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PubMed1999

Prevalence of congenital anomalies at birth among offspring of women at risk for a genetic disorder and with a normal second-trimester ultrasound.

The goal of this study was to determine the prevalence and the nature of congenital anomalies found at birth in offspring of women who had a normal second-trimester ultrasound and/or amniocentesis. Two groups of women were studied in our prenatal diagnosis clinic between 1991-1997. Group 1 consisted of pregnant women who had an amniocentesis for advanced maternal age (AMA), or for familial chromosomal or monogenic disorders. Group 2 consisted of pregnant women attending the prenatal diagnosis clinic and who had no indication for amniocentesis. Those with an abnormal ultrasound and/or amniocentesis were excluded. At the time of delivery, a questionnaire was sent pertaining to perinatal complications and the anomalies detected during the neonatal period. From a total of 15, 370 questionnaires sent from 1991-1997, 10,823 (group 1, n = 8,877; group 2, n = 1,946) were returned (overall response rate, 70.4%). Mean maternal age was 36 years in group 1 and 29 years in group 2. The prevalence of perinatal complications was similar in the two groups. In each group, the prevalence of all unforeseen anomalies was 2.9%. In group 1, the distribution of those anomalies was: major anomalies, 67.7%; minor anomalies, 23.9%; and multiple congenital anomalies (MCA), 8.3%. In group 2, the distribution was: major anomalies, 70.7%; minor anomalies, 24.1%; and MCA, 5.2%. In patients at risk for a genetic disease and consulting in a prenatal diagnosis clinic, the prevalence of all anomalies diagnosed at birth was 2.9%, even if the second-trimester ultrasound and amniocentesis results were normal. Therefore, it is important to inform those couples of this remaining risk.

Abnormalities, Multiple↗

PubMed2000

The efficiency of maternal transfer of lead and its influence on plasma IgE and splenic cellularity of mice.

Exposure to the well known environmental toxicant lead is typically assessed by blood and/or bone levels and has been implicated in the onset of a variety of diseases affecting multiple human systems. However, there are conflicting data regarding the efficiency of in utero versus lactational transfer of lead to offspring, and the immunomodulatory effects of lead in early life have not been well defined. Pregnant BALB/c mice were exposed to lead acetate in their drinking water beginning at approximately day 15 of gestation, and cross-fostering of exposed/nonexposed litters was performed at parturition. Significant increases of blood lead levels of all exposed offspring were found at 1 week of age with evidence for both transplacental and lactational transfer. Additionally, mice exposed to lead continuously beginning at approximately 6 days prior to birth showed significant decreases in their blood lead levels 2 weeks after weaning, despite continued exposure as adults. This result suggests maternal transfer of lead is more efficient than oral adult exposure and that substantial lead transfer occurs both transplacentally and lactationally. The incidence of childhood atopic responses including asthma has risen considerably in recent years, particularly within areas containing higher levels of environmental pollutants. Plasma IgE levels of 2-week-old neonates exposed to lead before and/or after birth were measured as an index of atopy. Neonates exposed to lead transplacentally and/or lactationally had significantly higher plasma IgE levels, a biomarker of atopy, and lower splenic white blood cell numbers than age-matched controls. These results resemble the lag in immunocompetency and increase in serum IgE noted in atopic children and suggest a role for environmental toxicants and non-allergen-specific immunology in the prevalence of atopy and asthma in children.

Aging↗

PubMed1986

Incidence and recurrence rate of abruptio placentae in Sweden.

It is desirable to identify those pregnancies that run an increased risk of abruptio placentae, as this disorder still is associated with a high perinatal mortality. Data were collected from the Swedish nationwide birth registry system on all 894,619 births in Sweden in the period 1973 to 1981. The overall incidence of abruptio placentae was 0.44%, with a perinatal mortality of 20.2% and a cesarean section frequency of 74.6%. The incidence of abruptio placentae was significantly increased in the case of twin birth, male offspring, mothers below 20 years of age, and with every delivery after the second one. A history of abruptio placentae increased the risk of a similar incident in a subsequent pregnancy by 10.2-fold. The frequency of cesarean section in subsequent parturitions remained high (32.1%) even in the absence of reabruptio placentae, thus demonstrating the need to identify further risk groups.

Abruptio Placentae↗

PubMed1992

Rubinstein-Taybi syndrome.

