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Response to Hydrolyzed Collagen Protein Supplementation in a Cohort of
Pregnant and Postpartum Women
Leon Baginski1, Marc Winter2, Thomas S Bailey3, Scott Capobianco4, Marsha Granese5, Freddie Granger MA6, Kurt Miller7, Kerry Price8, Sara Ramirez9, Craig
Salcido10, Frank Turner11* and Mary O’Toole12
1University of Michigan Medical School, Mission Obstetrics and Gynaecology, Mission Viejo, CA, USA
2University of California College of Medicine, Orange Coast Women's Medical Group, Laguna Hills, CA, USA
3University of Arizona Medical School, Mission OBGYN Medical Group, Mission Viejo CA, USA
4USC Medical School, Mission OBGYN Medical Group, Mission Viejo, CA, USA
5St. George's University, Mission OBGYN Medical Group, Mission Viejo, USA
6Mission Ob/Gyn Medical, Mission Viejo California, USA
7University of San Diego School of Medicine, Mission OBGYN Medical Group, Mission Viejo, USA
8University of Chicago Pritzger School of Medicine, Orange Coast Women's Medical Group, Laguna Hills, CA, USA
9University of Chicago Medical School, Mission OBGYN Medical Group, Mission Viejo, CA, USA
10University of New York Medical College, Mission OBGYN Medical Group, Mission Viejo, CA, USA
11Innovative Research Associates 415 Elmwood Ave, Sharon Hill, PA, USA
12Chicago Medical School, Orange Coast Women's Medical Group, Laguna Hills, CA, USA
*Corresponding author: Frank Turner, Innovative Research Associates 415 Elmwood Ave, Sharon Hill, PA, USA, Tel: 5403168030; E-mail: neuroma7@msn.com
Received date: August 21, 2016; Accepted date: September 26, 2016; Published date: September 30, 2016
Copyright: © 2016 Baginski L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution and reproduction in any medium, provided the original author and source are credited.
Abstract
There is overwhelming evidence that links maternal nutrition during pregnancy with fetal outcomes. This study
evaluated the safety and efficacy of Protiva treatment responses in pre and postpartum female subjects between the
ages of 19 years and 43 years who entered into this open label study. The protocol was designed to take a twice
daily collagen protein supplementation drink during the third trimester and for 10 weeks post-partum. The outcomes
were measured against a control group of patients who did not take the protein supplementation. The differences
between mean score for the physical health domain of WHOQOL-BREF scale in the Protiva group and the control
group were different and met statistical significance (p=0.0003). The study found that 100% of control patients and
95% of Protiva patients had initial serum protein levels below the normal median range and 27% of control patients
and 33% of Protiva patients were below normal range. With collagen protein supplementation we were able to
demonstrate improved quality of life and wound healing rates and 100% improvement in the protein levels for Protiva
patients and a 72% improvement over control patients. Protiva Pregnancy and Protiva New Mom was determined to
be safe and well tolerated when taken during pregnancy and postpartum during the study.
Keywords: Pregnancy protein; Protiva; Breast feeding
Introduction
ere is overwhelming evidence that links maternal nutrition
during pregnancy with fetal outcomes [1]. Pregnancy is associated with
physiologic changes that result in increased plasma volume and red
blood cells and decreased concentrations of circulating nutrient-
binding proteins and micronutrients. ere is an increased
requirement for vitamins and minerals during pregnancy relative to
the non-pregnant state [2]. e demand for protein during the second
and third trimester of pregnancy increases to 1.1 g/kg/day or
approximately 71 g, amounting to more than a 50% increase in protein
that is necessary for fetal growth and maternal milk production [3].
Normal blood total protein levels in a non-pregnant woman are
between 6.0 and 8.3 grams per deciliter (g/dL) [4]. In a study by
Rahman et al. [5], it was demonstrated that serum protein levels
uctuate during the three trimesters of pregnancy and they are further
impacted on the basis of parity and dietary protein consumption. e
mean total serum protein during rst, second and third trimesters
were found to be 6.85, 6.60 and 6.81 g%, respectively which were lower
than the mean value obtained in a group of non-pregnant women (7.55
g%). While some clinical laboratories currently report total protein
levels below 6.0 (g/dL) as normal in pregnancy, there is no data to
support that this is indeed “normal” or that it should be considered
safe. e levels of total protein and albumin that are necessary to
maximize fetal and maternal outcomes are poorly understood and
certainly open for debate.
