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PubMed1997

Alcohol dehydrogenase-2*3 allele protects against alcohol-related birth defects among African Americans.

Considerable variation in offspring outcome is observed after intrauterine alcohol exposure. The underlying mechanism may include genetic diversity in the enzymes responsible for alcohol metabolism. Of the known genetic polymorphisms, differences at the alcohol dehydrogenase-2 locus (ADH2) are likely most critical because the resulting enzymes are >30-fold different in their kinetic constants. To test whether differences in maternal or offspring ADH2 genotype are determinants of risk for alcohol-related birth defects, maternal-infant pairs (n = 243) were enrolled on the basis of maternal alcohol intake during pregnancy and maternal ADH2 genotype. Infant outcome was measured using the Bayley Scales of Infant Development Mental Index (MDI) at 12 months of age. Drinking during pregnancy was associated with lower MDI scores but only in the offspring of mothers without an ADH2*3 allele (P < .01, analysis of variance, post hoc). The offspring of drinking women with at least one ADH2*3 allele had MDI scores similar to those of nondrinking women of either ADH2 genotype. Lower MDI scores were associated with the three-way interaction among increasing alcohol intake and maternal and offspring absence of the ADH2*3 allele (P < .01, multiple linear regression). We suggest that the protection afforded by this allele is secondary to its encoding of the high-Km/high-Vmax ADH beta3 isoenzyme, which would provide more efficient alcohol metabolism at high blood alcohol concentrations. These observations are supportive of alcohol, rather than acetaldehyde, being the more important proximate teratogen and are the first observations of a specific genetic explanation for susceptibility differences to alcohol-related birth defects.

Abnormalities, Drug-Induced↗

PubMed2005

Maternal obesity and the risk for orofacial clefts in the offspring.

OBJECTIVE: To estimate whether obese women have an increased risk of orofacial clefts in their offspring, compared with average-weight women. DESIGN AND PARTICIPANTS: The study was based on information on maternal body mass index (BMI) collected in early pregnancy and on the existence of orofacial clefts in the offspring, ascertained from multiple sources. The study included 1686 women who had infants with an orofacial cleft and as controls all delivered women (n = 988,171) during the study period, 1992 through 2001. Infants with chromosome anomalies were excluded. The women were divided into underweight (BMI <19.8), average weight (reference group, BMI 19.8 to 26), overweight (BMI 26.1 to 29), and obese (BMI >29). Adjustments were made for year of birth, maternal age, parity, and maternal smoking. RESULTS: Obese (BMI >29) mothers had an overall increased risk for having an infant with orofacial clefts: odds ratio 1.30 (95% confidence interval 1.11 to 1.53). This increased risk was higher when the cleft was associated with other major malformations than when it was isolated. There was no statistically significant difference between the risk estimates for cleft lip and cleft palate. CONCLUSIONS: In this large sample, a positive association appears between maternal obesity in early pregnancy and orofacial clefts in the offspring. The explanation for this association is not known, but a relationship with undetected type 2 diabetes is one possibility.

Adult↗

PubMed2003

Females avoid manipulative males and live longer.

Female mate choice has been demonstrated in a wide variety of species and is now accepted as an important factor in sexual selection. One of the remaining questions, however, is why females prefer specific males. Do females or their offspring benefit from their choice? Or do females choose mates to minimize costs of mating? Here we show that, in the ovoviviparous cockroach Nauphoeta cinerea, where sexual selection has been well documented, females chose mates to avoid costly male manipulation. Females were partnered with preferred or nonpreferred mates, and fitness of the females measured. We found that females lived longer when they mated with preferred males. Female lifespan depended on the rate at which offspring developed from egg to parturition: slower development led to longer life. We manipulated the male pheromone and showed that the component of the pheromone blend that makes males attractive to females also delayed parturition. Thus, like other aspects of sexual conflict in this species, offspring development and thereby the mother's lifespan depended on exposure of females to specific components of the male pheromone. Males benefit from manipulating offspring development because females with accelerated parturition remained unreceptive whereas females with slower developing offspring readily remated after giving birth to their offspring. Our results suggest a hormone-like role for the male pheromone in N. cinerea and provide the first direct evidence of mate choice to avoid male manipulation. This study shows that dominant males may not be preferred males if they are manipulating females, why multiple components with contrasting effects can exist in a sexual signal, and emphasizes the complex fitness relationships that can arise in species with sexual conflict.

