NSIDRC Journal Article Alert — May 2, 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.

Sudden Infant Death

1. Takahashi S, Kanetake J, Moriya T, Funayama M
Sudden infant death from dilated cardiomyopathy with endocardial fibroelastosis
Leg Med (Tokyo). 2008 Apr 26 [Epub ahead of print]

Division of Forensic Medicine, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, 980-8575 Sendai, Japan.

A four-month-old female with no previous medical history suddenly collapsed and failed to recover despite 2h of resuscitation. An autopsy showed marked cardiomegaly (88g) with prominent dilatation of the left ventricle and a whitish opacity on the endocardial surface. The ductus arteriosus was patent, but both orifices were severely stenosed. Microscopically, the endocardium showed pronounced thickening with laminar deposition of elastic and collagen fibers. Additionally, there was a mixture of myocardial fibers with a marked "wavy" appearance and a scattering of mild interstitial lymphocytic infiltration. We believe that endocardial thickening in this infant met the diagnostic criteria for endocardial fibroelastosis (EFE). Although it is controversial whether primary EFE is a distinct pathologic entity or an epiphenomenon, we speculated that "dilated cardiomyopathy with EFE" had caused the decedent's death based on the appearance of the myocardial fibers.

2. Alm B, Wennergren G, Lagercrantz H
SIDS diagnosis should not be put to bed
Acta Paediatr. 2008 Apr 21 [Epub ahead of print]

Department of Paediatrics, University of Gothenburg, Queen Silvia Children's Hospital, Gothenburg, Sweden.

The finding that prone sleeping position and smoking are important risk factors for SIDS has considerably reduced the incidence. Although these risk factors can be found in many cases of SIDS, they cannot be regarded as causes of death. Conclusion: The diagnosis of SIDS must be adhered to, and risk factors must not be confused with diagnoses. A structured follow-up of all cases of SIDS can be a cost-effective mean to ensure that parents and researchers are given adequate information.

Bereavement

1. Barr P, Cacciatore J
Problematic emotions and maternal grief
Omega (Westport). 2007-2008;56(4):331-48

Royal Alexandra Hospital for Children, Sydney, Australia. peter@chw.edu.au

The study was an empirical examination of the relation of personality proneness to "problematic social emotions"--envy (Dispositional Envy Scale), jealousy (Interpersonal Jealousy Scale), and shame and guilt (Personal Feelings Questionnaire-2)--to maternal grief (Perinatal Grief Scale-33) following miscarriage, stillbirth, neonatal death, or infant/child death. The 441 women who participated in the study were enrolled from the Website, e-mail contact lists, and parent support groups of an organization that offers information and support to bereaved parents. All four problematic emotions were positively correlated with maternal grief. Envy, jealousy, and guilt made significant unique contributions to the variance in maternal grief. Overall, time lapse since the loss and the four problematic emotion predispositions explained 43% of the variance in maternal grief following child bereavement.

Miscarriage/Stillbirth/Prenatal Issues

1. Warland J, McCutcheon H, Baghurst P
Maternal Blood Pressure in Pregnancy and Stillbirth: A Case-Control Study of Third-Trimester Stillbirth
Am J Perinatol. 2008 Apr 28 [Epub ahead of print]

University of South Australia, Adelaide, South Australia.

An immense body of literature on the effects of hypertension on perinatal morbidity and mortality exists, but only a handful of studies have reported adverse outcomes associated with low maternal blood pressure during pregnancy. This study aimed to investigate if there is an increased risk of fetal loss associated with hypotension during pregnancy. A matched case-control study of stillbirth and maternal blood pressure was conducted in which maternal blood pressures for a total of 124 pregnancies culminating in stillbirth were compared with maternal blood pressures in 243 (matched) pregnancies resulting in a liveborn infant. Women whose diastolic blood pressures fell in a borderline range (60 to 70 mm Hg) were consistently at greater risk of stillbirth relative to normotensive pregnancies. Women who had three or more mean arterial pressure values </= 83 mm Hg during the course of their pregnancy were at nearly twice the risk of stillbirth (odds ratio 1.78; 95% confidence interval [CI] 1.06 to 2.99; P = 0.03). Systolic hypotension was not significantly associated with stillbirth, but proportionately more control women were noted to have systolic hypertension (SBP >/= 130 mmHg) than cases, and the adjusted odds of stillbirth in women who were hypertensive at either their first or last antenatal visit or whose antenatal average SBP was >/= 130 mm Hg were all very close to 0.4 (95% CI 0.37 to 0.43; P = 0.02 to 0.03) relative to normotensives. We concluded that maternal hypotension, particularly borderline hypotension, may be a contributory risk factor for stillbirth. Women with hypertension in pregnancy may now be at a decreased risk of stillbirth as a result of the close care and treatment they receive.