Many women nd it dicult to consume the recommended amount
of protein during pregnancy. Physicians and caregivers are oen short
on time and nd it dicult to address the many dietary concerns and
restrictions that face the gravid patient. Women looking for additional
protein during pregnancy may nd protein powders an easy and
convenient alternative to other forms of unprocessed protein.
Unfortunately, there is insucient data regarding the impact on these
drinks on either the mother or the fetus to routinely recommend them
during pregnancy. Without ecacy or safety information, physicians
are hard pressed to recommend for or against supplementation. is
Journal of Pregnancy and Child
Health Baginski et al., J Preg Child Health 2016, 3:5
DOI: 10.4172/2376-127X.1000275
Research Article OMICS International
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
study was undertaken to answer some of these questions and hopefully
guide caregivers in understanding the increased nutrient needs during
pregnancy and the benets of protein supplementation. It was also
prudent to continue the study into the postpartum period and during
breast feeding to assess any impact on lactation so as to help guide
pediatricians with respect to new-born responses to maternal
supplementation.
Aevum Life Science has developed two novel protein products
Protiva Pregnancy and Protiva New Mom, each specically formulated
with Hydrolyzed collagen as the protein source. Hydrolyzed collagen
was chosen because animal studies have demonstrated that high levels
of certain amino acids were associated with reduced litter size and the
health of ospring [6,7]. Among these amino acids that were studied,
Tryptophan was found to have the greatest negative impact on fetal
development. Collagen protein contains no Tryptophan and has the
lowest concentration of the other detrimental amino acids in
comparison to other protein sources. Hydrolyzed collagen is also easily
digested and absorbed because of the low molecular weight of the
peptides produced during hydrolysis. Adequate protein is a
requirement for proper wound healing from collagen synthesis,
angiogenesis, broblast proliferation and maintenance of tissue oncotic
pressure. Only Hydrolyzed collagen peptides have been demonstrated
to be chemotactic to dermal broblasts which are an essential
component in the healing process of damaged tissue [8].
In anticipation of abdominal or vaginal delivery, proper nutrition
pre and post-delivery is important in order to have a positive eect on
tissue healing [9]. Patients preparing to undergo surgery need peak
immune function to prevent infection, peak clotting function to reduce
bleeding and bruising. Adequate protein intake is necessary for
collagen formation and repair as well as other critical functions [10].
Studies of postoperative nutritional support have demonstrated
reduced morbidity and reduced length of hospital stay [11]. Huisman
et al. were able to demonstrate that low pre-surgical serum protein
levels were a predictor of increased risk for post-operative
complications [11-13].
Proper healing aer delivery, whether vaginal or by cesarean,
requires adequate macro and micronutrients. Not only is protein and
important component of the healing process but vitamins and minerals
also play a critical role. Vitamins A, C, E and D as well as the minerals
Copper and Zinc and Calcium have all been shown to play an
important role in proper wound repair [14-21]. eir role in the
healing process involves angiogenesis, induction of endothelial growth
factors with proliferation and dierentiation of human keratinocytes,
broblast proliferation as well as collagen maturation and stabilization.
Prospective randomized clinical trials support the use of
supplementation of Vitamin C, Vitamin E and trace elements in
critically ill patients for proper healing to take place [22].
is study was designed to: 1) determine the blood protein levels in
a group of women in their third trimester who were well nourished
with access to both adequate macro and micronutrients. 2) Provide
supplementation of protein with vitamins and minerals during
pregnancy, delivery and into the postpartum period. 3) Evaluate the
potential outcome dierences of patients taking supplemental protein
and vitamins and minerals compared to a control group. 4) To see if
there were any negative eects of collagen protein on fetal or maternal
outcomes.
Participants
Female subjects between 18 and 50 years of age in their nal
trimester of pregnancy were considered eligible to participate aer
evaluation of the inclusion/exclusion criteria and completion of
screening procedures.
Materials
e materials utilized in this study included Protiva Pregnancy and
Protiva New Mom.
Study patients were instructed to mix Protein Pregnancy and
Protiva New Mom with 8-10 oz of cold water in a blender or shaker
bottle and to avoid mixing them with milk or other protein containing
products.
