Covariation of fetal skull and maternal pelvis during the perinatal period in rhesus macaques and evolution of childbirth in primates.

A large brain combined with an upright posture in humans has resulted in a high cephalopelvic proportion and frequently obstructed labor. Fischer and Mitteroecker [B. Fischer, P. Mitteroecker, Proc. Natl. Acad. Sci. U.S.A. 112, 5655-5660 (2015)] proposed that the morphological covariations between the skull and pelvis could have evolved to ameliorate obstructed labor in humans. The availability of quantitative data of such covariation, especially of the fetal skull and maternal pelvis, however, is still scarce. Here, we present direct evidence of morphological covariations between the skull and pelvis using actual mother-fetus dyads during the perinatal period of Macaca mulatta, a species that exhibits cephalopelvic proportions comparable to modern humans. We analyzed the covariation of the three-dimensional morphology of the fetal skull and maternal pelvis using computed tomography-based models. The covariation was mostly observed at the pelvic locations related to the birth canal, and the forms of the birth canal and fetal skull covary in such a way that reduces obstetric difficulties. Therefore, cephalopelvic covariation could have evolved not only in humans, but also in other primate taxa in parallel, or it could have evolved already in the early catarrhines.

Nonverbal face-to-face interactions in macaques and humans: A translational pilot study.

Human and nonhuman primate mother-infant dyads engage in face-to-face interactions critical for optimal infant development. In semi-free-ranging rhesus macaques (Macaca mulatta), maternal primiparity and infant sex influence the expression of nonverbal face-to-face mother-infant interactions. However, whether similar patterns of variation exist in laboratory-housed macaques or human mothers is not well understood. Comparing both species would yield information regarding the translational validity of macaques to humans in this important social/developmental domain. In this pilot study, we first compared semi-free-ranging (n = 39) and laboratory-housed (n = 20) macaques, finding that laboratory-housed dyads, first-time mothers, and mothers of sons engaged in higher rates of face-to-face interactions regardless of housing. After translating the nonhuman primate coding scheme for use in a small but diverse group of human mother-infant dyads (N = 27; 44.4% African American, 18.5% American Indian, 7.4% Asian/Asian American, and 29.6% White), we found that, like macaques, human mothers of sons engaged in more face-to-face interactions; however, experienced (vs. first-time) mothers engaged in more interactions. Macaques and humans also engaged in species-specific interactions with their infants. We conclude that components of caregiver-infant nonverbal face-to-face interactions are translatable across human and nonhuman primate species and represent an exciting avenue for future caregiving work.

Body map proto-organization in newborn macaques.

Topographic sensory maps are a prominent feature of the adult primate brain. Here, we asked whether topographic representations of the body are present at birth. Using functional MRI (fMRI), we find that the newborn somatomotor system, spanning frontoparietal cortex and subcortex, comprises multiple topographic representations of the body. The organization of these large-scale body maps was indistinguishable from those in older monkeys. Finer-scale differentiation of individual fingers increased over the first 2 y, suggesting that topographic representations are refined during early development. Last, we found that somatomotor representations were unchanged in 2 visually impaired monkeys who relied on touch for interacting with their environment, demonstrating that massive shifts in early sensory experience in an otherwise anatomically intact brain are insufficient for driving cross-modal plasticity. We propose that a topographic scaffolding is present at birth that both directs and constrains experience-driven modifications throughout somatosensory and motor systems.

Development of functional connectivity within and among the resting-state networks in anesthetized rhesus monkeys.

