Comparative effect of Neospora caninum infection in BALB/c mice at three different gestation periods

Neospora caninum has been recognized as a major cause of infectious bovine abortion worldwide. In the present study, the effect of N. caninum infection in mice at the 3 gestation periods (first, second, and third period) was investigated. In dams, tissue distribution of N. caninum was evaluated by nested polymerase chain reaction. In the progeny, fetal mortality, stillbirth, litter size, neonatal mortality/morbidity, vertical transmission, and parasite burden in neonatal tissues were evaluated. Pregnant BALB/c mice were infected subcutaneously with 2 x 10(6) NC-1 tachyzoites on days 0, 7, or 14 of gestation. Dams from each group were sequentially killed during gestation and postpartum (PP). Pups were killed on days 1 and 7 PP. Infection on day 0 of gestation produced a high vertical transmission rate, although no changes in fetal mortality, stillbirth, and littermate size were observed. The highest level of vertical transmission, together with an increase in fetal mortality and stillbirth and a decrease in litter size, were observed when infection was done on day 7 of gestation. Finally, infection on day 14 of gestation produced the lowest vertical transmission. Furthermore, infection at any time during gestation compromised the postnatal development of pups, because neonates from infected dams showed less body weight and a delay in the hair development.     

Platyrrhine juvenile mortality in captivity and in the wild

I reviewed literature on juvenile mortality in the Platyrrhini in order to evaluate reproductive success in captive breeding. Juvenile mortality includes abortion, premature mortality, stillbirth and death of the unweaned young. The highest losses occur in the Callitrichidae (31% through 3 months of age; 86% through 6 months of age) and in Lagothrixspp. (around 50% through 1 month of age) among the Cebidae. High abortion rates occur in Saguinusand Aotus.High stillbirth incidences are reported for the Callitrichidae (Callithrixand Saguinus)and for the Cebidae (Saimiriand Aotus).Although most mortality occurs in the first week for most species, a considerable proportion of deaths occurs in the period from week 1 until weaning. Important causes of death are trauma and aberrant parental behavior. Prematurity plays an important role in perinatal death among the Callitrichidae. Dystocia is a major cause of stillbirth in Saimiri. Congenital malformations occur in Callithrix, Saguinus, Leontopithecus,and Saimiri.Infectious diseases play a secondary role in mortality, particularly during the first period of life. A higher mortality risk is present if the infant is male, if the litter size is different from two (Callitrichidae), if the mother is primiparous, captive born, or inexperienced, or if the group is small (Callitrichidae) or unstable (Cebidae).     

Contribution of twin pregnancy to perinatal mortality and fetal growth retardation; reversal of growth retardation after birth.

A survey of factors associated with perinatal mortality in 511 twins and fetal growth retardation and its reversal in 262 twins is presented. The incidence of stillbirth was almost 50% higher in twins than in singletons and the neonatal mortality was six times as high. Eighty percent of the neonatal deaths occurred in infants born prior to or at 30 weeks of gestation; 93% of the deaths were in infants weighing less than 1500 g and 75% occurred within 48 hours of birth. Fetal malnutrition was the main cause of stillbirth, and respiratory distress syndrome and asphyxia neonatorum were the main causes of neonatal death. One quarter of the twins had fetal growth retardation, a prevalence 10 times that in singletons. In almost all, the growth retardation was reversed by high-energy feedings. Although twins represented only 1% of all pregnancies and 2% of live births, they composed 12% of infants with early neonatal death and 17% of growth-retarded infants. A program is suggested for reduction of twin mortality and morbidity.     

Ovine toxoplasmosis: transmission, clinical outcome and control

Toxoplasma gondii is a significant cause of abortion in sheep. Infection is picked up from the environment and if initiated during pregnancy may cause fetal mortality. Infected sheep remain persistently infected with tissue cysts in brain and muscle (meat), and are also immune and would not be expected to abort again. The live tachyzoite vaccine (Toxovax) protects against abortion and this allows the suggestion that it may also reduce or prevent tissue cyst development in muscle. If this were so it raises the question of whether the vaccine could be used to make meat safer for human consumption.     

