NSIDRC Journal Article Alert — July 4, 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. Weber MA, Ashworth MT, Risdon RA, Hartley JC, Malone M, Sebire NJ
The role of post-mortem investigations in determining the cause of Sudden Unexpected Death in Infancy (SUDI)
Arch Dis Child. 2008 Jun 30. [Epub ahead of print]

Institute of Child Health, University College London, and Great Ormond Street Hospital for Children, United Kingdom.

Introduction: Several autopsy protocols have been suggested for investigating sudden unexpected deaths in infancy (SUDI). The aim of this study is to provide data on the utility of such post-mortem investigations from a large paediatric autopsy series in order to inform future policy. METHODS: Retrospective analysis of >1,500 consecutive post-mortem examinations carried out by specialist paediatric pathologists at a single centre during a 10-year period according to a common autopsy protocol that included the use of detailed ancillary investigations. SUDI was defined as the sudden unexpected death of an infant aged 7 to 365 days. All data capture and cause of death classification were carried out according to defined criteria. RESULTS: Of 1,516 paediatric post-mortem examinations, 546 presented as SUDI. In 202 infants (37%) death was explained by the autopsy findings. The other 344 cases (63%) remained unexplained. Of the explained deaths, over half (58%) were infective, most commonly due to pneumonia (22%). The component of the post-mortem examination which primarily determined the final cause of death was histological examination in 92 infants (46%), macroscopic examination in 61 (30%), microbiological investigations in 38 (19%), and clinical history in 10 (5%). CONCLUSION: This constitutes the largest single-institution autopsy study of SUDI. Ten years on from the CESDI SUDI studies, the ascertainment of a cause of death at autopsy has improved. However, with almost two thirds of SUDI remaining unexplained, alternative and/or additional diagnostic techniques are required to further improve detection rates of identifiable causes of death at autopsy.

2. Jackson HA, Accili EA
Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations
BMC Evol Biol. 2008 Jun 30;8(1):188. [Epub ahead of print]

ABSTRACT: BACKGROUND: Mutations in HERG and KCNQ1 potassium channels are associated with Long QT syndrome and atrial fibrillation, and more recently to sudden infant death syndrome and sudden unexplained death. In proteins other than HERG and KCNQ1, disease-associated amino acid mutations have been analyzed according to the chemical severity of the change and the location of the altered amino acid according to its conservation over metazoan evolution. Here, we present the first such analysis of arrhythmia-associated mutations (AAMs) in the HERG and KCNQ1 potassium channel genes. RESULTS: Using evolutionary analyses, AAMs in HERG and KCNQ1 were preferentially found at evolutionarily conserved sites and unevenly distributed among functionally conserved domains. Non-synonomous single nucleotide polymorphisms (nsSNPs) are under represented at evolutionarily conserved sites in HERG, but distribute randomly in KCNQ1. AAMs are chemically more severe, according to Grantham's Scale, than changes observed in evolution and their severity correlates with the expected chemical severity of the involved codon. Expected chemical severity also correlates with the proportion of a given amino acid associated with arrhythmias. At evolutionarily variable sites, the chemical severity of the changes is also correlated with the expected chemical severity of the involved codon. CONCLUSIONS: Unlike nsSNPs, AAMs preferentially locate to evolutionarily conserved, and functionally important, sites and regions within HERG and KCNQ1, and are chemically more severe than changes which occur in evolution. Expected chemical severity may contribute to the overrepresentation of certain residues in AAMs, as well as to changes observed in evolution.

3. Wilson RJ, Cummings K
Pituitary adenylate cyclase-activating polypeptide vital for neonatal survival and the neuronal control of breathing
Respir Physiol Neurobiol 2008 Jun 8. [Epub ahead of print]

