Association Between Vitamin D Deficiency and
Primary Cesarean Section
Anne Merewood MPH, IBCLC*; Supriya D. Mehta PhD, MHS**; Tai C. Chen PhD***;
Howard Bauchner MD****; Michael F. Holick PhD, MD****
*Assistant Professor of Pediatrics, Boston University School of Medicine
Division of General Pediatrics, 88 E Newton St., Vose 3, Boston Medical Center, Boston, MA,
**Assistant Professor of Epidemiology and Biostatistics
University of Illinois Chicago School of Public Health
958 SPHPI, M/C 923, 1603 W Taylor St
Chicago, IL 60612
***Professor of Medicine,
Division of Endocrinology, Diabetes and Nutrition
Department of Medicine
Boston University School of Medicine
Rm M-1022, 715 Albany St.
Boston MA 02118
**** Chief, Division of General Pediatrics,
Boston Medical Center
88 E Newton St., Vose 3,
Boston, MA, 02118
J Clin Endocrin Metab. First published ahead of print December 23, 2008 as doi:10.1210/jc.2008-1217
Copyright (C) 2008 by The Endocrine Society
*****Professor of Medicine, Physiology and Biophysics, Boston University School of Medicine
Boston University Medical Center
715 Albany St, Building M-1013
Boston, MA 02118
The study was funded by the US Department of Health and Human Services, Bureau of Maternal
Child Health: R40MC03620-02-00, and by the US Department of Agriculture Cooperative State
Research, Education, and Extension Service, Award No.: 2005-35200-15620
Correspondence of manuscript and requests for reprints:
Michael Holick, Professor of Medicine,
Division of Endocrinology, Diabetes and Nutrition
Department of Medicine
Boston University School of Medicine
Rm M-1022, 715 Albany St.
Boston MA 02118
Key words: vitamin D, cesarean section, 25-hydroxyvitamin D, pregnancy, vitamin D deficiency
Disclosure: A.M., S.M., T.C. and H.B. have nothing to declare. M.H. consults for Merck, P&G
and Quest Diagnostics, and received lecture fees from Merck and P& G.
Word count: 2,217; Tables: 2, Figures: 1
Background: At the turn of the 20th century, women commonly died in childbirth due to
“rachitic pelvis”. Although rickets virtually disappeared with the discovery of the hormone
“vitamin” D, recent reports suggest vitamin D deficiency is widespread in industrialized nations.
Poor muscular performance is an established symptom of vitamin D deficiency. The current US
cesarean birth rate is at an all-time high of 30.2%. We analyzed the relationship between maternal
serum 25-hydroxyvitamin D [25(OH)D] status, and prevalence of primary cesarean section.
Methods: Between 2005 and 2007, we measured maternal and infant serum 25(OH)D at birth,
and abstracted demographic and medical data from the maternal medical record, at an urban
teaching hospital in Boston, USA, with 2,500 births per year. We enrolled 253 women, of whom
43 (17%) had a primary cesarean.
Results: There was an inverse association with having a cesarean section and serum 25(OH)D
levels. We found that 28% of women with serum 25(OH)D <37.5 nmol/L had a cesarean section,
compared to only 14% of women with 25(OH)D >37.5nmol/L (p=0.012). In multivariable
logistic regression analysis controlling for race, age, education level, insurance status, and alcohol
use, women with 25(OH)D <37.5 nmol/L were almost 4 times as likely to have a cesarean than
women with 25(OH)D >37.5 nmol/L (AOR 3.84; 95% CI 1.71 to 8.62).
Interpretation: Vitamin D deficiency was associated with increased odds of primary cesarean
At the turn of the 20th century, rickets ran rampant in the newly industrialized cities of Europe
and north America, and “rachitic pelvis” was a common cause of death in childbirth.1 Cesarean
sections became established, in part, to manage this condition: “…malformed pelvises often
prohibited normal delivery. As a result the rate of cesarean section went up markedly.”2 Although
rickets virtually disappeared with the discovery of the hormone “vitamin” D and its subsequent
addition to milk, recent reports suggest its reemergence,3,4 and that vitamin D deficiency is
widespread in industrialized nations.5-7 Meanwhile, research into vitamin D deficiency, and
awareness of its range of acute and chronic consequences, has proliferated.8-12 Poor muscular
performance5,11-16 is an established symptom of vitamin D deficiency. The term rachitic pelvis has
fallen into disuse, but an association has been noted between cesarean birth and a “narrow
The current US cesarean birth rate is 30.2%,18 a “record high for the Nation;”18 up from 5% in
1970, and characterized by steep increases in primary as well as repeat cesareans.19 Common
reasons for cesareans in industrialized nations include dystocia,20 and failure to progress.21 Recent
research suggests that maternal calcium status plays a role both in preterm labor22 and in the
initiation of labor.23 This analysis assessed the relationship between maternal vitamin D status
(serum 25-hydroxyvitamin D [25(OH)D]) at birth, and primary cesarean section.
