Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy

S. E. Carlson; B. J. Gajewski; C. J. Valentine; S. A. Sands; A. R. Brown; E. H. Kerling; S. A. Crawford; C. S. Buhimschi; C. P. Weiner; M. Cackovic; E. A. DeFranco; D. P. Mudaranthakam; L. K. Rogers

doi:10.1016/j.clnu.2023.01.009

Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy

S. E. Carlson, B. J. Gajewski, C. J. Valentine, S. A. Sands, A. R. Brown, E. H. Kerling, S. A. Crawford, C. S. Buhimschi, C. P. Weiner, M. Cackovic, E. A. DeFranco, D. P. Mudaranthakam, L. K. Rogers

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. Objective: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. Study design: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks’ gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. Results: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. Conclusion: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. ClinicalTrials.gov (NCT02626299).

Original language	English
Pages (from-to)	235-243
Number of pages	9
Journal	Clinical Nutrition
Volume	42
Issue number	2
DOIs	https://doi.org/10.1016/j.clnu.2023.01.009
State	Published - Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Funding

This work was supported by grants from The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ( R01HD083292 ) and the Office of Dietary Supplements ( R01HD083292-03S1 ). The NICHD had no role in study design, data collection, data analysis, data interpretation, or writing of this article. Life's DHA™-S oil, DSM Nutritional Products LLC, Switzerland donated the investigational capsules for both trials but had no role in study design, data collection, data analysis, data interpretation, or writing of this article. This work was supported by grants from The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (R01HD083292) and the Office of Dietary Supplements (R01HD083292-03S1). The NICHD had no role in study design, data collection, data analysis, data interpretation, or writing of this article. Life's DHA™-S oil, DSM Nutritional Products LLC, Switzerland donated the investigational capsules for both trials but had no role in study design, data collection, data analysis, data interpretation, or writing of this article.

Funders	Funder number
Office of Dietary Supplements	R01HD083292-03S1
Office of Dietary Supplements
Eunice Kennedy Shriver National Institute of Child Health and Human Development	R01HD083292
Eunice Kennedy Shriver National Institute of Child Health and Human Development
DSM Nutritional Products, Inc

Keywords

Clinical trial adherence
DHA
Pregnancy
Preterm birth
Red blood cell phospholipid DHA

ASJC Scopus subject areas

Nutrition and Dietetics
Critical Care and Intensive Care Medicine

Access to Document

10.1016/j.clnu.2023.01.009

Cite this

Carlson, S. E., Gajewski, B. J., Valentine, C. J., Sands, S. A., Brown, A. R., Kerling, E. H., Crawford, S. A., Buhimschi, C. S., Weiner, C. P., Cackovic, M., DeFranco, E. A., Mudaranthakam, D. P., & Rogers, L. K. (2023). Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy. Clinical Nutrition, 42(2), 235-243. https://doi.org/10.1016/j.clnu.2023.01.009

@article{dff7157b067d4bf2843b01695add2fd0,

title = "Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy",

abstract = "Background: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. Objective: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. Study design: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks{\textquoteright} gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. Results: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. Conclusion: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. ClinicalTrials.gov (NCT02626299).",

keywords = "Clinical trial adherence, DHA, Pregnancy, Preterm birth, Red blood cell phospholipid DHA",

author = "Carlson, {S. E.} and Gajewski, {B. J.} and Valentine, {C. J.} and Sands, {S. A.} and Brown, {A. R.} and Kerling, {E. H.} and Crawford, {S. A.} and Buhimschi, {C. S.} and Weiner, {C. P.} and M. Cackovic and DeFranco, {E. A.} and Mudaranthakam, {D. P.} and Rogers, {L. K.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = feb,

doi = "10.1016/j.clnu.2023.01.009",

language = "English",

volume = "42",

pages = "235--243",

number = "2",

}

Carlson, SE, Gajewski, BJ, Valentine, CJ, Sands, SA, Brown, AR, Kerling, EH, Crawford, SA, Buhimschi, CS, Weiner, CP, Cackovic, M, DeFranco, EA, Mudaranthakam, DP & Rogers, LK 2023, 'Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy', Clinical Nutrition, vol. 42, no. 2, pp. 235-243. https://doi.org/10.1016/j.clnu.2023.01.009

TY - JOUR

T1 - Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy

AU - Carlson, S. E.

AU - Gajewski, B. J.

AU - Valentine, C. J.

AU - Sands, S. A.

AU - Brown, A. R.

AU - Kerling, E. H.

AU - Crawford, S. A.

AU - Buhimschi, C. S.

AU - Weiner, C. P.

AU - Cackovic, M.

AU - DeFranco, E. A.

AU - Mudaranthakam, D. P.

AU - Rogers, L. K.

PY - 2023/2

Y1 - 2023/2

N2 - Background: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. Objective: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. Study design: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks’ gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. Results: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. Conclusion: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. ClinicalTrials.gov (NCT02626299).

AB - Background: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. Objective: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. Study design: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks’ gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. Results: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. Conclusion: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. ClinicalTrials.gov (NCT02626299).

KW - Clinical trial adherence

KW - DHA

KW - Pregnancy

KW - Preterm birth

KW - Red blood cell phospholipid DHA

UR - http://www.scopus.com/inward/record.url?scp=85146677893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85146677893&partnerID=8YFLogxK

U2 - 10.1016/j.clnu.2023.01.009

DO - 10.1016/j.clnu.2023.01.009

M3 - Article

C2 - 36680919

AN - SCOPUS:85146677893

SN - 0261-5614

VL - 42

SP - 235

EP - 243

JO - Clinical Nutrition

JF - Clinical Nutrition

IS - 2

ER -

Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this