Study confirms advanced maternal age increases risk of PTB

A large, retrospective Canadian study published in PLOS One confirms that birth at age ≥ 40 confers a heightened risk of preterm birth (PTB) (< 37 weeks) and very preterm birth (< 32 weeks). The lowest risk of PTB and very preterm birth was among women aged 30 to 34. Women aged 20 to 24 had an increased risk of PTB second to that of women ≥ 40.

The researchers utilized data from the randomized, controlled trial QUARISMA, which compiled data for 184,000 births in 32 hospitals from 2008 to 2011 across Canada. They included women aged > 20 and excluded women with multiple pregnancies, fetal malformations, and intra-uterine fetal deaths from their analysis. They defined and compared five age categories (20-24, 25-29, 30-34, 35-39, and ≥ 40) in regard to maternal characteristics, pregnancy and obstetric complications, and risk factors for PTB, and then evaluated spontaneous and iatrogenic risk factors for PTB < 37 weeks for the different age groups. 

Adjusted odds ratios by age

Of the 165,282 births that were included in the study, the investigators noted a linear association between increasing maternal age and risk factors for PTB such as chronic hypertension, use of assisted reproductive technology (ART), pre-gestational and gestational diabetes, invasive procedures during pregnancy, and placenta previa. A U-shaped distribution linked to maternal age was observed for hypertensive disorders of pregnancy. A U-shaped curve (highest point 7.8% for women ≥ 40 and lowest 5.7% for 30- to 34-year-olds) was also observed for crude PTB rates < 37 weeks across the five age ranges.

When the group performed a multivariate analysis of the data and adjusted for confounders, they found adjusted odds ratios for PTB categorized by age again followed a U-shape distribution as follows: 

• 20 to 24 years: 1.08 (95% CI 1.01-1.15)
• 25 to 29 years: 1.03 (95% CI:0.98-1.08)
• 30 to 34 years: 1:00
• 35 to 39 years: 1.04 (95% 0.97-1.11)
• ≥ 40 years: 1.20 (95% CI 1:06-1.36)

Placenta previa, gestational diabetes, medical history, use of ART, and invasive procedures were more common to older mothers, whereas nulliparity, past drug use, and smoking were more common to younger women. Hypertensive disorders were least commonly found among the middle-aged groups. Placenta previa and hypertensive complications were linked to the highest risk of PTB < 37 weeks. PTB tended to occur spontaneously in women 20 to 24, but was more often linked to medical conditions in women ≥ 40 year.  

The study was notable for its large cohort and broad range of patients from across rural and urban areas of Canada. Limitations included lack of data on body mass index (BMI) in 28% of subjects, leading to the exclusion of BMI in the multivariate analysis-despite the fact that obesity was common in the population and is well known to be associated with prematurity. Data on Socioeconomics and previous PTB were also not available and not included in the analysis, the authors said. They concluded, however, that exclusion of these variables from the multivariate analysis was unlikely to have impacted the results of the study. The findings confirm two previous cohort studies performed in Finland and Denmark.