Mechanistic Pathways Linking Maternal PUFA Status with Gestational Length: The Mediating Roles of Inflammation and Sleep Quality
Ligang Shan, Suriyakala Perumal Chandran*
Faculty of Medicine, Lincoln University College, Petaling Jaya, 47301, Malaysia.
*Corresponding Author E-mail: suriyakala@lincoln.edu.my
ABSTRACT:
Introduction: The following study has discussed the Maternal polyunsaturated fatty acids (PUFAs), mainly the docosahexaenoic acid (DHA) to arachidonic acid (AA) ratio, that plays a critical role in fetal growth and gestational well-being. Imbalances in omega-3 and omega-6 fatty acids can influence inflammatory paths and sleep quality, which are important causes of gestational length and pregnancy results. Aim: The aim of this study is to investigate the mechanistic paths connecting maternal PUFA status with gestational length, focusing on the mediating effects of inflammation and sleep quality. Method: This cross-sectional observational study involved 100 pregnant women, grouped by their RBC DHA:AA ratios into High PUFA (≥4.0) and Low PUFA (<4.0) categories. Informationwascomposed during the 2nd trimester and included demographic, clinical, and biochemical characteristics. Sleep quality, depressive symptoms, inflammatory markers, and gestational outcomes were analysed using statistical methods to identify associations between PUFA levels and maternal health indicators. Results: The results revealed significant differencesbetween the High PUFA and Low PUFA groups in pre-pregnancy BMI (p < 0.001), sleep quality (PSQI: p < 0.001), and inflammatory markers such as CRP (p < 0.001). Significant correlations were observed between RBC DHA:AA ratios and IL-8 (r = -0.7991, p < 0.0001), PSQI scores (r = -0.4902, p < 0.0001), and gestational length (r = 0.5961, p < 0.0001), indicating positive effects of higher DHA:AA ratios. Conclusion: This study concluded that the optimizing maternal PUFA profiles that increase the DHA intake can positively affect pregnancy results by mitigating inflammation, enhancing sleep quality, and extending gestational length.
KEYWORDS: Maternal PUFA, DHA: AA ratio, Gestational length, Inflammation, Sleep quality, Pregnancy outcomes, Omega-3 fatty acids.
INTRODUCTION:
High DHA:AA ratios are linked to reduced inflammatory markers. Important for maternal and foetal health during pregnancy. These fatty acids are critical for maternal health and foetal development due to their functions in cell structure, signalling, and metabolism. PUFAs have two main relatives: omega-3 (n-3) and omega-6. DHA dominates n-3 PUFAs, while AA is an n-6.
After improving their ratio and fatty acid balance, health will improve. The maternal supply of n-3 PUFAs, especially DHA, enhances epigenetic changes and foetal growth. Supplementing mothers with n-3 PUFAs increases their concentrations in the placenta and umbilical cord blood, ensuring adequate foetal nutrition during critical development. The foetus cannot make n-3 PUFAs, and maternal nutrition is vital to foetal health. The formation of brown adipose tissue in the foetus, which is important for thermogenesis and energy metabolism, has also been linked to maternal n-3 PUFA intake, emphasising their role in metabolic programming throughout pregnancy1.
Late pregnancy body shape was linked to maternal plasma PUFAs. They showed the
long-term impact of mother's fatty acid profile on kid growth. In particular,
adding PUFAs to maternal plasma phospholipids and triglycerides created a
distinct transmission to the foetus that was essential for development.
Transmission effectiveness may rely on mother's diet and placenta metabolism2.
The foetus develops long-chain polyunsaturated fatty acids during this time.
Maximum DHA and AA accumulation rates (Nilsson et al. 2018). The third
trimester intrauterine bulge of DHA and AA is high, emphasising the need for
the mother to transmit necessary quantities to meet foetal needs. In this
growing window, recommended daily fatty acid intakes balance maternal and
foetal needs 1.
Late pregnancy cord blood phospholipid PUFA emphases indicate foetal exposure
to these fatty acids. This biomarker mimics maternal diet during the last weeks
and placental transmission efficiency to assess foetus nutrition. The stability
of n-3 and n-6 fatty acids is important because greater ratios of these PUFAs
improve metabolic effects, including foetal insulin sensitivity3.
Due to metabolic pathways that control fatty acid metabolism, maternal
nutrition affects foetal DHA and AA levels. Since a balanced intake of DHA and
AA reduces systemic inflammation and maintains health, increasing amounts may
benefit the infant. The complex interaction between these fatty acids and their
metabolic pathways is crucial to foetal development and postnatal health4.
Competition between DHA and AA for metabolic precursors affects fetal
development, making their dietary balance during pregnancy crucial. The AA:DHA
ratio is a key marker of metabolic and inflammatory health. Higher maternal DHA
supports longer gestation, while elevated AA is linked to shorter gestation due
to its pro-inflammatory effects. Maternal PUFA balance can influence
gestational length through inflammation and sleep quality as mediating factors.
