Objective
To assess the proportion of small for gestational age (SGA) and normal birthweight infants suspected of fetal growth restriction (FGR) during pregnancy, and to investigate obstetric and ...neonatal outcomes by suspicion of FGR and SGA status at birth.
Design
Population‐based study.
Setting
All French maternity units in 2010.
Population
Representative sample of singleton births (n = 14 100).
Methods
We compared SGA infants with a birthweight of less than the 10th percentile suspected of FGR, defined as mention of FGR in medical charts (true positives), non‐SGA infants suspected of FGR (false positives), SGA infants without suspicion of FGR (false negatives) and non‐SGA infants without suspicion of FGR (true negatives). Multivariable analyses were adjusted for maternal and neonatal characteristics hypothesised to affect closer surveillance for FGR and our outcomes.
Main outcome measures
Obstetric management (caesarean, provider‐initiated preterm and early term delivery) and neonatal outcomes (late fetal death, preterm birth, Apgar score, resuscitation at birth).
Results
21.7% of SGA infants (n = 265) and 2.1% of non‐SGA infants (n = 271) were suspected of FGR during pregnancy. Compared with true negatives, provider‐initiated preterm deliveries were higher for true and false positives (adjusted risk ratio aRR, 6.1 95% CI, 3.8–9.8 and 4.6 95% CI, 3.2–6.7), but not for false negatives (aRR, 1.1 95% CI, 0.6–1.9). Neonatal outcomes were not better for SGA infants if FGR was suspected.
Conclusion
Antenatal suspicion of FGR among SGA infants was low and one‐half of infants suspected of FGR were not SGA. The increased risk of provider‐initiated delivery observed in non‐SGA infants suspected of FGR raises concerns about the iatrogenic consequences of screening.
Objective
To investigate time trends in preterm birth in Europe by multiplicity, gestational age, and onset of delivery.
Design
Analysis of aggregate data from routine sources.
Setting
Nineteen ...European countries.
Population
Live births in 1996, 2000, 2004, and 2008.
Methods
Annual risk ratios of preterm birth in each country were estimated with year as a continuous variable for all births and by subgroup using log‐binomial regression models.
Main outcome measures
Overall preterm birth rate and rate by multiplicity, gestational age group, and spontaneous versus non‐spontaneous (induced or prelabour caesarean section) onset of labour.
Results
Preterm birth rates rose in most countries, but the magnitude of these increases varied. Rises in the multiple birth rate as well as in the preterm birth rate for multiple births contributed to increases in the overall preterm birth rate. About half of countries experienced no change or decreases in the rates of singleton preterm birth. Where preterm birth rates rose, increases were no more prominent at 35–36 weeks of gestation than at 32–34 weeks of gestation. Variable trends were observed for spontaneous and non‐spontaneous preterm births in the 13 countries with mode of onset data; increases were not solely attributed to non‐spontaneous preterm births.
Conclusions
There was a wide variation in preterm birth trends in European countries. Many countries maintained or reduced rates of singleton preterm birth over the past 15 years, challenging a widespread belief that rising rates are the norm. Understanding these cross‐country differences could inform strategies for the prevention of preterm birth.
Objective
To use data from routine sources to compare rates of obstetric intervention in Europe both overall and for subgroups at higher risk of intervention.
Design
Retrospective analysis of ...aggregated routine data.
Setting
Thirty‐one European countries or regions contributing data on mode of delivery to the Euro‐Peristat project.
Population
Births in participating countries in 2010.
Methods
Countries provided aggregated data about overall rates of obstetric intervention and about caesarean section rates for specified subgroups.
Main outcome measures
Mode of delivery.
Results
Rates of caesarean section ranged from 14.8% to 52.2% of all births and rates of instrumental vaginal delivery ranged from 0.5% to 16.4%. Overall, there was no association between rates of instrumental vaginal delivery and rates of caesarean section, but similarities were observed between some countries that are geographically close and may share common traditions of practice. Associations were observed between caesarean section rates for women with breech and vertex births and with singleton and multiple births but patterns of association for women who had and had not had previous caesarean sections were more complex.
Conclusions
The persisting wide variations in caesarean section and instrumental vaginal delivery rates point to a lack of consensus about practice and raise questions for further investigation. Further research is needed to explore the impact of differences in clinical guidelines, healthcare systems and their financing and parents’ and professionals’ attitudes to care at delivery.
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.
Stillbirth and in-hospital mortality rates associated with very preterm births (VPT) vary widely across Europe. International comparisons are complicated by a lack of standardized data collection and ...differences in definitions, registration, and reporting. This study aims to determine what proportion of the variation in stillbirth and in-hospital VPT mortality rates persists after adjusting for population demographics, case-mix, and timing of death.
Standardized data collection for a geographically defined prospective cohort of VPTs (22
-31
weeks gestation) across 16 regions in Europe. Crude and adjusted stillbirth and in-hospital mortality rates for VPT infants were calculated by time of death by using multinomial logistic regression models.
The stillbirth and in-hospital mortality rate for VPTs was 27.7% (range, 19.9%-35.9% by region). Adjusting for maternal and pregnancy characteristics had little impact on the variation. The addition of infant characteristics reduced the variation of mortality rates by approximately one-fifth (4.8% to 3.9%). The SD for deaths <12 hours after birth was reduced by one-quarter, but did not change after risk adjustment for deaths ≥12 hours after birth.
In terms of the regional variation in overall VPT mortality, over four-fifths of the variation could not be accounted for by maternal, pregnancy, and infant characteristics. Investigation of the timing of death showed that these characteristics only accounted for a small proportion of the variation in VPT deaths. These findings suggest that there may be an inequity in the quality of care provision and treatment of VPT infants across Europe.
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
Choice of growth chart strongly affected identification of high‐risk fetuses at the third trimester ultrasound.
Tweetable
Choice of growth chart strongly affected identification of high‐risk fetuses at the third trimester ultrasound.
Linked article This article is commented on by F Figueras, pp. 949 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471-0528.17108.
The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target ...site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade. Bcl-2 is vital during development, much less so in adults. It has also been noted that some cancers evade apoptosis and obtain a survival advantage through aberrant expression of Bcl-2. The new and remarkably diverse class of drugs, small-molecule inhibitors of Bcl-2 (molecular weight approximately 400 to 800 Daltons), is examined herein. We present the activities of these compounds along with clinical observations, where available. The effects of Bcl-2 inhibition on attenuation of tumor cell growth are discussed, as are studies revealing the potential for Bcl-2 inhibitors as antiangiogenic agents. Despite an enormous body of work published for the Bcl-2 family of proteins, we are still learning exactly how this group of molecules interacts and indeed what they do. The small-molecule inhibitors of Bcl-2, in addition to their therapeutic potential, are proving to be an important investigative tool for understanding the function of Bcl-2.
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