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Reduced reproductive efficiency in mice with schistosomiasis mansoni and in uninfected pregnant mice injected with antibodies against Schistosoma mansoni soluble egg antigens.

Female CBA/J mice were infected with approximately 15 cercariae of Schistosoma mansoni and mated with normal syngeneic males 7 weeks later. Uninfected mice were bred in parallel, and both groups were subsequently bred several more times. Pregnancies were documented by formation of vaginal plugs, and daily records were kept concerning the status of the pregnancies, delivery, and offspring. One hundred thirty-two pregnancies in uninfected mice resulted in 101 (77%) viable litters. In contrast, 133 pregnancies in mice infected with S. mansoni lead to 45 (34%) viable litters. The decreased number of viable litters born or raised by infected mothers resulted from maternal death during pregnancy (5%), spontaneous abortion (20%), and infanticide (42%). Observations of multiparous infected mice indicated that this reduced rate of production of viable, surviving offspring was not different in subsequent pregnancies nor influenced by the duration of the infection. At 2 weeks of age, offspring of infected mice weighed significantly less than offspring of equal-sized litters from uninfected mice, but this weight differential was not sustained beyond 2 weeks of age. Subsequent studies compared the effects on uninfected pregnant mice of injections of antibodies against S. mansoni soluble egg antigens (immunoaffinity-purified from sera of mice with 16 week S. mansoni infections) vs. normal mouse immunoglobulin. After repeated injections of these antibodies during multiple pregnancies, lowered reproductive efficiencies (37%) were observed as compared to parallel studies of pregnant mice injected with normal mouse immunoglobulin (67%).

Animals↗

Factors affecting risks of congenital malformations. II. Effect of maternal diabetes on congenital malformations.

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.

Central Nervous System↗

Cerebrocortical microdysgenesis is enhanced in c57BL/6J mice exposed in utero to acetazolamide.

A small percentage of C57BL/6 mice spontaneously develop focal collections of neurons in the molecular layer of the cerebral neocortex. Usually only one "ectopia" is present in each affected brain. Studies in other mouse strains have shown that these ectopias occur before birth, probably because of a breach in the superficial glial membrane during neuronal migration. The ectopias are heritable and are caused by multiple genes. C57BL/6J mice exposed prenatally to acetazolamide, a carbonic anhydrase-specific inhibitor and teratogen, develop an increased frequency of limb malformations, especially in the right forelimb. In the present study, we hypothesized that the prevalence and severity of ectopias would be increased in acetazolamide-exposed mice because carbonic anhydrase plays a key role in brain development. Further, we wanted to determine whether there was a correlation between the side of limb deformity and the hemisphere containing an ectopia. Thus, we injected C57BL/6J time-mated mice intraperitoneally on embryonic day 9 with either sodium acetazolamide (750 mg/kg) or water. Histological analysis of the brains from 105 acetazolamide-exposed offspring and 89 control offspring revealed no difference in the overall prevalence of cerebrocortical ectopias between the acetazolamide and control groups: 34% of the acetazolamide-exposed and 28% of the control mice had ectopias. There was, however, a striking difference in the shape and size of ectopias: 67% of the ectopias were large in the acetazolamide-exposed group in comparison to 32% in controls. The acetazolamide-exposed offspring also were more likely to have multiple ectopias. Thus, there may be a genetic predisposition for developing ectopias in some mouse strains, but epigenetic factors such as prenatal exposure to acetazolamide can influence their severity.

Acetazolamide↗

The association of maternal smoking with age and cause of infant death.

Linked birth certificate and infant death certificate data from Missouri for 1979-1983 were used to explore the association of maternal smoking with age and cause of infant death. The data included 305,730 singleton white livebirths, of which 2,720 resulted in infant deaths. Using multiple logistic regression to control for the confounding effects of maternal age, parity, marital status, and education, the authors found that smoking was associated with both neonatal and post-neonatal mortality and with each cause of death except congenital anomalies. The adjusted odds ratio for smoking was higher for postneonatal deaths than neonatal deaths and was particularly high for two causes: respiratory disease (odds ratio = 3.4) and sudden infant death syndrome (odds ratio = 1.9). A moderate odds ratio (about 1.4) was found for causes attributed to the International Classification of Diseases, 9th Revision Perinatal Conditions Chapter. Although the associations for neonatal deaths and perinatal conditions were partially attributable to the effect of maternal smoking in lowering birth weight, virtually none of the excess respiratory mortality and sudden infant death syndrome mortality among the offspring of smokers was attributable to birth weight differences between the infants of smokers and nonsmokers. This suggests that respiratory deaths and sudden infant death syndrome deaths may be related to the effect of passive exposure of the infant to smoke after birth.

