Paediatric and perinatal epidemiology最新文献

Background: In observational medication pregnancy safety studies, children are often followed from birth to 1 year of age. However, some major congenital malformations (MCM) may take longer to diagnose.

Objectives: We aimed to investigate the proportion of children with detected MCMs at different lengths of follow-up and compare them to the proportion detected at 1 year after birth.

Methods: This population-based register study included all singleton children liveborn in Sweden from 2006 to 2016. MCM were identified by ICD-10 codes in the Medical Birth Register and National Patient Register, aligned to the EUROCAT classification system. Cumulative proportion of children with detected MCM at birth, 90 days, 1, 2, and 3 years was calculated and compared between children born preterm and at term.

Results: In 1,138,113 liveborn children, the cumulative proportion of children with a detected MCM increased from 1.9% at birth to 3.1%, 3.9%, 4.4% and 4.7% at 90 days, 1, 2, and 3 years after birth, respectively, and varied by MCM subgroup. MCMs of the eye, ear-face-neck, nervous system and genitals were detected with the longest delay, with 31%-59% more detected at 3- versus 1-year follow-up. Compared to children born at term, the proportion of children with any MCM was 2.5 times higher amongst preterm children, with a higher proportion detected over the first 90 days for most MCM subgroups.

Conclusions: The proportion of children with a detected MCM varied by MCM subgroup and follow-up time. In pharmacoepidemiology studies of medication safety in pregnancy using Swedish national data, the length of child follow-up should be chosen in accordance with the expected age at detection if a specific subgroup of MCM is under investigation, for example, eye and genital MCM require longer follow-up for detection than abdominal wall and digestive system MCM. However, in most circumstances, 1 year of follow-up is sufficient.

Background: Low-dose aspirin prophylaxis is recommended for women at risk of preeclampsia. Capturing aspirin prophylaxis within administrative databases can be challenging since it is an over-the-counter medication. The Better Outcome Registry and Network (BORN) database, a perinatal health registry in Ontario, Canada, includes a formal variable that captures aspirin prophylaxis for preeclampsia. This variable has not been formally validated.

Objectives: To assess the accuracy of the aspirin prophylaxis variable in the BORN database against an electronic medical record (EMR).

Methods: This validation study comprised 200 randomly selected women who had a livebirth at St. Michael's Hospital (SMH) in Toronto, Ontario, from January 2018 to July 2022. Recorded aspirin prophylaxis in pregnancy and maternal sociodemographic characteristics were independently extracted by two abstractors. Accuracy of aspirin prophylaxis use in the BORN database was compared to that in the SMH EMR, expressed as sensitivity, specificity, positive (PPV) and negative predictive values (NPV), Cohen's kappa (κ), and overall percent agreement, with 95% confidence intervals (CI). Sensitivity analyses were performed to account for missing or unclear aspirin prophylaxis use.

Results: Among 200 women, 24 (12.0%) received aspirin prophylaxis - 12.5% within the SMH EMR and 8.0% in the BORN database. Women using aspirin were older (37.0 vs 33.0 years) and had higher median gravidity (3 vs. 2). Sensitivity and specificity of the BORN aspirin prophylaxis variable were 62.5% (95% CI 40.6, 81.2) and 100.0% (95% CI 97.3, 100.0), respectively. The corresponding positive and negative predictive values were 100.0% (95% CI 78.2, 100.0), and 93.8% (95% CI 88.6, 97.1), respectively. Cohen's κ was 0.74 (95% CI 0.58, 0.90), and overall percent agreement was 94.4% (95% CI 87.1, 100.0).

Conclusions: Aspirin use within the BORN database, based on a standard variable field, appears accurate enough for the potential use in epidemiological studies of aspirin prophylaxis for preeclampsia or as a covariate in related studies.

Background: While the benefits of levothyroxine are well-established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women.

Objective: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data.

Methods: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care. We emulated multiple nested trials (at each gestational week) and used an intention-to-treat approach to define levothyroxine use (≥1 prescription in the 7 days prior to trial entry), with eligible users matched to non-users (1:4) on time of diagnosis, gestational week of the first eligible trial and high-dimensional propensity score. Pregnancy losses included spontaneous abortion and stillbirth. A pooled logistic regression model with bootstrap resampling was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI).

Results: Based on 159,177 eligible person-trials (5781 women), the matched cohort included 181 initiators and 640 non-initiators of levothyroxine, with 57 pregnancy losses occurring during follow-up. Overall, the mean age of women was 32.2 years (SD 5.4), 25% were obese, 8% had type 2 diabetes and about 50% were nulliparous. After matching, women who initiated levothyroxine versus not had higher thyroid-stimulating levels during pregnancy and were more likely to have a history of hypothyroidism. The cumulative incidence of pregnancy loss was lower in initiators versus non-initiators of levothyroxine. The adjusted HR for pregnancy loss was 0.87 (95% CI 0.22, 1.56).

Conclusions: Although our assessment of the effect of initiation of levothyroxine for SCH in pregnancy precludes any definitive conclusions due to wide confidence intervals, this study illustrates the feasibility of using the target trial emulation framework to examine the effectiveness of medication use in pregnancy.

