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While prenatal iron supplementation reduces the incidence of iron deficiency and iron deficiency anemia in pregnancy, health outcomes for moms and babies are unclear, according to an updated U.S. Preventive Services Task Force (USPSTF) evidence report.

In a systematic review of 17 randomized trials with over 24,000 participants, iron supplementation was associated with a decreased risk of maternal iron deficiency anemia at term compared with placebo or no supplementation in four trials (relative risk 0.40, 95% CI 0.26-0.61), reported Amy Cantor, MD, MPH, of Oregon Health & Science University in Portland, and co-authors.

Six trials also showed that iron supplementation was associated with decreased risk of maternal iron deficiency at term compared with placebo or no supplementation (relative risk 0.47, 95% CI 0.33-0.67), they detailed in .

Approximately 5% of pregnant people have iron deficiency anemia, which comes with a risk of adverse maternal and fetal health outcomes.

Of note, the evidence report turned up no statistically significant differences in maternal quality of life, rates of gestational diabetes, maternal hemorrhage, hypertensive disorders of pregnancy, cesarean delivery, preterm birth, infant low birth weight, or infants small for gestational age with maternal iron supplementation compared with placebo or no supplementation, the authors noted.

In 2015, the USPSTF similarly determined there was insufficient evidence to assess the balance of benefits and harms of both screening pregnant women for iron deficiency anemia, as well as routine iron supplementation for pregnant women. Since then, five new randomized trials on the topic emerged, Cantor and team said, though no studies evaluated the benefits or harms of screening for iron deficiency or iron deficiency anemia during pregnancy.

Despite the inclusion of data from the five new trials, "conclusions were consistent with findings from the previous USPSTF review," the authors wrote.

Based on these findings, the USPSTF concluded in their updated that "the current evidence is insufficient to assess the balance of benefits and harms of screening [and routine supplementation] for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes" (I statements).

In also published in JAMA, Elaine Duryea, MD, and Catherine Spong, MD, both of the University of Texas Southwestern Medical Center in Dallas, noted that while the review focused on randomized trials, other study designs also provide valuable insight and randomized trials come with their own limitations.

"Indeed, the many traditional RCT [randomized clinical trial] designs and implementation approaches limit real-world applicability, discourage involvement and thus applicability to marginalized and underserved populations, and decrease the likelihood that the effect on rare outcomes such as severe maternal morbidity will be detected," Duryea and Spong wrote.

"Large, population-based studies provide additional useful evidence when examining uncommon outcomes with a high impact such as severe maternal morbidity and mortality, transfusion, and death," they added. "An RCT examining such rare outcomes may be cost-prohibitive and thus an ineffective method to approach several aspects of the question at hand."

In published in JAMA Network Open, Aaron Caughey, MD, MPH, PhD, also of Oregon Health & Science University, and colleagues, noted that the USPSTF was unable to find adequate studies to address key questions, "highlighting a significant gap in knowledge," and pointed to three issues.

"First, the insufficient evidence underscored by the USPSTF evidence review and recommendation statement is partly due to the lack of consensus regarding the routine use of screening for iron deficiency in pregnancy and on the screening thresholds for diagnosing iron deficiency," they wrote. "For example, although serum ferritin, a marker of body iron stores, has the highest sensitivity and specificity for diagnosing iron deficiency in pregnancy, there is not a consistently used diagnostic threshold."

"Second, although data to guide the management of iron deficiency in pregnancy are urgently needed, we emphasize the potential for worsening health disparities with a lack of recommendation for screening or oral iron supplementation in the setting of insufficient evidence," they continued. "In particular, this may affect Black women in the United States, who experience higher rates of iron deficiency and iron deficiency anemia compared with others."

"These disparities highlight the urgent need to prioritize studies on screening and treatment for those at risk of racial and ethnic inequities," they added.

Finally, they noted that because of the high prevalence of iron deficiency during pregnancy and the increased iron requirements, the doses used in most of the studies "are likely insufficient for adequate treatment and resulted in the lack of benefit observed."

They recommended that future guidelines "should include literature that differentiates between supplementation for prevention and treatment for diagnosed iron deficiency."

For the evidence report, Cantor and colleagues searched the Ovid Medline and Cochrane databases through May 24, 2023. They included studies from the U.S. and other countries with high United Nations Human Development Index (HDI) scores. Studies of nonpregnant people and those with nutritional deficiency were excluded.

In total, 17 randomized trials and one observational study that assessed the link between improved iron indices and health outcomes were included; 12 of the randomized trials were included in the 2015 review, while five others and the observational study were new.

Supplementation interventions included oral iron supplementation or iron-fortified foods. Screening studies compared screening with no screening or treatment with no treatment and interventions included routine blood tests and supplementation with oral or intravenous iron or iron-fortified foods.

The team noted several limitations, including that non-English articles were excluded and that some of the international studies from high HDI countries may have limited generalizability to the U.S. In addition, publication bias wasn't formally assessed and the methods used to pool studies may have resulted in overly narrow confidence intervals.