Animal (2014), 8:s1, pp 5–14 © The Animal Consortium 2014

doi:10.1017/S1751731114000731
animal

Prepartum and postpartum nutritional management to optimize

fertility in high-yielding dairy cows in confined TMR systems
J. K. Drackley† and F. C. Cardoso
Department of Animal Sciences, University of Illinois, 1207 West Gregory Drive, Urbana, Illinois, USA

(Received 25 February 2014; Accepted 6 March 2014; First published online 9 April 2014)

The 6 to 8-week period centered on parturition, known as the transition or periparturient period, is critical to welfare and
profitability of individual cows. Fertility of high-producing cows is compromised by difficult transitions. Deficiencies in either
nutritional or non-nutritional management increase risk for periparturient metabolic disorders and infectious diseases, which
decrease subsequent fertility. A primary factor impeding fertility is the extent of negative energy balance (NEB) early postpartum,
which may inhibit timing of first ovulation, return to cyclicity, and oocyte quality. In particular, pronounced NEB during the first
10 days to 2 weeks (the time of greatest occurrence of health problems) is critical for later reproductive efficiency. Avoiding
over-conditioning and preventing cows from over-consuming energy relative to their requirements in late gestation result in
higher dry matter intake (DMI) and less NEB after calving. A pooled statistical analysis of previous studies in our group showed
that days to pregnancy are decreased (by 10 days) by controlling energy intake to near requirements of cows before calving
compared with allowing cows to over-consume energy. To control energy intake, total mixed rations (TMR) must be well balanced
for metabolizable protein, minerals and vitamins yet limit total DM consumed, and cows must uniformly consume the TMR
without sorting. Dietary management to maintain blood calcium and rumen health around and after calving also are important.
Opportunities may exist to further improve energy status in fresh cows. Recent research to manipulate the glucogenic to lipogenic
balance and the essential fatty acid content of tissues are intriguing. High-producing cows that adapt successfully to lactation can
have high reproductive efficiency, and nutritional management of the transition period both pre- and post-calving must facilitate
that adaptation.

Keywords: transition period, reproduction, nutrition, metabolic disorders

Implications coordinated series of physiological events, including

Nutritional strategies and feeding management during pre-
calving and post-calving periods impact health, productivity
and fertility of high-producing dairy cows. Formulating diets to
meet requirements of the cows but avoid over-consumption of
energy may improve outcomes of the transition period and
lead to improved fertility. Management to improve cow
comfort and ensure good intake of the ration is pivotal
for success. Impacts of the transition program should be
evaluated in a holistic way that considers disease occurrence,
productivity and fertility.
Introduction
Reproductive success is critical to the profitability and
sustainability of dairy farms using confined total mixed ration
(TMR)-based systems. Successful reproduction depends on a
†
E-mail: drackley@illinois.edu
resumption of ovarian cyclicity postpartum, development
and ovulation of a viable oocyte, fertilization, restoration of
the uterus, embryo development and implantation, and
maintenance of pregnancy until fetal maturation (Butler,
2003; Garnsworthy et al., 2008). Dietary formulation and
feeding management during the dry period, peripartal per-
iod, and early postpartum (fresh) period may facilitate or
interrupt many of these steps before pregnancy is established
and maintained (Butler, 2003; Garnsworthy et al., 2008;
Thatcher et al., 2011). In high-producing dairy cows, con-
ception rates for normally cycling cows are high (>70%) but
many cows (>50%) undergo early embryonic loss and fail to
maintain the pregnancy (Diskin and Morris, 2008). A major
point of emphasis in relating nutrition and reproduction in
dairy cows is the extent and duration of negative nutrient
status and negative energy balance (NEB) in early lactation,
which is influenced heavily by nutritional and environmental
management during the period of transition from pregnancy
to lactation.

5
Drackley and Cardoso
The 6 to 8-week period centered on parturition, known as
the transition or periparturient period, is critical in deter-
mining welfare and profitability of individual cows during the
subsequent lactation (Drackley et al., 2005). Suboptimal
transition management programs lead to a high rate of
production disease in dairy herds (Mulligan and Doherty,
2008). Disturbances of metabolism during the transition may
have direct or indirect influences on fertility, and difficult
transitions have negative impacts on subsequent reproduc-
tion (Chapinal et al., 2012). A variety of nutritional strategies
to facilitate the metabolic and physiological adaptations
from gestation to lactation have been proposed (Friggens
et al., 2004; Roche et al., 2013).
The objectives of this paper are to review the causes of
NEB and its resulting metabolic disturbances, to relate how
these outcomes influence reproduction, and to consider how
different nutritional strategies prepartum and postpartum
may affect NEB and adequacy of other nutrients. Our central
theme is that prepartum and postpartum management that
promotes high dry matter intake (DMI) of properly balanced
diets after calving is the unifying factor between transition
success and reproductive success. Because of space limita-
tions we emphasize energy intake, with the recognition that
adequacy or balance of many other nutrients can modulate
fertility. Our review will focus on newer information relating
to the roles of nutrition and inflammation during the
transition.
Fertility, milk yield and peripartal health problems
A widespread assumption is that fertility of modern dairy
cows is decreasing, particularly for Holstein–Friesen genetics,
at least in part because of unintended consequences of
continued selection for high milk production. This assump-
tion has been challenged recently (LeBlanc, 2010; Bello et al.,
2012). There is a wide distribution of reproductive success
both within and among herds. For example, within five
California herds encompassing 6396 cows, cows in the
lowest quartile for milk yield in the first 90 days postpartum
(32.1 kg/day) were less likely to have resumed estrous cycles
by 65 days postpartum than cows in quartiles two (39.1 kg/day),
three (43.6 kg/day) or four (50.0 kg/day); milk production did
not affect risk for pregnancy (Santos et al., 2009). Changes in
management systems and inadequacies in management may
be more limiting for fertility of modern dairy cows than their
genetics per se.
Dairy cows are susceptible to production disorders and
diseases during the peripartal period and early lactation
(Mulligan et al., 2006; Ingvartsen and Moyes, 2013; Roche
et al., 2013). There is little evidence that milk yield per se
contributes to greater disease occurrence. However, peak
disease incidence (shortly after parturition) corresponds with
the time of greatest NEB, the peak in blood concentrations
of non-esterified fatty acids (NEFA), and the greatest
acceleration of milk yield (Ingvartsen et al., 2003). Peak milk
yield occurs several weeks later. Disorders associated with
6
postpartum NEB also are related to impaired reproductive
performance, including fatty liver (Rukkwamsuk et al., 1999;
Jorritsma et al., 2003) and ketosis (Walsh et al., 2007; McArt
et al., 2012). Cows that lost >1 body condition score (BCS)
unit (1 to 5 scale) had greater incidence of metritis, retained
placenta, and metabolic disorders (displaced abomasum,
milk fever, ketosis) as well as a longer interval to first breeding
than cows that lost <1 BCS unit during the transition (Kim
and Suh, 2003).
Indicators of NEB are highly correlated with lost milk
production, increased disease and decreased fertility (Ospina
et al., 2010; Chapinal et al., 2012). However, the extent to
which NEB is causative for peripartal health problems rather
than just a correlated phenomenon must be examined criti-
cally (Roche et al., 2013). For example, in transition cows
inflammatory responses may decrease DMI, cause alterations
in metabolism, and predispose cows to greater NEB or
increased disease (Bertoni et al., 2008; Graugnard et al.,
2012 and 2013; Ingvartsen and Moyes, 2013). Inducing a
degree of calculated NEB in mid-lactation cows similar to
what periparturient cows often encounter does not result
in marked increases in ketogenesis or other processes
associated with peripartal disease (Moyes et al., 2009).
