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Mythos and logos in Hesiod's Theogony, circa 700 B.C.

Hesiod's Theogony, a completely preserved poem, is dated from about 700 B.C. It depicts partly a development, partly a situation that has arisen in the course of time in the world. It constitutes an attempt to understand the cosmos as the product of a genealogical evolution, which can be seen as a process of successive separation, differentiation, and hierarchization. In this attempted picture of the world myth and reality are inextricably interwoven. Observations of natural phenomena as far as of congenital malformations are accordingly exaggerated and undergone mythical transformation. Entities enumerated in this genealogical poem, no matter whether they stand for parts and concrete phenomena of the physical world or intellectual properties and abstract concepts, behave, think, and act, and are accordingly though of, in anthropomorphic terms. Monogamy, polygamy, endogamy, exogamy, asexual and sexual reproduction, multiple conceptions and births, dominantly and recessively inherited traits, normal and abnormal offspring, and perceptions and notions on cosmogony, isogamy, and teratogenesis could be observed in the writing of the Theogony and interpreted by rational modern concepts.

Genetics↗

Determinants of bronchial responsiveness at school age in prematurely born children.

The bronchial challenge test using isocapnic hyperventilation of cold air (IHCA) was used to evaluate bronchial responsiveness in 63 offspring of multiple pregnancies when they were 8-15 years old. At birth, 27 (43%) children had had intrauterine growth retardation (IUGR, birth weight <-2 SD, or birth weight difference between twin pairs >1.3 SD). The median birth weight was 2,050 g (range, 800-3, 150), and the median gestational age was 35 weeks (range, 28-38). None of the children had asthma or suffered from asthma-like symptoms. In the interpretation of the IHCA test, a fall of 9% or more in the forced expiratory volume in 1 sec (FEV(1)) was considered as abnormal, and these children were classified as "cold air responders." The number of responders was 16 (25%); their baseline FEV(1)/forced vital capacity ratio (FEV(1)/FVC) and forced expiratory flow between 25-75% FVC (FEF(25-75)), but not FEV(1) were significantly lower than the corresponding values in nonresponders. No differences were found in perinatal or neonatal factors between responders or nonresponders. Eight (30%) of the 27 IUGR and 8 (22%) of the 36 appropriate for gestational age (AGA) children were IHCA responders. In particular, IUGR was not correlated with maximal FEV(1) falls following the IHCA test. Respiratory infections after the neonatal period were equally common in IUGR and AGA children; but infections were associated with subsequent IHCA responsiveness. Adenoidectomy, tonsillectomy, and/or myringotomy had been performed significantly more often in the responders than in the nonresponders. At least one of the above invasive procedures had been performed in 20 (32%) of the children; this group was termed the "ENT (ear, nose, throat) surgery group." Fifty-six percent of the responders, but only 26% of the nonresponders, belonged to the ENT surgery group (P = 0.02). We conclude that intrauterine growth retardation or prematurity is not associated with abnormal cold air responsiveness in the IHCA test.

Adolescent↗

Maternal and neonatal behavior.

Maternal and neonatal behavior differs among food-producing mammals, and our management must reflect these differences. Sows will show more elaborate preparturient behavior than the other species as they attempt to build a nest that will last for several days. Because the nest is the focal point of maternal behavior for several days, the sow does not need to recognize her piglets until they are about 1 week of age. Although this facilitates the fostering of piglets between litters, the teat order developed by piglets during the first day or two makes it difficult for alien piglets to suckle when first fostered. Piglets are weaned at a relatively early age, and this results in conflict as neonatal behavior persists in an environment that requires better developed feeding patterns. Restrictions placed on ewes and cows by confinement at the time of parturition may result in their being unable to select an appropriate birth site. Our management must accommodate these needs by providing sites that are protected from the harsh environment and also allow separation from the rest of the flock. This is particularly important for ewes bearing multiple young, for lambs frequently become separated from the ewe while she is caring for another lamb. Both cows and ewes must be allowed to bond to their offspring soon after birth if they are to provide adequate maternal care. Fostering in these species involves manipulation of identifying stimuli to overcome the dam's ability to recognize her own young shortly after birth. Suckling problems, due to pendulous udders on cows and multiple lambs in sheep, may require attention by the stockman shortly after birth. Weaning does not result in major behavioral problems in sheep or beef cattle that are weaned after the young are consuming solid feed on a regular basis. Dairy calves, which are initially weaned onto milk replacer at a very early age, may develop inappropriate sucking behaviors that persist beyond weaning onto a solid diet. Despite our growing knowledge of maternal and neonatal behavior, mortality among piglets, lambs, and calves is still high. However, many of the most recent findings have yet to be incorporated into management procedures or standard practice. As this occurs, we should be able to reduce losses of young animals.

