Prevention of Neural Tube Defects by Folic Acid Supplementation: A National Population-Based Study.

Folic acid supplementation is recommended for neural tube defect prevention during pregnancy. We conducted an observational, retrospective national registry study to determine the rate of dispensing of periconceptional folic acid after prescription in a sample of French women representative of the general population. Our study population (n = 186,061) was a representative sample of the French population, recorded in the Health Data System database on pharmacy dispensing of medication and mandatory reporting of pregnancy. Between 2006 and 2016, 14.3% of pregnant women had a prescription for folic acid supplementation during the month preceding conception and for the first 12 weeks of pregnancy. Of these prescriptions, 30.9% were issued before the start of pregnancy. This percentage was lower for first pregnancies. The rate of pharmacy dispensing during the preconception period increased progressively from 3.8% to 8.3% between 2006 and 2016. In France, the rate of pharmacy dispensing of periconceptional folic acid after medical prescription is very low and does not follow international recommendations. It seems essential to implement awareness-raising policies targeting the general population and physicians regarding effective periconceptional supplementation, particularly starting in the preconception period. Clarification of international recommendations and fortification of flour could improve the efficacy of folate supplementation at population level.

Acid folic and pregnancy: A mandatory supplementation.

Neural tube defects (NTD) occur in 0.5 to 2 per 1000 pregnancies with various handicaps for the affected child. It is now well established that folic acid deficiency (absolute or relative) is a predisposing factor to this type of malformation. Several randomized controlled trials showed that high-dose folic acid (4mg) is an essential factor for prevention of neural tube defects recurrence and significantly prevents the first occurrence of neural tube defects with a lower dose (0.4mg). Other etiologies can favor the occurrence of NTD such as MTHFR polymorphism, some antiepileptic therapies, obesity and pregestational mellitus diabetes. Necessity of a preconception folic acid supplementation or at least folate nutritional status evaluation should be known for all of us including patients and public.

Spinal cord malformations.

Malformations of the spinal cord are one of the most frequent malformations. They should be clearly divided into two completely different families of malformations: open dysraphisms and occult dysraphisms. Open dysraphism mostly consists in myelomeningocele (MMC). Its incidence is 1/1000 live births with a wide variation. Folic acid supplementation has been shown to reduce its risk. In most cases, the diagnosis is done prenatally by serum screening and ultrasound and may lead to termination of pregnancy. In case of decision to continue pregnancy, surgical treatment must be achieved during the first days of life, and in 50 to 90% of cases, a ventricular shunt must be installed. The follow-up of these children must be continued throughout life looking for late complications (Chiari II and syringomyelia, vertebral problems, neuropathic bladder, tethered cord). Occult dysraphisms are a heterogeneous group of malformations. Lipomas (filum and conus) are the most frequent and their treatment remains controversial. Diastematomyelia, neurenteric cysts, dermal sinus, and more complex forms (Currarino syndrome) belong to this group. Most of them can and must be diagnosed prenatally or at birth by careful examination of the lower back for the cutaneous stigmata of the disease to decrease the risk of neurological, urological, or orthopedic permanent handicap.

Hypothalamic-pituitary lesions in pediatric patients: endocrine symptoms often precede neuro-ophthalmic presenting symptoms.

OBJECTIVE: To evaluate whether analyses of clinical and endocrine presenting symptoms could help to shorten the time to diagnosis of hypothalamic-pituitary lesions in children. STUDY DESIGN: A retrospective, single-center, cohort study of 176 patients (93 boys), aged 6 years (range, 0.2-18 years), with hypothalamic-pituitary lesions was performed. RESULTS: The lesions were craniopharyngioma (n = 56), optic pathway glioma (n = 54), suprasellar arachnoid cyst (n = 25), hamartoma (n = 22), germ cell tumor (n = 12), and hypothalamic-pituitary astrocytoma (n = 7). The most common presenting symptoms were neurologic (50%) and/or visual complaints (38%), followed by solitary endocrine symptoms (28%). Precocious puberty led to diagnosis in 19% of prepubertal patients (n = 131), occurring earlier in patients with hamartoma than in patients with optic-pathway glioma (P < .02). Isolated diabetes insipidus led to diagnosis for all germ-cell tumors. For 122 patients with neuro-ophthalmic presenting symptoms, the mean symptom interval was 0.5 year (95% CI, 0.4-0.6 year), although 66% of patients had abnormal body mass index or growth velocity, which preceded the presenting symptom interval onset by 1.9 years (95% CI, 1.5-2.4 years) (P < .0001) and 1.4 years (95% CI, 1-1.8 years) (P < .0001), respectively. Among them, 41 patients were obese before diagnosis (median 2.2 years [IQR, 1-3 years] prior to diagnosis) and 35 of them had normal growth velocity at the onset of obesity. The sensitivity of current guidelines for management of childhood obesity failed to identify 61%-85% of obese children with an underlying hypothalamic-pituitary lesion in our series. CONCLUSIONS: Endocrine disorders occurred in two-thirds of patients prior to the onset of the neuro-ophthalmic presenting symptom but were missed. Identifying them may help to diagnose hypothalamic-pituitary lesions earlier.

Low bone mineral density and high incidences of fractures and vitamin D deficiency in 52 pediatric cancer survivors.

