Epidemiology of neural tube defects.

OBJECTIVE: To find the prevalence of neural tube defects (NTDs), and compare the findings with local and international data, and highlight the important role of folic acid supplementation and flour fortification with folic acid in preventing NTDs. METHODS: This is a retrospective study of data retrieved from the medical records of live newborn infants admitted to the Neonatal Intensive Care Unit (NICU), Security Forces Hospital (SFH), Riyadh, Saudi Arabia with NTDs spanning 14 years (1996-2009). All pregnant women on their first antenatal visit to the primary care clinic were prescribed folic acid 0.5 mg daily, or 5 mg if there is a family history of NTD. The pre-fortification prevalence is compared to post-fortification, before and after excluding syndromic, genetic, and chromosomal causes. The results were compared with reports from other parts of Saudi Arabia and internationally, through a literature search using MEDLINE. RESULTS: The prevalence of NTDs during the period was 1.2 per 1000 live births. The pre-fortification of flour with folic acid prevalence was 1.46 per 1000 live births. The post-fortification prevalence was 1.05 (p=0.103). After excluding syndromic, genetic, and chromosomal causes from calculation of the prevalence, there was a significant reduction in the prevalence, from 1.46 to 0.81 per 1000 live births (p=0.0088). Syndromic, genetic, and chromosomal causes were identified in 20 cases (19.4%). Only 2% of mothers received preconception folic acid, and only 10% of them received it during the first 4 weeks of gestation. CONCLUSION: Despite the implementation of fortification of flour with folic acid since 2001, the prevalence of NTDs in the Kingdom of Saudi Arabia is still high. This is due to the impact of genetic, syndromic, and chromosomal causes of NTD not preventable by folic acid. Other factors like unplanned pregnancy and lack of awareness of the role of folic acid in preventing nonsyndromic causes, play a significant role.

Genetic, chromosomal, and syndromic causes of neural tube defects.

OBJECTIVE: To ascertain the incidence, and describe the various forms of neural tube defects (NTDs) due to genetic, chromosomal, and syndromic causes. METHODS: We carried out a retrospective analysis of data retrieved from the medical records of newborn infants admitted to the Neonatal Intensive Care Unit with NTDs and their mothers spanning 14 years (1996-2009) at the Security Forces Hospital, Riyadh, Saudi Arabia. The cases were ascertained by a perinatologist, neonatologist, geneticist, radiologist, and neurologist. The literature was reviewed via a MEDLINE search. Only liveborn babies were included. Permission from the Educational Committee at the Security Forces Hospital was obtained prior to the collection of data. RESULTS: Out of 103 infants with NTDs admitted during this period, 20 (19.4%) were found to have an underlying genetic syndromic, chromosomal and/or other anomalies. There were 5 cases of Meckel-Gruber syndrome, 2 Joubert syndrome, one Waardenburg syndrome, one Walker-Warburg syndrome, 2 chromosomal disorders, 2 caudal regression, one amniotic band disruption sequence, one associated with omphalocele, one with diaphragmatic hernia, and 4 with multiple congenital anomalies. CONCLUSION: There is a high rate of underlying genetic syndromic and/or chromosomal causes of NTDs in the Saudi Arabian population due to the high consanguinity rate. Identification of such association can lead to more accurate provisions of genetic counseling to the family including preimplantation genetic diagnosis or early termination of pregnancies associated with lethal conditions.

A case of methotrexate embryopathy with holoprosencephaly, expanding the phenotype.

BACKGROUND: Methotrexate (MTX) embryopathy was described nearly 50 years ago, when this agent began to be used as a cancer treatment and abortifacient. In this report we describe a case with typical features of MTX syndrome together with new features to expand the phenotype. CASE: A 29-year-old woman decided to terminate her unwanted pregnancy because of ill health, as she had conceived soon after her last delivery by cesarian section. At 6 weeks of gestation, she took 2.5 mg of MTX 3 times a day for 7 days. The pregnancy termination failed, and the pregnancy was carried to term. A female infant was delivered who was growth retarded and had characteristic features of MTX embryopathy in addition to holoprosencephaly and other brain malformations, facial hypertrichosis, and long eyelashes--features that have not hitherto been described. CONCLUSIONS: We report the first case of holoprosencephaly in association with MTX exposure during the first 6 weeks of gestation. Physicians and the public should be aware of the effects of MTX on the fetus during pregnancy.