Maternal Stillbirth Research Articles

A single-center, retrospective analysis of 17 cases of hemolytic disease of the fetus and newborn caused by anti-M antibodies.

We aimed to summarize the laboratory findings and clinical features of hemolytic disease of the fetus and newborn (HDFN). We retrospectively analyzed the data for 17 infants with anti-M-induced HDFN (anti-M-HDFN) diagnosed between June 2013 and May 2019. Their maternal history, neonatal diagnosis on admission, and laboratory test results were compared with those of 15 infants with HDFN involving the ABO blood group system, 15 infants with HDFN involving the Rh system, and 15 premature infants. In the anti-M-HDFN group, 94.12% (16/17), 35.29% (6/17), and 17.65% (3/17) had free antibodies in plasma, a positive direct antiglobulin test, and a positive elution test, respectively. In 12 infants, free antibody reactions were stronger at 4°C than at 37°C, and the antibody titer at 4°C ranged from 1 to 512. All 17 infants with anti-M-HDFN developed anemia: 14 were treated with blood transfusion and 1 with neonatal exchange transfusion. Sixteen infants improved, and one died. Anti-M-HDFN had a higher rate of maternal stillbirth, lower gestational age, lower birthweight, and higher incidence of respiratory distress than other HDFN types. Anti-M may cause HDFN. It may present with varying degrees of anemia, low regenerative anemia, and low bilirubin levels. In addition, infants with anti-M-HDFN may have a negative elution test and direct antiglobulin test. These tests are helpful in examining antibody responses at a low temperature of 4°C.

Genotype-by-environment interactions at the trait level and total merit index level for milk production and functional traits in Brown Swiss cattle

The production environments of the German–Austrian Brown Swiss population show a wide range due to differences in topography, landscapes, local climates, and different farm management systems. Extensive production systems such as organic farming have become increasingly popular in recent decades because of interest in sustainability and consumer preferences. Compared with conventional farmers, organic farmers put more weight on fitness traits. Besides the official total merit index (TMI), a selection index applying relative economic weights (REWs) suitable for organic production systems is provided for Brown Swiss cattle in Germany. The aim of the study was to investigate genotype-by-environment interactions (GxE) for milk production traits and functional traits (including longevity, fertility traits, and calving traits) in a sample of the German–Austrian Brown Swiss population housed in Baden-Wuerttemberg (southern Germany) by applying bivariate and random regression sire models. For bivariate analyses, the production environment was binary classified by farm management system (organic and conventional) and altitude of farm location (above or below 800 m above sea level (ASL)). Milk energy yields (MEY) obtained from herd effects were used as continuously scaled environmental descriptor in the reaction norm approach. The TMIs for sires were calculated based on breeding values estimated with different models and environment-specific REWs to determine possible GxE at TMI levels and rerankings of sires. In bivariate analyses, genetic correlations at the trait level were high and ranged from rg = 0.99 (calving to first insemination, cystic ovaries, and maternal stillbirth rate) to rg = 0.79 (first insemination to conception for altitude). Except for the latter, no severe GxE were found at the trait level using the bivariate models. Fat yield was the only trait showing minor GxE in the reaction norm model approach. Investigating the environmental sensitivity at the TMI level revealed rank correlations between the different environment-specific TMIs that were close to unity, implying no severe reranking effects. The results show no need to account for different environments in Brown Swiss cattle breeding programs.

Maternal spontaneous abortion and the risk of attention-deficit/hyperactivity disorder in offspring: a population-based cohort study.