OBJECTIVE: To evaluate bone mineral density (BMD), fractures, and vitamin D deficiency in pediatric patients in complete remission of solid tumor; and to identify risk factors for these three abnormalities. STUDY DESIGN: Data were collected prospectively after completion of cancer treatment. Hormonal and vitamin D deficiencies were treated. The patients were evaluated again 1 year later. PATIENTS: 52 consecutive patients, 30 boys and 22 girls. Among them, 21 completed the second evaluation. MEASUREMENTS: A clinical examination, nutritional assessment, and laboratory workup were performed. BMD was measured by absorptiometry. RESULTS: Calcium intake was inadequate in 75% of patients and vitamin D reserves were low in 61.5%. BMD was low at the spine in 32.7%, and at the femur in 24% of patients. Spinal and femoral BMD Z-scores correlated significantly with each other. Femoral BMD Z-score showed significant positive correlations with changes in body mass index, urinary calcium/creatinine ratio, and time since treatment completion, and a significant negative correlation with treatment duration. Fractures were noted in 10 patients but were not correlated with BMD. In the 21 re-evaluated patients, no significant improvements were found in calcium intake, vitamin D status, or BMD Z-score. CONCLUSIONS: Survivors of childhood solid cancer have high rates of insufficient calcium intake, vitamin D deficiency, low bone mass and fractures.

Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index.

BACKGROUND: Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA). As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R) and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. METHODS: 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement), grade 1 (n = 8, compression without involvement), or grade 2 (n = 12, severe involvement). RESULTS: Despite having similar body mass indexes (BMI), the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, <0.05 and 0.02 respectively) and 1 patients (P < 0.02 and <0.03 for both insulin and HOMA). The grade 0 (5.8 +/- 4.9) and 1 (7.2 +/- 5.3) patients gained significantly less weight (kg) during the year after surgery than did the grade 2 (16.3 +/- 7.4) patients. The pre-surgery HOMA was positively correlated with these weight changes (P < 0.03). The data for the whole population before and 6-18 months after surgery showed increases in BMI (P < 0.0001), insulin (P < 0.005), and leptin (P = 0.0005), and decreases in sOB-R (P < 0.04) and ghrelin (P < 0.03). CONCLUSION: The hypothalamic involvement by the craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement.

Thalamic tumors in children: a reappraisal.

OBJECT: Two to five percent of pediatric brain tumors are located in the thalamus. The optimal management for these tumors remains unclear. The aim of this study was to determine whether clinical and neuroimaging features could guide treatment, and to what extent these features, together with histological diagnosis and treatment modalities, influenced survival. METHODS: The records of 69 children who presented with a thalamic tumor between 1989 and 2003 were retrospectively reviewed. Three groups of tumors were analyzed separately: 1) unilateral thalamic tumors (54 lesions); 2) thalamopeduncular tumors (six); and 3) bilateral thalamic tumors (nine). In the patients in whom a unilateral thalamic tumor was diagnosed, 33 had an astrocytic tumor. Of the 54 patients, 32 had a low-grade and 22 had a high-grade tumor. The survival rate was significantly better for patients with the following characteristics: symptom duration longer than 2 months (p < 0.001), lesions with low-grade histological features (p = 0.003), and tumor excision greater than 90% at surgery (p = 0.04). The perioperative morbidity and mortality rates were 37 and 4%, respectively. Fifty-four percent of the patients in this group had a long-term and independent survival. The thalamopeduncular tumors were mostly pilocytic astrocytomas, which had a good prognosis following surgery. The bilateral thalamic tumors in this series were mainly low-grade astrocytic lesions, and more than half of the children attained long-term survival (mean follow-up duration 4.5 years). CONCLUSIONS: The majority of tumors arising in the thalamus are astrocytic, of which less than half are high-grade lesions. Histological evaluations should be performed in all patients in whom resection is being considered for discrete lesions. Long-term survival is possible in patients with these tumors.

Influence of tumor location on the presentation and evolution of craniopharyngiomas.

OBJECT: This study was performed to optimize the management of craniopharyngiomas, particularly by identifying factors predicting weight changes to prevent obesity. METHODS: A series of 35 patients who had undergone surgery at a mean age of 7.4 +/- 3.7 years (standard deviation [SD]) and had been followed up until 14.9 +/- 5 years of age by the same endocrinologist were assigned to one of three groups according to their hypothalamic involvement: Group 1 (10 patients) had no involvement, Group 2 (eight patients) had compression without involvement, and Group 3 (17 patients) had severe involvement. Abnormal height and/or weight evolution indicated the craniopharyngioma in only 17% of the patients, although these elements were present at diagnosis in 85%. Before surgery, 85% of the patients lacked growth hormone, 24% lacked thyroid-stimulating hormone, 15% lacked adrenocorticotropin hormone, and 12% lacked antidiuretic hormone. All had complete hypothalamic-pituitary deficiencies after surgery. The body mass index (BMI) before surgery (mean SD 1.1 +/- 1.6) was positively correlated with BMI 1 year after surgery (mean SD 3.1 +/- 2), which correlated with the BMI at the last evaluation (mean SD 3.1 +/- 1.9; p < 0.0001 for both). Before surgery, patients in Group 3 had a greater BMI than did Group 1 (p < 0.02). The BMI of Group 1 patients did not change, but those of Groups 2 and 3 patients increased during the 1st year after surgery (p < 0.02 and p = 0.0003, respectively), with no further change. The changes occurred mainly during the first 3 months after surgery in Group 1, during the first 6 months in Group 2, and throughout the year in Group 3. CONCLUSIONS: The degree of hypothalamic involvement by the craniopharyngioma determines the presentation and predicts weight changes after surgery.