Adolescent↗

Effect of magnesium sulfate treatment on neonatal bone abnormalities.

OBJECTIVE: It has been reported that neonatal bone abnormalities occur as a result of long-term intravenous magnesium administration (MgSO4) to pregnant women. The purpose of this retrospective study was to evaluate the frequency of such abnormalities and the clinical background of both mothers and neonates. PATIENTS AND METHODS: We reviewed maternal (114 cases) and neonatal (139 cases) charts from all pregnant women who received intravenous MgSO4 administration for preterm labor and preeclampsia between June 1, 1992, and May 31, 1994. All chest X-ray films were obtained within 48 h after birth and reviewed by a doctor who was unaware of the clinical data. Radiolucent transverse metaphyseal bands of the proximal humerus were considered as abnormal. The subjects were divided into affected (group 1 and 1a) and unaffected (group 2 and 2a) groups. Neonates born to pregnant women given no MgSO4 at the same period, were considered as control. RESULTS: The total number of bone abnormalities in the offspring of mothers receiving MgSO4 amounted to 13 (11.4%). Group 1 consisted of 13 cases and group 2 of 101 cases. In the control group bone abnormalities were not observed (p < 0.05). Significant differences were found between groups 1 and 2 in the gestational ages at the start of MgSO4 administration and at delivery, and in the total duration of administration and doses of MgSO4. Also, cases of multiple pregnancy and pregnancy complicated with impaired glucose tolerance were more prevalent in group 1. According to the results obtained from 139 neonates, cases showing low Apgar and high magnesium score and those receiving respiratory support were more noticeable in group 1a (15 cases). CONCLUSIONS: The gestational ages and the total doses of MgSO4 in pregnant women were the main factors related to the onset of neonatal bone abnormalities, but other factors also have a possible bearing on the condition. In addition, the cases with onset of bone abnormality seemed to be associated with symptoms attributable to hypermagnesemia of neonates.

Bone Development↗

DNA polymorphism-diet-cofactor-development hypothesis and the gene-teratogen model for schizophrenia and other developmental disorders.

Three problems in identifying genes causing schizophrenia and other developmental disorders may be locus heterogeneity, high disease allele frequency, and unknown mode of inheritance. The DNA polymorphism-diet-cofactor-development (DDCD) hypothesis addresses the first two. The gene-teratogen model addresses the third. The DDCD hypothesis is that schizophrenia results in part from brain abnormality in utero from the aggregate effect of multiple mutations of small effect of genes related to important cofactors (e.g., folate, cobalamin, or pyridoxine) potentiated by maternal dietary deficiency of these cofactors and by pregnancy. The effect results from insufficiency of the cofactors and from resulting effects such as impaired DNA synthesis, immune deficiency, effects on niacin and serotonin metabolism, and teratogens, e.g., hyperhomocysteinemia. The hypothesis addresses all of the unusual features of schizophrenia: e.g., decreased brain gray matter, birth-month effect, geographical differences, socioeconomic predilection, association with obstetrical abnormalities, decreased incidence of rheumatoid arthritis, and association with famine and viral epidemics. In the gene-teratogen model, a teratogenic effect in utero produces a developmental disorder through a teratogenic locus and a modifying or specificity locus, as well as through environmental factors. An example is the major intrauterine effect seen in offspring of phenylketonuric mothers. Thus, the mode of inheritance of genes acting prenatally may in some cases be fundamentally different from that of genes acting postnatally. The model is interesting because it is simple and because teratogenic loci will be difficult to locate by conventional linkage mapping techniques due to misspecification of the affection status of both mother and affected children. A new study design is suggested for identifying teratogenic loci.

Alleles↗

Relationship of paternal factors to birth weight.

