Introduction
Over the past three decades, obesity rates have surged dramatically across the United States and worldwide. While recent data suggests a possible slowdown or leveling off in the prevalence of obesity among adults and children, the current figures remain alarming. Approximately 35.7% of adults and 18.4% of adolescents are classified as obese, compared to 14.5% and 6.1% respectively in 1971-1974. This increase is concerning because obesity is linked to serious health consequences, including premature mortality and elevated risks for diabetes, cardiovascular disease, certain cancers, sub-fertility, and depression.
Recognizing the profound influence of the intrauterine environment on future health outcomes, researchers have increasingly focused on this period as a predictor of later-life obesity. Studies have indicated that maternal starvation during the first half of pregnancy can significantly increase the risk of obesity in male offspring. Similarly, exposure to maternal diabetes in utero and larger size for gestational age have been associated with childhood obesity. Given the critical role of prenatal nutrition, the use of prenatal vitamins has come under scrutiny regarding its potential impact on offspring body fatness. Some researchers have hypothesized that prenatal vitamin intake may contribute to obesity by increasing the number of adipose tissue cells in the developing fetus. However, the existing human data on this association remains sparse.
This article aims to comprehensively explore the relationship between prenatal vitamin intake and weight gain or obesity, drawing upon existing research, including a study from the Nurses’ Health Study II (NHS II). This article will delve into the effects of prenatal vitamins and other supplements on gestational weight gain (GWG) and offspring body fatness.
Prenatal Vitamins and Childhood Obesity: Evidence from the Nurses’ Health Study II
One significant study investigating the link between prenatal vitamin intake and obesity was conducted using mother-daughter dyads from the Nurses’ Health Study II (NHS II) and the Nurses’ Mothers’ Cohort Study. The NHS II, initiated in 1989, recruited 116,478 female registered nurses aged 25 to 42 years across 15 US states. Participants in the Nurses’ Mothers’ Cohort Study provided information about their prenatal vitamin use during pregnancy with their nurse daughter, including whether they took the vitamins regularly.
The study analyzed data from 29,160 mother-daughter dyads to determine if in utero exposure to prenatal vitamins was associated with body fatness in childhood or adulthood. Information on body fatness at ages 5 and 10, body mass index (BMI) at age 18, weight in 1989 and 2009, waist circumference, and height were obtained from the daughters. Childhood body fatness was assessed using a nine-level drawing developed by Stunkard, where NHS II participants identified their body size at ages 5 and 10.
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The findings revealed that in utero exposure to prenatal vitamins was not associated with body fatness, either in childhood or adulthood. Specifically, women whose mothers took prenatal vitamins during pregnancy had a covariate-adjusted odds ratio of being obese in adulthood of 0.99 (95% CI 0.92 - 1.05, P-value = 0.68) compared to women whose mothers did not take prenatal vitamins. Similarly, these women had a covariate-adjusted odds ratio of having the largest body shape at age 5 of 1.02 (95% CI 0.90 - 1.15, P-value = 0.78).
Methodology and Statistical Analysis
The researchers used polytomous logistic regression to predict BMI in early adulthood and adulthood, as well as body fatness in childhood. Several potential predictors of obesity were considered in the statistical models, including:
- Age of the nurse at questionnaire return
- Maternal age at birth of the nurse
- Birth order of the nurse
- Mother’s education level
- Maternal BMI
- Consumption of dark leafy green vegetables during pregnancy
- Total activity level during pregnancy
- Maternal smoking habits
- Living situation with the nurse’s father at the time of birth
- Home ownership at the time of birth
- Father’s education and profession
- Preeclampsia and gestational diabetes
- Gestational weight gain
- Utilization of prenatal care during pregnancy
- Whether the nurse was ever breastfed
Missing data on covariates were addressed using missing indicators. Follow-up for the analyses began in 1989 at the NHS II study baseline and ended in 2009. BMI in 2009 was categorized into several levels, and polytomous logistic regression was used to estimate odds ratios for each BMI category relative to a reference group. Additional analyses modeled BMI in 2009 and at age 18 as continuous variables.
