Resource Center Journal Article Alert — September
12, 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 Medicin's PubMed database in
the last week.
Past issues of NSIDRC 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
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more details.
Sudden Infant Death
1. Patrick P, Lincoln A, Lorenz D, DeVault M, Dooley S
Infant sleep position in Oklahoma: evidence from PRAMS
J Okla State Med Assoc. 2008 Aug;101(8):182-7
Oklahoma State Department of Health, Oklahoma City, Oklahoma
73117-1299, USA.
BACKGROUND: The supine (back) sleep position has been found
to be an important factor in the reduction of sudden infant
death syndrome (SIDS). This paper will examine infant sleep
position in Oklahoma and offer recommendations to increase
safe sleep practices for Oklahoma infants. METHODS: Oklahoma
Pregnancy Risk Assessment Monitoring System (PRAMS) data were
used to estimate prevalence of sleep position among demographic
maternal groups and related health behaviors. Chi-square tests
were used to determine significance at p< 0.05. Logistic
regression modeling was used to produce adjusted odds ratios
to measure the association of selected independent variables
and sleep position. RESULTS: Fifty-six percent of Oklahoma
newborns were placed on their backs to sleep most of the time,
far short of the Healthy People 2010 goal of 70%. Almost 1
in 5 infants were placed on their stomachs to sleep, a known
risk factor for SIDS. Women between 100-184% of the federal
poverty level, African American women and mothers with more
than one child were those least likely to place their infants
on their backs to sleep. CONCLUSION: Overall, the issue of
not utilizing the recommended safe sleep position, the supine
position, is pervasive among all maternal groups in Oklahoma.
Significant differences were present for only a few variables
(race, income, parity) indicating a strong need for a consistent
message on sleep position for all Oklahoma parents and grandparents.
2. Sakai J, Kanetake J, Takahashi S, Kanawaku Y, Funayama
M
Gas dispersal potential of bedding as a cause for sudden infant
death
Forensic Sci Int. 2008 Sep 4. [Epub ahead of print]
Division of Forensic Medicine, Department of Public Health
and Forensic Medicine, Tohoku University School of Medicine,
Sendai, Japan.
We assessed the gas dispersal potential of bedding articles
used by 14 infants diagnosed with sudden unexpected infant
death at autopsy. Of these cases, eight exhibited FiCO(2) values
greater than 10% within 2.5min, six of which were found prone
and two supine. The results demonstrated that these eight beddings
had a high rebreathing potential if they covered the babies'
faces. We did not, however, take into account in our model
the large tissue stores of CO(2). As some bicarbonate pools
will delay or suppress the increase of FiCO(2), the time-FiCO(2)
graphs of this study are not true for living infants. This
model, however, demonstrated the potential gas dispersal ability
of bedding. The higher the FiCO(2) values, the more dangerous
the situation for rebreathing infants. In addition, FiO(2)
in the potential space around the model's face can be estimated
mathematically using FiCO(2) values. The FiO(2) graph pattern
for each bedding item corresponded roughly to the inverse of
the FiCO(2) time course. The FiO(2) of the above eight cases
decreased by 8.5% within 2.5min. Recent studies using living
infants placed prone to sleep reported that some babies exhibited
larger decreases in FiO(2) than increases observed in FiCO(2).
While the decrease of FiO(2) in our model is still theoretical,
CO(2) accumulation and O(2) deprivation are closely related.
If a striking O(2) deficiency occurs in a short period, babies
can lose consciousness before an arousal response is evoked
and all infants could be influenced by the poor gas dispersal
of bedding; the main cause of sudden death in infancy would
thus be asphyxia. When the bedding is soft, the potential for
trapping CO(2) seems to be high; however, it is impossible
to assess it by appearance alone. We sought to provide some
objective indices for the assessment of respiratory compromise
in relation to bedding using our model. When a baby is found
unresponsive with his/her face covered with poor gas dispersal
bedding, we should consider the possibility of asphyxia.
3. Rand CM, Berry-Kravis EM, Fan W, Weese-Mayer DE
HTR2A variation and sudden infant death syndrome: a case-control
analysis
Acta Paediatr. 2008 Sep 2. [Epub ahead of print]
Department of Pediatrics, Rush Children's Hospital at Rush
University Medical Center, Chicago, IL, USA.
