Maternal morbidity and mortality associated with mode of delivery in sickle cell disease.

This retrospective observational study compared pregnancy outcomes based on mode of delivery in women with homozygous sickle cell disease (HbSS) to women without (HbAA) using delivery records of 48,600 parturients between January 1992 and January 2020. Fisher's exact tests and Mann-Whitney's test were used to analyse variables based on sickle cell status. Vaginal delivery and HbSS were more associated with labour induction/augmentation (AOR = 2.4, (0.7-7.8)), intrapartum complications (AOR = 2.6, (0.5-14)), postpartum haemorrhage (AOR = 2.8 (0.5-15.2)) and postpartum infections (AOR = 9.6 (1.7-54.4)). Caesarean delivery resulted in more postpartum infections in the HbSS group (AOR = 23.6 (0.9-638.4)). Vaginal delivery in HbSS resulted in more intrapartum complications and postpartum haemorrhage but caesarean delivery greatly increased the risk of postpartum infections and hypertensive disorders. Sickle cell disease (SCD) did not confer increased risk of adverse perinatal outcomes regardless of mode of delivery.Impact StatementWhat is already known on this subject? Women with homozygous sickle cell disease (SCD) are at an increased risk of postpartum infections, undergoing caesarean delivery, admission to the neonatal intensive care unit and overall perinatal mortality when compared to women with normal haemoglobin genotype. Comparisons have been made between homozygous SS disease and haemoglobin SC disease revealing higher rates of maternal and foetal morbidity in both groups.What do the results of this study add? Studies comparing maternal and foetal morbidity based on mode of delivery are lacking. To our knowledge, this study is the first examine maternal and perinatal outcomes in women with SCD undergoing vaginal and abdominal delivery compared to women with normal haemoglobin. We found that vaginal delivery in SCD is associated with more postpartum haemorrhage and caesarean delivery was linked to more hypertensive disorders and postpartum infections then compared to women with normal haemoglobin. Converse to other reports, there was no difference in perinatal outcomes based on mode of delivery.What are the implications of these findings for clinical practice and/or further research? Caesarean delivery and SCD greatly increased the risk of postpartum infections and hypertensive disorders but did not confer a higher risk of postpartum haemorrhage. There were more maternal deaths in SCD women who underwent caesarean vs. vaginal delivery and this requires further study to determine the pregestational predictors of adverse outcomes. Women with SCD who achieve a successful primary vaginal delivery may have reduced risk of complications in subsequent pregnancies, possibly comparable to women without the disease.

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.

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.

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.

Fetal growth and birth size is associated with maternal anthropometry and body composition.

The objective was to investigate the association of maternal weight, height and body composition with fetal growth. We recruited 425 women at the University Hospital of the West Indies, Jamaica, who had singleton pregnancies, were less than 15 weeks gestation and had no systemic illness. Maternal weight, height and skinfold thicknesses were measured at the first antenatal visit and lean mass was calculated. Sonographic measurements of the fetus were made at 15, 25 and 35 weeks gestation. Weight, crown-heel length and head circumference were measured at birth. Analyses were confined to 360 (85%) women; 65 women did not complete the study. Maternal height was positively associated with femoral length at 25 and 35 weeks gestation and with head circumference at 35 weeks (all P < 0.02). Maternal weight was positively associated with abdominal circumference and femoral length at 25 weeks, and with larger head and abdominal circumference and longer femur at 35 weeks (all P < 0.02). Maternal lean mass had similar associations to maternal weight and they were both positively associated with estimated fetal weight (all P < 0.02). All three maternal measurements were positively associated with birthweight, length and head circumference. Maternal size was associated with fetal size as early as 25 weeks gestation, with height strongly associated with femoral length, and with weight and lean mass strongly associated with abdominal circumference.

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.

Developing a partnership to improve health care delivery to children <18 years with cancer and blood disorders in the English-speaking Caribbean: lessons from the SickKids-Caribbean Initiative (SCI).