Animals↗

Maternal thyroid disease and risk of birth defects in offspring: a population-based case-control study.

We investigated the relationship between maternal thyroid disease and the risk of birth defects in offspring using data from a large population-based, case-control study. Cases included 4904 stillborn and liveborn infants with major anomalies diagnosed in the first year of life and born to residents of metropolitan Atlanta between 1968 and 1980. Controls included 3027 normal babies, frequency-matched to cases by race, hospital of birth and quarter of birth. We compared mothers of cases and controls regarding history of physician-diagnosed hypothyroidism and hyperthyroidism before the infant's birth, age at diagnosis of thyroid condition, duration of illness, and intake of thyroid medications before and during pregnancy. Information obtained from maternal interviews was evaluated for concordance with hospital records. We adjusted for potentially confounding factors using conditional logistic regression analysis. Overall, there was no relationship between the risk of total birth defects and history of maternal hypothyroidism (odds ratio (OR) = 1.05, 95% C.I. 0.84-1.31), maternal hyperthyroidism (OR = 1.00, 95% C.I. 0.66-1.53), and intake of thyroid hormone and antithyroid drugs before and during pregnancy. In an analysis of 66 specific birth defects and defect groups, we found two statistically significant associations with hypothyroidism and three with hyperthyroidism which may reflect chance findings. In an evaluation of babies with multiple anomalies, we observed a two-fold increased risk with hypothyroidism but no discernible pattern of defects. The absolute risk of major birth defects in offspring of women with history of hypothyroidism can be estimated as 2.1%, a finding at odds with the 10-20% risk cited in the literature.

Abnormalities, Drug-Induced↗

Induction of T cell hyporesponsiveness to Bebaru in mice, and abnormalities in the immune responses of progeny of hyporesponsive males.

Non-specific hyporesponsiveness of cytotoxic T cells to alphaviruses and alloantigens was induced in male mice by multiple, large injections, starting at birth, of gamma-inactivated alphavirus, stock-grown in outbred mouse brains. Offspring of matings between 2 out of 17 treated males and normal females also exhibited significant non-specific hyporesponsiveness (in comparison with normal control mice), without prior exposure to gamma-inactivated alphavirus stock.

Alphavirus↗

Parotid gland enlargement and female reproductive performance in a Papua New Guinea highland population.

Swelling of the parotid salivary glands is commonly observed among males and females of highland Papua New Guinea. Evidence suggests that the condition is related to the highlanders' high starch consumption in the form of sweet potato. In this paper we regard parotid enlargement as an indicator of high energy intake and test its association with two measures of reproductive performance, the number of live births and living offspring, in a sample of 274 women from Lufa in the Eastern Highlands District of Papua New Guinea. Multiple regression analysis including maternal age showed that parotid enlargement is positively correlated with both measures of reproductive performance. Given that parotid gland enlargement in this population is due to persistent starch consumption, and that the condition represents above average energy intake, these results suggest that increases in energy intake relate to increases in reproductive performance in this sample of highland females.

Adult↗

Parental determinants of birth weight.

As part of a study on causes of variation in birth weight, questionnaire data on parental measures were related to offspring birth weights recorded in the Medical Birth Registry of Norway. A genetic analysis of parent-offspring covariances in birth weight indicated that about 60% of the variance in birth weight could be explained by effects of fetal genes, while no effects of maternal genes were detectable. Multiple regression analysis showed that height and weight of both parents and maternal smoking status were associated with variation in birth weight. Socioeconomic status, educational attainment and paternal smoking habit had no independent effects. The adult, parental variables could only explain 10% of the variation in mean offspring birth weight.

Birth Weight↗

Prenatal exposure to carbon monoxide: learning and memory deficits.

