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[Multiples births: a continuing problem with assisted reproductive techniques].

Assisted reproductive techniques (ART) such as in vitro fertilisation (IVF), ovulation induction and superovulation followed by insemination have caused a sharp increase in multiple birth prevalence rates. The perinatal morbidity of multiple birth infants is high because of the high incidence of premature birth. The social and psychological problems of multiple birth families are also considerable. In 1990 high-order multiple births were mainly the result of IVF. Although the number of IVF treatments has increased more than the number of other ART treatments, nowadays high-order multiple births are predominantly caused by superovulation. Since 1990 the number of high-order multiple births has stabilised, but the recent sharp increase in ART twins results in a further rise in births of severely preterm ART infants. More restraint should be practised in superovulation treatments to bring down the number of (high-order) multiple births.

Adult↗

Effect of prenatal exposure to ethanol on intestinal development of rat fetuses.

BACKGROUND: Chronic alcoholism in pregnant animals and humans lead to general growth impairment in their offspring, which show multiple birth defects and delayed grown (fetal alcohol syndrome). Here we study the maturation of the intestine under the effect of chronic exposure to ethanol in utero together with associated malnutrition. METHODS: Lactase, acid beta-galactosidase, maltase, and alkaline phosphatase activity profiles were monitored in 18-, 19-, 20-, and 21-day-old fetuses from rats kept under three nutritional treatments before and during gestation: alcohol-treated (25% ethanol in drinking water), fiber-treated (50% cellulose-diluted diet) as a control of the malnutrition associated with chronic alcoholism, and control or normal diet. Serum corticosterone determination and lactase immunolocalization were carried out. To detect possible direct effects of ethanol during the period of mucosa development, intestinal explants from 18-, 19-, and 20-day-old control fetuses were cultured either in the basal medium alone or in a medium containing 25 mM ethanol for 72, 48, and 24 h of incubation, respectively. RESULTS: Following chronic ethanol exposure in utero, intestinal weight and brush-border protein content and the specific activities of lactase, acid beta-galactosidase, maltase, and alkaline phosphatase were significantly lower than those of nutritional controls. Organ culture results, under the assay conditions stated, did not show a direct effect of ethanol 25 mM on prenatal mucosal functionality. CONCLUSIONS: All these results suggest that maternal malnutrition is not primarily responsible for the impaired intestinal maturation in rat fetuses from alcohol-treated mothers; indirect effects of ethanol and/or its derivatives throughout embryo-fetal development could be necessary to promote this intestinal delay.

Alcoholism↗

Less is more: the risks of multiple births. The Institute for Science, Law, and Technology Working Group on Reproductive Technology.

OBJECTIVE: To review the medical, social, and financial risks caused by the birth of multiples that need to be addressed in policy and practice. RESULT(S): Many risks of multiple births are described in the literature. The medical risks to the offspring include death, low birth weight, deformational plagiocephaly, and other physical and mental disabilities. Risks to the women include premature labor, premature delivery, pregnancy-induced hypertension, toxemia, gestational diabetes, and vaginal-uterine hemorrhage. Children born in multiples face difficulty socializing, developmental delays, and behavioral problems, whereas their parents risk exhaustion, depression, and anxiety. In addition to personal costs faced by families, society often bears the financial costs of overburdened hospitals, caps on insurance and/or inability of parents to cover expenses. CONCLUSION(S): Multiple births present potential acute and long-term medical risks to the pregnant woman and her children. However, more long-term follow-up research and more research on outcomes with higher-order multiples are needed. In designing practices and policies to improve the success of IVF while reducing the risk of multiples, it is important to balance the many interests involved. At a minimum, providers and patients need to be educated about the risks of multiple gestation so that steps can be taken to prevent adverse outcomes.

Female↗

[Maternal partiality in attachment with multiple birth children and the related factors].

