Abstract Disclosure: B. Tracey: None. T. Neal: None. M. Lightbourne: None. M.S. Startzell: None. E. Cochran: None. P. Stratton: None. R.J. Brown: None. Lipodystrophy (LD) is characterized by partial (PL) or total (generalized, GL) deficiency of adipose tissue, leading to diabetes mellitus (DM), dyslipidemia, and polycystic ovary syndrome. Prior reports suggest increased risk of gestational DM (GDM), preeclampsia, and miscarriage in PL; infertility is common in GL. We explored if pregnancy complications in LD were related to typical risk factors (age, race) and/or LD-specific risk factors (GL vs PL; genotype of PL). Pregnancy data in patients with LD obtained by interview and chart review included: number of pregnancies, use of assisted reproduction technology (ART), miscarriage, GDM or pre-gestational DM (pre-GDM), preeclampsia, and weight gain. 28 patients (22 White, 6 BIPOC) had 74 pregnancies at ages 19-39y. 7 with GL (6 AGPAT2, 1 BSCL2) had 21 pregnancies (3.0±2.4 per person). 13 pregnancies in 6 patients with GL occurred on metreleptin; 1 had 8 pregnancies (3 miscarriages) without metreleptin. 21 patients with PL (7 LMNA, 4 PPARG, 10 unknown genotype) had 53 pregnancies (17 LMNA, 10 PPARG, 26 unknown; mean 2.5±1.3 per person); none were on metreleptin. No pregnancy in GL and 10 (19%) in PL used ART (P=0.053). In PL with LMNA, PPARG, and unknown genotype, ART was used in 3 (18%), 3 (30%), and 4 (15%) pregnancies (P=0.6). 10 (48%) of pregnancies in GL and 18 (34%) in PL ended in miscarriage (P=0.3). 11 patients (3 GL [43%], 8 PL [38%]) had recurrent (≥2) miscarriages. 2 ectopic pregnancies and 1 elective abortion occurred in PL. In PL with LMNA, PPARG, and unknown genotype, miscarriage occurred in 7 (41%), 3 (30%), and 8 (31%) of pregnancies (P=0.7). Pre-GDM preceded all 13 pregnancies in 6 patients with GL; 1 patient had 8 pregnancies without pre-GDM. In all LD, pre-GDM preceded 7 (25%) pregnancies in patients ≤25y and 22 (48%) in those >25y (P=0.08). Among 30 pregnancies continuing ≥20 weeks without pre-GDM, GDM developed in 3 (25%) ≤25y, and 9 (50%) >25y (P=0.3). GDM did not differ by genotype: LMNA 3 (43%), PPARG 4 (57%), unknown 5 (45%); P>0.99. Among 44 pregnancies continuing ≥20 weeks, preeclampsia developed in 5 (45%) in GL and 13 (39%) in PL (P>0.99). Preeclampsia incidence did not differ by genotype in PL (22% LMNA, 14% PPARG, 41% unknown genotype; P=0.4), race (26% White, 56% BIPOC, P=0.1), or age (23% ≤25y, 35% >25y, P=0.7). Gestational weight gain was less in GL than PL (mean 6.8±3.7 kg GL, 14.3±8.3 kg PL, P=0.0002) but was similar by PL genotype (LMNA 13.8±6.2 kg, PPARG 12.1±5.5 kg, unknown 15.4±8.5 kg; P=0.6). In this large study of pregnancy in LD, overall complication rates were high compared with healthy US women (with rates of miscarriage of 20%, recurrent miscarriage of <5%, pre-GDM of 4%, GDM of 15%, preeclampsia of 6%), but few were enhanced by LD-specific or typical risk factors; sample size was small. Gestational weight gain was lower in GL than PL, likely due to low fat mass in GL. These findings provide guidance for monitoring pregnancies in LD. Presentation: 6/1/2024