Benefit of antenatal corticosteroids by year of birth among preterm infants in Canada during 2003-2017: a population-based cohort study.

OBJECTIVE: To evaluate the changes in the associations of antenatal corticosteroids (ACS) with neonatal mortality and severe neurological injury over time (2003-17). DESIGN: National, population-representative, retrospective cohort study. SETTING: Level III neonatal intensive care units participating in the Canadian Neonatal Network. POPULATION: All infants born at 230/7 -336/7 weeks of gestation (n = 43 456). METHODS: We estimated the associations between exposure to ACS and neonatal outcomes by year of birth. Year of birth was considered both continuously and categorically as three consecutive epochs. MAIN OUTCOME MEASURE: Neonatal mortality and severe neurological injury. RESULTS: The absolute rates of neonatal mortality and severe neurological injury decreased during the study period in both the ACS and No ACS groups. For infants born at 230/7 -306/7 weeks of gestation, ACS was associated with similar reductions in neonatal mortality across the three epochs (9.0% versus 18.1%, adjusted relative risk [aRR] 0.54, 95% CI 0.47-0.61 in 2003-09; 7.6% versus 19.6%, aRR 0.51, 95% CI 0.44-0.59 in 2010-13; and 7.3% versus 14.5%, aRR 0.56, 95% CI 0.46-0.68 in 2014-17) and in severe neurological injury (13.2% versus 25.8%, aRR 0.57, 95% CI 0.50-0.64 in 2003-09; 7.4% versus 17.4%, aRR 0.53, 95% CI 0.43-0.66 in 2010-14; and 7.2% versus 14.8%, aRR 0.59, 95% CI 0.48-0.74 in 2014-17). CONCLUSION: Despite the ongoing improvements in neonatal care of preterm infants, as reflected by the gradual decrease in the absolute rates of neonatal mortality and severe neurological injury, the association of ACS treatment with neonatal mortality and severe neurological injury among extremely preterm infants born at 23-30 weeks of gestation has remained stable throughout the study period of 15 years. TWEETABLE ABSTRACT: Despite the gradual decrease in the rates of neonatal mortality and severe neurological injury, antenatal corticosteroids remain an important intervention in the current era of neonatal care.

DEVELOPING twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study.

OBJECTIVE: To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN: A population-based retrospective cohort study (2007-2017). SETTING: Ontario, Canada. METHODS: Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS: For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS: We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT: Potential twin-specific OGTT thresholds for GDM were identified.

Vaginal progesterone, oral progesterone, 17-OHPC, cerclage, and pessary for preventing preterm birth in at-risk singleton pregnancies: an updated systematic review and network meta-analysis.

BACKGROUND: Recent progesterone trials call for an update of previous syntheses of interventions to prevent preterm birth. OBJECTIVES: To compare the relative effects of different types and routes of administration of progesterone, cerclage, and pessary at preventing preterm birth in at-risk women overall and in specific populations. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL, and Web of Science up to 1 January 2018. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing preterm birth in at-risk singleton pregnancies. DATA COLLECTION AND ANALYSIS: We used a piloted data extraction form and performed Bayesian random-effects network meta-analyses with 95% credibility intervals (CrI), as well as pairwise meta-analyses, rating the quality of the evidence using GRADE. MAIN RESULTS: We included 40 trials (11 311 women). In at-risk women overall, vaginal progesterone reduced preterm birth <34 (OR 0.43, 95% CrI 0.20-0.81) and <37 weeks (OR 0.51, 95% CrI 0.34-0.74), and neonatal death (OR 0.41, 95% CrI 0.20-0.83). In women with a previous preterm birth, vaginal progesterone reduced preterm birth <34 (OR 0.29, 95% CI 0.12-0.68) and <37 weeks (OR 0.43, 95% CrI 0.23-0.74), and 17α-hydroxyprogesterone caproate reduced preterm birth <37 weeks (OR 0.53, 95% CrI 0.27-0.95) and neonatal death (OR 0.39, 95% CI 0.16-0.95). In women with a short cervix (≤25 mm), vaginal progesterone reduced preterm birth <34 weeks (OR 0.45, 95% CI 0.24-0.84). CONCLUSIONS: Vaginal progesterone was the only intervention with consistent effectiveness for preventing preterm birth in singleton at-risk pregnancies overall and in those with a previous preterm birth. TWEETABLE ABSTRACT: In updated NMA, vaginal progesterone consistently reduced PTB in overall at-risk pregnancies and in women with previous PTB.

