Maternal smoking during pregnancy and conduct problems in high-risk youth: a developmental framework

Smoking during pregnancy is associated with adverse consequences for children. Most recently, it has been established as a risk factor for developmental psychopathology, specifically Conduct Disorder (CD). Although this association has been shown to be robust, developmental pathways from exposure to CD have not been established. We examined how prenatal exposure to cigarettes interacts with child and family factors to increase risk of CD symptoms in a longitudinal study of 10-year-old urban, African-American youth (N = 77). The effects of prenatal exposure at school age were moderated by child sex. Boys whose mothers smoked during pregnancy were significantly more likely to develop CD symptoms, but exposure did not increase risk in girls. A similar trend was found during infancy: prenatal smoking was associated with low sociability/negative emotionality only for boys. The effects of smoking during pregnancy were also moderated by the quality of the early caregiving environment. Exposed boys whose mothers were unresponsive during infancy were at increased risk of CD symptoms, but exposed boys with early responsive mothers were not. Prospective studies, with developmentally based measures of behavior across time, are critical for further elucidating pathways from prenatal exposure to cigarettes to the development of clinical disorder. The identification of a potentially modifiable, prenatal risk factor for early onset developmental psychopathology has important implications for prevention.     

Maternal smoking during pregnancy and child emotional problems: the relevance of maternal and child 5-HTTLPR genotype

Serotonin is involved in the development of neural circuits modulating emotional behavior. The short allele (s) of a polymorphism (5-HTTLPR) of the serotonin transporter gene is a risk factor for psychopathology in the presence of environmental stressors. Maternal smoking is associated with growth restriction of the human fetal brain and adverse effects of nicotine on the developing serotonin system have been documented. We hypothesized that maternal smoking interacts with both child and mother 5-HTTLPR genotype as a risk factor for later child emotional problems. In a sample of n?=?1,529 mother-child dyads, smoking habits were assessed by questionnaires during pregnancy. Child emotional problems were measured by the Child Behavior Checklist at the child's age of 3 years. Maternal smoking during pregnancy significantly increased the risk for emotional problems in children carrying the s-allele; β?=?0.24, P?=?0.03 (mother-report), and β?=?0.46, P?=?0.001 (father-report). In children heterozygous at 5-HTTLPR and exposed to maternal prenatal smoking (n?=?79) risk of emotional problems increased with each additional s-allele the mother carried. The associations between 5-HTTLPR and child emotional problems were not moderated by paternal prenatal smoking. These findings imply that the vulnerability for emotional problems in s-allele carriers may already originate in fetal life.     

Maternal smoking in pregnancy alters neonatal cytokine responses

BACKGROUND: Maternal cigarette smoking in pregnancy is an important, common and avoidable exposure that has been linked with elevated cord blood (CB) immunoglobulin E levels and subsequent asthma and allergic disease in childhood. Despite this, there is still very little information about the immunological effects of maternal smoking on the fetus. METHODS: This aim of this study was to compare cord blood mononuclear cell (CBMC) cytokine responses to allergens [ovalbumin (OVA) or house dust mite (HDM)] and mitogens [concanavalin A (ConA) or phytohemaglutinen (PHA)] in neonates whose mothers smoked throughout pregnancy (n = 17) with responses of neonates whose mothers never smoked (n = 40). Cell cultures were stimulated for 24 h and supernatants collected for cytokine detection by enzyme-linked immunosorbent assay [interleukin (IL)-13, IL-6, interferon (IFN)gamma and IL-10]. Cell pellets were also collected for cytokine mRNA detection (IL-5, IL-9, IFNgamma). RESULTS: Maternal smoking in pregnancy was associated with significantly higher neonatal T helper type 2 (IL-13 protein) responses to both HDM (P = 0.01) and OVA (P = 0.035). These effects remained statistically significant after allowing for confounding factors, including the effects of maternal atopy. Similar trends were also seen for IL-9mRNA, IL-5mRNA and IL-6 responses, although these were not statistically significant. Although IFNgamma mRNA responses to PHA (P = 0.015) and ConA (P = 0.025) were lower if mothers smoked in pregnancy, there were no differences in neonatal (Th1) IFNgamma protein responses to allergens or mitogens. CONCLUSIONS: These findings indicate that maternal cigarette smoking can modify aspects of fetal immune function and highlight the need for further studies in this area.     

