Differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology

BACKGROUND: Atopic dermatitis (AD) often develops in infancy as the first manifestation of the atopic phenotype. Wheezing is also common in infancy, but it is less clear whether infant wheezing should be considered as an atopic phenotype. If infant wheeze and AD share a common aetiology, this would indicate that infant wheezing is an atopic phenotype. OBJECTIVE: To investigate whether potential risk factors for infant wheeze and AD have similar effects on these 2 phenotypes, indicating a common etiology. METHODS: A total of 34.793 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, and prenatal, perinatal, and postnatal risk factors was collected by interview at 12 and 30 weeks of gestation, at 6 and 18 months of age, and by linkage to the Danish Medical Birth Register. Data were analyzed by binary and polytomous logistic regression models. RESULTS: The following variables had significantly differential effects on infant wheezing and AD: parental hay fever, parental asthma, parental AD, sex, maternal age, maternal occupation, smoking during pregnancy, season of birth, birth weight, gestational age, head circumference, breast-feeding, number of older siblings, day care attendance, and pets in the home. CONCLUSION: The majority of risk factors had differential effects on infant wheeze and AD indicative of a different etiology. Infant wheezing does not seem to be etiologically linked to the epidemic of atopic disease, and infant wheezing should not be used as an indicator of the atopic phenotype.     

Prenatal loss in the rat following moderate consumption of alcohol incorporated in a liquid diet

The teratogenic potential of alcohol in humans has now been confirmed, and a characteristic pattern of anomalies (Fetal Alcohol Syndrome) is found in infants born to mothers who are chronic alcoholics. The pathogenesis of the fetal alcohol syndrome is unclear: very little is known about the way alcohol acts during pregnancy and alters fetal growth and morphogenesis. The objective of this investigation was to determine the effects of a widely used ethanol liquid diet in the pregnant rat. The ethanol liquid test diet is based on the Lieber-De Carli formula. 20 Sprague-Dawley rats were matched closely by weights and assigned in pairs to either an alcohol treated or a pair-fed control group. Control animals received the same amount of the liquid diet with maltose-dextrins substituted isocalorically for the ethanol. Graduated tubes were used for the oral delivery of the diets. Ethanol was gradually introduced into the diet as follows: 100 Kcal/l, days 1-2; 200 Kcal/l, days 3-5; 350 Kcal/l, days 6-12. Following this initial treatment period, all animals were then given rodent pellets and tap water ad libitum. The mothers showed no overt signs of gross toxicity. The mean maternal weight gain of the ethanol treated animals did not differ significantly from the controls. The incidence of fetal resorptions was increased, intrauterine growth was not affected and the offspring at term appeared normal. The results indicate that moderate alcohol consumption during early gestation in the rat led to significant prenatal loss but proved to be non-teratogenic.     

Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design

BACKGROUND: Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD. METHOD: Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models. RESULTS: Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD. CONCLUSIONS: While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.     

Effects of alcohol and smoking during pregnancy on infant autonomic control

Prenatal exposure to smoking and alcohol increases the risk for Sudden Infant Death Syndrome (SIDS). Physiological changes associated with these exposures are not well studied. Full‐term infants were tested within the first 3 days of life. We hypothesized that maternal alcohol consumption and/or smoking during pregnancy would alter autonomic nervous system function. Newborns whose mothers smoked during pregnancy had lower beat‐to‐beat heart rate variability in quiet sleep. Infants whose mothers consumed alcohol had lower global heart rate variability, but only in active sleep. Unexposed infants demonstrated increases in heart rate with head‐up tilt and decreases in heart rate with head‐down tilt, but smoking and alcohol‐exposed infants showed no significant responses. These results indicate that autonomic function is altered by prenatal exposure to alcohol and smoking. Such markers may provide early identification of infants at greatest risk for SIDS. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 234–242, 2009     

Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age—in-vivo results

One hundred and sixty-two women with respiratory allergy to animal danders and/or pollens were randomly allocated to a diet consisting of either a very low ingestion of hens' egg and cows' milk or a daily ingestion of one hens' egg and about 11 of cows' milk during the last 3 months of pregnancy. One hundred and sixty-three infants were followed prospectively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly. No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy. The numbers of skin-prick tests positive to ovalbumin, ovomucoid, beta-lactoglobulin and cows' milk were likewise not influenced by differences in the maternal diet during late pregnancy. Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy.     