Sequelae and support after termination of pregnancy for fetal malformation.

A retrospective study examined the reactions to the termination of pregnancy for fetal malformation and the follow up services that were available. Women resident in Mid Glamorgan who had had a termination between 1977 and 1981 because of positive findings after midtrimester prenatal diagnostic tests for neural tube defect or chromosome abnormalities were interviewed at home using a semistructured interview schedule. Three retrospective internal comparison groups were formed from those women who had also had a spontaneous abortion, previous stillbirth, or neonatal death or previous termination for medicosocial reasons early in pregnancy. Of the 48 women interviewed, 37 (77%) experienced an acute grief reaction after the index pregnancy was ended. This reaction was akin to that documented after stillbirth or neonatal death. Twenty two women (46%) remained symptomatic six months after the pregnancy had been ended, some requiring psychiatric support, compared with no such reaction after spontaneous abortion or termination for medicosocial reasons. All the women who had previously had a stillbirth or neonatal death were visited at home either by the general practitioner or by the midwife after that event but such follow up was limited to only eight of the study group after termination for fetal malformation. The findings suggest that support is inadequate for these patients and that improved follow up and counselling services may lessen the adverse sequelae of termination for fetal malformation.     

Natural mortality and cause of death analysis of the captive chimpanzee (Pan troglodytes): A 35‐year review

We present the spontaneous causes of mortality for 137 chimpanzees (Pan troglodytes) over a 35‐year period. A record review of the pathology database was performed and a primary cause of mortality was determined for each chimpanzee. The most common causes of mortality were as follows: cardiomyopathy (40% of all mortalities), stillbirth/abortion, acute myocardial necrosis, chimpanzee‐induced trauma, amyloidosis, and pneumonia. Five morphologic diagnoses accounted for 61% of mortalities: cardiomyopathy, hemorrhage, acute myocardial necrosis, amyloidosis, and pneumonia. The most common etiologies were degenerative, undetermined, bacterial, traumatic, and neoplastic. The cardiovascular system was most frequently involved, followed by the gastrointestinal, respiratory, and multisystemic diseases. Degenerative diseases were the primary etiological cause of mortality of the adult captive chimpanzee population. Chimpanzee‐induced trauma was the major etiological cause of mortality among the perinatal and infant population. This information should be a useful resource for veterinarians and researchers working with chimpanzees.     

High risk maternal factors related to fetal wastage in rural Bangladesh

An analysis of the relationship between fetal mortality (early fetal death and stillbirth), pregnancy order, maternal age, and previous fetal deaths in a rural Bangladesh population characterized by high fertility and mortality and the virtual absence of obstetric and other medical care indicates that early fetal wastage and stillbirth are higher among pregnancy orders 1 and 6, or higher than among orders 2 and 3, with the increased risk particularly apparent among those pregnancies following 2 or more previous fetal deaths. The data consist of the 21,144 pregnancies that occurred to the women in Matlab, Bangladesh, 1966-1969. By a multiple regression technique allowing for pregnancy order and previous fetal deaths, adjustments were made for age of the mother, and after allowances were made for previous fetal deaths, adjustments were made for pregnancy order. Results show the fewest fetal deaths in 2nd and 3rd pregnancies, and most at the highest parities. 10% of all pregnancy terminations 1966-1969 were registered as fetal deaths. Women in the higher pregnancy orders who have not experienced previous fetal deaths or only 1 fetal death have only a slight increase in the risk of fetal death compared to women in pregnancy orders 2 and 3. It is concluded that the virtual absence of medical care facilities is responsible for the large numbers of fetal deaths due to complications of gestation, delivery, and environmental influences. It also results in a higher maternal mortality of women with pregnancy complications related to fetal deaths. This absence of obstetric care and the high maternal mortality in this population may allow only women without reproductive impairments to reach the higher pregnancy orders.     