Is a maternal history of spontaneous abortion (SA) associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring? Our results suggest an association between maternal history of SA and ADHD in offspring, with the risk increasing with the number of maternal SA and highest in the firstborn children whose mothers had had recurrent SAs after adjusting for a number of potential confounders. A history of SA has been associated with more complications in next pregnancies and adverse childbirth outcomes, which are risk factors for ADHD in the offspring. However, no previous study has investigated whether maternal SA increases risk of ADHD in the offspring. This population-based study included all live-born children in Denmark from 1 January 1995 to 31 December 2012 (n = 1 062 667). All children were followed from 3years of age until the day of ADHD diagnosis, death, emigration or 31 December 2016, whichever came first. There were 130 206 (12.2%) children born to mothers who had at least one SA. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 9.4years (interquartile range, 5.4-14.3), 25 747 children were diagnosed with ADHD. Overall, children of mothers with a history of SA had an increased rate of ADHD (HR, 1.11; 95% CI, 1.07 to 1.15). The HRs increased with the number of maternal SA, 1.09 (95% CI, 1.05 to 1.13) for one SA and 1.22 (95% CI, 1.12 to 1.33) for at least two SAs, respectively. These findings were consistent when we took into consideration a number of factors, such as maternal socioeconomic status, type of SA, birth order, parental history of psychiatric disorders, pregnancy characteristics and adverse birth outcomes. Misclassification of SA was possible as we used population-based register data to capture maternal history of SA. However, any misclassification of maternal history of SA would be non-differential with regard to the diagnosis of ADHD in offspring, which generally leads to underestimation of the associations. Furthermore, probabilistic sensitivity analysis suggested that only 1% of change in the estimate may have been due to misclassification of SA. SA is quite frequent (varying from 15 to 20%), and a small increase of neurodevelopmental problems in offspring could have major public health implications. This work was supported by grants from the National Natural Science Foundation of China (No. 81703237, No. 81530086 and No. 81761128035), National Key Research and Development Program (2018YFC1002801, 2016YFC1000505), Shanghai Municipal Commission of Health and Family Planning (No. 2017ZZ02026, No. 2017EKHWYX-02), the Novo Nordisk Foundation (NNF18OC0052029), the Danish Council for Independent Research (DFF-6110-00019), the Nordic Cancer Union (176673, 186200 and R217-A13234-18-S65), Karen Elise Jensens Fond (2016) and Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (2018YJRC03). All authors report no conflict of interest. NA.

STUDY OF MATERNAL RISK FACTORS CONTRIBUTING IN THE DEVELOPMENT OF CONGENITAL HYPOTHYROIDISM

ABSTRACT Background: The study was conducted to assess maternal factors contributing in the development of congenital hypothyroidism (CH) in their neonates whom were diagnosed by public health insurance newborn screening program during study period from January to December 2017 in Sharkia governorate. Methods: The study had been conducted on selected sample of 50 mothers; they are selected according to their neonates' thyroid profile and divided into two groups: Group 1 (cases): selected 25 mothers having neonates diagnosed with CH. Group 2 (control): selected 25 healthy neonates and their mothers. All mothers in our study were subjected to full history assessment, physical exam and specific laboratory testing including (TSH, Free T4, Free T3, Anti TPO and Anti TG). On other hand, baseline characteristics and screening laboratory results of neonates diagnosed with CH were obtained from their registered profiles in public health insurance organization in Sharkia governorate. Results: Clinical parameters of mothers included revealed that mothers having previous history of thyroid disorders as well as maternal abortion rates were higher in case group compared to control group and this difference was statistically significant. Clinical and demographic results of neonates diagnosed with CH, showed that neonatal birth weight was lower in case group compared to control group and this difference was statistically significant. The presence of maternal thyroid dysfunction (mainly hypothyroidism) was higher in case group compared to control group and this difference was statistically significant. Maternal auto-thyroid antibodies (Anti TPO and Anti TG) were higher in case group compared to control group and this difference was statistically significant. Conclusions: Maternal risk factors in our study contributing in the development of CH were highly related to the presence of maternal thyroid disorders either controlled on treatment or not. As well as, thyroid laboratory dysfunction (mainly sub/hypothyroidism) in mothers induced mostly by autoimmune thyroid state confirmed by presence of higher levels of auto-thyroid antibodies (Anti TPO and Anti TG) which proved to be significant and these autoimmune antibodies in its turn increase the rates of maternal miscarriage, neonatal prematurity and low birth weight as reported in our study. Abbreviations: CH= congenital hypothyroidism, TSH= Thyroid Stimulating Hormone, Anti TPO= anti thyroid peroxidase antibodies, Anti TG= anti thyroglobulin antibodies. Key words: congenital hypothyroidism, maternal, autoimmune thyroid.

Commentary on "Gay Male Only-Children: Evidence for Low Birth Weight and High Maternal Miscarriage Rates" from the Prenatal Thyroid Model Perspective.

Commentary on "Gay Male Only-Children: Evidence for Low Birth Weight and High Maternal Miscarriage Rates" from the Prenatal Thyroid Model Perspective.

