Impact of topical airway anesthesia on immediate postoperative cough/bucking: a systematic review and meta-analysis

Abstract Background Postoperative cough may occur after tracheal intubation, but it is indistinct which drug is best at diminishing these events. Additionally, airway reflexes are commonly accompanied by severe hemodynamics responses during emergence. Objectives To evaluate the role of topical airway anesthesia on immediate post-extubation cough/bucking and extubation time. Methods Randomized clinical trials from MEDLINE, EMBASE, CENTRAL, and LILACS published until December 23, 2020 were included. Our primary outcome was postoperative cough/bucking incidence which was compared between local anesthetics and controls. Extubation times were likewise considered. Predisposition appraisal and subgroup, affectability investigations were likewise performed. Results The pooled analysis found a 45% reduction in cough incidence after treatment with topical airway local anesthetic (RR = 0.55; 95% CI: 0.42 to 0.72; p< 0.001). The number needed to treat (NNT) was 4.61. The intervention showed no differences in reduction of the extubation time (mean difference = -0.07; 95% CI: -0.14 to 0.28; p= 0.49). Conclusion Topical airway anesthesia demonstrated better than placebo or no medication in reducing immediate post-extubation cough/bucking. Further studies could have this objective to combine the different ways to perform better outcomes for patients.

Impact of topical airway anesthesia on immediate postoperative cough/bucking: a systematic review and meta-analysis.

BACKGROUND: Postoperative cough may occur after tracheal intubation, but it is indistinct which drug is best at diminishing these events. Additionally, airway reflexes are commonly accompanied by severe hemodynamics responses during emergence. OBJECTIVES: To evaluate the role of topical airway anesthesia on immediate post-extubation cough/bucking and extubation time. METHODS: Randomized clinical trials from MEDLINE, EMBASE, CENTRAL, and LILACS published until December 23, 2020 were included. Our primary outcome was postoperative cough/bucking incidence which was compared between local anesthetics and controls. Extubation times were likewise considered. Predisposition appraisal and subgroup, affectability investigations were likewise performed. RESULTS: The pooled analysis found a 45% reduction in cough incidence after treatment with topical airway local anesthetic (RR.á=.á0.55; 95% CI: 0.42 to 0.72; p.á<.á0.001). The number needed to treat (NNT) was 4.61. The intervention showed no differences in reduction of the extubation time (mean difference = -0.07; 95% CI: -0.14 to 0.28; p.á=.á0.49). CONCLUSION: Topical airway anesthesia demonstrated better than placebo or no medication in reducing immediate post-extubation cough/bucking. Further studies could have this objective to combine the different ways to perform better outcomes for patients.

The impact of alfentanil supplementation on the sedation of bronchoscopy: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of alfentanil supplementation for the sedation of bronchoscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of alfentanil supplementation on the sedation during bronchoscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through December 2019 for randomized controlled trials (RCTs) assessing the effect of alfentanil supplementation versus placebo for the sedation during bronchoscopy. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs are included in the meta-analysis. Overall, compared with control group for bronchoscopy, alfentanyl supplementation is associated with significantly reduced coughing scores (Std. MD = -0.55; 95% CI = -0.96 to -0.14; P = 0.009) and dose of propofol (Std. MD = -0.34; 95% CI = -0.64 to -0.04; P = 0.03), but reveals the increase in hypoxemia (RR = 1.56; 95% CI = 1.17 to 2.08; P = 0.002). CONCLUSIONS: Alfentanyl supplementation benefits to reduce coughing scores and dose of propofol for bronchoscopy, but increases the incidence of hypoxemia. The use of alfentanyl supplementation for bronchoscopy should be with caution.

Effects of respiratory muscle training on cough function in neurological disorders: A systematic review with meta-analysis.

