Birthweight in Offspring of Mothers with High Prevalence of Helminth and Malaria Infection in Coastal Kenya

Results of studies on the associations of maternal helminth infection and malaria-helminth co-infection on birth outcomes have been mixed. A group of 696 pregnant women from the Kwale district in Kenya were recruited and tested for malaria and helminth infection at delivery. Birthweight was documented for 664 infants. A total of 42.7% of the mothers were infected with Plasmodium falciparum, 30.6% with Schistosoma haematobium, 36.2% with filariasis, 31.5% with hookworm, and 5.9% with Trichuris trichiura; co-infection was present in 46.7%. Low birthweight (LBW) (weight < 2,500 grams) was present in 15.4% of the offspring, and 8.3% had a weight z-score ≤ 2 SD below the World Health Organization mean. Only gravida, age, and locale had a significant association with LBW. The high prevalence of maternal infection coupled with a higher than expected percentage of LBW highlight a need for further investigation of the association of maternal co-infection with LBW.     

Low birth weight infants born to HIV-seropositive mothers and HIV-seronegative mothers in Chiang Rai, Thailand

The low birth weight (LBW) infant has a much higher risk of mortality and morbidity in infancy and early childhood. This study examined the effects of maternal HIV infection and other risk factors for LBW (< 2,500 g). A retrospective study of mothers who delivered at Mae Chan Hospital from 1997 to 2002 was conducted. Logistic regression was used to adjust for confounding factors. There were 266 infants born to HIV-seropositive mothers and 5,872 infants born to HIV-negative mothers. Low birth weight was significantly associated with maternal HIV status, gestational age, antenatal care, maternal age less than 20 years, and > 35 years. Maternal HIV positive status, young maternal age and gestational age were significant factors after adjusting for potential confounders. No significant effect of hilltribe on LBW was found. The results underline the need for nutritional surveillance and dietary counseling. HIV-seropositive women must receive early and continuing antenatal care for good pregnancy outcomes.     

Cord blood nesfatin-1 and apelin-36 levels in gestational diabetes mellitus

To assess maternal serum and cord blood apelin-36 and nesfatin-1 concentrations in pregnant women with and without gestational diabetes mellitus (GDM). Thirty pregnant women with GDM and 30 gestational age matched healthy pregnant subjects participated to the study. Maternal serum and cord blood nesfatin-1 and apelin-36 levels were measured with ELISA, at the time of birth. The relationships between maternal serum and cord blood nesfatin-1 and apelin-36 levels, anthropometric and metabolic parameters were also assessed. Maternal serum apelin-36 levels were found higher (13.5?±?8.3 vs. 9.6?±?5.9?ng/ml, P?=?0.001) and nesfatin-1 levels were found lower (5.5?±?8.1 vs. 8.1?±?23.9?ng/ml, P?=?0.001) in patients with GDM compared with control pregnant women. However, the cord blood apelin-36 levels (8.8?±?4.3 and 8.2?±?1.9?ng/ml, P?=?0.618) and nesfatin-1 levels (5.4?±?4.0 and 6.2?±?10.3?ng/ml, P?=?0.688) were similar in the GDM and control groups, respectively. Maternal serum apelin-36 and nesfatin-1 levels correlated positively with their respective cord blood levels. Maternal serum and cord blood apelin-36 levels correlated negatively with the gestational age and birth weight. Similarly maternal serum and cord blood nesfatin-1 levels correlated negatively with the gestational age, but there was no correlation with the birth weight. We did not find a correlation between maternal serum apelin-36 and nesfatin-1 levels, maternal age, BMI, fasting glucose, fasting insulin, and HOMA-IR. Also cord blood apelin-36 and nesfatin-1 levels did not correlate with the maternal age, BMI, HOMA-IR, cord blood glucose, and cord blood insulin levels. Our results indicate that apelin-36 concentrations increase and nesfatin-1 concentrations decrease in maternal serum of women with GDM.     

