Obstetric complications in pregnancies with life-limiting malformations.

PURPOSE OF REVIEW: The implementation of palliative care at birth has led to a significant rise in the number of couples who choose to continue with pregnancies complicated by life-limiting malformations (LLMs). Prenatal counselling and appropriate antenatal/perinatal management in these cases are poorly studied and may pose significant challenges. The purpose of this review is to outline specific obstetric risks and to suggest management for mothers who choose to continue with pregnancies with the most common LLMs. RECENT FINDINGS: In pregnancies complicated by LLMs where parents opt for expectant management, clinicians should respect parental wishes, whilst openly sharing potential serious maternal medical risks specific for the identified abnormalities. The focus of both antenatal and perinatal care should be maternal wellbeing rather than foetal survival. Follow-up ultrasound examinations and maternal surveillance should be aimed at achieving timely diagnosis and effective management of obstetric complications. A clear perinatal plan, agreed with the couples by a multi-disciplinary team including a foetal medicine specialist, a neonatologist and a geneticist, is crucial to reduce maternal morbidity. SUMMARY: This review provides a useful framework for clinicians who face the challenges of counselling and managing cases complicated by LLMs where parents opt for pregnancy continuation.

Reductions in child mortality by preventing spina bifida and anencephaly: Implications in achieving Target 3.2 of the Sustainable Development Goals in developing countries.

BACKGROUND: There is an opportunity to reduce child mortality by preventing folic acid-preventable spina bifida and anencephaly (FAP SBA) in developing countries. We estimated reductions in FAP SBA-associated child mortality in 69 countries with an immediate potential for mandatory fortification of wheat flour. METHODS: Using data from multiple sources, we estimated the percent reductions in neonatal, infant, and under-five mortality that would have occurred by preventing FAP SBA; and the contributions of these reductions toward each country's Sustainable Development Goals (SDG) for child mortality reduction. We used the combined prevalence of spina bifida and anencephaly in selected countries before fortification, and estimated preventable child mortality associated with FAP SBA, assuming 0.5 per 1,000 live births as minimum achievable prevalence from mandatory fortification. RESULTS: Annually, 56,785 live births with FAP SBA occurred in the 69 countries examined. Of these, about 49,680 (87%) would have resulted in deaths under age 5 years, and are preventable through mandatory folic acid fortification. On average, compared to current rates, prevention of FAP SBA would have reduced the neonatal, infant, and under-five mortality by 19% (95% uncertainty interval [UI]: 16-24%), 15% (UI: 13-17%), and 14%, (95% UI: 13-17%), respectively. Prevention of FAP SBA seemed to contribute toward achieving SDG on neonatal and under-five mortality in developing countries. CONCLUSIONS: Prevention of FAP SBA will lead to notable and immediate reductions in child mortality. Many countries have an opportunity to effectively move toward child mortality-related SDG targets with existing milling infrastructure for food fortification.

Total prevention of folic acid-preventable spina bifida and anencephaly would reduce child mortality in India: Implications in achieving Target 3.2 of the Sustainable Development Goals.

BACKGROUND: The potential to reduce child mortality by preventing folic acid-preventable spina bifida and anencephaly (FAP SBA) is inadequately appreciated. To quantify possible reduction in FAP SBA-associated child mortality in low- and middle-income countries, we conducted an analysis to demonstrate in India, a country with more than 25 million births and 1.2 million under-five deaths each year, the decrease in neonatal, infant, and under-five mortality that would occur through total prevention of FAP SBA. METHODS: We estimated the percent reductions in neonatal, infant, and under-five mortality that would have occurred in India in 2015 had all of FAP SBA been prevented. We also estimated the contributions of these reductions toward India's Sustainable Development Goals on child mortality indicators. We considered the overall prevalence of spina bifida and anencephaly in India as 5 per 1,000 live births, of which 90% were preventable with effective folic acid intervention. RESULTS: In the year 2015, folic acid interventions would have prevented about 116,070 cases of FAP SBA and 101,565 under-five deaths associated with FAP SBA. Prevention of FAP SBA would have reduced annually, neonatal, infant, and under-five mortality by 10.2%, 8.9%, and 8.3%, respectively. These reductions would have contributed 18.5% and 17.2% to the reductions in neonatal and under-five mortality, respectively, needed by India to achieve its 2030 Sustainable Developmental Goal Target 3.2 addressing preventable child mortality. CONCLUSIONS: Total prevention of FAP SBA clearly has a significant potential for immediate reductions in neonatal, infant, and under-five mortality in India, and similarly other countries.

