Dataset Information

Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births.

ABSTRACT:

Background

Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice.

Methods

We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors.

Findings

Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6-6.0 and 2.8-5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25-50% and 11-16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted.

Conclusions

We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions.

SUBMITTER: Ferrero DM

PROVIDER: S-EPMC5021369 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births.

Ferrero David M DM Larson Jim J Jacobsson Bo B Di Renzo Gian Carlo GC Norman Jane E JE Martin James N JN D'Alton Mary M Castelazo Ernesto E Howson Chris P CP Sengpiel Verena V Bottai Matteo M Mayo Jonathan A JA Shaw Gary M GM Verdenik Ivan I Tul Nataša N Velebil Petr P Cairns-Smith Sarah S Rushwan Hamid H Arulkumaran Sabaratnam S Howse Jennifer L JL Simpson Joe Leigh JL

PloS one 20160913 9

<h4>Background</h4>Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countr ...[more]

PMID: 27622562

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Project description:BackgroundEmerging studies suggest that ambient temperature during pregnancy may be associated with fetal growth, but the existing evidence is limited and inconsistent.ObjectivesWe aimed to evaluate the association of trimester-specific temperature with risk of being born small for gestational age (SGA) and birth weight-markers of fetal growth-among term births in the contiguous United States.MethodsWe included data on 29,597,735 live singleton births between 1989 and 2002 across 403 U.S. counties. We estimated daily county-level population-weighted mean temperature using a spatially refined gridded climate data set. We used logistic regression to estimate the association between trimester-specific temperature and risk of SGA and linear regression to evaluate the association between trimester-specific temperature and term birth weight z-score, adjusting for parity, maternal demographics, smoking or drinking during pregnancy, chronic hypertension, and year and month of conception. We then pooled results overall and by geographic regions and climate zones.ResultsHigh ambient temperatures ([Formula: see text] percentile) during the entire pregnancy were associated with higher risk of term SGA {odds ratio [OR] [Formula: see text] 1.041 [95% confidence interval (CI): 1.029, 1.054]} and lower term birth weight [standardized to [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) reduction in birth weight for infants born at 40 weeks of gestation]. Low temperatures ([Formula: see text] percentile) during the entire pregnancy were not associated with SGA [OR [Formula: see text] 1.003 (95% CI: 0.991, 1.015)] but were associated with a small decrement in term birth weight [standardized to [Formula: see text] (95% CI: [Formula: see text], [Formula: see text])]. Risks of term SGA and birth weight were more strongly associated with temperature averaged across the second and third trimesters, in areas the Northeast, and in areas with cold or very cold climates.ConclusionsAbove-average temperatures during pregnancy were associated with lower fetal growth. Our findings provide evidence that temperature may be a novel risk factor for reduced fetal growth. https://doi.org/10.1289/EHP4648.

Project description:BackgroundThe available data regarding morbidity and mortality associated with multiple gestation births is conflicting and contradicting.ObjectiveTo compare morbidity, mortality, and length of stay (LOS) outcomes between multiple gestation (twin, triplet and higher-order) and singleton births.MethodsData from the national multicenter Kids' Inpatient Database of the Healthcare Cost and Utilization Project from the years 2000, 2003, 2006, 2009, 2012, and 2016 were analyzed using a complex survey design using Statistical Analysis System (SAS) 9.4 (SAS Institute, Cary NC). Neonates with ICD9 and ICD10 codes indicating singletons, twins or triplets, and higher-order multiples were included. Mortality was compared between these groups after excluding transfer outs to avoid duplicate inclusion. To analyze LOS, we included inborn neonates and excluded transfers; who died inpatient and any neonates who appear to have been discharged less than 33 weeks PMA. The LOS was compared by gestational age groups.ResultsA total of 22,853,125 neonates were analyzed for mortality after applying inclusion-exclusion criteria; 2.96% were twins, and 0.13% were triplets or more. A total of 22,690,082 neonates were analyzed for LOS. Mean GA, expressed as mean (SD), for singleton, twins and triplets, were 38.30 (2.21), 36.39 (4.21), and 32.72 (4.14), respectively. The adjusted odds for mortality were similar for twin births compared to singleton (aOR: 1.004, 95% CI:0.960-1.051, p = 0.8521). The adjusted odds of mortality for triplet or higher-order gestation births were higher (aOR: 1.33, 95% CI: 1.128-1.575, p = 0.0008) when compared to the singleton births. Median LOS (days) was significantly longer in multiple gestation compared to singleton births overall (singletons: 1.59 [1.13, 2.19] vs. twins 3.29 [2.17, 9.59] vs. triplets or higher-order multiples 19.15 [8.80, 36.38], p < .0001), and this difference remained significant within each GA category.ConclusionMultiple gestation births have higher mortality and longer LOS when compared to singleton births. This population data from multiple centers across the country could be useful in counseling parents when caring for multiple gestation pregnancies.

Project description:BackgroundFetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight.Methods and findingsWe performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations.ConclusionsWe observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Project description:Study questionWhat are the socio-demographic characteristics of families in Norway who have children after assisted reproductive technology (ART), and have these characteristics changed over time?Summary answerParents who conceive through ART in Norway tend to be advantaged families, and their socio-demographic profile has not changed considerably over the period 1985-2014.What is known alreadyA small number of studies show that couples who conceive through ART tend to be socio-economically advantaged.Study design, size, durationNorwegian Population Register, the Medical Birth Register and the national data bases were linked to study all live births in Norway between 1985 and 2014.Participants/materials, setting, methodsThe sample consisted of 1?757?768 live births. Simple bivariate analyses were performed to describe the socio-demographic characteristics of parents who conceived through ART and changes in these characteristics over the time period 1985-2014. We used linear probability models to estimate the association between parental income and giving birth after ART from 2000 to 2014, before and after adjustment for maternal age at delivery, education and area of residence.Main results and the role of chanceParents conceiving through ART were more likely to be older, with the highest levels of income and education, and married. Their socio-demographic profiles did not change considerably during the period 1985-2014. In the unadjusted model, parents belonging to the top income quartile were 4.2 percentage points more likely (95% CI: 4.1 to 4.3) to have conceived through ART than parents who belonged to the bottom income quartile. Adjustment for maternal age only partially reduced the income disparities (for the top income quartile by 35% (??=?2.7 with 95% CI: 2.5 to 2.8)). Additional adjustment for maternal education, marital status and area of residence did not further attenuate the associations.Limitations, reasons for cautionThe data does not enable us to tell whether the lower numbers of children conceived through ART amongst more disadvantaged individuals is caused by lower success rates with ART treatment, lower demand of ART services or barriers faced in access to ART. The study focuses on Norway, a context characterised by high subsidisation of ART services.Wider implications of the findingsEven though in Norway access to ART services is highly subsidised, the results highlight important and persisting social inequities in use of ART. The results also indicate that children born after ART grow up in resourceful environments, which will benefit their development and well-being.Study funding/competing interest(s)This work was supported by European Research Council agreement n. 803959 (to A.G.), by Economic and Social Research Council grant ES/M001660/1 and by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The authors have no conflict of interest to declare.Trial registration numberNot applicable.

Dataset Information

Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births.

Background

Methods

Findings

Conclusions

Publications

Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births.

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