Effects of age,rearing, and separation stress on immunoglobulin levels in rhesus monkeys

The study reported here examined the effect of different rearing conditions and psychological stress on immunoglobulin levels in rhesus monkey infants. In the first experiment, 24 rhesus neonates were placed in one of the three following rearing conditions: Separated from their mothers and reared in the laboratory nursery; kept with their biological mothers; or removed at birth from their biological mothers and cross-fostered to adoptive rhesus mothers. Plasma samples were obtained from the nursery-reared infants immediately after birth and at weekly intervals for the next 30 days. Samples were also obtained from mother-reared and foster-reared infants on days 15 and 29. All samples were tested for IgG and IgM levels. The results indicated that neither rearing nor diet affected Ig levels. IgG levels were highest at birth and decreased progressively for the first 30 days, suggesting that placental transfer of maternal IgG is the critical determinant of IgG levels in primate infants as in humans. IgM changes were also similar to those in human infants: Low levels at birth, a significant increase from birth to day 15, and a moderate decline from day 15 to day 30. When IgG levels and IgM levels were correlated across the first month, many significant correlations were found which were consistent with human data relating both infant IgG and IgM levels to infant maturation. In the second experiment, 11 of the previously tested nursery infants were subjected to four consecutive social separations from peer groups at 6 months of age. Plasma samples were obtained before and after the first and fourth weeks of separation and tested for IgG and IgM levels. Small but significant decreases in both immunoglobulins were detected after 4 days of separation, particularly on the fourth week.     

Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants.

Pregnant women receiving daily supplements of 400 IU (10 microgram) of vitamin D2 from the 12th week of pregnancy had plasma calcium concentrations higher at 24 weeks but similar at delivery to those in control pregnant women who did not receive the supplements. Infants of the women receiving the supplements had higher calcium, lower phosphorus, and similar magnesium concentrations on the sixth day of life and a lower incidence of hypocalcaemia than infants of the control women. Plasma concentrations of 25-hydroxycholecalciferol, which showed a seasonal variation, were higher in mothers and infants in the treated group. Cord-blood calcium, magnesium, phosphorus, and 25-hydroxycholecalciferol concentrations correlated with maternal values at delivery. Breast-fed infants had higher calcium and magnesium and lower phosphorus and 25-hydroxycholecalciferol concentrations than artificially fed infants. A defect of dental enamel was found in a high proportion of infants (many of whom had suffered from hypocalcaemia) born to the control women. These results suggest that vitamin D supplementation during pregnancy would be beneficial for mothers, whose intake from diet and skin synthesis is appreciably less than 500 IU of vitamin D daily.     

Subjective assessment of rhesus monkeys over four successive years

Using behaviourally-defined adjectives and a 7-point scale, observers rated all individuals over a year old in a colony of rhesus monkeys every November for four years. Principal component analyses of the ratings provided a basis for the following scores each year: CONFIDENT, EXCITABLE, and SOCIABLE. Two- and three-year old females had higher EXCITABLE scores than males, and adult males were more CONFIDENT than adult females. At all ages, CONFIDENT scores were stable from year to year, whereas EXCITABLE and SOCIABLE scores were not stable until adulthood. However for primiparous females, only their EXCITABLE scores were stable from the ante-natal to post-natal year. One-year males who had had adverse experience in their first eight months were more EXCITABLE, but no less CONFIDENT or SOCIABLE than control males. Finally, correlations between scores of mothers and their yearlings showed that CONFIDENT mothers had CONFIDENT infants and SOCIABLE mothers had SOCIABLE infants, but EXCITABLE mothers had infants who were not CONFIDENT. Scores of mothers and their 1-year olds were also significantly correlated with some measures of their social behaviour taken when the infants were 8, 16, and 52 weeks old.     

Maternal fever and neural tube defects

It has been proposed that hyperthermia in the pregnant woman is associated with neural tube defects in her offspring. We analyzed retrospective interview data for a maternal history of probable febrile illness during the first trimester of pregnancy among mothers of infants with anencephaly or spina bifida. There were two control groups--mothers of infants with Down syndrome and mothers of infants with cleft lip or palate. With the Down syndrome group serving as controls, the incidence of febrile illness among mothers of all infants with neural tube defects was significantly elevated. With the cleft group as controls, the fever incidence was not significantly increased in the neural tube defect groups. When the combined cleft and Down syndrome controls were used, only mothers of the spina bifida group had an elevated fever incidence. Epidemiology data suggest an association of maternal fever during pregnancy with neural tube defects in the offspring.     

