NSIDRC Journal Article Alert — August 8, 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.

1. Malloy MH.
Impact of cesarean section on neonatal mortality rates among very preterm infants in the United States, 2000-2003.
Pediatrics. 2008 Aug;122(2):285-92.

Department of Pediatrics, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0526, USA. mmalloy@utmb.edu

OBJECTIVE: The objective of this analysis was to compare the neonatal mortality rates for infants delivered through primary cesarean section versus vaginal delivery, taking into consideration a number of potentially risk-modifying conditions. METHODS: US linked birth and infant death certificate files for 2000-2003 were used. Demographic, medical, and labor and delivery complications were abstracted from the files with infant information. The primary outcome examined was neonatal death (death at 0-27 days of age). Because of concern regarding misclassification of gestational age, a procedure was used to trim away births for which the birth weight for a specific gestational age was incongruous. Adjusted odds ratios were calculated for the risk of neonatal death relative to the mode of delivery (primary cesarean section versus vaginal delivery), using logistic regression analysis. RESULTS: There were data for 13,733 neonatal deaths and 106,809 survivors available from the trimmed data set for analysis for the 4-year period. More than 80% of pregnancies with delivery between 22 and 31 weeks of gestation experienced >or=1 risk factor. Adjusted odds ratios demonstrated significantly reduced risk of neonatal death for infants delivered through cesarean section at 22 to 25 weeks of gestation (adjusted odds ratios of 0.58, 0.52, 0.72, and 0.81 for 22, 23, 24, and 25 weeks, respectively). CONCLUSION: Cesarean section does seem to provide survival advantages for the most immature infants delivered at 22 to 25 weeks of gestation, independent of maternal risk factors for cesarean section.

Bereavement

1. Kennedy C, McIntyre R, Worth A, Hogg R.
Supporting children and families facing the death of a parent: part 1.
Int J Palliat Nurs. 2008 Apr;14(4):162-8.

School of Nursing, Midwifery and Social Care, Napier University, Edinburgh, UK.

AIM: To present findings from a review of key literature and from a scoping of current provision of support for children facing the death of a parent. A summary of the findings from these is reported here. METHODS: To set out the background and context to the evaluation of a new service aimed at supporting children and families facing the loss of a parent from cancer, key literature was reviewed and a scoping of current bereavement support for children and families was conducted using online searching, telephone and face-to-face communications. FINDINGS: The review processes uncovered a range of national and local bereavement services. Bereavement was reported as a normal life event and part of human experience. Health, education and social services personnel need to respond to individual needs, accepting that not all bereaved children require complex, long-term interventions. CONCLUSIONS: At national and global levels there was recognition that the needs of bereaved children require careful assessment. A complex range of initiatives have been developed across the UK aimed at supporting children facing the death of a family member. The fragmented nature of provision makes it difficult to be comprehensive or all-inclusive when describing service provision in this area.

2. Laurie A, Neimeyer RA.
African Americans in bereavement: grief as a function of ethnicity.
Omega (Westport). 2008;57(2):173-93.

University of Memphis, Tennessee 38152, USA.

Few empirical studies have explored the grieving process among different ethnic groups within the United States, and very little is known about how African Americans and Caucasians may differ in their experience of loss. The purpose of this study was to examine the African-American experience of grief, with particular emphasis on issues of identity change, interpersonal dimensions of the loss, and continuing attachments with the deceased. Participants were 1,581 bereaved college students (940 Caucasians and 641 African Americans) attending classes at a large southern university. Each participant completed the Inventory of Complicated Grief-Revised, the Continuing Bonds Scale, and questions regarding the circumstances surrounding his or her loss. Results revealed that African Americans experienced more frequent bereavement by homicide, maintenance of a stronger continuing bond with the deceased, greater grief for the loss of extended kin beyond the immediate family, and a sense of support in their grief, despite their tendency to talk less with others about the loss or seek professional support for it. Overall, African Americans reported higher levels of complicated grief symptoms than Caucasians, especially when they spent less time speaking to others about their loss experience. Implications of these findings for bereavement support services for African Americans were briefly noted.