Aim: The serotonergic (5-HT) system functions in central autonomic
regulation with homeostatic roles in cardiorespiratory control,
thermoregulation, arousal and sleep-wake cycling. Altered function
and development of this system in cases of sudden infant death
syndrome (SIDS) have been established, but the aetiology of
these disturbances remains unclear. The serotonin receptor,
HTR2A, functions within this system with roles in the homeostatic
response to hypoxia including excitatory effects on respiration,
gasping and rhythm generation, all functions potentially compromised
in SIDS. The objective of this study was to examine the relationship
between SIDS risk and HTR2A variation. Methods: All coding
regions, intron-exon boundaries and the promoter region of
HTR2A were PCR amplified and analysed by standard sequencing
in 96 SIDS cases and 96 matched controls. Results: Twenty-one
HTR2A variations were identified in this case-control cohort,
including four novel variations (c.C-1185A, c.T-923C, c.T-17C
and c.C50T). None of the variations identified showed a significant
association with SIDS. Conclusion: This report provides evidence
that despite known alterations of the 5-HT system in SIDS,
and the logical role for the HTR2A receptor, genetic variation
of HTR2A as studied in our cohort is not responsible for these
alterations. These results represent a further step in the
investigation of the aetiology of the altered serotonin system
in SIDS cases.
Other Infant Death
1. Sung TI, Wang JD, Chen PC
Increased risks of infant mortality and of deaths due to congenital
malformation in the offspring of male electronics workers
Birth Defects Res A Clin Mol Teratol. 2008 Sep 3. [Epub ahead
of print]
Institute of Occupational Medicine and Industrial Hygiene,
National Taiwan University College of Public Health, Taipei,
Taiwan.
BACKGROUND: There is limited evidence on the association between
paternal occupational exposure during preconception and infant
mortality and deaths due to congenital malformation. This retrospective
cohort study was conducted to determine if such an association
existed among male workers employed in an electronics factory.
METHODS:: We linked the databases of labor insurance, birth
registration, and national death registry, identified 7,202
male workers ever employed in this factory with 13,592 liveborn
children and 81 deaths in the first year after, excluding 861
children with potential maternal exposure from the same workplace.
Fathers employed in this factory during their preconceptional
periods (3 months prior to the conception) were considered
as exposed compared with those not employed during the same
periods. Poisson regression models were constructed to adjust
for potential confounding by child's sex, parity, multiple
births, year of birth, parental age at delivery, and educational
levels. RESULTS:: Based on 24 exposed cases, the rate ratios
(RRs) of infant mortality were increased to 5.06 (95% CI: 2.33-11.00)
and 2.81 (95% CI: 1.44-5.51) among liveborn children whose
fathers worked for >10 and 1-10 years, respectively, in
this factory during preconception. Maternal delivery age less
than 20 years, fathers with less than 10 years of education,
and multiple births were associated with increased risks of
infant mortality. When limited to 28 deaths with congenital
malformation, Poisson regression model showed an increased
risk for exposed pregnancies (RR = 3.75; 95% CI: 1.29-10.94),
especially among cardiac defects (RR = 5.06; 95% CI: 1.58-16.19).
CONCLUSIONS:: Our study suggests that paternal occupational
exposures, possibly to organic solvents during preconception,
might increase infant mortality and deaths due to congenital
malformation, especially for cardiac defects. However, the
small numbers of this study limited the generalization of its
findings. Birth Defects Research (Part A), 2008. (c) 2008 Wiley-Liss,
Inc.
2. Thompson DR, Clark CL, Wood B, Zeni MB
Maternal obesity and risk of infant death based on Florida
birth records for 2004
Public Health Rep. 2008 Jul-Aug;123(4):487-93
Florida Department of Health, Division of Family Health Services,
Tallahassee, FL 32399-1723, USA. dan_thompson@doh.state.fl.us.
OBJECTIVE: The purpose of this study was to assess the relationship
between pre-pregnancy maternal obesity and risk of infant death.
METHODS: In March 2004, maternal height and pre-pregnancy weight
were added to the data collected on the Florida birth certificate.
Using birth records linked to infant deaths, these data were
used to assess the relationship between pre-pregnancy maternal
obesity, as measured by body mass index, and infant death.
RESULTS: Pre-pregnancy maternal obesity was associated with
increased odds of infant death. The increased risk was found
with and without adjustments for maternal race, marital status,
age, education, trimester prenatal care began, first birth,
and tobacco use. CONCLUSION: There is a substantial and significant
association between pre-pregnancy maternal obesity and infant
death.
Miscarriage/Stillbirth/Prenatal Issues
1. Winther JF, Boice JD Jr, Svendsen AL, Frederiksen K, Stovall
M, Olsen JH
Spontaneous abortion in a danish population-based cohort of
childhood cancer survivors
J Clin Oncol. 2008 Sep 10;26(26):4340-6
Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden
49, DK-2100 Copenhagen, Denmark; jeanette@cancer.dk.