Rubinstein-Taybi Syndrome was first described in 1957 but only in 1963 as a distinguishable type of moderate mental retardation. The cause is still unknown although some type of genetic origin is possible. No consistent chromosomal abnormality has been demonstrated, the chromosomal analysis is normal, and cases are generally not considered hereditary. The recurrent risk for siblings is approximately 0.1% but may be as high as 50% for offspring of patients with the syndrome. The Rubinstein-Taybi syndrome is not at present detectable before birth and is evenly found in both males and females. The syndrome was thought to be rare but an increase in the number of reported cases each year suggests it is not as rare as estimated. It is thought to occur in about 1 in 300,000 births, and since it has become readily identifiable, more than 400 cases have been reported worldwide.

Abnormalities, Multiple↗

PubMed1999

Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study.

The temporal development of autoantibodies was studied in 1,353 offspring of parents with type 1 diabetes. Islet cell antibodies (ICAs) and autoantibodies to insulin (IAAs), glutamic acid decarboxylase, and IA-2 were measured at birth, 9 months, 2 years, and 5 years of age. At birth, no offspring had islet autoimmunity other than maternally acquired antibodies, which were shown to influence antibody prevalence up to age 6 months. Antibodies detected thereafter were likely to represent a true de novo production, since prevalences were the same for offspring from mothers and fathers with diabetes, antibodies detected at 9 months were almost always confirmed in the 2-year sample and were associated with an increased likelihood of having or developing other antibodies. By 2 years of age, autoantibodies appeared in 11% of offspring, 3.5% having more than one autoantibody. IAAs were detected most frequently, and few had autoantibodies in the absence of IAAs. In 23 offspring with multiple islet autoantibodies, IAAs preceded other antibodies in 10 cases and were first detected concurrently with other antibodies in 12 and after detection of other antibodies in 1. Development of additional antibodies and changes in levels, including decline of IAAs at older age, was frequent. Nine children, all with IAAs and ICAs, developed diabetes. Overall cumulative risk for disease by 5 years of age was 1.8% (95% CI 0.2-3.4) and was 50% (95% CI 19-81) for offspring with more than one autoantibody in their 2-year sample. Autoimmunity associated with childhood diabetes is an early event and a dynamic process. Presence of IAAs is a consistent feature of this autoimmunity, and IAA detection can identify children at risk.

Aging↗

PubMedDate not supplied

A population-based study of birth defects in Malaysia.

Birth defects are one of the leading causes of paediatric disability and mortality in developed and developing countries. Data on birth defects from population-based studies originating from developing countries are lacking. One of the objectives of this study was to determine the epidemiology of major birth defects in births during the perinatal period in Kinta district, Perak, Malaysia over a 14-month period, using a population-based birth defect register. There were 253 babies with major birth defects in 17,720 births, giving an incidence of 14.3/1000 births, a birth prevalence of 1 in 70. There were 80 babies with multiple birth defects and 173 with isolated birth defects. The exact syndromic diagnosis of the babies with multiple birth defects could not be identified in 18 (22.5%) babies. The main organ systems involved in the isolated birth defects were cardiovascular (13.8%), cleft lip and palate (11.9%), clubfeet (9.1%), central nervous system (CNS) (including neural tube defects) (7.9%), musculoskeletal (5.5%) and gastrointestinal systems (4.7%), and hydrops fetalis (4.3%). The babies with major birth defects were associated with lower birth weights, premature deliveries, higher Caesarean section rates, prolonged hospitalization and increased specialist care. Among the cohort of babies with major birth defects, the mortality rate was 25.2% during the perinatal period. Mothers with affected babies were associated with advanced maternal age, birth defects themselves or their relatives but not in their other offspring, and significantly higher rates of previous abortions. The consanguinity rate of 2.4% was twice that of the control population. It is concluded that a birth defects register is needed to monitor these developments and future interventional trials are needed to reduce birth defects in Malaysia.

Case-Control Studies↗

PubMed2005

Paternity and kinship patterns in polyandrous moustached tamarins (Saguinus mystax).

