Overview of Neonatal Lupus

Benay Johnson, MSN, RN, CPNP, NNP-BC

Disclosures

J Pediatr Health Care. 2014;28(4):331-341. 

In This Article

Pathophysiology

From embryologic studies we know that the fetus is protected from exposure to maternal blood up to a point. The barrier between the mother and fetus is not completely impermeable, especially with regard to bacterial and viral agents such as toxoplasmosis/other infections/rubella/cytomegalovirus/herpes simplex virus–2 (TORCH) infections (Jones & Wilson, 2011). Antibodies produced in the body aid in the protection against bacterial and viral exposure. Antibodies can cross the placental barrier (Nodine, Arruda, & Tolsma, 2011). It is the immunoglobulin G (IgG) class of antibodies from the mother that are small enough to permeate the placenta and gain access into the fetal circulation (Blickstein & Friedman, 2011). Anti–extractable nuclear antigen autoantibodies, which are in the IgG class (Zuppa et al., 2008), begin to cross the placenta at about 12 week's gestation. Autoantibodies are antibodies that are directed against the self and are recognized as part of an autoimmune disorder. In the case of NL, maternal antibodies are produced by the sensitization of the mother's immune system, resulting in autoantibodies (Blickstein & Friedman, 2011).

Antinuclear antibodies (ANAs) are found in patients whose immune system may be predisposed to inflammation against their own body tissue. If a patient tests positive for ANA, the presence of an autoimmune disorder is considered, but ANA can also be present within the healthy population (Sawalha, Diaz, & Harley, 2006). It is estimated that NL will develop in 1% of the infants of the women who test positive for ANA (Blickman & Friedman, 2011). The presence of anti-RNP is more of an indication of a mixed connective tissue disease (Sawalha et al., 2006). For this reason, ANA is thought to be a sensitive marker for SLE; however, the presence of ANA should not be the sole indicator leading to the diagnosis of SLE. ANA titers of less than 1:640 have been noted in healthy persons (Curran, 2012). Anti–double-stranded deoxyribonucleic acid (anti-dsDNA) is considered specific for SLE (Blickman & Friedman, 2011). Along with maternal ANA, the fetus will receive extractable nuclear antigen of anti–SS-A/Ro and/or anti–SS-B/La. Table 1 provides references for the common autoantibodies present in persons with SLE and other autoimmune connective tissue disorders.

Structurally, anti–SS-A/Ro is located inside the cell (Qu & Boutjdir, 2012). According to Zuppa et al. (2008) the classification of autoantibodies as anti–SS-A/Ro, anti–SS-B/La, or anti-RNP is dependent on the type of antibody the antigen reacts with, which can occur in any combination. In the majority of cases, the mother will have anti–SS-A/Ro and anti–SS-B/La antibodies (Pain & Beresford, 2007), along with a positive ANA titer. Autoantibodies are common in childbearing women (Jaeggi, Laskin, Hamilton, Kingdom, & Silverman, 2010). Mothers can be diagnosed with SLE before, during, or after pregnancy (Yang, Shih, & Yang, 2010) or can be asymptomatic at the time of delivery. NL can occur in the fetus or newborn if the mother carries a diagnosis of SLE, Sjögren syndrome, APS, or another autoimmune connective tissue disorder (Zuppa et al., 2008). The majority of cases result from mothers with SLE; however, out of these cases of SLE, NL will develop in only approximately 1% of infants (Blickman & Friedman, 2011). Autoimmune disease initiates the placental passage of anti–SS-A/Ro and anti–SS-B/La antibodies to the fetus (Pain & Beresford, 2007). These antibodies cross the placenta starting at 12 week's gestation (Buyon, Clancy, & Friedman, 2009). Although these autoantibodies have been documented to be the causative agent in NL, they do not appear to be the singular agent. It has been suggested that genetics may play a role (Inzinger, Salmhofer, & Binder, 2012), along with environmental factors (Buyon et al., 2009).

The wave of electrical activity of the heart travels from the sinoatrial node to the atrioventricular (AV) node as it passes to the His-Purkinje fibers that supply the ventricles. The sinoatrial node is the pacemaker of the heart, with the AV node taking control of this function, at a slower rate, if the conduction pathway is damaged. The rate of conduction among the fibers is one factor that determines filling of the ventricles. Cardiac output can be compromised if the conduction system becomes scarred or if fibrotic tissue forms.

They are the anti-SS-A/Ro and anti-SS-B/La antibodies that are thought to cross-react with the calcium channels in the myocardium, specifically in or around the AV node (Qu & Boutijdir, 2012). Anti–Ro/La autoantibodies have an affinity for adrenoceptors and muscarinic receptors, which bring these autoantibodies into the conduction system of the cardiac muscle (Blickman & Friedman, 2011), resulting in inflammation, scarring, and fibrosis (Laurinaviciene, Christesen, & Bygum, 2012). Fibrosis of the AV node leads to a delay in the conduction system, leading to heart block. The onset of heart block is noted to occur in the gestational period between 18 to 24 weeks (Zuppa et al., 2008). Jaeggi et al. (2010) cites a study published in 1991 that hypothesized that inflammation of the fetal AV node or surrounding tissue is initiated when anti–SSA/Ro antibodies cross the placenta and enter the cardiac tissue. Ongoing inflammation results in fibrosis, which in turn can progress to heart block and/or endocardial fibroelastosis (EFE). Diagnosed by echocardiogram, EFE is defined as diffuse thickening of the endocardium from proliferation of collagen and elastic fibers (Pises et al., 2009), which can be asymptomatic or require pacing (Sawalha et al., 2006). EFE can eventually progress to heart failure, leading to hydrops fetalis.

Jaeggi et al. (2010) associated high levels of anti-Ro antibodies in babies with cardiac manifestations. The authors state that although high levels of antibodies were present, this was not sufficient to explain the development of cardiac findings in NL. At the time of delivery, 22% to 40% of mothers are unaware of the presence of anti–SS-A/Ro or anti–SS-B/La antibodies within them (Pain & Beresford, 2007). These mothers may be asymptomatic (Zuppa et al., 2008), but 50% will later experience symptoms related to autoimmunity.

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