Cause-Specific Stillbirth and Neonatal Death According to Prepregnancy Obesity and Early Gestational Weight Gain: A Study in the Danish National Birth Cohort

Maternal obesity is associated with impaired fetal and neonatal survival, but underlying mechanisms are poorly understood. We examined how prepregnancy BMI and early gestational weight gain (GWG) were associated with cause-specific stillbirth and neonatal death. In 85,822 pregnancies in the Danish National Birth Cohort (1996–2002), we identified causes of death from medical records for 272 late stillbirths and 228 neonatal deaths. Prepregnancy BMI and early GWG derived from an early pregnancy interview and Cox regression were used to estimate associations with stillbirth or neonatal death as a combined outcome and nine specific cause-of-death categories. Compared to women with normal weight, risk of stillbirth or neonatal death was increased by 66% with overweight and 78% with obesity. Especially deaths due to placental dysfunction, umbilical cord complications, intrapartum events, and infections were increased in women with obesity. More stillbirths and neonatal deaths were observed in women with BMI < 25 and low GWG. Additionally, unexplained intrauterine death was increased with low GWG, while more early stillbirths were seen with both low and high GWG. In conclusion, causes of death that relate to vascular and metabolic disturbances were increased in women with obesity. Low early GWG in women of normal weight deserves more clinical attention.

[1]  L. Køber,et al.  Maternal weight change from prepregnancy to 18 months postpartum and subsequent risk of hypertension and cardiovascular disease in Danish women: A cohort study , 2021, PLoS medicine.

[2]  J. Manson,et al.  Association of spontaneous abortion with all cause and cause specific premature mortality: prospective cohort study , 2021, BMJ.

[3]  D. Muin,et al.  Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study , 2021, Scientific Reports.

[4]  S. Cnattingius,et al.  Maternal Obesity and Risk of Early-onset Neonatal Bacterial Sepsis: Nationwide Cohort and Sibling-controlled Studies. , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  A. Maiorana,et al.  The Burden of Placental Histopathology in Stillbirths Associated With Maternal Obesity. , 2020, American journal of clinical pathology.

[6]  J. Priest,et al.  Maternal Obesity and Diabetes Mellitus as Risk Factors for Congenital Heart Disease in the Offspring , 2020, Journal of the American Heart Association.

[7]  U. V. Ukah,et al.  Association between gestational weight gain and severe adverse birth outcomes in Washington State, US: A population-based retrospective cohort study, 2004–2013 , 2019, PLoS medicine.

[8]  Michael R. Kramer,et al.  The association between gestational weight gain z-score and stillbirth: a case-control study , 2019, BMC Pregnancy and Childbirth.

[9]  N. Heslehurst,et al.  Maternal obesity classes, preterm and post-term birth: a retrospective analysis of 479,864 births in England , 2019, BMC Pregnancy and Childbirth.

[10]  S. Siabani,et al.  The risk of cardiovascular disease in women with a history of miscarriage and/or stillbirth , 2019, Health care for women international.

[11]  A. Puertas,et al.  Maternal obesity and the risk of group B streptococcal colonisation in pregnant women , 2019, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology.

[12]  S. Cnattingius,et al.  Maternal Overweight and Obesity and Risk of Congenital Heart Defects. , 2019, Journal of the American College of Cardiology.

[13]  Han-Yang Chen,et al.  Association between Gestational Weight Gain Adequacy and Adverse Maternal and Neonatal Outcomes , 2018, American Journal of Perinatology.

[14]  J. Hutcheon,et al.  Good Practices for Observational Studies of Maternal Weight and Weight Gain in Pregnancy , 2018, Paediatric and perinatal epidemiology.

[15]  A. Caughey,et al.  The association between gestational weight gain and risk of stillbirth: a population-based cohort study. , 2017, Annals of epidemiology.

[16]  K. Joseph,et al.  The fetuses‐at‐risk approach: survival analysis from a fetal perspective , 2017, Acta Obstetricia et Gynecologica Scandinavica.

[17]  S. Maffoni,et al.  Folate status in women of childbearing age with obesity: a review , 2017, Nutrition Research Reviews.

[18]  G. Hu,et al.  Association of Gestational Weight Gain With Maternal and Infant Outcomes: A Systematic Review and Meta-analysis , 2017, JAMA.

[19]  J. Hutcheon,et al.  Patterns of Gestational Weight Gain in Early Pregnancy and Risk of Gestational Diabetes Mellitus , 2017, Epidemiology.

[20]  N. Heslehurst,et al.  Maternal body mass index and post‐term birth: a systematic review and meta‐analysis , 2017, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[21]  G. Britton,et al.  Blood-based biomarkers of adverse perinatal outcomes in maternal obesity , 2017, 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.

[22]  J. Hutcheon,et al.  Maternal obesity and gestational weight gain are risk factors for infant death , 2016, Obesity.

[23]  L. Myatt,et al.  Obesity and Placental Function , 2016, Seminars in Reproductive Medicine.

[24]  R. Platt,et al.  Maternal prepregnancy obesity and cause-specific stillbirth. , 2015, The American journal of clinical nutrition.

[25]  S. Cnattingius,et al.  Maternal overweight and obesity in early pregnancy and risk of infant mortality: a population based cohort study in Sweden , 2014, BMJ : British Medical Journal.

[26]  C. Ananth,et al.  Obesity and the risk of stillbirth: a population-based cohort study. , 2014, American journal of obstetrics and gynecology.

