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Address correspondence to: Sarbattama Sen, MD, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
Maternal body mass index (BMI) and systemic fatty acid (FA) concentrations affect inflammatory balance in pregnancy and play a key role in fetal growth and well-being. Little is known about how maternal BMI may affect the association between key FA concentrations and neonatal outcomes. The objective of this study was to examine the associations between the maternal omega (n)6:n3 FA ratio and neonatal outcomes according to maternal pre-pregnancy BMI category.
Methods
This study is a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of omega-3 FA supplementation to prevent recurrent preterm birth. At consent (16–22 weeks of pregnancy), women were randomized to either the intervention arm (2 g of n3 FAs) or the control arm (placebo). For the present analysis, the primary exposure was the ratio of proinflammatory to anti-inflammatory (n6:n3) FAs at 25 to 28 weeks of pregnancy. The primary outcome was fetal growth as measured by using birth-weight-for-gestational-age z score, birth-length-for-gestational-age z score, and head-circumference-for-gestational-age z score. BMI categories were defined as lean (18.5–24.9 kg/m²) and overweight/obese (OWOB) (≥25.0 kg/m²). Final analysis was stratified according to BMI and adjusted for education, race, parity, smoking status, total fish intake at the time of the blood draw, and number of days in the study at the time of delivery.
Findings
A total of 440 participants were included in this analysis; 49% were lean, and 51% were OWOB. After adjustment for covariates, a higher maternal n6:n3 FA ratio was associated with impaired fetal growth (birth-weight-for-gestational-age z score, β = –0.04 per unit increase in n6:n3; 95% CI, –0.07 to –0.01), 1 day shorter length of gestation (β = –0.14 week; 95% CI, –0.27 to –0.01), higher incidence of neonatal respiratory distress syndrome (odds ratio, 1.37; 95% CI, 1.04 to 1.80), and increased length of neonatal hospital stay (β = 0.29 day; 95% CI, 0.003 to 0.58) in OWOB, but not lean, participants.
Implications
Higher maternal inflammation during pregnancy, as measured by using the n6:n3 FA ratio, may be a marker of adverse perinatal and neonatal outcomes, particularly among OWOB women.
Maternal obesity is associated with short- and long-term sequelae in offspring, including increased risk for asthma, neurodevelopmental impairments, and predisposition for later metabolic syndrome and obesity.
The metabolism of n6 FAs (linoleic acid and arachidonic acid) leads to the release of pro-inflammatory eicosanoids into the systemic circulation. In contrast, n3 FAs are known to be relatively anti-inflammatory because the metabolism of n3 FAs (docosahexaenoic acid and eicosapentaenoic acid [EPA]) produce anti-inflammatory lipid mediators.
Previous studies have suggested that higher n6 FA concentrations and lower n3 FA concentrations (ie, a higher n6:n3 FA ratio) are associated with increased inflammation and a higher prevalence of metabolic co-morbidities, and could have negative implications for fetal development.
The effect of maternal omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during pregnancy and/or lactation on body fat mass in the offspring: a systematic review of animal studies.
Our group has previously shown that maternal obesity is associated with deficiency in micronutrients such as folate, vitamin B6, vitamin C, and vitamin E that are important in regulating inflammation.
We and others have also found that in mid-pregnancy, obese women had lower n3 FA concentrations and higher n6 FA levels compared with normal- weight mothers.
Monthe-Dreze C, Penfield-Cyr A, Smid M, Sen S. Maternal pre-pregnancy obesity attenuates response to omega-3 fatty acid supplementation during pregnancy. Abstract presented at Society for Reproductive Investigation, Orlando, FL, March 2017 and New England Perinatal Scientific Meeting, Newport, RI, March 2018; manuscript under review.
However, little is known about whether the association between systemic FA concentrations and fetal outcomes differs according to maternal BMI. The objective of the present study was to determine how maternal BMI modifies the association between the maternal mid-pregnancy n6:n3 FA ratio and fetal growth. We hypothesized that a higher maternal mid-pregnancy n6:n3 FA ratio would be associated with impaired fetal growth and adverse perinatal and neonatal outcomes, particularly in overweight and obese women.