Animals↗

PubMed1980

Studies of blood pressure in Tecumseh, Michigan. I. Blood pressure in young people and its relationship to personal and familial characteristics and complications of pregnancy in mothers.

Relationships between blood pressures (BPs) of young people and a number of personal, parental and familial characteristics have been assessed in the population of Tecumseh, Michigan. Systolic and fifth phase diastolic BPs were measured in 4500 persons under 20 years of age at the time of their first examination. Body size, fatness and heart rates of the subjects themselves were significantly related to their age- and sex-adjusted BP scores. The parents' BP scores were also correlated with those of the young subjects, and scores were significantly higher in those whose mothers had had high BP or toxemia in pregnancy of a stillbirth. A weak association between BP and socioeconomic circumstances was suggested by the slightly higher mean BP scores found in sons and daughters of men in blue collar jobs and of men and women with the least education. BP levels were not associated with birth order, sibship size or birth weight nor with the numbers of pregnancies, live births or abortions experienced by the mothers of young subjects. In a stepwise multiple regression, the most important determinants of BP were weight/height ratios of the subjects themselves and BP levels of their parents; a small additional effect of complications of pregnancy in the mother was detectable in the offspring 0--19 years laters.

Adolescent↗

PubMed1999

Pregnancy among women with congenitally corrected transposition of great arteries.

OBJECTIVES: The outcome of pregnancy in congenitally corrected transposition of the great vessels was studied in 22 women. BACKGROUND: Women with congenitally corrected transposition of the great vessels often reach childbearing age. Although reports on the outcome of pregnancy in these women are available, the number of patients is small. METHODS: The medical and surgical databases at the Mayo Clinic were reviewed, and 36 women >16 years old with congenitally corrected transposition of the great vessels were identified. All of them were contacted, and 22 who had pregnancies were identified and the outcome of pregnancy was evaluated. RESULTS: Twenty-two women had 60 pregnancies resulting in 50 live births (83%). Forty-four deliveries (88%) were vaginal and 6 (12%) were by cesarean section. One delivery was premature at 29 weeks. There was one successful twin pregnancy. There were 11 unsuccessful pregnancies. One patient developed congestive heart failure late in pregnancy because of systemic atrioventricular valve regurgitation and required valve replacement in the early postpartum period. One patient had a total of 12 pregnancies, including 1 twin pregnancy and 2 unsuccessful pregnancies. She had multiple pregnancy-related complications, including toxemia, congestive heart failure, endocarditis and myocardial infarction (single coronary artery). No other serious pregnancy-related maternal complications and no pregnancy-related deaths occurred. The mean birth weight of the infants (n = 32) was 3.2 +/- 0.4 kg. None of the 50 live offspring have been diagnosed with congenital heart disease. CONCLUSIONS: Successful pregnancy can be achieved in most women with congenitally corrected transposition of the great arteries. The rate of fetal loss and maternal cardiovascular morbidity is increased. Because of the small number of births, the risk of congenital heart disease in offspring of women with congenitally corrected transposition of the great arteries is uncertain.

Adult↗

PubMed2003

The Maternal Phenylketonuria International Study: 1984-2002.

