NSIDRC Journal Article Alert — October 31, 2008
Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center at Georgetown University.
This journal article alert provides selected items added to the National Library of Medicine's PubMed database in the last week.
Past issues of Resource Center journal alerts are available at http://www.sidscenter.org. Availability of full-text journal articles is often limited to subscribers or through inter-library loan. Please see your local library for copies of these articles, or view PubMed's How to Get the Journal Article for more details.
Miscarriage/Stillbirth/Prenatal Issues
1. Lovold A, Stanton C, Armbruster D How to avoid iatrogenic morbidity and mortality while increasing availability of oxytocin and misoprostol for PPH prevention? Int J Gynaecol Obstet. 2008 Oct 25. [Epub ahead of print]
Owen Sound, Ontario, Canada.
OBJECTIVE: Increased availability of oxytocin and misoprostol is needed to reduce the risk of postpartum hemorrhage. This review compiles rates and risks of adverse maternal and perinatal outcomes associated with use of these medications for labor induction and augmentation in low-income countries. Recommendations are proposed based on the findings. METHODS: We did a structured literature review using 5 databases followed by analysis of induction and augmentation rates from existing data. RESULTS: Combined induction and augmentation rates were documented in up to 50% of hospital-based deliveries identified in the databases. Data are sparse but suggest associations between induction/augmentation and stillbirth, neonatal resuscitation, and uterine rupture, and inappropriate administration of oxytocin and misoprostol both outside and inside healthcare systems in low-income countries. CONCLUSIONS: Guidelines for labor induction/augmentation are needed specifically for low resourced settings. Rigorous studies should be pursued to quantify the magnitude and effect of inappropriate induction and augmentation on maternal and perinatal morbidity and mortality. Programs are needed to ensure community-wide awareness of the adverse effects of the improper use of these drugs on mothers and babies, especially in out-of-hospital settings.
2. Prefumo F, Fratelli N, Ganapathy R, Bhide A, Frusca T, Thilaganathan B First trimester uterine artery Doppler in women with previous pre-eclampsia Acta Obstet Gynecol Scand. 2008 Oct 24:1-5. [Epub ahead of print]
Fetal Medicine Unit, Division of Obstetrics and Gynaecology, St George's, University of London, London, UK.
Objective. To assess the role of first trimester uterine artery Doppler in pregnancies previously complicated by pre-eclampsia. Design and setting. Case-control study in two tertiary referral hospitals. Sample. A total of 56 singleton pregnancies in women with a previous pregnancy complicated by pre-eclampsia (Group 1). For each case, two parous controls (Group 2) and two nulliparous controls (Group 3) with normal pregnancy outcome were matched. Methods. Doppler examination of the uterine arteries at 11-14 weeks' gestation. Main outcome measures. Mean uterine artery resistance index (UtARI) and notching. Pregnancy outcome. Results. UtARI did not vary significantly between the three groups (0.73, 0.70 and 0.71, respectively). Women in Group 1 had a significantly higher prevalence of uterine artery notching than those in Group 2 (73 vs 57%, p=0.04). In Group 1, the UtARI and prevalence of notching was not significantly increased when pregnancies were subsequently complicated by pre-eclampsia (p=0.60 and 0.61, respectively). However, in 12 pregnancies requiring delivery before 37 weeks due to pre-eclampsia, fetal growth restriction, abruption or intrauterine fetal death, the UtARI was significantly higher than in the 44 pregnancies with normal outcome (p=0.04). A combination of UtARI and notching showed sensitivities up to 75% and negative predictive values up to 88% for adverse outcome before 37 weeks. Conclusions. In pregnancies following a previous gestation complicated by pre-eclampsia, first trimester uterine artery Doppler findings are similar to those observed in nulliparous women. In these high-risk women, a combination of UtARI and notching can predict the risk of adverse outcome before 37 weeks.
3. Varli IH, Petersson K, Bottinga R, Bremme K, Hofsjo A, Holm M, Holste C, Kublickas M, Norman M, Pilo C, Roos N, Sundberg A, Wolff K, Papadogiannakis N The Stockholm classification of stillbirth Acta Obstet Gynecol Scand. 2008 Oct 24:1-10. [Epub ahead of print]
Department of Obstetrics and Gynaecology, Karolinska University Hospital, Solna, and Karolinska Institutet, Stockholm, Sweden.