The association of maternal factors with epibulbar dermoid of newborn: a retrospective, matched case-control study.

PurposeTo determine the association of maternal factors and exposure during pregnancy with the incidence in newborns of epibulbar dermoid (ED), a congenital ocular surface benign tumor.Patients and methodsThis is a retrospective, paired case-control study in which 121 children with ED (case group) and 121 children without ED (control group) were recruited. Questionnaire-based interviews with mothers of participants were performed and maternal medical records during pregnancy were reviewed. The questionnaire investigated basic information, personal history, environmental exposure, exposure to maternal diseases, symptoms and corresponding medical treatments during pregnancy, and parental socioeconomic status. The case and control participants were matched for sex, birth weight, gestational age, and parental socioeconomic status level. Univariate and multivariate logistic regression analyses were conducted with ED as the main outcome variable.ResultsFactors significantly associated with ED were: history of maternal inevitable miscarriage (odds ratio (OR), 2.59; 95% confidence intervals (CI), 1.13-5.90), common cold in the first trimester (OR, 3.94; CI, 1.74-8.93), and paternal smoke exposure >half a pack per day during pregnancy (OR, 4.81; CI, 1.74-13.28).ConclusionHistory of maternal miscarriage, common cold exposure in the first trimester, and paternal smoking (>half a pack per day) during pregnancy could result in significant risk factors for ED of newborns. These data also imply that paternal smoking delivers nicotine to maternal respiratory system and uterine microenvironment that may both affect microvascular development and predispose the fetus to future ED.

Association between a Maternal History of Miscarriages and Birth Defects.

Some studies, mainly in the older literature, observed a significant association between miscarriages and birth defects (BDs) occurring in the same sibship. However, few studies examined the BD/miscarriage relationship in depth. In addition nothing has been added to the underlying mechanisms possibly linking both events. The purpose of this work was to identify specific BDs associated with maternal miscarriages. In particular, it examined whether the risk depended on the number of losses, and to suggest the existence of specific factors for each BD/miscarriage association observed. The study relied on the Latin American Collaborative Study on Congenital Malformations (ECLAMC) database registries including 26,906 live and stillborn infants with one of 19 selected isolated BDs and 93,853 normal controls. Infants born to primigravid mothers were excluded from the present study. Demographic and reproductive variables were compared between control mothers With and Without previous miscarriages. The number, frequency, and distribution of miscarriages were observed for each BD and controls. A conditional logistic regression was applied to evaluate the miscarriage risk for each BD. Control mothers with previous miscarriages were older, had had more pregnancies, and were less educated. Three risk patterns of miscarriages were observed: a very high risk of miscarriages associated with gastroschisis, omphalocele, and talipes; only one miscarriage associated with spina bifida, and two or more miscarriages associated with hypospadias. These three patterns suggest that different factors underly each BD/miscarriage association: infertility for hypospadias, vascular disruption for gastroschisis and talipes, while for spina bifida, the much debated trophoblastic cell residue theory could not be discarded. Birth Defects Research 109:254-261, 2017. © 2017 Wiley Periodicals, Inc.

Genome-wide mapping of 10 calving and fertility traits in Holstein dairy cattle with special regard to chromosome 18

Over the last decades, a dramatic decrease in reproductive performance has been observed in Holstein cattle and fertility problems have become the most common reason for a cow to leave the herd. The premature removal of animals with high breeding values results in both economic and breeding losses. For efficient future Holstein breeding, the identification of loci associated with low fertility is of major interest and thus constitutes the aim of this study. To reach this aim, a genome-wide combined linkage disequilibrium and linkage analysis (cLDLA) was conducted using data on the following 10 calving and fertility traits in the form of estimated breeding values: days from first service to conception of heifers and cows, nonreturn rate on d 56 of heifers and cows, days from calving to first insemination, days open, paternal and maternal calving ease, paternal and maternal stillbirth. The animal data set contained 2,527 daughter-proven Holstein bulls from Germany that were genotyped with Illumina's BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). For the cLDLA, 41,635 sliding windows of 40 adjacent single nucleotide polymorphisms (SNP) were used. At each window midpoint, a variance component analysis was executed using ASReml. The underlying mixed linear model included random quantitative trait locus (QTL) and polygenic effects. We identified 50 genome-wide significant QTL. The most significant peak was detected for direct calving ease at 59,179,424 bp on chromosome 18 (BTA18). Next, a mixed-linear model association (MLMA) analysis was conducted. A comparison of the cLDLA and MLMA results with special regard to BTA18 showed that the genome-wide most significant SNP from the MLMA was associated with the same trait and located on the same chromosome at 57,589,121 bp (i.e., about 1.5 Mb apart from the cLDLA peak). The results of 5 different cLDLA and 2 MLMA models, which included the fixed effects of either SNP or haplotypes, suggested that the cLDLA method outperformed the MLMA in accuracy and precision. The haplotype-based cLDLA method allowed for a more precise mapping and the definition of ancestral and derived QTL alleles, both of which are essential for the detection of underlying quantitative trait nucleotides.

