Fetal malformations and fetal death in a case of parental thrombophilia.

B.T., a 26 year old pregnant woman who reached 41 weeks of gestation (gravida 1, para 0), came to our observation in June 1994, for a spontaneous onset of labour. She was taken care of elsewhere during pregnancy. The course of gestation had been normal and no risk factor was evident from both the clinical history and the analysis of the patient’s clinical condition. Laboratory tests were normal. Previous ultrasound scans revealed a fetal growth at the lower end of the normal range expected for gestational age, but Doppler studies showed that the fetus was healthy. The patient’s body weight was 64 kg (increased 10 kg during pregnancy) and blood pressure was 110/70 mmHg. After an uneventful labour, a female baby weighing 2600 g, with Apgar scores of 8/9, was delivered vaginally. However, the infant presented at birth a left dorsolumbar hemispondylia and an oesophageal atresia type III. None of these anomalies had been diagnosed prenatally through a serial sonographic follow-up. The neonatal karyotype was 46, XX. Subsequently, the presence of 13 ribs and a little paramedian schisis of the posterior arches of the first sacral vertebrae (spina bifida occulta) were also observed; moreover, hypoplasia of the corpus callosum was diagnosed by nuclear magnetic resonance. The infant underwent surgery repeatedly for correction of the oesophageal atresia and the hemispondylia. No correction of spina bifida occulta was considered necessary at that stage, given its entity and the absence of clinical neurological deficits. Currently the child is fourteen years old. A mild and transient gastro-oesophageal reflux, besides a 30° kyphosis and 25° scoliosis of the dorsolumbar tract of the rachis requiring physiotherapy, persist. Nevertheless, the child does not show any mental nor neurological deficits. In 2001, the woman, at 33 years of age, became pregnant again; however, fetal death occurred at 20 weeks’ gestation. No fetal malformations were revealed by the autopsy; however, the placenta showed largely extended infarctions. Since the woman desired a further pregnancy, though other investigations gave normal results, both parents underwent screening for thrombophilias. Eterozygosity for both the C677T and the A1298C mutation in the methylene tetrahydrofolate reductase (MTHFR) gene, as well as for the Factor V Leiden mutation (G1691A) were found in the woman. Eterozygosity for the C677T MTHFR gene mutation was also demonstrated in the husband. A screening for thrombophilias was therefore advised to be carried out in the live infant as well, which brought to the identification of eterozygosity for the Factor V Leiden mutation and homozygosity for the C677T MTHFR gene mutation. In 2003, the woman, (gravida 3, para 1), came to us again for obstetric care. Early therapy with low molecular weight heparin (enoxaparin) was carried out at a dose of 4000 units/day, in addition to treatment with folic acid and vitamins B6 and B12. The course of this pregnancy was uneventful. Blood coagulation tests, as well as the levels of Antithrombin III, Protein C, Protein S and homocysteine kept within normal ranges throughout the pregnancy. Screening for thrombophilias through amniocentesis revealed eterozygosity for the C677T MTHFR gene mutation. The prenatal ultrasound follow-up showed normal fetal growth and absence of anomalies. Doppler studies showed normal velocimetry patterns. A caesarean section was performed due to fetal face presentation at 39 weeks’ gestation, and a healthy male baby weighing 3050g, with Apgar scores 9/10, was delivered.