Miscarriage/Stillbirth/Prenatal Issues

1. Chilongozi D, Wang L, Brown L, Taha T, Valentine M, Emel L, Sinkala M, Kafulafula G, Noor RA, Read JS, Brown ER, Goldenberg RL, Hoffman I; for the HIVNET 024 Study Team.
Morbidity and Mortality Among a Cohort of Human Immunodeficiency Virus Type 1-Infected and Uninfected Pregnant Women and Their Infants From Malawi, Zambia, and Tanzania.
Pediatr Infect Dis J. 2008 Aug 1. [Epub ahead of print]

BACKGROUND:: Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions. METHODS:: Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling. RESULTS:: Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4-6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses. CONCLUSIONS:: The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.

2. Christiansen OB, Steffensen R, Nielsen HS, Varming K.
Multifactorial Etiology of Recurrent Miscarriage and Its Scientific and Clinical Implications.
Gynecol Obstet Invest. 2008 Aug 1;66(4):257-267. [Epub ahead of print]

Fertility Clinic 4071, Rigshospitalet, Copenhagen, Denmark.

A considerable proportion of recurrent miscarriage (RM) cases are caused by recurrent chromosomally abnormal conceptions. However, in younger patients and patients with multiple miscarriages, maternal causes seem to dominate. No single biomarker with a high predictive value of maternally caused RM has been identified. Non-genetic biomarkers in RM may not reflect conditions in the pregnant uterus and we rarely know whether they are causes or consequences of miscarriage. Studies of genetic biomarkers are probably the best way to reveal the pathophysiological mechanisms behind RM. Epidemiological and genetic studies suggest that RM due to maternal causes has a multifactorial background. The risk of RM in each patient is probably determined by the interaction of many genetic variants and environmental factors but only few of these have so far been identified. The genetic biomarkers for RM can probably be classified into three groups: (1) variants associated with excessive inflammatory responses and autoimmunity; (2) variants of importance for insulin and androgen sensitivity and turn-over, and (3) variants associated with thrombophilia. Identification of these markers will require whole genome association studies comprising thousands of individuals. Acknowledgement of the multifactorial background for RM has important implications for the management of patients in clinical practice.

3. Oliveras E, Ahiadeke C, Adanu RM, Hill AG.
Clinic-based surveillance of adverse pregnancy outcomes to identify induced abortions in Accra, Ghana.
Stud Fam Plann. 2008 Jun;39(2):133-40.

Health Systems and Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, G.P.O. 128, Dhaka, Bangladesh. eoliveras@icddrb.org

Reliable measures of induced abortion remain elusive, especially when the public perception is that the procedure is immoral or improper. This study draws on interviews using a modified preceding birth technique (PBT) with women attending antenatal and maternity clinics in Accra to compare rates of adverse pregnancy outcomes (stillbirths, miscarriages, and induced abortions) with rates from a household maternity history and the Ghana Demographic and Health Survey. The reports from the antenatal clinics produced some of the highest rates for adverse outcomes of pregnancy. In light of the generally high coverage of antenatal services found even in developing countries, the method based on the PBT holds promise for the improvement of reports of miscarriage and abortion worldwide.

4. Pittschieler S, Brezinka C, Jahn B, Trinka E, Unterberger I, Dobesberger J, Walser G, Auckenthaler A, Embacher N, Bauer G, Luef G.
Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy.
J Neurol. 2008 Jul 25. [Epub ahead of print]

Dept. of Neurology, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

BACKGROUND : Antiepileptic drugs (AEDs) like phenytoin (PHE), carbamazepine (CBZ), barbiturates and valproic acid (VPA) interfere with folic acid absorption and metabolism, which in turn can be the cause of adverse pregnancy outcome. OBJECTIVE: To study the prophylactic effect of folic acid supplementation with regard to spontaneous abortion and preterm delivery (fetal demise after week 20 of gestational age) in pregnant women receiving AED therapy, as well as benefits of most common dosage and preconceptional commencement. METHODS : Prospective examination of 104 patients, registered in EURAP from 1999-2004 at a single center and a retrospective analysis of data from our epilepsy databank completed with medical records and patients interviews of the Department of Neurology of Innsbruck University Hospital from 1971 to 1999. RESULTS : 388 pregnancies in 244 patients were analyzed. Pregnancies with folic acid supplementation showed significant reduction of spontaneous abortion. With regard to monotherapies, in the group of women taking VPA, supplementation of folic acid had significant benefit. Other examined monotherapies (CBZ, PHE, and PB) known to interfere with folic acid showed no significant results. CONCLUSIONS : This study confirms the prophylactic effect of folic acid supplementation on spontaneous abortion. For AED therapy, folic acid supplementation should be part of the therapy of every pregnant epileptic woman, especially for those treated with VPA.