Department of Physiology and Biophysics, University of Calgary, Calgary, AB, Canada.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an ancient neuropeptide that predates the evolution of vertebrates. While PACAP acts on multiple target organs and has multiple roles in development, neuronal network function and metabolic homeostasis, it also appears to play an important role in the control of breathing. Mice lacking pituitary adenylate cyclase-activating peptide (PACAP) die suddenly in the second week of life, a phenotype that is exaggerated by mild thermal stress and bares resemblance to human SIDS. Here we discuss several hypotheses as to why PACAP-signaling is important for neonatal survival, focusing on data demonstrating an important role in the control of breathing. We review data suggesting that (a) breathing and respiratory chemosensitivity is blunted in PACAP-deficient mice; (b) PACAP plays an important role in protecting neonatal breathing during thermal stress; and (c) PACAP-signaling occurs in a number of loci important for respiratory control including the carotid bodies (the main peripheral respiratory chemoreceptors) and nuclei in the hypothalamus, pons and medulla, as well as pathways involved in setting sympathetic-parasympathetic tone. Whether PACAP gene abnormalities contribute to Sudden Infant Death Syndrome (SIDS) by reducing respiratory system efficacy during environmental stress remains unanswered.

4. Pike J, Moon R
Bassinet Use and Sudden Unexpected Death in Infancy
J Pediatr. 2008 Jun 24. [Epub ahead of print]

Pediatric Residency Program, Children's National Medical Center, Washington, DC.

OBJECTIVE: To analyze risk factors in infants who die suddenly and unexpectedly in bassinets. STUDY DESIGN: A retrospective review of all deaths of infants involving bassinets reported to the Consumer Product Safety Commission (CPSC) between 1990 and 2004. RESULTS: For the 53 deaths analyzed, the mean age at death was 84 days. The cause of death was recorded as anoxia, asphyxiation, or suffocation in 85% and sudden infant death syndrome (SIDS) in 9.4%. In terms of position, 37% were placed prone for sleep, and 50% were prone when found dead. Additional items in the bassinet, including soft bedding, were noted in 74% of cases. Specific mechanical problems with the bassinets were noted in 17% of cases. CONCLUSIONS: The risk of sudden unexpected death in infants who sleep in bassinets can be reduced by following American Academy of Pediatrics guidelines, including positioning infants supine and avoiding soft bedding in bassinets. In addition, parents must ensure that the bassinet is mechanically sound and that no objects that can lead to suffocation are in or near the bassinet.

5. Fu LY, Colson ER, Corwin MJ, Moon RY
Infant Sleep Location: Associated Maternal and Infant Characteristics with Sudden Infant Death Syndrome Prevention Recommendations
J Pediatr. 2008 Jun 24. [Epub ahead of print

Goldberg Center for Community Pediatric Health, Children's National Medical Center, Washington, DC; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.

OBJECTIVE: To identify factors associated with infant sleep location. STUDY DESIGN: Demographic information and infant care practices were assessed for 708 mothers of infants ages 0 to 8 months at Women, Infants and Children centers. Generalized linear latent mixed models were constructed for the outcome, sleeping arrangement last night (room-sharing without bed-sharing versus bed-sharing, and room-sharing without bed-sharing versus sleeping in separate rooms). RESULTS: Two-thirds of the mothers were African-American. A total of 48.6% mothers room-shared without bed-sharing, 32.5% bed-shared, and 18.9% slept in separate rooms. Compared with infants who slept in separate rooms, infants who room-shared without bed-sharing were more likely to be Hispanic (odds ratio [OR], 2.58, 95% CI 1.11-5.98) and younger (3.66- and 1.74-times more likely for infants 0-1 month old and 2-3 months old, respectively, as compared with older infants). Compared with infants who bed-shared, infants who room-shared without bed-sharing were more likely to be 0 to 1 month old (OR, 1.57; 95% CI, 1.05-2.35) and less likely to be African-American (OR, 0.43; 95% CI, 0.26-0.70) or have a teenage mother (OR, 0.37; 95% CI, 0.23-0.58). CONCLUSIONS: Approximately one-third of mothers and infants bed-share, despite increased risk of sudden infant death syndrome (SIDS). The factors associated with bed-sharing are also associated with SIDS, likely rendering infants with these characteristics at high risk for SIDS.

6. Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Rand CM
Congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS): Kindred disorders of autonomic regulation
Respir Physiol Neurobiol. 2008 May 23. [Epub ahead of print]

Northwestern University Feinberg School of Medicine, Center for Autonomic Medicine in Pediatrics, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, United States.

Congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS) were long considered rare disorders of respiratory control and more recently have been highlighted as part of a growing spectrum of disorders within the rubric of autonomic nervous system (ANS) dysregulation (ANSD). CCHS typically presents in the newborn period with a phenotype including alveolar hypoventilation, symptoms of ANSD and, in a subset of cases, Hirschsprung disease and later tumors of neural crest origin. Study of genes related to autonomic dysregulation and the embryologic origin of the neural crest led to the discovery of PHOX2B as the disease-defining gene for CCHS. Like CCHS, SIDS is thought to result from central deficits in control of breathing and ANSD, although SIDS risk is most likely defined by complex multifactorial genetic and environmental interactions. Some early genetic and neuropathological evidence is emerging to implicate serotonin systems in SIDS risk. The purpose of this article is to review the current understanding of the genetic basis for CCHS and SIDS, and discuss the impact of this information on clinical practice and future research directions.

Other Infant Death

1. Arulampalam W, Bhalotra S
The linked survival prospects of siblings: evidence for the Indian states
Popul Stud (Camb). 2008 Jul;62(2):171-90

Department of Economics, University of Warwick, Coventry CV4 7AL, UK. wiji.arulampalam@warwick.ac.uk

This paper reports an analysis of micro-data for India that shows a high correlation in infant mortality among siblings. In 13 of 15 states, we identify a causal effect of infant death on the risk of infant death of the subsequent sibling (a scarring effect), after controlling for mother-level heterogeneity. The scarring effects are large, the only other covariate with a similarly large effect being mother's (secondary or higher) education. The two states in which evidence of scarring is weak are Punjab, the richest, and Kerala, the socially most progressive. The size of the scarring effect depends upon the sex of the previous child in three states, in a direction consistent with son-preference. Evidence of scarring implies that policies targeted at reducing infant mortality will have social multiplier effects by helping avoid the death of subsequent siblings. Comparison of other covariate effects across the states offers some interesting new insights.

Miscarriage/Stillbirth/Prenatal Issues

1. Gold KJ, Kuznia AL, Hayward R
How Physicians Cope With Stillbirth or Neonatal Death: A National Survey of Obstetricians
Obstet Gynecol. 2008 Jul;112(1):29-34

Departments of Family Medicine and Obstetrics & Gynecology, University of Michigan; and Robert Wood Johnson Clinical Scholars Program, Departments of Internal Medicine and Health Management and Policy, University of Michigan, and Veterans Administration Health Services Research and Development Service Center of Excellence, Ann Arbor, Michigan.

OBJECTIVE: To identify U.S. obstetricians' experiences and attitudes about perinatal death, their coping strategies, and their beliefs about the adequacy of their training on this topic. METHODS: A total of 1,500 randomly selected U.S. obstetricians were mailed a self-administered survey about their experiences and attitudes in dealing with perinatal death. Physicians received up to three copies of the survey, a reminder card, and a $2 cash incentive. Eight hundred four physicians (54%) completed the entire survey. RESULTS: Seventy-five percent of respondents reported that caring for a patient with a stillbirth took a large emotional toll on them personally, and nearly one in 10 obstetricians reported they had considered giving up obstetric practice because of the emotional difficulty in caring for a patient with a stillbirth. Talking informally with colleagues (87%) or friends and family (56%) were the most common strategies used by physicians to personally cope with these situations. CONCLUSION: Perinatal death has a profound effect on the delivering obstetrician, and a significant number of participants in our study have even considered giving up obstetrics altogether. Improved bereavement training may help obstetricians care for grieving families but also cope with their own emotions after this devastating event. LEVEL OF EVIDENCE: II.

