Maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder: a case–control study in Japan

Although maternal smoking during pregnancy has been shown to be associated with an increased risk of offspring attention-deficit/hyperactivity disorder (ADHD) in Western countries, there is no empirical evidence in non-Caucasian. Purpose of the present study is to examine the relationship between maternal smoking during pregnancy and offspring ADHD in Japanese population. A case-control study design was adopted. A total of 90 pairs of children with ADHD and mothers as well as 270 corresponding control pairs were recruited throughout the study period. A psychiatrist interviewed all the mothers of children with ADHD and control children and elicited information regarding their lifestyles during pregnancy, including active and passive smoking or drinking habits, as well as psychosocial and perinatal factors. Diagnosis of ADHD was made by each physician in charge according to DSM-IV diagnostic criteria. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) with adjustments for other possible confounding factors. Maternal active smoking during pregnancy was associated with an approximately twofold increased risk of offspring ADHD, even after adjusting for socioeconomic and perinatal confounding factors (OR 1.8 95% CI 0.9-3.6). However, the association was obviously attenuated when factors regarding parental psychopathological vulnerability were controlled (OR 1.3 95% CI 0.6-2.9). On the other hand, maternal passive smoking during pregnancy failed to show any material association with ADHD. These results suggested that a significant part of the association between maternal smoking during pregnancy, and ADHD might be explained by genetic factors including parental psychopathological vulnerability.     

Maternal drug histories and congenital abnormalities.

We obtained drug histories for the first trimester of pregnancy for 836 mothers of congenitally malformed babies and for an equal number of control mothers of normal babies from the same doctors'' practices. There was an association between the use of a hormonal pregnancy test and the subsequent birht of a malformed baby. There was also a greater use of barbiturates by mothers of affected children compared with mothers of control babies, mainly accounted for by treatment of epileptic mothers with phenobarbitone. For all other drugs usage was similar in both sets of mothers.     

Exogenous sex hormone exposure and the risk for VACTERL association

In several studies investigators have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. A group of malformations, the VACTERL (vertebral, anal, cardiac, trachea, esophageal, renal, limb-acronym) association, has been statistically associated with maternal exposure to exogenous sex hormones during the first trimester of pregnancy. The VACTERL association is a nonrandom group of major malformations that occur together more often than would be expected on the basis of chance. To assess this association, we conducted a case-control study of first-trimester exposure to sex hormones among mothers of 34 infants with the VACTERL association and of 1,024 comparison infants with one or more of ten major malformations or Down syndrome. The study subjects were malformed infants born between July 1970 and June 1979 and registered in a population-based birth defects registry. Information concerning the use of exogenous sex hormones during pregnancy was obtained by systematically interviewing the mothers of the malformed infants. Most of the mothers were interviewed within 6 months of their children's births. Each mother was interviewed within a year of her child's birth. We found an odds ratio of 0.98 (90% confidence limits 0.40, 2.38) for the relationship between VACTERL association and use of any sex hormone in the first trimester of pregnancy. Our study had adequate statistical power to detect a true relative risk of 2.8 or greater.     

Willing the Spirits to Reveal Themselves: Rural Kenyan Mothers' Responsibility to Restore Their Children's Health

Women's contributions to the improvement and maintenance of health are being acknowledged the world over. Recent studies show that most health care is domestic and that women provide nearly 95 percent of this care. Their role as healers, nurses, doctors, folk practitioners, and lay therapists has also been recognized. This research report analyses exorcism as a special function performed by Duruma mothers on behalf of their ailing children. The women represent their children and identify the spirit(s) responsible for illnesses. This role is based on Duruma recognition of the close relationship between mothers and their children, specifically through pregnancy, lactation, and daily contact. For local people who believe in the spirit world, mothers' spirits are held to be responsible for exorcising children's illnesses. Thus health production by Duruma women goes a step further than that of women in other communities. [mothers, childhood illnesses, traditional healing, Duruma, Kenya]     

Associations between Acetaminophen Use during Pregnancy and ADHD Symptoms Measured at Ages 7 and 11 Years

Objective

Our aim was to replicate and extend the recently found association between acetaminophen use during pregnancy and ADHD symptoms in school-age children.