PURPOSE Radiation induces germ-cell mutations in experimental
animals that result in adverse pregnancy outcomes, as does
uterine damage caused by high-dose radiotherapy. We assessed
the risks for spontaneous abortion and stillbirths among cancer
survivors who received radiotherapy and subsequently became
pregnant. PATIENTS AND METHODS We identified 1,688 female survivors
of childhood cancer in the Danish Cancer Registry. Radiation
doses to the ovary and uterus were characterized as high to
low. The pregnancy outcomes of survivors, 2,737 sisters, and
16,700 comparison women in the population were identified from
nationwide registries. The proportions of pregnancies among
survivors that resulted in a livebirth, stillbirth, or abortion
were compared with the equivalent proportions among the two
comparison groups, and proportion ratios (PRs) were computed
with sisters as referent. Results More than 34,000 pregnancies
were evaluated, 1,479 of which were among cancer survivors.
No significant differences were seen between survivors and
comparison women in the proportions of livebirths, stillbirths,
or all types of abortions combined. Survivors, however, had
a 23% excess risk for spontaneous abortion (PR, 1.23; 95% CI,
1.0 to 1.5), related primarily to prior radiation treatments
(PR, 1.58; 95% CI, 1.2 to 2.2) and especially high-dose radiotherapy
to the ovaries and uterus (PR, 2.8; 95% CI, 1.7 to 4.7). CONCLUSION
The pregnancy outcomes of survivors were similar to those of
comparison women. A slight excess risk for spontaneous abortion
may have resulted from uterine damage after high-dose pelvic
radiotherapy, consistent with previous studies, although radiation-induced
germinal mutations or decreased hypothalamic-pituitary-ovarian
function could not be ruled out.
2. Benagiano G, Bastianelli C, Farris M
Selective progesterone receptor modulators 1: use during pregnancy
Expert Opin Pharmacother. 2008 Oct;9(14):2459-2472
Professor and Dean University 'la Sapienza', Postgraduate
School of Gynaecology and Obstetrics, Policlinico Umberto I
degrees , Viale Regina Margherita 245, 00161 Roma, Italy, 2Associate
Professor University 'la Sapienza', Department of Gynaecology
and Obstetrics, Policlinico Umberto I degrees , Viale Regina
Margherita 245, 00161 Roma, Italy, 3Research Associate University
'la Sapienza', Department of Gynaecology and Obstetrics, Policlinico
Umberto I degrees , Viale Regina Margherita 245, 00161 Roma,
Italy +39 06 490 398 ; +39 06 4997 2455 ; Manuela.farris@uniroma1.it.
Background: A large number of synthetic compounds known as
selective progesterone receptor modulators can bind to progesterone
receptors: the ligands exhibit a spectrum of activities ranging
from pure antagonism to a mixture of agonism and antagonism.
Objectives: Only a dozen or so selective progesterone receptor
modulators have been tested to any significant extent: among
them are mifepristone (RU 486), asoprisnil (J867), onapristone
(ZK 98 299), ulipristal (CDB 2914), Proellex() (CDB 4124),
ORG 33628 and ORG 31710. Their clinical applications during
pregnancy are discussed. Methods: A careful evaluation of existing
major review papers and recently published articles was carried
out focusing on mifepristone, the most widely studied selective
progesterone receptor modulator, which was first used for the
voluntary interruption of an early gestation. Other selective
progesterone receptor modulators, especially those with partial
agonist action, have shown little activity during pregnancy
in animal models. Results/conclusions: Besides early and late
voluntary interruption of gestation, selective progesterone
receptor modulators have been tested in a variety of obstetrical
situations: to obtain a ripening of the cervix, for the medical
management of early embryonic loss and foetal death, for the
induction of labour at term and for the medical treatment of
extra-uterine pregnancies. The only applications that seem
worthy of large-scale utilisation during pregnancy are voluntary
interruption of early and late gestation, medical management
of early delayed miscarriage and late foetal demise.
3. Miller CM, Boulter NR, Ikin RJ, Smith NC
The immunobiology of the innate response to Toxoplasma gondii
Int J Parasitol. 2008 Aug 22. [Epub ahead of print]
Institute for the Biotechnology of Infectious Diseases, University
of Technology, Sydney, P.O. Box 123, Broadway, NSW 2007, Australia.
Toxoplasma gondii is a unique intracellular parasite. It can
infect a variety of cells in virtually all warm-blooded animals.
