In utero exposure to famine and subsequent fertility: The Dutch Famine Birth Cohort Study

OBJECTIVES: We hypothesized that if prenatal caloric restriction due to nutritional deprivation had affected development of the organs responsible for producing and regulating female reproductive hormones, a woman's fertility would be impaired. METHODS: Women born in Amsterdam from August 1, 1944, through April 15, 1946, a period encompassing a severe 5-month famine, were identified (n = 700; 85% response rate). Date of birth and vital status of all offspring were ascertained by home interview between 1987 and 1991. Famine exposure was inferred from the mother's date of birth. RESULTS: Of the study participants, 74 (10.6%) had no children. The remainder reported 1334 off-spring (1294 singletons, 20 pairs of twins), of whom 14 were stillborn and 22 died in the first 7 days of life. There was no detectable effect of famine exposure on age at menarche, the proportion having no children, age at first delivery, or family size. An excess of perinatal deaths occurred among offspring of famine-exposed women, particularly those exposed in their third trimester. CONCLUSIONS: Acute famine exposure in utero appears to have no adverse consequences for a woman's fertility. The excess perinatal mortality in the second generation is unexplained and should be confirmed by other studies.     

Size at birth, maternal nutritional status in pregnancy, and blood pressure at age 17: population based analysis

OBJECTIVE: To assess the effect of size at birth, maternal nutrition, and body mass index on blood pressure in late adolescence. DESIGN: Population based analysis of birth weight corrected for gestational age, mother's weight before pregnancy and weight gain in pregnancy, obtained from the Jerusalem perinatal study, and blood pressure and body mass index at age 17, available from military draft records. SETTING: Jerusalem, Israel. SUBJECTS: 10,883 subjects (6684 men and 4199 women) born in Jerusalem during 1974-6 and subsequently drafted to the army. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures measured at age 17 and their correlation with birth weight, size at birth, mother's body mass index and weight gain during pregnancy, and height and weight at age 17. RESULTS: Systolic and diastolic blood pressures were significantly and positively correlated with body weight, height, body mass index at age 17, and with mother's body weight and body mass index before pregnancy, but not with birth weight or mother's weight gain in pregnancy. CONCLUSION: Variables reflecting poor intrauterine nutrition, including low maternal body mass index before pregnancy, poor maternal weight gain in pregnancy, and being born small for gestational age, were not associated with a higher blood pressure in late adolescence.     

Father's effect on infant birth weight

OBJECTIVE: We sought to determine whether paternal size at birth and during young adulthood influences the birth weight of the offspring. STUDY DESIGN: This historic cohort study followed up girls born in Copenhagen during 1959 to 1961. Their pregnancies in 1974 to 1989 were traced through the Danish Population Register, and the Personal Identification Numbers of the fathers of the children were obtained. Paternal birth weight was obtained from midwifery records and adult stature from military draft records. RESULTS: Compared with fathers who weighed at least 4 kg at birth, fathers who weighed 3 to 3.99 kg at birth had infants who were 109 gm lighter, and fathers who weighed <3 kg had infants who were 176 gm lighter after adjustment for maternal birth weight and adult stature, smoking, and medical and socioeconomic factors. After adjustment, fathers in the lowest quartile of adult body mass index had infants that were 105 gm lighter than those of fathers in the highest quartile. Both paternal birth weight and adult body mass index exhibited significant trends in association with infant birth weight. CONCLUSION: Independently of maternal size, the father's physical stature, particularly his own size at birth, influences the birth weight of his children.     

Mothers' birth weight and survival of their offspring: population based study

OBJECTIVE: To test the hypothesis that a baby's survival is related to the mother's birth weight. DESIGN: Population based dataset for two generations. SETTING: Population registry in Norway. SUBJECTS: All birth records for women born in Norway since 1967 were linked to births during 1981-94, thereby forming 105104 mother-offspring units. MAIN OUTCOME MEASURES: Perinatal mortality specific for weight for offspring in groups of maternal birth weight (with 500 g categories in both). RESULTS: A mother's birth weight was strongly associated with the weight of her baby. Maternal birth weight was associated with perinatal survival of her baby only for mothers with birth weights under 2000 g. These mothers were more likely to lose a baby in the perinatal period (odds ratio 2.3, 95% confidence interval 1.4 to 3.7). Among mothers with a birth weight over 2000 g there was no overall association between mother's weight and infant survival. There was, however, a strong interaction between mother's birth weight, infant birth weight, and infant survival. Mortality among small babies was much higher for those whose mothers had been large at birth. For example, babies weighing 2500-2999 g had a threefold higher mortality if their mother's birth weight had been high (> or = 4000 g) than if the mother had been small (2500-2999 g). CONCLUSION: Mothers who weighed less than 2000 g at birth have a higher risk of losing their own babies. For mothers who weighed > or = 2000 g their birth weight provides a benchmark for judging the growth of their offspring. Babies who are small relative to their mother's birth weight are at increased risk of mortality.     

