Identifying Newborns with Hypoxic-Ischemic Encephalopathy in Hospital Discharge Data: A Validation Study.

Hospital discharge databases (HDDs) are increasingly used for research on health of newborns. Linkage between a French population-based cohort of newborns with hypoxic-ischemic encephalopathy (HIE) and national HDD showed that the HIE ICD-10 code was not accurately reported. Our results suggest that HDD should not be used for research on neonatal HIE without prior validation of HIE ICD-10 codes.

[Review of the literature on intrauterine and birthweight charts]. / Revue de la littérature des courbes intra-utérines et de poids de naissance.

OBJECTIVES: To describe the main intrauterine and birthweight charts and review the studies comparing their performance for the identification of infants at risk of adverse perinatal outcomes. METHODS: We carried out a literature search using Medline and selected the charts most frequently cited in the literature, French charts and those recently published. RESULTS: Current knowledge on the association between mortality and morbidity and growth anomalies (small and large for gestational age) mostly relies on the use of descriptive charts which describe the weight distribution in unselected populations. Prescriptive charts, which describe ideal growth in low risk populations, have been constructed more recently. Few studies have evaluated whether the thresholds used to identify infants at risk with descriptive charts (such as the 3rd or the 10th percentile) are applicable to prescriptive charts. There is a large variability in the percentage of fetuses or newborns identified as being at risk by each chart, with from 3 to 25% having with a weight under the 10th percentile, regardless of whether descriptive or prescriptive charts are used. The sensitivity and specificity of antenatal screening for small or large for gestational age newborns depends on the chart used to derive estimated fetal weight percentiles. CONCLUSION: There is marked variability between intrauterine growth charts that can influence the percentage of infants identified as having abnormal growth. These results show that before the adoption of a growth chart, it is essential to evaluate whether it adequately describes the population and its performance for identifying of infants at risk because of growth anomalies.

[Ante- and postnatal growth charts in France - guidelines for clinical practice from the Collège national des gynécologues et obstétriciens français (CNGOF) and from the Société française de néonatologie (SFN)]. / Les courbes de croissance anté- et postnatales en France ­ recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF) et de la Société française de néonatologie (SFN).

OBJECTIVE: To recommend the most appropriate biometric charts for the detection of antenatal growth abnormalities and postnatal growth surveillance. METHODS: Elaboration of specific questions and selection of experts by the organizing committee to answer these questions; analysis of the literature by experts and drafting conclusions by assigning a recommendation (strong or weak) and a quality of evidence (high, moderate, low, very low) and for each question; all these recommendations have been subject to multidisciplinary external review (obstetrician gynecologists, pediatricians). The objective for the reviewers was to verify the completeness of the literature review, to verify the levels of evidence established and the consistency and applicability of the resulting recommendations. The overall review of the literature, quality of evidence and recommendations were revised to take into consideration comments from external reviewers. RESULTS: Antenatally, it is recommended to use all WHO fetal growth charts for EFW and common ultrasound biometric measurements (strong recommendation; low quality of evidence). Indeed, in comparison with other prescriptive curves and descriptive curves, the WHO prescriptive charts show better performance for the screening of SGA (Small for Gestational Age) and LGA (Large for Gestational Age) with adequate proportions of fetuses screened at extreme percentiles in the French population. It also has the advantages of having EFW charts by sex and biometric parameters obtained from the same perspective cohort of women screened by qualified sonographers who measured the biometric parameters according to international standards. Postnatally, it is recommended to use the updated Fenton charts for the assessment of birth measurements and for growth monitoring in preterm infants (strong recommendation; moderate quality of evidence) and for the assessment of birth measurements in term newborn (expert opinion). CONCLUSION: It is recommended to use WHO fetal growth charts for antenatal growth monitoring and Fenton charts for the newborn.

Comparison of the performance of estimated fetal weight charts for the detection of small- and large-for-gestational age newborns with adverse outcomes: a French population-based study.

