The Danish Medical Birth Register Bliddal, Mette; Broe, Anne; Pottegård, Anton ...
European journal of epidemiology,
01/2018, Letnik:
33, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The Danish Medical Birth Register was established in 1973. It is a key component of the Danish health information system. The register enables monitoring of the health of pregnant women and their ...offspring, it provides data for quality assessment of the perinatal care in Denmark, and it is used extensively for research. The register underwent major changes in construction and content in 1997, and new variables have been added during the last 20 years. The aim was to provide an updated description of the register focusing on structure, content, and coverage since 1997. The register includes data on all births in Denmark and comprises primarily of data from the Danish National Patient Registry supplemented with forms on home deliveries and stillbirths. It contains information on maternal age provided by the Civil Registration System. Information on pre-pregnancy body mass index and smoking in first trimester is collected in early pregnancy (first antenatal visit). The individual-level data can be linked to other Danish health registers such as the National Patient Registry and the Danish National Prescription Registry. The register informs several other registers/databases such as the Danish Twin Registry and the Danish Fetal Medicine Database. Aggregated data can be publicly accessed on the Danish Health Data Authority web page (www.esundhed.dk/sundhedsregistre/MFR). Researchers can obtain access to individual-level pseudoanonymised data via servers at Statistics Denmark and the Danish Health Data Authority.
Acetaminophen (paracetamol) is the most commonly used medication for pain and fever during pregnancy in many countries. Research data suggest that acetaminophen is a hormone disruptor, and abnormal ...hormonal exposures in pregnancy may influence fetal brain development.
To evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD)-like behavioral problems or hyperkinetic disorders (HKDs) in children.
We studied 64,322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002.
Acetaminophen use during pregnancy was assessed prospectively via 3 computer-assisted telephone interviews during pregnancy and 6 months after child birth.
To ascertain outcome information we used (1) parental reports of behavioral problems in children 7 years of age using the Strengths and Difficulties Questionnaire; (2) retrieved HKD diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry prior to 2011; and (3) identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry. We estimated hazard ratios for receiving an HKD diagnosis or using ADHD medications and risk ratios for behavioral problems in children after prenatal exposure to acetaminophen.
More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at higher risk for receiving a hospital diagnosis of HKD (hazard ratio = 1.37; 95% CI, 1.19-1.59), use of ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk ratio = 1.13; 95% CI, 1.01-1.27). Stronger associations were observed with use in more than 1 trimester during pregnancy, and exposure response trends were found with increasing frequency of acetaminophen use during gestation for all outcomes (ie, HKD diagnosis, ADHD medication use, and ADHD-like behaviors; P trend < .001). Results did not appear to be confounded by maternal inflammation, infection during pregnancy, the mother's mental health problems, or other potential confounders we evaluated.
Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcome are frequent, these results are of public health relevance but further investigations are needed.
Maternal thyroid dysfunction may adversely affect fetal brain development, but more evidence is needed to refine this hypothesis. The aim of this study was to evaluate potential fetal programming by ...abnormal maternal thyroid function on child neurodevelopmental disorders.
The design was a case-cohort study within the Danish National Birth Cohort (1997-2003). From the eligible cohort of 71,706 women, a random 12% sub-cohort (n = 7624) was selected, and all women (n = 2276) whose child was diagnosed with seizures, specific developmental disorder (SDD), autism spectrum disorder (ASD), and/or attention-deficit/hyperactivity disorder (ADHD) up to December 31, 2010, were identified. All women had a blood sample drawn in early pregnancy (median week 9), and the stored sample was used for measurement of free thyroxine and thyrotropin. Method- and week-specific reference ranges were used for classification of maternal thyroid function. A weighted Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence intervals (CI) for neurodevelopmental disorders in children exposed to maternal thyroid dysfunction.