We studied patterns of genetic relatedness and paternity in moustached tamarins, small Neotropical primates living in groups of 1-4 adult males and 1-4 adult females. Generally only one female per group breeds, mating with more than one male. Twin birth are the norm. In order to examine the genetic consequences of this mating pattern, DNA was extracted from fecal samples collected from two principal and six neighboring groups. DNA was characterized at twelve microsatellite loci (average: seven alleles/locus). We addressed the following questions: Do all adult males have mating access to the reproductive female of the group? How is paternity distributed across males in a group? Can polyandrous mating lead to multiple paternity? Are nonparental animals more closely related to the breeders than to the population mean? And, are mating partners unrelated? Breeding females mated with all nonrelated males. In at least one group the father of the older offspring did not sire the youngest infant although he was still resident in the group. We also found evidence for multiple paternity in a supposed twin pair. Yet, within each group the majority (67-100%) of infants had the same father, suggesting reproductive skew. Relatedness within groups was generally high (average R = 0.31), although both nonrelated males and females occurred, i.e., immigrations of both sexes are possible. Mating partners were never found to be related, hence inbreeding seems to be uncommon. The results suggest that while the social mating system is polyandry, paternity is often monopolized by a single male per group.

Animals↗

PubMed2001

Gender effects in hearing loss in Dalmatians.

Brainstem auditory-evoked-response data were collected from 3101 Dalmatian dogs from 1984 to 1998 at the Veterinary Medicine Teaching Hospital at the University of California, Davis. Also collected were data on eye color and the presence or absence of a color-patch at birth. Our objective was to evaluate the role of gender in hearing loss, including the possibility that the probability of suffering unilateral or bilateral deafness was greater if the dam was hearing impaired than if the sire was hearing impaired. Results of a multiple-trait threshold-model analysis support the commonly held observation that females were more likely to be deaf than males. In addition, females were also more likely to have two blue eyes (a condition associated with an increased prevalence of deafness). However, gender differences in hearing loss were limited to these direct observations. There was no detectable difference in the prevalence of hearing loss between offspring of deaf mothers and the offspring of deaf fathers. Finally, there was no detectable decrease in the prevalence of hearing loss over the years covered in the data set - suggesting that Dalmatian breeders are not yet selecting against hearing problems.

Animals↗

PubMed1997

Congenital malformations and maternal occupation: a registry based case-control study.

OBJECTIVES: To investigate the relations between congenital malformations and maternal occupation during pregnancy with a registry based case-control study. METHODS: Analysis was performed on data derived from the Florence Eurocat registry surveillance programme. The study included cases with isolated conditions, including chromosomal anomalies (n = 1351), cases with multiple anomalies registered during the 1980-91 period (n = 440), and babies with no congenital malformations recognised at birth who were born from 1982 to 1989 and selected as controls (n = 3223). 11 categories were defined, 10 including cases with isolated malformations and one for cases with multiple congenital anomalies. Four categories of maternal occupation were selected for the study. Odds ratio (OR) values were adjusted for maternal origin, maternal and paternal education, number of previous live births, illness during pregnancy, and maternal age when the group of chromosomal anomalies was analysed. RESULTS: A notable and significant association between oral clefts and mothers involved in leather and shoe manufacturing was found (adjusted OR 3.9; 99% confidence interval (99% CI) 1.5 to 9.8) and the risk consistently increased when considering cases with isolated cleft palate separately (OR 5.4; 95% CI 1.8 to 13.4). Moreover, a significant risk was identified for the association between multiple anomalies and textile dye workers (adjusted OR 1.9; 99% CI 1.0 to 3.8). CONCLUSIONS: This study indicates a notable, significant relation between maternal occupation as a pelt or leather worker and orofacial clefts in offspring. This finding is in agreement with the suggested inheritance models. The dilution effect due to studying large and heterogeneous groups of workers and occupations limits the value of the study; but it provides a good example of the use of a large database to search for teratogenic risk with the aid of malformation registries.

Adult↗

PubMed2006

Pregnancy outcomes among female hairdressers who participated in the Danish National Birth Cohort.

OBJECTIVES: The Danish National Birth Cohort (DNBC) was used to examine pregnancy outcomes among female hairdressers and neurodevelopment in their offspring. METHODS: A population-based cohort study was conducted of 550 hairdressers and 3216 shop assistants (reference group) by using data from the Danish National Birth Cohort between 1997 and 2003. Information on job characteristics was reported by the women in the first interview (around 17 weeks of gestation). Pregnancy outcomes were obtained by linkage to the national registers. Developmental milestones were reported by the mother at the fourth interview, when the child was approximately 19 months old. Cox regression was applied to analyze fetal loss and congenital malformation. Logistic regression was used to analyze other pregnancy outcomes and developmental milestones. RESULTS: We found no significant differences in fetal loss, multiple births, gender ratio, preterm birth, small-for-gestational age, congenital malformations, or achievement of developmental milestones among the children of hairdressers and shop assistants. CONCLUSIONS: The results do not indicate that children of hairdressers in Denmark currently have a high risk of fetal impairment or delayed psychomotor development.