OBJECTIVE: The age-related changes in the resting-state networks (RSNs) exhibited temporally specific patterns in humans, and humans and rhesus monkeys have similar RSNs. We hypothesized that the RSNs in rhesus monkeys experienced similar developmental patterns as humans. METHODS: We acquired resting-state fMRI data from 62 rhesus monkeys, which were divided into childhood, adolescence, and early adulthood groups. Group independent component analysis (ICA) was used to identify monkey RSNs. We detected the between-group differences in the RSNs and static, dynamic, and effective functional network connections (FNCs) using one-way variance analysis (ANOVA) and post-hoc analysis. RESULTS: Eight rhesus RSNs were identified, including cerebellum (CN), left and right lateral visual (LVN and RVN), posterior default mode (pDMN), visuospatial (VSN), frontal (FN), salience (SN), and sensorimotor networks (SMN). In internal connections, the CN, SN, FN, and SMN mainly matured in early adulthood. The static FNCs associated with FN, SN, pDMN primarily experienced fast descending slow ascending type (U-shaped) developmental patterns for maturation, and the dynamic FNCs related to pDMN (RVN, CN, and SMN) and SMN (CN) were mature in early adulthood. The effective FNC results showed that the pDMN and VSN (stimulated), SN (inhibited), and FN (first inhibited then stimulated) chiefly matured in early adulthood. CONCLUSION: We identified eight monkey RSNs, which exhibited similar development patterns as humans. All the RSNs and FNCs in monkeys were not widely changed but fine-tuned. Our study clarified that the progressive synchronization, exploration, and regulation of cognitive RSNs within the pDMN, FN, SN, and VSN denoted potential maturation of the RSNs throughout development. We confirmed the development patterns of RSNs and FNCs would support the use of monkeys as a best animal model for human brain function.

Rhesus Macaque Brain Developmental Trajectory: A Longitudinal Analysis Using Tensor-Based Structural Morphometry and Diffusion Tensor Imaging.

The typical developmental trajectory of brain structure among nonhuman primates (NHPs) remains poorly understood. In this study, we characterized the normative trajectory of developmental change among a cohort of rhesus monkeys (n = 28), ranging in age from 2 to 22 months, using structural MRI datasets that were longitudinally acquired every 3-4 months. We hypothesized that NHP-specific transient intracranial volume decreases reported during late infancy would be part of the typical developmental process, which is driven by volumetric contraction of gray matter in primary functional areas. To this end, we performed multiscale analyses from the whole brain to voxel level, characterizing regional heterogeneity, hemispheric asymmetry, and sexual dimorphism in developmental patterns. The longitudinal trajectory of brain development was explained by three different regional volumetric growth patterns (exponentially decreasing, undulating, and linearly increasing), which resulted in developmental brain volume curves with transient brain volumetric decreases. White matter (WM) fractional anisotropy increased with age, corresponding to WM volume increases, while mean diffusivity (MD) showed biphasic patterns. The longitudinal trajectory of brain development in young rhesus monkeys follows typical maturation patterns seen in humans, but regional volumetric and MD changes are more dynamic in rhesus monkeys compared with humans, with marked decreases followed by "rebound-like" increases.

Evolution and transition of expression trajectory during human brain development.

BACKGROUND: The remarkable abilities of the human brain are distinctive features that set us apart from other animals. However, our understanding of how the brain has changed in the human lineage remains incomplete, but is essential for understanding cognition, behavior, and brain disorders in humans. Here, we compared the expression trajectory in brain development between humans and rhesus macaques (Macaca mulatta) to explore their divergent transcriptome profiles. RESULTS: Results showed that brain development could be divided into two stages, with a demarcation date in a range between 25 and 26 postconception weeks (PCW) for humans and 17-23PCWfor rhesus macaques, rather than birth time that have been widely used as a uniform demarcation time of neurodevelopment across species. Dynamic network biomarker (DNB) analysis revealed that the two demarcation dates were transition phases during brain development, after which the brain transcriptome profiles underwent critical transitions characterized by highly fluctuating DNB molecules. We also found that changes between early and later brain developmental stages (as defined by the demarcation points) were substantially greater in the human brain than in the macaque brain. To explore the molecular mechanism underlying prolonged timing during early human brain development, we carried out expression heterochrony tests. Results demonstrated that compared to macaques, more heterochronic genes exhibited neoteny during early human brain development, consistent with the delayed demarcation time in the human lineage, and proving that neoteny in human brain development could be traced to the prenatal period. We further constructed transcriptional networks to explore the profile of early human brain development and identified the hub gene RBFOX1 as playing an important role in regulating early brain development. We also found RBFOX1 evolved rapidly in its non-coding regions, indicating that this gene played an important role in human brain evolution. Our findings provide evidence that RBFOX1 is a likely key hub gene in early human brain development and evolution. CONCLUSIONS: By comparing gene expression profiles between humans and macaques, we found divergent expression trajectories between the two species, which deepens our understanding of the evolution of the human brain.