The overall frequency of abnormal maternal thyroid function was 12.5% in the sub-cohort and significantly higher among cases of ASD (17.9%; aHR = 1.5 CI 1.1-2.1), but not among other types of neurodevelopmental disorders (febrile seizures: 12.7%; epilepsy: 13.1%; SDD: 12.6%; and ADHD: 14.0%). However, evaluation of subtypes of maternal thyroid dysfunction showed that maternal overt hypothyroidism (thyrotropin >10 mIU/L) was a risk factor for epilepsy in the child (aHR = 3.5 CI 1.2-10), as was overt hyperthyroidism for cases diagnosed within the first year of life (aHR = 3.0 CI 1.03-8.4). Furthermore, both maternal hypothyroidism (aHR = 1.8 CI 1.1-2.7) and overt hyperthyroidism (aHR = 2.2 CI 1.1-4.4) were risk factors for ASD in the child, and isolated low free thyroxine was associated with ASD (aHR = 4.9 CI 2.03-11.9) and ADHD (aHR = 2.3 CI 1.2-4.3) in girls but not in boys.
Abnormal maternal thyroid function in early pregnancy was associated with epilepsy, ASD, and ADHD in the child, but associations differed by subtypes of exposure and by child age and sex. More evidence on subtypes and severity of maternal thyroid function is needed, and alternative outcomes of child neurodevelopment may be warranted.
The prevalence of autistic disorder (AD), a serious developmental condition, has risen dramatically over the past two decades, but high-quality population-based research addressing etiology is ...limited.
We studied the influence of exposures to traffic-related air pollution during pregnancy on the development of autism using data from air monitoring stations and a land use regression (LUR) model to estimate exposures.
Children of mothers who gave birth in Los Angeles, California, who were diagnosed with a primary AD diagnosis at 3-5 years of age during 1998-2009 were identified through the California Department of Developmental Services and linked to 1995-2006 California birth certificates. For 7,603 children with autism and 10 controls per case matched by sex, birth year, and minimum gestational age, birth addresses were mapped and linked to the nearest air monitoring station and a LUR model. We used conditional logistic regression, adjusting for maternal and perinatal characteristics including indicators of SES.
Per interquartile range (IQR) increase, we estimated a 12-15% relative increase in odds of autism for ozone odds ratio (OR) = 1.12, 95% CI: 1.06, 1.19; per 11.54-ppb increase and particulate matter ≤ 2.5 µm (OR = 1.15; 95% CI: 1.06, 1.24; per 4.68-μg/m3 increase) when mutually adjusting for both pollutants. Furthermore, we estimated 3-9% relative increases in odds per IQR increase for LUR-based nitric oxide and nitrogen dioxide exposure estimates. LUR-based associations were strongest for children of mothers with less than a high school education.
Measured and estimated exposures from ambient pollutant monitors and LUR model suggest associations between autism and prenatal air pollution exposure, mostly related to traffic sources.
Introduction:
Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications, but teratogenic effects of antithyroid drug (ATD) treatment have been ...described. Evidence is still lacking in regard to the safety and choice of ATD in early pregnancy.
Objective:
Our objective was to determine to which degree the use of methimazole (MMI)/carbimazole (CMZ) and propylthiouracil (PTU) in early pregnancy is associated with an increased prevalence of birth defects.
Methods:
This Danish nationwide register-based cohort study included 817 093 children live-born from 1996 to 2008. Exposure groups were assigned according to maternal ATD use in early pregnancy: PTU (n = 564); MMI/CMZ (n = 1097); MMI/CMZ and PTU (shifted in early pregnancy n = 159); no ATD (ATD use, but not in pregnancy n = 3543); and nonexposed (never ATD use n = 811 730). Multivariate logistic regression was used to estimate adjusted odds ratio (OR) with 95% confidence interval (95% CI) for diagnosis of a birth defect before 2 years of age in exposed versus nonexposed children.
