NSIDRC Journal Article Alert — August 22, 2008
Prepared by the National Sudden Infant Death 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.
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Sudden Infant Death
1. Ottaviani G, Lavezzi AM, Matturri L
Fibromuscular hyperplasia of the pulmonary artery in sudden
infant and perinatal unexpected death
Cardiovasc Pathol. 2008 Aug 12. [Epub ahead of print]
"Lino Rossi" Research Center for the Study and Prevention
of Unexpected Perinatal Death and SIDS, University of Milan,
Milan, Italy; Institute of Pediatrics and Neonatology, University
of Milan, Milan, Italy.
INTRODUCTION: The purpose of this study was to describe cases
presenting with fibromuscular hyperplasia of the pulmonary
arteries that could belong to the group of sudden infant death
syndrome (SIDS) and sudden unexpected perinatal death "gray
zone" or borderline cases. METHODS: In a total of 12 cases,
eight females and four males, ranging in age from 39 gestational
weeks to 93 postnatal days, dying suddenly and unexpectedly,
a fibromuscular hyperplasia of the pulmonary artery was detected.
Postmortem examinations were requested with a clinical SIDS
or sudden unexpected perinatal death. A complete autopsy was
performed, including close examination of the brainstem and
cardiac conduction system. RESULTS: Histological examination
showed the presence of various degrees of fibromuscular hyperplasia
with fibrosis of the right (six cases), left (five cases) or
both (one case) pulmonary arteries. CONCLUSIONS: In our cases,
fibromuscular hyperplasia of the pulmonary artery alone might
or might not have accounted for the sudden deaths, if it had
not been for the concomitant presence of hypoplasia of the
arcuate nucleus in the brainstem and/or cardiac conduction
system abnormalities. Therefore, they were classified as SIDS/sudden
unexpected perinatal death gray zone or borderline cases. Necropsy
studies of sudden infant and perinatal death should always
include an accurate gross and histological examination of the
pulmonary arteries, as well as of the brainstem and cardiac
conduction system.
Bereavement
1. Wijngaards-de Meij L, Stroebe M, Stroebe W, Schut H, Van
den Bout J, Van Der Heijden PG, Dijkstra I
The impact of circumstances surrounding the death of a child
on parents' grief
Death Stud. 2008;32(3):237-52
Department of Psychology, Faculty of Social Sciences, Utrecht
University, P.O. Box 80140, 3508 TC Utrecht, The Netherlands.
l.wijngaard@uu.nl.
A longitudinal study was conducted among bereaved parents
to examine the relationship between the circumstances surrounding
the death of their child and psychological adjustment. Two
hundred nineteen couples participated at 6, 13, and 20 months
post-loss. Examination was made of two categories of factors:
those that were determined by the particular death circumstances
(e.g., whether the parent was present at the death) versus
those over which parents themselves could have influence (e.g.,
choice of cremation or burial). Results indicated that some
but not all factors were related to adjustment over time. Importantly,
the feeling of having said goodbye to the child and presenting
the body for viewing at home were associated with lower levels
of the parents' grief. Implications for supporting bereaved
parents are discussed.
2. Keesee NJ, Currier JM, Neimeyer RA
Predictors of grief following the death of one's child: the
contribution of finding meaning
J Clin Psychol. 2008 Aug 12. [Epub ahead of print]
Memphis Veteran's Administration Medical Center.
This study examined the relative contribution of objective
risk factors and meaning-making to grief severity among 157
parents who had lost a child to death. Participants completed
the Core Bereavement Items (CBI; Burnett, Middleton, Raphael, & Martinek,
1997), Inventory of Complicated Grief (ICG; Prigerson et al.,
1995), questions assessing the process and degree of sense-making
and benefit-finding, and the circumstances surrounding their
losses. Results showed that the violence of the death, age
of the child at death, and length of bereavement accounted
for significant differences in normative grief symptoms (assessed
by the CBI). Other results indicated that the cause of death
was the only objective risk factor that significantly predicted
the intensity of complicated grief (assessed by the ICG). Of
the factors examined in this study, sense-making emerged as
the most salient predictor of grief severity, with parents
who reported having made little to no sense of their child's
death being more likely to report greater intensity of grief.
