NSIDRC Journal Article Alert — October 10, 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 Medicine's PubMed database in the last week.

Past issues of Resource Center 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.

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Sudden Infant Death

1. Coleman-Phox K, Odouli R, Li DK Use of a fan during sleep and the risk of sudden infant death syndrome Arch Pediatr Adolesc Med. 2008 Oct;162(10):963-8

Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.

OBJECTIVE: To examine the relation between room ventilation during sleep and risk of sudden infant death syndrome (SIDS). DESIGN: Population-based case-control study. SETTING: Eleven California counties. PARTICIPANTS: Mothers of 185 infants with a confirmed SIDS diagnosis and 312 randomly selected infants matched on county of residence, maternal race/ethnicity, and age. Intervention Fan use and open window during sleep. Main Outcome Measure Risk of SIDS. RESULTS: Fan use during sleep was associated with a 72% reduction in SIDS risk (adjusted odds ratio [AOR], 0.28; 95% confidence interval [CI], 0.10-0.77). The reduction in SIDS risk seemed more pronounced in adverse sleep environments. For example, fan use in warmer room temperatures was associated with a greater reduction in SIDS risk (AOR, 0.06; 95% CI, 0.01-0.52) compared with cooler room temperatures (0.77; 0.22-2.73). Similarly, the reduction associated with fan use was greater in infants placed in the prone or side sleep position (AOR, 0.14; 95% CI, 0.03-0.55) vs supine (0.84; 0.21-3.39). Fan use was associated with a greater reduction in SIDS risk in infants who shared a bed with an individual other than their parents (AOR, 0.15; 95% CI, 0.01-1.85) vs with a parent (0.40; 0.03-4.68). Finally, fan use was associated with reduced SIDS risk in infants not using pacifiers (AOR, 0.22; 95% CI, 0.07-0.69) but not in pacifier users (1.99; 0.16-24.4). Some differences in the effect of fan use on SIDS risk did not reach statistical significance. CONCLUSION: Fan use may be an effective intervention for further decreasing SIDS risk in infants in adverse sleep environments.

2. Moon RY, Calabrese T, Aird L Reducing the risk of sudden infant death syndrome in child care and changing provider practices: lessons learned from a demonstration project Pediatrics. 2008 Oct;122(4):788-98

Division of General Pediatrics and Community Health, Diana L and Stephen A Goldberg Center for Community Pediatric Health, Children's National Medical Center, Washington, DC 20010, USA. rmoon@cnmc.org

OBJECTIVE: The goal was to evaluate, through an American Academy of Pediatrics demonstration project, the effectiveness of a curriculum and train-the-trainer model in changing child care providers' behaviors regarding safe infant sleep practices. METHODS: Participating licensed child care centers and family child care homes were assigned randomly to intervention and control groups. Observers performed an initial unannounced visit to each site, to watch infants being placed for sleep, to inventory sleep policies, and to administer questionnaires to center staff members. Trainers then used the American Academy of Pediatrics curriculum in educational sessions at intervention sites. Three months later, observers conducted a follow-up observation at each site, and staff members completed a questionnaire about logistic barriers encountered in implementation of safe sleep recommendations. RESULTS: A total of 264 programs and 1212 providers completed the study; the care of 1993 infants was observed. Provider awareness of the American Academy of Pediatrics infant supine sleep position recommendation increased from 59.7% (both groups) to 64.8% (control) and 80.5% (intervention). Exclusive use of the supine position in programs increased from 65.0% to 70.4% (control) and 87.8% (intervention). Observed supine placement increased from 51.0% to 57.1% (control) and 62.1% (intervention). CONCLUSIONS: A sudden infant death syndrome risk reduction curriculum using a train-the-trainer model is effective in improving the knowledge and practices of child care providers. Perceived parental objections, provider skepticism about the benefits of supine positioning, and lack of program policies and training opportunities are important barriers to implementation of safe sleep policies. Continued education of parents, expanded training efforts, and statewide regulations, mandates, and monitoring are critical to ongoing efforts to decrease further the risk of sudden infant death syndrome in child care.