Protiva Pregnancy has been specically formulated for pregnant
women to provide 15 g of Hydrolyzed Collagen protein per serving.
Protiva Pregnancy contains no articial colors or avors, and is gluten,
lactose, soy and preservative free. One scoop provides 25% of the RDA
of Vitamin A, 80% of Vitamin C, 100% of Vitamin D, 50% of Calcium,
30% of Zinc and 50% of Copper.
Protiva New Mom has been specically formulated for women
following delivery and while breastfeeding and contains 15 g of
Hydrolyzed collagen protein per serving. Protiva New Mom also
contains no articial colors or avors, and is gluten, lactose, soy and
preservative free. It provides 50% of the RDA of Vitamin A, 625% of
Vitamin C, 100% of Vitamin D 50% of Vitamin E, 50% of Calcium, 30%
of Zinc and 50% of Copper. It also contains the additional amino acids
L-Leucine, L-Isoleucine and L-Valine.
Methods
Patient population selection
Study subjects were screened at 2 investigative sites in the United
States. Screening assessments were conducted, and if patients were
accepted into the study, study participants received Protiva Pregnancy
mailed to their homes. Screening procedures included: medical and
surgical history including medication history, review of inclusion/
exclusion criteria, physical examination (including height, weight and
BMI), vital signs (BP and HR). For patients who were selected into the
study, laboratory tests (chemistry and hematology) were taken and the
World Health Organization Quality of Life (WHOQOL)-BREF was
administered and completed prior to starting on the product. Subjects
returned to the site at 6 weeks post-delivery (Visit 2) and 10 week’s
post-delivery (Visit 3).
e following assessments were performed during those visits:
physical examination (including height, weight and BMI), vital signs
(BP and HR), review of adverse events (AEs) and concomitant
medications, laboratory tests (chemistry and hematology), Patient
Global Satisfaction with Treatment Scale (only completed for
treatment group), WHOQOL-BREF, REEDA Scale (only for subjects
that had an incision or laceration with or without repair at delivery)
and Protiva Pregnancy and Protiva New Mom accountability/
compliance assessment for the treatment group.
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 2 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
Study Design
is open-label study was designed to assess the ecacy and safety
of: 1) Protiva Pregnancy during the third trimester of pregnancy and 2)
Protiva New Mom during the rst 10 weeks following delivery. e
duration of this study was 14 weeks. Study patients were instructed to
consume Protiva Pregnancy twice daily (30 g) in their third trimester
of pregnancy until delivery and then switch to Protiva New Mom twice
daily until their 10 week postpartum visit. A control group of 27
subjects were included in the study that did not receive either of the
Protiva products. Clinical outcomes such as blood protein levels,
complication rates, and change in body mass index (BMI) were
measured. e clinical study statistically evaluated the improvement in
blood protein levels of study subjects from Screening to End of Study.
Blood protein levels were drawn on patients between weeks 30-32 of
pregnancy.
Evaluation of recovery following delivery was measured by the
REEDA scale change in scores (5 items with a score ranging from 0 to
3, higher score representing a greater level of tissue trauma with a
maximum of 15) was assessed using the non-parametric Wilcoxon
Rank Sum test.
Statistical Analysis
Statistical analyses were performed based on the treatment received
by the study subject. Primary and secondary endpoints are presented
by treatment received. e last observation carried forward (LOCF)
method was used for missing data in the primary analysis.
Statistical analysis of the study results included a Full Analysis Set
(FAS) as all subjects in the treatment group who received both Protiva
Pregnancy and Protiva New Mom had completed at least one post-
delivery assessment; and all subjects in the control group who
completed at least one post-delivery assessment were included in the
FAS.
e safety population included all subjects who took any of the
Protiva products. e ecacy population was comprised of all subjects
who took any Protiva product, and had both baseline and at least 1
post-delivery assessment. e completed ecacy population was
comprised of all subjects who received both Protiva Pregnancy and
Protiva New Mom, completed 10 weeks of Protiva New Mom and
completed all protocol specied study assessments.
Descriptive analyses of clinical laboratory tests, vital signs, BMI and
physical examinations were done on all subjects in the safety
population.
