There is limited evidence to support the use of customised centile charts to identify those at risk of stillbirth and infant death at term. We sought to determine birth weight thresholds at which ...mortality and morbidity increased and the predictive ability of noncustomised (accounting for gestational age and sex) and partially customised centiles (additionally accounting for maternal height and parity) to identify fetuses at risk.
This is a population-based linkage study of 979,912 term singleton pregnancies in Scotland, United Kingdom, between 1992 and 2010. The main exposures were noncustomised and partially customised birth weight centiles. The primary outcomes were infant death, stillbirth, overall mortality (infant and stillbirth), Apgar score <7 at 5 min, and admission to the neonatal unit. Optimal thresholds that predicted outcomes for both non- and partially customised birth weight centiles were calculated. Prediction of mortality between non- and partially customised birth weight centiles was compared using area under the receiver operator characteristic curve (AUROC) and net reclassification index (NRI).
Birth weight ≤25th centile was associated with higher risk for all mortality and morbidity outcomes. For stillbirth, low Apgar score, and neonatal unit admission, risk also increased from the 85th centile. Similar patterns and magnitude of associations were observed for both non- and partially customised birth weight centiles. Partially customised birth weight centiles did not improve the discrimination of mortality (AUROC 0.61 95%CI 0.60, 0.62) compared with noncustomised birth weight centiles (AUROC 0.62 95%CI 0.60, 0.63) and slightly underperformed in reclassifying pregnancies to different risk categories for both fatal and non-fatal adverse outcomes (NRI -0.027 95% CI -0.039, -0.016, p < 0.001). We were unable to fully customise centile charts because we lacked data on maternal weight and ethnicity. Additional analyses in an independent UK cohort (n = 10,515) suggested that lack of data on ethnicity in this population (in which national statistics show 98% are white British) and maternal weight would have misclassified ~15% of the large-for-gestation fetuses.
At term, birth weight remains strongly associated with the risk of stillbirth and infant death and neonatal morbidity. Partial customisation does not improve prediction performance. Consideration of early term delivery or closer surveillance for those with a predicted birth weight ≤25th or ≥85th centile may reduce adverse outcomes. Replication of the analysis with fully customised centiles accounting for ethnicity is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate ...between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. Methods The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. Findings Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15–24; 69 of 352 fetuses) for selective ultrasonography and 57% (51–62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2·9, 95% CI 2·4–3·5, p<0·0001). Of the 3977 fetuses, 562 (14·1%) were identified by universal ultrasonography with an estimated fetal weight of less than the 10th percentile and were at an increased risk of neonatal morbidity (relative risk RR 1·60, 95% CI 1·22–2·09, p=0·0012). However, estimated fetal weight of less than the 10th percentile was only associated with the risk of neonatal morbidity (pinteraction =0·005) if the fetal abdominal circumference growth velocity was in the lowest decile (RR 3·9, 95% CI 1·9–8·1, p=0·0001). 172 (4%) of 3977 pregnancies had both an estimated fetal weight of less than the 10th percentile and abdominal circumference growth velocity in the lowest decile, and had a relative risk of delivering an SGA infant with neonatal morbidity of 17·6 (9·2–34·0, p<0·0001). Interpretation Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of SGA infants. Combined analysis of fetal biometry and fetal growth velocity identified a subset of SGA fetuses that were at increased risk of neonatal morbidity. Funding National Institute for Health Research, Medical Research Council, Sands, and GE Healthcare.
Interaction between maternal obesity, intrauterine environment and adverse clinical outcomes of newborns has been described.
Using statewide birth certificate data, this retrospective, ...matched-control cohort study compared paired birth weights and complications of infants born to women before and after Roux-en-Y gastric bypass surgery (RYGB) and to matched obese non-operated women in several different groups. Women who had given birth to a child before and after RYGB (group 1; n=295 matches) and women with pregnancies after RYGB (group 2; n=764 matches) were matched to non-operated women based on age, body mass index (BMI) prior to both pregnancy and RYGB, mother's race, year of mother/s birth, date of infant births and birth order. In addition, birth weights of 13 143 live births before and/or after RYGB of their mothers (n=5819) were compared (group 3).
Odds ratios (ORs) for having a large-for-gestational-age (LGA) neonate were significantly less after RYGB than for non-surgical mothers: ORs for groups 1 and 2 were 0.19 (0.08-0.38) and 0.33 (0.21-0.51), respectively. In contrast, ORs in all three groups for risk of having a small for gestational age (SGA) neonate were greater for RYGB mothers compared to non-surgical mothers (ORs were 2.16 (1.00-5.04); 2.16 (1.43-3.32); and 2.25 (1.89-2.69), respectively). Neonatal complications were not different for group 1 RYGB and non-surgical women for the first pregnancy following RYGB. Pregnancy-induced hypertension and gestational diabetes were significantly lower for the first pregnancy of mothers following RYGB compared to matched pregnancies of non-surgical mothers.