3. Elliot JG, Ford DL, Beard JF, Fitzgerald KN, Robinson PJ, James AL Informed consent for the study of retained tissues from postmortem examination following sudden infant death J Med Ethics. 2008 Oct;34(10):742-6

West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. john.elliot@health.wa.gov.au

OBJECTIVE: To develop an approach for seeking informed consent to examine tissues retained from a previous study of sudden infant death syndrome (SIDS) as part of a study on asthma, and to document responses and participation rate. DESIGN: Pilot open-ended approach to 10 volunteer SIDS parents, followed by staged approach (newsletter, mail and telephone call) to seek consent from the target SIDS families for the asthma study. PARTICIPANTS: Parents (n = 10) of SIDS infants known to SIDS and Kids Victoria and parents of SIDS infants (n = 107) from the 1991-2 SIDS in Victoria case-control study. MAIN OUTCOMES: Qualitative responses of the piloted parents and study parents, and participation rates. RESULTS: The pilot group responses were used to refine the written material to be provided. Of the 72 families for which contact details were available, 45 gave verbal consent for contact by the Victorian Institute of Forensic Medicine regarding the asthma study, three refused and 24 did not respond to two letters. Thirty-three completed consent forms, all positive for participation in the asthma study, giving a positive response rate of 73% (33/45). CONCLUSIONS: The use of postmortem tissue for research is acceptable to the next of kin when an approach is sensitive to their concerns and needs and is made by experienced counsellors from a familiar organisation. Despite the painful memories evoked by the approach of the research group, the acceptance rate among those who could be contacted was high.

Other Infant Death

1. Ray B, Ward Platt MP Mortality of twin and singleton live births under 30 weeks' gestation - a population based study Arch Dis Child Fetal Neonatal Ed. 2008 Oct 6. [Epub ahead of print]

Northern Deanery, RVI, United Kingdom.

OBJECTIVE: To determine the mortality rates of live born twins compared to singletons of less than 30 weeks' gestation in relation to gestational age, mode of delivery and year of birth in a geographically defined population. Study DESIGN: We compared the early neonatal, late neonatal and infant death rates in 479 twin babies and 1538 singletons, live born between 23-29 completed weeks of gestation in the North of England over two epochs, 1998 - 2001, and 2002 - 2005. RESULTS: The twins and singletons had similar mortality rates except at the extreme of gestation (23-25 weeks) where twins had higher infant mortality (Odds Ratio 2.04 [95%CI 1.37 - 3.02]). This higher rate was attributable to early and late neonatal deaths (OR 1.86 [95%CI 1.28-2.72] and 2.11 [95%CI 1.13 - 3.94] respectively). When analysed in two epochs, the excess mortality was confined to babies born in 1998 - 2001. There was no effect of gender or chorionicity. CONCLUSIONS: The excess mortality among twins of less than 30 weeks' gestation was confined to neonatal deaths among babies of 25 weeks or less, and to the earlier epoch (1998 - 2001). In the modern era, there appears to be no excess mortality in neonates less than 30 weeks' gestation when compared with singletons.

2. Ramanathan R Choosing a Right Surfactant for Respiratory Distress Syndrome Treatment Neonatology. 2008 Oct 2;95(1):1-5. [Epub ahead of print]

Division of Neonatal Medicine, Department of Pediatrics, Women's and Children's Hospital, University of Southern California, Los Angeles, Calif., USA.

Respiratory distress syndrome (RDS) is the most common cause of respiratory insufficiency in preterm infants, especially those born at <30 weeks of gestation. Continuous positive airway pressure has been used since the 1970s as a primary mode of treatment for RDS. Surfactant therapy became available in the 1980s and has become the standard care for infants with or at risk for RDS. Surfactant therapy has been shown to decrease air leaks, neonatal and infant mortality as well as cost among survivors. Natural surfactants derived from animal sources containing surfactant proteins B (SP-B) and C (SP-C) as well as synthetic surfactants with functional SP-B- or SP-C-like protein mimics have been extensively evaluated in preterm neonates with or at risk for RDS. Evidence from randomized controlled trials indicates that treatment with natural surfactants results in faster weaning of supplemental oxygen and mean airway pressure, decreased duration of mechanical ventilation, and decreased mortality when compared to synthetic surfactants. Furthermore, at the present time, there are no approved synthetic surfactants available for use in preterm infants. Beractant, calfactant and poractant alfa are the three commonly used natural surfactants worldwide. Comparative studies including prospective randomized trials as well as large retrospective studies have shown significant differences in outcome and cost among these three natural surfactants. Of the eight prospective, randomized controlled trials and two retrospective studies involving the natural surfactant preparations, treatment with poractant alfa resulted in a significantly decreased mortality, decreased need for additional doses, faster weaning of oxygen and reduced hospital costs when compared to treatment with beractant or calfactant. These differences in outcome may be due to differences in phospholipid and SP-B content, amount of antioxidant phospholipids, plasmalogens, anti-inflammatory properties and viscosity among these three surfactants. Additional studies of administering surfactant non-invasively via laryngeal mask airway in preterm infants weighing >1,200 g and as an aerosol preparation are currently in progress. Copyright © 2008 S. Karger AG, Basel.

