NSIDRC Journal Article Alert — July 23, 2010
Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center at Georgetown University.
These articles have been selected from PubMed, a service of the National Library of Medicine that includes over 19 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources.
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Sudden Infant Death
1. Lavezzi AM, Corna MF, Matturri L
Ependymal alterations in sudden intrauterine unexplained death
and sudden infant death syndrome: possible primary consequence
of prenatal exposure to cigarette smoking
Neural Dev. 2010 Jul 19;5(1):17. [Epub ahead of print]
ABSTRACT: BACKGROUND: The ependyma, the lining providing a
protective barrier and filtration system separating brain parenchyma
from cerebrospinal fluid, is still inadequately understood
in humans. In this study we aimed to define, by morphological
and immunohistochemical methods, the sequence of developmental
steps of the human ependyma in the brainstem (ventricular ependyma)
and thoracic spinal cord (central canal ependyma) of a large
sample of fetal and infant death victims, aged from 17 gestational
weeks to 8 postnatal months. Additionally, we investigated
a possible link between alterations of this structure, sudden
unexplained fetal and infant death and maternal smoking. RESULTS:
Our results demonstrate that in early fetal life the human
ependyma shows a pseudostratified cytoarchitecture including
many tanycytes and ciliated cells together with numerous apoptotic
and reactive astrocytes in the subependymal layer. The ependyma
is fully differentiated, with a monolayer of uniform cells,
after 32 to 34 gestational weeks. We observed a wide spectrum
of ependymal pathological changes in sudden death victims,
such as desquamation, clusters of ependymal cells in the subventricular
zone, radial glial cells, and the unusual presence of neurons
within and over the ependymal lining. These alterations were
significantly related to maternal smoking in pregnancy. CONCLUSIONS:
We conclude that in smoking mothers, nicotine and its derivatives
easily reach the cerebrospinal fluid in the fetus, immediately
causing ependymal damage. Consequently, we suggest that the
ependyma should be examined in-depth first in victims of sudden
fetal or infant death with mothers who smoke.
Other Infant Death
1. Pasupathy D, Wood AM, Pell JP, Fleming M, Smith GC
Time of birth and risk of neonatal death at term: retrospective
cohort study
BMJ. 2010 Jul 15;341:c3498. doi: 10.1136/bmj.c3498
Department of Obstetrics and Gynaecology, University of Cambridge, and NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge CB2 2SW.
Comment in BMJ. 2010;341:c3087.
OBJECTIVE: To determine the effect of time and day of birth
on the risk of neonatal death at term. DESIGN: Population based
retrospective cohort study. SETTING: Data from the linked Scottish
morbidity records, Stillbirth and Infant Death Survey, and
birth certificate database of live births in Scotland, 1985-2004.
SUBJECTS: Liveborn term singletons with cephalic presentation.
Perinatal deaths from congenital anomalies excluded. Final
sample comprised 1,039,560 live births. MAIN OUTCOME MEASURE:
All neonatal deaths (in the first four weeks of life) unrelated
to congenital abnormality, plus a subgroup of deaths ascribed
to intrapartum anoxia. RESULTS: The risk of neonatal death
was 4.2 per 10,000 during the normal working week (Monday to
Friday, 0900-1700) and 5.6 per 10 000 at all other times (out
of hours) (unadjusted odds ratio 1.3, 95% confidence interval
1.1 to 1.6). Adjustment for maternal characteristics had no
material effect. The higher rate of death out of hours was
because of an increased risk of death ascribed to intrapartum
anoxia (adjusted odds ratio 1.7, 1.2 to 2.3). Though exclusion
of elective caesarean deliveries attenuated the association
between death ascribed to anoxia and delivery out of hours,
a significant association persisted (adjusted odds ratio 1.5,
1.1 to 2.0). The attributable fraction of neonatal deaths ascribed
to intrapartum anoxia associated with delivery out of hours
was 26% (95% confidence interval 5% to 42%). CONCLUSIONS: Delivering
an infant outside the normal working week was associated with
an increased risk of neonatal death at term ascribed to intrapartum
anoxia.
