LAUSR

Haemoglobin H Constant Spring (HbH-CS) (--/aa), the most common non-deletion a-thalassaemia, is one of the important health problems in Southeast Asia and South China, due to its high prevalence, accounting for 50% of HbH disease in Thai paediatric patients. The frequencies of a0 thalassaemia trait caused by the Southeast-Asia 2a gene deletion (--SEA) and the CS mutation in our population are 6 6% and 1–8%, respectively. The clinical severity of HbH-CS is widely variable. At the most severe, the fetuses develop hydrops fetalis in utero leading to stillbirth or neonatal death. Lal et al. reported that the severity of HbH-CS in postnatal life varies widely, from benign to life-threatening. However, the natural course of the disease in utero has never been thoroughly explored. The present study aimed to focus on the early detection, natural course of the disease in utero, and the treatment of some selected cases to primarily prevent fetal morbidity and mortality and for the possible prevention of residual hypoxic insult in adult life, known as fetal programming. Importantly, we also emphasise that in the areas of high prevalence, identification of fetuses at risk by screening the parents for a carrier of HbCS is warranted and that the fetuses at risk need surveillance for severe anaemia in utero. The prenatal course of four affected fetuses was longitudinally studied. All were recruited because of a suspicion of fetal anaemia after 20 weeks and were followed-up with serial ultrasound to monitor various pre-hydropic and hydropic signs. The middle cerebral artery peak systolic velocity (MCA-PSV) was used as a non-invasive tool to assess fetal anaemia. All were confirmed to have HbH-CS based on molecular studies. All showed signs of anaemia after midpregnancy; missed from routine anomaly screening at midpregnancy. Two cases (Case 2 and 3) illustrate the importance of intrauterine transfusion (IUT), which completely converted hydrops Figure S1 and S2, resulting in successful outcomes. The other two cases (Case 1 and 4) illustrate the natural course without intervention. Case 1, was hydropic and died in the neonatal period because of birth asphyxia as a consequence of anaemic hydrops; and Case 4, had progressive hydrops after 20 weeks and somewhat improved in third