Exposing pregnant rats to carbon monoxide (150 parts per million) produced only minor reductions in the birth weights of the pups and gave no evidence of overt teratogenesis. However, behavioral evaluation of learning and memory processes in a two-way avoidance task suggested a functional deficit in the central nervous system of the exposed offspring. Multiple dependent measures and specific control groups confirmed that this deficit was independent of nonassociative or motivational alterations.

Animals↗

Sex ratios of the offspring of patients with multiple sclerosis.

The sex ratios (proportions male) of the offspring of both male and female MS patients produced before disease onset are similar, and closely approximate Caucasian live birth sex ratios. The sex ratio of the offspring of male patients sired after disease onset is significantly lower than these values. In contrast, the sex ratio of the offspring born to female patients after disease onset is non-significantly higher. In short, MS patients produce unusual offspring sex ratios only after disease onset. It is suggested here that they do so as a consequence of a stress-induced reduction in testosterone levels in male patients, and possibly a stress-induced increase in testosterone in female patients. In any case, the data suggest that the sex ratios are a consequence of the disease and not a key to its cause(s).

Adult↗

[Reproductive and developmental toxicity study of suplatast tosilate (IPD-1151T) (4)--Perinatal and postnatal study in rats by oral administration].

In order to assess the effect of suplatast tosilate (IPD-1151T) on pregnancy of the rat, and the post natal development to maturity of the F1 generation, daily doses of 0 (control), 200, 600 and 1800 mg/kg/day were administered orally to female Wistar rats from day 17 of pregnancy to day 21 after delivery. All females were allowed to give birth and rear their young to weaning. F0 dams showed no treatment-related changes in general conditions including the state of delivery or nursing, gestation period, birth rate, or autopsy findings. The dams at 1800 mg/kg/day showed a tendency to reduction in body weight gain and a decrease in food consumption. F1 offspring showed no treatment-related changes in clinical signs on the birth day or during the nursing period, external examination on the birth day, general condition, physical or reflex development, open-field test, water multiple T-maze test, autopsy findings, organ weights, skeletal examination, reproductive ability, or histopathological examination on the reproductive organs of the animals of both sexes that failed to produce pregnancy. The offspring at 1800 mg/kg/day showed a reduction or its tendency in body weight gain. There were no treatment-related changes in any of reproductive parameters of F1 dams including external examination of F2 fetuses. The results suggest that the non-effective dose level of IPD-1151T is 600 and 1800 mg/kg/day for F0 dams in general toxicity and reproductive ability, respectively, and 600 mg/kg/day for F1 offspring in post natal development under the conditions of this study.

Abnormalities, Drug-Induced↗

Birth weight and cardiovascular risk factors in an epidemiological study.

Low birth weight has been proposed as a risk factor for development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease in the adult. To ascertain the extent to which birth weight was associated with cardiovascular risk factors, we examined 620 subjects (median age 48 years) in a cross-sectional study. Of these 317 were offspring of diabetic patients and 303 were offspring of non-diabetic control subjects. Known risk factors for development of cardiovascular disease were correlated to birth weight and examined as dependent variables by multiple linear regression. Age, body mass index (BMI), subjects gender along with parental gender, diabetes status of the parents, and birth weight were independent variables. The variance of the risk factors as dependent variables explained by age, gender, and BMI as independent variables was examined and birth weight was added as an independent variable. We found birth weight was inconsistently correlated to the different risk factors in the different groups of subjects. When adjusted for age, BMI, subject's gender, parental gender, and the diabetes status of the parents, birth weight was negatively correlated to fasting blood glucose. In offspring of diabetic patients the explained variance of risk factors did not change as we added birth weight to the model. In offspring of non-diabetic subjects we found that the explained variance of diastolic blood pressure, fasting blood glucose, HbA1c, and cholesterol increased 1-3% as birth weight was added to the model. We conclude that birth weight may not be a major risk factor for development of hypertension and cardiovascular disease in our population.

Adult↗

Congenital heart defects, maternal febrile illness, and multivitamin use: a population-based study.