Maternal alcohol consumption during pregnancy may delay the development of spontaneous fetal startle behaviour

Maternal alcohol consumption during pregnancy may delay the development of spontaneous fetal startle behaviour. Previous study indicated that fetuses exposed to alcohol exhibited a significantly higher incidence of spontaneous startles compared to fetuses not exposed at 20 weeks gestation. This study examined startle behaviour longitudinally from 20 to 35 weeks gestation to determine whether the previous results were due to 'developmental delay' or a 'permanent effect'. The number of spontaneous startles exhibited by fetuses of mothers who drank during pregnancy and fetuses whose mothers did not drink was recorded at 20, 25, 30 and 35 weeks gestation during a 45-min observation. The results indicate that exposure to alcohol during pregnancy significantly increases the exhibition of spontaneous startles by the fetus but across gestation there is significant catch-up in startle behaviour. The results suggest exposure to alcohol delays the natural maturation of spontaneous startle behaviour of the fetus but also has a smaller 'permanent' effect. It is suggested that these effects are mediated by alcohol exerting an effect on the inhibitory pathways controlling startle behaviour.     

Maternal fish intake during pregnancy and atopy and asthma in infancy

BACKGROUND: There is growing evidence that n-3 fatty acids have anti-inflammatory properties and may modulate immune response. Dietary intake of these nutrients during pregnancy could play a role in the risk of asthma and atopy in the offspring. METHODS: Using data from a cohort of women (n=462) enrolled during pregnancy and whose offspring were followed up to 6 years, we evaluated the impact of fish consumption during pregnancy on the incidence of atopy and asthma. Dietary intake was assessed by food frequency questionnaire (42 items) applied by an interviewer. RESULTS: Thirty-four percent of infants had a medical diagnosis of eczema at age 1 year, 14.3% of the children were atopic [based on skin prick test (SPT) at 6 years], and 5.7% had atopic wheeze at age 6 years. After adjusting for potential confounding factors, fish intake during pregnancy was protective against the risk of eczema at age 1 year, a positive SPT for house dust mite at age 6 years and atopic wheeze at age 6 years [odds ratio (OR)=0.73 95% confidence interval (CI) 0.55-0.98, OR=0.68, 95% CI 0.46-1.01 and OR=0.55, 95% CI 0.31-0.96, respectively]. For an increase in fish intake from once per week to 2.5 times per week, the risk of eczema at age 1 year decreased by 37%, and the risk of positive SPT at age 6 years by 35%. Stratification by breastfeeding showed that fish intake was significantly related to a decrease risk in persistent wheeze among non-breastfed children (P for interaction<0.05). No protective effect was observed among breastfed children. CONCLUSION: Our data suggest a protective effect of fish intake during pregnancy on the risk of atopy-related outcomes.     

Effects of prenatal testosterone propionate treatment on saccharin preference of adult rats exposed to ethanol in utero

Prenatal exposure to alcohol feminizes saccharin consumption patterns in adult male rats. To study the involvement of testosterone in this effect, testosterone propionate (TP) was administered to pregnant dams in an attempt to reverse that feminized saccharin consumption pattern in the male offspring. Female offspring were also studied to determine the effect of TP on saccharin preference in normal males and females. During the last week of gestation, dams were administered a liquid diet containing 35% ethanol derived calories, an isocaloric liquid diet containing no ethanol, or Purina Lab Chow. Half of the dams in each group received twice daily injections of TP, the other half were injected with the oil vehicle. Saccharin consumption of adult fetal alcohol exposed (FAE) males from dams administered oil or TP was significantly greater than controls, indicating that the feminized pattern of saccharin consumption of FAE males cannot be overcome with TP administration during the prenatal period. In controls, prenatal TP exposure alone was found to increase adult saccharin consumption in both sexes. Prenatal administration of TP was also found to markedly depress body weight of offspring of dams receiving the liquid diets compared to offspring from dams receiving the same diets plus oil injections. Body weights of offspring from TP or oil injected dams receiving the chow fed diets during pregnancy did not differ.     