Ethics
e protocol was reviewed by independent Institutional Review
Board (IRB). Prior to the initiation of the clinical trial, the Principal
Investigators obtained written and dated approval by the IRB for the
protocol and the informed consent form. e study was conducted in
compliance with IRB, informed consent regulations and International
Conference on Harmonization (ICH) Good Clinical Practice (GCP).
e Principal Investigator was responsible for performing the study in
accordance with the protocol and GCP/ICH guidelines and for
collecting, recording and reporting the data accurately and properly.
e principle investigator has not received nancial support from the
sponsor Aevum Life Science to perform this study. Prior to enrollment
in the study, an IRB approved written informed consent was obtained
from each subject.
Results
Patient disposition
e safety and ecacy analysis was conducted on 142 subjects
enrolled into the study. Of the 142 subjects, 109 completed the study
(i.e., returned for Visit 3), 6 subjects were lost to follow-up between
Visits 1 and 3, 17 subjects demonstrated noncompliance or lack of
cooperation, and 10 subjects had other reasons for discontinuation
such as moving out of the area.
Demography and baseline characteristics
One hundred and forty two (n=142) subjects were enrolled in the
trial are shown in Table 1 below, all were female, 132 (93%) were
Caucasian, and their mean age+SD [min, max] was 31.5+5.11 (19, 44)
years.
Characteristics All Subjects (N=142)
Age (years)
Mean (SD) 31.5 (5.11)
Median 32
Minimum, Maximum 19, 43
Gender
Female N (%) 142 (100%)
Race
Caucasian N (%) 132 (93%)
Black N (%) 2 (1.4%)
Asian N (%) 6 (4.2%)
Native American N (%) 2 (1.4%)
Height (in)
Mean (SD) 64.8 (2.81)
Median 65
Minimum, Maximum 54, 71
Weight (lb)
Mean (SD) 176.4 (32.20)
Median 170
Minimum, Maximum 104, 286
Table 1: Demography of the safety population.
Ecacy results
A total of 115 subjects were assigned to Protiva treatment and 27 to
no treatment at 2 centers and 113 (91 Protiva and 22 controls)
completed the primary endpoint evaluations at least at one of the post-
delivery visits 2 or 3.
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 3 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
Ecacy analyses results are shown in Table 2 were obtained from a
total of 113 (91 Protiva and 22 controls) who completed the primary
endpoint evaluations in at least one of the post-delivery visits 2 or 3.
PPS Population FAS Population
Control Group (N=11) Protiva Group (N=37) Control Group (N=22) Protiva Group (N=91)
Total Protein (g/dL)
Screening n 11 37 22 90
Observed Mean (SD) 6.1 (0.29) 6.2 (0.42) 6.1 (0.25) 6.1 (0.39)
Visit 2 n 11 37 18 78
Observed Mean (SD) 6.8 (0.40) 7.0 (0.35) 6.8 (0.37) 7.0 (0.35)
Mean Change (SD) 0.7 (0.41) 0.8 (0.40) 0.7 (0.38) 0.9 (0.37)
Visit 3 n 11 37 20 72
Observed Mean (SD) 6.8 (0.47) 7.0 (0.39) 6.9 (0.43) 7.1 (0.42)
Mean Change (SD) 0.7 (0.46) 0.8 (0.42) 0.8 (0.44) 0.9 (0.38)
Table 2: Improvement in nutritional status: Total protein, (PPS and FAS Population) (SD=Standard Deviation).
For the endpoint of total blood protein, based on treatment or no
treatment, ecacy analysis for the total blood protein, was based on
the dierence in blood protein levels of the Protiva group and the
Control group from Screening (Visit 1) to End of Study (Visit 3). e
primary endpoint was analyzed and the change from baseline values
was used for the lab chemistry endpoints. If a subject withdrew from
the study without undergoing the early termination assessments, the
data available up until that time was used for analysis. Missing values
were imputed using LOCF imputation method.
Physical Health Results
e dierences between mean score for the physical health domain
of WHOQOL-BREF scale in the Protiva group and the control group
was statistically signicant at the End of Study, i.e., visit 3 (Table 3:
P=0.0003 for FAS population and Table 4: p=0.0001 for PPS
population), meaning signicant improvement in the physical health
of subjects in the Protiva group compared to the control group. e
mean score of all four domains increased from screening to visit 3 in
the Protiva group meaning improvement in quality of life, while the
mean score of all four domains decreased from screening to visit 3 in
the control group. e number of responders of PGS scores for each of
the two post-delivery visits clearly shows much higher percentages of
subjects with a satisfaction rating of very satised (Visit 2: 46.1% vs.
