Novel splice site mutation in the growth hormone receptor gene in Turkish patients with Laron-type dwarfism.

Growth hormone (GH) is involved in growth, and fat and carbohydrate metabolism. Interaction of GH with the GH receptor (GHR) is necessary for systemic and local production of insulin-like growth factor-I (IGF-I) which mediates GH actions. Mutations in the GHR cause severe postnatal growth failure; the disorder is an autosomal recessive genetic disease resulting in GH insensitivity, called Laron syndrome. It is characterized by dwarfism with elevated serum GH and low levels of IGF-I. We analyzed the GHR gene for mutations and polymorphisms in eight patients with Laron-type dwarfism from six families. We found three missense mutations (S40L, V125A, I526L), one nonsense mutation (W157X), and one splice site mutation in the extracellular domain of GHR. Furthermore, G168G and exon 3 deletion polymorphisms were detected in patients with Laron syndrome. The splice site mutation, which is a novel mutation, was located at the donor splice site of exon 2/ intron 2 within GHR. Although this mutation changed the highly conserved donor splice site consensus sequence GT to GGT by insertion of a G residue, the intron splicing between exon 2 and exon 3 was detected in the patient. These results imply that the splicing occurs arthe GT site in intron 2, leaving the extra inserted G residue at the end of exon 2, thus changing the open reading frame of GHR resulting in a premature termination codon in exon 3.

Cyclic pamidronate therapy in children with osteogenesis imperfecta: results of treatment and follow-up after discontinuation.

BACKGROUND: Cyclic intravenous pamidronate treatment is widely used for symptomatic therapy of osteogenesis imperfecta (OI). However, data after discontinuation are very limited. AIM: The results of cyclical pamidronate treatment in 14 patients with moderate/severe OI and follow up of six of them after discontinuation are presented to assess the effects of pamidronate and its discontinuation. PATIENTS AND METHODS: Pamidronate was administered at a dosage of 0.5 mg/kg for 3 successive days every 2 months in 14 patients with OI aged 5.10 +/- 3.68 years. Treatment was stopped in six patients after a duration of 16.33 +/- 4.63 months, due to stable bone mineral density (BMD) values and/or no fracture in the last 6 months, or due to family demand. The main outcome measures were areal BMD (aBMD) of the lumbar spine, biochemical markers of bone metabolism, fracture rate, and clinical evaluation. RESULTS: Areal BMD and aBMD z-scores showed significant improvement during the treatment period. Both serum and bone-specific alkaline phosphatase values were significantly decreased. Fracture rate reduced significantly from 3.5 +/- 1.01 to 0.83 +/- 0.77 fractures/year. Bone pain, which was severe in five patients, disappeared just after the first cycle, and the activity and mobility of patients increased. aBMD and aBMD z-scores were decreased 1.5 years after discontinuation, although not statistically significant. Annual fracture rate increased significantly. Bone pain recurred in four patients. Pamidronate treatment was reinstituted in five of these patients at the end of 1.5 years. CONCLUSION: Cyclical pamidronate treatment is very effective in children with moderate/severe OI. This treatment should be started early enough before the occurrence of irreversible deformities and must be given for a longer time during the growth period.

Lipoprotein(a) levels in girls with premature adrenarche.