Parental alcohol use disorders and alcohol use and disorders in offspring: a community study

BACKGROUND: We examined the association between parental alcohol use disorders and patterns of alcohol consumption and DSM-IV alcohol use disorders in their offspring in a community-based sample of young adults. METHODS: Data are based on baseline and 4-year follow-up data of 2427 respondents aged 14-24 at baseline. Alcohol use and disorders in respondents were assessed using the Munich-Composite-international-Diagnostic-Interview with DSM-IV algorithms. Diagnostic information about parents was collected by family history information from the respondents, and by direct interview with one parent (cohort aged 14 to 17 years only). RESULTS: Although the association between maternal and paternal alcohol use disorders and non-problematical drinking in offspring was minimal, there was a strong effect for the transition to hazardous use and for alcohol abuse and dependence; the effect of parental concordance for transition into hazardous use was particularly striking. Maternal history was associated with a higher probability of progression from occasional to regular use, whereas paternal history was associated with progression from regular to hazardous use. Parental alcoholism increased the risk for first onset of hazardous use and alcohol dependence between the ages of 14-17, and for an earlier onset of the alcohol outcomes in offspring. The impact of parental alcohol use disorders was comparable for male and female offspring. CONCLUSIONS: Parental alcoholism predicts escalation of alcohol use, development of alcohol use disorders and onset of alcohol outcomes in offspring.     

Does light alcohol consumption during pregnancy improve offspring's cognitive development?

We posit that: (i) light alcohol consumption during pregnancy does not improve the cognitive development of human offspring and (ii) observational study outcomes indicating apparent protective effects arise from residual confounding due to socioeconomic status. Our hypotheses counter emerging hypotheses apparent in the epidemiological literature that light alcohol consumption during pregnancy improves offspring’s cognitive development. Determining the plausibility of this proposition is important given its potential to influence women’s alcohol consumption behavior during pregnancy. However, given ethical concerns, it is unlikely that a randomized control trial will be conducted to test this hypothesis. The veracity of alcohol’s purported positive effect on cognitive development is therefore explored here by comparing research evidence on light alcohol consumption to the evidence for folate and DHA supplementation intake during pregnancy. An alternative approach for further testing this hypothesis in observational studies is also suggested.     

Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study

BACKGROUND: Recommendations for primary prevention of allergic diseases in high-risk children include feeding with hydrolyzed formulas if breast-feeding is insufficient. OBJECTIVE: The primary objective of the German Infant Nutritional Intervention study was to investigate the allergy preventive effect of 3 hydrolyzed formulas compared with cow's milk formula in the first 3 years of life in a randomized, double-blind trial. METHODS: Between 1995 and 1998, 2252 newborns with atopic heredity were allocated to a group receiving cow's milk formula, partially or extensively hydrolyzed whey formula, or extensively hydrolyzed casein formula as a milk substitute for the first 4 months if breast-feeding was insufficient. Main outcome parameters were allergic manifestations, atopic dermatitis (AD), and asthma. RESULTS: After 3 years, 396 of 2252 children (17.6%) had dropped out. Breast-fed infants without formula feeding during the intervention (n = 889) were considered separately. A significant reduction of the incidence of AD was achieved with the extensively hydrolyzed casein formula in the intention-to-treat (ITT; n = 1363) and per protocol (PP; n = 904) analyses (ITT: population odds ratio [95% CI], 0.67 [0.45-0.99]; PP: adjusted odds ratio [OR(adj)], 0.53 [0.32-0.88]), and with the partially hydrolyzed whey formula in the PP analysis (ITT: population odds ratio, 0.76 [0.52-1.11]; PP:OR(adj), 0.60 [0.37-0.97]). None of the formulas reduced the incidence of asthma. CONCLUSION: The risk for AD, but not for asthma, can be reduced with certain cow's milk hydrolyzates in high-risk infants when breast-feeding is insufficient. CLINICAL IMPLICATIONS: Early nutritional intervention in high-risk children has significant influence on the incidence of AD, but not of asthma.     