Women were enrolled between 3/21/2005 and 3/20/2007, on the postpartum unit at Boston
Medical Center, an urban teaching hospital in Boston, Massachusetts, within 72 hours of giving
Enrollment was evenly distributed over time to ensure data were representative of season, as
seasonal sunlight exposure affects vitamin D status.3 Women were ineligible if they had spent
more than two months away from Boston during pregnancy, if they were not of Black, White, or
Hispanic race/ethnicity (due to low numbers of women available in other racial/ethnic groups); if
they did not speak English, French, or Spanish; if the infant was admitted to intensive care,
premature, or if the mother had a history of parathyroid, renal, or liver disease, or was using
illegal drugs. Women having a repeat cesarean were also excluded from this analysis, because of
the strong causal relationship between primary and repeat cesareans. Enrolled women answered a
questionnaire on the postpartum unit within 72 hours of birth, and venipuncture was performed
on the mother prior to discharge. None of the patients were receiving an IV infusion at the time
of the venipuncture.
Serum 25(OH)D, accepted as the indicator of vitamin D status in children and adults, was
measured by competitive protein binding as described by Chen et al.24 Since the serum half-life
for 25(OH)D is ~ 21 days, it was minimally influenced by fasting or changes in dietary intake
during a short fasting. This method measures both 25(OH)D2 and 25(OH)D3 equally well and
was compared with liquid chromatography tandem mass spectroscopy with excellent
correlation.25 The lower limit of detection was 12.5 nmol/L (5 ng/ml), and the intra- and inter-
assay coefficients of variation 5.0-10% and 10%-15%, respectively. The reference range was 50-
250 nmol/L (20-100 ng/ml).
Certain definitions pertinent to US, or more specific regional descriptions, are
summarized here. “GED” indicates Graduate Equivalency Degree, a high school diploma
alternative for individuals who do not graduate high school. Healthy Start is perinatal, state-
funded insurance for women who are ineligible for other insurance programs; it is frequently used
by women of illegal immigration status. The Special Supplemental Nutrition Program for
Women, Infants, and Children (WIC) provides food and nutrition counseling for low income
families with children under 5. In Massachusetts, applicant income must fall at or below 185% of
the federal poverty guidelines.
Outcome measures and data analysis
The dependent variable was maternal vitamin D deficiency, defined as serum 25(OH)D <37.5
nmol/L (15 ng/ml), per the Centers for Disease Control definition for adults.26 Recent research
has found 25(OH)D <37.5 to be an unacceptably low state of deficiency and that < 50 nmol/L is
considered to be vitamin D deficiency and 51-74 nmol/L as vitamin D insufficiency.3,7,8,11,12
Race/ethnicity and skin color were analyzed as two variables, because skin color by ethnicity
alone can vary from white to dark brown, and skin pigmentation affects vitamin D synthesis.3
Skin color (black, brown, or white) was based on the Fitzpatrick skin type matrix.27 Prenatal
vitamin use was analyzed by any reported use in each trimester (data in Table 1) as well as by
frequency of use in each trimester; neither measure was associated with type of delivery. Body
mass index (BMI) information before pregnancy was obtained from the medical record.
Continuous values of BMI were categorized for analysis (17-<25, 25-<30, 30-<35, 35+)
according to World Health Organization ranges
(http://www.who.int/bmi/index.jsp?intoPage=intro 3.html). Reasons for cesarean were obtained
from the mother’s medical record. Response frequencies for categorical variables are presented in
Table 1. Continuous variables (maternal age, BMI, and 25(OH)D level) are presented as medians
with binomially obtained 95% confidence intervals (CI) in Table 1.
The statistical significance of differences in maternal factors associated with cesarean delivery
was assessed using Pearson’s Chi-Square test. Multivariate logistic regression analysis tested all
variables with p-values <0.25 in univariate analysis. Backward selection techniques were used to
derive the final model, which maintained variables with p-values < 0.05. Statistical analyses were
conducted using Stata/SE 9.2 for Windows (Stata Corp., College Station, TX). The study
obtained approval from the Boston University Medical Center Institutional Review Board, and
women signed informed consent before participating.
Between March 21st, 2005 and March 20th, 2007, we enrolled 253 women, of whom 43 (17%) had
a primary cesarean section. In this same time period, 370 women refused enrollment, primarily
because they did not want blood drawn, on themselves or their infant. Based on a random sample
of 95 refusers, 51% of enrolled women were Hispanic, while only 30% of women who refused
had Hispanic race/ethnicity recorded in their medical record (p<0.001). This difference probably
arose from the practice of asking women who are enrolled in the study their race and whether or
not they are Hispanic, which is not done for the record. No other significant differences existed
between consented and refusing women with regard to age, infant birthweight, or gestational age.