UNLABELLED: Multiple births are associated with an increased risk of child abuse and neglect. It is reported that only one child is abused in almost cases, and most abusers are the mothers. Maternal partiality regarding attachment has been suggested as the reason for this tendency. This study investigated the prevalence of this phenomenon in families with multiple birth children and identified factors associated with increased risk. The subjects were 231 mothers of multiple birth children. The following results were obtained. 1. Overall, 10.0% of mothers with multiple birth children reported that they didn't equally attach themselves to all their offspring. 2. Mothers who didn't equally attach themselves exhibited significantly poor health conditions and a higher frequency of upper respiratory infections, compared with mothers who demonstrated no partiality. Moreover, they were more likely to complain of severe fatigue (physical and mental) and poor sleeping conditions. 3. The mothers who didn't equally attach themselves to all their multiple birth children had a higher rate of handicapped children. CONCLUSION: Mothers who do not equally attach themselves to all their multiple birth children show poor health conditions and a higher frequency of upper respiratory infections, and complain of severe fatigue and poor sleeping conditions. They also have a higher rate of handicapped children.

Adult↗

Obstetric care and proneness of offspring to suicide as adults: case-control study.

OBJECTIVE: To investigate any long term effects of traumatic birth and obstetric procedures in relation to suicide by violent means in offspring as adults. DESIGN: Prospective case-control study. SETTING: Stockholm, Sweden. SUBJECTS: 242 adults who committed suicide by violent means from 1978 to 1995, and who were born in one of seven hospitals in Stockholm during 1945-80, matched with 403 biological siblings born during the same period and at the same group of hospitals. MAIN OUTCOME MEASURES: Adverse and beneficial perinatal factors expressed as relative risks (odds ratios) and 95% confidence intervals, derived from logistic regression of cases matched with their siblings. RESULTS: For multiple birth trauma the estimated relative risks of offspring subsequently committing suicide by violent means were 4.9 (95% confidence interval 1.8 to 13) for men and 1.04 (0.2 to 4.6) for women. In mothers who received multiple opiate treatment during delivery, the estimated relative risk of offspring subsequently committing suicide was equal for both sexes (0.26, 0.09 to 0.69). CONCLUSION: Minimising pain and discomfort to the infant during birth seems to be of importance in reducing the risk of committing suicide by violent means as an adult.

Adult↗

Increased susceptibility to stress at a psychological assessment of stress tolerance is associated with impaired fetal growth.

BACKGROUND: This study aims to investigate the relationship between birthweight and psychological function, as evaluated by the results of a psychological conscript interview and assessment in young males, including an evaluation of stress susceptibility. METHODS: We performed a retrospective cohort study based on linked birth registry data and data from an assessment of psychological function during evaluation for military service. In all, 90 651 young males born 1973-1975, for whom birth record data were obtained from the Swedish Medical Birth Register, were investigated in addition to psychological stress susceptibility during their conscript evaluation in 1991-1994. The assessment of psychological functioning score, including the assessment of stress susceptibility, was used as the dependent variable in a multiple regression analysis in combination with the following independent variables: birthweight, adult weight, head circumference at birth, month of birth, gestational age, maternal parity, and maternal age. RESULTS: The mean value was 5.1 (SD 1.9) on the psychological assessment scale (range 1-9) of psychological level of functioning including evaluation of stress susceptibility, and 5.3 (1.6) on the general psychological performance (leadership) profile. A positive association was seen between birthweight and better assessment results up to a level of about 4000 g birthweight, but above that an inverse association was seen. Positive correlations (P < 0.001) were seen between psychological assessment score results and birthweight (r = 0.07), gestational age (0.03), head circumference (0.05), and maternal age (0.11), but inverse correlations with maternal parity (-0.11) and birth month of the offspring (-0.04). In multiple regression analyses, the strongest independent correlations were seen between increasing assessment scores and maternal age and birthweight (positive), as well as with maternal parity and offspring adult weight (negative). CONCLUSION: Young males at conscript testing show a better general psychological functioning score derived from psychological assessment, including evaluation of stress susceptibility, with increasing birthweight up to 4200 g. Above that birthweight an inverse association is noticed. Impaired fetal growth is predictive of suboptimal psychological functioning and increased stress susceptibility in males during early adult life.

Birth Weight↗

Acute ethanol exposure during pregnancy in rats: effects upon a multiple learning task.

Pregnant rats received 4.8 g/kg of 20% (v/v) ethanol IP or identical volume of saline during gestational Day 8. No signs of gross physical teratogenesis were evident in the offspring as expressed by litter size, weight and external malformations at birth. However, when offspring were subjected to a multiple fixed ratio-4/differential reinforcement of low rate of responding 10-sec ( FR 4/DRL 10 sec) schedule of reinforcement at 60 days of age, significant differences were observed in the performance of DRL 10-sec schedule that required visual discrimination and response inhibition, but not in the FR 4 schedule that required a relatively simple nondiscrimination task of active-response. Bar press rates were unaffected by prenatal treatment since no differences between groups were found in the number of total responses performed on either component of the multiple schedule. Present results are discussed in terms of either response perseveration or a lower aptitude to deal with low rates of responding-discrimination learning tasks on the animals prenatally exposed to alcohol.

