NSIDRC Journal Article Alert — July 18, 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.

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 How to Get the Journal Article for more details.

Other Infant Death

1. Ab Rahman A, Ahmad Z, Naing L, Sulaiman SA, Hamid AM, Daud WN
The use of herbal medicines during pregnancy and perinatal mortality in Tumpat District, Kelantan, Malaysia.
Southeast Asian J Trop Med Public Health. 2007 Nov;38(6):1150-7

Department of Community Medicine, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Krian, Kelantan, Malaysia. azriani@kb.usm.my

The objective of this case-control study was to determine the association between herbal medicine use during pregnancy and perinatal mortality in Tumpat District, Kelantan, Malaysia. Cases were mothers who gave birth from June 2002 to June 2005 with a history of perinatal mortality, while controls were those without a history of perinatal infant mortality. A total of 316 mothers (106 cases and 210 controls) were interviewed. The use of unidentified herbs prepared by traditional midwives and other types of herbal medicines during the first trimester of pregnancy were positively associated with perinatal mortality (OR = 5.24, 95% CI = 1.13; 24.23 and OR = 8.90, 95%, CI = 1.35; 58.53, respectively). The use of unidentified "Orang Asli" herbs and coconut oil during the third trimester of pregnancy were negatively associated with perinatal mortality in Tumpat (OR = 0.10, 95% CI = 0.02; 0.59 and OR = 0.48, 95% CI = 0.25; 0.92, respectively). These findings suggest the use of unidentified "Orang Asli" herbs and coconut oil in late pregnancy are protective against perinatal mortality, while the use of unidentified herbs prepared by traditional midwives and other types of herbal medicines in early pregnancy has an increased risk of perinatal infant mortality. Pharmacological studies to confirm and identify the compounds in these herbs and their effects on the fetus should be conducted in the future.

Miscarriage/Stillbirth/Prenatal Issues

1. Demirhan O, Pazarbasi A, Suleymanova-Karahan D, Tanriverdi N, Kilinc Y.Saudi
Correlation of clinical phenotype with a pericentric inversion of chromosome 9 and genetic counseling
Med J. 2008 Jul;29(7):946-51

Department of Medical Biology and Genetics, Faculty of Medicine, Cukurova University, Balcali, Adana, Turkey.

OBJECTIVE: To describe the history of 157 carriers of pericentric inversions on chromosome 9 [inv9] with karyotype analyses and evaluate the significance of these findings. METHODS: We studied the incidence, clinical significance, and genetic counseling of inv9 p11;q12, p11;q13, and p11;q21 patients who were referred to our laboratory from various clinics of the Medical Faculty, Cukurova University, Adana, Turkey retrospectively from 157 cases of 15528 cytogenetic analyses collected between May 1993 and February 2007. RESULTS: We found the incidence of inv9 to be 1.01%. From a review of 157 cases with inv9, it is concluded that the incidence of the spontaneous abortion group 30.6% appeared to be high among the adult patients with inv9. The 17 cases were found to have mental retardation, which gave an incidence of 10.8%. We here report the clinical and cytogenetic findings of 157 inv9 cases that had different problems. CONCLUSION: Although, inv9 has been considered to be a normal variant, our observation implies a possible association between inv9 and abnormalities, suggesting that a susceptibility locus for these phenotypes may be located at the breakpoint of the inversion on chromosome 9, which may lead to cloning of a susceptibility gene for unspecified abnormalities. These findings could be used widely in clinical genetics, and as an effective tool for genetic counseling and reproductive guidance.

2. Singhal S, Prasad S, Singh B, Prasad JK, Gupta HP
Effect of including growth factors and antioxidants in maturation medium used for in vitro culture of buffalo oocytes recovered in vivo
Anim Reprod Sci. 2008 Jun 5. [Epub ahead of print]

Department of Animal Reproduction, Gynaecology & Obstetrics, College of Veterinary and Animal Sciences, G.B. Pant University of Agriculture & Technology, Pantnagar 263145, Uttarakhand, India.

