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CME Author: Zeena Nackerdien

Study Authors: Annette K. Regan, Mika Gissler, et al.; and Mark A. Klebanoff

Target Audience and Goal Statement: Obstetricians, gynecologists, pediatricians, family physicians, primary care physicians

The goal was to assess the association between interpregnancy interval after stillbirth and birth outcomes in the subsequent pregnancy.

Question Addressed:

What were the risks between the inter-pregnancy interval after a stillbirth and the risks of preterm birth, small-for-gestational-age birth, and stillbirth in a subsequent pregnancy?

Study Synopsis and Perspective:

-- the death of a fetus in utero during the second half of pregnancy -- occurs in about 3.5 cases out of every 1,000 births in high-income countries. Stillbirths affect in the U.S. – a rate similar to that of infant death. Rates of early (at 20 to 27 weeks of gestation) and late fetal loss (≥28 weeks) over the last 2 decades have been relatively stable, decreasing by about 30%, according to one . have been identified and proposed may contribute to further stillbirth reductions. In addition, many women also want to know when they can become pregnant again after a stillbirth.

The new study by Annette Regan, PhD, of Curtin University in Perth, Australia, and colleagues reported in found that there was no reason to delay becoming pregnant again, at least for women in high-income regions.

Although the World Health Organization has advised waiting at least 2 years after a live birth and 6 months after a miscarriage or induced abortion before conceiving another child, the evidence to back up that inter-pregnancy interval is scant or mixed, Regan and co-authors said. Their literature review found that most existing studies were of inter-pregnancy intervals following a previous live birth or miscarriage rather than a stillbirth.

To fill this gap, Regan's team looked at 14,452 singleton births in women who previously had a stillbirth (at least 22 weeks gestation) in Finland (1987–2016), Norway (1980–2015), and Western Australia (1980–2015). Inter-pregnancy intervals were grouped as less than 6 months, 6-11 months, 12-23 months, 24-59 months, and more than 59 months.

The median pregnancy interval was found to be 9 months, and 9,109 women (63%) conceived within 12 months of the stillbirth and 37% within 6 months. A total of 228 of these pregnancies (2%) were stillbirths, 2,532 (18%) were preterm births, and 1,284 (9%) were small-for-gestational-age births.

Maternal smoking and low educational attainment were found to be more common in women with inter-pregnancy intervals longer than 24 months than in those with intervals shorter than 24 months. When compared with the results for women with inter-pregnancy intervals of 24-59 months, inter-pregnancy intervals of <6 months were not linked to an increased risk of adverse pregnancy outcomes, including the following:

• Subsequent stillbirth (pooled adjusted OR 1.09, 95% CI 0.63-1.91)

• Preterm birth (pooled adjusted OR 0.91, 95% CI 0.75-1.11)

• Small-for-gestational-age birth (pooled adjusted OR 0.66, 95% CI 0.51-0.85)

• Similarly, there were no increased odds of these outcomes when comparing inter-pregnancy intervals of 6-11 months versus 24-59 months

Additionally, the authors did not note any difference in the association between inter-pregnancy interval and birth outcomes by the gestational length of the previous stillbirth.

Study limitations, the team said, included unmeasured confounders, and since data came from high-income countries, the results may also not be generalizable to low-income or middle-income countries, countries without access to universal health care, or countries with a higher proportion of ethnic minority groups. In addition, information on miscarriages or induced abortions was not available, which could have led to overestimation of inter-pregnancy intervals in some women and limits the application of the findings to pregnancies with a minimum gestation of 22 weeks, the researchers stated.

Source Reference: , online Feb. 28, 2019; DOI: 10.1016/S0140-6736(18)32266-9

Comment: , online Feb. 28, 2019; DOI: 10.1016/S0140-6736(18)32430-9

Study Highlights: Explanation of Findings

Using pooled birth data recorded in Finland, Norway, and Western Australia over a 37-year period, the researchers showed that subsequent stillbirths were rare among 14,452 women whose most recent pregnancy ended in stillbirth after at least 22 weeks' gestation (n=228). About 63% of women became pregnant again within a year of their loss. Short inter-pregnancy intervals (<6 months or 6–11 months) were not associated with an increased risk of any study outcome.

"Our results consistently showed that an interpregnancy interval of less than 1 year was not associated with increased risk of adverse birth outcomes in the next pregnancy, compared with an interval of at least 2 years," Regan said in a press statement. "Our findings provide valuable evidence for recommended pregnancy spacing after a stillbirth. Approximately 3.5 in every 1,000 births in high-income countries are stillborn, and there is limited guidance available for planning future pregnancies. We hope that our findings can provide reassurance to women who wish to become pregnant or unexpectedly become pregnant shortly after a stillbirth."

Writing in an , Mark A. Klebanoff, MD, of the Research Institute at Nationwide Children's Hospital in Columbus, Ohio, said that the results of this study suggest that a pregnancy interval after stillbirth might be less important than previously assumed for women in high-income regions.

In addition, he said, although the authors did not emphasize this, there was some evidence for an association with reduced risk of small-for-gestational-age birth.

Limitations to the research, Klebanoff said, included a lack of information about pregnancy intention and planning and so the results might not apply to women in less favorable conditions, such as in situations of malnutrition, untreated chronic medical conditions, and poor access to quality medical and obstetric care.

"Rather than adhering to hard and fast rules, clinical recommendations should consider a woman's current health status, her current age in conjunction with her desires regarding child spacing and ultimate family size, and particularly following a loss, her emotional readiness to become pregnant again," he wrote.