We asked whether breastfeeding reduces the risk of epilepsy in childhood.
We included 69 750 singletons born between September 1997 and June 2003 in the Danish National Birth Cohort and observed them to August 2008. Information on breastfeeding was reported by mothers in two computer-assisted telephone interviews at 6 and 18 months after birth. Information on epilepsy (inpatients and outpatients) was retrieved from the Danish National Hospital Register. Cox proportional hazards regression models were used to estimate incidence rate ratios and 95% CIs.
Breastfeeding was associated with a decreased risk of epilepsy, with a dose-response like pattern. For example, children breastfed for 3 to 5, 6 to 8, 9 to 12, and = 13 months had a 26%, 39%, 50%, and 59% lower risk of epilepsy after the first year of life, respectively, compared with children who were breastfed for
To investigate whether children with a history of infantile colic showed impaired motor development at age 7 years compared with unaffected peers.
We studied 27,940 children from the Danish National Birth Cohort (1997-2002), including 1879 (6.8%) with a history of infantile colic. Infantile colic was defined according to the modified Wessel criteria as crying for more than 3 hours per day and more than 3 days per week. We compared the parental Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) scores in children with and without infantile colic after adjustment for intrauterine exposures, feeding type, parity, maternal age, socioeconomic status, Apgar score, gestational age, and birth weight.
Children with a history of infantile colic had an elevated risk of scoring above the predefined cutoff limit of possible or suspected developmental coordination disorder (OR, 1.3; 95% CI, 1.0-1.7; P = .034). The mean total DCDQ'07 score was -0.4 point (95% CI, -0.8 to 0) lower in children with a history of infantile colic. Moreover, they were at higher risk for a low total score (OR for a 10-point decrease, 1.1; 95% CI, 1.0-1.1; P = .006) and a low general coordination score (OR, 1.3; 95% CI, 1.1-1.5, P = .000) in the DCDQ'07. All associations appeared to be stronger among boys, but no statistically significant effect measure modification between infantile colic and sex was found.
We found no evidence of a strong association between infantile colic and developmental coordination disorder in this large Danish cohort.
We aimed to examine whether early life bereavement, as indicator of severe stress, was associated with an increased risk of schizophrenia later in life.Based on population registers, we established a cohort of all children born in Denmark (N?=?1 686 416) and Sweden (N?=?2 563 659) from 1973 to 1997. Children were categorized as exposed if they lost a first-degree relative during the first 18 years of life. Outcome is the first diagnosis of schizophrenia as either inpatient or outpatient. Log-linear Poisson regression models were used to estimate incidence rate ratios (IRRs).A total of 188,850 children (4.6%) experienced death of a first-degree relative from birth to 18 years of age. Compared with unexposed children, those exposed had overall a 39% higher risk of schizophrenia (=?1.39, 95% CI [confidence interval]: 1.32-1.47). The IRR was particularly high if the family member committed suicide (aIRR?=?2.11, 95% CI: 1.90-2.34) or died due to an injury or accident (aIRR?=?1.44, 95% CI: 1.27-1.63). The IRR of schizophrenia decreased with increasing child's age at bereavement (P?1 death during the first 18 years of life (aIRR?=?1.79, 95% CI: 1.46-2.19) had a higher risk than those with a single death (aIRR?=?1.37, 95% CI: 1.30-1.45).The study suggested that exposure to death of a first-degree relative before 18 years was associated with an increased risk of schizophrenia in later life. The complex mechanisms behind these associations remain to be elucidated.