2. Pelinescu-Onciul D
Subchorionic hemorrhage treatment with dydrogesterone
Gynecol Endocrinol. 2007 Oct;23 Suppl 1:77-81

Clinica de Obstetrica-Ginecologie, Filantropia University Hospital, Bucharest, Romania. dimitriepelinescu@yahoo.com

The objective of the study was to evaluate the efficacy of progestogenic therapy for the prevention of spontaneous abortions in patients with subchorionic hemorrhage. One hundred pregnant women with bleeding and ultrasonographic evidence of subchorionic hematoma were treated with oral dydrogesterone 40 mg/day. Only cases in which the embryo was viable were included. The follow-up included ultrasonography and intravaginal examination. Of the 100 pregnancies, 93 had a favorable evolution with maintenance of pregnancy. The abortion rate was therefore 7%. This compares with an abortion rate of 18.7% obtained in a previous study in women with subchorionic hematoma treated with micronized progesterone. The abortion rate was therefore reduced by up to 37% with dydrogesterone, as most cases had large-volume hematomas at the first visit and thus a poor prognosis. In conclusion, the marked immunomodulatory effect of dydrogesterone in maintaining a T helper-2 cytokine balance means that it is a good choice for preventing abortion in women suffering from subchorionic hemorrhage.

3. Küçük T, Deveci S
Clin Exp Obstet Gynecol. 2008;35(2):133-6
"Chromohysteroscopy" for evaluation of endometrium in recurrent miscarriage

Department Obstetrics and Gynecology, GATA School of Medicine, Ankara, Turkey. tansukucuk@gmail.com

PURPOSE: "Chromoendoscopy" results in 34 recurrent miscarriage (MR) patients in whom conventional hysteroscopy did not show any apparent endometrial pathology. METHOD: 5 ml of 1% methylene blue dye was introduced through the hysteroscopic inlet. RESULTS: The study group was classified according to the staining characteristics. Group I included 19 patients in whom focal dark staining was observed. Group II included 15 patients in whom diffuse light blue staining was observed. There was no significant difference between the two groups in age, smoking, status, BMI, number of miscarriages and in mean gestational age of the miscarriages. Time to hysteroscopy after the last miscarriage was shorter in Group I (63.9 vs 95.3 days). Then, the study group was classified according to the histopathology result. Group I included ten cases of endometritis while Group II included 24 cases with a normal histopathology. The mean number of miscarriages was higher in Group I (3.4 vs 2.5). CONCLUSION: Chromohysteroscopy improves the efficacy of hysteroscopy in RM cases and is warranted after three miscarriages in two cycles time.

4. Fleisch MC, Hoehn T
Intrauterine fetal death after multiple umbilical cord torsion-complication of a twin pregnancy following assisted reproduction
J Assist Reprod Genet. 2008 Jun 26. [Epub ahead of print]

Department of Obstetrics and Gynecology, Heinrich-Heine-University, Duesseldorf, Germany.

BACKGROUND: Patients requiring assisted reproductive techniques may have a higher rate of congenital malformations. Some rare complications of pregnancy might be related to such abnormalities. Torsions of the umbilical cord resulting in fetal death have previously been described exclusively in pregnancies following spontaneous conception. CASE: The case of 37 year old gravida I, para O woman with a twin pregnancy after intracytoplasmatic sperm injection and intrauterine death of one twin at approximately 30 weeks' gestation is presented. The surviving twin was delivered by cesarean section at 31 weeks after spontaneous onset of labor and recurrent fetal bradycardia. The intraoperative situs showed that the demised twin had suffered from multiple umbilical cord torsions leading to intrauterine hypoperfusion. CONCLUSION: Umbilical torsion leading to fetal death might represent a previously unrecognized complication in women requiring assisted reproductive techniques, but this problem is known to occur in pregnancies achieved by natural methods.

5. Luo ZC, Wilkins R
Degree of rural isolation and birth outcomes
Paediatr Perinat Epidemiol. 2008 Jul;22(4):341-9

Department of Obstetrics and Gynecology, Sainte-Justine Hospital, University of Montreal, Canada. zhong-cheng.luo@recherche-ste-justine.qc.ca

