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
OBJECTIVES: The aim of the study was to investigate reproductive outcomes such as birthweight, preterm births, and postterrm births among women working in research laboratories while pregnant. METHODS: Female university personnel were identified from a source cohort of Swedish laboratory employees, and the database was linked to the medical birth register. The first births of the women were included in the analysis, 249 pregnancies among the women with laboratory work and 613 pregnancies among the women without laboratory tasks. Information about exposure to various laboratory agents was obtained from a previous questionnaire investigation at the research group level according to a specific definition. The ponderal index and ratio between observed and expected birthweights were calculated. Logistic regression models were used for analyses of dichotomous outcomes (preterm, postterrm and birthweight). RESULTS: Exposure to laboratory work with solvents was associated with an increased risk of preterm births, the estimated odds ratio (OR) being 3.4 (1.0
Early treatment for cryptorchidism may be necessary to preserve fertility. International guidelines now recommend that congenital cryptorchidism be treated with orchiopexy before age 1 year. Acquired cryptorchidism should be treated at presentation. To our knowledge the rate of adherence to these guidelines in recent years is unknown. Thus, we present data on age at cryptorchidism diagnosis and orchiopexy in recent Danish birth cohorts.
A population of 508,964 Danish boys born alive from January 1, 1995 to December 31, 2009 was identified using the Danish Civil Registration System. Five birth cohorts were defined, including 1995 to 1997, 1998 to 2000, 2001 to 2003, 2004 to 2006 and 2007 to 2009. The boys were followed in the Danish National Patient Registry for a diagnosis of cryptorchidism and for an orchiopexy procedure. Data were analyzed using the Kaplan-Meier estimator and Cox regression models.
During followup 10,094 boys were diagnosed with cryptorchidism, of whom 5,473 underwent orchiopexy. Mean age at diagnosis in boys followed at least 6 years was 3.3 years (95% CI 3.3-3.4) in the 1995 to 1997 cohort, 3.1 (95% CI 3.1-3.2) in the 1998 to 2000 cohort and 2.9 (95% CI 2.8-2.9) in the 2001 to 2003 cohort while mean age at orchiopexy was 3.8 (3.7-3.9), 3.6 (3.5-3.7) and 3.3 years (3.2-3.4), respectively.
In the more recent birth cohorts of 1995 to 2009 we observed a shift toward younger age at cryptorchidism diagnosis and orchiopexy.
Menarcheal age is a predictor of several complications related to pregnancy and diseases later in life. We aimed to study if menarcheal age is a risk factor for pregnancy-related pelvic pain.
A nested case-control study was conducted within the Danish National Birth Cohort, a cohort of pregnant women, recruited during 1996-2002, and their children. In the second trimester of pregnancy the women provided information about age at menarche and potential confounders. Selection of cases (n?=?2227) was based on self-reported pelvic pain during pregnancy from an interview done 6 months post-partum. The controls (n?=?2588) were randomly selected among women who did not report pelvic pain. We used logistic regression analysis to calculate odds ratios (OR) for pregnancy-related pelvic pain according to age at menarche.
In the cohort, 18.5% of all pregnant women reported pregnancy-related pelvic pain. Compared to women who were 12-14 years old at menarche, the adjusted OR for overall pelvic pain were 1.4 (95% confidence interval [CI] 1.1-1.7) in women 11 years or younger and 0.8 (95%CI 0.6-0.9) in women 15 years or older. The corresponding adjusted OR for severe pelvic pain were 1.6 (95%CI 1.3-2.0) and 0.7 (95%CI 0.6-0.9). When age was analyzed as a continuous variable, the odds for overall and severe pelvic pain decreased with 14% and 16%, respectively, for each increasing year.
The risk of pregnancy-related pelvic pain decreased with increasing menarcheal age in an 'exposure-response' pattern. A low menarcheal age is a risk indicator and may be a risk factor for pregnancy-related pelvic pain.