OBJECTIVE: To compare the performance of estimated fetal weight (EFW) charts at the third trimester ultrasound for detecting small- and large-for-gestational age (SGA/LGA) newborns with adverse outcomes. DESIGN: Nationally representative observational study. SETTING: French maternity units in 2016. POPULATION: 9940 singleton live births with an ultrasound between 30 and 35 weeks of gestation. METHODS: We compared three prescriptive charts (INTERGROWTH-21st, World Health Organization (WHO), Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD]), four descriptive charts (Hadlock, Fetal Medicine Foundation, two French charts) and a French customised growth model (Epopé). MAIN OUTCOME MEASURES: SGA and LGA (birthweights <10th and >90th percentiles) associated with adverse outcomes (low Apgar score, delivery-room resuscitation, neonatal unit admission). RESULTS: 2.1% and 1.1% of infants had SGA and LGA and adverse outcomes, respectively. The sensitivity and specificity for detecting these infants with an EFW <10th and >90th percentile varied from 29-65% and 84-96% for descriptive charts versus 27-60% and 83-96% for prescriptive charts. WHO and French charts were closest to the EFW distribution, yielding a balance between sensitivity and specificity for SGA and LGA births. INTERGROWTH-21st and Epopé had low sensitivity for SGA with high sensitivity for LGA. Areas under the receiving operator characteristics curve ranged from 0.62 to 0.74, showing low to moderate predictive ability, and diagnostic odds ratios varied from 7 to 16. CONCLUSION: Marked differences in the performance of descriptive as well as prescriptive EFW charts highlight the importance of evaluating them for their ability to detect high-risk fetuses. TWEETABLE ABSTRACT: Choice of growth chart strongly affected identification of high-risk fetuses at the third trimester ultrasound.

Immune cell profiling in the joint following human and murine articular fracture.

OBJECTIVE: Human and in vivo animal research implicates inflammation following articular fracture as contributing to post-traumatic arthritis. However, relevant immune cell subsets present following injury are currently undefined. Immunophenotyping human and murine synovial fluid may help to identify immune cell populations that play key roles in the response to articular fracture. METHODS: Immunophenotyping by polychromatic flow cytometry was performed on human and mouse synovial fluid following articular fracture. Specimens were collected in patients with closed ankle fracture at the time of surgical fixation and from C57BL/6 mice with closed articular knee fracture. Immune cells were collected from injured and uninjured joints in mice via a novel cell isolation method. Whole blood samples were also collected. Immunohistochemistry (IHC) was performed on mouse synovial tissue to assess for macrophages and T cells. RESULTS: Following intra-articular fracture, the prominent human synovial fluid immune cell subset was CD3+ T cells, containing both CD4+ and CD8+ T cells. In mice, infiltration of CD45+ immune cells in synovial fluid of the fractured limb was dominated by CD19+ B cells and CD3+ T cells at 7 days after intra-articular fracture. We also detected adaptive immune cells, including macrophages, NK cells, dendritic cells and monocytes. Macrophage and T cell findings were supported by IHC of murine synovial tissue. CONCLUSIONS: Determining specific cell populations that mediate the immune response is essential to elucidating the chain of events initiated after injury and may be an important step in identifying potential immune signatures predictive of PTA susceptibility or potential therapeutic targets.

Using Robson's Ten-Group Classification System for comparing caesarean section rates in Europe: an analysis of routine data from the Euro-Peristat study.

OBJECTIVE: Robson's Ten Group Classification System (TGCS) creates clinically relevant sub-groups for monitoring caesarean birth rates. This study assesses whether this classification can be derived from routine data in Europe and uses it to analyse national caesarean rates. DESIGN: Observational study using routine data. SETTING: Twenty-seven EU member states plus Iceland, Norway, Switzerland and the UK. POPULATION: All births at ≥22 weeks of gestational age in 2015. METHODS: National statistical offices and medical birth registers derived numbers of caesarean births in TGCS groups. MAIN OUTCOME MEASURES: Overall caesarean rate, prevalence and caesarean rates in each of the TGCS groups. RESULTS: Of 31 countries, 18 were able to provide data on the TGCS groups, with UK data available only from Northern Ireland. Caesarean birth rates ranged from 16.1 to 56.9%. Countries providing TGCS data had lower caesarean rates than countries without data (25.8% versus 32.9%, P = 0.04). Countries with higher caesarean rates tended to have higher rates in all TGCS groups. Substantial heterogeneity was observed, however, especially for groups 5 (previous caesarean section), 6, 7 (nulliparous/multiparous breech) and 10 (singleton cephalic preterm). The differences in percentages of abnormal lies, group 9, illustrate potential misclassification arising from unstandardised definitions. CONCLUSIONS: Although further validation of data quality is needed, using TGCS in Europe provides valuable comparator and baseline data for benchmarking and surveillance. Higher caesarean rates in countries unable to construct the TGCS suggest that effective routine information systems may be an indicator of a country's investment in implementing evidence-based caesarean policies. TWEETABLE ABSTRACT: Many European countries can provide Robson's Ten-Group Classification to improve caesarean rate comparisons.

