Paediatric and perinatal epidemiology最新文献

Background: Limited longitudinal data exist on the associations of infertility with depressive symptoms across the lifecourse.

Objectives: To investigate how depressive symptoms change across specific life stages (pregnancy, postpartum, and midlife), with a focus on the differences between women with and without a history of infertility before index pregnancy.

Methods: Women enrolled in Project Viva (1999-2002) during early pregnancy (mean [SD] age 32.5 [4.7] years) completed the Edinburgh Postnatal Depression Scale (EPDS) in mid-pregnancy (median 27.9 weeks gestation) and at 6 months postpartum, and completed the Patient Health Questionnaire (PHQ-9) in midlife (2017-2021, 50.9 [5.1] years). We converted EPDS and PHQ-9 scores to externally standardised T-scores (mean = 50, SD = 10). We defined infertility before index pregnancy as ≥ 6 cycles to achieve pregnancy if ≥ 35 years of age or ≥ 12 cycles to achieve pregnancy if < 35 years of age, or claims for infertility treatments or prescriptions abstracted from medical records. We performed adjusted linear regression models to examine associations of infertility with depressive symptoms across the three-time spans (pregnancy-postpartum, postpartum-midlife, and pregnancy-midlife).

Results: Among 1368 participants, 281 (21%) experienced infertility at index pregnancy. Infertility was associated with a 1.83- point increase in depressive symptoms (T-score) between the postpartum period and midlife (adjusted $\beta$ 1.83, 95% confidence interval [CI] 0.00, 3.66). Infertility was unrelated to change in depressive symptoms between pregnancy and postpartum (adjusted $\beta$ 0.02, 95% CI -1.24, 1.28) or pregnancy and midlife (adjusted $\beta$ 1.30, -0.64, 3.23).

Conclusions: The experience of infertility among parous women is associated with a greater increase in depressive symptoms between the post-partum period and midlife.

Background: Infants born in the periviable period show an extremely high risk of infant death. At all gestational ages in the periviable period, non-Hispanic (NH) Black infants counterintuitively show relatively lower infant mortality risk than do NH white infants. The literature theorises that cohort variation over time in pregnancy loss (a form of left truncation in utero) could explain a portion of this survival advantage.

Objectives: We test this left truncation hypothesis in the US (Jan 1996 to Jun 2018) by focusing on NH Black singleton periviable males. We use twin sex ratios as a gauge of cohort left truncation against frail males.

Methods: We retrieved US birth and infant death records for all NH Black and NH white singleton infants born in the periviable range for 282 monthly conception cohorts. We used high and low outliers in the monthly sex ratio of extremely preterm twins (M:F), where a higher sex ratio indicates less selection against frail males. We applied augmented time-series methods which control for both autocorrelation and confounding.

Results: NH Black male periviable singleton infants show a stronger survival advantage (relative to NH whites) for cohorts with high outliers in left truncation (4.0 fewer deaths per 100 live births, 95% confidence interval 1.0, 7.2).

Conclusions: Elevated left truncation in utero may contribute to the survival advantage of NH Black male singletons in the periviable period. Observed racial/ethnic differences in infant mortality across conception cohorts vary, at least in part, from left truncation.

Background: In birth registries, incomplete recording of information leads to missing values. Multiple imputation (MI) by chained equations is a widely used method for analysing datasets with missing data. It is unknown whether using registry records from multiple pregnancies contributed by the same woman could potentially give more accurate values when resolving missing data.

Objectives: To investigate the relative performance of five methods to infer missing data on maternal characteristics using data from a medical birth registry, comparing longitudinal methods and MI with data from previous and future pregnancies.

Methods: We used data from the Medical Birth Registry of Norway (MBRN), selecting records among mothers with more than one pregnancy between 2004 and 2018. Longitudinal methods used reference pregnancies in three time directions: past, future and closest pregnancy record. MI was conducted with only index pregnancy records (single-pregnancy MI) and with both index and closest reference pregnancy records (multiple-pregnancy MI). Validity was assessed by comparing the actual values with inferred/imputed values. For continuous variables, we calculated the proportion of inferred values within predefined increments. For binary variables, we calculated five parameters: agreement rate, sensitivity, specificity, positive predictive value and negative predictive value.

Results: We included 578,670 pregnancies among 256,658 women. For continuous variables, the longitudinal methods showed the highest proportion within predefined increments, followed by multiple-pregnancy MI, and single-pregnancy MI showed the lowest value. For binary variables, longitudinal methods generally showed higher values among the five validity parameters than MI. Single-pregnancy MI had substantially lower agreement, while multiple-pregnancy MI performed similarly to longitudinal methods.

Conclusions: The longitudinal method outperformed MI in inferring missing data on maternal characteristics in a medical birth registry.

Background: In the United States, birthing parent-infant dyads may receive care from multiple healthcare systems. Linkage of an individual's electronic health records (EHR) across healthcare systems, in addition to birthing parent-infant linkage, may be necessary to obtain appropriate clinical data for perinatal health research.

