NSIDRC Journal Article Alert — April 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.

Sudden Infant Death

1: Hoppenbrouwers T, Hodgman JE, Ramanathan A, Dorey F.
Extreme and conventional cardiorespiratory events and epidemiologic risk factors for SIDS.
J Pediatr. 2008 May;152(5):636-41. Epub 2008 Feb 20.

LAC + USC Medical Center, Women's and Children's Hospital, Los Angeles, CA 90033, USA. hoppenbrou@earthlink.net

OBJECTIVE: To test the hypotheses that there is a lack of correlation between extreme events and epidemiologic risk factors for sudden infant death syndrome (SIDS), and if conventional events are normal, their numbers should increase once a circadian decrease in breathing rate is established. In addition, the number of events should decrease with maternal smoking. STUDY DESIGN: Three outcome variables were derived from the Collaborative Home Infant Monitoring Evaluation (CHIME) of 1082 infants: (1) at least 1 extreme event lasting > or = 30 seconds, (2) at least 1 conventional event lasting > or = 20 seconds, and (3) being part of the 50% of infants with the most events. RESULTS: Multivariate logistic regression analyses found that extreme events were not statistically associated with any known SIDS risk factors and occurred less often during the early morning. Healthy term infants had significantly fewer of these events compared with preterm infants, subsequent siblings of infants with SIDS, and infants with an apparent life-threatening event, a finding that was not evident after 43 weeks (3 weeks postterm). Conventional events increased during the night, whereas maternal smoking was associated with a decrease in conventional events. Apneic episodes persisting for > or = 40 seconds occurred in 1.8% of the infants. CONCLUSIONS: Extreme events are associated with immaturity and do not seem to be immediate precursors of or causally related to SIDS.

2: Troese M, Fukumizu M, Sallinen BJ, Gilles AA, Wellman JD, Paul JA, Brown ER, Hayes MJ.
Sleep fragmentation and evidence for sleep debt in alcohol-exposed infants.
Early Hum Dev. 2008 Apr 7 [Epub ahead of print]

Department of Psychology, University of Maine, Orono, ME, United States.

BACKGROUND:: Infants exposed prenatally to alcohol are at increased risk for poor neurodevelopmental outcome including Sudden Infant Death Syndrome. AIM:: To examine the relationship between prenatal alcohol exposure, sleep, arousal and sleep-related spontaneous motor movements in early infancy. STUDY DESIGN:: Low-income women (N=13) were interviewed regarding pre- and pregnancy rates of alcohol, cigarette smoking and other substance use in the perinatal period. Infants were examined in a laboratory nap study using EEG, videography and actigraphy at 6-8 weeks of age. Estimates of maternal pre- and pregnancy alcohol use were used to divide infants into high vs. low maternal alcohol use groups. SUBJECTS:: Mother-infant dyads recruited from a family practice clinic. OUTCOME MEASURES:: Sleep-related spontaneous movements, behavioral state, and maternal assessments of infant alertness and irritability. RESULTS:: Pre-pregnancy rates of alcohol consumption including binge drinking correlated with maternal report of poor infant alertness, and increased irritability. High maternal exposure groups showed increased sleep fragmentation, e.g. frequency and duration of wakefulness following sleep onset and decreased active sleep. Bout analysis of the temporal structure of sleep-related spontaneous movements showed significantly reduced bout duration associated with high maternal alcohol use. CONCLUSION:: These results present evidence that prenatal alcohol exposure disrupts postnatal sleep organization and suppresses spontaneous movements during sleep, and increased sleep fragmentation promotes sleep deprivation. Results are consistent with the SIDS model of chronic sleep debt and suggest that attenuated sleep-related movements should be examined as an important modulator of cardiorespiratory functions during sleep in high-risk groups.

Other Infant Death

1: Rohner GB, Pollard AJ.
Sustaining immunity after immunisation against encapsulated bacteria.
Hum Vaccin. 2007 Dec 17;4(4) [Epub ahead of print]

Infections by encapsulated bacteria are important causes of infant mortality worldwide. Over the last 20 years protein-polysaccharide conjugate vaccines have been developed to protect against the major invasive bacterial diseases of childhood, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib) and Neisseria meningitidis. These vaccines are highly immunogenic and have resulted in a huge reduction in the diseases caused by these bacteria in the countries that have introduced them in their immunisation schedules. However, it has been reported that infant immunisation is associated with a relatively short duration of antibody levels and vaccine effectiveness, despite the demonstrable presence of booster responses to further vaccine dose. In contrast, at older ages, more sustained protection has been described with just a single dose of a conjugate vaccine. Understanding the generation of long-term immunity, by protein-polysaccharide conjugate vaccines, is essential to reduce infant mortality through the improvement of vaccine formulation and scheduling.