Mapping hemispheric asymmetries of the macaque cerebral cortex during early brain development.

Studying cortical hemispheric asymmetries during the dynamic early postnatal stages in macaque monkeys (with close phylogenetic relationship to humans) would increase our limited understanding on the possible origins, developmental trajectories, and evolutional mechanisms of brain asymmetries in nonhuman primates, but remains a blind spot to the community. Via cortical surface-based morphometry, we comprehensively analyze hemispheric structural asymmetries in 134 longitudinal MRI scans from birth to 20 months of age from 32 healthy macaque monkeys. We reveal that most clusters of hemispheric asymmetries of cortical properties, such as surface area, cortical thickness, sulcal depth, and vertex positions, expand in the first 4 months of life, and evolve only moderately thereafter. Prominent hemispheric asymmetries are found at the inferior frontal gyrus, precentral gyrus, posterior temporal cortex, superior temporal gyrus (STG), superior temporal sulcus (STS), and cingulate cortex. Specifically, the left planum temporale and left STG consistently have larger area and thicker cortices than those on the right hemisphere, while the right STS, right cingulate cortex, and right anterior insula are consistently deeper than the left ones, partially consistent with the findings in human infants and adults. Our results thus provide a valuable reference in studying early brain development and evolution.

Annotation and cluster analysis of spatiotemporal- and sex-related lncRNA expression in rhesus macaque brain.

Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide range of biological processes and diseases. We applied comprehensive analyses of RNA-seq and CAGE-seq (cap analysis of gene expression and sequencing) to characterize the dynamic changes in lncRNA expression in rhesus macaque (Macaca mulatta) brain in four representative age groups. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age, and sex specificities. Spatiotemporal- and sex-biased changes in lncRNA expression were generally higher than those observed in mRNA expression. A negative correlation between lncRNA and mRNA expression in cerebral cortex was observed and functionally validated. Our findings offer a fresh insight into spatial-, age-, and sex-biased changes in lncRNA expression in macaque brain and suggest that the changes represent a previously unappreciated regulatory system that potentially contributes to brain development and aging.

Do young rhesus macaques know what others see?: A comparative developmental perspective.

Humans undergo robust ontogenetic shifts in the theory of mind capabilities. Are these developmental changes unique to human development or are they shared with other closely related non-human species? To explore this issue, we tested the development of the theory of mind capacities in a population of 236 infant and juvenile rhesus macaques (Macaca mulatta). Using a looking-time method, we examined what developing monkeys know about others' perceptions. Specifically, we tested whether younger monkeys predict that a person will reach for an object where she last saw it. Overall, we found a significant interaction between a monkey's age and performance on this task (p = .014). Juvenile monkeys (between two and 5 years of age) show a nonsignificant trend towards human infant-like patterns of performance, looking longer during the unexpected condition as compared to the expected condition, though this difference is nonsignificant (p = .09). However, contrary to findings in human infants, infant rhesus macaques show a different trend. Infant monkeys on average look slightly longer on average during the expected condition than the unexpected condition, though this pattern was not significant (p = .06). Our developmental results in monkeys provide some hints about the development of the theory of mind capacities in non-humans. First, young rhesus macaques appear to show some interest in the perception of other agents. Second, young rhesus seems able to make predictions based on the visual perspective of another agent, though the developmental pattern of this ability is not as clear nor as robust as in humans. As such, though an understanding of others' perceptions is early-emerging in human infants, it may require more experience interacting with other social agents in our non-human relatives.

Neonatal temperament and neuromotor differences are predictive of adolescent alcohol intake in rhesus monkeys (Macaca mulatta).