Nevertheless, early postpartal increases in NEFA and decreases
in glucose concentrations were strongly associated with preg-
nancy at first insemination in a timed artificial insemination
(TAI) program (Garverick et al., 2013). Although concentrations
of NEFA and glucose were not different between cows that
ovulated or did not before TAI, probability of pregnancy
decreased with greater NEFA and increased with greater
glucose concentrations at day 3 postpartum (Garverick et al.,
2013). In support of these findings, early occurrence of sub-
clinical ketosis is more likely to decrease milk yield and com-
promise fertility. McArt et al. (2012) found that cows with
subclinical ketosis detected between 3 and 7 days after calving
were 0.7 times as likely to conceive to first service and 4.5
times more likely to be removed from the herd within the first
30 days in milk compared with cows that developed ketosis at
8 days or later.
Cows that successfully adapt to lactation (Jorritsma et al.,
2003) and can avoid metabolic (Ingvartsen et al., 2003)
or physiological imbalance (Ingvartsen and Moyes, 2013)
are able to support both high milk production and successful
reproduction while remaining healthy. Decreased fertility
in the face of increasing milk production may be attributable
to greater severity of postpartal NEB resulting from
inadequate transition management or increased rates of
disease. Competition for nutrients between the divergent
outcomes of early lactation and subsequent pregnancy will
delay reproductive function. Because NEB interrupts repro-
duction in most species, including humans, inappropriate
nutritional management may predispose cows to both
metabolic disturbances and impaired reproduction. Cows
must make ‘metabolic decisions’ about where to direct
scarce resources, and in early lactation nutrients will be
directed to milk production rather than to the next pregnancy
(Friggens, 2003).

NEB and impaired fertility
Cows cannot consume sufficient energy-yielding nutrients
from voluntary DMI after calving to meet energetic require-
ments for milk production. Consequently, NEB occurs for a
period of days to weeks during early lactation. Although
studies have demonstrated a weak and variable relationship
between the degree of NEB and impaired fertility, the time
to NEB nadir and the direction and/or rate of change in NEB
appear to be stronger indicators (Whitaker et al., 1993; Butler,
2003; Reist et al., 2003). Possible mechanisms for detrimental
effects of NEB on reproduction include (1) delayed resumption
of ovarian cyclicity, through effects on hypothalamic, pituitary
and ovarian function, (2) impacts on oocyte or corpus luteum
(CL) ‘quality’, viability, or function, sometimes referred to as
‘follicular memory’ and (3) development of fatty liver (hepatic
lipidosis).
In general, fertility is greater in cows that ovulate sooner
after parturition (Butler, 2003; Bossaert et al., 2008; Galvão
et al., 2010b). During early postpartum NEB, the pulse
frequency of LH release, the size and development rate of
follicles, concentrations of estrogen and progesterone, and
size of the CL all are decreased (Jorritsma et al., 2003;
Garnsworthy et al., 2008). Successful ovulation depends on
estrogen production by the dominant follicle, restoration of
pulsatile LH secretion, and responsiveness of the ovary to LH.
The state of postpartum NEB is associated negatively with
reproductive performance in part because it interrupts these
three factors (Butler, 2003). Insulin, concentrations of which
generally reflect energy status and dietary adequacy, may be
a primary link between the metabolic and reproductive sys-
tems. Insulin is necessary to increase synthesis of IGF-1 in the
liver in response to elevated concentrations of somatotopin
(growth hormone; GH), to increase oestrodiol production
by the dominant follicle and to increase LH receptors for
ovulation and CL development (Lucy, 2000; Garnsworthy
et al., 2008). Lower insulin and IGF-1 during periods of NEB
thus may be related to eventual increases in days to first
ovulation, first estrus and conception, and decreased rates of
conception and pregnancy. For example, cows with low
postpartum progesterone, indicating lack of reproductive
cyclicity, had lower DMI, insulin and IGF-1 than cows with
elevated progesterone (Pushpakumara et al., 2003). More-
over, cows that failed to conceive had lower concentrations
of IGF-1 than cows that became pregnant (Pushpakumara
et al., 2003).
Extreme NEB also may negatively impact oocyte or CL
quality or viability due to reduced concentrations of proges-
terone and, most likely, low concentrations of IGF-1. Low
concentrations of insulin and IGF-1 have been linked to poor
quality of oocytes and CL (Jorritsma et al., 2003). Blood-
borne metabolites that directly result from responses to NEB,
including NEFA and β-hydroxybutyrate (BHBA), also may
negatively affect oocytes and CL because these metabolites
are elevated in follicular fluid of dominant follicles during
NEB (Leroy et al., 2004). However, NEFA and BHBA may only
be detrimental in the presence of low follicular concentrations
Transition nutritional management in TMR-fed herds
of glucose (Leroy et al., 2006). In contrast to the beneficial
effects of insulin on first ovulation, high insulin (reflecting
positive energy balance) at the time of breeding may be
detrimental to oocyte quality (Garnsworthy et al., 2008).
Fatty liver is negatively associated with fertility
(Rukkwamsuk et al., 1999), which may be an indirect effect
of the extreme NEB in these cows. However, there also may
be direct negative effects of hepatic lipid infiltration on
reproduction. Blood flow through the liver may be altered
by fat accumulation expanding cell volume and compressing
hepatic sinusoids. Alternately, lipid accumulation may
decrease the normal ability of hepatocytes to metabolize or
clear reproductive and metabolic hormones (Sangsritavong
et al., 2002; Reynolds et al., 2003; Lemley et al., 2008), thus
altering the normal signaling to reproductive tissues and
pituitary. A number of vital functions of the liver are affected
negatively by early postpartum ketosis and hepatic lipid
accumulation (Loor et al., 2007). An example is increased
apoptosis, identified through microarray analysis of liver
(Loor et al., 2007) and recently through more direct
functional assays (Tharwat et al., 2012).
Metabolic and physiological adaptations from
gestation to lactation
The classical homeorhetic adaptations in physiology and
metabolism that cows must negotiate to make successful
transitions from late pregnancy to early lactation have been
thoroughly described in previous reviews (Drackley et al.,
2001 and 2005; Ingvartsen 2006; Loor, 2010; Contreras and
Sordillo, 2011; Roche et al., 2013) and are only summarized
here in relation to subsequent fertility.
Endocrine adaptations
Changes in the endocrine and neuroendocrine systems drive
the altered partitioning of nutrients from foetal maturation to
milk synthesis between late pregnancy and early lactation
(Ingvartsen, 2006). During the dry period, concentrations of
insulin and leptin reflect energy balance and generally are
higher than in late lactation (Janovick et al., 2011). These
hormones promote and respond to, respectively, energy
storage in adipose tissue. During the last 3 weeks of preg-
nancy, nutrient demands by the foetal calf and placenta are
at their greatest (Bell et al., 2000). Cows should be able to
meet these requirements from the diet, although DMI may be
decreased by 10% to 30% compared with intake during the
early dry period. Although stressors and severe limitations in
DMI can lead to NEB before calving, the degree is much less
than what occurs following parturition.
Secretion of GH increases near parturition, with the timing
of increase dependent on nutrient status (Grum et al., 1996).
In the face of decreasing concentrations of insulin prepartum,
GH promotes mobilization of stored nutrients (primarily fat
from adipose tissue) to support milk production (Lucy, 2000).
Marked decreases in the primary GH receptor in liver (GHR-1A)
lead to sharply decreased hepatic secretion of IGF-1.
7
Drackley and Cardoso
This ‘uncoupling’ of the somatotropic axis prevents feedback
inhibition of GH secretion by IGF-1, thereby maintaining
elevated concentrations of GH (Lucy, 2000).