2. Metwally M, Ledger WL, Li TC. Ann NY
Reproductive endocrinology and clinical aspects of obesity in women
Acad Sci. 2008 Apr;1127:140-6

The Academic Unit of Reproductive and Developmental Medicine. The Jessop Wing, Tree Root Walk, Sheffield, S10 4ED, UK. m.metwally@sheffield.ac.uk.

Obesity is a growing worldwide problem and is associated with a wide range of adverse effects on the female reproductive system. The endocrinological changes in obesity that may cause these adverse effects are complex and include changes in circulating adipokines and sex steroids as well as insulin resistance. Considerable evidence suggests an adverse effect of obesity on the risk of miscarriage and other maternal and fetal complications. Obese patients are also more prone to infertility. The most important single method to improve reproductive performance in obese women is weight loss that can be achieved with lifestyle changes and diet. Antiobesity drugs may also be used and, in severe cases, bariatric surgery.

3. Bromer JG, Cetinkaya MB, Arici A
Pretreatments before the Induction of Ovulation in Assisted Reproduction Technologies: Evidence-based Medicine in 2007
Ann N Y Acad Sci. 2008 Apr;1127:31-40

M.D. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine. 333 Cedar St. New Haven, CT 06520, USA. aydin.arici@yale.edu.

Many pretreatment modalities used prior to ovulation induction have been proposed to increase the success rate in women undergoing assisted reproductive technologies. However, no clear evidence from well-designed clinical trials has shown a benefit of these treatments. We conducted a systematic review to explore the effect of different pretreatment therapies on outcomes of in vitro fertilization (IVF) cycles. Studies were limited to women treated prior to undergoing controlled ovarian hyperstimulation in IVF cycles with low-dose aspirin, metformin, growth hormone, oral contraceptives, or corticosteroid supplementation versus placebo or no supplementation. Searches were conducted in the Cochrane Library, MEDLINE, EMBASE, and ISI Proceedings, and all randomized controlled trials that evaluated the effectiveness of those therapies compared with placebo or no treatment in women before IVF were included. The main outcome measures considered were clinical pregnancy and live birth rates, miscarriage rate, number of oocytes retrieved, cycle cancellations, and the incidence of ovarian hyperstimulation syndrome. We conclude that, currently, no clear evidence indicates that using any of these pretreatment modalities is superior to no treatment in IVF cycles. Even when the studies are pooled, small sample size and low power preclude a complete assessment of adjuvant treatment modalities before ovulation stimulation in IVF cycles.

4. Williams EK, Hossain MB, Sharma RK, Kumar V, Pandey CM, Baqui AH
Birth Interval and Risk of Stillbirth or Neonatal Death: Findings from Rural North India
J Trop Pediatr. 2008 Apr 27 [Epub ahead of print]

Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD USA.

Short birth intervals have been associated with adverse birth outcomes. This study examines the association between preceding interval and risk of stillbirth or neonatal death in rural north India (n = 80 164). Adjusted odds ratios (OR) and 95% confidence interval (CI) of stillbirth and neonatal mortality were calculated. The odds of stillbirth were significantly greater among birth intervals of <18 months (OR 3.10; CI: 2.69-3.57), 18-35 months (OR 1.47; CI 1.30-1.68) and >59 months (OR 1.44; CI 1.19-1.73), compared with intervals of 36-59 months. Neonatal death was associated with birth intervals of <18 months (OR 4.12; CI 3.74-4.55) and 18-35 months (OR 1.78; CI 1.63-1.94), compared to births spaced 36-59 months. Previous history of either stillbirth or neonatal death was significantly associated with risk of stillbirth and neonatal death, respectively, as were multiple births.