BACKGROUND: Patients with neurological disorders can present the weakness of respiratory muscle and impaired cough function. Previous studies have shown that respiratory muscle strength training (RMT) is an effective method of improving the strength of respiratory muscle. The effects of RMT on cough function remain controversial. OBJECTIVE: We aimed to analyze randomized controlled trials (RCTs) that investigated the effects of RMT on cough function of patients with neurological disorders. METHODS: Pubmed, Medline, Embase, and the Cochrane Library were searched electronically for RCTs. Two reviewers independently performed data extraction and quality assessment. Data were analyzed by using RevMan 5.3 software of The Cochrane Collaboration. RESULTS: Five studies with 185 participants were included. The mean PEDro score was 6.2 (range 5 to 7), showing moderate methodological quality. Random-effects meta-analyses showed that respiratory muscle training improved peak expiratory cough flow of voluntary cough by 2.16 (95% CI 1.16 to 3.17) and involuntary cough by 2.84 (95% CI 1.29 to 4.39), with statistical significance (P < 0.0001, P = 0.0003). The experimental group had an improvement of 0.19 cmH2O (95% CI -0.12 to 0.5) on the maximal inspiratory pressure, 0.09 cmH2O (95% CI -0.23 to 0.42) on the maximal expiratory pressure, but with no statistical significance (P = 0.23, P = 0.58) between groups. CONCLUSION: Respiratory muscle training was considered as an effective method for improving cough function. However, this review was insufficient to conclude whether respiratory muscle training was effective in improving inspiratory and expiratory muscle strength, this was opposite with previous meta-analysis. These effects might due to the small samples and different diseases.

Standardized Extract of Atractylodis Rhizoma Alba and Fructus Schisandrae Ameliorates Coughing and Increases Expectoration of Phlegm.

Cough and phlegm frequently occur in respiratory diseases like upper respiratory tract infections, acute bronchitis, and chronic obstructive pulmonary diseases. To relieve these symptoms and diseases, various ingredients are being used despite the debates on their clinical efficacy. We aimed to investigate the effects of the extract CKD-497, composed of Atractylodis Rhizoma Alba and Fructus Schisandrae, in relieving cough and facilitating expectoration of phlegm. CKD-497 was found to inhibit inflammatory mediators such as interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-treated mouse macrophages and transient receptor potential cation channel 1 (TRPV-1)-overexpressed human bronchial epithelial cells stimulated by capsaicin. CKD-497 decreased the viscosity of the mucin solution. During in vivo experiments, CKD-497 reduced coughing numbers and increased expectoration of phlegm via mucociliary clearance enhancement. Collectively, these data suggest that CKD-497 possesses potential for cough and phlegm expectoration treatment.

A Randomized Trial of Nebulized Lignocaine, Lignocaine Spray, or Their Combination for Topical Anesthesia During Diagnostic Flexible Bronchoscopy.

BACKGROUND: The optimal mode of delivering topical anesthesia during flexible bronchoscopy remains unknown. This article compares the efficacy and safety of nebulized lignocaine, lignocaine oropharyngeal spray, or their combination. METHODS: Consecutive subjects were randomized 1:1:1 to receive nebulized lignocaine (2.5 mL of 4% solution, group A), oropharyngeal spray (10 actuations of 10% lignocaine, group B), or nebulization (2.5 mL, 4% lignocaine) and two actuations of 10% lignocaine spray (group C). The primary outcome was the subject-rated severity of cough according to a visual analog scale. The secondary outcomes included bronchoscopist-rated severity of cough and overall procedural satisfaction on a visual analog scale, total lignocaine dose, subject's willingness to undergo a repeat procedure, adverse reactions to lignocaine, and others. RESULTS: A total of 1,050 subjects (median age, 51 years; 64.8% men) were included. The median (interquartile range) score for subject-rated cough severity was significantly lower in group B compared to group C or group A (4 [1-10] vs 11 [4-24] vs 13 [5-30], respectively; P < .001). The bronchoscopist-rated severity of cough was also the least (P < .001), and the overall satisfaction was highest in group B (P < .001). The cumulative lignocaine dose administered was the least in group B (P < .001). A significantly higher proportion of subjects (P < .001) were willing to undergo a repeat bronchoscopy in group B (73.7%) than in groups A (49.1%) and C (59.4%). No lignocaine-related adverse events were observed. CONCLUSIONS: Ten actuations of 10% lignocaine oropharyngeal spray were superior to nebulized lignocaine or their combination for topical anesthesia during diagnostic flexible bronchoscopy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03109392; URL: www.clinicaltrials.gov.

Clinical Research on Prevention and Treatment of Respiratory Tract Complications With Acupoint Application After Operation Under General Anesthesia.