BACKGROUND: Hyperthermia acts as a teratogen in some animals where it can induce resorption of the fetus and fetal death. Fever during pregnancy, especially in the period of embryogenesis, is also suspected as being a risk factor for fetal death in human beings. We did a large cohort study in Denmark to investigate this possibility. METHODS: We interviewed 24040 women who were recruited in the first half of pregnancy to the Danish National Birth Cohort Study, and obtained information on the number of fever incidents during the first 16 weeks of pregnancy. For each fever episode, the highest measured body temperature, duration of incident, and gestational age were recorded. Outcomes of pregnancies were identified through linkage with the Civil Registration System and the National Discharge Registry. Cox's regression with time-dependent variables was used to estimate the relative risk of fetal death, taking delayed entry into account. FINDINGS: 1145 pregnancies resulted in a miscarriage or stillbirth (4.8%). During the first 16 pregnancy weeks 18.5% of the women experienced at least one episode of fever. However, we found no association between fever in pregnancy and fetal death before or after adjustment for known risk factors of fetal death (relative risk 0.95 [95% CI 0.80-1.13]). This finding was consistent irrespective of measured maximum temperature, duration and number of fever incidents, or the gestational time of the fever incident, and was observed for fetal death in all three trimesters of pregnancy. INTERPRETATION: We found no evidence that fever in the first 16 weeks of pregnancy is associated with the risk of fetal death in clinically recognised pregnancies.
Comment In: Lancet. 2002 Nov 16;360(9345):152612443584
BACKGROUND: The loss of a child is considered one of the most stressful events in the life of a parent. We hypothesized that parental bereavement increases the risk of hospital admission for a psychiatric disorder, especially for affective disorders. METHODS: We studied a cohort of 1,082,503 persons identified from national registers in Denmark who were born between 1952 and 1999 and had at least one child under 18 years of age during the follow-up period, from 1970 to 1999. Parents who lost a child during follow-up were categorized as "bereaved" from the date of death of the child. RESULTS: As compared with parents who did not lose a child, parents who lost a child had an overall relative risk of a first psychiatric hospitalization for any disorder of 1.67 (95 percent confidence interval, 1.53 to 1.83). Bereaved mothers had a higher relative risk of being hospitalized for any psychiatric disorder than bereaved fathers (relative risks, 1.78 [95 percent confidence interval, 1.60 to 1.98] and 1.38 [95 percent confidence interval, 1.17 to 1.63], respectively; P value for interaction, 0.01). The relative risks of hospitalization specifically for affective disorders were 1.91 (95 percent confidence interval, 1.59 to 2.30) and 1.61 (95 percent confidence interval, 1.15 to 2.27) for bereaved mothers and fathers, respectively. Among mothers, the relative risk of being hospitalized for any psychiatric disorder was highest during the first year after the death of the child but remained significantly elevated five years or more after the death. CONCLUSIONS: The risk of psychiatric hospitalization was increased among parents, especially mothers, who lost a child.
To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.
We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.
Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress.
Maternal infections during pregnancy have been associated with an increased risk for neurological outcomes in the child, including epilepsy. We examined cystitis antibiotics commonly used during pregnancy, as a marker of cystitis, and the risk of childhood epilepsy in a population-based cohort in Denmark.
We examined all liveborn singletons born in Denmark between January 1996 and September 2004, identified from the Danish National Birth Registry. Epilepsy diagnoses were obtained from the Danish National Hospital Register and maternal antibiotic use from the National Register of Medicinal Product Statistics. Cystitis antibiotics consisted of pivmecillinam, sulphamethizole and nitrofurantoin. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazard regression models.
The study followed 447629 singletons for up to 9.9 years and identified 2848 children diagnosed with epilepsy. We found slightly increased risks of epilepsy in children whose mothers had redeemed prescriptions during pregnancy for pivmecillinam HR=1.2 [95% CI 1.0, 1.4], sulphamethizole HR=1.2 [95% CI 1.1, 1.4] or nitrofurantoin HR=1.1 [95% CI 0.8, 1.5], compared with those unexposed. Among mothers with multiple redeemed prescriptions during pregnancy, adjusted HR were for pivmecillinam HR=1.3 [95% CI 1.1, 1.5], sulphamethizole HR=1.3 [95% CI 1.1, 1.5] and nitrofurantoin HR=1.3 [95% CI 1.0, 1.8].
Similar magnitudes of associations between chemically different drugs, used almost exclusively to treat cystitis, may suggest an impact of maternal infection on the fetal brain. However, direct drug effects or confounding factors are also possible explanations.