Anencefalia: presentación de 1 caso / Anencephaly. Presentation of a case

La anencefalia es una de las anomalías del tubo neural más comunes. Estas anomalías son defectos congénitos que afectan el tejido que crece en el cerebro y la médula espinal, el objetivo de la presente investigación es describir un caso de anencefalia que es un defecto congénito poco frecuente en el neonato en la fusión de varios sitios de cierre del tubo neural. Defecto en la fusión de varios sitios de cierre del tubo neural ocurre cuando el extremo encefálico o cabeza del tubo neural no logra cerrarse, generalmente entre el 23º y el 26º día del embarazo, dando como resultado una malformación cerebral congénita caracterizada por la ausencia parcial o total del cerebro, cráneo, y cuero cabelludo; su frecuencia varía entre 0.5 y 2 por cada 1 000 nacimientos. Se presenta un caso de un primer gemelar que nace con ausencia de cráneo, con puntuación de apgar bajo que a pesar de las medidas de sostén fallece a las 20 horas de edad(AU)

The anencephaly is one of the most common anomalies of the neural tube. These anomalies are congenital defects that affect the tissues that grow in the brain and the spinal cord, the objective of this investigation is to describe a case of anencephaly that is an infrequent congenital defect in the newborns in the fusion of several closing places of the neural tube. The defect in the fusion of several closing places of the neural tube occurs when the encephalic extreme or head of the neural tube does not close, generally between the 23º and the 26º day of the pregnancy, causing a congenital cerebral malformation characterized by the partial or total absence of the brain, skull, and scalp; its frequency varies between 0.5 and 2 per 1000 births. It is presented a case of a first twin who comes to the world with absence of skull, with a low apgar, and in spite of the ways to keep him alive, he died after 20 hours(EU)

[Impact of the fortification of food with folic acid on neural tube defects in Costa Rica]. / Impacto de la fortificación de alimentos con ácido fólico en los defectos del tubo neural en Costa Rica.

OBJECTIVE: Evaluate the impact of the fortification of food with folic acid on prevalence trends for neural tube defects (NTD) and the infant mortality rate (IMR) associated with this disorder in Costa Rica. METHODS: The surveillance data from the Congenital Disease Registry Center and the Central American Population Center were analyzed. The neural tube defects considered were anencephaly, spina bifida, and encephalocele. The trends from 1987-2009, as well as the differences in prevalence and mortality rates prior to and up to 12 years after food fortification with folic acid, were examined (95% confidence interval [CI]). The contribution of fortification to the decrease in the overall IMR was determined. RESULTS: During 1987-1997, prior to the period of food fortification with folic acid, NTD prevalence was 12/10 000 births (95% CI: 11.1-12.8), whereas in 2009 prevalence was 5.1/10 000 births (3.3-6.5). The IMR associated with NTD was 0.64/1 000 births (46-0.82) in 1997 and 0.19/1 000 births (0.09-9.3) in 2009. There were significant decreases in the IMR associated with NTD and the prevalence of NTD: 71%, and 58%, respectively (P < 0.05). The overall IMR decreased from 14.2/1 000 births in 1997 to 8.84/1 000 births in 2009 (P < 0.05). The decrease in the IMR associated with NTD contributed to an 8.8% decrease in the overall IMR from 1997 to 2009. CONCLUSIONS: Food fortification with folic acid caused a decrease in NTD at birth and the IMR associated with this malformation during the 1997-2009 period. It also led to a decrease in the overall IMR. There is a temporal relationship between the introduction of fortification policies and the decrease in prevalence and mortality associated with NTD. This intervention should be promoted in Latin American and Caribbean countries where it has not yet been implemented.

