Timing of nutritional insults

Timing of poor nutrition or nutritional interventions during pregnancy can have differential effects, especially when considering developmental windows of fetal and placental development. Placental development and organogenesis occur in early to mid-gestation, whereas the majority of fetal growth and organ maturation occur in late gestation. ^{Reference Fowden, Giussani and Forhead6} Even within ruminant species, there is variation in these windows. Placental growth is largely complete in the ewe and doe by mid-pregnancy, but it continues throughout pregnancy in the cow. ^{Reference Ferrell, Campion, Hausman and Martin35} Moreover, the competition of pregnancy with lactation varies among the species, as beef cattle females generally experience early gestation and commonly some of mid-gestation while lactating when maintaining a yearly calving interval. Dairy cattle females have overlap of all but very late gestation (approximately 60 days) with lactation. On the other hand, small ruminants experience pregnancy and lactation separately unless they reproduce twice per year or are maintained in lactation for dairying purposes.

Nutrient requirements of the dam increase dramatically during late pregnancy, ³² as rapid fetal growth occurs. Because most ruminant production systems are timed to have the high nutrient requirements of lactation coincide with plentiful forage availability, late gestation is frequently a time of poor nutrient availability in production settings despite this increase in nutrient needs. Additionally, most investigations of peripartum and perinatal outcomes in ruminants utilized nutritional treatments that occur during late gestation, regardless of their initiation time. For these reasons, this review will focus on the effects of maternal nutrition in late gestation. Some experiments include the entirety of pregnancy, whereas others focus on mid and late, late only, or even the last days of gestation. Timing of these treatments should be considered when interpreting results. It is well established that early and mid-pregnancy can affect placental and fetal development in ruminant species, even if birth weight is unchanged. ^{Reference Fowden, Giussani and Forhead6,Reference Caton, Hess, DelCurto, Bowman and Waterman17,Reference Kenyon and Blair36,Reference Du, Tong and Zhao37} From a review of sheep literature, it is clear nutrient intake during early or mid-gestation alone can also influence maternal and offspring behavior, passive transfer, thermoregulation, and lamb survival; ^{Reference Rooke, Arnott, Dwyer and Rutherford22} thus, more research is likely necessary to determine carryover effects from earlier in pregnancy.

Fetal growth and gestation length

Fetal growth, measured as birth weight in most of the studies cited in Tables 1–6, or as fetal weight in terminal or Cesarean section studies, is generally decreased by substantial (e.g., 30% or more reduction in nutrients) nutrient restriction in sheep ^{Reference Kenyon and Blair36,Reference Wallace38} but is not always affected by nutrient restriction in cattle. ^{Reference Perry, Copping, Miguel-Pacheco and Hernandez-Medrano14,Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39} Overnutrition of pregnant young primiparous ewes, ^{Reference Wallace38} heat stress during mid-gestation in ewes, ^{Reference Limesand, Camacho, Kelly and Antolic40,Reference Hay, Brown, Rozance, Wesolowski and Limesand41} and heat stress of dairy cows in late gestation ^{Reference Dado-Senn, Laporta and Dahl24} also generally cause intrauterine growth restriction, although likely by differing mechanisms. Birth weight is a major variable of interest because it affects postnatal survival, especially through three mechanisms: (1) being an indicator of fetal development and maturity, (2) ensuring a newborn ruminant is large enough to survive cold conditions or nutrient deficiency by having the body mass and presence of energy stores and protein for mobilization, and (3) allowing ruminant offspring to be small enough to not cause dystocia at birth due to fetopelvic disproportion. ^{Reference Holland and Odde42,Reference Dwyer43} Birth weight often serves as a crude proxy for development or maturity at birth that is possible to assess without euthanasia and dissection. It is a poor proxy, however, due to asymmetric fetal growth (e.g., brain sparing) and differential timing of growth, development, and maturation among tissues. Several tissues, such as the gastrointestinal tract, lungs, brain, brown adipose tissue, energy stores (glycogen and adipose), muscle, and many others are known to be affected my maternal nutrition during pregnancy. ^{Reference Fowden, Giussani and Forhead6,Reference Symonds, Sebert and Budge25,Reference Meyer and Caton44}

