NSIDRC Journal Article Alert — January 16, 2009

Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center at Georgetown University.

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Miscarriage/Stillbirth/Prenatal Issues

1. Norman J, Politz D, Politz L

Hyperparathyroidism during pregnancy and the effect of rising calcium on pregnancy loss - a call for earlier intervention

Clin Endocrinol (Oxf). 2008 Dec 5. [Epub ahead of print]

Norman Parathyroid Clinic Tampa, Florida.

SUMMARY Introduction: Hyperparathyroidism (HPT) during pregnancy is rare but poses a significant danger to mother and baby yet the incidence of pregnancy loss and its relationship to the degree of calcium elevation is not known. Design: A retrospective patient series from a single practice examined the past and current obstetrical histories of pregnant patients with primary HPT. Results: Over a 6 year period, 32 women ranging in age from 19 to 40 years of age had a total of 77 pregnancies while having elevated serum calcium levels due to primary HPT (incidence 0.7% of all women with primary HPT). Fifteen patients underwent parathyroidectomy during the second trimester resulting in an uneventful delivery of a healthy infant between 36 and 40 weeks gestation. There were no maternal or infant complications at surgery or during the subsequent delivery. Thirty of the remaining 62 pregnancies (48%) were lost, a rate that is 3.5-fold higher than expected (p<0.05). In those that did not have the HPT addressed after the first miscarriage, one third lost one or more additional pregnancies. Pregnancy loss occurred typically in the late first or early second trimester, with second trimester losses (30%) being six-fold higher than expected (p<0.01) and over 4 weeks later than typical (p<0.05). Fetal loss was seen at all levels of elevated maternal calcium but most were above 11.4 mg/dl (2.85 mmol/L). The rate of fetal loss increased directly with increasing maternal serum calcium levels (R=0.972). Conclusions: HPT during pregnancy is under recognized and is associated with a 3.5 fold increase in miscarriage rates. Pregnancy loss often occurs in the second trimester and is associated with multiple miscarriages when not addressed. Pregnancy loss is more common as calcium levels exceed 11.4 mg/dl (2.85 mmole/L), but can be seen at all elevated calcium levels. Emphasis is placed on earlier recognition and surgical cure prior to becoming pregnant, however, once pregnant, surgery should be offered early in the second trimester for those with calcium levels above 11.4 mg/dl.

2. Turton P, Evans C, Hughes P

Long-term psychosocial sequelae of stillbirth: phase II of a nested case-control cohort study

Arch Womens Ment Health. 2009 Jan 10. [Epub ahead of print]

Department of Mental Health, St. George's University of London, Cranmer Terrace, London, SW17 0RE, UK, pturton@sgul.ac.uk.

Stillbirth is associated with increased psychological morbidity in the subsequent pregnancy and puerperium. This study aimed to assess longer-term psychological and social outcomes of stillbirth and to identify factors associated with adverse outcome. We conducted seven-year follow-up of a cohort of women who were initially assessed during and after a pregnancy subsequent to stillbirth, together with pair-matched controls. All women were living with a partner at baseline and none had live children. Measured outcomes at follow-up included depression, posttraumatic stress disorder (PTSD) and partnership breakdown. Comparison variables included social and psychological factors and, for the stillbirth group, factors relating to the lost pregnancy. There were no differences between groups in case level psychological morbidity, but significantly higher levels of PTSD symptoms persisted in stillbirth group mothers who had case level PTSD 7 years earlier. Stillbirth group mothers were more likely to have experienced subsequent partnership breakdown. In the stillbirth group such breakdown was associated with having held the stillborn infant and having had case-level PTSD. Interpretations and clinical implications of these findings are discussed.

3. Tang SJ, Mayo MJ, Rodriguez-Frias E, Armstrong L, Tang L, Sreenarasimhaiah J, Lara LF, Rockey DC

Safety and utility of ERCP during pregnancy

Gastrointest Endosc. 2009 Jan 9. [Epub ahead of print]

Current affiliations: Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

BACKGROUND: ERCP is an important diagnostic and therapeutic tool in patients with biliary and pancreatic disease. Its utility and safety during pregnancy is largely unknown because it is not often required and because its use has been only infrequently reported in the published literature. OBJECTIVE: Our purpose was to report the clinical experience with ERCP during pregnancy. DESIGN: Retrospective review, single academic center. PATIENTS: All (consecutive) pregnant women who underwent ERCP at Parkland Memorial Hospital from 2000 to 2006. MAIN OUTCOME MEASUREMENTS: History, clinical data, hospital course, procedure-related complication rates and outcomes, and delivery and fetal outcomes were abstracted from medical records. RESULTS: During the study period, 68 ERCPs were performed on 65 pregnant women. The calculated ERCP rate was 1 per 1415 births. The common indications for ERCP in pregnancy were recurrent biliary colic, abnormal liver function tests, and dilated bile duct on US. ERCP was technically successful in all patients. The median fluoroscopy time was 1.45 minutes (range 0-7.2 minutes). There was no perforation, sedation-related adverse event, postsphincterotomy bleeding, cholangitis, or procedure-related maternal or fetal deaths. Post-ERCP pancreatitis was diagnosed in 11 patients (16%). None of these 11 patients had local or systemic complications. Fifty-nine patients had complete follow-up. Endoscopic therapy at the time of ERCP was undertaken in all patients. Furthermore, 9 patients (32.1%) underwent cholecystectomy in the first and second trimesters for either acute cholecystitis (6) or symptomatic gallstones (3). Term pregnancy was achieved in 53 patients (89.8%). Patients having ERCP in the first trimester had the lowest percentage of term pregnancy (73.3%) and the highest risk of preterm delivery (20.0%) and low-birth-weight newborns (21.4%). None of the 59 patients with long-term follow-up had spontaneous fetal loss, perinatal death, stillbirth, or fetal malformation. LIMITATION: Retrospective review. CONCLUSIONS: ERCP can be performed safely during pregnancy. Further, ERCP performed in pregnancy leads to specific therapy in essentially all patients. However, ERCP may be associated with a higher rate of post-ERCP pancreatitis than in the general population.

