Nutrient Deficiency, Pregnancy Related
Conditions
Brief summary
This study is designed to test the hypotheses that (1) the third trimester of pregnancy is a period of maternal systemic and ocular carotenoid depletion; (2) prenatal supplementation with 10 milligrams of lutein and 2 milligrams of zeaxanthin will have significant effects on ocular and systemic biomarkers of maternal and infant carotenoid status relative to a matched, standard-of-care prenatal supplement without added lutein and zeaxanthin; and (3) newborn infants with the highest systemic and ocular carotenoid status will have more mature foveal structure. Mothers will be enrolled in the study during their first trimester, and will take the study carotenoid or control supplements for 6 to 8 months. The final study outcome measurements of mothers and infants will be completed within two weeks of the baby's birth.
Interventions
DRUGCarotenoid Group
Softgel active ingredients: Lutein 10 mg and Zeaxanthin 2 mg in safflower oil
DIETARY_SUPPLEMENTControl Group
Placebo ingredients: Safflower oil
Sponsors
Paul S. Bernstein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Pregnant women, 18 or older of all races and ethnicities who have an uncomplicated obstetric history and plan to deliver either vaginally or by Caesarian section at the University of Utah for their current pregnancy.
Exclusion criteria
* Women who have regularly taken carotenoid supplements containing more than 0.5 mg of lutein and/or zeaxanthin daily during the six months prior to screening * Women who have significant eye disease associated with macular pigment abnormalities such as Stargardt disease, albinism, or macular telangiectasia type II (MacTel). * Women with conditions associated with high-risk pregnancy such as adolescent pregnancy, multifetal pregnancy, current or past history of diabetes, pre-eclampsia, previous premature delivery, drug abuse or other significant medical illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Maternal Macular Carotenoid Levels From Enrollment to Birth of Infant | up to 13 weeks gestation to birth | measured in units of macular pigment optical volume (MPOV). Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2 |
| Change in Maternal Serum Carotenoid Levels From Enrollment to Birth of Infant | up to 13 weeks gestation to birth | We are reporting only lutein + zeaxanthin concentrations. Unit of measurement is in nanograms per milliliter (ng/ml). Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2 |
| Change in Maternal Skin Carotenoid Levels From Enrollment to Birth of Infant | up to 13 weeks gestation to birth | Maternal skin carotenoid levels are measured in Raman units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infant Macular Carotenoid Levels as Determined by Macular Pigment Optical Density | Birth | Comparison of macular carotenoid levels of infants whose mothers received prenatal supplements without carotenoids to those mothers who received prenatal supplements with carotenoids. Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2 |
| Infant Serum Carotenoid Levels as Determined With High Performance Liquid Chromatography | Birth | Comparison of carotenoid levels of infants whose mothers received prenatal supplements without carotenoids to those mothers who received prenatal supplements with carotenoids. We are reporting only lutein + zeaxanthin concentrations. Unit of measurement is nanogram per milliliter (ng/ml). Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2 |
| Infant Skin Carotenoid Levels as Determined With Resonance Raman Spectroscopy | Birth | Comparison of carotenoid levels of infants whose mothers received prenatal supplements without carotenoids to those mothers who received prenatal supplements with carotenoids. Infant skin carotenoid levels are measured in Raman units. Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2 |
Countries
United States
Participant flow
Pre-assignment details
Only mothers were considered enrolled. One infant and one mother were considered one unit. The enrollment number and number of participants started/completed represents the number of dyads.
Participants by arm
| Arm | Count |
|---|---|
| Carotenoid Group The Carotenoid group will receive a commercially available prenatal vitamin/mineral/DHA softgel plus a softgel containing lutein/zeaxanthin in safflower oil.
Carotenoid Group: Softgel active ingredients: Lutein 10 mg and Zeaxanthin 2 mg in safflower oil | 21 |
| Control Group The Control group will receive the same prenatal vitamin/mineral/DHA softgel plus a softgel containing only safflower oil.