NKX2-5 molecular screening and assessment of variant rate and risk factors of secundum atrial septal defect in a Moroccan population

Objective:Secundum atrial septal defect (ASDII) has multifactorial etiology that is combination of environmental (e.g., mother’s exposure to toxicity, ethnicity) and genetic causes. Aim of the present study was to screen a Moroccan population with ASDII for NKX2-5 variants and to assess risk factors that may contribute to emergence of the disorder.Methods:Thirty-two non-syndromic ASDII patients were screened for NKX2-5 variants using direct sequencing of polymerase chain reaction-amplified coding regions. Risk factor rates were compared to general population and assessed using Fisher’s exact and chi-square tests. In this retrospective study, criteria of exclusion were suggestive or confirmed syndrome association.Results:Three heterozygous variants were detected in 4 patients. NKX2-5 variant rate in present cohort is estimated to be about 9.4%. Two prominent risk factors in the Moroccan population were highlighted: consanguinity, rate of which was significantly high at 30.8%, and previous maternal miscarriage or sibling sudden death, observed in 34.6% of cohort.Conclusion:Impact of identified variants was discussed and possible disease-predisposing effect is suggested. Findings indicate that ASD may be favored by consanguineous marriage and that NKX2-5 variant rate in ASD patients may be affected by ethnicity. High level of maternal miscarriage and sibling sudden death suggests potential non-sporadic nature as result of putative genetic defect.

Gay Male Only-Children: Evidence for Low Birth Weight and High Maternal Miscarriage Rates.

Recent findings suggest that there may be a maternal immune response underpinning the etiology of sexual orientation of gay male only-children. This maternal immune response appears to be distinct from that which is purported to explain the classic fraternal birth order effect found in studies of male sexual orientation. We tested two predictions related to the hypothesized maternal immune response in mothers of gay male only-children: (1) elevated fetal loss among mothers who have had gay male only-children and (2) lower birth weight in gay male only-children. Mothers of at least one gay son (n=54) and mothers of heterosexual son(s) (n=72) self-reported their pregnancy histories, including the birth weights of newborns and number of fetal losses (e.g., miscarriages). Mothers of gay male only-children (n=8) reported significantly greater fetal loss compared with mothers of males with four other sibship compositions (gay with no older brothers, gay with older brothers, heterosexual only-children, heterosexual with siblings) (n=118). Also, firstborn gay male only-children (n=4) had a significantly lower birth weight than firstborn children in the four other sibship compositions (n=59). Duration of pregnancy was not significantly different among the groups of firstborn children in the birth weight analyses. Thus, this study found further support for a distinct pattern of maternal immune response implicated in the etiology of male sexual orientation. Mechanisms that may underlie this potential second type of maternal immune response are discussed.

Genomic evaluation of a relatively small dairy cattle population by combination with a larger population