OBJECTIVE: The purpose of this report is to review the obstetric medical, psychological, and nutritional aspects and outcome of the women and offspring enrolled in the Maternal Phenylketonuria Study, which was established to assess the efficacy of a phenylalanine (Phe)-restricted diet in preventing the morbidity associated with this disorder. METHODS: A total of 382 women with hyperphenylalaninemia (HPA) were enrolled in the study and completed 572 pregnancies. Outcome measures were analyzed with chi2, Fisher exact text, analysis of variance, t test, Wilcoxon nonparametric test, and multiple logistic regression. Outcome measures were stratified according to maternal HPA classification and the time when dietary control was achieved. RESULTS: Optimal birth outcomes occurred when maternal blood Phe levels between 120 and 360 micromol/L were achieved by 8 to 10 weeks of gestation and maintained throughout pregnancy (trimester averages of 600 micromol/L). Mothers with mild HPA achieved similar birth outcomes as mothers who were in control preconceptually and those in control by 8 to 10 weeks of pregnancy. CONCLUSIONS: Before conception, counseling and early entrance into a prenatal care program is essential in achieving optimal fetal outcome in women with HPA. The achievement of pre- and periconceptional dietary control with a Phe-restricted diet significantly decreased morbidity in the offspring of women with HPA.

Analysis of Variance↗

PubMed2004

Reproductive factors and extreme levels of maternal serum alpha-fetoprotein: a population-based study.

BACKGROUND: Levels of maternal alpha-fetoprotein (AFP) are increased during multiple gestations and preeclampsia but little is known regarding AFP levels in relation to other reproductive factors. Consequently, the objective of this work was to describe the possible relationship between AFP levels during pregnancy and maternal age at birth, maternal age at first birth, parity, time since previous birth and gender of the offspring. METHODS: Based on national registries we obtained the reproductive history on a population-based cohort of 44 227 women who had serum AFP levels determined in gestational weeks 14-21 and whose present and previous pregnancies resulted in live-born singletons. RESULTS: Many previous births and an interval of less than 2 years since last birth were significantly associated with extremely low levels of AFP in the mother. However, age at first birth and age at present pregnancy did not influence the AFP level. Women who gave birth to a girl had AFP levels that were 5%[95% confidence interval (CI) 4-6%] lower than those of women who had a boy. Adjustment for birthweight did not significantly affect the estimate. CONCLUSIONS: Low serum AFP levels in pregnancy are significantly correlated with high parity and with a short interval between births. The significantly lower levels of AFP in women who gave birth to girls could indicate a possible gender-specific regulatory mechanism.

Adolescent↗

PubMed2002

[Chromosomal analysis of human sperm using multiple fluorescence in situ hybridization].

Now severe oligoasthenoteratozoospermic (OAT) patients could have offsprings because of the development of technique of intracytoplasmic sperm injection. But some researchers found these patients have increasing frequency of the aneuploid on the chromosome in their sperm. If the spermatozoa with chromosomal aneuploid were fertilized, it would be resulted in a higher rate of recurrent abortion, fetal abnormal and dead birth, so the analysis of the number of sperm chromosome will play an important role in detection on infertile men. There are many new development in the chromosomal analysis of human sperm using multi-FISH, now we have a review on them.

Aneuploidy↗

PubMed1986

Growth and development of children born to patients after cancer therapy.

Eighteen children born to parents who had previously received chemotherapy or radiotherapy were examined for physical health, growth, and development. The immunologic and the hematologic status of these children was also evaluated. Their ages ranged from birth to 15 years. The children had a careful history and physical examination to detect any abnormal symptoms or signs, and the parent's previous treatment was carefully documented. Four sets of parents had children while one of the parents was on active treatment (2 male and 2 female). Of the male patients, one patient's wife had a baby that was "small for gestational age" at birth and had transient failure to thrive; the other child was normal. Of the female patients, one offspring was small for gestational age at birth and the other was normal, but both continued to have failure to thrive for up to 17 months and 26 months, respectively. Ten parents procreated after being treated with chemotherapy and/or radiotherapy, to whom 14 children were born. One child was a stillbirth with multiple congenital abnormalities, and another child had trisomy 13-15 and died 6 months later. The other 12 children were normal at birth, but one child is under the 5th percentile for growth at twelve months of age. In all children studied, immune function test, complete blood count, and viral titers were considered normal for age. In our study, we found that three out of four children born to parents who were on chemotherapy had failure to thrive. Of the 14 children born to parents who conceived after being off chemotherapy, 11 were found to be normal in growth and development. These results imply that there is a high risk of complications in children born to parents who procreated while receiving chemotherapy. Further studies are needed to develop better guidelines for counseling cancer patients who want to have children.