Lipid metabolism
The profile of low insulin and high GH concentrations
orients the adipose tissues toward mobilization of stored
triacylglycerols (TAG). Lipogenesis is almost completely
inhibited, which decreases re-esterification of NEFA within
adipocytes. Decreased insulin also removes an important
anti-lipolytic influence on adipose tissue. Sensitivity and
response to catecholamines in adipose tissue is increased
by GH, resulting in greater lipolysis of TAG (Drackley et al.,
2001 and 2005; Roche et al., 2013). In addition, other
factors secreted in response to infection, stress or trauma,
most likely the cytokines (tumor necrosis factor-α (TNFα),
interleukin-1 and interleukin-6, among others) result in
increased concentrations of NEFA in blood and TAG in liver
(Contreras and Sordillo, 2011). Consequently, stressors and
poor nutritional management that decrease voluntary DMI
will result in large increases in TAG mobilization and conse-
quently NEFA concentrations immediately after calving.
Increased ketogenesis, which occurs when glucose supply is
limited during NEB, can result in ketosis (Drackley et al.,
2001). Fatty acids taken up in excess of what can be oxidized
to CO2 or ketone bodies are re-converted to TAG. Because
ruminant animals are unable to effectively export TAG from
the liver as very low density lipoproteins, TAG can accumu-
late and cause fatty liver (Drackley et al., 2001).
Glucose and protein metabolism
Dairy cows rely extensively on hepatic gluconeogenesis from
propionate to meet their glucose requirements. Limited DMI
after calving limits the supply of propionate for glucose synth-
esis, and therefore increase conversion of amino acids from the
diet or from skeletal muscle, particularly alanine and glutamine,
and glycerol from mobilized adipose TAG to glucose. Glu-
coneogenic activity of liver tissue increases around and after
calving to help maintain supply of glucose to the mammary
gland and prevent hypoglycoemia (Drackley et al., 2005).
Limited protein reserves exist in dairy cows, primarily in the
form of skeletal muscle protein. Muscle protein mobilization, as
estimated by plasma concentrations of 3-methyl-histidine, is
increased during the first week after calving compared with
prepartum values (van der Drift et al., 2012). Loss of muscle
mass may begin before calving and before the initiation of
fat mobilization (van der Drift et al., 2012). Maintenance of
maternal stores of protein is important for long-term health,
productivity and reproduction (Bell et al., 2000). Deficiency in
metabolizable protein supply may be linked to ketosis (van der
Drift et al., 2012; Lean et al., 2013a) and other peripartal dis-
eases (Roche et al., 2013), which in turn may decrease fertility.
Immune system function
Function of the immune system is depressed during the
transition period (Ingvartsen and Moyes, 2013). Decreased
ability of the immune system to respond to infectious
8
challenges likely is responsible for the high incidence of
environmental mastitis around calving, as well as the high
incidence of metritis. Retained placenta also has been linked
to failure of the immune system to recognize the placenta
as a foreign tissue (Kimura et al., 2002). Reasons for the
decreased immune function are not clear. Vitamins A and E
as well as trace minerals (selenium, copper, zinc) play a role
in immune function. Cows that seem to be the most stressed
by nutrition and environmental factors, as judged by exces-
sive loss of BCS, are the most likely to become ill. Negative
balances of energy or metabolizable protein may be a major
contributing factor (Ingvartsen and Moyes, 2013). Galvão
et al. (2010a) found that glycogen content of neutrophils
(reserve of glucose, the main fuel for neutrophil functions)
was lower in early postpartum cows, and was associated
with decreased functions of those cells. An inadequate supply
of metabolizable protein has been related to impaired function
of the immune system (Houdijk et al., 2001).
Calcium metabolism
The sudden onset of milk synthesis results in a tremendous
demand for calcium. As a result, concentrations of calcium
in blood can drop precipitously at calving, leading to milk
fever. Subclinical hypocalcaemia is more common, with more
than 40% of cows entering the second or greater lactation
affected (Reinhardt et al., 2011). Subclinical hypocalcaemia
contributes to disorders such as displaced abomasum and
ketosis by decreasing smooth muscle function critical for
normal function of the digestive tract (Horst et al., 1997),
which can result in decreased DMI. Hypocalcaemia may
compromise function of immune cells (Kimura et al., 2006).
Until the ability of the digestive tract to absorb calcium can
increase, calcium must be obtained from bone resorption.
Metabolic acidosis caused by a negative dietary cation-anion
difference (DCAD) favors mobilization of calcium from bone,
whereas high dietary potassium concentrations and positive
DCAD suppress mobilization (Horst et al., 1997; Lean et al.,
2013b). Magnesium participates in the regulation of bone
resorption (Horst et al., 1997).
Nutritional intervention to help prevent hypocalcaemia
likely must be instituted at least 14 days before calving to be
effective (Horst et al., 1997). DeGaris et al. (2010) reported
that increasing the number of days cows consumed a close-
up diet before calving increased pregnancy rates in two of
three commercial herds, and tended to increase the propor-
tion of cows pregnant at 6 weeks and 21 weeks after
beginning the insemination period.
Nutritional management to control NEB and
optimize fertility
Postpartal NEB results from initiation of milk synthesis,
but the degree of NEB in individual cows is poorly related
to milk production or milk energy secretion. The depth
and duration of NEB are highly related to DMI (Zurek et al.,
1995; Drackley et al., 2005). Consequently, feeding and
management strategies for dry cows, transition cows and

fresh cows should seek to meet nutrient requirements but
promote appetite and vigorous DMI after calving (Grummer
et al., 2004). In TMR systems, a diet must be formulated to
meet the nutrient needs of most cows within the group rather
than allotting amounts of concentrate based on milk produc-
tion. Proper nutritional formulation of the diet is essential to
ensure that supply of all nutrients will be in balance.
Some important factors to promote good appetites and
high DMI after calving include (1) minimizing environmental
stressors and keeping cows comfortable, (2) avoiding
excessive BCS, (3) preventing over-consumption of energy
relative to requirements during the dry period, (4) ensuring
adequate intake of forage effective fiber and avoiding
excessive intakes of rapidly fermentable starch in the post-
calving diet, (5) reducing the DCAD before calving but
increasing it in the fresh cow diet and (6) nutritional support
of the immune system (see earlier section). Nutritional
strategies proposed to assist cows in making these adapta-
tions have been reviewed (Friggens et al., 2004; Beever,
2006; Ingvartsen, 2006; Drackley and Dann, 2008; Lean
et al., 2013a and 2013b; Roche et al., 2013). Selected
aspects are discussed in the following sections.
Maximize cow comfort and minimize stressors
Non-nutritional management that maximizes cow comfort
and welfare plays a huge role in transition success. Bach et al.
(2008) found that non-nutritional management accounted for
>50% of the variation in mean milk production (20.6 to
33.8 kg/day) among 47 herds fed exactly the same TMR.
Although not demonstrated directly in dairy cows, a common
feature of environmental or behavioral stress in other animals
is disruption of barrier function of the gastrointestinal
epithelia, which may allow translocation of endotoxins and
cause systemic inflammation (Pearce et al., 2013). Ametaj
et al. (2005) found a strong relationship between blood
indicators of inflammation (acute phase proteins, TNFα) and
hepatic lipid accumulation in dairy cows. Emmanuel et al.
(2007 and 2008) demonstrated that increasing amounts of
barley grain increased concentrations of endotoxin in rumen
fluid, and at low rumen pH the transfer of endotoxin across the
rumen epithelium was increased. Intermittent administration
of endotoxin triggered metabolic and inflammatory responses
typically associated with displaced abomasum and retained
placenta (Zebeli et al., 2011). These findings raise the
fascinating prospect that at least some periparturient diseases
result from adverse ruminal conditions caused by excessive
grain in the precalving or fresh cow diet, perhaps aggravated
by overcrowding, heat stress or other stressors. Others also
have implicated inflammatory responses in alterations of
metabolism, occurrence of health problems and impaired
reproduction (Bertoni et al., 2008; Graugnard et al., 2012).