The method of delivery did not differ between mothers who enrolled in the study and those who
refused (76% vaginal delivery, and 24% cesarean section delivery, both groups).
Of the 277 women enrolled, 210 had vaginal deliveries and 67 had cesarean deliveries, of which
43 were primary cesareans. This analysis was limited to women with vaginal deliveries or
primary cesareans. Thus of the 253 eligible women enrolled, 43 (17%) had a primary cesarean.
Reasons for cesarean included: failure to progress (17/43); non-reassuring fetal tracing (11/43);
malpresentation (such as breech) (6/43), and 3 each of cephalopelvic disproportion, variable fetal
heart rate, and other.
We found that 28% of women with serum 25(OH)D <37.5 nmol/L had a primary cesarean
section, compared to only 14% of women with 25(OH)D >37.5 nmol/L (p=0.012; unadjusted
odds ratio (OR) = 2.43;95% CI 1.20-4.92). In addition, women who had cesareans had a lower
median 25(OH)D level than women who delivered vaginally (45.0 nmol/L vs 62.5 nmol/L,
p=0.007). Compared to women who had vaginal births, women who had cesareans were also
significantly more likely to be Caucasian/non Hispanic than Black and/or Hispanic (p=0.006);
OR=3.81; 95% CI: 1.47-9.86), to be US born (p=0.023; OR=2.14; 95% CI: 1.10 – 4.16), and to
have used alcohol in pregnancy (p=0.039; OR=2.92; 95% CI: 1.02 – 8.38 )(Table 1).
In multivariate logistic regression analysis controlling for race, age, education level, insurance
status, maternal birthplace, and alcohol use, (Table 2) women with vitamin D deficiency (< 37.5
nmol/L) were almost four times as likely to have a primary cesarean section as women without
deficiency (OR 3.84 95% CI: 1.71 to 8.62). Caucasian women and those who reported any
alcohol use during pregnancy also had increased likelihood of primary cesarean. Maternal
birthplace was no longer statistically significant. Figure 1 shows the association between
mother’s increasing 25(OH)D level in nmol/L, and decreasing predicted probability (from
multivariate analysis) of having a Cesarean section versus vaginal delivery. Thus, women with
the highest serum 25(OH)D had the lowest probability of requiring a Cesarean section.
In our analysis, women who were severely vitamin D deficient [25(OH)D < 37.5 nmol/L) at the
time of delivery had almost four times the odds of cesarean birth than women who were not
deficient. One explanation for our findings is the fact that skeletal muscle contains the vitamin D
receptor.8,11 Vitamin D deficiency has been associated with proximal muscle weakness,11 as well
as with suboptimal muscle performance and strength.5,11-16 Moreover, vitamin D deficiency is a
possible risk factor for pre-eclampsia 9, 28
Serum calcium status, which is regulated by vitamin D, plays a role in smooth muscle function in
early labor.23, 29 Papandreou, et al, reported significantly higher serum calcium levels in pregnant
women at the time of vaginal delivery compared to term women not in labor or women who did
not labor but delivered by scheduled cesarean.23 It was speculated that the higher serum calcium
levels played a role in the mechanism of initiation of labor. Since vitamin D is critically
important for the maintenance of calcium homeostasis, it is possible that vitamin D deficiency,
which causes a slight lowering of the serum calcium, is related to both skeletal muscle and
smooth muscle strength and may play a role in initiation of early labor. It is also possible that
vitamin D deficiency might be related to specific types of cesareans (such as, cephalopelvic
disproportion or failure to progress) than to others (such as breech), although we did not have a
large enough sample to be able to analyze this. This would be a critical area for future research.
There are other potential explanations for the association of vitamin D deficiency and cesarean
section. The simplest explanation is that the intravenous hydration would have diluted the blood
and give an artificially lower level of 25(OH)D. However, the amount of intravenous fluids
relative to the blood loss is essentially the same. We did a subset analysis of five women where
we obtained serum 25(OH)D before and after the cesarean section and they were statistically the
same, i.e., the 25(OH)D before surgery was 80 ± 25 nmol/L and after surgery 97 ± 33 nmol/L p >
0.1. Vitamin D status is linked to immune status.30, 31Certain infections have been associated with
preeclampsia, 32 and preeclampsia in turn increases the odds of cesarean.33 Vitamin D deficiency
may thus be a marker for a compromised immune system, and an associated, higher risk of
A study performed in 1994-95 by Brunvand et al 34 found no association between vitamin D
deficiency at the time of delivery, and obstructed labor, in a case control study of Indian women
giving birth in Karachi. His findings bear little relevance for the present study however; outcomes
were measured only for cesareans due to cephalopelvic disproportion, the sample consisted of
largely undernourished impoverished women, and 71% of study participants were severely
vitamin D deficient (25(OH)D <30 nmol/L). In addition, the paper does not satisfactorily clarify
the use of the term cephalopelvic disproportion (as opposed, for example, to alternative, yet
closely related reasons such as fetal distress). The specific validity of the term “cephalopelvic
disproportion” has been questioned for over 50 years.35, 36
We also found some interesting trends regarding other interactions in our baseline data (Table 1).