Implications for clinical work are discussed. (c) 2008 Wiley
Periodicals, Inc. J Clin Psychol 64:1-19, 2008.
Miscarriage/Stillbirth/Prenatal Issues
1. Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL
Effects of folate and vitamin B12 deficiencies during pregnancy
on fetal, infant, and child development
Food Nutr Bull. 2008 Jun;29(2 Suppl):S101-11; discussion S112-5.
School of Medicine, Trinity College Dublin, Ireland. amolloy@tcd.ie.
The importance of folate in reproduction can be appreciated
by considering that the existence of the vitamin was first
suspected from efforts to explain a potentially fatal megaloblastic
anemia in young pregnant women in India. Today, low maternal
folate status during pregnancy and lactation remains a significant
cause of maternal morbidity in some communities. The folate
status of the neonate tends to be protected at the expense
of maternal stores; nevertheless, there is mounting evidence
that inadequate maternal folate status during pregnancy may
lead to low infant birthweight, thereby conferring risk of
developmental and long-term adverse health outcomes. Moreover,
folate-related anemia during childhood and adolescence might
predispose children to further infections and disease. The
role of folic acid in prevention of neural tube defects (NTD)
is now established, and several studies suggest that this protection
may extend to some other birth defects. In terms of maternal
health, clinical vitamin B12 deficiency may be a cause of infertility
or recurrent spontaneous abortion. Starting pregnancy with
an inadequate vitamin B12 status may increase risk of birth
defects such as NTD, and may contribute to preterm delivery,
although this needs further evaluation. Furthermore, inadequate
vitamin B12 status in the mother may lead to frank deficiency
in the infant if sufficient fetal stores of vitamin B12 are
not laid down during pregnancy or are not available in breastmilk.
However, the implications of starting pregnancy and lactation
with low vitamin B12 status have not been sufficiently researched.
2. Badawy A, Mosbah A, Tharwat A, Eid M
Extended letrozole therapy for ovulation induction in clomiphene-resistant
women with polycystic ovary syndrome: a novel protocol.
Fertil Steril. 2008 Aug 13. [Epub ahead of print]
Department of Obstetrics and Gynecology, Mansoura University
Hospitals, Mansoura, Egypt.
OBJECTIVE: To evaluate the outcome of long letrozole therapy
for induction of ovulation in patients with clomiphene-resistant
polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized
controlled study. SETTING: University teaching hospital and
a private practice. PATIENT(S): The study comprised 218 patients
with clomiphene-resistant PCOS. INTERVENTION(S): Patients were
randomly allocated to treatment with either long letrozole
therapy (n = 108; 219 cycles) or short letrozole therapy (n
= 110; 225 cycles). MAIN OUTCOME MEASURE(S): Number of growing
and mature follicles, serum E(2) (pg/mL), serum P (ng/mL),
endometrial thickness, occurrence of pregnancy and miscarriage.
RESULT(S): The number of ovulating patients was greater in
the long letrozole group (65.7% vs. 61.8%), but without statistical
differences. The total numbersof follicles during stimulation
was significantly greater in the long letrozole group (6.7
+/- 0.3 vs. 3.9 +/- 0.4). The numbers of follicles >/=14
mm and >/=18 mm were significantly greater in the long letrozole
group. There was no significant difference in the pretreatment
endometrial thickness or endometrial thickness at the time
of hCG administration between the two groups. Pregnancy occurred
in 28 of 225 cycles in the short group (12.4%) and 38 of 219
cycles (17.4%) in the long letrozole group, and the difference
was statistically significant. CONCLUSION(S): The long letrozole
protocol (10 days) can produce more mature follicles and subsequently
more pregnancies than the short letrozole thrapy (5 days).
3. Dokouhaki P, Moghaddam R, Rezvany M, Ghassemi J, Novin
MG, Zarnani A, Akhondi MM, Ostadkarampour M, Mellstedt H, Razavi
A, Jeddi-Tehrani M
Repertoire and clonality of T-cell receptor Beta variable genes
expressed in endometrium and blood T cells of patients with
recurrent spontaneous abortion
Am J Reprod Immunol. 2008 Aug;60(2):160-71
Department of Immunology, School of Public Health, Tehran
University of Medical Sciences, Tehran, Iran and Transplant
Immunology, University of Toronto, Toronto, Canada.