Little is known about how birth outcomes vary in rural areas by degree of rural isolation. We conducted a retrospective cohort study of all births in Quebec, 1991-2000 to assess birth outcomes by the degree of rural isolation according to metropolitan influence as measured by work force commuting flows between rural and urban areas. Compared with urban areas, crude risks of preterm birth, small-for-gestational age birth, stillbirth, neonatal death and postneonatal death were similar in rural areas with strong metropolitan influence, but were significantly higher for preterm birth, stillbirth and postneonatal death in rural areas with weak or no metropolitan influence, and for neonatal death in rural areas with no metropolitan influence. Adjustment for maternal characteristics (age, mother tongue, education, marital status, parity, plurality and infant sex) attenuated the associations. The adjusted odds ratios [95% confidence intervals] were 1.36 [1.12, 1.64] for stillbirth in rural areas with weak metropolitan influence, 1.63 [1.14, 2.32] for neonatal death in rural areas with no metropolitan influence, 1.78 [1.21, 2.63] and 1.37 [1.07, 1.75] for postneonatal death in rural areas with weak and no metropolitan influence, respectively. Much higher neonatal death rates were observed for preterm or low-birthweight babies in rural areas with no metropolitan influence, suggesting inadequate access to optimal neonatal care. We conclude that birth outcomes in rural areas differ according to the degree of rural isolation. Fetuses and infants of mothers from rural areas with weak or no metropolitan influence are particularly vulnerable to the risks of death during the perinatal and postnatal periods.

6. Jellesen R, Strandberg-Larsen K, Jørgensen T, Olsen J, Thulstrup AM, Andersen
Maternal use of oral contraceptives and risk of fetal death
AM.Paediatr Perinat Epidemiol. 2008 Jul;22(4):334-40

National Institute of Public Health, Oster Farimagsgade 5A, DK-1399 Copenhagen, Denmark.

Intrauterine exposure to artificial sex hormones such as oral contraceptives may be associated with an increased risk of fetal death. Between 1996 and 2002, a total of 92 719 women were recruited to The Danish National Birth Cohort and interviewed about exposures during pregnancy. Outcome of pregnancy was identified through linkage to the Civil Registration System and the National Discharge Registry. The authors analysed the risk of fetal death after recruitment to the cohort by using proportional hazards regression models with gestational age as the underlying time scale. In total, 1102 (1.2%) women took oral contraceptives during pregnancy. Use of combined oestrogen and progesterone oral contraceptives (COC) or progesterone-only oral contraceptives (POC) during pregnancy was not associated with increased hazard ratios of fetal death compared with non-users, HR 1.01 [95% CI 0.71, 1.45] and HR 1.37 [95% CI 0.65, 2.89] respectively. Neither use of COC nor POC prior to pregnancy was associated with fetal death. Stratification by maternal age and smoking showed elevated risks of fetal death for women <30 years and smokers using oral contraception during pregnancy, but the interactions were not significant. In conclusion, there was no evidence that oral contraceptive use before or during pregnancy is associated with an increased risk of fetal death.

7. Kalter HD, Khazen RR, Barghouthi M, Odeh M
Prospective community-based cluster census and case-control study of stillbirths and neonatal deaths in the West Bank and Gaza Strip
Paediatr Perinat Epidemiol. 2008 Jul;22(4):321-33

Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. hkalter@jhsph.edu

Obstetric complications and newborn illnesses amenable to basic medical interventions underlie most perinatal deaths. Yet, despite good access to maternal and newborn care in many transitional countries, perinatal mortality is often not monitored in these settings. The present study identified risk factors for perinatal death and the level and causes of stillbirths and neonatal deaths in the West Bank and Gaza Strip. Baseline and follow-up censuses with prospective monitoring of pregnant women and newborns from September 2001 to August 2002 were conducted in 83 randomly selected clusters of 300 households each. A total of 113 of 116 married women 15-49 years old with a stillbirth or neonatal death and 813 randomly selected women with a surviving neonate were interviewed, and obstetric and newborn care records of women with a stillbirth or neonatal death were abstracted. The perinatal and neonatal mortality rates, respectively, were 21.2 [95% confidence interval (CI) 16.5, 25.9] and 14.7 [95% CI 10.2, 19.2] per 1000 livebirths. The most common cause (27%) of 96 perinatal deaths was asphyxia alone (21) or with neonatal sepsis (5), while 18/49 (37%) early and 9/19 (47%) late neonatal deaths were from respiratory distress syndrome (12) or sepsis (9) alone or together (6). Constraint in care seeking, mainly by an Israeli checkpoint, occurred in 8% and 10%, respectively, of 112 pregnancies and labours and 31% of 16 neonates prior to perinatal or late neonatal death. Poor quality care for a complication associated with the death was identified among 40% and 20%, respectively, of 112 pregnancies and labour/deliveries and 43% of 68 neonates. (Correction added after online publication 5 June 2008: The denominators 112 pregnancies, labours, and labour/deliveries, and 16 and 68 neonates were included; and 9% of labours was corrected to 10%.) Risk factors for perinatal death as assessed by multivariable logistic regression included preterm delivery (odds ratio [OR] = 11.9, [95% CI 6.7, 21.2]), antepartum haemorrhage (OR = 5.6, [95% CI 1.5, 20.9]), any severe pregnancy complication (OR = 3.4, [95% CI 1.8, 6.6]), term delivery in a government hospital and having a labour and delivery complication (OR = 3.8, [95% CI 1.2, 12.0]), more than one delivery complication (OR = 4.4, [95% CI 1.8, 10.5]), mother's age >35 years (OR = 2.9, [95% CI 1.3, 6.8]) and primiparity in a full-term pregnancy (OR = 2.6, [1.1, 6.3]). Stillbirths are not officially reportable in the West Bank and Gaza Strip and this is the first time that perinatal mortality has been examined. Interventions to lower stillbirths and neonatal deaths should focus on improving the quality of medical care for important obstetric complications and newborn illnesses. Other transitional countries can draw lessons for their health care systems from these findings.

8. Goy J, Dodds L, Rosenberg MW, King WD
Health-risk behaviours: examining social disparities in the occurrence of stillbirth
Paediatr Perinat Epidemiol. 2008 Jul;22(4):314-20

Department of Community Health and Epidemiology, Queen's University, Kingston, ON, Canada.

While an association between low socio-economic status (SES) and increased risk of stillbirth has been observed consistently over several decades, the pathways through which SES exerts these effects have not been established. Given that some key health-risk behaviours for stillbirth, including smoking and pre-pregnancy obesity, have strong relationships with SES, health-risk behaviours may serve as a channel through which low SES contributes to stillbirth outcomes. The objective of this study was to estimate the proportion of the relationship between low SES and the occurrence of stillbirth that is explained by health-risk behaviours in populations of Eastern Ontario and Nova Scotia (112 stillbirth cases and 398 controls). Both area and individual level influences of SES were assessed. The study population consisted of 112 cases (women delivering stillborn infants) and 398 controls. Odds ratios and 95% confidence intervals estimated by multivariable logistic regression were used to approximate relative risks. The contribution of health-risk behaviours to relationships between SES and stillbirth was assessed by a change in the relative risk estimate following omission of each health-risk behaviour from the model. Of the three measures of individual level SES examined (household income, education, Blishen occupational index), only household income was a statistically significant predictor of stillbirth. After controlling for individual level SES, no community level SES effects were observed for stillbirth. Adjustments for key health-risk behaviours (smoking) resulted in an 18.5% reduction in the odds ratio estimate for low SES, from 3.31 to 2.79. This large unexplained SES effect that remained highlights the need for research into other potential pathways that may account for increased risk of stillbirth among those of lower SES.

9. Yan J, Hales BF
p38 and JNK Mitogen-Activated Protein Kinase (MAPK) Signaling Pathways Play Distinct Roles in the Response of Organogenesis Stage Embryos to a Teratogen
J Pharmacol Exp Ther. 2008 Jun 24. [Epub ahead of print]

McGill University.