The objectives were to investigate the accuracy of genomic evaluations obtained for a small dairy cattle population (Israeli Holsteins) via joint evaluation with a larger population (Dutch Holsteins), and to evaluate the use of pedigree data from foreign bulls computed by Interbull without daughter records in Israel. The training population included 4,010 Dutch bulls and 713 Israeli bulls. The validation population included 185 Israeli bulls with daughter records for milk production traits and slightly fewer bulls for the nonproduction traits. Milk, fat, and protein yields, somatic cell score, longevity, female fertility, direct and maternal calving ease, direct and maternal stillbirth, and the Israeli breeding index were analyzed. The genomic prediction model was based on the Bayesian multi-QTL model of Meuwissen and Goddard, where the effects of dense single nucleotide polymorphisms across the whole genome are fitted directly, without the use of haplotypes or identical-by-descent probabilities. Correlations of May 2014 estimated breeding values (EBV14) with genomic EBV (GEBV) were higher than the correlations of EBV14 with parent averages (PA) computed from the June 2009 evaluation for all traits. For the Israel selection index, the difference between EBV14 and GEBV correlation on the one hand and EBV14 and PA computed using Interbull data on the other hand was 15 percentage points. For protein, the difference between the corresponding correlations was 14 percentage points. Generally, correlations of EBV14 with PA based on Israeli EBV only were similar to correlations of EBV14 with PA including Interbull evaluations. Relative to EBV14, milk production traits were biased upwards for both GEBV and PA, but the bias was greater for PA. The Y-intercepts of regressions of EBV14 were significantly different from zero for regression on GEBV for all 3 milk production traits and the Israeli selection index. This was not the case for regression of EBV14 on PA. The regression line intersected with the line of unbiased estimation near the EBV of the bulls with highest values. Because only bulls with high evaluations are of interest for selection, GEBV for these bulls were less biased compared with that of bulls with lower evaluations. The difference in mean EBV14 between bulls born during 2007–2008 selected by GEBV and PA was 65 units. If half of all inseminations are by young bulls, then the annual genetic gain obtained by implementation of genomic evaluation will be 8 units per year (65/8). Because annual gain is currently 107 units, this is a gain of 7%.

The placental growth factor (PGF) - a positional and functional candidate gene influencing calving ease and stillbirth in German dairy cattle

The bovine placental growth factor-encoding gene (PGF) was analysed as a positional and functional candidate gene for the maternal effect on stillbirth and calving ease in first parity. Prominent levels of PGF expression have been reported for the whole human placenta and umbilical vein endothelial cells. Modulation of angiogenesis, vessel remodelling and vascular permeability during implantation and placentation suggest an influence on trophoblast function during pregnancy. Changes of expression or protein function may therefore be crucial to pregnancy and parturition. By comparative sequencing of bulls with extreme approximate daughter yield deviations for calving traits, we identified 37 SNPs and two insertions/deletions within the PGF gene. Seventeen of the identified polymorphisms were genotyped in 368 selected bulls and tested for association with approximate daughter yield deviations for calving traits. In a single marker analysis, all SNPs were significantly associated with maternal stillbirth and calving ease first parity. The allele substitutions of the significant SNPs explain 8% to 14% and 8% to 15% of the additive genetic variance for maternal stillbirth and maternal calving ease first parity, respectively. There is no evidence that any of the polymorphisms identified within this study could be the causal mutation underlying the QTL, which is likely to be a regulatory mutation. In summary, we report polymorphisms in the bovine PGF gene significantly associated with the maternal effect on stillbirth and calving ease in animals under selection. These results should be confirmed and extended in further studies to identify the causal mutation underlying the QTL analysed.

Quantitative trait loci for milk production and functional traits in two Danish Cattle breeds

Quantitative trait loci (QTL) in Danish Jersey and Danish Red cattle were independently mapped by least squares regression analysis. For Jersey breed, five grandsire families were genotyped for 186 markers on 16 chromosomes (BTAs). Eight traits analysed were milk yield (MY), fat percentage (FP), protein percentage (PP), clinical mastitis (CM), somatic cell score (SCS), maternal stillbirth, maternal calf size (MCS) and maternal calving difficulty. For Red breed, nine grandsire families were genotyped for 166 markers on 18 BTAs. Six traits analysed were MY, FP, PP, CM, SCS and female fertility. Nine and five QTL were detected in Jersey and Red breed, respectively, in across family tests. In Jersey breed, the results indicate QTL for CM and MCS on BTA 3. Additionally, there is an indication of QTL for MCS and FP on BTA 1 and a tentative evidence for a QTL for MY on BTA 26. There is a high risk of detected QTL being false positives. The detected QTL in Jersey breed indicate interesting results from a breeding perspective, but a practical application should await genome-wide association studies.