OBJECTIVE: To investigate the relationship between paternal characteristics and birth weight. STUDY DESIGN: A total of 241 gravidas with uncomplicated, singleton, term pregnancies were studied. Maternal demographic and pregnancy-specific characteristics were used to calculate the expected birth weight for each fetus using a previously validated birth weight prediction equation. The additional independent predictive value of 4 paternal variables was assessed using multiple regression. RESULTS: Before adjustment for other variables, paternal height and weight significantly correlated with birth weight, but paternal age and body mass index did not. After controlling for maternal and pregnancy-specific factors that are known to influence fetal weight, only paternal height was significant as a predictive variable. The proportion of variance in birth weight that could be independently explained by paternal height was 2%. A 10-g gain in fetal weight was associated with each centimeter of increase in paternal height (P < .02). Using the resulting combination equation that included paternal height as a variable, 31% of the variance in term birth weight could be explained, and birth weights could be accurately predicted to within +/- 8.3% (+/- 288 g). Fathers with heights 2 SD above and below the mean had the term birth weight of their offspring increased and diminished by 125 g, respectively. CONCLUSION: Paternal height explains an independent portion of the variance in term birth weight among normal newborns of up to 250 g that cannot be explained by other maternal or pregnancy-specific factors. Paternal age, weight and body mass index do not independently influence birth weight.

Adult↗

[Management of triplet and quadruplet pregnancies].

The management of multiple pregnancies is analyzed on the basis of the results in a series of 34 triple pregnancies and 5 quadruple pregnancies. Hypertension of pregnancy occurred in 6 of the patients, a threat of severe premature delivery in 15 patients. Severe cardiovascular complications, related to beta-mimetics, occurred in one case. Delivery was virtually always by Caesarian, with a mean gestational age of 31 weeks and 5 days for the triple pregnancies and 30 weeks and 5 days for the quadruple pregnancies. In 8.4% of cases, the offspring showed severely retarded intrauterine growth. The total mortality rate was 11.7% for the triple pregnancies and 15% for the quadruple pregnancies. Most deaths during the neo-natal period occurred in offspring from 4 pregnancies in which delivery occurred before 28 weeks of amenorrhea. After 28 weeks of amenorrhea, the adjusted total mortality was 4.2% for the triple pregnancies and no offspring of a quadruple pregnancy died. The prevention of the risk of threatened very early premature delivery led us to propose routine hospitalization after 26 weeks of amenorrhea, in order to improve the foetal prognosis in this age group. Carrying out a Caesarian later, after about 34 weeks of amenorrhea for the triple pregnancies and 32 weeks of amenorrhea for the quadruple pregnancies, made it possible to reduce the incidence of delayed intra-uterine growth and in utero foetal death and also made it possible to schedule the date of delivery. Good obstetric-pediatric coordination is also an essential factor in improving the prognosis for these high-risk pregnancies.

Adult↗

Micronutrients and fetal growth.

Fetal undernutrition affects large numbers of infants in developing countries, with adverse consequences for their immediate survival and lifelong health. It manifests as intrauterine growth retardation (IUGR), defined as birth weight <10th percentile, which probably underestimates the number failing to achieve full growth potential. Birth weight is a crude measure of the dynamic process of fetal growth and does not capture effects of fetal undernutrition on body composition and the development of specific tissues. The link between maternal nutrition and fetal nutrition is indirect. The fetus is nourished by a complex supply line that includes the mother's diet and absorption, endocrine status and metabolism, cardiovascular adaptations to pregnancy and placental function. Micronutrients are essential for growth, and maternal micronutrient deficiency, frequently multiple in developing countries, may be an important cause of IUGR. Supplementation of undernourished mothers with micronutrients has several benefits but there is little hard evidence of improved fetal growth. However, this has been inadequately tested. Most trials have only used single micronutrients and many were inconclusive because of methodological problems. Several food-based studies (some uncontrolled) suggest benefits from improving maternal dietary quality with micronutrient-dense foods. One trial of a multivitamin supplement (HIV-positive mothers, Tanzania) showed increased birth weight and fewer fetal deaths. Well-conducted randomized controlled trials of adequate sample size and including measures of effectiveness are needed in populations at high risk of micronutrient deficiency and IUGR and should include food-based interventions and better measurements of fetal growth, maternal metabolism, and long-term outcomes in the offspring.

Developing Countries↗

Academic mothers have a pronounced seasonal variation in their offspring sex ratio.