7.4%; Visit 3: 42.6% vs. 3.7%) and satised (Visit 2: 22.6% vs. 0; Visit 3:
19.1% vs. 0) in the Protiva group compared to the Control group.
Visit WHOQOL-BREF domains Control Group Protiva Group p-value*
Screening Physical Health n 22 90 0.1774
Mean (SD) 27.9 (3.94) 26.7 (4.47) .
Median 29 27 .
Minimum, Maximum 17 , 34 12 , 35 .
Psychological n 22 91 0.1627
Mean (SD) 25.5 (2.61) 24.3 (3.48) .
Median 26 24 .
Minimum, Maximum 21, 29 9 , 30 .
Social Relationships n 22 90 0.5981
Mean (SD) 12.8 (1.60) 12.5 (1.82) .
Median 13 12 .
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 4 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
Minimum, Maximum 10, 15 6, 15 .
Environment n 22 91 0.2451
Mean (SD) 34.4 (3.99) 33.5 (3.75) .
Median 35 33 .
Minimum, Maximum 25, 40 23, 40 .
Visit 2 n 18 80
Mean (SD) 25.4 (6.22) 28.5 (3.40)
Median 26 29
Minimum, Maximum 14, 34 18, 34
n 18 78
Mean (SD) 23.9 (3.49) 24.8 (3.29)
Median 25 25
Minimum, Maximum 19, 29 15, 30
n 18 78
Mean (SD) 11.9 (2.03) 12.6 (1.69)
Median 12 12
Minimum, Maximum 8, 15 8, 15
n 17 80
Mean (SD) 33.7 (3.57) 34.6 (3.83)
Median 35 35
Minimum, Maximum 29, 39 24, 40
Visit 3 n 19 71
Mean (SD) 24.8 (5.48) 30.0 (3.22)
Median 23 30
Minimum, Maximum 16, 35 16, 35
n 19 70
Mean (SD) 23.7 (2.94) 24.8 (3.79)
Median 24 25
Minimum, Maximum 18, 29 11, 30
n 19 71
Mean (SD) 12.5 (1.90) 12.7 (2.02)
Median 12 13
Minimum, Maximum 9, 15 7, 15
n 19 71
Mean (SD) 34.2 (4.61) 34.8 (3.76)
Median 35 34
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 5 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
Minimum, Maximum 26, 40 23, 40
*P-values are calculated using Wilcoxon-Mann-Whitney U-test; SD=Standard Deviation
Table 3: Summary of the WHOQOL-BREF domains and comparisons between treatments (Full Analysis Set) (SD=Standard Deviation).
Visit WHOQOL-BREF domains Control Group Protiva Group p-value*
Screening Physical Health n 11 37 0.1176
Mean (SD) 28.0 (3.29) 26.0 (4.26) .
Median 29 27 .
Minimum, Maximum 22, 31 16, 33 .
Psychological n 11 37 0.3417
Mean (SD) 25.5 (2.70) 24.1 (3.77) .
Median 25 24 .
Minimum, Maximum 21, 29 13, 30 .
Social Relationships n 11 37 0.2384
Mean (SD) 12.8 (1.40) 12.2 (1.75) .
Median 13 12 .
Minimum, Maximum 10, 15 8, 15 .
Environment n 11 37 0.1283
Mean (SD) 34.7 (3.98) 32.9 (3.82) .
Median 35 32 .
Minimum, Maximum 26, 40 23, 40 .
Visit 2 Physical Health n 11 37 0.257
Mean (SD) 25.3 (6.77) 28.4 (3.47) .
Median 24 29 .
Minimum, Maximum 14, 34 20, 34 .
Psychological n 11 36 0.5283
Mean (SD) 24.0 (3.90) 24.7 (3.69) .
Median 24 25 .
Minimum, Maximum 19, 29 15, 30 .
Social Relationships n 11 37 0.2024
Mean (SD) 11.6 (2.20) 12.5 (1.84) .
Median 11 12 .
Minimum, Maximum 8, 15 8, 15 .
Environment n 10 37 0.4728
Mean (SD) 33.3 (3.65) 34.1 (3.65) .
Median 34 34 .