Objective. To design and validate a classification system for audit groups working with stillbirth. The classification includes well-defined primary and associated conditions related to fetal death. Design. Descriptive. Setting. All delivery wards in Stockholm. Population. Stillbirths from 22 completed weeks in Stockholm, Sweden. Methods. Parallel to audit work, the Stockholm stillbirth group has developed a classification of conditions related to stillbirth. The classification has been validated. Main outcome measure. The classification and the results of the validation are presented. Result. The classification with 17 groups identifying underlying conditions related to stillbirth (primary diagnoses) and associated factors which may have contributed to the death (associated diagnoses) is described. The conditions are subdivided into definite, probable and possible relation to the death. An evaluation of 382 cases of stillbirth during 2002-2005 resulted in 382 primary diagnoses and 132 associated diagnoses. The most common conditions identified were intrauterine growth restriction/placental insufficiency (23%), infection (19%), malformations/chromosomal abnormalities (12%). The 'unexplained' group together with the 'unknown' group comprised 18%. Validation was done by reclassification of 95 cases from 2005 by six investigators. The overall agreement regarding primary diagnosis was substantial (kappa =0.70). Conclusions. The Stockholm classification of stillbirth consists of 17 diagnostic groups allowing one primary diagnosis and if needed, associated diagnoses. Diagnoses are subdivided according to definite, probable and possible relation to stillbirth. Validation showed high degree of agreement regarding primary diagnosis. The classification can provide a useful tool for clinicians and audit groups when discussing cause and underlying conditions of fetal death.
4. Zhang X, Kramer MS Variations in Mortality and Morbidity by Gestational Age among Infants Born at Term J Pediatr. 2008 Oct 23. [Epub ahead of print]
Department of Pediatrics, McGill University Faculty of Medicine, Montreal, Quebec, Canada; Department of Epidemiology and Biostatistics, McGill University Faculty of Medicine, Montreal, Quebec, Canada.
OBJECTIVE: To examine the risks of infant death and neonatal morbidity by week of gestation at term. STUDY DESIGN: National U.S. birth cohort study on the basis of singleton live births in 1995-2001 at 37 to 41 completed weeks gestational age (GA), with exclusion of congenital anomalies. Main outcomes included neonatal, postneonatal, and cause-specific infant death; low-Apgar score at 5 minutes; receipt of neonatal mechanical ventilation >/=30 minutes; neonatal seizures; birth injury; and meconium aspiration syndrome. To reduce confounding by indication, we carried out a secondary analysis restricted to low-risk deliveries. RESULTS: In non-Hispanic white women, the mortality rate decreased with increasing GA from 37 to 39 weeks, remained stable from 39 to 40 weeks, and then (for neonatal death) increased at 41 weeks. Rates of low 5-minute Apgar score and mechanical ventilation showed a U-shaped relation across term GAs, and rates of meconium aspiration syndrome and birth injury rose with increasing GA. Results were similar among infants born to low-risk mothers and in non-Hispanic black women. CONCLUSIONS: Term infants show considerable heterogeneity across gestational age in neonatal and late infant outcomes, even when born to mothers at low risk. Recent trends toward earlier labor induction may have adverse health impacts.
5. Schrader M, Travis J Testing the Viviparity-Driven-Conflict Hypothesis: Parent-Offspring Conflict and the Evolution of Reproductive Isolation in a Poeciliid Fish Am Nat. 2008 Oct 24. [Epub ahead of print]
Department of Biological Science, Florida State University, Tallahassee, Florida 32306.
