Pregnancy in Complement-Mediated Thrombotic Microangiopathy: Maternal and Neonatal Outcomes

Natalja Haninger-Vacariu; Andreas Gleiss; Martina Gaggl; Christof Aigner; Renate Kain; Zoltán Prohászka; Ágnes Szilágyi; Dorottya Csuka; Georg A Böhmig; Raute Sunder-Plassmann; Gere Sunder-Plassmann; Alice Schmidt

doi:10.1016/j.xkme.2023.100669

Pregnancy in Complement-Mediated Thrombotic Microangiopathy: Maternal and Neonatal Outcomes

Kidney Med. 2023 May 16;5(7):100669. doi: 10.1016/j.xkme.2023.100669. eCollection 2023 Jul.

Affiliations

¹ Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
² Center for Medical Science, Institute of Clinical Biometrics, Medical University of Vienna, Vienna, Austria.
³ Department of Pathology, Medical University of Vienna, Vienna, Austria.
⁴ Research Laboratory, Department of Internal Medicine and Hematology, and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
⁵ Genetics Laboratory, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Abstract

Rationale & objective: Pregnancy, delivery, and neonatal outcomes in women with complement-mediated thrombotic microangiopathy (cTMA) have not been well described. A better understanding of these outcomes is necessary to provide women with competent pregnancy counseling.

Study design: Cohort study.

Setting and participants: Women with a history of cTMA and pregnancies enrolled into the Vienna thrombotic microangiopathy cohort.

Exposure: New onset or relapses of cTMA.

Outcomes: Pregnancy, delivery, and neonatal outcomes of pregnancies in women (a) before cTMA manifestation, (b) complicated by pregnancy-associated cTMA (P-cTMA), and (c) after first manifestation of cTMA or P-cTMA.

Analytical approach: Mixed models were used to adjust the comparison of pregnancy, delivery, and neonatal outcomes between conditions (before, with, and after cTMA) for repeated pregnancies using the mother's ID as random factor. In addition, the fixed factors, mother's age and neonate's sex, were used for adjustment. For (sex-adjusted and age-adjusted) centile outcomes, only the mother's age was used. Adjusted odds ratios were derived from a generalized linear mixed model with live birth as the outcome. Least squares means and pairwise differences between them were derived from the linear mixed models for the remaining outcomes.

Results: 28 women reported 74 pregnancies. Despite higher rates of fetal loss before the diagnosis of P-cTMA and preterm births with P-cTMA, most of the women were able to conceive successfully. Neonatal development in all 3 conditions of pregnancies was excellent. Pregnancy and neonatal outcomes were better in women with a pregnancy after the diagnosis of cTMA.

Limitations: Although our data set comprises a considerable number of 74 pregnancies, the effective sample size is lower because only 28 mothers with multiple pregnancies were observed. The statistical power for detecting clinically relevant effects was probably low. A recall bias for miscarriages cannot be ruled out.

Conclusions: Prepregnancy counseling of women with a history of cTMA can be supportive of their desire to become pregnant.

Keywords: Thrombotic microangiopathy; aHUS; abortion; cTMA; complement system; delivery; live birth; miscarriage; neonatal outcomes; pregnancy; pregnancy counseling.