Background: Off-label treatment of extremely preterm infants with diuretics and inhaled corticosteroids (ICS) for evolving bronchopulmonary dysplasia (BPD) is common. Their effectiveness in reducing mortality or BPD severity, and optimal treatment timing, are unclear.

Objectives: To determine whether diuretic treatment or ICS administration for infants with early evolving (between 10-27 days postnatal) and progressively evolving (28th-day-36th-week postnatal) BPD are independently associated with reduced mortality and moderate or severe BPD at 36-weeks postmenstrual age (PMA).

Methods: We examined neonates born before 28 weeks' gestation and admitted to neonatal intensive care units on postnatal Day 0 between 2006 and 2016 using data collected during routine care recorded within the Paediatric Health Information System (PHIS). An early evolving BPD cohort consisted of infants treated with oxygen, positive pressure or mechanical ventilation at 10 days postnatal. The progressively evolving BPD cohort consisted of infants treated with these modalities at 28 days. In new users, we evaluated the effect of diuretic and ICS treatment on mortality or BPD severity at 36 weeks PMA, adjusting for time-dependent confounding by respiratory status using marginal structural models.

Results: Early evolving BPD was present in 10,135 patients; progressively evolving BPD in 11,728. New diuretic exposure during early evolving BPD (adjusted risk ratio [aRR] 0.77, 95% confidence interval [CI] 0.65, 0.93) was associated with decreased mortality or moderate/severe BPD risk. New diuretics (aRR 0.86, 95% CI 0.75, 0.99) during progressively evolving BPD between 28-days-36-weeks PMA were less strongly associated with mortality or moderate/severe BPD reduction. There was no strong association for ICS in patients with early evolving (aRR: 1.40; 95% CI: 0.79, 2.51) or progressively evolving BPD (aRR 1.16, 95% CI 0.95, 1.49).

Conclusion: Diuretics, but not ICS, for evolving BPD were associated with mortality and BPD risk reduction.

Background: Children born with major congenital anomalies (CAs) have lower academic achievement compared with their peers, but the existing evidence is restricted to a number of specific CAs.

Objectives: To investigate academic outcomes at ages 11 and 16 in children with major isolated structural CAs and children with Down or Turner syndromes.

Methods: This population-based cohort study linked data on approximately 11,000 school-aged children born with major CAs in 1994-2004 registered by four regional CA registries in England with education data from the National Pupil Database (NPD). The comparison group was a random sample of children without major CAs from the background population recorded in the NPD that were frequency matched (5:1) to children with CAs by birth year, sex and geographical area.

Results: Overall, 71.9%, 73.0% and 80.9% of children with isolated structural CAs achieved the expected attainment level at age 11 compared to 78.3%, 80.6% and 86.7% of the comparison group in English language, Mathematics and Science, respectively. Children with nervous system CAs as a whole had the lowest proportion who achieved the expected attainment at age 11. At age 16, 46.9% of children with CAs achieved the expected level compared to 52.5% of their peers. Major CAs were associated with being up to 9% (95% confidence interval [CI] 8%, 11%) and 12% (95% CI 9%, 14%) less likely to achieve expected levels at ages 11 and 16, respectively, after adjustment for socioeconomic deprivation.

Conclusions: Although many children with isolated CAs achieved the expected academic level at ages 11 and 16, they were at higher risk of underachievement compared to their peers. These stark yet cautiously encouraging results are important for counselling parents of children with specific CAs and also highlight the possible need for special education support to reduce potential academic difficulties.

Background: No data exist at the population level on what tests are used to aid in the diagnosis of autism spectrum disorder in community practice.

Objectives: To describe autism spectrum disorder testing practices to inform autism spectrum disorder identification efforts.

Methods: Data are from the Autism and Developmental Disabilities Monitoring Network, a multi-site surveillance system reporting prevalence estimates and characteristics of 8-year-old children with autism spectrum disorder. Percentages of children with autism spectrum disorder who received any autism spectrum disorder test or a 'gold standard' test were calculated by site, sex, race, median household income, and intellectual ability status. Risk ratios were calculated to compare group differences.

Results: Of 5058 8-year-old children with autism spectrum disorder across 11 sites, 3236 (64.0%) had a record of any autism spectrum disorder test and 2136 (42.2%) had a 'gold standard' ADOS or ADI-R test. Overall, 115 children (2.3%) had both the ADOS and ADI-R in their records. Differences persisted across race, median household income, and intellectual ability status. Asian/Pacific Islander children had the highest percent receiving any ASD test (71.8%; other groups range: 57.4-66.0%) and White children had the highest percent receiving 'gold standard' tests (46.4%; other groups range: 35.6-43.2%). Children in low-income neighbourhoods had a lower percent of any test (62.5%) and 'gold standard' tests (39.4%) compared to medium (70.2% and 47.5%, respectively) and high (69.6% and 46.8%, respectively) income neighbourhoods. Children with intellectual disability had a lower percent of any ASD test (81.7%) and 'gold standard' tests (52.6%) compared to children without intellectual disability (84.0% and 57.6%, respectively).

Conclusions: Autism spectrum disorder testing practices vary widely by site and differ by race and presence of co-occurring intellectual disability, suggesting opportunities to standardise and/or improve autism spectrum disorder identification practices.