AIM: Elevated lipoprotein(a) (Lp(a)) level is a risk factor for cardiovascular disease (CVD). Women with polycystic ovary syndrome (PCOS) have higher Lp(a) and risk for CVD than controls. The girls with premature adrenarche (PA) were shown to share similar hormonal/metabolic properties with PCOS. We compared Lp(a) levels in PA, with healthy and PCOS girls. METHODS: In total, 25 PA, 20 controls and 10 girls with PCOS were evaluated. Lp(a), lipid profiles and insulin, glucose, free testosterone, dehydroepiandrosterone sulfate (DHEAS) and androstenedione levels were measured. A family history about CVD was obtained. RESULTS: The mean age of girls with PA, at time of the study, was 10.04 +/- 1.53, control 9.83 +/- 1.58 and PCOS was 16.58 +/- 1.46 years. The median (range) of Lp(a) levels were 22.5 (3.50-99.90), 9.6 (3.33-32.40) and 21.2 (5.89-85.65) mg/dL in PA, control and PCOS groups, respectively (P > 0.05). The median Lp(a)'s were 14.5 (3.50-87.00) and 24.30 (6.20-99.90) mg/dL, in prepubertal (Tanner 1) and pubertal PA girls (Tanner 2-5), respectively (P > 0.05). The median Lp(a) of prepubertal peers was 8.7 (3.33-21.17), while that of pubertal ones was 15.4 (4.72-32.40) mg/dL (P > 0.05). There was no difference between Lp(a) levels of pre-pubertal PA girls and their peers; however, significant difference was found in Lp(a) levels in pubertal stages of PA and healthy peers (P < 0.05). The positive family history of CVD was 60% in PA; 55% and 80% in the control and PCOS groups, respectively, with no statistical difference. Lp(a) level was correlated with DHEAS (r = 0.386, P = 0.008) and free testosterone (r = 0.337, P = 0.022) levels positively. There was no significant correlation between Lp(a) and body mass index, fasting insulin and fasting glucose/insulin ratio. CONCLUSIONS: Lipoprotein(a) levels in pubertal girls with PA differ significantly from healthy peers. However, to clarify whether the girls with PA have an additional risk for CVD with respect to Lp(a), further follow-up studies with larger number of patients are necessary.

Diagnostic value of salivary cortisol in children with abnormal adrenal cortex functions.

AIMS: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. The measurement of cortisol in saliva is a simple method, and as such it is important in the pediatric age group. In this research, the diagnostic value of measurement of salivary cortisol (SC) measurement was examined in adrenal insufficiency (AI). METHODS: Fifty-one patients, mean age 10.8 +/- 4.29, who were investigated for possible AI, were included. Basal cortisol levels were below 18 microg/dl. Adrenal function was determined by low-dose ACTH test. During the test, samples for SC were obtained simultaneously with serum samples (at 0-10-20-30-40 min). RESULTS: Mean basal serum cortisol level was 8.21 +/- 4.10 microg/dl (mean +/- SD). Basal SC was correlated to basal serum cortisol (r = 0.64, p < 0.001). A cut-off of 0.94 microg/dl for SC differentiated adrenal insufficient subjects from normals with a sensitivity and specificity of 80 and 77%, respectively. A peak SC less than 0.62 microg/dl defined AI with a specificity of 100%; however, sensitivity was 44%. CONCLUSION: Measurement of SC may be used in the evaluation of AI. It is well-correlated to serum cortisol. Peak SC in low-dose ACTH test can be used to differentiate patients with AI in the initial evaluation of individuals with suspected AI.

TNF-alpha levels in children with growth hormone deficiency and the effect of long-term growth hormone replacement therapy.

OBJECTIVE: Growth hormone (GH) has been suggested to modulate the release of some cytokines including TNF-alpha. To investigate TNF-alpha levels in children with GH deficiency (GHD), to evaluate alteration in TNF-alpha levels during recombinant human GH (rhGH) treatment, and to analyze possible correlations between TNF-alpha and GH, IGF-1 and IGFBP-3. DESIGN: Twenty-four children, aged 12.60+/-2.27 years, with isolated GHD and given rhGH therapy, as subcutaneous ingestion of 0.03-0.04mg/kg once-daily dose, were evaluated. Eleven had complete and 13 had partial GHD. Thirty-three healthy children were studied as controls. Age and sex distribution, body mass indexes of two groups were similar. In children with GHD, blood samples were drawn before (TNF-alpha0), and at 6 (TNF-alpha6) and 12 (TNF-alpha12) months of the treatment with rhGH. TNF-alpha was determined using a human TNF-alpha ELISA assay (Biosource International). RESULTS: TNF-alpha0 levels were significantly higher in children with GHD than in controls (41.79+/-25.04 and 8.63+/-4.48pg/ml, respectively, p<0.001) and decreased significantly during rhGH treatment (TNF-alpha0=41.79+/-25.04, TNF-alpha6=13.67+/-9.95, TNF-alpha12=10.86+/-6.61pg/ml, p<0.05). There was no correlation between TNF-alpha levels and BMI, IGF-1/logIGF1, IGFBP-3 levels and growth velocity of the patients with GHD. Although no correlation between TNF-alpha and peak GH levels after stimulation was present; a moderate reverse correlation between TNF-alpha and basal serum concentrations of GH (r=-0.512, p=0.046) was demonstrated. CONCLUSIONS: TNF-alpha levels are significantly higher in children with GHD than the controls, and long-term therapy with rhGH effectively reduces its level. Our data suggest that GH plays an inhibitory role on TNF-alpha release in humans. However, due to inconsistent results up to now, further prospective, controlled and long term studies are needed to elucidate the issue.