Results:
The prevalence of birth defects was high in children exposed to ATD in early pregnancy (PTU, 8.0%; MMI/CMZ, 9.1%; MMI/CMZ and PTU, 10.1%; no ATD, 5.4%; nonexposed, 5.7%; P < .001). Both maternal use of MMI/CMZ (adjusted OR = 1.66 95% CI 1.35–2.04) and PTU (1.41 1.03–1.92) and maternal shift between MMI/CMZ and PTU in early pregnancy (1.82 1.08–3.07) were associated with an increased OR of birth defects. MMI/CMZ and PTU were associated with urinary system malformation, and PTU with malformations in the face and neck region. Choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, and aplasia cutis were common in MMI/CMZ-exposed children (combined, adjusted OR = 21.8 13.4–35.4).
Conclusions:
Both MMI/CMZ and PTU were associated with birth defects, but the spectrum of malformations differed. More studies are needed to corroborate results in regard to early pregnancy shift from MMI/CMZ to PTU. New ATD with fewer side effects should be developed.
Perfluoroalkyl substances (PFASs) are widespread industrial pollutants that are extremely persistent in the environment. A previous study in the Danish National Birth Cohort (DNBC) found prenatal ...perfluorooctanoate (PFOA) exposure was associated with decreased birth weight, but had insufficient statistical power to evaluate adverse birth outcomes. Here, we conducted additional analyses in three samples originating from the DNBC for 3535 mothers and infant pairs to evaluate associations between prenatal PFASs exposures and low birth weight and preterm birth. Maternal plasma concentrations were measured for six types of PFASs in early pregnancy. Several PFASs were associated with a reduction in birth weight and gestational age. We estimated a nearly 2-fold increase in risks of preterm birth for the higher quartiles of PFOA and perflourooctanesulfonate (PFOS) exposure. In spline models, risk of preterm birth was increased for perfluorononanoic acid (PFNA), perfluoroheptane sulfonate (PFHpS) and perfluorodecanoic acid (PFDA) in higher exposure ranges. We also observed some elevated risks for low birth weight but these estimates were less precise. Our findings strengthen the evidence that in-utero PFASs exposures affect fetal growth. Future studies are needed to evaluate whether these associations persist with the decline of PFOA and PFOS in populations and should also investigate newer types of fluorinated compounds introduced more recently.
Objective: Potential neurotoxic effects of perfluorinated compounds (PFCs) have been reported in highly exposed animals, but whether these chemicals are neurotoxic in humans is not known. We ...therefore investigated whether prenatal exposure to perfluorooctanoic acid (PFOA) or perfluorooctane sulfate (PFOS), two of the most prevalent PFCs, are associated with behavioral or coordination problems in early childhood. Methods: We used data from the Danish National Birth Cohort, which enrolled mothers in early pregnancy, and we measured maternal blood levels of PFOA and PFOS using specimens drawn around 8 weeks of gestation. When the children reached 7 years of age, mothers completed the Strengths and Difficulties Questionnaire (SDQ, n = 787) and the Developmental Coordination Disorder Questionnaire (DCDQ, n = 526) to assess behavioral health and motor coordination of their children. SDQ scores above the 90th percentile were a priori defined to identify behavioral problems and DCDQ scores below the 10th percentile were defined as a potential DCD. Results: The median concentrations of PFOS and PFOA in maternal blood were 34.4 ng/mL interquartile range (IQR), 26.6-44.5 and 5.4 ng/mL (IQR, 4.0-7.1), respectively, similar to distributions reported for populations without occupational exposure. We found no association between higher SDQ scores and maternal levels of PFOS or PFOA, nor did we see any statistically significant association with motor coordination disorders. Conclusion: The findings suggest that background levels of PFOA and PFOS are not associated with behavioral and motor coordination problems in childhood. However, effects on other developmental end points, including cognitive, attentional, and clinical mental disorders not measured in this study, cannot be ruled out.
Objective:
Methimazole (MMI) and propylthiouracil (PTU) are both associated with birth defects and may also rarely be associated with agranulocytosis and liver failure. The frequency of these side ...effects when antithyroid drugs (ATDs) are used in the population in general or in pregnancy remains to be elucidated.