There are various respiratory tract complications in patients undergoing general anesthesia, with postoperative sore throat (POST) being the most commonly seen. Although measures have been taken to prevent and treat POST in clinical practice, the control of POST is still not satisfactory. In this study, 880 ASA patients with grade I to II general anesthesia were randomly assigned into control group and experimental group. After patients entered into the operating room, the plasters were applied to the designated points (Tianzhu, Lianquan, Dazhui, etc), and the clinical efficacy of acupoint application in prevention and treatment of respiratory tract complications after general anesthesia was observed. The results showed that patients starting using acupoint application before operation could significantly reduce the incidence of postoperative respiratory tract complications, and the effects lasted for up to 24 hours. In this study, acupoint application was used, providing a simple, safe, efficient, and durable approach to prevent and treat respiratory tract complications after operation under general anesthesia.

NMR based metabolomic comparison of the antitussive and expectorant effect of Farfarae Flos collected at different stages.

Farfarae Flos (FF) is widely used for the treatment of cough, bronchitis, and asthmatic disorders in the Traditional Chinese Medicine (TCM). According to the experience of TCM, only the flower bud can be used as herbal drug, and its medicinal quality becomes lower after blooming. However, the underlying scientific basis for this phenomenon is not fully understood. In this study, the chemical components and the bioactivities of the FF collected at three different development stages were compared systematically. NMR based fingerprint coupled with multivariate analysis showed that the flower buds differed greatly from the fully opened flower both on the secondary and primary metabolites, and the animal experiments showed that the fully opened flower exhibited no antitussive or expectorant effect. In addition, the endogenous metabolites correlated with the antitussive and expectorant effect of FF were also identified. These findings are useful for understanding the rationality of the traditional use of FF, and also suggested the components responsible for the antitussive and expectorant effect of FF.

Antitussive, expectorant, and anti-inflammatory activities of four caffeoylquinic acids isolated from Tussilago farfara.

CONTEXT: The flower bud of Tussilago farfara L. (Compositae) (FTF) is one of the traditional Chinese medicinal herbs used to treat cough, phlegm, bronchitic, and asthmatic conditions. OBJECTIVE: The objective of this study is to isolate four caffeoylquinic acids from the ethyl acetate extract (EtE) of FTF and to evaluate their antitussive, expectorant, and anti-inflammatory activities. MATERIALS AND METHODS: The structures of compounds 1-4 isolated from EtE were determined by spectral analysis. Mice were orally treated with these compounds and their mixture (in a ratio of 5:28:41:26 as in EtE) at doses of 10 and 20 mg/kg once daily for 3 d. The antitussive and expectorant activities were evaluated separately with the ammonia liquor-induced model and the phenol red secretion model. The anti-inflammation activity was evaluated using leukocyte count in the bronchoalveolar lavage fluid after ammonia liquor-induced acute airway inflammation. RESULTS: The four compounds were identified as chlorogenic acid (1), 3,5-dicaffeoylquinic acid (2), 3,4-dicaffeoylquinic acid (3), and 4,5-dicaffeoylquinic acid (4). All compounds, especially compound 4 (58.0% inhibition in cough frequency), showed a significant antitussive effect. However, the mixture was the most effective to inhibit the cough frequency by 61.7%. All compounds also showed a significant expectorant effect, while compound 2 was the most potent to enhance the phenol red secretion by 35.7%. All compounds significantly alleviated inflammation, but compound 4 showed the strongest effect to inhibit the leukocytosis by 49.7%. DISCUSSION AND CONCLUSION: The caffeoylquinic acids and their mixture, exhibiting significant antitussive, expectorant, and anti-inflammatory effects, could be considered as the main effective ingredients of FTF, and they may act in a collective and synergistic way.

[Efficacy and safety of acute bronchitis treatment in adults--a comparison of Bronchosol® syrup and synthetic preparations with ambroxol. Results of observational study]. / Skutecznosc i tolerancja syropu Bronchosol® w leczeniu ostrego zapalenia oskrzeli u doroslych. Porównanie z preparatami syntetycznymi zawierajacymi ambroksol--badanie obserwacyjne.