Cholestatic hepatitis as a result of severe cortisol deficiency in early infancy: report of two cases and review of literature.

Cholestatic hepatitis is identified as one of the features of hypopituitarism in the newborn, but the exact etiology of cholestasis in these cases has not been well established yet. We report here two infants, one with isolated glucocorticoid deficiency and the other with multiple pituitary hormone deficiency, indicating primary and central adrenal insufficiency, respectively, who presented with recurrent hypoglycemic seizures and cholestatic hepatitis. Severe cortisol deficiency in these cases was suggested to be the cause of cholestatic hepatitis. Review of the literature and our cases showed that the cortisol deficiency in both primary and central adrenal insufficiency occurring only during neonatal and early infancy period cause cholestatic hepatitis. The severity and the age of onset of cortisol deficiency are suggested to be the important predictors of cholestatic hepatitis in childhood.

Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: comparison of megadose methylprednisolone and conventional-dose prednisolone treatments.

During recent decades, the survival rate after childhood acute lymphoblastic leukemia (ALL) has improved substantially; consequently, the long-term side effects of ALL and its treatment have gained attention, of which osteoporosis is one of the most important. The purpose of the present study was to compare the influence of different treatment protocols that include high-dose methylprednisolone (HDMP) versus conventional-dose prednisolone (CDP) for remission-induction therapy on bone mineral density (BMD) and serum bone turnover markers in survivors of childhood ALL after cessation of chemotherapy. Thirty-six boy and 23 girl survivors, treated for ALL, were cross-sectionally studied, at a mean age of 11.7 years (range 6-19). Group 1 (n = 30) received CDP therapy (prednisolone, 2 mg/kg/day, orally) and group 2 (n = 29) received HDMP therapy (prednol-L, 900-600 mg/m2, orally). All other therapies were similar in both groups. Cranial irradiation was added for high-risk patients as soon as possible after consolidation therapy. We found that mean lumbar spine BMD z score value was -1.75 (0.83) SDS in group 1 and -1.66 (1.21) SDS in group 2. There is no difference between both groups (P = 0.736). The mean BMD z scores of prepubertal and pubertal patients were not significantly different in both groups. Comparison of serum bone turnover parameters of the patients revealed no difference between the two groups. Stepwise regression analysis revealed that lumbar spine BMD z scores was predicted by height SDS and the time past since cessation of therapy, but not age at diagnosis, BMI SDS, cranial radiotherapy, and puberty. Our study results showed that HDMP treatment did not deteriorate the bone mass any more than CDP treatment. These results proved that high-dose steroid therapy over a short period of time in remission-induction treatment would not affect the bone mass any more adversely than would conventional doses approximately 3 years after cessation of chemotherapy.

Global fibrinolytic capacity is decreased in girls with premature adrenarche: a new pathological finding?