Miscarriage/Stillbirth/Prenatal Issues
1. Shi Q, Hu M, Luo M, Liu Q, Jiang F, Zhang Y, Wang S, Yan
C, Weng Y
Reduced expression of Mad2 and Bub1 proteins is associated
with spontaneous abortions
Mol Hum Reprod. 2010 Jul 19. [Epub ahead of print]
Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
During early development of the human embryo, chromosomal imbalance and instability may cause spontaneous abortions. In this study, we observe aberrant chromosome numbers in nearly half of spontaneous abortion embryo samples, most of which show abnormalities in karotype. We also detect significantly reduced expression of two important mitotic checkpoint proteins, Mad2 and Bub1. To further investigate the role of Bub1 and Mad2 in chromosome missegregation, in embryogenesis, and in errors leading to spontaneous abortions, we use RNA interference technology to knock down Bub1 and Mad2 genes respectively to investigate possible effect of reduced expression of Mad2 and Bub1 on chromosome number, cell proliferation and cell cycle progression. Significant suppression of cell proliferation and increased abnormal chromosome numbers are detected. M phase arrest is observed in cultured villus cell lines with depleted Mad2 or Bub1 mRNA by RNAi technique. The results from the in vitro RNAi-mediated silencing model may provide an explanation for the observations in clinical samples of spontaneous abortions. Thus, our findings strongly suggest that the loss of spindle assembly checkpoint proteins, such as Bub1 and Mad2, may cause spontaneous abortions.
2. Ljunger E, Stavreus-Evers A, Cnattingius S, Ekbom A, Lundin
C, Annéren G, Sundström-Poromaa I
Ultrasonographic findings in spontaneous miscarriage: relation
to euploidy and aneuploidy
Fertil Steril. 2010 Jul 15. [Epub ahead of print]
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
OBJECTIVE: To evaluate a possible correlation between transvaginal ultrasound findings in miscarriages and cytogenetic analyses from chorionic villi obtained by dilatation and curettage. DESIGN: Prospective, population-based study. SETTING: University-based hospital. PATIENT(S): Five hundred seventy-six women with spontaneous miscarriage diagnosed between 6 and 12 completed pregnancy weeks. INTERVENTION(S): Transvaginal ultrasonography and dilatation and curettage. MAIN OUTCOME MEASURE(S): Cytogenetic analyses and ultrasound measurement of embryonic pole. RESULT(S): The mean gestational age was 9.5 weeks. Chromosomal analyses were successful in 259 cases, 159 with cytogenetic abnormalities and 100 euploidy. Empty gestational sacs were equally often found in euploidy and aneuploidy, whereas small embryonic or fetal poles were significantly more often associated with aneuploidy. CONCLUSION(S): A smaller than expected fetal size when a miscarriage is diagnosed during the first trimester is significantly associated with a chromosomal aberration. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
3. Stephenson MD, Kutteh WH, Purkiss S, Librach C, Schultz
P, Houlihan E, Liao C
Intravenous immunoglobulin and idiopathic secondary recurrent
miscarriage: a multicentered randomized placebo-controlled
trial
Hum Reprod. 2010 Jul 15. [Epub ahead of print]
University of Chicago Recurrent Pregnancy Loss Program, Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Avenue (MC 2050), Chicago, IL 60637, USA.
BACKGROUND Idiopathic secondary recurrent miscarriage may be associated with an abnormal maternal immune response to subsequent pregnancies. Intravenous immunoglobulin (IVIG) has been studied in randomized controlled trials (RCTs) with conflicting results. Therefore, a definitive trial was proposed. METHODS We conducted an investigator-initiated, multicentered, randomized, double-blinded, placebo-controlled trial comparing IVIG with saline in women with idiopathic secondary recurrent miscarriage, defined as a history of at least one prior ongoing pregnancy followed by three or more consecutive unexplained miscarriages. Subjects received either IVIG 500 mg/kg or the equivalent volume of normal saline. Preconception infusions were administered 14-21 days from the projected next menstrual period. With documentation of pregnancy, the subject received the same infusion every 4 weeks until 18-20 weeks of gestation. The primary outcome was an ongoing pregnancy of at least 20 weeks of gestation. RESULTS A total of 82 patients enrolled, of whom 47 had an index pregnancy. All ongoing pregnancies resulted in live births. Therefore, the live birth rates were 70% (16/23) in the IVIG group and 63% (15/24) in the control group (P = 0.760); odds ratio (OR) 1.37 [95% confidence interval (CI) 0.41-4.61]. Including only clinical pregnancies (embryo with cardiac activity at 6 weeks of gestation), the live birth rates were equivalent, 94% (16/17) and (15/16), respectively (P > 0.999); OR 1.07 (95% CI 0.06-18.62). Meta-analysis of randomized controlled trials (RCTs) evaluating IVIG for idiopathic secondary recurrent miscarriage revealed live birth rates of 70% (31/44) in the IVIG group and 62% (28/45) in the control group (P = 0.503); common OR 1.44 (95% CI 0.59-3.48). CONCLUSIONS This is the largest RCT to date in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis, which combined our study results with two prior RCTs, also showed no significant effect of treatment with IVIG. ClinicalTrials.gov NCT00606905
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