Objectives: To develop a privacy-preserving process to link the health records of patients shared by two health systems for a perinatal health study, and to assess data enhancements associated with the linkage.

Methods: We included pregnant patients who received care from at least one of two healthcare systems based in Minnesota, USA and their infants born between December 2020 and September 2022 who had at least one well visit. We identified infants from one health system with birthing parents who potentially received care in the second health system based on the infant's delivery hospital. We implemented a one-way matching process using an algorithm to generate unique hash values for each record at each health system. Specifically, we used four hash ID rules based on six identifiers available in the EHR at both sites plus a consistent salt.

Results: One health system identified 3524 infants with birthing parents who potentially received care in the second system. The second system identified 39,321 infants delivered at the hospitals of interest during the study period. The algorithm matched 3406 (96.7%) infant records. After applying the study eligibility criteria, the birthing-parent records gained through hash matching increased the study population by 7.2% from 8100 to 8686. Overall, 13.6% of the study population had data from the second health system. Some demographic and pregnancy characteristics differed from those with data from the first system only.

Conclusions: The hash matching approach can increase study size, patient diversity, and data completeness in a privacy-preserving manner for perinatal health studies among patients that use multiple healthcare systems.

Background: Physical activity has time-varying associations with injury risk among children. While previous activity may predispose to injury through tissue damage, fatigue and insufficient recovery, it may protect against injury by strengthening tissues and improving fitness and skills. It is unclear what the relevant time window and relative importance of past activity are with regard to current injury risk in children.

Objectives: The objectives of this study were to assess how previous activity patterns are associated with injury risk among children.

Methods: Our data source was the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-DK), a prospective cohort study of Danish school children conducted between 2008 and 2014. We applied flexible weighted cumulative exposure methods within a Cox proportional hazards model to estimate the time-varying association between the number of weekly activity sessions and time-to-first injury in each school year. We estimated several models with varying time windows and compared goodness-of-fit.

Results: Out of 1667 study participants, 986 (59.1%) were injured at least once, with a total of 1752 first injuries across school years. The best-fitting model included 20 weeks of past physical activity. Higher levels of activity performed 10-20 weeks ago were associated with decreased injury risk, while higher levels of activity performed 2-9 weeks ago were associated with higher injury risks. Compared to those who remained minimally active for the entire past 20-week period, children who were highly active in the past 10 weeks after being minimally active 11-20 weeks ago had an injury hazard ratio of 1.63 (95% confidence interval 1.18, 2.23).

Conclusions: Flexible weighted cumulative exposure methods suggest a complex temporal relationship between past physical activity history and injury in children.

Background: Generally, studies in perinatal epidemiology restrict cohort entry to 20 weeks of gestation, but exposures and outcomes may occur earlier. This restriction may introduce left truncation bias.

Objectives: To examine the impact of left truncation bias when estimating the causal effect of abruption on perinatal mortality in the context of abnormal placentation, with spontaneous abortion (SAB) as a censoring event.

Methods: Through 80 Monte Carlo simulation scenarios based on realistic clinical assumptions, we estimated risk differences (RD), risk ratios (RR) and bias parameters for the abruption-perinatal mortality association.

Results: Censoring by SAB ranged from 5.6% to 7.6% across simulation setups. The risk of mortality was underestimated in observable (left-truncated) data at ≥ 20 weeks compared to an unobservable cohort starting follow-up at placental implantation (conception cohort). Underestimation of risks was stronger among abruption pregnancies. RDs for the abruption-mortality association were biased by +1% to +3% among conceptions with normal implantation and by +5% to +43% among abnormal placentation. Due to the disproportionate underestimation of mortality among nonabruption pregnancies, RRs were overestimated by 1.1 to 1.2-fold for normal implantations and by 1.1 to 8.4-fold for abnormal implantations.

Conclusions: The findings of this simulation study highlight the critical importance of placentation in successful pregnancy. Abnormal placentation has profound consequences for unsuccessful pregnancies, remarkably increasing the risks of early losses, placental abruption and other obstetrical complications. This study underscores that left truncation can bias the abruption-perinatal mortality association, differentially by whether the placentation was normal or abnormal. However, defining the causal question regarding the abruption-perinatal mortality association requires consideration of the target population, which may include all conceptions. In studies of these effects, outcome follow-up capability may introduce left truncation bias. We do not prescribe one analytic approach to account for left truncation, but rather, the approach should be guided by the causal question.

Background: The occurrence of reproductive or pregnancy events, such as severe maternal morbidity (SMM), may reveal a predisposition to chronic disease and premature mortality. However, most studies have examined these exposures without considering their timing, severity, or recurrence.

Objectives: We propose using a weighted cumulative exposure (WCE) modelling approach to flexibly describe the relationship between reproductive events and longer-term health outcomes in a longitudinal cohort of pregnant women.