This study examined the effect of including one of two growth factors (100ng/ml IGF-1 or 20ng/ml EGF) in combination with one of two antioxidants (50muM cysteamine or 50muM beta-mercaptoethanol) in maturation, fertilization and subsequent development of buffalo oocytes. The oocytes were recovered by in vivo ovum pick-up technique from six Murrah buffalo heifers twice a week over a period of 16 weeks. Immediately after ovum pick-up oocytes recovered from six donors were allocated randomly to five different maturation treatments. The control treatment was the basic maturation medium (MM; TCM-199 supplemented with 10% FBS, 10IU/ml LH, 0.5mug/ml FSH, 1mug/ml estradiol-17beta and 50mug/ml gentamicin). The other four treatments consisted of the control maturation medium (MM) plus one combination of a growth factor and an antioxidant viz. IGF-1+cysteamine; IGF-1+beta-ME; EGF+cysteamine or EGF+beta-ME. The total number of oocytes assigned to each maturation treatment ranged from 31 to 66. After maturation in different maturation medium, media used for in vitro fertilization and subsequent development of embryo was same for all groups. Data were analysed using Chi-square test. The maturation rate observed for the growth factor plus antioxidant treatments was similar to that for the control (90.4%). The highest cleavage rate recorded in the IGF-1+cysteamine treatment (71.9%) which was significantly higher (P<0.05) than the IGF-1+beta-ME (45.2%) and EGF+beta-ME (46.4%) treatments, but not significantly differ from the control (63.8%) and EGF+cysteamine treatment (60.7%). The proportion of cleaved oocytes those developed to blastocyst stage was significantly higher in the IGF-1+cysteamine treatment (52.2%; P<0.05) than in the control (23.3%), the EGF+cysteamine (13.5%) or the EGF+beta-ME (7.7%) treatments, but did not differ significantly from the IGF-1+beta-ME (28.6%) treatment. Following non-surgical transfer of 15 embryos to 14 synchronized recipients, four became pregnant and only one recipient sustained the pregnancy as long as 4.5 months when spontaneous abortion occurred. It was concluded that supplementing the maturation medium with IGF-1+cysteamine improved the production of buffalo embryos significantly in vitro culture.

3. Meister R, Schaefer C
Statistical methods for estimating the probability of spontaneous abortion in observational studies-Analyzing pregnancies exposed to coumarin derivatives
Reprod Toxicol. 2008 Jun 26. [Epub ahead of print]

Department II, Mathematics, Physics, Chemistry, University of Applied Sciences, Technische Fachhochschule Berlin, Luxemburger Strasse 10, 13353 Berlin, Germany.

BACKGROUND: Spontaneous abortion rates are of general interest when investigating pregnancy outcome. In most studies observations are left truncated as pregnant women enter with a delay of several weeks after conception. Apart from spontaneous abortion pregnancy may end in induced abortion or live birth. These outcomes are considered as competing events (risks). Although statistical methods for handling this setting are available since more than 10 years, studies on pregnancy outcome after drug exposure usually report crude rates of spontaneous abortions, ignoring left truncation and competing risks. METHODS: The authors propose simple methods which remove bias inherent to crude rates. The probability of spontaneous abortion is estimated using an event-history based approach for the subdistribution of competing risks that handles left truncation appropriately. Variance estimation enables the construction of approximate confidence intervals and of a simple test-statistic for comparing rates between different cohorts. The proposed methods are applied to a comparative prospective study on the association of spontaneous abortion and exposure to coumarin derivatives. RESULTS: The naive analysis using crude rates gives substantially different results than those based on the proposed methods, with up to a twofold change. Correctly incorporating left truncation into the analysis may increase the variance of the estimators, relative to an ideal sample where all pregnancies are followed from the time of conception. The consequences of such truncation for study design are discussed. CONCLUSION: Combining corrections for left truncation and competing risks offers a powerful method for analyzing miscarriage risk.