5. Verret C, Jutand MA, De Vigan C, Begassat M, Bensefa-Colas L, Brochard P, Salamon R
Reproductive health and pregnancy outcomes among French gulf war veterans
BMC Public Health. 2008 Apr 28;8(1):141 [Epub ahead of print]

ABSTRACT: BACKGROUND: Since 1993, many studies on the health of Persian Gulf War veterans (PGWVs) have been undertaken. Some authors have concluded that an association exists between Gulf War service and reported infertility or miscarriage, but that effects on PGWV's children were limited. The present study's objective was to describe the reproductive outcome and health of offspring of French Gulf War veterans. METHODS: The French Study on the Persian Gulf War (PGW) and its Health Consequences is an exhaustive cross-sectional study on all French PGWVs conducted from 2002 to 2004. Data were collected by postal self-administered questionnaire. A case-control study nested in this cohort was conducted to evaluate the link between PGW-related exposures and fathering a child with a birth defect. RESULTS: In the present study, 9% of the 5,666 Gulf veterans who participated reported fertility disorders, and 12% of male veterans reported at least one miscarriage among their partners after the PGW. Overall, 4.2% of fathers reported at least one child with a birth defect conceived after the mission. No PGW-related exposure was associated with any birth defect in children fathered after the PGW mission. Concerning the reported health of children born after the PGW, 1.0% of children presented a pre-term delivery and 2.7% a birth defect. The main birth defects reported were musculoskeletal malformations (0.5%) and urinary system malformations (0.3%). Birth defect incidence in PGWV children conceived after the mission was similar to birth defect incidence described by the Paris Registry of Congenital Malformations, except for Down syndrome (PGWV children incidence was lower than Registry incidence.) CONCLUSIONS: This study did not highlight a high frequency of fertility disorders or miscarriage among French PGW veterans. We found no evidence for a link between paternal exposure during the Gulf War and increased risk of birth defects among French PGWV children.

6. Hoffman ML, Scoccia B, Kurczynski TW, Shulman LP, Gao W
Abnormal folate metabolism as a risk factor for first-trimester spontaneous abortion
J Reprod Med. 2008 Mar;53(3):207-12

Department of Obstetrics and Gynecology, University of Illinois Medical Center at Chicago, USA. hoffman1959@yahoo.com

OBJECTIVE: To assess the potential role of folic acid in early pregnancy loss by measuring homocysteine (hcy) levels in healthy, pregnant women who present with a current first-trimester miscarriage. STUDY DESIGN: This was a cross-sectional analysis comprising 13 patients aged 18-31 years old who had a scheduled dilatation and curettage for a first-trimester miscarriage. The controls were 15 patients of similar maternal age presenting for a first-trimester prenatal care visit. Following completion of a 21-item, structured questionnaire, patients were excluded from the study if they had any known risk factors for a first-trimester miscarriage. The remaining patients provided blood samples for measurement of homocysteine and red blood cell folate. Cases and controls were compared using a standard 2-sample t test. In order to detect a clinically relevant 2.3 micromol/L difference in homocysteine levels, 11 cases and 8 controls were needed. RESULTS: The mean hcy level in cases (5.8 umolmol/L) vs. controls (5.7 micromol/L) was not significantly different (p = 0.83), and all individual values fell within the normal range expected in pregnant women. Red blood cell folate levels (cases=586 ng/mL, controls=611 ng/mL) were also not significantly different (p = 0.72), and no cases of folate deficiency were detected. Maternal age (cases=26, controls=25) and gestational age (cases = 8.8 weeks, controls = 8.4 weeks) were similar between the 2 groups. CONCLUSION: In this community-based pilot study, abnormal folate metabolism was not an apparent risk factor for spontaneous first-trimester pregnancy loss.

7. Pal L, Jindal S, Witt BR, Santoro N
Less is more: increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth after in vitro fertilization
Fertil Steril. 2008 Apr 26 [Epub ahead of print]

Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx.

