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To determine the recurrence risk for patients with one prior pregnancy affected with neural tube defects (NTD), the authors have pooled data from eight testing centers. In 831 pregnancies studied because one sib was affected with an NTD, the recurrence rate was 3.0%, with 95% confidence limits of 2.0-4.3%, and 99% confidence limits of 1.8-4.8%. The recurrent lesion, whether spina bifida or anencephaly, tended to be concordant with the first to a significant degree. Only 12.2% of recurrent NTD were different from the first, with 95% confidence limits of 4.1-26.2%, and 99% confidence limits of 1.7-30.9%. Both an accurate recurrence risk and the information that a recurrent NTD lesions tends to be concordant with that in the first affected child are useful in the genetic counseling of patients in the United States and in the selection of appropriate prenatal diagnostic studies.

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Women with antiphospholipid antibodies (aPL = IgG anticardiolipin and/or lupus anticoagulants) and a history of either prior thrombotic events or pregnancy loss are at high risk during pregnancy for either another fetal death or thrombosis. The treatment of choice is anticoagulation with heparin. Both standard unfractionated heparin and low-molecular-weight heparin are used for prophylactic anticoagulation during pregnancy. The half-lives of either standard heparin, or low-molecular-weight heparin, and the peak values for each after subcutaneous injection, are lower than those in nonpregnant patients. Doses and injection intervals need to be adjusted when treating a pregnant woman. Clotting tests such as the activated partial thromboplastin time (aPTT) vary greatly during pregnancy, and the aPTT is often not even prolonged when antithrombotic levels of heparin are achieved. The aPTT is not a useful test when the patient has a lupus anticoagulant. Levels of plasma heparin are therefore needed to best care for pregnant women who need anticoagulation—even for prophylaxis. Low-dose aspirin is often added empirically to heparin for treatment of aPL during pregnancy, but its efficacy has not been evaluated. Intravenous infusions of gamma globulins (IVGG) have been used as additional therapy when prior treatment with heparin during pregnancy failed to save the fetus, when severe and early onset preeclampsia has complicated a prior pregnancy (in such cases efficacy is unproven), or when there is an additional medical complication (such as immune thrombocytopenia) for which IVGG is an appropriate treatment. There are some situations in which treatment with corticosteroids is the best, or the only choice. However, corticosteroids should not be combined with heparin for long-term treatment during pregnancy because the risk for vertebral fracture is so high.

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The established association between a relatively specific group of autoantibodies binding negatively charged phospholipids and poor pregnancy outcome has advanced treatment options for women with this diagnosis. Evidence for an association between systemic autoimmune disorders and otherwise unexplained obstetric complications, in the absence of a documented antiphospholipid antibody(s), is reviewed. The existence of autoantibodies with other specificities that could be related to fetal wastage has been suggested by associations between poor obstetric histories and nonspecific serologic abnormalities observed in women with no clinical signs of an autoimmune disorder. Because signs and symptoms of vasospasm such as Raynaud's phenomenon or placental infarction have been observed in women with a history of unexplained fetal demise, a search for autoantibodies recognizing antigens common to trophoblastic and vascular cell surfaces is suggested.

The first treatment of pregnant women with antiphospholipid antibody syndrome (APLS) employed high doses of corticosteroids, plus low dose aspirin, with the goal of suppressing production of the autoantibody. Corticosteroids (usually prednisone), even when much lower doses are used, and even when tapered after midpregnancy, have been associated with significant maternal and obstetric risks and side effects: the most important are osteomalacia and preterm delivery (often precipitated by premature rupture of the membranes). Since the publication of a randomized trial demonstrating equivalent live birth rates of about 75% whether heparin or prednisone was used for treatment (plus low dose aspirin), the use of adjusted doses of heparin, together with low dose aspirin, has replaced prednisone for treatment of pregnant women; although prednisone may still be needed to treat manifestations of associated autoimmune disorders. A recent randomized trial has shown that the addition of heparin to aspirin is probably superior to treatment with aspirin alone. To achieve prophylactic levels of plasma heparin equivalent to those measured in patients who are not pregnant and are treated with the usual dose of standard heparin of 5000 IU every 12 h, the heparin dose required for treatment of pregnant women is usually higher. For that reason, heparin doses should be adjusted using the nadir APTT, or better plasma heparin measured by a factor Xa inhibition assay at the 2 h post-injection peak. Although low molecular weight heparin has been shown to be useful in prevention of fetal resorption in a mouse model, and appears to be equally safe for treatment of pregnant women, we still have no published data to show therapeutic equivalency, with respect to treatment of APLS-complicated pregnancy, to standard heparin preparations, and none that demonstrate any lower risk for the complication of most concern when heparin is given to pregnant women-osteopenia. Similarly, intravenous infusion of gamma globulins (IVG) appears on the basis of case reports to be effective additional treatment in cases where standard therapy has failed. Gamma globulin preparations contain anti-idiotypic antibodies that have been shown to bind to patient antiphospholipid antibodies. The place for the addition of IVG to standard therapy has not been defined, but clinically significant and corticosteroid-resistant thrombocytopenia complicating antiphospholipid antibody syndrome might be one indication for primary treatment with IVG +/- low dose aspirin. Overall, live birth rates in most treatment studies are in the range of 70-80%. The reported birth rate information, however, cannot be compared between studies. None of the studies reported have used tools such as logistic regression analysis to allow for such significant predictors of live birth as the number of prior miscarriages, maternal age, medical history, or a history of fetal death (loss of a viable and chromosomally normal fetus after the 10th gestational week).