The authors studied the association between female and male alcohol intakes at the time of conception and the risk of spontaneous abortion, including early pregnancy loss detected by urinary human chorionic gonadotropin. After a nationwide mailing to about 50,000 members of four trade unions in Denmark in 1992-1994, 430 couples without previous pregnancy attempts were enrolled when birth control was discontinued, and they were followed until a clinically recognized pregnancy or for six menstrual cycles. Alcohol intake and potential confounding factors were reported in monthly questionnaires. Women collected morning urine for 10 days from the first day of vaginal bleeding in each cycle. The authors detected 186 pregnancies: 131 resulted in childbirth, and 55 resulted in spontaneous abortion (34 detected by urinary human chorionic gonadotropin). Depending on the intake in the cycle of conception and the adjustment factors, female alcohol intake was associated with 2-3 times the adjusted risk of spontaneous abortion compared with no intake, and male alcohol intake was associated with 2-5 times the adjusted risk. Only the adjusted relative risks for 10 or more drinks/week compared with no intake were statistically significant. Both male and female alcohol intakes during the week of conception increased the risk of early pregnancy loss.
The safety of small amounts of alcohol drinking and occasional binge-level drinking during pregnancy remains unsettled. We examined the association of maternal average alcohol intake and binge drinking (>or=5 drinks per sitting) with infant mortality, both in the neonatal and postneonatal period.
Participants were 79,216 mothers who were enrolled in the Danish National Birth Cohort in 1996-2002, gave birth to a live-born singleton, and provided information while they were pregnant on alcohol consumption during pregnancy. Information on infant mortality and causes of death was obtained from national registries and medical records.
During the first year of life, 279 children (0.35%) died, 204 during the neonatal period. Infant mortality was not associated with alcohol drinking, even at a consumption level of either 4+ drinks per week or 3+ occasions of binge drinking. Postneonatal mortality was associated with an intake of 4+ drinks per week (hazard ratio = 3.56 [95% confidence interval = 1.15-8.43]) and with 3+ binge episodes (2.69 [1.27-5.69]). When restricting analyses to term births, both infant mortality and postneonatal mortality were associated with a weekly average intake of 4+ drinks or 3+ binge episodes.
Among term infants, intake of at least 4 drinks of alcohol per week or binging on 3 or more occasions during pregnancy are associated with an increased risk of infant mortality, especially during the postneonatal period.
It has been suggested that maternal depression during pregnancy is associated with asthma in the offspring, but the role of medical treatment of depression is not known. Our goal was to examine whether prenatal antidepressant use increases the risk of asthma in the offspring.
A cohort study was performed among all live singletons born in Denmark between 1996 and 2007. Mothers who had a diagnosis of depressive disorder and/or who used antidepressants 1 year before or during the index pregnancy were identified. Using a Cox proportional hazards regression model, we estimated the hazard ratio (HR) for asthma in the offspring after antidepressant use during pregnancy.
Of the 733,685 children identified, 84,683 had a diagnosis of asthma. A total of 21,371 children were exposed to prenatal maternal depression (ie, a diagnosis of depressive disorder or use of antidepressants 1 year before or during pregnancy). Prenatal maternal depression was associated with childhood asthma (HR: 1.25 [95% confidence interval (CI): 1.20-1.30]). Overall, 8895 children were exposed to antidepressants in utero. Compared with children born to mothers with prenatal depression and no antidepressant use during pregnancy, the HR for asthma after any antidepressant use during pregnancy was 1.00 (95% CI: 0.93-1.08). HRs after use of selective serotonin reuptake inhibitors only, newer antidepressants only, and older antidepressants only were 0.95 (95% CI: 0.88-1.03), 1.11 (95% CI: 0.89-1.39), and 1.26 (95% CI: 1.02-1.55), respectively.
Antidepressant use during pregnancy generally did not increase the risk of asthma. Only use of older antidepressants was associated with an increased risk of asthma.
It is unknown if prenatal exposure to antiepileptic drugs (AEDs) increases the risk of low Apgar score in offspring.