死胎的病因及终止妊娠的方式分析

目的：探讨死胎的病因及终止妊娠的方式。方法：收集我院住院分娩的死胎病例23 例,对孕妇一般资料、死胎发生原因、终 止妊娠方式进行统计分析。结果：①死胎发生孕妇中,年龄＞36 岁者最多,共8 例,占34.8%,孕周在28-36+6 周的孕妇数最多,共 10 例,占43.5%,初产妇17 例,占73.9%,有流产史孕妇9 例,占39.1%;②在所有病因中,脐带因素占比最大,共11 例,占47.8%, 其次为胎盘因素和母体因素,各5 例,各占21.7%,胎儿原因与不明原因各2 例,各占8.7%;③在对终止妊娠方式的选择上,施行 羊膜腔穿刺引产例数最多,共13 例,占56.5%,其次为剖宫产,共5 例,占21.7%,米索流产3 例,占13.0%,自娩患者2 例,占 8.7%。结论：脐带因素为造成死胎发生的主要原因,其次为胎盘因素及母体因素,应对孕妇进行全面的孕期检查及孕期健康教育, 以减少死胎的发生,并选择合适的终止妊娠方式以减轻孕妇痛苦。     

A multiple pregnancy register in the north of England.

A regional population-based Multiple Pregnancy Register was established in 1998, with the aim of collecting detailed information on multiple pregnancies to enable research into mortality and morbidity in multiples. Multiple pregnancies are notified to the Register as soon as they are detected, irrespective of whether they resulted in a spontaneous abortion, termination of pregnancy or registered birth. Nine hundred and twenty-six twin pregnancies were recorded during 1998-99, giving a twinning rate of 14.8 per 1000 maternities (rate at birth 13.0 per 1000 maternities). Sixty one per cent of twin pregnancies were detected before 13 weeks of gestation. Chorionicity was determined in 82.6% of 849 twin maternities with at least one stillbirth or livebirth. The fetal loss rate before 24 weeks of gestation was 10.5% (194/1852). The perinatal and infant mortality rates were 40.6 per 1000 births and 32.6 per 1000 livebirths respectively. A prospective Multiple Pregnancy Register not only allows monitoring of trends in multiple birth rates and mortality, but also etiological research and long-term follow-up studies.     

Abortion and Calf Mortality in Danish Cattle Herds

The aetiology of abortions and calf mortality in 65 Danish cattle herds consisting of both dairy and beef breeds during a 1-year period is described. All observed aborted foetuses, stillborn calves, and calves dying before 6 months of age were necropsied, and relevant microbiological examinations were performed. A total of 240 calves and 66 abortions were submitted corresponding to a calf mortality rate of 7%. The abortion frequency could not be calculated. 43% of the calves died at day 0, while 22% were aborted, 15% died during the first week of life, 9% died from 1 to 4 weeks of age, and 11% died at the age of 1 to 6 months. The most common cause was neonatal pulmonic atelectasis (stillbirth) followed by foetal infections, pneumonia, and septicaemia.     

Inheritance of congenital heart disease

Congenital heart defects (CHD) are the most common developmental anomalies and are the leading noninfectious cause of mortality in newborn babies. It has been estimated that between four and ten live-born infants per 1000 have a cardiac malformation (0.4 to 1.0%), 40% of which are diagnosed in the first year of life. The European Registration of Congenital Anomalies (EUROCAT) reported a prevalence of 58.9/10,000 live births in the northern part of the Netherlands (0.6%). Hoffman estimated that the true prevalence of CHD may be as high as 53 per 1000 pregnancies (5.3%), including a 20% occurrence of heart defects in spontaneous abortion, a 10% occurrence in stillbirth, and a 1% occurrence in live birth.     

