Consensus definition of fetal growth restriction: a Delphi procedure.

OBJECTIVE: To determine, by expert consensus, a definition for early and late fetal growth restriction (FGR) through a Delphi procedure. METHOD: A Delphi survey was conducted among an international panel of experts on FGR. Panel members were provided with 18 literature-based parameters for defining FGR and were asked to rate the importance of these parameters for the diagnosis of both early and late FGR on a 5-point Likert scale. Parameters were described as solitary parameters (parameters that are sufficient to diagnose FGR, even if all other parameters are normal) and contributory parameters (parameters that require other abnormal parameter(s) to be present for the diagnosis of FGR). Consensus was sought to determine the cut-off values for accepted parameters. RESULTS: A total of 106 experts were approached, of whom 56 agreed to participate and entered the first round, and 45 (80%) completed all four rounds. For early FGR (< 32 weeks), three solitary parameters (abdominal circumference (AC) < 3(rd) centile, estimated fetal weight (EFW) < 3(rd) centile and absent end-diastolic flow in the umbilical artery (UA)) and four contributory parameters (AC or EFW < 10(th) centile combined with a pulsatility index (PI) > 95(th) centile in either the UA or uterine artery) were agreed upon. For late FGR (≥ 32 weeks), two solitary parameters (AC or EFW < 3(rd) centile) and four contributory parameters (EFW or AC < 10(th) centile, AC or EFW crossing centiles by > two quartiles on growth charts and cerebroplacental ratio < 5(th) centile or UA-PI > 95(th) centile) were defined. CONCLUSION: Consensus-based definitions for early and late FGR, as well as cut-off values for parameters involved, were agreed upon by a panel of experts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Previous pregnancy loss has an adverse impact on distress and behaviour in subsequent pregnancy.

OBJECTIVE: To investigate whether women with previous miscarriages or terminations have higher levels of anxiety, depression, stress, and altered behaviours in a subsequent pregnancy. DESIGN: A retrospective analysis of 5575 women recruited into the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study. SETTING: Auckland, New Zealand, Adelaide, Australia, Cork, Ireland, and Manchester, Leeds, and London, UK. POPULATION: Healthy nulliparous women with singleton pregnancies. METHODS: Outcomes were recorded at 15 and 20 weeks of gestation. MAIN OUTCOME MEASURES: Short-form State-Trait Anxiety Inventory (STAI) score, Perceived Stress Scale score, Edinburgh Postnatal Depression Scale score, and pregnancy-related behaviour measured using behavioural responses to pregnancy score. RESULTS: Of the 5465 women included in the final analysis, 559 (10%) had one and 94 (2%) had two previous miscarriages, and 415 (8%) had one and 66 (1%) had two previous terminations of pregnancy. Women with one previous miscarriage had increased anxiety (adjusted mean difference 1.85; 95% confidence interval, 95% CI 0.61-3.09), perceived stress (adjusted mean difference 0.76; 95% CI 0.48-1.03), depression (adjusted odds ratio, aOR 1.26; 95% CI 1.08-1.45), and limiting/resting behaviour in pregnancy (adjusted mean difference 0.80; 95% CI 0.62-0.97). In women with two miscarriages, depression was more common (aOR 1.65; 95% CI 1.01-2.70) and they had higher scores for limiting/resting behaviour in pregnancy (adjusted mean difference 1.70; 95% CI 0.90-2.53) at 15 weeks of gestation. Women with one previous termination displayed elevated perceived stress (adjusted mean difference 0.65; 95% CI 0.08-1.23) and depression (aOR 1.25; 95% 1.08-1.45) at 15 weeks of gestation. Women with two previous terminations displayed increased perceived stress (adjusted mean difference 1.43; 95% CI 0.00-2.87) and depression (aOR 1.67; 95% 1.28-2.18). CONCLUSIONS: This study highlights the psychological implications of miscarriage and termination of pregnancy.

Second-trimester maternal distress increases the risk of small for gestational age.

