The prenatal period is a phase of physiological and psychological change for both the mother and the fetus. This stage is indicated by rapid cellular, hormonal, and metabolic modifications that are crucial for supporting maternal well-being and optimal fetal growth (1). Several health factors like anemia, psychological stress, and sleep inadequacy require close monitoring during pregnancy, as they significantly influence the maternal and neonatal outcome (2).

Anemia is one of the predominant medical complications during pregnancy and is considered a major global public health concern. According to the World Health Organization (WHO, 2025), about 35.5% of pregnant women worldwide suffer from anemia. Although frequency has reduced from 40.3% (2000) to 33.5% (2023), anemia in pregnancy is still considered a major global health challenge (WHO global anemia estimates, 2025 (3). Maternal anemia is associated with serious complications like premature membrane rupture, postpartum hemorrhage, and impaired postpartum recovery. For the fetus, anemia increases the risk of low birth weight, preterm delivery, and neonatal asphyxia. Therefore, regular monitoring of hemoglobin (Hb) levels and timely treatment remain essential for prenatal care (4).

Along with anemia, psychological stress has developed as a serious but often underrecognized factor during pregnancy (5). Prenatal stress is associated with both maternal complications and adverse child outcomes, including altered neurodevelopment and increased susceptibility to metabolic disorders later in life (6).

Stress not only affects as a single factor but also contributes to anemia through mechanisms such as reduced nutrient absorption (iron and folate), increased hepcidin activity, systemic inflammation, and oxidative damage to erythrocytes (7). Sleep disturbance represents another interlinked factor, where stress disrupts sleep quality, while poor sleep further aggravates stress and fatigue (8). Nutrient deficiencies, including iron and magnesium depletion during chronic stress, additionally impair restorative sleep, creating a triangle of interconnected health burdens during pregnancy (9).

Management of stress, insomnia, and mild mental health symptoms in pregnancy presents unique clinical challenges. While non-pharmacological strategies such as relaxation techniques, lifestyle modification, and sleep hygiene are preferred as first-line interventions, many women may require additional therapeutic support (10). However, pharmacological treatment options remain limited due to concerns about placental transfer, teratogenic potential, neonatal adaptation syndromes, and maternal tolerability. This therapeutic dilemma has led to growing interest in alternative strategies, particularly herbal medicines, which are often perceived as natural and safe (11). In addition to routine supplementation, supportive therapies may play a complementary role in enhancing maternal well-being and addressing interconnected factors such as stress, sleep disturbance, and nutritional status (12).

Women are the primary users of herbal medicines and often continue their use during pregnancy, with prevalence ranging from 7% to 55% depending on geographic location, ethnicity, cultural traditions, and social status. Reported usage includes about 34% in Australia, nearly 50% in the European Union, and 6%–9% in the USA and Canada (13). The current study focused on Ashwagandha.

Ashwagandha (Withania somnifera), a traditional adaptogenic herb from Ayurvedic medicine, has received increasing scientific attention for its adaptogenic, antioxidant, anti-inflammatory, and neuroprotective properties. It regulates the hypothalamic-pituitary-adrenal (HPA) axis, normalizes cortisol levels, and exerts GABAergic and serotonergic effects, thereby promoting resilience to stress. Preliminary evidence also supports its role in enhancing cognitive performance, reducing fatigue, and improving sleep quality (14, 15). Preclinical investigations further support its safety, with orally administered Ashwagandha root extract (ARE) demonstrating a No Observed Adverse Effect Level (NOAEL) of 2,000 mg/kg body weight. Notably, no toxicity was observed in developing fetuses or pups when adult male and female rats received the extract during reproduction, highlighting its favorable safety profile in reproductive contexts (16).

Notably, a multi-herbal formulation containing Withania somnifera, Emblica officinalis, Asparagus racemosus, and Pueraria tuberosa has previously demonstrated efficacy and safety in managing anemia among pregnant women (17). However, the isolated efficacy and safety profile of Ashwagandha root extract during pregnancy has not been systematically evaluated. Given its growing popularity, elucidating its role in maternal health is both timely and essential.

In view of the need for safe and effective interventions addressing stress, anemia, and sleep disturbances during pregnancy, and the increasing use of herbal supplements in the pregnant population, the present investigation is designed to evaluate ARE as a single intervention. This study is a prospective, randomized, comparative, 12-week clinical trial aimed at rigorously assessing both the efficacy and safety of ARE in pregnant women.