Low birth weight and later development of insulin resistance and biochemical/clinical features of polycystic ovary syndrome

Reduced insulin sensitivity in adult life has been reported in subjects born at term small for gestational age (SGA) and in those born prematurely with very low birth weight (LBW) (<1,500 g). We assessed whether LBW (<2,500 g) young women, irrespective of whether they were born SGA or adequate for gestational age (premature AGA), exhibited a reduction in insulin sensitivity through a prospective historical design. The risk of developing biochemical and clinical features of polycystic ovary syndrome was also investigated. The study population included 35 LBW women (19 SGA [BW range, 1,000-2,400 g] and 16 premature AGA [BW range, 1,700-2,440 g]) aged 21.8 +/- 1.8 years and 35 term AGA controls, of similar age, recruited from a neonatal registry. All women underwent clinical, ultrasonographic, hormonal, and metabolic evaluations, including the composite insulin sensitivity index. Women under hormonal contraception (21.4%) were excluded from hormonal and metabolic analyses. Composite insulin sensitivity index was significantly lower in LBW women even when the 2 LBW subgroups, SGA and premature AGA, were analyzed separately (4.4 +/- 2.2 and 4.0 +/- 1.7, respectively) than in controls (6.9 +/- 4.4). The LBW women showed a significantly higher incidence proportion of irregular menses (14/35 [40%] vs 2/35 [5.7%]) and a significantly higher free androgen index (5.8 +/- 3.5 vs 3.9 +/- 3.2). They also showed a nonsignificantly higher proportion of hirsutism, acne, and polycystic ovaries. In conclusion, LBW (<2,500 g) young women, irrespective of whether they were SGA and premature AGA, exhibited a reduction in insulin sensitivity as compared with born at term AGA women. Furthermore, they exhibited an increased risk of developing clinical and biochemical features of polycystic ovary syndrome.     

Reduced sex hormone binding globulin and derived free testosterone levels in women with severe acne

Reduced circulating sex hormone binding globulin (SHBG) levels were found in 54% of a group of women with moderate to severe acne and in 60% of another group of twenty-three women who had acne complicated by hirsutism and/or irregular menstrual cycles. The concentrations of SHBG for the women with acne alone (mean 48 ± 24 nmol/l) and for those with acne and hirsutes (mean 39 ± 18 nmol/l) were compared with the SHBG concentrations of fifteen unaffected women with normal menstrual cycles (mean 70 ± 19 nmol/l). The differences in mean SHBG values for both groups of women with acne were significant ( P < 0·001) on comparison with the mean for the unaffected women.
Twenty-nine per cent of the women with acne had elevated testosterone values (mean testosterone concentration for the group 1·5 ± 0·3 nmol/l) and 41% had elevated'derived'free testosterone levels (mean 21 ± 6 pmol/l). Of the women with acne and hirsutes 65% had elevated plasma testosterone levels (mean 2·1 ± 0·6 nmol/l) and 89% had elevated free testosterone concentrations (mean 31 ± 10 pmol/l). The mean values for testosterone and free testosterone in the plasma of unaffected women (mean testosterone concentration 1·1 ± 0·3 nmol/l and free testosterone 13 ± 4 pmol/l) were significantly lower than in women with acne alone ( P < 0·01 and P < 0·001) and in women with acne and hirsutism ( P < 0·001).
This study indicates that a deficiency in SHBG and an elevation in'derived'free testosterone is a frequent finding in women with severe acne and may be a significant factor in the aetiology and/or perpetuation of this condition.     

Maternal soluble tumour necrosis factor receptor type 2 (sTNFR2) and adiponectin are both related to blood pressure during gestation and infant's birthweight