Non-nutritional stressors may decrease DMI and predis-
pose cows to postpartum health problems. Cows that
developed metritis (Hammon et al., 2006; Huzzy et al., 2007)
or ketosis (Goldhawk et al., 2009) after calving had lower
DMI or reduced feeding behavior before calving. Lower
prepartum DMI per se likely is not causative, because
Transition nutritional management in TMR-fed herds
individually fed cows restricted to 80% of their energy
requirements (fed in two meals daily) did not have greater
occurrence of metritis or ketosis (Dann et al., 2005 and 2006;
Douglas et al., 2006; Janovick et al., 2011).
Optimize BCS
The role of excessive BCS in contributing to transition
problems and impaired subsequent reproduction is well
established and has been discussed by many authors
(Drackley et al., 2005; Garnsworthy et al., 2008; Roche et al.,
2013). Cows with excessive body lipid reserves mobilize
more of that lipid around calving, have poorer appetites and
DMI before and after calving, have impaired immune func-
tion, have increased indicators of inflammation in blood and
may be more subjected to oxidative stress (Contreras and
Sordillo, 2011). What constitutes ‘excessive’ BCS relative
to the cow’s biological target remains controversial.
Garnsworthy (2007) argued that the average optimal BCS
has decreased over time with increased genetic selection for
milk yield, perhaps related to correlated changes in body
protein metabolism. Recommendations for optimal BCS at
calving have trended downward over the last two decades,
and in the authors’ opinion a score of about 3.0 (1 to 5 scale)
represents a good goal at present. Adjustment of average
BCS should be a longstanding project and should not be
undertaken during the dry period.
Prevent over-mobilization of body lipid
Health disorders related to excessive mobilization of body
TAG stores have been studied for many years but remain a
problem in many dairy herds. Such problems actually are
more relevant in modern TMR-fed dairy herds, particularly
with the increasing reliance on corn (maize) silage as a
primary forage in many areas of the world. For example, in
four large commercial herds (over 10 000 cows sampled),
McArt et al. (2012) found that peak incidence and prevalence
of subclinical ketosis (blood BHBA 1.2 to 2.9 mmol/l) was at
5 days postpartum, suggesting that problems in transition
may be highly involved in etiology. High concentrations of
NEFA before and after calving can decrease DMI, lead to
hepatic lipid accumulation and ketosis, negatively affect the
immune system, lead to oxidative stress and inflammation,
and are negatively associated with return to reproductive
function (Bosseart et al., 2008; Contreras and Sordillo, 2011).
In addition to management-related stressors and excessive
BCS, dietary energy management during the dry period and
prepartum period is important.
While use of ‘steam-up’ or ‘close-up’ diets before calving
has been widely recommended for many years, there is an
almost uniform lack of positive effects on health, production
or reproduction in the literature. The simplest and most easily
defended principle of nutrition for dairy cows during the dry
period and transition is to feed to meet but not greatly
exceed requirements (Drackley and Dann, 2008). Although
not new, this concept has been incorporated into practical
systems suitable for modern dairy management practices on
both small and large dairies.
9
Drackley and Cardoso
Manage pre-calving energy intake
Our research group has shown that controlling energy intake
during the dry period to near calculated requirements leads
to better transition success (Grum et al., 1996; Dann et al.,
2005 and 2006; Douglas et al., 2006; Janovick et al., 2011;
Graugnard et al., 2012 and 2013; Ji et al., 2012). Our
research drew from earlier reports that limiting nutrient
intakes to requirements of the cows was preferable to over-
consumption of energy (e.g. Kunz et al., 1985). Cows fed
even moderate-energy diets (1.50 to 1.60 Mcal NEL/kg DM)
will easily consume 40% to 80% more net energy for lacta-
tion (NEL) than required during both far-off and close-up
periods (Dann et al., 2005 and 2006; Douglas et al., 2006;
Janovick and Drackley, 2010). Cows in these studies were
all <3.5 BCS (1 to 5 scale) at dry-off, and were fed indivi-
dually TMR based on corn silage, alfalfa silage and alfalfa
hay with some concentrate supplementation. We have no
evidence that the extra energy and nutrient intake was
beneficial in any way. More importantly, our data indicate
that allowing cows to over-consume energy even to this
degree may predispose them to health problems during the
transition period if they face stressors or challenges that
limit DMI.
Our studies indicate that prolonged over-consumption of
energy during the dry period can decrease post-calving DMI
(Dann et al., 2006; Douglas et al., 2006; Janovick and
Drackley, 2010). Over-consuming energy results in negative
responses of metabolic indicators, such as higher NEFA and
BHBA in blood and more TAG in the liver after calving
(Douglas et al., 2006; Janovick et al., 2011). Alterations in
cellular and gene-level responses in liver (Loor et al., 2006
and 2007) and adipose tissue (Ji et al., 2012) potentially
explain many of the changes at cow level. Over-consumption
of energy during the close-up period increases the enzymatic
‘machinery’ in adipose tissue for TAG mobilization after
calving, with transcriptional changes leading to decreased
lipogenesis, increased lipolysis and decreased ability of
insulin to inhibit lipolysis (Ji et al., 2012). Controlling energy
intake during the dry period also improved neutrophil func-
tion postpartum (Graugnard et al., 2012) and so may lead to
better immune function.
Our data demonstrate that allowing dry cows to consume
more energy than required, even if cows do not become
noticeably over-conditioned, results in responses that would
be typical of overly fat cows. Because energy that cows
consume in excess of their requirements must either be
dissipated as heat or stored as fat, we speculated that the
excess is accumulated preferentially in internal adipose
tissue depots in some cows. Moderate over-consumption of
energy by non-lactating cows for 57 days led to greater
deposition of fat in abdominal adipose tissues (omental,
mesenteric, and perirenal) than in cows fed a high-bulk diet
to control energy intake to near requirements (Drackley
et al., 2014). The NEFA and signaling molecules released by
visceral adipose tissues travel directly to the liver, which may
cause fatty liver, subclinical ketosis and secondary problems
with liver function.
10
Data from our studies support field observations that
controlled-energy dry cow programs decrease health pro-
blems (Beever, 2006). Other research groups (Rukkwamsuk
et al., 1998; Holcomb et al., 2001; Holtenius et al., 2003;
Vickers et al., 2013) have reached similar conclusions about
controlling energy intake during the dry period, although not
all studies have shown benefits (Winkleman et al., 2008).
Application of these principles can be through controlled
limit-feeding of moderate energy diets or ad libitum feeding
of high-bulk, low-energy rations (Janovick and Drackley,
2010; Janovick et al., 2011; Ji et al., 2012) as proposed by
others (Beever, 2006).
Effects of controlling prepartum energy intake on fertility
Individual studies such as these lack statistical power to
accurately determine effects of diet on milk production, dis-
ease incidence and reproductive success. Therefore, Cardoso
et al. (2013) conducted a pooled statistical analysis of seven
studies (cow was the experimental unit) at the University of
Illinois to investigate associations between prepartum
energy feeding regimen and reproductive performance. Days
to pregnancy (DTP) was the dependent variable to assess
reproductive performance. Individual data for 408 cows
(354 multiparous and 54 primiparous) were included in the
analysis. The NEL intake (NELI) was calculated from each
cow’s respective dietary NEL density and average DMI.
Nutritional treatments applied prepartum were classified as
either controlled energy (CE; median NELI = 13.7 Mcal/day)
or high energy (HE; median NELI = 22.1 Mcal/day) diets fed
during the far-off (FO) or close-up (CU) dry periods.
The Cox proportional hazard model revealed a significant
difference in DTP between HE and CE during the CU period
(median = 167 and 157 days; hazard ratio = 0.696; Figure 1).
Cows fed HE diets during the last 4 weeks prepartum lost more
BCS (1 to 5 scale) in the first 6 weeks postpartum than those
fed CE (− 0.43 and − 0.30, respectively). Cows fed CE during
the FO period had lower concentration of NEFA in weeks 1, 2
and 3 of lactation compared with cows fed HE. Higher NEFA
concentration in week 1 postpartum was associated with a
greater probability of diseases (n = 251; odds ratio = 1.176).