Analysis of Variance↗

Reproductive factors, subfertility, and risk of neural tube defects: a case-control study based on the Oxford Record Linkage Study Register.

Periconceptual exposure to subfertility treatments is increasingly common, raising concerns about the possibility of malformations in the offspring. The authors conducted a case-control study to determine whether subfertility or its treatment was associated with increased risk of neural tube defects (NTDs). Cases were 694 women diagnosed with an NTD-affected pregnancy in Oxfordshire or West Berkshire, England, between 1970 and 1987. Cases were individually matched on maternal year of birth and year of index pregnancy to controls randomly selected from a computerized database. Data on demographic, reproductive, and obstetric factors were abstracted from patient hospital records. Overall, the period prevalences of subfertility and of subfertility treatment were 7% and 3%, respectively, No evidence was found that the risk of NTD-affected pregnancies was increased by either subfertility (odds ratio (OR) = 1.2, 95% confidence interval (CI): 0.7, 2.1) or its treatment (OR = 0.9, 95% CI: 0.4, 2.0). After adjustment, NTD-affected pregnancies were associated with female offspring (OR = 2.3, 95% CI: 1.8, 3.1), multiple birth (OR = 4.8, 95% CI: 1.2, 18.8), and higher numbers of pregnancies (p for trend = 0.005). The findings from this large, population-based study were wholly consistent with those from smaller studies that found no increased risk of NTD associated with exposure to fertility treatments but reported associations with various pregnancy outcomes.

Adult↗

Diabetic embryopathy and fuel-mediated organ teratogenesis: lessons from animal models.

The growing recognition that faulty maternal metabolism during early organogenesis may be implicated in the increased incidence of birth defects in pregnancies complicated by diabetes has prompted worldwide efforts to institute improved preconceptional metabolic regulation. However, the failure to identify the periods of greatest risk for diabetic embryopathy, the mediating teratogen(s), and the underlying mechanisms have complicated attempts to establish precise therapeutic guidelines and targets. Some of the reported in vivo and in vitro experiences with rodent models have been reviewed to derive relevant insights. Substantial literature indicates that diabetes (experimental as well as spontaneous) in pregnant rats and mice is attended by retardation of growth and developmental delay during embryogenesis, and a variable incidence of birth defects. Poor metabolic regulation of the diabetic mother during early organogenesis may also be followed by subsequent resorption of the conceptus at the site of implantation. Vulnerability to diabetes-related resorptions and all other forms of embryopathy appears to begin during the early postimplantation period and is greatest near the onset of neurolation. Overall susceptibility is markedly influenced by genetic factors and may be modified by the antecedent metabolic exposures of the conceptus ("carry-over effects"). Mediation for the anomalous embryo development in pregnancies of diabetic rodents appears to be multifactorial; all the aberrant fuels and fuel-related components of "the diabetic state" (e.g. high glucose; ketones; somatomedin inhibitor(s); osmolality, etc.) which have been tested to date display dysmorphogenic potential ("fuel-mediated organ terato-genesis") in vitro. All tissues in the conceptus appear to be at risk. Dose-response relationships for the individual metabolic teratogens may be influenced by additive and synergistic interactions so that the integrated possibilities cannot be assessed fully by measurements confined to a single fuel or fuel-related component. In the context of the day-to-day variability in diabetes "control" of the poorly regulated mother, and the relatively longer duration of organogenesis, these multifactorial possibilities may account for the multiple birth defects that can occur in individual offspring, and the seemingly non-specific pattern of diabetic embryopathy. Insulin therapy diminishes the dysmorphogenic effects of "the diabetic state" in rodents with experimental or spontaneous diabetes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Early development and spreading of autoantibodies to epitopes of IA-2 and their association with progression to type 1 diabetes.