3. Nilsson E, Hultman CM, Cnattingius S, Olausson PO, Björk C, Lichtenstein P Br J Psychiatry. 2008 Oct;193(4):311-5 Schizophrenia and offspring's risk for adverse pregnancy outcomes and infant death

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Emma.Nilsson@Socialstyrelsen.se

BACKGROUND: Women with schizophrenia are at increased risk for adverse pregnancy outcomes. It is not known whether offspring born to fathers with schizophrenia also have an increased risk. AIMS: To evaluate paternal and maternal influences on the association between schizophrenia and pregnancy outcomes. METHOD: A record linkage including 2 million births was made using Swedish population-based registers. The risk for adverse pregnancy outcomes was evaluated through logistic regression. RESULTS: Offspring with a mother or father with schizophrenia faced a doubled risk of infant mortality, which could not be explained by maternal behaviour alone during pregnancy. Excess infant death risk was largely attributable to post-neonatal death. Maternal factors (e.g. smoking) explained most of the other risks of adverse pregnancy outcomes among both mothers and fathers with schizophrenia. CONCLUSIONS: The risks to offspring whose fathers had schizophrenia suggest that, in addition to maternal risk behaviour, non-optimal social and/or parenting circumstances are of importance.

Miscarriage/Stillbirth/Prenatal Issues

1. Engel PJ, Smith R, Brinsmead MW, Bowe SJ, Clifton VL Male sex and pre-existing diabetes are independent risk factors for stillbirth Aust N Z J Obstet Gynaecol. 2008 Aug;48(4):375-83

Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.

AIM: To determine whether the risk of stillbirth is associated with male fetal sex, fetal growth and maternal factors in an Australian population. METHODS: A retrospective secondary data analysis of 16 445 singleton births was performed using a tertiary referral centre obstetric database (1995-1999). Univariate and multiple logistic regression analyses were performed. RESULTS: Stillbirth complicated 1% of the pregnancies in the study population, and 59% of stillbirths were associated with a male fetus. Significant characteristics associated with stillbirth were intrauterine growth restriction (IUGR), birth defects, gestational age, Aboriginal ethnicity, previous stillbirth, parity greater than three and placental abruption. Male stillbirths were more likely to occur at a later gestation (median gestation 30.5 weeks, range 20-43 weeks) compared to females (median 25 weeks, range 20-40 weeks), P = 0.01. Sixty per cent of IUGR fetuses were female (P < 0.001). Male sex (odds ratio (OR) 1.5, confidence interval (CI) 1.01, 2.17, P = 0.04) and maternal type 1 diabetes (OR 4.7, CI 1.58, 14.19, P = 0.006) were independently associated with stillbirth. CONCLUSION: Male fetal sex and pre-existing diabetes are independent risk factors for stillbirth. Diabetes remains a significant risk for stillbirth even with contemporary monitoring and clinical management. Those diabetic pregnancies where the fetus is male require appropriate monitoring and timely interventions to achieve an optimal outcome.

2. Salihu HM, Wilson RE, Alio AP, Kirby RS Advanced maternal age and risk of antepartum and intrapartum stillbirth J Obstet Gynaecol Res. 2008 Oct;34(5):843-50

Department of Epidemiology and Biostatistics, and Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida; Department of Family and Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