Smoking is a well-established risk factor for fetal growth restriction and other adverse pregnancy outcomes, and nicotine may be one of the chemical compounds that drive these associations. Nicotine replacement therapy (NRT) is a smoking cessation aid, which can facilitate smoking cessation. It is, however, unknown whether NRT used during pregnancy impairs fetal growth. The aim of this study was to estimate the association between the use of NRT during pregnancy and offspring birthweight. The study population consisted of 72 761 women enrolled in the Danish National Birth Cohort between 1996 and 2002. Information on NRT and potential confounders was obtained from two computer-assisted telephone interviews conducted in the second and third trimesters, respectively. Multiple linear regression in a multilevel model was used to estimate the association between NRT use and birthweight adjusted for gestational age and potential confounders. The adjusted analyses showed no significant association between the duration of NRT use and birthweight (b = 0.25 g per week of NRT use [95% CI -2.31, 2.81]) and neither was the type of NRT product (patch, gum, inhaler) associated with reduced birthweight. However, simultaneous use of more than one NRT product was associated with reduced birthweight (b = -10.73 g per week of NRT use [95% CI -26.51, 5.05]), although the association was not statistically significant. The results of this study suggest that maternal use of NRT in pregnancy does not seriously affect birthweight, but there could be a negative effect on birthweight associated with simultaneous use of more than one type of NRT product.
Elevated maternal body temperature during pregnancy is of clinical concern as side effects have been reported. We estimated the association between maternal fever and sauna bathing during pregnancy and risk of epilepsy in the offspring. We identified 86,810 liveborn singletons from the Danish National Birth Cohort (DNBC) and followed them for up to 9 years of age. Information on fever including number, timing, level, duration, and symptoms of each fever episodes was collected in two computer-assisted telephone interviews around 17 and 32 gestational weeks; information on maternal use of a sauna was collected in the latter interview, and information on epilepsy was obtained from the Danish National Hospital Register. We applied Cox regression models to estimate the incidence rate ratios (IRR) of epilepsy for children exposed to maternal fever and sauna bathing during pregnancy. Maternal sauna bathing during pregnancy was not associated with an increased risk of epilepsy. Maternal fever during pregnancy in general was not associated with an increased risk of epilepsy in the offspring [IRR = 1.01, 95% confidence interval (CI) 0.85, 1.19], and no dose-response pattern was found according to number, level and duration of fever. However we did find an increased risk of epilepsy among children exposed to at least 3 fever episodes (IRR = 1.88, 95% CI 1.19, 2.98), to maternal fever with symptoms in the urinary system (IRR = 4.86, 95% CI 1.56, 15.17), and to one-day maternal fever of 39.0-39.4?C (IRR = 2.79, 95% CI 1.60, 4.84). Our findings do not support a strong association between hyperthermia and epilepsy but the associations between underlying causes of fever, especially prenatal infections, call for more research.
Medications may be consumed periconceptionally before a woman knows she is pregnant. In this study, the authors evaluate the association of a prescription diet drug (Letigen) containing ephedrine (20 mg) and caffeine (200 mg) with spontaneous abortion (SAB) in the Danish National Birth Cohort.
Women were recruited during their first prenatal visit from 1996-2002. Pre-conception and early pregnancy medication use was reported on the enrollment form, and pregnancy outcome was determined by linking the mother's Civil Registration Number to the Medical Birth Registry and the National Hospital Discharge Register. Of 97,903 eligible pregnancies, 4,443 ended in SAB between 5 and 20 completed gestational weeks, inclusive. Letigen use was reported for 565 pregnancies. Cox regression models accounting for left truncation were fit to estimate the effect of pre-conception and early pregnancy Letigen use on SAB.
The estimated maternal age-adjusted hazard ratio for SAB was 1.1 (95% confidence interval 0.8-1.6) for any periconceptional Letigen use compared to no periconceptional use.
Although Letigen has high levels of caffeine (the recommended 3 pills/day are approximately equivalent to caffeine from 6 cups of coffee), periconceptional use does not appear to be associated with an appreciably increased hazard of clinically recognized SAB.
Cites: N Engl J Med. 1999 Nov 25;341(22):1639-4410572151