Gestation length is one determinant of birth weight and controlled by both the dam and fetus to some degree. ^{Reference Silver45} Ruminant models of altered gestational nutrition are variable in their effects on gestation length. Overnourished adolescent ewes seem to most consistently have shortened gestation lengths by 5 d on average (145 d in controls). ^{Reference Wallace38} Nutrient restriction, ^{Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39} dam primiparity, ^{Reference Meyer and Redifer23} and dry period heat stress ^{Reference Dado-Senn, Laporta and Dahl24} are inconsistent in decreasing gestation length, with the majority of papers reporting no difference. In many of the studies cited here or in the references given, birth weight differences do not appear to be due completely to altered days of fetal growth. Given the importance of not only size at birth but also the final maturation of organs prior to birth, ^{Reference Fowden, Giussani and Forhead6} change in gestation length caused by maternal nutrition or other stress is an important factor affecting neonatal survival.

Parturition difficulty and maternal behavior

One of the most common reasons for neonatal death loss in livestock species is dystocia or difficult parturition. ^{Reference Bellows, Patterson, Burfening and Phelps46–Reference Jacobson, Bruce and Kenyon48} Experiments investigating effects of maternal nutrition are rarely powered to observe statistical differences in dystocia rates. Despite this, data suggest that even though poor maternal nutrition during pregnancy often decreases birth weight, dystocia can increase after nutrient restriction or for animals with poor body condition score at parturition (Table 1). This occurred concurrently with birth weight that was either unchanged ^{Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39,Reference Ramírez-Vera, Terrazas and Delgadillo49} or decreased ^{Reference Kroker and Cummins50,Reference Dwyer, Lawrence, Bishop and Lewis51} in the controlled experimental studies shown in Table 1. Fetopelvic disproportion is likely a contributing cause of dystocia during undernutrition of primiparous females. ^{Reference Meyer and Redifer23,Reference Kroker and Cummins50,Reference Bellows and Short52} Although the mechanisms are unknown, maternal weakness or energy status probably plays a role in greater duration of labor or need for human assistance for normally-presented offspring. Abnormal fetal presentations were also increased ^{Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39,Reference Ramírez-Vera, Terrazas and Delgadillo49–Reference Dwyer, Lawrence, Bishop and Lewis51} in undernourished cattle, sheep, and goats, suggesting that altered maternal and/or fetal physiology hinders the ability of fetuses to obtain the appropriate birth position. Poor uterine tone is associated with incomplete fetal righting, ^{Reference Dufty53} which has been suggested to occur after nutrient restriction. ^{Reference Kroker and Cummins50} Lack of fetal muscle tone may also influence this, as fetal kinesis appears to have the end result of obtaining the birth posture. ^{Reference Fraser54} Given that prolonged labor or dystocia requiring human intervention is known to decrease vigor after birth, ^{Reference Dwyer55,Reference Homerosky, Timsit, Pajor, Kastelic and Windeyer56} increase perinatal stress, ^{Reference Pearson, Homerosky and Caulkett57} decrease transfer of passive immunity, ^{Reference McGee and Earley58} and ultimately increase neonatal mortality, ^{Reference Mee, Sánchez-Miguel and Doherty59} difficulty of parturition is a major effect of maternal nutrition that can program the neonatal period and beyond.