Beareavement

1: Rogers CH, Floyd FJ, Seltzer MM, Greenberg J, Hong J.
Long-term effects of the death of a child on parents' adjustment in midlife.
J Fam Psychol. 2008 Apr;22(2):203-11.

Department of Psychology, Georgia State University.

The death of a child is a traumatic event that can have long-term effects on the lives of parents. This study examined bereaved parents of deceased children (infancy to age 34) and comparison parents with similar backgrounds (n = 428 per group) identified in the Wisconsin Longitudinal Study. An average of 18.05 years following the death, when parents were age 53, bereaved parents reported more depressive symptoms, poorer well-being, and more health problems and were more likely to have experienced a depressive episode and marital disruption than were comparison parents. Recovery from grief was associated with having a sense of life purpose and having additional children but was unrelated to the cause of death or the amount of time since the death. The results point to the need for detection and intervention to help those parents who are experiencing lasting grief. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Miscarriage/Stillbirth/Prenatal Issues

1: Lash MM, Armstrong A.
Impact of obesity on women's health.
Fertil Steril. 2008 Apr 12 [Epub ahead of print]

Tufts–New England Medical Center, Boston, Massachuestts.

OBJECTIVE: To review the impacts of obesity on women's reproductive health and fertility. DESIGN: Literature review. SETTING: Academic medical center. PATIENT(S): Forty articles are referenced. The number of patients evaluated in each of the studies varies from 33 to 213,208. INTERVENTION(S): Articles were identified from an Ovid/Medline search using the search terms obesity, dysfunctional uterine bleeding, contraception, miscarriage, infertility, and weight loss. MAIN OUTCOME MEASURE(S): The impacts of obesity on reproductive health and fertility. RESULT(S): Obesity is associated with early puberty, aberrant menstrual patterns, decreased contraceptive efficacy, ovulatory disorders, an increased miscarriage rate, and worse assisted reproductive technology outcomes. Losing weight can ameliorate many of these problems. CONCLUSION(S): Obesity is one of the most significant causes of morbidity and mortality in the U.S. Providers must educate patients about the impacts of obesity on reproductive health and fertility.

2: Wood SL, Chen S, Ross S, Sauve R.
The risk of unexplained antepartum stillbirth in second pregnancies following caesarean section in the first pregnancy.
BJOG. 2008 May;115(6):726-31.

Department of Obstetrics and Gynecology, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada. stephen.wood@calgaryhealthregion.ca

OBJECTIVE: To determine if a previous caesarean section increases the risk of unexplained antepartum stillbirth in second pregnancies. STUDY DESIGN: Retrospective cohort study. SETTING: Large Canadian perinatal database. POPULATION: 158 502 second births. METHODS: Data were obtained from a large perinatal database, which supplied data on demographics, pregnancy complications, maternal medical conditions, previous caesarean section and pregnancy outcomes. MAIN OUTCOME MEASURES: Total and unexplained stillbirth. RESULTS: The antepartum stillbirth rate was 3.0/1000 in the previous caesarean section group compared with 2.7/1000 in the previous vaginal delivery group (P= 0.46). Multivariate logistic regression modelling, including terms for maternal age (polynomial), weight >91 kg, smoking during pregnancy, pre-pregnancy hypertension and diabetes, did not document an association between previous caesarean section and unexplained antepartum stillbirth (OR 1.27, 95% CI 0.92-1.77). CONCLUSION: Caesarean section in the first birth does not increase the risk of unexplained antepartum stillbirth in second pregnancies.

3: Gutiérrez Junquera C, Balmaseda E, Gil E, Martínez A, Sorli M, Cuartero I, Merinero B, Ugarte M.
Acute fatty liver of pregnancy and neonatal long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency.
Eur J Pediatr. 2008 Apr 12 [Epub ahead of print]

Servicio de Pediatría, Complejo Hospitalario Universitario de Albacete, Universidad de Castilla La-Mancha, Albacete, Spain, cgutierrezj@telefonica.net.

Here we report a 7-month-old girl with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency with hypoketotic hypoglycemia; the mother had a history of acute fatty liver in a previous pregnancy leading to fetal death at 34 weeks of gestation. The misense mutation 1528G > C was detected in both alleles in the proband and in one allele in both parents. We emphasize that screening for fatty acid oxidation disorders and specifically LCHAD deficiency should be performed in newborns from mothers with hepatic complications during pregnancy such as acute fatty liver of pregnancy or severe or recurrent HELLP syndrome.