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 6 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
Minimum, Maximum 29, 39 28, 40 .
Visit 3 Physical Health n 11 36 0.0001
Mean (SD) 23.6 (3.88) 30.1 (2.97) .
Median 22 31 .
Minimum, Maximum 19, 31 22, 35 .
Psychological n 11 36 0.1324
Mean (SD) 23.5 (2.50) 24.9 (3.49) .
Median 24 25 .
Minimum, Maximum 18, 27 15, 30 .
Social Relationships n 11 36 0.1535
Mean (SD) 12.0 (1.26) 12.7 (1.89) .
Median 12 13 .
Minimum, Maximum 10, 15 8, 15 .
Environment n 11 36 0.6583
Mean (SD) 34.2 (4.38) 34.8 (3.40) .
Median 33 34 .
Minimum, Maximum 27, 40 29, 40 .
*P-values are calculated using Wilcoxon-Mann-Whitney U-test; SD=Standard Deviation
Table 4: Summary of the WHOQOL-BREF domains and comparisons between treatments (PPS population).
Safety Results
e Protiva products were well tolerated.
•ere were no Serious Adverse Events reported during the study.
•e most frequently reported adverse events are summarized by
system organ class and preferred term in Table 5 below were
mastitis in 4.2%, depression in 4.2%, reproductive system and
breast disorders in 3.5%, renal and urinary disorders in 2.8% and
urinary tract infection in 2.8% of subjects.
•ere were no apparent treatment related changes in the vitals and
the BMI.
ere were no death or serious adverse events reported during the
study period covered by this clinical study report.
Primary System Organ Class Adverse Event (Preferred Term) Control Group (N=27)
Protiva Group
(N=115) Total (N=142)
Overall Total, n (%) 8 (29.6) 31 (27.0) 39 (27.5)
Blood and Lymphatic System Disorders - 2 (1.7) 2 (1.4)
Lymphadenopathy - 1 (0.9) 1 (0.7)
Thrombocytics - 1 (0.9) 1 (0.7)
Gastrointestinal Disorders 2 (7.4) 1 (0.9) 3 (2.1)
Abdominal pain 1 (3.7) - 1 (0.7)
Hemorrhoids 1 (3.7) 1 (0.9) 2 (1.4)
Gastrointestinal Disorders - Blood and lymphatic system disorders 1 (3.7) - 1 (0.7)
Oral pain 1 (3.7) - 1 (0.7)
Gastrointestinal Disorders - Surgical and Medical Procedures - 1 (0.9) 1 (0.7)
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 7 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
Abdominal pain - 1 (0.9) 1 (0.7)
Infections and Infestations 2 (7.4) 14 (12.2) 16 (11.3)
Breast infection - 1 (0.9) 1 (0.7)
Candida infection - 1 (0.9) 1 (0.7)
Cellulitis - 1 (0.9) 1 (0.7)
Cervicitis infection - 1 (0.9) 1 (0.7)
Cystitis 1 (3.7) 2 (1.7) 3 (2.1)
Group B Streptococcal infection 1 (3.7) - 1 (0.7)
Mastitis - 6 (5.2) 6 (4.2)
Urinary tract infection 1 (3.7) 3 (2.6) 4 (2.8)
Injury, Poisoning and procedural complications - 2 (1.7) 2 (1.4)
Seroma - 2 (1.7) 2 (1.4)
Investigations - Endocrine disorders - 1 (0.9) 1 (0.7)
Blood Prolactin increased - 1 (0.9) 1 (0.7)
Investigations - Hepatobiliary disorders - 1 (0.9) 1 (0.7)
Hepatic enzyme increased - 1 (0.9) 1 (0.7)
Investigations - Metabolism and Nutrition disorders 1 (3.7) - 1 (0.7)
Weight increased 1 (3.7) - 1 (0.7)
Psychiatric Disorders 1 (3.7) 5 (4.3) 6 (4.2)
Depression 1 (3.7) 5 (4.3) 6 (4.2)
Renal and Urinary Disorders 1 (3.7) 3 (2.6) 4 (2.8)
Dysuria 1 (3.7) 1 (0.9) 2 (1.4)
Hematuria - 2 (1.7) 2 (1.4)
Reproductive System and Breast Disorders 2 (7.4) 3 (2.6) 5 (3.5)
Bleeding - 1 (0.9) 1 (0.7)
Lactation disorder 1 (3.7) - 1 (0.7)
Menorrhagia - 1 (0.9) 1 (0.7)
Menstruation irregular - 2 (1.7) 2 (1.4)
Vaginal pain 1 (3.7) - 1 (0.7)
Reproductive System and Breast Disorders - General disorders and administration site
conditions - 1 (0.9) 1 (0.7)
Pelvic pain - 1 (0.9) 1 (0.7)
Skin and Subcutaneous Tissue Disorders - 2 (1.7) 2 (1.4)
Pruritus - 2 (1.7) 2 (1.4)
Table 5: Summary of treatment emergent adverse events (Safety population).