Cows that were fed HE during the dry period had greater odds
of experiencing displaced abomasum or ketosis than cows that
received CE.
Cows fed the CE regimen during the FO period had greater
concentrations of glucose in plasma during weeks 1 and 3
after calving than HE cows. In the first 2 weeks after calving,
cows that received HE in the FO period had higher concentra-
tions of total lipids and TAG and greater TAG : glycogen in
liver than CE. The positive effect of CE during the CU to
decrease DTP may be explained by increased NEL intake
during the first 4 weeks postpartum and lower incidence
of peripartal diseases. In addition, lower BCS loss during
the first 6 weeks postpartum and slightly higher glucose
concentration at week 3 likely contributed to improved
reproductive performance.
Our current working hypothesis to explain these results is
that cows over-consuming energy (especially from starch)

Figure 1 Survival function curves for days to pregnancy (DTP) for 332 Holstein cows fed either controlled energy (CE = blue) or high energy (HE = red)
during the last 4 weeks before calving. Blue and red lines represent median values for DTP when 50% of the cows were pregnant. Drawn from data in
Cardoso et al. (2013).
begin to display metabolic characteristics similar to human
type II diabetes or metabolic syndrome (Janovick et al.,
2011). Cows were in moderate to low BCS, but their meta-
bolic profiles resembled those seen in over-conditioned
cows. Cows that over-consumed during the first 5 weeks of
the dry period had similar blood glucose but greatly elevated
insulin (indirectly suggesting insulin resistance), and during
the close-up period had greater concentrations of NEFA and
BHBA than cows fed restricted amounts of the same diet or a
bulky low-energy diet (Dann et al., 2006). Although insulin
receptor function in adipose tissue was not impaired,
insulin’s anti-lipolytic signals were down-regulated so that
there was less suppression of TAG lipolysis (Ji et al., 2012).
Along with increased lipolytic gene expression (Ji et al.,
2012), this would lead to increased NEFA and then to
decreased DMI according to the hepatic oxidation theory of
intake control (Allen et al., 2009). Others have provided
evidence of insulin resistance due to over-consumption of
energy during the dry period (Holtenius et al., 2003).
Schoenberg and Overton (2011) demonstrated that cows fed
to slightly above requirements had greater decreases in
plasma NEFA in response to a glucose challenge compared
with cows that over-consumed energy, which agrees with
our in vitro metabolic data (Ji et al., 2012). We are currently
following up on several aspects related to these phenomena.
Management of CE diets
It is important to note that nutritionally complete diets must
be fed and that the TMR must be processed appropriately so
that cows do not sort the bulkier ingredients (Janovick and
Drackley, 2010). Feeding bulky forage separately from a
partial TMR or improper forage processing will lead to vari-
able intake among cows, with some consuming too
much energy and some too little. Underfeeding relative to
Transition nutritional management in TMR-fed herds
requirements, where nutrient balance also is likely limiting,
leads to increased incidence of retained placenta and metritis
(Mulligan et al., 2006). Merely adding a quantity of straw to a
diet is not the key principle; rather, the diet must be for-
mulated to limit the intake of energy (~1.3 Mcal NEL/kg DM,
to limit intake to about 15 Mcal/day for typical Holstein cows,
or 9 MJ ME/kg DM to limit intake to about 100 MJ/day) but
meet the requirements for protein, minerals and vitamins.
Reports of increased transition health problems or poor
reproductive success (Whitaker et al., 1993) with ‘low-energy’
dry cow diets must be examined carefully to discern whether
nutrient intakes were adequate.
Postpartum (fresh cow) dietary considerations
Less is known about diet formulation for the immediate
postpartum period to optimize transition success and sub-
sequent reproduction. Increased research is needed in this
area. Proper dietary formulation during the dry period or
close-up period will maintain or enable rumen adaptation
to higher grain diets after calving. Failure to do so may
compromise early lactation productivity. For example,
Silva-del-Rio et al. (2010) attempted to duplicate the dietary
strategy of Dann et al. (2006) by feeding either a low-energy
far-off diet for 5 weeks followed by a higher-energy diet for
the last 3 weeks before parturition, or by feeding the higher-
energy diet for the entire 8-week dry period. They found that
cows fed the higher-energy diet for only 3 weeks before
parturition produced less milk than cows fed the diet for
8 weeks (43.8 v. 48.5 kg/day). However, the far-off dry per-
iod diet contained 55.1% alfalfa silage and 38.5% wheat
straw but no corn silage. In comparison, the higher-energy
dry period diet and the early lactation diet both contained
35% corn silage. Ruminal adaptation likely was insufficient
for cows fed the higher energy diet for only 3 weeks.
11
Drackley and Cardoso
A major area of concern in the fresh cow period is sudden
increase in dietary energy density leading to subacute ruminal
acidosis (SARA), which can decrease DMI and digestibility of
nutrients (Mulligan and Doherty, 2008). Adequate physical
form of the diet, derived either from ingredients or mixing
strategy, must be present to stimulate ruminal activity
and chewing behavior (Zebeli and Metzler-Zebeli, 2012),
although good methods to quantify ‘adequacy’ remain
elusive. Dietary starch content and fermentability likely
interact with forage characteristics and ration physical form.
Dann and Nelson (2011) compared three dietary starch
contents (primarily from corn starch) in the fresh cow period
for cows fed a CE-type ration in the dry period. Milk
production was greatest when starch content was moderate
(23.2% of DM) or low (21.0% of DM) in the fresh cow diet
compared with high (25.5% of DM). If SARA decreases DMI
and nutrient availability to the cow, NEFA mobilization and
increased ketogenesis may follow. In addition, rapid starch
fermentation in the presence of NEFA mobilization leads to
bursts of propionate reaching the liver, which may decrease
feeding activity and DMI according the hepatic oxidation
theory (Allen et al., 2009). A moderate starch content (ca.
23% to 25% of DM) with starch of moderate fermentability
(e.g. ground dry corn rather than high-moisture corn or
ground barley) along with adequate effective forage fiber
may be the best strategy for fresh cows. Recent research also
has demonstrated that high grain diets can lead to greater
numbers of gram-negative bacteria such as Escherichia coli
with resulting increases in endotoxin present in the rumen,
which may decrease barrier function and inflammatory
responses in the cow (Zebeli and Metzler-Zebeli, 2012).
As discussed in a previous section, insulin enhances ovarian
follicle development but may impair oocyte quality and
development. Garnsworthy et al. (2008) proposed that feeding
a glucogenic diet (higher in starch) until cows resumed ovarian
cyclicity followed by a higher fat (lipogenic) diet during
the breeding period would improve reproductive success.
In subsequent research, the number of cows pregnant at
120 days was greater for cows fed a glucogenic (high-starch)
diet that increased insulin early postpartum followed by
the lipogenic diet (higher fat) during the breeding period
(Garnsworthy et al., 2009). More recent studies have not
confirmed this effect (Dyck et al., 2011; Gilmore et al., 2011)
although diets and experimental conditions differed and cow
numbers were limited. The aim to increase early postpartum
insulin by feeding higher starch diets must be tempered by the
need to maintain optimal rumen health and digestion.
Supplemental fats have been widely investigated as a way
to increase dietary energy intake and improve reproduction
(Thatcher et al., 2011). A novel strategy to use poly-
unsaturated fatty acid (PUFA) supplements to improve
reproduction has been reported (Silvestre et al., 2011). Cows
fed calcium salts of safflower oil from 30 days before to
30 days after calving, followed by calcium salts of fish oil to
160 days postpartum, had greater pregnancy rates and
higher milk production. The mechanism is believed to be
provision of greater amounts of linoleic acid (n-6 PUFA) until
12
early postpartum, which improves uterine health, followed
by greater amounts of n-3 PUFA from fish oil to decrease
early embryonic loss (Thatcher et al., 2011).