INTRODUCTION: Upper respiratory tract infections (URTI), including acute bronchitis, are the frequent health problems and the most common reason for acute cough in adults. Even though the infections are caused mainly by viruses, and their course is usually not complicated, febrifuges, i.a. mucokinetics, or antitussives are used in the treatment of URTI in order to improve the quality of life and safety of patients. THE AIM: To evaluate the efficacy and safety of Bronchosol® herbal syrup in comparison to ambroxol preparations in the treatment of acute bronchitis in adult patients. MATERIALS AND METHODS: The Bronchosol®/2013 study was a non-interventional, prospective, open-label, observational study. Data from adult patients treated with Bronchosol® syrup for acute bronchitis were collected and compared with data from patients treated for the same condition with ambroxol preparations. The severity of bronchitis symptoms was evaluated with the BSS (Bronchitis Severity Score) scale, and patients'quality of life wasassessed with the VAS (Visual Analogue Scale) scale. Between visits patients conducted self-observations and filled out observation diaries. Moreover, the data on adverse events were collected. RESULTS: In 87.68% of patients the infections were cured. Most of patients considered the studied drugs to be the agent decreasing the duration of infection and its intensity. The percentage of patients who declared that they had a less intense cough than during earlier infections was higher in the group of patients treated with Bronchosol® syrup in comparison to ambroxol treated patients (60.22% vs. 45.03%). 91.94% of patients treated with Bronchosol® considered this syrup to be very safe; in the ambroxol group such a declaration was made by 76.61% of patients. CONCLUSIONS: Bronchosol® syrup is an efficient, well-tolerated, and safe drug. Its efficacy in the treatment of acute bronchitis symptoms in adult patients is similar to the efficacy of ambroxol preparations.

Inhibition of cough reflex sensitivity by diphenhydramine during acute viral respiratory tract infection.

BACKGROUND: Currently available over-the-counter cough remedies historically have been criticized for lack of scientific evidence supporting their efficacy. Although the first-generation antihistamine diphenhydramine is classified as an antitussive by the United States Food and Drug Administration, to the authors' knowledge it has never been shown to inhibit cough reflex sensitivity in subjects with pathological cough. OBJECTIVE: To evaluate the effect of diphenhydramine on cough reflex sensitivity. SETTING: Montefiore Medical Center, an academic medical center in New York City. METHODS: Twenty two subjects with acute viral upper respiratory tract infection (common cold) underwent cough reflex sensitivity measurement employing capsaicin challenge on 3 separate days, 2 h after ingesting single doses of study drug (to coincide with peak blood concentrations), administered in randomized, double-blind manner: a multicomponent syrup containing diphenhydramine (25 mg), phenylephrine (10 mg), in a natural cocoa formulation; dextromethorphan (30 mg) syrup; and, placebo syrup. The standard endpoint of cough challenge was used: concentration of capsaicin inducing ≥5 coughs (C5). MAIN OUTCOME MEASURE: Effect on cough reflex sensitivity (C5). RESULTS: A significant difference (p = 0.0024) was established among groups, with pairwise analysis revealing a significant increase in mean log C5 (0.4 ± 0.55 (SD); p < 0.01) for the diphenhydramine-containing medication versus placebo, but not for dextromethorphan versus placebo. CONCLUSIONS: Our results provide the initial evidence of the ability of diphenhydramine to inhibit cough reflex sensitivity in subjects with acute pathological cough. Timing of cough reflex sensitivity measurement may not have allowed demonstration of maximal antitussive effect of dextromethorphan.

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

AIMS: The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. METHODS: In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. RESULTS: Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. CONCLUSIONS: We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses.

Randomized controlled trial of whole soy and isoflavone daidzein on menopausal symptoms in equol-producing Chinese postmenopausal women.