Abstract: The evolution of viviparity increases the potential for genomic conflicts between mothers and offspring over the level of maternal investment. The viviparity-driven-conflict hypothesis predicts that such conflicts will drive the evolution of asymmetrical reproductive isolation between populations with divergent mating systems. We tested this hypothesis using crosses between populations of a poeciliid fish that differ in their level of polyandry. Our results support the prediction of an asymmetry in the rate of spontaneous abortion in reciprocal crosses, with the highest rate occurring in crosses between females from a relatively monandrous population and males from a relatively polyandrous population. The patterns of offspring size were not consistent with the pattern predicted by the viviparity-driven-conflict hypothesis: crosses between a monandrous female and a polyandrous male did not produce larger offspring than the reciprocal cross. This discrepancy was due to the presence of an effect of the maternal population on offspring size: polyandrous females produced larger offspring than monandrous females. In addition, offspring size was positively correlated with maternal size in crosses involving a polyandrous male. We discuss these results in light of models for intra- and intergenomic epistasis and the rapid origin of asymmetric reproductive isolation in viviparous taxa.
6. Weichenhan D, Traut W, Göngrich C, Himmelbauer H, Busch L, Monyer H, Winking H A mouse translocation associated with Caspr5-2 disruption and perinatal lethality Mamm Genome. 2008 Oct 24. [Epub ahead of print]
Deutsches Krebsforschungszentrum, 69120, Heidelberg, Germany, d.weichenhan@dkfz-heidelberg.de.
We have previously described the paralogous mouse genes Caspr5-1, -2, and -3 of the neurexin gene family. Here we present the cytogenetic and molecular mapping of a null mutation of Caspr5-2 which was caused by reciprocal translocation between chromosomes 1 and 8 with breakpoints at bands 1E2.1 and 8B2.1, respectively. The translocation disrupts Caspr5-2 between exons 1 and 2 and causes stillbirth or early postnatal lethality of homozygous carriers. Because no other candidate genes were found, the disruption of Caspr5-2 is most likely the cause of lethality. Only rarely do homozygotes survive the critical stage, reach fertility, and are then apparently normal. They may be rescued by one of the two other Caspr5 paralogs. Caspr5-2 is expressed in spinal cord and brain tissues. Despite giving special attention to regions where in wild-type fetuses maximum expression was found, no malformation that might have caused death could be detected in fetal homozygous carriers of the translocation. We, therefore, suspect that Caspr5-2 disruption leads to dysfunction at the cellular level rather than at the level of organ development.
7. Bhattacharya S, Townend J, Shetty A, Campbell D, Bhattacharya S BJOG Does miscarriage in an initial pregnancy lead to adverse obstetric and perinatal outcomes in the next continuing pregnancy? 2008 Oct 8. [Epub ahead of print]
Dugald Baird Centre for Research on Women's Health, Aberdeen Maternity Hospital, Aberdeen, UK.
Objective To explore pregnancy outcomes in women following an initial miscarriage. Design Retrospective Cohort Study. Setting Aberdeen Maternity Hospital, Aberdeen, Scotland. Population All women living in the Grampian region of Scotland with a pregnancy recorded in the Aberdeen Maternity and Neonatal Databank between 1986 and 2000. Main outcome measures (A) Maternal outcomes: Pre-eclampsia, antepartum haemorrhage, threatened miscarriage, malpresenation, induced labour, instrumental delivery, Caesarean delivery, postpartum haemorrhage and manual removal of placenta. (B) Perinatal outcomes: preterm delivery, low birth weight, stillbirth, neonatal death, Apgar score at 5 minutes. Methods Retrospective cohort study comparing women with a first pregnancy miscarriage with (a) women with one previous successful pregnancy and (b) primigravid women. Data were extracted on perinatal outcomes in all women from the Aberdeen Maternity and Neonatal Databank between 1986 and 2000. Results We identified 1561 women who had a first miscarriage (1404 in the first trimester and 157 in the second trimester), 10 549 who had had a previous live birth (group A) and 21 118 primigravidae (group B). The miscarriage group faced a higher risk of pre-eclampsia (adj OR 3.3, 99% CI 2.6-4.6), threatened miscarriage (adj OR 1.7, 99% CI 1.5-2.0), induced labour (adj OR 2.2, 99% CI 1.9-2.5), instrumental delivery (adj OR 5.9, 99% CI 5.0-6.9), preterm delivery (adj OR 2.1, 99% CI 1.6-2.8) and low birthweight (adj OR 1.6, 99% CI 1.3-2.1) than group A. They were more likely to have threatened miscarriage (adj OR 1.5, 99% CI 1.4-1.7), induced labour (adj OR 1.3, 99% CI 1.2-1.5), postpartum haemorrhage (adj OR 1.4, 99% CI 1.2-1.6) and preterm delivery (adj OR 1.5, 99% CI 1.2-1.8) than group B. Conclusion An initial miscarriage is associated with a higher risk of obstetric complications.
