Our search for the antecedents of pregnancy disorders that lead to preterm delivery fueled our search for features common to these disorders. Although the 6 pregnancy disorders that lead to delivery much before term have distinct clinical presentations, our findings suggest that they can be divided into 2 broad groups on the basis of common characteristics. One group, characterized by the presence of infection and inflammation and the absence of indicators of impaired placentation, includes preterm labor, pPROM, placental abruption, and cervical insufficiency. “Spontaneous” preterm delivery has been defined as the group of entities that are neither maternal nor fetal indication/IUGR, and it typically includes complications such as preterm labor and pPROM. We prefer, however, to group these causes of preterm delivery under the description “inflammatory,” because it more accurately summarizes the observations made in this analysis, and to include placental abruption and cervical insufficiency under this umbrella.
The other group, characterized by infarcts and increased syncytial knots in the placenta, the relative absence of inflammation, and a higher neonatal mortality rate, includes preeclampsia and the entity identified as fetal indication/IUGR. The presence of increased syncytial knots and infarcts has been viewed as evidence of maternal-placental insufficiency (17
). Low-birth-weight z
scores, another indicator of placental function, are characteristic of infants delivered for fetal indication/IUGR and preeclampsia (19
). Intrauterine growth restriction has been attributed to a restricted arteriolar supply of the uterine-placental interface (21
). Delivery for preeclampsia and fetal indication/IUGR has been labeled “indicated” or “nonspontaneous” delivery. We, however, prefer to identify this group with the more pathophysiologically accurate term of “placental dysfunction.”
This study is unique in culturing placental stroma rather than amniotic fluid or fetal membranes. Nevertheless, the results are similar, recovering a diverse group of organisms with no one organism or class of organisms predominating (22
). We also observed that vaginal microorganisms occur preferentially in the placentas of women with preterm labor, pPROM, placental abruption, and cervical insufficiency regardless of whether delivery is vaginal or abdominal, suggesting that these organisms are not merely contaminants associated with the route of delivery but are biologically significant.
Our study is not unique in finding elevated frequencies of histologic inflammation in placentas from pregnancies complicated by preterm labor and pPROM (25
), nor is it unique in finding evidence that placental abruption is characterized by inflammatory processes (27
). However, our observations allow us to go the next step and suggest that the patterns of histologic changes and microbes recovered from placentas after both cervical insufficiency and abruption are similar to those of placentas delivered after preterm labor or pPROM.
We observed that demographic variables discriminate among the 6 pregnancy complications. As others have also observed, we found that maternal age (30
), educational attainment (34
), and race (35
) differ by cause of preterm delivery. Unlike others, we did not find that marital status (37
) and limited financial resources (39
) discriminate among the causes of preterm delivery.
Characteristics that are more specific to the physiology of the pregnancy itself such as maternal smoking, body mass index, and conception assistance also discriminate among the 6 disorders that lead to preterm delivery. Consistent with prior work, we observed that smoking was associated with reduced risk of preeclampsia (41
) and an increased risk of pPROM and placental abruption (8
). Similarly, we confirmed a positive association between increased body mass index and both fetal indication/IUGR and preeclampsia (46
Our data support the hypothesis that the intrauterine environment influences the risk of mortality in the preterm neonate (48
). Neonatal mortality was higher in pregnancy disorders associated with placental dysfunction than in those disorders associated with intrauterine inflammation.
In summary, we have found support for classifying the disorders leading to delivery well before term in 2 broad groups. What we call the “inflammatory” group and others call “spontaneous preterm delivery” includes preterm labor, pPROM, placental abruption, and cervical insufficiency and is characterized by evidence of infection and inflammation. The “placental dysfunction” group, otherwise classified as “indicated delivery,” includes preeclampsia and fetal indication/IUGR and is characterized by the relative absence of inflammation and the presence of infarcts, as well as increased syncytial knots in the placenta. Further work will be needed to suggest whether intervening at a point before the final common pathway of each group can potentially reduce the burdens that these disorders place on families and society.