OBJECTIVE: Dietary supplements containing soy or isoflavones are widely used as alternatives to hormone therapy. However, their efficacy is still inconclusive, and limited data on equol producers are available. The aim of this study was to examine the effect of whole soy (soy flour) or purified daidzein (one major soy isoflavone and the precursor of equol) on menopausal symptoms in equol-producing postmenopausal women, a population most likely to benefit from soy intervention. METHODS: This is a 6-month parallel-group, double-blind, randomized, placebo-controlled trial. Two hundred seventy equol-producing prehypertensive Chinese postmenopausal women were randomized to one of three treatment groups: 40 g of soy flour (whole soy group), 40 g of low-fat milk powder + 63 mg of daidzein (daidzein group), or 40 g of low-fat milk powder (placebo group) daily, each given as a solid beverage for 6 months. Changes in menopausal symptoms were assessed by a validated and structured symptom checklist at baseline and 6 months. RESULTS: Two hundred fifty-three participants completed the study according to protocol. Urinary isoflavones indicated good compliance with the interventions. Baseline menopausal symptoms were comparable among the three study groups. Intention-to-treat analysis indicated that there was no significant difference in the 6-month changes or percent changes in the total number of menopausal symptoms, in the five dimensions of symptoms, and in the frequencies of individual symptoms among the three treatment groups. CONCLUSIONS: Whole soy and purified daidzein have no significant effect on alleviation of menopausal symptoms among equol-producing postmenopausal women with prehypertension.

Effect of simultaneous supplementation of vitamin A and iron on diarrheal and respiratory tract infection in preschool children in Chengdu City, China.

OBJECTIVE: The goal of this study was to investigate whether vitamin A combined with iron supplementation for preschool children resulted in improved changes in children's infectious morbidity. METHOD: In this randomized placebo-controlled and blinded field intervention trial, totally 445 preschoolers, ages 3 to 6 y old, were randomly selected. All children were randomly divided into four groups: vitamin A supplement-only group (group I), iron supplement-only group (group II), vitamin A and iron supplement group (group III), and no vitamin A and ferrous sulfate as placebo-control (group IV) for 6 mo. The morbidity of diarrhea and respiratory infections, were collected during supplementation. RESULTS: There was evidence of the lowest incidence rate of respiratory-related illnesses and fewest symptoms of runny nose, cough, and fever for children in group III compared with children in groups I, II and IV (P < 0.05). Moreover, despite the undistinguished incidence rate of vomiting, nausea, and stomach pain, the rate of diarrhea-related illness was significantly lower for children in group III than for those in the other three groups. CONCLUSION: The beneficial affects on infectious morbidity over 6 mo, highlight the potential of vitamin A plus an iron supplement for preschool-aged children.

[Sugammadex reversal after extubation under muscle relaxation to prevent cough reflex in a patient with intractable spontaneous pneumothorax].

A 40-year-old man (168 cm tall and weighing 71 kg) with intractable pneumothorax was operated for resection of a bulla in the left lung. After insertion of epidural catheter via T 5-6 interspace, general anesthesia was induced and maintained with propofol, remifentanil and rocuronium. The duration of surgery was 1h 48 min and rocuronium given during surgery was 110 mg. After completion of surgery, the double-lumen tube was replaced with laryngeal mask airway to prevent cough reflex. However, infusion of sugammadex 200 mg induced mild cough reflex, resulting in air leakage from thoracic drainage. Because air leakage still continued after extubation, reoperation must be done and re-intubation was required. Since rocuronium 50 mg did not provide satisfactory muscle relaxation measured by train of four, additional dose of rocuronium 40 mg was administered and re-intubation was successfully performed without cough reflex. Reoperation lasted for 43 minutes and rocuronium infused was 100 mg. Nasal airway was inserted to prevent airway obstruction by the tongue and extubation was performed under muscle relaxation with infusion of rocuronium 10 mg. And then, immediate administration of sugammadex 400 mg could elicit spontaneous respiration without cough reflex.

A randomized, double-blind comparison of licorice versus sugar-water gargle for prevention of postoperative sore throat and postextubation coughing.