It has a worldwide distribution and, overall, around one-third
of people are seropositive for the parasite, with essentially
the entire human population being at risk of infection. For
most people, T. gondii causes asymptomatic infection but the
parasite can cause serious disease in the immunocompromised
and, if contracted for the first time during pregnancy, can
cause spontaneous abortion or congenital defects, which have
a substantial emotional, social and economic impact. Toxoplasma
gondii provokes one of the most potent innate, pro-inflammatory
responses of all infectious disease agents. It is also a supreme
manipulator of the immune response so that innate immunity
to T. gondii is a delicate balance between the parasite and
its host involving a coordinated series of cellular interactions
involving enterocytes, neutrophils, dendritic cells, macrophages
and natural killer cells. Underpinning these interactions is
the regulation of complex molecular reactions involving Toll-like
receptors, activation of signalling pathways, cytokine production
and activation of anti-microbial effector mechanisms including
generation of reactive nitrogen and oxygen intermediates.
4. Weghofer A, Munné S, Brannath W, Chen S, Barad D,
Cohen J, Gleicher N
The impact of LH-containing gonadotropin stimulation on euploidy
rates in preimplantation embryos: antagonist cycles
Fertil Steril. 2008 Sep 5. [Epub ahead of print]
Department of Obstetrics and Gynecology, Medical University
Vienna, Vienna, Austria; The Center for Human Reproduction
and the Foundation for Reproductive Medicine, New York, New
York.
OBJECTIVE: To evaluate effects of luteinizing hormone (LH)-containing
gonadotropins (human menopausal gonadotropin, hMG) on ploidy
of human cleavage-stage embryos in gonadotropin releasing hormone
(GnRH) antagonist cycles. DESIGN: Retrospective matched cohort
study. SETTING: Two academically affiliated private fertility
centers, private preimplantation genetics laboratory, and medical
school. PATIENTS(S): One hundred four consecutive in vitro
fertilization cycles (IVF) with preimplantation genetic diagnosis
in women aged 30 to 45 years. INTERVENTION(S): Antagonist cycles
with ovarian stimulation by either recombinant follicle stimulating
hormone (FSH) alone, or in combination with human menopausal
gonadotropin (FSH/hMG). MAIN OUTCOME MEASURE(S): After matching
patients for age and gonadotropin dosage, embryo ploidy, pregnancy,
and miscarriage rates were evaluated. RESULT(S): Euploidy rates
(FSH, 29.4% vs. FSH/hMG, 25.7%) and number of euploid embryos
(FSH, 2.1 +/- 1.6 vs. FSH/hMG, 1.9 +/- 1.5) were similar between
both groups, although trended in favor of FSH-only stimulation.
FSH-only stimulation, however, demonstrated significantly higher
clinical pregnancy rates per cycle start (FSH: 34.6% vs. FSH/hMG:
11.5%) and per embryo transfer (FSH: 40% vs. FSH/hMG: 15%).
CONCLUSION(S): Because this study involved mostly women of
advanced reproductive age, at least in such an age category,
LH-containing stimulation causes adverse effects on pregnancy
rates, although whether such an adverse effect on ploidy exists
in parallel requires further investigation. These observations
point toward embryo-independent adverse effects on implantation
(luteal phase) in antagonist cycles with hMG costimulation.
5. Vergani P, Cozzolino S, Pozzi E, Cuttin MS, Greco M, Ornaghi
S, Lucchini V
Identifying the causes of stillbirth: a comparison of four
classification systems
Am J Obstet Gynecol. 2008 Sep;199(3):319.e1-4
Department of Obstetrics and Gynecology, University of Milano-Bicocca,
Monza, Italy.
OBJECTIVE: To identify the classification protocol for stillbirth
that minimizes the rate of unexplained causes. STUDY DESIGN:
All stillbirths at > 22 weeks from 1995-2007 underwent a
workup inclusive of fetal ultrasonography, amniocentesis for
karyotype and cultures, placental histology, fetal autopsy,
skin biopsy, total body X-ray, maternal testing for thrombophilias,
TORCH, Parvovirus spp, thyroid function, indirect Coombs, Kleiheuer-Betke
test, and genital cultures. To such a cohort, we applied the
4 most commonly used classification protocols. RESULTS: The
stillbirth rate during the study period was 0.4% (154/37,958).