Abnormalities, Multiple↗

PubMed2001

Synthesis of direct and maternal genetic components of economically important traits from beef breed-cross evaluations.

Published information on relative performance of beef breed crosses was used to derive combined estimates of purebred breed values for predominant temperate beef breeds. The sources of information were largely from the United States, Canada, and New Zealand, although some European estimates were also included. Emphasis was on maternal traits of potential economic importance to the suckler beef production system, but some postweaning traits were also considered. The estimates were taken from comparison studies undertaken in the 1970s, 1980s and 1990s, each with representative samples of beef breeds used in temperate agriculture. Weighting factors for breed-cross estimates were derived using the number of sires and offspring that contributed to that estimate. These weights were then used in a weighted multiple regression analysis to obtain single purebred breed effects. Both direct additive and maternal additive genetic effects were estimated for preweaning traits. Important genetic differences between the breeds were shown for many of the traits. Significant regression coefficients were estimated for the effect of mature weight on calving ease, both maternal and direct additive genetic, survival to weaning direct, and birth weight direct. The breeds with greater mature weight were found to have greater maternal genetic effects for calving ease but negative direct genetic effects on calving ease. A negative effect of mature weight on the direct genetic effect of survival to weaning was observed. A cluster analysis was done using 17 breeds for which information existed on nine maternal traits. Regression was used to predict breed-cross-specific heterosis using genetic distance. Only five traits, birth weight, survival to weaning, cow fertility, and preweaning and postweaning growth rate had enough breed-cross-specific heterosis estimates to develop a prediction model. The breed biological values estimated provide a basis to predict the biological value of crossbred suckler cows and their offspring.

Animals↗

PubMed2003

Parental and birth characteristics in relation to testicular cancer risk among males born between 1960 and 1995 in California (United States).

OBJECTIVE: We explored birth and parental risk factors for testicular cancer, examining risk factors for all testicular cancers and by histologic type. METHODS: We linked 1645 testicular cancer cases to live singleton birth certificates, selecting three random controls per case, matched by sex and date of birth. We used conditional multiple logistic regression to assess the mutually adjusted effects of parental and birth characteristics on testicular cancer risk. RESULTS: Sons of Black mothers had a lower risk than those of White mothers (adjusted odds ratio (AOR) = 0.38, 95% confidence interval (CI)=0.12, 1.22). Increasing maternal age was associated with an increased risk in offspring (AOR=1.03 for each year of maternal age, 95% CI=1.01, 1.05). Sons of primiparous and low-multiparous women had increased risks compared to sons of high-multiparous women (AOR=1.22, 95% CI=1.04, 1.44; and AOR=1.31, 95% CI=1.12, 1.54, respectively). Among seminomas, term infants with birth weights of 1500-2499 g had a higher risk compared to term, normal birth weight infants (AOR=2.69, 95% CI=1.40, 5.17; p-value for homogeneity=0.008). CONCLUSIONS: Markers of higher estrogen exposure in the mother (age and parity) are associated with increased testicular cancer risk, and factors associated with fetal growth retardation may be associated with seminoma testicular cancer.

Adolescent↗

PubMed1994

The childhoods of multiple problem adolescents: a 15-year longitudinal study.

This paper examines the life history of a small group of adolescents (3%) who were identified during the course of a longitudinal study of a birth cohort of New Zealand children as displaying multiple problem behaviours at the age of 15 years. This group was characterised by conduct disorder, police contact, substance abuse behaviours, early onset sexual activity, suicidal ideation, mood disorders and lowered self esteem. Statistical biographies of this group of young people showed that many were the offspring of seriously disadvantaged, dysfunctional and disorganised home environments. The implications of these findings for the understanding and treatment of multiple problem behaviours in adolescence are discussed.