Methods

Participants were members of the Auckland Birthweight Collaborative Study, a longitudinal study of 871 infants of European descent sampled disproportionately for small for gestational age. Drug use during pregnancy (acetaminophen, aspirin, antacids, and antibiotics) were analysed in relation to behavioural difficulties and ADHD symptoms measured by parent report at age 7 and both parent- and child-report at 11 years of age. The analyses included multiple covariates including birthweight, socioeconomic status and antenatal maternal perceived stress.

Results

Acetaminophen was used by 49.8% of the study mothers during pregnancy. We found significantly higher total difficulty scores (Strengths and Difficulty Questionnaire parent report at age 7 and child report at age 11) if acetaminophen was used during pregnancy, but there were no significant differences associated with any of the other drugs. Children of mothers who used acetaminophen during pregnancy were also at increased risk of ADHD at 7 and 11 years of age (Conners’ Parent Rating Scale-Revised).

Conclusions

These findings strengthen the contention that acetaminophen exposure in pregnancy increases the risk of ADHD-like behaviours. Our study also supports earlier claims that findings are specific to acetaminophen.     

Incidence of Neoplasms in Children Born after Influenza Epidemics

Following a recent report that neoplasia of the lymphatic and haematopoietic tissues is commoner than average in children whose mothers have had influenza in pregnancy, the incidence of neoplasms in 1954-68 in children of the Manchester Hospital Region was examined in relation to date of birth. There were no significant differences between cohorts born in different quinquennia. Incidence among children born after six influenza epidemics in 1951-68 was no higher than among other children born in these years. It is concluded that if there is an association between maternal influenza and childhood neoplasia it is probably due to factors such as immunological deficiencies which may predispose independently to both conditions.     

The influence of mother's active smoking during pregnancy on body mass index of newborns

Many investigations have noted bad influence of smoking during pregnancy. In the present article, the influence of mothers smoking during pregnancy on the body mass index (BMI), birth weight and birth length are examined. This retrospective research included 219 children: Group I: 109 children from rural area of east Slavonia (born in General Hospital-Vinkovci) and group II: 110 children from industrial area (born in Zagreb). The questioned subjects were divided into two groups depending on mothers smoking during pregnancy: newborns of mothers who didn't smoke during pregnancy (subgroup A) and newborns of mother who did smoke 10 or more cigarettes per day during pregnancy (subgroup B). Anthropometric parameters (BMI, birth length and birth weight) in newborns of non-smoking mothers were statistically higher (p < 0.05) than in newborns of smoking mothers. Moderate correlation between birth length and birth weight in newborns of non-smoking and smoking mothers from rural area and from non-smoking mothers in urban area was statistically significant, but correlation in the group in newborns of smoking mothers from Zagreb was not statistically significant. Results of this research show that smoking during pregnancy significantly influences the birth weight and birth length. Further investigation is needed, to investigate the lack of correlation between the birth length and birth weight in newborns of smoking mothers from industrial city.     

Genotoxicity of cigarette smoking in maternal and newborn lymphocytes

Tobacco smoke contains a large number of substances known to induce DNA damage and to be hazardous to human health. Several reviews and meta-analyses have reported an association between maternal or paternal smoking habits and genetic-related diseases, such as cancer, in children. The aim of the present study was to evaluate the level of DNA damage in lymphocytes of active- and passive-smoking mothers and in their newborns, using the comet assay. A total of 40 active smokers, 40 passive smokers, and 40 non-smokers, and their respective newborns, were evaluated. The active smokers presented a statistically significant increase of DNA damage when compared to the non-smokers and passive-smokers. No significant difference was observed between passive and non-smoking women. Similar results were detected in newborns. Those born to active-smoking mothers presented higher levels of DNA damage than those from passive- and non-smoking mothers. Additionally, no significant difference was detected between newborns from non-smoking and passive-smoking mothers. Also, no statistically significant difference in DNA damage was observed between mothers and their respective newborns, and a positive correlation in the level of DNA damage was detected between them. Logistic regression analyses showed positive associations between DNA damage, spontaneous abortion and smoking status. In conclusion, our data indicate that tobacco exposure during pregnancy has genotoxic effects for both mother and child, and it can be considered an important risk factor for childhood cancer or other genetic-related diseases.     