Women who had undergone RYGB not only had lower risk for having an LGA neonate compared to BMI-matched mothers, but also had significantly higher risk for delivering an SGA neonate following RYGB. RYGB women were less likely than non-operated women to have pregnancy-related hypertension and diabetes.
The C statistic is a commonly reported measure of screening test performance. Optimistic estimation of the C statistic is a frequent problem because of overfitting of statistical models in small data ...sets, and methods exist to correct for this issue. However, many studies do not use such methods, and those that do correct for optimism use diverse methods, some of which are known to be biased. We used clinical data sets (United Kingdom Down syndrome screening data from Glasgow (1991-2003), Edinburgh (1999-2003), and Cambridge (1990-2006), as well as Scottish national pregnancy discharge data (2004-2007)) to evaluate different approaches to adjustment for optimism. We found that sample splitting, cross-validation without replication, and leave-1-out cross-validation produced optimism-adjusted estimates of the C statistic that were biased and/or associated with greater absolute error than other available methods. Cross-validation with replication, bootstrapping, and a new method (leave-pair-out cross-validation) all generated unbiased optimism-adjusted estimates of the C statistic and had similar absolute errors in the clinical data set. Larger simulation studies confirmed that all 3 methods performed similarly with 10 or more events per variable, or when the C statistic was 0.9 or greater. However, with lower events per variable or lower C statistics, bootstrapping tended to be optimistic but with lower absolute and mean squared errors than both methods of cross-validation.
The land and ocean absorb on average just over half of the anthropogenic emissions of carbon dioxide (CO2) every year. These CO2 "sinks" are modulated by climate change and variability. Here we use a ...suite of nine dynamic global vegetation models (DGVMs) and four ocean biogeochemical general circulation models (OBGCMs) to estimate trends driven by global and regional climate and atmospheric CO2 in land and oceanic CO2 exchanges with the atmosphere over the period 1990–2009, to attribute these trends to underlying processes in the models, and to quantify the uncertainty and level of inter-model agreement. The models were forced with reconstructed climate fields and observed global atmospheric CO2; land use and land cover changes are not included for the DGVMs. Over the period 1990–2009, the DGVMs simulate a mean global land carbon sink of −2.4 ± 0.7 Pg C yr−1 with a small significant trend of −0.06 ± 0.03 Pg C yr−2 (increasing sink). Over the more limited period 1990–2004, the ocean models simulate a mean ocean sink of −2.2 ± 0.2 Pg C yr−1 with a trend in the net C uptake that is indistinguishable from zero (−0.01 ± 0.02 Pg C yr−2). The two ocean models that extended the simulations until 2009 suggest a slightly stronger, but still small, trend of −0.02 ± 0.01 Pg C yr−2. Trends from land and ocean models compare favourably to the land greenness trends from remote sensing, atmospheric inversion results, and the residual land sink required to close the global carbon budget. Trends in the land sink are driven by increasing net primary production (NPP), whose statistically significant trend of 0.22 ± 0.08 Pg C yr−2 exceeds a significant trend in heterotrophic respiration of 0.16 ± 0.05 Pg C yr−2 – primarily as a consequence of widespread CO2 fertilisation of plant production. Most of the land-based trend in simulated net carbon uptake originates from natural ecosystems in the tropics (−0.04 ± 0.01 Pg C yr−2), with almost no trend over the northern land region, where recent warming and reduced rainfall offsets the positive impact of elevated atmospheric CO2 and changes in growing season length on carbon storage. The small uptake trend in the ocean models emerges because climate variability and change, and in particular increasing sea surface temperatures, tend to counter\\-act the trend in ocean uptake driven by the increase in atmospheric CO2. Large uncertainty remains in the magnitude and sign of modelled carbon trends in several regions, as well as regarding the influence of land use and land cover changes on regional trends.
Stillbirth Smith, Gordon CS, Prof; Fretts, Ruth C, MD
Lancet,
11/2007, Letnik:
370, Številka:
9600
Journal Article, Book Review
Recenzirano
Summary In the UK, about one in 200 infants is stillborn, and rates of stillbirth have recently slightly increased. This recent rise might reflect increasing frequency of some important maternal risk ...factors for stillbirth, including nulliparity, advanced age, and obesity. Most stillbirths are related to placental dysfunction, which in many women is evident from the first half of pregnancy and is associated with fetal growth restriction. There is no effective screening test that has clearly shown a reduction in stillbirth rates in the general population. However, assessments of novel screening methods have generally failed to distinguish between effective identification of high-risk women and successful intervention for such women. Future research into stillbirth will probably focus on understanding the pathophysiology of impaired placentation to establish screening tests for stillbirth, and assessment of interventions to prevent stillbirth in women who screen positive.
Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of ...neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-reviewed journals reported greater effects than did unpublished studies ( r2 9·3%, p=0·009). Trial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, final quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest efficacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profiling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.
Summary Background The Apgar score has been used worldwide as an index of early neonatal condition for more than 60 years. With advances in health-care service provision, neonatal resuscitation, and ...infant care, its present relevance is unclear. The aim of the study was to establish the strength of the relation between Apgar score at 5 min and the risk of neonatal and infant mortality, subdivided by specific causes. Methods We linked routine discharge and mortality data for all births in Scotland, UK between 1992 and 2010. We restricted our analyses to singleton livebirths, in women aged over 10 years, with a gestational age at delivery between 22 and 44 weeks, and excluded deaths due to congenital anomalies or isoimmunisation. We calculated the relative risks (RRs) of neonatal and infant death of neonates with low (0–3) and intermediate (4–6) Apgar scores at 5 min referent to neonates with normal Apgar score (7–10) using binomial log-linear modelling with adjustment for confounders. Analyses were stratified by gestational age at birth because it was a significant effect modifier. Missing covariate data were imputed. Findings Complete data were available for 1 029 207 eligible livebirths. Across all gestational strata, low Apgar score at 5 min was associated with an increased risk of neonatal and infant death. However, the strength of the association (adjusted RR, 95% CI referent to Apgar 7–10) was strongest at term (p<0·0001). A low Apgar (0–3) was associated with an adjusted RR of 359·4 (95% CI 277·3–465·9) for early neonatal death, 30·5 (18·0–51·6) for late neonatal death, and 50·2 (42·8–59·0) for infant death. We noted similar associations of a lower magnitude for intermediate Apgar (4–6). The strongest associations were for deaths attributed to anoxia and low Apgar (0–3) for term infants (RR 961·7, 95% CI 681·3–1357·5) and preterm infants (141·7, 90·1–222·8). No association between Apgar score at 5 min and the risk of sudden infant death syndrome was noted at any gestational age (RR 0·6, 95% CI 0·1–4·6 at term; 1·2, 0·3–4·8 at preterm). Interpretation Low Apgar score at 5 min was strongly associated with the risk of neonatal and infant death. Our findings support its continued usefulness in contemporary practice. Funding None.
To determine whether fetal overgrowth precedes the diagnosis of gestational diabetes mellitus (GDM) and to quantify the interrelationships among fetal overgrowth, GDM, and maternal obesity.
We ...conducted a prospective cohort study of unselected nulliparous women and performed ultrasonic measurement of the fetal abdominal circumference (AC) and head circumference (HC) at 20 and 28 weeks of gestational age (wkGA). Exposures were diagnosis of GDM ≥28 wkGA and maternal obesity. The risk of AC >90th and HC-to-AC ratio <10th percentile was modeled using log-binomial regression, adjusted for maternal characteristics.
Of 4,069 women, 171 (4.2%) were diagnosed with GDM at ≥28 wkGA. There was no association between fetal biometry at 20 wkGA and subsequent maternal diagnosis of GDM. However, at 28 wkGA, there was an increased risk of AC >90th percentile (adjusted relative risk 2.05 95% CI 1.37-3.07) and HC-to-AC ratio <10th percentile (1.97 1.30-2.99). Maternal obesity showed similar associations at 28 wkGA (2.04 1.62-2.56 and 1.46 1.12-1.90, respectively). The combination of GDM and obesity was associated with an approximately fivefold risk of AC >90th (4.52 2.98-6.85) and approximately threefold risk of HC-to-AC ratio <10th percentile (2.80 1.64-4.78) at 28 wkGA. Fetal AC >90th percentile at 28 weeks was associated with an approximately fourfold risk of being large for gestational age at birth.
Diagnosis of GDM is preceded by excessive growth of the fetal AC between 20 and 28 wkGA, and its effects on fetal growth are additive with the effects of maternal obesity.
Summary Background Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess ...safety of such an approach in patients with left ventricular dysfunction after myocardial infarction. Methods In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2–4 weeks after myocardial infarction (with left ventricular ejection fraction of 25–45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5–3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov , NCT00893360. Findings Between May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. Interpretation We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. Funding US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.
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