Maternal smoking and alcohol consumption during pregnancy as risk factors for sudden infant death

A population based case control study was conducted to examine alcohol consumption and maternal smoking during pregnancy and the risk of SIDS in an Irish population. Each SIDS case (n = 287) was compared with control infants (n = 832) matched for date and place of birth for infants born from 1994 to 2001. Conditional logistic regression was used to investigate differences between Cases and Controls establishing Odds Ratio's (OR) and 95% Confidence Intervals (CI). Mothers who smoked were 3 times more likely to have a SIDS Case, and a dose response effect was apparent, with mothers smoking 1-10 cigarettes/day OR 2.93 (CI 1.50-5.71), and those smoking > 10 cigarettes/day OR 4.36 (CI 2.50-7.61). More Case mothers consumed alcohol during pregnancy than Control mothers and, within drinkers, the amount of alcohol consumed was also greater (p < 0.05). A dose response with frequency of drinking was apparent. The adjusted odds ratio for those consuming alcohol in all three trimesters was 3.59 (CI:1.40-9.20). Both of these risk factors are modifiable and need to be incorporated into antenatal education from a SIDS point of view.     

Maternal regulator cells during murine pregnancy

Helper and suppressor cells have been identified in lymph nodes of multiparous pregnant mice using one-way mixed lymphocyte reactions. Primiparous C57Bl and C57Bl/10ScSn females during pregnancy and immediately post-partum gave unaltered MLR reactivity compared to virgin controls when stimulated with paternal or third-party alloantigens. In contrast, multiparity produced strain-dependent alterations in responsiveness: C57Bl females being hyporesponsive while C57Bl/10ScSn mice were hyper-responsive to these antigens. To evaluate regulator activity, the cells were treated with mitomycin C and mixed with normal syngeneic MLR responder populations. Results showed that mixtures of para-aortic and inguinal lymph node cells from pregnant C57Bl females suppressed while those from pregnant C57Bl/10ScSn increased normal virgin MLR responses. Treatment of the regulator cells with anti-Thy-1.2 plus complement showed that suppressor activity was predominantly non-T cell in nature while C57Bl/10ScSn helper activity was wholly T cell-dependent. The regulator cells appeared to be non-specific since they were found in syngeneically as well as allogeneically mated females but covert specificity could not be totally excluded. Embryo resorption in the C57Bl strain was associated with helper rather than suppressor activity. These results suggest that suppressor cells are not essential for the maintenance of pregnancy and that the presence of regulator cells probably reflects the normal homeostatic mechanisms controlling the maternal immune response to the conceptus.     

Increasing selectivity of interlimb coordination during spontaneous movements in 2- to 4-month-old infants

In the field of motor development, a question exists whether spontaneous activity in early infancy serves as a precursor to later-emerging goal-directed behaviors. To answer this question, it is necessary to investigate in detail the properties of spontaneous movements in individual infants. In the current study, we longitudinally examined the spontaneous movements of the end points of the limbs in 6 infants aged 2–4 months. Examinations were carried out every week by using a motion analysis system, and the number of recordings performed for each infant varied from 6 to 9 times. Our major finding was that there was an age-related increase in the velocity and position correlation between arms and between legs, whereas there was no significant change in the velocity, duration, and amplitude of movements of individual limbs. That is, the pattern of spontaneous movements changes from a general activity involving all the limbs to an activity involving more selective interlimb coordination from 2 to 4 months of age. These findings suggest that the dissociated movements of a selective combination of arms or legs during spontaneous movements may be a precursor to functionally dissociated movements during goal-directed behaviors.     