Methodology of a multistate study of congenital hearing loss: preliminary data from Utah newborn screening

The association between prenatal exposure to alcohol and growth is linear, and effects have been measured at levels of exposure that are considerably below one drink per day. Thus, with respect to growth deficits, there is no safe level of drinking during pregnancy. Alcohol exposure during gestation causes growth deficits among the offspring at birth and during infancy. At older ages, however, growth deficits are reported in some, though not all, studies. Exposed offspring who grow up in more privileged environments are apparently able to make up their growth deficits, while those raised in less optimal circumstances do not. This means that there is an interaction between the environment in which a child is raised and the expression of the effects of prenatal alcohol exposure. The long-term implications of growth deficits are not yet well understood.     

The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study,a randomized double-blind trial

BACKGROUND: The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial. OBJECTIVE: We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow's milk formula (CMF) in high-risk infants. METHODS: Between 1995 and 1998, 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and randomly assigned at birth to one of 4 blinded formulas: CMF, partially hydrolyzed whey formula, extensively hydrolyzed whey formula, and extensively hydrolyzed casein formula (eHF-C). The primary end point at 1 year of age was the presence of allergic manifestation, which was defined as atopic dermatitis (AD), gastrointestinal manifestation of food allergy, allergic urticaria, or a combination of these factors. RESULTS: At 12 months per protocol, analysis was performed on 945 infants exposed to study formula: 304 (13.5%) infants had left the study, 138 (6.1%) infants were excluded because of noncompliance, and 865 infants were exclusively breast-fed the first 4 months of life. The incidence of allergic manifestation was significantly reduced by using eHF-C compared with CMF (9% vs 16%; adjusted OR, 0.51; 95% CI, 0.28-0.92), and the incidence of AD was significantly reduced by using eHF-C (OR, 0.42; 95% CI, 0.22-0.79) and partially hydrolyzed whey formula (OR, 0.56; 95% CI, 0.32-0.99). Family history of AD was a significant risk factor and modified the preventive effect of the hydrolysates. CONCLUSIONS: Prevention of allergic diseases in the first year of life is feasible by means of dietary intervention but influenced by family history of AD. The preventive effect of each hydrolyzed formula needs to be clinically evaluated.     

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.     

Feature of food allergy developed during infancy (1)--relationship between infantile atopic dermatitis and food allergy]

BACKGROUND: Most of food allergy (FA) cases during childhood start as infantile atopic dermatitis (AD) at the ages of a few months old. We tried to clarify the association between infantile AD and FA during infancy. METHODS: We analyzed relationship between AD and FA during infancy among patients with 208 cases, who had visited our outpatient clinic with chief complaint of "eczema" from 1998 to 2000. RESULTS: Among 208 cases, 148 cases (71%) were diagnosed as infantile AD, moreover 109 cases (74%) were diagnosed as FA among infantile AD. The most frequent food antigens among infantile AD were egg (72.3%), cow's milk (39.9%), wheat (12.2%) and soybean (7.4%), respectively, in addition to these food antigens, food allergy was widely recognized against peanuts, sesame, meats, buckwheat, fishes and potato. In terms of food antigen, 44 cases with single food allergy against egg were seen out of 46 single allergy cases, whereas 36 cases with double food allergy against both egg and cow's milk were seen in 63 multiple food allergy cases. Although the value of antigen specific IgE against egg and cow's milk was recognized for the diagnosis of food allergy during infancy, even cases with negative IgE against those foods were proved to be food allergy by food elimination and provocation tests. In contrast to egg and cow's milk, positive IgE against rice, soybean, and wheat did not always correlate with the results of the diagnosis of food allergy. Concerning risk factors of AD, family history of any allergy diseases and passive smoking were recognized in comparison with infantile eczema. Neither the nutrition method nor incomplete elimination of diet during pregnancy and lactation had anything to do with the development of AD. CONCLUSION: When infantile AD cases were not improved by environmental control, skin care and application of steroid ointment, it would be important for doctors to think of the possibility of FA.     