Prosimian juvenile mortality in zoos and primate centers

I review literature on juvenile mortality of captive prosimians in order to evaluate the available information on captive breeding. Juvenile mortality includes abortion, premature mortality, stillbirth, and death of the unweaned young. Prosimian juvenile mortality ranges between 25 and 45% in captive populations. It is generally lower in the Lemuroidea, particularly the Cheirogaleidae, than in the Lorisoidea. Mortality is particularly high in the Lorisinae. Most mortality, including a high stillbirth rate, occurs on the first day and during the first 10 days thereafter. Stress, maternal neglect and traumatic insults, not infrequently linked to each other, are the most frequently reported causes of death. The percentage of congenital malformations tends to be high in some colonies. Sex of the infant and parity seem to be important risk factors for juvenile mortality, whereas litter size does not appear to be important. Based on few data, wild- caught females appear to have higher breeding success than those born in captivity. Synchronized births in lemuroids and isolated births in Galagoare more likely to result in successfully weaned infants.     

Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus

The aim of this study was to investigate possible associations of -2548 G/A polymorphism in leptin gene promoter and pregnancy-associated diseases with abnormal fetal growth such as preeclampsia and gestational diabetes. The study was also focused on whether it is rather maternal or fetal variants that determines the pathological growth status. Peripheral or cord blood samples obtained from 49 preeclamptic women and their 39 newborns, 53 healthy controls and their 53 healthy newborns and 48 patients with gestational diabetes mellitus were evaluated for leptin gene (LEP) locus -2548 genotypes. The significantly higher risk for gestational diabetes mellitus was observed in the presence of an allele (AA and AG genotypes) against carriers of GGgenotype(OR=2.84, 95%CI1.14-7.07,p=0.02). Thereisa significant risk of diabetes mellitus associated to A allele (OR=1.79, 95%CI 1.02-3.14, p=0.03). Furthermore, evaluations of preeclamptic patients' data revealed a significant association of genotype distribution and delivery and spontaneous abortion rate, where the GG carriers performed the highest pregnancy rate while the AG carriers performed the lowest spontaneous abortion rate. Our results support the hypothesis for -2548 G/A leptin gene polymorphism involvement in ethiopathogenesis of pregnancy-associated diseases with abnormal fetal growth, especially gestational diabetes mellitus.     

Genetische Risiken der assistierten Reproduktion

Infertility patients have to be counseled about the genetic risks before treatment. Chromosomal anomalies can be found in 5% of subfertile men and in cases of azoospermia the frequency even rises to 15%. Therefore a chromosome analysis should be performed in men with a sperm count <20 million/ml and also in their partners. Klinefelter’s syndrome as well as a Robertsonian translocation can cause male subfertility. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and deletions in the Y chromosome have been described as being more frequent in these cases. Regarding pregnancy and neonatal outcome of children, patients have to be counseled about the increased risk of complications. The abortion rate is increased by 1.3-fold, although this is most likely caused by the subfertility of the couple and other risk factors and not caused by the therapy. Complications during pregnancy, such as preeclampsia, growth retardation, stillbirth and a low birth weight are more common after assisted reproduction. The incidence of congenital anomalies is increased by 1.3-fold after in vitro fertilization (IVF) as well as after intracytoplasmic sperm injection (ICSI) therapy.     

The present and future of whole-exome sequencing in studying and treating human reproductive disorders

The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Whole-exome sequencing (WES) is widely used to detect genetic variations associated with human diseases and has recently been successfully applied to unveil genetic causes of unexplained recurrent spontaneous abortion (URSA) and fetal malformations. Here, we review the current discovery and diagnosis strategies to identify the underlying pathogenic mutations of URSA and fetal malformations using WES technology and propose to further develop WES, both to advance our understanding of these diseases and to eventually lead to targeted therapies for reproductive disorders.     

Nominations sought for Mindel C. Sheps Award

Abstract

The relationship between early fetal wastage or stillbirth and pregnancy spacing was examined in a population characterized by prolonged lactation, minimal nutrition, and high fertility and mortality. The highest risk of early fetal death was found among those pregnancies conceived less than twelve months after the birth of a surviving breast‐fed infant. Lactation as a possible causal factor is discussed. A significant inverse relationship was apparent for second trimester fetal deaths and pregnancy intervals, but not for third trimester deaths. This finding is surprising when one considers that fetal weight gain, and presumably nutrient demand, increases most rapidly during the third trimester.     