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 8 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
Blood Protein Level Results
One hundred percent (100%) of the control patients presented with
an initial blood protein level below the mean pregnancy average of 6.6
(g/dL) and 27% had an initial blood protein level below 6.0 (g/dL).
Ninety-Five per cent (95%) of the study patients that took Protiva, had
an initial blood protein level below the mean pregnancy average of 6.6
(g/dL) and 33% had an initial blood protein level below 6.0 (g/dL).
At six weeks post-delivery, 94% of the patients taking Protiva
improved their blood protein levels above the mean pregnancy average
of 6.6 (g/dL) as seen in Figure 1 below. is compares to 64% of the
control group who improved blood protein levels above the mean
pregnancy average of 6.6 (g/dL).
Figure 1: Percentage of patients with protein levels greater than 6.6
at 6 weeks postpartum.
At ten weeks post-delivery, 86% of study patients who took Protiva
maintained their blood protein levels above the mean of 6.6 (g/dL) as
seen in Figure 2 below. is compares to only 50% of the control
group.
Aer 14 weeks of treatment, 100% of the study patients who took
Protiva demonstrated improved blood protein levels in subsequent
visits, compared to only 86% of the control patients.
Figure 2: Percentage of patients with protein levels greater than 6.6
at 10 weeks postpartum.
Discussion
Pregnancy and lactation place increased nutritional demands on the
pregnant woman. ere is an overall increased need for calories to
achieve adequate gestational weight gain. e need for protein likewise
also increases for proper fetal and placental growth and development.
e amount of increase depends upon the woman’s starting weight and
body composition as well as current protein intake [23]. e average
non-pregnant woman needs approximately 46 g of protein daily and
this increase to 71-76 g/d in pregnancy [24-27]. Approximately 400 g
of protein is turned over in 24 h and of this 25% is replaced by dietary
intake [28]. It is impossible to accurately determine for any individual
their dietary and nutrient requirement. Current measure of height,
weight and BMI, although reasonable markers for malnutrition, are
poor for assessing inadequate nutrition or poor dietary habits [29].
Most studies done on maternal protein and calorie supplementation
have been performed in countries or regions of the world where both
caloric and protein restriction are common [30-33]. It has been widely
assumed that industrialized countries, with abundantly available
calories and protein should have adequate maternal nutrition and
certainly adequate protein intake. Studies, however, have shown that
women do not increase consumption of protein to proper levels as
pregnancy progresses [27]. Dietary advice by caregivers and physicians
is time consuming and dicult to standardize. Furthermore, there are
oen many barriers to getting pregnant woman to consume increased
volumes of whole protein foods. Studies addressing dietary
intervention and counselling have disappointing compliance rates and
lower than expected achievement of target endpoints [33-36].
Our current study looked to address a way to determine the
underlying protein status in a group of healthy women from a
community where food and protein resources are abundant, and then
determine if protein supplementation would have an impact on the
measurement parameters and pregnancy outcomes. What we found
with respect to underlying protein and albumin levels was very
interesting. e fact that the great majority of patients had serum levels
below the normal median and even completely below the normal range
was not necessarily new. It was surprising that in an auent area with
Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
Page 9 of 11
J Preg Child Health, an open access journal
ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
nutritional abundance that such a high percentage would fall into this
low range. With collagen protein supplementation we were able to
demonstrate a 94-100% improvement in protein levels in study
patients. e control patients showed a much lower improvement even
with dietary advice and overall the protein group showed a 72%
improvement over control patients. It is not entirely clear why protein
levels decease during pregnancy, but simple hemodilution cannot
explain all of the decrease as levels begin to go down as early as the rst
trimester [37] while other serum protein of hepatic origin remain
stable or increase [38]. What is known is that protein is important for
many aspects of fetal/placental growth and maternal well-being during
and aer childbirth.