The effects of turbulent transitions on reproduction are
established early postpartum, likely during the first 10 days
to 2 weeks postpartum (Butler, 2003; McArt et al., 2012;
Garverick et al., 2013). By 8 weeks postpartum, >95% of
cows should be at or above energy balance (Sutter and
Beever, 2000). Use of targeted prepartum and postpartum
strategies may minimize health problems and lessen NEB,
and thereby improve subsequent fertility. Combinations of
strategies such as the glucogenic-lipogenic concept and the
n-6/n-3 concept seem especially intriguing and worthy of
continued investigation.
Conclusion
In TMR systems, formulation and delivery of appropriate
diets that limit total energy intake to requirements but also
provide proper intakes of all other nutrients before calving
can help lessen the extent of NEB after calving. Effects of
such diets on indicators of metabolism are generally positive,
suggesting the potential to lessen effects of periparturient
diseases on fertility. Strategies for diet formulation to
improve DMI and lessen NEB of fresh cows are less well
researched, but the balance between adequate physically
effective fiber and starch fermentability is critical. Continued
development of innovative strategies such as manipulation
of glucogenic to lipogenic nutrients and essential fatty acid
supply should pay dividends to fertility.
Acknowledgements
The authors acknowledge the support of the USDA-CSREES
system in preparation of this article.
References
Allen MS, Bradford BJ and Oba M 2009. Board invited review: the hepatic
oxidation theory of the control of feed intake and its application to ruminants.
Journal of Animal Science 87, 3317–3334.
Ametaj BN, Bradford BJ, Bobe GB, Nafikov RA, Lu Y, Young JW and Beitz DC
2005. Strong relationships between mediators of the acute phase response and
fatty liver in dairy cows. Canadian Journal of Animal Science 85, 165–175.
Bach A, Valls N, Solans A and Torrent T 2008. Association between nondietary
factors and dairy herd performance. Journal of Dairy Science 91, 3259–3267.
Beever DE 2006. The impact of controlled nutrition during the dry period on
dairy cow health, fertility and performance. Animal Reproduction Science 96,
212–226.
Bell AW, Burhans WS and Overton TR 2000. Protein nutrition in late pregnancy,
maternal protein reserves and lactation performance in dairy cows. Proceedings
of the Nutrition Society 59, 119–136.
Bello NM, Stevenson JS and Tempelman RJ 2012. Invited review: milk produc-
tion and reproductive performance: Modern interdisciplinary insights into an
enduring axiom. Journal of Dairy Science 95, 5461–5475.
Bertoni G, Trevisi E, Han X and Bionaz M 2008. Effects of inflammatory conditions
on liver activity in puerperium period and consequences for performance in
dairy cows. Journal of Dairy Science 91, 3300–3310.
Bossaert P, Leroy JL, De Vliegher S and Opsomer G 2008. Interrelations between
glucose-induced insulin response, metabolic indicators, and time of first ovula-
tion in high-yielding dairy cows. Journal of Dairy Science 91, 3363–3371.

Butler WR 2003. Energy balance relationships with follicular development, ovulation
and fertility in postpartum dairy cows. Livestock Production Science 83, 211–218.
Cardoso FC, LeBlanc SJ, Murphy MR and Drackley JK 2013. Prepartum nutritional
strategy affects reproductive performance in dairy cows. Journal of Dairy Science
96, 5859–5871.
Chapinal N, Leblanc SJ, Carson ME, Leslie KE, Godden S, Capel M, Santos JE,
Overton MW and Duffield TF 2012. Herd-level associations of serum metabolites
in the transition period with disease, milk production, and early lactation
reproductive performance. Journal of Dairy Science 95, 5676–5682.
Contreras GA and Sordillo LM 2011. Lipid mobilization and inflammatory
responses during the transition period of dairy cows. Comparative Immunology,
Microbiology and Infectious Diseases 34, 281–289.
Dann HM and Nelson BH 2011. Early lactation diets for dairy cattle – focus
on starch. In Proceedings of the 2011 Cornell Nutrition Conference for Feed
Manufacturers, Syracuse, NY, USA.
Dann HM, Morin DE, Murphy MR, Bollero GA and Drackley JK 2005. Prepartum
intake, postpartum induction of ketosis, and periparturient disorders affect the
metabolic status of dairy cows. Journal of Dairy Science 88, 3249–3264.
Dann HM, Litherland NB, Underwood JP, Bionaz M, D’Angelo A, McFadden JW
and Drackley JK 2006. Diets during far-off and close-up dry periods affect
periparturient metabolism and lactation in multiparous cows. Journal of Dairy
Science 89, 3563–3577.
DeGaris PJ, Lean IJ, Rabiee AR and Heur C 2010. Effects of increasing days of
exposure to prepartum transition diets on reproduction and health in dairy cows.
Australian Veterinary Journal 88, 84–92.
Diskin MG and Morris DG 2008. Embryonic and early foetal losses in cattle and
other ruminants. Reproduction in Domestic Animals 43 (suppl. 2), 260–267.
Douglas GN, Overton TR, Bateman HG, Dann HM and Drackley JK 2006.
Prepartal plane of nutrition, regardless of dietary energy source, affects
periparturient metabolism and dry matter intake in Holstein cows. Journal of
Dairy Science 89, 2141–2157.
Drackley JK and Dann HM 2008. A scientific approach to feeding dry cows. In
Recent advances in animal nutrition – 2007 (ed. PC Garnsworthy and J Wiseman),
pp. 43–74. Nottingham University Press, Nottingham, UK.
Drackley JK, Overton TR and Douglas GN 2001. Adaptations of glucose and
long-chain fatty acid metabolism in liver of dairy cows during the
periparturient period. Journal of Dairy Science 84 (E. suppl.), E100–E112.
Drackley JK, Wallace RL, Graugnard D, Vasquez J, Richards BF and Loor JJ 2014.
Visceral adipose tissue mass in non-lactating dairy cows fed diets differing in
energy density. Journal of Dairy Science 97 (in press).
Drackley JK, Dann HM, Douglas GN, Janovick Guretzky NA, Litherland NB,
Underwood JP and Loor JJ 2005. Physiological and pathological adaptations in
dairy cows that may increase susceptibility to periparturient diseases and
disorders. Italian Journal of Animal Science 4, 323–344.
Dyck BL, Colaz MG, Ambrose DJ, Dyck MK and Doepel L 2011. Starch source and
content in postpartum dairy cow diets: effects on plasma metabolites and
reproductive processes. Journal of Dairy Science 94, 4636–4646.
Emmanuel DG, Dunn SM and Ametaj BN 2008. Feeding high proportions of
barley grain stimulates an inflammatory response in dairy cows. Journal of Dairy
Science 91, 606–614.
Emmanuel DG, Madsen KL, Churchill TA, Dunn SM and Ametaj BN 2007.
Acidosis and lipopolysaccharide from Escherichia coli B:055 cause hyperper-
meability of rumen and colon tissues. Journal of Dairy Science 90, 5552–5557.
Friggens NC 2003. Body lipid reserves and reproductive cycle: towards a better
understanding. Livestock Production Science 83, 219–236.
Friggens NC, Andersen JB, Larsen T, Aaes O and Dewhurst RJ 2004. Priming the
dairy cow for lactation: a review of dry cow feeding strategies. Animal Research
53, 453–473.
Galvão KN, Flaminio MJBF, Brittin SB, Sper R, Fraga M, Caixeta L, Ricci A, Guard CL,
Butler WR and Gilbert RO 2010a. Association between uterine disease and
indicators of neutrophil and systemic energy status in lactating Holstein cows.
Journal of Dairy Science 93, 2926–2937.
Galvão KN, Frajblat M, Butler WR, Brittin SB, Guard CL and Gilbert RO 2010b.
