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PubMed1996

The Countess Margaret of Henneberg and her 365 children.

According to an obscure medieval legend, the Countess Margaret of Henneberg, a notable Dutch noblewoman, gave birth to 365 children in the year 1276. The haughty Countess had insulted a poor beggar woman carrying twins, since she believed that a pair of twins must have different fathers, and that their mother must be an adultress. She was punished by God, and gave birth to 365 minute children on Good Friday, 1276. The Countess died shortly after, together with her offspring, in the village of Loosduinen near The Hague. The Countess and her numerous brood were frequently described in historical and obstetrical works. To this day, a memorial tablet and two basins, representing those in which the 365 children were baptized, are to be seen in the church of Loosduinen.

Art↗

PubMed2004

Stress during pregnancy affects general intellectual and language functioning in human toddlers.

Prenatal maternal stress has been shown to impair functioning in nonhuman primate offspring. Little is known about the effects of prenatal stress on intellectual and language development in humans because it is difficult to identify sufficiently large samples of pregnant women who have been exposed to an independent stressor. We took advantage of a natural disaster (January 1998 ice storm in Québec, Canada) to determine the effect of the objective severity of pregnant women's stress exposure on general intellectual and language development of their children. Bayley Mental Development Index (MDI) scores and parent-reported language abilities of 58 toddlers of mothers who were exposed to varying levels of prenatal stress were obtained at 2 y of age. The hierarchical multiple regression analyses indicated that the toddlers' birth weight and age at testing accounted for 12.0% and 14.8% of the variance in the Bayley MDI scores and in productive language abilities, respectively. More importantly, the level of prenatal stress exposure accounted for an additional 11.4% and 12.1% of the variance in the toddlers' Bayley MDI and productive language abilities and uniquely accounted for 17.3% of the variance of their receptive language abilities. The more severe the level of prenatal stress exposure, the poorer the toddlers' abilities. The level of prenatal stress exposure accounted for a significant proportion of the variance in the three dependent variables above and beyond that already accounted for by non-ice storm-related factors. We suspect that high levels of prenatal stress exposure, particularly early in the pregnancy, may negatively affect the brain development of the fetus, reflected in the lower general intellectual and language abilities in the toddlers.

Birth Weight↗

PubMed1980

Pericentric inversion (13) with two different recombinants in the same family.

A family is described in which a pericentric inversion (13) was discovered in the father after the birth of an abnormal baby. In a further pregnancy amniocentesis was carried out. The fetal karyotype showed a rec(13)dup p,inv(13)(p11q22). The fetus's abnormalities were similar to those observed in the first child. Family studies showed that a first cousin, mentally retarded, had a rec(13)dup q,inv(13)(p11q22) karyotype. In this family, the risk of occurrence of a recombinant in offspring of an inversion carrier could be as high as 40%.

Abnormalities, Multiple↗

PubMed1986

The relationship between juvenile laryngeal papillomatosis and maternal condylomata acuminata.

This study attempted to delineate the relationship between juvenile laryngeal papillomatosis (JLP) in children and a history of maternal condyloma at the time of their birth. Over a period of 53 years, from 1930 to 1983, 44 children with the clinical diagnosis of JLP were identified. A maternal history of genital condyloma at the time of their birth was sought. Sixteen had incomplete records. Of the remaining 28, 15 children (54%) had a maternal history of vulvar condyloma at the time of delivery or pregnancy. The association between maternal condyloma and JLP needs to be recognized since the latter causes considerable morbidity and occasional mortality. Additional studies are indicated to establish if cesarean section is necessary in pregnant patients with genital condyloma to prevent JLP in their offspring.

Adult↗

PubMed1985

Multiple embryo-transplant offspring produced from quartering a bovine embryo at the morula stage.

A non-surgical embryo collection was completed on a day 7 superovulated Chianina donor cow. Because all but two of the ova from the collection were unfertilised and a surplus of potential recipients was available, one embryo (an excellent quality late morula) was dissected into four equal portioned 'quarter' embryos using a simplified micromanipulation procedure. Each quarter embryo was then placed in a 0.25 ml French straw and non-surgically transplanted to four different crossbred beef recipient females. The remaining embryo was similarly transplanted to a herd mate recipient as an intact embryo. One recipient returned to oestrus, one recipient had an extended post transfer cycle and the two remaining recipients produced a live quarter embryo transplant calf each within 24 hours of the other. The intact embryo placed in a herd mate recipient did not produce a transplant calf. To the authors' knowledge, these transplant offspring are the first live births reported from a non-surgically collected later-stage bovine morula (day 7), which had been dissected into quarters and then individually transplanted non-surgically to recipient females. The procedure was relatively simple to perform and was completed in less than one hour.

