Are short interpregnancy intervals risky for older mothers?

November 13, 2018

Results of a population-based study provide new perspectives on the interaction between spacing of pregnancies, maternal age, and the health of mothers and their offspring. PLUS: How do pessaries compare with progesterone for preventing early PTB? ALSO: Opioid abuse in rural mothers and babies - What are the risks?

Adverse pregnancy outcomes are known to be associated with getting pregnant less than 18 months after giving birth. But are such short interpregnancy intervals even riskier in mothers who are older? Results of a population-based study provide new perspectives on the interaction between spacing of pregnancies, maternal age, and the health of mothers and their offspring.

Published in JAMA, the findings, according to the researchers, represent “robust evidence to guide clinicians counseling women considering short interpregnancy intervals.” Unlike the methodology used in previous studies in this area, the authors said, their database allowed them to control for stillbirth and neonatal loss in the index birth and to accurately measure intervals between pregnancies.

Conducted in British Columbia, Canada, the cohort study focused on analysis of data from nearly 150,000 pregnancies. The participants were women with two or more singleton pregnancies from 2004 to 2014 and the data were analyzed from January 1 to July 20, 2018.

The authors looked at risks of maternal mortality or severe morbidity (e.g., mechanical ventilation, blood transfusion > 3 U, intensive care unit admission, organ failure, death), small-for-gestational age [SGA], fetal and infant composite outcome (stillbirth, infant death < third birthweight percentile for gestational age and sex, delivery < 28 weeks), and spontaneous and indicated preterm birth (PTB). Risks of each outcome for 3- to 24-month interpregnancy intervals were estimated, according to maternal age at birth (20-34 and ≥ 35 years). For each age group, the researchers then calculated adjusted risk ratios (aRRs) comparing predicted risks at 3- 6-, 9- and 12-month intervals with risks at 18-month intervals. Sensitivity analyses also were performed to assess the potential role of other factors in explaining any differences.

In women aged ≥ 35, the researchers found that maternal mortality or severe morbidity risks were increased at 6-month versus 18-month interpregnancy intervals (0.62% at 6 months vs. 0.26% at 18 months; aRR 2.35; 95% CI, 2.03-2.80). However, the same was not the case in women aged 20 to 34 (0.23% at 6 months vs. 0.25% at 18 months; aRR 0.92; 95% CI, 0.83-1.02).

In women aged 20 to 34 years versus those aged ≥ 35, increased adverse fetal and infant outcome risks were more pronounced (20.0% at 6 months vs. 14% at 18 months; aRR 1.42; 95% CI 1.36-1.47 and 2.1% at 6 months vs. 1.8% at 18 months; aRR 1.15; 95% CI 1.01-1.31, respectively). Risks of spontaneous PTB at 6-month interpregnancy intervals were increased in both age groups, but to a lesser extent in the older women (5.3% at 6 months vs 3.2% at 18 months; aRR 1.65; 95% CI 1.62-1.68 and 5.0% at 6 months vs 3.6% at 18 months; aRR 1.40; 95% CI 1.31-1.49, respectively). Maternal age did not significantly affect the modest increases in risks of SGA and indicated PTB with short interpregnancy intervals. Sensitivity analyses suggested that observed associations were not fully explained by unmeasured confounding.

The authors said their findings, “suggest that the optimal interpregnancy interval is closer to 18 months, with a range of 12 to 24 months having risks that generally are comparable to the nadir at 18 months.” In the case of women aged ≥ 35, they believe that counseling to encourage an interpregnancy interval of 12 or 18 months would help reduce risks. But they acknowledged that in this population, a subsequent pregnancy in a short window of time after the first one often is planned. 

How do pessaries compare with progesterone for preventing early PTB?

While prophylactic use of progesterone has been found to significantly lower rates of preterm birth (PTB), transvaginal placement of a cervical pessary has emerged as a viable alternative. Those two treatments have now been compared in a randomized, noninferiority trial published in Obstetrics & Gynecology.

For the multicenter study, researchers look at the efficacy of progesterone and a cervical pessary in averting spontaneous PTB (sPTB) before 34 weeks’ gestation in women with short cervixes detected by transvaginal ultrasonography (TVUS). 

Conducted from August 2012 to April 2017 in 27 hospitals in Spain, the research included 243 pregnant women with singleton pregnancies and a short cervix (≤ 25 mm) during second-trimester TVUS. They were randomized to a cervical pessary or vaginal progesterone. 