Change in food availability during pregnancy: Is it related to adult sudden death from cerebro- and cardiovascular disease in offspring?

Maternal access to food during pregnancy affects birth weight and other characteristics of offspring. It has been suggested that fluctuations in food availability during infancy, ranging from plentiful to starvation, may influence cerebro-cardiovascular risk factors for the offspring during adult life. This study was designed to test the correlation between food availability changes during life before birth and adult sudden death from disease. This was a follow-up study of ancient cohorts in the parish of Skellefteå, Sweden, comprising 7,572 individuals born between 1805 and 1849 and still alive at age 40. Food availability variations in the parish during their prenatal life were ascertained from historical sources, the main outcome measures being overall mortality and mortality from sudden death in the age range 40–70 years. The risk of sudden death was almost doubled for those whose mothers were struck by a poor harvest during the early stages of pregnancy, but who experienced a good harvest toward the end. Yet almost the same over-risk was evident for the converse case: plentiful food supply in early pregnancy followed by a poor harvest toward the end. A stable maternal access to food during pregnancy is important for the offspring's risk of sudden death from cerebro- and cardiovascular disease as an adult. Am. J. Hum. Biol. 12:447–453, 2000. © 2000 Wiley-Liss, Inc.     

Maternal anxiety disorders prior to conception, psychopathology during pregnancy and early infants’ development: a prospective-longitudinal study

Family-genetic studies suggest that anxiety disorders run in families and that mechanisms of familial transmission might act as early as during pregnancy. The aims of the Maternal Anxiety in Relation to Infant Development (MARI) Study are to prospectively investigate the course of pregnancy in women with and without anxiety disorders prior to conception from early pregnancy to postpartum focussing on (a) maternal psychopathology, (b) maternal perinatal health, and (c) offspring outcomes that are supposed to be early indicators/ antecendents for later anxiety disorders. The MARI Study is a prospective-longitudinal study program with seven waves of assessment: T1 (baseline: week 10 to 12 of gestation), T2 (week 22 to 24 of gestation), T3 (week 35 to 37 of gestation), T4 (10 days postpartum), T5 (2 months postpartum), T6 (4 months postpartum), and T7 (16 months postpartum). Overall, N?=?306 pregnant women were enrolled during early pregnancy (T1) and allocated to one of the following initial diagnostic groups: no AD: no anxiety nor depressive disorder prior to pregnancy (N?=?109), pure D: pure depressive disorder(s) prior to pregnancy (N?=?48), pure A: pure anxiety disorder(s) prior to pregnancy (N?=?84), and comorbid AD: comorbid anxiety and depressive disorders prior to pregnancy (N?=?65). Overall, N?=?284 mothers could be retained until T6 (retention rate: 92.8 %) and N?=?274 until T7 (retention rate: 89.5 %). Clinical and psychosocial measures were used including a standardized diagnostic interview (CIDI-V) with dimensional scales and standardized observation paradigms (mother-infant-relationship, infant temperament and neuropsychological development). Dimensional anxiety and depression liability indices were developed to reflect the severity of anxiety and depressive disorders prior to pregnancy and to ease longitudinal modelling. Findings from this study will contribute to improved knowledge about the natural course of anxiety disorders during transition to parenthood and associated outcomes that are assumed to be early indicators of later psychopathology in the offspring. Results are expected to provide new insights into mechanisms of familial transmission and clues for targeted prevention and early intervention.     

