Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology

Objective To investigate the proportion of stillbirths at term associated with abnormal growth using customized birth weight percentiles and to compare histological placental findings both in underweight stillborn fetuses and in live births. Methods A retrospective case-control study of 150 singleton term stillbirths. The livebirth control groups included 586 cases of low-risk pregnancies and 153 late fetal growth restriction fetuses. Stillbirths and livebirths from low-risk pregnancies were classified using customized standards for fetal weight at birth, as adequate for gestational age (AGA; 10-90th percentile), small (SGA; <10th percentile) or large for gestational age (LGA; >90th percentile). Placental characteristics in stillbirth were compared with those from livebirths using four categories: inflammation, disruptive, obstructive and adaptive lesions. Results There was a higher rate of SGA (26% vs 6%, p<0.001) and LGA fetuses (10.6% vs 5.6%, p<0.05) in the stillbirth group. Among stillbirth fetuses, almost half of the SGA were very low birthweight (≤3°percentile) (12% vs 0.3%, p<0.001). The disruptive (7.3% vs 0.17%;p<0.001), obstructive (54.6% vs 7.5%;p<0.001) and adaptive (46.6% vs 35.8%;p<0.001) findings were significantly more common in than in livebirth-low risk. Placental characteristics of AGA and SGA stillbirth were compared with those of AGA and FGR livebirth. In stillbirths-SGA we found a higher number of disruptive (12.8% vs 0%; p<0.001), obstructive (58.9% vs 23.5%;p<0.001) and adaptive lesions (56.4% vs 49%; p 0.47) than in livebirth-FGR. Conclusion The assessment of fetal weight with customized curves can identify fetuses which have not reached their genetically determined growth potential and are therefore at risk for adverse outcomes. Placental evaluation in stillbirths can reveal chronic histological signs that might be useful to clinical assessment, especially in underweight fetuses.

[1]  M. Cozzolino,et al.  Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology , 2016, PloS one.

[2]  A. Coomarasamy,et al.  Late intrauterine fetal death and stillbirth , 2016 .

[3]  A. Baschat,et al.  A uniform management approach to optimize outcome in fetal growth restriction. , 2015, Obstetrics and gynecology clinics of North America.

[4]  F. Mecacci,et al.  Placental histology in clinically unexpected severe fetal acidemia at term. , 2015, Early human development.

[5]  D. Cantonwine,et al.  Identification of pathologically small fetuses using customized, ultrasound and population‐based growth norms , 2014, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[6]  N. Sebire,et al.  Systematic review of placental pathology reported in association with stillbirth. , 2014, Placenta.

[7]  J. Gardosi,et al.  Preventing stillbirths through improved antenatal recognition of pregnancies at risk due to fetal growth restriction. , 2014, Public health.

[8]  E. Gratacós,et al.  Update on the Diagnosis and Classification of Fetal Growth Restriction and Proposal of a Stage-Based Management Protocol , 2014, Fetal Diagnosis and Therapy.

[9]  F. Mecacci,et al.  Autophagy in placentas from acidotic newborns: an immunohistochemical study of LC3 expression. , 2013, Placenta.

[10]  J. Stanek Hypoxic patterns of placental injury: a review. , 2013, Archives of pathology & laboratory medicine.

[11]  S. Romagnoli,et al.  Abnormal spiral arteries modification in stillbirths: the role of maternal prepregnancy body mass index , 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[12]  I. Cetin,et al.  Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death. , 2012, Early human development.

[13]  J. Stanek Utility of Diagnosing Various Histological Patterns of Diffuse Chronic Hypoxic Placental Injury , 2012, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[14]  C. Vogt,et al.  How Important is Placental Examination in Cases of Perinatal Deaths? , 2011, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[15]  Radek Bukowski,et al.  Stillbirth and fetal growth restriction. , 2010, Clinical obstetrics and gynecology.

[16]  R. Fretts Stillbirth epidemiology, risk factors, and opportunities for stillbirth prevention. , 2010, Clinical obstetrics and gynecology.

[17]  M. Candiani,et al.  Thrombosis of the umbilical vessels revisited. An observational study of 317 consecutive autopsies at a single institution. , 2010, Human pathology.

[18]  J. van der Meer,et al.  Diverse Placental Pathologies as the Main Causes of Fetal Death , 2009, Obstetrics and gynecology.

[19]  D. Kidron,et al.  Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation. , 2009, Placenta.

[20]  ACOG Practice Bulletin No. 102: management of stillbirth. , 2009, Obstetrics and gynecology.