Animals↗

PubMedDate not supplied

Unilateral bowing of long bones and multiple congenital anomalies in a child born to a mother with gestational diabetes.

We report on a new-born girl with multiple congenital anomalies consisting of major skeletal anomalies restricted to the left side, cleft palate, ventricular and atrial septal defect, retromicrognathia, short neck, dysplastic low-set ears and large birth weight. The left-side bony anomalies include shortening and bowing of the femur and tibia, hypoplasia of the fibula, hip dislocation, clubfoot and mild shortening of the long tubular bones in the left arm with elbow dislocation. The pregnancy was complicated by insulin-dependent gestational diabetes mellitus in the mother. The radiographic features were not consistent with the diagnosis of campomelic dysplasia, kyphomelic dysplasia or other skeletal dysplasias characterized by bowing and shortening of the long bones. To our knowledge, the multiple congenital anomalies, including major skeletal malformations, present in our case have never been simultaneously reported until now. A maternal diabetes syndrome in this infant is probable. The occurrence of major congenital malformations in offspring of women with gestational diabetes is reviewed and discussed. We provide evidence that gestational diabetes mellitus could be teratogenic. We recommend a careful diabetic control in every woman with a history of gestational diabetes.

Abnormalities, Multiple↗

PubMed2004

Perinatal predictors of atopic dermatitis occurring in the first six months of life.

OBJECTIVE: Previous studies of predictors of atopic dermatitis have had limited sample size, small numbers of variables, or retrospective data collection. The purpose of this prospective study was to investigate several perinatal predictors of atopic dermatitis occurring in the first 6 months of life. DESIGN: We report findings from 1005 mothers and their infants participating in Project Viva, a US cohort study of pregnant women and their offspring. The main outcome measure was maternal report of a provider's diagnosis of eczema or atopic dermatitis in the first 6 months of life. We used multiple logistic regression models to assess the associations between several simultaneous predictors and incidence of atopic dermatitis. RESULTS: Cumulative incidence of atopic dermatitis in the first 6 months of life was 17.1%. Compared with infants born to white mothers, the adjusted odds ratio (OR) for risk of atopic dermatitis among infants born to black mothers was 2.41 (95% confidence interval [CI]: 1.47, 3.94) and was 2.58 among infants born to Asian mothers (95% CI: 1.27, 5.24). Male infants had an OR of 1.76 (95% CI: 1.24, 2.51). Increased gestational age at birth was a predictor (OR: 1.14; 95% CI: 1.02, 1.27, for each 1-week increment), but birth weight for gestational age was not. Infants born to mothers with a history of eczema had an OR of 2.67 (95% CI: 1.74, 4.10); paternal history of eczema also was predictive, although maternal atopic history was more predictive than paternal history. Several other perinatal, social, feeding, and environmental variables were not related to risk of atopic dermatitis. CONCLUSIONS: Black and Asian race/ethnicity, male gender, higher gestational age at birth, and family history of atopy, particularly maternal history of eczema, were associated with increased risk of atopic dermatitis in the first 6 months of life. These findings suggest that genetic and pre- and perinatal influences are important in the early presentation of this condition.

Cohort Studies↗

PubMedDate not supplied

Do "helpers at the nest" increase their parents' reproductive success?

"Helpers at the nest," usually offspring of a preceding litter who contribute by feeding the young to increase the reproductive success of a breeding pair, are known in many species of birds and mammals. Although similar behaviors were described by ethnological observations in several human societies, there is a lack of data on their existence and role. This study of 794 reproductive life histories of post-menopausal Berber women of Southern Morocco aims to provide such information. Results show that the presence of "probable helpers" in the household is related to higher fertility scores and is associated with improved survival of offspring to sexual maturity. In contrast to sparse observations from other human societies, there is no indication that child caretaking would be specific to eldest daughters. Although the association between offspring survival and helping patterns seems highly probable, there is no confirmation that child caretaking per se is the relevant variable. Contrary to nonhuman helpers at the nest, workloads of children range from housekeeping to light agricultural tasks, and are not focused on assisting younger siblings. The improvement of reproductive success is probably the result of multiple interactions, among which the network of kinship would play a role at both the levels of economy and reciprocal assistance.

Adolescent↗

PubMed2006

[Prenatal exposure to birth control pills: risk of fetal death and congenital malformations].

