Pregnancy in sickle cell-haemoglobin C (SC) disease. A retrospective study of birth size and maternal weight gain.

OBJECTIVE: To assess pregnancy and fetal outcomes in Jamaican subjects with sickle cell-haemoglobin C (SC) disease. STUDY DESIGN: A retrospective chart review over 21 years (1992-2012) of all pregnancies in SC disease and a comparison group matched by gender and date of delivery in mothers with a normal haemoglobin (AA) phenotype at the University Hospital of the West Indies, Jamaica. There were 118 pregnancies in 81 patients with SC disease and 110 pregnancies in 110 in the normal comparison group. Corrections were made for repeat pregnancies from the same mother. Outcome measures included maternal weight at 20, 25, 30, 35 and 38 weeks gestation, maternal pregnancy complications, birth weight, head circumference and crown heel length and were used to analyse possible predictors of birth weight. RESULTS: First antenatal visits occurred later in women with SC disease, who also had lower haemoglobin level and lower systolic blood pressure. The prevalence of pregnancy-induced hypertension, pre-eclampsia, ante-partum or postpartum haemorrhage did not differ between genotypes. Maternal weight gain was significantly lower in SC disease and there was a significantly lower birth weight, head circumference, and gestational age. CONCLUSIONS: Pregnancy in SC disease is generally benign but mothers had lower weight gain and lower birth weight babies, the difference persisting after correction for gestational age.

Unlike pregnant adult women, pregnant adolescent girls cannot maintain glycine flux during late pregnancy because of decreased synthesis from serine.

During pregnancy, glycine and serine become more important because they are the primary suppliers of methyl groups for the synthesis of fetal DNA, and more glycine is required for fetal collagen synthesis as pregnancy progresses. In an earlier study, we reported that glycine flux decreased by 39% from the first to the third trimester in pregnant adolescent girls. As serine is a primary precursor for glycine synthesis, the objective of this study was to measure and compare glycine and serine fluxes and inter-conversions in pregnant adolescent girls and adult women in the first and third trimesters. Measurements were made after an overnight fast by continuous intravenous infusions of 2H2-glycine and 15N-serine in eleven adolescent girls (17·4 (se 0·1) years of age) and in ten adult women (25·8 (se 0·5) years of age) for 4 h. Adolescent girls had significantly slower glycine flux and they made less glycine from serine in the third (P<0·05) than in the first trimester. Baby birth length was significantly shorter of adolescent girls (P=0·04) and was significantly associated with third trimester glycine flux. These findings suggest that the pregnant adolescent cannot maintain glycine flux in late pregnancy compared with early pregnancy because of decreased synthesis from serine. It is possible that the inability to maintain glycine synthesis makes her fetus vulnerable to impaired cartilage synthesis, and thus linear growth.

Indian women of childbearing age do not metabolically conserve arginine as do American and Jamaican women.

BACKGROUND: In a previous study in pregnant American women, we reported that arginine flux and nitric oxide synthesis increased in trimester 2. More recently, we reported that Indian women do not increase arginine flux during pregnancy as their American or Jamaican counterparts do. OBJECTIVE: The purpose of this study was to determine whether Indian women of childbearing age are producing less arginine and/or catabolizing more arginine and therefore have less available for anabolic pathways than do Jamaican and American women. METHODS: Thirty healthy women aged 28.3 ± 0.8 y from the United States, India, and Jamaica (n = 10/group) were given 6 h primed, constant intravenous infusions of guanidino-¹5N2-arginine, 5,5-²H2-citrulline, ¹5N2-ornithine, and ring-²H5-phenylalanine, in addition to primed, oral doses of U-¹³C6-arginine in both the fasting and postprandial states. An oral dose of deuterium oxide was also given to determine fat-free mass (FFM). RESULTS: Compared with American women, Indian and Jamaican women had greater ornithine fluxes (µmol · kg fat FFM⁻¹ · h⁻¹) in the fasting and postprandial states (27.3 ± 2.5 vs. 39.6 ± 3.7 and 37.2 ± 2.0, respectively, P = 0.01), indicating greater arginine catabolism. However, Jamaican women had a higher endogenous arginine flux than did Indian and American women in the fasting (66.1 ± 3.1 vs. 54.2 ± 3.1 and 56.1 ± 2.1, respectively, P = 0.01) and postprandial (53.8 ± 2.2 vs. 43.7 ± 4.9 and 42.8 ± 3.1, respectively, P = 0.06) states. As a consequence, Indian women had lower arginine bioavailability (µmol · kg FFM⁻¹ · h⁻¹) in the fasting state (42.0 ± 2.6) than did American (49.9 ± 1.3, P = 0.045) and Jamaican (55.5 ± 3.5, P = 0.004) women, as well as in the postprandial state (40.7 ± 3.5 vs. 51.8 ± 1.2 and 57.5 ± 3.2, respectively, P = 0.001). CONCLUSION: Compared with American and Jamaican women, Indian women of childbearing age have a decreased arginine supply because of increased arginine catabolism without an increase in arginine flux.