Abortion, Spontaneous↗

PubMed1965

Marmosets (hapiladae): breeding seasons, twinning, and sex of offspring.

Our records on marmosets, primarily Oedipomidas oedipus, plus data from the literature, confirm that these animals customarily have twins. Demonstrated chimerism for several tissues is significant, for virtually all twins are of biovular origin. Furthermore, a single birth may often be a survivor of twins. Births occur during any month, but springtime appears to be the most common period. An average interval of 240 days between births predicts the production level of a captive colony. A gestation period of about 140 days appears to be a valid estimate.

Animals↗

PubMed1993

Holoprosencephaly: a family showing dominant inheritance and variable expression.

A family with probable dominant holoprosencephaly is presented with five affected subjects in two sibships, the offspring of healthy sisters who are presumed gene carriers. Of the affected children, three had cebocephaly and died shortly after birth. One had left choanal atresia, retinal coloboma, a single central maxillary incisor, microcephaly, short stature, and learning problems. Another had only a single central maxillary incisor. The occurrence of hypotelorism, microcephaly, and unilateral cleft lip and palate as minor manifestations of the gene in possible and probable gene carriers is discussed.

Abnormalities, Multiple↗

PubMed1975

Postnatal stimulation of hepatic microsomal enzymes following administration of TCDD to pregnant rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) administered to pregnant rats at 3 mu-g/kg as a single oral dose during early, middle, or late gestation caused marked elevations of some maternal hepatic microsomal enzymes for at least 10 weeks after treatment. This dose was not teratogenic and fetal rates of glucuronidation of testosterone and p-nitrophenol (PNP) were unaffected. Increases in fetal liver benzpyrene hydroxylase (BPH) activities were evident during late gestation although cytochrome P-450 and cytochrome b-5 contents were unchanged. The offspring of pregnant rats administered TCDD had markedly elevated hepatic PNP UDP-glucuronyltransferase (UDPGT) BPH, and microsomal cytochrome contents whereas the perinatal development of testosterone UDPGT was unchanged. PNP glucuronidation attained a maximal 8-fold increase above controls by 3 weeks after birth and activities were twice that of controls 8 weeks after birth (adults). Maximal increases in benzpyrene hydroxylation rates occurred one day after birth when in the prenatally exposed group activities were approximately 20 times higher than controls. Foster mother experiments demonstrated that the postnatal inductive effect resulted both from exposure of newborns to TCDD via maternal milk and the activation of an inducing mechanism occurring after birth. Tese data demonstrate that multiple factors are responsible for the induction of hepatic microsomal enzymes in the newborn following administration of TCDD to pregnant rats.

Animals↗

PubMed1992

Unbalanced karyotype due to adjacent 1 segregation of t(11;22)(q23.3;q13.2).

The 11q;22q translocations, whatever the breakpoints may be, are of particular interest because of their propensity to 3:1 segregation of the chromosomes at meiosis I. Until now, no unbalanced karyotype resulting from 2:2 adjacent segregation was published among offspring of 11q;22q translocation carriers. The authors report the case of an unbalanced karyotype due to adjacent 1 segregation of a maternal translocation (11;22)(q23.3;q13.2). The proband's karyotype was 46,XX,-22,+der(22)(11;22)(q23.3;q13.2)mat. This finding demonstrates that adjacent 1 segregation is possible in t(11;22) with breakpoints at 11q23 and 22q13, and can lead to birth of viable infants.

Abnormalities, Multiple↗

PubMed2005

Prevalences and transmission routes of Campylobacter spp. strains within multiple pig farms.