Population-based study using health registers in Denmark.
We identified all 677 021 singletons born in Denmark from 1997 to 2008 and linked the Apgar score from the Medical Birth Register with information on the women's prescriptions for AEDs during pregnancy from the Danish Register of Medicinal Product Statistics. We used the Danish National Hospital Registry to identify mothers diagnosed with epilepsy before birth of the child. Results were adjusted for smoking and maternal age.
Among 2906 children exposed to AEDs, 55 (1.9%) were born with an Apgar score =7 as compared with 8797 (1.3%) children among 674 115 pregnancies unexposed to AEDs (adjusted relative risk (aRR)=1.41 (95% CI 1.07 to 1.85). When analyses were restricted to the 2215 children born of mothers with epilepsy, the aRR of having a low Apgar score associated with AED exposure was 1.34 (95% CI 0.90 to 2.01) When assessing individual AEDs, we found increased, unadjusted RR for exposure to carbamazepine (RR=1.86 (95% CI 1.01 to 3.42)), valproic acid (RR=1.85 (95% CI 1.04 to 3.30)) and topiramate (RR=2.97 (95% CI 1.26 to 7.01)) when compared to unexposed children.
Prenatal exposure to AEDs was associated with increased risk of being born with a low Apgar score, but the absolute risk of a low Apgar score was
From *The Danish Epidemiology Science Centre, Department of Epidemiology, Institute of Public Health, and the †National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark; the ‡Department of Neurology and Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark; and the §School of Public Health, Department of Epidemiology, University of California at Los Angeles, Los Angeles, CA.
BACKGROUND:: Low Apgar scores are associated with high risk of neonatal death, cerebral palsy, and mental retardation, but the association between Apgar scores and long-term risk of epilepsy remains unresolved. METHODS:: We carried out a population-based cohort study of 1,538,732 live newborns in Denmark between 1 January 1978 and 31 December 2002 by using national registers. The Apgar scores at 1 or 5 minutes were recorded by midwives following standardized procedures. We obtained information on epilepsy by linking the cohort with the National Hospital Register. Cohort members were followed from birth until onset of epilepsy, death, emigration, or 31 December 2002, whichever came first. RESULTS:: The incidence rate of epilepsy increased consistently with decreasing Apgar scores. The incidence rate of epilepsy was 628 per 100,000 person-years for those with 5-minute Apgar scores of 1 to 3 and 86 per 100,000 person-years for those with a score of 10; the resulting incidence rate ratio was 7.1 (95% confidence interval = 5.8-8.8). The incidence rate ratios of epilepsy associated with low Apgar scores were particularly high in early childhood but remained high into adulthood. The association did not change after excluding children with cerebral palsy, congenital malformations, or a parental history of epilepsy. CONCLUSIONS:: Neonates with a suboptimal Apgar score have a higher risk of epilepsy that lasts into adult life. These findings suggest that prenatal or perinatal factors play a larger role in the etiology of epilepsy than has previously been recognized.
To examine the association between low serum vitamin D concentration and estimates of male reproductive function.
From a Danish pregnancy cohort established in 1984-1987, 347 sons were selected for a study conducted in 2005-2006.
Semen parameters and reproductive hormones were related to vitamin D concentrations in 307 men.
Semen characteristics and reproductive hormones.
A high vitamin D level was unexpectedly associated with lower crude median total sperm count and percentage of normal morphology sperm and a high level of crude median sex hormone-binding globulin and FSH. After adjustment, the associations attenuated to nonsignificant associations, except for sex hormone-binding globulin. Additionally, adjusted free androgen index was lower at higher vitamin D levels, and men with high vitamin D had 11% (95% confidence interval, 1%-20%) lower free androgen index compared with men with low vitamin D.
These results do not indicate that low vitamin D is a risk factor for poor semen quality in a population of young healthy men, but we may not have enough men with low vitamin D levels to detect an effect. New studies should include a larger proportion of vitamin D-deficient men.