While skin color, independent of race/ethnicity, and based on the Fitzpatrick skin type matrix,27
was not related to risk of cesarean delivery, women who self identified as being non-Hispanic
whites had a significantly elevated risk of cesarean delivery; 38% of non-Hispanic whites
underwent primary cesareans, compared to 14% of non Hispanic blacks, and 15 % of Hispanics
(p=0.006). This is not reflective of national data, where the primary cesarean rate among Black,
non-Hispanic primiparas is approximately one percentage point higher than the rate in Hispanic
and White, non-Hispanic women.37
Drinking milk in pregnancy, and reported use of sunscreen, were both marginally related with an
increased risk of cesarean, but both these risks disappeared in the multivariate model and were
probably a result of small sample size or confounding variables. On the other hand, maternal
report of alcohol use during pregnancy was strongly associated with an increased risk of cesarean
even after multivariate analysis, an unanticipated finding that clearly requires further
Maternal vitamin D deficiency is a widespread public health problem. Lee, et al,38 reported that
50% of mothers, and 65% of newborns infants were severely vitamin D deficient [25(OH)D < 30
nmol/L] at the time of birth despite the fact that the mother was taking a prenatal vitamin
containing 400 IU of vitamin D and drinking two glasses of vitamin D fortified milk (100 IU/8
oz. glass). This mirrors the observation of Hollis, et al,39 and Bodnar, et al,40 who found a high
incidence of vitamin D deficiency in pregnant and lactating women. While other factors, such as
increased liability for obstetricians41 undoubtedly play a role in the staggering rise in primary
cesareans, the rate of primary cesareans with no medical or obstetrical indication is also rising;
the current US rate of primary cesareans “with no reported medical or obstetrical indication” is
between 3% and 7%.19 As Declerc et al noted in a study to examine reasons for cesarean
increases, apparent risk factors remained stable: “shifts in primary cesarean rates during the study
period were not related to shifts in maternal risk profiles.”37 A randomized clinical trial is now
needed to determine if adequate vitamin D supplementation during pregnancy to raise blood
levels of 25(OH)D above at least 37.5 nmol/L can reduce the cesarean section rate and whether
increasing it above 75 nmol/L provides any additional reduction as suggested by our data..
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Figure 1: Mother’s 25(OH)D Level in nmol/L and predicted probability of Primary Cesarean
Table 1: Characteristics of study sample by delivery mode
Median age in years (95% CI)
Black non Hispanic
Caucasian non Hispanic
Season of birth
Median Maternal Body Mass Index
Maternal Body Mass Index (BMI)
< High school
111 (85) 19 (15)
43 (83) 9 (17)
(24.0 – 26.1)
(23.1 – 25.8)
67 (87) 10 (13)
Table 1 Continued
Any prenatal vitamin use
Drank milk in pregnancy
Ever used sunscreen
Drank alcohol in pregnancy
Median maternal 25(OH)D nmol/L
Maternal 25(OH)D nmol/L
25(OH)D < 37.5
* p-value determined by Wilcoxon rank sum test. 95% Confidence Interval for mothers’ median
age, BMI; 25(OH)D is binomially obtained.
+ Fisher’s exact test used where expected cell value was less than 5.
Not all cells sum to 253 because of missing data
Table 2: Multivariate logistic regression analysis: Factors Associated with
Having Primary Cesarean Section Delivery, N=250*
Used alcohol during pregnancy
Mother’s educational status
Less than high school or GED
High school or GED
Greater than high school
Mother’s insurance status
Mother’s age in years
The model is adjusted for all variables presented. “ref” indicates reference
*Women with missing data were excluded from multivariate analysis
0 Download full-text
Predicted Probability of Cesarean Section
0 50 100150 200
This graph shows the association between mother’s increasing 25(OH)D level in nmol/L, and decreasing
predicted probability of having a Cesarean section versus vaginal delivery, with a quadratically fit line. The
predicted probabilities of Cesarean section are derived from a multivariate logistic regression model
controlling for mother’s age, education, insurance status, and race. Additionally, the model controls for
reporting ever drinking alcohol during pregnancy, as this was statistically significant in univariate analysis
and remained statistically significant at the p<0.05 level in multivariate analysis.