A total of 102 pregnant women were assessed for eligibility, of whom 70 met the inclusion criteria and were randomized to receive either ARE supplementation (n = 35) or SOC (n = 35) (Figure 1; Supplementary Table S1). During the study, three participants in the ARE group and four in the SOC group were lost to follow-up, resulting in 32 and 31 participants, respectively, included in the per-protocol (PP) efficacy analysis. Safety analyses were conducted on the intent-to-treat (ITT) population, which included all randomized participants (ARE: n = 35; SOC: n = 35).

At baseline, the hematological parameters, including Hb, RBC count, haematocrit, MCHC, MCV, and RDW, were comparable in the ARE and SOC groups (Table 1).

In this 12-week study involving pregnant women, the addition of oral supplementation with Ashwagandha root extract (ARE) along with oral iron therapy resulted in significant improvements in hematological parameters, particularly Hb, MCHC, and RDW, compared with oral iron therapy alone. The observed increase in Hb and enhanced RBC quality, as reflected by improved and reduced RDW, suggests a beneficial stimulatory effect of ARE on erythropoiesis (20). These findings align with preclinical studies reporting that withanolides in ARE may enhance hematopoietic activity by promoting erythroid progenitor proliferation, modulating iron metabolism, and supporting hemoglobin synthesis, mechanisms that are particularly beneficial during pregnancy when increased blood volume and iron demands heighten susceptibility to anemia (16).

Baseline Hb levels in both groups indicate that the majority of participants had mild anemia. Though the increase in Hb observed in the ARE group at Week 12 was statistically significant compared with SOC alone; the absolute between-group difference (0.28 g/dL) was modest. Given that baseline hemoglobin values were near the lower limit of normal for pregnancy, the observed magnitude of change is likely to have limited clinical relevance at the individual level. Consequently, the hematological findings should be interpreted as supportive rather than definitive evidence of therapeutic benefit (17).

Although RBC count showed a trend toward improvement (0.21 million/µL; p = 0.088) with ARE, hematocrit changes with ARE were comparable to SOC, indicating that ARE primarily enhanced red cell quality rather than total blood volume expansion. The significant reduction in RDW suggests a more uniform erythrocyte population, which may translate to improved oxygen-carrying capacity and maternal-fetal health outcomes (21).

Importantly, ARE supplementation demonstrated a favorable tolerable profile across multiple organ systems. Liver enzymes were largely stable, with a modest but significant decrease in AST (–0.70 U/L; 95% CI: −1.20 to −0.20; p = 0.007; Cohen's d = –0.707), while ALT, ALP, and bilirubin levels remained unchanged (22). Renal markers (creatinine, BUN), cardiac marker CK-MB, and thyroid parameters (TSH, T4, and T3) showed no significant changes, supporting systemic tolerability during pregnancy (23). The absence of adverse changes in these parameters is critical in the prenatal population, reinforcing the suitability of ARE as a suitable adjunct for hematological support (24).

Overall, this study demonstrates that ARE supplementation in pregnant women effectively improves erythrocyte indices, enhances RBC quality, and is well-tolerated, suggesting a beneficial role for Ashwagandha in supporting maternal hematological health without compromising hepatic, renal, cardiac, or thyroid function. The observed reductions in perceived stress and improvements in sleep parameters among pregnant women receiving ARE are consistent with the known adaptogenic and anxiolytic properties of the herb (14, 15). Mechanistic studies indicate that withanolides, the primary bioactive constituents of ARE modulate the hypothalamic–pituitary–adrenal (HPA) axis, attenuating cortisol release and enhancing resilience to psychosocial stressors (25). By dampening HPA axis hyperactivity, ARE may reduce physiological stress responses, facilitating improvements in both perceived stress and sleep quality (14, 15). These findings are particularly reassuring given that the supplementation was administered in the second trimester, a period when maternal and fetal physiology are highly sensitive to external interventions. The absence of adverse effects confirms that ARE is tolerable when administered along with standard prenatal care.