OBJECTIVE: Tumour necrosis factor alpha (TNF-alpha) and adiponectin are strongly related to insulin sensitivity; insulin resistance of pregnancy is a major determinant of infant's birthweight. We aimed to study the contributions of maternal serum concentrations of soluble TNF-alpha receptors (sTNFR1 and sTNFR2) and adiponectin to infant's birthweight. DESIGN: Cross-sectional, hospital-based study of insulin sensitivity during gestation. PATIENTS: Fifty-one healthy women with uncomplicated pregnancy and delivery (except for elective Caesarian section) and their healthy newborn infants. measurements Maternal blood levels of glucose, insulin, glycosylated haemaglobin (HbA1c), sTNFR1, sTNFR2 and adiponectin at delivery; cord-blood levels of sTNFR1, sTNFR2 and adiponectin. RESULTS: At delivery, maternal sTNFR2 correlated with systolic blood pressure (SBP; r = 0.38, P = 0.005). In multiple regression analyses, SBP and HbA1c were independent predictors of sTNFR2, explaining 18 and 7% of its variance, respectively; insulin resistance index (HOMA-IR), body mass index at delivery and SBP were independent predictors of adiponectin, explaining 15, 8 and 7% of its variance, respectively. Both maternal sTNFR2 and SBP were negatively correlated with infant's birthweight (r = -0.28, P = 0.04 and r = -0.36, P = 0.01 respectively, adjusted for sex and gestational age). In multivariate regression analyses, infant's sex and either maternal sTNFR2 or adiponectin were independent predictors of infant's birthweight, each explaining between 6 and 9% of birthweight variance. Further addition of maternal SBP to these models revealed that this variable was the main predictor of infant's birthweight, explaining 13% of its variance. CONCLUSIONS: Maternal sTNFR2 and adiponectin are independently related to both maternal blood pressure and infant's birthweight in uncomplicated pregnancy. The contributions of the TNF-alpha system and adiponectin to hypertensive disorders of pregnancy and fetal growth merit further studies.     

The impact of a pure anti-androgen (flutamide) on LH, FSH, androgens and clinical status in idiopathic hirsutism

OBJECTIVES We assessed in women the effects of androgen suppression on gonadotrophin secretion and the therapeutic efficacy of the pure anti-androgen flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide). DESIGN AND SUBJECTS Ten women, aged 28-35 years, using an intrauterine device for contraception, were selected for this study. All women had idiopathic hirsutism with or without acne and seborrhoea. Flutamide was administered orally in a dose of 250 mg twice daily for 1 year. Basal body temperature was recorded and pelvic ultrasonography performed before and every 3 months during treatment. LH pulse frequency and amplitude (Cluster analysis) and basal and GnRH-stimulated plasma LH and FSH levels were determined on day 5 of the cycle prior to flutamide treatment, and after 6 and 12 months of therapy. Plasma total testosterone (T), non-SHBG bound T, androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), androstanediol glucuronide (3α-diol G) and sex hormone binding globulin (SHBG) levels were measured before and every 3 months during therapy, on day 5 of the cycle. Plasma oestradiol and progesterone levels were determined on day 22 of the studied cycles. RESULTS Disappearance of acne and seborrhoea occurred after 2 months with a marked improvement of hirsutism at 6 months. At 12 months, hirsutism had disappeared with a Ferriman and Galiwey score < 7. No adverse side-effects, apart from transient diarrhoea in two patients, were reported with this flutamide dose. None of the patients had any disturbance of menstrual cycles which remained ovulatory. The pure anti-androgen flutamide induced no significant change in LH pulsatile profile, nor in LH and FSH responsiveness to GnRH. Plasma concentrations of steroids were not altered. Plasma SHBG and 3al-diol G levels did not change during flutamide treatment. CONCLUSION Flutamide, which interacts only with the androgen receptor, is effective for hirsutism, acne and seborrhoea, and does not disturb menstrual cyclicity or ovulation. It may represent a treatment of choice for essential hirsutism in women using safe contraceptive methods.     