Methods: Application of the WCE modelling approach is accomplished in three steps. First, relative weights are estimated from a multivariable Cox proportional hazards model corresponding to the association of each reproductive risk factor with a given health outcome. Then, a longitudinal dataset is constructed in which all reproductive predictors are recorded at regular intervals (every 3 months), beginning 42 days after each woman's first birth in the cohort and ending at an outcome or censoring event. A new multivariable Cox model applied to this longitudinal dataset, incorporating time-varying WCE-derived reproductive risk scores along with simple time-varying reproductive and non-reproductive predictors, is estimated. Finally, adjusted WCE-based hazard ratios (HR) associated with different reproductive event exposure histories are calculated.

Results: In the cohort of 1,992,972 births in Canada (excluding Quebec), 2008-2021, with mean (SD) follow-up time in the longitudinal dataset of 7.3 ± 3.8 years, we propose to use the WCE approach to predict outcomes such as premature cardiovascular disease (16,846 cardiovascular hospitalisations observed, or 1.19 per 1000 person-years).

Conclusions: Use of flexible WCE modelling to quantify risks of pregnancy events such as SMM, adjusted for reproductive and non-reproductive CVD risk factors, will account for variation in timing and severity of these events and will capture their cumulative effects across a woman's reproductive trajectory. This approach can refine estimates of etiologic associations and inform novel clinical prediction models with the potential to predict postpartum long-term health outcomes for a given woman based on her unique reproductive history.

Background: Medication use during pregnancy for attention-deficit/hyperactivity disorder (ADHD) is increasing, but evidence on its safety in pregnancy for foetal health is limited, with little attention to time-related biases in observational research.

Objective: To determine the association between ADHD medication use in early and late pregnancy and the risk of preterm birth.

Methods: This population-based cohort study utilised data from national registers, including records on births, prescription medications, specialist healthcare visits, hospitalisations and educational attainment, to account for relevant potential confounders. We included singleton births delivered between 22 and 44 gestational weeks among pregnant individuals with ADHD medication use in the year before conception from Norway (2009-2020) and Sweden (2007-2019). ADHD medications (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine and guanfacine) were assessed during early (conception to 21 gestational weeks) and late pregnancy (22-36 gestational weeks). The main outcome was preterm birth, defined as a live birth before 37 completed weeks of pregnancy. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using log-binomial regression and flexible parametric survival modelling to determine the risk of preterm birth in early and late pregnancy, respectively.

Results: Among 11,075 pregnancies, early pregnancy ADHD medication use was associated with higher preterm birth risk with ≥ 2 filled prescriptions (aRR 1.29, 95% CI 1.08, 1.53), but not as ≥ 1 prescription (aRR 1.08, 95% CI 0.93, 1.25). Any medication use in late pregnancy increased preterm birth risk (aHR 1.15, 95% CI 0.95, 1.39). For every 30 days of cumulative exposure to ADHD medication, the risk of preterm birth increased in late pregnancy (aHR 1.07, 95% CI 1.02, 1.12), but not in early pregnancy (aHR 1.01, 95% CI 0.97, 1.05).

Conclusions: ADHD medication may modestly increase the risk of preterm birth, especially with atomoxetine early and methylphenidate late in pregnancy, and with longer durations of use.

Background: An evidence gap exists concerning the timing of delivery at 37-42 weeks and the risk of attention-deficit hyperactivity disorder (ADHD) in offspring.

Objective: To determine the association between timing of delivery in low-risk pregnancies at term (37-42 weeks) gestations and ADHD in offspring.

Methods: This population-based cohort study comprised 1,424,453 singletons in Sweden and 403,765 in British Columbia (BC), Canada, live-born at 37-42 completed weeks to low-risk pregnant women between 2000 and 2018. Children were followed up from age 1 until the date of death, emigration, their first diagnosis, or December 2020 (study's end date). The exposure was time of delivery assessed through gestational age, and the outcome was the diagnosis of ADHD. Cox regression models were used to examine the association between gestational age at delivery and ADHD.

Results: During the follow-up period, 59,989 children in Sweden were diagnosed with ADHD (4.5 per 1000 child-years). Correspondingly, in BC, during the same period, there were 27,445 children diagnosed with ADHD (7.4 per 1000 child-years). In Sweden, the adjusted hazard of ADHD was 10%, 6%, and 3% higher at 37, 38, and 39 weeks gestation compared with those born at ≥ 38, ≥ 39, and ≥ 40 weeks, respectively. In BC, the corresponding hazards were 9%, 6%, and 3%, respectively. Both regions showed no elevated ADHD risks for infants born at 40 weeks compared to those born at ≥ 41 weeks, with slightly lower rates at 40 weeks.

Conclusions: In low-risk pregnancies, births at 37 and 38 weeks were associated with a higher ADHD risk, while births at 40 weeks showed no increased risk compared with those born at later gestations.