Adolescent↗

PubMed1994

Family characteristics and offspring growth in various countries. III. Regression of offspring's stature in relation to parent's and family's factors in Japan and Korea.

1219 offspring 2-48 years old were examined in 578 Japanese and in 672 Korean families. To obtain age-independent values, we used 100-point T-scores. A multiple regression analysis, shows that the (tall) stature of Japanese offspring dependent on the genetic factor (tall stature of parents) in about 13%, on (large) family and apartment size in 0.4-1.5%, for sons also on (good) education and income of parents in 0.72%, and for daughters on (young) age of parents at child birth. In Korea, the (tall) stature of offspring was significantly related to the genetic factor (tall parents), which explained 1.8% of the variance for sons and 13% for daughters, and also to the (large) family apartment size, which explained 2.6% of the variance for sons and 0.84% for daughters. These results show in a different light the results obtained from the analysis of family types, and they provide evidence for the importance of the analysis of sets of traits in the form of family types, going beyond the importance of other multivariate techniques.

Adolescent↗

PubMed1977

[On the transplacental induction of tumours by N-ethyl--N-nitrosourea in different species (author's transl)].

The transplacental activity of N-ethyl-N-nitrosourea (ENU) was tested in rats, rabbits, Syrian golden hamsters, Dzungarian dwarf hamsters, guinea pigs, dogs, and rhesus monkeys. In the offspring of rats, multiple tumours of the central and peripheral nervous system were found in 100 per cent, whereas in rabbits kidney tumours developed. In Syrian golden hamsters, the application led mostly to neoplasms of the thyroid gland. Dzungarian dwarf hamsters and monkeys prooved to be resistant. 9 out of 15 dogs died shortly after birth. In two dogs a carcinoma of the thyreoid gland and one of an ovary were found. Because of an infection, the experiments with guinea pigs were to be interrupted untimely. Therefore, a final answer is impossible. Own results were compared with the findings of other authors. The significance of the different susceptibility in distinct species is discussed.

Animals↗

PubMed1996

Multiple but different genetic factors underlie enflurane and isoflurane requirements studied through backcross analysis in C57BL and ddN mice.

We performed a classic backcross analysis to examine the basic genetic nature of enflurane (ENF) and isoflurane (ISO) anesthetic requirement in two inbred mice strains, C57BL (BL) and ddN. We have previously reported different ENF and ISO anesthetic requirements in these two strains. BL (n = 22) and ddN (n = 26) mice were used as parents and were reciprocally crossed to produce F1 hybrid mice. Each F1 offspring was crossed to its parent to produce backcross siblings (BF1). Anesthetic end point was determined as the loss of righting reflex. Measurement of anesthetic requirement was performed during 8-12 wk after birth. Although ddN mice showed slightly less resistance to ENF and ISO compared with our previous report, they were more resistant than BL mice. Multivariate regression analysis of parents' and F1 hybrids' data revealed that, while maternal factors and factors on autosomes were related to both anesthetics, the factors on the X chromosome were ENF specific. A wide variation in anesthetic requirements among BF1 progeny suggested multifactorial inheritance. The regression equations obtained did not always predict anesthetic requirement in BF1 progeny. These discrepancies may be due to the epistatic interaction of related genes. We conclude that multiple but different genetic factors are involved in determining ENF and ISO anesthetic requirements in BL and ddN mice.

Anesthetics, Inhalation↗

PubMed1999

Immunoglobulin G insulin autoantibodies in BABYDIAB offspring appear postnatally: sensitive early detection using a protein A/G-based radiobinding assay.