OBJECTIVES: Environmental and socio-demographic factors can influence the variation of the human sex ratio at birth (SRB = the ratio of males to males plus females). In particular, findings of seasonal, parental education, birth order, and maternal age effects on the SRB are not always in agreement, and a number of works report minimal variation. SETTING: Here, we investigated the seasonality of SRB in academic and non-academic mothers employed at the University of Vienna, and who gave birth between 1963 and 2000 (n = 1932 births). METHODS: All data were available from an anonymous employee database. RESULTS: Both groups, academic and non-academic mothers do not differ between their overall SRB. In academic mothers the SRB is significantly (P = 0.004) increased during the springtime and decreased during the summertime. Although in non-academic mothers the trend is comparable, it is far less pronounced and not significant (P = 0.345). When a multiple logistic model was applied to the data of academic mothers the only significant influencing factor on the SRB is the season, while birth order of children and mothers' age at childbirth has no effect. None of the three independent variables influence the SRB in non-academic mothers. MAIN FINDINGS: These findings suggest a more flexible SRB rate in academic mothers than in non-academics within the seasons. CONCLUSION: We conclude that the significant seasonal variation of the SRB in academic women cannot be merely interpreted as an effect of socio-economic status but more likely as the interaction between socio-economic and environmental working conditions.

Austria↗

Fertility in South Australian commercial Merino flocks: relationships between reproductive traits and environmental cues.

High levels of reproductive loss have been reported in commercial Merino flocks (n=68) from the cereal/livestock and high rainfall zones in South Australia (Kleemann DO, Walker SK. Fertility in South Australian commercial Merino flocks: sources of reproductive wastage. Theriogenology 2005;63:2075-88). Relationships between reproductive traits (estrus, ovulation, fertility, fecundity, lamb survival) and environmental end points (liveweight, condition score, temperature at mating, chill index at lambing) are reported in this paper. They were analysed within season of mating (October to December; January to March) and age of ewe (maiden as 1.5-year-old, mature as older). Incidence of estrus was positively related (P<0.05) to condition score in the October to November interval. Return rate to service was positively (P<0.05) influenced and fertility was negatively (P<0.05) influenced by the number of days ambient temperatures were > or =32.0 degrees C during mating, indicating that high ambient temperatures may reduce embryo survival. Liveweight and, to a lesser extent, condition score, accounted for significant proportions of variation associated with ovulation rate (39.3 and 12.7%, respectively). Ovulations per 100 ewes increased by 1.8 per kg increase in liveweight over all flocks. Ovulatory response to liveweight increased (P<0.01) from the October to December to the January to March period of mating (1.5 versus 3.4 ovulations per kg, respectively). Overall, a flock's fertility and fecundity increased by 0.27 and 1.42% per kg increase in liveweight, respectively. Reproductive wastage from partial failure of multiple ovulations (PFMO) was positively related to liveweight (P<0.01) and ovulation rate (P<0.001). Survival of single lambs was positively and curvilinearly related to maternal liveweight and condition score measured in late pregnancy (P<0.05). Linear relationship of these variables for twin lamb survival was significant for condition score only. Single and twin lamb survival were also positively related to liveweight and condition score at mating (P<0.05). We concluded that nutritional cues have a major impact on reproductive traits in commercial Merino flocks in South Australia; it sets the potential number of lambs (ovulation rate) and influences survival of lambs as early as at mating. Indications are that high ambient temperatures may influence embryo survival. It is recommended that future research efforts focus on: (a) prenatal nutritional influences on the physiology of mother-offspring behaviours at birth; and (b) possible peri-conceptional dietary factors controlling embryo loss resulting from partial failure of twin ovulations, to improve reproductive efficiency in the Merino.

Animals↗

The hairless gene in androgenetic alopecia: results of a systematic mutation screening and a family-based association approach.

BACKGROUND: Genetic disposition and androgen dependence are important characteristics of the common patterned loss of scalp hair known as androgenetic alopecia (AGA). The genetic factors contributing to AGA are currently unknown. The human hairless gene (HR) has recently been cloned and mutations have been reported in families with autosomal recessive universal congenital alopecia and papular atrichia. The main feature of these disorders is persistent complete absence of hair at or shortly after birth. This suggests that HR is essential and specific for the development of hair. OBJECTIVES: To test the hypothesis that HR may be involved in AGA. METHODS: We systematically screened HR for genetic variability by means of single-strand conformation analysis (SSCA) in 46 unrelated men with AGA. To test for an involvement of HR in the development of AGA, seven common variants were genotyped in 61 families with 93 affected offspring. The results were analysed with the transmission/disequilibrium test (TDT). RESULTS: SSCA showed 15 single nucleotide substitutions: eight missense mutations, four silent mutations and three mutations in exon-flanking intronic sequences. TDT results showed a marginally significant association between AGA and variants 3379-29G/T (P = 0.024) and 2611-68C/T (P = 0.047). These results, however, did not remain significant after applying the conservative Bonferroni correction for multiple testing. CONCLUSIONS: Our results do not provide evidence for a strong involvement of HR in the development of AGA, although a minor role cannot be fully excluded.