Identifying predictors of teenage alcohol use disorder (AUDs) is a major health initiative, with studies suggesting that there are distinct personality-related traits that underlie patterns of alcohol intake. As temperament is biologically based, identifiable early in life, and stable across time, it is considered the foundation of personality. As such, we hypothesized that neonatal temperament traits would predict anxiety-mediated adolescent alcohol consumption. To test this, N = 145 rhesus macaque (Macaca mulatta) infants (14 days of age), reared in a neonatal nursery (n = 82) or in a control condition with their mothers (n = 63) were assessed with a widely used standardized nonhuman primate testing battery, the Infant Behavioral Assessment Scale (IBAS), modeled after the Brazelton Neonatal Assessment Scale, evaluating visual orienting, temperament, motor maturity and, more recently, sensory sensitivity. As adolescents (3-4 years of age), these same subjects were allowed unfettered access to a sweetened-alcohol solution for 1 hr/day, 4 days/week, over 5-7 weeks. Subjects were allowed to self-administer alcohol while housed alone (n = 70) or socially in their home cage (n = 55). Linear regressions showed that alcohol intake was predicted by neonatal orienting ability (ß = -.35; p = .01), state control (ß = -.19; p = .04), and motor maturity (ß = -.24; p = .01). Poor neonatal orienting, state control (ease of consolability), and motor maturity were associated with higher adolescent alcohol intake in rhesus monkeys. These findings suggest that neonatal temperament is predictive of patterns of adolescent alcohol intake. To the extent that these results generalize to humans, they provide evidence that early-life temperament and neurodevelopment may be important risk factors for adolescent AUDs and that the IBAS may be used as an assessment tool for identifying such risk.

A new look at neurobehavioral development in rhesus monkey neonates (Macaca mulatta).

The Brazelton Neonatal Behavioral Assessment Scale (NBAS) evaluates a newborn infant's autonomic, motor, state, temperament, and social-attentional systems, which can help to identify infants at risk of developmental problems. Given the prevalence of rhesus monkeys being used as an animal model for human development, here we aimed to validate a standardized test battery modeled after the NBAS for use with nonhuman primates called the Infant Behavioral Assessment Scale (IBAS), employing exploratory structural equation modeling using a large sample of rhesus macaque neonates (n = 1,056). Furthermore, we examined the repeated assessments of the common factors within the same infants to describe any changes in performance over time, taking into account two independent variables (infant sex and rearing condition) that can potentially affect developmental outcomes. Results revealed three factors (Orientation, State Control, and Motor Activity) that all increased over the 1st month of life. While infant sex did not have an effect on any factor, nursery-rearing led to higher scores on Orientation but lower scores on State Control and Motor Activity. These results validate the IBAS as a reliable and valuable research tool for use with rhesus macaque infants and suggest that differences in rearing conditions can affect developmental trajectories and potentially pre-expose infants to heightened levels of cognitive and emotional deficiencies.

Impacts of early social experience on cognitive development in infant rhesus macaques.

Although much is known about the influences of early life experiences on the neurobiology and behavior of macaque models of child development, there is scant literature on cognitive development with respect to early rearing. Here, we examined the effects of rearing condition on affective reactivity and cognitive development in infant rhesus macaques. Infants were pseudo-randomly assigned to one of the two rearing conditions: nursery reared (NR, N = 32; 16 peer-reared, 16 surrogate-peer-reared) or mother-peer-reared (MPR, N = 7). During the first month of life, infants were administered the Primate Neonatal Neurobehavioral Assessment (PNNA). Beginning at 4 months old, infants were tested on cognitive tasks that assessed reward association, cognitive flexibility, and impulsivity. We found no gross cognitive differences between MPR and NR infants. However, MPR infants were more reactive than NR infants on the PNNA. Additionally, reactivity on the PNNA correlated with impulsivity, such that infants who were more reactive at 1 month of age completed fewer trials correctly on this task at 8-10 months. These findings are the first to directly compare cognitive development in MPR and NR infants, and add to the existing literature elucidating the influences of early social experience on temperament and development.

New approaches to quantify social development in rhesus macaques (Macaca mulatta): Integrating eye tracking with traditional assessments of social behavior.

The nonhuman primate provides a sophisticated animal model system both to explore neurobiological mechanisms underlying complex behaviors and to facilitate preclinical research for neurodevelopmental and neuropsychiatric disease. A better understanding of evolutionarily conserved behaviors and brain processes between humans and nonhuman primates will be needed to successfully apply recently released NIMH guidelines (NOT-MH-19-053) for conducting rigorous nonhuman primate neurobehavioral research. Here, we explore the relationship between two measures of social behavior that can be used in both humans and nonhuman primates-traditional observations of social interactions with conspecifics and eye gaze detection in response to social stimuli. Infant male rhesus macaques (Macaca mulatta) serving as controls (N = 14) for an ongoing study were observed in their social rearing groups and participated in a noninvasive, longitudinal eye-tracking study. We found significant positive relationships between time spent viewing eyes of faces in an eye tracker and number of initiations made for social interactions with peers that is consistent with similar observations in human populations. Although future studies are needed to determine if this relationship represents species-typical social developmental processes, these preliminary results provide a novel framework to explore the relationship between social interactions and social attention in nonhuman primate models for neurobehavioral development.