Reciprocal links among differential parenting, perceived partiality, and self-worth: a three-wave longitudinal study.

This study examined reciprocal links between parental differential treatment, siblings' perception of partiality, and self-worth with 3 waves of data from 384 adolescent sibling dyads. Results suggest that birth-order status was significantly associated with self-worth and perception of maternal and paternal differential treatment. There was a consistent across-time effect of self-worth on perception of parental partiality for later born siblings, but not earlier born siblings, and a consistent effect of differential treatment on perception of partiality for earlier born but not later born siblings. The results contribute new insight into the associations between perception of differential parenting and adolescents' adjustment and the role of birth order. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contribution of parental blood pressures to association between low birth weight and adult high blood pressure: cross sectional study

OBJECTIVE: To examine the possibility that low birth weight is a feature of the inherited predisposition to high blood pressure. DESIGN: Cross sectional study. SETTING: Primary care medical centre in Edinburgh. SUBJECTS: One offspring of 452 families (231 men and 221 women aged 16-26 years) in whom blood pressure, weight, and height were measured in 1986 and whose parents had blood pressure measured in 1979. Birth weights were obtained from case records (270 offspring) or by questionnaires sent to the mothers (182 offspring). MAIN OUTCOME MEASURES: Birth weight and adult systolic blood pressure in offspring in relation to parental blood pressure. RESULTS: If parental blood pressures were not considered, a 1 kg decrease in birth weight was associated with a 2.24 mm Hg increase in systolic blood pressure of offspring (P = 0.06) after correction for current weight and sex. However, parental blood pressures correlated positively with blood pressure of offspring, and higher maternal blood pressure was associated with lower birth weight (-3.03 g/mm Hg, P < 0.01). After correction for parental blood pressures, a 1 kg decrease in birth weight was associated with only a 1.71 mm Hg increase in the systolic blood pressure of the offspring (P = 0.15). CONCLUSIONS: Low birth weight is a feature of the inherited predisposition to hypertension, perhaps because it is associated with higher maternal blood pressure during pregnancy. Parental blood pressure may be an important confounding factor in the relation between low birth weight and subsequent hypertension.     

The effect of maternal smoking on birth weight in twin pregnancies

Information on 869 076 singletons and 17 566 twins, born during the period 1983-1991, was obtained from the Swedish Medical Birth Registry. Data on birth weight, gestational duration, vital status, and maternal smoking habits during pregnancy were analyzed in order to investigate whether twinning potentiates the effect of maternal smoking on birth weight and perinatal mortality. The individual birth weights were expressed as percentages of mean birth weight, where mean birth weights of singletons and twins were calculated separately. The birth weight reducing effect of maternal smoking was found to be of the same magnitude among twins and singletons weighing > 90% of mean birth weight. For infants weighing < 90% of mean birth weight, maternal smoking had a significantly stronger effect on birth weight among singletons than among twins. When gestational duration was taken into consideration, this difference was less pronounced. The effect of maternal smoking on gestational duration was stronger among singletons than twins. The smoking-related risk increase of perinatal death was of about the same magnitude among twins and singletons.     

Role of the prenatal environment in the development of obesity

Establishing that prenatal life is a critical or sensitive period for the development of obesity may focus basic research and clinical prevention efforts on this period. This review summarizes evidence that the intrauterine environment influences the risk of later obesity and considers the mechanisms by which this may occur. The association between birth weight and adult weight suggests that there are enduring effects of the intrauterine environment on later obesity risk. We examine whether the maternal factors of diabetes, obesity, and pregnancy weight gain alter the intrauterine environment and thereby increase the risk of later obesity in the offspring. Of these maternal factors, evidence is strongest for the role of maternal diabetes. No single mechanism explains how these maternal factors could change the intrauterine environment to increase obesity risk. However, all potential mechanisms involve an altered transfer of metabolic substrates between mother and fetus, which may influence the developing structure or function of the organs involved in energy metabolism.     

