Paediatric and perinatal epidemiology最新文献

Background: Survey data are essential in paediatric epidemiology, providing valuable insights into child health outcomes. The potential outcomes framework has advanced causal inference using observational data. However, traditional design-based adjustments, especially sample weights, are often overlooked. This omission limits the ability to generalise findings to the broader population.

Objective: This study demonstrates three approaches for estimating the population average treatment effect (PATE) in a practical example, examining the impact of household second-hand smoke (SHS) exposure on blood pressure in school-aged children.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, we assessed the effect of household SHS exposure, a non-randomised treatment, on blood pressure in school-aged children. We applied estimators based on Inverse Probability of Treatment Weighting (IPTW), G-computation, Targeted Maximum Likelihood Estimation (TMLE), and regression adjustment. Models without adjustments were run for comparison. We examined point estimates and the efficiency of the estimates obtained from these methods.

Results: The largest differences were observed between the unadjusted regression models and the fully adjusted methods (IPTW, G-computation, and TMLE), which account for both confounding and survey weights. While the inclusion of the sample weights leads to wider confidence intervals for all methods, G-computation and TMLE showed comparatively narrower confidence intervals. Confidence intervals for the models not adjusted for sample weights were likely underestimated.

Conclusions: This study highlights the important role of sample weights in causal inference. Generalisability of the average treatment effect as estimated on data sampled using common survey designs to a defined population requires the use of sample weights. The estimators described provide a framework for incorporating sample weights, and their use in health research is recommended.

Background: Preeclampsia is a common pregnancy complication associated with maternal and neonatal mortality. Early aspirin treatment lowers the risk of preeclampsia in high-risk pregnancies. However, knowledge of aspirin's effects and possible side effects outside clinical trials is sparse, and the evaluation of maternal and foetal safety regarding aspirin treatment is hindered by the inherent risk of confounding by indication.

Objectives: To study if the introduction of national guidelines recommending aspirin as preeclampsia prophylaxis affects clinical practice in Denmark, measured by aspirin use and investigate if the guideline change was related to the proportion of preeclampsia, preterm delivery, postpartum haemorrhage (PPH), placental abruption or neonatal intracranial haemorrhage.

Methods: All singleton pregnancies (1997-2016) identified in the nationwide Danish registries (gestational age ≥ 10 weeks) were included. The population was divided into persons at high or low risk of preeclampsia, according to the 2012 Danish National Guideline for Prevention and Treatment of Preeclampsia. Aspirin use was estimated based on redeemed prescriptions. The proportion of outcomes was compared using interrupted time series analyses.

Results: Of 1,323,750 pregnant persons, 2.0% (n = 25,826) were considered at high risk of preeclampsia. After the 2012 guideline change, aspirin use in high-risk pregnancies increased from 2.2% to 12.4% in 4 years, a 0.88 (95% confidence interval [CI] 0.83, 0.93) percentage point change for every half year. Severe preeclampsia slightly decreased from 6.0% to 5.2% after the guideline change, with a -0.22 (95% CI -0.43, -0.01) percentage point change for every half year, while preterm delivery rates remained unchanged. PPH increased in high-risk pregnancies. There was no difference in the risks of placental abruption or neonatal intracranial haemorrhage.

Conclusions: After the introduction of preventive aspirin treatment, aspirin use in high-risk pregnancies increased, and severe preeclampsia decreased. However, PPH increased, while rates of preterm delivery, placental abruption and neonatal intracranial haemorrhage remained unchanged.

Background: Pregnancy loss is recognised as a competing event in studies of prenatal medication use. A healthy live birth also precludes subsequent pregnancy outcomes, yet is often censored in time-to-event analyses.

Objectives: Using a Monte Carlo simulation, we examined bias resulting from censoring versus accounting for healthy live birth as a competing event in estimates of the total effect of prenatal medication use on pregnancy outcomes.