Malaria in pregnancy and its consequences for the infant in rural Malawi

Maternal malaria and anaemia, pregnancy and infant outcomes are reviewed among a cohort of mothers and their babies living in Chikwawa district, southern Malawi. Overall, 4104 women were screened at first antenatal visit and 1523 at delivery. Factors independently associated with moderately severe anaemia (MSA; < 8 g haemoglobin/dl) in primigravidae were malaria (relative risk = 1.9; 95% confidence interval = 1.6-2.3) and iron deficiency (relative risk = 4.2; 95% confidence interval = 3.5-5.0). Only iron deficiency was associated with MSA in multigravidae. After controlling for antimalarial use, parasitaemia was observed in 56.3% of the HIV-infected primigravidae and 36.5% of the non-infected (P = 0.04). The corresponding figures for multigravidae were 23.8% and 11.0%, respectively (P = 0.002). Over 33% of the infants born alive to primigravidae were of low birthweight (LBW; < 2500 g), and 23.3% of all newborns had foetal anaemia (< 12.5 g haemoglobin/dl cord blood). LBW was significantly associated in primigravidae with pre-term delivery, placental malaria and frequency of treatment with sulfadoxine-pyrimethamine (SP), and in multigravidae with pre-term delivery, adolescence, short stature and MSA. LBW was significantly reduced with a second SP treatment in primigravidae, and with iron-folate supplementation in multigravidae. Mean haemoglobin concentrations were significantly lower in the infant who had been LBW babies than in the others, and significantly associated with parity, peripheral parasitaemia at delivery and placental malaria. At 1 year post-delivery, life status was known for 364 (80.7%) of the 451 infants enrolled in the follow-up study. Independent risk factors for post-neonatal mortality were maternal HIV infection, LBW, and iron deficiency at delivery. This study identifies priorities for improving the health of pregnant women and their babies in this rural area of Malawi.     

The influence of prematurity and low birthweight on transplacental antibody transfer in a rural West African population

OBJECTIVE: To determine the influence of prematurity and low birthweight (LBW) on transplacental antibody transfer. METHOD: In a physician-blinded, cross-sectional study of 213 mother--baby pairs in the labour ward of Bansang Hospital, The Gambia, paired maternal and cord serum samples were tested for specific IgG antibody titres for measles virus (MeV), herpes simplex virus type 1 (HSV1), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), tetanus toxoid (TT) and diphtheria toxoid (DT) antigens using enzyme linked immunosorbent assay (ELISA). RESULTS: Prematurity was significantly associated with reduced placental antibody transfer for MeV, HSV1, TT, DT, RSV and VZV. Maternal antibody transfer for MeV, HSV1, TT, DT, RSV and VZV was significantly lower in neonates with LBW than in babies with adequate birthweight (ABW). CONCLUSION: Materno--foetal transfer of antibodies is impaired in prematurity and LBW babies in this Gambian population. Reduction in antibody transfer may further predispose these already vulnerable neonates to bacteria and viral infections. Therefore, alternative vaccination strategies, including earlier vaccination schedules, are needed to provide better protection to these young infants.     

Frequency of prenatal care visits by ethnic minority mothers and association with infant birthweight in Bac Kan Province, Vietnam

The objective of this cross-sectional study was to evaluate the association between prenatal care visits and infant birthweight among ethnic minority mothers in the mountainous Bac Kan province.This was done by comparing the frequency and timing of first prenatal care visit of 32 mothers with low birthweight (LBW) infants and 32 mothers with normal birthweight (NBW) infants. During pregnancy, mothers of NBW infants underwent 3.4+/-1 (mean) prenatal care visits and mothers of LBW infants 2.8+/-0.9 (P = 0.02). Mothers of NBW infants underwent their first prenatal care visit at 13.1+/-5.7 weeks of gestation, one week earlier than mothers of LBW infants. The frequency of prenatal care visit are probably associated with a decreased risk of LBW among ethnic minority mothers in Bac Kan province.     