In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (<18 years) with cancer and blood disorders in the partner countries. Core activities included filling a human resource gap by training paediatric haematologists/oncologists and specialised registered nurses; improving capacity to diagnose and treat diverse haematology/oncology cases; developing and maintaining paediatric oncology databases; creating ongoing advocacy activities with international agencies, decision makers, and civil society; and establishing an integrated administration, management, and funding structure. We describe core program components, successes, and challenges to inform others seeking to improve health service delivery in a multidisciplinary and complex partnership.

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 in vivo glycine fluxes of adolescent girls and adult women during early and late pregnancy.

During pregnancy, growth of the foetus depends on an adequate glycine supply because it is needed for synthesis of fetal DNA, collagen and serine. Since pregnant adolescent girls give birth to lower birth weight babies, it is possible that they do not produce sufficient glycine to meet overall demands as their adult counterparts, especially after an overnight fast. The objective of the study was to measure and compare the flux of glycine among adolescents and adult women in the first and third trimesters of pregnancy. Glycine flux was measured by continuous intravenous infusion of (2)H(2)-glycine in eight overnight fasted adolescents and in eight adult women in the first and third trimesters of pregnancy. There was a significant interaction between subject's age and time of pregnancy (P = 0.02), as weight-specific glycine flux decreased by 39 % from trimesters 1 to 3 in the adolescents but increased by approximately 5 % in the adults. Whole body glycine flux also decreased significantly in the adolescent group (P < 0.05) from trimesters 1 to 3, and this was associated with a significant reduction in plasma glycine concentration. In trimester 3, there was a positive correlation between glycine flux and the subject's age indicating that younger subjects had slower fluxes. These findings suggest that after a brief period of food deprivation, the pregnant adolescent cannot maintain glycine production as her adult counterpart in late pregnancy. It is possible that this inability to maintain endogenous glycine production makes her foetus more vulnerable to impaired growth if food deprivation becomes more frequent or is prolonged.

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.

Retained placenta in homozygous sickle cell disease.

OBJECTIVE: To document an increased prevalence of retained placenta in mothers with homozygous sickle cell disease. METHODS: A retrospective review (January 1, 1992, to December 31, 2005) at the University Hospital of the West Indies revealed 174 singleton deliveries in women with sickle cell disease who were matched by delivery date and age 1:1 with 174 mothers with normal hemoglobin phenotype. Cesarean delivery in 62 mothers (36%) with sickle cell and in 41 women with normal hemoglobin (24%) left 112 sickle cell and 133 normal hemoglobin pregnancies with spontaneous deliveries. Retained placenta was defined by an interval of at least 30 minutes. Duration and details of the third stage of delivery were obtained by review of records. Duration of delivery stages was assessed by Kaplan-Meier survival charts and tested using the log rank test. Known risk factors were sought by logistic regression or exact logistic regression when the number of outcomes was small. RESULTS: First-stage duration was similar in maternal genotypes (sickle cell 470 minutes [median] compared with normal hemoglobin 335 minutes [median]), but in sickle cell disease, the second stage was slightly delayed (sickle cell 16 minutes compared with normal hemoglobin 15 minutes) and the third stage (sickle cell 7 minutes compared with normal hemoglobin 6 minutes). Retained placenta occurred in 20 mothers (17.9%) with sickle cell (interval 30-340 minutes) compared with four among the women in the control group (3.0%, 30-107 minutes). Apart from a weak association with combined oxytocin and misoprostol, there were no significant associations with known risk factors or with hematologic indices within sickle cell disease. CONCLUSION: Retained placenta is common among mothers with sickle cell disease, and the lack of association with known risk factors suggests that maternal sickle cell disease may be a risk factor. LEVEL OF EVIDENCE: II.

Morbidity, mortality and antimicrobial resistance of pneumococcal infections in the Jamaican paediatric and adult populations.