Neurodevelopment at 2 years and umbilical artery Doppler in cases of very preterm birth after prenatal hypertensive disorder or suspected fetal growth restriction: EPIPAGE-2 prospective population-based cohort study.

OBJECTIVE: To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders. METHODS: The study population comprised all very preterm (22-31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods. RESULTS: The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4-93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8-1.9). CONCLUSION: Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee.

OBJECTIVE: Acute synovial inflammation following joint trauma is associated with posttraumatic arthritis. Synovial macrophages have been implicated in degenerative changes. In this study, we sought to elucidate the role of intra-articular macrophages in the acute inflammatory response to fracture in the mouse knee. METHOD: A closed articular fracture was induced in two models of synovial macrophage depletion: genetically-modified MaFIA mice administered AP20187 to induce programmed macrophage apoptosis, and wild-type C57BL/6 mice administered clodronate liposomes, both via intra-articular injection. Synovial inflammation, bone morphology, and levels of F4/80+ macrophages, NOS2+ M1 macrophages, and CD206+ M2 macrophages were quantified 7 days after fracture using histology and micro-computed tomography. RESULTS: Intra-articular macrophage depletion with joint injury did not reduce acute synovitis or the number of synovial macrophages 7 days after fracture in either macrophage-depleted MaFIA mice or in clodronate-treated C57BL/6 mice. In macrophage-depleted MaFIA mice, macrophage polarity shifted to a dominance of M1 macrophages and a reduction of M2 macrophages in the synovial stroma, indicating a shift in M1/M2 macrophage ratio in the joint following injury. Interestingly, MaFIA mice depleted 2 days prior to fracture demonstrated increased synovitis (P = 0.003), reduced bone mineral density (P = 0.0004), higher levels of M1 macrophages (P = 0.013), and lower levels of M2 macrophages (not statistically significant, P=0.084) compared to control-treated MaFIA mice. CONCLUSION: Our findings indicate that macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury and suggest that inhibition of macrophage function can have prominent effects on joint inflammation and bone homeostasis after joint trauma.

Antenatal detection of fetal growth restriction and risk of stillbirth: population-based case-control study.

OBJECTIVES: Antenatal surveillance of intrauterine growth aims to detect growth-restricted fetuses (FGR), which face increased risk of stillbirth. Improving their detection could be an effective strategy for prevention of stillbirth. The French REPERE study was conducted to estimate the association between antenatal detection of FGR and risk of stillbirth. METHODS: REPERE is a case-control study performed in three French districts with a combined total of approximately 30 000 births annually. Cases were singleton small-for-gestational-age (SGA) stillbirths ≥ 24 weeks' gestation and without severe congenital anomaly, between 2012 and 2014, identified using a population-based stillbirth registry; controls were live births fulfilling the same inclusion criteria over a 9-week period from 7 April to 8 June 2014. Data were extracted by trained investigators from medical records and ultrasound reports. SGA was defined as birth weight < 10th percentile of French customized standards. FGR was defined by the presence of at least one of seven predefined parameters (suspected FGR mentioned in medical records or in ultrasound report, suspected faltering growth mentioned in an ultrasound report, documented abdominal circumference or estimated fetal weight < 10th percentile, referral for additional ultrasound examination to monitor growth or abnormal umbilical artery Doppler). We used logistic regression to estimate crude and adjusted odds ratios (ORs) for the association between detection of FGR and risk of stillbirth. Included covariables were parity, maternal medical history, vascular complications during pregnancy and birth-weight percentile, which are known to be associated with risk of detection of FGR and of stillbirth. RESULTS: During the study period, there were 92 182 births ≥ 22 weeks' gestation, including 669 stillbirths, of which 79 were singleton SGA stillbirths ≥ 24 weeks and without severe congenital anomaly. Of these cases, 44.3% (35/79) had FGR detected, compared with a detection rate of 36.2% in controls (154/426). The crude OR expressing the association between detection of FGR and risk of stillbirth was 1.4 (95% CI, 0.9-2.3) and the OR adjusted for parity, presence of risk factors for FGR, presence of vascular disorder and birth-weight percentile was 0.6 (95% CI, 0.3-1.0). Among deliveries ≥ 28 weeks, detection rates were 38.3% vs 36.0% for cases and controls, with an adjusted OR of 0.5 (95% CI, 0.2-1.0). CONCLUSION: Antenatal detection of FGR was protective against stillbirth, but over 40% of stillbirths among SGA fetuses occurred despite detection of FGR, pointing to the need to improve management following detection. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Essential variables for reporting research studies on fetal growth restriction: a Delphi consensus.