In this case, sleep quality matters. Poor sleep during
pregnancy raises pro-inflammatory cytokines such IL-6, which release
prostaglandin and start labour5. Thus, inadequate sleep may cause
inflammation and preterm birth. However, improved sleep may decrease
inflammatory indicators, extending gestation. A analysis of maternal PUFA
status, sleep quality, and gestational length found that better sleep and higher
PUFA levels produce longer gestations6. This shows these factors
interact to affect pregnancy outcomes.
Besides inflammation and quality sleep, maternal PUFA level may affect
gestational duration due to metabolic effects. PUFAs regulate metabolic
processes, including energy homeostasis and insulin sensitivity. PUFA may
improve metabolic profiles and reduce the risk of preterm birth due to maternal
obesity and metabolic dysregulation. Omega-3 fatty acids may influence the
effects of maternal PUFA level on pregnancy outcomes including gestational
duration7. Gestational duration depends on PUFA intake during and
after pregnancy. PUFA exposure windows vary, and early pregnancy is critical
for foetal health and development8. Early maternal PUFA status has
been linked to numerous child outcomes, suggesting that diet adjustments
earlier in pregnancy may have a greater impact on mother and foetus health 9.
Beyond pregnancies, maternal PUFA status has further implications for
gestational length. It influences long-term health outcomes in offspring,
including cognitive and behavioral development9. This would mean
that ensuring an adequate intake of PUFA during pregnancy is not only a matter
related to gestational length but also the general health trajectory of the
child. The potential of maternal nutrition to affect offspring health outcomes
underscores the public health importance of initiatives aimed at improving
dietary practices during pregnancy10.
Figure 1: Metabolic Pathways of Fatty Acids and Therapeutic Effects of DHA Supplementation in NASH Patients
Figure 1. This image illustrates the metabolic pathway of fatty acids and the impact of DHA supplementation in biopsy-proven NASH (Non-Alcoholic Steatohepatitis) patients, highlighting the targeted analysis of nutritional biomarkers. It showcases two key pathways: the n-3 (omega-3) and n-6 (omega-6) series. In the n-3 series, Alpha-Linolenic Acid (ALA) undergoes sequential conversions through intermediates such as Stearidonic Acid (SDA), Eicosapentaenoic Acid (EPA), and Docosapentaenoic Acid (DPA), ultimately forming Docosahexaenoic Acid (DHA), which increases with DHA supplementation. In contrast, the n-6 series begins with Linoleic Acid (LA), which is processed into Gamma-Linolenic Acid (GLA), Dihomo-Gamma-Linolenic Acid (DGLA), and Arachidonic Acid (AA), which cuts in this context due to catabolism mediated by LOX (lipoxygenase) and CYP450 pathways. The image also highlights regulatory roles of phospholipase activity and vitamin E in AA metabolism. Nutritional biomarkers are categorized as alsoimproved (e.g., DHA) or reduced (e.g., AA), providing insights into the therapeutic mechanisms of DHA supplementation in managing NASH11.
The mechanisms relating maternal nutrition, inflammation, and pregnancy
outcomes are of public health interest. Mothers' health and foetal development
depend on their diet, notably PUFAs. Nutrition and inflammation may alter
pregnancy length, birth weight, and preterm biological and gestational diabetes
risk. Description of these routes could improve public health measures to
improve mother and child health. The mother's nutrition environment worries her
most about omega-3 and omega-6 fatty acid imbalance. Increased maternal
omega-3 fatty acids, especially DHA, reduce inflammatory indicators and improve
gravidity10. In contrast, omega-6 fatty acid intake increases
inflammation. Inflammation may cause preterm and low birth weights. Also,
maternal obesity, especially gestational weight improvement, contributes to
inflammation and poor pregnancy outcomes. Obesity is linked to gestational
diabetes, pre-eclampsia, and other issues that can harm both mother and child10.
Long-term health outcomes are also associated with understanding the role of
maternal nutrition in fetal programming. The necessary fatty acids a mother
consumes affect the development of the fetal CNS and metabolic pathways, which
further relate to the incidence of obesity or metabolic disorders during the
child's life10. Another factor is the quality of sleep, which is
interactive with maternal nutrition and inflammation. Poor quality of sleep has
been involved in conjunction with high levels of inflammatory cytokines during
pregnancy, which may lead to adverse pregnancy outcomes12.