Differential effects of maternal heroin and methadone use on birthweight

An analysis of birthweights of 337 neonates in relation to history of maternal narcotic usage was undertaken. Mean birthweight of infants born to mothers abusing heroin during the pregnancy was 2,490 gm, an effect primarily of intrauterine growth retardation. Low mean birthweight (2,615 gm) was also seen in infants born to mothers who had abused heroin only prior to this pregnancy, and mothers who had used both heroin and methadone during the pregnancy (2,535 gm). Infants born to mothers on methadone maintenance during the pregnancy had significantly higher mean birthweights (2.961 gm), but lower than the control group (3,176 gm). A highly significant relationship was observed between maternal methadone dosage in the first trimester and birthweight, i.e., the higher the dosage, the larger the infant. Heroin causes fetal growth retardation, an effect which may persist beyond the period of addiction. Methadone may promote fetal growth in a dose-related fashion after maternal use of heroin.     

The dynamics of reciprocal sibling interaction: Are context and maternal behaviour important?

Dyadic behaviors characterizing sibling exchanges, symmetry of dyadic styles and the influence of context (degree of task structure and maternal absence or presence) on sibling interaction were investigated. Additionally, associations between maternal interaction styles and the affective quality of the sibling relationship were examined. Twenty-six sibling pairs and their mothers participated in 3 play sessions. First born siblings were aged 5.3–7.1 yrs and second born siblings were aged 3.2–3.8 yrs. Findings reveal reciprocity within dyads for cooperative and rivalrous behaviors. Balanced and unbalanced patterns of sibling interaction were identified. Task structure did not influence sibling interaction (holding maternal presence constant). Maternal presence or absence was associated with a quantitative and qualitative change in sibling interaction. Maternal styles (attentive responsiveness, active engagement, praise) were differentially related to the quality of the sibling interaction in maternal presence versus absence. The sibling dyad is discussed as an important context for learning about the dynamics of social relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predicted and actual fetal weight throughout the last trimester

The aim of our study was to obtain, in normal pregnancies, references values of predicted and actual fetal weight for both male and female fetuses and for fetuses born to nulliparous and multiparous women between weeks 28 and 41 of gestation. Predicted fetal weight curves represented calculations of weight in the third trimester based on weight data obtained during the second trimester. These curves were obtained from 134 ultrasonograms obtained between weeks 20 and 27. Actual fetal weight curves represented the values calculated from third trimester measurements and were based on 374 ultrasonograms obtained between weeks 28 and 41. For predicted fetal weight minor differences were found between male and female fetuses and between fetuses born to nulliparous and multiparous women. For actual weights, differences increased progressively for gender and parity during the last trimester. Predicted weights progressed at a steeper rate, and this effect was stressed in cases of female fetuses and fetuses born to nulliparous women. If predicted weights reflect normal growth, differences between fetal gender or maternal parity might be due to environmental influences. Therefore, it might not be justified to construct separate weight charts differentiated by sex or parity.     

Beta-cell mass and proliferation following late fetal and early postnatal malnutrition in the rat

We have recently shown that maternal food restriction during late pregnancy in rats decreased beta-cell mass in the offspring at birth, without altering beta-cell proliferation. The aim of the present work was to determine: 1) whether sustained maternal undernutrition until weaning (R group) more dramatically alters beta-cell mass in the offspring and if normal food supply from weaning until adulthood could reverse the deleterious effects and; 2) if altered beta-cell proliferation was responsible for the decreased beta-cell mass. Beta-cell fraction and proliferative capacity were determined during the suckling period and at adult age after ad libitum feeding from weaning in the R animals and in age-matched controls (C group). At day 21, the offspring born and nursed by food-restricted mothers (R animals) showed a 66% reduction in beta-cell mass and number, which did not increase from birth to weaning, although beta-cell proliferation remained normal. At 3 months of age, R animals had 35% decreased beta-cell fraction, with a 50% decrease in the head of the pancreas. In that area, beta-cell proliferation was similar to that of the controls. In the tail of the pancreas, beta-cell fraction was only slightly impaired but beta-cell proliferation was increased by 37%, as compared with the controls. This increase was associated with a shift in islet size distribution towards medium and large islets compared with the head of pancreas from these R animals. No regional variations of beta-cell fraction, proliferation or islet size distribution were observed in adult control animals. In conclusion, prolonged malnutrition until weaning impairs beta-cell development but not beta-cell proliferation. Subsequent re-nutrition is followed by increased beta-cell proliferation but this is insufficient to fully restore beta-cell mass.     