About 1% of pregnant women uses oral contraceptives during the first part of their pregnancy and thereby exposes their offspring to artificial estrogens. Artificial estrogens, such as oral contraceptives, accidentally used during pregnancy may have a negative impact on the fetus. This article reviews the literature on prenatal exposure to oral contraceptives and the risk of congenital malformations and fetal death. The conclusion is that prenatal exposure to oral contraceptives may be associated with a slightly elevated risk of certain specific congenital malformations.

Abnormalities, Drug-Induced↗

PubMed1996

Birthweight as a risk factor for breast cancer.

BACKGROUND: The mammary gland is largely undifferentiated before birth and may be particularly susceptible to intrauterine influences that could increase the risk of cancer through acceleration of cell proliferation or other pregnancy-related processes. Studies of migrant populations, animal data, and limited epidemiological evidence suggest that breast cancer may originate in utero. In a nested case-control study we assessed whether birthweight and other perinatal factors are associated with risk of breast cancer. METHODS: This case-control study was nested within the cohorts of the two Nurses' Health Studies. We used self-administered questionnaires to obtain information from the mothers of 582 nurses with invasive breast cancer and the mothers of 1569 nurses who did not have breast cancer (controls). Information on risk factors for breast cancer during adulthood were obtained from the nurses; multiple logistic regression analysis adjusted for these risk factors. FINDINGS: Birthweight was a significant predictor of breast-cancer risk. With women who weighed 4000 g or more at birth as the reference category, the adjusted odds ratios for breast cancer were 0.86 (95% CI 0.59-1.25) for birthweights of 3500-3999 g, 0.68 (0.48-0.97) for birthweights of 3000-3499 g, 0.66 (0.45-0.98) for birthweights of 2500-2999 g, and 0.55 (0.33-0.93) for birthweights below 2500 g (p for trend 0.004). Prematurity was not significantly associated with risk of breast cancer. INTERPRETATION: Birthweight is significantly associated with breast-cancer risk, which suggests that intrauterine factors or processes affect the risk of breast cancer in the offspring. High concentrations of pregnancy oestrogens may have an important role in breast carcinogenesis, but other pregnancy hormones or intrauterine factors may also be involved.

Adult↗

PubMed2006

3-M syndrome: a report of three Egyptian cases with review of the literature.

The 3-M syndrome is a rare autosomal recessive disorder. It is characterized by prenatal and postnatal growth retardation associated with characteristic features. In this study, we report on three patients from two unrelated families, including two male sibs, with the characteristic features and radiological findings of the 3-M syndrome. The main features in our cases were low birth weight, short stature, malar hypoplasia, anteverted nostrils with a fleshy nasal tip, long philtrum, pointed full chin, short broad neck, broad chest with transverse grooves of anterior thorax and hyperlordosis. An orodental examination revealed characteristic findings, some of which were not reported before. Prominent premaxilla, hypoplastic maxilla, thick patulous lips, high-arched palate, median fissured tongue, delayed eruption of teeth with enamel hypocalcification and malocclusion were present in our three studied cases. Radiographic studies showed slender long bones and ribs, a narrow pelvis and foreshortened vertebral bodies. Our reported cases are the offspring of healthy consanguineous parents, confirming the autosomal recessive pattern of inheritance in the syndrome. Cases were reported from different countries all over the world. To our knowledge, these are the first reported Egyptian patients with this rare disorder. This syndrome may be underreported because of the phenotypic overlap with other low birth dwarfism syndromes. Recent identification of a gene mutated in some cases of 3-M syndrome will aid diagnosis.

Abnormalities, Multiple↗

PubMed2004

A longitudinal analysis of reproductive skew in male rhesus macaques.

One of the basic tenets of sexual selection is that male reproductive success should be large in polygynous species. Here, we analysed 6 years of molecular genetic data from a semi-free-ranging population of rhesus macaques (Macaca mulatta), using Nonac's B index, to assess the level of male reproductive skew in the study troop. On average, the top sire in each year produced 24% of the infants, while 71% of troop males sired no offspring at all. Consequently, 74% of infants had at least one paternal half-sibling in their own birth cohort. Reproductive success was greatest for high-ranking males, males who spent the whole mating season in the troop and males of 9-11 years of age. Heterozygosity for major histocompatibility complex (MHC) class II gene DQB1 was the strongest single predictor of male reproductive success. A negative relationship suggestive of female mate choice was noted between the B index and the proportion of extragroup paternities. Reproductive skew was not associated with relatedness among potential sires or with female cycle synchrony. We conclude that reproductive skew in male rhesus macaques is best accounted for by the 'limited-control' model, with multiple factors interacting to regulate individual reproductive output.