The Microbiome, Intestinal Function, and Arginine Metabolism of Healthy Indian Women Are Different from Those of American and Jamaican Women.

BACKGROUND: Indian women have slower arginine flux during pregnancy compared with American and Jamaican women. Arginine is a semi-essential amino acid that becomes essential during periods of rapid lean tissue deposition. It is synthesized only from citrulline, a nondietary amino acid produced mainly in the gut. The gut is therefore a key site of arginine and citrulline metabolism, and gut microbiota may affect their metabolism. OBJECTIVE: The objective of this study was to identify differences in the gut microbiota of nonpregnant American, Indian, and Jamaican women and characterize the relations between the gut microbiota, gut function, and citrulline and arginine metabolism. METHODS: Thirty healthy American, Indian, and Jamaican women (n = 10/group), aged 28.3 ± 0.8 y, were infused intravenously with [guanidino-15N2]arginine, [5,5-2H2]citrulline, and [15N2]ornithine and given oral [U-13C6]arginine in the fasting and postprandial states. Fecal bacterial communities were characterized by 16S rRNA gene sequencing. RESULTS: In the fasting state, Indian women had lower citrulline flux than did American and Jamaican women [7.0 ± 0.4 compared with 9.1 ± 0.4 and 8.9 ± 0.2 µmol ⋅ kg fat-free mass (FFM)-1 ⋅ h-1, P = 0.01] and greater enteral arginine conversion to ornithine than did American women (1.4 ± 0.11 compared with 1.0 ± 0.08 µmol ⋅ kg FFM-1 ⋅ h-1, P = 0.04). They also had lower mannitol excretion than American and Jamaican women (154 ± 37.1 compared with 372 ± 51.8 and 410 ± 39.6 mg/6 h, P < 0.01). Three dominant stool community types characterized by increased abundances of the genera Prevotella, Bacteroides, and Bacteroides with Clostridium were identified. Indian women had increased mean relative abundances of Prevotella (42%) compared to American and Jamaican women (7% and < 1%, P = 0.03) which were associated with diet, impaired intestinal absorptive capacity, and arginine flux. CONCLUSIONS: These findings suggest that dysregulated intestinal function and a unique gut microbiome may contribute to altered arginine metabolism in Indian women.

Adaptation of in vivo amino acid kinetics facilitates increased amino acid availability for fetal growth in adolescent and adult pregnancies alike.

During pregnancy, adult women with a normal BMI synthesise extra amino acids after an overnight fast by increasing body protein breakdown and decreasing amino acid oxidation. It is not known whether adolescent girls can make these adaptations during pregnancy. The present study aimed to measure and compare the protein, glutamine and alanine kinetics of adult women and adolescent girls at early-, mid- and late-pregnancy. Kinetics were measured in the overnight fasted state using intravenous infusions of 13C-leucine, 15N-glutamine and 15N-alanine in ten adults and twenty adolescents aged 14-17 years in the first and second trimesters (phase 1 study) and infusions of 13C-leucine and 15N2-urea in ten adults and eleven adolescents aged 16-17 years in the first and third trimesters (phase 2 study). In phase 1 study, there were no significant differences between the groups with regard to any of the kinetic parameters measured. In both groups, leucine flux increased (P< 0.05), the percentage of leucine flux oxidised decreased (P< 0.05) and non-oxidative leucine disposal to protein synthesis increased (P< 0.05) from the first to the second trimester. In phase2 study, leucine flux was significantly slower (P< 0.05) in the adult group than in the adolescent group during both trimesters, and whole-body leucine flux and non-oxidative leucine disposal increased significantly in the adolescent group (P< 0.05, respectively) and were higher in the adult group from the first to the third trimester. These results suggest that similar to their adult counterparts after an overnight fast, adolescent girls with a normal BMI provide extra amino acids required for net protein deposition during pregnancy by increasing protein breakdown and decreasing amino acid oxidation.