OBJECTIVE: Global fibrinolytic capacity (GFC) is a sensitive method reflecting all of the molecular components involved in the process of fibrinolysis. Recently, a decrease in GFC has been shown in women with polycystic ovary syndrome (PCOS). Girls with premature adrenarche (PA) have been shown to have hyperinsulinemia and dyslipidemia in addition to hyperandrogenemia, similar to women with PCOS. The aim of this study was to evaluate GFC levels in girls with PA. PATIENTS AND METHODS: Twenty-five girls with PA, who had developed pubic/axillary hair at age of 7.09 +/- 0.74 (5.1-7.9) years, were studied at the age of 10.04 +/- 1.53 years and compared with 20 age-matched healthy controls and 10 girls with PCOS (mean age 16.58 +/- 1.46 years). RESULTS: Median DHEAS and free testosterone levels were significantly higher in girls with PA than in the control group. The median serum sex hormone binding globulin (SHBG) level was higher in controls than in both PA and PCOS groups (49.85, 38.60 and 21.30 nmol/l, respectively). The median fasting glucose:insulin ratio (FGIR) levels were similarly low in PA and PCOS groups, while it was significantly higher in controls. The FGIR levels were less than 7 in 52% of girls with PA and 50% of girls with PCOS; however, in controls, only 5% of girls had FGIR <7. Median GFC in girls with PA (1.67 microg/ml) and PCOS (1.06 microg/ml) were significantly lower than that of the controls (3.48 microg/ml, p <0.001). The GFC level correlated positively with SHBG and FGIR. CONCLUSION: A reduction in GFC was demonstrated in girls with PA compared to healthy controls. This important finding, newly added to previous ones, may strengthen the view that PA is not a benign condition, and also points to the presence of potential risk factors for vascular diseases in these girls starting from childhood.

Endocrinological outcome of different treatment options in children with craniopharyngioma: a retrospective analysis of 66 cases.

Craniopharyngioma is one of the leading causes of hypothalamic-pituitary dysfunction in childhood, caused either by the tumor itself or the consequences of treatment. Tumor management in terms of recurrence rate, quality of life and complications is still controversial. Sixty-six patients with craniopharyngioma at pediatric age were reviewed for symptoms, signs, types of treatment, recurrence rates, complications, and endocrinological outcome. The majority of symptoms was related to the neurological system. Complaints only affecting the endocrinological system were seen in 6% of patients. The most frequent complaints were headache and vomiting (74.2%). The main endocrinological complaints were polyuria and polydipsia (15%), and lassitude (10.6%). Although short stature was a symptom in 9.1% of patients, it was a finding in 39.7% of patients. Plain skull X-rays raised the suspicion of intracranial tumor in more than 90% of children with craniopharyngioma. Recurrence rates were independent of the extent of tumor removal (total or subtotal). The frequency of endocrine dysfunction increased significantly after treatment. The most frequent hypothalamic-pituitary dysfunction was growth hormone deficiency (100%) and gonadotropin deficiency (80%). Hypothyroidism was diagnosed in 74% of patients. The frequency of hypothalamic-pituitary dysfunction was not affected by the extent of tumor removal. Radiotherapy did not increase the frequency of endocrine dysfunctions further. In conclusion, growth follow-up in childhood seems to be an important indicator of craniopharyngioma in early diagnosis. Radiotherapy and extent of tumor removal - either total or subtotal - did not influence endocrine outcome.

Influence of iodine supplementation on serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels in severe iodine deficiency.

Iodine deficiency is an important public health problem worldwide. In addition to severe consequences such as brain damage, developmental delay, deficits in hearing and learning, it also has a negative impact on growth. The negative impact of severe iodine deficiency (SID) on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) was shown previously. In this study we aimed to analyze the impact of iodine supplementation on growth and growth factors of children with SID. One hundred and four children (63 boys and 41 girls) aged 5-15 years participated in the study. Height standard deviation scores (HSDS), and serum levels of IGF-I and IGFBP-3 were assessed both before and six months after a single dose of iodized oil. Serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were also analysed to investigate the mechanisms by which alterations of iodine status may influence growth. Pubertal children had lower HSDS six months after iodine supplementation, while that of prepubertal children remained unchanged. IGF-I and IGFBP-3 levels decreased significantly and FT4 levels were suppressed six months after the supplementation, while TSH was normalized. These findings suggest a negative impact of iodine supplementation on growth factors in the short-term, which may be a direct effect of iodine repletion or an indirect effect caused by alterations in thyroid function. It may also be related to the method of supplementation used. Further studies are necessary to resolve these issues, as well as to examine the impact of iodine supplementation on growth in the long-term.

Trimethoprim-sulfamethoxazole induced prolonged hypoglycemia in an infant with MHC class II deficiency: diazoxide as a treatment option.