Patients and Methods
Participants
This study was a secondary analysis of a cohort that consisted of women recruited from the Maternal-Fetal Medicine Units Network omega-3 trial. This analysis was approved by the Brigham and Women's/Partners Institutional Review Board and conducted in accordance with the Declaration of Helsinki. Participants consented to participate in a randomized controlled trial of n3 FA supplementation in pregnancy to prevent recurrent preterm birth at 1 of 17 US centers (clinicaltrials.gov, NCT00135902).
Participants were recruited from 13 academic medical clinics in the United States between January 2005 and October 2006. All participants had a history of at least 1 previous preterm birth and a current singleton pregnancy between 16 and 22 weeks’ gestation. Weekly 17-hydroxy progesterone injections (250 mg) were provided for preterm birth prevention to all study participants. Exclusion criteria for the parent study were intake of a fish oil supplement in excess of 500 mg per week, allergy to fish, anticoagulation therapy, clotting disorder, hypertension, White's classification D or higher diabetes, evidence of a major congenital anomaly, drug or alcohol abuse, seizure disorder, uncontrolled thyroid disease, a current or planned cerclage, or a plan to deliver elsewhere or before 37 weeks’ gestation.
A total of 852 mothers were recruited and were randomized to receive either a placebo (inert mineral oil) or 2 g of n3 FA (800 mg of docosahexaenoic acid + 1200 mg of EPA) supplementation daily, via oral capsules, for the remainder of their pregnancy. For this secondary analysis, we further excluded participants who had a uterine anomaly, pre-gestational or gestational diabetes, preeclampsia, or gestational hypertension, or an infant with a congenital malformation, as these factors all have a potential impact on fetal growth. We also excluded participants if they had an intrauterine fetal demise, stillbirth or neonatal death, those who did not have a recorded pre-pregnancy BMI, or had a BMI <18.5 kg/m2. Lastly, we excluded those who did not have FA concentrations measured at the mid-pregnancy study time point because this period was the main exposure for this study. Data from 440 mother–infant dyads were used in the final analysis (see the Supplemental Figure in the online version at doi:10.1016/j.clinthera.2018.08.011).
Exposure
For the present analysis, the primary exposure was the plasma ratio of proinflammatory to anti-inflammatory FAs (n6:n3 FA ratio) in mid-pregnancy. Whole blood samples were collected at 25 to 28 weeks’ gestation in EDTA tubes and centrifuged to separate plasma from the red blood cell fraction. Plasma samples were snap-frozen and stored at –70°C until they were shipped to a central laboratory for individual measurement by using previously described methods.
Briefly, phospholipids were separated by using thin-layer chromatography on hard-layer silica gel plates in equilibrated tanks of prepared hexane/ethyl ether/acetic acid (70:30:1, v/v/v). Phospholipids were eluted with chloroform methanol, and FAs were then extracted by using modification of a previously described procedure.
FAs were methylated with 14% boron trifluoride methanol and analyzed by using gas chromatography. Individual FA methyl esters were identified by comparison of retention times with known FA methyl ester standards (Nu-Chek-Prep, Elysian, Minnesota). The concentrations of four n3 FAs (EPA, docosahexaenoic acid, α-linolenic acid, and eicosatrienoic acid) and four n6 FAs (arachidonic acid, linoleic acid, dihomo-γ-linolenic acid, and docosapentaenoic acid) were assayed and reported as percent weight of total FAs. Total n3 and n6 FAs were calculated by adding the individual values of the constituent FAs and the ratio of n6:n3 FA calculated from these sums.
Outcomes
The primary outcome for the present analysis was fetal growth as measured by using the following: (1) birth-weight-for-gestational age z score (BWGA-Z); (2) birth-length-for-gestational-age z score; and (3) head-circumference-for-gestational-age z score. All z scores were calculated by using the Fenton 2013 clinical calculator.
There were insufficient numbers of small- and large-for-gestational-age infants within this cohort to utilize this outcome. Other secondary neonatal clinical outcomes included gestational age at birth, infant growth percentiles using small-for-gestational-age and large-for-gestational-age measures at birth, length of hospital stay following birth (LOS), need for ventilation following birth, need for supplemental oxygen following birth, respiratory distress syndrome (RDS), and neonatal intensive care unit admission. All neonatal outcome data were extracted after delivery by the study team of the parent trial from a medical record review of labor, delivery, and nursery records.