We assessed the relation between febrile illness during pregnancy and cardiac defects in the offspring in a population-based case-control study in metropolitan Atlanta. Case infants (905) with cardiac defects were actively ascertained from multiple sources. Control infants (3,029) were infants without birth defects who were selected from birth certificates by stratified random sampling. We compared those whose mothers reported febrile illness from 1 month before pregnancy through the third month of pregnancy with those whose mothers reported no illness during the same period. Febrile illness was positively associated with the occurrence of heart defects in the offspring (odds ratio [OR] = 1.8; 95% confidence interval = 1.4-2.4). When influenzalike illness was the reported febrile illness, the OR was 2.1 (95% confidence interval = 0.8-5.5). The association with febrile illness was strongest for tricuspid atresia (OR = 5.2), left obstructive defects (OR = 2.7), transposition of the great arteries (OR = 1.9), and ventricular septal defects (OR = 1.8). These ORs were generally lower among mothers who used multivitamins during the periconceptional period.

Adolescent↗

Aging unmasks adverse effects of gestational exposure to methylmercury in rats.

The consequences of developmental exposure to methylmercury on behavior in aged animals were investigated. Methylmercury exposure was arranged by placing 0, 0.5 or 6.4 ppm Hg in the drinking water of female rats at least 4 weeks before mating and continuing until post-natal (PN) day 16. Brain Hg concentrations in cohorts of low- and high-dose offspring were 0.5 and 9.1 ppm at birth and 0.04 and 0. 52 ppm at weaning (described in another report). Lever pressing of female offspring was maintained under a Multiple Differential Reinforcement of High Rate 9:4 Extinction schedule of food reinforcement (Mult DRH 9:4 EXT). Under the DRH 9:4 schedule, a food reinforcer was delivered when nine responses occurred within 4 s. Under the Extinction schedule, responding had no programmed consequences. No exposure-related differences in reinforcement rate under the DRH schedule or discrimination between the DRH and extinction components were apparent initially. At 950 days of age, the overall response rates of controls had shown a gradual decline over the previous 500 days to about 80% of their beginning levels, but, otherwise, most controls were healthy. A gradual decline in the reinforcement rate began to appear in low- and high-dose rats at about 500 and 800 days of age, respectively. Microanalyses of the nine-response burst maintained by the DRH schedule revealed that the lever-press duration increased, the inter-response time (IRT) was unaffected, and the time between response bursts increased. Overall, the nine-response burst remained intact as a coherent response unit. The increased time between response bursts caused the decline in reinforcement rate. All rats displayed these effects as they aged, but the mercury-exposed rats did so sooner.

Aging↗

Transplacental effects of 3'-azido-2',3'-dideoxythymidine (AZT): tumorigenicity in mice and genotoxicity in mice and monkeys.

BACKGROUND: When given during pregnancy, the drug 3'-azido-2',3'-dideoxythymidine (AZT) substantially reduces maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1). However, AZT has been shown to be carcinogenic in adult mice after lifetime oral administration. In this study, we assessed the transplacental tumorigenic and genotoxic effects of AZT in the offspring of CD-1 mice and Erythrocebus patas monkeys given AZT orally during pregnancy. METHODS: Pregnant mice were given daily doses of either 12.5 or 25.0 mg AZT on days 12 through 18 of gestation (last 37% of gestation period). Pregnant monkeys were given a daily dose of 10.0 mg AZT 5 days a week for the last 9.5-10 weeks of gestation (final 41%-43% of gestation period). AZT incorporation into nuclear and mitochondrial DNA and the length of chromosomal end (telomere) DNA were examined in multiple tissues of newborn mice and fetal monkeys. Additional mice were followed from birth and received no further treatment until subjected to necropsy and complete pathologic examination at 1 year of age. An anti-AZT radioimmunoassay was used to monitor AZT incorporation into DNA. RESULTS: At 1 year of age, the offspring of AZT-treated mice exhibited statistically significant, dose-dependent increases in tumor incidence and tumor multiplicity in the lungs, liver, and female reproductive organs. AZT incorporation into nuclear and mitochondrial DNA was detected in multiple organs of transplacentally exposed mice and monkeys. Shorter chromosomal telomeres were detected in liver and brain tissues from most AZT-exposed newborn mice but not in tissues from fetal monkeys. CONCLUSIONS: AZT is genotoxic in fetal mice and monkeys and is a moderately strong transplacental carcinogen in mice examined at 1 year of age. Careful long-term follow-up of AZT-exposed children would seem to be appropriate.

Animals↗

Teratologic evaluation of 178 infants born to mothers who attempted suicide by drugs during pregnancy.