Maternal behavior during labor and especially postpartum is critical for neonates to thrive in their new extra-uterine environment. ^{Reference Dwyer, Conington and Corbiere2,Reference Nevard, Pant, Broster, Norman and Stephen60} Although this is not commonly reported in cattle maternal nutrition studies, impaired mothering behavior of ewes and does following poor gestational nutrition was observed in four experiments shown in Table 1. Dwyer et al. hypothesized that altered circulating estradiol:progesterone affects maternal behavior after nutrient restriction ^{Reference Dwyer, Lawrence, Bishop and Lewis51} and that priming effects on the brain may differ in first parity ewes. ^{Reference Dwyer and Smith61} Some of these maternal behavioral changes appear to be associated with slower or less responsiveness to offspring, ^{Reference Dwyer, Lawrence, Bishop and Lewis51,Reference Corner, Kenyon, Stafford, West and Morris62,Reference Olazábal Fenochio, Vera Ávila, Serafín López, Medrano Hernández, Sánchez Saucedo and Terrazas García63} possibly due to exhaustion from prolonged labor or energy substrate depletion. ^{Reference Dwyer, Lawrence, Bishop and Lewis51,Reference Ramírez-Vera, Terrazas and Delgadillo64} Dams with poor nutrition also have more time and/or attention diverted away from offspring in the early postnatal period, sometimes toward eating, ^{Reference Dwyer, Lawrence, Bishop and Lewis51} which is logical given the metabolic status of nutrient-restricted dams at parturition. For example, our lab observed that late gestational nutrient restriction decreased circulating glucose and triglycerides in primiparous beef females at 1 h postpartum, ^{Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39} and Ramirez-Vera et al. ^{Reference Ramírez-Vera, Terrazas and Delgadillo64} observed that feeding corn supplement during only the last 12 d prepartum increased blood glucose from kidding to 4 h postpartum. Additionally, we observed that late gestationally nutrient-restricted heifers stood more in the peripartum period, indicating more restless behavior. ^{Reference Johnson, Redifer, Wichman, Rathert-Williams and Meyer65} Together, these data suggest that nutrient-restricted females may be more focused on seeking feed than caring for their offspring after birth. Amniotic fluid is an important olfactory signal that encourages maternal behavior, ^{Reference Poindron, Lévy and Keller66} so altered consumption of amniotic fluid and grooming behavior of offspring (Table 1) may also lead to the other maternal behaviors observed, including poorer attachment to offspring, ^{Reference Dwyer, Lawrence, Bishop and Lewis51} increased aggressiveness, ^{Reference Ramírez-Vera, Terrazas and Delgadillo64} and less receptivity to suckling. ^{Reference Ramírez-Vera, Terrazas and Delgadillo64} It is unclear if reduced amniotic fluid consumption in dams with poor maternal nutrition ^{Reference Ramírez-Vera, Terrazas and Delgadillo64} is due to poor maternal responsiveness to and grooming of offspring, increased searching for feed, or other altered states in the dam. Overall, these datasets suggest that more research investigating effects of gestational nutrition on maternal peripartum behavior is warranted given its important role in neonatal survival.

Vigor at birth

Ruminant offspring behavior immediately after birth, often referred to as “vigor,” is especially important for these precocious species that need to stand, walk, and suckle quickly to obtain transfer of passive immunity. ^{Reference Dwyer43} Vigor is influenced by many perinatal factors that are negatively affected by poor maternal nutrition during pregnancy, including fetal growth and development, gestation length, size at birth, difficulty and length of parturition, and maternal behavior. ^{Reference Dwyer, Conington and Corbiere2} Thus, it is not surprising that neonatal vigor is affected by maternal nutrition, as shown in Table 2. Vigor can be difficult to quantify, as many experiments not cited used subjective vigor scores with a limited range (e.g., 1–3), usually without clear definitions such as “very vigorous” or “weak.” More useful objective measures include: (1) behavioral latency times to important milestones such as attempting to stand, successfully standing, and suckling; (2) vigor scores that are taken at specific times and have specific definitions (e.g., Matheson et al. ^{Reference Matheson, Rooke and McIlvaney67} ); (3) documentation of occurrences of normal or abnormal behaviors or interventions (as proportion of time, number of behaviors, proportion of offspring displaying, etc.); or (4) physiological indicators of vigor such as those similar to the APGAR score in humans (e.g., Homerosky et al. ^{Reference Homerosky, Caulkett, Timsit, Pajor, Kastelic and Windeyer68} ). These can be very difficult to measure in extensive environments due to lack of proximity of researchers to animals, but these also can be challenging to obtain without human obstruction of normal behavior in intensive research environments where humans and livestock are in close proximity. This likely explains the relative lack of robust datasets in ruminants, especially beef cattle. Moreover, more artificial environments usually necessary for intensive perinatal data collection may actually lessen or negate vigor differences observed in the farm or ranch setting, as improved management, ambient temperatures, housing, and other aspects of intensive research are inconsistent with many conditions in the field.