OBJECTIVE: To determine if attempts to maximize oocyte yield during ovarian stimulation translates into improved outcome of in vitro fertilization (IVF) cycles. DESIGN: Retrospective study. SETTING: Academic tertiary care IVF center. PATIENT(S): 806 de-identified nondonor IVF cycles. INTERVENTION(S): Evaluation of fresh nondonor IVF cycles (n = 806) for the period January 1, 1999, to December 30, 2001. MAIN OUTCOME MEASURE(S): Cycle cancellation, clinical pregnancy, spontaneous miscarriage, and live birth after IVF. RESULT(S): Advancing age, independent of ovarian reserve status (reflected by early follicular phase FSH and estradiol) augured a worse prognosis for all outcomes. Higher gonadotropin use lowered cycle cancellations but was associated with a statistically significantly reduced likelihood of clinical pregnancy and live birth and a trend toward a higher likelihood for spontaneous miscarriage after IVF. CONCLUSION(S): Our data add to the accruing literature suggesting adverse influences of excess gonadotropin use on IVF outcomes. Although an aggressive approach to controlled ovarian hyperstimulation results in a statistically significant reduction in cycle cancellations, the excessive use of gonadotropins detrimentally influences live birth after IVF.

8. Jerzak M, Kniotek M, Mrozek J, Górski A, Baranowski W
Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage
Fertil Steril. 2008 Apr 26 [Epub ahead of print]

Department of Gynecology and Gynecologic Oncology, Military Institute of Health Sciences.

OBJECTIVE: To evaluate the effect of sildenafil on peripheral natural killer (NK) cell activity in women with a history of recurrent miscarriage (RM). DESIGN: Observational study. SETTING: University teaching hospital. PATIENT(S): Thirty-eight nonpregnant women with a history of RM and 37 healthy women with previous successful pregnancy outcomes. INTERVENTION(S): Patients self-administered sildenafil suppositories (25 mg intravaginally, four times a day) for 36 days. MAIN OUTCOME MEASURE(S): Peripheral blood NK-cell activity before and after vaginal sildenafil therapy in the RM women was measured using flow cytometry. In addition, the influence of 10 mug and 400 ng sildenafil on NK-cell activity after in vitro culture were determined. Uterine artery blood flow and endometrial thickness were recorded using Doppler ultrasound with an intravaginal probe. RESULT(S): The NK-cell activity was significantly decreased after vaginal sildenafil therapy. Endometrial thickness was significantly increased after such therapy. CONCLUSION(S): Vaginal sildenafil might be an interesting therapeutic option before conception in women with histories of reproductive failure.

9. Reichman D, Laufer MR, Robinson BK
Pregnancy outcomes in unicornuate uteri: a review
Fertil Steril. 2008 Apr 24 [Epub ahead of print]

Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

OBJECTIVE: To elucidate the impact of unicornuate uteri on pregnancy outcomes as evidenced by historical and contemporary studies. DESIGN: Publications related to unicornuate uterus were identified through MEDLINE and other bibliographic databases. SETTING: Literature review in an academic research environment. PATIENT(S): Premenopausal women with confirmed unicornuate uterus based on surgical or radiological evidence who were undergoing gynecologic and obstetrical care. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of ectopic pregnancy, miscarriage, preterm delivery, intrauterine fetal demise, and live birth. RESULT(S): Our review revealed 20 studies of varying size and design that had commented on pregnancy outcomes in unicornuate uteri. These studies ranged in date from 1953 to 2006 and from a sample size of one to 55 patients. In total, we examined 290 women with unicornuate uterus reported in the literature. Of those patients, 175 conceived, to carry a total of 468 pregnancies. Incidence data in the literature reveal that unicornuate uterus occurs in 1:4020 women in the general population; the anomaly, however, is significantly more common in infertile women, as in women with repeated poor outcomes. Our review revealed rates of 2.7% ectopic pregnancy, 24.3% first trimester abortion, 9.7% second trimester abortion, 20.1% preterm delivery, 10.5% intrauterine fetal demise, and 49.9% live birth. CONCLUSION(S): Unicornuate uterus is a Mullerian anomaly with prognostic implications for poorer outcomes during pregnancy. The rates of adverse outcomes have likely been historically overestimated. Although it is unclear whether interventions before conception or early in pregnancy such as resection of the rudimentary horn and prophylactic cervical cerclage decidedly improve obstetrical outcomes, current practice suggests that such interventions may be helpful. Women presenting with a history of this anomaly should be considered high-risk obstetrical patients.