5. Plunkett BA, Fitchev P, Doll JA, Gerber SE, Cornwell M, Greenstein EP, Crawford SE.
Decreased expression of pigment epithelium derived factor (PEDF), an inhibitor of angiogenesis, in placentas of unexplained stillbirths.
Reprod Biol. 2008 Jul;8(2):107-20.

Northwestern University Feinberg School of Medicine, 250 E. Superior St., Suite 05-2175, Chicago, IL 60611, USA. p-beth@northwestern.edu.

Normal placental vascular development depends upon the complex interactions between angiogenic inducers and inhibitors within the placenta. Alterations within the placental microenvironment can promote an imbalance in angiogenic mediators which may be associated with adverse perinatal outcomes. The purpose of this study was to investigate the placentas of infants with unexplained stillbirth as compared to live-born infants and to determine whether alterations in angiogenic inducer vascular endothelial growth factor (VEGF) or inhibitor pigment epithelium-derived factor (PEDF) are associated with altered angiogenesis, vascular remodeling and stillbirth. Placentas of 22 unexplained stillbirths and 44 age-matched live-born controls were scored for microvascular density (MVD), vasculopathy and microvascular permeability. A subset was scored for expression of angiogenic inducer VEGF and inhibitor pigment epithelium-derived factor. Stillborn placentas demonstrated higher MVD than controls (mean+SD: 116.6+/-46.3 v. 60.8+/-13.5, respectively, p<0.001). Vasculopathy was present in 10/22 (45%) stillbirths compared to 0/44 (0%) controls (p<0.001); increased vascular permeability was present in 15/22 (68%) cases and 5/44 (11%) controls (p<0.001). PEDF expression was significantly lower in stillborn placentas (1.7+/-0.3) than live-born controls (3.6+/-0.8, p<0.01) while VEGF expression was similar (3.3+/-0.7 v. 3.7+/-0.4, respectively, p>0.05). In conclusion, we found that unexplained stillbirth is associated with loss of angiogenic inhibitor PEDF, vasculopathy and heightened angiogenesis in the placenta.

6. Daskalakis G, Anastasakis E, Papantoniou N, Mesogitis S, Antsaklis A.
Second trimester amniocentesis in assisted conception versus spontaneously conceived twins.
Fertil Steril. 2008 Jul 31. [Epub ahead of print]

First Department of Obstetrics and Gynecology, Alexandra Maternity Hospital, Athens University, Athens, Greece.

OBJECTIVE: To compare the outcome of amniocentesis in twins conceived with assisted reproduction technology (ART) versus spontaneously conceived twins. DESIGN: Retrospective analysis of case records between 1993 and 2006. SETTING: University-affiliated tertiary center for fetal medicine. PATIENT(S): 167 ART twin pregnancies and 275 spontaneous twin pregnancies. INTERVENTION(S): Genetic amniocentesis. MAIN OUTCOME MEASURE(S): Comparison of pregnancy loss rate and perinatal outcome between the ART and spontaneous twin-pregnancy groups. RESULT(S): The fetal loss rate was similar between the two groups (4.2% vs. 4.0% in the ART twins and spontaneous twins, respectively), although the interval between amniocentesis to miscarriage was statistically significantly shorter in the ART twins than the spontaneous twins (6.2 and 20.1 days, respectively). In all cases, fetal loss refers to the loss of the entire pregnancy. The preterm delivery rate before 37 weeks was statistically significantly higher in the ART group (64.1%) compared with controls (49.5%). CONCLUSION(S): Amniocentesis in ART twins carries a fetal loss rate similar to spontaneous twins. However, ART twins have a statistically significantly increased risk of preterm delivery especially before 32 weeks' gestation.

7. Joó JG, Beke A, Papp Z, Rigó J, Papp C.
Single umbilical artery in fetopathological investigations.
Pathol Res Pract. 2008 Jul 30. [Epub ahead of print]

1st Department of Obstetrics and Gynecology, Faculty of General Medicine, Semmelweis University, 1088 Budapest, Hungary.