The RoDeCo classification provided the lowest rate of unexplained
stillbirth (14.3%) compared with Wigglesworth (47.4%), de Galan-Roosen
(18.2%), and Tulip (16.2%) classifications. Mean gestational
age at stillbirth in unexplained vs explained stillbirth was
similar in the 4 protocols. CONCLUSION: Adoption of a consistent
and appropriate workup protocol can reduce the rate of unexplained
stillbirth to 14%.
6. Qiao J, Wang L, Li R, Zhang X
Microarray evaluation of endometrial receptivity in Chinese
women with polycystic ovary syndrome
Reprod Biomed Online. 2008 Sep;17(3):425-35
Reproductive Medicine Centre, Peking University Third Hospital,
Beijing 100083, China.
Patients with polycystic ovary syndrome (PCOS) have lower
pregnancy and higher miscarriage rates, possibly due to decreased
endometrial receptivity. In this study, endometrium was processed
for RNA extraction and hybridization of chemically fragmented,
biotinylated, complementary RNA on high-density oligonucleotide
microarrays, and screened for 21,571 genes. Real-time polymerase
chain reaction (PCR) was used to verify the result. Genes found
to be down-regulated in the endometrium during the implantation
window in PCOS patients included those whose activity was integral
to membrane function, adhesion, invasive growth and the cytoskeleton.
Among these genes, some have previously been associated with
endometrial receptivity (by microarray research or other methods)
and some have never previously been associated with endometrial
receptivity. Using real-time PCR, expression of transmembrane
4 superfamily member 4 (TM4SF4) and matrix metalloproteinase
26 (MMP26) was found to be significantly decreased during the
implantation window in patients with PCOS (P= 0.003). TM4SF4
has been demonstrated to be associated with adhesion; MMP26
has been shown to be related to degradation of extracellular
matrix. It is suggested the down-regulated gene expression
during the implantation window in patients with PCOS indicates
differential gene expression in the endometrium between PCOS
and normal women during the implantation window. This might
affect endometrial receptivity.
7. Hapangama DK, Turner MA, Drury JA, Martin-Ruiz C, Von Zglinicki
T, Farquharson RG, Quenby S
Endometrial telomerase shows specific expression patterns in
different types of reproductive failure
Reprod Biomed Online. 2008 Sep;17(3):416-24
School of Reproductive and Developmental Medicine, University
of Liverpool, Liverpool Women's Hospital, Crown Street, Liverpool,
L8 7SS, UK. dharani.hapangama@liverpool.ac.uk.
In order to assess whether markers of cell senescence are
related to reproductive failure, the expression of telomerase
and telomere length in endometrial biopsies from women with
and without reproductive failure were assessed. This pilot
study included 45 women of whom 10 had idiopathic recurrent
loss of empty gestational sacs, 10 had idiopathic recurrent
fetal loss (miscarriage following identification of fetal cardiac
activity), 10 had recurrent implantation failure and 15 had
two or more normal pregnancies (control group). An endometrial
sample was collected during the window of implantation from
each woman. The mean endometrial telomere length was determined
by quantitative polymerase chain reaction. Telomerase expression
was evaluated by immunohistochemistry. The endometria of the
control group showed virtually no telomerase immunoreactivity
during the window of implantation. However, the immunostaining
for telomerase was significantly and differentially increased
in various endometrial cellular compartments in women with
recurrent reproductive failure (P < 0.05). There were no
significant differences in mean telomere length between groups.
These data provide a novel insight into the biological correlates
of clinical types of recurrent reproductive failure and suggest
that specific alterations in the regulation of endometrial
cell fate are associated with different types of recurrent
reproductive failure.
8. Belloc S, Cohen-Bacrie P, Benkhalifa M, Cohen-Bacrie M,
De Mouzon J, Hazout A, Ménézo Y
Effect of maternal and paternal age on pregnancy and miscarriage
rates after intrauterine insemination
Reprod Biomed Online. 2008 Sep;17(3):392-7
Laboratoire d'Eylau, 55 rue Saint Didier, 75116 Paris, France;
Unité AMP Eylau La Muette, 46-48 rue Nicolo 75116, Paris,
France.
More than 17,000 intrauterine insemination (lUI) cycles were
analysed retrospectively with respect to outcome according
to differing aetiologies of infertility. The quantity and motility
of spermatozoa in the final preparation used for insemination
had a positive effect on the outcome, as classically observed
in the past. It was found that advanced maternal age had a
negative effect on the pregnancy rate and was associated with
increased miscarriage rate. More interestingly, an exactly
parallel effect was found for paternal age. The impact of increased
age on necrospermia and sperm DNA structure is discussed as
a probable direct cause of this paternal effect.
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
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info@sidscenter.org
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