Adult↗

Long-term learning deficits and changes in unlearned behaviors following in utero exposure to multiple daily doses of cocaine during different exposure periods and maternal plasma cocaine concentrations.

Although the possible behavioral neurotoxic effects of in utero exposure to cocaine have been the subject of numerous experiments, only a limited number of different types of animal models of cocaine exposure, critical periods, or long-term effects of such exposures have been investigated. In the present experiment, the effects of multiple daily SC exposures to cocaine (20 mg/kg/dose x 5 doses per day) were investigated when administered to gravid Sprague-Dawley CD rats on embryonic days E7-12 or E13-18 compared to weight-matched, vehicle injected, pair-fed controls. Effects of exposure were assessed on general development, olfactory orientation behavior, early locomotion, startle reactivity, spontaneous motor activity, and learning on two different tasks (Morris and Cincinnati water mazes). The multiple cocaine dosing regimen produced maternal peak serum concentrations of cocaine 3 times higher than that of a single dose (approximately 1550 vs. approximately 550 ng/mL). Early-exposed cocaine offspring had lower olfactory orientation scores and reduced postweaning rearing and hole-poke motor activity, whereas late-exposed cocaine offspring had increased postweaning locomotor, rearing, and hole-poke activity. On the Morris hidden platform maze, the cocaine early-exposed females had longer latencies on acquisition than controls. On the Cincinnati multiple-T water maze, the early-exposed cocaine females and the late-exposed cocaine males had increased errors, whereas the early-exposed cocaine males had reduced errors. The effects on measures of learning, when taken together, and in light of their being in the early-exposed group, suggest that embryonic cocaine exposure may have subtle effects on cognition in the offspring as adults. Such effects represent a form of neurotoxicity not previously associated with prenatal cocaine exposure.

Animals↗

Factors associated with fetal macrosomia in offspring of gestational diabetic women.

OBJECTIVE: To determine whether there is a relationship between birthweight and interval between 1-h and 3-h glucose tolerance test (GTT) as well as other factors. METHODS: We performed a retrospective analysis of our computerized diabetes database for the years 1992-1997. Ninety-four women with gestational diabetes fulfilled the inclusion criteria (i.e., singleton gestation, term delivery, absence of medical conditions, and known interval between 1-h and 3-h GTT). They were evaluated based on prepregnancy body mass index (BMI), mean glucose values, interval between diagnostic testing, and gestational age of 3-h GTT. RESULTS: Subjects with GDM had a mean glucose value of 96.8 mg/dl and average prepregnancy BMI of 29.3 kg/m2. When GDM subjects with and without macrosomic infants were compared, mean glucose values (97.4 vs. 96.6 mg/dl) and mean interval (18.1 vs. 17.0 days) between diagnostic testing did not significantly differ. However, maternal prepregnancy BMI was higher in the group of women who gave birth to macrosomic infants (32.2 vs. 28.22 kg/m2, P = 0.008). Using stepwise multiple regression, maternal prepregnancy BMI was the only variable found to be predictive of macrosomia. CONCLUSION: We were unable to show a statistical relationship between interval of diagnostic testing and rate of macrosomia. However, we demonstrated a clear relationship between maternal BMI and infant birthweight.

Adult↗

Perinatal outcome in twin pregnancies complicated by gestational diabetes mellitus: a comparative study.

The purpose of this study is to compare perinatal outcomes of twin pregnancies complicated by gestational diabetes (GDM) with those unaffected by GDM. A total of 1,154 twin pregnancies who delivered at Cheil General Hospital, between January 1998 and December 2002 were recruited to participate in a retrospective analysis. Out of these twin pregnancies, 37 women were had GDM. Four pregnancies exposed to GDM were excluded due to the loss of medical records; therefore 33 twin pregnancies exposed to GDM were enrolled. We matched the GDM pregnancies with pregnancies unaffected by GDM in a 1:2 ratio; therefore there were 33 GDM/66 without GDM who delivered during the study period. Our findings show that there were no significant differences including birth weight, Apgar score, respiratory distress syndrome, meconium aspiration pneumonia, transient tachypnea of new born, hyperbilirubinemia, hypoglycemia, hypocalcemia and congenital anomalies. Therefore, well controlled GDM may not increase perinatal complications in twin pregnancies. Careful pregnancy management and fetal surveillance in twin pregnancies is important to decrease perinatal complications and maintain a sound pregnancy and healthy offspring.