Design:
All individuals registered as the parent of a live-born child in Denmark, 1973–2008, were identified (n = 2 299 952) and studied from 1995 through 2010 for the use of ATDs. Outcomes were agranulocytosis, liver failure, and birth defects in their offspring. To evaluate the frequency of these side effects associated with the use of ATDs in pregnancy, all live-born pregnancies (n = 830 680), 1996–2008, were identified in a subanalysis.
Results:
In the population studied, 28 998 individuals redeemed prescriptions of ATDs (exposure in 2115 pregnancies), which was associated with 45 cases of agranulocytosis (one in pregnancy) and 10 cases of liver failure (one in pregnancy). This corresponded to 41 and 11 cases of agranulocytosis and liver failure per 5 million inhabitants during a 10-year period (agranulocytosis: 0.16% of ATDs exposed MMI: 0.11% vs PTU: 0.27%, P = .02; liver failure: 0.03% of ATDs exposed MMI: 0.03% vs PTU: 0.05%, P = .4). The majority (83%) developed the side effect within 3 months of ATD treatment and 25% during hyperthyroidism relapse. The use of ATDs in pregnancy was associated with birth defects in 3.4% of exposed children (44 cases per 5 million inhabitants per 10 y), and the frequency of birth defects after ATD exposure was 75 times higher than both maternal agranulocytosis and liver failure in pregnancy.
Conclusions:
In the Danish population in general, ATDs associated birth defects and agranulocytosis had similar frequencies and were more common than liver failure, whereas for the use of ATDs in pregnancy, birth defects were dominant. The burden of side effects to the use of ATDs can be reduced by restricting the use of ATDs in early pregnancy.
In a Danish population study using health registers, agranulocytosis caused by antithyroid drugs was 4 times more frequent than liver failure. Both were very rare in pregnancy, where birth defects were the dominant side effect.
Prenatal maternal smoking has been associated with attention-deficit/hyperactivity disorder (ADHD) in children, but the causal nature of this association is still under scrutiny. We examined the ...association with maternal smoking and nicotine replacement use during pregnancy, using association with paternal smoking as a marker of potential genetic or social confounding.
We included 84 803 singletons who participated in the Danish National Birth Cohort. Information on parental smoking was reported by the mothers during pregnancy. Children with ADHD were identified from the Danish Psychiatric Central Register, the Danish National Patient Register, and the Register of Medicinal Product Statistics by the International Classification of Diseases, 10th Revision diagnosis or medication. We also used hyperactivity/inattention score of the parent-reported Strengths and Difficulties Questionnaire, included in the 7-year follow-up of the National Birth Cohort.
Maternal and paternal smoking during pregnancy were associated with an elevated risk of ADHD defined by hospital diagnosis, medication, and hyperactivity/inattention score, but the association was stronger for maternal smoking than for paternal smoking. Compared with children born to nonsmoking mothers and smoking fathers, children born of smoking mothers and nonsmoking fathers had a higher risk of ADHD (adjusted hazard ratio = 1.26; 95% confidence interval, 1.03 to 1.53). We also saw a higher risk of ADHD in children of mothers who used nicotine replacement during pregnancy.
Our findings indicate that the association between prenatal maternal smoking and ADHD may overestimate a causal link, but nicotine exposure or related factors may still play a causal role.
Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of ...abnormal maternal thyroid function per se remains unclarified.
To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy.
Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC), 1997 to 2016; 8830 children from the Danish National Birth Cohort (DNBC), 1997 to 2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011 to 2015.
Birth defects diagnosed before 2 years of age.
In the NRBC, altogether 2718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% CI, 6.7% to 6.8%) in nonexposed children and higher after exposure to methimazole/carbimazole (9.6%; 95% CI, 8.2% to 11.2%) and propylthiouracil (8.3%; 95% CI, 6.7% to 10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs 12.6%, P = 0.8) and the NDRPC (15.1 vs 15.4%, P = 0.8).
Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.
PDF