8. Hossein-Zadeh NG, Nejati-Javaremi A, Miraei-Ashtiani SR, Kohram H An observational analysis of twin births, calf stillbirth, calf sex ratio, and abortion in Iranian holsteins J Dairy Sci. 2008 Nov;91(11):4198-205
Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, 31587-77871 Karaj, Iran.
Calving records of Holstein dairy cows from April 1998 to September 2006 comprising 16 herds with 104,572 calving events representing 4,045 twin births were used to evaluate reported twinning rate, calf sex ratio, stillbirth, and abortion rates in single and twin births. Overall, the reported twinning rate was 3.9%, and twinning increased with parity [1.1% for primiparous cows vs. 5.7% for cows in their fourth or greater lactation; odds ratio (OR) = 5.50]. Regardless of parity, the greatest twinning rate was observed when conception occurred in fall season from September to December (OR = 1.17). Calf stillbirth was greater after twin births, with 18.8% of twin calving events resulting in one or both calves as stillborn, compared with 4.0% for singleton births (OR = 7.58). Calf stillbirth for multiparous cows was 2.9% for single births and 18.0% for twin births (OR = 7.08), whereas for primiparous cows, stillbirth was 6.6% for singletons and 27.7% for twins (OR = 5.85). Calf sex ratios (male, M; female, F) were 52.4% M and 47.6% F for singleton calves and 28.2% MM, 48.9% MF, and 22.9% FF for twin calves. The mean abortion rate was 13.4%, with 13.8% for single births and 4.2% for twin births (OR = 1.22). Abortion rate for multiparous cows was 15.9% for single births and 4.0% for twin births (OR = 4.31), whereas for primiparous cows, abortion rate was 9.4% for single births and 5.4% for twin births (OR = 1.89). Although milk production, as a causative factor associated with twinning, increased in recent years, twinning rate decreased over the years.
9. Cleveland LM, Minter ML, Cobb KA, Scott AA, German VF Lead hazards for pregnant women and children: part 2: more can still be done to reduce the chance of exposure to lead in at-risk populations Am J Nurs. 2008 Nov;108(11):40-7; quiz 47-8
University of Texas Health Science Center, San Antonio, USA. clevelandl@uthscsa.edu
In the United States the risk of lead exposure is far higher among poor, urban, and immigrant populations than among other groups. And even slightly elevated blood lead levels increase children's risk of significant neurobehavioral problems extending through adolescence. Research has shown that blood lead levels in pregnant women well below the Centers for Disease Control and Prevention's "level of concern" of 10 micrograms per deciliter can cause miscarriage, premature birth, low birth weight, and subsequent developmental delays in their children. Despite these well-established dangers of lead exposure, routine prenatal lead screening and education is not a standard of care in the United States.Part 1 of this two-part article (October) presented the case of a pregnant woman with lead poisoning and described the epidemiology of lead exposure in the United States, the main sources of it, and its effects on a pregnant woman and her developing fetus and child. Part 2 describes recommendations for prenatal screening and strategies for dealing with lead exposure when it occurs: education, reduction in environmental exposure, treatment options, and developmental surveillance.
10. de Medeiros SF, Norman RJ Human choriogonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights Hum Reprod Update. 2008 Oct 22. [Epub ahead of print]
Department of Gynaecology and Obstetrics, Faculty of Medical Sciences, Federal University of Mato Grosso, Rua Marechal Deodoro, 1055, Apto. 1302, 78005-101 Cuiabá, Mato Grosso, Brazil.