Impacto de la fortificación de alimentos con ácido fólico en los defectos del tubo neural en Costa Rica / Impact of the fortification of food with folic acid on neural tube defects in Costa Rica

OBJETIVO: Evaluar el impacto de la fortificación de alimentos con ácido fólico en las tendencias de las prevalencias de los defectos del tubo neural (DTN) y la tasa de mortalidad infantil (TMI) por este trastorno en Costa Rica. MÉTODOS: Se analizaron los datos de vigilancia del Centro de Registro de Enfermedades Congénitas y el Centro Centroamericano de Población. Se consideraron defectos del tubo neural la anencefalia, la espina bífida y el encefalocele. Se examinaron las tendencias durante 1987-2009, así como las diferencias de tasas (intervalo de confianza [IC] 95 por ciento) de prevalencia y mortalidad antes de la fortificación de alimentos con ácido fólico y hasta 12 años después de su implementación. Se determinó el aporte de la fortificación al descenso en la TMI general. RESULTADOS: En 1987-1997, previo al período de fortificación de alimentos con ácido fólico, la prevalencia de DTN fue de 12/10 000 nacidos (IC95 por ciento: 11,1-12,8), mientras que en 2009 fue de 5,1/10 000 nacidos (3,3-6,5). La TMI por DTN en 1997 fue de 0,64/1 000 nacimientos (46-0,82) y en 2009 de 0,19/1 000 (0,09-0,3). La TMI por DTN y su prevalencia disminuyeron en forma significativa, 71 por ciento y 58 por ciento respectivamente (P < 0,05). La TMI general disminuyó de 14,2/1 000 nacidos en 1997 a 8,84/1 000 en 2009 (P < 0,05). El descenso en la TMI por DTN contribuyó a una caída de 8,8 por ciento en la TMI general entre 1997 y 2009. CONCLUSIONES: La fortificación de alimentos con ácido fólico provocó una reducción de DTN al nacimiento y de la TMI por esta malformación durante el período 1997-2009, así como también el descenso de la TMI general. Existe relación de temporalidad entre el inicio de las políticas de fortificación y el descenso de la prevalencia y mortalidad por DTN. Se debe pro-mover esta intervención en los países de América Latina y el Caribe donde todavía no ha sido implementada.

OBJECTIVE: Evaluate the impact of the fortification of food with folic acid on prevalence trends for neural tube defects (NTD) and the infant mortality rate (IMR) associated with this disorder in Costa Rica. METHODS: The surveillance data from the Congenital Disease Registry Center and the Central American Population Center were analyzed. The neural tube defects considered were anencephaly, spina bifida, and encephalocele. The trends from 1987-2009, as well as the differences in prevalence and mortality rates prior to and up to 12 years after food fortification with folic acid, were examined (95 percent confidence interval [CI]). The contribution of fortification to the decrease in the overall IMR was determined. RESULTS: During 1987-1997, prior to the period of food fortification with folic acid, NTD prevalence was 12/10 000 births (95 percent CI: 11.1-12.8), whereas in 2009 prevalence was 5.1/10 000 births (3.3-6.5). The IMR associated with NTD was 0.64/1 000 births (46-0.82) in 1997 and 0.19/1 000 births (0.09-9.3) in 2009. There were significant decreases in the IMR associated with NTD and the prevalence of NTD: 71 percent, and 58 percent, respectively (P < 0.05). The overall IMR decreased from 14.2/1 000 births in 1997 to 8.84/1 000 births in 2009 (P < 0.05). The decrease in the IMR associated with NTD contributed to an 8.8 percent decrease in the overall IMR from 1997 to 2009. CONCLUSIONS: Food fortification with folic acid caused a decrease in NTD at birth and the IMR associated with this malformation during the 1997-2009 period. It also led to a decrease in the overall IMR. There is a temporal relationship between the introduction of fortification policies and the decrease in prevalence and mortality associated with NTD. This intervention should be promoted in Latin American and Caribbean countries where it has not yet been implemented.