10. Liddell HS, Lo C. J
Laparoscopic cervical cerclage: a series in women with a history of second trimester miscarriage
Minim Invasive Gynecol. 2008 May-Jun;15(3):342-5. Epub 2008 Mar 20.

Ascot Integrated Hospital, Remuera, Auckland, New Zealand.

We sought to develop a laparoscopic technique for placement of a cervical cerclage in women with a history of failed vaginal cerclage and recurrent miscarriage. This was a case series, design classification III. The study took place at The Recurrent Miscarriage Clinic at National Women's Hospital, Auckland, New Zealand. Ten women with a history of second trimester miscarriage after failed vaginal cerclage, and 1 woman with a history of second trimester miscarriage and findings of a clinically deficient cervix were studied. A laparoscopic cervical cerclage was placed before pregnancy. No intraoperative or postoperative complications were experienced. Ten of 11 women subsequently became pregnant and all delivered live babies by cesarean section in the third trimester. Laparoscopic cervical cerclage is feasible and effective. Outcomes are good in a particularly high-risk group of women with cervical incompetence, who have had failed vaginal cerclage and have a history of recurrent pregnancy loss.

11. Bahtiyar MO, Funai EF, Rosenberg V, Norwitz E, Lipkind H, Buhimschi C, Copel JA.
Stillbirth at Term in Women of Advanced Maternal Age in the United States: When Could the Antenatal Testing Be Initiated?
Am J Perinatol. 2008 Apr 24 [Epub ahead of print].

Yale University School of Medicine, Section of Maternal-Fetal Medicine, New Haven, Connecticut.

We sought to determine if advanced maternal age (AMA) is a risk factor for intrauterine fetal demise (IUFD). We used a U.S. Centers for Disease Control and Prevention database and analyzed outcomes in women 15 to 44 years of age with term singleton gestations. Cox proportional hazards models and Cochran-Mantel-Haenszel tests were used. Results were controlled for maternal race and smoking. After excluding congenital anomalies and medical complications, 6,239,399 singleton term deliveries were identified. When compared with women 25 to 29 years of age, the risk of IUFD increased with advancing age: 30 to 34 years, odds ratio [OR] = 1.24 (95% confidence interval [CI], 1.13 to 1.36); 35 to 39 years, OR = 1.45 (95% CI, 1.21 to 1.74), and 40 to 44 years, OR = 3.04 (95% CI, 1.58 to 5.86). The risk of IUFD for women 40 to 44 years of age at 39 weeks is comparable with that of 42 weeks in those 25 to 29 years of age. We concluded that AMA is an independent predictor of IUFD, and a strategy of antenatal testing in those >/= 40 years of age beginning at 38 weeks may be considered.

12. Parast MM, Crum CP, Boyd TK
Placental histologic criteria for umbilical blood flow restriction in unexplained stillbirth
Hum Pathol. 2008 Apr 18 [Epub ahead of print]

Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Approximately 50% of stillbirths are unexplained after fetopsy and placental examination. Fatal hypoxic injury due to restriction of umbilical blood flow ("cord accident") may be causal in a subset of these stillbirths. We reviewed placental slides of 62 cases of third-trimester stillbirth from our autopsy files over a 5-year period to define criteria and estimate the frequency of cord accident as a cause of stillbirth. By correlating clinical and autopsy information-with placental gross and histologic findings-from a series of index cases with a strong presumptive evidence of cord accident, histologic criteria for cord accident were established. "Minimal histologic criteria," suggestive of cord accident, were defined as vascular ectasia and thrombosis within the umbilical cord, chorionic plate, and/or stem villi. A definitive diagnosis of cord accident required in addition regional distribution of avascular villi or villi showing stromal karyorrhexis. Of 27 stillbirth cases with a cause of death determined to be other than cord accident, only 3 (11%) met all histologic criteria for cord accident (specificity of 89%). In contrast, of 25 stillbirth cases with an unknown cause of death, a significantly larger subset (13 cases or 52%) met the criteria for cord accident (P = .0038). Thus, we find nonacute cord compression implicated in over half of "unexplained" fetal deaths. This is the first report to establish histologic criteria in the diagnosis of cord accident, the application of which could significantly reduce the proportion of unexplained third-trimester stillbirth.

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