What is the safest mode of birth for extremely preterm breech singleton infants who are actively resuscitated? A systematic review and meta-analyses.

BACKGROUND: The safest delivery mode of extremely preterm breech singletons is unknown. OBJECTIVES: To determine safest delivery mode of actively resuscitated extremely preterm breech singletons. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov from January 1994 to May 2017. SELECTION CRITERIA: We included studies comparing outcomes by delivery mode in actively resuscitated breech infants between 23+0 and 27+6 weeks. DATA COLLECTION AND ANALYSIS: We synthesised data using random effects, generated odds ratios, 95% confidence intervals and number-needed-to-treat (NNT). Our primary outcomes were death (neonatal, before discharge, or by 6 months) and severe intraventricular haemorrhage (grades III/IV), stratified by gestational age (23+0 -24+6 , 25+0 -26+6 , 27+0 -27+6 weeks). MAIN RESULTS: We included 15 studies with 12 335 infants. We found that caesarean section was associated with a 41% decrease in odds of death between 23+0 and 27+6 weeks [odds ratio (OR) 0.59, 95% CI 0.36-0.95, NNT 8], with the greatest decrease at 23+0 -24+6 weeks (OR 0.58, 95% CI 0.44-0.75, NNT 7). The OR at 25+0 -26+6 and 27+0 -27+6 weeks were 0.72 (95% CI 0.34-1.52) and 2.04 (95% CI 0.20-20.62), respectively. We found that caesarean section was associated with 49% decrease in odds of severe intraventricular haemorrhage between 23+0 and 27+6 weeks (OR 0.51, 95% CI 0.29-0.91, NNT 12), whereas the OR at 25+0 -26+6 and 27+0 -27+6 was 0.29 (95% CI 0.07-1.12) and 0.91 (95% CI 0.27-3.05), respectively. CONCLUSIONS: Caesarean section was associated with reductions in the odds of death by 41% and of severe intraventricular haemorrhage by 49% in actively resuscitated breech singletons < 28 weeks of gestation. The data are mostly observational, which may be inherently biased, and scarce on other morbidities, necessitating thorough discussion between parents and clinicians. TWEETABLE ABSTRACT: Caesarean section associated with lower odds of death and severe intraventricular haemorrhage in actively resuscitated breech singletons <28 weeks.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.

What accounts for ethnic differences in newborn skinfold thickness comparing South Asians and White Caucasians? Findings from the START and FAMILY Birth Cohorts.

OBJECTIVE: South Asians are a high-risk group for type 2 diabetes and coronary heart disease. We sought to determine ethnic differences in newborn adiposity comparing South Asians (SA) to White Caucasians (Whites). METHODS: Seven hundred ninety pregnant women (401 SA, 389 Whites) and their full-term offspring from two birth cohorts in Canada were analyzed. Pregnant women completed a health assessment including a 75-g oral glucose tolerance test to assess for dysglycemia. Birthweight, length, waist and hip circumference, and triceps and subscapular skinfold thickness (a surrogate measure of body adiposity) were measured in all newborns. Multivariate regression was used to identify maternal factors associated with newborn skinfold measurements. RESULTS: South Asian women were younger (30.1 vs 31.8 years, P<0.001), their prepregnancy body mass index was lower (23.7 vs 26.2, P<0.0001) and gestational diabetes was substantially higher (21% vs 13%, P=0.005) compared with Whites. Among full-term newborns, South Asians had lower birthweight (3283 vs 3517 g, P=0.0001), had greater skinfold thickness (11.7 vs 10.6 mm; P=0.0001) and higher waist circumference (31.1 vs 29.9 cm, P=0.0001) compared with Whites. Risk factors for newborn skinfold thickness included South Asian ethnicity (standardized estimate (s.e.): 0.24; P<0.0001), maternal glucose (s.e.: 0.079; P=0.04) and maternal body fat (s.e.: 0.14; P=0.0002). CONCLUSIONS: South Asian newborns are lower birthweight and have greater skinfold thickness, compared with White newborns, and this is influenced by maternal body fat and glucose. Interventions aimed at reducing body fat prior to pregnancy and gestational diabetes during pregnancy in South Asians may favorably alter newborn body composition and require evaluation.