Effect of early postpartum ovulation on fertility in dairy cows. Reproduction in
Domestic Animals 45, e207–e211.
Garnsworthy PC 2007. Body condition score in dairy cows: targets for production
and fertility. In Recent advances in animal nutrition – 2006 (ed. PC Garnsworthy
and J Wiseman), pp. 61–86. Nottingham University Press, Nottingham, UK.
Transition nutritional management in TMR-fed herds
Garnsworthy PC, Sinclair KD and Webb R 2008. Integration of physiological
mechanisms that influence fertility in dairy cows. Animal 2, 1144–1152.
Garnsworthy PC, Fouladi-Nashta AA, Mann GE, Sinclair KD and Webb R 2009.
Effect of dietary-induced changes in plasma insulin concentrations during the
early post partum period on pregnancy rate in dairy cows. Reproduction 137,
759–768.
Garverick HA, Harris MN, Vogel-Bluel R, Sampson JD, Bader J, Lamberson WR,
Spain JN, Lucy MC and Youngquist RS 2013. Concentrations of nonesterified
fatty acids and glucose in blood of periparturient dairy cows are indicative of
pregnancy success at first insemination. Journal of Dairy Science 96, 181–188.
Gilmore HS, Young FJ, Patterson DC, Wylie ARG, Law RA, Kilpatrick DJ, Elliott CT
and Mayne CS 2011. An evaluation of altering nutrition and nutritional strate-
gies in early lactation on reproductive performance and estrous behavior of
high-yielding Holstein-Friesian dairy cows. Journal of Dairy Science 94,
3510–3526.
Goldhawk C, Chapinal N, Veira DM, Weary DM and von Keyserlingk MA 2009.
Prepartum feeding behavior is an early indicator of subclinical ketosis. Journal of
Dairy Science 92, 4971–4977.
Graugnard DE, Moyes KM, Trevisi E, Khan MJ, Keisler D, Drackley JK,
Bertoni G and Loor JJ 2013. Liver lipid content and inflammometabolic indices in
peripartal dairy cows are altered in response to prepartal energy intake and
postpartal intramammary inflammatory challenge. Journal of Dairy Science 96,
918–935.
Graugnard DE, Bionaz M, Trevisi E, Moyes KM, Salak-Johnson JL, Wallace RL,
Drackley JK, Bertoni G and Loor JJ 2012. Blood immunometabolic indices and
polymorphonuclear leukocyte function in peripartum dairy cows are altered by
level of dietary energy prepartum. Journal of Dairy Science 95, 1749–1758.
Grum DE, Drackley JK, Younker RS, LaCount DW and Veenhuizen JJ 1996.
Nutrition during the dry period and hepatic lipid metabolism of periparturient
dairy cows. Journal of Dairy Science 79, 1850–1864.
Grummer RR, Mashek DG and Hayirli A 2004. Dry matter intake and energy
balance in the transition period. Veterinary Clinics North America Food Animal
Practice 20, 447–470.
Hammon DS, Evjen IM, Dhiman TR, Goff JP and Walters JL 2006. Neutrophil
function and energy status in Holstein cows with uterine health disorders.
Veterinary Immunology and Immunopathology 113, 21–29.
Holcomb CS, Van Horn HH, Head HH, Hall MB and Wilcox CJ 2001. Effects of
prepartum dry matter intake and forage percentage on postpartum performance
of lactating dairy cows. Journal of Dairy Science 84, 2051–2058.
Holtenius K, Agenäs S, Delavaud C and Chilliard Y 2003. Effects of feeding
intensity during the dry period. 2. Metabolic and hormonal responses. Journal of
Dairy Science 86, 883–891.
Horst RL, Goff JP, Reinhardt TA and Buxton DR 1997. Strategies for preventing
milk fever in dairy cattle. Journal of Dairy Science 80, 1269–1280.
Houdijk JGH, Jessop NS and Kyriazakis I 2001. Nutrient partitioning between
reproductive and immune functions in animals. Proceedings of the Nutrition
Society 60, 515–525.
Huzzey JM, Veira DM, Weary DM and von Keyserlingk MA 2007. Prepartum
behavior and dry matter intake identify dairy cows at risk for metritis. Journal of
Dairy Science 90, 3220–3233.
Ingvartsen KL 2006. Feeding- and management-related diseases in the transi-
tion cow. Physiological adaptations around calving and strategies to reduce
feeding-related diseases. Animal Feed Science and Technology 126, 175–213.
Ingvartsen KL and Moyes K 2013. Nutrition, immune function and health of
dairy cattle. Animal 7 (suppl. 1), 112–122.
Ingvartsen KL, Dewhurst RJ and Friggens NC 2003. On the relationship between
lactational performance and health: is it yield or metabolic imbalance that cause
production diseases in dairy cattle? A position paper. Livestock Production Sci-
ence 83, 277–308.
Janovick NA and Drackley JK 2010. Prepartum dietary management of energy
intake affects postpartum intake and lactation performance by primiparous and
multiparous Holstein cows. Journal of Dairy Science 93, 3086–3102.
Janovick NA, Boisclair YR and Drackley JK 2011. Prepartum dietary energy
intake affects metabolism and health during the periparturient period in primi-
parous and multiparous Holstein cows. Journal of Dairy Science 94, 1385–1400.
Ji P, Osorio JS, Drackley JK and Loor JJ 2012. Overfeeding a moderate energy diet
prepartum does not impair bovine subcutaneous adipose tissue insulin trans-
duction and induces marked changes in peripartal gene network expression.
Journal of Dairy Science 95, 4333–4351.
13
Drackley and Cardoso
Jorritsma R, Wensing T, Kruip TA, Vos PL and Noordhuizen JP 2003. Metabolic
changes in early lactation and impaired reproductive performance in dairy cows.
Veterinary Research 34, 11–26.
Kim IH and Suh GH 2003. Effect of the amount of body condition loss from the
dry to near calving periods on the subsequent body condition change, occurrence
of postpartum diseases, metabolic parameters and reproductive performance in
Holstein dairy cows. Theriogenology 60, 1445–1456.
Kimura K, Reinhardt TA and Goff JP 2006. Parturition and hypocalcemia blunts
calcium signals in immune cells of dairy cattle. Journal of Dairy Science 89,
2588–2595.
Kimura K, Goff JP, Kehrli ME Jr and Reinhardt TA 2002. Decreased neutrophil
function as a cause of retained placenta in dairy cattle. Journal of Dairy Science
85, 544–550.
Kunz PL, Blum JW, Hart IC, Bickel J and Landis J 1985. Effects of different
energy intakes before and after calving on food intake, performance and
blood hormones and metabolites in dairy cows. Animal Production 40,
219–231.
Lean IJ, Van Saun R and Degaris PJ 2013a. Energy and protein nutrition
management of transition dairy cows. Veterinary Clinics North America Food
Animal Practice 29, 337–366.
Lean IJ, Van Saun R and Degaris PJ 2013b. Mineral and antioxidant manage-
ment of transition dairy cows. Veterinary Clinics North America Food Animal
Practice 29, 367–386.
LeBlanc S 2010. Assessing the association of the level of milk production
with reproductive performance in dairy cattle. Journal of Reproduction and
Development 56 (suppl.), S1–S7.
Lemley CO, Butler ST, Butler WR and Wilson ME 2008. Short communication:
insulin alters hepatic progesterone catabolic enzymes cytochrome P450 2C and
3A in dairy cows. Journal of Dairy Science 91, 641–645.
Leroy JL, Vanholder T, Opsomer G, Van Soom A and de Kruif A 2006. The in vitro
development of bovince oocytes after maturation in glucose and β-hydroxy-
butyrate concentrations associated with negative energy balance. Reproduction
in Domestic Animals 41, 119–123.