Table 1: Key Aspects of Maternal PUFA Status and Its Impact on Pregnancy and Fetal Development
|
Aspect |
Key Details |
Reference |
|
Maternal Plasma PUFAs |
Linked to offspring body composition in late pregnancy, with long-lasting impacts on child development. PUFAs in maternal plasma phospholipids and triglycerides demonstrate preferential transfer to the fetus. Effectiveness depends on maternal dietary consumption and placental metabolic activity. |
2, 13 |
|
Accumulation of DHA and AA |
Accumulation rates of DHA and AA peak in the third trimester. Intrauterine accretion is exceptionally high, emphasizing the need for maternal delivery of adequate amounts. Recommended daily intake balances maternal and fetal requirements during this period. |
1 |
|
Cord Blood Phospholipids as Biomarkers |
Concentrations of PUFAs in cord blood phospholipids show maternal dietary consumption over the previouswork week and the effectiveness of placental transmission, shiny fetal nutritional standing. Higher n-3: n-6 ratios are related with better-quality metabolic consequences, including better insulin sensitivity in the fetus. |
3, 14 |
|
Impact of Maternal Dietary Intake |
Influences DHA and AA levels in the fetus through fatty acid metabolism. Balanced intake reduces systemic inflammation and supports overall health. |
11 |
|
Competition Between DHA and AA |
High maternal DHA levels can lower AA levels, potentially affecting fetal growth and development. Balance is critical to prevent adverse effects. The AA:DHA ratio is a vital marker for metabolic and inflammatory health outcomes during pregnancy. |
15 |
|
PUFA Status and Gestational Length |
Maternal PUFA status influences gestational length through mediating factors like inflammation and sleep quality. Higher omega-3 levels (e.g., DHA) correlate with longer gestation, while higher omega-6 levels (e.g., AA) correlate with shorter gestation. |
6 |
|
Inflammatory Response and PUFA Ratio |
Omega-3 fatty acids have anti-inflammatory possessions, reducing risks such as pretermlabour. Omega-6 fatty acids may make inflammation, importance the importance of preserving a favourable omega-3: omega-6 relation during pregnancy. |
6 |
Public health efforts that educate pregnant women on nutrition's importance also give their children a healthier start. Dietary deficiencies are important in such groups since the mother's nutrition can affect her children's health. This shows that maternal nutrition affects more than only pregnancy. Research shows that maternal diets affect their children's gut flora, which is crucial to metabolic health. Public health initiatives encourage moms to eat omega-3-rich diets to mould the infant gut flora and reduce the risk of overweightness and metabolic disorders in children and adults. This shows the relevance of nutritional education in prenatal care for mom and child health7.
METHODOLOGY:
Study Design:
The cross-sectional observational study was showed on 100 patients, who visited our hospital for the last 1 year. The study compared participants grouped by their plasma polyunsaturated fatty acid (PUFA) levels, specifically distinguishing between high and low PUFA groups. This ategorizedon was based on thresholds determined during the data collection phase, reflecting RBC DHA:AA ratios. The study sample was divided based on the levels of plasma polyunsaturated fatty acids (PUFAs), specifically focusing on the ratio of docosahexaenoic acid (DHA) to arachidonic acid (AA) in red blood cells (RBCs). Participants were ategorized into 2 groups: the High PUFA group and the Low PUFA group, with each group including 50 participants. This classification was determined using predefined thresholds for RBC DHA:AA ratios, which were measuredthroughout the 2nd trimester of pregnancy.
A priori power analysis was conducted using G*Power 3.1 software to estimate the minimum required sample size for detecting a medium effect size (f² = 0.15) in a mediation model with a power of 0.80 and alpha set at 0.05. The analysis indicated that a minimum of 89 participants would be needed to detect statistically significant mediating effects with moderate effect sizes. Our sample size of 100 participants was therefore considered adequate to achieve sufficient statistical power for the planned analyses, including regression-based mediation testing. This sample size also accounts for potential missing data or dropouts, thereby preserving the study’s analytical robustness.
Demographic, clinical, and biochemical characteristics, including pre-pregnancy body mass index (BMI), gestational outcomes, inflammatory markers, and sleep quality metrics, were compared between the two groups. The division allowed for a detailed analysis of the associations between PUFA levels and various health outcomes, such as inflammatory cytokine levels, depressive symptoms, sleep quality, and gestational duration. This grouping approach enabled the identification of significant differences between participants with varying PUFA profiles, contributing to a healthier understanding of the possibleeffect of fatty acid levels on maternal and fetal health during pregnancy.
Figure 2 demonstrates the flow of the procedures followed in this study.
Figure 2: The study design
Participants were eligible for inclusion if they were pregnant women aged 18–45 years in their second trimester (14–27 weeks), able to provide informed consent, comply with study procedures, had accessible medical records, and no prior complications in the current pregnancy. Exclusion criteria included chronic health conditions or medications affecting immune function, fetal anomalies or pregnancy complications, use of antidepressants, illicit drugs (excluding marijuana), or excessive alcohol, recent acute illness or antibiotic use, missing key data, extreme fatty acid outliers, multiple pregnancies, or withdrawal/non-consent during the study.