OBJECTIVE: To determine, by expert consensus using a Delphi procedure, a minimum reporting set of study variables for fetal growth restriction (FGR) research studies. METHODS: A panel of experts, identified based on their publication record as lead or senior author of studies on FGR, was asked to select a set of essential reporting study parameters from a literature-based list of variables, utilizing the Delphi consensus methodology. Responses were collected in four consecutive rounds by online questionnaires presented to the panelists through a unique token-secured link for each round. The experts were asked to rate the importance of each parameter on a five-point Likert scale. Variables were selected in the three first rounds based on a 70% threshold for agreement on the Likert-scale scoring. In the final round, retained parameters were categorized as essential (to be reported in all FGR studies) or recommended (important but not mandatory). RESULTS: Of the 100 invited experts, 87 agreed to participate and of these 62 (71%) completed all four rounds. Agreement was reached for 16 essential and 30 recommended parameters including maternal characteristics, prenatal investigations, prenatal management and pregnancy/neonatal outcomes. Essential parameters included hypertensive complication in the current pregnancy, smoking, parity, maternal age, fetal abdominal circumference, estimated fetal weight, umbilical artery Doppler (pulsatility index and end-diastolic flow), fetal middle cerebral artery Doppler, indications for intervention, pregnancy outcome (live birth, stillbirth or neonatal death), gestational age at delivery, birth weight, birth-weight centile, mode of delivery and 5-min Apgar score. CONCLUSIONS: We present a list of essential and recommended parameters that characterize FGR independent of study hypotheses. Uniform reporting of these variables in prospective clinical research is expected to improve data quality, study consistency and ultimately our understanding of FGR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

How do late terminations of pregnancy affect comparisons of stillbirth rates in Europe? Analyses of aggregated routine data from the Euro-Peristat Project.

OBJECTIVE: To describe how terminations of pregnancy at gestational ages at or above the limit for stillbirth registration are recorded in routine statistics and to assess their impact on comparability of stillbirth rates in Europe. DESIGN: Analysis of aggregated data from the Euro-Peristat project. SETTING: Twenty-nine European countries. POPULATION: Births and late terminations in 2010. METHODS: Assessment of terminations as a proportion of stillbirths and derivation of stillbirth rates including and excluding terminations. MAIN OUTCOME MEASURES: Stillbirth rates overall and excluding terminations. RESULTS: In 23 countries, it is possible to assess the contribution of terminations to stillbirth rates either because terminations are rare occurrences or because they can be distinguished from spontaneous stillbirths. Where terminations were reported, they accounted for less than 1.5% of stillbirths at 22+ weeks in Denmark, between 13 and 22% in Germany, Italy, Hungary, Finland and Switzerland, and 39% in France. Proportions were much lower at 24+ weeks, with the exception of Switzerland (7.4%) and France (39.2%). CONCLUSIONS: Terminations represent a substantial proportion of stillbirths at 22+ weeks of gestation in some countries. Countries where terminations occur at 22+ weeks should publish rates with and without terminations in order to improve international comparisons and the policy relevance of stillbirth statistics. TWEETABLE ABSTRACT: For valid comparisons of stillbirth rates, data about late terminations of pregnancy are needed.

Changes in management policies for extremely preterm births and neonatal outcomes from 2003 to 2012: two population-based studies in ten European regions.