Animals↗

PubMed2001

Pair approximation for lattice models with multiple interaction scales.

Pair approximation has frequently proved effective for deriving qualitative information about lattice-based stochastic spatial models for population, epidemic and evolutionary dynamics. Pair approximation is a moment closure method in which the mean-field description is supplemented by approximate equations for the frequencies of neighbor-site pairs of each possible type. A limitation of pair approximation relative to moment closure for continuous space models is that all modes of interaction between individuals (e.g., dispersal of offspring, competition, or disease transmission) are assumed to operate over a single spatial scale determined by the size of the interaction neighborhood. In this paper I present a multiscale pair approximation which allows different sized neighborhoods for each type of interaction. To illustrate and test the approximation I consider a spatial single-species logistic model in which offspring are dispersed across a birth neighborhood and established individuals have a death rate depending on the population density in a competition neighborhood, with one of these neighborhoods nested inside the other. Analysis of the steady-state equations yields several qualitative predictions that are confirmed by simulations of the model, and numerical solutions of the dynamic equations provide a close approximation to the transient behavior of the stochastic model on a large lattice. The multiscale pair approximation thus provides a useful intermediate between the standard pair approximation for a single interaction neighborhood, and a complete set of moment equations for more spatially detailed models.

Animals↗

PubMed2005

Hypospadias in sons of women exposed to diethylstilbestrol in utero.

BACKGROUND: Diethylstilbestrol (DES) is a synthetic estrogen that was widely prescribed to pregnant women before 1971. DES increases the risk of breast cancer in women who took the drug and the risk of reproductive tract abnormalities in their offspring. Dutch investigators have reported a 20-fold increase in risk of hypospadias among sons of women who were exposed to DES in utero. We assessed this relation in data from an ongoing study of DES-exposed persons. METHODS: Several U.S. cohorts of women with documented exposure in utero to DES have been followed by mailed questionnaires since the 1970s. Comparison subjects are unexposed women of the same ages. In 1997, participants were asked about congenital abnormalities in their children. We calculated prevalence odds ratios for the risk of hypospadias in sons of exposed mothers relative to sons of unexposed mothers using generalized estimating equations to adjust for multiple sons per mother and controlling for maternal age at the son's birth. RESULTS: We obtained data from 3916 exposed and 1746 unexposed women. These women reported a total of 13 liveborn sons with hypospadias (10 exposed, 3 unexposed). The prevalence odds ratio for risk of hypospadias among the exposed was 1.7 (95% confidence interval = 0.4-6.8). CONCLUSIONS: Our findings do not support a greatly increased risk of hypospadias among the sons of women exposed to DES in utero, as has been previously reported.

Diethylstilbestrol↗

PubMed2005

Risk of specific congenital abnormalities in offspring of women with diabetes.

AIMS: To assess the extent to which the increased risk of congenital abnormalities seen in women with pre-gestational insulin-treated diabetes mellitus is unspecific or related to the embryology of specific organs. METHODS: Cases with congenital abnormalities were identified in the population-based Hungarian Congenital Abnormality Registry from 1980 to 1996 with two newborn children without congenital abnormality selected from the National Birth Registry as controls. We adjusted for parity, maternal age, and use of antipsychotic drugs. RESULTS: Among cases we found 63/22,843 babies with maternal diabetes compared with 50/38,151 in the control group [adjusted prevalence odds ratio (POR) 2.1; 95% CI 1.5-3.1]. The association was strongest for the following congenital abnormalities: renal agenesis (POR: 14.8; 95% CI, 3.5-62.1), obstructive congenital abnormalities of the urinary tract (POR: 4.3; 95% CI, 1.3-13.9), cardiovascular congenital abnormalities (POR: 3.4; 95% CI, 2.0-5.7), and multiple congenital abnormalities (POR: 5.0; 95% CI, 2.4-10.2). CONCLUSIONS: These data indicate that pre-gestational maternal diabetes is associated with strong teratogenic effects on the kidney, urinary tract, and heart, and strongly associated with multiple congenital abnormalities. We found no material association between diabetes and spinal congenital abnormalities and limb deficiencies.

Abnormalities, Drug-Induced↗

PubMed2001

Congenital thyrotoxicosis in premature infants.