Does non-pharmacological therapy for antenatal depression reduce risks for the infant?

Depression during pregnancy has been associated with an increased risk of adverse outcomes for the infant such as preterm birth. These risks are not reduced with pharmacological treatment, but the effect of non-pharmacological therapies is unknown. We performed a systematic review to assess the risk of adverse perinatal outcomes in non-pharmacologically treated depressed women compared to non-depressed women. We found no studies that met our inclusion criteria, highlighting a critical need for research on this topic.

The combined effects of maternal depression and excess weight on neonatal outcomes.

OBJECTIVE: Maternal overweight/obesity and depression are among the most prevalent pregnancy complications, and although individually they are associated with poor pregnancy outcomes, their combined effects are unknown. Owing to this, the objective of this study was to determine the prevalences and the individual and combined effects of depression and overweight/obesity on neonatal outcomes. METHODS: A retrospective cohort study of all singleton hospital births at >20 weeks gestation in Ontario, Canada (April 2007 to March 2010) was conducted. The primary outcome measure was a composite neonatal outcome, which included: stillbirth, neonatal death, preterm birth, birth weight <2500 g, <5% or >95%, admission to a neonatal special care unit, or a 5-min Apgar score <7. RESULTS: Among the 70,605 included women, 49.7% had a healthy pre-pregnancy BMI, whereas 50.3% were overweight/obese; depression was reported in 5.0% and 6.2%, respectively. Individually, depression and excess pre-pregnancy weight were associated with an increased risk of adverse neonatal outcomes, but the highest risk was seen when they were both present (16% of non-depressed healthy weight pregnant women, 19% of depressed healthy weight women, 20% of non-depressed overweight/obese women and 24% of depressed overweight/obese women). These higher risks of adverse neonatal outcomes persisted after accounting for potential confounding variables, such as maternal age, education and pre-existing health problems (adjusted odds ratio (OR) 1.22, 95% confidence interval (CI) 1.13-1.33, adjusted OR 1.23, 95% CI 1.18-1.28 and adjusted OR 1.42, 95% CI 1.31-1.54, in the last three groups above, respectively, relative to non-depressed healthy weight women). There was no significant interaction between weight category and depression (P=0.2956). CONCLUSIONS: When dually present, maternal overweight/obesity and depression combined have the greatest impact on the risk of adverse neonatal outcomes. Our findings have important public health implications given the exorbitant proportions of both of these risk factors.

Pregnancy complications associated with the co-prevalence of excess maternal weight and depression.

OBJECTIVES: Obesity and depression have become prevalent pregnancy complications, individually associated with adverse perinatal health outcomes. Despite the co-prevalence of these two risk factors, their combined effects on maternal health are yet to be studied. The objective of this study was to examine the combined associations of overweight/obesity and depression with maternal and delivery complications. METHODS: A retrospective cohort study of women with singleton gestations at >20 weeks, in Ontario, Canada (April 2007 to March 2010), was conducted. Our primary outcomes were a composite of maternal complications (for example, gestational hypertension, pre-eclampsia, preterm premature rupture of membranes and so on), and a composite of delivery complications (for example, caesarean delivery, shoulder dystocia, postpartum haemorrhage and so on). RESULTS: The study population consisted of 70 605 women, of whom 50.3% were overweight/obese. Depression was reported in 5.0% of normal-weight women and 6.2% of overweight/obese women. The proportion of women with maternal complications was the highest among the overweight/obese depressed pregnant women (16% of normal-weight non-depressed, 22% of normal-weight depressed, 22% of overweight/obese non-depressed and 29% of overweight/obese depressed, P<0.001), as was the proportion of women with delivery complications (44%, 49%, 50% and 53%, respectively, P<0.001). Overweight/obese depressed pregnant women also experienced the highest odds of the composite of maternal complications and the composite of delivery complications (adjusted odds ratio (OR): 1.55, 95% confidence interval (CI): 1.35-1.77 and OR: 1.27, 95% CI: 1.13-1.42, respectively) after adjustment for potential confounders. CONCLUSIONS: The combined associations of excess weight and depression with adverse pregnancy outcomes are important to recognize in order to focus counselling and care, both before and during pregnancy.