[27]  S. Tonstad,et al.  Maternal body mass index and the risk of fetal death, stillbirth, and infant death: a systematic review and meta-analysis. , 2014, JAMA.

[28]  M. J. Charron,et al.  Animal models of in utero exposure to a high fat diet: a review. , 2014, Biochimica et biophysica acta.

[29]  M. Blomberg Maternal Obesity, Mode of Delivery, and Neonatal Outcome , 2013, Obstetrics and gynecology.

[30]  S. Cnattingius,et al.  Maternal Obesity and Risk of Preterm Delivery , 2014 .

[31]  V. Filippi,et al.  Effect of maternal obesity on neonatal death in sub-Saharan Africa: multivariable analysis of 27 national datasets , 2012, The Lancet.

[32]  H. Minakami,et al.  Prevalence of hyperglycemia during pregnancy according to maternal age and pre‐pregnancy body mass index in Japan, 2007–2009 , 2012, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[33]  J. Thorp,et al.  Excessive Early Gestational Weight Gain and Risk of Gestational Diabetes Mellitus in Nulliparous Women , 2012, Obstetrics and gynecology.

[34]  S. Cnattingius,et al.  Mortality in infants of obese mothers: is risk modified by mode of delivery? , 2012, Acta obstetricia et gynecologica Scandinavica.

[35]  U. Kesmodel,et al.  Effect of Prepregnancy Maternal Overweight and Obesity on Pregnancy Outcome , 2011, Obstetrics and gynecology.

[36]  J. Rankin,et al.  Maternal body mass index and the risk of fetal and infant death: a cohort study from the North of England. , 2011, Human reproduction.

[37]  K. Thornburg,et al.  Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. , 2011, Endocrinology.

[38]  Youth,et al.  Weight Gain During Pregnancy: Reexamining the Guidelines , 2010 .

[39]  J. Davis,et al.  Maternal obesity and markers of inflammation in pregnancy. , 2009, Cytokine.

[40]  K. Kleinman,et al.  Weight gain in pregnancy and risk of maternal hyperglycemia. , 2009, American journal of obstetrics and gynecology.

[41]  J. Rankin,et al.  Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. , 2009, JAMA.

[42]  Aimin Chen,et al.  Maternal Obesity and the Risk of Infant Death in the United States , 2009, Epidemiology.

[43]  M. Frydenberg,et al.  Does Low Participation in Cohort Studies Induce Bias? , 2006, Epidemiology.

[44]  M. Frydenberg,et al.  Prepregnancy Obesity and Fetal Death: A Study Within the Danish National Birth Cohort , 2005, Obstetrics and gynecology.

[45]  Mogens Vestergaard,et al.  Pre‐pregnancy weight and the risk of stillbirth and neonatal death , 2005, BJOG : an international journal of obstetrics and gynaecology.

[46]  Michal Abrahamowicz,et al.  A proportional hazards model with time-dependent covariates and time-varying effects for analysis of fetal and infant death. , 2004, American journal of epidemiology.

[47]  M. Cedergren Maternal Morbid Obesity and the Risk of Adverse Pregnancy Outcome , 2004, Obstetrics and gynecology.

[48]  W. Ferrell,et al.  Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. , 2002, The Journal of clinical endocrinology and metabolism.

[49]  Henrik Toft Sørensen,et al.  The Danish National Birth Cohort - its background, structure and aim , 2001, Scandinavian journal of public health.

[50]  A. Many,et al.  Third‐Trimester Unexplained Intrauterine Fetal Death Is Associated With Inherited Thrombophilia , 2001, Obstetrics and gynecology.

[51]  J. Pell,et al.  Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129 290 births , 2001, The Lancet.

[52]  A. Astrup,et al.  Obesity : Preventing and managing the global epidemic , 2000 .

[53]  A. Selbing,et al.  Intrauterine growth curves based on ultrasonically estimated foetal weights , 1996, Acta paediatrica.

[54]  S. Greenland Dose‐Response and Trend Analysis in Epidemiology: Alternatives to Categorical Analysis , 1995, Epidemiology.

[55]  K. Helweg-larsen,et al.  [Classification of perinatal and neonatal deaths. Fetal, obstetrical and neonatal causes]. , 1991, Ugeskrift for laeger.

[56]  E. Hey,et al.  Classifying perinatal death: an obstetric approach , 1986, British journal of obstetrics and gynaecology.

[57]  E. Hey,et al.  Classifying perinatal death: fetal and neonatal factors , 1986, British journal of obstetrics and gynaecology.

[58]  J. Dobner,et al.  Body mass index and the risk of infection - from underweight to obesity. , 2018, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[59]  Gordon C. S. Smith Screening and prevention of stillbirth. , 2017, Best practice & research. Clinical obstetrics & gynaecology.

[60]  Chuan-lai Hu,et al.  Maternal pre-pregnancy obesity and the risk of macrosomia: a meta-analysis , 2017, Archives of Gynecology and Obstetrics.

[61]  S. Tonstad,et al.  Maternal BodyMass Index and the Risk of Fetal Death , Stillbirth , and Infant Death , 2014 .

[62]  T. Lander,et al.  Neonatal and perinatal mortality: country, regional and global estimates. , 2006 .

[63]  Gordon C. S. Smith Estimating risks of perinatal death. , 2005, American journal of obstetrics and gynecology.

[64]  Who Consultation on Obesity Obesity: preventing and managing the global epidemic. Report of a WHO consultation. , 2000, World Health Organization technical report series.

[65]  F. Quaade,et al.  Comparison of self-reported height and weight with controlled height and weight in women and men. , 1981, International journal of obesity.