OBJECTIVES: Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex. DESIGN AND PATIENTS: The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays. RESULTS: Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25--36 week) and median B Wt was 1.96 kg (0.50--2.62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1--16 days) and mean age at commencement of treatment was 12 days (7--26 days). Two infants received propylthiouracil and five received a combination of carbimazole and propranolol. Four became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supple-mentation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort. CONCLUSIONS: This is a large series of extremely small and premature infants with neonatal thyro-toxicosis. Presentation was nonspecific. The diagnosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme low birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recognition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.

Antithyroid Agents↗

PubMed2002

Pregnancy outcome post renal transplantation.

BACKGROUND: The success in performing organ transplantations and prevention of rejection has resulted not only in a substantial increase in life expectancy, but also improvement in the patients' quality of life. Thus, women who underwent organ transplantation are now reaching puberty and the age of reproduction. This has presented new challenges regarding the teratogenicity and the long-term effect of immunosuppressive medications used by these patients. Previous studies have shown that pregnancies after renal transplantation are associated with an increased risk for both the mother and the fetus. There is, however, very little information available on neonatal and long-term pediatric follow-up of babies born to mothers who have undergone renal transplantation and have been exposed to immunosuppressive medications, compared to controls. We report the experience of our center, the largest in Canada, regarding the prenatal and long-term postnatal outcome of pregnancies after renal transplantation. METHODS: This is a retrospective case series reporting the outcome of 44 consecutive pregnancies followed by the Toronto Renal Transplant Program. Follow-up data were gathered on the 32 live born children by either a return visit to the clinic or by telephone interview. Medical, as well as developmental information, was gathered on all children and the study group was compared to controls, matched for maternal age (+/-2 years) and smoking status, obtained through the Motherisk Program. RESULTS: Of the 44 pregnancies followed by us, there were 32 live-born children delivered by 26 mothers and 12 stillborn/abortuses. Twenty-six pregnancies were treated with cyclosporine, azathioprine and prednisone, 13 with azathioprine and prednisone and five with cyclosporine and prednisone. The mean gestational age at delivery in the study group was 36.5 +/- 2.7 weeks compared to 40.2 +/- 1.6 weeks in the control group (P < 0.001). The mean birthweight in the study group was 2.54 +/- 0.67 kg, compared to 3.59 +/- 0.53 kg in the control group (P < 0.0001). In the study group there was one child with multiple anomalies and four stillbirths compared to zero in the control group. There were also six spontaneous abortions and two therapeutic abortions in the study group. On follow-up (from 3 months to 11 years of age) there was one child with insulin-dependent diabetes mellitus, two children with asthma and one child with recurrent otitis media. Developmental follow-up revealed one child with moderate to severe sensorineural hearing loss, one child with a learning disability and one child with pervasive developmental disorder. In none of these cases were there signs of perinatal asphyxia. CONCLUSION: There are significantly more stillbirths, preterm deliveries and increased incidence of low birth weight in the transplant group. Most pregnancies in the study group went well, however, and their offspring had normal postnatal growth and development. Further studies with long-term pediatric follow-up are needed to delineate their outcome and rule out possible long term effects of the immunosuppressive medication on their growth, development, reproduction and general health.

Abortion, Spontaneous↗

PubMed2004

17alpha-ethinylestradiol reduces the competitive reproductive fitness of the male guppy (Poecilia reticulata).

Whether endocrine disruption in an individual male is actually translated into reduced reproductive success in a natural competitive environment is extremely difficult to predict. Here, we have used paternity analysis to provide new information on the ability of an endocrine disruptor to deleteriously affect male guppy reproductive fitness by including the effect of intermale competition. Groups of male guppies were exposed to 10.5, 44.4, or 112 ng/L of the synthetic estrogen 17alpha-ethinylestradiol (EE2) from birth to adulthood. Subsequently, an exposed male competed against an unexposed male for the opportunity to fertilize a receptive female. The successful males siring the majority of the offspring in each brood were then identified using microsatellites in genetic paternity analysis. Only the highest dose of EE2 produced harmful effects with a significantly female-biased sex ratio, significant reductions in male sperm count, testis weight, body coloration and courtship behavior, and a significant increase in body size. These feminizing effects were translated into a highly significant reduction in fertility, where only 1 of the 17 exposed males sired offspring in competition with unexposed males. The evidence suggests that EE2-treated males have reduced reproductive fitness compared with untreated males, possibly the result of EE2 effects on multiple fitness traits. To our knowledge, this is the first study providing evidence of endocrine disruption at the population level that has included the ecologically highly relevant effect of sexual competition on male reproductive fitness.

Animals↗