Need for sharp phenotypes in QTL detection for calving traits in dairy cattle

The aim of the study was to investigate whether parity-specific phenotypes provide a clearer picture of quantitative trait loci (QTL) affecting calving traits in German Holsteins than breeding values estimated across parities. In experiment I, approximate daughter yield deviations were calculated by applying a univariate sire model assuming unrelated sires used as phenotypes in a QTL mapping study. These results were compared with those obtained using deregressed estimated breeding values obtained from the routine German sire evaluation (experiment II). In experiment I, 17 chromosome-wise significant QTL were found for the first parity, but only 12 for the second parity. Only three QTL for maternal stillbirth, located on BTA7, 15 and 23, showed an experiment-wise significance. Experiment II revealed 15 chromosome-wise significant QTL. The results differed markedly between first and second parity within experiment I, as well as between experiment I and II. The present study showed that parity-specific daughter yield deviations are beneficial for mapping QTL for calving traits. Furthermore, it is expected that the use of sharper phenotypes will also be advantageous for QTL fine mapping and the identification of candidate genes.

Quantitative Trait Loci Affecting Calving Traits in Danish Holstein Cattle

The objectives of this study were 1) to detect quantitative trait loci (QTL) affecting direct and maternal calving traits at first calving in the Danish Holstein population, 2) to distinguish between pleiotropic and linked QTL for chromosome regions affecting more than one trait, and 3) to detect QTL affecting stillbirth and calving difficulties but not calf size that could be used in selection to improve calving performance. Progeny-tested sons (2,297) were genotyped for 356 microsatellites in 34 grandsire families on all 29 autosomes. A total of 27 significant QTL on 17 chromosomes were detected using a between-families linear regression model. For the direct calving traits, 4 QTL significantly affected calving difficulty, 5 QTL affected stillbirth, and 7 QTL affected calf size subjectively assessed by the farmer as a categorical trait. When the maternal components of the same traits were tested, there were significant effects of 3 QTL on calving difficulty, 6 QTL on stillbirth, and 2 QTL on calf size. The variance component mapping approach was used to estimate the relative posterior probability of linkage and pleiotropic models. The most probable model indicated a pleiotropic QTL on chromosome 12 and 25 and a linked QTL on chromosome 7 and 26. Chromosome 18 seemed to harbor a QTL with a pleiotropic effect on the direct calving traits and linked to maternal stillbirth. Markers on chromosomes 3, 4, 7, 10, 12, 18, 21, 24, 26, and 28 can be used to select new breeding candidates to produce daughters with more efficient calving performance.

Genetic Analysis of Calving Difficulty and Stillbirth in Norwegian Red Cows

The objectives of this study were to infer genetic parameters for stillbirth (SB) and calving difficulty (CD) and to evaluate phenotypic and genetic change for these traits in the Norwegian Red breed. Stillbirth is recorded as a binary trait and calving difficulty has 3 categories: 1) easy calving, 2) slight problems, and 3) difficult calving. The overall mean frequency of SB in Norwegian Red was 3% at first calving and 1.5% for second and later calvings; mean frequency of the category “difficult calving” was 2 to 3% for heifers and 1% for cows at second and later calvings. Mean stillbirth rate has remained unchanged from 1978 to 2004. The proportion of the category “difficult calving” has not changed over the years, but the “slight problems” category increased from 4 to 7% for heifers and from 2 to 3% for cows. A total of 528,475 first-calving records were analyzed with a Bayesian bivariate sire-maternal grandsire threshold liability model. Posterior means of direct and maternal heritabilities were 0.13 and 0.09 for CD, and 0.07 and 0.08 for SB, respectively. Strong genetic correlations were found between direct SB and direct CD (0.79), and between maternal SB and maternal CD (0.62), whereas all genetic correlations between direct and maternal effects within or between traits were close to zero. These positive correlations are favorable in the sense that selection for one of the traits would result in a favorable selection response for the second trait. No genetic correlations between direct and maternal effects imply that bulls should be evaluated both as sire of the calf (direct) and sire of the cow (maternal). No genetic change for SB was found, and a slight genetic improvement for CD was detected.