Pre-pregnancy BMI was calculated by using self-reported pre-pregnancy weight and height abstracted from the medical chart. Because our objective was to assess if BMI modified the association between maternal plasma n6:n3 FA ratio and outcomes, participants were stratified according to maternal pre-pregnancy BMI into 2 categories: lean (18.5–24.9 kg/m²) and overweight/obese (OWOB) (≥25.0 kg/m²). We combined overweight (25.0–29.9 kg/m2) and obese (≥30.0 kg/m²) into 1 BMI category because there were no statistical differences in the exposure and outcome associations between obese and overweight women. The associations between our exposure and outcomes stratified according to BMI category were then examined. We also wanted to examine whether the strength of the association differed according to treatment group (n3 supplemented–women vs control subjects), so this factor was also considered an effect modifier.
Statistical Analysis
Descriptive statistics were used to characterize and compare sociodemographic variables according to BMI category. Mean maternal plasma n6:n3 FA ratio and infant outcomes were compared between BMI categories by using Student's t test for continuous variables or the χ2 test for categorical variables. Unadjusted associations were examined between maternal plasma n6:n3 FA ratios and infant outcomes by using linear regression. To determine whether the strength of associations differed according to BMI category or treatment group, interaction terms were calculated. If the interaction term was significant (P < 0.1), a stratified analysis was then conducted. The final multivariable regression analyses were stratified according to BMI category and/or treatment group and adjusted for maternal race, education, parity, smoking status, total fish intake at the time of the blood draw, and the number of days in the study at the time of delivery. We defined statistical significance a priori for the primary associations as P < 0.05. Analysis was conducted by using Stata release 13 (StataCorp, College Station, Texas).
Results
Cohort Characteristics
A total of 440 mother–infant dyads were included in this analysis (Table 1): 49% were lean, and 51% were OWOB. There were no significant differences in clinical characteristics between participants who were included and excluded from this secondary analysis. OWOB participants were more likely to be non-white, have fewer years of education, be multiparous, and to have smoked during their pregnancy (Table I). The mean (SD) mid-pregnancy plasma n6:n3 FA ratio of OWOB participants (8.0 [4.3]) was higher than that of lean participants (6.8 [4.2]; P = 0.01). Forty-nine percent of participants were in the treated group and 51% in the control group, and these groups did not differ in demographic characteristics. As expected, the mean (SD) mid-pregnancy plasma n6:n3 FA ratio was higher in the control arm compared with the treatment arm (control vs treatment, 8.9 [3.9] vs 6.0 [4.1]; P < 0.001).
Table ICharacteristics of maternal and infant participants according to body mass index (BMI) subgroup.
Characteristic
All Women (N = 440)
Lean: BMI <25 kg/m² (n = 215)
OWOB: BMI ≥25 kg/m² (n = 225)
P
Maternal age at consent, mean (SD), y
27.5 (5.5)
27.6 (5.5)
27.5 (5.5)
0.91
Gestational age at consent, mean (SD), wk
19.3 (1.7)
19.3 (1.7)
19.4 (1.7)
0.57
BMI at consent, mean (SD), kg/m²
26.3 (6.2)
21.6 (1.6)
30.8 (5.6)
<0.001*
Race/ethnicity
<0.001*
White
212 (48%)
123 (57%)
89 (40%)
Black
152 (34%)
51 (24%)
100 (44%)
Hispanic
64 (15%)
31 (15%)
33 (15%)
Other
12 (3%)
9 (4%)
3 (1%)
Years of schooling
0.001*
Some high school
80 (18%)
28 (13%)
52 (23%)
Completed high school
115 (26%)
53 (25%)
62 (28%)
Some college
117 (27%)
54 (25%)
63 (28%)
Completed college
128 (29%)
80 (37%)
48 (21%)
Parity
0.003*
1
202 (46%)
116 (54%)
86 (38%)
2
128 (29%)
57 (26%)
71 (32%)
>2
110 (25%)
42 (20%)
68 (30%)
No. of prior preterm births
0.38
1
321 (73%)
163 (76%)
158 (70%)
2
92 (21%)
41 (19%)
51 (23%)
>2
27 (6%)
11 (5%)
16 (7%)
Smoking status
0.01*
Yes
69 (16%)
24 (11%)
45 (20%)
Length of supplementation at (corresponding to delivery, mean (SD), d)
125.6 (22.0)
125.3 (20.6)
125.9 (23.2)
0.80
Servings of fish intake per week in mid-pregnancy
0.95
0
151 (34%)