Aim: We sought to assess the risk of antepartum and intrapartum stillbirth subtypes among women of advanced age. Methods: This is a retrospective cohort study using the Missouri maternally linked data containing births from 1978 to 1997. We examined the impact of maternal age on total, antepartum and intrapartum stillbirth across five maternal age group quintiles (20-24, 25-29, 30-34, 35-39 and >/=40) using mothers aged 20-24 years as the referent category. By means of the Cox proportional hazards regression models we obtained adjusted hazards ratios that quantified the magnitude of association between maternal age and the stillbirth subtypes. Results: The rates of antepartum and intrapartum stillbirth were greatest for older mothers (9.3/1000 and 1.2/1000 respectively) and lowest for gravidas aged 25-29 years (3.6/1000 and 0.8/1000 respectively). After adjusting for potentially confounding characteristics, older mothers still remained at greatest risk for antepartum and intrapartum stillbirth (adjusted hazards ratio = 3.6, 95% confidence interval = 2.9-4.4; and adjusted hazards ratio = 2.7, 95% confidence interval = 2.0-3.6 for antepartum and intrapartum stillbirth respectively). The risks for the two subtypes of stillbirth also increased with ascending maternal age in a dose-dependent pattern. Conclusions: As the demographic distribution of pregnant women persistently shifts to the right, care-providers will be increasingly confronted with elevated risks for adverse fetal outcomes among older mothers. Our results confirm this phenomenon and add new findings in relation to the elevated risk for intrapartum stillbirth among mothers advanced for age.

3. Nawaz FH, Khalid R, Naru T, Rizvi J Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome? J Obstet Gynaecol Res. 2008 Oct;34(5):832-7

Department of Obstetrics and Gynaecology, Aga Khan University Karachi Pakistan, Karachi, Pakistan.

Aim: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. It is associated with hyperinsulinemia and insulin resistance which is further aggravated during pregnancy. This mechanism has a pivotal role in the development of various complications during pregnancy. In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation. Its therapeutic use during pregnancy is, however, a recent strategy and is a debatable issue. At present, evidence is inadequate to support the long-term use of insulin-sensitizing agents during pregnancy. It is a challenge for both clinicians and researchers to provide good evidence of the safety of metformin for long-term use and during pregnancy. This study aimed to evaluate pregnancy outcomes in women with PCOS who conceived while on metformin treatment, and continued the medication for a variable length of time during pregnancy. Methods: This case-control study was conducted from January 2005 to December 2006 at the antenatal clinics of the Department of Obstetrics and Gynecology, Aga Khan University, Karachi, Pakistan. The sample included 137 infertile women with PCOS; of these, 105 conceived while taking metformin (cases), while 32 conceived spontaneously without metformin (controls). Outcomes were measured in three groups of cases which were formed according to the duration of use of metformin during pregnancy. Comparison was made between these groups and women with PCOS who conceived spontaneously. Results: All 137 women in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women were followed up during their course of pregnancy; data forms were completed once they had delivered. Cases were divided into three groups: group A, 40 women who stopped metformin between 4-16 weeks of pregnancy; group B, 20 women who received metformin up until 32 weeks of gestation; and group C; 45 women who continued metformin throughout pregnancy. All the groups were matched by age, height and weight. Comparison was in terms of early and late pregnancy complications, intrauterine growth restriction and live birth rates. In groups A, B and C the rate of pregnancy-induced hypertension/pre-eclampsia was 43.7%, 33% and 13.9% respectively (P < 0.020). Rates of gestational diabetes requiring insulin treatment in groups A and B were 18.7% and 33.3% compared to 2.5% in group C (P < 0.004). The rate of intrauterine growth restriction was significantly low in group C: 2.5% compared to 19.2% and 16.6% in groups A and B respectively (P < 0.046). Frequency of preterm labor and live birth rate was significantly better in group C compared to groups A and B. Overall rate of miscarriages was 7.8%. Controls were comparable to group A in terms of early and late pregnancy complications. Conclusion: In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction. No congenital anomaly, intrauterine death or stillbirth was reported in this study.

4. Ankum WM Management of first trimester miscarriage Br J Hosp Med (Lond). 2008 Jul;69(7):380-3

Department of Obstetrics and Gynecology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

This article summarizes current knowledge about first trimester miscarriages from the clinician's perspective. The epidemiology of spontaneous miscarriage, its natural course and clinical findings are discussed together with the diagnostic management and therapeutic options, which include expectant, medical and surgical management.

5. Toth B, Bastug M, Scholz C, Arck P, Schulze S, Kunze S, Friese K, Jeschke U Leptin and peroxisome proliferator-activated receptors: impact on normal and disturbed first trimester human pregnancy Histol Histopathol. 2008 Dec;23(12):1465-75

Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Grosshadern, Munich, Germany.