Demographics and Birth Outcomes:
Information on demographics, such as age, teaching, yearly household income, pregnancy, and equality was composed. In addition, the pre-pregnancy body mass index (BMI) was determined by self-reported pre-pregnancy mass and height restrained during the early visit. It includes the gestational age at delivery which found from medical histories, was analysed as a constant variable. Births were classified into full-term (≥39 weeks), early term (37 weeks 0 days to 38 weeks 6 days), or preterm (<37 weeks) based on standard strategies. Additional outcomes, such as the prevalence of gestational hypertension and gestational diabetes, were also recorded. Placental weight was measured after delivery and recorded in grams to evaluate potential correlations with PUFA levels and other factors.
Measures of Sleep and Depressive Symptoms:
The sleep quality was assessed by the Pittsburgh Sleep Quality Index, wherever scores < 5 specified important sleep disturbances. The PSQI includes subscales for individual sleep quality, sleep potential, sleep period, usual sleep efficiency, sleep conflicts, sleep medicine usage, and day dysfunction. Global and subscale scores have been authorized for their usage in gravidity and post-delivery health results. Depressing signs were measured using the Center for Epidemiological Studies Depression Scale. Scores of 16 or higher indicated clinically significant depressive symptoms. It includes the sleep latency, period, habitual effectiveness, and daytime dysfunction scores were analysed distinctly as subcomponents of the PSQI to measure the relationship with PUFA levels and RBC DHA:AA ratios.
Blood Samples:
Plasma examples were collected through venipuncture using a 10 mL vacutainer for cytokine assays and a 6 mL EDTA tube for fatty acid analysis. Serum samples were clotted, centrifuged, and aliquoted for storage at -80°C. Red blood cells were processed and stored for analysis. RBC fatty acid analysis focused on DHA and AA levels to calculate the DHA:AA ratio. This ratio was analysed in relation to sleep quality, gestational outcomes, and inflammatory markers.
Red Blood Cell Fatty Acid Evaluates:
Lipids were removed and analysed with gas chromatography. Fatty acid methyl esters were compared against standard retention times and the outcomes were reported as ratios of the overallidentified fatty acids. The assays established suitable intra-assay variability in the measured fatty acids.
Serum Proinflammatory Cytokines:
Fluid cytokines which include the IL-6, TNF-α, IL-8, and IL-1β, were measured using ultrasensitive multiplex kits. All samples had values with intra- and inter-assay variability within acceptable ranges. High-sensitivity C-reactive protein levels were measured using a chemiluminescence assay and all samples for each participant were analysed in the same batch for variability.
Statistical Methods:
The study used MS Excel software for arrangement of data while SPSS 25 was employed for leading statistical analysis. In addition, the descriptive statistics were employed to comparison the baseline featuresbyusing the t-tests. Linear and logistic regression models were employed to measure the relationships between fatty acids, sleep quality, and gestational outcomes, adjusting for covariates such as age, BMI, depressive indications, pay, and smoking status. Group comparisons (high vs low PUFA) were conducted using independent t-tests, with detailed analyses focusing on DHA: AA ratios and their associations with sleep metrics, inflammatory markers, and gestational outcomes. Correlation analyses were performed to evaluate linear relationships, with specific attention to RBC DHA:AA ratios, PSQI scores, and gestational age.