Prevalence of mental health conditions after military blast exposure, their co-occurrence, and their relation to mild traumatic brain injury.

PRIMARY OBJECTIVES: To measure common psychiatric conditions after military deployment with blast exposure and test relationships to post-concussion syndrome (PCS) symptoms and mild traumatic brain injury (mTBI) history. RESEARCH DESIGN: Cross-sectional. METHODS AND PROCEDURES: Service members or Veterans (n = 107) within 2 years of blast exposure underwent structured interviews for mTBI, post-traumatic stress disorder (PTSD) and multiple mood and anxiety diagnoses. MAIN OUTCOMES AND RESULTS: MTBI history and active PTSD were both common, additionally 61% had at least one post-deployment mood or anxiety disorder episode. Psychiatric diagnoses had a high degree of comorbidity. Most dramatically, depression was 43-times (95% CI = 11-165) more likely if an individual had PTSD. PCS symptoms were greater in those with post-deployment PTSD or mood diagnosis. However, neither mTBI nor blast exposure history had an effect on the odds of having PTSD, mood or anxiety condition. CONCLUSIONS: These findings support that psychiatric conditions beyond PTSD are common after military combat deployment with blast exposure. They also highlight the non-specificity of post-concussion type symptoms. While some researchers have implicated mTBI history as a contributor to post-deployment mental health conditions, no clear association was found. This may partly be due to the more rigorous method of retrospective mTBI diagnosis determination.

Increased cardiovascular risk after pre-eclampsia in women with dysglycaemia.

AIMS: Compared with women with uncomplicated pregnancies, women with a history of pre-eclampsia have two to five times the risk of cardiovascular disease. It is not known whether this risk is related to albuminuria, a known cardiovascular risk factor that is part of the definition of pre-eclampsia and that often persists after delivery. Our objective was to determine if the high risk of cardiovascular disease in women with pre-eclampsia is accounted for by known cardiovascular risk factors including albuminuria. METHODS: We performed a cross-sectional analysis of 4080 dysglycaemic women enrolled in a large randomized controlled trial who provided an obstetric history and had at least one delivery. Blood pressure, height, weight, waist circumference and hip circumference were measured. An oral glucose tolerance test, lipids, an electrocardiogram and an albumin/creatinine ratio from a first morning urine sample were obtained. RESULTS: There were 3613 women with no history of pre-eclampsia during their pregnancies, 108 with severe pre-eclampsia and 359 with non-severe pre-eclampsia. Women with a history of severe pre-eclampsia had higher rates of previous cardiovascular disease than women with non-severe pre-eclampsia or women without pre-eclampsia (87, 72 and 72%, P = 0.0019). The high risk of previous cardiovascular disease in women with a history of severe pre-eclampsia (odds ratio 2.67, 95% CI 1.52-4.70) persisted after adjustment for albuminuria (odds ratio 2.74, 95% CI 1.55-4.83) and also after adjusting for other covariates including albuminuria (odds ratio 3.03, 95% CI 1.69-5.44). CONCLUSION: Even after accounting for cardiovascular risk factors including albuminuria, a history of severe pre-eclampsia is independently associated with a threefold higher risk of cardiovascular disease.

How often are late preterm births the result of non-evidence based practices: analysis from a retrospective cohort study at two tertiary referral centres in a nationalised healthcare system.

OBJECTIVE: To determine the proportion, characteristics, and predictors of late preterm birth (LPTB) in relation to evidence-based (EB) and non-evidence based (NEB) indications. DESIGN: Retrospective cohort study. SETTING: Two Canadian tertiary referral centres. POPULATION: All live singleton LPTBs over 1 year from 2010 to 2011, excluding major congenital anomalies. METHODS: Indications for LPTB were classified a priori as EB (i.e. based on practice guidelines or on evidence from randomised controlled trials) or NEB. Data were abstracted from maternal antenatal and labour records. Univariate analyses were completed using Fischer's exact, Pearson's chi-square, or analysis of variance (anova) F-tests. Logistic regression included gestation at birth, delivery provider, previous stillbirth, previous caesarean section, corticosteroid administration, and previous preterm birth as predictors for NEB LPTB. MAIN OUTCOME MEASURES: The proportion, characteristics, and predictors of women with NEB versus EB LPTBs. RESULTS: Of 524 LPTBs, 25.2% (n = 132) were NEB. Logistic regression revealed that NEB LPTBs were less likely if patients were delivered by their own doctor or their doctor's practice partner (OR 0.53, 95% CI 0.34-0.83). However, NEB LPTBs were more likely in women who had experienced a previous stillbirth (OR 2.57, 95% CI 1.20-5.49). CONCLUSIONS: Approximately one-quarter of LPTBs are NEB. Further research is needed to see if a review of the indications for LPTB, and subsequent reduction in NEB LPTBs, translates into improved neonatal outcomes and cost savings.