Methods: We simulated 2000 cohorts of 7500 conceptions with chronic hypertension under 12 treatment profiles. Ongoing pregnancies were indexed into the trial and randomly assigned to initiate or not initiate antihypertensives. Using time-to-event methods, we estimated absolute risks, risk differences (RD) per 100 pregnancies, and risk ratios (RR) for two outcomes, mirroring a prior trial: (i) composite fetal death or severe prenatal preeclampsia and (ii) small for gestational age (SGA) live birth. For the composite outcome, we conducted analyses where non-preeclamptic live birth was: (1) a censoring event and (2) a competing event. For SGA live birth, we conducted analyses where fetal death and non-SGA live birth were: (1) censoring events; (2) a competing event and censoring event, respectively; and (3) competing events.

Results: For the composite outcome, censoring non-preeclamptic live births overestimated the absolute risk by 42.3 to 49.1 percentage points; RD and RR estimates were biased (e.g., RD bias range -6.18 to 0.46). For SGA live birth, analyses censoring non-SGA live births (with or without fetal death as a competing event) overestimated absolute risk by 30.0 to 37.7 and 40.9 to 52.4 percentage points on average; RD and RR estimates were biased (e.g., RD bias range -7.45 to 0.79 and -9.62 to 1.81, respectively). Analyses in which healthy live births were modelled as competing events produced unbiased risks, RDs and RRs.

Conclusions: Censoring healthy live births resulted in overestimated risks as well as biased and imprecise total treatment effect estimates. Such inaccuracies about risks undermine informed patient-provider decision-making.

Background: Uterine fibroids, a common gynaecologic condition, are often underdiagnosed, potentially biasing results in epidemiologic studies due to measurement error.

Objectives: To examine how varying sensitivity in detecting uterine fibroids impacts effect estimates, using the association with hypertension onset as an example.

Methods: Three simulation studies were conducted (N = 100,000), considering true population prevalences of uterine fibroids of 5%, 20% and 60%. The first study varied detection sensitivity between 0% and 100%. The second examined differential sensitivity by symptom status (asymptomatic vs. symptomatic). The third assessed differential sensitivity by racialised groups. Specificity remained fixed at 90%, and true risk ratios (RRs) for the association with hypertension were set at 1.3 and 1.8.

Results: Decreasing sensitivity biased results towards the null, with low-sensitivity methods (e.g., self-report) showing the largest bias and high-sensitivity methods (e.g., transvaginal ultrasonography) the least bias. At low fibroid prevalence (5%), even gold-standard ascertainment introduced bias due to imperfect specificity, whereas this concern diminished at higher prevalence. Assuming a dose-response relationship between fibroids and hypertension based on symptom status, results remained biased towards the null unless sensitivity was 100% and prevalence was high (60%); bias was most pronounced at low prevalence. When only symptomatic fibroids were associated with hypertension, increasing sensitivity biased results away from the null by capturing more asymptomatic cases. Studies using low-sensitivity methods may fail to identify a true effect among Black females while identifying it among White females, potentially exacerbating disparities. Detection bias, where those with fibroids are more likely to have hypertension detected, could result in bias away from the null.

Conclusions: Underdiagnosis of uterine fibroids can bias results towards the null, particularly with self-report or modest effect estimates, potentially obscuring true effects. When only symptomatic fibroids were associated with the outcome, the bias was away from the null. Results varied by symptom status and race, highlighting the need to prioritise sensitive ascertainment methods, employ sensitivity analyses and improve reliability across diverse gynecologic conditions and health disparities.

Background: People who recently gave birth are strongly advised to wait 6 months before attempting pregnancy. Interpregnancy intervals (IPI) of ≥ 18 months are considered optimal. Current guidance is not tailored based on maternal characteristics (e.g., age).

Objectives: We evaluated whether maternal age modifies IPI-preterm birth (PTB) associations.

Methods: From a US retrospective cohort of multiparae (1997-2011), we categorised IPI: < 6, 6-11, 12-17, 18-23 (reference), 24-59 or ≥ 60 months. PTB occurred before 37 0/7 weeks' gestation. We estimated risk ratios (RR) between IPI and PTB using modified Poisson regression, adjusted for potential confounders and stratified by age at prior delivery: < 25 (n = 2484), 25-29 (n = 1626) or ≥ 30 (n = 1209) years. We conducted quantitative bias analysis to adjust for volunteer bias and dependent misclassification between IPI and gestational length (since both are calculated using the estimated start of pregnancy). We computed E-values when RR lower bounds of the 95% simulation intervals were > 1.00.