Problem Recurrent spontaneous abortion (RSA) is a relatively
common disorder, the underlying causes of which are thought
to be immunological in most cases. Method of study Expression
profile and clonality pattern of T-cell receptor beta variable
(TCRBV) genes in endometrium and blood of patients with RSA
were investigated by semi-quantitative reverse transcriptase
polymerase chain reaction (RT-PCR) using BV gene-specific primers.
Relative expression of each BV family was determined and clonal
expansion of the over-expressed genes was assessed by analysis
of CDR3 length polymorphism. Results Compared to blood, relative
expression of four TCRBV genes was significantly higher in
the endometrium of RSA group. Over-expressed genes, except
for TCRBV3, all had restricted and oligoclonal patterns of
expression in the endometrium. Conclusion Endometrial T cells
have a skewed TCRBV repertoire with restricted transcript heterogeneity,
which is shared by both groups and minor variations observed
in this pattern in RSA patients may reflect more recent and/or
repeated exposure to nominal antigens or superantigens.
4. Yu G, Sun Y, Foerster K, Manuel J, Molina H, Levy GA, Gorczynski
RM, Clark DA
LPS-Induced Murine Abortions Require C5 but not C3, and are
Prevented by Upregulating Expression of the CD200 Tolerance
Signaling Molecule
Am J Reprod Immunol. 2008 Aug;60(2):135-40.
Toronto General Research Institute & CIHR Group on Cellular
and Molecular Mechanisms of Organ Injury, Institute of medical
Sciences, University of Toronto, Toronto, ON, Canada.
Problem Lipopolysaccharide (LPS) acts via tlr4 to promote
Th1 cytokine secretion and abortions. LPS is an essential co-factor
in spontaneous abortion in the CBA x DBA/2 model and in stress-triggered
abortions. In the CBA x DBA/2 model, C3a, C5a, and fgl2 prothrombinase
participate in triggering inflammation that terminates embryo
viability. As fgl2 prothrombinase (via thrombin) can generate
C5a, it was predicted that LPS-driven abortions (which require
fgl2) would be independent of C3. CD200Fc can prevent abortions
in the CBA x DBA/2 model, but an action through Fc could not
be excluded. Method of study C3(-/-) and C5(-/-) knock-out
mice on a B6 background were syngeneically mated and Salmonella
enteritidis LPS was administered i.p. on day 6.5 or pregnancy
along with 2 mg progesterone in sesame oil s.c. The total number
of implants and the number of resorbing embryos were counted
on day 13.5 of pregnancy. CD200-rtTA double transgenic homozygous
males (B6 background) mated with B6(+/+) females were similarly
treated. To up-regulate CD200 expression in embryonic trophoblasts,
doxycycline was added to the drinking water from the time of
mating. Results The LPS boosted the abortion rate from 15.5%
(control) to 42.0% in C3(-/-) mice (chi(2) = 9.28, P < 0.005).
In C5(-/-) mice, there was no increase in abortion rate with
LPS compared to progesterone-treated controls (22.8%versus
26.3%, P = NS). LPS-treated transgenic mice given LPS + progesterone
had a 42.5% abortion rate, but when the mice were given doxycycline
to induce expression of CD200 by the embryo, the abortion rate
was only 8.3% (chi(2) = 14.40, P < 0.005, Fisher's exact
test P = 0.00007). Conclusion C5, but not C3, appears necessary
for LPS-driven abortions. Up-regulation of CD200 can prevent
LPS-driven abortions, possibly by altering dendritic cells
to promote Treg cell development or by a direct suppressive
action on macrophages and mast cells that also express CD200
receptors.