Obesity among offspring of women with type 1 diabetes

OBJECTIVE: To determine subsequent growth and body composition of children born to women with type 1 diabetes compared with controls. DESIGN: Prospective cohort study. SETTING: Follow-up of offspring born to women with type 1 diabetes and controls from an earlier study of diabetes and lactation. SUBJECTS: Seventeen nondiabetic offspring of women with type 1 diabetes and 18 offspring of control women (age range 5.9 to 9.0 years). OUTCOME MEASURES: Anthropometric measures at follow-up included height, weight, triceps and subscapular skinfold thickness. Information on usual nutrient intakes and physical activity patterns was elicited through questionnaires. Body composition was determined from skinfold thickness measures and bioelectrical impedance analysis. A child was identified as obese if he or she met at least 2 of the following 4 criteria for obesity: (1) weight-for-height equal to or greater than 120% of the National Center for Health Statistics (NCHS) reference median plus triceps skinfold greater than the 85th percentile; (2) body mass index (BMI) greater than the 95th percentile for age and sex; (3) percent body fat (from impedance measures) equal to or greater than 25 for boys and 30 for girls; or (4) percent body fat (from sum of skinfold measures) equal to or greater than 25 for boys and 30 for girls. RESULTS: There were 7 obese children in the type 1 diabetes group and none in the control group (p = 0.007). Obese children did not differ from nonobese children in birth weight, body fat patterning, nutrient intake, physical activity patterns, maternal pregravid weight or blood glucose control during the last trimester of pregnancy. Mothers of obese children, however, had fewer years of education and gained more weight during pregnancy compared with mothers of nonobese children in the type 1 diabetes group (p < 0.05). CONCLUSION: Obesity during childhood is a significant problem among nondiabetic children of women with type 1 diabetes. The association of childhood obesity with lower maternal education and excessive pregnancy weight gain warrants further investigation.     

Idiopathic normal pressure hydrocephalus: analysis of factors related to cerebrospinal fluid dynamics determining functional prognosis

OBJECTIVE: To examine the effect of maternal smoking on the relationship between maternal hemoglobin levels and pregnancy outcome. DESIGN: A prospective study of healthy parous women from early pregnancy and of their infants. SETTING: Three Scandinavian university hospitals covering all deliveries from well defined geographical areas. SUBJECTS: Smoking (669) and non-smoking (368) mothers, para 1 and 2 and with > or = 37 weeks of gestational length. MAIN OUTCOME MEASURES: Birth weight and placental weight. Ponderal Index and Placental Index as measures of possible discordant fetal and placental growth. RESULTS: In non-smoking mothers the hemoglobin levels in the three trimesters had no relation to birth weight. In smoking mothers a significantly lower birth weight was seen with a high hemoglobin level in the third trimester, but hemoglobin levels in early or mid-pregnancy had no association to birth weight. Smoking mothers also had a significantly greater fall in hemoglobin concentration from first to second and third trimester as compared to non-smokers although ferritin levels were similar in smokers and non-smokers, implying similar iron stores. The ratio of placental weight to the weight of the newborn was significantly higher in smokers, but no association was found to different hemoglobin levels. CONCLUSIONS: Fetal growth impairment associated with maternal smoking is even more pronounced in smoking mothers with high hemoglobin levels in late pregnancy. Smoking mothers were also found to have disproportional fetal/placental growth with relatively high placental weights. In non-smoking mothers hemoglobin levels had no relation to birthweight.     

The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors

BACKGROUND: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors. METHODS: We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data. RESULTS: In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. CONCLUSIONS: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.     

Indirect maternal effects of oxacillin administered to pregnant mice on the postnatal immune response of the offspring

Effects of oxacillin administered to pregnant or nursing randombred NMRI mice on the humoral immune response of their offspring were studied. The primary humoral response of male offspring to immunization by sheep red blood cells (SRBC) on the 24th postnatal day was assayed. Spectrophotometric determination of SRBC lysis by anti-SRBC IgM antibodies produced by spleen cells was used. Treatment of pregnant mice with oxacillin (70 mg/kg body weight) from the 12th to 16th day of pregnancy resulted in an enhancement of the spleen IgM antibody response in their offspring. The same treatment of nursing mothers, either on postnatal days 1-4 or 13-16, depressed the humoral response of the offspring. When the litters of control mothers and mothers treated with oxacillin from the 11th to 15th day of pregnancy were cross-fostered at birth, the offspring born of saline-treated mothers and nursed by oxacillin-treated mothers as well as the offspring born to oxacillin-treated mothers and nursed by control mothers produced significantly higher amounts of spleen anti-SRBC IgM than the control offspring. The results suggest that the alteration of the immune response in offspring of mice treated by oxacillin during pregnancy was induced not only in the prenatal period, but also postnatally by factors originating from effects of oxacillin on the maternal organism.     

