Effect of supplementation of complex milk lipids in pregnancy on fetal growth: results from the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial

Abstract

Background

Gangliosides (GAs) are important for neuronal function and development of the brain, accumulating rapidly in the fetal brain during the last trimester of pregnancy. No study in humans has investigated whether maternal supplementation of GAs during pregnancy has an effect on fetal growth, particularly of the head circumference.

Objective

To evaluate the effect of maternal dietary supplementation of complex milk lipids (CML; gangliosides and phospholipids) from the milk fat globule membrane (MFGM) during pregnancy on fetal growth.

Design

Double-blind three-arm parallel randomized controlled trial of 1500 pregnant women from the Chongqing Municipality of China, recruited between 11 and 14 weeks of pregnancy. Intervention was in the form of supplementation with: control maternal milk formulation containing a minimum of 2 mg GA per serving (4 mg GA per day) versus a CML-enriched (CML-E) maternal milk formulation containing a minimum of 4 mg GA per serving (8 mg GA per day) versus no maternal milk supplementation, but with standard obstetric care including prenatal folic acid supplementation. Main outcomes and measures were ultrasonographically-derived estimates of fetal growth in head circumference (HC) & biparietal diameter (BPD) (primary outcomes); and abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) (secondary outcomes) (Clinical trial registry: ChiCTR-IOR-16007700).

Results

Supplementation with CML-E milk had no effects on size at midpregnancy or growth trajectories in any of the fetal biometric dimensions.

Conclusions

Supplementation of CML from the MFGM from the end of the first trimester did not have any effects on fetal growth. The absence of any adverse growth outcomes suggests that maternal MFGM supplementation during pregnancy is safe and using CML-E milk formula can be a method of providing an increased GA and phospholipid supply in early life, which has been associated with neurodevelopmental benefits.

Clinical trial registry

ChiCTR-IOR-16007700 (http://www.chictr.org.cn/enindex.aspx)

Keywords:

• Complex lipids
• fetal growth
• gangliosides
• randomized clinical trial
• ultrasound

Disclosure statement

The design and conception of the study was led by the principal investigators. The funders had no role in data collection and analysis or decision to publish.

Angela Rowan and Sophie Gallier are employed by Fonterra Co-operative Group Ltd.; the other authors have no financial conflicts of interest to disclose that may be relevant to this work.

Author’s contributions

(1) HZ, H-BQ, PNB designed research (project conception, development of overall research plan, and study oversight); (2) YX, TZ, HZ conducted research (hands-on conduct of the experiments and data collection); (3) SG, AR provided essential reagents or provided essential materials; (4) TN and RTS analyzed data or performed statistical analysis; (5) TN, RTS, SG, PNB wrote paper; 6) PNB had primary responsibility for final content.

Data availability

The corresponding author confirms that we will make the data (in deidentified form) used in the manuscript, code book, and analytic code available to editors upon request either before or after publication for checking.

Additional information

Funding

This work was supported by the New Zealand Primary Growth Partnership postfarm gate dairy program, funded by Fonterra Co-Operative Group Ltd., New Zealand and the New Zealand Ministry for Primary Industries. The PGP programme (https://www.mpi.govt.nz/funding-and-programmes/sustainable-food-and-fibre-futures/primary-growth-partnership/completed-pgp-programmes/transforming-the-dairy-value-chain/) was transforming the dairy value chain and the project was under the Theme 5 (Transforming the dairy value chain through robust human nutrition and health benefits). Souza, RT has been awarded a PhD scholarship from the CAPES Foundation, an agency under the Ministry of Education of Brazil, process 88881.134095/2016-01.