Adverse perinatal outcomes of HIV-1-infected women in relation to malaria parasitemia in maternal and umbilical cord blood

Malaria infection during pregnancy increases the risk of adverse birth outcomes among HIV-infected women. The role of umbilical cord parasitemia is not well characterized. We examined the risk of adverse perinatal outcomes in relation to maternal or umbilical cord Plasmodium falciparum parasitemia among 275 HIV-infected women from Tanzania, who participated in a randomized trial of zinc supplementation during pregnancy. Maternal parasitemia (> or = 1/microL) at the first antenatal visit was associated with increased risk of low birth weight < 2,500 g (adjusted relative risk [ARR] = 2.66; P = 0.01) and preterm delivery < 37 weeks (ARR = 1.87; P = 0.06). Maternal parasitemia at delivery was associated with preterm delivery (ARR = 2.27; P = 0.008), intrauterine growth retardation (ARR = 1.92; P = 0.03), and neonatal death (ARR = 3.22; P = 0.07). Cord parasitemia was associated with a large and significant increase in the risk of neonatal death (ARR = 8.75; P = 0.003). Maternal parasitemia at the first antenatal visit was strongly related to parasitemia at delivery, and the latter was associated with cord blood parasitemia. CD4 cell counts, parity, or assignment to the zinc arm (25 mg daily) were not associated with parasitemia in maternal or cord blood at delivery. Successful treatment of HIV-infected women who present to the first prenatal visit with malaria parasitemia and avoidance of reinfection are likely to decrease the risk of adverse outcomes during pregnancy and the early postpartum period. Cord blood parasitemia is a strong predictor of neonatal death. The potential effect of zinc supplementation on clinical malaria outcomes deserves future investigation.     

Maternal nutrition and socio-economic status as determinants of birthweight in chronically malnourished African women

The birthweight is the most important determinant of mortality and morbidity in the neonatal period and may have an influence on health in adult life. The high rate of low birthweight in developing countries is therefore a major health problem. Maternal malnutrition is usually assumed to be a causal factor but other environmental factors are also involved. In this study we analysed maternal nutritional and socio-economic factors as determinants of birthweight in term infants from a rural African society characterised by a high rate of chronic malnutrition. Relations of maternal weight, gestational weight gain, parity, socio-economic status and infant sex with birthweight were analysed in 1 477 women and child pairs. The selected women were followed from early pregnancy and had an uncomplicated delivery at term of a living singleton child. The gestational weight gain was 5.6 (SD 6.0) kg and the mean birthweight 2.933 kg (SD 408). Maternal weight, representing the maternal long-term nutritional situation, was the most important independent determinant of birthweight, accounting for 13.0% of the variance in birthweight. The weight gain, representing the short-term nutritional situation, explained only 5.6% of the variance. Birthweight increased by 20 g (CI 18–23) for each kg maternal weight and by 15g (CI 12–18) for each kg gestational weight gained. The socio-economic difference in birth-weight was 153 g (CI 109–196) 88 of which (CI 48–128) remained unexplained after adjustment for differences in maternal weight, parity and gender. Improved long-term nutritional situation and living conditions seems to be the most important prerequisites to counteract low birthweight in developing countries.     

Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) has been shown to cause a reduction in quality of life. This study examines the extent of different PCOS symptoms on quality-of-life, psychosocial well-being and sexual satisfaction. METHODS: Complete metabolic, hormonal, clinical and psychosocial data were obtained from a total of 120 women with PCOS. Patients were compared with 50 healthy women to establish reductions in quality-of-life and emotional well-being. In addition, the correlation between psychosocial variables and the major clinical PCOS features obesity (body mass index (BMI)), excessive body hair (hirsutism score), acne, hyperandrogenism (serum testosterone levels), disturbed insulin regulation (area under the insulin response curve and homeostasis model assessment of insulin resistance), menstrual cycle disturbances and infertility were analyzed. RESULTS: PCOS patients showed significant reductions in quality-of-life, increased psychological disturbances, and decreased sexual satisfaction when compared with healthy controls. BMI and hirsutism scores, but not the presence of acne, were associated with physical aspects of quality-of-life and sexual satisfaction. No clear effect of androgens or insulin resistance on psychosocial variables was detected. Similarly, the type of menstrual cycle disturbances or infertility had no impact on psychological well-being. CONCLUSION: In PCOS, changes in appearance, particularly obesity and hirsutism, reduce physical dimensions of quality-of-life and decrease sexual satisfaction. The role of biochemical, endocrine and metabolic parameters as well as menstrual irregularities and infertility appeared to be less important. Clinicians should pay attention to the psychosocial dimensions of PCOS on an individual basis, regardless of symptom severity or treatment response.     