In this work, faecal samples were collected from 15 pig farms to determine the Campylobacter prevalences at different times during the rearing period and to visualize the exchange of strains among the pig population by genotyping specific isolates. All isolated strains were identified as C. coli. Whereas no Campylobacter were detectable in the faeces of piglets at the day of birth, the Campylobacter incidence rose within days to 32.8%. After transfer to the nursery unit the prevalence increased to 56.6%. Approximately two-thirds of the pigs remained C. coli shedders in the fattening unit. In contrast to most farms, one farm expressed a very low Campylobacter incidence during the whole rearing period. Amplified fragment length polymorphism (AFLP) analysis was performed on all C. coli isolates of one farm. Clonal strains were identified from the brood sows and their offsprings or neighbouring piglets. After moving to the nursery unit, new genotypes appeared in that pig group but the original C. coli strains largely remained within that group. C. coli genotypes, identified during the fattening period, replaced the previously isolated genotypes. Transportation to the abattoir had no significant influence on the shedding rate of C. coli. The detection rate before transportation was 79.1% and decreased slightly to 78.2% (n=330). Additionally, eleven of 1474 environmental samples from different sources of the pig farms were positive for C. coli. This study demonstrates the importance of pigs as a reservoir for C. coli. Maternal C. coli strains are the primary source of infection but non-related genotypes from different sources appear during the rearing period and these latter strains constitute largely the final C. coli flora.

Animals↗

PubMed1985

Abnormalities in offspring associated with prenatal marihuana exposure.

5 newborn infants, whose mothers acknowledged steady use of marihuana prior to and during pregnancies, displayed symptoms of intrauterine growth retardation, neurological problems, and abnormal morphogenesis. These findings fit in with the experimental studies and surveys of pregnant human populations which have indicated that cannabis products have teratogenic potential, though rigorous proof must await further information.

Abnormalities, Multiple↗

PubMed1989

Nitrosatable drug exposure during pregnancy and adverse pregnancy outcome.

Recent investigations have suggested that drugs that are amines can undergo endogenous or exogenous nitrosation reactions to form N-nitroso compounds. These compounds have been extensively characterized in animal models as carcinogens, mutagens and teratogens. In order to examine the possible effects of exposure to nitrosatable drugs during gestation on pregnancy outcome, data were utilized from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. Pregnancy outcomes for 6061 pregnancies in which the mother ingested a drug known to undergo nitrosation were compared with 6921 randomly sampled pregnancies without such exposure. The major outcome factors of interest were birth defects, fetal, neonatal and infant death and birthweight. Our findings suggest that no significant increases in risk of fetal, neonatal and infant death or low birthweight were associated with nitrosatable drug exposure during pregnancy. However, the risk of a tumour in the offspring of exposed mothers was increased (relative risk, RR = 2.29; 95% Cl 0.99-5.26). Increases in relative risk of major malformations was also observed and this increase was greater when exposure during the first four months of pregnancy was examined separately (RR = 1.33; 1.11-1.58). There were specific individual malformations that were observed to have increased relative risks (for example: eye malformations, hydrocephaly, craniosynostosis and meningomyelocoele/meningocoele) but interpretation was difficult due to multiple comparisons and some of these observations were associated with wide confidence intervals. These types of adverse pregnancy outcomes were consistent with animal study outcomes.

Abnormalities, Drug-Induced↗

PubMed2003

In vitro oocyte culture and somatic cell nuclear transfer used to produce a live-born cloned goat.

The use of an in vitro culture system was examined for production of somatic cells suitable for nuclear transfer in the goat. Goat cumulus-oocyte complexes were incubated in tissue culture medium TCM-199 supplemented with 10% fetal bovine serum (FBS) for 20 h. In vitro matured (IVM) oocytes were enucleated and used as karyoplast recipients. Donor cells obtained from the anterior pituitary of an adult male were introduced into the perivitelline space of enucleated IVM oocytes and fused by an electrical pulse. Reconstituted oocytes were cultured in chemically defined medium for 9 days. Two hundred and twenty-eight oocytes (70%) were fused with donor cells. After in vitro culture, seven somatic cell nuclear transfer (SCNT) oocytes (3%) developed to the blastocyst stage. SCNT embryos were transferred to the oviducts of recipient females (four 8-cell embryos per female) or uterine horn (two blastocysts per female). One male clone (NT1) was produced at day 153 from an SCNT blastocyst and died 16 days after birth. This study demonstrates that nuclear transferred goat oocytes produced using an in vitro culture system could develop to term and that donor anterior pituitary cells have the developmental potential to produce term offspring. In this study, it suggested that the artificial control of endocrine system in domestic animal might become possible by the genetic modification to anterior pituitary cells.

Abnormalities, Multiple↗