BACKGROUND: One small study suggests that gargling with licorice before induction of anesthesia reduces the risk of postoperative sore throat. Double-lumen tubes are large and thus especially likely to provoke sore throats. We therefore tested the hypothesis that preoperative gargling with licorice solution prevents postoperative sore throat and postextubation coughing in patients intubated with double-lumen tubes. METHODS: We enrolled 236 patients having elective thoracic surgery who required intubation with a double-lumen endotracheal tube. Patients were randomly assigned to gargle 5 minutes before induction of anesthesia for 1 minute with: (1) Extractum Liquiritiae Fluidum (licorice 0.5 g); or (2) Sirupus Simplex (sugar 5 g); each diluted in 30 mL water. Sore throat and postextubation coughing were evaluated 30 minutes, 90 minutes, and 4 hours after arrival in the postanesthesia care unit, and the first postoperative morning using an 11-point Likert scale by an investigator blinded to treatment. RESULTS: The incidence of postoperative sore throat was significantly reduced in patients who gargled with licorice rather than sugar-water: 19% and 36% at 30 minutes, 10% and 35% at 1.5 hours, and 21% and 45% at 4 hours, respectively. The corresponding estimated treatment effects (relative risks) were 0.54 (95% CI, 0.30-0.99, licorice versus sugar-water; P = 0.005), 0.31 (0.14-0.68) (P < 0.001), and 0.48 (0.28-0.83) (P < 0.001). CONCLUSION: Licorice gargling halved the incidence of sore throat. Preinduction gargling with licorice appears to be a simple way to prevent a common and bothersome complication.

Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in chronic cough.

INTRODUCTION: Chronic cough is a common clinical problem and there is a shortage of effective treatments for it. Within the group of transient receptor potential ion channels a receptor for the cooling substance menthol has been identified. This study aimed to assess whether pre-inhalation of dissolved, nebulised menthol could increase capsaicin cough thresholds and influence spirometric values. METHODS: Fourteen patients with chronic cough and airway sensitivity to environmental irritants and 15 control subjects were tested on three occasions. Each one inhaled a 1 mL of nebulised menthol solution of 0.5% or 1% or placebo (saline with 0.05% menthol) at each visit in a randomized and double-blind order. They were then provoked by capsaicin inhalation. RESULTS: Patients' cough thresholds differed significantly from the controls' on all three provocations (P < 0.0001). After inhalation of 1% menthol, the patients' cough thresholds were significantly higher (P < 0.02) compared to after placebo inhalation and to after 0.5% menthol inhalation (P < 0.05). The patients' peak inspiratory flows were significantly reduced after inhalation of the placebo (saline) (P < 0.05) but not after inhalation of 0.5% or 1% menthol. Forced inspiratory flows 50% were lowered after inhalation of placebo and of 0.5% menthol (P < 0.05) but not after 1% menthol. Among the controls, forced inspiratory flows 50% were lowered after only placebo inhalation (P < 0.05). CONCLUSIONS: In patients with chronic cough, pre-inhalation of menthol reduces cough sensitivity to inhaled capsaicin and influences inspiratory flows. The findings may provide scientific support for the common practice of using menthol as a reliever for variant airway discomfort. The use of menthol in different cigarette brands could be questioned since it could conceal the natural irritation following smoking.

Prenatal docosahexaenoic acid supplementation and infant morbidity: randomized controlled trial.

OBJECTIVE: Long-chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA) influence immune function and inflammation; however, the influence of maternal DHA supplementation on infant morbidity is unknown. We investigated the effects of prenatal DHA supplementation on infant morbidity. METHODS: In a double-blind randomized controlled trial conducted in Mexico, pregnant women received daily supplementation with 400 mg of DHA or placebo from 18 to 22 weeks' gestation through parturition. In infants aged 1, 3, and 6 months, caregivers reported the occurrence of common illness symptoms in the preceding 15 days. RESULTS: Data were available at 1, 3, and 6 months for 849, 834, and 834 infants, respectively. The occurrence of specific illness symptoms did not differ between groups; however, the occurrence of a combined measure of cold symptoms was lower in the DHA group at 1 month (OR: 0.76; 95% CI: 0.58-1.00). At 1 month, the DHA group experienced 26%, 15%, and 30% shorter duration of cough, phlegm, and wheezing, respectively, but 22% longer duration of rash (all P ≤ .01). At 3 months, infants in the DHA group spent 14% less time ill (P < .0001). At 6 months, infants in the DHA group experienced 20%, 13%, 54%, 23%, and 25% shorter duration of fever, nasal secretion, difficulty breathing, rash, and "other illness," respectively, but 74% longer duration of vomiting (all P < .05). CONCLUSIONS: DHA supplementation during pregnancy decreased the occurrence of colds in children at 1 month and influenced illness symptom duration at 1, 3, and 6 months.