[Anencephaly related infant mortality in Argentina: spatial and temporal analysis (1998-2007)]. / Mortalidad infantil por anencefalia en la Argentina: Análisis espacial y temporal (1998-2007).

OBJECTIVE: Analyze the spatial and temporal distribution of infant mortality by anencephaly in Argentina in relation with folic acid fortification phases. POPULATION AND METHODS: Data came from certificates of live births and deaths in children under 1 year, for the 1998-2007 period (Argentine Ministry of Health). The infant mortality rate attributable to anencephaly for Argentina, geographical regions, provinces and departments were estimated according to the different phases of mandatory fortification with folic acid. Secular trend of infant mortality rate attributable to anencephaly and death risk due to anencephaly, spatial distribution by infant mortality rate attributable to anencephaly cluster and its correlation to latitude and longitude were also analyzed. RESULTS: Reduced risk of mortality due to anencephaly (53%) was observed at national level. The greatest decline occurred in Cuyo (69%) and lowest in the Northeast (35%) at regional level. Considerable infant mortality rate attributable to anencephaly heterogeneity was found at departmental level and less at provincial level. A cluster of 5.15/10 000 infant mortality rate attributable to anencephaly was identified in the northeast of Buenos Aires province, consisting of 29 departments, significantly different from the rest of the country. CONCLUSIONS: While there was a statistically significant negative secular trend of infant mortality rate attributable to anencephaly, spatial disparities persist. The geographical distribution of anencephaly would guide the search for environmental/ genetic risk factors and strengthen primary prevention strategies, through mandatory fortification, folate intake and folic acid supplementation.

Mortalidad infantil por anencefalia en la Argentina: análisis espacial y temporal (1998-2007) / Anencephaly related infant mortality in Argentina: spatial and temporal analysis (1998-2007)

Objetivo. Analizar la distribución espacial y temporal de la mortalidad infantil por anencefalia en la Argentina en relación a las fases del procesode fortificación con ácido fólico. Población y métodos. Los datos provinieron de los certificados de recién nacidos vivos y de defunción de menores de 1 año, período 1998-2007 (Ministerio de Salud). Se calculó: a) la tasa de mortalidad infantil por anencefalia para la Argentina, regiones geográficas, provincias y departamentos de acuerdo a las distintas fases de fortificación obligatoria con ácido fólico; b) la tendencia secular de la tasa de mortalidad infantil por anencefalia y el riesgo de mortalidad por anencefalia; c) la distribución espacial por análisis de agrupamiento y de su correlación conla latitud y la longitud geográficas. Resultados. Se observó a nivel nacional una reducción del riesgo de mortalidad por anencefalia del 53 por ciento. A nivel regional el mayor descenso se observó en Cuyo (69 por ciento) y el menor en el Noreste argentino (35 por ciento). Se constató una gran eterogeneidad a nivel departamental y, en menor medida, en el provincial. Se identificó un agrupamiento integrado por 29 partidos del norestede Buenos Aires con una tasa de mortalidad infantil por anencefalia de 5,15/10 000 nacidos vivos, significativamente mayor a la nacional,de 3,10/10 000 nacidos vivos. Conclusiones. Se observó una tendencia secular negativa estadísticamente significativa de la tasa de mortalidad infantil por anencefalia, pero persisten disparidades espaciales. La distribución geográfica de anencefalia permitiría orientar la búsqueda de factores de riesgo ambientales/genéticos y reforzar estrategias de prevención primaria, por medio de la fortificación obligatoria,el consumo de folatos y la suplementación con ácido fólico.

