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Stillbirth
- 1. Stillbirth N.L. Meyer University of Tennessee
- 10. Maternal Risk Factors Sickle cell disease Multiple gestation Malaria Smoking Poor nutritional status Infection – Parvovirus B19, syphilis, streptococcal infection, listeria Congenital anomalies Hypertensive disease, preeclampsia Hypertensive disease – complications of preeclampsia and eclampsia Medical disease – diabetes, SLE, renal disease, thyroid, cholestasis Infection – syphilis and gram-negative infection Growth restriction/placental anomalies Obstructed prolonged labor and associated asphyxia, infection, injury Congenital and karyotypic anomalies Developing Countries Developed Countries
- 12. Most Frequent Types of Stillbirth According to GA Fretts et al. Ob Gyn 1992;79:35-9 Fretts and Usher. Contem Rev Ob Gyn 1997;9:173-9 Abruptio placenta (12%) Abruptio placenta (18%) Anomalies (14%) Fetal malnutrition (14%) Fetal malnutrition (19%) Abruptio placenta (14%) Unexplained (40%) Unexplained (26%) Infection (19%) 37+ weeks 28 - 37 weeks 24 - 27 weeks
- 17. Advanced Maternal Age Antepartum vs Intrapartum Maternal age (yrs) Rate per 1000 Saliu et al. J Obstet Gynaecol 2008;34:843
- 19. Obesity 11 / 1000 ≥ 40 8 / 1000 30 – 39.9 5.5 / 1000 < 30 Stillbirth Rate per 1000 BMI
- 21. Chromosomal Abnormalities Korteweg et al 2008 Ob Gyn 111;865 28% Fetal tissue sampling 85% Amniocentesis / CVS Success Rate Method
- 23. Chromosomal Abnormalities Korteweg et al 2008 Ob Gyn 111;865
- 27. Thrombophilia Gonen R et al. Absence of association of inherited thrombophilia with unexplained third-trimester intrauterine fetal death. AJOG 2005;192:742-6
- 33. Silver et al. Work-up of stillbirth: a review of the evidence. AJOG 2007;196:433-444.
- 36. Antepartum Testing Protocol Weeks et al.
Notas do Editor
- WHO suggests live birth has birth weight 500 gm, gestational age of 22 weeks, and body length of 25 cm “ any sign of life” criteria Fetal heart rate Breathing Movement of voluntary muscles 350 g is 50 th percentile for 20 weeks gestation TCA Fetal death reported when ≥500 g or ≥22 weeks Birth and death certificates are not generated after miscarriage ability to call a fetal loss a stillbirth is important
- 6.2/1000 live births and fetal deaths (total births = live births+fetal deaths) AA have 2x risk stillbirth Some of this increase can be attributed to access to and quality of medical care Even with adequate access , still have higher rate of stillbirth Higher rates diabetes, HTN, abruption, PPROM
- In July 2009 the Urban Child Institute in Memphis looked at the discrepancies in still births in Tennessee counties Concluded that differences were related to reporting different GA/weight
- Between 24-27 weeks, most common cause if stillbirth is infection (19%) Contribution of infection to stillbirth rate is difficult to define Some pathogens clearly causally associated with stillbirth Parvo CMV Toxo Other pathogens might be associated with increased risk of stillbirth but strong evidence of causal relation is absent Ureaplasma urealyticum Mycoplasma hominis GBS
- Nulliparity OR 1.2 – 1.4
- 24-27 weeks, most common cause still birth Infection Stillbirth related to infection occur most frequently in fetuses <1000 g Abruption Anomalies 21% unexplained Stillbirth related to abruption has decreased over decades After 28 weeks, unexplained stillbirth increases Fetal death that is unexplained by fetal, placental, maternal, or obstetric factors represents 25-60% of all fetal deaths Diagnosis of exclusion Depends on rigorousness of stillbirth assessment
- Diagnostic criteria for determining if a fetal death is due to an infection are not well defined and complicated by high frequency of asymptomatic maternal vaginal colonization of some potential pathogens.