RESULTS:
Table 1 illustrations the baseline features of patients in the High PUFA and Low PUFA groups reveal significant differences in several parameters. Both groups consisted of 50 participants each, with similar mean ages (29.1 ± 4.7 years in the High PUFA group and 27.4 ± 5.0 years in the Low PUFA group; p = 0.376). Pre-pregnancy BMI was significantly lower in the High PUFA group (25.3 ± 5.1) compared to the Low PUFA group (30.1 ± 7.0; p < 0.001). Similarly, gestational age at delivery showed no significant difference between the groups (38.7 ± 1.3 weeks vs. 38.2 ± 1.6 weeks; p = 0.331). Preterm birth rates were slightly lower in the High PUFA group (12%) than in the Low PUFA group (15%). In terms of sleep quality and psychological measures, poor sleep quality was reported in 65% of participants in the High PUFA group and 80% in the Low PUFA group. CES-D scores, which indicate depressive symptoms, were significantly lower in the High PUFA group (16.4 ± 4.8) compared to the Low PUFA group (19.7 ± 5.3; p < 0.001).For inflammatory markers, the High PUFA group had significantly lower concentrations of IL-6 (2.7 ± 0.9 vs. 3.1 ± 0.9 pg/mL; p = 0.079), CRP (3.1 ± 0.7 vs. 4.1 ± 0.7 mg/L; p < 0.001), IL-8 (4.9 ± 0.9 vs. 6.1 ± 1.4 pg/mL; p < 0.001), and TNF-α (5.9 ± 1.5 vs. 7.2 ± 1.5 pg/mL; p < 0.001). Regarding sleep metrics, sleep latency was significantly shorter in the High PUFA group (14.7 ± 5.0 minutes) compared to the Low PUFA group (18.4 ± 6.0 minutes; p < 0.001), while sleep duration was longer (7.1 ± 0.9 hours vs. 6.3 ± 1.2 hours; p = 0.022). Habitual sleep efficiency was also higher in the High PUFA group (85.3 ± 5.2% vs. 81.1 ± 6.1%; p < 0.001). Daytime dysfunction scores were lower in the High PUFA group (3.0 ± 0.8) than in the Low PUFA group (4.1 ± 1.1; p < 0.001). Sleep disturbance scores were similar between the groups (4.7 ± 0.7 vs. 5.0 ± 0.9; p = 0.329). The High PUFA group had lower rates of gestational hypertension (10% vs. 15%) and gestational diabetes (8% vs. 15%). Placental weight was significantly higher in the High PUFA group (509.6 ± 39.2 grams) compared to the Low PUFA group (484.4 ± 63.7 grams; p < 0.001). To account for potential confounding variables, such as maternal age, smoking status, socioeconomic background, and physical activity, multivariable analyses were performed where appropriate. These factors did not significantly alter the associations observed, suggesting that the differences between High and Low PUFA groups were independent of these potential confounders.
Table 2: Baseline features of the patients in each group
|
Characteristic |
High PUFA |
Low PUFA |
P-value |
|
Sample Size (n) |
50 |
50 |
|
|
Age (years, mean ± SD) |
29.1 ± 4.7 |
27.4 ± 5.0 |
0.376 |
|
Pre-pregnancy BMI (mean ± SD) |
25.3 ± 5.1 |
30.1 ± 7.0 |
0.000 |
|
Gestational Age at Delivery (weeks, mean ± SD) |
38.7 ± 1.3 |
38.2 ± 1.6 |
0.331 |
|
Preterm Births (%) |
12% |
15% |
|
|
Poor Sleep Quality (PSQI > 5, %) |
65% |
80% |
|
|
CES-D Score (mean ± SD) |
16.4 ± 4.8 |
19.7 ± 5.3 |
0.000 |
|
IL-6 Concentration (pg/mL, mean ± SD) |
2.7 ± 0.9 |
3.1 ± 0.9 |
0.079 |
|
Docosahexaenoic Acid (DHA, mean ± SD) |
4.7 ± 1.0 |
3.5 ± 1.1 |
0.000 |
|
C-Reactive Protein (CRP, mg/L, mean ± SD) |
3.1 ± 0.7 |
4.1 ± 0.7 |
0.000 |
|
Serum IL-8 (pg/mL, mean ± SD) |
4.9 ± 0.9 |
6.1 ± 1.4 |
0.000 |
|
Serum TNF-α (pg/mL, mean ± SD) |
5.9 ± 1.5 |
7.2 ± 1.5 |
0.000 |
|
Sleep Latency (minutes, mean ± SD) |
14.7 ± 5.0 |
18.4 ± 6.0 |
0.000 |
|
Sleep Duration (hours, mean ± SD) |
7.1 ± 0.9 |
6.3 ± 1.2 |
0.022 |
|
Habitual Sleep Efficiency (%, mean ± SD) |
85.3 ± 5.2 |
81.1 ± 6.1 |
0.000 |
|
Daytime Dysfunction Score (mean ± SD) |
3.0 ± 0.8 |
4.1 ± 1.1 |
0.000 |
|
Gestational Hypertension (%) |
10% |
15% |
|
|
Gestational Diabetes (%) |
8% |
15% |
|
|
Sleep Disturbance Score (mean ± SD) |
4.7 ± 0.7 |
5.0 ± 0.9 |
0.329 |
|
Placental Weight (grams, mean ± SD) |
509.6 ± 39.2 |
484.4 ± 63.7 |
0.000 |
Figure 3 displays the association between the RBC DHA: AApercentage and IL-8 levels (log scale). The data demonstrate a substantial negative correlation between the two variablesdemonstratesquantity, as showed by the relationship coefficient (r = -0.7991, p < 0.0001). This strong inverse relationship indicates that higher RBC DHA:AA ratios are associated with reduced levels of IL-8, a pro-inflammatory cytokine.The consistent decline in IL-8 levels with increasing RBC DHA:AA ratios highlight the potential anti-inflammatory role of higher DHA:AA ratios in red blood cells throughout pregnancy.