Effect of short-term hypothyroidism on reproduction in the bitch

Hypothyroidism in bitches has been reported to cause a variable interestrus interval, infertility, abortion, and stillbirth. The objective of this study was to evaluate the effect of experimentally induced hypothyroidism in bitches on fertility, pregnancy, parturition, and neonatal health. Eighteen healthy multiparous bitches were used; hypothyroidism was induced (by radioiodine administration) in nine bitches and the remaining nine served as untreated controls. After breeding, bitches were evaluated for pregnancy, fetal resorption, gestation length, litter size, duration and strength of uterine contractions (during parturition), interval between delivery of pups, viability of pups at birth, periparturient survival, and weight of pups at birth through 4 weeks of age. Bitches were bred a median of 19 weeks after induction of hypothyroidism. All bitches became pregnant and delivered term litters. There was no difference in the interestrus interval, litter size, or gestation length between hypothyroid and control bitches. Duration of uterine contractions was longer, but contraction strength was weaker in hypothyroid than control bitches; however, the interval between delivery of pups was not affected. Periparturient puppy mortality was significantly higher in litters from hypothyroid bitches. Viability scores and weight at birth were significantly lower in pups from hypothyroid bitches than controls. There was no difference between groups in pup weight gain during the first 4 weeks, in the interval from birth to the eyes opened, or to the onset of walking. Although hypothyroidism of relatively short duration did not affect fertility, it prolonged parturition and reduced pup survival in the periparturient period.     

Effects of retention of fetal membranes on subsequent reproductive performance of dairy ewes

Seventy-one pairs of ewes with or without retention of fetal membranes in the previous lambing season, were included in a cohort study of 25 flocks in southern Greece; in 27 pairs regulation of the breeding cycle was applied, whilst in the other 44 pairs natural mating took place. The following measures of reproductive performance were calculated: cycling rate, mating rate, return-to-estrus rate, abortion rate, lambing rate, total lambs born per ewe, liveborn lambs per ewe, stillbirth rate, lamb-bodyweight per ewe; furthermore, the incidence risk of retention of fetal membranes during the lambing examined in this study was also calculated. No statistically significant differences were observed in the reproductive performance among ewes that had or had not retained their fetal membranes during the previous lambing, whether the breeding cycle was regulated or not. The incidence risk of retention of fetal membranes among ewes that had not retained its placenta in the previous lambing was 1.6%, whilst that among ewes that had retained its placenta in the previous lactation was 0%. It is concluded that retention of fetal membranes did not appear to adversely affect subsequent reproductive performance of ewes.     

Pregnancy and Crohn's Disease

Of 77 married women with Crohn''s disease, 25 were sterile. In the remaining 52 (98 pregnancies) the risks of prematurity, stillbirth, abortion, or congenital abnormality were not increased. There was no evidence that pregnancy exerted adverse effects on the course of the disease or increased the mortality rate. Sterility was the main problem encountered.     

Ljungan virus: a commentary on its association with fetal and infant morbidity and mortality in animals and humans

Epidemiologic and experimental data support the notion that Ljungan virus (LV), endemic in some rodent populations in Sweden, Denmark, and the United States, can cause morbidity and mortality in animals and humans. LV infection can cause type I diabetes mellitus, myocarditis, and encephalitis in bank voles and experimental mice, and lemmings. Mouse dams infected with LV experience high rates of stillbirth that may persist across generations, and their fetuses may develop cranial, brain, and limb malformations. In humans, epidemiologic and serologic data suggest that LV infection correlates with intrauterine fetal death, malformations, placental inflammation, myocarditis, encephalitis, and Guillain-Barré syndrome. The proposed role of LV infection in SIDS is unconvincing. Further research is necessary to clarify the role of LV infection in animal and human disease.