Hyperinsulinemic hypoglycemia associated with trimethoprim-sulfamethoxazole (TMP-SMX) has generally been reported in adults who had renal impairment or in patients with AIDS using high dose TMP-SMX. We present a 5 month-old infant with immunodeficiency due to major histocompatibility complex class II expression defect, developing hypoglycemic convulsion on the third day of high dose TMP-SMX administration. High insulin and C-peptide levels were documented at the time of hypoglycemia. To overcome hypoglycemia while TMP-SMX tapered off, diazoxide was administered which resolved hypoglycemia in 2 months.

Serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels in severe iodine deficiency.

Iodine deficiency is an important public health problem worldwide. It is well known that it has severe consequences such as brain damage, developmental delay, deficits in hearing and learning and lower intellectual attainment. It also has a negative impact on growth. In this study, we aimed to address this issue and we assessed height standard deviation scores of children living in an area of severe iodine deficiency in comparison to those living in a mild iodine deficiency area. Serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), thyroxine (T4), and thyroid stimulating hormone (TSH) were also analyzed to investigate the mechanisms by which iodine depletion leads to growth failure. Pubertal children in a severe iodine deficient SID area had lower height standard deviation scores (HSDS), IGF-I and IGFBP-3 levels than those living in mild iodine deficient MID area. Similar findings could not be elucidated in the prepubertal age group. The major determinants of HSDS were age, IGF-I, IGFBP-3 and TSH. IGF-I and IGFBP-3 were negatively correlated with T4. These findings suggest that iodine deficiency has a negative impact on growth, as well as IGF-I and IGFBP-3 levels. This effect seems to be due to the derangements in thyroid hormone economy arising from iodine depletion. The degree of this impact may be related to the duration of iodine depletion or may be dependent on the developmental stage of the organism at the time of iodine depletion.

The effects of tonsillectomy and adenoidectomy on serum IGF-I and IGFBP3 levels in children.

OBJECTIVE: Obstructive adenoid and tonsillar hyperplasia may present with retardation of growth. Interruption of growth hormone-insulin-like growth factor I axis resulting from abnormal nocturnal growth hormone secretion is among the postulated causes. Growth hormone (GH) mediates its anabolic effects on tissues through insulin-like growth factor I (IGF-I). Most of the circulating IGF-I is bound to insulin-like growth factor binding protein 3 (IGFBP3). The objective of this study is to determine blood serum levels of IGF-I and IGFBP3 in patients with adenoid and tonsillar hypertrophy. Furthermore, we want to investigate the effect of tonsillectomy and adenoidectomy (T&A) on these levels. STUDY DESIGN: The blood serum levels of IGF-I and its binding protein IGFBP3 were examined in 41 randomly selected children with a diagnosis of upper airway obstruction resulting from hypertrophic tonsils and adenoids. METHODS: Blood samples were taken preoperatively and repeated at 3 to 6 months (mean, 4.3 mo) following T&A operation. Coated-tube immunoradiometric assay (IRMA) method was used to analyze IGF-I and IGFBP3 levels. RESULTS: Thirty-two of 41 children were eligible for the analysis. When the preoperative and postoperative results were compared, it was found that there was a statistically significant increase in serum IGF-I and IGFBP3 levels in these 32 children (P <.001). In 7 of the 32 patients, the preoperative serum IGF-I levels were below normal. Postoperatively these levels increased within normal range. This was also statistically significant (P = .016). CONCLUSION: These findings revealed that obstructive adenoid and tonsillar hypertrophy may cause decreased serum IGF-I levels by affecting the GH-IGF-I axis, and T&A is an effective therapeutic measure in these patients.

Responses of bone turnover markers and bone mineral density to growth hormone therapy in children with isolated growth hormone deficiency and multiple pituitary hormone deficiencies.