OBJECTIVE: To identify the teratogenic risk of large doses of various drugs taken by women in attempting suicide. METHODS: This population-based, prospective, epidemiologic study involved 559 women with pregnancy verified by a serum pregnancy test who were admitted to the toxicologic inpatient clinic in Budapest responsible for providing health services to chemically poisoned individuals from a population of 3 million. Each self-poisoned woman was matched for age and gestational age with a control selected from among participants in periconceptional care. RESULTS: Two of 559 self-poisoned pregnant women died. One hundred seventy-eight infants born to mothers who poisoned themselves during pregnancy either were examined personally or had appropriate medical data available. After excluding eight infants with fetal alcohol syndrome born to heavy-drinking mothers, the rate of congenital abnormalities in study infants (9.0%) did not significantly exceed the rate of control infants (6.1%). Thus, no teratogenic effect of drugs used for self-poisoning could be identified, even though large doses of drugs were used in 27 cases between the 3rd and 8th weeks of fetal development. This sample was not large enough to evaluate single drugs separately. CONCLUSION: Drugs taken by women in attempting suicide do not seem to pose a risk for structural birth defects in the offspring.

Abnormalities, Drug-Induced↗

Congenital and hereditary anomalies in the rhesus monkeys (Macaca mulatta) of Cayo Santiago.

During seven annual birth seasons, from January 1976 to July 1982, 963 infants were born in the Cayo Santiago, Puerto Rico, colony of free-ranging rhesus monkeys (Macaca mulatta). The reproductive rate for mature females, 4 years of age and older, ranged between 74.1% and 84.7%, with a cumulative mean of 80.8% over 7 years. Live births comprised 95.3% of the total and the secondary sex ratio was 109 male to 100 female births. No twinning was observed. Aborted and stillborn monkeys represented 4.7% of all births. The percentage of stillborn females was greater than that of males (4.0% vs. 3.1%). Neonatal death, defined as mortality within 48 hours postpartum, occurred in 0.8% of the live births. Two cases of congenital abnormalities were observed. The first was an anencephalic, acranial female and the second a congenitally blind male. Both infants were born to matrilineally unrelated 7-and 8-year-old multiparous females with no prior history of delivering malformed offspring. The incidence of each defect, based on 963 births, was 0.10%, with a cumulative incidence of 0.20% for all teratisms seen during the study. Multiple occurrences of a rare, nonpathological and nonlethal hereditary anomaly were also seen. Five "golden" macaques were born into two genetically distinct social groups within the last 2 years of observation. The incidence of this phenotype, based on five cases, was 0.52%, 52 times the expected rate (.01%).

Animals↗

Morphometric and neurodevelopmental outcome at age five years of the offspring of women who continued to exercise regularly throughout pregnancy.

OBJECTIVE: To test the hypothesis that continuing regular, vigorous, sustained exercise throughout pregnancy adversely affects morphometric and neurodevelopmental outcome in offspring at 5 years of age. STUDY DESIGN: The offspring of 20 women who exercised were compared with those of 20 physically active control subjects. The women and their offspring were matched for multiple prenatal and postnatal variables known to influence outcome. All women were enrolled before the index pregnancy, monitored throughout, and had clinically normal antenatal, intrapartum, and postnatal courses. Morphometric measures were obtained at birth and at 5 years of age by a single, trained observer. Neurodevelopment was assessed by developmental psychologists masked to maternal exercise status. Data were analyzed with an unpaired Student t test. RESULTS: At birth, head circumference and length were similar, but the offspring of the exercising women weighed less (3.40 +/- 0.80 vs 3.64 +/- 0.70 kg) and had less fat (10.5% +/- 0.9% vs 15.1% +/- 0.6%). At 5 years of age, head circumference and height were similar, but the offspring of the women who exercised weighed less (18.0 +/- 0.5 vs 19.5 +/- 0.6 kg) and had a lower sum (sigma) of five site skinfolds (37 +/- 1 vs 44 +/- 2 mm). Motor, integrative, and academic readiness skills were similar. However, the exercise offspring performed significantly better on the Wechsler scales (125 +/- 2 vs 116 +/- 3) and tests of oral language skills (119 +/- 2 vs 109 +/- 3). CONCLUSIONS: These data refute the hypothesis and suggest that exercise during pregnancy reduces the subcutaneous fat mass of the offspring.

Adult↗