Results: Estimates were imprecise due to small numbers. However, in terms of general patterns, PTB risk was highest with < 6 months IPI in all age groups (covariate-adjusted RR point estimates ≥ 1.30). The strongest associations were observed among 25-29 years. For ≥ 30 years, PTB risk was lowest with 6-17 months IPI. After multiple bias adjustments, estimates tended to move downward, but similar patterns remained. For 25-29 years, the lower bound of the 95% simulation interval for < 6 versus 18-23 months IPI was > 1.00, with an E-value of 3.82, suggesting unmeasured confounding would need to be very strong to explain the association.

Conclusions: Estimates were imprecise. However, our study adds to growing evidence that IPI associations may be weaker among older individuals. Older individuals with shorter IPI may have lower PTB risk than those with currently recommended IPI, but more research is needed.

Background: Globally, Down syndrome is the most common chromosomal anomaly, often co-occurring with cardiac or gastrointestinal anomalies. There is a lack of robust data on specific healthcare needs of children with Down syndrome compared to children with other major congenital anomalies.

Objectives: To quantify the healthcare needs of children with Down syndrome in the first year of life compared to children with major congenital anomalies in a large population-based cohort across Europe.

Methods: The EUROlinkCAT study was a multicentre data linkage study between congenital anomaly registries in Europe and hospital and mortality databases. Children born between 1st January 1997 and 31st December 2014 were included. Summary statistics were used to compare differences between children (those with Down syndrome compared to all major anomalies) and regions. Random-effects meta-analysis was used to pool results related to survival, need for intensive care and ventilation support.

Results: A total of 3554 children were born with Down syndrome out of 89,081 children with major congenital anomalies. The pooled 1-year survival was 95.4%. In every region, > 80% of children with Down syndrome had a hospital admission excluding the birth admission. Hospital length of stay in the first year was higher for children with Down syndrome compared to those with all anomalies (median: 14 versus 7 days). Despite having similar need for ventilation support (9.7% vs. 8.4%), children with Down syndrome had higher rates of intensive care admission than all children with anomalies (24.8% vs. 13.0%).

Conclusions: There is a high need for hospital care for children born with Down syndrome in the first year of life. Future work should continue to explore the long-term prognosis for children with Down syndrome to ensure their care needs are met.

Background: Population-based data are needed to reliably assess the impact of SARS-CoV-2 infection during pregnancy.

Objectives: To estimate the population-based incidence of SARS-CoV-2 infection and its severe forms in the obstetric population, identify risk factors of severe SARS-CoV-2 infection (severe COVID-19) and describe delivery, maternal and neonatal outcomes by disease severity, using a definition of severity based on organ dysfunction.

Methods: A prospective population-based study conducted over the three first pandemic waves between March 2020 and April 2021 in 281 maternity hospitals in six French regions included all women with SARS-CoV-2 infection during pregnancy or within 7 days post-partum, whether symptomatic or not, hospitalised or not. Severe COVID-19 forms were defined a priori using clinical, biological and management criteria of organ dysfunction. We calculated infection and severe infection rates and studied associations between sociodemographic, medical and pregnancy characteristics and severe COVID-19 by univariate and multivariate modified Poisson regression modelling.

Results: From a population of 385,214 deliveries in the participating regions, 6015 women with SARS-CoV-2 infection were identified, including 337 severe cases. The rates of severe COVID-19 were 1.1, 0.9 and 3.6 per 1000 deliveries during the first, second and third pandemic waves, respectively, and the proportions of severe COVID-19 were 8.6%, 3.4% and 9.3%, respectively. On multivariate analysis, the risk of severe COVID-19 was associated with younger and older age, migrant status, living with > 4 people, overweight or obesity, chronic hypertension or diabetes and infection ≥ 22 weeks of gestation rather than earlier in pregnancy. Neonatal morbidity occurred mostly with severe maternal infection.

Conclusion: Using an organ-based definition of severity and population-based data, rates of severe COVID-19 appeared lower than in previous studies. A permanent perinatal surveillance system is needed to assess efficiently and rapidly the impact of future pandemics.