Caffeine intake and low birth weight: a population-based case-control study

The authors conducted a matched case-control study to investigate the effects of caffeine intake during pregnancy on birth weight. From January to November 1992, in the first 24 hours after delivery, 1,205 mothers (401 cases and 804 controls) were interviewed and their newborns were examined to assess birth weight and gestational age by means of the method of Capurro et al. (J Pediatr 1978;93:120-2). The cases were children with birth weight < 2,500 g and gestational age > or = 28 weeks. Cases and controls were matched for time of birth and hospital of delivery and were recruited from the four maternity hospitals in Pelotas, southern Brazil. Daily maternal caffeine intake during pregnancy for each trimester was estimated. To assess caffeine intake, 10% of the mothers were reinterviewed at their households and samples of reported information on drip coffee and maté (a caffeine-containing drink widely used in South America) were collected and sent to the laboratory for caffeine determination through liquid chromatography. When instant coffee was reported, the weight of powder was measured using a portable scale, and caffeine intake was estimated from a reference table. Caffeine intake from tea, chocolate, soft drinks, and medicines was estimated from a reference table. Analyses were performed by conditional logistic regression. Crude analyses showed no effect of caffeine on low birth weight, preterm births or intrauterine growth retardation. The results did not change after allowing for confounders.     

Functional and morphometric evaluation of offspring kidney after intrauterine undernutrition

Pregnant rats were subjected to 50% food restriction during the first or the second half of pregnancy, or throughout pregnancy. The effects of intrauterine food restriction, on kidney function and morphometry were studied in newborn and adult (3 months) offspring. No differences in glomerular diameter were observed in newborn restricted rats compared with controls. The number of glomeruli was significantly lower both in newborn and 3-month-old restricted rats. However, glomerular diameter was increased in 3-month-old rats, which suggests that hypertrophic stimuli were present. The medulla/cortex ratio increased in adult rats submitted to food restriction during pregnancy, a finding that agrees with the preserved sodium and acid excretion, and the normal osmolar and free water clearance observed in these groups. These results show that the reduction in glomerular number is still present 3 months after birth in the progeny of mothers submitted to severe food restriction during pregnancy, suggesting impairment of glomerulogenesis even after birth. Intra utero undernutrition can be regarded as an experimental model of glomerular hypertrophy.     

Effects of transforming growth factor-beta1 and basic fibroblast growth factor on proliferation of cell cultures derived from human vestibular nerve schwannoma

Stress during pregnancy, or prenatal stress, is known to alter offspring behavior, morphology and physiology. We found that a heat, light and restraint stressor applied during the third trimester of pregnancy: 1) decreased the weight gain of adult female rats during pregnancy; 2) reduced the weight of pups, as well as the anogenital distance of male offspring, at birth; and 3) increased the number of ultrasonic vocalizations emitted by pups during isolation in a novel environment on Postnatal Day 14. These results closely approximate those we previously observed after peripheral administration of corticotropin-releasing factor to pregnant females during the third trimester. Together, the studies strongly suggest a role for corticotropin-releasing factor and/or other hormones of the hypothalamic-pituitary-adrenal system in mediating some of the effects of gestational stress.     

Becoming a sibling: "With a little help from my friends."

The qualities of children's friendships that may promote the development of positive sibling relationships were examined. 30 3- to 5-yr-old 1st-born children whose families were expecting a 2nd child participated in longitudinal assessments of parent–child, sibling, and best-friend peer relationships. Families were studied from the last trimester of pregnancy to 14 mo following the new child's birth. Peer relationship variables, particularly, the overall quality of peer play, engagement in fantasy play, and conflict management were found to be significant predictors of the quality of children's interactions with their 6- and 14-mo-old siblings. Results are discussed in terms of the functions friendships may hold for helping children make the transition to the sibling role. (PsycINFO Database Record (c) 2010 APA, all rights reserved)