Our study also showed an improvement in overall quality of life
scores and wound healing indices as measured by the WHOQOL-
BREF and REEDA pre and post study evaluations. We did not
anticipate that patients who entered the study apparently healthy and
without underlying depressive disorders, would have such dramatic
improvement in both of these outcomes. It is understood that amino
acids are important to many body and brain functions and that
inadequate protein intake can worsen depression or mental illness [39].
To what degree protein supplementation helps with quality of life
assessments has not been studied in pregnant women and this report
makes for interesting future direction of study for pregnant patients.
e addition of the vitamins A, C, E and the minerals Zinc, Copper
and Calcium are necessary for the dierent phases of wound healing
and have studies showing their ecacy and importance. Vitamin D has
been shown to be of value both for the mother and fetus [40] however
we did not intend to measure maternal or fetal eects of
supplementation alone. Studies looking at the use of supplemental
vitamins have had mixed results and there is little evidence that
vitamin supplements improve fetal outcomes when looking at
stillbirth, neonatal death, preterm birth, etc. [40,30]. eir use in our
study was an adjunct to protein supplementation for proper healing of
vaginal lacerations, episiotomies or caesarean section incisions. Based
on the responses from the patient REEDA evaluations it appears that
there was indeed a signicant improvement in the supplementation
compared to the control group.
Of note was that there was no dierence in adverse events between
the two groups and no apparent impact on breast feeding or other
post-delivery parameters with regards to breastfeeding or new-born
problems. is should reassure pediatricians and lactations specialists
who encounter patients taking collagen protein supplementation and
how they counsel them about stopping or continuing with the
supplementation.
is study appears to be the rst of its kind to look at the physical
and quality of life of mothers taking collagen protein supplementation
during pregnancy. It is also unique in measuring the response to
supplementation with respect to wound healing aer delivery. e fact
that there were no adverse outcomes in the study group points to the
safety of collagen protein supplementation during pregnancy. ere are
no theoretical risks to collagen as it is comprises 65% of the protein
content in animals and thus is a major constituent of what is consumed
when eating animal proteins in the diet. e form provided for the
study group was easy to consume, readily available and highly eective
in supplementing the pregnant woman’s diet to improve maternal
outcomes and at the same time provide adequate protein to her
developing fetus. When protein is limited in the diet, there is the
concern that the fetus may be at risk for both short and long term
health consequences [41-45]. is study did not address fetal growth,
neonatal parameters or long term infant health. However, it would
appear prudent that since fetal health is directly dependent on
maternal health and nutrition, that providing proper nutrition to the
mother would maximize the potential for a healthy fetus and new-
born.
Key Message
Pregnancy and lactation place increased nutritional demands on the
pregnant woman. e need for protein also increases, for proper fetal
and placental growth and development. e average non-pregnant
woman needs approximately 46 g of protein daily and this increase to
71-76 (g/dL) in pregnancy.
is study found the great majority of patients had initial serum
levels below the normal median and even completely below the normal
range. With collagen protein supplementation we were able to
demonstrate improved quality of life and wound healing and 100%
improvement in protein levels in study patients and a 72%
improvement over control patients.
Acknowledgement
Marsha Kmec who's tireless help to retrieve dicult to nd
references was critical to the success of this project Carolyn Patchett
RNP for her support and leadership at site #2 Marianina Elena Mata de
la Garza for her incredible phlebotomy skills.
Contributor Statement
Leon Baginski, M.D is the principle investigator, rst author and
editor for this original research article. Marc Winter MD is the second
author for this original article. Mary O’Toole, M.D. is the principle
investigator, site number 2. Frank Turner, DPM is the editor and
medical writer for this original research article. Innovative Research
Associates is the contracted CRO for this original research article.
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Citation: Baginski L, Winter M, Bailey TS, Capobianco S, Granese M, et al. (2016) Response to Hydrolyzed Collagen Protein Supplementation in
a Cohort of Pregnant and Postpartum Women. J Preg Child Health 3: 275. doi:10.4172/2376-127X.1000275
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ISSN:2376-127X
Volume 3 • Issue 5 • 1000275