Mitogen-activated protein kinase (MAPK) signaling plays an important role during embryo development. We hypothesize that MAPK activation is a determinant of the fate of organogenesis-stage embryos exposed to insult. To test this hypothesis, CD1 mice were exposed to a model teratogen, hydroxyurea, on gestational day 9. Hydroxyurea exposure triggered a dramatic, transient increase in the activation of p38 MAP kinases and c-Jun N-terminal kinases (JNKs) in embryos, without activating extracellular-signal regulated kinases 1 and 2 (ERKs 1/2). Selectively blocking p38 MAP kinases with SB203580 enhanced hydroxyurea-induced fetal mortality without affecting growth retardation or the incidence of deformities among surviving fetuses. In contrast, selectively blocking JNKs with L-JNKI1 did not affect hydroxyurea-induced fetal death but increased the incidence of hindlimb defects observed. Thus, p38 MAP kinases and JNKs play distinct roles in protecting the conceptus against insult. Pharmacological inhibition of teratogen exposure induced MAPK activation has adverse consequences on the embryo.

10. Wax JR, Watson WJ, Miller RC, Ingardia CJ, Pinette MG, Cartin A, Grimes CK, Blackstone J
Prenatal sonographic diagnosis of hemivertebrae: associations and outcomes
J Ultrasound Med. 2008 Jul;27(7):1023-7

MMC Ob/Gyn Associates, 887 Congress St, Suite 200, Portland, ME 04102 USA. waxj@mmc.org.

OBJECTIVE: The purpose of this study was to evaluate associated anomalies and outcomes of fetuses with prenatally diagnosed hemivertebrae. METHODS: Fetuses with prenatally diagnosed hemivertebrae, excluding those associated with spina bifida, were identified by searching the prospectively maintained ultrasound databases of 4 institutions from 1997 to August 2007. Associated birth defects were tabulated by organ system and hemivertebra location. Outcomes included karyotypes, gestational ages, and routes and outcomes of deliveries. RESULTS: Nineteen fetuses had a diagnosis of hemivertebrae at a mean gestational age +/- SD of 20.5 +/- 5.4 weeks. Fourteen (73.7%) fetuses had additional anomalies, of which 5 (35.7%) were syndromic (4 with cloacal exstrophy and omphaloceles and 1 with Jarcho-Levin syndrome). Karyotypes were normal in all 11 available cases, each of which had additional anomalies. Fourteen (73.7%) neonates were live born at a mean gestational age of 34.9 +/- 4.3 weeks, of which 7 (50%) were born by cesarean delivery. Ten neonates (71.4%) were delivered before term, and 4 (28.6%) were growth restricted (<10th percentile). Two (14.3%) of these neonates died; both had cloacal exstrophy and large omphaloceles. The remaining pregnancies were terminated (4 [21.1%]) or had a fetal death (1 [5.3%]). CONCLUSIONS: Most fetuses with prenatally diagnosed hemivertebrae have additional anomalies, often syndromic, which affect the prognosis. Affected pregnancies have high rates of cesarean delivery and growth restriction. Neonates with nonisolated hemivertebrae are more often delivered before term and have higher mortality rates.

11. Hartley RS, Hitti J
Increasing rates of sex-discordant twins no longer correspond to decreasing perinatal mortality rates
J Perinat Med. 2008;36(3):228-34

Department of Biology, Seattle University, Seattle, WA 98122, USA. rhartley@seattleu.edu

OBJECTIVE: To analyze dizygotic twinning rates and outcomes over a 25-year period. METHODS: Birth and fetal death certificates from 1980-2004 in Washington State, USA, were analyzed retrospectively to find factors associated with the increase in sex-discordant twins through time. "Low" and "high" fertility treatment groups were defined according to demographic traits. Perinatal mortality was defined as fetal or neonatal death of one or both twins and Weinberg's rule was used to estimate mortality for monozygotic and dizygotic pairs. RESULTS: Controlling simultaneously for maternal age, race, parity, and education did not eliminate the trend of increasing sex-discordant twins from 1992-2004 (M-H chi2 P=0.001). The "low" fertility group had a non-significant decline in sex-discordant twins (M-H chi2 P=0.24), whereas the "high" fertility group had a significant increase (M-H chi2 P=0.001). Perinatal mortality decreased for monozygtic twin pairs throughout the study period, but decreased until the mid-1990s and then increased slightly through 2004 for the dizygotic twin pairs. CONCLUSION: Advancing maternal age and increasing use of fertility treatments are largely responsible for the increase in dizygotic twins from 1980-2004 and may also be responsible for the stalling of the decline in perinatal mortality rate.

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