Objective. Analyze the spatial and temporal distribution of infant mortality by an encephaly in Argentina in relation with folic acid fortification phases.Population and methods. Data came from certificates of live births and deaths in children under 1 year, for the 1998-2007 period (Argentine Ministry of Health). The infant mortality rate attributable to an encephaly for Argentina, geographical regions, provinces and departments were estimated according to the different phases of mandatory fortification with folic acid. Secular trend of infant mortality rate attributable to anencephaly and death risk due to anencephaly, spatial distribution by infant mortality rate attributable to anencephaly cluster and its correlation to latitude and longitude were also analyzed. Results. Reduced risk of mortality due to anencephaly (53%) was observed at national level. The greatest decline occurred in Cuyo (69%) and lowest in the Northeast (35%) at regional level. Considerable infant mortality rate attributable to anencephaly heterogeneity was found at departmental level and less at provincial level. A cluster of 5.15/10 000 infant mortality rate attributable to anencephaly was identified in the northeast of Buenos Aires province, consisting of 29 departments, significantly different from the rest of the country. Conclusions. While there was a statistically significant negative secular trend of infant mortality rate attributable to anencephaly, spatial disparities persist. The geographical distribution of anencephaly would guide the search for environmental/ genetic risk factors and strengthen primary prevention strategies, through mandatory fortification, folate intake and folic acid supplementation.

Mortalidad infantil por anencefalia en la Argentina: análisis espacial y temporal (1998-2007) / Anencephaly related infant mortality in Argentina: spatial and temporal analysis (1998-2007)

Objetivo. Analizar la distribución espacial y temporal de la mortalidad infantil por anencefalia en la Argentina en relación a las fases del procesode fortificación con ácido fólico. Población y métodos. Los datos provinieron de los certificados de recién nacidos vivos y de defunción de menores de 1 año, período 1998-2007 (Ministerio de Salud). Se calculó: a) la tasa de mortalidad infantil por anencefalia para la Argentina, regiones geográficas, provincias y departamentos de acuerdo a las distintas fases de fortificación obligatoria con ácido fólico; b) la tendencia secular de la tasa de mortalidad infantil por anencefalia y el riesgo de mortalidad por anencefalia; c) la distribución espacial por análisis de agrupamiento y de su correlación conla latitud y la longitud geográficas. Resultados. Se observó a nivel nacional una reducción del riesgo de mortalidad por anencefalia del 53 por ciento. A nivel regional el mayor descenso se observó en Cuyo (69 por ciento) y el menor en el Noreste argentino (35 por ciento). Se constató una gran eterogeneidad a nivel departamental y, en menor medida, en el provincial. Se identificó un agrupamiento integrado por 29 partidos del norestede Buenos Aires con una tasa de mortalidad infantil por anencefalia de 5,15/10 000 nacidos vivos, significativamente mayor a la nacional,de 3,10/10 000 nacidos vivos. Conclusiones. Se observó una tendencia secular negativa estadísticamente significativa de la tasa de mortalidad infantil por anencefalia, pero persisten disparidades espaciales. La distribución geográfica de anencefalia permitiría orientar la búsqueda de factores de riesgo ambientales/genéticos y reforzar estrategias de prevención primaria, por medio de la fortificación obligatoria,el consumo de folatos y la suplementación con ácido fólico.(AU)

Objective. Analyze the spatial and temporal distribution of infant mortality by an encephaly in Argentina in relation with folic acid fortification phases.Population and methods. Data came from certificates of live births and deaths in children under 1 year, for the 1998-2007 period (Argentine Ministry of Health). The infant mortality rate attributable to an encephaly for Argentina, geographical regions, provinces and departments were estimated according to the different phases of mandatory fortification with folic acid. Secular trend of infant mortality rate attributable to anencephaly and death risk due to anencephaly, spatial distribution by infant mortality rate attributable to anencephaly cluster and its correlation to latitude and longitude were also analyzed. Results. Reduced risk of mortality due to anencephaly (53%) was observed at national level. The greatest decline occurred in Cuyo (69%) and lowest in the Northeast (35%) at regional level. Considerable infant mortality rate attributable to anencephaly heterogeneity was found at departmental level and less at provincial level. A cluster of 5.15/10 000 infant mortality rate attributable to anencephaly was identified in the northeast of Buenos Aires province, consisting of 29 departments, significantly different from the rest of the country. Conclusions. While there was a statistically significant negative secular trend of infant mortality rate attributable to anencephaly, spatial disparities persist. The geographical distribution of anencephaly would guide the search for environmental/ genetic risk factors and strengthen primary prevention strategies, through mandatory fortification, folate intake and folic acid supplementation.(AU)

Neonate with meroacrania: radiological findings and review of the literature.