Growth hormone deficiency (GHD) is an important cause of decreased bone mass in childhood and adolescence. The role of other pituitary hormone deficiencies on bone mass is still a query in children. Thirty-nine children (28 with isolated GHD [IGHD] and 11 with multiple pituitary hormone deficiency [MPHD]) were investigated to show the effects of IGHD vs MPHD on bone status. Bone turnover markers (calcium, phosphate, alkaline phosphatase [ALP] Bone ALP [BALP], osteocalcin [OSC], carboxyterminal propeptide of type-1 collagen [CPP-I], parathyroid hormone [PTH]) were measured before and every four months during growth hormone (GH) therapy; bone mineral density (BMD) of the lumbar spine was measured before and every six months during therapy. All bone turnover markers except calcium and PTH increased significantly during 1 year of GH therapy. There were no differences in the levels of bone turnover markers between children with IGHD and MPHD at baseline, and after 4, 8 and 12 months of therapy. Lumbar spine BMD SDS of all patients increased significantly during 1 year of therapy (p = 0.035 after 6 months and p <0.001 after 12 months compared with baseline). BMD SDS of both IGHD and MPHD groups were similar at baseline and after 6 and 12 months of therapy (p = 0.235, p = 0.295 and p = 0.384). Height SDS (HtSDS) at baseline was the most important predictor of baseline BMD SDS in children with GHD (t = 4.166, p <0.001). DeltaHtSDS was also positively related to deltaBMD SDS after 1 year of GH therapy. In conclusion, there was no difference in bone status of the patients with IGHD and MPHD at baseline. GH therapy yielded similar increases in bone mass in both groups. Increase in height contributed to increase in BMD during 1 year of GH therapy.

Feminizing Sertoli cell tumor associated with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by the association of mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps and with an increased risk of developing gonadal sex tumors besides other malignancies. We describe a 7 1/2 year-old boy with PJS and bilateral gynecomastia. He has had buccal pigmentation since 1.5 years and had been operated for rectal polyp excision at 3.5 years. On physical examination, his height was at the 90th percentile, and his height age and bone age were 9 and 10 1/2 years, respectively. Increased melanotic buccal pigmentation of the lips and bilateral gynecomastia were noticed. Both of the testes were firm, non-tender and smooth on the surface, and each measured 8 ml. Hormonal measurements were all in the prepubertal range. Testis ultrasonography showed bilateral hyperechogenic areas within the glands. When he was operated for invagination and an ileum segment full of polyps was resected, bilateral testicular biopsies were also performed. Histopathological evaluation of the testes revealed bilateral multicentric benign Sertoli cell tumors. The aromatase inhibitor testolactone was started to slow skeletal maturation. On the basis of this and previous reports, PJS associated with sex-cord tumors is increasingly recognized in males as well as in females.

Risk factors for vitamin D deficiency in breast-fed newborns and their mothers.

OBJECTIVES: Vitamin D plays a critically important role in the development, growth, and mineralization of the skeleton during its formative years, and performs an equally essential role in maintaining a healthy mineralized skeleton for adults of all ages. We evaluated the vitamin D status and risk factors for vitamin D deficiency in healthy breast-fed newborns and their nursing mothers. METHODS: Serum 25-hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels were measured in 54 newborns and their nursing mothers whose ages ranged from 18 to 38 y. The relation between serum 25OHD level and demographic factors was analyzed. Bone mineral density was measured in the mothers with a serum 25OHD level below 25 nmol/L to determine the extent of bone mineralization. RESULTS: The mean serum 25OHD level in the 54 mothers was 29.11 +/- 10.47 nmol/L. Forty-six percent of the mothers had serum 25OHD levels below 25 nmol/L. The risk factors for low maternal serum 25OHD level were found in decreasing order of importance as follows: low socioeconomic class (odds ratio [OR] = 8.1, P = 0.000), being covered (OR = 4.3, P = 0.023), and low educational level (OR = 3.5, P = 0.033). The mean serum 25OHD level in the newborns was 18.62 +/- 8.00 nmol/L. Eighty percent of the newborns had serum 25OHD levels below 25 nmol/L. There was a significant correlation between the serum 25OHD levels of the newborns and their mothers (r = 0.63, P = 0.01). The most important risk factor for low serum 25OHD level in the newborn was a maternal 25OHD level below 25 nmol/L (OR = 15.2, P = 0.002), followed a covered mother (OR = 6.8, P = 0.011). Bone mineral densitometry showed osteopenia in 40% of the women with serum 25OHD levels below 25 nmol/L. All women were from a lower socioeconomic class and 80% were covered. CONCLUSIONS: Vitamin D deficiency is still a common and serious health problem of women of reproductive age and their babies in developing countries at the outset of a new millennium.