4. Sher G, Keskintepe L, Keskintepe M, Maassarani G, Tortoriello D, Brody S

Genetic analysis of human embryos by metaphase comparative genomic hybridization (mCGH) improves efficiency of IVF by increasing embryo implantation rate and reducing multiple pregnancies and spontaneous miscarriages

Fertil Steril. 2009 Jan 8. [Epub ahead of print]

Department of Obstetrics and Gynecology, University of Nevada School of Medicine, Reno, Nevada; Sher Institute for Reproductive Medicine, Las Vegas, Nevada.

OBJECTIVE: To assess the benefit of selecting blastocysts for cryotransfer based upon prior comparative genomic hybridization (CGH) karyotyping of blastomeres derived from their cleaved embryos of origin. Implantation and birth rates per transfer of previtrified CGH-tested blastocysts were compared with those following the transfer of nonCGH-tested fresh and warmed embryos. DESIGN: In vitro studies. SETTING: Private infertility clinic. PATIENT(S): Women undergoing infertility treatment. INTERVENTION(S): Three groups of women with similar clinical and demographic characteristics were compared. Group A underwent transfer of warmed blastocysts derived from CGH-normal day 3 embryos. Group B underwent embryo transfer of warmed blastocysts derived from nonkaryotyped vitrified embryos. Group C underwent fresh transfers with non-CGH-tested blastocysts. MAIN OUTCOME MEASURE(S): Implantation and birth rates per embryo after the cryotransfer of CGH-tested blastocysts. RESULT(S): The birth rate per transfered blastocyst in group A was 48%, versus 15% for group B and 19% for group C. The birth rate per embryo transfer was 60% for group A, and 33% for group B and 36% for group C. The miscarriage rate was 4% in group A, 8% in group B, and 12% in group C. CONCLUSION(S): The transfer of previously vitrified blastocysts derived from CGH-normal embryos significantly improves implantation and birth rates per embryo transfered and reduces the miscarriage rate. Vitrification does not compromise this enhancement.

5. Samsioe A, Papadogiannakis N, Hultman T, Sjöholm A, Klitz W, Niklasson B

Ljungan virus present in intrauterine fetal death diagnosed by both immunohistochemistry and PCR

Birth Defects Res A Clin Mol Teratol. 2009 Jan 9. [Epub ahead of print]

Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Section of Internal Medicine, Stockholm, Sweden.

OBJECTIVES: Following up on prior evidence from animal and human studies of Ljungan virus (LV) in intrauterine fetal death (IUFD), we examine additional cases of IUFD using two standard assays of viral detection: immunohistochemistry (IHC) and real time RT-PCR. MATERIALS AND METHODS: Frozen and formalin-fixed specimens from IUFD cases were tested for the presence of LV using real time RT-PCR and IHC, respectively. Formalin-fixed organs from terminated pregnancies diagnosed as trisomy 21 were used as controls in the IHC assay. RESULTS: Presence of LV was demonstrated in all five IUFD cases by IHC and further confirmed in three of these cases by real time RT-PCR. Only one of 18 trisomy 21 controls was LV positive by IHC. CONCLUSION: The presence of LV in IUFD patients has been confirmed by two different assays. Birth Defects Research (Part A), 2009. (c) 2008 Wiley-Liss, Inc.

6. Lee HH, Hong SH, Shin SJ, Ko JJ, Oh D, Kim NK

Association study of vascular endothelial growth factor polymorphisms with the risk of recurrent spontaneous abortion

Fertil Steril. 2009 Jan 6. [Epub ahead of print]

Department of Obstetrics and Gynecology, Teachers College, Cheju National University, Jeju, South Korea; Institute for Clinical Research, College of Medicine, Pochon CHA University, Seongnam, South Korea, Teachers College, Cheju National University, Jeju, South Korea.

OBJECTIVE: To investigate the association of vascular endothelial growth factor (VEGF) polymorphisms (-2578C>A, -1154G>A, -634G>C, 936C>T) with idiopathic recurrent spontaneous abortion (RSA) in Koreans. DESIGN: Prospective case-control study. SETTING: University-based hospital. PATIENT(S): Two hundred and fifteen patients with a history of two or more unexplained consecutive pregnancy losses and 113 healthy controls with at least one live birth and no history of pregnancy loss. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses were performed for the -2578C>A and 936C>T genotypes. Real-time PCR was also used to analyze the -1154G>A and -634G>C genotypes. RESULT(S): The GA (adjusted odds ratio [AOR] 2.774; 95% confidence interval [CI] 1.512-5.092; P=0.005) genotype of the VEGF -1154G>A polymorphism was significantly different between women with idiopathic RSA and controls. The difference in overall (GA + AA) frequency was also marginally significant between the controls and patients with idiopathic RSA (AOR, 2.006; 95% CI, 1.158-3.473; P=0.052). The differences in frequencies of the A-A-G-T (P=0.0508) and C-A-G-T (P=0.0604) haplotypes of the VEGF polymorphisms (-2578C>A, -1154G>A, -634G>C, 936C>T) were marginally significant between the patient and control groups. CONCLUSION(S): This study suggests that VEGF polymorphisms and haplotypes are a genetic determinant for the risk of idiopathic RSA in Korean women.

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