75 (35%)
76 (34%)
≤1
165 (38%)
79 (37%)
86 (38%)
>1
124 (28%)
61 (28%)
63 (28%)
Gestational age at birth, wk
0.58
<32
25 (6%)
12 (6%)
13 (6%)
32–37
125 (28%)
66 (31%)
59 (26%)
>37
290 (66%)
137 (64%)
153 (68%)
Infant growth percentiles
0.89
SGA
31 (7.06%)
16 (7.48%)
15 (6.67%)
AGA
383 (87.24%)
188 (87.85%)
195 (86.67%)
LGA
25 (5.69%)
10 (4.67%)
15 (6.67%)
Infant z scores
BWGA-Z
–0.014 (0.86)
–0.037 (0.82)
0.007 (0.90)
0.59
BLGA-Z
0.281 (0.95)
0.301 (0.95)
0.262 (0.95)
0.67
HCGA-Z
0.049 (1.04)
0.052 (0.98)
0.047 (1.11)
0.96
Infant sex
0.32
Female
224 (51%)
104 (49%)
120 (53%)
Maternal mid-pregnancy n6:n3 ratio, mean (SD)
7.4 (4.3)
6.8 (4.2)
8.0 (4.3)
0.007*
Treatment group
0.39
Treated
216 (49%)
101 (47%)
115 (51%)
Control
224 (51%)
114 (53%)
110 (49%)
AGA = appropriate for gestational age; BLGA-Z = birth-length-for-gestational-age z score; BWGA-Z = birth-weight-for-gestational-age z score; HCGA-Z = head-circumference-for-gestational-age z score; LGA = large for gestational age; n6:n3 = omega-6 to omega-3 fatty acid ratio; OWOB = overweight/obese; SGA = small for gestational age. *p<0.05
Maternal Plasma n6:n3 FA Ratio and Fetal Growth Outcomes
In the fully adjusted analysis of all participants, each one point in maternal plasma n6:n3 FA ratio was associated with a 0.02 lower infant BWGA-Z (β = –0.02 z score per unit n6:n3; 95% CI, –0.04 to –0.001). This association differed according to BMI category (interaction P = 0.068), such that in the stratified analysis, a higher maternal plasma n6:n3 FA ratio was associated with slightly lower fetal growth among OWOB participants (β = –0.04; 95% CI, –0.07 to –0.01) but not lean participants (β = –0.003; 95% CI, –0.03 to 0.02). There was also evidence of effect modification by treatment group (interaction P = 0.06). Thus, within the OWOB-treated group, one point of maternal n6:n3 FA ratio was associated with a 0.04 lower infant BWGA-Z (β = –0.04; 95% CI, –0.07 to –0.005) but not in the OWOB control group (β = –0.04; 95% CI, –0.09 to 0.02).
The maternal plasma n6:n3 FA ratio was not associated with infant birth-length-for-gestational-age z score in all participants (β = 0.006; 95% CI, –0.02 to 0.03) or in any subgroup. Similarly, the maternal plasma n6:n3 FA ratio was not associated with infant head-circumference-for-gestational-age z score in all participants (β = –0.01; 95% CI, –0.04 to 0.01) or in any subgroup (Table II).
Table IIAssociation (β [95% CI]) between maternal omega-6:omega-3 fatty acid ratio and fetal growth outcomes.
β adjusted for: maternal race, education, parity, smoking status, total fish intake at the time of the blood draw, and the number of days in the study at the time of delivery. *p<0.05
Birth-weight-for-gestational-age z score
All women
–0.03 (–0.05 to –0.008)*
–0.02 (–0.04 to –0.001)*
Lean
–0.01 (–0.03 to 0.02)
–0.003 (–0.03 to 0.02)
Overweight/obese
–0.05 (–0.07 to –0.02)*
–0.04 (–0.07 to –0.01)*
Birth-length-for-gestational-age z score
All women
–0.003 (–0.03 to 0.02)
0.006 (–0.02 to 0.03)
Lean
0.001 (–0.03 to 0.03)
0.01 (–0.02 to 0.04)
Overweight/obese
–0.004 (–0.04 to 0.03)
0.002 (–0.03 to 0.03)
Head-circumference-for-gestational-age z score
All women
–0.02 (–0.04 to 0.01)
–0.01 (–0.04 to 0.01)
Lean
–0.02 (–0.05 to 0.01)
–0.01 (–0.05 to 0.02)
Overweight/obese
–0.02 (–0.05 to 0.02)
–0.01 (–0.05 to 0.03)
aβ adjusted for: maternal race, education, parity, smoking status, total fish intake at the time of the blood draw, and the number of days in the study at the time of delivery. *p<0.05
Maternal Plasma n6:n3 FA Ratio and Gestational Age at Birth
The maternal n6:n3 plasma FA ratio was not associated with infant gestational age at birth in the overall cohort (β = –0.01 week per n6:n3 unit; 95% CI, –0.04 to 0.03). Interestingly, there was evidence of effect modification according to BMI within the control group (interaction P = 0.03). In the stratified analysis, in the OWOB control group, a one unit increase in maternal plasma n6:n3 FA ratio was associated with delivering 1 day earlier (β = –0.14 week per unit n6:n3; 95% CI, –0.27 to –0.01). There was a trend in the opposite direction (although this did not exclude the null) in the lean control group (β = 0.09; 95% CI, –0.06 to 0.24) (Figure 1).