Leroy JL, Vanholder T, Delanghe JR, Opsomer G, Van Soom A, Bols PE,
Dewulf J and de Kruif A 2004. Metabolic changes in follicular fluid of the
dominant follicle in high-yielding dairy cows early post partum. Theriogenology
62, 1131–1143.
Loor JJ 2010. Genomics of metabolic adaptations in the peripartal cow. Animal
4, 1110–1139.
Loor JJ, Everts RE, Bionaz M, Dann HM, Morin DE, Oliveira R, Rodriguez-Zas SL,
Drackley JK and Lewin HA 2007. Nutrition-induced ketosis alters metabolic and
signaling gene networks in liver of periparturient dairy cows. Physiological
Genomics 32, 105–116.
Loor JJ, Dann HM, Janovick Guretzky NA, Everts RE, Oliveira R, Green CA,
Litherland NB, Rodriguez-Zas SL, Lewin HA and Drackley JK 2006. Plane of
nutrition prepartum alters hepatic gene expression and function in dairy cows as
assessed by longitudinal transcript and metabolic profiling. Physiological
Genomics 27, 29–41.
Lucy MC 2000. Regulation of ovarian follicular growth by somatotropin and
insulin-like growth factors in cattle. Journal of Dairy Science 83, 1635–1647.
McArt JA, Nydam DV and Oetzel GR 2012. Epidemiology of subclinical ketosis in
early lactation dairy cattle. Journal of Dairy Science 95, 5056–5066.
Moyes KM, Drackley JK, Salak-Johnson JL, Morin DE, Hope JC and Loor JJ 2009.
Dietary-induced negative energy balance has minimal effects on innate immunity
during a Streptococcus uberis mastitis challenge in dairy cows during midlactation.
Journal of Dairy Science 92, 4301–4316.
Mulligan FJ and Doherty ML 2008. Production diseases of the transition cow.
Veterinary Journal 176, 3–9.
Mulligan FJ, O’Grady L, Rice DA and Doherty ML 2006. A herd health approach
to dairy cow nutrition and production diseases of the transition cow. Animal
Reproduction Science 96, 331–353.
Ospina PA, Nydam DV, Stokol T and Overton TR 2010. Association between
the proportion of sampled transition cows with increased nonesterified fatty
acids and β-hydroxybutyrate and disease incidence, pregnancy rate, and milk
production at the herd level. Journal of Dairy Science 93, 3595–3601.
Pearce SC, Mani V, Weber TE, Rhoads RP, Patience JE, Baumgard LH and Gabler
NK 2013. Heat stress and reduced plane of nutrition decreases intestinal
integrity and function in pigs Journal of Animal Science 91, 5183–5193.
14
Pushpakumara PG, Gardner NH, Reynolds CK, Beever DE and Wathes DC 2003.
Relationships between transition period diet, metabolic parameters and fertility
in lactating dairy cows. Theriogenology 60, 1165–1185.
Reinhardt TA, Lippolis JD, McCluskey BJ, Goff JP and Horst RL 2011. Prevalence
of subclinical hypocalcemia in dairy herds. Veterinary Journal 188, 122–124.
Reist M, Erdin DK, von Euw D, Tschümperlin KM, Leuenberger H, Hammon HM,
Morel C, Philipona C, Zbinden Y, Künzi N and Blum JW 2003. Postpartum
reproductive function: association with energy, metabolic and endocrine status
in high yielding dairy cows. Theriogenology 59, 1707–1723.
Reynolds CK, Aikman PC, Lupoli B, Humphries DJ and Beever DE 2003.
Splanchnic metabolism of dairy cows during the transition from late gestation
through early lactation. Journal of Dairy Science 86, 1201–1217.
Roche JR, Bell AW, Overton TR and Loor JJ 2013. Nutritional management of the
transition cow in the 21st century – a paradigm shift in thinking. Animal Pro-
duction Science 53, 1000–1023.
Rukkwamsuk T, Wensing T and Geelen MJ 1998. Effect of overfeeding during
the dry period on regulation of adipose tissue metabolism in dairy cows during
the periparturient period. Journal of Dairy Science 81, 2904–2911.
Rukkwamsuk T, Wensing T and Kruip TA 1999. Relationship between tria-
cylglycerol concentration in the liver and first ovulation in postpartum
dairy cows. Theriogenology 51, 1133–1142.
Sangsritavong S, Combs DK, Sartori R, Armentano LE and Wiltbank MC 2002.
High feed intake increases liver blood flow and metabolism of progesterone and
estradiol-17beta in dairy cattle. Journal of Dairy Science 85, 2831–2842.
Santos JE, Rutigliano HM and Sa Filho MF 2009. Risk factors for resumption
of postpartum estrous cycles and embryonic survival in lactating dairy cows.
Animal Reproduction Science 110, 207–221.
Schoenberg KM and Overton TR 2011. Effects of plane of nutrition and
2,4-thiazolidinedione on insulin responses and adipose tissue gene expression in
dairy cattle during late gestation. Journal of Dairy Science 94, 6021–6035.
Silva-del-Rio N, Fricke PM and Grummer RR 2010. Effects of twin pregnancy and
dry period strategy on milk production, energy balance, and metabolic profile in
dairy cows. Journal of Animal Science 88, 1048–1060.
Silvestre FT, Carvalho TS, Francisco N, Santos JE, Staples CR, Jenkins TC and
Thatcher WW 2011. Effects of differential supplementation of fatty acids during
the peripartum and breeding periods of Holstein cows: I. Uterine and metabolic
responses, reproduction, and lactation. Journal of Dairy Science 94, 189–204.
Sutter F and Beever DE 2000. Energy and nitrogen metabolism in Holstein-
Friesen cows during early lactation. Animal Science 70, 503–514.
Tharwat M, Takamizawa A, Hosaka YZ, Endoh D and Oikawa S 2012. Hepato-
cyte apoptosis in dairy cattle during the transition period. Canadian Journal of
Veterinary Research 76, 241–247.
Thatcher W, Santos JE and Staples CR 2011. Dietary manipulations to improve
embryonic survival in cattle. Theriogenology 76, 1619–1631.
Van der Drift SG, Houweling M, Schonewille JT, Tielens AG and Jorritsma R
2012. Protein and fat mobilization and associations with serum β-hydroxy-
butyrate concentrations in dairy cows. Journal of Dairy Science 95, 4911–4920.
Vickers LA, Weary DM, Veira DM and von Keyserlingk MA 2013. Feeding a
higher forage diet prepartum decreases incidences of subclinical ketosis in
transition dairy cows. Journal of Animal Science 91, 886–894.
Walsh RB, Walton JS, Kelton DF, LeBlanc SJ, Leslie KE and Duffield TF 2007. The
effect of subclinical ketosis in early lactation on reproductive performance of
postpartum dairy cows. Journal of Dairy Science 90, 2788–2796.
Whitaker DA, Smith EJ, da Rosa GO and Kelly JM 1993. Some effects of nutrition
and management on the fertility of dairy cattle. Veterinary Record 133, 61–64.
Winkleman LA, Elsasser TH and Reynolds CK 2008. Limit-feeding a high-energy
diet to meet energy requirements in the dry period alters plasma metabolite
concentrations but does not affect intake or milk production in early lactation.
Journal of Dairy Science 91, 1067–1079.
Zebeli Q and Metzler-Zebeli BU 2012. Interplay between rumen digestive disorders
and diet-induced inflammation. Research in Veterinary Science 93, 1099–1108.
Zebeli Q, Sivaraman S, Dunn SM and Ametaj BN 2011. Intermittent parenteral
administration of endotoxin triggers metabolic and immunological alterations
typically associated with displaced abomasum and retained placenta in peri-
parturient dairy cows. Journal of Dairy Science 94, 4968–4983.
Zurek E, Foxcroft GR and Kennelly JJ 1995. Metabolic status and interval to first
ovulation in postpartum dairy cows. Journal of Dairy Science 78, 1909–1920.