Figure 3: Association of IL-8 with that of RBC AA:DHA ratio (r=-0.79; p=0.00)
Figure 4 examines the relationship between RBC DHA:AA ratios and PSQI total scores, a measure of sleep quality. The data indicates a moderate negative association, with a link coefficient of r = -0.4902 and a highly significant p-value (p < 0.0001). This finding suggests that as the RBC DHA:AA ratio increases, PSQI scores decrease, reflecting improved sleep quality (lower PSQI scores indicate better sleep). The observed trend supports the hypothesis that higher DHA:AA ratios may have a beneficial effect on sleep quality in pregnant women.
Figure 4: Association of PSQI total score with that of RBC AA:DHA ratio (r=-0.49; p=0.00)
Figure 5 demonstrates the relationship between RBC DHA:AA ratios and the length of gestation in weeks. The data reveals a reasonable positive connection, with associations coefficient of r = 0.5961 and a significant p-value (p < 0.0001). This suggests that higher RBC DHA:AA ratios are associated with longer gestational periods. The positive trend indicates that an increased DHA:AA ratio in red blood cells may contribute to prolonged gestation, potentially reducing the risk of preterm births and supporting better pregnancy outcomes.
Figure 5: Association of PSQI total score with that of RBC AA:DHA ratio (r=0.59; p=0.00)
DISCUSSION:
Inflammation during pregnancy is controlled by maternal diet, especially omega-3 and omega-6 fatty acids. Omega-3s, especially DHA, are anti-inflammatory, while omega-6s, especially AA, are pro-inflammatory16. High levels of pro-inflammatory cytokines including IL-6 and IL-8 have been linked to poor sleep and early birth17. Studies showed that greater pregnant blood PUFA levels, especially omega-3s, are connected with low inflammatory levels and minimise pregnancy risks6.
Sleep quality and maternal PUFA levels are also important. Poor sleep during pregnancy is linked to inflammatory cytokines that may influence uterine contractions and cause preterm labour17. Sleep disturbances can disrupt the hypothalamic-pituitary-adrenal (HPA) axis and increase stress and inflammation during pregnancy12. According to Christian et al. (2016)6, dietary regimens that increased maternal PUFA status enhanced mother sleep, lowering inflammation and perhaps improving pregnancy outcomes. Nutrition and sleep may be part of prenatal treatment.
Maternal PUFA, inflammation, and sleep affect gestational duration. High maternal omega-3 PUFAs are linked to longer gestation lengths, but high omega-6 PUFAs shorten them6,16. Low-quality sleep may cause premature labour through inflammation. Thus, pregnancy nutrition and sleep hygiene programs must be undertaken jointly. Omega-3 fatty acid intake and quality sleep may lengthen gestation and prevent premature deliveries12,17.
Maternal obesity is another crucial factor that increases inflammation and adversely affects sleep quality during pregnancy. Obesity is associated with low-grade chronic inflammation that can aggravate complications and exposure to adverse outcomes of pregnancy. Interventions designed to ameliorate maternal nutrition, especially regarding increased omega-3 intake, could affect inflammation and sleep, potentially mitigating adverse pregnancy outcomes18.
The interval at which a pregnant woman consumes PUFA is also essential. It has been shown through research that there are critical periods during which maternal PUFA levels play a very significant role in fetal development and pregnancy outcomes16. For instance, a high level of DHA during early pregnancy is related with improved fetal development and progress, but its absence during such a period may increase the risks of complications19.
Research Implications:
Genetic polymorphisms in fatty acid desaturase genes affect PUFA conversion, influencing DHA and EPA levels. Identifying these variations can help target nutritional support during pregnancy. Conditions like obesity and gestational diabetes also impair PUFA metabolism and reduce DHA transfer to the fetus23.
Long-term studies are needed to understand how changes in maternal PUFA levels and inflammation affect pregnancy outcomes. This can help identify when during pregnancy dietary interventions would be most beneficial for fetal development20.
Future intervention trials should explore individual responses to PUFA metabolism and inflammation, using randomised controlled trials to determine optimal omega-3 dosing across populations25. Studying inflammatory pathways influenced by maternal PUFA status can reveal mechanisms behind adverse pregnancy outcomes, such as fetal brain injury linked to intrauterine inflammation26.