Pessaries were inserted by an ob/gyn and patients in the progesterone group were instructed in self-insertion and told to use 200 mg/day. The treatment was initiated between 20 1/7 and 23 6/7 weeks’, with clinical visits monthly until delivery, during which cervical length was measured transvaginally. Both treatments were discontinued between 37 0/7 and 37 4/7 weeks of gestation. The primary outcome for the study was the proportion of spontaneous births before 34 weeks’ gestation. 

Spontaneous delivery before 34 weeks’ gestation occurred in 14% (18/125) of the pessary group compared with 14% (17/118) in the progesterone group with an absolute risk reduction of –0.01% (95% CI –8.84 to 8.83%). The rate of adverse events was 16% in the pessary group and 11% in the progesterone group. In subgroup analysis, among patients whose cervixes could not be seen on ultrasound at baseline, the authors observed fewer sPTB before 34 weeks’ gestation in the progesterone group compared with the pessary group (26% vs 7%, = .02, respectively). 

The authors believe their findings illustrate noninferiority of the cervical pessary compared with vaginal progesterone for prevention of sPTB before 34 weeks’ gestation in women with short cervixes. The 95% CI of the difference in the rate of this outcome between groups exceeded the prespecified noninferiority margin of 4% although the observed rates of sPTB at < 34 weeks were similar for both treatment groups (14% vs 14%). However, the pessary group had higher rates of intolerability and adverse events (vaginal discomfort and discharge) than the pessary group. These findings suggest that vaginal progesterone should be considered the first option. But the findings, the researchers said, also suggest that for women reluctant to use daily medication, the pessary could be considered an effective alternative. 

Opioid abuse in rural mothers and babies: What are the risks?

Opioid-related hospitalizations among reproductive-age women have been steadily increasing over the past 10 years as have rates of neonatal abstinence syndrome (NAS). Because maternal opioid use disorder (OUD) and NAS disproportionately affect rural communities, it’s important to understand factors that lead to those conditions and a new study of nearly 1 million births adds to that knowledge base.

Published in The Journal of Rural Health, the analysis was designed to identify differences in incidence and sociodemographic correlates associated with diagnosis of maternal OUD and NAS in rural residents. The researchers used hospital discharge data from the 2007-2014 National Inpatient Sample (NIS) to analyze 942,798 deliveries by rural residents and 981,090 infants born to rural residents. The authors used ICD-9-CM codes to identify deliveries and patient clinical characteristics. 

To assess the role of type of hospitals, the authors classified institutions into three categories. Rural micropolitan counties had population centers of 10,000-50,000 and rural noncore counties had population centers >10,000 people. A hospital was considered a teaching hospital if it had a residency program, was a member of the Council of Teaching Hospitals, or had a ratio of full-time equivalent interns and residents to bed of 0.25 or higher. 

Approximately 71% of rural residents in the analysis gave birth at a rural hospital. The remaining births were distributed evenly between urban nonteaching (14.8%) and urban teaching hospitals (14.5%). Micropolitan residents were more likely than noncore residents to give birth in a rural hospital (76.2% vs 61.7%). In terms of demographics, patients most likely to give birth at a rural hospital were younger and not white, had Medicaid coverage, and used tobacco or had a substance use disorder. 

Aggregated prevalence of maternal OUD was 8.9 per 1000 deliveries among rural residents who gave birth at urban teaching hospitals. OUD prevalence at rural hospitals was 4.3 per 1000 births and prevalence at urban nonteaching hospitals was 3.6 per 1000 births. Prevalence of NAS was higher than that of OUD across all hospital categories, with urban teaching hospitals again recording the highest rates (16.7 per 1000 births, 4.7 per 1000 births at rural hospitals and 5.0 per 1000 births and urban nonteaching hospitals). 

Significant correlations between patient demographics and OUD were found to be tobacco use, at least one mental health disorder, and chronic pain diagnosis. Odds of NAS were significantly higher among infants with Medicaid as primary payer and those born in urban hospitals. 

The authors believe their research illustrates the need for discussions about how to better allocate resources to assist rural hospitals with resources to help treat OUD and NAS. Even though nearly half of all rural residents with both maternal OUD and preterm birth (48.3%) deliver at rural hospitals, the highest rates of OUD and NAS diagnosis were in urban teaching hospitals. The researchers believe that could possibly indicate that higher-risk rural patients are being referred to urban hospitals as a result of lower levels of maternal care at rural hospitals. The authors also believe that resources to help combat maternal OUD and NAS should be distributed to all hospital settings because these diagnoses are increasing and rural hospitals may be less equipped to handle the complex needs of patients who often require longer hospital stays following delivery.