BACKGROUND: The effect of prenatal distress on the risk of a small for gestational age (SGA) infant is uncertain. We have addressed the influences of prenatal stress, anxiety and depression on the risk of SGA. We also examined the effects of infant sex and timing of distress during pregnancy on any observed associations. METHOD: The study population comprised 5606 healthy nulliparous pregnant women who participated in the international prospective Screening for Obstetric and Pregnancy Endpoints (SCOPE) study. Women completed the Perceived Stress Scale (PSS), the short form of the Spielberger State-Trait Anxiety Inventory (STAI) and the Edinburgh Postnatal Depression Scale (EPDS) at 15 ± 1 and 20 ± 1 weeks' gestation. SGA was defined as birthweight below the 10th customized percentile. Logistic regression was used for data analysis, adjusting for several potential confounders such as maternal age, body mass index (BMI), smoking, socio-economic status and physical exercise. RESULTS: The risk of SGA was increased in relation to mild [adjusted odds ratio (aOR) 1.35, 95% confidence interval (CI) 1.07-1.71], moderate (aOR 1.26, 95% CI 1.06-1.49), high (aOR 1.45, 95% CI 1.08-1.95) and very high stress scores (aOR 1.56, 95% CI 1.03-2.37); very high anxiety score (aOR 1.45, 95% CI 1.13-1.86); and very high depression score (aOR 1.14, 95% CI 1.05-1.24) at 20 ± 1 weeks' gestation. Sensitivity analyses showed that very high anxiety and very high depression increases the risk of SGA in males but not in females whereas stress increases the risk of SGA in both males and females. CONCLUSIONS: These findings suggest that prenatal stress, anxiety and depression measured at 20 weeks' gestation increase the risk of SGA. The effects of maternal anxiety and depression on SGA were strongest in male infants.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies.

Reduced infant birth weight in the North West of England consequent upon 'maternal exposure' to 7/7 terrorist attacks on central London.

The effect of media coverage of the London terrorist attacks on 7 July 2005 on pregnancy outcome in mothers living in the North Western region of England was assessed. Pregnant women exposed to media coverage of these attacks had infants with mean birth weight lowered by 16 g and increased risks of a small and very small for gestational age infant (odds ratio 1:10 and 1:09, respectively). This small, but significant reduction in birth weight may indicate excess glucocorticoid exposure within the fetus, which could contribute to fetal programming and an increased likelihood of disease in adult life.

Revision knee replacement surgery in the NHS: A BASK surgical practice guideline.

BACKGROUND: Revision knee replacement (KR) is both challenging for the surgical team and expensive for the healthcare provider. Limited high quality evidence is available to guide decision-making. AIM: To provide guidelines for surgeons and units delivering revision KR services. METHODS: A formal consensus process was followed by BASK's Revision Knee Working Group, which included surgeons from England, Wales, Scotland and Northern Ireland. This was supported by analysis of National Joint Registry data. RESULTS: There are a large number of surgeons operating at NHS sites who undertake a small number of revision KR procedures. To optimise patient outcomes and deliver cost-effective care high-volume revision knee surgeons working at high volume centres should undertake revision KR. This document outlines practice guidelines for units providing a revision KR service and sets out: The current landscape of revision KR in England, Wales and Northern Ireland. Service organisation within a network model. The necessary infrastructure required to provide a sustainable revision service. Outcome metrics and auditable standards. Financial mechanisms to support this service model. CONCLUSIONS: Revision KR patients being treated in the NHS should be provided with the best care available. This report sets out a framework to both guide and support revision KR surgeons and centres to achieve this aim.

Risk factors for small-for-gestational-age infants by customised birthweight centiles: data from an international prospective cohort study.