Despite this, poorer vigor after birth in ruminant livestock is likely to exist and contribute to reduced neonatal survival caused by poor maternal nutrition (Table 2) and resembles differences observed between offspring born to primiparous and multiparous dams (Table 7 ^{Reference Meyer and Redifer23} ). Latency times to stand and suckle are generally related, ^{Reference Wichman, Bronkhorst, Wook, Stephenson, Meyer and Radunz69} and prolonged latency times are associated with increased mortality. ^{Reference Dwyer, Lawrence and Bishop70} Small size at birth is often associated with poorer vigor, especially in small ruminants. ^{Reference Dwyer, Lawrence, Bishop and Lewis51} Not all reduced vigor observed appears to be caused by intrauterine growth restriction, as our lab reported increased latency time to attempt to stand and stand, along with poorer vigor scores at 20 min of age, in a study in which late gestational nutrient restriction did not reduce calf birth weight. ^{Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39,Reference Wichman, Redifer and Meyer71} Dwyer et al. ^{Reference Dwyer, Lawrence, Bishop and Lewis51,Reference Dwyer72} hypothesized that poorer vigor of small lambs is caused by developmental differences, including impaired neurodevelopment, but this is not well known in ruminants. Because many factors other than fetal growth and development play a role in neonatal vigor, it is also important to consider dystocia, duration of parturition, maternal behavior, and perinatal metabolism when investigating vigor as well. Unfortunately, few researchers study vigor in this area in a meaningful way or measure all of these variables at once. Overall, it is clear that vigor of neonatal ruminants is affected by maternal nutrition, which is likely to impact the ability of compromised offspring to obtain adequate nutrients and immunoglobulins postnatally.

Colostrum production and transfer of passive immunity

The most studied aspect of neonatal ruminant programming other than birth weight and gestational length is colostrum production. This is likely due to colostrum’s importance in providing transfer of passive immunity, concentrated initial nutrients, substrates for heat production, and hydration. As shown in Table 3 and previously reviewed by others, ^{Reference McGee and Earley58,Reference Hare, Fischer-Tlustos, Wood, Cant and Steele73,Reference Banchero, Milton, Lindsay, Martin and Quintans74} maternal nutrition during gestation generally alters yield of colostrum in non-dairy ruminant livestock. In general, both undernutrition ^{Reference Mellor and Murray75–Reference Wallace, Milne, Adam and Aitken81} and overnutrition ^{Reference Swanson, Hammer and Luther78,Reference Meyer, Reed and Neville80–Reference Wallace, Shepherd, Milne and Aitken84} decreased colostrum yield in sheep, and nutrient restriction predominantly decreased colostrum yield in cattle. ^{Reference Odde20,Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39,Reference Kennedy, Gaspers and Mordhorst85} In many datasets, this decreased yield is associated with a greater concentration of immunoglobulins (Ig) and/or total protein, ^{Reference Odde20,Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39,Reference Banchero, Perez Clariget, Bencini, Lindsay, Milton and Martin77,Reference Swanson, Hammer and Luther78,Reference Wallace, Milne, Adam and Aitken81,Reference Wallace, Bourke, Da Silva and Aitken82} resulting in less colostrum that is more concentrated. Despite this, total Ig masses were decreased by nutrient restriction ^{Reference Swanson, Hammer and Luther78,Reference McGee, Drennan and Caffrey86} and overnutrition ^{Reference Swanson, Hammer and Luther78,Reference Wallace, Milne, Adam and Aitken81,Reference Wallace, Bourke, Da Silva and Aitken82} in some studies. When it is measured, nutrient yield is decreased by poor nutrition, ^{Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39,Reference Swanson, Hammer and Luther78,Reference Meyer, Reed and Neville80–Reference Wallace, Bourke, Da Silva and Aitken82} whether nutrient concentrations are affected or not. These are similar trends to those observed when comparing primiparous and multiparous ruminant dams (Table 7, ^{Reference Meyer and Redifer23} ) although our lab observed that parity differences are more dramatic in nature than those caused by peripartum body condition score. ^{Reference Meyer, Redifer and Rathert-Williams87} Many of these studies suggest that colostrogenesis, the transfer of Ig from circulation to the mammary gland, is less affected than lactogenesis by gestational nutrition.