Acrania is a developmental abnormality characterized by a partial or complete absence of calvaria with complete but abnormal development of brain tissue. Acrania is a relatively common malformation and affects about 1 in 1000 newborns. Meroacrania refers to absence of the cranium with the exception of the occipital bone. Brain stem and cerebellum develop normally, but cerebral parenchyma tissue is covered with a thin membrane and severely dysmorphic supratentorial brain is also seen. The other system findings are normal. Magnetic resonance imaging findings of one neonate with meroacrania have been reported in medical literature. Other radiographic and computed tomography findings have not yet been reported. We report a female neonate with meroacrania with discussion of etiology, pathogenesis, radiological findings, and differential diagnosis.

Defecto del cierre del tubo neural: acrania: a propósito de un caso / Neural tube defect closing: acrania: a purpose of a case

Las malformaciones congénitas son un problema poco frecuente; considerando todas las malformaciones en conjunto, éstas se presentan en menos del 2 por ciento de los recién nacidos. Los defectos del cierre del tubo neural: anencefalia, espina bifida, acrania y meningocele, al igual que la mayoría de las malformaciones congénitas, son un grupo de afecciones de etiología multifactorial, producto de la interacción de factores genéticos y ambientales. Los factores genéticos actúan en un sistema poligenético, en el que se tienen que considerar los riesgos de recurrencia, cálculos de heredabilidad, la frecuencia de consanguineidad y las variaciones raciales, los factores ambientales, las infecciones virales, agentes físicos como la hipertemia (fiebre), deficiencia o alteraciones del metabolismo del ácido fólico, así como la exposición a diversas substancias químicas.

Spontaneous pregnancy outcome after prenatal diagnosis of anencephaly.

Parents are usually told that many anencephalic offspring die in utero or soon after delivery, and many obstetricians offer elective termination of the pregnancy. Following the personal experience of the first author, a personal website was created with the intention of providing information and exchanging views with other parents confronted with a prenatal diagnosis of anencephaly. Data were collected from 211 pregnancies where the parents opted not to terminate pregnancy. These data revealed that polyhydramnios was a feature in 56 (26%) pregnancies, death in utero in 15 (7%) pregnancies, 72 (34%) babies were born prematurely (<37 weeks of gestation), 113 (53%) at term and 21 (10%) after 42 weeks. Stillbirth, presumably resulting from intrapartum death, occurred in 43 (20%) deliveries. One hundred and fifty-three (72%) of anencephalic offspring were liveborn, of those, 103 (67%) died within 24 hours but 6/211 survived 6 or more days (maximum 28 days). Continuation of pregnancy after a diagnosis of anencephaly is medically safe and should be considered as an option.

Anencefalia: presentación de un caso clínico / Anencephaly: a clinical case

La anencefalia es una malformación del sistema nervioso, causado por la falla del cierre del neuroporo anterior durante la embriogénesis. Su incidencia es de 1 en 1.000 embarazos en Estados Unidos. Los recién nacidos con anencefalia generalmente sobreviven sólo pocas horas o días, y excepcionalmente se han descrito casos de sobrevida de algunas semanas. Existen numeroso estudios que sugieren la existencia de factores genéticos y ambientales en la génesis de este trastorno, por ejemplo, mutaciones en el gen que codifica la enzima metilentetrahidrofolato reductasa, elevados niveles plasmáticos de homocisteína y bajos de folato en madres de niños con defectos del tubo neural y factores ambientales diversos. La mayoria de los casos son diagnosticados mediante ultrasonografía precozmente durante el embarazo (antes de las 20 semanas). Se presenta un caso clínico de recién nacido con anencefalia, en el Hospital de Salamanca, que tuvo una sobrevida excepcionalmente prolongada y se revisa el tema

Folate levels and N(5),N(10)-methylenetetrahydrofolate reductase genotype (MTHFR) in mothers of offspring with neural tube defects: a case-control study.

