Predicting preeclampsia from a history of preterm birth

Abstract

ObjectiveTo assess whether women with a history of preterm birth, independent on the presence of prelabour rupture of the membranes (PROM) and growth deviation of the newborn, are more likely to develop preeclampsia with preterm or preterm birth in a subsequent pregnancy.MethodsWe conducted a population-based cohort study, based on Medical Birth Registry of Norway between 1967 and 2012, including 742,980 women with singleton pregnancies who were followed up from their 1st to 2nd pregnancy. In the analyses we included 712,511 women after excluding 30,469 women with preeclampsia in the first pregnancy.ResultsAfter preterm birth without preeclampsia in the first pregnancy, the risk of preterm preeclampsia in the second pregnancy was 4–7 fold higher than after term birth (odds ratios 3.5; 95% confidence interval (CI) 3.0–4.0 to 6.5; 95% CI 5.1–8.2). The risk of term preeclampsia in the pregnancy following a preterm birth was 2–3 times higher than after term birth (odds ratios 1.6; 95% CI 1.5–1.8 to 2.6; 95% CI 2.0–3.4). After spontaneous non-PROM preterm birth and preterm PROM, the risk of preterm preeclampsia was 3.3–3.6 fold higher than after spontaneous term birth. Corresponding risks of term preeclampsia was 1.6–1.8 fold higher. No significant time trends were found in the effect of spontaneous preterm birth in the first pregnancy on preterm or term preeclampsia in the second pregnancy.ConclusionsThe results suggest that preterm birth, regardless of the presence of PROM, and preeclampsia share pathophysiologic mechanisms. These mechanisms may cause preterm birth in one pregnancy and preeclampsia in a subsequent pregnancy in the same woman. The association was particularly evident with preterm preeclampsia.

Revisiting the Table 2 fallacy: A motivating example examining preeclampsia and preterm birth

“…Preeclampsia is often investigated as a risk factor for preterm birth, typically resulting in strong relative risks between 2.5-4.5. [13][14][15][16][17][18] Preeclampsia is a pregnancy-specific disorder complicating 6%-10% of all pregnancies in the United States. 19 It is diagnosed at or after 20 weeks of gestation, and defined by a combination of elevated blood pressure (diastolic blood pressure ≥90 mm Hg) and proteinuria (>300 mg in 24 hours) or elevated blood pressure plus thrombocytopenia, renal insufficiency, impaired liver function, pulmonary oedema or cerebral symptoms.…”

“…14,15,17 Risk factors for preeclampsia include maternal obesity, older age, African-American race, low socioeconomic status, alcohol abuse, diabetes, and previous preterm birth. 16,[22][23][24][25] Because these and other risk factors for preeclampsia are also associated with preterm birth, their potential for confounding the effects of preeclampsia on preterm birth must be considered. Given their association with preterm birth, authors may report effect estimates of these confounders alongside the effect estimate for preeclampsia, 13,18 and even more commonly when evaluating preeclampsia as one of multiple risk factors for preterm birth.…”

“…Over the past two decades, rates of preterm birth have been rising in developed countries, increasingly resulting in investigations into the multifactorial causes. Preeclampsia is often investigated as a risk factor for preterm birth, typically resulting in strong relative risks between 2.5‐4.5 . Preeclampsia is a pregnancy‐specific disorder complicating 6%‐10% of all pregnancies in the United States .…”

“…Risk factors for preeclampsia include maternal obesity, older age, African‐American race, low socioeconomic status, alcohol abuse, diabetes, and previous preterm birth . Because these and other risk factors for preeclampsia are also associated with preterm birth, their potential for confounding the effects of preeclampsia on preterm birth must be considered.…”

Causal models: Specification, fitting, reporting, and interpretation

“…The reference to preterm birth subtypes as “indications” for preterm birth suggests some lack of attention to substantive details. Similarly, a causal link between a history of preterm birth and subsequent preeclampsia seems unlikely, even though such an association has been documented in a (non‐causal) predictive model . The association between previous preterm birth and preeclampsia is preferably expressed as being the product of an unknown common cause(s).…”