Behavioral and adrenocortical responses of rhesus macaque mothers to infant separation in an unfamiliar environment

The behavioral and adrenocortical responses of rhesus macaque mothers to a series of four consecutive 4-day separations from their 5-month old infants in an unfamiliar environment were examined. A biphasic behavioral response to separation was observed, with passive behavior, locomotion, and vocalization highest on Day 1 of separation, and self-directed behaviors and environmental exploration peaking during Days 2–4. Stereotyped locomotion increased, and passive behavior decreased, across successive weeks of separation. The rhesus mothers exhibited substantial cortisol elevations one and two hours postseparation, with cortisol decreasing on the fourth day of separation. The cortisol response was strongest during the first week of separation, but robust elevations occurred in response to repeated separations. No signs of behavioral depression were observed. The results indicate that infant separation combined with removal to a novel environment can be a potent stressor for rhesus macaque mothers.     

Prior experience of risk and individual differences in enterprise shown by rhesus monkey infants in the second half of their first year

A review of the literature suggested that animals exposed to more risk in their social groups should be more enterprising. Rhesus monkey infants of 37 to 44 weeks were attracted to bait in places out of their mothers' reach. The tests were run in the home pen, in the absence of social companions apart from a sibling in its second year of life, if present. In each test the bait was a sawdust and grain mixture, with two or three raisins, and enterprise was measured in terms of the number of raisins taken. Before the test period, the infants had lived in small stable captive social groups. Infants of non-top-ranking mothers took more raisins than infants of top-ranking mothers, if infants subject to high levels of aggression from their own mothers or from the adult males in their groups, were excluded. Observations of the group in a competitive foraging situation confirmed that non-to-ranking infants should be at greater risk than top-ranking ones. The infants receiving notably high levels of aggression from their mothers or the adult males in their groups took more raisins than the remainder. These results are consistent with the view that experience of risk in a social group can promote enterprise in rhesus monkey infants of less than a year old. The problems of assessing “risk” faced by socially living animals, and the mechanisms whereby experience of risk could enhance enterprise, ere discussed.     

Social development in three species of macaque (Macaca mulatta, M. fascicularis, M. tonkeana): A preliminary report on the first ten weeks of life

The development of social relations was studied in 11 infant monkeys over the first ten weeks of life : 5 subjects in a rhesus macaque group ($\text{Macaca mulatta}$), 3 in a long-tailed macaque group ($\text{M. fascicularis}$) and 3 in a Tonkean macaque group ($\text{M. tonkeana}$). Tonkean infants were found to interact with many different group members because of the permissiveness of their mothers, while social contacts of rhesus and long-tailed infants are less varied due to the restrictiveness of their mothers. These differences were consistent with patterns of adult-adult interactions, Tonkean macaques showing less intense agonistic interactions than the other two species.     

Epilepsy and Pregnancy: A Report from the Oxford Record Linkage Study

The files of the Oxford Record Linkage Study were used to identify 223 infants delivered to 168 epileptic women as the result of 218 pregnancies. There were six stillbirths, two of which were grossly malformed. It was shown that the population of epileptic mothers differed significantly from the total reproducing population in respect of social class. Each pregnancy resulting in a livebirth was therefore matched exactly for social class, civil status, maternal age, parity, hospital, and year of delivery with three control deliveries resulting in livebirths. The defects noted at birth were abstracted from the Record Linkage files, and any subsequent hospital admissions or deaths of the children were also abstracted.There were highly significant excesses of congenital abnormalities among the infants born to epileptic mothers (13·8% of livebirths had some degree of defect of congenital origin compared with 5·6% of controls, P <0·0005). It was shown that neither the frequency with which the mother had fits nor the length of time she had had the epilepsy seemed to bear any relation to the frequency of defects in the offspring—with the exception of the two mothers who developed epilepsy in the first     

