No maternal effect in childhood leukaemia with neurofibromatosis.
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1. It was found that the environment determined by the hen, namely protein, fat and moisture, had no effect on the growth of the embryo during the first 14 d of development. 2. The amount of protein available influenced growth during the last week of incubation but the amount of fat and water had no effect. 3. The regression of embryo on egg weight for the pooled data of large (mean 62 g) and small (53 g) eggs was 0.85 +/- 0.06 at day 20. 4. Embryos from large eggs were significantly heavier than those from small eggs on day 20: this difference persisted to the end of the experiment at 56 d of age when it had increased to 100 g. 5. A 1-g difference in egg weight was reflected in about a 10-g difference in chick weight at 56 d of age.
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The effect of maternal diabetes on the risk of congenital malformations was investigated in 23,695 pregnancies of white mothers, inclucing 339 patients of the Joslin Clinic, and in 24,742 pregnancies of Negro mothers, drawn from the prospective Collaborative Perinatal Project. Of these, 372 mothers had gestational diabetes and 567 had overt diabetes (before and during pregnancy). Pregnancy outcomes studied included stillbirths and live births. Among core women (excluding the Joslin Clinic cases), the frequencies of diabetic pregnancies were 1.31% and 1.18% for white and Negro mothers, respectively; in both groups, approximately two thirds of these pregnancies had gestational diabetes. There was no increase in malformation risk in the pregnancies of mothers with gestational diabetes over that of nondiabetic mothers in either racial group. However, the risk of malformation for white mothers with overt diabetes was double that of nondiabetic mothers for both major and minor categories of malformations. The incidences of major and minor types of malformations in the pregnancies of white mothers with overt diabetes were 17.94% and 10.94%, respectively, compared to the corresponding incidences of 8.34% and 6.25% for the white nondiabetic group. In Negro mothers with overt diabetes, a smaller increase of risk was seen only in major malformations; the incidences were 13.64% and 8.45% for the diabetic and nondiabetic groups, respectively. The increased risks for malformations were distributed generally throughout the organ systems. Multiple malformations occurred more frequently in the overt diabetic than in the nondiabetic group, suggesting that maternal diabetes must act adversely an an early stage of fetal development. Two cases with the caudal regression syndrome were observed in children of diabetic mothers, whereas none was found among births from nondiabetic mothers. Insulin (or analog) therapy of diabetes neither decreased nor increased the risk of malformation in the fetus. However, duration of diabetes had a significant effect on the malformation risk: the longer the mother had the disease, the higher was the incidence of malformations in the fetus. Paternal diabetes did not contribute to increase in risk. These observations suggest that maternal diabetes per se, through its adverse effects on maternal metabolism, is the responsible factor for the increase of malformations in the offspring.
A new method to estimate the correlation between additive direct genetic effects (Ao) and additive maternal genetic effects (Pm) on body weight was devised to apply to crossfostering data in mice. The correlation between Ao on body weight at 42 days (adult age) and Am on body weight at 12 days (preweaning age) was estimated as 0.561. The nature of this correlation was defined genetically.
Line crossfostering techniques were used to study differences among selected and control lines of mice in direct genetic and postnatal maternal genetic influences on preweaning (day 12) body weight and composition. The lines were selected for high (H6) and low (L6) 6-week body weight and the control line (C2) was maintained by random selection. There were positive correlated responses to selection in both direct genetic and postnatal maternal genetic effects on body weight and weights of all body components (P less than 0.01) except for water and ash weight in H6. The correlated responses in postnatal maternal genetic effects were of the same order of magnitude as those in direct genetic effects. Correlated responses were greater in L6 than in H6. Correlated responses in direct genetic effects were positive (P less than 0.01) for water percent in H6 and ether extract percent in L6, and negative (P less than 0.01) for water percent and lean percent in L6. Correlated responses in postnatal maternal genetic effects were positive for ether extract percent and negative for water percent (P less than 0.01). Correlated responses were far greater in L6 than in H6 and were greater for postnatal maternal genetic effects than for direct genetic effects. Analyses of covariance results indicated line differences in the relative growth rates of the body components.
The effects of smoking during pregnancy on maternal body composition and the fetoplacental unit were investigated serially in well-matched groups of 29 normal, healthy primigravid smokers and 31 nonsmokers. The babies of smokers were lighter by an average of 138 g, and there was a greater proportion of small-for-dates infants among smokers compared with nonsmokers. There was a failure in expansion of mean plasma volume and total body water in patients who smoked throughout pregnancy compared with nonsmokers. No differences were demonstrated in serum protein, intravascular protein mass, serum albumin, intravascular albumin mass, serum electrolytes, serum osmolality, urinary estriol excretion, fetal biparietal diameter, or weekly growth rate between the 2 groups. The concentration of serum heat-stable alkaline phosphatase at 34 and 38 weeks' gestation, during the second stage of labor, and in the early puerperium was significantly higher in smokers. It is postulated that smoking unfavorably alters maternal body composition which is manifested in poor overall performance with the consequent production of smaller infants. The effects of tobacco smoke on the fetus may possibly be mediated via the placenta.