[21]  D. Roberts,et al.  Fetal Vascular Obstructive Lesions: Nosology and Reproducibility of Placental Reaction Patterns , 2004, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[22]  R. Redline,et al.  Amniotic Infection Syndrome: Nosology and Reproducibility of Placental Reaction Patterns , 2003, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[23]  S. Cnattingius,et al.  Perinatal outcome in SGA births defined by customised versus population‐based birthweight standards , 2001, BJOG : an international journal of obstetrics and gynaecology.

[24]  C. Langston,et al.  Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists. , 1997, Archives of pathology & laboratory medicine.

[25]  M. Divon,et al.  Identification of the small for gestational age fetus with the use of gestational age-independent indices of fetal growth. , 1986, American journal of obstetrics and gynecology.

[26]  A. Coomarasamy,et al.  Late intrauterine fetal death and stillbirth , 2016 .

[27]  S. Cnattingius,et al.  Advanced Maternal Age and Stillbirth Risk in Nulliparous and Parous Women , 2015, Obstetrics and gynecology.

[28]  A. Baschat,et al.  A uniform management approach to optimize outcome in fetal growth restriction. , 2015, Obstetrics and gynecology clinics of North America.

[29]  F. Mecacci,et al.  Placental histology in clinically unexpected severe fetal acidemia at term. , 2015, Early human development.

[30]  D. Cantonwine,et al.  Identification of pathologically small fetuses using customized, ultrasound and population‐based growth norms , 2014, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[31]  N. Sebire,et al.  Systematic review of placental pathology reported in association with stillbirth. , 2014, Placenta.

[32]  J. Gardosi,et al.  Preventing stillbirths through improved antenatal recognition of pregnancies at risk due to fetal growth restriction. , 2014, Public health.

[33]  C. Parker,et al.  Fetal Growth and Risk of Stillbirth: A Population-Based Case–Control Study , 2014, PLoS medicine.

[34]  E. Gratacós,et al.  Update on the Diagnosis and Classification of Fetal Growth Restriction and Proposal of a Stage-Based Management Protocol , 2014, Fetal Diagnosis and Therapy.

[35]  F. Mecacci,et al.  Autophagy in placentas from acidotic newborns: an immunohistochemical study of LC3 expression. , 2013, Placenta.

[36]  J. Stanek Hypoxic patterns of placental injury: a review. , 2013, Archives of pathology & laboratory medicine.

[37]  Asad Malik,et al.  Maternal and fetal risk factors for stillbirth: population based study , 2013, BMJ.

[38]  Hypoxic Patterns of Placental Injury , 2013 .

[39]  S. Romagnoli,et al.  Abnormal spiral arteries modification in stillbirths: the role of maternal prepregnancy body mass index , 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[40]  I. Cetin,et al.  Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death. , 2012, Early human development.

[41]  J. Stanek Utility of Diagnosing Various Histological Patterns of Diffuse Chronic Hypoxic Placental Injury , 2012, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[42]  C. Vogt,et al.  How Important is Placental Examination in Cases of Perinatal Deaths? , 2011, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[43]  Radek Bukowski,et al.  Stillbirth and fetal growth restriction. , 2010, Clinical obstetrics and gynecology.

[44]  R. Fretts Stillbirth epidemiology, risk factors, and opportunities for stillbirth prevention. , 2010, Clinical obstetrics and gynecology.

[45]  M. Candiani,et al.  Thrombosis of the umbilical vessels revisited. An observational study of 317 consecutive autopsies at a single institution. , 2010, Human pathology.

[46]  J. van der Meer,et al.  Diverse Placental Pathologies as the Main Causes of Fetal Death , 2009, Obstetrics and gynecology.

[47]  D. Kidron,et al.  Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation. , 2009, Placenta.

[48]  C. Sufrin Erratum: The 'exhibit mall' at the American College of Obstetricians and Gynecologists (ACOG) annual Clinical Meeting: Reflections on Consumerism and Medicine (Obstetrics and Gynecology (2008) 112 (1355-1359) , 2009 .

[49]  ACOG Practice Bulletin No. 102: management of stillbirth. , 2009, Obstetrics and gynecology.

[50]  D. Roberts,et al.  Fetal Vascular Obstructive Lesions: Nosology and Reproducibility of Placental Reaction Patterns , 2004, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[51]  R. Redline,et al.  Amniotic Infection Syndrome: Nosology and Reproducibility of Placental Reaction Patterns , 2003, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[52]  S. Cnattingius,et al.  Perinatal outcome in SGA births defined by customised versus population‐based birthweight standards , 2001, BJOG : an international journal of obstetrics and gynaecology.

[53]  C. Langston,et al.  Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists. , 1997, Archives of pathology & laboratory medicine.

[54]  M. Divon,et al.  Identification of the small for gestational age fetus with the use of gestational age-independent indices of fetal growth. , 1986, American journal of obstetrics and gynecology.