Genetic Evaluation of Stillbirth in United States Holsteins Using a Sire-Maternal Grandsire Threshold Model

A sire-maternal grandsire threshold model was used for genetic evaluation of stillbirth in US Holsteins. Calving ease and stillbirth records for herds reporting at least 10 dead calves were extracted from the Animal Improvement Programs Laboratory database. About half of the 14million calving ease records in the database had a known livability score, mostly from herds processed by Dairy Records Management Systems (Raleigh, NC). Calf livability scores of 2 and 3, representing calves born dead and calves that died within 48h of parturition, respectively, were combined into a single category. The model included effects of herd-year, year-season, parity-sex, sire, birth year group of sire, maternal grandsire (MGS), and birth year group of MGS. Herd-year, sire, and MGS were random effects. Mean predicted transmitting abilities, expressed as the expected percentage of stillbirths, were 7.9 and 8.6 for direct and maternal stillbirths, respectively. Mean reliabilities for both the direct and maternal effects were 45%. Correlations among domestic and Interbull stillbirth solutions on the underlying scale for bulls with at least 90% reliability ranged from 0.63 to 0.90 across countries for direct stillbirths and from 0.69 to 0.96 for maternal stillbirths, indicating that results were generally consistent with those from other countries. There was no evidence of a genetic trend for either trait. More complete recording of stillbirth scores would improve reliabilities and could allow for evaluations of other breeds.

Sudden infant death syndrome in Japan 1995–1998

This study examined the effects of birth characteristics, which reported on birth certificates, on sudden infant death syndrome (SIDS) based on vital statistics between 1995 and 1998 in Japan. One thousand eight hundred and fifty-nine cases of SIDS and 4,787,537 live births were analyzed. The mortality rate from SIDS was 0.388 SIDS deaths per 1000 live births. Based on multivariate analysis using Poisson regression model, risk factors associated with significantly increased SIDS rates included low birth weight, being a male infant, young maternal age, late birth in multiparity, maternal stillbirth experience, residential region of Kyusyu, Tokai or Hokuriku, and employment status as “unemployed or unknown”. However, there was no significant difference between single and multiple birth groups after adjusting other characteristics. A decreasing postnatal age of death was observed as birth weight increased. However, there was no difference in postconceptional age of death between birth weight groups. Preterm infants died of SIDS at a later postnatal age than term infants, but there appeared to be little difference in postconceptional age of death amongst preterm infants. This association between birth characteristics and SIDS were consistent with other studies from western countries, suggesting that recommendations for SIDS in western countries are also applicable for Japan.

Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study.

In a historical cohort study of all singleton live births in Northern Ireland from 1971–86 (n=434 933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (⩾35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96–2.31) but no association with maternal age. High birth weight (⩾3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18–2.33). Children of mothers with a previous miscarriage or increased gestation (⩾40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29–0.80, and 0.67; 95% CI=0.48–0.94). Children born into more crowded households (⩾1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35–0.91 and 0.58; 95% CI=0.21–1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood.British Journal of Cancer (2002) 86, 356–361. DOI: 10.1038/sj/bjc/6600012 www.bjcancer.com© 2002 The Cancer Research Campaign

Risk of epilepsy in offspring of affected women: association with maternal spontaneous abortion.

Previously, the authors found that risk of spontaneous abortion was increased in the pregnancies of women with epilepsy compared with their same-sex siblings, which could have implications for risk of epilepsy in their offspring. An association between a history of spontaneous abortion in the mother and risk of epilepsy in her live-born offspring may arise through selective loss of fetuses with a genetic susceptibility to epilepsy or through intrauterine environmental factors that may predispose the mother to a spontaneous abortion and to epilepsy in her live-born children. The authors examined the relation of a history of spontaneous abortion to the risk of idiopathic or cryptogenic epilepsy in 791 live-born offspring of 385 women with cryptogenic localization-related epilepsy (probands) ascertained from voluntary organizations. A semistructured telephone interview with probands and additional family informants, supplemented by medical record review, was used to obtain information on seizures and other risk factors in probands and relatives. Live-born offspring of women with a history of spontaneous abortion were four or five times as likely to develop epilepsy as were children of women without (12.8% versus 4.7%; rate ratio = 4.6, 95% CI: 2.3-9.0). Cumulative incidence of epilepsy was 21.9% in offspring of women with a history of spontaneous abortion and a family history of epilepsy, compared with 4.7% in offspring of women with neither risk factor. These results suggest that a history of spontaneous abortion is associated with increased risk of epilepsy in live-born offspring and may be a marker for genetic susceptibility for epilepsy in the mother.