INTRODUCTION Raynaud’s phenomenon involves episodic vasospasm of the fingers and toes in response to cold. Generally, the condition is recurrent and long lasting, however, it’s generally mild with few morbidities. In contrast, secondary Raynaud’s is associated with more severe autoimmune diseases such as scleroderma (1).

Research shows that Raynaud’s phenomenon is caused by vasospasm of the small arteries of the digits likely due to endothelial dysregulation of cytokines, growth factors, and prostaglandins (2).

Blogs and case reports suggest that patients with Raynaud’s phenomenon may have higher rates of vascular complications during pregnancy, however, this has not been sufficiently evaluated. In a published case report, authors describe a patient with Raynaud’s phenomenon whose pregnancies ended in a spontaneous abortion, then an intrauterine fetal demise, and then placental insuffiency resulting in a cesarean section for fetal indications (3). In a study of 67 women with Raynaud’s phenomenon there was an increased rate of premature births and a lower mean weight of full-term babies. The study failed to find any neonatal deaths or other serious adverse outcomes. They hypothesize these findings may be a manifestation of vascular disease (4).

A literature search failed to find any systemic surveys to further elucidate the relationship between Raynaud’s phenomenon and pregnancy complications.

KEYWORDS: pregnancy complications, Raynaud’s, autoimmune

PURPOSE •  We hypothesize that pregnant patients with Raynaud’s phenomenon

experience higher rates of hypertensive disorders and other pregnancy complications associated with placental insufficiency.

•  Consequently, patients may have higher rates of emergent deliveries and poor neonatal outcomes. Anecdotal data support these theories; however, the objective data are lacking.

•  The aim of our study is to elucidate the rates of pregnancy complications in patients with Raynaud’s phenomenon.

•  This knowledge will ultimately assist obstetricians in counseling and caring for these patients.

ASSOCIATION BETWEEN RAYNAUD’S PHENOMENON AND PREGNANCY COMPLICATIONS

Kate C Arnold, MD ● Dena E White, MD ● Caroline J Flint, MD Dept of Obstetrics & Gynecology; The University of Oklahoma Health Sciences Center; Oklahoma City, OK

METHODS An institutional review board-approved survey was published online with a link to it on the Raynaud’s Association website and their Facebook page. The survey includes 32 questions regarding demographics, Raynaud’s phenomenon, and pregnancy complications. All females with Raynaud’s phenomenon were eligible for the survey. Currently, 7,280 people ‘like’ Raynaud’s Association on Facebook. No incentives were given, the survey was voluntary and anonymous. Given the overall rate of pre-eclampsia in the US of 3.4%, we need a sample size of 100 to detect a difference of 1% using a p value of 0.5 (5). Simple statistics such as mean and standard deviations will be calculated and data from our study will be compared with national data providing averages of pregnancy complications using Pearson chi squared tests.

DISCUSSION Raynaud’s during pregnancy was associated with poorer outcomes than the general population for conception, pregnancy, delivery, and perinatal outcomes. Around conception, patient’s with Raynaud’s had double the incidence of having 3 or more miscarriages and also double the incidence of infertility. Perinatal complications such as preterm birth, perinatal mortality, NICU admissions, and abruption were all increased. Mode of delivery was fairly comparable, however, patients with Raynaud’s were significantly more likely to have an emergency cesarean section. Hypertensive disorders also appear to be increased with an overall prevalence of 24% and a rate of preeclampsia of 9.5% with the national average being 3.4 % (5).

Overall our results support the hypothesis that the vascular dysfunction seen in Raynaud’s may be associated with poor obstetric outcomes. Weaknesses of our study are the retrospective nature and the fact that we were forced to rely on patient understanding of medical diagnoses. One surprising finding was that there was no significant difference in outcomes between primary and secondary Raynaud’s, suggesting that primary Raynaud’s may be as significant as a diagnosis of Lupus and other autoimmune diseases.

CONCLUSION Patients with Raynaud’s phenomenon appear to be at increased risk for vascular complications during pregnancy such as hypertensive disorders, emergent deliveries, and poor neonatal outcomes. Obstetric providers should be aware of their increased risk and manage pregnancies accordingly. Additionally, while primary Raynaud’s is thought to be more innocuous than secondary, our data showed no difference in obstetrical outcomes. Further studies will need to confirm this.

REFERENCES 1. Gelber AC, Wigley FM, Stallings RY, Bone LR, Barker AV, Baylor I, Harris CW, Hill MN, Zeger SL, Levine DM.