BACKGROUND: Neural tube defects (NTDs) have been associated with biochemical factors involved in the conversion of homocysteine to methionine as folate deficiency and the mutation 677T in the N(5),N(10)-methylenetetrahydrofolate reductase gene (MTHFR). METHODS: A case-control study was performed to detect this mutation in 38 unrelated women with NTD deceased products and 31 mothers without antecedents of NTD offspring. All products were born in Nuevo León (northeastern Mexico) during 1997. Erythrocyte and plasmatic folate levels and the genotype of the 677 polymorphism at the MTHFR locus were analyzed in both groups. RESULTS: Although no significant differences were found in mean blood folate levels, the percentage of women in the case group with erythrocyte folate levels <160 ng/mL was significantly higher than in the control group (75 vs. 51.2%, p <0.05). The proportion of women with plasma folate levels <3.5 ng/mL was higher in the case group (16.2 vs. 0%, p <0.01). Genotype analysis demonstrated a significantly higher proportion of 677T homozygous mothers with NTD products (39.6 vs. 9.1%, p <0.05). Allele frequencies for the 677T mutation were 0.55 and 0.36 for cases and controls, respectively. The odds ratio (OR) for having a NTD product was 6.1 (95%, CI 1.56-23.6) for homozygous 677T mothers vs. homozygous 677C and heterozygous mothers. Significantly low levels of erythrocyte folate were found in the 677C homozygous case group and in plasma folate in the 677C/677T heterozygous case mothers. CONCLUSIONS: Our study suggests that folate deficiency and MTHFR unfavorable genotype in mothers are important risk factors for severe NTD phenotype in our population.

Sex differences in prevalence of congenital neural defects after periconceptional famine exposure.

The purpose of this investigation was to examine the sex distribution of deaths from spina bifida in birth cohorts exposed and unexposed to severe periconceptional famine. For this purpose, we compared the risk of deaths from spina bifida between birth cohorts exposed and unexposed to the Dutch Hunger Winter of 1944-1946. In males, the relative risk of death from spina bifida was 2.62 [95% confidence interval (CI) = 1.14-6.01]. In females, the relative risk for spina bifida was 0.59 (95% CI = 0.14-2.37). The sex ratio (male:female) for deaths from spina bifida in the exposed birth cohort was 2.74; a female predominance was not seen in any other birth cohort. Deaths from anencephaly and other central nervous system disorders did not exhibit this male predominance in the exposed birth cohort. These findings indicate that severe periconceptional nutrient deficiency may have a greater effect on the occurrence of spina bifida in males vs females. Other potential explanations include sex-specific effects of prenatal famine on prenatal or postnatal survival rates of cases.

Survival of infants with neural tube defects in Western Australia 1966-1990.

To investigate the survival of infants with neural tube defects in Western Australia from 1966 to 1990, cases of neural tube defects were ascertained from multiple sources. Survival of infants with anencephaly, spina bifida, and encephalocoele was examined separately, and four birth cohorts were compared: 1966-1972 (when most surviving infants were actively treated), 1973-1979 (a period of stringent application of selection criteria for treatment), 1980-1985 (some relaxation of selection criteria), and 1986-1990 (further relaxation of selection criteria). There was an increase in terminations of pregnancies affected with anencephaly over the study period, and a fall in the proportion of both liveborn and stillborn infants with anencephaly. Most liveborn infants (76.4%) died in the first 24 hours, and none survived longer than 5 days. Most infants with encephalocoele (76.4%) were liveborn, and survival was poorest in the 1973-1979 cohort, although the difference in survival across cohorts just failed to attain a formal level of significance. For spina bifida, there was an increase in terminations of affected pregnancies over the study period. Survival of liveborn infants with spina bifida was poorest in the 1973-1979 cohort, and greatest in the most recent cohort. These improvements in survival are likely to be the result of relaxation of selection criteria for treatment, improvements in treatment and, to a lesser extent, selective termination of affected pregnancies.