Mother-infant contact and maternal maintenance activities among free-ranging rhesus monkeys

Mother-infant dyads were observed among three populations of rhesus monkeys (Macaca mulatta) in India and Nepal. Physical contact between mothers and infants, essential for effective maternal care in rhesus, was found to be influenced by the mothers' feeding behavior. As early as the second week of life, infants exhibited a diminished probability of being in contact with their mothers if their mothers were feeding rather than resting. Rhesus mothers disproportionately rejected their infants within feeding contexts, indicating that mothers were actively discouraging contact attempts by their infants during feeding bouts—perhaps because an active infant, if it remained in contact, would diminish its mother's foraging efficiency. In contrast to the mothers' feeding behavior, mother-infant contact was found to be little influenced by maternal locomotion. Most infants were found to be neither disproportionately in, nor out of contact while their mothers were in motion. However, as the amount of time mothers spent walking increased, so did the probability that infants would be carried. These data suggest that rhesus mothers behave so as to minimize their energetic costs during locomotion.     

Maternal transmission of SIVsmm in rhesus macaques

Fifteen SIV-infected rhesus monkeys delivered 13 livebirths and two stillbirths; one livebirth died at three days of age. While all infants were culture-negative for SIV at birth, nine had maternal antibodies that disappeared by six months of age. Three infants subsequently seroconverted and became virus positive at 9–15 months. Milk samples from all mothers were virus-negative at parturition but samples from four animals were virus-positive at nine and 12 months. This study documents maternal transmission of SIV and suggests transmission by breast-feeding.     

Fatal attraction: interest in infants and infant abuse in rhesus macaques.

This study investigated whether infant abuse by female rhesus macaques (Macaca mulatta) is a phenomenon specific to their own offspring or reflects a general tendency to interact negatively with infants. Several aspects of the relationship between maternal behavior, infant handling, and infant harassment were also investigated. Study subjects were 20 group-living rhesus mothers with their infants observed during the first 12 weeks of lactation. The results of this study indicate that abusive mothers are highly attracted to infants in general but that infant abuse is a phenomenon specific to their own offspring. Infant harassment is not an accidental by-product of infant handling or the result of maternal inexperience but it is likely related to reproductive competition among lactating females. Maternal behavior and infant handling may be regulated by similar proximate mechanisms, but probably have different adaptive functions and evolutionary history across the Primate order. Am J Phys Anthropol 110:17-25.     

Induction of Labour for Prevention of Stillbirth from Rh Hemolytic Disease

The fate of 80 infants delivered after induction of labour in 72 Rh-sensitized mothers was studied to determine whether the stillbirth rate could be reduced. Labour was induced at 32 to 39 weeks of gestation; the criteria for induction were based on the history of previously affected infants, and a maternal Rh-antibody titre of 1/40 or greater, using an indirect antiglobulin technique. Nine mothers were delivered by Cesarean section. It was estimated that 26 infants were so severely affected as to be unlikely to have survived to term. However, only seven died, and one was stillborn. Two of these would normally have survived, one being Rh-negative. These two cases demonstrated the main danger in this method of management. There was a probable saving of 18 infants. In 22 mothers there was no history of previous delivery of an affected infant; in all 22 the infants survived, though six probably would not have survived to term. In 15 pregnancies in which the mothers had had a previous stillbirth, 12 infants survived. Sixty-seven infants required a total of 116 exchange transfusions. Despite the hazards it is concluded that early induction has an important place in management of Rh hemolytic disease.     

Maternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosus

Most studies on the relationship of maternal diabetes to cardiovascular malformations (CVM) have been prospective investigations of pregnancy outcome and therefore could not identify associations with rare cardiac lesions. The results of a retrospective study shed new light on the risks of specific cardiac defects in diabetic pregnancies. The Baltimore-Washington Infant Study, a population-based case-control investigation of CVM, provides information on maternal diabetes reported in personal interviews. Among 2259 mothers of cases, 35 (1.5%) reported diabetes present before pregnancy (called "overt") and 95 (4.2%) reported diabetes only during pregnancy (called "gestational"). Among 2,801 mothers of controls, 14 (0.5%) had overt diabetes and 83 (3.0%) had gestational diabetes. Malformation-specific risks were expressed as odds ratios (OR) with 99.5% confidence intervals (CI). The strongest associations with overt maternal diabetes were found with double outlet right ventricle (OR 21.33; 99.5% CI 3.34, 136.26), and truncus arteriosus (OR 12.81; 99.5% CI 1.43, 114.64). No significant diagnosis-specific associations were found with gestational diabetes. Non-cardiac malformations were present in 23% of infants with CVM whose mothers had overt diabetes and in 26% of infants with CVM whose mother had gestational diabetes, in 32% of infants with CVM whose mothers did not have diabetes, and in 4% of controls. Double outlet right ventricle and truncus arteriosus are malformations dependent upon neural-crest-cell-derived ectomesenchymal tissues; these are precisely the conotruncal abnormalities that result from experimental ablation of the neural crest in chick embryos. The association with diabetes suggests a further etiologic link between these two lesions.     

Serotonin transporter gene variation, infant abuse, and responsiveness to stress in rhesus macaque mothers and infants

A functional polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene has been associated with variation in anxiety and hypothalamus-pituitary-adrenal (HPA) axis function in humans and rhesus macaques. Individuals carrying the short allele are at a higher risk for developmental psychopathology, and this risk is magnified in short allele carriers who have experienced early life stress. This study investigated the relationship between 5-HTTLPR allelic variation, infant abuse, and behavioral and hormonal responses to stress in rhesus macaques. Subjects were 10 abusive mothers and their infants, and 10 nonabusive mother-infant pairs. Mothers and infants were genotyped for the rh5-HTTLPR, and studied in the first 6 months of infant life. For mothers and infants, we measured social group behavior, behavioral responses to handling procedures, and plasma concentrations of ACTH and cortisol under basal conditions and in response to stress tests. The proportion of individuals carrying the short rh5-HTTLPR allele was significantly higher among abusive mothers than controls. Among mothers and infants, the short allele was associated with higher basal cortisol levels and greater hormonal stress responses in the infants. In addition, infants who carried the short rh5-HTTLPR allele had higher anxiety scores than infants homozygous for the long allele. The rh5-HTTLPR genotype also interacted with early adverse experience to impact HPA axis function in the infants. These results are consistent with those of previous studies which demonstrate associations between serotonergic activity and anxiety and stress reactivity, and add additional evidence suggesting that genetic variation in serotonergic function may contribute to the occurrence of abusive parenting in rhesus macaques and modulate emotional behavior and HPA axis function.     

Early agonistic experience and rank acquisition among free-ranging infant rhesus monkeys

Several aspects of agonistic experience are described for freeranging infant rhesus monkeys (Macaca mulatta)on Cayo Santiago. Even before infants are fully integrated with peers in rank dominance based on maternal ranks,infants of highranking mothers tend to be threatened less frequently by other members of the group and are less likely to be threatened by unfamiliar individuals than are infants of lowranking mothers. There is no evidence that fearful interactions between pairs of infants are related to their mother’s ranks before 22 weeks of age. However, an imperfect hierarchy can be constructed for infants between 27 and 30 weeks of age. At this age,infants of higherranking mothers are also more likely to receive protection when threatened than are infants of lowerranking mothers. When protected, their protectors are less likely to emit fearful gestures to the infants’ threatener. Close female relatives appear to play a large role in the protection of infants and may be more directly responsible for the differences described above than the mother, other relatives, or other highranking members of the group. It is suggested that more than one mechanism, including intervention by the mother and by close female relatives,may be important in rank acquisition among peers.     