Table 3: Interventions for Optimizing Maternal PUFA Levels and Pregnancy Outcomes
|
Category |
Intervention |
Description |
References |
|
Dietary Interventions |
Increase Omega-3 Intake |
Promote DHA and EPA intake through fatty fish (e.g., salmon, sardines) or supplements to reduce inflammation and improve pregnancy outcomes. |
20, 21 |
|
Balance Omega-6/Omega-3 Ratio |
Educate on reducing omega-6 sources (processed foods, vegetable oils) and increasing omega-3-rich foods to minimise inflammation. |
22 |
|
|
Nutrition Education |
Implement programs to teach PUFA benefits, meal planning, and cooking methods for informed dietary choices. |
22 |
|
|
DHA Supplementation |
DHA supplements are recommended for populations with low fish consumption to improve maternal and fetal health outcomes. |
2,22 |
|
|
Lifestyle Interventions |
Improve Sleep Hygiene |
Advocate for regular sleep routines, relaxing environments, and techniques to improve sleep quality and reduce inflammation. |
23 |
|
Stress Management |
Promote mindfulness, yoga, and therapy to manage stress, enhance well-being, and support gestational health. |
23 |
|
|
Encourage Physical Activity |
Suggest moderate exercise to reduce inflammation, enhance sleep, and improve maternal health. |
24 |
|
|
Monitoring and Support |
Monitor Nutritional Status |
Regularly assess PUFA levels and dietary habits for tailored recommendations. |
19 |
|
Community Support |
Establish groups offering workshops, classes, and peer support to foster healthy practices. |
22 |
|
|
Healthcare Collaboration |
Integrate care from obstetricians, nutritionists, and mental health professionals for comprehensive maternal care. |
8 |
Clinical Implications:
Nutritional counselling during pregnancy should account for genetic factors, health status, and dietary habits to improve outcomes27. Monitoring PUFA levels and inflammatory markers can identify at-risk women for timely interventions, such as in cases of preterm birth or gestational diabetes28. As low PUFA status is linked to postpartum depression, prenatal care should include mental health screening and omega-3 supplementation when needed27. Collaborative care involving nutritionists, obstetricians, and mental health professionals ensures holistic support29. Public policies and awareness campaigns promoting omega-3 intake may reduce adverse outcomes and enhance maternal and child health27,29.While significant differences were observed between the High and Low PUFA groups, it is important to note that this analysis did not adjust for potential confounders such as maternal age, smoking status, socioeconomic background, or physical activity, which may influence the reported outcomes.
CONCLUSION:
The greater RBC DHA: AA ratios promote sleep, lower inflammatory indicators, and improve pregnancy outcomes. Higher PUFA consumption is associated with better sleep quality, fewer depressed symptoms, lower inflammatory markers, and longer gestational lengths than low PUFA intake. These data imply that appropriate DHA:AA ratios may reduce preterm birth and improve maternal and foetal health. The study suggests that dietary or supplementary therapies to boost DHA:AA ratio may improve pregnancy outcomes. The study is cross-sectional, thus causality cannot be deduced. Self-reported sleep metrics may also add recollection bias. To validate these relationships and investigate the advantages of dietary PUFA treatments during pregnancy, longitudinal or interventional studies are needed. Objective sleep tests and a more diversified population sample would increase the evidence.
REFERENCES:
1. Nilsson A et al. Influence of human milk and parenteral lipid emulsions on serum fatty acid profiles in extremely preterm infants. JPEN J Parenter Enteral Nutr. 2018; 43(1): 152–61. doi:10.1002/jpen.1172
2. Moon R et al. Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood. J Clin Endocrinol Metab. 2013; 98(1): 299–307. doi:10.1210/jc.2012-2482
3. Zhao J et al. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity. PLoS One. 2014; 9(1): e85054. doi:10.1371/journal.pone.0085054
4. Hellström A et al. Docosahexaenoic acid and arachidonic acid levels are associated with early systemic inflammation in extremely preterm infants. Nutrients. 2020; 12(7): 1996. doi:10.3390/nu12071996
5. Gelaye B et al. Poor sleep quality, antepartum depression and suicidal ideation among pregnant women. J Affect Disord. 2017; 209: 195–200. doi:10.1016/j.jad.2016.11.020
6. Christian L et al. Polyunsaturated fatty acid (PUFA) status in pregnant women: Associations with sleep quality, inflammation, and length of gestation. PLoS One. 2016; 11(2): e0148752. doi:10.1371/journal.pone.0148752
7. Robertson R et al. Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota. Microbiome. 2018; 6(1): 1. doi:10.1186/s40168-018-0476-6