OBJECTIVE: To identify clinical and ultrasound variables associated with the birth of small-for-gestational-age (SGA) infants by customised centiles, subclassified according to whether their mothers were normotensive or developed hypertensive complications. DESIGN: Prospective, multicentre cohort study. SETTING: Participating centres of the Screening for Pregnancy Endpoints (SCOPE) study in Auckland, New Zealand, Adelaide, Australia, Manchester and London, UK, and Cork, Ireland. POPULATION: The 3513 nulliparous participants of the SCOPE study. METHODS: Women were interviewed at 15 ± 1 weeks, and had ultrasound growth measurements and umbilical and uterine Doppler studies at 20 ± 1 weeks. Variables associated with SGA infants were identified using logistic regression. MAIN OUTCOME MEASURES: Small for gestational age (i.e. a birthweight of less than the tenth customised centile), normotensive-SGA and hypertensive-SGA. Comparison groups for statistical analyses were non-SGA, normotensive non-SGA and hypertensive non-SGA. RESULTS: Among 376 (10.7%) SGA infants, 281 (74.7%) were normotensive-SGA and 95 (25.3%) were hypertensive-SGA. Independent risk factors for normotensive-SGA were low maternal birthweight, low fruit intake pre-pregnancy, cigarette smoking, increasing maternal age, daily vigorous exercise, being a tertiary student, head and abdominal circumference of less than the tenth centile and increasing uterine artery Doppler indices at the 20-week scan. Protective factors were: high green leafy vegetable intake pre-pregnancy, and rhesus-negative blood group. Risk factors for hypertensive-SGA were conception by in vitro fertilisation, previous early pregnancy loss and femur length of less than tenth centile at the 20-week scan. CONCLUSIONS: Risk factors for infants who are SGA by customised centiles have been identified in a cohort of healthy nulliparous women. A number of these factors are modifiable; however, further studies are needed to replicate these findings.

Relationship between maternal growth, infant birthweight and nutrient partitioning in teenage pregnancies.

OBJECTIVE: Teenagers are susceptible to delivering small-for-gestational-age (SGA) infants. Previous studies suggest that maternal growth may contribute, as a result of preferential nutrient partitioning to the mother. We investigated the impact of maternal growth on birthweight in pregnant teenagers in the UK, and examined endocrine mediators of nutrient partitioning. DESIGN: A prospective observational multicentre study, About Teenage Eating, conducted between 2004 and 2007. SETTING: Four hospitals in socially-deprived areas of Manchester and London. POPULATION: A total of 500 pregnant adolescents (14-18 years of age) with a singleton pregnancy were recruited at 10-21 weeks of gestation, with follow-up studies on 368 subjects. A cohort of 80 pregnant adults (25-40 years of age) provided a control group for determining growth. METHODS: Skeletal growth, weight gain and skinfold thickness were measured from first to third trimester, together with maternal levels of micronutrients and metabolic hormones: insulin-like growth factor (IGF) system and leptin. Dietary analyses were performed. MAIN OUTCOME MEASURE: SGA birth. RESULTS: Maternal growth was not associated with SGA birth: growing mothers delivered more large-for-gestational-age infants (OR 2.51; P < 0.05). Growers had greater weight gain (P < 0.001), fat accrual (P < 0.001) and red cell folate concentrations (P < 0.01) than non-growers. Maternal IGF-I (P < 0.01) and leptin (P < 0.001) were positively associated with maternal and fetal growth, whereas IGF-I (P < 0.001) was negatively associated. Teenagers that were underweight at booking or with low weight gain were at greater risk of SGA birth. CONCLUSIONS: Maternal growth was not detrimental to fetal growth in this UK population of teenagers. Greater weight gain and higher concentrations of IGF-I in growing teenagers may provide anabolic drive for maternal and fetal growth.

THA with the ABG I prosthesis at 15 years. Excellent survival with minimal osteolysis.

UNLABELLED: Following recent reports of poor results with the hydroxyapatite-coated ABG I prosthesis, we report the survival of a series of 63 patients (69 hips) at a mean of 15 years (range, 13-17 years). In total, eight patients had revision procedures. The reason for revision was acetabular loosening in all cases. In only one case was there associated clinical and radiographic loosening of the femoral stem. The 15-year survival of the acetabular component was 86.9% (95% confidence interval, 71.7%-96.0%) and the 15-year survival of the femoral component was 98.6% (95% confidence interval, 88.8%-100.0%). Periacetabular osteolysis was seen in 10 of 59 (17%) surviving hips. In these hips the components remained well fixed owing to the remaining bone-component contact. There was no difference in the Oxford hip score between patients with well-fixed hips and evidence of osteolysis and patients with hips without evidence of osteolysis. Multivariate analysis failed to reveal any factors associated with the presence of osteolysis (gender, age at primary surgery, Oxford hip score, cup abduction, and acetabular polyethylene wear rates). The ABG I prosthesis continues to show excellent long-term results. Ongoing radiographic review is recommended to detect progressive osteolysis that otherwise remains clinically silent until failure. LEVEL OF EVIDENCE: Level IV, Case series. See Guidelines for Authors for a complete description of levels of evidence.