Insulin autoantibodies (IAA) are early sensitive markers of pre-diabetes in the young. The aim of this study was to assess whether, using IgG-specific measurement with a protein A/G assay, IAA are already present at birth, and whether this assay is suitable for early autoantibody screening. Cord blood and follow-up samples from offspring of parents with type 1 diabetes included in the BABYDIAB study were analyzed. Although insulin antibodies in cord blood from children of mothers with type 1 diabetes were readily detected and correlated well with levels in the maternal circulation, no insulin binding was detected in 247 cord blood samples from children of father probands. IgG IAA were detected at 2 yr in all 21 children who had multiple islet autoantibodies or who later developed type 1 diabetes, but were confirmed in only 6 of 58 with IAA by the conventional IAA assay in the absence of other islet autoantibodies. False positive IAAs in the conventional assay were often attributable to hemolysis. Hemolysis did not affect protein A/G IAA measurement, and results in whole capillary blood samples were comparable to those in corresponding serum samples (r2 = 0.99). These data show that IgG IAA appear early and after birth, and that the protein A/G IAA assay is sufficiently sensitive for early screening. The specificity of this assay requires further evaluation.

Adolescent↗

PubMed1994

Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants.

Compound null mutations of retinoic acid receptor (RAR) genes lead to lethality in utero or shortly after birth and to numerous developmental abnormalities. In the accompanying paper (Lohnes, D., Mark., M., Mendelsohn, C., Dollé, P., Dierich, A., Gorry, Ph., Gansmuller, A. and Chambon, P. (1994). Development 120, 2723-2748), we describe malformations of the head, vertebrae and limbs which, with the notable exception of the eye defects, were not observed in the offspring of vitamin A-deficient (VAD) dams. We report here abnormalities in the neck, trunk and abdominal regions of RAR double mutant mice, which include: (i) the entire respiratory tract, (ii) the heart, its outlow tract and the great vessels located near the heart, (iii) the thymus, thyroid and parathyroid glands, (iv) the diaphragm, (v) the genito-urinary system, and (vi) the lower digestive tract. A majority of these abnormalities recapitulate those observed in the fetal VAD syndrome described by Joseph Warkany's group more than fourty years ago [Wilson, J. G., Roth, C. B. and Warkany, J. (1953) Am. J. Anat., 92, 189-217; and refs therein]. Our results clearly demonstrate that RARs are essential for vertebrate ontogenesis and therefore that retinoic acid is the active retinoid, which is required at several stages of the development of numerous tissues and organs. We discuss several possibilities that may account for the apparent functional redundancy observed amongst retinoic acid receptors during embryogenesis.

Abnormalities, Multiple↗

PubMed2004

Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities.

BACKGROUND: The 1984-1991 Hungarian randomized controlled trial (RCT) of periconceptional multivitamin supplementation containing folic acid (0.8 mg) showed a significant reduction in the first occurrence of neural tube defects (NTDs), and of urinary tract and cardiovascular abnormalities, but no reduction in orofacial clefts. A controlled cohort trial was designed to confirm or deny these results. METHODS: Supplemented women were recruited from the Hungarian Periconceptional Service using the same multivitamin as the Hungarian RCT. Unsupplemented pregnant women were recruited in the standard regional antenatal care clinics and were matched to each supplemented pregnant woman on the basis of age, socioeconomic status, place of residence, and year of pregnancy. RESULTS: A total of 3056 informative offspring were evaluated in each cohort. The occurrence of congenital cardiovascular malformations (31 vs. 50) was reduced (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.38-0.96) in the supplemented cohort, accounted for mainly by ventricular septal defects (5 vs. 19; OR, 0.26; 95% CI, 0.09-0.72). There was no significant difference (14 vs. 19) in the occurrence of urinary tract defects between the two cohorts, but stenosis/atresia of pelvic-ureteric junction (2 vs. 13) showed a significant reduction (OR, 0.19; 95% CI, 0.04-0.86). The protective effect of the folic acid-containing multivitamin for NTDs (one offspring in the supplemented vs. nine in the unsupplemented cohort) was confirmed (OR, 0.11; 95% CI, 0.01-0.91). There was, however, no protective effect on orofacial clefts or on multiple congenital abnormalities. CONCLUSIONS: The results of this cohort-controlled trial support the findings of the previous Hungarian RCT. The primary prevention of some major structural birth defects by multivitamins containing folic acid or by folic acid has great public health importance.

Adult↗