4. Cocksedge KA, Li TC, Saravelos SH, Metwally M
Reprod Biomed Online. 2008 Jul;17(1):151-60
A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage

Reproductive Medicine and Surgery Unit, University of Sheffield, Sheffield Teaching Hospitals, Jessop Wing, Tree Root Walk, Sheffield, S10 2SF, UK.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is associated with recurrent miscarriage. Despite the many studies that have investigated the prevalence of PCOS in recurrent miscarriage, the extent to which PCOS contributes remains highly uncertain. The majority of these studies have used the polycystic ovary morphology alone to define PCOS and the results are extremely variable due to a variety of diagnostic and selection criteria used. Only a very small number of studies have investigated the prevalence of hyperandrogenaemia in recurrent miscarriage. Most crucially, to the authors' knowledge, there is not yet a single publication which has investigated the true prevalence of the complete syndrome of PCOS in recurrent miscarriage using the Rotterdam criteria. Hence there is an urgent need to reappraise the prevalence of PCOS in recurrent miscarriage using the Rotterdam criteria. The possible mechanisms by which PCOS could cause recurrent miscarriage are considered: hyperandrogenaemia, obesity and hyperinsulinaemia are the most likely candidates, although further work is clearly needed. This paper also reviews the possible treatment options for women diagnosed with recurrent miscarriage associated with PCOS. There is some evidence to suggest that weight loss, ovarian drilling and metformin could help to reduce the rate of miscarriage.

5. Arck PC, Rücke M, Rose M, Szekeres-Bartho J, Douglas AJ, Pritsch M, Blois SM, Pincus MK, Bärenstrauch N, Dudenhausen JW, Nakamura K, Sheps S, Klapp BF
Early risk factors for miscarriage: a prospective cohort study in pregnant women
Reprod Biomed Online. 2008 Jul;17(1):101-13

Centre of Internal Medicine and Dermatology, Division of Psycho-Neuro-Immunology, Charité, University Medicine Berlin, Germany. petra.arck@charite.de.

Many pregnancies are lost during early gestation, but clinicians still lack tools to recognize risk factors for miscarriage. Thus, the identification of risk factors for miscarriage during the first trimester in women with no obvious risk for a pregnancy loss was the aim of this prospective cohort trial. A total of 1098 women between gestation weeks 4 and 12 in whom no apparent signs of a threatened pregnancy could be diagnosed were recruited. Demographic, anamnestic, psychometric and biological data were documented at recruitment and pregnancy outcomes were registered subsequently. Among the cases with sufficiently available data, 809 successfully progressing pregnancies and 55 subsequent miscarriages were reported. In this cohort, risk of miscarriage was significantly increased in women at higher age (>33 years), lower body mass index (< or =20 kg/ m(2)) and lower serum progesterone concentrations (< or =12 ng/ml) prior to the onset of the miscarriage. Women with subsequent miscarriage also perceived higher levels of stress/demands (supported by higher concentrations of corticotrophin-releasing hormone) and revealed reduced concentrations of progesterone-induced blocking factor. These risk factors were even more pronounced in the subcohort of women (n = 335) recruited between gestation weeks 4 and 7. The identification of these risk factors and development of an interaction model of these factors, as introduced in this article, will help clinicians to recognize pregnant women who require extra monitoring and who might benefit from therapeutic interventions such as progestogen supplementation, especially during the first weeks of pregnancy, to prevent a miscarriage.

6. Ali CR, Khashan AS, Horne G, Fitzgerald CT, Nardo LG
Implantation, clinical pregnancy and miscarriage rates after introduction of ultrasound-guided embryo transfer
Reprod Biomed Online. 2008 Jul;17(1):88-93

Department of Reproductive Medicine, St Mary's Hospital, CMMC University Hospitals, Manchester M13 0JH, UK. rchougle@hotmail.com.