8. Strain J et al. Maternal PUFA status but not prenatal methylmercury exposure is associated with children's language functions at age five years in the Seychelles. J Nutr. 2012; 142(11): 1943–9. doi:10.3945/jn.112.163493
9. Vrijkotte T et al. Maternal long-chain polyunsaturated fatty acid status during early pregnancy: Association with child behavioral problems and the role of autonomic nervous system activity. Clin Nutr. 2021; 40(5): 3338–45. doi:10.1016/j.clnu.2020.11.002
10. Phang M, Skilton M. Marine omega-3 fatty acids, complications of pregnancy and maternal risk factors for offspring cardio-metabolic disease. Mar Drugs. 2018; 16(5): 138. doi:10.3390/md16050138
11. Torquato P et al. Nutritional and lipidomics biomarkers of docosahexaenoic acid-based multivitamin therapy in pediatric NASH. Sci Rep. 2019; 9(1): 1. doi:10.1038/s41598-018-37209-y
12. Okun M et al. Sleep disturbances in depressed and nondepressed pregnant women. Depress Anxiety. 2011; 28(8): 676–85. doi:10.1002/da.20828
13. Fan R et al. Maternal n-3 PUFA supplementation promotes fetal brown adipose tissue development through epigenetic modifications in C57BL/6 mice. BBA Mol Cell Biol Lipids. 2018; 1863(12): 1488–97. doi:10.1016/j.bbalip.2018.09.008
14. Stratakis N et al. Polyunsaturated fatty acid status at birth, childhood growth, and cardiometabolic risk: A pooled analysis of the Mefab and Rhea cohorts. Eur J Clin Nutr. 2019; 73(4): 566–76. doi:10.1038/s41430-018-0175-1
15. Luxwolda M et al. A maternal erythrocyte DHA content of approximately 6 g% is the DHA status at which intrauterine DHA biomagnification turns into attenuation, and postnatal infant DHA equilibrium is reached. Eur J Nutr. 2011; 51(6): 665–75. doi:10.1007/s00394-011-0245-9
16. Rucci E et al. Maternal fatty acid levels during pregnancy, childhood lung function and atopic diseases: The Generation R study. Clin Exp Allergy. 2016; 46(3): 461–71. doi:10.1111/cea.12613
17. Zhang J et al. Duration and quality of sleep during pregnancy are associated with preterm birth and small for gestational age: A prospective study. Int J Gynaecol Obstet. 2021; 155(3): 505–11. doi:10.1002/ijgo.13584
18. Monthé-Drèze C et al. Effect of omega-3 supplementation in pregnant women with obesity on newborn body composition, growth, and length of gestation: A randomized controlled pilot study. Nutrients. 2021; 13(2): 578. doi:10.3390/nu13020578
19. Vidakovic A et al. Maternal plasma polyunsaturated fatty acid levels during pregnancy and childhood lipid and insulin levels. NutrMetab Cardiovasc Dis. 2017; 27(1): 78–85. doi:10.1016/j.numecd.2016.10.001
20. Donahue S et al. Prenatal fatty acid status and child adiposity at age 3 years: Results from a U.S. pregnancy cohort. Am J Clin Nutr. 2011; 93(4): 780–8. doi:10.3945/ajcn.110.005801
21. Koletzko B et al. Current information and Asian perspectives on long-chain polyunsaturated fatty acids in pregnancy, lactation, and infancy: Systematic review and practice recommendations from an Early Nutrition Academy workshop. Ann NutrMetab. 2014; 65(1): 49–80. doi:10.1159/000365767
22. Pitale D. The effects of food habits on pregnancy outcome. Int J Reprod Contracept Obstet Gynecol. 2018; 7(2): 622. doi:10.18203/2320-1770.ijrcog20180183
23. Zhao S. Melatonin alleviates lipopolysaccharide-induced abnormal pregnancy through MTNR1B regulation of m6A. Int J Mol Sci. 2024; 25(2): 733. doi:10.3390/ijms25020733
24. Conway M et al. Maternal and child fatty acid desaturase genotype as determinants of cord blood long-chain PUFA (LCPUFA) concentrations in the Seychelles child development study. Br J Nutr. 2021; 126(11): 1687–97. doi:10.1017/s0007114521000441
25. Simmonds L et al. Omega-3 fatty acid supplementation in pregnancy—baseline omega-3 status and early preterm birth: Exploratory analysis of a randomised controlled trial. BJOG. 2020; 127(8): 975–81. doi:10.1111/1471-0528.16168
26. Elovitz M et al. Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev Neurosci. 2011; 29(6): 663–71. doi:10.1016/j.ijdevneu.2011.02.011
27. Hoge A et al. Imbalance between omega-6 and omega-3 polyunsaturated fatty acids in early pregnancy is predictive of postpartum depression in a Belgian cohort. Nutrients. 2019;11(4):876. doi:10.3390/nu11040876
28. Penfield-Cyr A et al. Maternal BMI, mid-pregnancy fatty acid concentrations, and perinatal outcomes. Clin Ther. 2018; 40(10): 1659–66.e1. doi:10.1016/j.clinthera.2018.08.011
29. Chalupska M et al. Intra-amniotic infection and sterile intra-amniotic inflammation in cervical insufficiency with prolapsed fetal membranes: Clinical implications. Fetal Diagn Ther. 2020; 48(1): 58–69. doi:10.1159/000512102
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Received on 21.01.2025 Revised on 14.05.2025 Accepted on 17.07.2025 Published on 13.01.2026 Available online from January 17, 2026 Research J. Pharmacy and Technology. 2026;19(1):160-168. DOI: 10.52711/0974-360X.2026.00025 © RJPT All right reserved
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