Symptoms of Raynaud's phenomenon in an inner-city African-American community: prevalence and self-reported cardiovascular comorbidity. Journal of clinical epidemiology. 1999;52(5):441-6. PubMed PMID: 10360339.

2. Block JA, Sequeira W. Raynaud's phenomenon. Lancet. 2001;357(9273):2042-8. doi: 10.1016/S0140-6736(00)05118-7. PubMed PMID: 11438158.

3. Babenerd J, Flenker H. Pregnancy in a patient with Raynaud's disease. Archives of gynecology. 1979;227(2):119-23. PubMed PMID: 485219.

4. Kahl LE, Blair C, Ramsey-Goldman R, Steen VD. Pregnancy outcomes in women with primary Raynaud's phenomenon. Arthritis and rheumatism. 1990;33(8):1249-55. PubMed PMID: 2390127.

5.  Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. Bmj. 2013;347:f6564. doi: 10.1136/bmj.f6564. PubMed PMID: 24201165; PubMed Central PMCID: PMC3898425

6.  .”Preterm birth” http://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm. CDC. 3/31/2015.

7.  “Infertility” http://www.cdc.gov/nchs/fastats/infertility.htm. CDC. 3/31/15 8.  “Primary cesarean section rates 2006-2012). http://www.cdc.gov/nchs/data/nvsr/nvsr63/nvsr63_01.pdf.

CDC. 3/31/15. 9.  “RCOG statement on emergency caesarean section rates” June 4, 2013. 10.  Oyelese Y, Ananth CV. “Placental Abruption.” Obstetrics and Gynecology Oct 2006. 108(4)1005-1016. 11.  Alijotas-Reig J, Garrido-Gimenez G. “Current Concepts and New Trends in the Diagnosis and

Management of Recurrent Miscarriage.” Obsetrical and Gynecological Survey CME Review Article. Colume 68 (3). 2013.

12.  Gregory ECW, MacDorman FM, Martin JA. “Trends in Fetal and Perinatal Mortality in the United States, 2006-2012.” NCHS Data Brief, No 169, Nov 2014.

13.  Osteman MJK, Martin JA, Matthews TJ, Hamilton B. “Expanded Data from the new Birth Certificate, 2008.” National Vital Statistics Report. Vol 59(7). CDC. http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_07.pdf

CLASSIFICATION OF RAYNAUD’S

•  Primary: no underlying illness, onset in 20s-30s, mild symptoms, no ulceration or systemic vasospasm

•  Secondary = Raynaud’s Syndrome: has an associated autoimmune disorder, onset usually after 40 yo, generally progressive digital damage and visceral organ involvement

Pregnancy issue Incidence in general population

Raynaud's (n=138)

Primary Raynaud's (n=66)

Secondary Raynaud's (n=30)

Preterm birth 11% 6 28 (27%) 13 (16%) 10 (29%) Infertility 10.9% 7 31 (25%) 16 (24%) 7 (23%) History of primary cesarean section

21.9% 8 34 (33%)  8 (27%)  8 (27%)

Emergency Cesarean Section

3.89 26 (25%) 14 (25%) 6 (20%)

Abruption 1% 10 6 (5.8%) 2 (3.6%) 4 (13%) Ever had miscarriage 15%11 43 (41%) 18 (33%) 15 (50%)

3 Or more miscarriages 1-3%11 7 (6.7%) 1 (1.8%) 3 (10%)

Perinatal Mortality 0.63%12 3 (2.7%) 1 (1.7%) 0 (0%)

NICU Admission 14.4%13 35 (32%) 20 (33%) 10 (33%)

RATES OF PREGNANCY COMPLICATIONS IN PATIENTS WITH RAYNAUD’S PHENOMENON

Note: some patients did not know their diagnosis and are only included in broader Raynaud's group.

Figures 1 and 2: Photographs showing affected by Raynaud’s Figure 1: Hnnds: mayoclinic.org. Figure 2: Feet. www.northcoastfootcareblog.com/wp-content/uploads/2008/01/Raynaud's-2.jpg

RESULTSPreconception counseling showed that 13% of patients with primary Raynaud’s and 31% of patients with secondary Raynaud's were counseled by a medical professional that their pregnancy would be high risk. Twenty four percent reported problems with hypertension. Additional outcomes are listed in table format. Of note, none of the p values comparing outcomes for primary versus secondary outcomes reached statistical significance.

Condition Reported Rate in Raynaud's Patients

PreEclampsia without magnesium

11 (9.5%)

PreEclampsia with magnesium

9 (7.8%)

Gestational hypertension without magnesium

13 (11.2%)

Gestational hypertension with magnesium

8 (6.9%)

RATES OF HYPERTENSIVE DISORDERS