Colostrum yield and composition differences observed are likely a culmination of several physiological and metabolic changes due to gestational nutrition, such as mammary gland development and blood flow, endocrine signaling for colostrogenesis and lactogenesis, and substrate availability for lactogenesis. Mammary development, colostrogenesis, and lactogenesis are controlled through the intricate coordination of hormones affected by gestational nutrition, including progesterone, estradiol, prolactin, and glucocorticoids. ^{Reference Banchero, Milton, Lindsay, Martin and Quintans74,Reference Bigler, Gross, Baumrucker and Bruckmaier88,Reference Barrington, McFadden, Huyler and Besser89} Progesterone and estradiol were both increased by nutrient restriction in late gestation ewes, ^{Reference Wallace38,Reference Dwyer, Lawrence, Bishop and Lewis51,Reference Vonnahme, Neville, Perry, Redmer, Reynolds and Caton90,Reference Lemley, Meyer and Neville91} whereas prolactin and cortisol were decreased. ^{Reference Banchero, Perez Clariget, Bencini, Lindsay, Milton and Martin77,Reference Lemley, Meyer and Neville91} Placental size may play a role in mammary development and subsequent colostrum and milk yield, as mammary:fetal growth appear to be consistent based on litter size, ^{Reference Mellor92} and placental lactogen may be the link for this relationship. ^{Reference Mellor92,Reference Forsyth93} Reduced placental growth is hypothesized be the major cause of poor colostrum production in overnourished ewes, ^{Reference Wallace38} although these ewes were able to increase milk production shortly postpartum in one study. ^{Reference Meyer, Reed and Neville80} Additionally, lactose production depends on the substrate glucose, which is often decreased in circulation for nutrient-restricted females. ^{Reference Redifer, Wichman, Rathert-Williams, Freetly and Meyer39,Reference Mellor, Flint, Vernon and Forsyth76,Reference Banchero, Perez Clariget, Bencini, Lindsay, Milton and Martin77} As reviewed by Banchero et al., ^{Reference Banchero, Milton, Lindsay, Martin and Quintans74} even short-term starch-based supplementation (e.g., cereal grains) can increase colostrum yield, likely through provision of additional propionate for gluconeogenesis or post-ruminal starch for glucose absorption, although greater progesterone clearance associated with increased nutrient intake may also be involved. As shown in Table 3, both type of nutrients supplemented and species affect if short-term diet changes alter colostrum production in ruminants. ^{Reference Ramírez-Vera, Terrazas and Delgadillo49,Reference McGee, Drennan and Caffrey86,Reference Olivera-Muzante, Fierro and Durán94,Reference Banchero, Quintans and Vazquez95}

Ruminant neonates are born agammaglobulinemic, and they rely on transfer of passive immunity via colostrum. ^{Reference Weaver, Tyler, VanMetre, Hostetler and Barrington96} Serum Ig or total protein concentrations are used to determine success or failure of this passive transfer, ^{Reference Todd, McGee and Tiernan97} although thresholds are not universally agreed upon. Colostrum is generally the focus of passive transfer studies, but neonates must have dams with good maternal behavior and adequate udder morphology, and they also must be vigorous enough to stand and successfully suckle while small intestinal Ig absorption is possible. As shown in Table 4 and previously reviewed, ^{Reference McGee and Earley58} serum Ig concentrations were both decreased ^{Reference Odde20,Reference McGee, Drennan and Caffrey86,Reference Silva, Muller, Cavalieri and Fordyce98,Reference Tillquist, Kawaida and Reiter99} and increased ^{Reference Waldner19,Reference Odde20,Reference Wichman, Redifer and Meyer71,Reference Hammer, Thorson and Meyer100} by poor maternal nutrition. When serum Ig was increased, this was concomitant with greater colostrum Ig concentrations in two studies. ^{Reference Odde20,Reference Wichman, Redifer and Meyer71} This is likely because neonates were able to consume more Ig quickly in the first meal after birth when small intestinal Ig absorption potential is greatest. ^{Reference Matte, Girard, Seoane and Brisson101} Colostrum Ig may not be the only reason for this, as Hammer et al. ^{Reference Hammer, Thorson and Meyer100} observed that lambs born to nutrient-restricted ewes had elevated serum IgG at 24 h even after consuming artificial colostrum relative to body weight. Because small intestinal development is affected by maternal nutrition, ^{Reference Meyer and Caton44} it is possible that Ig transport capacity was enhanced, as was observed previously for intrauterine growth restricted neonates. ^{Reference Sangild102} Conversely, both maternal primiparity ^{Reference Meyer and Redifer23} and heat stress during the dry period ^{Reference Dahl, Tao and Laporta103} appear to have more consistent negative effects on transfer of passive immunity.