Atypical hypothyroidism and the very low birthweight infant.

Results of thyroid screening tests were examined retrospectively on 311,282 infants born in Massachusetts from January 1, 1993 to December 31, 1996. During this period, 118 infants were found to have typical hypothyroidism, characterized by a low thyroxine (T4) and an elevated thyrotropin (TSH) on the initial newborn-screening specimen. Of these, 98 were normal birthweight (NBW, > or = 2,500 g), 9 were low birthweight (LBW, 1,501-2,499 g), and 11 were very low birthweight (VLBW, < or = 1,500 g). Atypical hypothyroidism as defined here is characterized by a low T4 and normal TSH concentration on the initial screening specimen, followed by and elevated TSH level on a repeat blood specimen. This phenomenon occurred in 18 infants, of whom 4 were NBW, 4 were LBW, and 10 were VLBW. The incidence of combined typical and atypical hypothyroidism was: NBW, 1:3051; LBW, 1:1589; VLBW, 1:153, with the highest incidence of atypical hypothyroidism in the VLBW category (48% of cases in this weight category, 56% of all cases of atypical hypothyroidism). In addition, screening programs using a primary TSH screen will miss infants with atypical hypothyroidism. In view of these results, it is suggested that T4 measurements be obtained routinely in all LBW and VLBW infants, with additional routine repeat blood specimens.     

Placental monocyte infiltrates in response to Plasmodium falciparum malaria infection and their association with adverse pregnancy outcomes

Maternal anemia and low birth weight (LBW) may complicate malaria in pregnancy, and placental monocyte infiltrates have been associated with LBW, and anecdotally with anemia. We examined placental pathology from 357 Malawian women. Intervillous monocyte infiltrates were frequent in placental malaria and were not seen in uninfected placentas. Histology was grouped according to a 5-point scale. Dense monocyte infiltrates and presence of intramonocytic malaria pigment were associated with anemia and LBW. Of factors associated with LBW and/or anemia in univariate analysis, gravidity (P = 0.002), number of antenatal clinic (ANC) visits (P < 0.001), malaria pigment in fibrin (P = 0.03), and monocyte malaria pigment (P = 0.0001) remained associated with lower birth weight by multivariate analysis. Associated with maternal anemia were HIV infection (P < 0.0001), intervillous monocyte numbers (P < 0.0001), number of ANC visits (P = 0.002), and recent febrile symptoms (P = 0.0001). Pigment-containing placental monocytes are associated with anemia and LBW due to malaria, and may have a causative role in their development.     

Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight

Aims/hypothesis Low birthweight (LBW) and rapid postnatal weight gain, or catch-up growth, are independent risk factors for the development of obesity and diabetes during adult life. Individuals who are both small at birth and have postnatal catch-up growth are at the highest risk. We hypothesised that dietary interventions designed to attenuate catch-up growth in LBW subjects may have long-term beneficial consequences.Materials and methods We used our previously described mouse model of LBW-associated diabetes, created by restricting maternal food intake to 50% during the last week of gestation. Control (C) dams and dams that had been subjected to undernutrition (U) were then provided either chow ad libitum after delivery or 50% food restriction on a per-day basis from delivery until weaning. We designated the resulting four groups control-control (CC), undernutrition-control (UC), control-undernutriton (CU) and undernutrition-undernutrition (UU), indicating the prenatal and postnatal experimental conditions, respectively. Carbohydrate metabolism and adiposity were assessed prospectively in offspring until age 6 months.Results Males that were small at birth and exhibited early postnatal catch-up growth developed glucose intolerance and obesity by age 6 months. In contrast, LBW mice without catch-up growth (UU) remained smaller than controls (CC), and glucose intolerance and obesity was prevented. Similarly, mice with normal birthweight that had blunted catch-up growth (CU) were leaner and had better tolerance test than CC mice. Catch-up growth during the first week of life correlated better than birthweight with glucose, fat mass and glucose tolerance up to 6 months of age.Conclusions/interpretation Prevention of early catch-up growth reversed the development of glucose intolerance and obesity in our mouse model of LBW-associated diabetes.     

Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche

To determine the adrenal contribution to elevated plasma androgens in 31 young hyperandrogenemic women with acne and/or hirsutism, we compared their responses to ACTH with those of 14 normal women. Each subject was given a low dose (10 micrograms/m2) of synthetic ACTH-(1-24) (Cortrosyn) after administration of 1.5 mg dexamethasone the night before the test. Thirty and 60 min responses of plasma 17 alpha-hydroxypregnenolone (17-Preg), 17 alpha-hydroxyprogesterone, (17-prog), dehydroepiandrosterone (DHEA), androstenedione, 11-deoxycortisol, and cortisol were measured. Eighteen (58%) patients had increased responses of at least one 17-ketosteroid or adrenal androgen precursor. All patients had cortisol responses within the range of those of the 14 normal subjects. Nine patients (29%) had evidence of steroid biosynthetic enzyme deficiencies, either mild congenital adrenal hyperplasia or the heterozygote state; after ACTH, 4 of these patients had elevated 17-prog in the range of values in heterozygote carriers of 21-hydroxylase deficiency, 2 had elevated levels of 11-deoxycortisol compatible with 11 beta-hydroxylase deficiency, and 3 had elevated levels of 17-Preg and DHEA, suggestive of 3 beta-hydroxysteroid dehydrogenase deficiency. Another 9 subjects (29%) had 17-ketosteroid (DHEA and/or androstenedione) hyperresponsiveness to ACTH with associated elevated 17-Preg responses. As a group, their patterns suggested relatively deficient 3 beta-hydroxysteroid dehydrogenase and relatively hyperactive C lyase without impairment of cortisol secretion. This pattern resembles exaggerated adrenarche, and we postulate that these 9 patients have hyperplasia of the zona reticularis. Neither basal levels of plasma androgens (free testosterone and DHEA sulfate) nor menstrual history predicted which patients would have abnormal ACTH responses. Although 5 of 11 (45%) patients with acne alone had abnormal responses to ACTH, 10 of 14 patients with acne and hirsutism (71%) had abnormal responses to ACTH. We conclude that an adrenal contribution is found in about half of hyperandrogenemic women with acne and/or hirsutism. This adrenal androgen hyperresponsiveness is heterogeneous. Some patients may have mild forms of congenital adrenal hyperplasia. However, functional androgenic hyperresponsiveness to ACTH, which resembles an exaggeration of adrenarche, is the most common abnormality found. Such findings may provide an explanation for the clinical observation of exacerbations of acne with stress.     

The relation of insulin, leptin and IGF-1 to birthweight in offspring of women with type 1 diabetes

OBJECTIVE: Maternal diabetes is associated with excess foetal growth. We have assessed the influence of maternal diabetes on hormones associated with foetal growth and the relationship of these hormones to birthweight. DESIGN: Case-control study. PATIENTS: Singleton offspring of mothers with type 1 diabetes (ODM, n = 140) and control mothers (Control, n = 49). MEASUREMENTS: Birthweight, cord blood insulin, proinsulin, 32-33 split proinsulin, leptin, IGF-1, IGFBP-3, cortisol. RESULTS: Maternal diabetes was associated with higher birthweight (ODM 3.80 +/- 0.69 kg; Control; 3.56 +/- 0.52 kg, P = 0.02) and marked increases in insulin (median [interquartile range]: ODM 110 [60-217] pmol/l; Control 22 [15-37] pmol/l; P < 0.0001) and leptin (ODM 32 [15-60] ng/ml; Control 9 [4-17] ng/ml; P < 0.0001) but no absolute difference in IGF-1 (ODM 7.9 [6.2-9.8] nmol/l, Control 7.5 [6.2-9.8] nmol/l, P = 0.24) or its principle binding protein IGFBP-3 (ODM 1.63 +/- 0.38 micro g/ml, Control 1.63 +/- 0.28 micro g/ml; P = 0.12). Individually, insulin, insulin propeptides, leptin, IGF-1 and IGFBP-3 were significantly (P < 0.05) correlated with birthweight (in ODM and Control). IGF-1 and leptin were positively related to birthweight independently of each other and insulin in both ODM and Control. By contrast, insulin showed independent relationships to birthweight in ODM (P < 0.0001) but not in Control (P = 0.4). CONCLUSIONS: Maternal diabetes is associated with marked elevation of insulin and leptin in cord blood of their offspring. Hormonal correlates of birthweight differ between ODM and Control with an independent relationship of insulin to birthweight observed only in ODM.     