Intergenerational effects of mother's early rearing experience on offspring treatment and socioemotional development.

This longitudinal study spans two generations of rhesus monkeys. First, the study investigates the effects of early rearing experiences on the maternal behavior of first-generation mothers (rates of premature infant rejection) and, second, the study investigates the effects of maternal rejection on the behavior of second-generation infants. Rhesus macaque mother-infant dyads (Macaca mulatta-N = 176) were observed twice weekly, with each session lasting 300 s. First-generation mothers were raised in one of three conditions: as mother-reared controls (MR; [n = 95]), in peer groups (PR; raised without adults but with constant access to three same-aged peers [n = 49]), or with an inanimate surrogate (SPR; raised with an inanimate fleece-covered, surrogate mother and limited daily peer-group interactions [n = 32]). Second-generation infants were all raised by their differentially reared mothers and statistically grouped into one of two groups: those that were rejected by their mothers beginning at a more-typical weaning age (controls), starting in the third month of life (n = 108), and those that were prematurely rejected, with mothers showing rejections before the third month of infant life (n = 68). Overall, PR mothers exhibited the highest rates of premature infant rejection, except for month 1 of infant life, when SPR mothers exhibited the highest rates of rejection. Intriguingly, after month 1, SPR mothers showed high rates of infant cradling and seldom rejected their infants. Independent of their mothers' early rearing environment, prematurely rejected infants displayed more aggression and passive vigilance, and were cradled and groomed less by their mothers, and there was evidence that the overall rates of rejection after the first 2 months of life had a cumulative negative effect on the developing infant. Post hoc analyses of plasma cortisol levels showed that the prematurely rejected infants had higher cortisol concentrations, suggesting a high level of stress in the prematurely rejected infants. These results suggest that maternal presence during infancy has long-term effects on a female's future maternal skills which, in turn, have intergenerational consequences for the socioemotional development of second-generation infants.

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span.

This investigation compared the microbiomes colonizing teeth during the initiation, progression, and resolution of periodontitis in nonhuman primates (Macaca mulatta) at different ages. Subgingival plaque samples were collected at baseline; 0.5, 1, and 3 months following ligature-induced periodontitis; and following naturally occurring disease resolution at 5 months. Samples were analyzed using 16S amplicon sequencing to identify bacterial profiles across age groups: young (<3 years of age), adolescent (3 to 7 years), adult (12 to 15 years), and aged (17 to 23 years). α-Diversity of the microbiomes was greater in the adult/aged samples than in the young/adolescent samples. ß-Diversity of the samples demonstrated clear age group differences, albeit individual variation in microbiomes between animals within the age categories was noted. Phylum distributions differed between the young/adolescent animals and the adult/aged animals at each of the time points, showing an enrichment of the phyla Spirochetes, Fusobacteria, and Bacteroidetes associated with periodontitis. Major differences in the top 50 operational taxonomic units (OTUs) were noted in the young and adolescent microbiomes during initiation and progression postligation compared to the adult and aged animals. The proportions of a large number of species in the top 50 OTUs were lower at baseline and in resolved disease microbiomes in the young samples, while profiles in adolescent animals were more consistent with the disease microbiomes. Microbiome profiles for resolution for adults and aged animals appeared more resilient and generally maintained a pattern similar to that of disease. Use of the model can expand our understanding of the crucial interactions of the oral microbiome and host responses in periodontitis.

Towards germline gene therapy of inherited mitochondrial diseases.

Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.

Steroid hormone concentrations in milk predict sex-specific offspring growth in a nonhuman primate.