Control Group: Placebo ingredients: Safflower oil | 20 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 |
Baseline characteristics
| Characteristic | Control Group | Carotenoid Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 21 Participants | 41 Participants |
| Age, Continuous | 29.1 years STANDARD_DEVIATION 3.7 | 30.8 years STANDARD_DEVIATION 3.1 | 29.9 years STANDARD_DEVIATION 1.2 |
| Alcohol intake frequency Never | 20 Participants | 20 Participants | 40 Participants |
| Alcohol intake frequency Occasional | 0 Participants | 1 Participants | 1 Participants |
| Body mass index (BMI) | 25.4 kg/m^2 STANDARD_DEVIATION 4.6 | 23.9 kg/m^2 STANDARD_DEVIATION 3.7 | 24.7 kg/m^2 STANDARD_DEVIATION 4.1 |
| Estimated dietary intake of lutein and zeaxanthin | 3.6 mg/day STANDARD_DEVIATION 3.1 | 4.3 mg/day STANDARD_DEVIATION 5.9 | 4.0 mg/day STANDARD_DEVIATION 4.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 20 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Maternal macular carotenoid levels | 7002 unitless STANDARD_DEVIATION 2502 | 8809 unitless STANDARD_DEVIATION 3001 | 7906 unitless STANDARD_DEVIATION 2883 |
| Maternal serum carotenoid levels | 217.0 ng/ml STANDARD_DEVIATION 82.5 | 257.6 ng/ml STANDARD_DEVIATION 116.7 | 237.3 ng/ml STANDARD_DEVIATION 102.3 |
| Maternal skin carotenoid levels | 39436 Raman units STANDARD_DEVIATION 8733 | 39981 Raman units STANDARD_DEVIATION 9495 | 39709 Raman units STANDARD_DEVIATION 9021 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 21 Participants | 41 Participants |
| Region of Enrollment United States | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Smoking habit Never smoked | 20 Participants | 21 Participants | 41 Participants |
| Smoking habit Smoked | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 6 / 24 | 8 / 23 |
| serious Total, serious adverse events | 2 / 24 | 0 / 23 |
Outcome results
Primary
Change in Maternal Macular Carotenoid Levels From Enrollment to Birth of Infant
measured in units of macular pigment optical volume (MPOV). Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2
Time frame: up to 13 weeks gestation to birth
Population: Participants who did not complete the final study visit were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carotenoid Group | Change in Maternal Macular Carotenoid Levels From Enrollment to Birth of Infant | 12244 unitless | Standard Error 688 |
| Control Group | Change in Maternal Macular Carotenoid Levels From Enrollment to Birth of Infant | 7343 unitless | Standard Error 470 |
Primary
Change in Maternal Serum Carotenoid Levels From Enrollment to Birth of Infant
We are reporting only lutein + zeaxanthin concentrations. Unit of measurement is in nanograms per milliliter (ng/ml). Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2
Time frame: up to 13 weeks gestation to birth
Population: Participants who did not complete the final study visit were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carotenoid Group | Change in Maternal Serum Carotenoid Levels From Enrollment to Birth of Infant | 1030.2 Nanograms per milliliter | Standard Error 86.8 |
| Control Group | Change in Maternal Serum Carotenoid Levels From Enrollment to Birth of Infant | 252.0 Nanograms per milliliter | Standard Error 33.4 |
Primary
Change in Maternal Skin Carotenoid Levels From Enrollment to Birth of Infant
Maternal skin carotenoid levels are measured in Raman units.
Time frame: up to 13 weeks gestation to birth
Population: Participants who did not complete a final study visit were excluded from final data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carotenoid Group | Change in Maternal Skin Carotenoid Levels From Enrollment to Birth of Infant | 55419 Raman units | Standard Error 2421 |
| Control Group | Change in Maternal Skin Carotenoid Levels From Enrollment to Birth of Infant | 38475 Raman units | Standard Error 1932 |
Secondary
Infant Macular Carotenoid Levels as Determined by Macular Pigment Optical Density
Comparison of macular carotenoid levels of infants whose mothers received prenatal supplements without carotenoids to those mothers who received prenatal supplements with carotenoids. Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2
Time frame: Birth
Population: We report macular pigment optical density for infants whose mothers consented to ophthalmic imaging for their infant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carotenoid Group | Infant Macular Carotenoid Levels as Determined by Macular Pigment Optical Density | 0.05 unitless | Standard Error 0.01 |
| Control Group | Infant Macular Carotenoid Levels as Determined by Macular Pigment Optical Density | 0.04 unitless | Standard Error 0.01 |
Secondary
Infant Serum Carotenoid Levels as Determined With High Performance Liquid Chromatography
Comparison of carotenoid levels of infants whose mothers received prenatal supplements without carotenoids to those mothers who received prenatal supplements with carotenoids. We are reporting only lutein + zeaxanthin concentrations. Unit of measurement is nanogram per milliliter (ng/ml). Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2
Time frame: Birth
Population: We report data on infants for whom we were able to obtain a blood sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carotenoid Group | Infant Serum Carotenoid Levels as Determined With High Performance Liquid Chromatography | 270.5 nanograms per milliliter | Standard Error 29.1 |
| Control Group | Infant Serum Carotenoid Levels as Determined With High Performance Liquid Chromatography | 54.5 nanograms per milliliter | Standard Error 6.6 |
Secondary
Infant Skin Carotenoid Levels as Determined With Resonance Raman Spectroscopy
Comparison of carotenoid levels of infants whose mothers received prenatal supplements without carotenoids to those mothers who received prenatal supplements with carotenoids. Infant skin carotenoid levels are measured in Raman units. Details regarding methods and criteria used to assess this outcome measure and interpret the values are in the published protocol available at https://doi.org/10.1186/s13063-021-05244-2
Time frame: Birth
Population: We report data on infants for whom we were able to obtain skin carotenoid measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carotenoid Group | Infant Skin Carotenoid Levels as Determined With Resonance Raman Spectroscopy | 31656 Raman units | Standard Error 1279 |
| Control Group | Infant Skin Carotenoid Levels as Determined With Resonance Raman Spectroscopy | 23011 Raman units | Standard Error 869 |