Prenatal antiepileptic exposure associates with neonatal DNA methylation differences

Antiepileptic drugs (AEDs) are used to treat a variety of neuropsychiatric illnesses commonly encountered in women during their reproductive years, including epilepsy and bipolar disorder. Despite their widespread use, the impact of prenatal exposure on fetal development remains obscure. To evaluate whether AEDs taken by pregnant mothers influence DNA methylation patterns in their neonates, DNA was extracted from the umbilical cord blood of 201 neonates whose mothers were treated for neuropsychiatric illness during pregnancy and interrogated across 27,578 CpG sites using the Illumina HumanMethylation27 BeadChip. The association of each methylation value with the cumulative duration of prenatal AED exposure was examined using a linear mixed model. The average methylation level across all CpG sites was calculated for each subject, and this global methylation measure was evaluated similarly. Neonates with a longer duration of AED exposure in pregnancy showed a decrease in average global methylation (p = 0.0045). Further, DNA methylation of CpG sites in 14 genes significantly decreased with the duration of prenatal AED exposure even after adjusting for multiple comparisons (FDR < 0.05). For a small subset (n = 19) of these neonates, a second tissue, placenta, was available in addition to cord blood. Methylation of 3 of these 14 CpG sites was also significantly decreased in placental tissue. These novel data suggest decreased DNA methylation in neonates of mothers who took AEDs during pregnancy. The long-term stability and potential impact of these changes warrant further attention, and caution may be warranted before prescribing AEDs to pregnant women.     

Prenatal antiepileptic exposure associates with neonatal DNA methylation differences

Antiepileptic drugs (AEDs) are used to treat a variety of neuropsychiatric illnesses commonly encountered in women during their reproductive years, including epilepsy and bipolar disorder. Despite their widespread use, the impact of prenatal exposure on fetal development remains obscure. To evaluate whether AEDs taken by pregnant mothers influence DNA methylation patterns in their neonates, DNA was extracted from the umbilical cord blood of 201 neonates whose mothers were treated for neuropsychiatric illness during pregnancy and interrogated across 27,578 CpG sites using the Illumina HumanMethylation27 BeadChip. The association of each methylation value with the cumulative duration of prenatal AED exposure was examined using a linear mixed model. The average methylation level across all CpG sites was calculated for each subject, and this global methylation measure was evaluated similarly. Neonates with a longer duration of AED exposure in pregnancy showed a decrease in average global methylation (p = 0.0045). Further, DNA methylation of CpG sites in 14 genes significantly decreased with the duration of prenatal AED exposure even after adjusting for multiple comparisons (FDR < 0.05). For a small subset (n = 19) of these neonates, a second tissue, placenta, was available in addition to cord blood. Methylation of 3 of these 14 CpG sites was also significantly decreased in placental tissue. These novel data suggest decreased DNA methylation in neonates of mothers who took AEDs during pregnancy. The long-term stability and potential impact of these changes warrant further attention, and caution may be warranted before prescribing AEDs to pregnant women.     

Spina Bifida and Potatoes

The results of a retrospective survey of the dietetic and other habits of the mothers of 83 children with spina bifida (mostly schoolchildren with meningomyelocele) were compared with 85 carefully matched controls. The survey was particularly concerned with the consumption of or contact with potatoes by the mothers. No significant differences were found in the amount of potatoes eaten as reported by the mothers (mean for spina bifida group 3·60 1b (1630 g), and for controls 3·98 1b (1800 g) per week). Of the seven other comparisons associated with potatoes only one (obtaining them from the chip shop or restaurant) was significant, the mothers of the children with spina bifida being more likely to obtain some of them from this source.When examining other aspects of diet it was found that the mothers of spina bifida children reported a lower consumption of a number of important foods, though the deficiency was not significant in any instance. These mothers were also significantly more likely to have been prescribed drugs other than iron and vitamins early in pregnancy and to have reported a wider variety of illnesses.The results in general do not support the hypothesis that the quantity of potatoes taken is important. They do lend support to the view that poor dietary habits are associated with a higher incidence of spina bifida irrespective of social class. Furthermore, general ill health in the mother may be implicated.     