Domestic violence during pregnancy and risk of low birthweight and maternal complications: a prospective cohort study at Mulago Hospital, Uganda

OBJECTIVES: To investigate whether domestic violence during pregnancy is a risk factor for antepartum hospitalization or low birthweight (LBW) delivery. METHODS: A prospective cohort study was conducted in Mulago hospital, Kampala, Uganda, among 612 women recruited in the second pregnancy trimester and followed up to delivery, from May 2004 through July 2005. The exposure (physical, sexual or psychological violence during pregnancy) was assessed using the Abuse Assessment Screen. The relative and attributable risks of LBW and antepartum hospitalization were estimated using multivariate logistic regression analysis. RESULTS: The 169 women [27.7% 95% CI (24.3-31.5%)] who reported domestic violence during pregnancy did not differ significantly from the unexposed regarding sociodemographic characteristics, but differed significantly (P < 0.05) regarding domicile variables (had less household decision-making power, more resided in extended families and more had unplanned pregnancy). They delivered babies with a mean birthweight 2647.5 +/- 604 g, on average 186 g [(95% CI 76-296); P = 0.001] lower than those unexposed. After adjusting for age, parity, number of living children, pregnancy planning, domicile and number of years in marriage, the relative risk (RR) of LBW delivery among women exposed to domestic violence was 3.78 (95% CI 2.86-5.00). Such women had a 37% higher risk of obstetric complications (such as hypertension, premature rupture of membranes and anaemia) that necessitated antepartum hospitalization [RR 1.37 (95% CI 1.01-1.84)]. CONCLUSION: In this pregnancy cohort, domestic violence during pregnancy was a risk factor for LBW delivery and antepartum hospitalization.     

Determinants of low birthweight,small‐for‐gestational‐age and preterm birth in Lombok,Indonesia: analyses of the birthweight cohort of the SUMMIT trial

Objective To examine the determinants of low birthweight (LBW), small‐for‐gestation (SGA) and preterm births in Lombok, Indonesia, an area of high infant mortality. Methods Data from The Supplementation with Multiple Micronutrient Intervention Trial (SUMMIT), a double‐blind cluster‐randomised controlled trial, were analysed. The odds ratio of factors known to be associated with LBW, SGA and preterm birth was assessed and adjusted for the cluster design of the trial using hierarchical logistic regression. Determinants included constitutional, demographic and psychosocial factors, toxic exposure, maternal nutrition and obstetric history and maternal morbidity during and prior to pregnancy. Population attributable risks of modifiable determinants were calculated. Results A cohort of 14 040 singleton births was available for analysis of LBW, with 13 498 observations for preterm births and 13 461 for SGA births. Determinants of LBW and SGA were similar and included infant’s sex, woman’s education, season at birth, mothers’ residence, household wealth, maternal mid‐upper arm circumference (MUAC), height and a composite variable of birth order and pregnancy interval. Socioeconomic indicators were also related to preterm births and included mother’s education, residence and household wealth, while nutritional‐related factors including low MUAC and birth order and interval were associated with preterm birth but not maternal height. Nausea was protective of preterm birth, while diarrhoea was associated with higher odds of preterm birth. Oedema during pregnancy was protective of SGA but associated with higher odds of preterm delivery. Around 33%, 13% and 13% of the determinants of LBW, SGA and preterm births were preventable. Conclusion Women’s education, maternal nutrition and household wealth and family planning are key factors to improving birth outcomes.