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BJOG. 2011 Dec;118(13):1617-29. doi: 10.1111/j.1471-0528.2011.03128.x. Epub 2011 Sep 6.

The natural history of pregnancy: diseases of early and late gestation.

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Department of Obstetrics and Gynaecology and the School of Population and Public Health, University of British Columbia and the Children's and Women's Health Centre of British Columbia, Vancouver, BC, Canada.



To identify the disease processes underlying the increasing rate of gestational age-specific perinatal mortality observed under the fetuses-at-risk model.


Retrospective cohort study.


USA and Nova Scotia, Canada.


Births in the USA (1995 and 2005) and Nova Scotia, Canada (1988-2007).


Incidence rates of perinatal death and serious neonatal morbidity were calculated using the fetuses-at-risk approach (e.g. cumulative incidence of stillbirth during any gestational week per 1000 fetuses at risk of stillbirth).


Perinatal mortality and serious neonatal morbidity.


Perinatal mortality rates increased with advancing gestation. Rates of bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leucomalacia and retinopathy of prematurity were highest in early gestation, whereas rates of meconium aspiration syndrome and aspiration pneumonitis were highest at late term and post-term gestation. Respiratory depression (i.e. delay in initiating and maintaining respiration after birth, low 5-minute Apgar score or seizures caused by neonatal encephalopathy) showed an increase from 34 weeks onwards. The increase in perinatal mortality rates at late gestation was congruent with increases in respiratory depression. Other findings included a high incidence of respiratory distress syndrome at late gestation, a nonspecific pattern in the gestational age-specific rates of necrotising enterocolitis and high rates of sudden infant death syndrome at late gestation.


The natural history of pregnancy is characterised by diseases of early and late gestation, with the latter largely determining patterns of gestational age-specific perinatal mortality. These findings have implications for obstetric theory and provide insight into various contemporary phenomena, including the rise in iatrogenic late preterm birth.

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