expression on the fetal heart, in particular if there was evidence of myocardial inflammation, EFE, and/or incomplete heart block.66,92 The use of transplacental glucocorticoids for antibody-mediated fetal heart block remains controversial among specialists because the treatment will not reverse AV block that is already complete at the time of diagnosis because of the potential of adverse effects on the developing fetus, and because survival is often attained without prenatal intervention Thus an alternative approach, advocated by others, could be to restrict transplacental treatment to the compromised fetus; but this may carry an increased risk of postnatal cardiomyopathy.87,88,93 The following transplacental medication may be used to treat cardiac NLE Dexamethasone and Betamethasone Dexamethasone and betamethasone are potent synthetic glucocorticoids that are only minimally metabolized by the placenta and easily pass to the fetus, making these agents useful for direct fetal treatment Dexamethasone is often preferred, as it can be given as a single oral dose per day Unless the fetus is near term at the time of NLE diagnosis, we usually start dexamethasone at a dose of 8 mg/day for 2 weeks; this is then reduced to 4 mg/day to around 28 weeks and to 2 mg/day for the remainder of pregnancy Maternal IVIG (1 g/kg every 3 weeks) is added if we detect EFE, incomplete heart block, or both.66,92,94 We would not offer prenatal treatment, but close observation for a late pregnancy referral after 32 weeks of gestation with isolated fetal CHB, ventricular rates greater than 50 beats/min, and no obvious evidence of EFE or heart failure as survival to birth without disease progression is expected.94 Results The potential benefits of transplacental dexamethasone plus or minus IVIG include reduction of cardiac inflammation, reversal or stabilization of incomplete heart block, as well as improvement or resolution of AV valvar regurgitation, effusions, fetal hydrops, and/or EFE.65,66,78,85,95–101 There has also been improvement in outcome coinciding with the introduction of perinatal dexamethasone for CHB at our center.85 Current survival rates exceed 95% at 1 month and 90% at 10 years of life, which is significantly improved from our historical outcome data (Fig 9.2) and compared with predominantly untreated patient cohorts.82,85,87–89,93 FIG 9.2 Impact of transplacental fetal treatment with (Steroid) and without (No steroid) dexamethasone on fetal and postnatal outcome The survival was best with a protocol-guided approach (Tx protocol), which was introduced in 1997 (A) Survival by era of diagnosis (B) Survival with protocol-guided prenatal treatment (From Jaeggi ET, Fouron JC, Silverman ED, Ryan G, Smallhorn J, Hornberger LK Transplacental treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease Circulation 2004;110[12]:1542–1548.) Risks It is important to recognize that dexamethasone given at doses greater than 1.5 mg/day suppresses hypothalamic-pituitary-adrenal function A gradual reduction in maternal dosing is required if dexamethasone is given for more than 2 weeks Possible maternal adverse effects include an increased susceptibility to infection, changes in mood―such as irritability, euphoria, mania, depression, and/or anxiety―as well as weight gain, fluid retention, arterial hypertension, glucose intolerance, insomnia, hirsutism, striae, impaired wound healing, stomach irritation, and headache However, we have not observed any serious maternal events in our experience of more than 70 treated mothers Possible effects on the pregnancy include oligohydramnios and fetal growth restriction.85,102 Few if any other significant adverse effects on the fetus have been documented This includes no negative impact on the physical, mental, and neurologic performance of children and young adults after prenatal exposure to steroids.103–107 Similarly, CHB and dexamethasone were not associated with neurocognitive impairment in school-age children.108 Risks of IVIG treatment are mainly exposure to blood products and allergic reactions β-Sympathomimetic Agents The β1-adrenergic actions of salbutamol and terbutaline can be used to increase fetal cardiac output by an increase in heart rate and a decrease in systemic vascular resistance.109,110 Such stimulation is recommended for fetal heart rates that are persistently below 50 to 55 beats/min or when there is significantly reduced cardiac contractility.11,94 When given orally to the mother at or close to the maximal recommended daily doses, salbutamol (10 mg every 8 hours, maximum of 40 mg/day)85 and terbulatin (2.5 to 7.5 mg every 4–6 hours, maximum of 30 mg/day)111 will typically increase the ventricular rate by 5 to 10 beats/min This chronotropic effect usually persists for many weeks Both compounds are rapidly absorbed from the gastrointestinal tract but incompletely cross the placenta, so an umbilical cord–maternal drug ratios of only about 50% can be expected.112 Adrenergic maternal side effects include tremor, palpitations, and sweating, which usually improve or resolve with continuation of drug therapy.85,111 More serious maternal adverse events or intolerable symptoms that require a change in drug treatment have not been reported and were not observed by us with the use of oral salbutamol β-Agonists should be used cautiously in mothers with diabetes, hypertension, hyperthyroidism, and a history of seizures or tachyarrhythmias