Fetal growth in women with homozygous sickle cell disease: an observational study.

OBJECTIVES: To assess fetal growth and whether lower birthweight to mothers with homozygous sickle cell (SS) disease is related to maternal body composition or to clinical events in pregnancy. STUDY DESIGN: A prospective study of 41 pregnant women with SS disease and 41 women with a normal (AA) phenotype attending the antenatal clinic, University Hospital of the West Indies, Kingston, Jamaica. Maternal anthropometry, body composition and fetal sonographic measurements were assessed at 15, 25, and 35 weeks' gestation from December 2005 to April 2008. Birth measurements were performed within 24h of delivery. Differences between maternal genotypes and between their offspring were assessed using 2-sample t-tests. Multiple linear regression was used to control for baby's gender and gestational age at delivery. Fetal growth was compared in SS mothers with and without admission for sickle-related complications including bone pain crisis, acute chest syndrome, pregnancy-induced hypertension and urinary tract infection. RESULTS: Mothers with SS disease had lower weight, body fat, fat mass and lean body mass throughout pregnancy but correlation with birth size did not reach statistical significance. Sonographically, babies of SS mothers had smaller abdominal circumference, femoral length and a lower estimated fetal weight at 35 weeks. Birth measurements confirm lower birthweight, crown-heel length and head circumference but the differences were no longer significant after adjustment for baby gender and gestational age at delivery. Bone pain crisis in pregnancy was associated with a significantly reduced crown-heel length at birth. CONCLUSION: Lower birthweight in babies of mothers with SS disease is largely the result of the lower gestational age. Fetal sonography showed no growth differences by maternal genotype until 35 weeks' gestation and a reduced crown-heel length in offspring of SS mothers was associated with bone pain crises in pregnancy.

Arginine flux, but not nitric oxide synthesis, decreases in adolescent girls compared with adult women during pregnancy.

NO has been proposed as a mediator of vascular expansion during pregnancy. Inability to increase NO synthesis and/or production of its precursor, arginine, may contribute to pregnancy-induced hypertension. Adolescents have a higher incidence of gestational hypertension. It is not known whether pregnant adolescents can produce sufficient arginine to meet overall demands. Our objective was to measure and compare the arginine flux and NO synthesis rates of pregnant adolescents and adult women. Arginine, citrulline, and NO kinetics were measured by i.v. infusions of (15)N(2)-argininine and (2)H(2)-citrulline in 8 adolescents and 8 adult women in the fasted state at the end of the first and the beginning of the 3rd trimesters of pregnancy. Arginine flux decreased (P < 0.05) from trimester 1 to 3 in the adolescents but not in the adult women. NO synthesis rate did not change significantly in either group from trimester 1 to 3. In trimester 3, there was a positive association (r = 0.55; P = 0.02) between arginine flux and participants' age, indicating that flux was slower in the younger participants. These findings suggest that after a brief period of food deprivation, the pregnant adolescent cannot maintain arginine production like her adult counterpart in late pregnancy. This inability to maintain arginine production seems to be related to her younger age. It does not, however, affect her ability to synthesize NO in late pregnancy.

Comparing the glucose kinetics of adolescent girls and adult women during pregnancy.