4: Yu D, Wong YM, Cheong Y, Xia E, Li TC.
Asherman syndrome--one century later.
Fertil Steril. 2008 Apr;89(4):759-79.

Hysteroscopic Center, Fu Xing Hospital, Capital Medical University, Beijing, People's Republic of China. yudanny2006@yahoo.com.cn

OBJECTIVE: To provide an update on the current knowledge of Asherman syndrome. DESIGN: Literature review. SETTING: The worldwide reports of this disease. PATIENT(S): Patients with Asherman syndrome who presented with amenorrhea or hypomenorrhea, infertility, or recurrent pregnancy loss. INTERVENTION(S): Hysteroscopy and hysteroscopic surgery have been the gold standard of diagnosis and treatment respectively for this condition. MAIN OUTCOME MEASURE(S): The etiology, pathology, symptomatology, diagnosis, treatment, and reproductive outcomes were analyzed. RESULT(S): This syndrome occurs mainly as a result of trauma to the gravid uterine cavity, which leads to the formation of intrauterine and/or intracervical adhesions. Despite the advances in hysteroscopic surgery, the treatment of moderate to severe Asherman syndrome still presents a challenge. Furthermore, pregnancy after treatment remains high risk with complications including spontaneous abortion, preterm delivery, intrauterine growth restriction, placenta accrete or praevia, or even uterine rupture. CONCLUSION(S): The management of moderate to severe disease still poses a challenge, and the prognosis of severe disease remains poor. Close antenatal surveillance and monitoring are necessary for women who conceive after treatment.

5: Glinoer D.
The systematic screening and management of hypothyroidism and hyperthyroidism during pregnancy.
Trends Endocrinol Metab. 1998 Dec;9(10):403-11.

Department of Internal Medicine, Thyroid Investigation Clinic, University Hospital Saint-Pierre, 322 Rue Haute, B-1000 Brussels, Belgium.

Altogether, thyroid function abnormalities during pregnancy can affect up to 10% of all women. The high prevalence of both hypo- and hyperthyroidism, the obstetrical repercussions associated with thyroid dysfunction in the mothers, as well as the potential role of maternal thyroid dysfunction as an influence on fetal development constitute solid arguments for a further increase of our knowledge of the pathophysiological processes underlying the alterations of thyroid function related to the pregnant state. In this review, the focus will be on the most clinically relevant aspects associated with hypothyroidism [autoimmune thyroid disorders (AITDs), subfertility, risk of miscarriage, risk of hypothyroidism in women with AITD and treatment of hypothyroid women] and with hyperthyroidism (clinical presentations during pregnancy, Graves' disease and its management, fetal hyperthyroidism in women with antithyroid-stimulating hormone receptor antibodies and gestational transient thyrotoxicosis associated with human chorionic gonadotropin stimulation of the maternal thyroid gland). I also propose a global strategy for the systematic screening of hypo- and hyperthyroidism in the pregnant state.

6: Leung WC, Leung KY, Lau ET, Tang MH, Chan V.
Alpha-thalassaemia.
Semin Fetal Neonatal Med. 2008 Apr 9 [Epub ahead of print]

Department of Obstetrics & Gynaecology, Kwong Wah Hospital, 25, Waterloo Road, Kowloon, Hong Kong.

Alpha-thalassaemia is one of the most common human genetic disorders. Couples in which both partners carry alpha(0)-thalassaemia traits have a 25% risk of having a fetus affected by homozygous alpha-thalassaemia or haemoglobin Bart's disease, with severe fetal anaemia in utero, hydrops fetalis, stillbirth or early neonatal death, as well as causing various maternal morbidities. This disorder is common in southeast Asia and southern China, and the expanding populations of southeast Asian immigrants in the US, Canada, UK and Europe mean that this disorder is no longer rare in these countries.

7: Ottaviani G, Matturri L.
Histopathology of the cardiac conduction system in sudden intrauterine unexplained death.
Cardiovasc Pathol. 2007 Oct 10 [Epub ahead of print]

Institute of Pathology, University of Milan, “Lino Rossi” Research Center, Milan, Italy.