Neonatal thermoregulation and metabolism

Neonatal ruminants are often born into ambient conditions that are outside of their thermoneutral zone, which is more narrow and at higher temperatures than adults. ^{Reference Carstens104,Reference Symonds and Lomax105} Thermoregulation is accomplished through both shivering and non-shivering thermogenesis, as ruminants are born with brown adipose tissue to provide the latter for use early in life. ^{Reference Symonds, Pope and Budge106} Most research investigating the effects of maternal nutrition on the ruminant neonate’s ability to thermoregulate has evaluated brown adipose tissue masses (predominantly perirenal fat) and its expression of uncoupling protein 1 (UCP1), which allows for heat production in mitochondria of brown adipose tissue, as reviewed by Symonds et al. ^{Reference Symonds, Pope and Budge106} and shown in Table 5. Effects of nutrient restriction during late pregnancy are inconsistent, ^{Reference Alexander107–Reference Hyatt, Budge, Walker, Stephenson and Symonds110} likely based on timing and other factors such as cold stress of the dam. ^{Reference Symonds, Sebert and Budge25,Reference Symonds, Pope and Budge106} Moreover, lower circulating triiodothyronine (T ₃ ) in neonates born to nutrient-restricted dams ^{Reference Hough, McCarthy, Kent, Eversole and Wahlberg111,Reference Camacho, Meyer and Neville112} suggests that these animals may have more shivering thermogenesis than brown adipose tissue use, as brown adipose tissue must produce T₃ to perform nonshivering thermogenesis. ^{Reference Symonds and Lomax105}

Given the main goal of thermoregulation is to maintain neonatal body temperature, it is surprising that few studies investigated the effect of maternal nutrition on body temperatures of neonates in normal production environments. Our lab observed subtle differences in rectal temperatures of beef calves born to nutrient-restricted dams, but this occurred in a fall-calving experiment in which conditions were closer to thermoneutral. ^{Reference Wichman, Redifer and Meyer71} It was previously observed that calves born to both protein ^{Reference Carstens, Johnson, Holland and Odde113} and energy ^{Reference Ridder, Young and Anderson114} restricted dams had decreased metabolic rate in thermoneutral conditions. Moreover, lambs born to nutrient-restricted ewes had decreased survival time during starvation in both cold and thermoneutral conditions. ^{Reference Alexander115} This is likely due to less brown adipose tissue as well as less white adipose presence at birth. ^{Reference Alexander115} Temperature must be regulated and basal metabolism must be maintained before a neonate can grow or develop; thus, is it critical to better understand the effects of maternal nutrition on thermoregulation and its subsequent effects on metabolism.

Nutrient availability to ruminant neonates may be of greater concern than passive transfer following poor maternal nutrition due to lack of colostral nutrients, challenges of thermoregulation, and altered body stores or metabolic rate. Despite this, neonatal metabolism is not consistently studied in ruminant models of maternal nutrition, especially in those relevant to production agriculture or when whole animal measures shown in Tables 1–5 are considered. When investigated, the metabolites, hormones, and other blood chemistry studied are somewhat conflicting (Table 6; reviewed by Meyer and Redifer ^{Reference Meyer and Redifer23} for maternal parity). Nevertheless, the data support that maternal nutrition during pregnancy can alter neonatal metabolism, showing decreased nutrients in circulation, ^{Reference Kennedy, Gaspers and Mordhorst85,Reference Olivera-Muzante, Fierro and Durán94,Reference LeMaster, Taylor, Ricks and Long116} increased markers of stress, ^{Reference Wichman, Redifer and Meyer71,Reference Kennedy, Gaspers and Mordhorst85,Reference Kume, Toharmat and Kobayashi117} and altered circulating hormones ^{Reference Hough, McCarthy, Kent, Eversole and Wahlberg111,Reference Camacho, Meyer and Neville112,Reference LeMaster, Taylor, Ricks and Long116,Reference Maresca, Lopez Valiente, Rodriguez, Long, Pavan and Quintans118,Reference Tillquist, Reed and Kawaida119} or endocrine-related gene expression. ^{Reference Hyatt, Butt, Budge, Stephenson and Symonds120} This is likely due to a combination of factors, including fetal nutrient supply and development, parturition difficulty, colostrum yield and quality, and energy stores for mobilization. Overall, potential negative effects of maternal nutrition are additive, resulting in altered metabolism and stress, but rarely are these factors measured concurrently.