BACKGROUND: Fetal energy demands are met mostly from oxidation of maternally supplied glucose. In pregnant adults this increased glucose requirement is met by an increase in gluconeogenesis. It is not known, however, whether, like their adult counterparts, pregnant adolescent girls can increase gluconeogenesis-hence, glucose production. OBJECTIVE: Our objective was to measure glucose kinetics in 8 pregnant adolescents and 8 adult women. DESIGN: We measured glucose kinetics after an overnight fast by using a primed-constant 6-h U-(13)C-glucose infusion at the end of trimester 1 and early trimester 3. RESULTS: From trimester 1 to trimester 3, whole-body glucose production increased significantly in both groups (P < 0.01). However, whereas the weight-specific rate in adults increased by 18.2%, it increased by only 14.3% in adolescents. In adults, the increase in whole-body glucose production was largely due to a significant increase (P < 0.01) in the rate of gluconeogenesis, but in adolescents there was no change in whole-body gluconeogenesis, and weight-specific gluconeogenesis actually decreased by 11.7%. In both groups, the rate of whole-body glycogenolysis increased significantly (P < 0.05) in trimester 3, and in adolescents, it increased by 95%. CONCLUSIONS: These findings suggest that, in the fasted state in late pregnancy, pregnant adolescents cannot increase weight-specific glucose production by the same magnitude as their adult counterparts. Furthermore, whereas adult women increase glucose production primarily through gluconeogenesis, adolescents do so through glycogenolysis.

Weight retention within the puerperium in adolescents: a risk factor for obesity?

OBJECTIVE: The present study aimed to investigate weight retention and body composition in the postpartum period between adolescent girls and older women. DESIGN: A prospective cohort study. Anthropometry and skinfold thickness measurements were performed at the first antenatal visit and at 6 weeks postpartum. An FFQ was administered at 6 weeks postpartum to explore the relationship between diet and postpartum weight retention. SETTING: Clinics at the University of the West Indies, Kingston, Jamaica. SUBJECTS: Recruitment included women aged 19 years and younger (adolescent girls) and 20 years and older (older women). RESULTS: Three hundred and forty women were studied. Adolescent girls had significantly lower measurements compared with the older women at the first antenatal visit and at 6 weeks postpartum. Dietary intakes of energy and macronutrients were similar in both groups. Postnatal assessments showed that adolescent girls retained more weight (P = 0.003) and a greater percentage of body fat (P < 0.002) than older women. In multiple regression analyses, 0.982 kg more fat mass was retained postpartum in the adolescent group compared with the older women, while there was no significant difference in lean body mass retained between the two groups. CONCLUSIONS: Adolescent girls retained more weight postpartum and this was predominantly fat mass as opposed to lean body mass.

Association of growth in utero with cognitive function at age 6-8 years.

BACKGROUND: Size at birth is associated with later cognitive development. The timing of growth faltering in utero may affect developmental consequences. AIM: To determine whether growth in utero is related to cognitive outcomes in childhood. A secondary aim was to determine any associations between maternal nutritional status and cognition. STUDY DESIGN AND SUBJECTS: Subjects were participants in a prospective cohort study of developmental origins of adult disease. Eligible subjects were aged 6-8 years at their next scheduled visit to the study clinic and their mothers had abdominal ultrasound measurements at 14, 25 and 35 weeks gestation. 186 of 264 eligible children attended the clinic and were tested. OUTCOME MEASURES: Raven's Progressive Matrices (reasoning ability), Peabody Picture Vocabulary Test (receptive vocabulary) and Digit Span Forwards (auditory working memory). RESULTS: In multiple regression analyses controlling for children's age and socioeconomic status, head circumference at 14 weeks gestation was significantly associated with reasoning ability. The difference between the lowest and highest quartiles was equivalent to 0.4 S.D. No other significant associations with fetal growth were found. Maternal weight gain was not associated with cognitive scores; however, change in triceps skinfold between 25 and 35 weeks gestation was positively associated with reasoning ability and remained a significant predictor when included in the regression model. CONCLUSIONS: There were few associations between growth in utero and cognition. Growth in head circumference in early gestation and maternal nutrition in late gestation may affect later cognitive ability. Further research in this area is needed to confirm these results.

The Human Ruminant

A five-month-old female infant was admitted to the Tropical Metabolism Research Unit with a weight for age of 49 percent and no evidence of oedema giving rise to a diagnosis of marasmus (Wellcome Classification). The underlying reason for her malnutrition was the Infant Rumination syndrome. This is an uncommon disorder which is thought to have a psychological component. A lack of awareness of the syndrome often leads to delay in diagnosis.