Follow-up of children born of bromocriptine-treated mothers

A survey carried out in France at the beginning of 1984 concerning development of children born of mothers treated with bromocriptine (BC) during part or all of the pregnancy showed the absence of any adverse effects of BC in 64 children born from 53 mothers. In 60 cases, BC was prescribed (2.5-7.5 mg/day) for hyperprolactinemia; 23 mothers were treated with BC for 4 weeks or less, and 23 others for 30 weeks or more. After a follow-up of between 6 months and 9 years, all children are normal. Psychological development in the 23 children born to mothers treated with BC during more than 30 weeks of pregnancy actually appears more precocious, with excellent scholastic performance in the oldest.     

Intelligence and physical features of children of women with epilepsy

The teratogenicity of maternal epilepsy has been attributed to several factors, including the antiepileptic drugs taken to prevent seizures during pregnancy, the occurrence of seizures during pregnancy, and the factors in the mother that caused her to have epilepsy. We have addressed the hypothesis that the children of women who have a history of epilepsy (seizure history), but who took no antiepileptic drugs (AED) and had no tonic-clonic seizures in pregnancy, have an increased risk of malformations and diminished intelligence. The frequency of cognitive dysfunction was determined in 57 seizure history and 57 matched control children aged 6-l6 years. The masked evaluation of the children included a physical and neurologic examination and testing with the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a systematic physical examination for the features of the fetal AED syndrome. The evaluation of both parents of each child included a test of reasoning (Ravens Progressive Matrix) and a physical examination. There were no differences between the two groups of children in either IQ scores or physical features; none of the seizure history children was judged to have the "anticonvulsant face" or digit hypoplasia. This study had 80% power to rule out a difference of seven or more IQ points between the two groups, based on a two-sided test at a 5% level of significance. Our confidence in concluding that there was no difference between seizure history and control infants was strengthened by the fact that no statistically significant differences were observed with respect to multiple outcomes, including eight related measures of intelligence. Thirty (53%) of the seizure history mothers resumed taking AED after the birth of the child we evaluated. Additional studies are needed to address the teratogenicity of the antiepileptic drugs as monotherapy.     

Limb reduction defects in the first generation and deafness in the second generation of intrauterine exposed fetuses to diethylstilbestrol

Maternal treatment with diethylstilbestrol (DES) during pregnancy can produce vaginal adenocarcinoma and other abnormalities of the vagina in her daughters when they reach adolescence or adulthood, miscarriages and absence of full term infants. Concerning malformations in newborns whose mothers were treated with DES, clitoromegaly and malformations of the uterus were reported in females and genital lesions in males. However, the frequencies of major congenital anomalies were not greater than expected. We report three cases of limb reduction defects (LRD) in the first generation of children whose mothers were treated with DES during pregnancy, and two children (one male, one female) with deafness in the second generation after intrauterine exposure to DES. The LRD were not associated with other congenital anomalies. The malformed children with LRD were born between 1965 and 1973. The deafness was also isolated. The two mothers who have no hearing problems and who are healthy were exposed in utero to DES in 1963 and 1965, respectively. Their children were born in 1989 and 1994, respectively. In conclusion, the association of LRD and hearing loss with intrauterine exposure to DES could be coincidental. However, some hypothesis may explain these associations. Congenital hearing loss in the second generation may suggest a transgenerational effect.     

Weight growth in infants born to mothers who smoked during pregnancy.

OBJECTIVE--To determine whether maternal smoking during pregnancy causes impairment in growth after birth. DESIGN--Longitudinal study. SETTING--Six medical university centres of six towns of north, central, and south Italy. SUBJECTS--12,987 babies (10,238 born from non-smoking mothers, 2276 from mothers smoking one to nine cigarettes a day, and 473 from mothers smoking > or = 10 cigarettes a day) entered the study. MAIN OUTCOME MEASURES--Difference in weight gain between children born to smoking mothers and those born to non-smoking mothers. Weight was measured at birth and at 3 and 6 months of age. Maternal smoking habit was derived from interview on third or fourth day after delivery. RESULTS--Compared with children born to mothers who did not smoke during pregnancy, the birth weights of children born to mothers who smoked up to nine cigarettes a day were 88 g (girls) and 107 g (boys) lower; in children born to mothers who smoked > or = 10 cigarettes a day weights were 168 g and 247 g lower. At six months of age for the first group the mean weight for girls was 9 g (95% confidence interval -47 g to 65 g) higher and for boys 64 g (-118 g to -10 g) lower than that of children born to mothers who did not smoke. The corresponding figures for the second group were 28 g (-141 g to 85 g) lower for girls and 24 g (-136 g to 88 g) lower for boys. CONCLUSIONS--The deficits of weight at birth in children born to mothers who smoked during pregnancy are overcome by 6 months of age. These deficits are probably not permanent when smoking habit during pregnancy is not associated with other unfavourable variables (such as lower socioeconomic class).     