OBJECTIVE: To investigate changes in maternity and neonatal unit policies towards extremely preterm infants (EPTIs) between 2003 and 2012, and concurrent trends in their mortality and morbidity in ten European regions. DESIGN: Population-based cohort studies in 2003 (MOSAIC study) and 2011/2012 (EPICE study) and questionnaires from hospitals. SETTING: 70 hospitals in ten European regions. POPULATION: Infants born at <27 weeks of gestational age (GA) in hospitals participating in both the MOSAIC and EPICE studies (1240 in 2003, 1293 in 2011/2012). METHODS: We used McNemar's Chi2 test, paired t-tests and conditional logistic regression for comparisons over time. MAIN OUTCOMES MEASURES: Reported policies, mortality and morbidity of EPTIs. RESULTS: The lowest GA at which maternity units reported performing a caesarean section for acute distress of a singleton non-malformed fetus decreased from an average of 24.7 to 24.1 weeks (P < 0.01) when parents were in favour of active management, and 26.1 to 25.2 weeks (P = 0.01) when parents were against. Units reported that neonatologists were called more often for spontaneous deliveries starting at 22 weeks GA in 2012 and more often made decisions about active resuscitation alone, rather than in multidisciplinary teams. In-hospital mortality after live birth for EPTIs decreased from 50% to 42% (P < 0.01). Units reporting more active management in 2012 than 2003 had higher mortality in 2003 (55% versus 43%; P < 0.01) and experienced larger declines (55 to 44%; P < 0.001) than units where policies stayed the same (43 to 37%; P = 0.1). CONCLUSIONS: European hospitals reporting changes in management policies experienced larger survival gains for EPTIs. TWEETABLE ABSTRACT: Changes in reported policies for management of extremely preterm births were related to mortality declines.

Gestational age at diagnosis of early-onset fetal growth restriction and impact on management and survival: a population-based cohort study.

OBJECTIVE: To investigate the impact of gestational age (GA) at diagnosis of fetal growth restriction (FGR) on obstetric management and rates of live birth and survival for very preterm infants with early-onset FGR. DESIGN: Population-based cohort study. SETTING: All maternity units in 25 French regions in 2011. POPULATION: Fetuses diagnosed with FGR before 28 weeks of gestation among singleton births between 22 and 31 weeks of gestation without severe congenital anomalies. METHODS: We studied the effects of GA at diagnosis on perinatal management and outcomes. We used multivariable regression to identify antenatal factors (maternal characteristics, ultrasound measurements and sex) associated with the probability of live birth. MAIN OUTCOMES MEASURES: Live birth and survival to discharge from neonatal care. RESULTS: A total of 436 of 3698 fetuses were diagnosed with FGR before 28 weeks (11.8%); 66.9% were live born and 54.4% survived to discharge. 50% were live born when diagnosis occurred before 25 weeks, 66% at 25 weeks and >90% at 26 and 27 weeks of gestation. In all, 94.1% of live births were by prelabour caesarean, principally for maternal indications before 26 weeks. Low GA at diagnosis, an estimated fetal weight or abdominal circumference below the third centile and male sex were adversely associated with live birth in adjusted models. CONCLUSION: Gestational age at FGR diagnosis had an impact on the probability of live birth and survival, after consideration of other perinatal characteristics. Investigations of the outcomes of births with early-onset FGR need to include stillbirths and information on the GA at which FGR is diagnosed. TWEETABLE ABSTRACT: Evaluations of active management of pregnancies with early onset growth restriction should include stillbirths.

Impact of stillbirths on international comparisons of preterm birth rates: a secondary analysis of the WHO multi-country survey of Maternal and Newborn Health.

OBJECTIVE: To evaluate the extent to which stillbirths affect international comparisons of preterm birth rates in low- and middle-income countries. DESIGN: Secondary analysis of a multi-country cross-sectional study. SETTING: 29 countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: 258 215 singleton deliveries in 286 hospitals. METHODS: We describe how inclusion or exclusion of stillbirth affect rates of preterm births in 29 countries. MAIN OUTCOME MEASURES: Preterm delivery. RESULTS: In all countries, preterm birth rates were substantially lower when based on live births only, than when based on total births. However, the increase in preterm birth rates with inclusion of stillbirths was substantially higher in low Human Development Index (HDI) countries [median 18.2%, interquartile range (17.2-34.6%)] compared with medium (4.3%, 3.0-6.7%), and high-HDI countries (4.8%, 4.4-5.5%). CONCLUSION: Inclusion of stillbirths leads to higher estimates of preterm birth rate in all countries, with a disproportionately large effect in low-HDI countries. Preterm birth rates based on live births alone do not accurately reflect international disparities in perinatal health; thus improved registration and reporting of stillbirths are necessary. TWEETABLE ABSTRACT: Inclusion of stillbirths increases preterm birth rates estimates, especially in low-HDI countries.