The purpose of this study was to compare the reproductive outcome of ultrasound-guided (USG) embryo transfers versus clinical touch embryo transfers. A statistically powered retrospective analysis of women undergoing fresh and frozen embryo transfers in a National Health Service-based tertiary referral centre in the Department of Reproductive Medicine, St Mary's Hospital, Manchester was carried out. A total of 1723 embryo transfers were included in the analysis. The implantation rate was significantly higher in the USG embryo transfer group compared with the non-USG embryo transfer group (fresh: 19.9 versus 9.5%, P < 0.0001; frozen: 13.1 versus 7.3%, P < 0.0004). The clinical pregnancy rate was also significantly higher in the former group (fresh: 26.9 versus 12.5%, P < 0.0001; frozen: 15.6 versus 8.9%, P < 0.0015). For the frozen embryos, the miscarriage rate was significantly elevated among the USG embryo transfer group [unadjusted rate ratio (RR) = 1.65, 95% CI: 1.04, 2.62], but this was of borderline significance when the model was adjusted for the potential confounders (adjusted RR = 1.56, 95% CI: 0.997, 2.45). There was no difference in the ectopic pregnancy rates between the two groups. The findings of this study show that the practice of USG embryo transfer is associated with statistically higher implantation and clinical pregnancy rates in IVF.

7. Wang CW, Horng SG, Chen CK, Wang HS, Huang HY, Lee CL, Soong YK
Reprod Biomed Online. 2008 Jul;17(1):20-6
Ovulation induction with tamoxifen and alternate-day gonadotrophin in patients with thin endometrium

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fu-Hsing Street, Kwei-Shan, Tao-Yuan, Taiwan. cwwang@adm.cgmh.org.tw.

Tamoxifen has been reported to be oestrogenic on the lower genital tract. To evaluate its potential positive effect on the endometrium, and consequently early miscarriage and ongoing pregnancy rate, a prospective study was employed in patients for intrauterine insemination who failed to develop an adequate endometrial thickness in a previous ovulatory cycle. Ovarian stimulation was initiated with tamoxifen 40 mg/day from day 3 of the menstrual cycle for 7 days or clomiphene 100 mg/day for 5 days, in combination with 150 IU of human menopausal gonadotrophin on alternate days starting on day 4. Human chorionic gonadotrophin (HCG) was administered when at least one leading follicle was larger than 20 mm. Intrauterine insemination was accomplished 24-36 h after HCG injection and luteal phase supplement was achieved with micronized progesterone 200 mg transvaginally per day. It was found that tamoxifen-treated patients required more stimulation days and used more gonadotrophin, but recruited less follicles larger than 14 mm than clomiphene-treated patients. However, a significantly increased endometrial thickness (P < 0.001) and pregnancy rate (P = 0.015), decreased early miscarriage rate (P = 0.001) and thus improved ongoing pregnancy (P < 0.001) rate were noted in tamoxifen-treated patients. These results suggest that although tamoxifen may not be a first-line treatment in patients with adequate endometrium, it may be a promising alternative for patients with thin endometrium.

8. Arendas K, Qiu Q, Gruslin A
Obesity in pregnancy: pre-conceptional to postpartum consequences
J Obstet Gynaecol Can. 2008 Jun;30(6):477-88

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The Ottawa Hospital, University of Ottawa, Ottawa ON.

Objective: To review the effects of obesity on reproduction and pregnancy outcome. Methods: A search of the literature was performed using key word searching and citation snowballing to identify English language articles published between January 1, 2000, and December 31, 2006, on the subject of obesity and its effects on pregnancy. Once the articles were identified, a thorough review of all results was conducted. Results and conclusions were compiled and summarized. Results: Obesity during pregnancy was linked with maternal complications ranging from effects on fertility to effects on delivery and in the postpartum period, as well as many complications affecting the fetus and newborn. The maternal complications associated with obesity included increased risks of infertility, hypertensive disorders, gestational diabetes mellitus, and delivery by Caesarean section. Fetal complications included increased risks of macrosomia, intrauterine fetal death and stillbirth, and admission to the neonatal intensive care unit. Conclusion: Obesity causes significant complications for the mother and fetus. Interventions directed towards weight loss and prevention of excessive weight gain must begin in the pre-conception period. Obstetrical care providers must counsel their obese patients regarding the risks and complications conferred by obesity and the importance of weight loss. Maternal and fetal surveillance may need to be heightened during pregnancy; a multidisciplinary approach is useful. Women need to be informed about both maternal and fetal complications and about the measures that are necessary to optimize outcome, but the most important measure is to address the issue of weight prior to pregnancy.

Prepared by the
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