In pregnancy, when both physiological and psychological stress can adversely affect maternal and fetal outcomes, these adaptogenic effects are particularly relevant (26). The present findings demonstrate that ARE supplementation not only lowers perceived stress scores but also improves multiple dimensions of sleep, including sleep latency, duration, and subjective quality. These improvements are likely mediated via HPA axis modulation and consequent reductions in stress-related hyperarousal, highlighting a direct mechanistic link between the biological effects of ARE and beneficial outcomes in this population (25).

Beyond stress and sleep, ARE supplementation demonstrated hematopoietic benefits, with observed improvements in erythropoiesis (27). The observed sleep benefits align with prior mechanistic studies showing that ARE promotes restorative sleep through HPA axis modulation and cortisol reduction. In the context of pregnancy, improved sleep latency and quality may translate into better maternal energy, mood regulation, and overall well-being (9, 15). Furthermore, these benefits may reduce reliance on pharmacologic sleep aids, offering a non-pharmacologic strategy for managing pregnancy-related sleep disturbances (28).

Taken together, the convergence of mechanistic evidence and clinical findings highlights the efficacy of ARE in pregnant women. By modulating the HPA axis, reducing cortisol levels, and exerting anxiolytic and adaptogenic effects, ARE supplementation may provide meaningful improvements in stress resilience, sleep quality, and hematopoietic health, without compromising maternal systemic safety (14, 15). These data support the potential role of ARE as a safe and efficacious adjunctive intervention for enhancing maternal well-being during pregnancy (17).

The absence of adverse events in this study, along with stable hepatic, renal, cardiac, and thyroid parameters, supports compliance with safety requirements typically expected for prenatal supplementation. These findings provide preliminary evidence that ARE may be integrated into maternal health strategies without violating regulatory standards.

While the present study demonstrates beneficial effects of ARE on hematological parameters, stress, and sleep in pregnant women, several limitations should be acknowledged. First, the sample size was relatively small, which may limit the generalizability of findings and the statistical power for detecting less pronounced effects. Second, the study duration was limited to 12 weeks; longer-term effects on maternal and fetal outcomes remain unknown. Third, this was a single-center study, and multi-center trials would help confirm the reproducibility of these findings across diverse populations. Fourth, fetal health outcomes were not assessed; although no maternal adverse events were reported, future studies are planned to monitor fetal development and growth parameters to ensure a comprehensive safety evaluation. The use of multiple paired and unpaired t-tests, rather than repeated-measures or mixed-effects modeling, represents a methodological limitation and may not fully account for within-subject correlations over time. Finally, while hematologic and sleep-related outcomes were rigorously monitored, other potential effects of ARE on metabolic or immunological parameters during pregnancy were not explored and could benefit from further investigation.

This study employed an open-label design, which introduces the potential for performance and detection bias, particularly for subjective, patient-reported outcomes such as perceived stress (PSS-10) and sleep quality (PSQI). While objective hematological and biochemical parameters are less susceptible to expectancy effects, self-reported measures may have been influenced by participants’ awareness of receiving an herbal intervention perceived as beneficial. Consequently, improvements in stress and sleep should be interpreted as associations rather than causal effects.

Given the ethical considerations in pregnancy, particularly the need to provide all participants with standard-of-care hematinic supplementation, a placebo arm was not included. Instead, participants were randomized to receive either ARE plus hematinic or hematinic alone. This design allowed evaluation of the additive benefit of ARE while ensuring no participant was deprived of essential antenatal care. The absence of a placebo-only control limits attribution of observed effects exclusively to the herbal intervention, particularly for subjective outcomes.

Routine fetal ultrasound scans were not incorporated into the study protocol, as all participants continued to receive standard antenatal care under their obstetricians. However, it was planned that in the event that an AE or SAE with potential fetal implications was reported, a fetal ultrasound scan was to be performed at the discretion of the treating physician to ensure maternal and fetal safety.

In this randomized 12-week study involving pregnant women, adjunctive administration of Ashwagandha root extract (ARE) along with standard hematinic therapy was associated with modest improvements across maternal hematological parameters and patient-reported stress and sleep outcomes. The extract was well tolerated in the short term, with no clinically significant abnormalities observed in routine biochemical safety markers. Based on these findings, ARE appears to be helpful and well-tolerated, and is proposed to serve as a beneficial adjunctive option for supporting hematological health, stress resilience, and sleep quality in pregnant women.