Cardiac changes during sleep in sleep-deprived infants

OBJECTIVE: To evaluate the influence of a brief period of sleep deprivation on cardiac autonomic controls during sleep in healthy infants. DESIGN: Twelve healthy infants with a median age of 8 weeks (range, 7 to 18 weeks) were recorded polygraphically during a morning and an afternoon nap in a sleep laboratory. They were sleep deprived for approximately 2 hours, either in the morning or in the afternoon, before being allowed to fall asleep. Six infants were sleep deprived before the morning nap, and 6 before the afternoon nap. During both naps, their sleep, breathing, and heart-rate characteristics were continuously recorded. Spectral analysis of heart rate was evaluated as a function of sleep stages. Two major peaks were recognizable: a low-frequency component related to sympathetic and parasympathetic activities and a high-frequency component reflecting parasympathetic tonus. The ratio of low-frequency to high-frequency powers was calculated as an index of sympathovagal interaction. RESULTS: When sleep deprived, the infants had an increase in basal heart rate during non-rapid eye movement sleep (P=.021). With sleep deprivation, the ratio of low-frequency to high-frequency powers increased in non-rapid eye movement sleep (P=.005). These findings were consistent with an increase in sympathetic tone. CONCLUSION: Infants exposed to short-term sleep deprivation manifest changes in cardiac autonomic controls during sleep. These findings could be relevant to mechanisms associated with the sudden infant death syndrome.     

Transepidermal water loss during sleep in infants

Transepidermal water evaporation rate (ER) was measured in 207 infants with a mean postnatal age of 12.7 +/- 10.6 weeks. Measurements were made from the forehead with the use of an Evaporimeter during polygraphic sleep recordings performed under standard conditions. ER values were computed in g/m2 X h. Evaporation rates were significantly lower during rapid eye movement (REM) sleep (8.5 +/- 4.4 g/m2 X h), compared to values measured during quiet wakefulness (11.6 +/- 7.4) or non-REM (NREM) sleep (11.2 +/- 7.6). The differences were not related to age, sex, weight, or rectal temperature, as shown by a covariance analysis. These data, recorded in normal infants, indicate the need to consider the state of sleep or wakefulness of the subjects when comparing results of water evaporation studies.     

Maternal and fetal responses to exercise during pregnancy

Exercise has numerous effects on the pregnant woman, the developing fetus, and the placenta. In turn, pregnancy affects the ability to perform physical activity. During pregnancy, increased metabolism at rest results almost exclusively from the gestational increase in mass. Because of this increase, a higher cardiorespiratory effort is required to perform a given amount of external work. One would expect the result to be some training effect, unless a more sedentary lifestyle is adopted. The possibility that maximal O2 consumption may increase during pregnancy has not been studied extensively, yet it is a most important variable that puts other changes in perspective. The sedentary lifestyle commonly adopted in late pregnancy in most western societies may reflect a cultural rather than a physiological phenomenon. In contrast to the physiological alterations in the mother and despite the reductions in uterine blood flow during maternal exercise, physiological changes in the fetus are small. Relatively minor changes occur in the blood concentrations of O2 and substrates during prolonged exhaustive exercise. In addition, despite a temperature increase of 1 to 2 degrees C, there is little evidence for significant alteration in fetal metabolism, cardiovascular hemodynamics, or blood catecholamine concentrations. These observations suggest that acute exercise normally does not represent a major stress for the fetus. Of course, most of the information concerning the fetus is derived from studies in experimental animals, particularly in sheep. In humans the upright position and increased uterine contractibility may affect the fetal responses differently. Virtually nothing is known about the physiological effects of exercise training on the fetus. The most likely effect may be a relatively small reduction in birth weight in some species, but this needs further investigation. Further studies are also needed for a more complete understanding of the mechanisms involved in the remarkably effective mechanisms that account for the relative homeostasis of the fetus during maternal exercise.     

Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants

Animal data indicate that developmental tetrachlorodibenzo-p-dioxin exposure alters immune function; however, the potential immunotoxicity of dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) in the developing infant is an understudied area. The aim of the current study is to examine the association between maternal and early postnatal PCB concentrations in relation to total infant serum immunoglobulin concentrations determined at 6-months-of-age. We selected 384 mother-infant pairs participating in a birth cohort study in Eastern Slovakia. PCB concentrations of several congeners were determined in maternal and cord serum samples and in infant serum samples collected at 6-months-of-age using gas chromatography with electron capture detection. Total immunoglobulin (Ig) G, A, and M concentrations were determined by nephelometry, and IgE concentrations were determined by enzyme-linked immunoassay. Linear regression models with adjustment for potential confounding factors were used to estimate the associations between maternal, cord, and 6-month infant PCB concentrations and total serum immunoglobulins. The median maternal serum concentration of PCB-153 was 140?ng/g lipid, ≈10-fold higher than concentrations in childbearing-age women in the United States during the same period. Maternal, cord, or 6-month infant PCB concentrations were not associated with total serum immunoglobulin levels at 6 months, regardless of the timing of PCB exposure, PCB congener, or specific immunoglobulin. In this population, which has high PCB concentrations relative to most populations in the world today, we did not observe any association between maternal and early postnatal PCB concentrations and total immunoglobulin measures of IgG, IgA, IgM, or IgE.     

Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants

Animal data indicate that developmental tetrachlorodibenzo-p-dioxin exposure alters immune function; however, the potential immunotoxicity of dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) in the developing infant is an understudied area. The aim of the current study is to examine the association between maternal and early postnatal PCB concentrations in relation to total infant serum immunoglobulin concentrations determined at 6-months-of-age. We selected 384 mother-infant pairs participating in a birth cohort study in Eastern Slovakia. PCB concentrations of several congeners were determined in maternal and cord serum samples and in infant serum samples collected at 6-months-of-age using gas chromatography with electron capture detection. Total immunoglobulin (Ig) G, A, and M concentrations were determined by nephelometry, and IgE concentrations were determined by enzyme-linked immunoassay. Linear regression models with adjustment for potential confounding factors were used to estimate the associations between maternal, cord, and 6-month infant PCB concentrations and total serum immunoglobulins. The median maternal serum concentration of PCB-153 was 140?ng/g lipid, ?10-fold higher than concentrations in childbearing-age women in the United States during the same period. Maternal, cord, or 6-month infant PCB concentrations were not associated with total serum immunoglobulin levels at 6 months, regardless of the timing of PCB exposure, PCB congener, or specific immunoglobulin. In this population, which has high PCB concentrations relative to most populations in the world today, we did not observe any association between maternal and early postnatal PCB concentrations and total immunoglobulin measures of IgG, IgA, IgM, or IgE.     

Maternal airways function during normal pregnancy.

Forced vital capacity, Forced expiratory volume in 1 second, expiratory flow rates and V max at different lung volumes were statistically unchanged during the course of pregnancy compared to non pregnant control group. There was no restrictive or obstructive defects during the course of pregnancy despite the added mechanical load to the respiratory apparatus by the gravid uterus.     

Maternal alcohol consumption during pregnancy and fetal startle behaviour

The startle behaviour of the fetus (both spontaneous and elicited) was examined in fetuses of mothers who drank alcohol and mothers who did not. Fetuses exposed to alcohol showed a higher frequency of spontaneous startles and were less likely to exhibit a normal startle in response to a vibroacoustic stimulus. These differences illustrate a teratogenic effect of alcohol on CNS functioning in utero, possibly associated with brainstem damage.     

Sounds elicit relative left frontal alpha activity in 2-month-old infants

As one kind of sounds, human voices are important for language acquisition and human–infant relations. Human voices have positive effects on infants, e.g., soothe infants and evoke an infant's smile. Increased left relative to right frontal alpha activity as assessed by the electroencephalogram (EEG) is considered to reflect approach-related emotions. In the present study, we recorded the EEG in thirty-eight 2-month-old infants during a baseline period while listening to sounds, i.e., human voices. Infants displayed increased relative left frontal alpha activity in response to sounds compared to the baseline condition. These results suggest that sounds can elicit relative left frontal activity in young infants, and that this approach-related emotion presents early in life.     

Sounds elicit relative left frontal alpha activity in 2-month-old infants

As one kind of sounds, human voices are important for language acquisition and human–infant relations. Human voices have positive effects on infants, e.g., soothe infants and evoke an infant's smile. Increased left relative to right frontal alpha activity as assessed by the electroencephalogram (EEG) is considered to reflect approach-related emotions. In the present study, we recorded the EEG in thirty-eight 2-month-old infants during a baseline period while listening to sounds, i.e., human voices. Infants displayed increased relative left frontal alpha activity in response to sounds compared to the baseline condition. These results suggest that sounds can elicit relative left frontal activity in young infants, and that this approach-related emotion presents early in life.