Energy substrate use to thermoregulate is an important portion of metabolism for many ruminant neonates. Because ruminant neonates have a glucose deficit in the first hours of life while consuming and digesting colostrum, they mobilize glycogen, begin gluconeogenesis, and mobilize non-esterified fatty acids from adipose to support basal metabolism. ^{Reference Hammon, Steinhoff-Wagner, Schönhusen, Metges and Blum121} Amino acids are also deaminated and used for gluconeogenesis or energy pathways during this period. ^{Reference Hammon, Steinhoff-Wagner, Schönhusen, Metges and Blum121} Ambient temperature is of course less affected by the dam but more influenced by location, climate, season, and management factors (e.g., housing and bedding). These make it necessary to consider the non-nutritional aspects of studies when interpreting results. For example, our lab observed that neonatal calf metabolism is affected by season of birth, where spring-born calves showed greater energy mobilization and more indicators of stress, but fall-born calves had more signs of dehydration. ^{Reference Wichman, Redifer, Rathert-Williams, Duncan, Payne and Meyer122} In fact, we observed that calves born to first parity dams in a cold environment (spring-born) had greater circulating non-esterified fatty acids from adipose mobilization and urea nitrogen from amino acid deamination, likely to make up for their lower serum glucose while attempting to maintain body temperature. ^{Reference Duncan, Stoecklein, Foote and Meyer123} In calves born into a more thermoneutral environment (fall-born), circulating glucose and triglycerides were less for calves born to primiparous dams, likely due to colostrum nutrient availability, but without the increase in non-esterified fatty acids or urea nitrogen (Meyer et al., unpublished). This is a good example of why it is especially important to report parturition location, timing (e.g., month or season at minimum), ambient temperatures, and housing or pasture conditions to allow for interpretation of neonatal data.

In addition to considering these factors, timing of sampling of neonatal ruminants is inconsistent and can even vary within an experiment. Our lab reported that beef calf blood chemistry ^{Reference Larson-Peine, Heller and Rathert-Williams124} as well as complete blood cell count ^{Reference Wichman, Redifer and Meyer71} change dramatically during the first 48 h of life, and these differ from adult reference intervals. In general, we observe patterns to vary widely from pre-suckling (“0 h”) to 24 h of age across multiple datasets, and these patterns diverge between dam nutritional planes ^{Reference Wichman, Redifer and Meyer71} and parities ^{Reference Duncan, Stoecklein, Foote and Meyer123} as well as seasons of birth. ^{Reference Wichman, Redifer, Rathert-Williams, Duncan, Payne and Meyer122} For these reasons, it is critical to establish consistent sampling times, consider using multiple sampling times, select sampling times based on study objectives, and compare neonates to a control population or similar animals in the literature rather than adult reference values.

Neonatal and pre-weaning survival

The ultimate reason to study measures in Tables 1–6 is that all contribute to the neonatal ruminant’s ability to survive. ^{Reference Perry, Copping, Miguel-Pacheco and Hernandez-Medrano14} As reviewed for sheep by Rooke et al., ^{Reference Rooke, Arnott, Dwyer and Rutherford22} nutrient restriction at various stages of gestation can result in reduced pre-weaning survival. Despite this, many studies cited there and within this review observed no differences in neonatal or pre-weaning mortality, as many of the experiments were not adequately powered for binomial measures such as morbidity or mortality. Additionally, many studies had intensive or improved management as part of study design or to facilitate data collection, which likely prevented some normal health challenge and death. It is not unusual to need additional disease pressure or challenge to realize differences in mortality. For example, Corah et al. ^{Reference Corah, Dunn and Kaltenbach125} observed 10% calf death at birth when beef cows were nutrient restricted for 100 d prepartum, but only 3% calf death loss for dams nutrient restricted and then fed a high plane of nutrition for 30 d pre-calving. Results were even more dramatic at weaning, where 19% of remaining calves died pre-weaning for the continuously restricted group, but no death losses occurred for the refed group. This was likely due to scours affecting the herd during this experiment. Although calves born to both groups were affected by scours (52% vs. 33%), this disease presence likely was necessary to cause pre-weaning mortality differences.