Figure 1Predicted associations derived from the final linear regression model of maternal omega-6 to omega-3 (n6:n3) fatty acid ratio with infant gestational age at delivery within the control group according to maternal body mass index (BMI) category (maternal BMI category as an effect modifier).
Maternal Plasma n6:n3 FA Ratio and Secondary Neonatal Outcomes
A higher maternal plasma n6:n3 FA ratio was associated with higher odds of RDS in infants of OWOB participants (odds ratio, 1.37; 95% CI, 1.04 to 1.80). After adjustment for gestational age, this association was attenuated (odds ratio, 1.34; 95% CI, 0.98 to 1.82). There was no association between maternal plasma n6:n3 FA ratio and odds of RDS in infants born to lean participants (odds ratio, 1.02; 95% CI, 0.88 to 1.17).
There was no association between maternal n6:n3 FA ratio and infant LOS in all women (β = 0.13 day per unit n6:n3 FA ratio; 95% CI, –0.08 to 0.35). However, when stratified according to maternal BMI, a higher maternal plasma n6:n3 FA ratio was also associated with longer LOS for infants born to OWOB women such that a 3.4 unit higher maternal n6:n3 FA ratio was associated with 1 day longer neonatal LOS (β = 0.29 day per unit n6:n3 FA ratio; 95% CI, 0.003 to 0.58). There was no association between maternal plasma n6:n3 FA ratio and neonatal LOS in lean participants (β = –0.03 day per unit n6:n3; 95% CI, –0.36 to 0.31). The association between n6:n3 ratio and neonatal LOS was markedly different in OWOB women versus lean women in the control group (interaction P = 0.047) (Figure 2). In contrast, among women who received n3 supplementation, maternal BMI category did not change the strength of the association between n6:n3 ratio, and neonatal LOS BMI category did not modify the association between maternal plasma n6:n3 FA ratio and infant LOS (interaction P = 0.63).
Figure 2Associations (β) of maternal omega-6 to omega-3 (n6:n3) fatty acid to neonatal length of hospital stay according to body mass index and treatment subgroup. *Indicates interaction (P < 0.05) between lean and overweight/obese participants within the control group.
The maternal plasma n6:n3 FA ratio was not associated with infant need for oxygen, infant need for ventilation, or infant neonatal intensive care unit admission in any participant or according to BMI category.
Discussion
In this secondary analysis of a trial of n3 supplementation to prevent recurrent preterm birth, we found that a higher systemic n6:n3 FA ratio mid-gestation in OWOB pregnant women was associated with decreased fetal growth, shorter length of gestation, and higher odds of RDS. The magnitude of these associations was small, but statistically significant, and may lay the foundation for future studies in this high-risk group. These findings also suggest that the n6:n3 FA ratio may be an important metabolic marker with implications for fetal growth and health in OWOB pregnant women.
We found that increased inflammatory load, specifically plasma n6:n3 FA ratio, is associated with impaired fetal growth. This finding is consistent with previous studies examining the association between maternal FA concentrations and offspring growth and body composition outcomes. Meher et al
reported that higher mid-pregnancy n6 FA levels were associated with lower infant birth weight and head circumference. They also showed that lower maternal n3 and higher n6 FA levels at delivery were associated with low birth weight. Grootendorst-van Mil et al
Maternal plasma n-3 and n-6 polyunsaturated fatty acids during pregnancy and features of fetal health: fetal growth velocity, birth weight and duration of pregnancy.
reported that higher maternal n3:n6 FA ratio in mid-pregnancy was associated with higher ultrasound-measured growth velocity of fetal weight, length, and head circumference. Here, we additionally report that the association between maternal FA concentrations and fetal growth may be strongest in OWOB women, who have higher baseline inflammation levels.