Provision of revision knee surgery and calculation of the effect of a network service reconfiguration: An analysis from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Revision knee replacement (KR) is technically challenging, expensive, and outcomes can be poor. It is well established that increasing surgeon and unit volumes results in improved outcomes and cost-effectiveness for complex procedures. The aim of this study was to 1) describe the current provision of revision KR in England, Wales and Northern Ireland at the individual surgeon and unit level and 2) investigate the effect on workload of case distribution in a network model. METHODS: Current practice was mapped using NJR summary statistics containing all revision KR procedures performed over a three-year period (2016-2018). Units were identified as revision centres based on threshold volumes. Units undertaking <20 revisions per year were classified as Primary Arthroplasty Units (PAUs) in calculations on the effect of workload centralisation. RESULTS: Revision KR was performed by 1353 surgeons at 232 NHS sites. The majority of surgeons and units were low-volume; >1000 surgeons performed <7 and 125 sites performed <20 procedures per year. Reallocation of work from these 125 PAUs (1235 cases, 21% of total workload) to a network model with even redistribution of cases between centres undertaking revision surgery would result in an additional average annual case increase of 11 per unit per year (range six to 14). CONCLUSIONS: Revision KR workload re-allocation would lift all revision centres above a 30 per year threshold and would appear to be a manageable increase in workload for specialist revision KR centres. Case complexity and local referral agreements will significantly affect the real increase in workload; these factors were not incorporated here.

Sex ratio at birth following prenatal maternal exposure to severe life events: a population-based cohort study.

BACKGROUND: A reduction in the sex ratio at birth has been linked to maternal condition during and before pregnancy. A recent study reported an association between maternal exposure to severe life events and sex ratio at birth using the Danish national register. We attempted to replicate that study using a new Danish cohort. METHODS: Mothers of all singleton live births (n = 1.35 million births) in Denmark, between 1 January 1980 and 31 December 2002, were linked to data on their children and partners. The old cohort consisted of babies born between 1980 and 1992 (n = 699 362), whereas the new cohort consisted of babies born between 1993 and 2002 (n = 633 451). We defined exposure as death or serious illness in older children and partners in the first trimester or in the 6 months before conception. Sex ratio at birth was defined as the proportion of male live births. RESULTS: During the study period, there were 1,349,099 singleton live births (692,870 boys and 656,229 girls). The sex ratio at birth in the new cohort was 0.5134. In the new cohort, prenatal exposure to severe life events was not associated with a reduction in the sex ratio at birth [relative risk = 1.00 (95% confidence interval: 0.95-1.05)]. CONCLUSIONS: In the new cohort, we did not find strong evidence that, in a stable western population, prenatal exposure to severe life events is associated with a reduction in the sex ratio at birth.

Rates of preterm birth following antenatal maternal exposure to severe life events: a population-based cohort study.

BACKGROUND: Preterm birth and other pregnancy complications have been linked to maternal stress during pregnancy. We investigated the association between maternal exposure to severe life events and risk of preterm birth. METHODS: Mothers of all singleton live births (n = 1.35 million births) in Denmark between 1 January 1979 and 31 December 2002 were linked to data on their children, parents, siblings and partners. We defined exposure as death or serious illness in close relatives in the first or second trimesters or in the 6 months before conception. Log-linear binomial regression was used to estimate the effect of exposure on preterm birth, very preterm birth and extremely preterm birth. RESULTS: There were 58 626 (4.34%) preterm births (<37 weeks), 11 732 (0.87%) very preterm births and 3288 (0.24%) extremely preterm births in the study cohort. Severe life events in close relatives in the 6 months before conception increased the risk of preterm birth by 16% (relative risk, RR = 1.16, [95% CI: 1.08-1.23]). Severe life events in older children in the 6 months before conception increased the risk of preterm birth by 23% (RR = 1.23, [95% CI: 1.02-1.49]) and the risk of very preterm birth by 59% (RR = 1.59, [95% CI: 1.08-2.35]). CONCLUSIONS: Our population-based cohort study suggests that maternal exposure to severe life events, particularly in the 6 months before pregnancy, may increase the risk of preterm and very preterm birth.