Autoimmunity precedes clinical type 1 diabetes, and indicators of maturing autoimmune responses may be useful markers for disease prediction. To study this, epitope maturation of autoantibodies to the related protein tyrosine phosphatase (PTP)-like autoantigens IA-2 and IA-2beta was examined in sequential samples from birth in a cohort of 21 offspring developing multiple islet autoantibodies and a similar cohort of 48 relatives of patients with type 1 diabetes recruited at an older age. Initial reactivity in offspring was heterogeneous against the IA-2 juxtamembrane region (10/21) and PTP domains (13/21), and both specificity and extent of initial IA-2/IA-2beta autoantibodies were associated with HLA class II genotype. Intra-IA-2 epitope spreading and/or intermolecular spreading to IA-2beta epitopes were observed in seven offspring. In contrast, in older relatives, IA-2/IA-2beta Ab reactivity was stable and spreading rare. Development of diabetes in children was associated with the presence of Abs to the IA-2 juxtamembrane region (risk by age 5 yr, 52% vs 0% in those with PTP domain Abs only; p < 0.02), and 5 of 26 relatives who developed diabetes had IA-2 Abs only against the juxtamembrane region. The findings show that autoantibody reactivity to IA-2/IA-2beta is dynamic in the young, show that the juxtamembrane region of IA-2 is an early IA-2 autoantibody target, and suggest that these Abs are a risk factor for development of type 1 diabetes in infancy.

Adult↗

Toxoplasma gondii--an environmental contaminant.

Toxoplasma gondii, the causal agent of toxoplasmosis, is a ubiquitous protozoan parasite which has the potential to infect man and all warm-blooded animals. It has as its definitive host the cat. Infections acquired by the human adult are generally subclinical. However, if acquired for the first time during pregnancy, the parasite can invade the developing foetus. Under these circumstances infection can result in abortion, stillbirth or production of live-born offspring with severe multiple organ involvement. Alternatively, offspring can be symptomless at birth but may manifest neurological and ocular sequelae of toxoplasmosis in later life. The degree of clinical involvement is thought to be dependent upon the time of acquisition of infection by the pregnant female. Recent investigations have been concerned with behavioural aspects of predator-prey relationships between cats and rodents. Since these aspects affect the spread of toxoplasmosis in the environment, they have strong epidemiological and ecological implications. Toxoplasma infection in the environment, they have strong epidemiological and ecological implications. Toxoplasma infection in mice is associated with subtle alterations in exploratory behaviour which are almost certainly maladaptive, rendering infected mice more susceptible to predation by cats. Consequently the behavioural abnormalities in mice associated with Toxoplasma infection would be of major importance for the continuation of the life-cycle of the parasite. Ingestion of Toxoplasma-infected mice leads to oocyst production in cats and this opens up the well-known pathway whereby Toxoplasma infection reaches the human species.

Animals↗

Genital mycoplasmas and birth weight in offspring of primigravid women.

The relationship between colonization of pregnant women by Ureaplasma and Mycoplasma and the outcome of pregnancy in a study of 104 women is reported. There were eight abortions but no multiple births or stillbirths. Excluding abortions, the mean gestational length was 39.6 weeks and the corrected mean birth weight was 3.28 kilograms. There was no relationship between maternal colonization by genital mycoplasmas and reduction in birth weight of the offspring, but five of the eight women who aborted harbored Ureaplasma, suggesting an increased trend toward abortion in women harboring Ureaplasma.

Birth Weight↗

Toward a theory of human multiple birthing: sociobiology and r/K reproductive strategies.

Using symbols from population biology, a continuum of reproductive strategies can be distinguished ranging from r, the production of large numbers of offspring provided with minimal care, to K, the production of few offspring nurtured intensively. While all humans are at the K end of the continuum, some are proposed to be more so than others. If multiple egg production is part of an r-reproductive strategy, certain facts may be ordered. Compared to mothers of singletons, for example, mothers of DZ twins have a lower age of menarche, a shorter menstrual cycle, a higher number of marriages, a higher rate of coitus, more illegitimate children, a closer spacing of births, a greater fecundity, more wasted pregnancies, a larger family, an earlier menopause, and an earlier mortality. Further, all twins have a shorter gestation period, a lower birth weight, and a greater incidence of infant mortality, with DZ twins having a greater frequency of health disorders, a higher mortality rate, and a lower rate of enrollment in volunteer registries. Multiple birthing also occurs more frequently in families of lower than of higher social status, and in those of African than of European and especially than of Oriental descent.

Animals↗

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 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↗