Detailed Findings from the NHS II Study
The study found that 67% of the nurse mothers took prenatal vitamins during pregnancy with their nurse daughter, while 33% did not. In 2009, the mean BMI of the adult nurse daughters was 27.3 kg/m2, and at age 18, the mean BMI was 21.1 kg/m2. Women whose mothers regularly took prenatal vitamins during pregnancy were slightly younger at baseline than women whose mothers did not take prenatal vitamins during pregnancy.
In the age-adjusted analysis, in utero exposure to prenatal vitamins was significantly associated with BMI in 2009 only for those with a BMI of 34 kg/m2 or higher, compared to the reference group of 23- < 25 kg/m2. The age-adjusted odds ratio for having a BMI of 34 or greater was 0.90 (95% CI 0.82-0.98) compared to those with a BMI of 23 - < 25 kg/m2. Additional covariates related to the nurse, including age at menarche, age at first birth, smoking status, parity, and income, were also considered in a separate model.
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Prenatal vitamin intake was also unrelated to BMI in 2009 when BMI was modeled as a three-level categorical variable. The age-adjusted OR for being overweight compared to normal weight was 1.00 (95% CI 0.94-1.07), and for being obese compared to normal weight was 0.99 (95% CI 0.92 -1.05). In utero exposure to prenatal vitamins was significantly associated with BMI at age 18 in the age-adjusted analysis, only for those with a BMI of 25 kg/m2 or higher. The age-adjusted OR was 0.85 (95% CI 0.77-0.93) comparing those with a BMI of 25 kg/m2 to the reference group of 20 - < 22 kg/m2.
Limitations of the Study
The study acknowledges several limitations. The lack of detailed information on prenatal vitamin intake and the reliance on mothers' recall from several decades earlier may introduce recall bias. However, the researchers believe that any bias would likely be directed toward the null, as an association between vitamin use during pregnancy and offspring overweight was not suspected. Additionally, the timing of prenatal vitamin intake was unknown, which could be a critical determinant of the outcome.
Despite these limitations, the study has several strengths, including a large sample size and comprehensive data on potential confounders.
Multimicronutrient Supplementation and Gestational Weight Gain
Another crucial aspect of prenatal health is gestational weight gain (GWG). GWG below or above the Institute of Medicine (IOM) recommendations has been associated with adverse perinatal outcomes. A 2-stage meta-analysis of individual participant data, including 45,507 women from 14 trials and 6237 women from 4 trials, examined the effects of multiple micronutrient supplements (MMSs) and small-quantity lipid-based nutrient supplements (LNSs) on GWG compared with iron and folic acid supplements only.
The study found that MMSs resulted in a greater percentage adequacy of GWG [weighted mean difference (WMD): 0.86%; 95% CI: 0.28%, 1.44%; P < 0.01] and higher GWG at delivery (WMD: 209 g; 95% CI: 139, 280 g; P < 0.01) than among those in the control arm. Women who received MMSs had a 2.9% reduced risk of severely inadequate GWG (RR: 0.971; 95% CI: 0.956, 0.987; P < 0.01). No association was found between small-quantity LNSs and GWG percentage adequacy (WMD: 1.51%; 95% CI: −0.38%, 3.40%; P = 0.21).
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Metabolic Changes During Pregnancy
Pregnancy is characterized by significant metabolic changes, increasing the requirements for nutrients and energy intake. As pregnancy progresses, the maternal basal metabolic rate increases, reaching 10%-20% more than nonpregnancy rates. Weight gain is primarily due to fat deposition and placental development during the first trimester, with the fastest weight gain occurring in the second trimester and slightly decreasing in the third trimester. In the later trimesters, weight gain is more related to fetal growth, maternal fat stores, and total body water accretion.
Undernutrition is common among women in low- and middle-income countries (LMICs), placing them at higher risk of multiple micronutrient deficiencies due to food insecurity, low dietary diversity, and the increased demands of the developing fetus. The UN International Multiple Micronutrient Antenatal Preparation (UNIMMAP) tablet, containing 15 micronutrients including 30 mg Fe and 0.4 mg folic acid, is the most widely available prenatal MMS. Prenatal small-quantity lipid-based nutrient supplements (LNSs), providing ∼120 kcal/d, offer another strategy for delivering vitamins, minerals, essential fatty acids, and macronutrients not incorporated in MMS tablets.