Women's intentions to breastfeed: a population-based cohort study.

OBJECTIVE: Given that intention to breastfeed is a strong predictor of breastfeeding initiation and duration, the objectives of this study were to estimate the population-based prevalence and the factors associated with the intention to breastfeed. DESIGN: Retrospective population-based cohort study. SETTING: All hospitals in Ontario, Canada (1 April 2009-31 March 2010). POPULATION: Women who gave birth to live, term, singletons/twins. METHODS: Patient, healthcare provider, and hospital factors that may be associated with intention to breastfeed were analysed using univariable and multivariable regression. MAIN OUTCOME MEASURES: Population-based prevalence of intention to breastfeed and its associated factors. RESULTS: The study included 92,364 women, of whom 78,806 (85.3%) intended to breastfeed. The odds of intending to breastfeed were higher amongst older women with no health problems and women who were cared for exclusively by midwives (adjusted OR 3.64, 95% CI 3.13-4.23). Being pregnant with twins (adjusted OR 0.73, 95% CI 0.57-0.94), not attending antenatal classes (adjusted OR 0.58, 95% CI 0.54-0.62), having previous term or preterm births (adjusted OR 0.79, 95% CI 0.78-0.81, and adjusted OR 0.87, 95% CI 0.82-0.93, respectively), and delivering in a level-1 hospital (adjusted OR 0.85, 95% CI 0.77-0.93) were associated with a lower intention to breastfeed. CONCLUSIONS: In this population-based study ~85% of women intended to breastfeed their babies. Key factors that are associated with the intention to breastfeed were identified, which can now be targeted for intervention programmes aimed at increasing the prevalence of breastfeeding and improving overall child and maternal health.

The recurrence risk of severe de novo pre-eclampsia in singleton pregnancies: a population-based cohort.

OBJECTIVE: Previous studies have found recurrence risks of severe pre-eclampsia as high as 40%. Our objective was to determine both the recurrence risk of severe de novo pre-eclampsia and risk factors associated with it in a contemporaneous population. STUDY DESIGN: Population-based retrospective cohort study. POPULATION: Women who had two or more singleton liveborn or stillborn hospital deliveries in Ontario, Canada between April 1994 and March 2002 and without a history of chronic hypertension. METHODS: International Classification of Disease codes were used to identify patients in the Canadian Institute for Health Information Discharge Abstract Database. MAIN OUTCOME MEASURES: The absolute and adjusted risks of recurrent severe de novo pre-eclampsia were determined. RESULTS: Between 1 April 1994 and 30 March 2002, there were 185 098 women with two or more singleton deliveries >20 weeks in the province of Ontario, Canada. There were 1954 women who had severe de novo pre-eclampsia in the index pregnancy, 133 of whom had recurrent severe pre-eclampsia, for a risk of recurrent severe pre-eclampsia of 6.8% (95% CI 5.7-7.9%). The risk of recurrent severe de novo pre-eclampsia was increased in women with pre-existing renal disease (adjusted OR 17.98, 95% CI 3.50-92.52) and those >35 years of age (adjusted OR 3.79, 95% CI 2.04-7.04, reference 20-25 years). CONCLUSIONS: The recurrence risk of severe de novo pre-eclampsia in our population-based cohort study (6.8%) is lower than previously published reports in selected populations.

Parental and child genetic contributions to obesity traits in early life based on 83 loci validated in adults: the FAMILY study.

BACKGROUND: The genetic influence on child obesity has not been fully elucidated. OBJECTIVE: This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5 years old. METHODS: A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5 years of age, and age-specific and sex-specific weight and BMI Z-scores were computed. RESULTS: The GRS was significantly associated with birthweight Z-score (P = 0.03). It was also associated with weight/BMI Z-score gain between birth and 5 years old (P = 0.02 and 6.77 × 10-3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5 years (P = 5.91 × 10-3 and 5.08 × 10-3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5 years were significantly greater compared with the paternal effects by Z test (P = 1.53 × 10-6 and 3.75 × 10-5 , respectively). CONCLUSIONS: SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs.