Adult↗

Avoiding multiple pregnancies in ART: multiple pregnancies: a test case for the moral quality of medically assisted reproduction.

Although most professional societies have issued guidelines to diminish the number of embryos to be transferred during assisted reproduction techniques, the incidence of multiple pregnancies remains unacceptably high. The negative psychological, social and medical consequences for the patients and their offspring easily outweigh the benefits in terms of increased success rates. Multiple pregnancies would never be tolerated if the 'best interest of the child' standard was applied as strictly to these consequences, as it is to controversial family forms. The persistence of high multiple pregnancy rates is largely due to the pressure brought to bear on the physicians to increase the overall success rate. The fertility specialist should inform the patients about the risks and benefits of a multiple transfer but ultimately the specialist should decide how many embryos to transfer. Multifetal reduction is an ethically acceptable solution if, and only if, the physician has taken all reasonable steps to prevent the occurrence of a multiple pregnancy. Finally, an additional strategy to decrease the incidence of multiple pregnancies is proposed, i.e. to extend the professional responsibility of the fertility specialist to all steps of procreation including pregnancy, birth and neonatal care.

Child↗

Fetal effects of epidermal growth factor deficiency induced in rats by autoantibodies against epidermal growth factor.

We have used rats with epidermal growth factor (EGF) autoantibodies to study the role of EGF deficiency during perinatal development. The study was focused on organs known to contain EGF or its receptor. Compared with controls, the offspring of autoimmune rats had a higher perinatal mortality and a lower birth weight. The weight of the lungs was particularly low in the offspring of EGF-immunized rats, and morphologically the lungs from the surviving pups seemed atelectatic and had alveolar duct dilatation, which indicates mild respiratory distress syndrome. Judged from immunohistochemical studies, the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight ratio was lower in pups from EGF-immunized rats. This difference was, however, not significant (p = 0.07), but flow cytometric analyses showed a significantly lower proportion of the liver cells from newborn EGF-deficient pups to be in S-phase and indicated that these cells were larger than liver cells from controls. To study possible alterations in EGF binding, 125I-EGF was injected i.v. in newborn rats. 125I-EGF bound in all the organs investigated. The binding is listed in decreasing order: liver, gut, skin, kidney, and lungs. In the pups from EGF-immunized rats, the lungs and the skin bound a significantly higher amount than the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗

Reduced birthweight and length in the offspring of females exposed to PCDFs, PCP, and lindane.

The objective of this study was to investigate a broad range of adverse health outcomes and their potential association to wood preservative used in daycare centers. This article focuses on reproductive effects. A sample of 221 exposed teachers was provided by the employer's liability insurers. A comparison group (n = 189) insured by the same two organizations was recruited from nonexposed daycare centers. In a face-to-face interview, job history and reproductive history of 398 female teachers were ascertained. Data on exposure were provided, including measurements on concentration of pentachlorophenol (PCP) and lindane in wood panels, and of PCP, lindane, polychlorinated dibenzo-p-dioxins and dibenzofurans in indoor air. An exposure matrix based on individual job history, independent exposure information from each center, and reproductive history was set up with regard to the vulnerable time windows for each pregnancy. Using this approach, 49 exposed and 507 nonexposed pregnancies were identified, including 32 exposed and 386 nonexposed live births. For subgroup analyses the observations were restricted to independent pregnancies, excluding multiple and consecutive births. The data were analyzed with linear regression techniques, taking confounders into account. The crude median difference between exposed and nonexposed was 175 g in birthweight and 2 cm in length. Controlling for confounders, the results show a significantly reduced but weight (p = 0.04) and length (p = 0.02) in exposed pregnancies, even after restricting the data to independent pregnancies and pregnancies for which data could be validated from the mother's health cards. These differences were not explained by differences in gestational age indicating that a toxic effect, which could cause small-for date newborns, might have affected the fetus.

Adult↗