Implications of Gestational Weight Gain
GWG is widely recognized as an indicator of adequate nutrition during pregnancy. Inadequate GWG has been consistently associated with adverse birth outcomes such as prematurity, small-for-gestational-age birth, low birth weight, and infant mortality. Conversely, excessive GWG has been linked to increased risks of large-for-gestational-age birth, macrosomia, cesarean delivery, gestational diabetes, and subsequent maternal obesity. Demographic surveillance data from sub-Saharan Africa and India suggest that average weight gain among pregnant women is only ∼60% of the recommended amount for normal-weight women.
Given that weight gain during pregnancy is routinely monitored in prenatal clinical care, it represents a modifiable risk factor for adverse birth and maternal outcomes. This highlights the importance of understanding the effects of prenatal nutritional supplements on GWG.
Systematic Review and Meta-Analysis of Nutritional Supplements and GWG
A systematic review and meta-analysis were conducted using individual participant data from randomized controlled trials to examine the effects of MMSs and small-quantity LNSs on GWG among pregnant women in LMICs. The review included randomized controlled trials of prenatal nutrient supplements from LMICs published after January 2000 up to December 2021. Trials conducted exclusively among pregnant women with a health condition, such as anemia, HIV, or diabetes, were excluded.
The analysis included 16 trials with a combined sample size of 50,927 pregnant women. In all trials, women in the control arm were provided daily supplementation of iron with or without folic acid or had access to prenatal supplementation from local health services. Data were analyzed using multiple linear regression models to examine the association between MMSs or small-quantity LNSs and continuous outcomes, including percentage adequacy of GWG and estimated total GWG at delivery. Modified Poisson regression with robust variance estimation was used to estimate the association between MMSs or small-quantity LNSs compared with iron and folic acid only and binary outcomes, including severely inadequate, inadequate, and excessive GWG.
Characteristics of Included Trials
The mean GWG percentage adequacy was 77%, ranging from 60% to 107% across the 16 trials included in the analysis. Pregnant women who received maternal MMSs had greater percentage adequacy of GWG and estimated total GWG at delivery than those in the control arm. Study-specific results demonstrated that in 9 of the 14 trials, MMSs had positive effects on percentage adequacy of GWG.
Individual data from 4 trials of small-quantity LNSs were included in the analysis. In the study-specific analysis, maternal small-quantity LNSs were positively associated with GWG percentage adequacy in 3 of the 4 trials.
The Importance of Adequate Nutrient Intake During Pregnancy
A recent study from researchers at the University of Colorado Anschutz Medical Campus indicates that 90% of pregnant women do not receive adequate nutrients from food alone and must rely on supplements to meet their nutritional needs. Insufficient intake of certain nutrients can lead to pre-term birth, low birthweight, birth defects, and other health challenges. Conversely, excessive intake could alter a baby’s body development and increase the risk of future health problems.
The study followed 2,450 women throughout their pregnancy and analyzed their dietary intake to determine if they were meeting the nutritional guidelines recommended by the National Institutes of Health (NIH) for vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids. The results highlighted an ongoing need for prenatal vitamin options that are low cost and convenient, while still containing the optimal amounts of key nutrients.
Risks Associated with Excessive Supplement Intake
While prenatal supplements are essential for providing extra vitamins and minerals needed before and during pregnancy, it is crucial to avoid excessive intake. Some individuals take prenatal supplements based on unproven claims or the misconception that more nutrients are always better. Taking iron and folic acid at levels higher than the suggested amounts can increase the risk of health problems. For folic acid as a supplement, the maximum daily amount is 1,000 mcg for adults. Exceeding these limits can lead to adverse effects, such as masking symptoms of vitamin B-12 deficiency or affecting zinc levels in the body.
Dietary Recommendations for Pregnant Women
Most of the time, a nutritious, balanced diet makes taking any dietary supplement unnecessary for healthy adults who are not pregnant. Iron and folate are found naturally in many foods, such as spinach. Pregnant women should focus on consuming a diet rich in fruits, vegetables, whole grains, and lean protein sources to meet their nutritional needs.