Single umbilical artery (SUA) is a relatively common malformation that may call attention to the possibility of associated malformations (often chromosome aberrations). The current study aimed at surveying malformations associated with SUA on the basis of fetopathological investigations, analyzing the role of history, summarizing the clinically important factors emerging together with this malformation. In this study, we processed the details of 204 cases in which SUA was confirmed fetopathologically after miscarriage or induced abortion between 1990 and 2007. In our sample, SUA occurred in 7.38% of the cases. The history was positive in almost 30% of the cases. The majority of the cases had a positive obstetric and the minority of them a positive genetic history. The highest association of SUA with other malformations was found for craniospinal ones, but an association with cardiovascular malformations should also be mentioned. Regarding the individual types of malformation, SUA was most commonly associated with hydrocephalus, but Potter's sequence, trisomy 21, and atrioventricular septal defect also reached a higher rate in associated SUA. Previously published articles dealing with associated malformations found that urogenital malformations were most commonly associated with SUA. 'Itemizing' the different non-chromosomal malformations in association with SUA, we found that hydrocephalus, Potter's sequence, and atrioventricular septal defect were the most frequent malformations, while in earlier studies, the association with non-chromosomal malformations such as vertebral malformations, imperforated anus, cheilognathopalatoschisis, and renal agenesis occurred more frequently than usual.

8. Barton JR, Sibai BM.
Prediction and prevention of recurrent preeclampsia.
Obstet Gynecol. 2008 Aug;112(2):359-72.

Division of Maternal-Fetal Medicine, Central Baptist Hospital, Lexington, Kentucky; and the Divison of Maternal-Fetal Medicine, University of Cincinnati, Cincinnati, Ohio.

Women with a history of previous preeclampsia are at increased risk of preeclampsia and other adverse pregnancy outcomes in subsequent pregnancies. The magnitude of this risk is dependent on gestational age at time of disease onset, severity of disease, and presence or absence of preexisting medical disorders. The objective in the management of these patients is to reduce risk factors by optimizing maternal health before conception and to detect obstetric complications as early as possible. This objective can be achieved by formulating a rational approach that includes preconception evaluation and counseling, early antenatal care, frequent monitoring of maternal and fetal well-being, and timely delivery. First-trimester ultrasound examination is essential for accurate dating and establishing fetal number. Laboratory studies are obtained to assess the function of different organ systems that are likely to be affected by preeclampsia and to establish a baseline for future assessment. Recent studies have confirmed that there is no single biomarker that can be clinically useful for the prediction of recurrent preeclampsia. Combinations of biomarkers and biophysical parameters appear promising, but more data are needed to confirm their use in clinical practice. Supplementation with fish oil, calcium, or vitamin C and E and the use of antihypertensives have been shown to be ineffective in the prevention of recurrent preeclampsia and are not recommended. Supplementation with low-dose aspirin may be offered on an individualized basis. Because women with previous preeclampsia are at increased risk for adverse pregnancy outcomes (preterm delivery, fetal growth restriction, abruptio placentae, and fetal death) in subsequent pregnancies, we recommend more frequent monitoring for signs and symptoms of severe hypertension or preeclampsia than that recommended for normal pregnancy. This monitoring may include more frequent prenatal visits, home blood pressure monitoring, or nursing contacts. For patients with a prior pregnancy complicated by preeclampsia with fetal growth restriction, we recommend serial ultrasound evaluation of fetal growth and amniotic fluid volume. The development of severe gestational hypertension, fetal growth restriction, or recurrent preeclampsia requires maternal hospitalization.

9. Tan J, Surti B, Saab S.
Pregnancy and cirrhosis.
Liver Transpl. 2008 Aug;14(8):1081-91.

Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.

As the treatment of cirrhosis improves, pregnancy in patients with cirrhosis is likely to become more common. Although maternal and fetal mortality is expected to similarly improve, pregnant patients with cirrhosis face unique risks. These include higher rates of spontaneous abortion and prematurity and a potential for life-threatening variceal hemorrhage, hepatic decompensation, splenic artery aneurysm rupture, and postpartum hemorrhage. Pregnancy outcome may be influenced by the underlying etiology of liver disease, as in viral and autoimmune hepatitis. Medications also impact the course of pregnancy, and must be tailored appropriately during this time.

Prepared by the
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