The effects of: a, maternal diet; b, cyclic-3',5'-adenosinemonophosphate (cyclic AMP) and c, clofibrate on hepatic lipogenesis in fetal rats were studied. The experimental diets contained 22% protein, 40--50% carbohydrate, adequate vitamins, and minerals. In addition, the fat-containing diets were supplemented with either 15% corn oil, 25% corn oil, or 5% cholesterol + 10% oleic acid. In the clofibrate feeding studies, 0.3% (w/v) of the ethyl ester was added to a stock ration or to fat-free diet. Lipogenesis was measured in liver slices incubated with [2-14C]pyruvate, [1-14C]acetate, or 3H2O. In addition, activities of lipogenic enzymes were measured in cytosol fractions from liver homogenates. The effec-s of the experimental diets on liver composition were also examined. Lipogenic activity was higher in fetal than in maternal liver. When 15% corn oil was added to the maternal diet, fatty acid synthesis in fetal liver did not decrease as it did in maternal liver. Maternal fasting decreased fetal fatty acid synthesys by 50% when measured with 14C and less than 10% when measured with 3H2O. Although the addition of cholesterol to the maternal diet decreased cholesterol synthesis in maternal liver, no such decrease was observed in fetal liver. Changes in enzyme activities paralleled alterations in lipogenesis in maternal but not in fetal liver. Corn oil feeding or fasting increased the rate of transfer of linoleate from the dam to the fetus. However, accumulation of linoleate in fetal liver did not correlate with a decreased rate of fatty acid synthesis as it did in maternal liver. Maternal hepatic glycogen stores were depleted by fasting, but glycogen levels in fetal liver remained high under these conditions.
The maternal age distribution of 45,X abortuses was significantly lower than that of chromosomally normal abortuses in two co-ordinated studies. One, carried out in Geneva, included 44 X-monosomic abortuses and the other, in Hiroshima, was based on 38 abortuses with a 45,X karyotype. It was deduced that 45,X conceptuses result from either non-disjunction during paternal meiosis or anaphase lag during meiosis or mitosis, and that anaphase lag is more frequent among young couples than among older ones.
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Rodents have been used by many investigators for studies of the effects that maternal diabetes during pregnancy may have on developing fetuses. In Wistar rats, the induction of mild chronic diabetes at the onset of pregnancy by alloxan or streptozotocin results in abnormalities of the nervous system and the heart, recognized in embryos at 11--13 days' gestation. Thus, early organogenesis is evidently affected in these embryos. With a method which enables rat embryos to be cultured in vitro in serum for the period of their early organogenesis, the growth and differentiation of embryos from normal and from diabetic rats can be observed in some detail. It is also possible to compare the effects of normal and of diabetic maternal serum on their development. The results reported here show that embryos from diabetic animals are more likely to be retarded or abnormal than those from non-diabetic animals when cultured in identical serum. The development of both types of embryo is more successful in diabetic than in non-diabetic serum, however, possibly because of the higher glucose content of diabetic serum. Cultures of fetal organs may also be used as test systems for the effects of diabetic maternal serum. Sacral vertebrae, some of which fail to ossify in fetuses from daibetic rats, are now being grown in media containing diabetic serum. It is planned to test the effects of insulin on these cultures.
The effect of glucose on the release of insulin from the pancreas of 19.5- to 21.5-day-old rat fetuses has been studied in utero. Fetal hyperglycemia was induced by a square-wave glucose infusion into pregnant rats over a period of 150 min. The infusion of glucose raised the fetal blood glucose concentration to that of the mother and induced a rapid increase of plasma insulin levels on day 19.5 of gestation. There was a progressive rise of the insulin response as the gestation proceeded, with an increase of the two phases of the hormonal secretion. Maternal hypothermia induced by pentobarbital anesthesia decreased markedly the insulin response to hyperglycemia in the mothers and their fetuses. In fetuses decapitated on day 18.5 and studied on day 21.5, the increase of plasma insulin concentration after a 1-hour hyperglycemia was similar to that in the littermate control fetuses.
Effects of maternal interference on social behavior toward mother and exploratory play were examined in a laboratory experimental paradigm. Subjects were 40 1-year-olds and their mothers. Mothers of the 20 interference-group infants were instructed periodically to physically interfere with their child's independent object play during the first half of the observation session. A postinterference free-play period immediately followed. The 20 control-group infants were permitted by mother to play freely throughout the session. Groups were matched for exposure to play materials. Despite its aversiveness, interference had no subsequent effect on infant social initiatives to mother, responsiveness to mother's social bids, or exploratory play.