Maternal geohelminth infections are associated with an increased susceptibility to geohelminth infection in children: a case-control study

Background

Children of mothers infected with soil-transmitted helminths (STH) may have an increased susceptibility to STH infection.

Methods and Findings

We did a case-control study nested in a birth cohort in Ecuador. Data from 1,004 children aged 7 months to 3 years were analyzed. Cases were defined as children with Ascaris lumbricoides and/or Trichuris trichiura, controls without. Exposure was defined as maternal infection with A. lumbricoides and/or T. trichiura, detected during the third trimester of pregnancy. The analysis was restricted to households with a documented infection to control for infection risk. Children of mothers with STH infections had a greater risk of infection compared to children of uninfected mothers (adjusted OR 2.61, 95% CI: 1.88–3.63, p<0.001). This effect was particularly strong in children of mothers with both STH infections (adjusted OR: 5.91, 95% CI: 3.55–9.81, p<0.001). Newborns of infected mothers had greater levels of plasma IL-10 than those of uninfected mothers (p = 0.033), and there was evidence that cord blood IL-10 was increased among newborns who became infected later in childhood (p = 0.060).

Conclusion

Our data suggest that maternal STH infections increase susceptibility to infection during early childhood, an effect that was associated with elevated IL-10 in cord plasma.     

Association between Maternal Smoking during Pregnancy and Low Birthweight: Effects by Maternal Age

Background

Maternal smoking during pregnancy has been consistently related to low birthweight. However, older mothers, who are already at risk of giving birth to low birthweight infants, might be even more susceptible to the effects of maternal smoking. Therefore, this study aimed to examine the modified association between maternal smoking and low birthweight by maternal age.

Methods

Data were obtained from a questionnaire survey of all mothers of children born between 2004 and 2010 in Okinawa, Japan who underwent medical check-ups at age 3 months. Variables assessed were maternal smoking during pregnancy, maternal age, gestational age, parity, birth year, and complications during pregnancy. Stratified analyses were performed using a logistic regression model.

Results

In total, 92641 participants provided complete information on all variables. Over the 7 years studied, the proportion of mothers smoking during pregnancy decreased from 10.6% to 5.0%, while the prevalence of low birthweight did not change remarkably (around 10%). Maternal smoking was significantly associated with low birthweight in all age groups. The strength of the association increased with maternal age, both in crude and adjusted models.

Conclusions

Consistent with previous studies conducted in Western countries, this study demonstrates that maternal age has a modifying effect on the association between maternal smoking and birthweight. This finding suggests that specific education and health care programs for older smoking mothers are important to improve their foetal growth.     

Risk of breast cancer in relation to the interval since last full term pregnancy.

OBJECTIVE--To examine whether the risk of breast cancer is increased by a recent term pregnancy. DESIGN--Population based case-control study. SETTING--Eight areas in the United States. SUBJECTS--Cases were 2279 multiparous women residents of the eight areas aged 25-49 who were diagnosed as having breast cancer during 1980-2. Controls were 2357 multiparous women selected from the same areas by random digit dialing. MAIN OUTCOME MEASURE--Relative risk of developing breast cancer according to the time interval since last full term pregnancy. RESULTS--The distribution of intervals since the last term pregnancy was similar in cases and controls. Adjusted for age, parity, and age at first term pregnancy, the odds ratios observed for categories of years since the last full term pregnancy were: 0-2 years, odds ratio 1.16 (95% confidence interval 0.84 to 1.59); 3-6 years, odds ratio 1.21 (0.95 to 1.54); 7-9 years, odds ratio 1.04 (0.84 to 1.38); > or = 10 years, odds ratio 1.00 (reference). CONCLUSIONS--Among multiparous women aged 25-49 years there was no association between the risk of breast cancer and the time interval since the last full term pregnancy.