In situ imaging of microstructure formation in electronic interconnections.

The development of microstructure during melting, reactive wetting and solidification of solder pastes on Cu-plated printed circuit boards has been studied by synchrotron radiography. Using Sn-3.0Ag-0.5Cu/Cu and Sn-0.7Cu/Cu as examples, we show that the interfacial Cu6Sn5 layer is present within 0.05 s of wetting, and explore the kinetics of flux void formation at the interface between the liquid and the Cu6Sn5 layer. Quantification of the nucleation locations and anisotropic growth kinetics of primary Cu6Sn5 crystals reveals a competition between the nucleation of Cu6Sn5 in the liquid versus growth of Cu6Sn5 from the existing Cu6Sn5 layer. Direct imaging confirms that the ß-Sn nucleates at/near the Cu6Sn5 layer in Sn-3.0Ag-0.5Cu/Cu joints.

The effects of morbid obesity on maternal and neonatal health outcomes: a systematic review and meta-analyses.

Morbidly obese (Class III, body mass index [BMI] ≥ 40 kg m(-2)) women constitute 8% of reproductive-aged women and are an increasing proportion; however, their pregnancy risks have not yet been well understood. Hence, we performed meta-analyses following the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guideline, searching Medline and Embase from their inceptions. To examine graded relationships, we compared Class III obesity to Class I and I/II, and separately to normal weight. We found important effects on all three primary outcomes in morbidly obese women: preterm birth <37 weeks was 31% higher compared with Class I (relative risk [RR] 1.31 [1.19, 1.43]) and 20% higher than Class I/II (RR 1.20 [1.13, 1.27]), large-for-gestational age was higher (RR 1.37 [1.29, 1.45] and RR 1.30 [1.24, 1.36] compared with Class I and I/II, respectively), while small-for-gestational age was lower (RR 0.89 [0.84, 0.93] compared with Class I, with nearly identical reductions for Class I/II). Morbidly obese women have higher risks of preterm birth, large-for-gestational age and numerous other adverse maternal and infant health outcomes, relative to not only normal weight but also Class I or I/II obese women. These findings have important implications for screening and care of morbidly obese pregnant women, to try to decrease adverse outcomes.

Can we safely recommend gestational weight gain below the 2009 guidelines in obese women? A systematic review and meta-analysis.

A systematic review was conducted to determine the risk of adverse pregnancy outcomes with gestational weight gain (GWG) below the 2009 Institute of Medicine guidelines compared with within the guidelines in obese women. MEDLINE, Embase, Cochrane Register, CINHAL and Web of Science were searched from 1 January 2009 to 31 July 2014. Quality was assessed using a modified Newcastle-Ottawa scale. Three primary outcomes were included: preterm birth, small for gestational age (SGA) and large for gestational age (LGA). Eighteen cohort studies were included. GWG below the guidelines had higher odds of preterm birth (adjusted odds ratio [AOR] 1.46; 95% confidence interval [CI] 1.07-2.00) and SGA (AOR 1.24; 95% CI 1.13-1.36) and lower odds of LGA (AOR 0.77; 95% CI 0.73-0.81) than GWG within the guidelines. Across the three obesity classes, the odds of SGA and LGA did not show any notable gradient and remained unexplored for preterm birth. Decreased odds were noted for macrosomia (AOR 0.64; 95% CI 0.54-0.77), gestational hypertension (AOR, 0.70; 95% CI 0.53-0.93), pre-eclampsia (AOR 0.90; 95% CI 0.82-0.99) and caesarean (AOR 0.87; 95% CI 0.82-0.92). GWG below the guidelines cannot be routinely recommended but might occasionally be individualized for certain women, with caution, taking into account other known risk factors.

Melatonin concentration in human blood and cerebrospinal fluid: relationship to stress.

In 35 daytime paired blood and cerebrospinal fluid (CSF) samples from 15 patients, melatonin levels in CSF were undetectable or detectable but not higher than blood levels. During pneumoencephalography in 6 patients, no significant elevation of blood melatonin levels was observed, whereas cortisol concentration increased.