The development of allergy in high-risk children

Background It is uncertain as to what extent the development of allergic disease in childhood is predictable during early infancy. A number of environmental factors have been suspected of increasing the risk of acquiring allergy, but the evidence is conflicting. Objective To observe the development of atopy and allergic disease in a cohort of high-risk children so as to determine the importance of certain environmental factors and to study the relationship between early and later manifestations. Methods A cohort of infants, all at high risk of allergy, was followed up from birth to the age of 7 years. In half, selected at random, cow's milk protein was avoided for 4 months. Skin-prick tests were performed and serum IgE measured in infancy and at 7 years, when an AlaTOP test was also performed. Results Skin sensitivity to egg in the first year of life was strongly associated with eczema, asthma, mite sensitivity and serum IgE at the age of 7 years, when mother's atopic history was associated with AlaTOP status, father's atopic history with skin sensitivity, and male sex with both. Maternal smoking during pregnancy was associated positively with IgE at 3 months and negatively with skin sensitivity at 7 years. The development of allergy was unrelated to infant feeding method or number of older siblings. Conclusion Allergic disease in childhood is to a large degree determined before birth or during infancy.     

Effect of maternal ethanol administration on physical growth of the offspring in rats

To study the effects of maternal alcohol consumption on the postnatal growth and physical development of the offspring, female Sprague-Dawley rats (200-220 g) were assigned to one of 3 groups. Group I (alcohol) received alcohol in drinking water (up to 20% v/v) for at least 4 weeks prior to mating, and 30% (v/v) throughout gestation. Purina Lab Chow was ad libitum. Group II (pair-fed) received the same amount of chow as was consumed by alcohol-fed animals, and an amount of corn starch calorically equivalent to the amount of alcohol consumed. Group III (ad libitum) were given chow and water ad libitum. Postnatally all animals were given chow and water ad libitum until day 51 post conception (PC). During pregnancy alcohol provided about 28% of the calories in group I, and the total calorie intakes of the alcohol and pair-fed groups were approximately 60% of that of the ad libitum controls. Weights at birth of offspring of pair-fed and ad libitum control mothers are not significantly different, but the offspring of animals given alcohol show a weight deficit of 28%, compared to the ad libitum controls. During the ensuing four weeks weight shows no indication of catching up to the controls. Total length shows the same pattern as body weight. Skeletal and muscle measurements are significantly less (p less than 0.01) in young of alcohol treated mothers than in those of the ad libitum control mothers. Skeletal maturity in the alcohol group lags behind (p less than 0.01) that of the pair-fed and ad libitum control groups and catch-up is not evident to day 51 PC. It is concluded that young born to animals given alcohol prior to and throughout gestation are physically and developmentally retarded and fail to catch up to the controls during the first four weeks after birth, although not exposed to alcohol postnatally.     

The risk for congenital heart defects in offspring of individuals with congenital heart defects

BACKGROUND: Congenital heart defects (CHDs) occur in approximately 1% of all live births. Although most CHDs are of unknown etiology, a family history of CHDs is a known risk factor, and offspring of individuals with CHDs are at a higher risk of having CHDs. The aim of this study was to investigate the relative risk for CHDs to offspring of individuals with CHDs. METHODS: The prevalence rates of CHDs in offspring of 203 individuals with CHDs and 282 individuals without CHDs were investigated. The study participants completed a questionnaire that included information on medical and reproductive history, lifestyle indicators, and family history of CHDs and other congenital malformations. The prevalence rates of CHDs in offspring were calculated. RESULTS: The prevalence of CHDs was 3.1% (18/575) in offspring of individuals with CHDs and 1.3% (8/589) in offspring of individuals without CHDs. The adjusted odds ratio for CHDs to offspring of parents with CHDs was 1.73 (95% confidence interval [95% CI] 0.89-2.44, p=0.02). The estimated relative risk for offspring to females with CHD was higher than for males [2.3 (95% CI 1.1-4.7, p=0.03) versus 1.31 (95% CI 0.48-4.30, p=0.66), respectively]. There was no suggestion of association between CHDs and maternal smoking, alcohol consumption, and use of medication during pregnancy. CONCLUSIONS: Offspring of parents with CHDs are at a higher risk for CHDs compared with the general population. Couples where one member is affected with CHD should receive pre-conceptional or pre-natal genetic counseling and should be informed about the magnitude of the potential risk of CHDs to the offspring.