FETAL THERAPY

Fetal therapeutics is still in fetal stage, though rapid advances in antenatal diagnosis have opened new vistas to prevent or manage fetal disease in utero. These interventions may be divided into three categories: (a) preventive interventions in high-risk pregnancy, (b) medical interventions in prenatally-diagnosed cases, and (c) surgical interventions in congenital malformations.

IVH/PVH: IntraventricularZperiventricular hemorrhage, HDN: Hemolytic disease of newborn, ITP: Immune thrombocytopenic purpura, ART: Anti-retroviral therapy, CAH: Congenital adrenal hyperplasia, IEM: Inborn errors of metabolism, LBW: Low birth weight.

Table 12.4 enlists some disorders for which fetal therapy is possible or will be possible shortly, along with modes of intervention. However, some specific strategies are as follows:

Steroids in prematurity: Administration of IM Dexa­methasone (Four doses of 6 mg at 12 hourly interval) or IM betamethasone (Two doses of 12 mg at 12 hourly interval), at least 24 hours before delivery is an established intervention in mothers, likely to deliver lt;34 weeks of gestation. This simple measure reduces the risk of hyaline membrane disease (HMD) and intraventricular hemorrhage (IVH) in preterms by ~30-50%. However, it is contraindicated in presence of chorioamnionitis.

Phenobarbitone in Rh-isoimmunization: Administration of PO phenobarbitone (60 mg OD) for 2 weeks before anticipated time of delivery reduces the severity of neonatal hyperbilirubinemia and need for exchange transfusion. Phenobarbitone therapy has also been claimed to reduce risk of IVH/PVH in preterms, though not supported by evidence.

Folic acid supplements in neural tube defects: In mothers with history of previous birth with neural tube neural tube defects, PO folic acid 0.4 mg (4 mg OD for secondary prevention) once a day from two month before the expected conception to the end of first trimester, reduces the risk of recurrence gt; 50%.

Anti-retroviral therapy in HIV +ve mothers: Risk of perinatal HIV transmission from mother to the baby is known to reduce from 30-40% in untreated cases to lt;5% with appropriate antiretroviral therapy to mother, irrespective to her own health.

Intrauterine blood transfusion in Rh-HDN, via cordocentesis, may be life-saving in severe anemia with fetal hematocrit lt;20%. Repeated simple or exchange transfusions are often necessary till 32 weeks of gestation, followed by elective preterm delivery. In non-immune hydrops, IV albumin infusion may be used to prevent further fluid exudation.

Steroid therapy in congenital adrenal hyperplasia (CAH), with PO dexamethasone (1 mg OD) is indicated throughout pregnancy from 10th week onwards in prenatally detected CAH or history of previous CAH delivery, to prevent virilization of fetus.

Magnesium sulphate in mother undergoing preterm labor given as 4 gm/kg IV loading dose over 30 minutes followed by 1 gm/hour for 24 hours is known to reduce the risk of cerebral palsy and developmental delay.

Megavitamin therapy in inborn errors of metabolism may be useful to prevent mental retardation in prenatally detected cases of methyl-malonic acidemia (IV vitamin B₁₂ 5 mg OD) or multiple carboxylase deficiency (PO biotin 10 mg OD), when given in last trimester.

Steroid therapy in maternal immune thrombo­cytopenia (ITP), during last 2 weeks may prevent fetal isoimmunization. However, prenatally detected isoimmune thrombocytopenia needs platelet infusions and IVIG therapy via cordocentesis to prevent severe fetal hemorrhage.

12.3.5