Recent in vitro and in vivo studies emphasize the impact of leptin, peroxisome proliferator-activated receptors (PPAR) and PPAR coactivators (retinoic X receptor a (RXR), amplified in breast cancer-3 gene (AIB3)) on placental and fetal development. Therefore, the frequency and distribution pattern of PPAR, RXR, AIB3 and leptin expression in normal human first trimester pregnancy, miscarriage and hydatidiform mole was investigated by immunohistochemistry and double immunofluorescence staining. Enhanced expression of PPAbeta/delta, RXR and AIB3 was identified in miscarried placentas. With regard to hydatidiform mole, increased expression of PPARgamma and PPARbeta/delta was observed, whereas RXR was significantly down-regulated. Leptin expression was lowest in miscarriage and highest in mole pregnancies. In contrast to trophoblast tissue, expression of leptin in glandular epithelial cells of the decidua was increased in miscarriage. PPAR and leptin expressing cells at the feto-maternal interface were identified as extravillous trophoblast (EVT) by double immunofluorescence and CK7 staining. In summary, significantly reduced leptin expression was accompanied by enhanced PPARbeta/delta, RXR and AIB3 expression in miscarried placentas. However, in mole pregnancy, up-regulation of leptin and increased expression of PPAR was detected. RXR, on the other hand, was down-regulated in mole decidua. So far, the study results implicate strong regulatory interaction of PPARs, their coactivators and leptin in human placentas. PPAR and leptin are potential targets for new treatment strategies concerning pregnancy disorders, such as miscarriage. The increasing knowledge about the role of PPARs and leptin in normal and disturbed pregnancy may help to improve pregnancy outcome.

6. Fellman J, Eriksson AW Maternal age and temporal effects on stillbirth rates Twin Res Hum Genet. 2008 Oct;11(5):558-66

1 Folkhälsan Institute of Genetics, Department of Genetic Epidemiology, Finland.

Abstract Stillbirth rates among single and multiple births show markedly decreasing temporal trends. In addition, several studies have demonstrated that the stillbirth rates are dependent on maternal age, in general, showing a U- or J-shaped association with maternal age. In this study, the temporal trends in and the effect of maternal age on the stillbirth rate were considered simultaneously. Our goal was to split the variation into temporal trends and maternal age effects. We applied two-dimensional analysis of variance because no linear association between maternal age and stillbirth rate can be assumed. The temporal trends of stillbirth rates also were not clearly linear. However, the possibility of applying regression analyses based on linear time trends was also considered. Our study is mainly based on official data from England and Wales for the period between 1927 and 2004. These results were compared with registered birth data from Finland between 1937 and 1997. The best fit was obtained when the models were built for the logarithm of the stillbirth rate. Our interpretation of this result is that an association exists between the effects of the factors and the mean stillbirth rate, and consequently, a multiplicative model was applied. Relatively high stillbirth rates were observed among twin births of young mothers and among all births of older mothers.

7. Ford AA, Wylie BJ, Waksmonski CA, Simpson LL Maternal Congenital Cardiac Disease: Outcomes of Pregnancy in a Single Tertiary Care Center Obstet Gynecol. 2008 Oct;112(4):828-833

Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York; Division of Maternal-Fetal Medicine, Massachusetts General Hospital, Boston, Massachusetts; and Division of Cardiology, Columbia University Medical Center, New York, New York.

OBJECTIVE: To evaluate contemporary perinatal and cardiac outcomes of pregnancies in women with major structural congenital heart disease. METHODS: Obstetric, neonatal, and cardiac outcomes were abstracted retrospectively from medical records of all women with congenital cardiac disease delivering at our institution from 2000-2007 and compared by type of structural defect. Predictors of adverse cardiac or obstetric events were identified. RESULTS: Over the 7-year study period, 74 deliveries occurred in 69 women with congenital heart disease, median age 28 years. There were three right-obstructive defects, 14 left-obstructive defects, four right-regurgitant defects, 19 conotruncal defects, 19 shunts, and four miscellaneous lesions. There were 21 adverse cardiac events in 15 pregnancies (20.2%); these were defined as maternal death, congestive heart failure, myocardial infarction, stroke, the need for urgent cardiac intervention, or arrhythmia requiring treatment. There were 44 adverse obstetric events in 34 pregnancies (45.9%), defined as preterm delivery, stillbirth, preeclampsia, small for gestational age, or neonatal intensive care unit admission. Patients with shunt morphology were more likely to experience adverse obstetric and cardiac outcomes. CONCLUSION: Pregnancy in women with underlying major congenital heart defects poses increased risks to both mother and fetus. Nonetheless, favorable maternal and neonatal outcomes occur in the majority of patients. LEVEL OF EVIDENCE: III.

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