BACKGROUND: Sudden intrauterine unexplained death (SIUD) is one of the most heartbreaking tragedies that any parent can experience. It remains poorly understood and incompletely examined both morphologically and functionally. The aim of this work is to examine the likely role of cardiac conduction system in relation to sudden and unexplained fetal death. METHODS: We analyzed and compared the autopsy results in 15 cases of SIUD (6 males and 9 females, ranging in age from 35 to 40 weeks) and 11 cases of intrauterine explained death (IED). A complete autopsy was performed, focusing on the examination of the cardiac conduction system on serial sections. RESULTS: The following findings were observed: resorptive degeneration (33% of SIUD, 36% of IED), dispersion or septation of the atrioventricular (AV) junction (60% of SIUD, 64% of IED), islands of the conduction system in the central fibrous body (80% of SIUD, 73% of IED), Mahaim fibers (20% of SIUD), cartilaginous metahyperplasia (20% of SIUD, 18% of IED), an AV node (AVN) tongue (13% of SIUD), hemorrhage of the cardiac conduction system (7% of SIUD, 9% of IED), left-sided bifurcation (7% of SIUD), an intramural right bundle (7% of SIUD), central fibrous body hypoplasia (7% of SIUD), and thickening of the conduction system arteries (13% of SIUD). CONCLUSIONS: Most of the abnormal cardiac conduction findings were detected only in SIUD and were absent in controls, i.e., Mahaim fibers, AVN tongue, left-sided bifurcation, intramural right bundle, and central fibrous body hypoplasia. We are convinced that these cardiac conduction abnormalities, in association with altered neurovegetative stimuli, could underlie potentially malignant arrhythmias.

8: Nørgaard M, Pedersen L, Gislum M, Erichsen R, Søgaard KK, Schønheyder HC, Sørensen HT.
Maternal use of fluconazole and risk of congenital malformations: a Danish population-based cohort study.
J Antimicrob Chemother. 2008 Apr 9 [Epub ahead of print]

Department of Clinical Epidemiology, Aarhus University Hospital, Denmark.

Objectives Fluconazole is widely used for the treatment of candidiasis. Although the drug is also prescribed to pregnant women, data on the safety of use of fluconazole during pregnancy are limited. We examined the association between the maternal use of fluconazole during pregnancy and the risk of congenital malformations. Patients and methods In this population-based cohort study in Northern Denmark, we included 1079 women who had a live birth or a stillbirth after the 20th week of gestation and who redeemed at least one prescription for fluconazole during the first trimester. The reference cohort comprised 170 453 pregnant women who redeemed no fluconazole prescription during pregnancy. The women were identified through the Danish Medical Birth Registry. Data on drug use, birth outcome and covariates were extracted from population-based healthcare databases. We used logistic regression to estimate the prevalence odds ratio (POR) for congenital malformations after fluconazole exposure, while adjusting for maternal smoking, parity, maternal age and concurrent prescriptions for antiepileptics or antidiabetics. Results Among 1079 women who filled a fluconazole prescription during the first trimester, 797 (74%) received a total of 150 mg of fluconazole, 235 (22%) received 300 mg of fluconazole, 24 (2%) received 350 mg of fluconazole and 23 (2%) received 600 mg of fluconazole. These women gave birth to 44 (4.1%) children with congenital malformations. The 170 453 women without fluconazole prescriptions gave birth to 6152 (3.6%) children with congenital malformations. For congenital malformations overall, the adjusted POR associated with the first-trimester fluconazole use was 1.0 (95% confidence interval: 0.8-1.4). Conclusions We found no overall increased risk of congenital malformations after exposure to short-course treatment with fluconazole in early pregnancy.

9: Nørgaard M, Skriver MV, Sørensen HT, Schønheyder HC, Pedersen L.
Risk of miscarriage for pregnant users of pivmecillinam: a population-based case-control study.
APMIS. 2008 Apr;116(4):284-91.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Few data exist on the risk of miscarriage after exposure to pivmecillinam. We therefore conducted a population-based case-control study in a Danish county with 0.5 million inhabitants during the period 1997-2002. We included 1,599 women with a miscarriage recorded in the Hospital Discharge Registry and selected 10 controls per case among primiparous women who had a live birth during the study period. Controls were selected from the Danish Medical Birth Registry. We obtained data on use of pivmecillinam and sulfamethizole from a prescription database. Five cases (0.30%) and 24 controls (0.15%) were exposed to pivmecillinam in the last week before the miscarriage/index date. After adjustment for maternal age, use of antidiabetics or antiepileptics, the odds ratio for miscarriages among users of pivmecillinam compared with non-users was 2.03 (95% confidence interval: 0.77-5.33) and the corresponding odds ratio for use of sulfamethizole was 1.53 (95% confidence interval: 0.76-3.09). Exposure within 2 to 12 weeks before the miscarriage was not associated with an increased risk. We concluded that use of pivmecillinam was associated with an increased risk of miscarriage, but the risk was not significantly (p=0.64) different from the risk associated with use of sulfamethizole.

Prepared by the
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