5. Emanuelli M, Cecati M, Sartini D, Stortoni P, Corradetti
A, Giannubilo SR, Turi A, Tranquilli AL
Placental Alpha Hemoglobin Stabilizing Protein (AHSP) and recurrent
miscarriage
Cell Stress Chaperones. 2008 Aug 15. [Epub ahead of print]
Institute for Biochemical Biotechnologies, Università Politecnica
delle Marche, Ancona, Italy.
AHSP inhibits cellular production of the reactive oxygen species.
Reduced AHSP indicates reduced protection against oxidative
stressors. Our objective was to investigate AHSP levels in
recurrent miscarriage (RM). Trophoblast was collected from
women of 10 weeks gestation: voluntary abortion controls (VA,
n = 10); spontaneous first miscarriage with subsequent normal
pregnancy (SMSN, n = 15) or with subsequent miscarriage (SMSM,
n = 5); RM previously investigated (RMPS, n = 5) or not previously
investigated (RM, n = 5). AHSP mRNA and protein were determined
using real-time quantitative polymerase chain reaction (PCR)
and Western blot, respectively. One-way ANOVA was performed
to assess statistical significance (p < 0.05). ahsp mRNA
levels were maximally reduced in RM and RMPS (8.0 x 10(-6)
+/- 1.3 and 8.1 x 10(-6) +/- 0.7, respectively) compared with
SMSN and VA (16.1 x 10(-6) +/- 2.3 and 26.1 x 10(-6) +/- 2.7,
respectively). SMSM showed levels significantly reduced as
well (9.0 x 10(-6) +/- 2.3). In RM, a reduced defense from
oxidative stressors is evident at first miscarriage, identifying
women at high risk for subsequent eventful pregnancy. Reduced
AHSP may identify women at risk of experiencing further miscarriages.
6. Freedman L, Landy U, Steinauer J
When There's a Heartbeat: Miscarriage Management in Catholic-Owned
Hospitals
Am J Public Health. 2008 Aug 13. [Epub ahead of print]
University of California, San Francisco.
As Catholic-owned hospitals merge with or take over other
facilities, they impose restrictions on reproductive health
services, including abortion and contraceptive services. Our
interviews with US obstetrician-gynecologists working in Catholic-owned
hospitals revealed that they are also restricted in managing
miscarriages. Catholic-owned hospital ethics committees denied
approval of uterine evacuation while fetal heart tones were
still present, forcing physicians to delay care or transport
miscarrying patients to non-Catholic-owned facilities. Some
physicians intentionally violated protocol because they felt
patient safety was compromised. Although Catholic doctrine
officially deems abortion permissible to preserve the life
of the woman, Catholic-owned hospital ethics committees differ
in their interpretation of how much health risk constitutes
a threat to a woman's life and therefore how much risk must
be present before they approve the intervention.
7. Sedano S, Gaffney G, Mortimer G, Lyons M, Cleary B, Murray
M, Maher M
Activated Protein C Resistance (APCR) and Placental Fibrin
Deposition
Placenta. 2008 Aug 12. [Epub ahead of print]
National Diagnostics Centre, National University of Ireland,
Galway, Ireland.
Activated protein C resistance (APCR) results in an ineffective
anticoagulant response leading to an increased risk of thrombosis,
particularly during pregnancy. Adverse pregnancy outcomes including
pre-eclampsia (PET), intrauterine growth restriction (IUGR),
recurrent miscarriage and placental abruption have been linked
with thrombotic lesions compromising the utero-placental circulation.
Using histological staining including Martius Scarlet Blue
(MSB) and Haematoxylin and Eosin (H&E) and microscopy,
we studied placental fibrin deposition and histological abnormalities
in subjects (n=23) with APCR (APCR group), based on a ratio
of less than or equal to 2.1s with the Coatest((R)) classic
test and subjects (n=11) with an APC ratio in the normal range,
greater than 2.1s (APCN group). Fibrin deposition was significantly
higher (3.3-fold) in the APCR group compared to the APCN group.
An inverse correlation between APC ratio and placental fibrin
deposition was determined for the study group. Histological
abnormalities were more than 2-fold higher in the APCR group
compared to the APCN group. Molecular screening identified
common thrombophilic mutations, FVL and FII-G20210A in the
APCR group but not in the APCN group.
Prepared by the
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