BACKGROUND: Pneumococcal infections are a leading global cause of morbidity and mortality, complicated by the increasing antimicrobial resistance of pneumococcal isolates. OBJECTIVE: To evaluate morbidity and mortality associated with both invasive pneumococcal disease (IPD) and non-IPD in Jamaica in both the paediatric and adult population. Pneumococcal isolates (n= 94) were collected over a 2-year period (2008-2009). METHODS: Risk factors for poor clinical outcomes: death, complicated disease and length of hospitalization (LOH) were evaluated and antimicrobial resistance patterns were determined by Kirby-Bauer disc diffusion. RESULTS: The case fatality rate was 6.8%. Independent mortality risk factors included complicated disease [OR 30.9 (3.4-276.6)] and diabetes mellitus [OR 8.3 (1.4-48.8)]. Independent risk factors for the development of complicated disease included sickle cell disease [OR 36.5 (4.2-320.3)] and sepsis [OR 3.5 (1.2-10.4)]. The LOH was increased most in patients with invasive disease (4.6-fold) and resistance to ceftriaxone (4.3-fold). Penicillin (16.0%) and erythromycin (14.9%) resistance was most prevalent, while ceftriaxone (4.3%) resistance was least prevalent. CONCLUSIONS: The high burden of IPD in at-risk groups in our population and the associated increase in morbidity and mortality underlie the need for improved preventive and therapeutic management strategies in these patients.

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.

Factors Affecting the Choice and Desire to Exclusively Breastfeed in Jamaica: A Cross-Sectional Study at 6 Weeks Postpartum.

BACKGROUND: Exclusive breastfeeding rates (EBRs) may be influenced by sociodemographic and sociocultural factors, including maternal age, socioeconomic status, education, and breastfeeding knowledge. The EBR in Jamaica has been low and declining, leaving a need for better determination of the specific local contributory factors. OBJECTIVES: This study aimed to better elucidate the factors that influence mothers exclusively breastfeeding, including antenatal intentions to breastfeed, mothers' knowledge of the benefits of breastfeeding, and mothers' infant feeding practices in general, inclusive of breastfeeding, formula feeding, and complementary feeding. METHODS: A cross-sectional survey was conducted using a 52-item interviewer-administered questionnaire with mothers attending their 6-week postnatal clinic visit. Sociodemographic data were collected on all participants as well as data regarding participants' breastfeeding knowledge, attitudes, and practices. Statistical analyses were done using χ(2) tests, t tests, and risk analyses. RESULTS: Two hundred participants were interviewed; the mean ± SD age of participants was 26.2 ± 6.46 years (range, 15-46 years). The EBR in this study sample was 32%. Sociodemographic factors, including maternal age and socioeconomic status, as well as antenatal and postnatal breastfeeding sessions, did not significantly affect the likelihood of exclusively breastfeeding at 6 weeks postpartum. The only factor significantly associated with the EBR was mothers' belief that exclusively breastfeeding was able to ensure infant satiety. CONCLUSION: Antenatal and postnatal breastfeeding sessions should place more emphasis on dispelling maternal myths and misperceptions regarding signs of satiety and hunger in infants and reinforcing the knowledge that breast milk alone is sufficient for the first 6 months of life.

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.

Bridging the Distance in the Caribbean: Telemedicine as a means to build capacity for care in paediatric cancer and blood disorders.

Over the past 50 years, survival for children in high-income countries has increased from 30% to over 80%, compared to 10-30% in low and middle income countries (LMIC). Given this gap in survival, established paediatric cancer treatment centres, such as The Hospital for Sick Children (SickKids) are well positioned to share clinical expertise. Through the SickKids Centre for Global Child Health, the SickKids-Caribbean Initiative (SCI) was launched in March 2013 to improve the outcomes and quality of life for children with cancer and blood disorders in the Caribbean. The six participating Caribbean countries are among those defined by the United Nations as Small Island Developing States, due to their small size, remote location and limited accessibility. Telemedicine presents an opportunity to increase their accessibility to health care services and has been used by SCI to facilitate two series of interprofessional rounds. Case Consultation Review Rounds are a forum for learning about diagnostic work-up, management challenges and treatment recommendations for these diseases. To date, 54 cases have been reviewed by SickKids staff, of which 35 have been presented in monthly rounds. Patient Care Education Rounds provide nurses and other staff with the knowledge base needed to safely care for children and adolescents receiving treatment. Five of these rounds have taken place to date, with over 200 attendees. Utilized by SCI for both clinical and non-clinical meetings, telemedicine has enhanced opportunities for collaboration within the Caribbean region. By building capacity and nurturing expert knowledge through education, SCI hopes to contribute to closing the gap in childhood survival between high and low-resource settings.