- Stillbirth rate 4x higher than singletons
- Childbearing increasing among older women Older women are at increased risk for adverse outcomes Low birth weight Preterm Fetal mortality Significant proportion of perinatal deaths in older women are related to lethal congenital and chromosomal abnormalities Increased risk of unexplained stillbirth late in pregnancy persists in older women even after controlling for risk factors such as HTN, DM, previa, multiple gestation AMA remains as independent risk factor after accounting for medical conditions that occur in older women Increased risk associated with anomalies has been reduced with prenatal diagnostic testing and availability of abortions Peak rise period in older mothers between 37-41 weeks but NO studies to examine differential risk antepartum vs intrapartum
- Mature gravidas at increased risk of various adverse outcomes Low birth weight Preterm SGA Stillbirth Link between advanced maternal age and stillbirth but little information on timing of in utero death Stillbirth defined In utero death > 20 weeks Excluded congenital malformations and chromosomal abnormalities Women 35-39 were more than 2-fold as likely to experience intrapartum stillbirth while those 40 or greater were 3x as likely Highest risk of stillbirth exhibited among mothers in oldest age group Higher levels of obstetric complications in older women could contribute to elevated risk for still birth Information on pregnancy complications not readily available in this data base Etiologic factors for antepartum and intrapartum stillbirth have been suggested to be different Preeclampsia, HTN, abnormal placental conditions are more likely to cause antepartum stillbirth Excess of these conditions in older women may explain 4-fold increment in occurrence of antepartum stillbirth among older women Intrapartum stillbirth more likely to result from fetal distress, obstructed labor Indication of access to and quality of care during delivery Different risk estimates for antepartum vs intrapartum stillbirth with maternal age may reflect dynamics in distribution and patterns of these etiologic factors as women age
- Thinner women may be better able to perceive fetal movement Hyperlipidemia Increased endothelial dysfunction Platelet aggregation Clinically significant atherosclerosis Sleep studies show obese women snore more and have increased apnea-hypoxia events Increased episodes oxygen destauration Snoring associated with pregnancy induced hypertension and growth restriction
- Karyotypic analysis underestimates genetic contribution to stillbirth 50% karyotype cell culture unsuccessful
- One of several studies which challenge association between thrombophilia and complications No difference in study and control group Findings are consistent with studies from Germany and Austria
- Most important tests in still birth evaluation Autopsy Identification of birth defects and morphologic abnormalities suggesting genetic or developmental abnormalities Determine and/or confirm other causes of stillbirth Infection Anemia Hypoxia Metabolic abnormalities Comparative genomic hybridization Scan genome for differences from normal reference genome without mitotic activity Detects only copy number changes relative to the average in the entire specimen Does not detect triploidy No information on chromosome architecture Cannot discern translocation from non-dysjunction Down’s Does not detect balanced chromosomal rearrangements Only detects changes in substantial percentage of cells
- After autopsy and histologic evaluation, pathologist can proceed with appropriate culture and nucleic acid specimens for bacteria and viruses taken for organisms suspected on basis of histology Parvovirus serology may be useful Implicated in meaningful proportion of cases RPR Syphilis is a generally accepted cause of stillbirth TORCH serology questionable Toxo, rubella, CMV, HSV Traditionally advised but titers rarely clinically useful Routine placental bacterial cultures may be useful but problematic Avoid vaginal wall contamination Culture between membranes Ureaplasma and mycoplasma in addition to aerobic and anaerobic cultures may be useful Incidence in live-born pregnancies unknown Nucleic acid based tests for bacterial or viral products may be more sensitive but also associated with more false positive results
- FMH common cause of stillbirth – screening advised KBT Fetal cells in maternal blood Elution of hemoglobin from adult cells Acid resistant fetal hemoglobin remains intact Statistical imprecision in quantifying FMH
- Testing cases characterized by placental insufficiency appropriate given apparent pathophysiology of these conditions Limited evidence that treatment in subsequent pregnancy improves outcomes Some heritable thrombophilias are present in a large proportion of normal individuals – positive test may be unrelated to stillbirth
- Recurrent stillbirth 2 unexplained previous stillbirths at 37 and 38 weeks 35 weeks gestation with decreased FM 3 days after negative CST D/C’d home after reactive NST Returned 16 hours later with no FM x 5 hrs IUFD confirmed
- Nonrecurring conditions Testing of limited value Affected mothers better served with screeening, education, counseling Recur but not predictable Unlikely to benefit from testing in subsequent pregnancies.
- Rates of delivery for abnormal or equivocal testing were 16.3% at or before 39 weeks and 1% before 36 weeks
- Must be considered in any strategy that may lead to iatrogenic late preterm birth