We further report that a higher maternal plasma n6:n3 FA ratio was associated with a shorter length of gestation in the OWOB participants. Other groups have reported similar findings. Grootendorst-van Mil et al
reported that a higher n3:n6 FA ratio was associated with a longer length of gestation, and others have reported associations between markers of inflammation, such as interleukin-8, and length of gestation.
Our study examines the role of maternal BMI or maternal inflammation in this association and also highlights the importance of biomarkers that are able to reflect both sides (the balance of proinflammatory and anti-inflammatory) of a particular biologic pathway.
The parent study found no benefit in the overall cohort of n3 FA supplementation on length of gestation or birth weight.
However, in the present study, we report that a higher n6:n3 FA ratio was associated with shorter gestation in OWOB women. This finding may be due to the higher baseline levels of intrinsic systemic inflammation, which influences the balance of n6:n3 FAs, or maternal diet, as obesity is associated with consumption of a more proinflammatory, typically “Western” diet, rich in n6 FAs.
Both the intrinsic metabolic state and dietary differences associated with obesity have been shown to contribute to the abnormal metabolic environment of obese pregnancy. The accretion of adipose tissue and concurrent macrophage accumulation in overweight and obese individuals leads to increased expression of systemic pro-inflammatory cytokines,
which is associated with a chronic state of dysregulated systemic inflammation. In addition, the typical “Western” diet is high in trans and saturated FAs and low in polyunsaturated FAs, leading to an increased systemic inflammatory load.
In contrast, we report here that in infants born to OWOB women, a higher plasma n6:n3 FA ratio was associated with higher odds of RDS, likely related to the shorter length of gestation. Animal models suggest that a maternal diet high in n3 fatty acids leads to a higher phosphatidylcholine fraction in fetal lung, which is critical for surfactant biosynthesis.
Future studies should examine whether this benefit is dependent on maternal inflammatory balance, source of FAs, or dietary status.
Strengths of the present study include availability of detailed data regarding participant and neonatal characteristics that were available through the parent study.
Given that the parent study was a randomized trial, there was less residual confounding than observational studies, although we did additionally adjust for characteristics that may have been unbalanced when participants were categorized according to BMI group. In addition, FA measures were conducted by using gold standard methods. Our study findings have limited generalizability, given the inclusion and exclusion criteria of the parent trial. All of the women in the trial had experienced a previous preterm delivery and were taking progesterone, which could also affect systemic inflammatory balance. We do not have detailed dietary information for participants either pre-pregnancy or during pregnancy. We were also limited in terms of the lack of long-term follow-up data and measurements on infants.
Conclusions
The present study showed that the maternal plasma n6:n3 FA ratio during pregnancy may be associated with key perinatal health outcomes such as fetal growth and length of gestation in OWOB women. Future studies should also examine whether nutritional intervention or supplementation of n3 FAs, specifically in OWOB women, may improve perinatal health outcomes.
Acknowledgments
This study was funded by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23 HD 074648 to Dr. Sen).
All authors designed the research. Ms. Penfield-Cyr and Dr. Monthe-Dreze conducted research, and analyzed the data or performed statistical analysis; all authors wrote and revised the paper; and Dr. Sen had primary responsibility for final content. All authors have read and approved the final manuscript.
Conflicts of Interest
The authors have indicated that they have no conflicts of interest nor have they received previous support from industry or organizations that might have influenced this work.
The effect of maternal omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during pregnancy and/or lactation on body fat mass in the offspring: a systematic review of animal studies.
Monthe-Dreze C, Penfield-Cyr A, Smid M, Sen S. Maternal pre-pregnancy obesity attenuates response to omega-3 fatty acid supplementation during pregnancy. Abstract presented at Society for Reproductive Investigation, Orlando, FL, March 2017 and New England Perinatal Scientific Meeting, Newport, RI, March 2018; manuscript under review.
Maternal plasma n-3 and n-6 polyunsaturated fatty acids during pregnancy and features of fetal health: fetal growth velocity, birth weight and duration of pregnancy.
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