The relationship among circulating insulin-like growth factor (IGF)-I, IGF-binding proteins-1 and -2, and birth anthropometry: a prospective study.

Fetal IGF-I is a determinant of birth weight, but whether maternal IGF-I plays a significant role is controversial. We sought to examine the relationships among maternal IGF-I, IGF-binding protein (IGFBP)-1, and IGFBP-2, with maternal and newborn anthropometry, in a cohort of 325 nondiabetic pregnant women of African origin. Blood was collected for IGF-I, IGFBP-1, and IGFBP-2 at 9, 25, and 35 wk gestation and in cord blood at delivery. In the second and third trimesters, maternal IGF-I was significantly correlated (P < 0.005) with maternal body mass index and triceps skinfold thickness. Maternal IGFBP-1 and -2 had an inverse correlation (P < 0.0001), with maternal anthropometry. Maternal IGF-I at 35 wk, and fetal IGF-I by cord blood were significantly correlated with birth weight (P = 0.001 and 0.048, respectively). IGFBP-1 in the third trimester and cord blood were negatively correlated with birth weight (P = 0.012 and 0.002). In multiple regression analyses, maternal IGF-I at 35 wk, fetal IGF-I, maternal weight at the first antenatal visit, gender, and gestational age were significant independent factors in the determination of birth weight. In conclusion, maternal IGF-I levels, especially during late pregnancy, positively influence birth weight.

Outcome of pregnancy in homozygous sickle cell disease.

OBJECTIVE: Previous reports on pregnancy in homozygous sickle cell (SS) disease are biased by hospital-based, more severely affected subjects and may have underestimated recurrent early pregnancy losses. We report pregnancy outcome in a representative sample of SS subjects subsequently referred to as "subjects" or "sickle cell subjects," and matched normal controls followed from birth. METHODS: The outcomes of 94 pregnancies in 52 subjects and 157 pregnancies in 68 controls followed in a cohort study from birth are presented. Outcome measures included the age at menarche, interval to first pregnancy, outcome of pregnancy, and maternal complications. Possible predictors of low birth weight are assessed. Outcomes were compared by the Kaplan-Meier analysis for interval to first pregnancy and by Student t test, chi(2) test, or Fisher exact test, as appropriate. Correction was made for multiple testing, and multiple linear regression was used for analysis of birth weight. RESULTS: Compared with controls, SS subjects had later menarche (median age 15.4 versus 13.0 years) and first pregnancy (median age 23.7 versus 20.1 years), and more spontaneous abortions (36% versus 10%). Babies of SS subjects had a lower gestational age (P <.001) and lower birth weight (P <.001), the latter being significantly affected by sickle-related events in pregnancy. There was no difference in pregnancy-induced hypertension, preeclampsia, or antepartum or postpartum hemorrhage, but a retained placenta was marginally more common in SS subjects (Fisher exact test, P =.007 after adjustment for multiple testing). Two SS subjects died, a mortality rate of 2.1%. CONCLUSION: The increased fetal loss and maternal morbidity in mothers with homozygous sickle cell disease is confirmed. LEVEL OF EVIDENCE: II-2

The effect of earlier puberty on cardiometabolic risk factors in Afro-Caribbean children.

An earlier onset of puberty is associated with increased cardiometabolic risk. We investigated whether this relation was independent of faster childhood growth or current size in an Afro-Caribbean birth cohort (n=259). Anthropometry was measured at birth and then 6-monthly. Tanner staging started at age 8 years. Cardiometabolic risk factors were measured at mean age 11.5 years. In boys, pubarchal stage and testicular size were associated with lower high-density lipoprotein cholesterol, higher systolic blood pressure, and higher homeostasis model assessment of insulin resistance score, but not after adjusting for current body mass index (BMI) or rate of growth (up to age 8 years). In girls, earlier menarche and greater breast development were associated with higher fasting glucose even after adjusting for current BMI or prior growth. Pubarchal stage was associated with systolic blood pressure, even after adjusting for current BMI and prior growth. We concluded that earlier puberty is independently associated with cardiometabolic risk in girls but not in boys.

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.