BACKGROUND Human chorionic gonadotrophin (hCG) is measured in serum and urine for the early detection of ectopic pregnancy, patients with higher risk of miscarriage, embryos or fetuses with chromosome abnormalities, prediction of pre-eclampsia or fetal growth restriction and identification or follow-up of trophoblast neoplasia. This review examines basic knowledge on the heterogeneity of hCG protein core and sugar branches and its relevance to assays used in a clinical setting. METHODS The databases Scielo and Medline/Pubmed were consulted for identification of the most relevant published papers. Search terms were gonadotrophin, glycoprotein structure, hCG structure and molecular forms of hCG. RESULTS The synthesis of alpha (hCGalpha) and beta (hCGbeta) peptide chains and their further glycosylation involve the complex action of different enzymes. After assembly, hCG reaches the cell surface and is secreted as a bioactive heterodimer. The complex cascade of enzymes acting in hCG secretion results in heterogeneous molecular forms. The hCG molecules are differently metabolized by the liver, ovary and kidney, but the majority of hCG forms are excreted in the urine. Intact hCG, hCGalpha, hCGbeta, hyperglycosylated (hCGh), nicked (hCGn) and core fragment of hCGbeta (hCGbetacf) forms have relevant clinical use. The immunogenicity of each hCG variant, their epitopes distribution and the available antibodies are important for the development of specific assays. Depending on the prevalent form or proportion in relation to the intact hCG, the choice of assay for measurement of a specific molecule in a particular clinical setting is paramount. CONCLUSIONS Measurement of hCG and/or its related molecules is useful in clinical practice, but greater awareness is needed worldwide regarding the use of new sensitive and specific assays tailored for different clinical applications.
11. Caro MR, Buendía AJ, Del Rio L, Ortega N, Gallego MC, Cuello F, Navarro JA, Sanchez J, Salinas J Chlamydophila abortus infection in the mouse: A useful model of the ovine disease Vet Microbiol. 2008 Sep 13. [Epub ahead of print]
Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de Murcia, 30100 Campus de Espinardo, Murcia, Spain.
Chlamydophila (C.) abortus is an obligate intracellular bacterium able to colonize the placenta of several species of mammals, which may induce abortion in the last third of pregnancy. The infection affects mainly small ruminants resulting in major economic losses in farming industries worldwide. Furthermore, its zoonotic risk has been reported in pregnant farmers or abattoir workers. Mouse models have been widely used to study both the pathology of the disease and the role of immune cells in controlling infection. Moreover, this animal experimental model has been considered a useful tool to evaluate new vaccine candidates and adjuvants that could prevent abortion and reduce fetal death. Future studies using these models will provide and reveal information about the precise mechanisms in the immune response against C. abortus and will increase the knowledge about poorly understood issues such as chlamydial persistence.
12. Trogstad L, Magnus P, Skjærven R, Stoltenberg C Previous abortions and risk of pre-eclampsia Int J Epidemiol. 2008 Oct 21. [Epub ahead of print]
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
BACKGROUND: The risk of pre-eclampsia is reduced for second and later births. The causes and mechanisms behind this reduction are unknown. The aim of the study was to estimate the risk of pre-eclampsia in primiparous women according to history of spontaneous and induced abortions, while controlling for several potentially confounding factors. METHODS: The sample consisted of 20 846 primiparous women participating in the Norwegian Mother and Child Cohort Study (MoBa). Information on abortions and confounders were self-reported in postal questionnaires. The diagnosis of pre-eclampsia was retrieved from the Medical Birth Registry of Norway. Estimation and confounder control was performed with multiple, logistic regression. RESULTS: One previous induced abortion reduced the risk moderately [odds ratio (OR) 0.84, 95% confidence interval (CI) 0.69-1.02]. Two or more induced abortions reduced the risk more significantly (OR 0.36, 95% CI 0.18-0.73). Adjustment for confounders did not change the estimates. CONCLUSIONS: The protective effect of two prior induced abortions was similar to what is commonly seen after one birth. Spontaneous abortions may to a larger extent than induced abortions be associated with other factors, such as infertility, that may increase the risk of pre-eclampsia. Normal pregnancies interrupted in early pregnancy may induce immunological changes that reduce the risk of pre-eclampsia in a subsequent pregnancy.
Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center Georgetown University 2115 Wisconsin Avenue, N.W., Suite 601 Washington, DC 20007 (866) 866-7437 toll free (202) 687-7466 local (202) 784-9777 fax info@sidscenter.org http://www.sidscenter.org