OBJECTIVES: In humans and other mammals, maternal hormones are transferred to offspring during lactation via milk and may regulate postnatal development, including the pace of early growth. Here, we used a nonhuman primate model to test the hypotheses that milk cortisol and dehydroepiandrosterone-sulfate (DHEAS) concentrations reflect maternal characteristics, and that changes in these hormones across lactation are associated with early postnatal growth rates. METHODS: Demographic information, morphometrics, and milk samples were collected from rhesus macaque mothers and their infants at the California National Primate Research Center in Davis, California. Using linear models, we examined the relationship between maternal traits and milk hormone concentrations (N = 104 females) and explored the effect of milk hormones on the rate of offspring growth (N = 72 mother-infant dyads), controlling for available milk energy. RESULTS: Contrary to previous studies, we found that milk cortisol concentrations were categorically higher in multiparous females than in primiparous females. However, milk DHEAS concentrations decreased with maternal parity. Neither milk cortisol nor DHEAS were related to maternal rank. Finally, changes in milk hormones predicted offspring growth in a sex-specific and temporal manner: increases in cortisol from peak to late lactation predicted faster female growth, and increases in DHEAS concentrations from early to peak and peak to late lactation predicted faster male growth. CONCLUSIONS: Our findings shed light on how hormonal components of milk have sex-specific effects on offspring growth during early postnatal life with varying temporal windows of sensitivity.

Adaptive developmental plasticity in rhesus macaques: the serotonin transporter gene interacts with maternal care to affect juvenile social behaviour.

Research has increasingly highlighted the role that developmental plasticity-the ability of a particular genotype to produce variable phenotypes in response to different early environments-plays as an adaptive mechanism. One of the most widely studied genetic contributors to developmental plasticity in humans and rhesus macaques is a serotonin transporter gene-linked polymorphic region (5-HTTLPR), which determines transcriptional efficiency of the serotonin transporter gene in vitro and modifies the availability of synaptic serotonin in these species. A majority of studies to date have shown that carriers of a loss-of-function variant of the 5-HTTLPR, the short (s) allele, develop a stress-reactive phenotype in response to adverse early environments compared with long (l) allele homozygotes, leading to the prevalent conceptualization of the s-allele as a vulnerability allele. However, this framework fails to address the independent evolution of these loss-of-function mutations in both humans and macaques as well as the high population prevalence of s-alleles in both species. Here we show in free-ranging rhesus macaques that s-allele carriers benefit more from supportive early social environments than l-allele homozygotes, such that s-allele carriers which receive higher levels of maternal protection during infancy demonstrate greater social competence later in life. These findings provide, to our knowledge, the first empirical support for the assertion that the s-allele grants high undirected biological sensitivity to context in primates and suggest a mechanism through which the 5-HTTLPR s-allele is maintained in primate populations.

Standard growth and diarrhea-associated growth faltering in captive infant rhesus macaques (Macaca mulatta).

Reference growth studies of captive rhesus macaque infants have not accounted for diarrhea and the potential for growth stunting or growth faltering. Healthy infants without diarrhea could be used to build a standard growth chart and a tool used to detect growth faltering associated with diarrhea. We hypothesized infants who develop diarrhea during the first year of life would experience decreased linear weight gain compared to healthy infants, and we used healthy infants to establish standard growth of male and female infants. We hypothesized the lower 3rd percentile of standard growth would be cut-off criteria used in screening for diarrhea-associated growth faltering. Using a retrospective cohort of 6,510 infant weight records in a multiple linear regression, daily weight gain through the first year of life was determined by sex, housing type, and health status. Male standard growth was 4.1 g/day (95%CI: 4.0-4.2 g/day) in corrals and 4.7 g/day (95%CI: 4.5-4.8 g/day) in shelter housing. Female standard growth was 4.0 g/day (95%CI: 3.8-4.2 g/day) in corrals and 4.4 g/day (95%CI: 4.0-4.7 g/day) in shelter housing. Diarrhea was significantly associated with decreased linear weight gain by up to 34% during the first year of life. Odds of growth faltering of infants, defined as those falling below the 3rd percentile of standard growth, were at least 8.9 higher given a history of diarrhea compared to healthy. The growth faltering cut-off criteria had a sensitivity of at least 53% for males and females to screen for diarrhea in infants between 6 and 12 months in shelters housing. Interinstitutional collaborations of infant rhesus macaque weight records would refine the standard growth charts and cut-off criteria, and additional morphometric data would provide a more nuanced picture of growth stunting.