Group and matriline differences in the behaviour of rhesus monkey infants

A ‘Monte Carlo’ method was developed for characterizing matrilines of rhesus monkey infants (Macaca mulatta) born to their mothers within six similar captive social groups, according to behavioural measures, and for characterizing social groups according to their matrilines' median scores. Eight- and 16-week-old infants differed according to their groups, but not according to their matrilines, in measures of their activity in the vicinity of their mothers, and the frequencies with which social companions other than the mother initiated social contacts with them while they were out of contact with their mothers. Sixteen-week-olds differed according to their groups in the frequencies with which their mothers rejected them, and 8-week-olds in the frequencies of the social contacts they initiated with companions other than mother while off their mothers. When tested with their mothers, in a mildly disturbing situation away from other social companions, 52-week-olds differed according to their group of origin in time spent out of contact with their mothers. Different groups were seen as producing infants differing in ‘enterprise’ from their eighth week, in the sense of being ready to initiate social contacts with others while off their mothers at 8 weeks, and of being off their mothers in the test at 52 weeks. Cases where the 8-week measures did not reflect infant enterprise could be explained in terms of other aspects of the relationships involving the infants and their mothers in the social group. In particular, matrilines differed consistently in dominance status, and some mothers also received high levels of aggression from other adults. Mothers receiving high levels of aggression were more responsible for maintaining proximity with their 8-week-old infants, and their 8-week-olds were less often involved in social contacts with others.     

The social grooming of captive female rhesus monkeys: Effects of the births of their infants

We observed the grooming interactions of 13 female rhesus monkeys (Macaca mulatta)before and for 12 weeks after the births of their infants. Mothers groomed for similar amounts of time before and after the birth of their infants, but after the birth, the grooming they directed to their infants may have been at the expense of that directed to other partners. Lactating females did not receive more grooming from other females but were approached more often, suggesting that they were more attractive. Mothers that groomed their infants most groomed others least, as if grooming time was limited for each mother or as if she was trying to compensate for avoiding interactions with other partners. Mothers of male infants groomed others more than mothers with female infants did, which might be due to mothers with daughters receiving more aggression and therefore avoiding interaction. Experienced and high-ranking mothers groomed their newborn infants considerably more than primiparous mothers did in the 24 hr following birth. Grooming was preferentially directed at close kin before the births of the infants. Mothers tended to groom higher-ranked partners more than they were groomed by them, and they tended to receive more grooming from lower-ranked partners than they gave, as suggested in models of rank attractiveness.     

Outcome of respiratory illness occurring in the first year of life.

This paper describes the outcome of respiratory illness presented by a birth cohort of infants in the first year of life who were born to mothers in two inner London group general practices in terms of the ventilatory capacity measured at their fifth birthday. A history of two or more episodes of "lower" respiratory illness in the first year of life was associated with a significant reduction in peak expiratory flow when compared with those who had no such history. Boys had significantly higher peak flow rates than girls; those whose parents were in manual occupations had significantly lower peak flow rates than those whose parents were in non-manual occupations. There was a significant interaction between sex and social class.     

The prediction of thyroid function in infants born to mothers with chronic thyroiditis

To elucidate the relationship between the mother's TSH-receptor antibody activities and the status of thyroid dysfunction in their offspring, blood was taken from 5 mothers with chronic thyroiditis with potent thyrotropin (TSH)-receptor blocking activity, and the potency of TBII and TSBAb activity was assayed more quantitatively. In those mothers whose infants suffered from neonatal hypothyroidism, the 50% inhibition of binding of labeled TSH to its receptors was obtained at more than 30 to 50-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 30-fold dilution. Similarly, in those mother whose infants suffered from neonatal hypothyroidism, the 50% inhibition of TSH-induced cAMP accumulation was obtained at approximately 400 to 3000-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 50-fold dilution. On the other hand TBII activity was much less potent in serum from patients with Graves' disease. These results suggested that the titration of serum with dilution to obtain 50% inhibition of labelled TSH binding to its receptor may be the simplest way to predict thyroid dysfunction of the newborn infants born to mothers with chronic thyroiditis.     

Neural tube defects and first trimester operations

Swedish health care registries were used to identify women who had surgery during pregnancy and their offspring. Among the 2,252 infants born to women who had first trimester operations during 1973-1981, six had definite diagnoses of neural tube defects (expected number, 2.5). Scrutiny of the records showed that 572 operations occurred during gestational weeks 4-5, the period of neural tube formation, and that the mothers of five of the six infants with neural tube defects had an operation during that period (expected number of neural tube defects, 0.6) although one of the offspring probably had Meckel's syndrome. The relationship between neural tube defects and operation during pregnancy is discussed including the possibility that the association may be random.